Asherman's syndrome watch

When available studies are limited, expert opinions count

2011-12-14T17:32:00.000-08:00

As a strong believer in evidence-based medicine, the lack of the highest quality of studies and sometimes of sound scientific interpretation in articles about Asherman’s syndrome is disappointing. It can be difficult to accurately assess information on AS from different sources when primary studies may be deficient in study design, use outdated techniques of diagnosis or treatment, have small sample sizes, are carried out retrospectively, randomization/allocation concealment are absent and when comparisons between primary studies is impossible due to differences in methods of treatment. Unfortunately some of these limitations are difficult, if not impossible to overcome. However, there is still room for improvement in studies about AS. There is also a lot we can learn about AS by correctly interpreting data that is already available, and by taking note of the knowledge acquired from specialists with extensive expertise on the topic. To be knowledgible about AS requires more than having the letters MD behind your name, learning about AS through a 10 minute lecture at University and skimming through a few papers on it. To be an expert requires decades of experience with diagnosing and treating it and the ability to think scientifically (objectively), something doctors are not actually taught routinely which is only really pertinent to doctors that are involved in research.

Dr Charles March of California Fertility Partners is a respected authority on Asherman’s syndrome. He is board certified in Obstetrics and Gynecology and fellowship trained in Reproductive Endocrinology and Infertility and was a Professor at University of Southern California. Not only is he a great surgeon who is popular with patients, but I believe he is currently the doctor with the most knowledge about Asherman’s syndrome. This is probably due to the fact that he has over 30 years of experience in dealing with patients that have Asherman’s syndrome and that he is additionally a fertility specialist and obstetrician which enables him to clearly see the causes and repercussions of the condition. He also has a particular interest in the condition and clearly enjoys talking and educating others about it.

His most recent review article,‘Management of Asherman’s syndrome’, appeared in Reproductive Biomedicine Online this year. His articles show that he is a wealth of information on all aspects of AS. Anyone can write a narrative review by consolidating previous data and supporting their arguments with cherry-picked information they have read, sometimes from old or inaccurate sources, but only those who have strong critical appraisal skills and the know-how that comes from decades of experience can offer so much valuable insight and advice on a topic. My next blog will focus on the relevant discussions and kernels of wisdom found in Dr March’s review on Asherman’s syndrome.

Indispensable technique becomes disposable to boost its use

2011-11-24T05:02:00.000-08:00

A new single-use disposable hysteroscope (http://hcp.obgyn.net/conference-insider/aagl2011/content/article/1760982/1976908 and http://hcp.obgyn.net/conference-insider/aagl2011/content/article/1760982/1980724) is being investigated by Dr Paul Indman in hopes that, once FDA-approved for commercial use, it will encourage more gynecologists to carry out diagnostic hysteroscopy in an office setting. Dr Indman believes that it is just as important for a gynaecologist to be able to look inside the uterus as it is for an ear doctor to look inside the ear. While nothing seems more evident, fewer than 10% of Obgyns in the US are trained to perform in-office hysteroscopy. This is due to a number of factors including the lengthy preparation and costs of setting up traditional hysteroscopy. Conventional ones are large and cumbersome, and need to be sterilised before each use. Besides the actual hysteroscope, a video camera, monitor and lighting are necessary to perform the procedure. The new hysteroscope is hand-held with a plastic disposable hysteroscope and a reusable handle that has a monitor, light source and a high resolution camera the size of a pin-head incorporated into it. Currently, plastic disposable curettes are used for D&C, so there is no basis for the concern that this will increase pollution to the environment. Hopefully it will be available in the near future and more gynaecologists and fertility specialists will take an interest in using this less-invasive technology to improve diagnosis of women’s health problems. Note: There is another similar device that is available for ~ 300 USD: http://medgadget.com/2007/01/femsuites_femey.html

(Disclaimer: It is up to medical professionals who are trained in hysteroscopy to assess the performance of these products. I am not in a position to endorse them).

Hysteroscopy is gold-standard method for the evaluation of the uterine cavity to diagnose conditions such as intrauterine adhesions, endometrial polyps and fibroids and structural malformations such as septate uterus. Operative hysteroscopy is used for treating the diagnosed condition where microscissors or other instruments are used for tissue dissection. A resectoscope is a hysteroscope which is equipped with loop that uses electrical energy for cutting, although the loop can be used without thermal energy as a mechanical cutting tool.

Operative hysteroscopy is also used by some gynecologists to remove retained products of conception in select patients and/or situations. It may raise eyebrows among some medicaI professionals who have been trained to rely on blind curettage (D&C) for a wide range of diagnostic and therapeutic indications, but there should be no reason why it is not routinely used in Gynecology, including for ERPC when expectant or medical management fail to completely empty the uterus after a miscarriage, instead of blind curettage. There are a number of publications describing hysteroscopic curettage (1-7) for removing RPOC. Blind curettage is the most common cause of intrauterine adhesions (Asherman’s syndrome), which leads to infertility necessitating corrective surgery. The lack of Obgyns suitably trained in hysteroscopy is another reason why hysteroscopy has not replaced the D&C. Unfortunately, the use of hysteroscopy in Gynecology is even declining from the time it was first invented in the 1980s. Hysteroscopy is the logical progression from blind scraping invented over a century ago. It’s hard to believe that over a century later this comparatively rudimentary technique for women is still being used. Minimally invasive techniques are routinely used in Urology (e.g. in-office cytoscopy). Women also need to empower themselves and support more precise and safer methods by choosing hysteroscopy over blind curettage. Most gynaecologists perform blind curettage without giving a second thought to any long term risks involved. They may not be aware of the future problems it has caused their patients unless the patient specifically contacts them to tell them.

Finally, this article by Dr Keith Isaacson(8) is not new, but it outlines the uses of hysteroscopy, compares office and hospital hysteroscopy and dispels the common misconceptions about it that are hindering its widespread use, such as poor reimbursements and a difficult learning curve. http://www.obpmedical.com/v/vspfiles/assets/images/office%20hysteroscopy%20-%20a%20valuable%20but%20under-%20utilized%20technique.pdf

REFERENCES

Nicopoullos JDM, Treharne A, Raza A and Richardson R. The use of a hysteroscopic resectoscope for repeat evacuation of retained products of conception procedures: a case series. Gynecological Surgery. 2010; 7(2):163-6. Abstract http://www.springerlink.com/content/384125gp81055401/
M.H. Emanuel, F.W. Jansen and D. Schoot The Hysteroscopic Morcellator, an Effective Technique for the Removal of Residual Trophoblastic Tissue Journal of Minimally Invasive Gynecology Volume 16, Issue 6, Supplement 1, 2009, Page S85.
Faivre E, Deffieux X, Mrazguia C, Gervaise A, Chauveaud-Lambling A, Frydman R, Fernandez H. Hysteroscopic management of residual trophoblastic tissue and reproductive outcome: a pilot study. J Minim Invasive Gynecol. 2009 Jul-Aug;16(4):487-90. Abstract www.ncbi.nlm.nih.gov/pubmed/19573826
T. Dankert & M. Vleugels. Hysteroscopic resection of retained placental tissue:a feasibility study Gynecol Surg . 2008; 5:121–124. Free article www.springerlink.com/index/w4021j484l211057.pdf
F. Leone, T. Bignardi, C. Marciante, E. Bertazzoli, P. Mustoni, E. Ferrazzi and L. DSC 74: Hysteroscopy for Selective Removal of Residual Trophoblastic Tissue. Journal of Minimally Invasive Gynecology 2005;12(5), Supplement 1: 30-1.
Cohen SB, Kalter-Ferber A, Weisz BS, Zalel Y, Seidman DS, Mashiach S, Lidor AL, Zolti M and Goldenberg M. Hysteroscopy May Be the Method of Choice for Management of Residual Trophoblastic Tissue. The Journal of the American Association of Gynecologic Laparoscopists 2001;8(2):199-202. Abstract
Goldenberg, M, Schiff E, Achiron, R. Lipitz, S. Mashiach, S. Managing residual trophoblastic tissue. Hysteroscopy for directing curettage. J Reprod Med. 1997;42(1)26-8. Abstract www.ncbi.nlm.nih.gov/pubmed/9018641
Isaacson K. Office hysteroscopy: a valuable but under-utilized technique.Current Opinion in Obstetrics and Gynecology 2002, 14:381-385. Free article http://www.obpmedical.com/v/vspfiles/assets/images/office%20hysteroscopy%20-%20a%20valuable%20but%20under-%20utilized%20technique.pdf

Endometrial injury subfertility and superfertility: a decidual link.

2011-07-19T01:32:00.000-07:00

Miscarriages occur in approximately 20% of pregnancies. Recurrent pregnancy loss (RPL), affects 1-2% of couples and is defined as three or more consecutive miscarriages. Broadly speaking, the most common cause is chromosomal abnormalities of the embryo. Other causes of RPL include immunological factors (e.g. Lupus), blood clotting disorders a.k.a. thrombophilias (e.g. antiphospholipid syndrome) and uterine factors which are less well understood. The authors of the review article, The molecular basis of recurrent pregnancy loss: impaired natural embryo selection, examine uterine factor infertility and its relation to recurrent miscarriage.

Researchers have noted that many women with recurrent and consecutive miscarriages, have unusually high pregnancy rates, conceiving within an average of 3 months or less. These women are dubbed ‘superfertile’, though the concept of superfertility in humans is anecdotal and not based on clinical diagnostic testing. Three percent of the population is estimated to be superfertile, compared to 18% estimated to be subfertile (Tietz, 1950; Evers, 2002). It has already been hypothesized that recurrent miscarriage is a consequence of impaired natural embryo selection, in other words, the inability of the uterus to filter out poor quality embryos destined to miscarry (Quenby, 2002). In their review, Teklenburg et al examine the biological plausibility of superfertility as a pathological entity leading to apparent infertility. They use results from their own studies and others to lead to the hypothesis that cyclic changes in the endometrium ensure normal implantation, and that a dysfunctional endometrium associated with superfertility will lead to perturbations in the endometrial decidual response, delayed implantation and poor embryo selection resulting in defective placental formation and miscarriage, regardless of embryo karyotype. This would explain why karyotype analysis of miscarried embryos from superfertile women reveal both chromosomally normal and abnormal embryos.

To arrive at this theory, they examined the implantation window of the embryo and its coordination with endometrial development. There is clinical evidence that an unresponsive endometrium during the window of implantation is a cause of subfertility. Thus, one would expect that persistent endometrial receptivity will result in higher implantation rates but would also include embryos of poor quality (i.e. superfertility). Central to the process of implantation is decidualization, which occurs about 10 days after ovulation regardless of pregnancy status. This is the process by which endometrial stromal cells differentiate into decidual cells giving the endometrium properties necessary for placenta formation. Inadequate decidualization leads to miscarriage or obstetric complications such as preterm birth. Underlying implantation is a complex molecular cross-talk between the embryo and the endometrium, a process triggered by the hormone progesterone which is responsible for maintaining the endometrium’s integrity during a viable pregnancy. Several types of molecular regulators including growth hormones, transcription factors, and cytokines are needed to mediate the implantation process. The window during which the endometrium is receptive to embryo implantation occurs approximately 6 days after ovulation, lasting for around 5 days. The proposals that miscarriages may be caused by impaired embryo selection or conception outside of the normal implantation window are not new. There is already some evidence from studies to support that impaired embryo selection underlying a short time to pregnancy is a cause of sporadic miscarriages.

Cyclic decidualization in the absence of pregnancy results in menstruation. Researchers have tried to explain from an evolutionary standpoint, why a process which results in the ‘punitive’ occurrence of repeated menstruation arose. One possible explanation is uterine preconditioning which protects the uterine tissues from hyperinflammation and oxidative stress resulting from deep trophoblast invasion during pregnancy. Another possible explanation put forth by Teklenburg et al in this review is embryo natural selection. In human co-culture studies, their group recently observed that blastocysts were unable to trigger a maternal response in endometrial stromal cells which had not been decidualized, yet they were able to in decidualizing cells. This led them to hypoethsize that an important function of decidualization is to provide endometrial stromal cells the ability to act as biosensors of embryo quality (Teklenburg et al, 2010a). Therefore the failure of the endometrial stromal cells to undergo an appropriate decidualization would lead not only to late implantation of poorer quality embryos but also to early placental failure regardless of embryonic karyotype. Thus, the ability of the decidualized endometrium to terminate the window of implantation could be just as important for a viable pregnancy as its ability to become receptive.

They propose that this instrinsic failure of endometrial stromal cells to mount an appropriate decidual response is due to a reversible programming of endometrial cells, most likely epigenetic changes such as DNA methylation.

Implications for Asherman's syndrome?

This hypothesis can potentially explain many causes of uterine factor infertility as well as their current treatments. For example, inflammatory signals are important epigenetic modifiers (Backdahl et al, 2009). Although the review does not mention Asherman's syndrome, it could be speculated that tissue injury from D&Cs resulting in inflammation can lead to epigenetic modification that underlies recurrent miscarriage. Of course this may happen even if the injury does not lead to intrauterine adhesion formation. The persistence of epigenetic modification from the initial trauma could also explain why even after corrective surgery women who had Asherman's syndrome may continue to experience miscarriage or perhaps even become ‘superfertile’ from a defective decidual response. Although superfertility in Asherman’s syndrome has not been previously reported to my knowledge, it is biologically plausible if the theory about epigenetic modification subsequent to endometrial injury is correct. It could also explain why women may become infertile even in the presence of few intrauterine adhesions. Conversely, local injury using endometrial biopsy has been used to improve pregnancy rates in subfertile women, lending support to the theory that tissue injury can modify the decidual response (for the better in this case). How injury can increase fertility in some cases or reduce it in others is unclear, but would probably be related to the extent and location of the injury and baseline fertility characteristics specific to the woman. An interesting study would be to compare decidualization in women with and without Asherman’s syndrome through the expression of uterine proteins and factors involved in decidualization. The potential link between endometrial injury and superfertility may also explain the obstetric complications encountered in women with a history of Asherman’s syndrome such as placenta accreta and percreta, intrauterine growth restriction and preterm birth since these are all related to impaired placental function.

If the above hypothesis is correct, the bad news is that prenatal genetic diagnosis (PGD) and comparative genomic hybridization (CGH) would not be effective treatments for recurrent miscarriage since even chromosomally normal embryos would abort in the presence of a defective decidual response. Variations in the prevalence of superfertile versus subfertile or infertile patients in different studies could explain the conflicting efficacies reported for these techniques. There is at least some hope for women with recurrent miscarriage; the authors point out that even after 3 consecutive miscarriages many women with RPL go on to have a successful pregnancy. (Rai and Regan, 2006). The authors also noted that many of the drugs used in the management of RPL (progesterone, DHEA, glucocorticoids and heparin) directly modulate the decidual response and that the timing of their administration could be the critical factor in their outcome.

A better understanding of the endometrium and its decidual response may hold the key to preventing recurrent miscarriage and future obstetric complications. Perhaps the confirmation of an association between endometrial injury, defective decidualization and recurrent pregnancy loss would further support the need to switch to non-invasive and minimally invasive gynecological and obstetric treatments.

REFERENCES

Backdahl L, Bushell A, Beck S. Inﬂammatory signalling as mediator of epigenetic modulation in tissue-speciﬁc chronic inﬂammation. Int J Biochem Cell Biol 2009;41:176 – 184.

Evers JL. Female subfertility. Lancet 2002;360:151 – 159.

Quenby S, Vince G, Farquharson R, Aplin J. Recurrent miscarriage: a defect in nature’s quality control? Hum Reprod 2002;17:1959 – 1963.

Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601 – 611.

a. Teklenburg G, Salker M, Molokhia M, Lavery S, Trew G, Aojanepong T, Mardon HJ, Lokugamage AU, Rai R, Landles C et al. Natural selection of human embryos: decidualizing endometrial stromal cells serve as
sensors of embryo quality upon implantation. PLoS ONE 2010;5:e10258.

Teklenburg G, Salker M, Heijnen C, Macklon NS, Brosens JJ. The Molecular basis of recurrent pregnancy loss: impaired natural embryo selection. Mol Human Reprod. 2010;16(12): 886-895.

Tietze C, Guttmacher AF, Rubin S. Time required for conception in 1727 planned pregnancies. Fertil Steril 1950;1:338– 346.

Articles on Asherman's syndrome: Reproductive outcomes and Obstetric complications

2011-04-27T22:41:00.000-07:00

The final section on references to peer-reviewed publications on Asherman's syndrome have been uploaded under pages (please see relevant tab above or click here). It includes case reports, studies and reviews of reproductive outcomes (pregnancy rates, live birth rates), obstetric complications in women with a past history of Asherman's syndrome (e.g. placenta accreta, IUGR etc.), as well as in women who have untreated intrauterine adhesions at the time of pregnancy. I also included some articles on fertility complications in women who have had Asherman's syndrome, such as thin endometrium. I will continue updating all pages with new articles when they are published. I also intend to add other articles such as those on stem cells, uterine transplantation, hysteroscopy, treatment of thin endometrium, and general articles on misoprostol and the risks of D&C, so stay tuned.

A genetic predisposition: from speculation to opinion to 'fact' without any data (Part II)

2011-03-27T00:20:00.000-07:00

In my last blog post I presented the ‘evidence’ (or lack thereof) on which the theory of a genetic/constitutional predisposition for Asherman's syndrome was based. To recap the gist of these observations which pass for proof:

a) some women develop a severe form of IUA after undergoing the ‘same’ traumatic procedures as others who do not acquire AS, and

b) some women respond more ‘favourably’ to treatment than others who suffer from recurrent adhesions.

Before deconstructing these observations, the most obvious argument against a genetic basis is the lack of familial clustering of the ‘pathology’. Assuming a polygenic mode of inheritance (as opposed to a Mendelian one) it would be expected that those with a first degree relative with Asherman’s syndrome would have a higher risk of developing AS than those without a close relative who has the condition. I have yet to read a study of identical twins with Asherman’s syndrome, let alone any study showing the sisters or daughters of patients having a higher risk. In over a century since its first report, there is no evidence of familial clustering to lend support to this theory. Nor is there any evidence that women with scarring defects (eg. keloids) or connective tissue disorders (Marfan’s syndrome, Ehlers-Danlos syndrome) are more prone to AS as one might expect.

How can trauma be quantified when surgery is blind?

As for the ‘evidence’ above, with regards to a), what proof is there that the women who develop severe IUA actually underwent the exact same trauma as those who did not acquire it? This is a an unfounded statement given differences in doctor’s skill, technique and more importantly, the mis- or under-diagnosis of AS and the blind nature of D&Cs- the number one cause of AS. The problem with bind surgery is that one relies on guess work and instinct to not scrape too deeply. ‘Too deeply’ can be one millimeter too much. How is it possible to detect this difference when not even an ultrasound is used during the procedure? Even with visualization it is not possible to tell where the functional endometrium ends and the basal endometrium begins. However, techniques which utilize visualization for intrauterine surgery (i.e. hysteroscopy) are inherently less risky with regards to instrumental injury because they allow the surgeon to only scrape/dissect/remove parts of the endometrium which need to be treated thus sparing underlying and adjacent tissue from potential injury. Furthermore, each woman has a different anatomy, and different location of retained products of conception. Some have retroverted uteri, others have Mullerian malformations, and the shape, widths and lengths of uteri vary enough between women to be a significant factor with regards to acquiring an injury during a blind procedure. A D&C consists of blindly scraping away the top layer of the endometrium (the functional layer) which can vary in thickness between women but is often not thicker than a few millimeters in most parts. It is simply impossible for a clinician or midwife to know whether they have scraped into the basal endometrium, particularly when no visual guidance is used.

In summary, the above argument is akin to saying that not all smokers develop lung cancer therefore lung cancer is not caused by cigarettes. Why not theorize that those who develop lung cancer have a genetic predisposition instead? (Note: this comment was intended to highlight the absurdity of believing that cigarette smoking does not cause lung cancer, and hence the absurdity of believing that the fact that all women who have D&Cs do not acquire Asherman's syndrome proves that the condition is not caused by D&Cs but is instead genetic. I later learned that the famous statistician RA Fisher actually theorized half a century ago that people who are genetically predisposed to lung cancer are also genetically predisposed to becoming smokers. Of course this theory was refuted by a study of monozygotic twins versus dizygotic twins who were discordant for cigarette smoking, and it turns out, lung cancer risk. This example points out how easily theories can be taken seriously just because an expert, or in this case, a genius put it forth, and that experts too have biases which affect their views (he smoked and was a consultant for the tobacco industry!). These theories, will not hold up against evidence from well-designed studies, but until these are done, they impede medical progress).

Recurrence depends on initial severity and treatment methods

With respect to the second part of the argument, the fact that some women respond more ‘favourably’ to treatment than others who suffer from recurrent adhesions can be rationally explained in other ways.

Firstly, it is not surprising that some women need more than one hysteroscopic adhesiolysis surgeries than others, depending on severity. This has been known for many years and reported in the literature. The more damage incurred on the endometrium, the higher the rate of IUA recurrence, and the more surgeries needed for correction, although at some point, damage is too great to allow for endometrial regeneration resulting in recurrent adhesions or fibrotic endometrium.

Another important point to consider is that hysteroscopy was not used for diagnosis or treatment when the observation about treatment outcomes was made. Asherman’s syndrome was still ‘treated’ with blind D&C, the same procedure which is responsible for most cases of AS. This would understandably result in inconsistent outcomes. The absence of accurate diagnosis (and hence classification) in those days also distorted the correlation between severity and outcome. A patient with seemingly severe AS presenting with total amenorrhea may ‘inexplicably’ have had a better outcome after surgery than someone with supposedly less severe AS who had some menstrual flow. We now know that amenorrhea is not always due to severe and widespread adhesions. It can be due to cervical adhesions alone. As the rest of the uterus may be intact in such cases, the reproductive prognosis is better than a patient who has deep adhesions in part of her uterus but no outflow obstruction (and thus has menstrual bleeding, albeit reduced flow).

With regards to treatment, estrogen therapy was not carried out as part of post surgical therapy in the past. It is generally accepted that estrogen supplementation plays an important role in the prevention of adhesion recurrence following surgery/adhesioloysis by stimulating endometrial regeneration. Thus in the absence of hysteroscopic adhesiolysis, uterine stents and estrogen therapy, more severe cases were less treatable than they are today.

It is well known that the functional endometrium is regenerated from the underlying basal endometrial layer. As a simple analogy, imagine the lining of the uterus as a lawn. The grass seeds would be the stem cells from which the grass grew with the addition of water (i.e. estrogen). The functional layer would be the grass, and the roots would be the basal endometrium. If someone came along to trim the lawn (i.e. D&C) and accidentally dug out the roots of the grass, the grass would regrow after watering only in the areas where there were either some residual roots, or seeds. Imagining that the seeds are in a slightly deeper layer of soil (for the purpose of this analogy), if the gardener dug very deeply so that even the seeds were removed, no amount of watering would regrow the grass. This could happen in a patch of grass or the whole lawn. In this simple analogy the bald patches would be endometrial sclerosis (unstuck Asherman’s), but adhesions would result if two bald patches came into contact with eachother in the uterus.

More recently, the presence of endometrial stem cells at the myometrial junction was reported. These should be able to transform into endometrial stem cells with the right stimulation. The discovery of the existence of endometrial stem cells could explain why in some cases an apparently denuded endometrium (ie.no visible endometrium) will regenerate while in other cases it will not. Or why some women have recurring adhesions while others do not. This would explain why estrogen therapy after hysteroscopic adhesiolysis can in some cases stimulate the regerenation of endometrium while other cases of IUA are recurrent no matter the dose of estrogen therapy and the length of uterine barrier therapy. Endometrium is what keeps the myometrial layer of the uterus from adhering to opposing walls of the uterus. Once again, it is imposible to observe with the naked eye whether stem cells have been removed by curettage or not which would give rise to ‘paradoxical’ outcomes between patients with the ‘same’ severity of injury. In addition, differences in methods for dissecting adhesions can account for differing outcomes. Mechanical methods for adhesion dissection may also be preferable to methods which utilize thermal energy as the latter may damage adjacent tissue.

A modern perspective on an old problem

Authors need to re-evaluate the validity of assumptions, speculations and theories made in publications written when conditions and standards differed greatly to those of today, taking into consideration medical progress. Although older papers are still important and interesting to read, they need to be interpreted carefully and in the context of limitations in medical technology and critical thinking, lower standards needed for proof and gaps in scientific understanding at the time they were written. Blind repetition of theories cited from papers that were published decades ago without any questioning is simply archaic, unrigorous and unscientific. If there is a case for a genetic or constitutional basis for AS, data from well designed studies would be more persuasive than citing theories which lack any experimental support of any kind. In what seems to be a recurring theme in AS, absence of evidence may not be evidence of absence, but by today’s standards in medicine only presence of evidence is evidence of presence.

A genetic predisposition: from speculation to opinion to 'fact' without any data (Part I)

2011-02-22T22:54:00.000-08:00

The theory that Asherman’s syndrome has a ‘constitutional’ or ‘genetic’ basis has been making rounds for a while. It is time to critical appraise this idea with a view of our understanding of modern medicine.

From where did this theory originate and is there any evidence to support it? From my own thorough research of the literature on Asherman’s syndrome, having read most of the peer reviewed publications dating back to the early 60s, the first mention of the possibility of a hypothetical constitutional factor comes from a publication by Foix et al in 1966 (1). They write: (page 1028): "Besides the above-mentioned presidposing factors, there appears sometimes to be a constitutional element, for some of our patients treated for adhesions after each of several induced abortions, always developed new ones.” Thus they give no supporting references or evidence other than their own subjective observations.

Most reviews or studies mentioning this theory cite a review paper by Schenker and Margoliath in 1982 (2). In it they elaborate on the same ideas, citing a case series by Polishuk and Sadovsky in 1973 (3) as ‘support’. Schenker and Margoliath’s rationale was that:

a) some women develop a severe form of IUA after undergoing the ‘same’ traumatic procedures as others who do not acquire AS, and

b) some women respond more ‘favourably’ to treatment than others who suffer from recurrent adhesions.

They go further and conjecture that 28 women plucked from studies they compiled from the literature ‘may have possessed this predisposing factor, which might have been the reason for the development of IUA after normal delivery or following abortion without subsequent curettage, or even when lacking any attributable trauma.” This is a very bold, if not preposterous assertion to make about patients they have never examined or treated. Needless to say, diagnosis from a distance by third party observers is not a credible source of evidence.

The Polishuk and Sadovsky paper also fails to provide any proof. In fact, Polishuk and Sadovsky themselves never mentioned the idea of a genetic predisposition in their paper or set out to prove such a theory. Instead, they present a case series of 11 patients who have recurrent adhesions, one of three types of adhesions, they explain. Adhesions recurred in all cases after curettage for removal of adhesions or following abortion in a new pregnancy. They suggest that the patients in their study may have had extensive endometrial ‘repair’ i.e. fibrosis, where the endometrium is replaced by connective tissue, which they attempted to treat by removing it. Their understanding of cellular physiology, like their contemporaries, is incorrect but excusable given what was known at the the time it was written. They conclude that their treatment was not encouraging. It should not be surprising to doctors today that blind lysis using curettage is not a successful treatment for IUA or that the removal of fibrotic tissue does not result in endometrial regeneration. I will explain later...(Part II)

Since the speculation by Foix et al and later Schenker and Margoliath, numerous authors have subsequenty made it a habit to include this under etiology of AS, apparently without much thought. The theory also seems to have gained credibility with authors stating it as a fact rather than a hypothesis without any further ‘evidence’. The quality of referencing in many articles about Asherman’s syndrome is lacking. Some authors even cite other reviews which never made the speculation. Clearly, many authors simply copy references from other papers without ever reading the original article to confirm or verify what was actually written.

Back in 1948 Asherman himself seemed to have understood that the underlying cause of IUA are usually trauma from instrumentation (although severe infection, especially endometrial tuberculosis can also cause physical injury to the lining) when he named the condition ‘traumatic amenorrhea’ (4). Unfortunately, the medical community has since been trying to attribute other causes or factors necessary for its development (another example of this is ‘subclinical infection’) perhaps to redeem their dependence on blind curettage as a standard procedure, and also to compensate for their lack of understanding about cellular physiology and insight into the condition. The condition has also been renamed (or misnomered) ‘Asherman’s syndrome’ which distances it from an iatrogenic cause. The word ‘traumatic’ made some doctors feel uncomfortable (5):

(See Discussion Dr John Morton LA California): “The nomenclature also is objectionable. The “traumatic” part of the phrase indicates an iatrogenic lesion, which may not always be justified. (my edit: This is true, but many if not most cases are actually iatrogenic since surgery is involved).

(…)

Dr Jones (closing):It is true that the term “traumatic” is not wholly satisfactory, but it is the term most frequently used in current literature to describe the abnormality under discussion. H W Jones Jr has suggested that the term “postcurettage atresia of the endometrial cavity” is more descriptive, and this may avoid the iatrogenic connotation of the word “traumatic”.

(…)

Thus, there must be an inflammatory factor in the etiology of intrauterine adhesions (my edit: Trauma to the tissue causes inflammation-not to be confused with infection). Parenthetically this too underlines Dr Morton’s objection to the term ‘traumatic’.”

I won’t go into why the above reasoning is incorrect here, my point was to display the obvious discomfort doctors felt in acknowledging an iatrogenic etiology, which probably contributed to its eventual name change as well as the reason why the medical community is so willing to accommodate other unproven causes of Asherman’s syndrome. It’s as if the mentality with regards to Asherman’s syndrome is caught in a time warp where principles of modern medicine such as using modern techniques, well designed studies, objectivie interpretation of data and the requirement of evidence have been temporarily waived.

Although it is natural to consider the possibility that any condition may have a genetic basis, a current understanding of adhesions, the advent of hysteroscopy and techniques to view inside the uterus, a century of observations and plain common sense suggest that such an explanation is not only based on speculation and flawed thinking, and cannot obscure the lack of even the weakest level of research evidence (eg. a case study) exists to support it. Next time I will explain exactly why.

We know now that adhesions (whether intra unterine or intra abdominal) are not a pathological response: they are a normal physiological response to injury adjacent mucosa. Adhesions are only pathological in the sense that they can lead to pathologies such as infertility, bowel obstruction and pain, depending on their location. They are the end result of normal wound healing, of which inflammation (not to be confused with infection) is an inherent process. They occur very commonly in intraabdominal surgery because there is no regenerative layer unlike the uterus which is lined with a regenerative endometrium. Yet no intraabdominal surgeon has attempted to label the condition as ‘genetic’ or ‘constitutional. However, not surprisingly, the endometrium will not regenerate if it is entirely removed, which should not occur during curettage, but which may happen unintentionally due to the blind nature of the procedure. The situation in the uterus then becomes analogous to that in the peritoneum, and adhesion formation ensues.

Lastly, with regards to Polishuk and Sadovsky’s paper, if anything, these cases should highlight the dangers of blind curettage as a method of treating Asherman’s syndrome and miscarriage, the latter particularly in women who have had Asherman’s syndrome. It would appear that endometrial damage leading to AS predisposes to further adhesions probably by facilitating injury, even after previous treatment to restore an open cavity. This is consistent with the observation that even after corrective surgery, women who have a history of Asherman’s syndrome are at an increased risk of specific obstetric complications. It is therefore of no surprise that the common underlying characteristic of these complications is a defective utero-placental interface.

REFERENCES

Foix A, Bruno RO, Davison T, Baltasar L. The pathology of postcurettage intrauterine adhesions. Am J Obst & Gynec.1966; 96(7):1027-33.
Schenker JG, Margoliath EJ. Intrauterine adhesions: an updated appraisal. 1982; 37(5):593-610.
Polishuk WZ, Sadovsky E. A syndrome of recurrent intrauterine adhesions. Am J Obstet Gynecol 1975 151-8.
Asherman J, Amenorrhoea traumatic (Atretica). J Obstet Gynecol 1948; Br Emp 55:23.
Jones W. Traumatic Intrauterine adhesion; a report of 8 cases with emphasis on therapy. Am J Obstet & Gynec 1964; 89(3):304-13.

Articles on Asherman's syndrome Diagnosis, Classification and Treatment

2011-01-25T22:33:00.000-08:00

Further publications on Asherman's syndrome have been added to the site. These include those on the Diagnosis, Classification and Treatment of Asherman's syndrome. Please click here or on the relevant tab in the menu above to view these references.

Previously a page with references to studies on the Etiology, Incidence and Prevention of Asherman's syndrome was added. Click here or on the relevant tab in the menu above for more.

Further references to publications on Asherman's syndrome by topic will be added to the site in the near future.

Alternative perspectives?

2011-01-04T19:19:00.000-08:00

Some months ago, a fellow Asherman’s syndrome (AS) sufferer who writes the blog Alternative Asherman’s had a missed miscarriage after AS and wrote of her experience (Three steps backwards) using misoprostol, linking it to the blog about my own experience using misoprostol. I feel it is necessary to clarify certain points in her experience as they may be inadvertantly misleading and appear to implicate misoprostol in what apparently ensued. She has also since updated her blog to clarify her interpretation of her experience.

Misoprostol is a non-invasive uterotonic drug that expels the uterine contents in a way that is analogous to a natural miscarriage. Scarring and subsequent adhesions are the result of physical injury (or severe infection) to the basal endometrium. In fact management of miscarriage with misoprostol has been shown to prevent adhesion formation compared to blind D&C (Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. J Am Assoc Gynecol Laparosc.2002; 9 (2): 182–185.). Misoprostol can be used to expel the contents of the uterus for either pregnancy termination, after a missed or incomplete miscarriage has occured or for labour induction. It also dilates the cervix and is useful prior to hysteroscopic surgery. Unfortunately, misoprostol is often referred to as a 'pregnancy termination drug' despite its various uses.

With regards to misoprostol's efficacy it should be noted that she obtained Chinese herbs from her accupuncturist to help 'prepare her body for miscarriage'. (See her comment below). This is unnecessary. It is not advised to mix Chinese or any other alternative or over the counter drug/herb with the treatment prescribed by your qualified ObGyn. Any responsible qualified homeopath/alternative medicine practitioner (some are MDs) would not dispense drugs whose effects and interactions with drugs prescribed by another specialist is not known and has not been vigorously trialed. There is no regulation or standardization of alternative drugs (herbs, extracts, etc.) so their concentrations, compositions quality and therefore effects and interactions vary greatly. We don't know if using these herbs could have interfered with misoprostol's effect in some way (for example, reducing its efficacy by blocking the same receptors targeted by misoprostol).

She was told that she developed IUA after using misoprostol and prior to hysteroscopic surgery to remove retained products. Her hysteroscopic surgeon said that the RPOC from an incomplete evacuation led to fibrous scar tissue formation. While I have heard about this anecdotally, I have not seen any reports of women developing IUA from RPOC in the absence of severe infection. It is also difficult to reconcile the observation of dense scar tissue with products retained for just 5 weeks when scar tissue is not complete until about 8 weeks. Anecdotally, I personally had substantial retained products for 3 weeks after my second trimester miscarriage treated with misoprostol and did not develop IUA. RPOC and retained placenta can be managed conservatively (under medical supervision).

However, she does mention that she may have already had some recurrence of IUA before her pregnancy as her Obstetrician noticed what appeared to be synechiae on ultrasound. This appears to be an important clue.

She says that there were dense adhesions whereas she previously had had only mild adhesions at initial diagnosis.One possible way to explain the deterioration of her condition could lie in the initial treatment of her AS: she had a uterine cook balloon inserted following adhesiolysis. While I underwent the same procedure without any apparent complications like hundreds of others (a proportion of whom have gone on to have children), it is possible that if the stent was not removed properly, or if it somehow adhered to raw surfaces in the uterus, it could have caused damage on removal (the balloon is deflated and simply pulled out). This explanation would also be consistent with her ObGyn's observation of scar tissue during a prenatal scan. Note also that there is limited data from studies on the benefits of using the Foley catheter and IUDs after surgical lysis and no controlled or comparative trials on the Cook balloon. Some Asherman’s syndrome specialists even believe that stents can stunt endometrial regrowth.

A well researched and routinely used drug like misoprostol should not be treated with suspicion compared to many other medical and even pseudo medical treatments the same women undergo without questioning, from unproven and potentially harmful altnernative drugs to contraversial fertility therapies to treatments of Asherman’s syndrome on which there are comparatively less data and of a lower quality. This leads me to wonder whether it is the attitude of the treating doctor(s) which influences patients' perceptions of treatments. I agree that more doctors need to be trained in the use of misoprostol for miscarriage (and in particular among women with a history of AS) and that a followup hysteroscopy may be needed depending on clinical symptoms and gestational age at time of miscarriage to ensure there are no retained products of conception. Followup hysteroscopy may also be necessary in women with a history of AS if the miscarriage passed naturally as there is a possible tendency towards retained tissue from scarring. We already know that women with past AS are at an increased risk of abnormally invasive placentation such as placenta accreta. Retained tissue and placenta accreta may be different ends of a spectrum of abnormalities associated with placental invasion in a defective endometrium. Whether misoprostol is necessary to evacuate miscarriages that occur very early on in the pregnancy (prior to 7 weeks) is also questionable. These can be managed expectantly. It is especially risky to perform a blind D&C in women who already have suffered damage to their uterine lining. It is time for miscarriage management as a whole to be reviewed in light of advances in medical therapy and hysterosopic alternatives.

Update Dec '10: Clinical trials and patents relevant to Asherman's syndrome

2010-12-02T22:21:00.000-08:00

Clinical trials:

There are a number of trials involving the use of misoprostol for miscarriage management (note: I am not including studies on misoprostol use for pregnancy terminations because this choice is already routinely available to women who abort. It is not routinely- let alone occasionally-available to those who miscarry). As a blog which promotes prevention, these are naturally included. Below is more information and links to the studies.

Optimal Treatment of Miscarriage OR
Which is the Optimal Treatment for Miscarriage With a Gestational ac in the Uterus and Which Factors Can Predict if the Treatment Will be Successful?Region Skane, Kvinnokliniken, University Hopsital MAS Malmo Sweden.
Study type: Open labelled randomized trial (parallel assignment).
Aim: To compare the number of women with a complete miscarriage after 10 days between expectant management versus treatment with 800 micrograms of misoprostol intravaginally in women with an an incomplete miscarriage before 14 weeks and a gestational sac retained in the uterus.
link: http://clinicaltrials.gov/ct2/show/NCT01033903?term=miscarriage&rank=5

A Randomized Trial of Two Regimens of Misoprostol for Second Trimester Termination for Intrauterine Fetal DeathAmerican University of Beirut Medical Center
Study type: Open labelled, randomized controlled crossover trial.
Aim: To compare the safety, efficacy and patient satisfaction of vaginal versus sublingual administration of misoprostol (400 mcg every 4 hours until delivery. Time frame=24 hours)
link: http://clinicaltrials.gov/ct2/show/NCT00141895?term=misoprostol&rank=7

Sublingual Misoprostol Versus Standard Surgical Care for the Treatment of Incomplete AbortionGynuity Health Projects, Egypt, Mauritania, Niger.
Study type: Open labeled randomized controlled trial.
Aim: To compare the safety and efficacy of 400 mcg sublingual misoprostol to standard surgical curretage (D&C or MVA) for incomplete abortion (ie. retained products of conception). Presumably either spontaneous or induced.
link: http://clinicaltrials.gov/ct2/show/NCT00466999?term=misoprostol&rank=50

Non Surgical Management for Uterine Residua After Pregnancy Termination, Abortion or DeliveryHaEmek Medical Center, Israel
Study type: open labelled randomized trial (parallel assignment)
Aim:To compare the outcome of misoprostol treatment (intravaginal, 800 mcg) and expectant management in the case of intrauterine residua after completion of pregnancy.
link: http://clinicaltrials.gov/ct2/show/NCT01134926?term=misoprostol&rank=56

Misoprostol for Treatment of Fetal Death at 14-28 Weeks of PregnancyGynuity, California, Illinois, Boston, New York.
Study type: Double blinded randomized trial, parallel assignment.
Aim: To establish the safety and effectiveness of two different doses of the prostaglandin E1 analogue misoprostol administered buccally as a treatment for fetal death at 14 - 28 weeks, inclusive, of pregnancy.
link: http://clinicaltrials.gov/ct2/show/NCT00671060?term=misoprostol&rank=24

Effect of Colony Stimulating Factor on Poor Endometrial Development During IVF
Official Title: G-CSF and Endometrial Growth, Embryo Implantation and Pregnancy Following FET or Donor ET
The Center for Human Reproduction (CHR) is conducting a double-blind, randomized cross over trial to investigate the effect of G-CSF on endometrial thickness in women who have failed reaching minimal endometrial thickness by standard treatments. Outcome measures will include endometrial thickness (must be >7mm for transfer), implantation and pregnancy rates compared to control patients. The study will be conducted in women undergoing transfer of previously cryopreserved embryos or transfer of embryos from donor eggs.

There are published studies on the use of Vitamin E (tocopherol), Pentoxyfilline, and Sildenafil in women with a thin endometrium (some of whom have a history of Asherman’s syndrome (1-4)). To my knowledge this is the first trial using G-CSF for this purpose.
For more information see:
http://clinicaltrials.gov/ct2/show/NCT01202643?term=asherman+syndrome&rank=1

Safety of Leaving Cook Balloon Uterine Stent in Uterus for One Month
The Department of Obstetrics and Gynecology, Shin-Kong Wu-Ho-Su Memorial Hospital in Taiwan is conducting an open label randomized controlled trial to investigate the feasibility of leaving an intrauterine Cook balloon in the uterus for 1 month. The experimental arm of the study will be fitted with a uterine Cook stent while the control will not. Both groups will have swabs taken for culture just before hysteroscopic adhesiolysis and 30 days later, during second look hysteroscopy to evaluate the outcome of surgery.

The practice of leaving a Cook Balloon stent in the uterus for this length of time is used by some Asherman’s syndrome specialists in cases of severe and recurrent intrauterine adhesions (personal communication). In the above study there is no mention of antibiotic use, however the specialists that use the Cook balloon or Foley catheter prescribe antibiotic prophylaxy during the entire therapy to prevent the potential infection. The results of the study will also reveal the effectiveness of the Cook balloon in preventing adhesion recurrence compared to no stent. Previously there was a study comparing the IUD (3 cycles) to the Foley catheter (10 days), however the method of ‘adhesiolysis’ was blind D&C, not dissection of adhesions under direct hysteroscopic view (5). As blind D&C is the most common cause of intrauterine adhesions, it is difficult to know if the previous findings are due to the barrier method used or to fortuitous variations in the success of ‘surgery’ which is carried out blindly.

For more information see: http://clinicaltrials.gov/ct2/show/NCT01167296?term=uterine+adhesions&rank=2

SIGnificance of Routine Hysteroscopy Prior to a First 'in Vitro Fertilization'(IVF) Treatment Cycle (inSIGHT)
A multicenter single-blinded (caregiver) randomized intervention trial is being undertaken in the Netherlands to assess the cost effectiveness of screening women for intauterine abnormalities using hysteroscopy and SIS (saline infusion sonography) prior to fertility treatment (IVF/ICSI). If abnormalities are found (defined as the existence of a septum, endometrial polyp, submucous myoma, adhesions or endometritis) these will be treated on the spot, using scissors, Versapoint, grasping forceps, polypsnare or antibiotics. The primary outcome measure is cumulative ongoing pregnancy rate and live birth after randomization within 18 months of IVF/ICSI. Secondary outcome measures include cumulative implantation rates, miscarriage rates, and comparative cost calculations.

Studies have shown that minor intrauterine abnormalities can be found in 11-40% of infertile women with a normal tranvaginal sonography. Detection and treatment of these abnormalities by office hysteroscopy have led to a 9-13% increase in pregnancy rate. Therefore, it is increasingly advised to screen all infertile women on intracavitary pathology prior to the start of IVF/ICSI.

Note that women with recurrent miscarriage are excluded from the study, when it is known that women with uterine abnormalities (congenital or acquired) are at a risk of repeated pregnancy loss. This exclusion is perhaps added in order to eliminate women who have other causes of infertility that are not due to anatomical anomalies and which cannot be diagnosed and corrected via hysteroscopy. However, this possible bias could have been avoided by excluding women who tested positive for other conditions known to cause recurrent miscarriage. I also wonder how effective outcomes will be in the experimental arm if IVF/ICSI is commenced immediately after treatment, without assessing the state of the cavity (IUA often recur, and IUA are a common consequence of septum correction and myomectomy). Furthermore, would it not be possible to answer this clinical question by reviewing the prevalence of uterine abnormalities in infertile and subfertile women, the cumulative implantation, pregnancy and live birth rates following treatment of these conditions, and analyzing the costs versus benefits ratio? For example, if past studies have shown that more than 10% of infertile women have an intrauterine pathology, and 40% of these women have a live birth after treatment, is it not justified to perform a diagnostic hysteroscopy prior to IVF/ICSI?

For more information: http://clinicaltrials.gov/ct2/show/NCT01242852?term=uterine+adhesions&rank=8

Note: There appears to be an error in the table describing the intervention and control arms of the study.

Patents

Patent Applications:
WO 2010/05/054068 A2 Cyclic adenosine monophosphates (cAMPs) for reducing the formation of adhesions. This world patent application claims the use of various derivatives of cAMPs for the reduction of adhesion formation for reducing inflammation or tissue damage after abdominal or pelvic surgery.
Jackson, EK. Cyclic adenosine monophosphates for reducing the formation of adhesions. 14 May 2010.
More info http://www.ibridgenetwork.org/university-of-pittsburgh/cyclic-adenosine-monophosphates-for-reducing-the-formation-of

In contrast to adhesion barriers, the invention would not involve placing a foreign body in the surgical cavity. Present adhesion barriers can cause immunological reactions. Also, the cyclic adenosine monophosphates are naturally-occuring substances and therefore should be quite safe. The cyclic adenosine monophosphates can be quickly and easily administered with a syringe. It can be used in minimally-invasive surgery, the future of surgery, and should be effective even if blood is in the surgical field. It is likely that the invention will be more efficacious than existing adhesion barriers.

Theoretically it could also be useful for intrauterine adhesions as many of the gel barriers used for pelvic surgery are also being used/trialled post adhesiolysis in Asherman’s syndrome treatment.So far there are only limited data on the efficacy of gel barriers in the treatment of Asherman’s syndrome (6-8). One of the difficulties of using gels is that they do not stay in a fixed position which is essential for them to be effective.

Granted Patents:
2005/0084,508 A61K Topical anesthesia formulation for bodily cavities
Innovators: Vancaillie, Thierry G; Hewitt, Alan Ernest
A topical anesthetic used for in-office hysteroscopy has recently been patented. The pH is adjusted to that of the body’s to optimize the effectiveness of the anesthetic.One of the inventors is an Asherman’s syndrome specialist. He has also developed a device for administering the anesthetic.
More info: http://www.patentbuddy.com/patentdetails/2402425

References
1. Acharya S, Yasmin E, & Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies – a report of 20 cases Human Fertility, December 2009; 12(4): 198–203.
2. Batailles N, Oliviennes F, Lefaix JL, Chaouat G, Frydman R, Delanian S. Combined treatment by pentoxifylline and tocopherol for recipient women with a thin endometrium enrolled in an oocyte donation programme. Hum Rep 2002;17(5):1249-53.
3. Sher G, Fisch D. Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development. Fertil Steril. 2002 Nov;78(5):1073-6.
4. Zinger M, Liu Thomas JH, MA. Successful Use of Vaginal Sildenafil Citrate in Two Infertility Patients with Asherman’s Syndrome. JOURNAL OF WOMEN’S HEALTH 2006;15(4):,442-4.
5. Orhue AA, Aziken ME, Igbefoh JO. A comparison of two adjunctive treatments for intrauterine adhesions following lysis. Int J Gynaecol Obstet; 2003;82:49-56.
6. Abbott J, Thomson A, Vancaillie T. SprayGel following surgery for Asherman’s syndrome may improve pregnancy outcome. J Obstet Gynaecol 2004;24:710-1.
7. Acunzo G, Guida M, Pellicano M, Tommaselli GA, Di Spiezio Sardo A, Bifulco G, et al. Effectiveness of auto-cross-linked hyaluronic acid gel in the prevention of intrauterine adhesions after hysteroscopic adhesiolysis: a prospective, randomized, controlled study. Hum Reprod2003;18:1918-21.
8. Metwally M, Watson A, Lilford R, Vandekerckhove P. Fluid and pharmacological agents for adhesion prevention after gynaecological surgery. Cochrane Database Syst Rev2006;(2): CD001298. doi: 10.1002/14651858.CD001298.pub3.

Relevant links:
Understanding Clinical Trials

Articles on Asherman's syndrome Etiology, Incidence, Prevention

2010-11-18T20:12:00.000-08:00

A selection of publications about Asherman's syndrome including reviews and journal articles on its etiology, incidence and prevention is being added to the site. It can be found here or alternatively, click on the relevant tab in tab menu at the top of the page. There will be another page with articles on Diagnosis, Classification, Treatment, Reproductive Outcomes and Obstetric Complications soon.

When infertility or recurrent miscarriage persist after treatment of Asherman's syndrome

2010-10-21T18:46:00.000-07:00

For many women who have had Asherman's syndrome, the journey to having a baby is not over with the removal of adhesions. While many doctors will use this to support their theory that they had other underlying fertility problems to begin with, it is equally possible that in some cases, Asherman's syndrome has lasting effects on fertility. Sometimes these are obvious such as inaccessible ostia (adhesions are sometimes too risky to remove) or thin endometrium. Most doctors agree that a lining of at least 8 mm at the time of ovulation is ideal for implantation. There could be other defects that persist after surgical correction such as reduced blood flow to the uterus. There is some disagreement as to whether procedures which reduce blood flow to the uterus, such as uterine artery embolization (UAE) can reduce fertility by affecting ovarian reserve. There is another intriguing link between blood flow and egg quality: it is known that endometriosis reduces egg quality although the mechanism is unknown. This makes me wonder whether I have endometriosis (I've never had a laparoscopy). There is something incongruent about having so many eggs of such poor quality. Unfortunately there is little research and few artifical reproductive techniques which focus on the quality of the endometrium. These few studies will be the topic of a future blog. There is also little research on improving egg quality as most fertility specialists are skeptical that this is possible due to currently accepted dogma on egg development.

Many women with a history of AS end up undergoing fertility treatments. Personally, I experienced infertility for 1.5 years even after AS correction (surgery and estrogen therapy) when I had had no problems conceiving to begin with. Then I went from being infertile to now conceiving once every two months but miscarrying. I have had 5 miscarriages in one year. All of my pregnancies have been naturally conceived. The last 3 have been very early miscarriages. Of course my first thought was that I might have some recurrence adhesions from my last hysteroscopic removal of RPOC in March. An in-office diagnostic hysteroscopy ruled out this possibility. I had molecular karyotyping (MLPA) of my last miscarriage which revealed trisomy 9, 20 and triallelic markers on the X chromosome. This indicates problems with egg quality. The first pregnancy after AS occurred a few months after 2 cycles of unsuccessful IVF. I wonder whether the effect of IVF hormones had a beneficial effect on my endometrium and egg development. My plan is to now find a fertility specialist who is willing to work with me on a protocol that does not include egg retrieval and in vitro fertilization (since I conceive very easily without it), but rather one that concentrates on improving the uterine environment. My idea is to use low dose aspirin (to improve blood flow to the uterus) and low doses of FSH to stimulate about 2 follicles (to double my chances of a healthy embryo) , undergo 'in vivo' fertilization and start taking progesterone pessaries after ovulation (for luteal phase support). FSH stimulates follicles to grow which in turn secrete estrogen to thicken the endometrial lining. Some women with past AS find that their endometrium responds more favourably to this ovarian stimulation than to estrogen pills. I'm also considering the use of DHEA, a controversial hormone which is alleged to improve ovarian reserve and quality, resulting in fewer miscarriages (and presumably aneuploidies).

Unfortunately, a few of the fertility specialists I have seen in the past have been very unflexible and biased in their thinking. Many have their own 'pet' theories about what works and what doesn't without the backup of proper studies. While they are happy to point out that my suggestions have no rigorous evidence of efficacy, they seem oblivious to the fact that their own suggestions also lack robust data and in addition, are often expensive, time consuming, painful and with possible adverse effects on health. When I once pointed this out, a well respected specialist told me to stop thinking like a scientist! He also told me that if I 'really' wanted a baby I would be willing to try risky treatments! There are still many unknowns in the area of infertility and fertility doctors don't know everything (even if some of them think they do!). For instance, this specialist convinced me that my inability to conceive was due to my low AMH levels (an indicator of poor ovarian reserve in my case due to being over 40) and in his words, I would never conceive without IVF, although he couldn't explain how IVF would improve ovarian reserve or egg quality. As an aside, I have very low FSH levels (3 when I was 42) which are meant to indicate excellent ovarian reserve. I didn't know it at the time he said this, but I was already pregnant. I went on to have 4 more pregnancies afterwards. Unfortunately my problem now is recurrent miscarriage, but his statement is still untrue. No one has been able to give me a reasonable explanation as to why I have gone from being unable to conceive for 1.5 years despite treatment for IUA, to conceiving every 2 months.

Below is a link to a chart detailing which tests and treatments are scientifically supported and which are not. Most have not been proven to be useful, although it is possible that in future there will be evidence to support them. It is up to the individual to decide, after considering risks and benefits, whether to proceed with them.

Infertility Tests and Therapies Questioned (Bupa)

More information on the validity of tests and therapies for infertility/recurrent miscarriage:

Cochrane Reviews: Immunotherapy for recurrent miscarriage (Full article: click here)
Note that this systematic review is comprised of studies where exclusion criteria included women with abnormal immune tests (eg. auto-antibody, cytotoxic antibodies, IgA deficiency etc.). Bascially, this review found that in women with recurrent miscarriage without any demonstrated abnormal immune function, there is no significant evidence that immunotherapy is useful (which one would expect). Still, many fertility specialists are eager to use these therapies on such patients.

RCOG: Implantation and Early Development - study group statement.

Miscarriage, Infertility, Antibodies and the Immune System Dr Licciardi's Infertility Blog

Effect of Asherman’s syndrome on infant health

2010-09-29T00:14:00.000-07:00

Over a century after the condition was first reported, there are as of yet no analytical studies on the health of children born to women with a history of AS or even on pregnancies conceived with adhesions present. The only data available in the literature are from isolated case reports.

As mentioned elsewhere, the proportion of births after Asherman’s syndrome treatment (ie. births / total number of women treated) are around 40% across all classifications. Reproductive outcome is correlated with severity at diagnosis, with mild cases having a highest live birth ‘rates’ (‘proportion’ is actually the correct terminology) and severe cases having the lowest live birth proportion.

The risks associated with abnormally invasive placenta (accreta, percreta, increta) and low lying placenta (previa) mainly affect the mother at delivery. These can lead to significant blood loss and emergency hysterectomy. Massive hemorrhaging is a life threatening situation for the mother and requires blood transfusions. Conversely, IUGR, preterm birth and IC present a risk for the fetus.

The majority of gestations following the surgical correction of adhesions are uncomplicated and presumably healthy babies are delivered. This is partly because most women who are able to carry pregnancies have an adhesion free uterus with relatively healthy endometrium while in those with severe endometrial injury (resulting in IUA with or without fibrosis) pregnancy is less likely even after surgery, and any pregnancy achieved would generally miscarry early on.

A retrospective case control study found no difference in pregnancy outcome aside from birthweight in pregnancies with and without IUA (1). It should be noted that case-control studies and in general, retrospective studies are not the most rigorous in terms of evidence. Presumably, the extent, severity and location of uterine adhesions affect the course and outcome of the pregnancy. However, if adhesions are only mild and filmy they can stretch or even divide as the uterus grows with the pregnancy. The latter was described in a case report by Klatsky et al (2) (see cases below). As no two cases of AS are identical, it is difficult to predict the outcome and therefore close monitoring of the pregnancy by a high risk obstetrician is advised for regular screening for potential complications such as cervical incompetence, IUGR, premature labour, invasive placenta, and pre eclampsia. Regular screening will also assist in the detection of fetal abnormalities and potentially improve their management. Home births are not advisable in women with past AS even if the pregnancy appears to be progressing without problems, as invasive placenta may not be detected until the time of delivery and this could lead to serious life threatening situations.

Prematurity and neonatal complications

Most health complications in newborns delivered to women with past (or current) AS would probably be related to prematurity, as women with AS (past or current) are more likely to deliver preterm. Prematurity may be caused by other known complications associated with AS such as IUGR. Depending on the extent of prematurity, such birth defects could include neurological problems (eg. cerebral palsy, apnea of prematurity, retinopathy of prematurity), respiratory problems (eg. respiratory distress syndrome), cardiovascular problems (eg. patent ductus arteriosus), gastrointestinal/metabolic disorders (eg. rickets, inguinal hernia), hematological conditions (eg. jaundice, anemia) and infections (eg. sepsis, UTI). Obviously neonatal mortality is another possible complication of premature birth and generally, the earlier the birth, the more severe the complications. Babies born during the second trimester due to cervical incompetence (as a result of previous cervical dilations associated with the index injury leading to AS and/or surgical correction of AS) are often too young to survive outside the body, and even if they do they will have severe and life long complications.

Effect of IUA during pregnancy: four case reports with different outcomes

It is very important that the uterus is assessed for adhesions after treatment of Asherman’s syndrome before conception is attempted/advised. Adhesions are known to recur in moderate and severe cases, and further surgery may be required. Complications will be increased if pregnancy occurs in the presence of thick adhesions. This is highlighted in the examples from case reports below. Note that the first example is one where the patient underwent endometrial ablation (EA) which is a procedure that mimics very severe AS. It is unclear whether the patient was counseled for the risks of a future pregnancy. Usually both IUA and extensive fibrosis are present. In fibrosis the endometrium is replaced with scar tissue to varying extents (hence it is also known as sclerotic endometrium or ‘unstuck’ Asherman’s syndrome due to the absence of adhesions). This is the most severe form of AS. Fibrosis occurs mainly as a result of thermal energy use in the uterus. Electrosurgery (e.g. resectoscope, laser etc.) also leads to IUA because of damage to the basal endometrium. EA is procedure used to treat abnormally heavy bleeding in which the endometrium is intentionally and irreversibly destroyed using thermal ablation. First reported in 1981, EA has been gaining popularity as a less invasive alternative to hysterectomy. Unfortunately damage may also occur unintentionally when these same instruments are used for other purposes such as the resectioning of uterine fibroids or polyps or the dissection of adhesions during the treatment of Asherman’s syndrome. Instead of having their fertility restored, the patient may end up with more severe adhesions and fibrosis than originally. Therefore mechanical dissection of adhesions may have better outcomes. EA should not be undertaken in women who desire future fertility and they should be informed about potential dangers of pregnancies if they fall pregnant. I have seen doctors on the internet advertizing endometrial ablation reversal in women who wish to conceive after having had the procedure. This practice is highly questionable given the high risk of severe pregnancy complications and the low chance of a live birth after EA. Pregnancy rates following EA are in the vicinity of 0.2-0.7% (3,4) with perinatal mortality reported to be 11.8% (4)

Severe AS from EA and birth defects

1. Mukul and Linn (5) reported amniotic band syndrome (ABS) in a pregnancy following endometrial ablation. The patient had three prior pregnancies and one birth. ABS , also called Amniotic Constriction Band Syndrome, is a set of congenital birth defects believed to be caused by entrapment of fetal parts (usually a limb or digits) in fibrous amniotic bands while in utero. The patient had undergone rollerball EA 7 years earlier without complications. Ultrasonography at 7 weeks revealed evidence of amniotic band syndrome: synechiae (i.e. IUA) were seen in the midquadrant of the uterus, creating amniotic sheets and bands with small compartments. The entire lower uterine segment was empty except for the right leg and a loop of umbilical cord poking through the lower uterine synechia. The fetus was of normal size but with clubbed feet, a distorted spine, and ventriculomegaly.

The patient underwent preterm labour and membranes ruptured at 26 weeks. A male infant was delivered via emergency C-section. An emergency hysterectomy was performed. The infant’s birth defects were described as follows:

“There were positional deformities in the neck, an asymmetric chest, severe scoliosis confirmed by X-ray, bilateral clubbed feet, and very limited movement of all long extremities consistent with arthrogryposis. The right lower extremity was swollen, cyanotic, denuded of skin, and without perfusion or pulses. Areas of significant necrosis on the posterior thigh of the right lower extremity were noted.”

Prognosis was poor and the parents decided to withdraw ventilation support. The infant died 6 hours after delivery.

One theory on the cause of ABS is that it occurs when the inner membrane (amnion) ruptures without injury to the outer membrane (chorion), exposing the fetus to fibrous tissue (bands) from the ruptured amnion which can entangle body parts, leading to congenital abnormalities. Another theory is that vascular disruption occurs. The latter would explain the presence of cleft lip in ABS cases. Either theory could account for its description in women with severe injury to the endometrium. Both IUA and fibrosis resulting from EA would lead to vascular disruption.

Mild to moderate IUA during pregnancy

In the three examples below, patients developed IUA from uterine curettage (i.e. D&C). One case ended in the term birth of a healthy baby while the other two resulted in congenital abnormalities. It appears that the severity of the adhesions affects outcome.

2. Klatsky et al (3) report of a pregnancy complicated by endometrial scarring which ended in a term birth of a healthy infant. The patient, a 39 year old woman, had a history of D&C for therapeutic abortion followed by three miscarriages, the last of which was completed by D&C. An ultrasound at 19 weeks identified a thick band crossing the lower uterine segment with the placenta inserting alongside it. Mullerian fusion anomalies were ruled out. Doppler flow imaging demonstrated flow along the synechia to the overlying placenta. At 25 weeks the patient passed half a cup of bright red blood. An ultrasound revealed a thinning scar with placenta still implanted on both sides and a small subchorionic hematoma. At 31 weeks ultrasound demonstrated a reduced scar with placenta visible on only one side. The patient presented at term with premature rupture of the membranes and a fetus in breech presentation. She underwent cesarean delivery. No uterine anomalies or adhesions were found, presumabley the thin uterine adhesion was evacuated with the placenta. The infant had no morphological abnormalities.

3. Deering et al (6) report a case of head entrapment of a second twin by intrauterine synechiae leading to long term health complications. The 40 year old patient had a history of two uterine curettages (ie. D&C) , one for first trimester miscarriage and a second for menorrhagia. CVS was undertaken during first trimester revealing normal male karyotypes. Diagnostic hysteroscopy and lysis of adhesions was not performed prior to IVF resulting in a twin pregnancy. She presented at 19 weeks for evaluation due to a shortened cervix and pronounced funneling (symptoms of cervical insufficiency). A McDonald cerclage was placed. Ultrasound examination also revealed a moderate sized uterine synechiae wrapped around the neck and placenta of twin B. Twin B was affected by IUGR, weighing less than the third percentile for gestational age. The development of growth restriction and discordance in twin B is thought to result from the combination of the contracted space available for twin B’s head to grow, the compression of the umbilical cord against the fetal neck by the uterine band, and the implantation of the placenta in an abnormal portion of the uterus with a potentially inadequate blood supply.

Cesarean delivery was undertaken at 26 weeks due to fetal distress of twin B and head entrapment. As seen on ultrasonography a thick uterine band was tightly constricting the neck of twin B. The location of the tissue was consistent with the uterine synechia observed on hysterosalpingogram before IVF. Twin A did well and was discharged from the NICU at 3 months. Twin B remained in the NICU until 5 months of age, at which time he was discharged to a longer-term pediatric care facility for continued care. This case demonstrates that significant uterine synechia might result in intrauterine head entrapment, as well as IUGR.

4. Baumler et al (7) report a case of premature birth of an infant with prolonged pulmonary distress syndrome and severe kyphoscoliosis (90 degrees) in a patient with IUA. The patient was 37 years of age with a history of two first trimester miscarriages and evacuation of retained products of conception (ERPC or D&C). Preterm labor occurred at 28 weeks. Midtrimester 2D, 3D and real-time 4D ultrasound revealed a horizontal miduterine separation in the form of an ‘egg-timer’. The uterine cavity was separated in two superimposed cavities. The fetus and the placenta were located in the upper part of the uterus, and the right arm of the fetus and part of the umbilical cord extended in the lower part of the uterus, through an opening in the separating horizontal membrane. The kyphoscoliosis, thought to be due to severe oligoamnios was managed conservatively.
The mother’s operative hysteroscopy carried out 6 months later confirmed both clinically and histologically the presence of a transversal muscular synechia.

The examples above illustrate the importance of diagnosing and removing IUA prior to IVF or conception. Furthermore, thick adhesions restrict the growth of the uterus, possibly increasing pressure on the cervix and leading to CI or preterm labor. The patient in the example above (6) may not even have needed IVF as her fertility problems may have been due to Asherman’s syndrome which could have been surgically corrected and allowed a better pregnancy outcome. Not only are the chances of pregnancy reduced, the health of the mother and infant are compromised as well with the presence of IUA. It is particularly irresponsible to perform IVF in patients without confirming an architecturally normal uterus. There is unfortunately a tendency for some clinicians to believe that IUA are harmless and asymptomatic (3) but this case shows that even a single thick band can have significant repercussions during pregnancy. As all cases are not treatable, in particular more severe ones where there is a tendency for scars to reform and irreversible fibrosis to occur, prevention of AS wherever possible is the best and easiest strategy available.

REFERENCES

1. Ball RH, Buchmeier SE, Longnecker M. Clinical significance of sonographically detected uterine synechiae in pregnant patients. J Ultrasound Med. 1997 Jul;16(7):465-9. Abstract

2. Klatsky PC, Tran ND, Strachowski L. A pregnancy complicated by endometrial scarring. Fertil Steril. 2009 Jun;91(6):2707-8. Epub 2008 Nov 20 Abstract

3. Cook JR, Seman E. Pregnancy following endometrial ablation: case history and literature review. Obstet Gynecol Surv 2003;58:551– 6. Abstract

4. Pugh CP, Crane JM, Hogan TG. Successful intrauterine pregnancy after endometrial ablation. J Am Assoc Gynecol Laparosc 2000;7:391– 4. Abstract

5 Mukul LV, Linn JG. Pregnancy complicated by uterine synechiae after endometrial ablation. Obstet Gynecol. 2005 May;105(5 Pt 2):1179-82. Abstract

6 Deering SH, Heller J, Winkel C, Landy HJ. Intrauterine head entrapment of a second twin by a uterine synechia. Obstet Gynecol. 2003 Oct;102(4):693-5. Abstract

7 Bäumler M, Faure JM, Couture A, Flunker S, Boulot P. Prenatal 3D ultrasound and MRI assessment of horizontal uterine synechia. Prenat Diagn. 2008 Sep;28(9):874-5.

The Miscarriage Study: 400 vs 800 mcg misoprostol

2010-08-31T01:05:00.000-07:00

Mater Mother’s Hospital in Queensland has been conducting a randomized controlled trial comparing two doses of misoprostol (800 mcg versus 400 mcg) for the medical management of miscarriage. More information can be found in the brochure for The Miscarriage Study on their website:

http://brochures.mater.org.au/Home/Brochures/Mater-Mothers--Hospitals/Miscarriage

Medical management is only available to women participating in the Miscarriage Study. Surgery or expectant management is offered as standard care options to women who choose not to participate.

The web brochure explains that the study is being carried out because currently there is no agreement on the most effective dose for misoprostol use in miscarriage. However it points out that 800mcg is the most common dose used in studies. While it is true that researchers have not determined a dosage/regimen which is as effective as D&C i.e. the ‘optimum’ protocol for medical management using misoprostol, preliminary guidelines based on hundreds of studies have been produced by the expert group convened by WHO in Bellagio in February 2007. They are published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) and can be read here. According to these guidelines, 600-800 mcg misoprostol is the recommended dose for first trimester miscarriage. The guidelines for misoprostol use according to indication and gestational age are also available at: http://www.misoprostol.org/ This website also provides excellent resources to clinicians interested in information about misoprostol use and the misoprostol debate.

The researchers have chosen to study quite a low dosage of misoprostol to reduce side effects. However, it has already been established that even 600-800 mcg is not as effective for first trimester miscarriage as the standard care D&C (it remains questionable as to why it is imperative for medical management to be equally as effective as D&C for it to be used when medical management offers the advantages of being non-invasive, cheap, free of anesthetics and safer for future fertility than D&C).The drug is inexpensive, so cost is evidently not an issue. Furthermore, the optimum dose for use in termination up to 7 weeks is 800 mcg (in combination with mifepristone). A recent study found that this dose should not be lowered (link). Apparently misoprostol side effects for termination are not a concern for women. One would imagine the same for women who miscarry.

Misoprostol is listed in the Standard Drug List of Queensland Hospitals for use in miscarriage and is currently used in this hospital for the treatment of other pregnancy complications. The Therapeutic Goods Administration (TGA), which is the Australian equivalent of the FDA in the US, has not approved of its use in pregnancy in Australia.

However, the Queensland Health and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists support its use in the treatment of miscarriage. Despite this, misoprostol use for first trimester miscarriage remains uncommon in Australia. The drug is quite commonly used for miscarriage management in European countries. In contrast, a combined misoprostol/mifepristone regimen is offered by most if not all services in Australia specializing in pregnancy termination. It has also become common practice for labour induction despite the fact that there is not more evidence to support its use for this indication than for miscarriage. Interestingly, expectant management is considered acceptable although it is not more effective than for miscarriage management in clinical trials. Health professionals excuse the restricted access to misoprostol for miscarriage management with the pretext that misoprostol is not TGA approved, yet misoprostol use in ALL obstetric/gynecologic indications is not approved (misoprostol was developed for the treatment and prevention of ulcers). The unlicensed use of misoprostol for terminations is cunningly circumvented by a legal loophole which allows its use in combination with mifepristone which is only TGA approved for use in pregnancy termination. Unlicensed use of misoprostol in labour induction, curiously, does not seem to hinder clinicians from using it for labour induction even though substantially less is known about the short and long term effects it may have on infants exposed to it. Misoprostol is also used in the treatment of osteoarthritis and marketed under the name Arthrotec. Curiously, there is no debate over the unlicensed use of misoprostol for arthritis. Yet none of the above has lead to questioning the objective validity behind the selective use of misoprostol for some unlicensed obstetric (or other) indications but not for miscarriage management. Why is it that the only people who seem to be prevented from using misoprostol are women who miscarry?

Most women who miscarry have no choice but to undergo a costly D&C, potentially leading to long term adverse effects on fertility (Asherman’s syndrome) and a host of possible future obstetric complications (placenta accreta, percreta, previa, IUGR, pre eclampsia, preterm birth, cervical insufficiency leading to second trimester loss, and uterine rupture). It is ironic that the very women who desire a pregnancy most are also those who are exposed to iatrogenic infertility and/or pregnancy complications arising from surgical management. Disappointing overall reproductive outcomes (40%) and associated healthcare costs (not to mention patient discontent) do not make the approach of relying on treatment of Asherman’s syndrome a paradigm. The restriction of a safe, inexpensive and non-invasive alternative such as misoprostol for miscarriage management can be considered unethical and perhaps even discriminatory as it is available to other populations of women for unlicensed obstetric/gynecological indications.

The Mater Mother’s Hospital webpage mentions potential complications from surgical management (D&C) without specifically naming Asherman’s syndrome (intrauterine adhesions and/or fibrosis) or cervical insufficiency (from cervical dilation). It also quotes the risk of complications from D&C as 1:200-500 surgeries, a greatly underestimated frequency (see Frequency of intrauterine adhesions after curettage).

It is encouraging to see local studies on misoprostol for miscarriage management. Even if 400 ug will turn out to have a significantly lower success rate than 800 ug, exposure to women and clinicians could help promote awareness about it and increase its demand/use. Perhaps it is a sign that Australia is finally ready to implement medical management as a routine care option.

Misoprostol for miscarriage management: the facts and the fiction

2010-07-19T02:31:00.000-07:00

This is my latest Youtube video presentation. It explains the truth behind often repeated misinformation about misoprostol.

Misoprostol for miscarriage management is underused despite evidence of its efficacy and safety. It is an ideal alternative to D&C. It can also prevent Asherman's syndrome which mainly occurs from D&C, a blind surgery. This clip clarifies concerns about misoprostol which may be hindering its use by clinicians and patients alike.

Recent and upcoming articles on Asherman's syndrome (July 2010)

2010-07-12T06:15:00.000-07:00

There are two articles in press about Asherman's syndrome in peer-reviewed medical journals.

One is titled: Human amnion as a temporary biologic barrier after hysteroscopic lysis of severe intrauterine adhesions: pilot study, by Amer et al. in Egypt will appear in The journal of minimally invasive gynecology. To read the abstract, please click here. It is a continuation of and follow-up on the reproductive outcome of patients from a previous study published four years earlier by the same group (Amnion graft following hysteroscopic lysis of intrauterine adhesions, Amer I and Abd-El-Maeboud J Obstet Gynecol Res Vol 32, No. 6:559-566, 2006). Although the method could be promising, there are restrictions for using amnion in Western countries due to fears of cross-contamination between donors and recipients (ie. women treated for Asherman's syndrome with the tissue). Amnion is obtained from fresh amniotic membranes shortly after birth from 'donor' patients undergoing elective cesarean section. These donor patients are screened for hepatitis B, hepatitis C, syphilis and HIV. The tissue is placed around an intrauterine balloon and inserted in the uterus following hysteroscopic lysis of intrauterine adhesions and left in place for 2 weeks. Amnion was previously used in developed countries for different gynecologic reconstructive surgeries but was abandoned after the outbreak of Creuzfeldt Jakob disease (CJD), the human variant of 'mad cow' disease. It is an incurable and fatal transmissible degenerative neurological disorder for which there is no test to screen infected tissue. I will wait until the article is published before making further comments. There is one contradiction of note in the abstract; although the patients in the study were reported to have severe intrauterine adhesions, they were described as having infertility with or without menstrual disorders such as amenorrhea or hypomenorrhea. It seems inconsistent to have severe adhesions without any changes in menstrual bleeding, and suggests that perhaps the diagnosis of severity was exaggerated. Severe adhesions are more difficult to treat and tend to recur more frequently than mild ones. Severe adhesions are also associated with poorer fertility outcomes.

The second article in press is: Separated from birth: An initial examination suggested Asherman's syndrome (Oakes and Fisseha, Am J Obstet Gynecol, 2010). This is a case study where a patient appeared to have intrauterine adhesions following a C-section (a rare cause of Asherman's syndrome), but on closer inspection turned out to have a uterine dehiscence from a hysterotomy scar. Uterine dehiscence is the incomplete separation of the myometrium at a uterine scar site.

The article Impact of previous uterine artery embolization on fertility. (Berkane N, Moutafoff-Borie C. Curr Opin Obstet Gynecol. 2010 Jun;22(3):242-7) suggests that Asherman's syndrome is a possible risk after uterine artery embolization (UAE). In another recent study (Fertility and pregnancy following pelvic arterial embolisation for postpartum haemorrhage. Sentilhes L, Gromez A, Clavier E, Resch B, Verspyck E, Marpeau L.BJOG. 2010 Jan;117(1):84-93) researchers claim that pelvic arterial embolisation for postpartum hemorrhage does not affect future fertility even though around 12% of study participants were diagnosed with Asherman's syndrome after the procedure and a further 11% exhibited symptoms of it although they declined diagnostic hysterocopy. However it is unclear from the article whether the intrauterine adhesions were pre-existing, or if they resulted from additional procedures carried out in addition to PAE to stem blood flow, such as manual removal of placenta or uterine packing. UAE and PAE are uterine-sparing alternatives to hysterectomy which employs a vascular radiological technique to treat pospartum hemorrhage and fibroids.

A new cause of Asherman's syndrome, B-lynch suture, was recently reported in Development of Asherman syndrome after conservative surgical management of intractable postpartum hemorrhage. (Goojha CA, Case A, Pierson R. Fertil Steril. 2010 Mar 25.) B-lynch suture is a 'conservative' surgical compression technique for managing postpartum hemorrhage.

I have also been told that there will be a case report on the association between pregnancy after Asherman's syndrome and an obstetric complication not previously reported, pre-eclampsia. This is consistent with the fact that pre-eclampsia is caused by ischemia and the presence of insufficient blood flow to the placenta in Asherman's syndrome that sometimes persist even after treatment. This will be added to the list of complications in post AS pregnancies I have already written about.

There will also be a study published on reproductive outcomes following treatment where pregnancy rates were about 60%, live birth rates 40% and miscarriage rates were supposedly equivalent to those of the general population.

FAQs Asherman's syndrome

2010-07-02T01:44:00.000-07:00

Please see the new page on frequently asked questions about Asherman's syndrome. You can also click on the relevant tab button in the tab bar at the top of the page to view it.

Focus on the medical literature: Misoprostol for early pregnancy failure is underused despite efficacy and safety .

2010-06-15T00:20:00.000-07:00

Article: Provider knowledge, attitudes, and treatment preferences for early pregnancy failure.

Dalton VK, Harris LH, Gold KJ, Kane-Low L, Schulkin J, Guire K, Fendrick AM. Am J Obstet Gynecol. 2010 Jun;202(6):531.e1-8. Epub 2010

The American Journal of Obstetrics & Gynecology has recently published an article, ‘Provider knowledge, attitudes and treatment preferences for early pregnancy failure’ (EPF),which explores the relationship between health provider attitudes and associated factors and the methods they use for treating miscarriage. Ever since acquiring Asherman’s syndrome from a D&C for an incomplete miscarriage because I was spuriously denied medical management, I have been curious to find out what proportion of Obstetricians offer misoprostol to their patients. This will vary from country to country. My understanding is that many countries in continental Europe are more progressive in adopting misoprostol use than the US, England, Australia and New Zealand. I know from personal experience that in Australia the use of misoprostol for first trimester or early second trimester miscarriage management is rare. I have also learned that even when it is used, the hospital protocols are strict and dosages are in accordance with only second trimester termination, as illogical and ineffective as this may be for other gestational ages.

My interest in the article of course stems from an angle of Asherman’s syndrome prevention, whereas cost effectiveness was the main interest of the study. For this reason, the researchers were focused on the frequency of misoprostol and office uterine evacuations, both of which are far less expensive than operating room (OR) surgical evacuations. This is mainly due to operating room and anesthesiologist costs of OR D&C (the patient is awake during in-office D&C). Thus, the authors consider all treatment options (expectant or medical management, office, and OR procedures) to be reasonable, and that patient preferences should be the deciding factor in treatment choice. It should be mentioned that the same group authored case reports alerting that even gentle manual vacuum aspiration (MVA) (a type of office uterine evacuation) can lead to symptomatic IUA ie. Asherman’s syndrome (1). This is not surprising given that blind instrumentation is involved.

There is a plethora of clinical studies in the medical literature supporting the efficacy and safety of misoprostol (click here) for treatment of early pregnancy failure (2,3) as well as for abortion. Yet there is a discrepancy between the established research findings and its level of use in practice. Although the problem of failing to adopt evidence-based treatments is a common problem it is especially so in women’s health (4,5,6). Therefore, practitioners are usually slow to offer new treatment methods, even when these are known to be effective, safe, and offer advantages to traditional treatments. Thus, clinicians have the power to influence patient treatment, rather than letting the patient choose how her miscarriage is managed (7,8). It is unclear whether all treatment options are routinely offered or available to women who experience early pregnancy failure (9).

The study hypothesized that most providers do not routinely offer patients all acceptable treatment options, and that factors such as knowledge and perceived obstacles to adopting new methods might be associated with sex, specialty, years of practice, and training.

In particular they sought answers from health providers with respect to each treatment method regarding :

-attitudes about treatment safety (and I would add efficacy) (Treatment Preference)
-perceptions of patient acceptance of options (Perception of patient preferences)
-provider comfort with the options (Use of treatments)

For misoprostol and office uterine evacuations they looked at additional factors.

The study was carried out as a written survey which was sent out to Obstetrician-gynecologists (‘Obgyns’), certified nurse midwives/midwives (‘nurses/midwives’), and family physicians (‘GPs’) in the United States.

From the point of view of Asherman’s syndrome prevention, the focus will be on the paper’s relevant outcomes with regards to use of the non-invasive alternatives misoprostol and expectant management compared to OR surgical evacuation (ie. D&C). Also, I am adding a few interpretations which were not mentioned in the article. These are in blue font.

D&C

Treatment preference-Obgyns preferred uterine evacuation in the operating room over other methods (45.7%)(No surprise there…)
Perception of patient preferences -Interestingly, Obgyns believed OR D&C was the more preferable treatment than their patients (28.4% vs 15.5%; P<.001, perceived Obgyn and patient rank, respectively). It is unclear whether this reflects a higher level of confidence than their patients in the procedure or if the preference is influenced by financial factors. Note that 21.8% of Obgyns in the study expressed concern regarding reimbursement for in office uterine evacuations- the identical procedure to their self-declared preferred method, the much costlier operating room D&C including anesthesiologist.
Use of treatments -Obgyns reported using OR D&C more than the other options and nurses/midwives and GPs. -38.9% of Obgyns used D&C in over half of all patients in the past 6 months.

Expectant management
Treatment preference
-Nurses/midwives and GPs were the most likely to prefer expectant management (55.2% and 64.5% , respectively)
-Obgyns were the least likely to report expectant management as their most preferred treatment
Perception of patient preferences
-Health provider’s belief regarding patient preference of expectant management mirrored their own.
Use of treatments
-Obgyns were less likely than the others to use expectant management (12.3% compared to 30.4% and 43.4% for nurses/midwives and GPs, respectively).

Misoprostol
Treatment preference
-Obgyns, nurses/midwives and GPs chose misoprostol as the second preferred treatment method (33.2%, 61.8% and 60.7% respectively).
Perception of patient preferences
-Health provider’s belief regarding patient preference of misoprostol management mirrored their own.
Use of treatments
Misoprostol (along with office uterine evacuations) were the least commonly used treatment options.
-Most providers had not used misoprostol at all in the past 6 months for EPF treatment.
- Over the last 6 months, 52.7% of Obgyns reported not using it even once.
- Obgyns were still more likely than the others to use misoprostol but only 5% of them reported using it in over half of their patients in the last 6 months.
-67.9% and 84.1% of nurses/midwives and GPs, respectively, reported not ever using misoprostol in the last 6 months.

Provider factors influence on use of misoprostol
-sex and race: Not associated with use of misoprostol
-Safety: providers who believed that misoprostol is safe used it more than those that did not. Disturbingly, 29.7% of Obgyns, 36.2% of nurses/midwives, and 37.8% of GPs did not agree with the statement “Misoprostol is safe.”
(This mindset counters evidence-based medicine and requires further examining).
-Low patient demand: 34.7% of GPs claimed little patient demand was a barrier, versus 18.2% of Obgyns and 15.7% of nurses/midwives. (Is this really a valid excuse not to at least offer it?)
-prior induced abortion training: Not significantly associated with misoprostol use.
(I wonder if training in misoprostol use specifically for EPF management exists)
-Other perceived obstacles to using misoprostol included lack of surgical or nursing backup/support. (Paradoxically these do not appear to hinder the preference of nurses/midwives or GPs for expectant management).

Conclusions
-EPF management is still largely dominated by operating room uterine evacuations (Obgyns) and expectant management (nurses/midwives and GPs) even though the efficacy and safety of misoprostol is well established.

-targeting inaccurate beliefs about the safety of misoprostol and clarifying patient preferences may increase the willingness of providers to adopt new practices to meet patient needs.

Note: -This study does not delineate how much patient preferences account for current treatment patterns, however:

-Women vary in their treatment preferences, therefore providing access to a wide range of services will improve care.

-clinical trials suggest that misoprostol is acceptable and may be preferred by many women over surgical evacuation especially when successful and when surgery is performed without anesthesia eg. in office (10,11,12,13).

-Improvements in services for EPF, one of the most common clinical problems encountered by women of reproductive age, will have a strong impact on patient experience and satisfaction (I would add also from the point of view of Asherman’s syndrome prevention).

REFERENCES

1. Dalton, VK, Saunders, NA, Harris, LH, Williams, JA, and Lebovic, DI. Intrauterine
adhesions after manual vacuum aspiration for early pregnancy failure. Fertil Steril
2006;85(6):1823 e1-3.

2. Zhang, J, Gilles, JM, Barnhart, K, Creinin, MD, Westhoff, C, and Frederick, MM.
A comparison of medical management with misoprostol and surgical management
for early pregnancy failure. N Engl J Med 2005;353(8):761-9.

3. Trinder J, Brocklehurst P, Porter R, Read M, Vyas S, Smith L. Management of miscarriage: expectant, medical, or surgical? Results of randomized controlled trial (miscarriage treatment (MIST) trial). BMJ 2006;332:1235-40.

4. Cabana MD, Kim C. Physician adherence to preventive cardiology guidelines for women. Women’s Health Issues 2003;13:142-9.

5. Haagen EC, Nelen WL, Hermens RP, Braat DD, Grol RP, Kremer JA. Barriers to physician adherence to a subfertility guideline. Hum Reprod 2005;20:3301-6.

6. Harper CC, Blum M, de Bocanegra HT, et al. Challenges in translating evidence to practice: the provision of intrauterine contraception. Obstet Gynecol 2008;111:1359-69.

7. Gurmankin AD, Baron J, Hershey JC, Ubel PA. The role of physicians’ recommendations in medical treatment decisions. Med Decis Making 2002;22:262-71.

8. Molnar AM, Oliver LM, Geyman JP. Patient preferences for management of first-trimester incomplete spontaneous abortion. J Am Board Fam Pract 2000;13:333-7.

9. Dalton VK, Harris LH, Clark SJ, Cohn L, Guire K, Fendrick AM. Treatment patterns for early pregnancy failure in Michigan. J Women’s Health 2009;18:1-7.

10. Moodliar, S, Bagratee, JS, and Moodley, J. Medical vs. surgical evacuation of firsttrimester spontaneous abortion. Int J Gynaecol Obstet 2005;91(1):21-6.

11. Bique, C, Usta, M, Debora, B, Chong, E, Westheimer, E, and Winikoff, B. Comparison of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion. Int J Gynaecol Obstet 2007;98(3):222-6.

12. Lee, DT, Cheung, LP, Haines, CJ, Chan, KP, and Chung, TK. A comparison of the psychologic impact and client satisfaction of surgical treatment with medical treatment of spontaneous abortion: a randomized controlled trial. Am J Obstet Gynecol 2001;185(4):953-8.

13. Graziosi GC, Bruinse HW, Reuwer PJ, Mol BW. Women’s preferences for misoprostol in case of early pregnancy failure. Eur J Obstet Gynecol Reprod Biol 2005;124:184-6.

Cochrane review: Medical treatments for incomplete miscarriage (less than 24 weeks)

2010-06-04T00:08:00.000-07:00

This systematic review was published in January. I'm adding a link to it in the RELEVANT LINKS section to the right. Or click here to have access to the complete article (then click on a link in the left window).

"Women experiencing miscarriage at less than 13 weeks should be offered an informed choice." (from the abstract)

Failed medical management or a failure to comply with accepted guidelines?

2010-05-26T00:04:00.000-07:00

Only 4 months after an in utero fetal demise at 14 weeks, I had a first trimester miscarriage at 8 weeks. I had conceived (naturally again) after only a month of trying and the pregnancy was suspected by chance at a follow up for my previous miscarriage only a few days after implantation. I’d had my next ultrasounds at 5 weeks, just under 8 weeks-where a heart rate of 151 bpm was detected- and then at 9 weeks, where there was no longer any cardiac activity.
As if this was not bad enough, I was again faced with how to cope with the physical side of this loss without incurring damage to my previously scarred uterus. Misoprostol was of course my method of choice. I learned that I would have to be admitted as an in-patient according to this hospital’s treatment protocol, although I know that in other countries misoprostol management of first trimester miscarriage (and abortion) are routinely done on an out-patient basis. This of course would increase the cost of the procedure. Once I was admitted, I learned that I would be given the same protocol as for second trimester terminations. This is because the hospital only has protocols in place using misoprostol for late abortions.

I should clarify that in Australia, misoprostol is rarely used for first trimester miscarriage. This was an exception for them and I am relieved that I was not forced into having a D&C which caused this whole debacle to begin with.

What worried me was that the accepted dosage for second trimester terminations (400 mcg every 3 hours up to 5 times) is lower per administration than that recommended for first trimester miscarriage. According to guidelines published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) a woman with a first trimester miscarriage should be given 2 doses of 800 mcg of misoprostol (vaginally) 3 hours apart. This is because early in a pregnancy, there are fewer prostaglandin receptors to which misoprostol binds than later in pregnancy.

While I received the same protocol for my previous second trimester miscarriage as for second trimester abortion, the accepted protocols for these two indications are much more similar and was thus it was more effective. However, this dosage is not considered effective for first trimester pregnancy failure and with good reason, as I subsequently found out: it simply does not work. On the first day I received 5 doses but none of them produced contractions that were strong enough to evacuate the uterus. There seemed to be less uterine contractions and bleeding after the first few administrations as though the effects were wearing off. I was given a 12 hour break before starting again. I requested that the drug be given orally instead this time. I had even less of a reaction, not even nausea or diarrhea which are commonly reported side effects of oral misoprostol. The following day, I agreed to hysteroscopic removal with my Asherman’s syndrome specialist.

According to this specialist, my cervix was slightly dilated but not enough for the gestational sac to pass through. The gestational sac had implanted slightly low in the uterine cavity (future placenta previa?), and in the anterior wall, in a region where I’d had scarring from my D&C and adhesions. Tissue obtained during the hysteroscopy did not grow in culture so I was unable to find out the karyotype of the embryo, or subsequently, the gender. It is possible that I miscarried because by chance the embryo implanted in a region where I’d had previous scarring and possible fibrosis, and the blood supply was not sufficient to maintain the pregnancy. If so, this is much more upsetting than if the baby was chromosomally abnormal and would not have survived anyway. I will never know for sure what caused this miscarriage, but an Asherman’s related cause cannot be either confirmed or ruled out.

It is quite possible that I would have required hysteroscopy to remove retained products, as I had previous uterine scarring from Asherman's syndrome, and the embryo also implanted in the area of the previous scarring. However, had I been given the correct dosage, I may not have needed to wait another day to respond to a drug which was given in too low a quantity to be effective anyway.

I noticed that on my hysteroscopic surgery report written under ‘reason for hysteroscopy’ was ‘failed medical management of miscarriage.’ This made me wonder if doctors and nurses would look at my file and incorrectly conclude that misoprostol was an ineffective drug for miscarriage, rather than realizing that the dose I had been given was inappropriate and not officially recommended for my stage of pregnancy. I wonder how many other women who claim their miscarriage management with misoprostol was a ‘failure’ were also given a dose not suited to their gestational age. From a patient perspective, I wonder why it is not possible for my hospital to provide treatment according to published recommendations for that indication (rather than according to a protocol used for another indication ie. second trimester abortion)? What is the logic in applying a protocol which goes against evidence-based medicine? I hope that instead of discouraging doctors, my experience will go towards persuading this hospital to broaden the current protocol so that women with first trimester miscarriage will benefit from misoprostol. For misoprostol to be effective and safe, it needs to be used according to established guidelines which take into account factors such as gestational age and indication.

Doctor’s orders: in support of Ashermans syndrome prevention and/or alternatives to D&C.

2010-05-14T01:39:00.000-07:00

Here's what the doctors have written over the years in support of preventing Asherman's syndrome from occuring and more recently, in support of alternative methods to D&C for miscarriage management. This list is not exhaustive and I may add to it in future. There is so much evidence in the medical literature and knowledge among some doctors at least, that it is difficult to reconcile it with current medical practices. 'Translational research' might be the current buzz word at research centers, hospitals and universities, but how quickly this progress is incorporated into routine or widespread practice is entirely another matter. This is where patients need to speak up to encourage change, and why patients need to educate themselves and others first. Reading the research is the only way to get an overall view of the established facts rather than relying only on second hand information from others who may have vested interests or other agendas.

(my additions are in blue)

1. Toaf and Ballas, 1978 (1):

"Peurperal curettage…was discontinued in Israel after publication of Asherman’s observations.”

This is not so in the US, UK, Australia and many other countries. Also, curettage remains standard care for treating miscarriage in many countries (while abortion is now usually carried out medically).

2. Li et al, 2001 (2):

After vaginal delivery, a retained placenta may cause a risk to maternal health because of hemorrhage or infection. …manual removal of the retained placenta is a routine procedure. ..This invasive procedure increases risk of trauma*, rupture of uterus, hemorrhage, postpartum infection, and anesthetic complications.”

* Asherman’s syndrome may result

“In all 18 parturients, spontaneous expulsion of the placenta developed in an average interval of 12 min (range from 5 to 35 min) after rectal insertion of misoprostol.”

3. Friedler et al, 1993 (3):

“The incidence of IUA might be lower following medical evacuation of the uterus, thus avoiding any intra-uterine instrumentation; however, use of progesterone antagonists (ie, mifepristone) for this purpose is not yet approved by the Israeli Ministry of Health.”

4. Chapman and Chapman, 1990 (4):

“One must also note that the suction curette is capable of causing synechiae, usually, however in the region of the internal os.”
“It is noteworthy that, of the 11 patients with isthmus stenosis, six of them were attributable to termination of pregnancy, of which all but one had been performed by suction curettage”
“It goes without saying that, in view of the seriousness of the sequelae, the best management is prevention…”

3. Tam et al, 2002 (5):

“No cases of IUA were found in patients managed conservatively or by medical evacuation, whereas 2 cases (7.7%) of filmy IUA were detected in those managed by surgical evacuation.”

“We therefore recommend expectant management and medical evacuation as first-line treatment for complete abortion* and incomplete abortion*, respectively. Surgical evacuation should be the treatment of choice when {these methods} fails or is contraindicated.”
*ie miscarriage

6. Goldenberg et al, 1997 (6):
“Selective curettage of residual trophoblastic tissue directed by hysteroscopy is an easy and short procedure and might be preferable to conventional, nonselective, blind curettage.”

“…areas not covered by residual tissue…are not subject to surgical trauma during the selective procedure and presumably are therefore exposed to lower risks of inflammation, scarring and adhesion formation”

“Incomplete removal of the residua is more likely to occur during repeated conventional curettage, even if guided by ultrasonography, as had occurred in two of our patients. Direct visualization of the cavity allows…the exact location and extent of the residual tissue to be resected.”

7. Yu et al, 2008 (7):

“Prevention of Asherman Syndrome
Prevention is always better than cure. To prevent the formation of endometrial fibrosis and adhesions, it is essential that any trauma to the uterus be avoided, especially in the pregnant or postpartum state.”

They go on to recommend:
“Avoid postpartum or postabortion curettage”
“Diagnosis of retained products of conception …present a clinical challenge.
…Saline infusion sonohysterography (SHG) has enhanced our ability to diagnose retained products of conception (8)”
“…transvaginal B-mode ultrasonography combined with color velocity imaging and pulsed Doppler to detect retained trophoblastic tissue…could be useful to…select patients suitable for conservative management.(9)”
“Transvaginal duplex Doppler ultrasonography is also an effective noninvasive method for evaluating patients with persistent postpartum hermorrhage (10).”

"…hysteroscopy should be considered an effective method for diagnosis and treatment of retained products of conception." They cite the Goldenberg et al (6) study (see above).
…
“Select medical management of miscarriages
When termination of early pregnancy is necessary, medical treatment should be considered instead of surgical options.”
They cite the Tam et al study (5)(see above).

“Since its introduction, the uptake of medical abortion has been steadily increasing in countries where it has been available for routine use….Similarly, in the management of incomplete miscarriage or delayed miscarriage, expectant or medical treatment should be considered.”

7. Chung et al, 1995 (11):

“The accepted management of spontaneous abortion has not changed substantially in 60-70 years.”

“The policy of routine, universal evacuation of retained products of conception (ERPC) became the accepted form of management around the 1930s to combat [these*] complications. However, this approach may no longer be appropriate in all cases.”
*hemorrhage, infection.

“…in the United Kingdom, 90% of spontaneous abortions are managed [by ERPC] (12). Confidence in routine ERPC as the unquestioned ‘gold standard’ may no longer be justified. There may be alternative approaches that are less invasive but equally effective without incurring greater morbidity.”

“Transvaginal sonography can identify approximately one in three women with a spontaneous abortion who do not have a significant amount of retained tissue in the uterus.”

“Surgical intervention in {women who do not have a significant amount of retained tissue in the uterus} may unnecessarily incur iatrogenic complications without therapeutic gain.”

8. Demetroulis et al, 2001 (13):

“Surgical curettage under anaesthesia accounts for almost three-quarters of emergency gynaecological operations performed in the UK (14). However, dilatation and suction evacuation of the uterus under anaesthesia has certain morbidity, such as the risk of anaesthesia, uterine perforation, intrauterine adhesions, cervical trauma, and infections leading to infertility, pelvic pain and increased chance of ectopic pregnancy.”

9. Moodliar et al, 2005 (15):

“Moreover, surgical evacuation of retained products of conception (ERPC) is performed in the operating room, which significantly increases costs. Inherent in the procedure are the possible complications of perforation, hemorrhage, cervical trauma, intrauterine adhesions and postinstrumentation endometritis.”

“As an alternative, medical management has been found to be cost-effective and associated with fewer complications…Yet in South Africa*, incomplete abortion is still being managed by surgical evacuation.”

*in Australia and in many other countries too!

10. Muffley et al, 2002 (16):

“Curettage has been traditionally used as the surgical method of treatment. It has been estimated that approximately 100,000 uterine curettages are performed annually in the United States, at a total yearly cost of >100 million (17). Uterine curettage is associated with …hemorrhage and infection. Uterine adhesions, impaired future fertility, cervical trauma, uterine perforation, and anesthesia errors are also other potential sequelae of curettage.”

“In the late 1980s single-dose methotrexate therapy was introduced for the treatment of unruptured ampullary ectopic gestations (18). Nearly 10 years later, this medical therapy has replaced laparotomy or laparoscopy in many circumstances (19). At this time, however, medical treatment of early pregnancy failure is still in its infancy in the United States. On completion of multicenter randomized clinical trials, we believe that medical treatment will replace surgical therapy as the initial treatment of early pregnancy failure.”

(I hope so!)

Comment by Dr Lisa Fall:
“Firstly, as the trend toward later childrearing continues, we are faced with an increased incidence of pregnancy failure because of advancing gestational [ sic maternal] age. Our patients are interested in noninvasive options for treatment to avoid possible complications that may have an impact on future fertility.”
(Yup, that was me, but I was refused)
11. Zhang et al, 2005 (20):

“For most of the 20th century, dilatation and curettage was the commonly accepted approach to early pregnancy failure. This practice can be traced back to the late 19th and early 20th centuries, when illegally induced abortions commonly resulted in hemorrhage and sepsis (21). With the legalization of abortion and the availability of antibiotics, these problems have become rare. In more recent years, the medical community began to question whether immediate evacuation by surgical intervention was necessary for uncomplicated cases of early pregnancy failure (12,17).”

12. Stockheim et al, 2006 (22):

“Over the past decade, elective medical termination of pregnancy using a protocol that includes mifepristone and misoprostol was accepted into wide practice. This drug regimen was consistently shown to be associated with high success rates of 90-95% (23-26). However, medical treatment of pregnancy failure (blighted ovum or spontaneous abortion) has not yet gained wide acceptance.”

“Misoprostol is an effective and safe treatment for early pregnancy failure and could replace surgical curettage in over two-thirds of the patients.”

13. Creinin et al, 2006 (27):

“As clinicians and researchers, we must ask why women with an undesired normal pregnancy can receive a treatment regimen that is more effective than that tested for women with a desired abnormal pregnancy. The information presented in this analysis will allow us to better tailor misoprostol treatment for early pregnancy failure.”

I would also add, why women with an undesired normal pregnancy only have access to the mifepristone/misoprostol regimen which preserves fertility while those who miscarry do not.

14. Pang et al, 2001 (28):

“Misoprostol is justified as a first line treatment in the management of miscarriage in all cases because firstly it will avoid surgical intervention altogether in a proportion and secondly, in those who need it, misoprostol reduces surgery-related morbidity, mainly by priming the cervix (29.)”

15. Blanchard et al, 2004 (30):

“A growing body of research evidence indicates that medical treatment of incomplete abortion with misoprostol is an effective alternative to surgical intervention. Misoprostol could be an important alternative to dilatation and curettage or manual vacuum aspiration for treatment of incomplete abortion, allowing women to avoid surgical intervention and the attendant risks. Misoprostol is inexpensive and widely available and may also be more acceptable to women than the current standard of care.”

16. Shaw D, The International Federation of Gynecology and Obstetrics (FIGO) President (31):

“Furthermore, women have the right to benefit from advances in scientific knowledge and since women brought unapproved, reproductive health use of misoprostol to the attention of health professionals, it is especially fitting that they now benefit from the research into such use.”

17. The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, 2009 (32):

“In addition, there is increasing evidence that misoprostol is a safe, effective,and acceptable method to achieve uterine evacuation for women needing postabortion* care.”

“Misoprostol may be used to treat women with an incomplete and missed abortion.”

* Postabortion care: “… refers to a specific set of services for women experiencing problems from all types of spontaneous or induced abortions.”
REFERENCES

1. Toaff R, Ballas S (1978). Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome). Fertil. Steril. 30 (4): 379–87.
2. Li YT, Yin CS, Chen FM. Rectal administration of misoprostol for the management of retained placenta- a preliminary report. Chinese Medical Journal (Taipei) 2001;64:721-4.
3. Friedler S, Margalioth EJ, Kafka I, Yaffe H. (1993). Incidence of postabortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study. Hum Reprod 8 (3): 442–444.
4. K Chapman and R Chapman. Asherman's syndrome: a review of the literature, and a husband and wife's 20-year world-wide experience. J R Soc Med. 1990 September; 83(9): 576–580.

5. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. (2002). Intrauterine adhesions after conservative and surgical management of spontaneous abortion. J Am Assoc Gynecol Laparosc. 9 (2): 182–185.

6. Goldenberg, M., Schiff, E.' Achiron, R.' Lipitz, S.' Mashiach, S. Managing residual trophoblastic tissue. Hysteroscopy for directing curettage. J Reprod Med. 1997;42(1)26-8.
7. Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome-one century later. Fertil Steril 2008;89(4):759-779.

8. Wolman I, Gordon D, Yaron Y, Kupferminc M, Lessing JB, Jaffa AJ. Transvaginal sonohysterography for the evaluation and treatment of retained products of conception. Gynecol Obstet Invest 2000;50:73-6.
9. Alcazar JL. Transvaginal ultrasonography combined with color velocity imaging an dpulsed Doppler to detect residual trophoblastic tissue. Ultrasound Obstet Gynecol 1998; 11:54-8.

10. Achiron R, Goldenberg M, Lipitz S, Mashiach S. Transvaginal duplex Doppler ultrasonography in bleeding patients suspected of having residual trophoblastic tissue. Obstet Gynecol1993;81:507-11.
11. Chung, TK, Cheung, LP, Leung, TY, Haines, CJ, and Chang, AM. Misoprostol in
the management of spontaneous abortion. Br J Obstet Gynaecol 1995;102(10):832-
5.

12. Macrow, P and Elstein, M. Managing miscarriage medically. BMJ 1993;306(6882):876.
13. Demetroulis, C, Saridogan, E, Kunde, D, and Naftalin, AA. A prospective randomized control trial comparing medical and surgical treatment for early pregnancy failure. Hum Reprod 2001;16(2):365-9.

14. McKee M, Priest P, Ginzlet M et al. Can out-of-hours operating in gynecology be reduced? Arch Emerg Med 1992;9:290-8.
15. Moodliar S, Bagratee JS, Moodley J. Medical vs surgical evacuation of first-trimester spontaneous abortion. Int J Gynecol Obstet 2005;91:21-6.

16. Muffley, PE, Stitely, ML, and Gherman, RB. Early intrauterine pregnancy failure: a randomized trial of medical versus surgical treatment. Am J Obstet Gynecol 2002;187(2):321-5; discussion 325-6.
17. Ballagh SA, Harris HA, Demasio K.Is curettage needed for uncomplicated incomplete spontaneous abortion? Am J Obstet Gynecol 1998;179:1279-82.
18. Stovall, TG, Ling, FW, and Buster, JE. Outpatient chemotherapy of unruptured ectopic pregnancy. Fertil Steril 1989;51(3):435-8.
19. Lipscomb, GH, Bran, D, McCord, ML, Portera, JC, and Ling, FW. Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998;178(6):1354-8.
20. Zhang, J, Gilles, JM, Barnhart, K, Creinin, MD, Westhoff, C, and Frederick, MM. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005;353(8):761-9.

21. Hertig AT, Livingstone RG. Spontaneous, threatened and habitual abortion: their pathogenesis and treatment. N Engl J Med 1944;230:797-806.

22. Stockheim D, Machtinger R, Wiser A, Dulitzky M, Soriano D, Goldenberg M, Schiff E, Seidman D. A randomized prospective study of misoprostol or mifepristone followed by misoprostol when needed for the treatment of women with early pregnancy failure. Fertil Steril 86(4):956-60.
23. World Health Organization Task Force on post-ovulatory methods of fertility regulation. Comparison of two doses of two doses of mifepristone in combination with misoprostol for early medical abortion: a randomized trial. BJOG 2000;107:524-30.
24. Hausknecht RU. Methotrexate and misoprostol to terminate early pregnancy. N Engl J Med 1995;333:537-40.
25. Peyron R, Auberny E, Targosz V, Silvestre L, Renault M, Elkik F et al. Early termination of pregnancy with mifepristone (RU 486) and the orally active prostaglandin misoprostol. N Engl J Med 1993;328:1509-13.
26. Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misprostol in the United States. N Engl J Med 1998;338:1241-7.
27. Creinin MD, Huang X, Westhoff C, Barnhart K, Gilles JM, Zhang JZ. Factors related to successful misoprostol treatment for early pregnancy failure. Obstet Gynecol 2006; 107(4):901-907.

28. Pang MW, Lee TS, Chung TKH. Incomplete miscarriage: a randomized controlled trial comparing oral with vaginal misoprostol for medical evacuation. Hum Rep 2001;16(11):2283-7.
29. Chung TKH, Cheung LP, Sahota DS et al. Spontaneous abortion: short term complications following either conservative or surgical management. Aust NZ J Obstet Gynaecol 2001; 38:61-4.
30. Blanchard K, Taneepanichskul S, Kiriwat O, Sirimai K, Svirirojana N, Mavimbela N, Winikoff B. Two regimens of misoprostol for treatment of incomplete abortion. Obstetrics & Gynecology 2004;103(5 Pt1): 860-5.
31. Shaw, D. Misoprostol for reproductive health: Dosage recommendations. International Journal of Gynecology and Obstetrics 2007; 99:S155.

32. ACOG Committee on International Affairs. Committee Opinion: Misoprostol for postabortion care. Obstetrics & Gynecology 2009; 113(2) Part I:465-8.

Ashermans syndrome in the news: The secret syndrome leaving women infertile

2010-05-03T01:20:00.000-07:00

A recent article on Asherman’s syndrome (AS) appeared in the UK Daily mirror. It was about Sophie Blake, a TV presenter in the UK, who acquired Asherman’s syndrome as a result of two D&Cs to remove retained placenta after giving birth. It is unfortunate that her situation was not handled differently, as postpartum D&C has been reported to result in Asherman’s syndrome in 25% of cases (1). There are usually alternatives, and in some countries such as Israel, post partum D&C is no longer performed because of AS risks (2).

Toaff and Ballas, 1978
“Puerperal curettage….was discontinued in Israel after publication of Asherman’s observations*”.
*1948!!

Publicity about Asherman’s syndrome is important, and it always helps to have a public figure bring awareness to an overlooked condition. However, according to the article, the moral of the story is to seek early treatment when there is actually no evidence that fertility is more likely to be restored if treatment is sought early. Studies have shown that fertility outcomes are correlated with severity of adhesions (3), however there have been no studies on the effect of length of the condition on fertility. Sometimes damage is too great to be corrected and the uterus will rescar at every attempt to surgically remove adhesions and hormonally stimulate endometrial growth, even when early treatment was commenced. Other times, adhesions are not so severe and treatment after years will result in a live birth. Although treatment by an experienced AS specialist should always be sought, fertility outcome will be dependent most of all on the severity of initial injury (ie. D&C, intrauterine surgery with or without endometritis) which led to the scarring. When too many endometrial cells are removed to allow the endometrium to regenerate, this leads to recurrent adhesions and/or widespread fibrosis. In many cases even some of the underlying myometrium is removed. It is simple, without further progress in treatment strategies, there is nothing that can be done to replenish regenerative tissue that has been removed during curettage or other uterine surgery.

Early treatment does not guarantee success-just as late treatment does not guarantee failure

“Ideally corrective surgery should be performed within six months of the adhesions forming before they get too large”
This suggests that intrauterine adhesions continue to get worse over time, which is not true. Injury results in scarring anywhere in the body, and scarring is not progressive after a certain time point. Adhesions occur when scarring occurs internally and tissues are in direct contact with each other during the healing process. IUA formation is a normal physiological response to trauma-albeit trauma that is usually iatrogenic and should not have occurred in the first place. The consequences of this normal response are pathological because adhesions can lead to infertility, miscarriage and/or obstetric complications when they occur in the uterus. In actuality, IUA formation begins immediately after injury or corrective surgery and is complete by around 6-8 weeks according to Asherman’s syndrome specialists (unfortunately I am unable to find a reference for this, however studies where hysteroscopic followups are performed after D&C mention waiting 6-8 weeks at least). This is even supported in the article:

“I was devastated the scarring had come back so quickly,”

After 8 weeks, IUA do not continue to form/progress. Therefore, someone with stage I AS diagnosed 3 months after surgery will not go on to have stage IV 3 years later, because their adhesions have already fully formed by 8 weeks. There is one study which asserts that women who had early followup compared to late follow up hysteroscopy following adhesiolysis had less severe adhesions, and that early treatment would give a better outcome (4). However, early followup was 2-4 weeks after the initial surgery while late followup was 8-16 months. Thus adhesions may appear to be less ‘severe’ in the early followup group simply because they had not fully formed. The main advantage of early treatment (ie. before 6-8 weeks) is that it makes it easier for the doctor to dissect adhesions and not cause new ones inadvertently. However, in practical terms, it is highly unlikely that women will be diagnosed with AS within 6-8 weeks after a surgery (let alone treated), therefore it is usually applied as a treatment strategy after adhesiolysis instead of a uterine stent (5).

“It makes me seethe because if Asherman’s is caught early it’s totally treatable.”
“It’s treatable in the early stages, but it took two years for me to get a diagnosis.”

It is suggested that had she had surgery sooner, she would have possibly reversed the damage and regained her fertility. This is unlikely. Very severe adhesions tend to recur (3) inspite of surgery or hormone therapy. Early intervention will not make much of a difference because the extent of the initial damage is such that too many regenerative endometrial cells have been removed during the initial trauma.

It has been hypothesized (but not been proven) that the adhesive process can be progressive because adhesions limit uterine muscular activity thereby reducing perfusion of sex steroids to the endometrium which atrophy as the consequence (6). However, endometrial atrophy, which would lead to thin endometrium or fibrosis, is different to IUA. Most current classification systems only take adhesion type and extent into consideration, not fibrosis.

On the other hand, it is possible that someone with moderately severe adhesions which are treatable may develop fibrosis if treatment is not sought for years. Fibrosis would impact on fertility, not by causing IUA, but by limiting blood flow to an area of the uterus.

As one never knows whether their case is severe or not, by all means seek treatment with an AS specialist, but the best prognosis is severity.

Prevalence versus incidence“While the exact number of Asherman’s sufferers is not known, it’s estimated that 5% of D&Cs cause the condition – that’s about 3,000 new cases a year.”

The article confuses the estimated prevalence rate of Asherman’s syndrome (5%) with incidence rate after D&C. The prevalence of AS is 5%, meaning that roughly 1 in 20 women in the general population have AS. This does not however mean that the incidence rate of AS after a D&C is 5%. Incidence is the percentage of women who develop AS from a particular procedure, such as D&C. Studies have reported rates varying between 7.7 and 30% after D&C for miscarriage (7,8,9,10,11), and 25% from D&C for post partum retained placenta 2-4 weeks after delivery (2). The reason the incidence is higher than the prevalence is that not all women will have a miscarriage, and not all women who miscarry will have a missed or incomplete miscarriage or will be treated by D&C. Furthermore, there will be undiagnosed cases of AS (either because the woman does not desire more children or her infertility remains ‘unexplained’), and obviously not every woman in the population will undergo diagnosis for IUA. One should also remember that there are other causes of AS including other intrauterine surgery and genital tuberculosis (12) and these carry different incidence rates too.

It is important to report the correct incidence rate after a procedure such as D&C because this gives women a better idea of risks and helps her to make an informed decision before consenting to the procedure. There are almost always equally effective alternatives to D&C such as drugs or minimally invasive surgery like hysteroscopy which incur no or less damage.

Prevention: more information and accuracy needed

“Doctors are increasingly opting for less-invasive methods including suction or the use of tablets”

It’s unfortunate that the focus of the story was on preventing infertility through early treatment-which is misleading-rather than on promoting alternatives to D&C.
There is one sentence about prevention, and sadly it contains an inaccuracy as well as an omission. Suction D&C has never been proven to prevent AS, let alone reduce the incidence rates of AS:

Chapman and Chapman, 1990: (13)
“It is noteworthy that, of the 11 patients with isthmus stenosis, six of them were attributable to termination of pregnancy, of which all but one had been performed by suction curettage”

Dalton et al, 2006 (14)
“Intrauterine adhesions are a possible complication of office MVA (manual vacuum aspiration), even in the absence of sharp curettage, and should be considered when discussing treatment options for EPF (early pregnancy failure) with patients."

“After 262 office MVAs for first trimester pregnancy losses, we have identified 5 cases of IUAs…”

There is also no guarantee that your doctor will use only suction D&C, as many will use blunt or sharp instruments as well during the same procedure.

The mysterious ‘tablets’ mentioned allude to misoprostol, a prostaglandin E1 analogue which can evacuate the uterus after miscarriage, delivery or during termination, by causing uterine contractions. Referred to as medical management of miscarriage or retained placenta, or medical abortion depending on the situation where it is used, misoprostol is a non-invasive method which has been shown to prevent IUA compared to suction D&C in a clinical trial (7).

Here you can find out more about how misoprostol can prevent AS if you have a miscarriage. It can also prevent recurrence of AS in women who have a miscarriage after having had the condition.
REFERENCES

1. Toaff R, Ballas S (1978). "Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome)". Fertil. Steril. 30 (4): 379–87.

2. Jensen, P.A. and W.B. Stromme, Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol, 1972. 113(2): p. 150-7.

3. Valle RF, and Sciarra JJ (1988). "Intrauterine adhesions: Hystreoscopic diagnosis, classification, treatment and reproductive outcome". . Am J Obstet 158 (6Pt1): 1459–1470.

4. Shokeir, T.A., M. Fawzy, and M. Tatongy, The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications. Arch Gynecol Obstet, 2008. 277(5): p. 423-7.

5. Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril. 2008;90(2):409-14.

6. March CM. (1995). "Intrauterine adhesions". Obstet Gynecol Clin N Am 22: 98–103.

7. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. (2002). "Intrauterine adhesions after conservative and surgical management of spontaneous abortion". J Am Assoc Gynecol Laparosc. 9 (2): 182–185.

8. Adoni A, Palti Z, Milwidsky A, Dolberg M. (1982). "The incidence of intrauterine adhesions following spontaneous abortion". Int J Fertil. 27 (2): 117–118.

9. Golan, A., et al., Hysteroscopic findings after missed abortion. Fertil Steril, 1992. 58(3): p. 508-10.

10. Romer, T European Journal of Obstetrics & Gynecology and Reproductive Biology
Volume 57, Issue 3, December 1994, Pages 171-173

11. Friedler S, Margalioth EJ, Kafka I, Yaffe H. (1993). "Incidence of postabortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study". Hum Reprod 8 (3): 442–444.

12. Kodaman PH, Arici AA. (2007). "Intra-uterine adhesions and fertility outcome: how to optimize success?". Curr Opin Obstet Gynecol 19 (3): 207–214.

13. K Chapman and R Chapman. Asherman's syndrome: a review of the literature, and a husband and wife's 20-year world-wide experience. J R Soc Med. 1990 September; 83(9): 576–580.

14. Dalton VK, Saunders NA, Harris LH, Williams JA, Lebovic DI (2006). "Intrauterine adhesions after manual vacuum aspiration for early pregnancy failure". Fertil. Steril. 85 (6): 1823.e1–3

The DO’s and DON’T's (and maybe’s) of Managing Intrauterine Adhesions.

2010-04-21T04:28:00.000-07:00

Based on: AAGL: Practice Report: Practice Guidelines for Management of Intrauterine Synechiae, The Journal of Minimally Invasive Gynecology Vol. 17, No.1 2010.
Practice committee members:

Malcolm Munro MD, FRCS(C), FACOG
Rafaele F.Valle,MD
Jason A. Abbott, PhD,FRANZCOG,MRCOG
Angus J.M. Thompson, MRCOG
Keith B. Isaacson, MD
Adolf Gallinat, MD
Volker R. Jacobs, MD, PhD, MBA
Fred M. Howard MD
Andrew I. Sokol, MD
Linda D. Bradley, MD

Recently, the Practice Committee of the AAGL developed guidelines for the management of intrauterine adhesions (IUA), published in the Journal of Minimally Invasive Gynecology (2010). This is a welcome initiative, and long-awaited, with over one century passing since the first description of Asherman’s syndrome in the literature (1). Although these guidelines were based on studies published in peer-reviewed medical journals, there are limitations and room for more specific guidelines, as the authors themselves acknowledge, due to a lack of comparative studies and rigorous medical evidence from randomized controlled trials (RCTs). For example, studies were conducted using different surgical modalities, surgical tools, adjunctive therapies, and hormone therapy protocols. Many studies are also old and/or conducted retrospectively. One of the difficulties of studying IUA is that it is under diagnosed so that many women may not realize they have it. This results in a small sample size for studies, especially when patient treatment is spread between different centers. Additionally, the skills of the surgeon are important in influencing outcome which makes comparisons between different studies difficult. Consequently, drawing meaningful conclusions on treatment is problematic. To circumvent these shortcomings, the authors classified data based on the highest level of evidence found in the data and graded them according to a system outlined by the US Preventive Services Task Force. In most cases the evidence is based primarily on consensus and expert opinion (Level C). Hopefully trials will be forthcoming which meet today’s strict standards of clinical research, and recommendations which are stronger and more specific will result from them.

The goal of IUA management is to restore the volume and architecture of the uterine cavity and its communication with the fallopian tubes and cervical canal by removing IUA, preventing their recurrence and regenerating deficient endometrial growth.

Below is a summary of the recommendations of the article. My additional comments are in blue font.DIAGNOSISHysteroscopy is the most accurate method for diagnosis of IUA and should be chosen over HSG and SHG (although the latter are reasonable alternatives if hysteroscopy is not available).
(Grade B)

CLASSIFICATION
Although there are several classification systems, none is considered superior over the other, probably reflecting inadequacies in all current systems. (Grade C)

An accurate and universal classification system for IUA is important for enabling the comparison of studies and providing prognostic indicators of fertility outcome. (Grade B)

TREATMENT
DO's:

Only expert hysteroscopists familiar with IUA treatment should attempt to treat extensive or dense adhesions. (Level C)(Surgeons who are inexperienced may inadvertantly cause further irreparable damage).
Direct visualization of the uterus during hysteroscopic lysis of adhesions using a tool for dissection is the treatment of choice for IUA which underlies infertility, recurrent pregnancy loss, pain or other related symptoms. (Level C).

In some women expectant management may be acceptable. (Level C)
(ie. if adhesions are thin and filmy and/or cover a small surface area treatment benefits may not outweigh treatment risks).

Estrogen therapy with or without progestin may reduce reformation of IUAs. (Level B)(Estrogen therapy dose and length will depend on severity. See also Recommendations for Future Research).
MAYBE's:

Gel barriers such as hyaluronic acid and auto-cross-linked hyaluronic acid gel may reduce IUA recurrence follow surgical correction, however there is not enough data on pregnancy outcomes following their use, so should not be used without more rigorous trials. (Level A)
(Potential problems with gel barriers are that they are difficult to keep in place, become less viscous at body temperature, draining out of the uterus. See also Recommendations for Future Research).

Foley catheter or IUD should not be used routinely after corrective surgery without further data from trials supporting their benefit. This is because they may increase the risk for infection. (Level C)
(There have been reports of IUDs puncturing the uterus. Also, some doctors also believe that intrauterine pressure from balloons can hinder endometrial regeneration. However, both the Foley catheter and the Cook stent-which curiously was not mentioned in the article-have been used successfully (2)).

Supporting or refuting the use of prophylactic antibiotics before, during or after surgical adhesiolysis. (Level C)
(However, antibiotic prophylaxis should be used in the case of barriers, as a foreign object inside the uterus increases the risk of infection. See also Recommendations for Future Research).

Medications to improve blood flow to the endometrium should be used only after being supported by rigorous research. (Level C)(These include low-dose aspirin, Coenzyme Q-10, vitamin E, and Sildenafil citrate.ie. Viagra, and even herbal remedies such as raspberry leaf tea).
Prevention of complications (eg. perforation) or improved outcomes with the use of external imaging techniques or laparoscopy, however these techniques may have advantages in case perforation does occur. (Level B)(Another advantage is that laparoscopy allows the surgeon to view the pelvic cavity where there may be endometriosis (3), especially in the more severe cases where laparoscopy is often used).
DON’T's:

There is no evidence to support blind D&C or blind cervical probing in the treatment of IUA (Level C)(The authors state that D&C should not be used because it does not permit accurate diagnosis and classification. The bigger concern should be that blind curettage may cause further and irreversible damage and is the underlying cause of most IUA (4)).
Copper (inflammatory), progestin-releasing (suppress endometrium) and T-shaped IUDs (small surface area) should not be used after adhesiolysis. (Level C)

Laparotomy should be considered as a last resort (eg. when hysteroscopic surgery fails) (Level C)
Electrosurgery/laser: There is some disagreement over which tools are best suited for adhesiolysis. Some surgeons prefer to use microscissors and stress that thermal energy tools offer no advantage over scissor dissection with regards to either speed or hemostasis (2). Furthermore, these modalities (including resectoscope, Nd:YAG laser, monopolar/bipolar electrode) deliver energy that can cause injury to surrounding tissues and therefore some believe it is prudent to avoid them for the treatment of IUA (2). Indeed, electrosurgical tools are normally used for endometrial ablation which burns away endometrium and intentionally induces Asherman’s syndrome in women with excessive bleeding. However, other doctors claim that in experienced hands these tools are safe. Which ever the case, this is an issue which probably needs to be further examined to refute any safety concerns.POSTOPERATIVE ASSESSMENT:Follow-up evaluation of the uterine cavity is recommended after treatment of IUA. (Level B).(This is an important factor in determining outcome as adhesions may reform and further surgery may be needed. If a pregnancy occurs in a uterus with IUA, there is a higher likelihood of infertility, miscarriage and pregnancy complications (5). Patients should undergo either HSG, SHG, or in-office hysteroscopy (with as narrow cervical dilation as possible) in order to verify the uterine cavity is free of adhesions. A mid-cycle scan should also be used to measure the endometrial thickness at ovulation. Ideally this should measure 7-8 mm for implantation to be successful. Some women with corrected IUA have thin endometrium which may require hormone treatment to thicken. If adhesions blocking the ostium are present, natural conception is not possible and IVF will be recommended).
RECOMMENDATIONS FOR FUTURE RESEARCH:

1. Prospective trials on the effect of intraoperative and postoperative antibiotic prophylaxis on surgical and fertility outcome.(I don’t know of doctors who do not use antibiotics during or after operative hysteroscopy. Also, the article states: “…it has been proposed that infection may be a primary cause of IUAs…” Antibiotic prophylaxis is wise for preventing infections whether or not they lead to IUA. However, at this stage, there is actually no evidence to support that most IUAs result from infection, whether frank or subclinical. In fact, there is limited evidence to the contrary (6,7). Also see The subclinical infection myth).2. Prospective trials of adjunctive hormone therapy efficacy with respect to surgical and fertility outcome.(The optimum dosage of estrogen (E2 with or without progestin, P4) and length of treatment have not been studied. Progynova (Estradiol valerate) a synthetic version of a naturally occurring estrogen or Premarin, a combination of around 11 conjugated equine estrogens extracted from pregnant mare urine, are usually used. These compounds have not been compared to each other in trials).
3. Prospective trials of barrier method (IUD, Foley catheter and gel adhesion barriers) efficacy with respect to surgical and fertility outcome.
(Presumably the Cook stent, which is used by some doctors (2), should also be included in trials. Regarding the use of gel adhesion barriers which are potentially the least invasive and risky type of barrier, one questions why there is not more research on their use to prevent IUA from occurring in the first place. If gel barriers are therapeutic for reducing IUA reformation after hysteroscopic adhesiolysis perhaps their use after D&C and other primary intrauterine surgery would reduce the incidence of IUA. There is so far only one study and results show only 10% of women who received Seprafilm after curettage for miscarriage developed IUA vs 50% amongst controls (8)).
4. Stem cells for future treatment: As discussed in a previous blog, some cases are currently not treatable because the extent of damage to the basal endometrium (sometimes curettage even removes part of the underlying myometrium) from which the functional layer regenerates. This leads to persistently thin endometrium or reformation of IUA after corrective surgery and excludes the possibility of carrying a pregnancy. Surrogacy is the only option in such cases. However Dr Chaitanya Nagori and Dr Sonal Panchal of Nagori Institute of Infertility in India claim to have used stem cell technology to thicken the endometrium in women who underwent excessive ‘cleaning’ up of the uterus (ie. a euphemism for D&C), although they do not mention the presence of IUA. The process involved isolating adult stem cells from the bone marrow of the patient, transplanting the purified stem cells into the patient’s uterine cavity under transvaginal sonographic guidance, and stimulating the production of endometrial angiogenic stem cells by administering estrogen before IVF treatment. Using this technique they reportedly were able to increase ‘negligible’ endometrial growth to 6mm three months after the transfer and estrogen therapy. Although they assert that IVF drugs alone did not increase the patient’s endometrial measurement, it remains to be proven whether this effect is due to the post-transplant estrogen treatment or from the stem cell therapy. Nonetheless, the concept of using stem cells for tissue repair in the uterus is intriguing, and possibly the best hope in future for very severe cases of IUA (uterine transplant is another future possibility). This could be more convincing if recurrent IUA was prevented with stem cells following hysteroscopic adhesiolysis. Definitive proof would be obtained if the stem cells and their progeny were biochemically labeled so as to be identifiable from the original tissue. This could be done in animal studies, for example. The great advantage of stem cells is that they have the capacity to differentiate into a range of cells that are necessary to rebuild a normal uterus, from myometrium and endometrium to the blood vessels which supply them with blood and hormones. Furthermore, as the stem cells are derived from the patient’s own bone marrow ie. autologous adult stem cells, there is no risk of either rejection or ethical controversy (as with embryonic stem cells). Unfortunately at this stage there are no published studies on this treatment.
REFERENCES

1. Fritsch H, Ein Fall von volligem Schwaund der Gebormutterhohle nach Auskratzung. Zentralbl Gynaekol 1894; 18:1337-1342.

2. March, CM; Miller, CE. Hysteroscopic lysis of intrauterine adhesions. Ob.Gyn. News 2006; 41(23):36-37. Abstract

3. Palter. SF, High Rates of Endometriosis in Patients With Intrauterine Synechiae (Asherman's Syndrome). Fertility and Sterility 2005; 86 (null):S471-S471. Link

4. Palter S, Spyrou P. Asherman’s syndrome: Etiologic factors, patterns of pregnancy loss, and treatment results. Results from an international registry. Fertility and Sterility 2003; 80(3):36-7. Link

5. March CM. Intrauterine adhesions. Obstet Gynecol Clin N Am 1995;22(3):491-505. Abstract

6. Jensen, P.A. and Stromme, W.B. Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol 1972; 113: 150–4.

7. Polishuk, SO Anteby and D Weinstein, Puerperal endometritis and intrauterine adhesions, Int Surg 1975;60:418–420. Abstract

8. Tsapanos VS, Stathopoulou LP, Papathanassopoulou VS, Tzingounis VA. The role of Seprafilm bioresorbable membrane in the prevention and therapy of endometrial synechiae. Biomed Material Res. 2002;63:10-14. Abstract

Related Links:Good news: Grow endometrium by stem cells. (Times of India)

Recommendation Grading:
Level A: Recommendations are based on good and consistent scientific evidence.
Level B: Recommendations are based on limited or incomsistent scientific evidence.
Level C: Recommendations are based primarily on consensus and expert opinion.

Complications in post Ashermans syndrome Pregnancies (Part II)

2010-04-08T20:20:00.000-07:00

Continued from Part I
Click here for pregnancies in the presence of intrauterine adhesions (synechiae).

Cervical incompetence/insufficiency
Cervical incompetence or insufficiency is when the involuntary muscle of the cervix is structurally weak and unable to sustain the weight of the growing fetus. Effacement (shortening and thinning of the cervical walls) occurs prematurely and in the absence of contractions, resulting in bulging of the amniotic membranes, leading to rupture and premature birth. This often occurs during the second trimester before the fetus is able to survive outside the uterus. Cervical incompetence is associated with AS although it is thought to result not from having had scarring but rather as a consequence of frequent dilations of the cervix during procedures such as D&C and hysteroscopy- which itself is used to correct AS. The less widely and less often the cervix is dilated, the better, as frequent dilations of over 8mm put women at an increased risk of cervical incompetence in subsequent pregnancies. In order to monitor for CI, transvaginal ultrasound measurements of the cervix should be undertaken beginning during second trimester at around 16 weeks. Women cannot sense or predict its occurrence and it is also difficult for Obgyns to predict and prevent even with close monitoring as it may have a very sudden onset. It is thought that the increased rate of second trimester pregnancy loss in women with past AS is due to CI. In one study, 3 of 15 pregnancies (20%) were complicated with second trimester fetal loss (9) probably caused by CI. Cervical incompetence may be managed with bed rest and cervical cerclage (9). Cerclage is a cervical stitch sewn to prevent the cervix from opening and it may be placed vaginally or abdominally. Cerclage is a controversial obstetric procedure and studies are continuing to investigate how effective it is. Therapeutic cerclage is used when the cervix is showing signs that it is dangerously shortened ( under 2cm) or funneling, however it is not always effective at this stage and pregnancy loss may still occur. ‘Prophylactic’ cerclages are usually indicated in women with a past history of CI ie. whom have already experienced CI in a previous pregnancy. Because cerclage itself carries the risk of infection, inflammation, and rupture of membranes, it is not routinely recommended in women with past AS. Instead, monitoring of cervical length and therapeutic cerclage if needed is recommended. Interestingly, a study on women with short cervix during pregnancy (under 1.5 cm measured around 22 weeks of gestation) found that progesterone supplementation reduced spontaneous delivery before 34 weeks compared to placebo (25).

Possibilities for prevention of CI include the reduction/replacement of D&C with drugs or expectant management, the use of smaller instruments necessitating less dilation during hysteroscopic surgery (11), and the use of misoprostol for cervical priming (instead of mechanical force for dilation).

IUGR
IUGR (intrauterine growth restriction, or fetal growth restriction) refers to a condition where the fetus is smaller than expected for its gestational age (less than the 10th percentile). Newborns with IUGR are termed small for gestational age (SGA). IUGR is caused by a reduction in oxygen and nutrients delivered to the growing fetus due to a lack of adequate blood flow to the placenta. As the endometrium of women with past AS may be damaged, blood flow to the uterus and placenta may be suboptimal, leading to poor placenta perfusion. There are also other causes of IUGR including high blood pressure, diabetes, cigarette smoking, substance abuse, malnutrition, and kidney disease. A lack of oxygen reduces the fetal heart rate and puts the life of the fetus at great risk. IUGR may be early or late-onset, however the earlier the onset, the greater the risks. Risks include premature delivery, stillbirth, and long-term growth problems in children. Diagnosis is made by ultrasound measurements of the fetal size and fetal weight estimation. Doppler flow studies can be used in conjunction with ultrasound to measure the quantity and velocity of blood flow in the fetal brain and umbilical cord. IUGR cannot be predicted or reversed, however its possible presence should be closely monitored in women with a past history of AS. Placenta previa, another potential complication of AS, is also associated with IUGR. Bed rest and increased maternal nutrition may help, as may aspirin therapy to improve blood flow. If IUGR is threatening the well being of the fetus, early delivery may be necessary ie. via C-section. Yasmin and Adeghe (26) report a case of early-onset symmetrical fetal growth restriction in a patient with treated AS. At 20 weeks the fetal measurements corresponded with 18 weeks. A detailed scan at 29 weeks revealed measurements under the 3rd centile with oligohydroamnios and uterine artery flow suggested poor placental perfusion. The baby was delivered via C-section at 29 weeks. The placenta was calcified and partially adherent to the uterine wall. Interestingly, there are no other published studies mentioning IUGR as a complication of AS, although one would not expect it to be a rare consequence. It is possible that some cases of IUGR in women with a history of AS have been attributed to other causes, as there are potentially many confounding risk factors.

Premature Birth
Premature or preterm birth is defined as spontaneous labour followed by birth before 37 weeks of gestation. The duration of most pregnancies is around 40 weeks, with babies born between 37 and 42 weeks considered full term. There are several factors which are linked to prematurity which makes it difficult to always know the exact cause. Certain life style factors (smoking, drinking/drugs, stress etc.), and medical conditions (diabetes, hypertension, infections, underweight or obesity etc.) are associated with prematurity. Certain women are also predisposed to premature delivery: those with twin/triplet ie. multiple pregnancies, women with previous premature birth, and women with uterine or cervical abnormalities (congenital or acquired). The overall rate of premature birth in the US is 12.8% (27). However, in women with a past history of AS rates of premature delivery from 17.912-50% have been reported (9, 10, 28, 29, 30) In some cases, but not all, prematurity occurred in conjunction with abnormal placentation (eg. adherant placenta, placenta accrete and/or previa etc). Other studies have linked prematurity to induced surgical (ie. D&C) abortion but not to medical abortion, which supports a correlation between endometrial trauma and premature delivery. Note that most terminations are now carried out medically (however, unfortunately, standard management of missed or incomplete miscarriage continues to be D&C in many countries, more for cultural reasons rather than medical ones).

Premature birth is the leading cause of neonatal mortality and morbidity. Infants born prematurely are at an increased risk for both short and long-term health complications. The earlier the birth, the higher the risk for health complications. Complications are more likely to occur and with more severity in infants born before 32 weeks than after. As medical care continues to improve, infants are surviving at earlier gestational ages, however the current limit for viability is generally around 24 weeks. Potential health complications of ‘premies’ include:

-neurological problems (eg. cerebral palsy, apnea of prematurity, retinopathy of prematurity),
-respiratory problems (eg. respiratory distress syndrome),

-cardiovascular problems (eg. patent ductus arteriosus),

-gastrointestinal/metabolic disorders (eg. rickets, inguinal hernia),

-hematological conditions (eg. jaundice, anemia) and

-infections (eg. sepsis, UTI).

Pregnancy loss due to cervical insufficiency (CI), which occurs without labour and has a different etiology, is not considered premature birth. However, cervical cerclage and progesterone supplementation may be used to prevent/manage both conditions. Progesterone derivatives have been shown to reduce the frequency of premature delivery both in women with previous premature delivery (31) and women with short cervix (25).

Uterine rupture

The most common factor predisposing to uterine rupture is a uterine scar. This may be caused by D&C, C-section or hysteroscopic surgery (eg. myomectomy, reparation of congenital uterine malformations etc.). Not surprisingly, there have been several reports of uterine rupture among women with a past history of AS (7, 32, 33, 34, 35). In most of these cases, prior uterine perforation occurred during hysteroscopic adhesiolysis , however in rupture has also been reported in women without prior perforation (33). The thinning, weakened and increased fibrosis of the myometrium undoubtedly predispose to rupture of the uterus (2, 36).

This long list of potentially serious complications supports the recommendation that women who have had AS, even after correction, should be carefully monitored by a high risk Obstetrician, and preferably one who is aware of the reported complications in order to optimize the well-being of the pregnancy and the patient. These serious complications also add to a growing list of reasons why prevention of AS from occurring is more compelling than relying solely on treatment of the condition. In all of these complications endometrial damage is the common denominator which has the potential to affect placental attachment, uterine/cervical strength and/or placental perfusion. Finally, it is interesting to note that while complications and sequelae readily attributed to C-sections are being closely monitored and the number of C-sections is being audited by hospitals and organizations such as the WHO with a view to reducing their frequency (37), the same is not being done for D&C. Why not? A reduction in D&C rates would lead to fewer obstetric complications necessitating C-sections. Furthermore, the public health costs of diagnosis, surgical correction, treatment for infertility and obstetric complications resulting from D&C should be reason enough to reduce the reliance on this procedure-not to mention the impact on women's health and well-being.

REFERENCES
(numbering continued from Part I)

2.Yu, D, Wong, YM, Cheong, Y, Xia, E, and Li, TC. Asherman syndrome--one
century later. Fertil Steril 2008;89(4):759-79. Abstract

9. Capella-Allouc S, Morsad F, Rongieres-Bertrand C, et al. (1999). "Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility". Hum Reprod 14 (5): 1230–1233. Abstract11. Fernandez H, Al Najjar F, Chauvenaud-Lambling et al. (2006). "Fertility after treatment of Asherman's syndrome stage 3 and 4". J Minim Invasive Gynecol 13 (5): 398–402. Link to complete article

25. Fonseca EB, Celik E, Parra M, Singh M, Nicolaides KH; Fetal Medicine Foundation Second Trimester Screening Group. Progesterone and the Risk of Preterm Birth Among Women with a Short Cervix. New England Journal of Medicine, 2007;375:(5)2, 2007; 462-469. Link to pdf
26. Yasmin H, Adeghe JH. Severe early-onset intrauterine growth restriction (IUGR) in a woman with Asherman's syndrome. J Obstet Gynaecol. 2004 ;24(3):312-4. Abstract

27. Martin, J.A., et al. Births: Final Data for 2006. National Vital Statistics Reports, volume 57, number 7, January 7, 2008.

28. Yu D, Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman’s syndrome. Fertil Steril 2007; 89(3):715-22. Abstract.
29. P.McComb, B.Wagner. Simplified therapy for Asherman"s syndrome. Fertility and Sterility; 68(6):1047-1050. Abstract
30. Protopapas A, Shushan A, Magos A. Myometrial scoring: a new technique for the management of severe Asherman's syndrome. 1998;69(5):860-4.Abstract
31. Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of Recurrent Preterm Delivery by 17 Alpha-Hydroxyprogesterone Caproate. New England Journal of Medicine, 2003;348(24):2379-85. Link to pdf
32. Deaton JL, Maier D, Andreoli J Jr. Spontaneous uterine rupture during pregnancy after treatment of Asherman's syndrome. Am J Obstet Gynecol. 1989;160(5 Pt 1):1053-4. Abstract

33. Shiau CS, Hsieh CC, Chiang CH, Hsieh TT, Chang MY, Chang Gung. Intrapartum spontaneous uterine rupture following uncomplicated resectoscopic treatment of Asherman's syndrome. Med J. 2005 Feb;28(2):123-7. Abstract with link to free article

34. Gürgan T, Yarali H, Urman B, Dagli V, Dogan L. Uterine rupture following hysteroscopic lysis of synechiae due to tuberculosis and uterine perforation. Hum Reprod. 1996;11(2):291-3. Abstract35. Hulka JF.Uterine rupture after treatment of Asherman's syndrome. Am J Obstet Gynecol. 1990 May;162(5):1352-3.
36. Felmus LB, Pedowitz P, Nassberg S. Spontaneous rupture of the apparently normal uterus during pregnancy. A review. Obstet Gynecol Surv 1953;8(2):155-172.

37. Nils Chaillet, Eric Dubé, Marylène Dugas, Diane Francoeur, Johanne Dubé, Sonia Gagnon, Lucie Poitras, Alexandre Dumont. Identifying barriers and facilitators towards implementing guidelines to reduce caesarean section rates in Quebec. Bulletin of the World Health Organisation 2007;85(10):733-820. Complete article

Complications in post AS Pregnancies (Part I)

2010-03-31T04:33:00.000-07:00

Over the decades it has become apparent that women with a past history of Asherman’s syndrome (AS) are at an increased risk for serious obstetric complications in pregnancies that occur after successful treatment. While it was already known that those who were able to conceive without surgical correction had complicated pregnancies, it has also emerged that even after treatment, patients ran a higher risk for certain obstetric complications. Presumably this is due to the fact that even if intrauterine adhesions have been removed, acquired defects in endometrial function may persist. For example, the most severe form of Asherman’s syndrome is known as ‘unstuck’ Asherman’s syndrome where there are no intrauterine adhesions, but instead the endometrium is completely replaced by scar (connective) tissue (fibrosed, or sclerotic). Varying degrees of fibrosis may be still present in the ‘corrected’ uterus, especially if adhesions were dense and fibrous with no visible endometrium covering them on hysteroscopic view. Hormone therapy attempts to restore endometrial growth and function, however damage may be too extensive in some areas.

Although there have been numerous studies on pregnancy complications following treatment, many Obstetricians are not well informed about either the nature of these risks or of their prevalence. Awareness of these risks would allow doctors and their teams to be prepared for emergency situations which may arise and better manage the complications, safe-guarding the lives and health of both patients and their offspring.

It should be emphasized that of critical importance is that the uterine cavity is clear of adhesions (or that adhesions are minimal (ie. less than around 10% of the uterine cavity and filmy) before a patient is given the all clear to try to conceive. Thus, corrective surgery and hormonal treatment should be followed up with either HSG, SHG, or in-office/diagnostic hysteroscopy. Adhesions, especially severe ones, are known to recur and in this case further surgery is often required. Also, adhesions are preferably dissected using a mechanical method such as microscissors instead of methods which utilize thermal energy (monpolar knife, Nd:YAG laser) as the latter can necrose endometrial tissue (1) and are used in endometrial ablation procedures to treat women with excessive uterine bleeding. However, there is still the potential for complications because an adhesion-free uterus does not equate with a perfectly functioning endometrium (presumably the same reasoning applies to the correlation between AS severity and live birth outcomes). It may be thinner, irregular in thickness and/or there may be regions of fibrosis where blood flow is less than optimal and the endometrium is unresponsive to hormones.

The reported obstetric complications in women with corrected AS include:
-Miscarriage (?)
-Abnormal placentation such as:
placenta accreta
placenta increta
placenta percreta
placenta previa
uterine sacculation
-Cervical incompetency
-IUGR (intrauterine growth retardation)
-Premature birth
-Uterine rupture
Note: There is some evidence that preeclampsia may also be another complication after AS.

Miscarriages
Although to date there is not any clear indication of an increased incidence of miscarriage among women with corrected AS, it is not difficult to imagine that the same underlying causes of obstetric complications often encountered in second or third trimester could give rise to miscarriages when encountered at an earlier stage of pregnancy. For example, poor placental perfusion is an underlying cause of IUGR. However, if the embryo by chance implanted in an area where there was fibrosis or where the endometrium was particularly thin, this could also have an effect on blood flow to the area surrounding the gestational sac, leading to a first trimester miscarriage. (Those interested in the link between miscarriage and uterine blood flow should refer to: Burton and Jauniaux Placental oxidative stress: from miscarriage to preeclampsia. J Soc Gynecol Investig 2004,11:342-52.) In a review of published obstetric outcomes, Yu et al (2) observe that the rate of miscarriages in women post AS (20%) does not differ from those of the general population (20-25%). However, the rate of 20-25% represents an average of women of all ages (the rate is 14% in women under 35 and 40% among women over 40 (3)) while most of the pregnancies reported in the literature among AS patients appear to have occurred in women under 35. Thus it is possible that the miscarriage rate is actually higher if compared to the expected rate for their corresponding age group.

Abormal Placentation

Abnormal placentation is when the placenta has either implanted too low in the uterus (placenta previa) or has attached too deeply and is described as ‘morbidly adherent’. Placenta accreta and its more severe variants, placenta increta and placenta percreta, occur when the placenta has implanted too deeply, causing problems with placental detachment at delivery. These conditions arise when there is a defect in the decidua basalis allowing the anchoring villi to adhere in varying depths in the uterine wall or even beyond. Placenta increta is characterized by a total or partial absence of the decidua basalis and imperfect development of the fibrinoid layer. The myometrium is penetrated in varying depths in placenta increta. Placenta percreta is the most severe of these conditions where the placenta invades the entire myometrium sometimes even extending into the adjacent bladder or bowels. There are case reports and studies providing evidence on the correlation between placenta accreta (4,5,6,7,8,9,10,11,12), increta (7, 13) and previa (6,7) and a history of AS.

The incidence of these abnormalities is very low in the general population, 1 in 2500-7000, however among women with a history of AS it has been reported to affect 5%-31% of pregnancies (6,7, 8,9,11), a significant increase. As the basal endometrium has been damaged in women who have had Asherman’s syndrome (or a history of curettage) it is not surprising that this complication has been reported. What is surprising is that there are still many Obstetricians who are unaware of the association between Asherman’s syndrome (or D&C) and abnormally invasive placenta. Cesarean section is thought to be the most common cause of placenta accreta, however whether studies on the correlation took other factors such as prior intrauterine surgeries (D&C being the next most common gynecological surgery, but also hysteroscopic removal of myomas etc) into consideration is unclear. Another risk factor for accreta is suberosal uterine myomas (placental invasion into retroplacental or intraplacental fibroids can occur) (12). Another risk is smoking, while indirect risk factors include maternal age older than 35 years and elevated alpha-fetoprotein levels (12).

Often, it is difficult to predict abnormally invasive placenta in a pregnancy from diagnostic tools and the discovery is made at delivery. Thus ObGyns must be aware of a history of scarring in the uterus, not just from C-section but also from D&C, and be prepared for such serious complications to avoid maternal and infant morbidity and mortality. Sonography remains the primary diagnostic tool for detecting abnormally invasive placenta, however there are reports that MRI is superior, provided skilled interpretation is available.

The consequence of these complications during delivery is serious, with massive hemorrhage a major complication. Placenta accreta accounts for 7% of maternal mortality while morbidity includes massive transfusions, uroglogic injury, and fistula formation (12). Hysterectomy is the usual treatment of choice, however other options include uterine artery embolization (UAE)* and conservative management once the patient’s bleeding has been stabilized (14). The latter option allows fertility to be preserved by avoiding hysterectomy and preventing potential AS from a D&C. Note that D&C is sometimes performed in case of retained placenta, however this may lead to (or exacerbate AS) as has been reported to occur in 25% of women up to 4 weeks after delivery (15). In conservative management, prophylactic antibiotics are administered with ultrasound supervision. If the retained tissue is not expelled naturally after a period of time, it can be removed hysteroscopically (16).

Invasive placentation may also complicate first or second trimester pregnancy loss, causing heavy post D&C hemorrhage (17, 18, 19). It therefore appears that once the endometrium is damaged, a vicious cycle of complications can ensue. It would be interesting to conduct a comparative study on the incidence of RPOC in women with and without prior D&C/intrauterine surgery.

Unfortunately there is no way to prevent abnormal placentation in women with past AS. Prevention of AS through the use of drugs or hysteroscopy for RPOC following incomplete/missed miscarriage (2,20, 21) or delivery (16, 22) instead of blind D&C may prevent or at least reduce the severity of abnormal placentation. In a review of placenta accreta of Fox (23) from 1945-1969, 30.2% of all cases occurred in women who previously underwent uterine curettage. Although this review was carried out when C-sections were infrequent, D&C continues to be one of the most commonly performed procedures and it is not improbable that some cases of accreta which are attributed to C-section may actually have been caused by a prior D&C undergone by the patient.

*Note: uterine artery embolization may permanently reduce blood flow to uterus and lead to infertility and/or other complications.

Placenta previa
In most healthy pregnancies, the placenta attaches in the upper segment of the uterus (either at the posterior, anterior, or lateral walls of the uterus), also known as the fundus. Placenta previa is when the placenta attaches too low in the cervix, partially or completely covering the cervix. Most cases correct themselves as the uterus grows, however in about 0.5% of pregnancies, previa persists. It can occur alone or in combination with placenta accreta, increta or percreta. It may happen because other parts of the endometrium are damaged and unfit for implantation, or conversely because the endometrium in that area is thinner and it is therefore easier for the embryo to implant. Although C-section is a widely known cause, there is less emphasis and awareness about scarring from D&C as an important underlying cause. Placenta previa can be diagnosed via ultrasound, usually becoming apparent some time after 20 weeks of gestation (ie. at the time of the anatomy scan). Painless bleeding after 20 weeks is a symptom. As the placenta is partially or totally covering the cervix, this impedes vaginal delivery and C-section must be carried out instead. Around 1 in 200 pregnancies are affected, and presumably this incidence is higher in women with past AS. As with invasive placenta, previa can lead to hemorrhage at delivery, premature labour or delivery, and maternal or infant death. Once again, prevention is not possible in those with scarred/damaged uteri, however prevention of intrauterine scarring through reduction or replacement of D&C is a possibility.

Uterine sacculation

A sacculation or diverticulum of the pregnant uterus is a sac that is contiguous with the myometrium and opening into the uterine cavity and bearing no anatomic relationship to the cornual structures. There is at least one report of uterine sacculation occurring in a study of patients treated for AS (7). The sacculation occurred in a patient who developed minimal adhesions after an intrauterine device perforated the uterus and was removed laparascopically. It is thought to result from trauma to the myometrium secondary to injury, usually from curettage (24). Uterine sacculation predisposes to fetal malpresentation, increased fetal morbidity and mortality, abnormal placentation, uterine rupture, and postpartum hemorrhage.

Part II: Cervical incompetence, IUGR, premature birth, uterine rupture
See Part IIFor information on pregnancies where adhesions (synechiae) are present, please also see:
Effect of Asherman's syndrome on infant health.

Complete article

10. Zikopoulos, KA, Kolibianakis, EM, Platteau, P, de Munck, L, Tournaye, H,
Devroey, P et al. Live delivery rates in subfertile women with Asherman's
syndrome after hysteroscopic adhesiolysis using the resectoscope or the Versapoint
system. Reprod Biomed Online 2004;8(6):720-5. Abstract
11. Fernandez H, Al Najjar F, Chauvenaud-Lambling et al. (2006). "Fertility after treatment of Asherman's syndrome stage 3 and 4". J Minim Invasive Gynecol 13 (5): 398–402.. doi:10.1016/j.jmig.2006.04.013. Link to complete article.

12. Placenta accreta: An association with fibroids and Asherman syndrome. Al-Serehi A, Mhoyan A, Brown M, Benirschke K, Hull A, Pretorius D. J Ultrasound Med 2008;27:1623-28. Abstract

13. Feng ZC, Huang YL, Sun JF, Yang BY, Xue BR, Zhuang LQ. Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesion. Clinical analysis of 70 patients. Chin Med J (Engl). 1989 Jul;102(7):553-8. Abstract

14.Kayem G, Davy C, Goffinet F, Thomas C, Clément D, Cabrol D. Conservative versus extirpative management in cases of placenta accreta. Obstet Gynecol. 2004 Sep;104(3):531-6. Abstract

15.Eriksen, J and Kaestel, C. The incidence of uterine atresia after post-partum
curettage. A follow-up examination of 141 patients. Dan Med Bull 1960;7:50-1. Abstract
16. Goldenberg M, Schiff E, Achiron R, Lipitz S, Mashiach S. Managing residual trophoblastic tissue; Hysteroscopy for directing curettage. J Reprod Med. 1997;42(1):26-8. Abstract

17. Liu X, Fan G, Jin Z, Yang N, Jiang Y, Gai M, Guo L, Wang Y, Lang J. Lower uterine segment pregnancy with placenta increta complicating first trimester induced abortion: diagnosis and conservative management. Chin Med J. 2003;116:695–698. Abstract

18. Ecker JL, Sorem KA, Soodak L, Roberts DJ, Safon LE, Osathanondh R. Placenta increta complicating a first-trimester abortion. A case report. J Reprod Med. 1992;37:893–895. Abstract

19. Harden MA, Walters MD, Valente PT. Postabortal hemorrhage due to placenta increta: a case report. Obstet Gynecol. 1990;75:523–526. Abstract

20. Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. (2002). "Intrauterine adhesions after conservative and surgical management of spontaneous abortion". J Am Assoc Gynecol Laparosc. 9 (2): 182–185. doi:10.1016/S1074-3804(05)60129-6. Abstract

21. Friedler S, Margalioth EJ, Kafka I, Yaffe H. (1993). "Incidence of postabortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study". Hum Reprod 8 (3): 442–444. Abstract

22. Li, YT, Yin, CS, and Chen, FM. Rectal administration of misoprostol for the
management of retained placenta--a preliminary report. Zhonghua Yi Xue Za Zhi
(Taipei) 2001;64(12):721-4. Abstract

23. Fox, H. Placenta accreta, 1945-1969. Obstet Gynecol Surv. 1972; 27:475-90. Link to a related article

24. Hess OW. Diverticulum of the pregnant uterus. Am J Obstet Gynecol 1950;59:391-7.

How AS causes infertility or miscarriages

2010-02-19T02:59:00.000-08:00

Asherman’s syndrome (AS) can lead infertility in a number of ways. No two cases are identical and it can manifest as infertility according to how and which parts of the reproductive anatomy is affected. AS is characterized by intrauterine adhesions (IUA) and/or fibrosis (non-functional scar tissue).

Infertility may be caused by adhesions occluding the tubal ostia, uterine cavity, or the cervix, thereby interfering with the migration of sperm or implantation of the embryo (1). The presence of defective endometrium in the fundus and ostia which are partially obliterated by the adhesions may also predispose women to tubal and cervical pregnancies (2,3). Partial obstruction of tubes can lead to pregnancy complications such as ectopic pregnancy because the fertilized egg may be physically impeded from migrating to the uterus for implantation. If ostial obstruction is so extensive that it cannot be corrected through hysteroscopic adhesiolysis, in vitro fertilization is the only possibility for a biological offspring (providing that the rest of the uterus is functional and adhesion free). Cervical pregnancy (another form of ectopic pregnancy) may occur if the embryo implants in the cervix. Adhesions involving the cervix may result in the cervix being closed (outlet obstruction). This obviously prevents the sperm from encountering the egg. It has also been noted that in women with outlet obstruction due to adhesions blocking the lower uterus or cervix, endometrial measures are thinner than in women where adhesions are limited to the upper uterus (4). It is thought that the underlying cause of this is a feedback loop to prevent haematometra from occurring. Haematometra is the formation of a large clot of blood from trapped menstrual debris and it very rarely occurs in the former subgroup of women.

Another possible way Asherman’s syndrome can result in infertility is by causing endometriosis. Some authors have noted that women with extensive adhesions either in the uterus or cervix, blocking menstrual flow, later develop endometriosis (5). This was discovered because laparoscopic (keyhole) surgery is sometimes carried out at the same time as hysteroscopy when performing adhesiolysis of IUA. Laparoscopy helps to prevent uterine perforation in severe cases where it may be difficult to judge the limits of the uterine cavity. Endometriosis is the growth of endometrial lining outside of the uterus. It can occur anywhere in the body, though most commonly occurs in the abdomen. Although the cause(s) of endometriosis remain unknown, one of the theories put forth by John A. Sampson is known as the theory of retrograde menstruation. It speculates that a back flow of blood and debris through the fallopian tubes and into the abdomen enables its implantation to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as endometriosis. (As an aside to those who practice yoga, this is why inverted positions such as headstands are avoided during menstruation). Endometriosis itself can lead to infertility by causing pelvic adhesions (Note: not to be confused with intrauterine adhesions which occur INSIDE the uterus). Pelvic adhesions (or extrauterine adhesions) can twist and distort the fallopian tubes and prevent fertilization or implantation.

Many women who have had Asherman’s syndrome develop a thin endometrium even after surgical correction and hormonal therapy to stimulate endometrial regeneration. An optimal thickness of the endometrium (>8mm) is considered to be one of the prerequisites for successful implantation of the embryo. Thin endometrium can be caused by either too much of the endometrium having been removed during D&C (or other uterine surgery) or cervical obstruction (as described above). A thin endometrium may be unresponsive to hormones (6) and may lead to infertility in the form of implantation failure or early miscarriages known as ‘chemical pregnancies’ due to a lack of blood supply and poor placental perfusion. Thin endometrium can also occur in women who have had D&Cs, even if they did not develop Asherman’s syndrome. In fact, a recent study found that the endometrium of women is thinner for about 6 months after a D&C (7). A recent study suggests that treatment with tocopherol (ie. vitamin E) and pentoxifylline may help to thicken the endometrium (8), improving implantation. Of course IUA must be removed before pregnancy can be attempted.

The exact mechanisms by which IUA predispose to miscarriages are unknown, however, it is suspected that constrictions of the uterine cavity by adhesions, lack of adequate functional endometrium to support implantation and defective vascularisation of the residual endometrial tissue due to fibrosis may account for repeated pregnancy loss (9). If an embryo implants in an adhesion or a fibrotic region, it will not grow successfully because it will not have an adequate blood supply, essential for providing the growing embryo with oxygen and nutrients. This can lead to miscarriage. Interestingly, this is analogous to the situation where women with Mullerian malformations such as septate uterus often undergo miscarriage when the embryo implants in the septum (10). If IUAs obstruct the openings of one or both of the fallopian tubes (known as ostia) this prevents the sperm from fertilizing the egg (which normally happens in the fallopian tubes after ovulation).

There is another potential cause of second trimester miscarriage which has been often reported in women with a past history of Asherman’s syndrome: cervical incompetence, also known and cervical insufficiency, however, I will write about this under a future blog topic, post-Asherman’s syndrome obstetric complications, since these miscarriages are not due to adhesions or fibrosis per se but to previous dilations of the cervix during surgeries.

As a consequence of the above, many women who have untreated Asherman’s syndrome are either unable to conceive, or suffer from repeated miscarriages. However, depending on the location, extent and severity of IUA/fibrosis, patients may conceive and carry a pregnancy without treatment. This is not recommended and is usually a chance finding on ultrasound when an adhesion or synechia is detected. There have been isolated case reports of successful and uncomplicated pregnancies in the presence of IUA (11). In the best case scenario, the adhesions are minimal and thin, stretching with the pregnancy such that it does not impinge on the growth of the fetus or uterus. However, women are strongly advised to use contraception to avoid pregnancy until surgical correction of adhesions to avoid pregnancy complications. In women who conceive without removal of adhesions, the reproductive outcome is usually poor: in one well known study, it was reported that of the 46% of patients with untreated IUA who conceived, 40% of the pregnancies ended in spontaneous miscarriage, 12% of which were ectopic. Of the viable pregnancies, 23% delivered prematurely and 13% had placenta accreta with only 53% delivering viable infants (12). Obviously, the more severe the classification of AS, the more likely complications are to occur if a pregnancy occurs. On the other hand, pregnancy itself is probably less likely to occur in more severe cases. Note that these complications may also occur in women after treatment of Asherman’s syndrome, however not as frequently. This will be covered in a future blog.

The moral of the story is: get treated by a trusted Asherman’s specialist if you have Asherman’s syndrome and make sure the uterine cavity is clear (via a follow up hysteroscopy or HSG) and that adhesions have not recurred before trying to conceive. Even better, avoid getting Asherman’s syndrome by using alternatives to D&C.

References

1.Yu, D, Wong, YM, Cheong, Y, Xia, E, and Li, TC. Asherman syndrome--one century later. Fertil Steril 2008;89(4):759-79.

2. Dicker, D, Feldberg, D, Samuel, N, and Goldman, JA. Etiology of cervical pregnancy. Association with abortion, pelvic pathology, IUDs and Asherman's syndrome. J Reprod Med 1985;30(1):25-7.

3. Forssman, L. Posttraumatic intrauterine synechiae and pregnancy. Obstet Gynecol 1965;26(5):710-3.

4. Lo ST, Ramsay P, Pierson R, Manconi F, Munro MG, Fraser IS. Endometrial thickness measured by ultrasound scan in women with uterine outlet obstruction due to intrauterine or upper cervical adhesions.Hum Reprod. 2008 ;23(2):306-9. Link

5. Palter. SF, High Rates of Endometriosis in Patients With Intrauterine Synechiae (Asherman's Syndrome). Fertility and Sterility 2005; 86 (null):S471-S471. Link

6. Shufaro, Y, Simon, A, Laufer, N, and Fatum, M. Thin unresponsive endometrium--a possible complication of surgical curettage compromising ART outcome. J Assist Reprod Genet 2008;25(8):421-5.

7. Moon KS, Richter KS, Levy MJ, Widra EA. Does dilation and curettage versus expectant management for spontaneous abortion in patients undergoing in vitro fertilization affect subsequent endometrial development? Fertil Steril. 2009;92(5):1776-9. PMID 19560759

8. Acharya S, Yasmin E, Balen AH. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies--a report of 20 cases. Hum Fertil (Camb). 2009;12(4):198-203. Link

9. Polishuk, WZ and Sadovsky, E. A syndrome of recurrent intrauterine adhesions. Am J Obstet Gynecol 1975;123(2):151-8.

10. Golan, A, Schneider, D, Avrech, O, Raziel, A, Bukovsky, I, and Caspi, E.
Hysteroscopic findings after missed abortion. Fertil Steril 1992;58(3):508-10.

11. Klatsky PC, Tran ND, Strachowski L. A pregnancy complicated by endometrial scarring. Fertil Steril. 2009;91(6):2707-8.

12. Schenker, JG and Margalioth, EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril 1982;37(5):593-610.

Medical management of miscarriage snubbed by doctors

2010-02-09T22:52:00.000-08:00

The following are examples of the medical community's exclusion of medical management as a choice to women who have miscarried. Some countries including Australia and the UK seem to be in the dark ages when it comes to offering misoprostol and/or mifepristone.

The first example is the Royal Women's Hospital in Victoria (Australia). Their website boasts:

"We are also a major teaching hospital and a medical research leader of world renown...We are an advocate for improvements in women’s health and well-being."

Yet, when you look up miscarriage management there is a detailed table comparing expectant management (natural expulsion aka waiting to miscarry) to surgical management (ie. D&C). There is simply no mention of medical management (eg. misoprostol), as if it did not exist.

Sydney IVF is, according to its website, 'Australia's leading centre for infertility and IVF treatment.' It even has a Miscarriage Management Program which promises close monitoring for women with recurrent miscarriage. One could be mistaken for thinking that a center specializing in miscarriage management for recurrent miscarriages would offer medical management as the risk of Asherman's syndrome increases with each D&C. However, it's protocol for managing miscarriages is limited to D&C or natural expulsion:

"It is important to be certain all the tissue relating to the pregnancy is removed, either naturally, or with a D&C (a "curette")."

The website has an extensive glossary of medical terms. Misoprostol is not included.

The third offender is the Women's Health website (UK) which describes only two choices for miscarriage, D&C or natural expulsion. Unfortunately it also fails to mention Asherman's syndrome as a possible complication.

And these are just drops in the ocean.

Meanwhile, abortion clinics in Australia are quick to advertize that they offer the 'abortion pill' . They are referring to misoprostol and mifepristone. It's unfortunate that these drugs have become synonymous with abortions when they can also be used effectively for treatment of miscarriage. These drugs should be made available to ALL women, not just those wanting to terminate a pregnancy. As a society, we must ask why women with an undesired normal pregnancy can receive a treatment regimen that is safer (ie. drugs such as misoprostol) than that standardly used for women with a desired abnormal pregnancy.

As for surgical termination, the website claims that : "In expert hands, termination of pregnancy is the safest procedure in gynaecology." This is absolutely false. Not only because I can think of several other gynecological procedures which are much safer such as hysteroscopy when performed by experts, ultrasound, HSG, SHG, and pap smears. Just as D&C can cause Asherman's syndrome following miscarriage, it can do so when performed for termination, REGARDLESS of whether you have 'infections or endometriosis' as mentioned on the website. Most studies on Asherman's syndrome include women who acquired the condition from surgical termination (as well as other D&Cs and uterine surgery). Therefore medical abortion can also prevent Asherman's syndrome. I believe that if the trend for medical abortion continues, there will be very few cases of AS in this population of women.

Database of ObGyns who offer misoprostol for treatment of miscarriage

2010-02-02T22:35:00.000-08:00

As I've mentioned before, in some countries there are not many ObGyns who offer misoprostol (Cytotec) for treating missed or incomplete miscarriages. This is unfortunate because it is known to be effective and does not carry the risks and potential complications such as infertility that standard care D&C does.

All women should be given a choice in the treatment of their own bodies, provided that their decision does not put their own life at risk.

Therefore I'm putting together a database of Obgyns from all over the world who do offer women the choice of medical management (eg. misoprostol/cytotec, mifepristone) so that women will have a resource if they find themselves in need.

If you are either a patient who has been treated with drugs for managing miscarriage, or a doctor who believes in a patient's right to choose and are experienced in the use of medical management of miscarriage, please contact me on:

ashermansprevention@gmail.com

Thank you.

Note to Doctors: Let me know if you have any concerns about having your names made public. I can always keep the database private and offer the names of doctors in specific areas confidentially to those who request it.

A hidden cause of ‘unexplained’ infertility and miscarriages: ignorance about AS

2010-01-30T23:01:00.000-08:00

Asherman’s syndrome remains a cause of infertility –ie. the inability to conceive or carry a pregnancy- the latter sometimes resulting in repeat miscarriages- which is often overlooked. This is because both doctors and women alike are often unaware of this ‘syndrome’ which rarely gets a mention outside of infrequent gynecological journal articles or anti-abortion propaganda (which ignores the fact that a D&C for any reason or intrauterine surgery can cause the condition). Furthermore, it may be difficult to make a link between a surgery and problems or complications which may occur years later. Another reason is that it is incorrectly thought of as being a rare condition, despite reports of up to 30% of women developing intrauterine adhesions (IUA) after D&C for missed miscarriage and 25% if D&C is performed following delivery (1,2).

Ironically, perhaps another reason it remains so hidden is due to its very symptoms: infertility and miscarriages. Unfortunately, even among highly educated medical professionals, there remains a tendency to consider women who exhibit these as having other fertility flaws rather than to contemplate that problems could be the result of a routine procedure they or a colleague carried out. I was dismayed to have read so many peer-reviewed medical articles where this view is expressed. In fact, Dr. Joseph Asherman, the doctor who described the condition in detail in 1948 and whose name the condition was coined after, quite strangely believed that "adhesions are certainly not to blame for the incapacity to conceive" (3). Of course, this view is certainly refuted today. I will write about this and other errors Dr Asherman (and others) made in a future blog. With all due respect, one should keep in mind that his speculations were based on what he could extrapolate from the imaging techniques and medical and scientific knowledge available in the 1940s and 1950s. Today we are in a much better position to analyze medical conditions. However many study authors continue to suggest that any failure to achieve pregnancy or live birth after 'successful' treatment of IUA as ‘evidence’ of other additional underlying fertility issues even though there could be endometrial dysfunction due to fibrosis for which there are currently no accurate tests. Current live birth outcomes are around 40% at best. This means that they attribute at least 60% of post AS infertility to hypothetical additional infertility factors. Therefore, secondary infertility is often incorrectly labeled as primary infertility.

It is of no surprise that Asherman's syndrome was first noted in a woman who developed amenorrhea after a postpartum curettage (6). If she had not 'proven' her fertility by giving birth her infertility would surely be ascribed to some other undefined cause. Thus, if a childless woman who has a D&C to treat a miscarriage and develops AS, many doctors are less likely to investigate it and put down her future infertility (and prior miscarriage) to other 'unknown' fertility problems. It does not help that the older a woman, the more likely she is to have a miscarriage and therefore undergo a D&C- and develop AS. Age-related infertility can then be the excuse, and if you are a woman aged 40 or over and have ever been to see a fertility specialist as I have, you will have this drummed into you like a mantra. (On a personal note, this is why it especially sucks to get AS after the miscarriage of a first pregnancy when you are an older woman!!!). Most D&Cs are carried out for miscarriage, and proportionally more miscarriages occur in older women at the same time as their natural fertility is declining.

Also unfortunate is that the indirect association between women who do have other fertility problems and AS is often thought to be a direct association. The correlation is due to the fact that women with fertility problems are more likely to miscarry, and therefore have D&Cs-the cause of AS- however unfortunately some doctors will only look at the simplest assocation. There is a review article (4) which misleadingly describes Mullerian defects (eg. septate uterus) as a cause of AS due to 'stagnation of menstrual debris or old blood inside the uterine cavity'. This assertion has no basis whatsoever, nor have I read any similar claim in any other peer-reviewed medical article. (Note: incidentally, that article which is ironically titled 'Ashermans syndrome (IUA): Has there been any progress over the last 20 years?' is undoubtedly the most unconventional review on Asherman's syndrome I have ever come across. Perhaps I can go into the details of this in a blog of its own). In fact it has already been noted that women with Mullerian defects often have had several miscarriages and D&Cs, and it is the latter which increases their risk of developing AS (5). Furthermore, it doesn't take a rocket scientist to realize that blindly scraping in any uterus, let alone an unusually shaped uterus with a wall in the middle, is likely to result in injury leading to IUA. In reality, the only female population that is ‘predisposed’ to AS is anyone who is likely to undergo D&C or intrauterine surgery more frequently than the 'normal' population, whatever the reason might be. No wonder there is so little sympathy or admission of responsibility by the medical community when it is in their interest to blame the patient’s age or other undefined fertility issues for infertility instead of standard medical care.

Even when menstrual disturbances -which are hallmarks of AS- are reported by patients they are either brushed aside as imaginary, explained as normal for one’s age or following miscarriage, or put down to other ‘proof’ of other fertility problems.

The sayings:

“Science progresses best when observations force us to alter our preconceptions.” (Vera Rubin)

“Those who have excess faith in their theories or in their ideas are not only poorly disposed to make discoveries, but they also make very poor observations.” (Claude Bernard)

come to mind.

The bad news is that if Gyns/ObGyns are missing (intentionally or not) the link between cause and effect (ie. D&C and infertility/miscarriages) and making biased and incorrect assumptions about other causes of infertility to ‘explain’ reproductive outcome failure, this gives less incentive for doctors to replace the current standard of care for miscarriage with drugs such as misoprostol or hysteroscopic removal of retained tissue instead. Instead, these attitudes help to maintain the status quo and enables D&Cs to continue to be used widely and indiscrimminately, ignoring the risks.

The most accurate method for diagnosis of IUA is hysteroscopy because it allows a direct view of the inside of the uterus however it is not routinely carried out during infertility workups. Couples considering artificial reproductive technology (ART) are referred for other diagnostic procedures such as ultrasound and HSG however these may not accurately detect the presence of IUA. Also, there is currently no test available for endometrial function which is essential to proper embryo implantation and successful pregnancy. Unfortunately there are few gynecologists who are trained to perform hysteroscopy. Only 15% of US doctors perform office hysteroscopy (7). In comparison, 100% of urologists use office cytoscopy to evaluate bladder pathology. I find it disconcerting that hysteroscopy is such an underutilized technique and question if this would be the case if those likely to benefit from it were men (similarly, would D&C continue to be used if it caused male infertility?). Perhaps our own inaction and passivity as women are in part to blame. Undergoing IVF in the presence of AS is a very expensive waste of time and once again, it is the patient (and broader community if fertility treatment is government subsidized, as in some countries) who suffers most from it, not the fertility specialists! (on the contrary...) IVF is bound to fail if the cavity is not suited for embryo implantation/growth. Even if a patient has other fertility problems such as blocked tubes or her husband has poor sperm quality, the patient must first correct IUA, if present, to enable her to conceive and carry a pregnancy through IVF.

Prospective studies in women with infertility and/or recurrent miscarriages who underwent diagnostic hysteroscopy revealed AS rates of 19-23.6% (8)(9)(10)(11). In other words, 1 in 4 to 1 in 5 women who are infertile or suffer repeat miscarriages have been shown to have IUA. For this reason, diagnostic hysteroscopy should be considered by any woman with unexplained infertility especially if she has ever had a D&C or intrauterine surgery for ANY reason. It especially makes sense to investigate the cavity further if she is either considering IVF or has had unsuccessful IVF treatments. The recommendation to use hysteroscopy in infertility workups appears to be controversial. Interestingly, diagnostic D&Cs are far more commonly used in gynecology even though they carry more risks and provide zero information about the presence of IUA. In the following

presentation about hysteroscopy, the debate about the use of hysteroscopy is outlined with studies. Provided the doctor performing hysteroscopy is properly trained and experienced (in my opinion many more gynaecologists need to be) the benefits of hysteroscopy in women with infertility or recurrent miscarriage may far outweigh the risks.

Quoting from the presentation:

“It is no more acceptable for a gynecologist to insert a sharp curette into a uterine cavity blindly to discover and remove suspected pathology than it is for an orthopedist to insert a curette into a knee joint blindly.”

REFERENCES

1. Adoni, A, Palti, Z, Milwidsky, A, and Dolberg, M. The incidence of intrauterine
adhesions following spontaneous abortion. Int J Fertil 1982;27(2):117-8.

2. Eriksen, J and Kaestel, C. The incidence of uterine atresia after post-partum
curettage. A follow-up examination of 141 patients. Dan Med Bull 1960;7:50-1.

3. Asherman J. Traumatic intrauterine adhesions and their effect on fertility. Int J Fertil 2:49, 1957.

4. Panayotidis C, Weyers S, Bosteels J, van Herendael B.5. Intrauterine adhesions (IUA): has there been progress in understanding and treatment over the last 20 years? (2009) Gynecol Surg 6(3):197-211.

5. Golan, A, Schneider, D, Avrech, O, Raziel, A, Bukovsky, I, and Caspi, E.
Hysteroscopic findings after missed abortion. Fertil Steril 1992;58(3):508-10.

6. Fritsch, H. Ein Fall von volligem Schwaund der Gebormutterhohle nach
Auskratzung Zentralbl Gynaekol 1894;18:1337-1342.

7. Isaacson, K. Office hysteroscopy: a valuable but under-utilized technique. Curr
Opin Obstet Gynecol 2002;14(4):381-5.

8. Raziel, A, Arieli, S, Bukovsky, I, Caspi, E, and Golan, A. Investigation of the
uterine cavity in recurrent aborters. Fertil Steril 1994;62(5):1080-2.

9. Preutthipan, S and Linasmita, V. Reproductive outcome following hysteroscopic
lysis of intrauterine adhesions: a result of 65 cases at Ramathibodi Hospital. J Med
Assoc Thai 2000;83(1):42-6.

10. Ventolini, G, Zhang, M, and Gruber, J. Hysteroscopy in the evaluation of patients
with recurrent pregnancy loss:

11. Dendrinos, S, Grigoriou, O, Sakkas, EG, Makrakis, E, and Creatsas, G.
Hysteroscopy in the evaluation of habitual abortions. Eur J Contracept Reprod
Health Care 2008;13(2):198-200.

Miscarriage management after Asherman’s syndrome

2009-12-15T23:42:00.000-08:00

Unfortunately, I can now talk from experience about how miscarriages can be dealt with post Asherman’s syndrome (AS), and what to expect. I lost my pregnancy at 14 weeks due to a trisomy 21 detected by karyotype analysis and QF-PCR of chorionic villi sampling. The first inkling that something was wrong was at the 12 week scan. Actually, the blood serum levels of PAPP-A and bHCG I’d had during the 11th week already showed a problem, but it wasn’t until my ultrasound that I learned of this. The ultrasound only confirmed that things were not right. Only two weeks earlier I’d had another ultrasound and all seemed fine- the heart beat, the CRL, etc. Now the nuchal fold measured 7mm and there was hydrops- an accumulation of fluid around the fetus. I was told there was a high probability that the pregnancy would end spontaneously.

Fast forward to week 14 and there was no longer a heartbeat.

I’d always talked about misoprostol and ironically now I would have to use it myself. There was no way on earth I’d undergo another D&C (suction curettage or whatever you want to called this blind invasive procedure)- the procedure which caused Asherman’s syndrome when I had it 3 years earlier for a blighted ovum. I could not risk exacerbating the condition. If only my initial ObGyn had agreed to treat me with misoprostol I could have avoided all the surgery and heart ache that followed. I’m quite sure I’d have a child by now.

Since I was relatively far into the pregnancy and the fetus had developed to 14 weeks before dying spontaneously, I booked in the hospital for the misoprostol induction. I don’t know which hospitals/ObGyns use misoprostol regularly, however, in the interest of informing women, my procedure was performed at the Royal Hospital for Women in Randwick (Sydney). I’m sure there are other hospitals (and doctors) that are familiar with misoprostol use, and yes, it is completely legal even if it has not been approved by the TGA (Australia's equivalent of the FDA) for gynecological indications for dubious reasons. By the way, the doctor who refused to give me misoprostol works at St George Hospital. I’d be interested to know if that hospital carries out medical management of miscarriage- please drop me a line or comment below if you know.

In total, I was given a dose of 1 mg (milligram) of misoprostol over the course of a day. Initially, one pill ie. 200 mcg (vaginal) was given to test for any adverse reactions, allergies etc. I began cramping but there was no bleeding. About 5 hours later cervical dilation was checked (closed) and I was given 400 mcg (2 pills). The cramping intensified, but again, there was no bleeding. Shortly after my third and final dose, about 5 hours after the last dose, I began having strong contractions. It was quite painful so I’d definitely recommend panadeine forte. Strangely, there was still no bleeding unlike with my first miscarriage which began like a period. About 40 minutes after my final dose, the waters broke and amniotic fluid spilled out soaking the bed. After this point the pain stopped although I was still feeling crampy for at least a week afterwards. Roughly half an hour after the waters broke, I delivered the tiny baby. The umbilical cord was thin and weak and broke off from the placenta. It is at this point that I began bleeding. I continued bleeding heavily throughout the night and the next day. I also bled strongly for about a week afterwards and on and off during the following week. The placenta should have come out soon afterwards but it was not until 3.5 hours passed that it did. Luckily I’d discussed the possibility of retained placenta previously with my ObGyn and we agreed to wait it out (normally most doctors would jump at the opportunity to do a D&C in this situation) while the nurses and midwives monitored me closely for signs of infection and hemorrhage. As it’s difficult to know if the placenta is complete on visual inspection, and women with a history of Asherman’s syndrome- even after surgical correction- are at an increased risk of placental conditions such as placenta accreta, percreta, increta, and previa, I knew retained placenta was a possibility.

Before the placenta delivered my temperature reached 40 C and the midwife was somewhat concerned, however misoprostol itself can cause fever. The morning after, my blood pressure was 90 on 60 (normally it is around 110-115/65-70) and I was told this could be due to blood loss.

The next morning I underwent an ultrasound to check for retained placental fragments. Around 32 mls of material was found in the uterus but it was impossible to tell whether this was simply blood and blood clots, or if there were retained products of conception (RPOC). Doppler flow analysis suggested that there were retained placental fragments in the posterior of the uterus- the same area where the placenta had implanted in this pregnancy. I had another ultrasound a week after the first. The second ultrasound showed that the fluid in the uterus had roughly halved, but it was still not possible to tell for sure via ultrasound whether there were retained products.

In the following week I bled little despite having around 18 mls of content in my uterus so I became concerned that perhaps there were retained fragments. This would not be a surprise given my pregnancy reached second trimester and my previous history of Asherman’s syndrome. I contacted my trusted Asherman’s syndrome specialist for a hysteroscopic procedure to remove any retained fragments of placenta. This procedure was done 3 weeks after the misoprostol treatment. It turns out I did have many retained fragments which were gently scraped off using the hysteroscope itself. Luckily I did not have any clinical infection from the retained tissue (perhaps just 'subclinical' ;) ?). There were no adhesions. I was given prophylactic antibiotics to prevent infection after the surgery.

I should also mention that to prevent any possible adhesions, I was prescribed 2mg/day progynova (a synthetic estrogen) for 28 days by an Asherman’s syndrome specialist. The other option was Premarin (0.625 mg). These help the endometrium grow and thereby prevent uterine walls from adhering in the case of scarring.

I’m now awaiting my next period after which I’ll have a mid cycle scan to measure endometrial thickness at ovulation, and either an in--office hysteroscopy or an HSG to check for adhesions. Hopefully the removal of RPOCs did not cause any scarring.
Note that the dose of misoprostol I was given was decided according to my pregnancy stage (14 weeks) and status (fetal demise). Doses vary and guidelines should be adhered to.

Here is a summary of my suggestions (as a non MD) if you find yourself in this situation:

1. Don’t have a D&C for a miscarriage as it can cause further damage especially if you have had AS previously. Also, your endometrium may get thinner each time you have a D&C.

2. Misoprostol helps clear out most of the uterine contents. It is more painful than a D&C but worth it in the long run- unless you are not interested in preserving your fertility. NOTE: If you have had a previous Cesarean section or uterine perforation or severe AS, discuss with your ObGyn to see if misoprostol is safe for you (or you may need to take a lower dose than what I was given).

3. You should have estrogen therapy to prevent adhesions from forming. I'm not sure if this is 100% necessary but Asherman's specialists recommend it. Some women didn't use it because of adverse reactions to estrogen (blood clots etc.) and they did not develop adhesions.
4. You will probably have retained tissue and require a hysteroscopy (not a blind D&C!!) to remove it. In most cases if you have had a missed miscarriage you will need to either use misoprostol or, alternatively, wait to miscarry before hysteroscopy can be effective, otherwise there is just too much tissue and blood to work with.

5. Have a mid cycle scan to measure endometrial thickness after your first post-treatment period and always check that your uterine cavity is free of adhesions before you attempt to conceive again just in case. An in-office hysteroscopy is best but failing that, an HSG can be done.

There are also some implications that can be speculated:

1. It may take a few hours for the placenta to deliver when using misoprostol post AS if you are beyond the first trimester.

2. It is likely that if you have had AS, you will have retained products after every future miscarriage. Hysteroscopic removal of tissue allows the doctor to view your uterus as he/she clears it. Note: Hysteroscopy itself can cause complications if undertaken by an unexperienced or unskilled doctor. Please see only a highly experienced specialist.

3. You should anticipate that you may have placenta accreta in a future pregnancy particularly if the placenta does not deliver when expected or you have had confirmed RPOC. Obviously, any woman with past AS should be monitored throughout their pregnancy by a high-risk Obstetrician.

I will try to write about the known pregnancy complications in women with a history of AS in the near future.

There are two more interesting points: Initially I believed that I may not get RPOC because the placenta had implanted in a region which was never affected by intrauterine adhesions. The fact that it is possible to get RPOC in a new, previously unaffected area suggests that perhaps the placenta implants deeply because the endometrium is slightly thinner than it should be ideally. Or maybe blood flow to the uterus is somehow affected and in order for the pregnancy to establish the placenta needs to invade the endometrium more deeply.

Secondly, I have to question once again whether there is any truth at all to the unfounded claim by certain doctors that Asherman’s syndrome can occur ‘spontaneously’ after miscarriage. I would have to have actual evidence to believe this. In my own case I had no adhesions 2 weeks after miscarrying using misoprostol-and this is even after having had intrauterine adhesions in the past (from a D&C). In other words they did not reoccur, nor did any new ones develop. I suspect that if I was treated with blind D&C rather than misoprostol, lo and behold I would develop ‘spontaneous’ adhesions in a new region: the posterior region of my uterus (where the RPOC were). It doesn't make sense for such an evolutionarily destructive mechanism to occur in nature (unless extremely rarely).

In retrospect, I have to wonder why my first Obgyn (ie the one who caused me to have AS) so steadfastly rejected my request to use misoprostol instead of a D&C when it can be used even until the third trimester. He made me believe that it could only be used until 8 or 10 weeks. I also wonder why, as a doctor who was aware about Asherman’s syndrome, my strong concern about acquiring it, and knew of the Asherman’s syndrome support group, he did not refer me for a hysteroscopic removal the supposed RPOC I had? What, may I ask, is the purpose of informing gynecologists about Asherman’s syndrome if they will continue to perform damaging D&Cs while refusing to offer other options? ‘Consent’ for D&Cs is hardly possible when other options are not made available. Please, let us not make Obstetricians/gynecolgists believe that treatment is so simple and effective that causing Asherman’s syndrome is just a little glitch with few consequences for the patient.

Finally, my experience has shown once again that prevention of Asherman’s syndrome is best: the condition leads to a cycle of costly and lengthy complications with retained products (not to mention possible obstetric complications in future pregnancies) which could be avoided if medical management (ie. misoprostol) was used in the first instance.

Misprostol for miscarriage management to prevent Asherman's syndrome

2009-11-26T19:10:00.000-08:00

Misoprostol (also known as Cytotec produced by Pfizer) is a synthetic prostaglandin E1 analogue which causes uterine contractions that empty the uterus. Initially developed for the treatment of gastric ulcers, misoprostol was found to have numerous gynecological indications including treatment of missed or incomplete miscarriage (or termination), or retained placenta following full term delivery, postpartum hemorrhaging (PPH) and labour induction. The advantage of using misoprostol for miscarriage/retained placenta management is the avoidance of the invasive, costly and potentially damaging D&C procedure (eg. Asherman's syndrome).

Misoprostol is on the WHO essential medicine list for abortion induction (in combination with mifepristone) and labour induction. Earlier this year the ACOG published a committee opinion supporting the worldwide availability of misoprostol for postabortion care (both spontaneous and induced), acknowledging its ability to prevent needless deaths in developing nations (1). It has been approved in more than 85 countries since 1985. Yet in all but 4 countries (France, Brazil, Taiwan and Egypt) it has only been approved for use in gastric ulcers. It seems that the major obstacle to the US’s FDA approval of misoprostol for gynecological indications is the original manufacturer's refusal to permit the drug to be used for pregnancy-related applications for moral rather than medical reasons: misoprostol can also be used for terminations (2). As long as those with other agendas can proclaim that misoprostol is 'not FDA (or TGA in Australia) approved' and is being used ‘off-label’, they can continue to at least imply that the reasons for this are safety-related, creating fear or uncertainty in patients and doctors alike. In fact, misoprostol is one of the most widely studied prostaglandins and has undergone hundreds of clinical trials for over 20 years. In comparison, by today's high safety and medical ethics standards, there is little doubt that the century-old blind, invasive D&C would fail to gain approval for routine use. Off label use of medication is not only legal, it is also safe when backed by years of clinical trials assessing safety. Unbeknownst to many, off label use of other Obstetric drugs is commonplace.

Could there be another underlying conflict in the D&C versus misoprostol/medical management- a hidden competition between doctors who perfom surgery and the pharmaceutical industry which produces the drug over financial gain from miscarriages/terminations? From the publications of some doctors at least it would appear that the pharmaceutical industry bowing to anti-abortion lobbyists (2) is the main obstacle rather than the collective rejection of doctors to use misoprostol. Having said this, some doctors remain ignorant about its use and hesitant to learn more. More needs to be done to educate doctors on the use of misoprostol for medical management of miscarriage, beginning in medical school where they are instead trained to peform D&Cs for just about every gynecological condition encountered.

To date there is one randomized control trial comparing the use of misoprostol to D&C for treatment of miscarriage with regards to intrauterine adhesion outcomes. Not surprisingly, this study suggests misoprostol would reduce the incidence of intrauterine adhesions (3). Although these results seem intuitive, in medicine (and science) studies are always needed as evidence, especially when a ‘standard’ treatment is to be usurped by a newer method which some doctors seem inexplicably reluctant to embrace. More such studies would also be helpful in putting to rest the ‘subclinical’ infection myth or other unsubstantiated hypotheses on the etiology of Asherman’s syndrome which somehow shift blame away from instrumentation to a yet unproven and uncharacterized patient factor (eg. patient constitution or a ‘naturally’ occurring physiological phenomenon in the absence of surgery).

Unfortunately, for a variety of reasons Gynecological/Obstetric practice has been slow to keep up with research with regards to the use of medical management for miscarriage. Although there are thankfully some doctors who have incorporated misoprostol management of miscarriage into their arsenal of treatments, my experience is that they are far too few and far between at least in some countries. This is inexcusable given the risks of infertility and future obstetric complications in women who have undergone D&C, still regarded as the 'standard care' for treating missed or incomplete miscarriages. Not only is misoprostol effective, it can be used in both first and second trimester pregnancy losses.

The misoprostol.org website provides a useful table summarizing guidelines for using misoprostol for different obstetric indications and at different stages of pregnancy. Like any drug, it must be used according to guidelines and under medical supervision.

I also came across a very helpful website where women shared their experiences with using misoprostol for miscarriage.

I am adding the site to the links to the right of this blog in the hope that it will help enlighten women to the existence of medical management and what to expect. It is a longer process to use misoprostol (and more painful particularly if used for second trimester losses), however these disadvantages pale significantly against the potential complications of D&C. The more women who become aware about Asherman's syndrome and future high risk pregnancies, the more will request misoprostol treatment, hopefully forcing changes in practice and policies of standard treatment for miscarriage.

REFERENCES

1. ACOG. ACOG Committee Opinion No. 427: Misoprostol for postabortion care.
Obstet Gynecol 2009;113(2 Pt 1):465-8.

2. Misoprostol and the debate over off-label drug use (Commentary): BJOG: an International Journal of Obstetrics and Gynaecology
March 2005, Vol. 112, pp. 269–272. Link to full pdf

3. Tam, WH, Lau, WC, Cheung, LP, Yuen, PM, and Chung, TK. Intrauterine
adhesions after conservative and surgical management of spontaneous abortion. J
Am Assoc Gynecol Laparosc 2002;9(2):182-5.

In Memory

2009-11-17T23:31:00.001-08:00

Name: Sema

Sex: female

Gestational age: 14 weeks

Length: 11.5 cm

Weight: 40 g

Date of death: 12/11/09

Cause of death: trisomy 21

"Before you were conceived I wanted you, before you were born I loved you."

Future research:How stem cells may one day improve Asherman's syndrome treatment

2009-09-22T21:57:00.000-07:00

Currently the gold standard for treatment of Asherman’s syndrome is surgery to remove/cut adhesions (hysteroscopic adhesiolysis or synechiolysis) and hormonal therapy to regenerate any residual endometrium. One of the challenges in treating Asherman’s syndrome is the propensity of intrauterine adhesions to reform again during the healing process. To try to overcome this, some doctors place a saline-filled stent (Foley or Cook) or an IUD in the uterus after surgery in order to keep the walls of the uterus and cervix apart during the healing process. If there is little endometrium regrowth adhesions will continue forming again in the same areas. Hormone therapy (2-4mg/day estrogen for up to 2 months followed by progestin (P) to induce a withdrawal bleed) is also used in addition to surgery to prevent adhesions from reforming by promoting regrowth of endometrium. It is also thought that it generally improves the thickness and quality of endometrium- some patients end up with thin endometrium or fibrosis (scar tissue with no viable endometrium) after instrumental trauma from surgery precipitating Asherman’s syndrome (usually a D&C). Adhesion reformation following corrective surgery correlates with the severity of adhesions. According to one study adhesion reformation occurs in 50% of severe cases and 21.6% of moderate cases (1). Sometimes multiple surgeries are needed to correct uterine architecture.

The problem is that if one does not have enough endometrium because it has been scraped away, either adhesions or fibrosis will continue to be a problem no matter how many surgeries are undertaken or how much hormonal stimulation is given.

As you can see from a previous post, the live birth rates after corrective surgery are not very high for moderate to severe cases. To understand why this treatment is not effective in all patients one needs to understand the physiology of the endometrium and adhesion formation. The outermost layer of the uterus is lined by the endometrium which sits above the muscle layer, the myometrium. The endometrium itself is comprised of two layers. The functional layer is outermost and is shed on a monthly basis during menstruation. The underlying basal layer is necessary to produce the functional layer each month. If permanent damage is incurred to the basal layer, the functional layer will not be able to regenerate. Without the regeneration of endometrium the bare myometrium underlying the endometrium will begin to stick to other areas devoid of endometrium as soon as the injury occurs. Adhesion formation is the normal physiogical response to injury whether this is in the uterus or elsewhere in the abdominal cavity. Adhesion formation begins immediately after scar formation from instrumental injury and will be complete by 8 weeks. Any area where injured tissue can come into contact with other injured tissue, adhesions form. Adhesions are a serious health problem related to surgery, not just in the uterus but also in the abdomen and intestines. However abdominal or intestinal surgery does not have alternatives whereas uterine evacuation does. In other words, D&C is not the only available method for effectively emptying the uterus after miscarriage or delivery, however staggeringly, it remains standard care for the former in many advanced countries.

So the problem comes down to endometrial regeneration (or the lack of it). Some tissue in the body is able to regenerate. For example, cells in the the gut and bone marrow regularly divide to repair damaged or worn out tissue. In other tissues such as the heart and brain, cells are only stimulated to divide under special circumstances. Endometrium is another such tissue. Tissue regeneration is due to the activity of stem cells which have special properties. Initially it was thought that only embryonic stem cells had the capacity to differentiate. More recently the existence of adult stem cells was discovered. Adult stem cells are undifferentiated cells usually found in little islands or "niches" in tissues and organs. They are generally thought to have a more limited ability to differentiate than embryonic stem cells which can develop into any type of cell in the body. Adult stem cells, on the other hand, are already partially committed to certain cell lineages. Adult stem cells are thought to play a role in tissue maintenance and reparation in the tissues they are found.

Recently the existence of endometrial adult stem cells was reported in the scientific literature (2). However, if all of the basal and stem cells have been removed from a large part of the uterus, it is impossible to resolve the problem of recurrent adhesion formation and/or fibrosis. Sadly, current therapy can only remove bands of scar tissue and promote endometrial regeneration in areas where there is some remaining basal cells or even perhaps stem cells. Put simply, current treatment will not be successful if the patient does not have enough residual endometrium to regenerate. In theory, the identification of endometrial stem cells in the junction between the endometrium and myometrium opens the possibility of future therapy for damaged endometrium. Stem cells can be introduced either from a donor, or better yet, from the same patient whose stem cells have proliferated in a culture medium. Once inside the right tissue and with the appropriate stimulation, they will be able to differentiate into basal endometrial cells and fill in any 'bald' patches of endometrium. Adhesion formation or sclerosis should no longer be a problem. The advantage of using the patients own cells is that it will avoid immune rejection. The use of adult stem cells also avoids any obstacles from those citing ethical problems in using embryonic stem cells. Note that I have greatly simplified the process in the scenario above.

Stem cell research, both adult and embryonic, are still in their infancy. Most stem cell researchers are focusing on regeneration of heart tissue or other major organs as an alternative to organ transplantation. The problem is that there is little if any research on endometrial regeneration and in particular for the treatment of Asherman’s syndrome. In the past basic research was carried out to improve endometrial growth in animals where AS was artificially produced. This type of research no longer seems to exist. Instead, there is research on uterus transplantation which is much more complex and difficult to achieve. As long as endometrial research remains stalled there is little hope that treatment will continue to progress much beyond what has been attained today- which leaves much to be desired if treatment is regarded as the primary solution to the problem of Asherman’s syndrome.

REFERENCES

1. Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reproductive outcome. Am J Obstet Gynecol. 1988 Jun;158(6 Pt 1):1459-70.
Abstract

2. Gargett BE, Chan RW. Endometrial stem/progenitor cells and proliferative disorders of the endometrium. Minerva Ginecol. 2006 Dec;58(6):511-26.
Abstract

‘Victims’ in miscarriage headlines are luckier than they think

2009-09-15T19:29:00.000-07:00

Oh no. Not another story about a woman who goes to hospital emergency with an impending miscarriage and gets given painkillers and told to go home (click here for 'story'). Or miscarries in the hospital toilet. I don’t know why, but Sydney newspapers abound with such stories. It started off with the famous Jana Horska story. Yesterday I read in the Sydney Morning Herald that women will now be offered D&Cs straight away. OK, I’ve kept silent long enough. When women think that miscarriage and the pain that goes with it are the worst things than can happen to them, I must enlighten them about Asherman’s syndrome. Especially when their complaints have prompted hospitals to consider carrying out even more D&Cs, the number one cause of Asherman’s syndrome.

One in four pregnancies ends in miscarriage. I too had a miscarriage so I know what I’m talking about. I was around 14 weeks into the pregnancy. Mine was a missed miscarriage detected via ultrasound at 11 weeks. The fetus either died (fetal demise) and was resorbed or stopped developing very early on (anembryonic gestation). I was offered a D&C straight away by my ObGyn. I recalled vaguely hearing about the risks of D&C and future fertility. I was 39 and was not about to take a chance. My ObGyn insisted that Asherman’s syndrome and uterine perforation were ‘extremely rare’ (see what the real incidence rates are. Not rare at all!). Still, if there was a chance I could avoid it altogether by waiting to miscarry naturally, I would take that option. I had no other choice as he flatly refused to give me medication (misoprostol). The ObGyn was visibly irritated and disappointed in my choice to avoid a D&C.

The shock and sadness of losing the pregnancy was soon replaced with impatience to miscarry naturally so I could avoid a D&C, and start trying to conceive again with my fertility intact. My goal was to avoid a D&C at all costs. I was relieved when one Sunday morning about 3 weeks later, I finally began to bleed. At first it was like a normal period. As the day progressed the bleeding got heavier, and so did the cramps. By 11 PM I could no longer contain my cries of pain. My husband shut the windows, worried the neighbours might think he was beating me! Finally around midnight when I could no longer stand the pain I sent my husband to an all night pharmacy to get the strongest painkiller available without prescription. He tried to convince me to go to the hospital instead. “Are you nuts?” I retorted. “They’ll just tell me to have a D&C”. Not only that, but I’d have to stifle my moans and sit upright in uncomfortable clothes, surrounded by strangers and without access to a clean toilet. At home I could make as much noise as I wanted in my loose nighty and stand on all fours if that was the most comfortable position. The toilet was less than a meter from my bed and I wouldn’t have to compete with 50 other patients for it while waiting in emergency. He came back with a box of Panadeine forte containing codeine and that took the edge off the labour-like cramps. At some point after midnight I felt a ‘pop’ and instantaneous relief. Instinctively I knew the gestational sac must have burst and I rushed to the toilet. I continued to bleed heavily but was glad everything was coming out.

Later that day I had an appointment with the ObGyn who seemed rather disappointed that I miscarried by myself. Somewhat wistfully, he said that on ultrasound it appeared that there was no remaining tissue. What a relief that was to hear. But for some reason, he insisted I return a few days later to make sure everything was OK. When I returned later that week his story changed. This time he said it appeared that I had large ‘products of conception’ and that I had no other choice than to have a D&C. What??? I asked about drugs again. He refused again, saying they would be ‘ineffective.’ Reluctantly, I had the D&C, got stage 3 Asherman’s syndrome and the rest is history. (Here’s my story).

I’m convinced that the D&C was needless. I lost my fertility for no reason at all.

I wonder if these women who are sent home without a D&C realize how lucky they are to not go through what I did? Instead of noticing something is wrong with their periods, or are no longer able to conceive or miscarry repeatedly… instead of having to find a doctor who believes them and who is aware about the existence of Asherman’s syndrome and is trained to diagnose it with hysteroscopy… instead of having to undergo hysteroscopic surgery and hormone therapy to remove adhesions and salvage any viable endometrium in the hope that they will be able to have a baby in future… they get to try to conceive again right away with any complications whatsoever! And they’re the ones who are complaining! As a victim of D&C, I guarantee you, a miscarriage is nothing compared to the pain of possible loss of fertility and serious future pregnancy complications from D&C.

I wonder, do these women realize that there is absolutely nothing any hospital or doctor can do to stop the miscarriage from happening? They probably miscarried because the babies were not normal and there is unfortunately nothing that can change that. If they really want to be of help, they should insist that hospitals offer medical management with misoprostol and mifepristone in addition to expectant management, which also evacuates the uterus safely. Instead, I fear their indignant cries have resulted in a policy to systematically use D&C to manage miscarriage and will result in an increase in Asherman’s syndrome cases.

When will the lesson be learned? What is the world coming to when no one says a word about the risks of reproductive mutilation from systematic blind D&C, yet C-sections and male circumcision are made out to be the most dangerous,needless and wicked surgery known to humankind?!

Related link:

Here is a youtube clip I made about miscarriage management

This is another website which aims to raise awareness about the risks of D&C: http://www.dandcnow.info/

The cycle of Asherman's syndrome needs to be broken with prevention

2009-09-11T19:51:00.000-07:00

In my next blog I will explain why it is that current treatment (surgery and hormone therapy) can never be a cure for all women who have been diagnosed with Asherman’s syndrome (AS). However I also want to explain why my position on prevention as the best approach is unwavering. I’ve always maintained that I would continue to spread my word about prevention even if I was lucky enough to have a baby after AS treatment. This is because I realize that I would be one of the lucky minority if I did. Just because I may be fortunate enough to have a child after my diagnosis and treatment doesn’t mean I should forget about all of the others who didn’t. It’s not about how ‘hard’ you try or how ‘deserving’ you are- one has to understand that the body has its limits according to the damage that was incurred and other factors. I would realize that my case may not have necessary been as severe or my situation not as dire as others who were inflicted with this condition. It would be unfair to the women who have done all they possibly could to achieve a live birth but didn’t succeed to not acknowledge that each case is different not only in severity but also the circumstances in which it happens. As a PhD scientist (molecular microbiology) I know there are no hidden Asherman’s experts out there: all of the ones who are truly experts have peer reviewed published papers on outcomes in their patients following treatment. That is the nature of these careers. One is judged and recognized according to their publication record. And I have read those papers and know what the outcomes are. I would feel daft to go around telling other women not to worry about getting Asherman's syndrome because it can be treated when a) according to statistics from the best doctors, the majority of women will not have a live birth after AS, and b) it doesn't have to happen in the first place. I know also that personally, I could never forget what happened to me for no justifiable reason. Imagine if someone almost accidentally killed you through a preventable and routine careless act but you were saved by a treatment which has a 50% failure rate at best- would you think it was better to promote the treatment , or would you want to do something to prevent another person from possibly losing their life? If I will ever be fortunate to have a child after Asherman’ s syndrome it doesn’t mean that it is still acceptable to damage women through the systematic use of D&C when alternatives exist. I cannot forget the years of suffering, of fearing I will never have a child, the sleepless nights, the tears, the time lost waiting for treatment as I now had to race against my biological clock, the negative pregnancy tests month after month, the failed IVF, the worries that even if I were to become pregnant post AS pregnancies are high risk, none of that will ever be ‘worth it’. For me, to say something is ‘worth it’, it has to be something challenging that I chose for myself, not what someone (ie a treating Dr) did to me. For example, my PhD- those were some of the most difficult and challenging years of my life, performing experiments until late at night and on weekends, reading hundreds of papers, spending months writing my thesis. But I wanted to do, and it was worth it! Without all that hard work I wouldn't have achieved it. On the other hand, it should not be a struggle to have a child when nothing is wrong with you in the first place. Isn't there enough infertility and heartache in the world without doctors causing Asherman's syndrome?

As women we are expected to be martyrs and put up with all kinds of assaults on our bodies without complaining. It’s supposed to be the very essence of being a caring, nurturing Madonna, to put ourselves last. I prefer to be proactive and warn women about the dangers of D&C, and let doctors know it is not OK to perform D&Cs at the drop of a hat. It’s not acceptable to pretend there are no alternatives and to keep silent when prolife activists prevent drug companies from seeking FDA approval for drugs which can prevent fertility loss and even mortality because they also happen to be used for abortion.

You see, it’s not just about me. Of course I’m angry that it happened to me, especially given the particular circumstances- I was 39 and it was my first pregnancy that ended in miscarriage. Given my age I was extremely concerned about future fertility. I had asked about the risks of D&C and in particular about AS only to be told it was rare, I had asked for alternatives like misoprostol only to be told it was ineffective and refused. I had put up a brave stand to avoid D&C by waiting to miscarry myself (which I did) and after all of that I was told that I had RPOC and had to have a D&C or risked getting AS from an infection (balogna!). The pathology report showed that I only had a blood clot and some tiny fragments and no infection. But it's not that I am a disgruntled, childless older woman: even if I were to have a child, it’s the principle that I find objectionable- that women are continuing to go through this needless suffering because doctors will not give up an archaic surgery even when other safer and cheaper medical options have been developed.

Once again, to be clear, I encourage all women who have been diagnosed with Asherman’s syndrome: please seek help from an expert for treatment if you want to have a chance of having a child. I won’t ever regret having treatment even if I don’t succeed in having a child because I know without it there would be no possibility of it. I gave myself the best odds that I could in a situation which never should have happened to me in the first place. But just because it happened to me it doesn’t mean it should continue happening to others! There is nothing I gain out of pain and suffering of other women. It makes me somewhat angry that other women who have had it before me have done nothing to prevent it from happening to me and others. It makes me somewhat resentful that the information I was after about D&C risks and alternatives for miscarriage management were not readily available to me at the time that I needed it. And I refuse to continue that cycle which is why I am doing everything possible to warn and educate women about the big coverup about Asherman’s syndrome and D&C risks and the existence of cheaper and safer alternatives. Not to mention the exaggeration of treatment success to patients as an excuse to hinder prevention. Of course, anything that promotes further dependence on doctors is encouraged and supported by the medical community while prevention is ignored. It’s time to break the cycle-now.

Some women speak of the spiritual journey AS has given them in a way where they almost sound thankful that it happened to them! All I can say it that I don' t understand people who are thankful for unnecessary damage to be inflicted upon themselves. Only someone who didn’t feel they were worthy or seriously deluded would think it was a blessing in disguise. Asherman’s syndrome was never ‘meant to be’. It only happens because many doctors are unwilling to offer alternatives to D&Cs and nothing is being done about it.

In my ‘journey’ I have learned a lot from having Asherman’s syndrome. I have learned that there is an urgent need for women to speak out against the routine use of D&C for miscarriage. I have learned that women should at the very least be given the right to choose which treatment option they prefer. I have learned that women must pressure doctors and the government to approve of all drugs which can help to safely evacuate the uterus and that these should be the first line of therapy for miscarriage and other indications instead of D&C. I have learned that not all doctors act in the best interest of their patients so patient activism is required for change.

Treatment of Asherman's syndrome is not a panacea, Part III

2009-09-08T00:00:00.000-07:00

Continued from Part II

In my last post in this series on treatment of Asherman's syndrome I posted the actual live birth rate outcomes according to studies published peer reviewed medical journals to show why it is not the promising solution that it is often promoted as, and why prevention would be a better approach. The gold standard for treatment of intrauterine adhesions (Asherman’s syndrome) is hysteroscopic adhesiolysis (synechiolysis) and hormonal therapy. Most studies so far focus on fertility outcomes following a particular treatment method.

Yet one needs to be cautious when evaluating outcomes because some studies are presented in ways which may mislead the inexperienced or lay reader into believing that the success rates are higher than they actually are. If you have read some of the original abstracts or papers I cited in the references of my last post, you may notice that some of the results I have given differ from those apparently reported by the authors. This is because I gave live birth rates as total number of births per total number of patients treated, which gives a complete and accurate picture of the outcomes. As I explained before, the reason I did this is to include women who may never have conceived as it is very possible that surgery did not restore their fertility. Below are some other examples of how data presentation can be misleading.

Data Presentation

'Success rates’ after surgery may not be what you had in mind. I think most patients like myself are interested in achieving a live birth. Sometimes the author is referring to menstrual outcome. Yasmin et al (1), report that 95% of women in their study resumed normal menstruation. Unfortunately, this is not closely correlated to live birth rate. Accordingly, only 1 patient out of 20 treated ie.5% went on to have a live birth (although followup was short). Restoration of menses is known to be an unreliable criteria for future fertility. In my view this is partly because it is self-reported.

Even pregnancy or conception rates per patients treated or live birth rates per total pregnancies do not necessarily reflect live birth outcomes realistically because not only do 1 in 4-5 pregnancies end in miscarriage under the best of circumstances, women with a history of Asherman’s syndrome are also prone to second trimester pregnancy loss and preterm delivery (2). Other women with residual scarring may conceive but repeatedly miscarry with no live births.

In one study (3) the abstract says that live birth rate was 86.1%. Not only was this an overall rate in a study group where mild and moderate cases greatly outnumbered severe cases (71 vs 18), it is also calculated per pregnancy (instead of per patients treated). This can be gleaned from Table 3 where a 66.6% live birth rate was given among women with severe condition at presentation. In other words, two thirds of the women with severe Asherman’s who were able to conceive after treatment went on to deliver a live baby. This is good but not that inspiring when you consider that most women in this group were not able to conceive. In fact, only 4 out of 18 (22%) women with severe AS in this study had a live birth. Another example of this occurs in Table 6 of Yu et al, 2008 (4) review where outcomes are given in terms of live births/pregnancies.

Perhaps reporting data in this way is seen as acceptable by some because doctors are all too eager to put down the inability to conceive after treatment to ‘other fertility issues’, particularly in women who have had the cruel misfortune of being inflicted with Asherman’s syndrome before having a child. The ridiculous premise is that unless women have a live birth prior to developing this iatrogenic condition, they cannot 'prove' they were ever fertile (infertile unless proven otherwise). Unless these ‘other causes of infertility’ are clearly described and (depending on the cause) pre-existing, there is no evidence to suggest that these women were infertile to begin with and should be discarded from outcomes. If the studies were conducted according to the highest standards, women with ‘other fertility issues’ would be excluded from studies to begin with and not after the fertility results are known. This brings me to…

Study design

Besides data presentation, it is also important to take into account how the study was conducted because this too has important implications on outcomes. Unfortunately, studies on Asherman’s syndrome have not been conducted to meet most rigorous scientific methodology-RCTs, making it difficult to assess the exact outcomes. I have mentioned the lack of RCTs in an earlier post. It follows that there are currently no systematic reviews or meta-analyses of the studies either since they are not conducted to stringent standards.

RCTs are clinical trials which have to meet certain criteria in order for the results to be considered unbiased, accurate and of statistical significance. In summary, studies must be done prospectively, they must be randomized with respect to treatment strategies depending on the outcome measure(s), there must be blinding of the doctors, investigators with regard to diagnoses/assessment of outcome with regards to treatment, a clear definition of exclusion and inclusion criteria for patients must be set in order to avoid outcome bias, and there must be enough participants in the/each study group(s) such that statistical analyses can be deemed to have significant value.

RCTs can be carried out to test the efficacy of a particular treatment, or to compare the efficacies of two or more different treatments. Most Asherman's studies focus on fertility outcomes following a given treatment protocol. The risk for potential bias comes mainly from unclearly defined patient inclusion/exclusion criteria, retrospective analyses and sample size and composition.

With regards to study design, the most blatant weakness is when studies are done retrospectively. This means that the doctor/investigator chooses the data to present after they already know the outcomes. This approach introduces the possibility of bias in outcomes because they may select, for example, all of the patients who went on to have live births after treatment, but leave out a portion of those who did not regain their fertility from the study without ever mentioning it. This would obviously make the success rate of treatment appear to be higher than in actuality. Most studies are now carried out prospectively.

Even if a study is done prospectively there are ways in which the outcome can be premeditatingly skewed to enhance outcomes. This is why in proper RCTs everything about the study (except for the results and conclusions) is decided in detail in advance and recorded in a repository. This leaves little space for modifications which can incorporate bias.

If exclusion/inclusion criteria are not stringent from the outset, some of the women who did not achieve a pregnancy could still be discounted on account that they had ‘other' fertility problems. Some authors write their study before allowing a reasonable followup time (1,5) and suggest that the success rate is potentially higher because at the time of writing it was too soon for X number of patients to try to conceive. Others may include patients with ongoing pregnancies (4,6,7,8) which may later not eventuate in live birth on complete followup. In one study, (9) live birth rates were reported as 83% a figure that sticks out like a sore thumb compared to other studies. It turns out that the study, which was done on 365 women, only included 186 patients in the live birth rate outcome. The justification for this was the 179 patients who were left out did not desire a pregnancy. Call me skeptical but I find it hard to believe that 179 women would undergo surgery just to get their periods back. If you include all 365 women in the study the live birth rates don’t look quite as remarkable -42.7%- blending in with the rates recorded by other studies.

Another thing to keep in mind is patient composition: how many have mild, moderate and severe disease? Since an increase in disease severity is associated with a poorer prognosis in terms of live births, a study group consisting of proportionally fewer severe cases could artificially bump up the live birth rate. Therefore it is important to either indicate this by giving a breakdown of outcomes according to disease severity, or to carry out studies where there are equal numbers of patients of the different disease classifications. Many studies will report overall birth rates among patients without giving a breakdown according to disease severity at presentation. It is up to the reader to do their own calculations.

I think the above examples show why proper RCTs are needed to not just to compare different methods of treatment, but to give accurate data regarding live birth outcomes. It would also be of help if there was a more standard way of reporting outcomes such as live births per total patients treated.

REFERENCES

1. Yasmin H, Nasir A, Noorani KJ. Hystroscopic management of Asherman’s syndromeJ Pak Med Assoc. 2007 Nov;57(11):553-5.

2. Capella-Allouc, S, Morsad, F, Rongieres-Bertrand, C, Taylor, S, and Fernandez, H. Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility. Hum Reprod 1999;14(5):1230-3.

3. Roy KK, Baruah J, Sharma JB, Kumar S, Kachawa G, Singh N.Reproductive outcome following hysteroscopic adhesiolysis in patients with infertility due to Asherman's syndrome. Arch Gynecol Obstet. 2009

4. Yu, D, Li, TC, Xia, E, Huang, X, Liu, Y, and Peng, X. Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman's syndrome. Fertil Steril 2008;89(3):715-22.

5. A. Thomson, J. Abbott, A. Kingston, M. Lenart, T. Vancaillie. Fluoroscopically guided synechiolysis for patients with Asherman’s syndrome: menstrual and fertility outcomes. Fertil Steril, 2007; Volume 87(2):405-410

6. Goldenberg, M, Sivan, E, Sharabi, Z, Mashiach, S, Lipitz, S, and Seidman, DS. Reproductive outcome following hysteroscopic management of intrauterine septum and adhesions. Hum Reprod 1995;10(10):2663-5.

7. Robinson, JK, Colimon, LM, and Isaacson, KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril 2008;90(2):409-14.

8. Protopapas, A, Shushan, A, and Magos, A. Myometrial scoring: a new technique for the management of severe Asherman's syndrome. Fertil Steril 1998;69(5):860-4.

9. Feng, Z, Yang, B, Shao, J, and Liu, S. Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesions after induced abortions: clinical analysis of 365 cases. Gynaecol Endosc 1999;8(2):95-98.

Treatment of Asherman's syndrome is not a panacea, Part II

2009-08-28T00:29:00.000-07:00

Continued from Part I

One century after its first description, treatment of Asherman’s syndrome (1) has not progressed enough to ensure that a high percentage of patients will regain fertility. I hope that one day it will be 100% treatable but it seems that this is a long way off and not a top priority for researchers or funding bodies. As important as treatment is for the women who have been diagnosed with Asherman’s syndrome, it is still difficult to justify why so little is being done to prevent it in the first place. Not all cases are preventable depending on the cause, but most are. Most cases (over 90% according to one study) (2) are caused by D&C and yet there are alternatives to D&C for every indication for which it is used. When D&C continues to be standard care for miscarriage management most cases of Asherman’s syndrome will continue to occur in women who have miscarried.

Asherman’s syndrome was first described in 1894 (1) and later further characterized in 1948(3). In those days there were no other options to D&C so naturally treatment (or more selective use of D&C) was the only solution to the problem. The situation today is very different with the discovery of drugs and hysteroscopy to replace D&C. These approaches would undoubtedly reduce the incidence of Asherman’s syndrome.

Unfortunately treatment is not a panacea. The outcomes of studies speak for themselves (see below). They range from 27% to 43% and include women of different classification severities (so presumably this rate is even less inspiring for women with more severe presentation). Note that all of these studies are recent. The most accurate way to present these results is to report number of live births per total patients treated because some women will either never conceive or give birth after treatment. Reporting live births per pregnancy is deceptive because the women who never got pregnant are discounted from the outcomes. It is very possible that some women never conceived because the endometrial damage they sustained and which led to Asherman’s syndrome was permanent and not able to be repaired by treatment enough to allow for successful implantation. Absence of adhesions does not imply that the endometrium is functioning properly- there could be fibrosis or very thin unresponsive endometrium. Unfortunately, to this date, there is no test which can ensure that the entire endometrium is functional. In the next part of this discussion about treatment (Part III), I will discuss in further detail the results from studies and difficulties in conducting studies on Asherman's syndrome.

Studies of modern success rates (#live births/#patients treated) after treatment of Asherman’s syndrome:

STUDY	REF	BIRTHS/PATIENTS	BIRTH RATE
1. Zikopoulos et al, 2004	(4)	20/46	43.5%
2. Fernandez et al, 2006	(5)	21/64	32.8%
3. Thomson et al, 2007	(6)	8/27	29.6%*
4. Yu et al, 2008	(7)	25/85	29%
5. Robinson et al, 2008	(8)	4/15	27% **
6. Pabuccu et al, 2008	(9)	22/71	31%

* the paper itself quotes a 47% live birth rate but excludes 10 women ie. one third of the patient sample size from the calculation on the basis that they were not trying for pregnancy.

**the paper quotes a 46% (7/15) live birth rate, however 3 of those pregnancies were still ongoing at the time of publication.

The real outcomes, including the results of treatment by the best doctors in the field according to the Asherman's Syndrome International Support Group don’t look as inspirational in statistics as they do when presented as personal success stories.

Are these live birth rates high enough to justify treatment as the best solution to the problem of iatrogenic Asherman’s syndrome? Or that D&C should continue to be used routinely or as ‘standard care’?

I will not get into the serious obstetric complications sometimes encountered in future pregnancies (should patients be fortunate enough to be able to conceive and carry a pregnancy). I have saved this for another post as it is a whole other area that needs to be discussed in detail.

There is another very important reason for women to told the true success rates of treatment (and about future obstetric complications): awareness will undoubtedly create a push among patients and and more importantly women, in general, for prevention by using alternatives to D&C…

Continued in Part III

REFERENCES

1. Fritsch, H. Ein Fall von volligem Schwaund der Gebormutterhohle nach Auskratzung Zentralbl Gynaekol 1894;18:1337-1342.

2. Schenker, JG and Margalioth, EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril 1982;37(5):593-610.

3. Asherman, JG. Amenorrhea traumatica (atretica). J Obstet Gynaec Brit Emp 1948;55(23).

4. Zikopoulos, KA, Kolibianakis, EM, Platteau, P, de Munck, L, Tournaye, H, Devroey, P et al. Live delivery rates in subfertile women with Asherman's syndrome after hysteroscopic adhesiolysis using the resectoscope or the Versapoint system. Reprod Biomed Online 2004;8(6):720-5. Abstract

5. Fernandez, H, Al-Najjar, F, Chauveaud-Lambling, A, Frydman, R, and Gervaise, A. Fertility after treatment of Asherman's syndrome stage 3 and 4. J Minim Invasive Gynecol 2006;13(5):398-402. Abstract

6. Thomson Angus J M; Abbott Jason A; Kingston Ashley; Lenart Meegan; Vancaillie Thierry G. Fluoroscopically guided synechiolysis for patients with Asherman's syndrome: menstrual and fertility outcomes. Fertility and sterility 2007;87(2):405-10. Abstract

7. Robinson, JK, Colimon, LM, and Isaacson, KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril 2008;90(2):409-14. Abstract

8. Yu, D, Li, TC, Xia, E, Huang, X, Liu, Y, and Peng, X. Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman's syndrome. Fertil Steril 2008;89(3):715-22. Abstract

9. Pabuccu Recai; Onalan Gogsen; Kaya Cemil; Selam Belgin; Ceyhan Temel; Ornek Turkan; Kuzudisli Ebru. Efficiency and pregnancy outcome of serial intrauterine device-guided hysteroscopic adhesiolysis of intrauterine synechiae. Fertility and sterility 2008;90(5):1973-7.
Abstract

Treatment of Asherman's syndrome is not a panacea (Part I)

2009-08-14T05:27:00.000-07:00

Not all that long ago Asherman’s syndrome patients may have been told to forget about ever having a(nother) child. Treatment has come a long way with the advent of hysteroscopy, hormonal treatment, stents and adhesive barriers. It’s not surprising that before these were available, success rates were very low and often more damage was incurred from ‘treatment’ resulting in worse outcomes. One of the reasons for this is that some doctors used to treat Asherman’s syndrome by performing a blind D&C to break apart intrauterine adhesions they couldn’t even see. It’s hard to imagine why anyone would think that performing the same procedure as the one which usually causes the condition could fix things, but lots of doctors did- and some continue to do so with disastrous consequences.

Some doctors might still have the attitude that anyone whom they cannot treat successfully should give up hope, even if they are not highly skilled or experienced in the treatment of intrauterine adhesions. However, a new and equally detrimental view is being encouraged among sufferers: that treatment has come so far that anyone who is diagnosed stands a very good chance of conceiving and delivering a healthy baby (provided they go to the right doctors). While it’s true that some doctors have much more training, experience and expertise in the treatment of Asherman’s syndrome, the harsh reality is that the overall success rate is not above 50% (and lower for the moderate to severe cases)- even with the best doctors. If anyone tells you that there are doctors who have higher success rates with moderate to severe cases than 50%, they are either not being truthful or simply don’t know (or prefer not to accept) the reality.

It’s a bitter pill to swallow, but women need to be made aware of this fact. Not to crush any optimism, but to give realistic expectations, and perhaps to avoid the costs and heartbreak of ‘unexplained infertility’ following ‘successful’ treatment. There is a very fine line between giving encouragement and creating false hope. You may read of success stories, you may hear of women overcoming seemingly astonishing odds, and photos of women beaming with their babies, praising their ‘miracle’ doctors, but make no mistake: these are the faces and stories of less than 50% of women who are diagnosed with IUA and get treatment by the best doctors. But they do not reflect the reality for more than half of women diagnosed with Asherman’s syndrome. The latter are the women who fade into the background, the ones doctors and patients alike would like to forget about, or blame the lack of success on other reasons. Let us not underestimate the significance of the initial trauma underlying the Asherman’s syndrome. Some of us got a worse deal than the others. Worst of all, there is no clear way of predicting whether treatment will be successful or even knowing if it was successful. The only way to know is to try to conceive. If you do have a baby, your treatment was successful. If you don’t, your treatment may not have fully restored your fertility (or you have other causes of unexplained infertility). But let’s not exaggerate the likelihood of the latter- why would someone who was previously capable of getting pregnant suddenly have ‘unexplained infertility’ after having had Asherman’s syndrome? Fibrosis from Asherman’s syndrome can affect blood flow to the endometrium and reduce the chance of implantation or maintaining a pregnancy. I’m not saying one should not seek treatment. By all means, please do whatever is necessary to improve your chances of regaining your fertility! But don’t be too surprised if you don’t end up with a success story.

The attitude of the medical community is also to blame for encouraging the view that treatment is the best answer to the problem. For reasons which evade me, they seem to think it is more logical to subject all women to blind surgery causing Asherman's syndrome in a non-negligible proportion of them, and then to attempt surgical correction and hormonal therapy on those who do develop IUA in the hope that at most 50% of them will have a child (30-40% with moderate to severe IUA, 80% with mild IUA). Not to mention that these future pregnancies are at risk of serious complications, like placenta accreta, preterm delivery, intrauterine growth restriction, cervical incompetence etc. How logical is this? What is the advantage or logic in performing two (or more) expensive, difficult and potentially risky uterine surgeries- one which can cause damage, and one (or more) to repair the damage of the first surgery? Why not nip it at the bud and not cause damage to begin with?

Why not simply use drugs or hysteroscopy to empty the uterus, preventing scarring in the first place? When you consider that there are ways of emptying the uterus without blind surgery (either by using drugs like misoprostol or mifepristone, or visually guided hysteroscopy) the surgical approach makes no sense whatsoever. Is the approach of D&C followed by corrective surgery in the best interest of patients? Absolutely not.

In my next post I will include modern studies on outcomes of treatment as evidence.

Continued in Part II

Asherman's syndrome after curettage is not rare

2009-08-04T22:39:00.000-07:00

Asherman's syndrome is ‘uncommon’. How many times have I come across that sentence or a variation of it (Asherman’s syndrome is ‘rare’ or even ‘extremely rare’ etc.). They were my ObGyn’s famous last words too. Oh, how I wish they were true. A simple google search of Asherman’s syndrome will show that many links contain this inaccuracy. Even the reputable ncbi/nih writes:

"Asherman syndrome is a rare condition. In most cases, it occurs in women who have had several dilatation and curettage (D&C) procedures."

No true!!! It often happens after a single D&C procedure. How often? Well, according to various studies published in peer-reviewed medical journals, the actual incidence of intrauterine adhesions (IUA) after D&C for miscarriage ranges between 7.7% and 30%, and after a repeat procecure, up to 40%. To be clear, some of these studies are not new. However, there is no reason to suspect that incidence rates would change as the techniques used are for the most part the same. The main cause of IUA is blind instrumentation in a uterus softened by the presence of hormones (as in pregnancy). Even the more recent manual vacuum aspiration has been associated with IUA (Dalton et al, 2006). Furthermore, sharp/blunt/suction D&C are often all used in the same procedure. Anyone who is familiar with the literature on Asherman’s syndrome will know that the references below are cited as references in recent review papers (see Yu et al,2008; Kodaman and Arici, 2007). [Obviously an institutional (or personal) subscription is needed to view the entire article]. Another potential criticism about these studies is that they are not RCTs. (One is an RCT but it does not meet the criteria for inclusion in the Cochrane Collaboration 's library (click here for more details). For non-scientists/doctors, I will describe what RCTs and the Cochrane library are in further detail in a later blog. For now, suffice to say that RCTs meet the most rigorous standards of scientific methodology.) Unfortunately, to date there are NO RCTs on Asherman’s syndrome (including etiology and treatment) in the Cochrane database.

Nevertheless, according to the available studies on the topic, the following incidence rates have been reported:

1. Adoni et al (1982) found the incidence of IUA to be 30.9% after D&C for a ‘late’ miscarriage. This is taken to mean a missed miscarriage where the products of conception have not been expelled despite the pregnancy’s failure. IUA were detected via hysterography.

2. Golan et al.(1992) did a prospective analysis of 60 women and found that 16.7% of women undergoing D&C for missed miscarriage had IUA detected by hysteroscopy (gold standard method of diagnosis).

3. Friedler et al (1993) also did a prospective study on women with missed miscarriages who underwent D&C and found that 16 of the 98 patients, or 16.3%, had IUA detected by hysteroscopy.

4. Romer et al’s (1994) prospective study diagnosed IUA in 30.2% of women who had D&C for either missed or incomplete miscarriage. This was diagnosed hysteroscopically.

5. Westendorp et al (1998) prospectively examined wome who had repeat D&C for incomplete miscarriage or retained POC (after either miscarriage or delivery) and found that on hysteroscopy, a whopping 40% of them had IUA. 30% were severe.

6. Tam et al (2002) performed a prospective study on IUA incidence after D&C for missed or incomplete miscarriage and compared it to women treated expectantly or using misoprostol. They found that 7.7% of women in the D&C group developed IUA while none developed it in the misoprostol group or expectant group. Again, hysteroscopy, was used for detection.

7. Eriksen and Kaestel (1960) reported in their retrospective analysis that approximately 25% of women undergoing post partum curettage developed IUA.

I don’t know about you, but I find all this unsettling. Why didn’t anyone tell me this before I had a D&C?!

Asherman’s syndrome is thought to affect 5% of the population. I don’t recall if there is a particular reference for this, but I know I’ve heard a few Asherman’s syndrome specialists say it. Of course it is difficult to know the exact prevalence as many cases are not diagnosed. Also, some women may have it but not desire a further pregnancy so they never find out if they are infertile or have pregnancy complications associated with Asherman’s syndrome.

What is striking is that this incidence (5%), is not very different from the rate of conditions such as PCOS, another cause of infertility (which, by the way, is not iatrogenic...) Yet, when do you ever hear people say: PCOS is a rare condition?! You will read everywhere that PCOS is ‘common’ or ‘exceedingly common’. There are entire sections of gynecology journals devoted to this condition and hundreds of studies. Asherman’s syndrome, in contrast, is largely ignored by the medical community. Are doctors repeating the supposed ‘rarity’ of Asherman’ syndrome to make women feel that D&Cs are safer than they really are?

Perhaps this misconception once served a purpose- to prevent doctors from hesitating to perform D&Cs in situations where uterine evacuation was necessary and in a time when there was no other option, and to prevent patients from fearing a necessary treatment. Today this myth no longer serves a purpose. D&C is no longer a ‘necessary evil’ as there are other methods such as hysteroscopic guidance or uterus-evacuating drugs to obtain the same result- minus the serious complications.
The first step towards change would be to accept that Asherman’s syndrome is NOT rare.

References (in order of appearance in text)
Dalton VK, Saunders NA,Harris LH, Williams JA, Lebovic DI. Intrauterine adhesions after manual vacuum aspiration for early pregnancy failure. Fertil Steril 2006;85(6):1823 e1-3.
Kodaman, PH and Arici, A. Intra-uterine adhesions and fertility outcome: how to optimize success? Curr Opin Obstet Gynecol 2007;19(3):207-14.

Yu, D, Wong, YM, Cheong, Y, Xia, E, and Li, TC. Asherman syndrome--one century later. Fertil Steril 2008;89(4):759-79.

Adoni, A, Palti, Z, Milwidsky, A, and Dolberg, M. The incidence of intrauterine adhesions following spontaneous abortion. Int J Fertil 1982;27(2):117-8.

Golan, A, Schneider, D, Avrech, O, Raziel, A, Bukovsky, I, and Caspi, E. Hysteroscopic findings after missed abortion. Fertil Steril 1992;58(3):508-10.

Friedler, S, Margalioth, EJ, Kafka, I, and Yaffe, H. Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy--a prospective study. Hum Reprod 1993;8(3):442-4.

Romer, T. Post-abortion-hysteroscopy--a method for early diagnosis of congenital and acquired intrauterine causes of abortions. Eur J Obstet Gynecol Reprod Biol 1994;57(3):171-3.

Tam, WH, Lau, WC, Cheung, LP, Yuen, PM, and Chung, TK. Intrauterine adhesions after conservative and surgical management of spontaneous abortion. J Am Assoc Gynecol Laparosc 2002;9(2):182-5.

Westendorp, IC, Ankum, WM, Mol, BW, and Vonk, J. Prevalence of Asherman's syndrome after secondary removal of placental remnants or a repeat curettage for incomplete abortion. Hum Reprod 1998;13(12):3347-50.

Eriksen J, Kaestel C. The incidence of uterine atresia after post-partum curettage. A follow-up examination of 141 patients. Dan Med Bull 1960; 7:50-1.

Update on latest articles (29/7/09)

2009-07-28T19:28:00.000-07:00

I just did my regular NCBI Pubmed search using the keywords Asherman's syndrome and intrauterine adhesions and was glad to see 2 new articles:

1. Faivre E, Deffieux X, Mrazguia C, Gervaise A, Chauveaud-Lambling A, Frydman R, Fernandez H. Hysteroscopic management of residual trophoblastic tissue and reproductive outcome: a pilot study. J Minim Invasive Gynecol. 2009 Jul-Aug;16(4):487-90.

Click here to read abstract. This one is an observational study.

2. Thomson AJ, Abbott JA, Deans R, Kingston A, Vancaillie TG. The management of intrauterine synechiae. Curr Opin Obstet Gynecol. 2009 Aug;21(4):335-41.

Click here to read abstract. This one is a review on treatment and outcomes.

I haven't read them yet but will do so as soon as I get them, and will pass on any relevant information/comments. I am particularly happy to see that the first article proposes the use of hysteroscopic guidance instead of blind surgical curettage (ie. D&C) to remove retained products of conception (trophoblastic tissue). This would certainly be a step in the right direction. Prof. Herve Fernandez has notably another publication on hysteroscopic outcomes in patients with severe Asherman's syndrome.

The group leader of the second article, A/Prof Thierry Vancaillie, practices in Sydney, Australia, where I live and is one of a handful of 'A list' Asherman's specialists from around the world who who was recommended to me by the Asherman's International Support Group. He officially diagnosed my intrauterine adhesions.

Law suits and Asherman's syndrome: another failure for victims

2009-07-23T23:01:00.000-07:00

You would think that if a ObGyn that performed a 'straightforward, routine' D&C which resulted in intrauterine adhesions and infertility (ie. Asheman's syndrome) you would have legal recourse. Think again. The vast majority of these cases end up with the patient not winning any damages. Incredible but, sadly, true. This is why I am so gung-ho on replacing D&Cs with drug alternatives which currently exist. It's simple madness to go through with a D&C which can decimate your fertility while the doctor gets away with it scot free. No wonder D&C continues to be such a popular surgery- there is no incentive to stop or at least be a little more discrimminating in its use when doctors are not held accountable for the outcomes. So simple too, even an intern can do it and no one will find out if it was a disaster until the damage is already done!

I would love for there to be an open list of doctors who caused Asherman's syndrome from D&Cs that were deemed to be simple and straighforward, not in any life-threatening emergency situation, for example (I'm more sympathetic to doctors who faced emergencies). This list would at least warn other women to avoid those doctors and have well-deserved repercussions on their wallets. It is afterall, their duty to care for their patients and not cause them harm and if they caused Asherman's syndrome from such a 'straightforward' procedure, they clearly breached their contract as a medical professional.

OK, I contend that it is difficult, maybe impossible, to not cause any damage from a D&C when you are poking objects into a small, soft, and fragile organ you cannot even see. But this is my point: if doctors want to continue pretending that it's acceptable to do D&Cs and stubbornly refuse to offer cheaper and less invasive drugs or a visually guided method like hysteroscopy, they should be held responsible for the consequences. As the situation stands, they continue to have their cake and eat it too. D&Cs, unlike hysteroscopy, do not require much skill (it’s hard to judge the outcome when the organ is concealed), and unlike misoprostol, it is financially rewarding to hospitals, Gyns/ObGyns, and anesthesiologists. Why would they want to work harder than they already do or earn less?

So why do these legal suits lose? One obvious reason is that medical malpractice suits have always been difficult to win because doctors are very well protected. Doctors are extremely supportive of each other and it is difficult to find a doctor who is willing to give expert medical advice in a case implicating a peer. This probably stems from reciprocity: "I'll scratch your back, if you scratch mine." Who knows if said medical expert will not face a malpractice suit (justified or not) some time in their career...

What perplexes me is that a lawyer can take on a medical case without having a medical or scientific degree or understanding basic health issues. Come to think of it, it is also somewhat disturbing that doctors don't need to be taught how to think objectively and critically to practice medicine, but I digress...

Defense lawyers and doctors will come up with all sorts of excuses to dismiss a valid medical case against them. This is where the Asherman's syndrome myths come in so handy. They are ‘facts’ which continue to be accepted without real evidence, often hypothesized decades ago at a time when well respected doctors in the field could formulate opinions without any scientific basis or need for clinical trials (no wonder some of them developed a ‘God complex’) and their peers believed them and even today continue to cite their published theories in the guise of ‘evidence’ in peer-reviewed medical journal articles. These opinions, in particular about Asherman’s syndrome, have over the years transformed into ‘dogma’ which medical school students are indoctrinated with. Somehow no one ever asks “Why are we blindly accepting what this doctor 50 years ago suggested when they didn’t have the advances in knowledge, diagnostic/surgical tools and understanding of evidence based medicine that we have today? ” Which leads me to wonder, as medicine is becoming more and more scientific in nature (evidence-based medicine), will this change the expected outcomes of some cases? I think it will inevitably do so. But there is still a long way to go.

I also wanted to mention a legal perspective which has always riled me in relation to Asherman's syndrome (I would think it also applies to other medical injuries affecting fertility): in a court of law where the nature of injury and of suffering are apparently graded, it makes no difference whether you had 10 children or none before the injury leading to infertility. Now, I know from the Asherman's International Support Group that such an attitude is promoted to keep the peace and encourage bonding (“we’re all in the same boat”), but to think that the law makes no distinction between someone who has been prevented from ever reproducing (a basic human right according to the United Nations charter) and someone who has done so is just plain cruel. There is no 'scientifically correct' answer to this, but one would think that the logical and instinctive answer is that the condition has more consequences for those who never had children before the injury than those who have.

It is difficult to find information about Asherman’s syndrome law suits on the internet, and judging by the number of visits this particular entry gets, it would appear to be an area that many women would like to learn more about. I have downloaded the few articles on lawsuits I have been able to find and will write another blog entry (one day) about what I find out from them. From a quick scan though, what I can say is that it appears that most of the successful lawsuits do not stem from injury of the D&C per se which caused Asherman’s syndrome, but from ‘negligence’ of a doctor to correctly identify and remove retained products of conception/placenta. It would appear that the law considers D&Cs an inherent risk, although curiously, women who give their ‘informed consent’ are rarely told of the specific risks of Asherman’s syndrome or the correct incidence rates.

The failure of justice for Asherman’s syndrome sufferers who underwent routine D&Cs for standard care is yet another argument in favour of Asherman’s syndrome prevention by replacing D&Cs with medical management or hysteroscopy…

(Opinion) Asherman's syndrome and abortion: A convenient misconception?

2009-07-09T01:08:00.000-07:00

In my last post I brought up the issue of abortion because usually the topic of Asherman's syndrome only gets mentioned by the public in the context of abortion which is very misleading. I just want to remind you that the intention of this blog is not about abortion, but about Asherman's syndrome, D&C safety, medical ethics and alternatives to D&C.

As I mentioned in my last post, one reason for the misconception linking Asherman's syndrome only to abortion is that doctors rarely address the point by clarifying that:

-There are ways to perform abortions without the use of surgery (D&C), therefore safely, so the point is irrelevant, and

-The same surgery as that used for abortions (D&C) is used commonly in gynecology and obstetrics.

In this youtube clip Dr Paul Indman, who is experienced in the treatment of Asherman's syndrome, states that the condition is more often seen in women after a D&C for miscarriage or retained placenta, especially when repeated, than in women who have had a D&C for abortion.

Despite this medically known fact, this and many other myths about Asherman's syndrome continue to linger. Please watch my youtube clip.

Many women who have had Asherman’s syndrome from a D&C, myself included, feel strongly that D&Cs should not be performed, whether they are for miscarriages, diagnostic purposes or for abortion. Yet many doctors-even some Asherman's syndrome experts- are adamant that D&Cs can never be replaced, something which I as a PhD scientist and student of Public Health and Evidence Based Medicine know for a fact is untrue after having read several clinical trials on misoprostol use for miscarriage management (1)(2)(3)(4)(5). In some parts of Europe misoprostol has gained acceptance as a valid alternative to D&C. Perhaps the absence of anti-abortion activists and strong religious influences accounts for the widespread availability of misoprostol and mifepristone in Switzerland and some parts of Europe.

Therefore doctors continue to perform D&C even though it is known that complications can occur, and that there are some good alternatives including drugs for uterine evacuation (eg. miscarriage, retained placenta, abortion) and hysteroscopy for uterine surgery (eg. fibroids, polyps) and in selected cases for miscarriage management (6). Only about 15% of US Gynecologists are trained in office hysteroscopy. The drug misoprostol, for example, is very cheap and there are no surgery related costs including anesthesia or operating room costs. Yet women in developed countries continue to have their reproductive organ-their endometrium-mutilated by the continued use of D&Cs.

Could it be that many doctors see it's in their best interest to stick to D&Cs which are more financially rewarding than prescribing drugs and less skill intensive than hysteroscopy? It may even be convenient that this whole D&C safety issue can be covered up by the abortion debate. There's nothing like a moral controversy to hide inconvenient truths. It is also a good way to deny responsibility for what is really an iatrogenic condition, avoiding law suits. In fact, doctors refrain from using the word 'iatrogenic' when describing Asherman's syndrome, yet it is more often than not the case. Their attitude towards abortion is different though. Abortion is a woman's choice, and they reason that if she chooses to have an abortion and her uterus ends up scarred by the D&C, it was the result of her own choice (not really because anyone should be given informed consent, but that is how some people might see it). They may feel it is more important to warn women about the risks of abortions- which she could (and perhaps in their mind 'should') choose not to have- than a miscarriage, which a woman has no control over. Or they may reason that women who abort should be given drugs instead of surgery to reduce the risk of infertility resulting from her own decision. I saw this inconsistent line of thinking in a paper and felt it was offensive. The medical community is doing a big disservice to women when it does not point out that these complications happen to women who never chose to miscarry, or have D&Cs imposed on them for other reasons. It is equally unacceptable for women to develop fertility and/or obstetric complications from a D&C for treating a miscarriage or for other reasons that were not of her own choice. All women need to be protected equally from potential harm.

Whether the present situation is due to ignorance, moral confusion or denial on the part of many doctors about possible complications from D&C and alternative treatments, something needs to be done to change current mentality and awareness of the problem. Already over a century has passed since the link between Asherman's syndrome and D&C was first made (7). In some countries at least, blind surgery continues...and worst of all, possibly due to a warped argument of 'morality'.

References

(Please note that in medical terminology, 'abortion' is often used s a synonym for 'miscarriage' and does not refer to elective termination...which probably fuels myths among people who don't understand this.)

1. Moodliar, S, Bagratee, JS, and Moodley, J. Medical vs. surgical evacuation of first-trimester spontaneous abortion. Int J Gynaecol Obstet 2005;91(1):21-6.

2. Bique, C, Usta, M, Debora, B, Chong, E, Westheimer, E, and Winikoff, B. Comparison of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion. Int J Gynaecol Obstet 2007;98(3):222-6.

3. Weeks, A, Alia, G, Blum, J, Winikoff, B, Ekwaru, P, Durocher, J et al. A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion. Obstet Gynecol 2005;106(3):540-7.

4. Shwekerela, B, Kalumuna, R, Kipingili, R, Mashaka, N, Westheimer, E, Clark, W et al. Misoprostol for treatment of incomplete abortion at the regional hospital level: results from Tanzania. Bjog 2007;114(11):1363-7.

5. Dao, B, Blum, J, Thieba, B, Raghavan, S, Ouedraego, M, Lankoande, J et al. Is misoprostol a safe, effective and acceptable alternative to manual vacuum aspiration for postabortion care? Results from a randomised trial in Burkina Faso, West Africa. Bjog 2007;114(11):1368-75.

6. Goldenberg, M., Schiff, E.' Achiron, R.' Lipitz, S.' Mashiach, S. Managing residual trophoblastic tissue. Hysteroscopy for directing curettage. J Reprod Med. 42(1)26-8.

7.Fritsch, H. Ein Fall von volligem Schwaund der Gebormutterhohle nach Auskratzung Zentralbl Gynaekol 1894;18:1337-1342.

Opinion: Abortion debate masks real issues on D&C safety

2009-07-05T21:13:00.000-07:00

Unfortunately, I have become all too aware of the distortion of medical facts and findings since being diagnosed with Asherman' syndrome in 2007 following a D&C for incomplete miscarriage (I have never had an abortion). High on the list of misinformation about Asherman's syndrome, a complication of D&C, is that it is caused only by abortion. One can never repeat enough that Asherman's syndrome as well as other complications result from D&C, NOT 'abortion' per se. Abortion is just a 'reason' for performing the D&C, the same way a miscarriage, or retained placenta for example, are. As I explained in the introductory blog, D&C is (unfortunately) used commonly in gynecology and obstetrics to treat everything from fibroids and polyps to miscarriage and postpartum hemorrhage. There is sufficient evidence in the medical literature (and I will provide this in a future post) that the incidences of Asherman's syndrome are roughly the same or even lower following D&C performed for termination, than those following miscarriage and delivery.

It is well known that women who undergo repeated dilation and curettage (or even a single dilation of over 12 mm) are at a high risk of cervical incompetence (cervical insufficiency) which is thought to account for second trimester pregnancy loss in women with a history of Asherman's syndrome (1). This particular complication is not caused by the endometrial damage itself (ie. adhesions or fibrosis of Asherman's syndrome) but as a by-product of the stretching or dilating (as in 'dilation and curettage of D&C) of the cervix during D&C (which caused the Asherman's syndrome) and also during corrective surgery to remove adhesions (hysteroscopic adhesiolysis).

Prolife proponents will often twist medical research findings to benefit their own anti-abortion agenda. Whenever a study shows increased obstetric or fertility complications following D&C, the message blaring from these lobbyists will be that abortion (not the medical technique of dilation and curettage) is the cause. As such, they completely ignore these risks apply equally to women who have a D&C for other causes, such as miscarriage, retained post partum placenta or other indications. By associating the procedure with such a highly contentious topic, all reasonable debate about the medical safety of the medical procedure is overtaken by an emotional moral debate about people's personal opinions regarding a woman's right to choose versus an embryos right to life.

For example, an oral presentation given at the recent 25th annual meeting of ESHRE (European Society of Human Reproduction and Embryology) in Amsterdam (28 June-1 July 2009. Click here to read the original press release on the oral presentation) "Complications early in pregnancy or in previous pregnancies adversely affect existing or subsequent pregnancies" summarized that:

"The researchers found that a history of one or more miscarriages nearly doubled the risk in an ongoing pregnancy of preterm premature rupture of the membrane that surrounds the baby in the womb, and increased the risk of premature or very premature delivery."

and

"Recurrent miscarriages (three or more miscarriages) increased the risk in a subsequent pregnancy of all of these conditions; in addition, it increased the risk of placenta praevia (where the placenta partially or completely blocks the cervix) six-fold and congenital malformations nearly two-fold."

Then there is the logical mention of abortion since the two are linked to D&C:

"If a previous pregnancy had to be terminated for any reason, this increased the risk of premature rupture of the membrane, premature and very premature delivery in subsequent pregnancies."

It seems obvious that the reason for these complications is that D&Cs are often used to treat miscarriages AND for terminations. Hence, women who have been exposed to D&Cs for either miscarriages or abortion would both be at a risk for D&C-related complications.

Yet prolife proponents insist on interpreting medical data as above with a moral view instead of a scientifically rigorous one. This is demonstrated by the scientifically illogical reasoning of Josephine Quintavalle, of the campaign group Comment On Reproductive Ethics, in response to the above findings:

"There's a logic. The body is protecting a healthy baby. By producing an abortion, you destroy that protection and make the cervix - the neck of the womb - more vulnerable.
And if you make the cervix more vulnerable, you are more at risk of a premature baby."

The problem with that explanation is that the cervix is weakened whether or not there is a 'baby' (healthy or not) in the womb because cervical dilation (D&C stands dilation and curettage) stretches the cervix open so that instruments can access the uterus. If the cervix had some sort of 'moral' sensor as Ms Quintavalle seems to believe, D&Cs and dilations for reasons other than abortion should not lead to cervical insufficiency or preterm births. The medical fact however is that the same complications occur after an abortion as after repeated dilation even if there is a dead baby inside (ie. a miscarriage) or the remains of a miscarriage, or polyps, or for any reason a D&C is used, or a cervix is mechanically stretched.

What has been happening for decades is that complications of D&C are being hijacked by those on the prolife side of the abortion debate as 'arguments' against abortion. They also hope it can be used to scare women from terminating pregnancies. This simplistic argument overlooks the fact that there are ways to abort without surgery: mifepristone (RU486) and misoprostol (Cytotec), to name the most popular drugs which can be used instead of D&C. (Note: Not surprisingly, the prolifers in the know about this also disseminate false information about the risks of these drugs to scare women). They are also behind the movement banning these drugs from being carried by most pharmacies or prescribed by private doctors. Unfortunately, this fixation on the rights of embryonic life is at the expense of the thousands, if not millions, of women who are only given the option of D&C for other indications. It seems that to these prolifers, it is more important to prevent abortion than to prevent all women, even those who miscarry or have delivery complications, from being subjected to the risks and complications of D&C including future infertility and/or life-threatening obstetric complications such as placenta accreta. In other words, they consider an embryo to have have more of a right to life than an adult woman. The biggest irony, however, is that these drugs which can replace D&C are often only available in abortion clinics but not to women who miscarry! As a society, we should be asking ourselves why this is so.

Meanwhile, I frequently hear from those on the prochoice side of the abortion debate, denials about the risks associated with abortion probably because they do not want to have this 'inconvenient truth' tarnish women's 'freedom of choice'. Presumably they are also unaware that drugs can replace D&C so the argument is invalid to begin with. What they also fail to realize is that D&Cs are hardly a 'feminist'option. Consider what the procedure is: a doctor inserts sharp and/or an extremely powerful suctioning instrument into a sexual reproductive organ which contains fragile tissue (the endometrium) necessary for implantation and a normal pregnancy and then scrapes at it without even being able to see what they are doing! On top of this, the doctor usually doesn't tell them that complications are not uncommon and that if he makes a mistake and renders them infertile, chances are he will get away with it ($1,000 richer). In my opinion, a woman's right includes the right to be accurately informed about the true risks of a procedure and the right to be given other available options regarding what is done to her body.

So the real issue here-that is, the health and fertility risks of blind surgery (D&C)- is being clouded by the abortion debate. Who benefits from this? Certainly NOT women.

As someone who developed Asherman's syndrome after a D&C for incomplete miscarriage, I feel that the myth that only abortion causes complications should be actively dispelled. Firstly, it stigmatizes all women who have Asherman's syndrome by associating their condition with the highly controversial issue of abortion. It suggests that any woman with Asherman's syndrome is 'responsible' for her situation when in truth she may have done nothing of her choosing to cause it. It may also be one of the reasons that women with Asherman's syndrome often prefer to stay anonymous about it. The second reason it must be dispelled is because it is a distraction from the real issue-the risks of D&C. It hides the fact that in the 21st century, women are being subjected to blind surgery of the reproductive organs, which causes injury (possibly impairing fertility) in up to 31% of cases (2) DESPITE THE EXISTENCE OF SAFE, NON-INVASIVE, EFFECTIVE ALTERNATIVES. The uninformed view that only abortion causes complications will come as a rude shock to women who get these complications from D&Cs (or uterine surgery) for other reasons. But it is too late for them. The third and most important reason it must be debunked in particular is that the misinformation about risks is the reason why D&Cs continue to be performed for all types of reasons and why complications from them continue to occur. Prevention is not being practiced even though use of drugs could significantly reduce the number of D&Cs and subsequent complications.

There is undoubtedly much ignorance in the public arena concerning gynecological procedures and what they are used for unless people have undergone it themselves or have a medical or paramedical background. This explains in part why these false ideas continue to flourish. What is less clear is why the medical community does not step forward to dismiss these so-called arguments. Could this possibly be because D&Cs are one of the most common procedures on women of reproductive age and that admitting that all D&Cs carry a risk would mean this veritable 'industry' of blind surgery (and associated income)? Little experience is needed to perform D&Cs, unlike hysteroscopy, and if drugs such as misoprostol can replace D&Cs, the money will go to the pharmaceutical companies that produce it, instead of the ObGyn, Hospital and Anesthesiologist. Also, could an uneasiness with performing terminations be the reason why medical management is used for abortions but not for miscarriages? In other words, do doctors themselves, or medical bodies feel it is 'unethical' to perform abortions and so prefer to gain as little from it as possible or play a less active role in the procedure than with a D&C?

Surgery- and complications from that surgery-do not discrimminate between what is morally 'right' or 'wrong'- people do. Science cannot answer whether it is ethical to terminate a pregnancy but it can frame the debate by showing that complications from D&C exist, regardless of the moral context in which it is used. For the informed person, the issue should not be 'should abortions must be banned because of possible complications?' but 'should the medical community continue to perform D&Cs on women-for any reason- when these complications exist and alternatives are available?'

References:

(1) Capella-Allouc S, Morsad F, Rongieres-Bertrand C, et al. (1999). "Hysteroscopic treatment of severe Asherman's syndrome and subsequent fertility". Hum Reprod 14 (5): 1230–1233. PMID 10325268
(2) Adoni A, Palti Z, Milwidsky A, Dolberg M. (1982). "The incidence of intrauterine adhesions following spontaneous abortion". Int J Fertil. 27 (2): 117–118.