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.
Tuesday, February 9, 2010
Tuesday, February 2, 2010
Database of ObGyns who offer misoprostol for treatment of miscarriage
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.
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.
Saturday, January 30, 2010
A hidden cause of ‘unexplained’ infertility and miscarriages: ignorance about AS
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. What all of this suggests is that doctors are and have always been reluctant not only to admitting responsibility for injuring, but also that the current treatment cannot restore reproductive function in every case (even if the uterine cavity is open). 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 shockingly ignorant 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 jaw-droppingly ill-informed review on Asherman's syndrome I have ever come across. Perhaps I can go into the details of all of the inaccuracies 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 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 do not detect the presence of IUA and 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 bizarre 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 complacency 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 even though they carry more risks and provide zero information about the presence of IUA. In the following
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.
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.
Tuesday, December 15, 2009
Miscarriage management after Asherman’s syndrome
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 gram 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 110-15/65-70) 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.
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.
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 gram 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 110-15/65-70) 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.
Thursday, November 26, 2009
Misprostol for miscarriage management to prevent Asherman's syndrome
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.
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.
Tuesday, November 17, 2009
In Memory
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."
Monday, October 19, 2009
The 'subclinical' infection myth (Part I)
Many doctors will have you believe that infection at the time of surgery (eg D&C) is always a factor in the development of intrauterine adhesions (Asherman’s syndrome-AS). I’m not talking about endometrial tuberculosis which is a known cause of AS which occurs primarily in developing countries. I’m talking about the garden variety bacterial infections. Yet there is no convincing medical evidence that this is so. To be fair, the more rational articles state that the role of infection in the development of AS is controversial (1),(2),(3). While I agree it may be possible that a very severe infection may in some cases lead to endometrial damage and ensuing AS, many doctors think that AS occurs as a result of infection even in women with no signs of infection. This is because many women who develop AS do not have signs of infection when they were operated on or afterwards. It's important to point out that prophylactic use of antibiotics is routine during D&C and yet D&C is still the number one cause of AS. In my own case, I was given very strong doses of metronidazole and cephalosporin as prophylactic treatment a week prior to my D&C (for incomplete miscarriage) and continued for a week after and yet I still developed moderately severe AS. I had no signs of infection before I started the antibiotics nor afterwards.
It was Rabau and David (1963) who initially put forth the idea that infection is the 'primum movens' of adhesions (4). Others disagreed. Polishuk et al (1975) concluded that infection alone does not play a role in the formation of IUA after cesarean section (5). They found no difference in the incidence of IUA in women with and without severe clinical endometritis (ie. uterine infection) who had undergone c-section. In another study, Jensen and Stromme (1972) found that infection was not implicated in the formation of IUA: none of the women who developed IUA after curettage had any sign of infection; there was no detectable difference in the number of inflammatory cells, the amount of degeneration, and the tissue edema in the pathologic examination of the uterine material curetted from patients with and without IUA (6).
To overcome this paradox of absence of symptoms of infection, some doctors have now ‘ingeniously’ coined the theory that ‘subclinical’ infection underlies all cases of AS. In other words, infection that cannot be proven (no signs of fever, discharge etc) is now supposedly considered to be one of the underlying causes of AS. Such reasoning is not evidence-based and cunningly absolves itself from the normal obligation of evidence-based medicine to be proven. Scientific/medical evidence is when you can prove a theory, not when you cannot disprove it because of a catch-22.
There are many findings which make it highly unlikely that ‘subclinical’ infection underlies AS:
1. the failure of antibiotics to prevent AS
2. the fact that many women who do have infections but do not have D&C do not develop AS*
3. the fact that there is no difference in the rate of infections in women who do and do not go on to develop AS
4. the fact that most women with PID, despite having tubal adhesions, do not have AS
5. the fact that many women who develop AS after D&C do not have tubal adhesions (because the damage is caused by instrumentation and the curette is unable to reach the inside of the tubes).
6. the fact that women who undergo medical uterine evacuation (ie with drugs instead of D&C) do not develop AS
7. Since subclinical infections harbor no symptoms, who is to say that women who never go on to develop AS also had them?
* With the exception of genital tuberculosis.
I want to share some anecdotal ‘evidence’ with regards to point 2. which is almost as valid as any case report. I have an aunt who gave birth in Cyprus many years ago with only the help of a traditional midwife. The whole placenta did not deliver but the midwife didn’t inform my aunt who later became seriously ill with high fever and other signs of infection. Finally, about a week later a blackened piece of necrosed placenta was expelled. She obviously had a bad infection and yet she never had any future problems conceiving two more children. She never had any miscarriages, obstetric complications or delivery problems which would be indicative of AS or endometrial damage.
Similarly, my grandmother was hospitalized for septicemia after my mother’s birth and she too went on to have two more children without any complications whatsoever.
The only reason why doctors would insist that infection IS a factor in the development of AS without actual evidence is to be able to exonerate themselves from blame for the unfortunate consequence of surgery they performed. And better yet, to lay the blame on the patient.
Even if it were true, the fact would still remain that AS is more often than not an iatrogenic condition because it is a well known fact that invasive surgery is a risk factor for infection. D&C introduces the possibility of bringing foreign bacteria into a woman’s uterus or even of bringing bacteria in the lower genital tract into the uterus where it can spread to the tubes and cause PID which can lead to tubal factor infertility. This itself should be a reason why D&C should not be performed. It also does not clear AS from being an iatrogenic condition if infection is either introduced or spread by surgery.
Not only will antibiotic prophylaxis NOT prevent AS, it can also be harmful as I experienced personally. I was prescribed high doses of metronidazole and cephalosporin a week prior to my D&C for miscarriage. I had no signs of infection, but the doctor assured me that because “AS only develops as a result of infection” I was keen to take all preventative measures. I continued until about a week after the surgery. Five months later, still brainwashed by the "infection is the cause of AS” theory, I requested to be given prophylactic antibiotics prior to my diagnostic hysteroscopy, just in case I acquired an infection that would later cause or exacerbate adhesions. I even requested more antibiotics from my GP to make sure I was covered for a week after the diagnostic hysteroscopy. Then 5 months later again I underwent operative hysteroscopy to remove the stage III adhesions I had been diagnosed with. Once again I took prophylactic antibiotics, not just to cover for surgery, but for the whole length of time I had a uterine stent inserted (2 weeks). One month later I was hospitalized with Clostridium difficile pseudomembranous colitis. This is a potentially life-threatening condition which occurs when the normal intestinal flora is wiped out by antibiotic use, usually broad spectrum antibiotics. This allows the pathogenic bacteria Clostridium difficile to rapidly multiply and colonise the intestines, releasing harmful toxins which cause bleeding and can perforate the bowel and cause death. I should emphasize that I am otherwise very healthy with no underlying medical conditions. I’d never been hospitalized before. I was treated with another antibiotic- vancomycin, which targets C. difficile. It is also the most powerful antibiotic available, often given as a last resort when all other antibiotics fail. I was concerned about developing resistence to vancomycin for this reason. As a result of my C. difficile colitis I will have to be very careful about antibiotic use in future. It is ironic that I acquired not one, but TWO iatrogenic illnesses as a consequence of D&C.
Abusing antibiotics is never a good idea as it leads to antibiotic resistance, and without effective antibiotics for common illnesses we will revert to an age where people died of simple bacterial infections. Furthermore, it is unreasonable to believe that antibiotics can prevent AS and although prophylaxis may offer some protection against other conditions (eg. PID), it should be used carefully and sparingly. Antibiotic use should not be used to offer patients a false sense of security that they will not develop AS after D&C as I learned. It should NOT be regarded as a valid form of prevention of AS.
REFERENCES
1. Kodaman PH, Arici AA. (2007). "Intra-uterine adhesions and fertility outcome: how to optimize success?". Curr Opin Obstet Gynecol 19 (3): 207–214.
2. Yu D, Li T, Xia E, Huang X, Peng X. (2008). "Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman's syndrome". Fertility and Sterility 89 (3): 715–722.
3. Schenker JG, Margalioth EJ. (1982). "Intra-uterine adhesions: an updated appraisal". Fertility and Sterility 37 (5): 593–610.
4. RABAU E, DAVID A. INTRAUTERINE ADHESIONS: ETIOLOGY, PREVENTION, AND TREATMENT. Obstet Gynecol. 1963;22:626–629.
5. Polishuk, SO Anteby and D Weinstein, Puerperal endometritis and intrauterine adhesions, Int Surg 60 (1975), pp. 418–420.
6. Jensen, P.A. and Stromme, W.B. (1972) Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am. J. Obstet. Gynecol., 113, 150–154.
It was Rabau and David (1963) who initially put forth the idea that infection is the 'primum movens' of adhesions (4). Others disagreed. Polishuk et al (1975) concluded that infection alone does not play a role in the formation of IUA after cesarean section (5). They found no difference in the incidence of IUA in women with and without severe clinical endometritis (ie. uterine infection) who had undergone c-section. In another study, Jensen and Stromme (1972) found that infection was not implicated in the formation of IUA: none of the women who developed IUA after curettage had any sign of infection; there was no detectable difference in the number of inflammatory cells, the amount of degeneration, and the tissue edema in the pathologic examination of the uterine material curetted from patients with and without IUA (6).
To overcome this paradox of absence of symptoms of infection, some doctors have now ‘ingeniously’ coined the theory that ‘subclinical’ infection underlies all cases of AS. In other words, infection that cannot be proven (no signs of fever, discharge etc) is now supposedly considered to be one of the underlying causes of AS. Such reasoning is not evidence-based and cunningly absolves itself from the normal obligation of evidence-based medicine to be proven. Scientific/medical evidence is when you can prove a theory, not when you cannot disprove it because of a catch-22.
There are many findings which make it highly unlikely that ‘subclinical’ infection underlies AS:
1. the failure of antibiotics to prevent AS
2. the fact that many women who do have infections but do not have D&C do not develop AS*
3. the fact that there is no difference in the rate of infections in women who do and do not go on to develop AS
4. the fact that most women with PID, despite having tubal adhesions, do not have AS
5. the fact that many women who develop AS after D&C do not have tubal adhesions (because the damage is caused by instrumentation and the curette is unable to reach the inside of the tubes).
6. the fact that women who undergo medical uterine evacuation (ie with drugs instead of D&C) do not develop AS
7. Since subclinical infections harbor no symptoms, who is to say that women who never go on to develop AS also had them?
* With the exception of genital tuberculosis.
I want to share some anecdotal ‘evidence’ with regards to point 2. which is almost as valid as any case report. I have an aunt who gave birth in Cyprus many years ago with only the help of a traditional midwife. The whole placenta did not deliver but the midwife didn’t inform my aunt who later became seriously ill with high fever and other signs of infection. Finally, about a week later a blackened piece of necrosed placenta was expelled. She obviously had a bad infection and yet she never had any future problems conceiving two more children. She never had any miscarriages, obstetric complications or delivery problems which would be indicative of AS or endometrial damage.
Similarly, my grandmother was hospitalized for septicemia after my mother’s birth and she too went on to have two more children without any complications whatsoever.
The only reason why doctors would insist that infection IS a factor in the development of AS without actual evidence is to be able to exonerate themselves from blame for the unfortunate consequence of surgery they performed. And better yet, to lay the blame on the patient.
Even if it were true, the fact would still remain that AS is more often than not an iatrogenic condition because it is a well known fact that invasive surgery is a risk factor for infection. D&C introduces the possibility of bringing foreign bacteria into a woman’s uterus or even of bringing bacteria in the lower genital tract into the uterus where it can spread to the tubes and cause PID which can lead to tubal factor infertility. This itself should be a reason why D&C should not be performed. It also does not clear AS from being an iatrogenic condition if infection is either introduced or spread by surgery.
Not only will antibiotic prophylaxis NOT prevent AS, it can also be harmful as I experienced personally. I was prescribed high doses of metronidazole and cephalosporin a week prior to my D&C for miscarriage. I had no signs of infection, but the doctor assured me that because “AS only develops as a result of infection” I was keen to take all preventative measures. I continued until about a week after the surgery. Five months later, still brainwashed by the "infection is the cause of AS” theory, I requested to be given prophylactic antibiotics prior to my diagnostic hysteroscopy, just in case I acquired an infection that would later cause or exacerbate adhesions. I even requested more antibiotics from my GP to make sure I was covered for a week after the diagnostic hysteroscopy. Then 5 months later again I underwent operative hysteroscopy to remove the stage III adhesions I had been diagnosed with. Once again I took prophylactic antibiotics, not just to cover for surgery, but for the whole length of time I had a uterine stent inserted (2 weeks). One month later I was hospitalized with Clostridium difficile pseudomembranous colitis. This is a potentially life-threatening condition which occurs when the normal intestinal flora is wiped out by antibiotic use, usually broad spectrum antibiotics. This allows the pathogenic bacteria Clostridium difficile to rapidly multiply and colonise the intestines, releasing harmful toxins which cause bleeding and can perforate the bowel and cause death. I should emphasize that I am otherwise very healthy with no underlying medical conditions. I’d never been hospitalized before. I was treated with another antibiotic- vancomycin, which targets C. difficile. It is also the most powerful antibiotic available, often given as a last resort when all other antibiotics fail. I was concerned about developing resistence to vancomycin for this reason. As a result of my C. difficile colitis I will have to be very careful about antibiotic use in future. It is ironic that I acquired not one, but TWO iatrogenic illnesses as a consequence of D&C.
Abusing antibiotics is never a good idea as it leads to antibiotic resistance, and without effective antibiotics for common illnesses we will revert to an age where people died of simple bacterial infections. Furthermore, it is unreasonable to believe that antibiotics can prevent AS and although prophylaxis may offer some protection against other conditions (eg. PID), it should be used carefully and sparingly. Antibiotic use should not be used to offer patients a false sense of security that they will not develop AS after D&C as I learned. It should NOT be regarded as a valid form of prevention of AS.
REFERENCES
1. Kodaman PH, Arici AA. (2007). "Intra-uterine adhesions and fertility outcome: how to optimize success?". Curr Opin Obstet Gynecol 19 (3): 207–214.
2. Yu D, Li T, Xia E, Huang X, Peng X. (2008). "Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asherman's syndrome". Fertility and Sterility 89 (3): 715–722.
3. Schenker JG, Margalioth EJ. (1982). "Intra-uterine adhesions: an updated appraisal". Fertility and Sterility 37 (5): 593–610.
4. RABAU E, DAVID A. INTRAUTERINE ADHESIONS: ETIOLOGY, PREVENTION, AND TREATMENT. Obstet Gynecol. 1963;22:626–629.
5. Polishuk, SO Anteby and D Weinstein, Puerperal endometritis and intrauterine adhesions, Int Surg 60 (1975), pp. 418–420.
6. Jensen, P.A. and Stromme, W.B. (1972) Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am. J. Obstet. Gynecol., 113, 150–154.
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