tag:blogger.com,1999:blog-38573357663216997482024-03-19T02:49:02.242-07:00Asherman's syndrome watchA blog that aims to increase awareness about the condition, particularly its causes and sequelae, encourage scientifically sound discussions about it, and promote its prevention.Unknownnoreply@blogger.comBlogger46125tag:blogger.com,1999:blog-3857335766321699748.post-79173688459628193842013-05-15T02:07:00.001-07:002013-05-15T02:07:18.509-07:00Steps in the right direction
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<span style="font-family: Calibri;">Since first starting this blog in 2009, medical management
of miscarriage has become more accessible in Australia. To my knowledge, the
Royal Prince Alfred Hospital routinely offers medical management as an
alternative to surgical and expectant management. The Royal Hospital for Women
also mentions it as one the services it provides (<a href="http://www.seslhd.health.nsw.gov.au/rhw/Manuals/documents/Early%20Pregnancy/Miscarriage%20-%20Medical%20Management.pdf" target="_blank">link to protocol</a>).
Also, during a course I took as part of my degree, lectures by fertility
specialists have included the topic of intrauterine adhesions/Asherman’s
syndrome and the use of medical management for miscarriage. A study on the
prevalence of IUA after repeat curettage (D&C) has been awarded funding by
the Australasian Gynaecological Endoscopy Society. These are all positive steps,
and signs that the condition and medical management of miscarriage are gaining
awareness. Of course, further awareness by the public and non-specialist
doctors is still necessary, that is why this site exists. I will no longer be
blogging except to complete older posts, but this site will continue to be
available as a source of information for clinicians, patients and all women
faced with a decision about whether to undergo a D&C or those who are
experiencing symptoms of IUA and are looking for an answer. </span></div>
<span style="font-family: "Calibri","sans-serif"; font-size: 11pt; line-height: 115%; mso-ansi-language: EN-AU; mso-ascii-theme-font: minor-latin; mso-bidi-font-family: "Times New Roman"; mso-bidi-language: AR-SA; mso-bidi-theme-font: minor-bidi; mso-fareast-font-family: Calibri; mso-fareast-language: EN-US; mso-fareast-theme-font: minor-latin; mso-hansi-theme-font: minor-latin;">Good bye and good luck. <span style="mso-tab-count: 1;"> </span></span>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-86370622041922529222012-08-02T00:30:00.001-07:002012-08-02T00:33:44.045-07:00When EBM is not really EBMThis post might seem a bit off-topic, but it's relevant to anyone who is interested in any type of human research. As you might be aware of, I'm a strong believer in evidence based medicine (EBM) and am currently studying for a Masters in Clinical Epidemiology. I find it scary that there even exist doctors who are against the concept of EBM (see <a href="http://www.kevinmd.com/blog/2011/10/evidence-based-medicine-removes-physicians-autonomy.html">http://www.kevinmd.com/blog/2011/10/evidence-based-medicine-removes-physicians-autonomy.html</a>). However, I've also become aware of the highjacking of EBM to suit researchers' or governments' agendas. I have sometimes been stuck by the contradiction between what I am being taught and what is being touted as 'accepted evidence' or a 'valid' study the next minute. Of course researchers are human and we all have our opinions and beliefs (not to mention prejudices) that will spill over into research. Many researchers become interested in a topic because of a personal experience which sparked an interest in contributing to or improving research in that area because they had gained a personal insight into the problem that previous researchers missed. Improving patient care is a great reason to support human research and EBM. On the other hand, there are researchers who, motivated by personal gain whether this is career advancement, religious/'moral' beliefs, or financial gain, manipulate research using their credentials as 'evidence based researchers' to bias research outcomes. This is the complete opposite of what they are claiming to be doing, to the great detriment of EBM. Sometimes fear underlies their motivations because their research or investigation could show something the government or their peers did not want to acknowledge, resulting in law suits, medical scandals, or ridicule and it could spell the end of their career. The following article from the Indian Journal of Medical Ethics outlines some of the ways research can be exploited to 'prove' what the researchers want it to prove:<br />
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Evidence based medicine: can the evidence be trusted? by Prathap Tharyan<br />
<a href="http://www.issuesinmedicalethics.org/issue194.html"><strong><span style="font-size: x-small;">Indian J Med
Ethics.2011 Oct-Dec;8(4)</span></strong></a>
<br />
<form action="http://www.ijme.in/cgi-bin/getpdf.cgi" id="pdf" method="post" name="pdf">
<input id="thefunc" name="thefunc" type="hidden" value="extr" /><input id="login" name="login" type="hidden" value="ijme" /><input id="password" name="password" type="hidden" value="#{7a0c0c6b3ce1ae6dd8a7312d53bff813}" /><input id="pdf" name="pdf" type="hidden" value="issue194.html.pdf" /><input id="start" name="start" type="hidden" value="203" /><input id="end" name="end" type="hidden" value="209" />Link to full text article:</form>
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<a href="http://www.issuesinmedicalethics.org/194ed203.html">http://www.issuesinmedicalethics.org/194ed203.html</a><br />
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No one can claim to have no agendas whatsoever when it comes to conducting their particular research. One could argue that researchers should be able to design and analyse their own research according to what they have been taught about EBM to reduce bias and to critically appraise research undertaken by others by those standards. I'm not sure all researchers are able to do this, particularly if they have been taught about scientific thinking after their formal education, not as part of it. It takes a special mind to question what professors may be teaching you are established 'facts' and no one wants to be accused of 'arrogance'. However, not everyone is capable of scientific thinking, lateral thinking or thinking outside the box, no matter how successful, experienced, skilled or well-respected they may be. <br />
<br />
For some areas of Gynecology and Obstetrics (such as Asherman's syndrome) it has not even reached the stage where EBM is being used much at all, so its manipulation is not the biggest problem. The first hurdle is to actually apply EBM to the field, which is desperately needed. There are however some areas where I can see some manipulation (not necessarily machiavellian) already, for example studies about misoprostol where low doses and short periods for assessing outcome are being used to 'prove' how poorly it performs compared to D&C. Another pitfall I see is something called 'intention to treat' or ITT. Although ITT is a non-controversial and accepted concept in EBM and I agree with all other aspects of EBM, this is one area that I question. ITT means that in a randomized controlled trial (RCT) those assigned to the experimental group (new treatment being tested) should be analyzed according to belonging to that group, and those assigned to the control (no treatment or standard treatment) should be analyzed according to the control group, REGARDLESS of whether they actually undergo those treatments. The rationale behind this is that, if for example 80% of the people in the experimental group decide not to take the new medicine, the drug will not be a success no matter how well it works because of patient non-compliance. This could be due to severe side-effects or inconvenience (you have to inject it whereas the standard drug can be taken orally). While I can understand its usefulness in assessing feasability of a treatment, it can be very misleading about actual outcomes, efficacy and even causal mechanisms. Imagine a study comparing the outcome of intrauterine adhesions (IUA) following miscarriage management by misoprostol or surgical curettage (D&C). If a low ineffective dose of misoprostol is dictated by the study design, or if the researchers decide that treatment will be evaluated after 48 hours instead of a week or two, or if they mistakenly diagnose retained products of conception by ultrasound (a common occurrence) after misoprostol treatment in a large portion of participants, these women will automatically be given the standard treatment which is D&C- in this case, the exact same treatment as the 'control' group! This means that study results according to ITT could inaccurately find that misoprostol 'causes' IUA and infertility, rather than that the misoprostol regimen was not given a fair go of success. In fact, even with irreproachable statistical methods, ITT can find that there is either 'no significant difference' or a significantly 'higher' rate of IUA among women in the misoprostol treatment group than in the D&C group depending on chance or on inclusion criteria (they may have included women with past D&Cs in both groups. See the MIST study). Although the logic is flawed, researchers could probably get away with arguing that this was 'proof' that IUA was not necessarily caused by instrumental injury to the endometrium and draw other naive conclusions, preventing progress in the field or prevention of the condition. <br />
<br />
The point of this post is to highlight that there is yet a long way to go in achieving trustworthy EBM, but it should remain the goal of all medical research and practice. Another important thing to note is that what may be accepted as medically 'sound' today (due to poorly designed studies masquerading as evidence based research) could appear ridiculous in a century- and vice versa. A good example of this is the Hungarian Obstetrician Ignaz Semmelweis, who first understood that the cause of 'childbed fever' (puerperal fever) was contamination by Obstetricians with unclean hands. How did this observation he proved affect his career? He was shunned by his peers who were 'offended' by the suggestion they wash their hands ("the nerve of him!"), and his views were dismissed ironically as being 'unscientific' (despite his experimental evidence that washing hands reduced mortality rates to below 1%) only because he was unable to explain why. It was only after his death that knowledge about microorganisms explained the association (the germ theory of disease), and his ideas about hand hygiene became understood and accepted into practice. He is one of the doctors whose rationale led to the emergence EBM, but he died alone (ironically of septicemia) with no glory, in a mental asylum (because of course anyone who rallied against accepted dogma was 'mentallly ill', see Foucault's biopower theory) and betrayed by all. I can see why some researchers would rather go with the flow, but to me Semmelweis was a courageous hero, ahead of his time in his thinking, while his detractors thought they were being scientific by parroting ideas they didn't fully comprehend ...or simply were not brave or caring enough about their patients.<br />
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<br />Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-258996639542901342012-06-19T00:34:00.000-07:002012-07-01T23:21:23.818-07:00Insights from an Asherman's syndrome expert (Part II)<br />
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<span style="font-family: Calibri;">Apologies for the long delay... To
recap, in my last blog post I gave a brief background about Dr Charles March of
California Fertility Partners and his vast experience on Asherman’s syndrome (AS),
which he summarizes in his last review, Management of Asherman’s syndrome
(1). Dr March’s article emphasizes many important
issues that are often overlooked and reconsiders the validity of accepted
beliefs. It’s clear throughout that he has given a lot of critical as well as
practical thought to different aspects of Asherman’s syndrome. <span style="mso-spacerun: yes;"> </span>The review starts off with a background
including the epidemiology of AS, symptoms and diagnosis, then management,
which he summarizes by the acronym PRACTICE, for <b style="mso-bidi-font-weight: normal;">pr</b>evention, <b style="mso-bidi-font-weight: normal;">a</b>nticipation,
<b style="mso-bidi-font-weight: normal;">c</b>omprehensive <b style="mso-bidi-font-weight: normal;">t</b>herapy, timely surveillance of subsequent pregnancies, <strong>i</strong>nvestigation (potential treatments
like anti-adhesive gels and vitamin supplementation to improve blood flow), and
<b style="mso-bidi-font-weight: normal;">c</b>ontinuing <b style="mso-bidi-font-weight: normal;">e</b>ducation (continuing medical education courses and literature). </span></div>
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<span style="font-family: Calibri;">I’ll focus on the parts of the review containing relevant
insights which I have not encountered in other reviews, or which are important
enough that repeating them is warranted. </span></div>
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<span style="font-family: Calibri;">General</span></div>
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<div class="MsoListParagraphCxSpFirst" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-indent: -18pt;">
<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">1.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">Asherman’s
syndrome is not rare.</b> He points out that most physicians believe that AS
occurs <span style="mso-spacerun: yes;"> </span>rarely and fail to diagnose it
even when a patients exhibits obvious symptoms. Table 1. (page 64 of the
article) displays convincingly that AS is not rare by showing the prevalence of
AS in different populations of women undergoing hysteroscopy, and the incidence
of AS after various procedures</span></div>
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<div class="MsoListParagraphCxSpLast" style="margin: 0cm 0cm 10pt 36pt; mso-list: l0 level1 lfo1; text-indent: -18pt;">
<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">2.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">The term
‘syndrome’ does not correctly describe the condition.</b> This is because the
condition has varying symptoms and pathology, from endometrial sclerosis
without intrauterine adhesions (IUA), to IUA without endometrial sclerosis. However,
he points out that Asherman’s syndrome encompasses all of the different
possible manifestations of endometrial injury, from all possible causes and
varying symptoms. For this reason he continues using the term instead of IUA or
traumatic amenorrhea. </span></div>
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<span style="font-family: Calibri;">Etiology</span></div>
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<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">3.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">AS most
commonly occurs after dilation and curettage during or shortly after a
pregnancy. However, diagnostic curettage may also lead to AS.</b> Ignorance
about this continues. I’ve heard several doctors who are not experts on AS and
probably haven’t read the literature on it claim that the condition only occurs
where there has been pregnancy and never in its absence. This old belief has
been proven to be untrue. Interestingly, Dr March mentions that curettage used
to be used during laparoscopy to investigate infertility, observing that this
probably caused more harm than good. It is very refreshing to hear doctors
reflect on their predecessors’ or colleagues’ mistakes and admitting that
sometimes what seems like a progressive approach turns out to be a step
backwards. </span></div>
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<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">4.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">There is
no evidence that uterine malformations such as Mullerian anomalies are more
prone to developing adhesions,</b> even though there is very strong evidence
that the two are associated. He points out that the correlation can be
explained by the high miscarriage rate- and subsequent D&Cs- among this
group of women. Another reminder that correlation is not evidence of causation.
The bottom line is that injury from surgical trauma (or TB in some countries)
is what causes AS, and there is a tendency for some authors to mystify the
condition by neglecting the obvious associated risk factor i.e. women with
Mullerian anomalies tend to have more D&Cs which lead to AS.<b style="mso-bidi-font-weight: normal;"> </b></span></div>
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<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-indent: -18pt;">
<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">5.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">There is
no evidence that infection leads to AS.</b> Dr March notes that infections
occurred in less than 1% of his patients. The Polishuk case series (2) showed that
among 171 women who underwent C-sections, of the 28 who had severe
endometritis, none developed de-novo adhesions (the one patient who did develop
cervical adhesions already had a previous history of AS from several
miscarriages treated by D&C (her AS was also ‘treated’ by D&C). <span style="mso-spacerun: yes;"> Furthermore, there are no studies whatsoever that show any evidence that endometritis alone leads to AS.</span></span></div>
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<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-indent: -18pt;">
<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">6.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">Endometriosis
may develop in AS with outflow obstruction and patent fallopian tube(s) if
treatment is delayed</b>. This is an important point that isn’t mentioned
enough in my opinion. It’s also another good reason why AS should be prevented or if it's too late, treated to prevent further problems:
it can lead to 2 fertility problems for the price of one (a bargain nobody
wants). </span></div>
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<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">7.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">Inexperienced
operators can inadvertently cause uterine damage. </b>New instrumentation and
technologies for intrauterine surgeries are proven to be safe by experts,
however they may not be so harmless if inexperienced operators use them.</span></div>
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<span style="font-family: Calibri;">Diagnosis</span></div>
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<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">8.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">Menstruation
and withdrawal bleeding cannot rule out AS.</b> Some women with IUA have normal
periods (‘eumenorrhea’) and some women with amenorrhea have withdrawal bleeding
after hormone administration. Therefore hysteroscopy is the gold standard for
diagnosis. (HSG and SIS can lead to false positives). However, the opposite is
true: women with hypomenorrhea or amenorrhea after intrauterine surgery are
likely to have IUA. </span></div>
<br />
<br />
<div class="MsoListParagraphCxSpMiddle" style="margin: 0cm 0cm 0pt 36pt; mso-list: l0 level1 lfo1; text-indent: -18pt;">
<span style="mso-bidi-font-family: Calibri; mso-bidi-theme-font: minor-latin;"><span style="mso-list: Ignore;"><span style="font-family: Calibri;">9.</span><span style="font-size-adjust: none; font-stretch: normal; font: 7pt/normal "Times New Roman";">
</span></span></span><span style="font-family: Calibri;"><b style="mso-bidi-font-weight: normal;">HSG and
SIS can rule out IUA, but cannot rule out endometrial sclerosis</b>, which can
be diagnosed by hysteroscopy. On the other hand, one important advantage of HSG
is that it provides information on the patency of fallopian tubes, which
hysteroscopy does not. Single or bilateral tubal obstruction is in some cases
caused by AS if adhesions occlude the ostia/ostium, so it is important to
confirm after corrective surgery that the adhesions have not reformed. A
partial or complete obstruction of one or both ostium can lead to tubal
pregnancy or infertility. </span></div>
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<br /></div>
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<span style="font-family: Calibri;">Next time: Dr March’s advice about prevention, treatment and
monitoring of post-AS pregnancies.</span></div>
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<br /></div>
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<span style="font-family: Calibri;">References</span></div>
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<span style="font-family: Calibri;">March C. Management of Asherman’s syndrome <a abstractlink="yes" alsec="jour" alterm="Reprod Biomed Online." aria-expanded="false" href="http://www.ncbi.nlm.nih.gov/pubmed/21549641#" role="button" title="Reproductive biomedicine online."><span style="font-family: Times New Roman;">Reprod Biomed Online.</span></a></span><span style="font-family: Times New Roman;"> 2011 Jul;23(1):63-76. </span></div>
<div class="MsoNormal" style="margin: 0cm 0cm 10pt;">
<span style="font-family: Verdana, sans-serif; font-size: x-small;">Polishuk WZ, Anteby SO, Weinstein D. Puerperal endometritis and intrauterine adhesions. </span><a abstractlink="yes" alsec="jour" alterm="Int Surg." aria-expanded="false" href="http://www.ncbi.nlm.nih.gov/pubmed/1158622#" role="button" title="International surgery."><span style="font-family: Verdana, sans-serif; font-size: x-small;">Int Surg.</span></a><span style="font-family: Verdana, sans-serif; font-size: x-small;"> 1975 Aug;60(8):418-20.</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-20402688570837475102011-12-14T17:32:00.000-08:002011-12-14T17:41:11.412-08:00When available studies are limited, expert opinions count<div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: "Trebuchet MS", sans-serif;">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<span style="mso-spacerun: yes;"> </span>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,<span style="mso-spacerun: yes;"> </span>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.</span></div><span style="font-family: "Trebuchet MS", sans-serif;"> </span><br />
<div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: "Trebuchet MS", sans-serif;">Dr Charles March of California Fertility Partners is a respected authority on Asherman’s syndrome. He is <span lang="EN" style="color: #534d3e; font-family: "Arial","sans-serif"; mso-ansi-language: EN;">board certified in Obstetrics and Gynecology and fellowship trained in Reproductive Endocrinology and Infertility and was a Professor at University of Southern California. </span>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.</span></div><span style="font-family: "Trebuchet MS", sans-serif;"> </span><br />
<div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: "Trebuchet MS", sans-serif;">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.</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-1290847596262052202011-11-24T05:02:00.000-08:002011-11-24T05:03:43.993-08:00Indispensable technique becomes disposable to boost its use<span style="font-family: Arial, Helvetica, sans-serif;">A new single-use disposable hysteroscope (</span><a href="http://hcp.obgyn.net/conference-insider/aagl2011/content/article/1760982/1976908"><span style="color: blue; font-family: Arial, Helvetica, sans-serif;">http://hcp.obgyn.net/conference-insider/aagl2011/content/article/1760982/1976908</span></a><span style="font-family: Arial, Helvetica, sans-serif;"> and </span><a href="http://hcp.obgyn.net/conference-insider/aagl2011/content/article/1760982/1980724"><span style="color: blue; font-family: Arial, Helvetica, sans-serif;">http://hcp.obgyn.net/conference-insider/aagl2011/content/article/1760982/1980724</span></a><span style="font-family: Arial, Helvetica, sans-serif;">) 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: </span><a href="http://medgadget.com/2007/01/femsuites_femey.html"><span style="color: blue; font-family: Arial, Helvetica, sans-serif;">http://medgadget.com/2007/01/femsuites_femey.html</span></a><br />
<span style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: Arial, Helvetica, sans-serif;">(Disclaimer: <span style="mso-spacerun: yes;"> </span>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).</span></div><span style="font-family: Arial, Helvetica, sans-serif;"> 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. </span><br />
<span style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: Arial, Helvetica, sans-serif;">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. <span style="mso-spacerun: yes;"> </span></span></div><span style="font-family: Arial, Helvetica, sans-serif;">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. </span><a href="http://www.obpmedical.com/v/vspfiles/assets/images/office%20hysteroscopy%20-%20a%20valuable%20but%20under-%20utilized%20technique.pdf"><span style="color: blue; font-family: Arial, Helvetica, sans-serif;">http://www.obpmedical.com/v/vspfiles/assets/images/office%20hysteroscopy%20-%20a%20valuable%20but%20under-%20utilized%20technique.pdf</span></a><span style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
<span style="font-family: Arial, Helvetica, sans-serif;"> </span><br />
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</div><div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: Arial, Helvetica, sans-serif;">REFERENCES</span></div><ol><li><span style="font-family: Arial, Helvetica, sans-serif;"><span style="color: #222222; font-family: "Arial","sans-serif"; line-height: 115%;">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. </span><span style="color: red; font-family: "Arial","sans-serif"; line-height: 115%;">Abstract</span><span style="color: #222222; font-family: "Arial","sans-serif"; line-height: 115%;"> <a href="http://www.springerlink.com/content/384125gp81055401/"><span style="color: blue;">http://www.springerlink.com/content/384125gp81055401/</span></a> </span> </span></li>
<li><span style="font-family: Arial, Helvetica, sans-serif;"> 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. </span></li>
<li><span style="font-family: Arial, Helvetica, sans-serif;"> 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. <span style="color: red; font-family: "Arial","sans-serif"; line-height: 115%;">Abstract</span><span style="color: #222222; font-family: "Arial","sans-serif"; line-height: 115%;"> <a href="http://www.ncbi.nlm.nih.gov/pubmed/19573826"><span style="color: blue;">www.ncbi.nlm.nih.gov/pubmed/19573826</span></a> </span> </span></li>
<li><span style="font-family: Arial, Helvetica, sans-serif;"> T. Dankert & M. Vleugels. Hysteroscopic resection of retained placental tissue:a feasibility study Gynecol Surg . 2008; 5:121–124. <span style="color: red; font-family: "Arial","sans-serif"; line-height: 115%;">Free article</span><span style="color: #222222; font-family: "Arial","sans-serif"; line-height: 115%;"> <a href="http://www.springerlink.com/index/w4021j484l211057.pdf"><span style="color: blue;">www.springerlink.com/index/w4021j484l211057.pdf</span></a> </span> </span></li>
<li><span style="font-family: Arial, Helvetica, sans-serif;"> 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. </span></li>
<li><span style="font-family: Arial, Helvetica, sans-serif;"> 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. </span><a href="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7W6G-4GBW3M2-6&_user=10&_origUdi=B7MDF-4XJG3MC-C8&_fmt=high&_coverDate=05%2F31%2F2001&_rdoc=1&_orig=article&_origin=article&_zone=related_art&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=10627be5f76770b50d46740a46363117"><span style="color: red;"><span style="font-family: Arial, Helvetica, sans-serif;">Abstract </span></span></a></li>
<li><span style="font-family: Arial, Helvetica, sans-serif;"> 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. <span style="color: red; font-family: "Arial","sans-serif"; line-height: 115%;">Abstract </span><span style="color: #222222; font-family: "Arial","sans-serif"; line-height: 115%;"><a href="http://www.ncbi.nlm.nih.gov/pubmed/9018641"><span style="color: blue;">www.ncbi.nlm.nih.gov/pubmed/9018641</span></a></span><span style="font-family: "Arial","sans-serif"; line-height: 115%;"> </span> </span></li>
<li><div class="MsoNormal" style="margin: 0cm 0cm 10pt;"><span style="font-family: "Arial","sans-serif"; line-height: 115%;"><span style="font-family: Arial, Helvetica, sans-serif;">Isaacson K. Office hysteroscopy: a valuable but under-utilized technique.Current Opinion in Obstetrics and Gynecology 2002, 14:381-385. <span style="color: red;">Free article</span> </span><a href="http://www.obpmedical.com/v/vspfiles/assets/images/office%20hysteroscopy%20-%20a%20valuable%20but%20under-%20utilized%20technique.pdf"><span style="color: blue; font-family: Arial, Helvetica, sans-serif;">http://www.obpmedical.com/v/vspfiles/assets/images/office%20hysteroscopy%20-%20a%20valuable%20but%20under-%20utilized%20technique.pdf</span></a><span style="font-family: Calibri;"></span></span> </div></li>
</ol>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-55346579728235686902011-07-19T01:32:00.000-07:002011-11-24T00:09:35.160-08:00Endometrial injury subfertility and superfertility: a decidual link.<div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">antiphospholipid syndrome</span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">) and </span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">uterine factors which are less well understood.</span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"> 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. </span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span><br />
<br />
<span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">Implications for Asherman's syndrome?</span><br />
<span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"> </span></div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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 </span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">reported </span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span></div><div class="MsoNormal" style="background: white;"><br />
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</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">REFERENCES </span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"> Evers JL. Female subfertility. Lancet 2002;360:151 – 159.</span></div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"> </span></div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">Quenby S, Vince G, Farquharson R, Aplin J. Recurrent miscarriage: a defect in nature’s quality control? Hum Reprod 2002;17:1959 – 1963.</span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">Rai R, Regan L. Recurrent miscarriage. Lancet 2006;368:601 – 611.</span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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<br />
sensors of embryo quality upon implantation. PLoS ONE 2010;5:e10258. </span></div><div class="MsoNormal" style="background: white;"><br />
</div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"> 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.</span><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"> </span></div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;"><br />
</span></div><div class="MsoNormal" style="background: white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">Tietze C, Guttmacher AF, Rubin S. Time required for conception in 1727 planned pregnancies. Fertil Steril 1950;1:338– 346.</span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-51086735324509151112011-04-27T22:41:00.000-07:002011-04-27T22:43:25.729-07:00Articles on Asherman's syndrome: Reproductive outcomes and Obstetric complicationsThe final section on references to peer-reviewed publications on Asherman's syndrome have been uploaded under pages (please see relevant tab above or <a href="http://ashermansprevention.blogspot.com/p/reproductive-outcomes-and-obstetric.html">click here</a>). 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.Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-3857335766321699748.post-34514046455863639962011-03-27T00:20:00.000-07:002011-09-08T05:38:28.330-07:00A genetic predisposition: from speculation to opinion to 'fact' without any data (Part II)<div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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:</span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">a) some women develop a severe form of IUA after undergoing the ‘same’ traumatic procedures as others who do not acquire AS, and </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">b) some women respond more ‘favourably’ to treatment than others who suffer from recurrent adhesions. </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><b><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">How can trauma be quantified when surgery is blind?</span></b></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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 <span style="background: none repeat scroll 0% 0% rgb(255, 255, 255);">vary enough between women to be a significant factor with regards to acquiring an injury during a blind procedure</span><span style="background-color: white;">.</span> 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. </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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? (<b>Note:</b> 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). </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><b><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">Recurrence depends on initial severity and treatment methods</span></b></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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). </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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. </span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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.</span></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><b><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">A modern perspective on an old problem</span></b></div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><br />
</div><div class="MsoNormal" style="background: none repeat scroll 0% 0% white;"><span style="color: black; font-family: "Arial","sans-serif"; font-size: 10pt;">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 <i>only presence of evidence is evidence of presence. </i></span></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-84255332533939020402011-02-22T22:54:00.000-08:002011-11-25T01:01:46.791-08:00A genetic predisposition: from speculation to opinion to 'fact' without any data (Part I)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.<br />
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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.<br />
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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:<br />
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a) some women develop a severe form of IUA after undergoing the ‘same’ traumatic procedures as others who do not acquire AS, and<br />
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b) some women respond more ‘favourably’ to treatment than others who suffer from recurrent adhesions.<br />
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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.<br />
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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)<br />
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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.<br />
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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):<br />
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(See Discussion Dr John Morton LA California): <span style="color: #e06666;">“The nomenclature also is objectionable. The “traumatic” part of the phrase indicates an iatrogenic lesion, which may not always be justified.</span><span style="color: black;"> (my edit: This is true, but many if not most cases are actually iatrogenic since surgery is involved).</span><br />
<div style="color: orange;"><span style="color: #e06666;">(…)</span></div><div style="color: orange;"><span style="color: #e06666;">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”.</span></div><div style="color: orange;"><span style="color: #e06666;">(…)</span></div><div style="color: orange;"><span style="color: #e06666;">Thus, there must be an inflammatory factor in the etiology of intrauterine adhesions </span><span style="color: black;">(my edit: Trauma to the tissue causes inflammation-not to be confused with infection). </span><span style="color: #e06666;">Parenthetically this too underlines Dr Morton’s objection to the term ‘traumatic’.”</span></div><div style="color: orange;"><br />
</div>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.<br />
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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.<br />
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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.<br />
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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.<br />
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<b>REFERENCES</b><br />
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<ol><li> Foix A, Bruno RO, Davison T, Baltasar L. The pathology of postcurettage intrauterine adhesions. Am J Obst & Gynec.1966; 96(7):1027-33.</li>
<li>Schenker JG, Margoliath EJ. Intrauterine adhesions: an updated appraisal. 1982; 37(5):593-610.</li>
<li>Polishuk WZ, Sadovsky E. A syndrome of recurrent intrauterine adhesions. Am J Obstet Gynecol 1975 151-8.</li>
<li>Asherman J, Amenorrhoea traumatic (Atretica). J Obstet Gynecol 1948; Br Emp 55:23.</li>
<li>Jones W. Traumatic Intrauterine adhesion; a report of 8 cases with emphasis on therapy. Am J Obstet & Gynec 1964; 89(3):304-13.</li>
</ol>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-27934361767879348882011-01-25T22:33:00.000-08:002011-02-01T23:41:10.688-08:00Articles on Asherman's syndrome Diagnosis, Classification and TreatmentFurther 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 <a href="http://ashermansprevention.blogspot.com/p/articles-on-diagnosis-classification.html">click here</a> or on the relevant tab in the menu above to view these references.<br />
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Previously a page with references to studies on the Etiology, Incidence and Prevention of Asherman's syndrome was added. <a href="http://ashermansprevention.blogspot.com/p/publications-etiology-incidence.html">Click here</a> or on the relevant tab in the menu above for more. <br />
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Further references to publications on Asherman's syndrome by topic will be added to the site in the near future.Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-9726937903630329092011-01-04T19:19:00.000-08:002011-01-14T00:29:37.067-08:00Alternative perspectives?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 (<a href="http://alternativeashermans.blogspot.com/2010/06/three-steps-backward.html">Three steps backwards</a>) 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.<br />
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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 (<span style="font-family: Trebuchet MS;">Tam WH, Lau WC, Cheung LP, Yuen PM, Chung TK. J Am Assoc Gynecol Laparosc.2002; 9 (2): 182–185.</span>). 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. <br />
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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). <br />
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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).<br />
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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.<br />
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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.<br />
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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. <strong>Followup hysteroscopy may also be necessary in women with a history of AS if the</strong> <strong>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.</strong> 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.Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-3857335766321699748.post-54345885234371258442010-12-02T22:21:00.000-08:002011-02-01T23:13:26.670-08:00Update Dec '10: Clinical trials and patents relevant to Asherman's syndrome<span style="font-size: large;"><b>Clinical trials:</b></span><br />
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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. <br />
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<b>Optimal Treatment of Miscarriage</b> OR<br />
<b>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?</b>Region Skane, Kvinnokliniken, University Hopsital MAS Malmo Sweden.<br />
<b>Study type:</b> Open labelled randomized trial (parallel assignment).<br />
<b>Aim:</b> 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.<br />
<b>link:</b> <a href="http://clinicaltrials.gov/ct2/show/NCT01033903?term=miscarriage&rank=5">http://clinicaltrials.gov/ct2/show/NCT01033903?term=miscarriage&rank=5</a> <br />
<br />
<b>A Randomized Trial of Two Regimens of Misoprostol for Second Trimester Termination for Intrauterine Fetal Death</b>American University of Beirut Medical Center<br />
<b>Study type:</b> Open labelled, randomized controlled crossover trial.<br />
<b>Aim: </b>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) <br />
<b>link: </b><a href="http://clinicaltrials.gov/ct2/show/NCT00141895?term=misoprostol&rank=7">http://clinicaltrials.gov/ct2/show/NCT00141895?term=misoprostol&rank=7</a> <br />
<br />
<b>Sublingual Misoprostol Versus Standard Surgical Care for the Treatment of Incomplete Abortion</b>Gynuity Health Projects, Egypt, Mauritania, Niger.<br />
<b>Study type:</b> Open labeled randomized controlled trial.<br />
<b>Aim:</b> 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.<br />
<b>link:</b> <a href="http://clinicaltrials.gov/ct2/show/NCT00466999?term=misoprostol&rank=50">http://clinicaltrials.gov/ct2/show/NCT00466999?term=misoprostol&rank=50</a> <br />
<br />
<b>Non Surgical Management for Uterine Residua After Pregnancy Termination, Abortion or Delivery</b>HaEmek Medical Center, Israel<br />
<b>Study type:</b> open labelled randomized trial (parallel assignment)<br />
<b>Aim:</b>To compare the outcome of misoprostol treatment (intravaginal, 800 mcg) and expectant management in the case of intrauterine residua after completion of pregnancy.<br />
<b>link: </b><a href="http://clinicaltrials.gov/ct2/show/NCT01134926?term=misoprostol&rank=56">http://clinicaltrials.gov/ct2/show/NCT01134926?term=misoprostol&rank=56</a> <br />
<br />
<b>Misoprostol for Treatment of Fetal Death at 14-28 Weeks of Pregnancy</b>Gynuity, California, Illinois, Boston, New York. <br />
<b>Study type:</b> Double blinded randomized trial, parallel assignment.<br />
<b>Aim:</b> 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. <br />
<b>link:</b> <a href="http://clinicaltrials.gov/ct2/show/NCT00671060?term=misoprostol&rank=24">http://clinicaltrials.gov/ct2/show/NCT00671060?term=misoprostol&rank=24</a> <br />
<br />
<b>Effect of Colony Stimulating Factor on Poor Endometrial Development During IVF</b><br />
Official Title: <b>G-CSF and Endometrial Growth, Embryo Implantation and Pregnancy Following FET or Donor ET</b><br />
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. <br />
<br />
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. <br />
For more information see:<br />
<a href="http://clinicaltrials.gov/ct2/show/NCT01202643?term=asherman+syndrome&rank=1">http://clinicaltrials.gov/ct2/show/NCT01202643?term=asherman+syndrome&rank=1</a> <br />
<br />
<b>Safety of Leaving Cook Balloon Uterine Stent in Uterus for One Month</b><br />
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.<br />
<br />
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.<br />
<br />
For more information see: <a href="http://clinicaltrials.gov/ct2/show/NCT01167296?term=uterine+adhesions&rank=2">http://clinicaltrials.gov/ct2/show/NCT01167296?term=uterine+adhesions&rank=2</a> <br />
<br />
<br />
<b>SIGnificance of Routine Hysteroscopy Prior to a First 'in Vitro Fertilization'(IVF) Treatment Cycle (inSIGHT)</b><br />
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.<br />
<br />
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. <br />
<br />
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? <br />
<br />
For more information: <a href="http://clinicaltrials.gov/ct2/show/NCT01242852?term=uterine+adhesions&rank=8">http://clinicaltrials.gov/ct2/show/NCT01242852?term=uterine+adhesions&rank=8</a> <br />
<br />
Note: There appears to be an error in the table describing the intervention and control arms of the study.<br />
<br />
<b><span style="font-size: large;">Patents </span></b><br />
<br />
<b>Patent Applications:</b><br />
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. <br />
Jackson, EK. Cyclic adenosine monophosphates for reducing the formation of adhesions. 14 May 2010.<br />
More info <a href="http://www.ibridgenetwork.org/university-of-pittsburgh/cyclic-adenosine-monophosphates-for-reducing-the-formation-of">http://www.ibridgenetwork.org/university-of-pittsburgh/cyclic-adenosine-monophosphates-for-reducing-the-formation-of</a> <br />
<br />
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.<br />
<br />
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. <br />
<br />
<b>Granted Patents:</b><br />
2005/0084,508 A61K Topical anesthesia formulation for bodily cavities <br />
Innovators: Vancaillie, Thierry G; Hewitt, Alan Ernest<br />
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. <br />
More info: <a href="http://www.patentbuddy.com/patentdetails/2402425">http://www.patentbuddy.com/patentdetails/2402425</a> <br />
<br />
<br />
References<br />
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.<br />
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.<br />
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. <br />
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.<br />
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.<br />
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.<br />
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. <br />
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.<br />
<br />
<b><span style="font-size: large;">Relevant links:</span></b><br />
<a href="http://clinicaltrials.gov/ct2/info/understand">Understanding Clinical Trials </a>Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-3857335766321699748.post-89702087929175624532010-11-18T20:12:00.000-08:002011-02-01T23:14:44.718-08:00Articles on Asherman's syndrome Etiology, Incidence, PreventionA 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 <a href="http://ashermansprevention.blogspot.com/p/publications-etiology-incidence.html">here</a> 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.Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-55065981970462402922010-10-21T18:46:00.000-07:002011-02-01T23:02:04.367-08:00When infertility or recurrent miscarriage persist after treatment of Asherman's syndromeFor 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. <br />
<br />
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). <br />
<br />
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. <br />
<br />
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. <br />
<br />
<a href="http://www.bupa.co.uk/health_information/html/health_news/220903infertility.html">Infertility Tests and Therapies Questioned</a> (Bupa)<br />
<br />
More information on the validity of tests and therapies for infertility/recurrent miscarriage:<br />
<br />
Cochrane Reviews: <a href="http://www2.cochrane.org/reviews/en/ab000112.html">Immunotherapy for recurrent miscarriage</a> (Full article: <a href="http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD000112/pdf_standard_fs.html">click here</a>) <br />
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 <i>without</i> 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.<br />
<br />
<a href="http://www.rcog.org.uk/womens-health/clinical-guidance/implantation-and-early-development-study-group-statement">RCOG: Implantation and Early Development - study group statement.</a><br />
<br />
<a href="http://infertilityblog.blogspot.com/2007/07/miscarriage-infertility-antibodies-and.html">Miscarriage, Infertility, Antibodies and the Immune System</a> Dr Licciardi's Infertility BlogUnknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-84217051106895180742010-09-29T00:14:00.000-07:002010-10-03T17:23:58.694-07:00Effect of Asherman’s syndrome on infant healthOver 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. <br />
<br />
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.<br />
<br />
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. <br />
<br />
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. <br />
<br />
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. <br />
<br />
<strong>Prematurity and neonatal complications</strong><br />
<br />
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.<br />
<br />
<strong>Effect of IUA during pregnancy: four case reports with different outcomes</strong><br />
<br />
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) <br />
<br />
<strong>Severe AS from EA and birth defects</strong><br />
<br />
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. <a href="http://www.amnioticbandsyndrome.com/">ABS</a> , 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. <br />
<br />
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:<br />
<br />
“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.” <br />
<br />
Prognosis was poor and the parents decided to withdraw ventilation support. The infant died 6 hours after delivery.<br />
<br />
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. <br />
<br />
<strong>Mild to moderate IUA during pregnancy</strong><br />
<br />
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.<br />
<br />
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. <br />
<br />
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. <br />
<br />
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. <br />
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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.<br />
The mother’s operative hysteroscopy carried out 6 months later confirmed both clinically and histologically the presence of a transversal muscular synechia.<br />
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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. <br />
<br />
<br />
<strong>REFERENCES</strong><br />
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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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/9315197">Abstract</a><br />
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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 <a href="http://www.ncbi.nlm.nih.gov/pubmed/19022431">Abstract</a><br />
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3. Cook JR, Seman E. Pregnancy following endometrial ablation: case history and literature review. Obstet Gynecol Surv 2003;58:551– 6. <a href="http://www.ncbi.nlm.nih.gov/pubmed/12886166">Abstract</a><br />
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4. Pugh CP, Crane JM, Hogan TG. Successful intrauterine pregnancy after endometrial ablation. J Am Assoc Gynecol Laparosc 2000;7:391– 4. <a href="http://www.ncbi.nlm.nih.gov/pubmed/10924635">Abstract</a><br />
<br />
5 Mukul LV, Linn JG. Pregnancy complicated by uterine synechiae after endometrial ablation. Obstet Gynecol. 2005 May;105(5 Pt 2):1179-82. <a href="http://www.ncbi.nlm.nih.gov/pubmed/15863573">Abstract</a><br />
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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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/14550997">Abstract</a><br />
<br />
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.<br />
<div align="left"></div>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-30879400292003786242010-08-31T01:05:00.000-07:002011-02-01T23:35:31.242-08:00The Miscarriage Study: 400 vs 800 mcg misoprostolMater 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: <br />
<br />
<a href="http://brochures.mater.org.au/Home/Brochures/Mater-Mothers--Hospitals/Miscarriage">http://brochures.mater.org.au/Home/Brochures/Mater-Mothers--Hospitals/Miscarriage</a><br />
<br />
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. <br />
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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 <a href="http://www.misoprostol.org/File/Introduction_Weeks.pdf">here</a>. 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: <a href="http://www.misoprostol.org/">http://www.misoprostol.org/</a> This website also provides excellent resources to clinicians interested in information about misoprostol use and the misoprostol debate. <br />
<br />
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 (<a href="http://www.thedoctorschannel.com/video/3435.html">link</a>). Apparently misoprostol side effects for termination are not a concern for women. One would imagine the same for women who miscarry.<br />
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<br />
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. <br />
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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. <span style="color: black;">Interestingly, expectant management is considered acceptable although it is not more effective than for miscarriage management in clinical trials.</span> <span style="color: red;">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</span> (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. <span style="color: red;">Why is it that the only people who seem to be prevented from using misoprostol are women who miscarry? </span><br />
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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. <br />
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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 <a href="http://ashermansprevention.blogspot.com/p/ashermans-syndrome-after-curettage-is.html">Frequency of intrauterine adhesions after curettage</a>). <br />
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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.Unknownnoreply@blogger.com1tag:blogger.com,1999:blog-3857335766321699748.post-4970755231220669922010-07-19T02:31:00.000-07:002010-07-30T21:16:33.245-07:00Misoprostol for miscarriage management: the facts and the fictionThis is my latest Youtube video presentation. It explains the truth behind often repeated misinformation about misoprostol.<br />
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<div class="separator" style="clear: both; text-align: center;"><iframe allowfullscreen='allowfullscreen' webkitallowfullscreen='webkitallowfullscreen' mozallowfullscreen='mozallowfullscreen' width='320' height='266' src='https://www.blogger.com/video.g?token=AD6v5dz0QHRx8bCzPGeBdWIDpfDArjpAkFB9q1BBvOzi_3nPyNmxnpl7p8jXqasNs494bZ5WIRlZatzcANl38juaGA' class='b-hbp-video b-uploaded' frameborder='0'></iframe></div><div class="separator" style="clear: both; text-align: center;"><br />
</div>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.Unknownnoreply@blogger.com2tag:blogger.com,1999:blog-3857335766321699748.post-80671585562204383152010-07-12T06:15:00.000-07:002010-07-14T01:30:21.829-07:00Recent and upcoming articles on Asherman's syndrome (July 2010)There are two articles in press about Asherman's syndrome in peer-reviewed medical journals. <br />
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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 <a href="http://www.ncbi.nlm.nih.gov/pubmed/20576472">click here</a>. 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 (<a href="http://www.ncbi.nlm.nih.gov/pubmed/17100817">Amnion graft following hysteroscopic lysis of intrauterine adhesions</a>, 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 <em>with or without menstrual disorders such as amenorrhea or hypomenorrhea</em>. 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.<br />
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The second article in press is: <a href="http://www.ncbi.nlm.nih.gov/pubmed/19832826">Separated from birth: An initial examination suggested Asherman's syndrome</a> (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. <br />
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The article <a href="http://www.ncbi.nlm.nih.gov/sites/pubmed20386442">Impact of previous uterine artery embolization on fertility</a>. (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 (<a href="http://www.ncbi.nlm.nih.gov/pubmed/19832826">Fertility and pregnancy following pelvic arterial embolisation for postpartum haemorrhage.</a> 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. <br />
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A new cause of Asherman's syndrome, B-lynch suture, was recently reported in <a href="http://www.ncbi.nlm.nih.gov/pubmed/20347081">Development of Asherman syndrome after conservative surgical management of intractable postpartum hemorrhage.</a> (Goojha CA, Case A, Pierson R. Fertil Steril. 2010 Mar 25.) B-lynch suture is a 'conservative' surgical compression technique for managing postpartum hemorrhage.<br />
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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 <a href="http://ashermansprevention.blogspot.com/2010/03/complications-in-post-as-pregnancies.html">complications in post AS pregnancies</a> I have already written about. <br />
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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.Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-81299356640447860042010-07-02T01:44:00.000-07:002010-09-29T00:50:51.447-07:00FAQs Asherman's syndromePlease see the new page on <a href="http://ashermansprevention.blogspot.com/p/faqs-on-ashermans-syndrome.html">frequently asked questions about Asherman's syndrome. </a>You can also click on the relevant tab button in the tab bar at the top of the page to view it.Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-9534761734975658422010-06-15T00:20:00.000-07:002010-06-17T03:58:22.736-07:00Focus on the medical literature: Misoprostol for early pregnancy failure is underused despite efficacy and safety .<span style="font-family: "Trebuchet MS", sans-serif;">Article: <a href="http://www.ncbi.nlm.nih.gov/pubmed/20227674">Provider knowledge, attitudes, and treatment preferences for early pregnancy failure. </a></span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
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<span style="font-family: "Trebuchet MS", sans-serif;">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</span><br />
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<span style="font-family: "Trebuchet MS", sans-serif;">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. </span><br />
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</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><br />
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</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">There is a plethora of clinical studies in the medical literature supporting the efficacy and safety of misoprostol (<a href="http://www.misoprostol.org/File/Bibliography.php">click here</a>) 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).</span><br />
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</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><br />
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</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">In particular they sought answers from health providers with respect to each treatment method regarding :</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-attitudes about treatment safety (and I would add efficacy) (<span style="background-color: yellow;">Treatment Preference</span>)</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-perceptions of patient acceptance of options (<span style="background-color: yellow;">Perception of patient preferences</span>)</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-provider comfort with the options (<span style="background-color: yellow;">Use of treatments</span>)</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">For misoprostol and office uterine evacuations they looked at additional factors.</span><br />
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</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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. </span><br />
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</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: #ead1dc;">From the point of view of <strong>Asherman’s syndrome prevention</strong>, the focus will be on the paper’s relevant outcomes with regards to use of the non-invasive alternatives <strong>misoprostol and expectant management compared to OR surgical evacuation (ie. D&C).</strong> Also, I am adding a few interpretations which were not mentioned in the article. These are in <span style="color: blue;">blue</span> font.</span></span><br />
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<table border="1" cellpadding="1" style="width: 500px;"><tbody>
<tr><td><span style="font-family: "Trebuchet MS", sans-serif;"><span style="font-family: "Trebuchet MS", sans-serif; font-size: large;"><strong>D&C</strong></span></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif; font-size: large;"></span><br />
<span style="background-color: yellow;"><span style="font-family: "Trebuchet MS", sans-serif;"><em>Treatment preference</em></span></span><span style="background-color: white; font-family: "Trebuchet MS", sans-serif;"><span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;">-</span>Obgyns preferred uterine evacuation in the operating room over other methods (45.7%)</span><span style="background-color: white; color: blue; font-family: "Trebuchet MS", sans-serif;">(No surprise there…)</span> <br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Perception of patient preferences</em></span> <span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-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). </span><span style="background-color: white;"></span><span style="background-color: white; color: blue; font-family: "Trebuchet MS", sans-serif;">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. </span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Use of treatments</em></span> <span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-Obgyns reported using OR D&C more than the other options and nurses/midwives and GPs.</span> <span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-38.9% of Obgyns used D&C in over half of all patients in the past 6 months.</span></td></tr>
</tbody></table><br />
<table border="1" cellpadding="1" style="width: 500px;"><tbody>
<tr><td><span style="background-color: white; font-family: "Trebuchet MS", sans-serif; font-size: large;"><strong>Expectant management</strong></span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Treatment preference</em></span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;">-<strong>Nurses/midwives and GPs were the most likely to prefer expectant management (55.2% and 64.5% , respectively)</strong></span></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-Obgyns were the least likely to report expectant management as their most preferred treatment</span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Perception of patient preferences</em></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-Health provider’s belief regarding patient preference of expectant management mirrored their own.</span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Use of treatments</em></span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;">-<strong>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).</strong></span><span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;"></span></span></td></tr>
</tbody></table><br />
<table border="1" cellpadding="1" style="width: 500px;"><tbody>
<tr><td><span style="background-color: white; font-family: "Trebuchet MS", sans-serif; font-size: large;"><strong>Misoprostol</strong></span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Treatment preference</em></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-Obgyns, nurses/midwives and GPs chose misoprostol as the second preferred treatment method (33.2%, 61.8% and 60.7% respectively).</span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Perception of patient preferences</em></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-Health provider’s belief regarding patient preference of misoprostol management mirrored their own.</span><br />
<span style="background-color: yellow; font-family: "Trebuchet MS", sans-serif;"><em>Use of treatments</em></span><br />
<span style="background-color: white; color: black; font-family: "Trebuchet MS", sans-serif;"><strong>Misoprostol (along with office uterine evacuations) were the least commonly used treatment options.</strong></span><br />
<span style="background-color: white; color: black; font-family: "Trebuchet MS", sans-serif;"><strong>-Most providers had not used misoprostol at all in the past 6 months for EPF treatment.</strong></span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;"><span style="color: black;"><strong>- Over the last 6 months, 52.7% of Obgyns reported not using it even once.</strong></span></span></span> <br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;">- Obgyns were still more likely than the others to use misoprostol but <strong><span style="color: black;">only 5% of them reported using it in over half of their patients in the last 6 months.</span></span></span></strong><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;">-<strong><span style="color: black;">67.9% and 84.1% of nurses/midwives and GPs, respectively, reported not ever using misoprostol in the last 6 months.</span></span></span></strong><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
<span style="background-color: white;"></span></span></td></tr>
</tbody></table><br />
<br />
<table border="1" cellpadding="1" style="width: 500px;"><tbody>
<tr><td><span style="background-color: white; font-family: "Trebuchet MS", sans-serif; font-size: large;"><strong>Provider factors influence on use of misoprostol</strong></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-<em><span style="background-color: yellow;">sex and race:</span></em> Not associated with use of misoprostol</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><span style="background-color: white;">-<em><span style="background-color: yellow;">Safety:</span></span></span></em> providers who believed that misoprostol is safe used it more than those that did not. <span style="color: black;"><strong>Disturbingly, 29.7% of Obgyns, 36.2% of nurses/midwives, and 37.8% of GPs did not agree with the statement “Misoprostol is safe.”</strong></span><br />
<span style="background-color: white; color: blue; font-family: "Trebuchet MS", sans-serif;">(This mindset counters evidence-based medicine and requires further examining).</span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-<em><span style="background-color: yellow;">Low patient demand:</span></em> 34.7% of GPs claimed little patient demand was a barrier, versus 18.2% of Obgyns and 15.7% of nurses/midwives. <span style="color: blue;">(Is this really a valid excuse not to at least offer it?)</span></span></span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-<em><span style="background-color: yellow;">prior induced abortion training:</span></em> Not significantly associated with misoprostol use.</span><br />
<span style="background-color: white; color: blue; font-family: "Trebuchet MS", sans-serif;">(I wonder if training in misoprostol use specifically for EPF management exists)</span><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif;">-<em><span style="background-color: yellow;">Other perceived obstacles</span></em> to using misoprostol included lack of surgical or nursing backup/support.</span> <span style="color: blue;">(Paradoxically these do not appear to hinder the preference of nurses/midwives or GPs for expectant management).</span></td></tr>
</tbody></table><br />
<span style="background-color: white; font-family: "Trebuchet MS", sans-serif; font-size: large;"><strong>Conclusions</strong></span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-<strong>EPF management is still largely dominated by operating room uterine evacuations</strong> (Obgyns) <strong>and expectant management</strong> (nurses/midwives and GPs) even though the efficacy and safety of misoprostol is well established. </span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-targeting <strong>inaccurate beliefs about the safety of misoprostol and clarifying patient preferences</strong> may increase the willingness of providers to adopt new practices to meet patient needs. </span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">Note: -This study does not delineate how much patient preferences account for current treatment patterns, however: </span><br />
<br />
<span style="font-family: "Trebuchet MS", sans-serif;">-Women vary in their treatment preferences, therefore providing access to a wide range of services will improve care.</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-clinical trials suggest that <strong>misoprostol is acceptable and may be preferred by many women</strong> <span style="color: blue;"><span style="color: black;">over surgical evacuation</span> especially when successful and when surgery is performed without anesthesia eg. in office (10,11,12,13).</span></span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">-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 <span style="color: blue;">(I would add also from the point of view of Asherman’s syndrome prevention).</span> </span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;"><strong>REFERENCES</strong></span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">1. Dalton, VK, Saunders, NA, Harris, LH, Williams, JA, and Lebovic, DI. Intrauterine</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">adhesions after manual vacuum aspiration for early pregnancy failure. Fertil Steril</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">2006;85(6):1823 e1-3.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">2. Zhang, J, Gilles, JM, Barnhart, K, Creinin, MD, Westhoff, C, and Frederick, MM.</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">A comparison of medical management with misoprostol and surgical management</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">for early pregnancy failure. N Engl J Med 2005;353(8):761-9.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">4. Cabana MD, Kim C. Physician adherence to preventive cardiology guidelines for women. Women’s Health Issues 2003;13:142-9.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span><span style="font-family: "Trebuchet MS", sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS", sans-serif;">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.</span>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-16146324097590758322010-06-04T00:08:00.000-07:002010-06-04T00:57:11.639-07:00Cochrane review: Medical treatments for incomplete miscarriage (less than 24 weeks)This systematic review was published in January. I'm adding a link to it in the RELEVANT LINKS section to the right. Or <a href="http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD007223/frame.html">click here</a> to have access to the complete article (then click on a link in the left window).<br />
<br />
<span style="color: blue;">"Women experiencing miscarriage at less than 13 weeks should be offered an informed choice." </span><span style="color: black;">(from the abstract)</span>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-39074529209032948142010-05-26T00:04:00.000-07:002011-02-01T23:00:08.969-08:00Failed medical management or a failure to comply with accepted guidelines?<span style="font-family: "Trebuchet MS",sans-serif;">Only 4 months after an <a href="http://ashermansprevention.blogspot.com/2009/12/miscarriage-after-ashermans-syndrome.html">in utero fetal demise at 14 weeks</a>, 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. </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">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. </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">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. </span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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 <a ?target="_blank"" href="http://www.misoprostol.org/File/Guide1triabn.php">International Journal of Gynecology and Obstetrics (2007, vol. 99)</a> 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. </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">While I received the same protocol for my previous second trimester miscarriage as for second trimester abortion, the </span><a ?target="_blank"" href="http://misoprostol.org/File/guidelines.php"><span style="font-family: "Trebuchet MS",sans-serif;">accepted protocols for these two indications are much more similar</span></a><span style="font-family: "Trebuchet MS",sans-serif;"> 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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">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. </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-26969425031842610752010-05-14T01:39:00.000-07:002011-02-01T23:11:05.945-08:00Doctor’s orders: in support of Ashermans syndrome prevention and/or alternatives to D&C.<span style="font-family: "Trebuchet MS",sans-serif;">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. </span><br />
<br />
<span style="font-family: Trebuchet MS;">(my additions are in <span style="color: blue;">blue</span>)</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>1. Toaf and Ballas, 1978 (1):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">"Peurperal curettage…was discontinued in Israel after publication of Asherman’s observations.”</span><br />
<br />
<span style="color: blue; font-family: "Trebuchet MS",sans-serif;">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).</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>2. Li et al, 2001 (2):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">* <span style="color: blue;">Asherman’s syndrome may result</span></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>3. Friedler et al, 1993 (3):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“The incidence of IUA might be lower following medical evacuation of the uterus, thus avoiding any intra-uterine instrumentation; however, use of progesterone antagonists (<span style="color: blue;">ie, mifepristone</span>) for this purpose is not yet approved by the Israeli Ministry of Health.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>4. Chapman and Chapman, 1990 (4):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“One must also note that the suction curette is capable of causing synechiae, usually, however in the region of the internal os.” </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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”</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“It goes without saying that, in view of the seriousness of the sequelae, the best management is prevention…”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>3. Tam et al, 2002 (5):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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 {<span style="color: blue;">these methods</span>} fails or is contraindicated.”</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">*ie miscarriage</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>6. Goldenberg et al, 1997 (6):</b></span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Selective curettage of residual trophoblastic tissue directed by hysteroscopy is an easy and short procedure and might be preferable to conventional, nonselective, blind curettage.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“…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”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.” </span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>7. Yu et al, 2008 (7):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Prevention of Asherman Syndrome</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">They go on to recommend:</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Avoid postpartum or postabortion curettage”</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Diagnosis of retained products of conception …present a clinical challenge.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">…Saline infusion sonohysterography (SHG) has enhanced our ability to diagnose retained products of conception (8)”</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“…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)”</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Transvaginal duplex Doppler ultrasonography is also an effective noninvasive method for evaluating patients with persistent postpartum hermorrhage (10).”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">"…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).</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">…</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Select medical management of miscarriages</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">When termination of early pregnancy is necessary, medical treatment should be considered instead of surgical options.”</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">They cite the Tam et al study (5)(see above).</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>7. Chung et al, 1995 (11):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“The accepted management of spontaneous abortion has not changed substantially in 60-70 years.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“The policy of routine, universal evacuation of retained products of conception (ERPC) became the accepted form of management around the 1930s to combat [<span style="color: blue;">these</span>*] complications. However, this approach may no longer be appropriate in all cases.” </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">*hemorrhage, infection.</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“…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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.” </span><span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Surgical intervention in {<span style="color: blue;">women who do not have a significant amount of retained tissue in the uterus</span>} may unnecessarily incur iatrogenic complications without therapeutic gain.”</span><span style="font-family: "Trebuchet MS",sans-serif;"> </span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>8. Demetroulis et al, 2001 (13):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>9. Moodliar et al, 2005 (15):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">*<span style="color: blue;">in Australia and in many other countries too!</span></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>10. Muffley et al, 2002 (16):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.” </span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">(<span style="color: blue;">I hope so!)</span></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">Comment by Dr Lisa Fall:</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <br />
<span style="color: blue; font-family: "Trebuchet MS",sans-serif;">(Yup, that was me, but I was refused)</span><span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><span style="font-family: "Trebuchet MS",sans-serif;"><b>11. Zhang et al, 2005 (20):</b></span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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).”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>12. Stockheim et al, 2006 (22):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.” </span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Misoprostol is an effective and safe treatment for early pregnancy failure and could replace surgical curettage in over two-thirds of the patients.”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>13. Creinin et al, 2006 (27):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="color: blue; font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>14. Pang et al, 2001 (28):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.)”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>15. Blanchard et al, 2004 (30):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>16. Shaw D, The International Federation of Gynecology and Obstetrics (FIGO) President (31):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“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.”</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;"><b>17. The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion, 2009 (32):</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“In addition, there is increasing evidence that misoprostol is a safe, effective,and acceptable method to achieve uterine evacuation for women needing postabortion* care.” </span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">“Misoprostol may be used to treat women with an incomplete and missed abortion.”</span> <span style="font-family: "Trebuchet MS",sans-serif;"><br />
</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">* Postabortion care: “… refers to a specific set of services for women experiencing problems from all types of spontaneous or induced abortions.”</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;"><b>REFERENCES</b></span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">1. Toaff R, Ballas S (1978). Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome). Fertil. Steril. 30 (4): 379–87.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">7. Yu D, Wong YM, Cheong Y, Xia E, Li TC. Asherman syndrome-one century later. Fertil Steril 2008;89(4):759-779.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">11. Chung, TK, Cheung, LP, Leung, TY, Haines, CJ, and Chang, AM. Misoprostol in</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">the management of spontaneous abortion. Br J Obstet Gynaecol 1995;102(10):832-</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;">5.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">12. Macrow, P and Elstein, M. Managing miscarriage medically. BMJ </span><span style="font-family: "Trebuchet MS",sans-serif;">1993;306(6882):876.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">13. Demetroulis, C, Saridogan, E, Kunde, D, and Naftalin, AA. A prospective </span><span style="font-family: "Trebuchet MS",sans-serif;">randomized control trial comparing medical and surgical treatment for early </span><span style="font-family: "Trebuchet MS",sans-serif;">pregnancy failure. Hum Reprod 2001;16(2):365-9.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">15. Moodliar S, Bagratee JS, Moodley J. Medical vs surgical evacuation of first-trimester spontaneous abortion. Int J Gynecol Obstet 2005;91:21-6.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">16. Muffley, PE, Stitely, ML, and Gherman, RB. Early intrauterine pregnancy failure: a </span><span style="font-family: "Trebuchet MS",sans-serif;">randomized trial of medical versus surgical treatment. Am J Obstet Gynecol </span><span style="font-family: "Trebuchet MS",sans-serif;">2002;187(2):321-5; discussion 325-6.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">17. Ballagh SA, Harris HA, Demasio K.Is curettage needed for uncomplicated incomplete spontaneous abortion? Am J Obstet Gynecol 1998;179:1279-82.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">18. Stovall, TG, Ling, FW, and Buster, JE. Outpatient chemotherapy of unruptured </span><span style="font-family: "Trebuchet MS",sans-serif;">ectopic pregnancy. Fertil Steril 1989;51(3):435-8.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">19. Lipscomb, GH, Bran, D, McCord, ML, Portera, JC, and Ling, FW. Analysis of </span><span style="font-family: "Trebuchet MS",sans-serif;">three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. </span><span style="font-family: "Trebuchet MS",sans-serif;">Am J Obstet Gynecol 1998;178(6):1354-8.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">20. Zhang, J, Gilles, JM, Barnhart, K, Creinin, MD, Westhoff, C, and Frederick, MM. </span><span style="font-family: "Trebuchet MS",sans-serif;">A comparison of medical management with misoprostol and surgical management </span><span style="font-family: "Trebuchet MS",sans-serif;">for early pregnancy failure. N Engl J Med 2005;353(8):761-9.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">21. Hertig AT, Livingstone RG. Spontaneous, threatened and habitual abortion: their pathogenesis and treatment. N Engl J Med 1944;230:797-806.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">24. Hausknecht RU. Methotrexate and misoprostol to terminate early pregnancy. N Engl J Med 1995;333:537-40.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">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.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span><br />
<span style="font-family: "Trebuchet MS",sans-serif;"></span><span style="font-family: "Trebuchet MS",sans-serif;">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.</span> <br />
<span style="font-family: "Trebuchet MS",sans-serif;"> </span><span style="font-family: "Trebuchet MS",sans-serif;">31. Shaw, D. Misoprostol for reproductive health: Dosage recommendations. International Journal of Gynecology and Obstetrics 2007; 99:S155. </span><br />
<br />
<span style="font-family: "Trebuchet MS",sans-serif;">32. ACOG Committee on International Affairs. Committee Opinion: Misoprostol for postabortion care. Obstetrics & Gynecology 2009; 113(2) Part I:465-8.</span>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-40595191165083017382010-05-03T01:20:00.000-07:002011-02-01T23:30:29.457-08:00Ashermans syndrome in the news: The secret syndrome leaving women infertile<span style="font-family: trebuchet ms;">A <a href="http://www.mirror.co.uk/life-style/real-life/2010/04/29/the-secret-syndrome-leaving-women-infertile-115875-22219119/" target="'_blank">recent article</a> on <a href="http://en.wikipedia.org/wiki/Asherman" target="'_blank">Asherman’s syndrome</a> (AS) appeared in the UK Daily mirror. It was about <a href="http://en.wikipedia.org/wiki/Sophie_Blake" target="'_blank">Sophie Blake</a>, 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). </span><br />
<span style="font-family: trebuchet ms;"></span><br />
<span style="font-family: trebuchet ms;">Toaff and Ballas, 1978<br />
<span style="color: #000099;">“Puerperal curettage….was discontinued in Israel after publication of Asherman’s observations*”.</span><br />
*1948!!<br />
<br />
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. <span style="color: #000099;">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.</span> 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, <a href="http://ashermansprevention.blogspot.com/2009/09/without-new-breakthroughs-treatment.html" target="'_blank">without further progress in treatment strategies</a>, there is nothing that can be done to replenish regenerative tissue that has been removed during curettage or other uterine surgery.<br />
<br />
<b>Early treatment does not guarantee success-just as late treatment does not guarantee failure</b><br />
<br />
<span style="color: #ff6600;"><span style="color: #990000;">“Ideally corrective surgery should be performed within six months of the adhesions forming before they get too large”</span></span><br />
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:<br />
<br />
<span style="color: #000099;">“I was devastated the scarring had come back so quickly,”</span><br />
<br />
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).<br />
<br />
<span style="color: #990000;">“It makes me seethe because if Asherman’s is caught early it’s totally treatable.”</span><br />
<span style="color: #990000;">“It’s treatable in the early stages, but it took two years for me to get a diagnosis.”</span><br />
<br />
<br />
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.<br />
<br />
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.<br />
<br />
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.<br />
<br />
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.<br />
<br />
<b>Prevalence versus incidence</b><span style="color: #990000;">“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.”</span><br />
<br />
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.<br />
<br />
<span style="color: #000099;">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.</span></span><br />
<span style="font-family: trebuchet ms;"><span style="color: #000099;"></span><br />
<b>Prevention: more information and accuracy needed</b><br />
<br />
<span style="color: #660000;">“Doctors are increasingly opting for less-invasive methods including suction or the use of tablets”</span><br />
<br />
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.<br />
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:<br />
<br />
<span style="color: #000099;">Chapman and Chapman, 1990: (13)<br />
“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”</span><br />
<br />
Dalton et al, 2006 (14)<br />
<span style="color: #000099;">“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."</span><br />
<br />
<span style="color: #000099;">“After 262 office MVAs for first trimester pregnancy losses, we have identified 5 cases of IUAs…”</span><br />
<br />
<br />
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.<br />
<br />
The mysterious ‘tablets’ mentioned allude to <span style="color: #000099;"><a href="http://www.misoprostol.org/" target="'_blank">misoprostol</a></span>, 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). </span><br />
<span style="font-family: trebuchet ms;"></span><br />
<span style="font-family: trebuchet ms;">Here you can find out more about how <a href="http://ashermansprevention.blogspot.com/2009/11/misprostol-for-miscarriage-management.html" target="'_blank">misoprostol can prevent AS if you have a miscarriage</a>. It can also prevent recurrence of AS in women who have a <a href="http://ashermansprevention.blogspot.com/2009/12/miscarriage-after-ashermans-syndrome.html" target="'_blank">miscarriage after having had the condition</a>.</span><span style="font-family: trebuchet ms;"></span><span style="font-family: trebuchet ms;"><br />
REFERENCES<br />
<br />
1. Toaff R, Ballas S (1978). "Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome)". Fertil. Steril. 30 (4): 379–87. </span><br />
<span style="font-family: trebuchet ms;"><br />
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.<br />
<br />
3. Valle RF, and Sciarra JJ (1988). "Intrauterine adhesions: Hystreoscopic diagnosis, classification, treatment and reproductive outcome". . Am J Obstet 158 (6Pt1): 1459–1470.<br />
<br />
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.<br />
<br />
5. Robinson JK, Colimon LM, Isaacson KB. Postoperative adhesiolysis therapy for intrauterine adhesions (Asherman's syndrome). Fertil Steril. 2008;90(2):409-14.<br />
<br />
6. March CM. (1995). "Intrauterine adhesions". Obstet Gynecol Clin N Am 22: 98–103.<br />
<br />
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.<br />
<br />
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.<br />
<br />
9. Golan, A., et al., Hysteroscopic findings after missed abortion. Fertil Steril, 1992. 58(3): p. 508-10.<br />
<br />
10. Romer, T European Journal of Obstetrics & Gynecology and Reproductive Biology<br />
Volume 57, Issue 3, December 1994, Pages 171-173<br />
<br />
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.<br />
<br />
12. Kodaman PH, Arici AA. (2007). "Intra-uterine adhesions and fertility outcome: how to optimize success?". Curr Opin Obstet Gynecol 19 (3): 207–214.<br />
<br />
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.<br />
<br />
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 </span>Unknownnoreply@blogger.com0tag:blogger.com,1999:blog-3857335766321699748.post-25747530585209729242010-04-21T04:28:00.000-07:002011-02-01T23:24:44.885-08:00The DO’s and DON’T's (and maybe’s) of Managing Intrauterine Adhesions.<span style="font-family: trebuchet ms;">Based on: </span><span style="font-family: trebuchet ms;"><b><a href="http://www.ncbi.nlm.nih.gov/pubmed/20129325">AAGL: Practice Report: Practice Guidelines for Management of Intrauterine Synechiae, The Journal of Minimally Invasive Gynecology Vol. 17, No.1 2010. </a></b><br />
Practice committee members:<br />
<br />
Malcolm Munro MD, FRCS(C), FACOG<br />
Rafaele F.Valle,MD<br />
Jason A. Abbott, PhD,FRANZCOG,MRCOG<br />
Angus J.M. Thompson, MRCOG<br />
Keith B. Isaacson, MD<br />
Adolf Gallinat, MD<br />
Volker R. Jacobs, MD, PhD, MBA<br />
Fred M. Howard MD<br />
Andrew I. Sokol, MD<br />
Linda D. Bradley, MD<br />
<br />
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.<br />
<br />
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.<br />
<br />
Below is a summary of the recommendations of the article. My additional comments are in </span><span style="font-family: trebuchet ms;"><span style="color: #000099;">blue font.</span></span><span style="font-family: trebuchet ms;"><b>DIAGNOSIS</b>Hysteroscopy 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).<br />
(Grade B)</span><br />
<span style="font-family: trebuchet ms;"><br />
<b>CLASSIFICATION</b><br />
Although there are several classification systems, none is considered superior over the other, probably reflecting inadequacies in all current systems. (Grade C)<br />
<br />
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)<br />
<br />
<br />
<b>TREATMENT</b><br />
<b>DO's:</b><br />
<br />
Only expert hysteroscopists familiar with IUA treatment should attempt to treat extensive or dense adhesions. (Level C)</span><span style="font-family: trebuchet ms;"><span style="color: #000099;">(Surgeons who are inexperienced may inadvertantly cause further irreparable damage).</span><br />
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).<br />
<br />
In some women expectant management may be acceptable. (Level C)<br />
<span style="color: #000099;">(ie. if adhesions are thin and filmy and/or cover a small surface area treatment benefits may not outweigh treatment risks).</span><br />
<br />
Estrogen therapy with or without progestin may reduce reformation of IUAs. (Level B)</span><span style="font-family: trebuchet ms;"><span style="color: #000099;">(Estrogen therapy dose and length will depend on severity. See also Recommendations for Future Research).</span><br />
<b>MAYBE's:</b><br />
<br />
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)<br />
<span style="color: #000099;">(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).</span><br />
<br />
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)<br />
<span style="color: #000099;">(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)).</span><br />
<br />
Supporting or refuting the use of prophylactic antibiotics before, during or after surgical adhesiolysis. (Level C)<br />
<span style="color: #000099;">(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).</span><br />
<br />
Medications to improve blood flow to the endometrium should be used only after being supported by rigorous research. (Level C)</span><span style="font-family: trebuchet ms;"><span style="color: #000099;">(These include low-dose aspirin, Coenzyme Q-10, vitamin E, and Sildenafil citrate.ie. Viagra, and even herbal remedies such as raspberry leaf tea).</span><br />
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)</span><span style="font-family: trebuchet ms;"><span style="color: #000099;">(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).</span><br />
<b>DON’T's:</b><br />
<br />
There is no evidence to support blind D&C or blind cervical probing in the treatment of IUA (Level C)</span><span style="font-family: trebuchet ms;"><span style="color: #000099;">(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)).</span><br />
Copper (inflammatory), progestin-releasing (suppress endometrium) and T-shaped IUDs (small surface area) should not be used after adhesiolysis. (Level C)<br />
<br />
Laparotomy should be considered as a last resort (eg. when hysteroscopic surgery fails) (Level C)<br />
</span><span style="font-family: trebuchet ms;"><span style="color: #000099;"><b>Electrosurgery/laser:</b> 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.</span></span><span style="font-family: trebuchet ms;"><b>POSTOPERATIVE ASSESSMENT:</b>Follow-up evaluation of the uterine cavity is recommended after treatment of IUA. (Level B).</span><span style="font-family: trebuchet ms;"><span style="color: #000099;">(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).</span><br />
<b>RECOMMENDATIONS FOR FUTURE RESEARCH:</b><br />
<br />
1. Prospective trials on the effect of intraoperative and postoperative antibiotic prophylaxis on surgical and fertility outcome.</span><span style="color: #000099;"><span style="font-family: trebuchet ms;">(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 </span><a href="http://ashermansprevention.blogspot.com/2009/10/subclinical-infection-myth-part-i.html" target="_blank"><span style="font-family: trebuchet ms;">The subclinical infection myth</span></a><span style="font-family: trebuchet ms;">).</span></span><span style="font-family: trebuchet ms;">2. Prospective trials of adjunctive hormone therapy efficacy with respect to surgical and fertility outcome.</span><span style="font-family: trebuchet ms;"><span style="color: #000099;" target="_blank">(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).</span><br />
3. Prospective trials of barrier method (IUD, Foley catheter and gel adhesion barriers) efficacy with respect to surgical and fertility outcome.<br />
<span style="color: #000099;" target="_blank">(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)).</span><br />
</span><span style="color: #000099;"><span style="font-family: trebuchet ms;">4. Stem cells for future treatment: <a href="http://ashermansprevention.blogspot.com/2009/09/without-new-breakthroughs-treatment.html">As discussed in a previous blog</a>, 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 </span><a href="http://timesofindia.indiatimes.com/city/ahmedabad/Good-news-Grow-endometrium-by-stem-cells/articleshow/5312307.cms" target="_blank"><span style="font-family: trebuchet ms;">stem cell technology to thicken the endometrium</span></a><span style="font-family: trebuchet ms;"> 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.</span></span><br />
<span style="font-family: trebuchet ms;">REFERENCES<br />
<br />
1. Fritsch H, Ein Fall von volligem Schwaund der Gebormutterhohle nach Auskratzung. Zentralbl Gynaekol 1894; 18:1337-1342.<br />
<br />
2. March, CM; Miller, CE. Hysteroscopic lysis of intrauterine adhesions. Ob.Gyn. News 2006; 41(23):36-37. </span><a href="http://www.obgynnews.com/article/S0029-7437%2806%2972455-7/preview" target="_blank"><span style="font-family: trebuchet ms;">Abstract</span></a><span style="font-family: trebuchet ms;"><br />
<br />
3. Palter. SF, High Rates of Endometriosis in Patients With Intrauterine Synechiae (Asherman's Syndrome). Fertility and Sterility 2005; 86 (null):S471-S471. </span><a href="http://linkinghub.elsevier.com/retrieve/pii/S0015028205027019" target="_blank"><span style="font-family: trebuchet ms;">Link</span></a><span style="font-family: trebuchet ms;"><br />
<br />
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. </span><a href="http://link%20%20http//www.fertstert.org/article/S0015-0282%2803%2901900-9/abstract" target="_blank"><span style="font-family: trebuchet ms;">Link</span></a><span style="font-family: trebuchet ms;"><br />
<br />
5. March CM. Intrauterine adhesions. Obstet Gynecol Clin N Am 1995;22(3):491-505. </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/8524533" target="_blank"><span style="font-family: trebuchet ms;">Abstract </span></a><br />
<br />
<span style="font-family: trebuchet ms;">6. Jensen, P.A. and Stromme, W.B. Amenorrhea secondary to puerperal curettage (Asherman's syndrome). Am J Obstet Gynecol 1972; 113: 150–4.<br />
<br />
7. Polishuk, SO Anteby and D Weinstein, Puerperal endometritis and intrauterine adhesions, Int Surg 1975;60:418–420. </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/1158622" target="_blank"><span style="font-family: trebuchet ms;">Abstract</span></a><span style="font-family: trebuchet ms;"><br />
</span><br />
<span style="font-family: trebuchet ms;">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. <a href="http://www.ncbi.nlm.nih.gov/pubmed/11787023">Abstract</a> </span><br />
<span style="font-family: trebuchet ms;"></span><br />
<span style="font-family: trebuchet ms;">Related Links:</span><a href="http://timesofindia.indiatimes.com/city/ahmedabad/Good-news-Grow-endometrium-by-stem-cells/articleshow/5312307.cms" target="_blank"><span style="font-family: trebuchet ms;">Good news: Grow endometrium by stem cells.</span></a><span style="font-family: trebuchet ms;"> (Times of India)<br />
<br />
Recommendation Grading:<br />
Level A: Recommendations are based on good and consistent scientific evidence.<br />
Level B: Recommendations are based on limited or incomsistent scientific evidence.<br />
Level C: Recommendations are based primarily on consensus and expert opinion.</span>Unknownnoreply@blogger.com2