Friday, August 28, 2009

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

Continued from Part I

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

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

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

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

1. Zikopoulos et al, 2004 (4)20/46 43.5%
2. Fernandez et al, 2006 (5) 21/64 32.8%
3. Thomson et al, 2007 (6)8/27 29.6%*
4. Yu et al, 2008 (7)25/85 29%

5. Robinson et al, 2008
(8)4/15 27% **
6. Pabuccu et al, 2008 (9)22/71 31%

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

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

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

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

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

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

Continued in Part III


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

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

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

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

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

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

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

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

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


Friday, August 14, 2009

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

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

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

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

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

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

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

Continued in Part II

Tuesday, August 4, 2009

Asherman's syndrome after curettage is not rare

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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