Miscarriage management after Asherman’s syndrome

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

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

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

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

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

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

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

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

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

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


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

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


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

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

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

There are also some implications that can be speculated:

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

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

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

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

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

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

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

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

Misprostol for miscarriage management to prevent Asherman's syndrome

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

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

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

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

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

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

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

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

REFERENCES

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

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

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