Mater Mother’s Hospital in Queensland has been conducting a randomized controlled trial comparing two doses of misoprostol (800 mcg versus 400 mcg) for the medical management of miscarriage. More information can be found in the brochure for The Miscarriage Study on their website:
http://brochures.mater.org.au/Home/Brochures/Mater-Mothers--Hospitals/Miscarriage
Medical management is only available to women participating in the Miscarriage Study. Surgery or expectant management is offered as standard care options to women who choose not to participate.
The web brochure explains that the study is being carried out because currently there is no agreement on the most effective dose for misoprostol use in miscarriage. However it points out that 800mcg is the most common dose used in studies. While it is true that researchers have not determined a dosage/regimen which is as effective as D&C i.e. the ‘optimum’ protocol for medical management using misoprostol, preliminary guidelines based on hundreds of studies have been produced by the expert group convened by WHO in Bellagio in February 2007. They are published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) and can be read here. According to these guidelines, 600-800 mcg misoprostol is the recommended dose for first trimester miscarriage. The guidelines for misoprostol use according to indication and gestational age are also available at: http://www.misoprostol.org/ This website also provides excellent resources to clinicians interested in information about misoprostol use and the misoprostol debate.
The researchers have chosen to study quite a low dosage of misoprostol to reduce side effects. However, it has already been established that even 600-800 mcg is not as effective for first trimester miscarriage as the standard care D&C (it remains questionable as to why it is imperative for medical management to be equally as effective as D&C for it to be used when medical management offers the advantages of being non-invasive, cheap, free of anesthetics and safer for future fertility than D&C).The drug is inexpensive, so cost is evidently not an issue. Furthermore, the optimum dose for use in termination up to 7 weeks is 800 mcg (in combination with mifepristone). A recent study found that this dose should not be lowered (link). Apparently misoprostol side effects for termination are not a concern for women. One would imagine the same for women who miscarry.
Misoprostol is listed in the Standard Drug List of Queensland Hospitals for use in miscarriage and is currently used in this hospital for the treatment of other pregnancy complications. The Therapeutic Goods Administration (TGA), which is the Australian equivalent of the FDA in the US, has not approved of its use in pregnancy in Australia.
However, the Queensland Health and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists support its use in the treatment of miscarriage. Despite this, misoprostol use for first trimester miscarriage remains uncommon in Australia. The drug is quite commonly used for miscarriage management in European countries. In contrast, a combined misoprostol/mifepristone regimen is offered by most if not all services in Australia specializing in pregnancy termination. It has also become common practice for labour induction despite the fact that there is not more evidence to support its use for this indication than for miscarriage. Interestingly, expectant management is considered acceptable although it is not more effective than for miscarriage management in clinical trials. Health professionals excuse the restricted access to misoprostol for miscarriage management with the pretext that misoprostol is not TGA approved, yet misoprostol use in ALL obstetric/gynecologic indications is not approved (misoprostol was developed for the treatment and prevention of ulcers). The unlicensed use of misoprostol for terminations is cunningly circumvented by a legal loophole which allows its use in combination with mifepristone which is only TGA approved for use in pregnancy termination. Unlicensed use of misoprostol in labour induction, curiously, does not seem to hinder clinicians from using it for labour induction even though substantially less is known about the short and long term effects it may have on infants exposed to it. Misoprostol is also used in the treatment of osteoarthritis and marketed under the name Arthrotec. Curiously, there is no debate over the unlicensed use of misoprostol for arthritis. Yet none of the above has lead to questioning the objective validity behind the selective use of misoprostol for some unlicensed obstetric (or other) indications but not for miscarriage management. Why is it that the only people who seem to be prevented from using misoprostol are women who miscarry?
Most women who miscarry have no choice but to undergo a costly D&C, potentially leading to long term adverse effects on fertility (Asherman’s syndrome) and a host of possible future obstetric complications (placenta accreta, percreta, previa, IUGR, pre eclampsia, preterm birth, cervical insufficiency leading to second trimester loss, and uterine rupture). It is ironic that the very women who desire a pregnancy most are also those who are exposed to iatrogenic infertility and/or pregnancy complications arising from surgical management. Disappointing overall reproductive outcomes (40%) and associated healthcare costs (not to mention patient discontent) do not make the approach of relying on treatment of Asherman’s syndrome a paradigm. The restriction of a safe, inexpensive and non-invasive alternative such as misoprostol for miscarriage management can be considered unethical and perhaps even discriminatory as it is available to other populations of women for unlicensed obstetric/gynecological indications.
The Mater Mother’s Hospital webpage mentions potential complications from surgical management (D&C) without specifically naming Asherman’s syndrome (intrauterine adhesions and/or fibrosis) or cervical insufficiency (from cervical dilation). It also quotes the risk of complications from D&C as 1:200-500 surgeries, a greatly underestimated frequency (see Frequency of intrauterine adhesions after curettage).
It is encouraging to see local studies on misoprostol for miscarriage management. Even if 400 ug will turn out to have a significantly lower success rate than 800 ug, exposure to women and clinicians could help promote awareness about it and increase its demand/use. Perhaps it is a sign that Australia is finally ready to implement medical management as a routine care option.
Showing posts with label miscarriage management. Show all posts
Showing posts with label miscarriage management. Show all posts
Tuesday, August 31, 2010
Monday, July 19, 2010
Misoprostol for miscarriage management: the facts and the fiction
This is my latest Youtube video presentation. It explains the truth behind often repeated misinformation about misoprostol.
Misoprostol for miscarriage management is underused despite evidence of its efficacy and safety. It is an ideal alternative to D&C. It can also prevent Asherman's syndrome which mainly occurs from D&C, a blind surgery. This clip clarifies concerns about misoprostol which may be hindering its use by clinicians and patients alike.
Wednesday, May 26, 2010
Failed medical management or a failure to comply with accepted guidelines?
Only 4 months after an in utero fetal demise at 14 weeks, I had a first trimester miscarriage at 8 weeks. I had conceived (naturally again) after only a month of trying and the pregnancy was suspected by chance at a follow up for my previous miscarriage only a few days after implantation. I’d had my next ultrasounds at 5 weeks, just under 8 weeks-where a heart rate of 151 bpm was detected- and then at 9 weeks, where there was no longer any cardiac activity.
As if this was not bad enough, I was again faced with how to cope with the physical side of this loss without incurring damage to my previously scarred uterus. Misoprostol was of course my method of choice. I learned that I would have to be admitted as an in-patient according to this hospital’s treatment protocol, although I know that in other countries misoprostol management of first trimester miscarriage (and abortion) are routinely done on an out-patient basis. This of course would increase the cost of the procedure. Once I was admitted, I learned that I would be given the same protocol as for second trimester terminations. This is because the hospital only has protocols in place using misoprostol for late abortions.
I should clarify that in Australia, misoprostol is rarely used for first trimester miscarriage. This was an exception for them and I am relieved that I was not forced into having a D&C which caused this whole debacle to begin with.
What worried me was that the accepted dosage for second trimester terminations (400 mcg every 3 hours up to 5 times) is lower per administration than that recommended for first trimester miscarriage. According to guidelines published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) a woman with a first trimester miscarriage should be given 2 doses of 800 mcg of misoprostol (vaginally) 3 hours apart. This is because early in a pregnancy, there are fewer prostaglandin receptors to which misoprostol binds than later in pregnancy.
While I received the same protocol for my previous second trimester miscarriage as for second trimester abortion, the accepted protocols for these two indications are much more similar and was thus it was more effective. However, this dosage is not considered effective for first trimester pregnancy failure and with good reason, as I subsequently found out: it simply does not work. On the first day I received 5 doses but none of them produced contractions that were strong enough to evacuate the uterus. There seemed to be less uterine contractions and bleeding after the first few administrations as though the effects were wearing off. I was given a 12 hour break before starting again. I requested that the drug be given orally instead this time. I had even less of a reaction, not even nausea or diarrhea which are commonly reported side effects of oral misoprostol. The following day, I agreed to hysteroscopic removal with my Asherman’s syndrome specialist.
According to this specialist, my cervix was slightly dilated but not enough for the gestational sac to pass through. The gestational sac had implanted slightly low in the uterine cavity (future placenta previa?), and in the anterior wall, in a region where I’d had scarring from my D&C and adhesions. Tissue obtained during the hysteroscopy did not grow in culture so I was unable to find out the karyotype of the embryo, or subsequently, the gender. It is possible that I miscarried because by chance the embryo implanted in a region where I’d had previous scarring and possible fibrosis, and the blood supply was not sufficient to maintain the pregnancy. If so, this is much more upsetting than if the baby was chromosomally abnormal and would not have survived anyway. I will never know for sure what caused this miscarriage, but an Asherman’s related cause cannot be either confirmed or ruled out.
It is quite possible that I would have required hysteroscopy to remove retained products, as I had previous uterine scarring from Asherman's syndrome, and the embryo also implanted in the area of the previous scarring. However, had I been given the correct dosage, I may not have needed to wait another day to respond to a drug which was given in too low a quantity to be effective anyway.
I noticed that on my hysteroscopic surgery report written under ‘reason for hysteroscopy’ was ‘failed medical management of miscarriage.’ This made me wonder if doctors and nurses would look at my file and incorrectly conclude that misoprostol was an ineffective drug for miscarriage, rather than realizing that the dose I had been given was inappropriate and not officially recommended for my stage of pregnancy. I wonder how many other women who claim their miscarriage management with misoprostol was a ‘failure’ were also given a dose not suited to their gestational age. From a patient perspective, I wonder why it is not possible for my hospital to provide treatment according to published recommendations for that indication (rather than according to a protocol used for another indication ie. second trimester abortion)? What is the logic in applying a protocol which goes against evidence-based medicine? I hope that instead of discouraging doctors, my experience will go towards persuading this hospital to broaden the current protocol so that women with first trimester miscarriage will benefit from misoprostol. For misoprostol to be effective and safe, it needs to be used according to established guidelines which take into account factors such as gestational age and indication.
As if this was not bad enough, I was again faced with how to cope with the physical side of this loss without incurring damage to my previously scarred uterus. Misoprostol was of course my method of choice. I learned that I would have to be admitted as an in-patient according to this hospital’s treatment protocol, although I know that in other countries misoprostol management of first trimester miscarriage (and abortion) are routinely done on an out-patient basis. This of course would increase the cost of the procedure. Once I was admitted, I learned that I would be given the same protocol as for second trimester terminations. This is because the hospital only has protocols in place using misoprostol for late abortions.
I should clarify that in Australia, misoprostol is rarely used for first trimester miscarriage. This was an exception for them and I am relieved that I was not forced into having a D&C which caused this whole debacle to begin with.
What worried me was that the accepted dosage for second trimester terminations (400 mcg every 3 hours up to 5 times) is lower per administration than that recommended for first trimester miscarriage. According to guidelines published in a supplement to the International Journal of Gynecology and Obstetrics (2007, vol. 99) a woman with a first trimester miscarriage should be given 2 doses of 800 mcg of misoprostol (vaginally) 3 hours apart. This is because early in a pregnancy, there are fewer prostaglandin receptors to which misoprostol binds than later in pregnancy.
While I received the same protocol for my previous second trimester miscarriage as for second trimester abortion, the accepted protocols for these two indications are much more similar and was thus it was more effective. However, this dosage is not considered effective for first trimester pregnancy failure and with good reason, as I subsequently found out: it simply does not work. On the first day I received 5 doses but none of them produced contractions that were strong enough to evacuate the uterus. There seemed to be less uterine contractions and bleeding after the first few administrations as though the effects were wearing off. I was given a 12 hour break before starting again. I requested that the drug be given orally instead this time. I had even less of a reaction, not even nausea or diarrhea which are commonly reported side effects of oral misoprostol. The following day, I agreed to hysteroscopic removal with my Asherman’s syndrome specialist.
According to this specialist, my cervix was slightly dilated but not enough for the gestational sac to pass through. The gestational sac had implanted slightly low in the uterine cavity (future placenta previa?), and in the anterior wall, in a region where I’d had scarring from my D&C and adhesions. Tissue obtained during the hysteroscopy did not grow in culture so I was unable to find out the karyotype of the embryo, or subsequently, the gender. It is possible that I miscarried because by chance the embryo implanted in a region where I’d had previous scarring and possible fibrosis, and the blood supply was not sufficient to maintain the pregnancy. If so, this is much more upsetting than if the baby was chromosomally abnormal and would not have survived anyway. I will never know for sure what caused this miscarriage, but an Asherman’s related cause cannot be either confirmed or ruled out.
It is quite possible that I would have required hysteroscopy to remove retained products, as I had previous uterine scarring from Asherman's syndrome, and the embryo also implanted in the area of the previous scarring. However, had I been given the correct dosage, I may not have needed to wait another day to respond to a drug which was given in too low a quantity to be effective anyway.
I noticed that on my hysteroscopic surgery report written under ‘reason for hysteroscopy’ was ‘failed medical management of miscarriage.’ This made me wonder if doctors and nurses would look at my file and incorrectly conclude that misoprostol was an ineffective drug for miscarriage, rather than realizing that the dose I had been given was inappropriate and not officially recommended for my stage of pregnancy. I wonder how many other women who claim their miscarriage management with misoprostol was a ‘failure’ were also given a dose not suited to their gestational age. From a patient perspective, I wonder why it is not possible for my hospital to provide treatment according to published recommendations for that indication (rather than according to a protocol used for another indication ie. second trimester abortion)? What is the logic in applying a protocol which goes against evidence-based medicine? I hope that instead of discouraging doctors, my experience will go towards persuading this hospital to broaden the current protocol so that women with first trimester miscarriage will benefit from misoprostol. For misoprostol to be effective and safe, it needs to be used according to established guidelines which take into account factors such as gestational age and indication.
Tuesday, February 9, 2010
Medical management of miscarriage snubbed by doctors
The following are examples of the medical community's exclusion of medical management as a choice to women who have miscarried. Some countries including Australia and the UK seem to be in the dark ages when it comes to offering misoprostol and/or mifepristone.
The first example is the Royal Women's Hospital in Victoria (Australia). Their website boasts:
"We are also a major teaching hospital and a medical research leader of world renown...We are an advocate for improvements in women’s health and well-being."
Yet, when you look up miscarriage management there is a detailed table comparing expectant management (natural expulsion aka waiting to miscarry) to surgical management (ie. D&C). There is simply no mention of medical management (eg. misoprostol), as if it did not exist.
Sydney IVF is, according to its website, 'Australia's leading centre for infertility and IVF treatment.' It even has a Miscarriage Management Program which promises close monitoring for women with recurrent miscarriage. One could be mistaken for thinking that a center specializing in miscarriage management for recurrent miscarriages would offer medical management as the risk of Asherman's syndrome increases with each D&C. However, it's protocol for managing miscarriages is limited to D&C or natural expulsion:
"It is important to be certain all the tissue relating to the pregnancy is removed, either naturally, or with a D&C (a "curette")."
The website has an extensive glossary of medical terms. Misoprostol is not included.
The third offender is the Women's Health website (UK) which describes only two choices for miscarriage, D&C or natural expulsion. Unfortunately it also fails to mention Asherman's syndrome as a possible complication.
And these are just drops in the ocean.
Meanwhile, abortion clinics in Australia are quick to advertize that they offer the 'abortion pill' . They are referring to misoprostol and mifepristone. It's unfortunate that these drugs have become synonymous with abortions when they can also be used effectively for treatment of miscarriage. These drugs should be made available to ALL women, not just those wanting to terminate a pregnancy. As a society, we must ask why women with an undesired normal pregnancy can receive a treatment regimen that is safer (ie. drugs such as misoprostol) than that standardly used for women with a desired abnormal pregnancy.
As for surgical termination, the website claims that : "In expert hands, termination of pregnancy is the safest procedure in gynaecology." This is absolutely false. Not only because I can think of several other gynecological procedures which are much safer such as hysteroscopy when performed by experts, ultrasound, HSG, SHG, and pap smears. Just as D&C can cause Asherman's syndrome following miscarriage, it can do so when performed for termination, REGARDLESS of whether you have 'infections or endometriosis' as mentioned on the website. Most studies on Asherman's syndrome include women who acquired the condition from surgical termination (as well as other D&Cs and uterine surgery). Therefore medical abortion can also prevent Asherman's syndrome. I believe that if the trend for medical abortion continues, there will be very few cases of AS in this population of women.
The first example is the Royal Women's Hospital in Victoria (Australia). Their website boasts:
"We are also a major teaching hospital and a medical research leader of world renown...We are an advocate for improvements in women’s health and well-being."
Yet, when you look up miscarriage management there is a detailed table comparing expectant management (natural expulsion aka waiting to miscarry) to surgical management (ie. D&C). There is simply no mention of medical management (eg. misoprostol), as if it did not exist.
Sydney IVF is, according to its website, 'Australia's leading centre for infertility and IVF treatment.' It even has a Miscarriage Management Program which promises close monitoring for women with recurrent miscarriage. One could be mistaken for thinking that a center specializing in miscarriage management for recurrent miscarriages would offer medical management as the risk of Asherman's syndrome increases with each D&C. However, it's protocol for managing miscarriages is limited to D&C or natural expulsion:
"It is important to be certain all the tissue relating to the pregnancy is removed, either naturally, or with a D&C (a "curette")."
The website has an extensive glossary of medical terms. Misoprostol is not included.
The third offender is the Women's Health website (UK) which describes only two choices for miscarriage, D&C or natural expulsion. Unfortunately it also fails to mention Asherman's syndrome as a possible complication.
And these are just drops in the ocean.
Meanwhile, abortion clinics in Australia are quick to advertize that they offer the 'abortion pill' . They are referring to misoprostol and mifepristone. It's unfortunate that these drugs have become synonymous with abortions when they can also be used effectively for treatment of miscarriage. These drugs should be made available to ALL women, not just those wanting to terminate a pregnancy. As a society, we must ask why women with an undesired normal pregnancy can receive a treatment regimen that is safer (ie. drugs such as misoprostol) than that standardly used for women with a desired abnormal pregnancy.
As for surgical termination, the website claims that : "In expert hands, termination of pregnancy is the safest procedure in gynaecology." This is absolutely false. Not only because I can think of several other gynecological procedures which are much safer such as hysteroscopy when performed by experts, ultrasound, HSG, SHG, and pap smears. Just as D&C can cause Asherman's syndrome following miscarriage, it can do so when performed for termination, REGARDLESS of whether you have 'infections or endometriosis' as mentioned on the website. Most studies on Asherman's syndrome include women who acquired the condition from surgical termination (as well as other D&Cs and uterine surgery). Therefore medical abortion can also prevent Asherman's syndrome. I believe that if the trend for medical abortion continues, there will be very few cases of AS in this population of women.
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