Recurrent miscarriage affects about 1% of all women of child
bearing age.
50% of all early pregnancy loss are due to chromosomal aberration,
most common being aneuploidy.
Progestogens play an important role in implantation,
cytokine balance, natural killer cell activity, arachidonic acid release and
myometrial contractility. It is secreted by corpus luteum till 7-8 weeks, when
the function is taken over by developing placenta. Lack of progesterone support
in the luteal phase increases the chances of early pregnancy loss; hence
progesterone is often used specially in women with history of recurrent
pregnancy loss!
Results of a recent large RCT published in the November issue of New England Journal of Medicine concluded that Progesterone Doesn't Improve
Outcomes After Recurrent Miscarriages.
This large multicenter, double-blind, placebo-controlled,
randomized trial recruited 1568 women aged 18-39 years with a history of three
or more consecutive or nonconsecutive first-trimester pregnancy losses. Women
with anatomical, medical or hematological causes that explain the reason behind
miscarriages were excluded from the study.
The study group (n=404) were assigned to receive 400mg of
vaginal micronized progesterone , while the control group ( n=432) received a similar
looking placebo as soon as the pregnancy were confirmed till 12 weeks of
naturally conceived pregnancy.
The live birth rate in progesterone group was 65.8% vs. 63.3%
in placebo group. The rate of ectopic pregnancy, congenital anomalies, miscarriage
and still birth rates were also comparable in both the groups.
A Cochrane review in 2013 based on smaller number of trials
and subject reported lower rate of miscarriage with progesterone support. This
large RCT lead us to a different conclusion.
Management of women with RPL is a challenge in itself, as
these women are very anxious and apprehensive and ask for some form of ‘therapy’
to avert a loss again. Over the years many other modalities like heparin, aspirin
and acupuncture have been evaluated with mixed results.
There are many unanswered question in therapy of RPL,
including the definition of RPL, the evaluation and the timing of starting treatment.
Progesterone is an important part of regimen offered, being having endometrial
supportive and immune-modulating effects.
Different studies have come up with different results; the
study also differed in patient population, mode and type of progesterone and
the initiation of treatment since pregnancy confirmation.
Whatever the results and conclusions of different trials may
be, the psychological and placebo effect of the progesterone cannot be
overlooked for patients who have a high level of anxiety and are afraid of
another loss.
References:
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