I recently went to the annual national meeting for Reproductive Endocrinology and Infertility specialist, ASRM (American Society of Reproductive Medicine) in Oct 2019 and I learnt something about progesterone and miscarriage which I wanted to share with women.
In May 2019, a publication in the New England Journal of Medicine (high impact and respected journal for publishing important clinical trials) had an article titled A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. This study was conducted in United Kingdom and wanted to ask the question : does giving vaginal progesterone twice daily increase the live birth rate (birth at or after 34 weeks) in women between 16-39 years old if they presented with vaginal bleeding and a early pregnancy (less than 12 weeks pregnancy) inside the uterus documented by ultrasound? 4153 women volunteered and were randomly assigned either vaginal progesterone suppositories or placebo suppositories (no medicine), their doctors and the women did not know what they got. They continued this until 16 weeks of pregnancy and then stopped. The results showed that 75% of women who received progesterone had live births compared with 72% of women who did not receive progesterone. The conclusion from this large clinical trial is that giving vaginal progesterone twice daily at the dose that they tested (400 mg) did not change the live birth rate for pregnant women with vaginal bleeding before 12 weeks of pregnancy.
However, the researchers then looked at different groups of women within the study to see if any specific types of women would a benefit from progesterone. For women who had no history of miscarriage, there was no benefit to using vaginal progesterone. For women who had a history of 1 or 2 prior miscarriages there was minimal benefit, 76% live birth rate for women using progesterone compared to 72% live birth rate for women with no progesterone. Importantly, one group benefited significantly, women who have had 3 or more prior miscarriages. For these women with multiple losses, 72% had a live birth if they took progesterone compared with live birth rate of 57% for those who did not take progesterone. The authors discussed that this is an observation that has to be validated in future studies. Therefore, the take home is that women with ultrasound documented pregnancy less than 12 weeks and vaginal bleeding with a history of at least one prior miscarriage MAY benefit from starting vaginal progesterone twice daily if they start bleeding before 12 weeks of pregnancy, however, future studies will need to be performed to support this to become DEFINITELY benefit.
Reassuring, in this study, there were no obvious harmful effects such as birth weight differences or increase in birth defects in the babies when progesterone was given. Importantly though, the authors discuss that their study was not large enough to show any true increase in birth defects with use of progesterone.
As a physician, I weigh up the benefits versus the harm to patients and involve patients actively in this decision when offering treatments. Therefore, with this study, offering vaginal progesterone to pregnant women with vaginal bleeding with three or more miscarriages will likely benefit outweigh the harm. For women with 1-2 prior miscarriages there should be a discussion of balancing minimal benefit vs harm.
For those who answered my survey on what women want from a MD led miscarriage site. This is the first of my blogs on research in the miscarriage which all respondents said would be of interest. Hope this helps.