Currently, in Canada, a thorough workup into the cause of a pregnancy loss isn’t recommended until a woman experiences three or more miscarriages. Recurrent miscarriages are estimated to occur in 1-1.5% of the population, and are defined as three or more pregnancy losses before 20 weeks 1. The trauma of experiencing one miscarriage—let alone three—is significant, and a more thorough workup into the underlying cause of a miscarriage(s) should be considered earlier on.
Identifiable causes of recurrent miscarriage can often be found, such as genetic defects, clotting disorders and autoimmune disease. In up to 50% of cases, however, no underlying causes can be uncovered. In these situations, women are left with very few treatment options and are commonly instructed to continue trying.
An insufficient level of progesterone at the time of implantation or early on in pregnancy has been identified as another possible cause of recurrent miscarriage, and could be treated accordingly1.
Progesterone's Role in Pregnancy
Progesterone is a steroid hormone that’s released after ovulation, in the second half of the menstrual cycle. It’s the hormone responsible for the rise in temperature women experience post-ovulation, which can be monitored with a BBT. If there is no fertilized egg and no implantation occurs in a cycle, both estrogen and progesterone fall and the menstrual cycle restarts.
If implantation does occur, progesterone levels should continue to rise to support the pregnancy. In the first three months of pregnancy, a tissue in the ovary called the corpus luteum is what produces progesterone. After three months of pregnancy, the placenta should take over the production of progesterone until birth.
A rise in progesterone is what prepares the endometrial layer of the uterus for implantation and stops contractions of the muscular uterine wall. Progesterone also has important anti-inflammatory and immune-modulatory functions that are crucial in sustaining an early pregnancy.
Progesterone and Miscarriage Prevention
There’s a great deal of debate within the medical community surrounding progesterone supplementation’s effectiveness in pregnancy to reduce miscarriage. Some of the evidence to date supports progesterone supplementation, and finds that it reduces miscarriage risk. In contrast, other research contradicts this and finds no benefit.
One randomized control trial looked at using progesterone suppositories in women experiencing recurrent miscarriages with no explainable cause2. In this study, progesterone was given to women starting in the luteal phase of their cycle, before pregnancy was confirmed, and continued with the progesterone supplementation until 28 weeks along. In comparison to the control group who did not receive any progesterone, these women had almost half the number of miscarriages2.
In contrast, a similarly designed study found that progesterone supplementation was not associated with a decrease in miscarriage rates3.
A more comprehensive review done in 2018 looked at 13 different trials using progesterone to prevent recurrent miscarriage. The review concluded that giving progesterone can probably prevent miscarriage, and this treatment was most indicated in women who had up to three miscarriages4. This study also found that there was no difference in miscarriage rate if the progesterone was used as a suppository, orally, or as an injection4.
Is Progesterone Supplementation Safe?
Considering the contradicting data listed above, deciding whether to use this treatment or not can be challenging. In these situations, looking at the safety data around the treatment can help guide this decision.
There’s no current evidence that taking progesterone in pregnancy could lead to any fetal harm. The same 2018 review mentioned above found no impact on newborn death, low birth weight, or newborn birth defects in women using progestens in pregnancy4.
Progesterone also has a long history of use in late pregnancy to prevent preterm birth. Data looking at late pregnancy progesterone use in 11,188 women found no negative effect of progesterone on infant mortality5.
Given the conflicting research findings, it can’t be conclusively said that progesterone supplementation in pregnancy can reduce miscarriage. However, considering the positive safety profile and research studies to date, supplementing with progesterone in pregnancy should be a consideration in women, especially those experiencing recurrent miscarriages and in those whose blood tests show low progesterone levels.
Follow the links below for additional information about miscarriage, and key pregnancy hormones:
- Recurrent pregnancy loss is defined as three or more miscarriages before 20 weeks of pregnancy and occurs in 1-1.5% of the population
- Possible root causes of recurrent pregnancy loss include genetic, autoimmune, and clotting disorders
- In 50% of recurrent miscarriages a root cause can not be identified
- Low progesterone on implantation and/or early in pregnancy has been suggested as a possible cause of recurrent pregnancy loss
- Research to date is conflicting on whether progesterone supplementation in early pregnancy can reduce miscarriage rates
- Progesterone supplementation in pregnancy is not associated with harm to the baby or mother and has been used safely in late pregnancy to prevent preterm birth
(1) Hussain, M., Cahill, D., & El-Hakim, S. (2012). Progesterone supplementation in women with otherwise unexplained recurrent miscarriages. Journal Of Human Reproductive Sciences, 5(3), 248. doi: 10.4103/0974-1208.106335
(2) Ismail, A., Abbas, A., Ali, M., & Amin, A. (2017). Peri-conceptional progesterone treatment in women with unexplained recurrent miscarriage: a randomized double-blind placebo-controlled trial. The Journal Of Maternal-Fetal & Neonatal Medicine, 31(3), 388-394. doi: 10.1080/14767058.2017.1286315
(3) Coomarasamy, A., Williams, H., Truchanowicz, E., Seed, P., Small, R., & Quenby, S. et al. (2015). A Randomized Trial of Progesterone in Women with Recurrent Miscarriages. New England Journal Of Medicine, 373(22), 2141-2148. doi: 10.1056/nejmoa1504927
(4) Haas, D., Hathaway, T., & Ramsey, P. (2018). Progestogen for preventing miscarriage in women with recurrent miscarriage of unclear etiology. Cochrane Database Of Systematic Reviews. doi: 10.1002/14651858.cd003511.pub4
(5) Ahn, K., Bae, N., Hong, S., Lee, J., Lee, E., & Jee, H. et al. (2017). The safety of progestogen in the prevention of preterm birth: meta-analysis of neonatal mortality. Journal Of Perinatal Medicine, 45(1). doi: 10.1515/jpm-2015-0317