Progesterone Therapy to Reduce Recurrent Miscarriage Risk
The use of progesterone therapy to reduce miscarriage risk has been a topic of debate in the medical community for many years due to conflicting results in research. Recently, in November of 2021, the National Institute of Health and Care Excellence (NICE) made an exciting new recommendation! NICE now officially recommends progesterone therapy for women with early pregnancy bleeding and at least 1 previous miscarriage to reduce miscarriage risk (1).
Progesterone is a sex hormone that is produced after ovulation and is essential for a healthy pregnancy. It prepares the endometrium (the lining of the uterus) for implantation each cycle and rising levels throughout pregnancy are needed to carry to term. Progesterone also has important anti-inflammatory and immune-modulatory functions that are crucial in sustaining an early pregnancy.
The Official NICE Recommendation
This new recommendation comes after researchers reassessed a previous study that was published in the New England Journal of Medicine in 2019 (2). This study originally concluded that progesterone therapy did not reduce miscarriage risk, however, after taking a closer look at a smaller subset it was determined that women with a history of recurrent miscarriages (three or more) did show a significant reduction in miscarriage with progesterone therapy (2). Women with a history of one or two miscarriages also experienced a smaller but reduced risk with progesterone therapy (2).
The official NICE recommendation is as follows; progesterone can be considered as a therapy to reduce miscarriage risk in those who have vaginal bleeding in a current pregnancy and have previously had at least one miscarriage (1). The recommended treatment is 400mg of micronized progesterone twice a day and should be continued until 16 weeks of pregnancy (2).
Is Progesterone Therapy Safe?
Research to date shows that progesterone is very safe in pregnancy for both mom and baby. A review published in 2018 found no impact on newborn death rates, risk of low birth weight in babies, or newborn birth defects in women using progesterone therapy in pregnancy (3).
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 mortality (4).
Are There Other Treatment Options to Reduce Miscarriage Risk?
Although the new NICE criteria are very exciting, there is much more to miscarriage prevention than progesterone therapy.
The first step for anyone with a history of miscarriages is a thorough assessment to investigate the presence of risk factors. This includes comprehensive thyroid testing including looking for the presence of thyroid antibodies. Elevated thyroid antibodies have been found in many studies to be associated with increased miscarriage risk and rates even if the thyroid hormones themselves are normal (5).
Patients should have their metabolic health assessed including insulin and blood sugar levels. Elevated insulin levels are an independent risk factor for miscarriage (6). Research has found that high insulin can impact the formation of the placenta which allows for a healthy exchange of blood and nutrition to the growing baby (7). Other research suggests that elevated insulin can impact the expression of certain proteins that have an important role in the immune response within the endometrial lining which may also be playing a role in the increased miscarriage risk (6). You can read more about insulin and why I always test this hormone in my article here.
Vitamin D levels should be assessed in all women and men trying to conceive or with a history of miscarriages. A systematic review found that there was a high prevalence of Vitamin D deficiency in women experiencing recurrent losses (8). One study found that women with sufficient Vitamin D levels in the pre-conception period were more likely to carry to term than those with Vitamin D deficiency (9).
Markers of immune system function, autoimmunity and clotting factors should also be assessed in select patients.
The above are just some of the factors that have been identified in research to contribute to miscarriage risk and are all treatable through traditional medicine, naturopathic medicine or in many cases a combination of both.
In my practice, identifying any risk factor for miscarriage and treating it along with diet and lifestyle considerations as well as considering progesterone therapy when indicated has been the most successful approach!
A Final Note
If you have experienced a loss before, please know that you did nothing to cause this loss. Miscarriage is a devastating but unfortunately very common experience, with 1 in 4 pregnancies resulting in miscarriage. The majority of miscarriages are caused by genetic issues within the egg and sperm and the vast majority of couples will go on to have healthy pregnancies to term following one or more miscarriages.
If you are struggling with recurrent losses, you deserve a proper and thorough assessment to try and identify any risk factors.
Looking For More Fertility Support?
Understanding your risk factors and getting a thorough workup when trying to conceive and if you have experienced a miscarriage before is incredibly important. Naturopathic medicine has many tools that can support you along your fertility journey. You can read more about our fertility approach here, and reach out to the clinic if you have any questions!
References:
Jacqui Wise, 2021. NICE recommends progesterone to prevent early miscarriage. [online] Available at: <https://www.bmj.com/content/375/bmj.n2896> [Accessed 4 January 2022].
Coomarasamy, A., Devall, A., Cheed, V., Harb, H., Middleton, L., Gallos, I., Williams, H., Eapen, A., Roberts, T., Ogwulu, C., Goranitis, I., Daniels, J., Ahmed, A., Bender-Atik, R., Bhatia, K., Bottomley, C., Brewin, J., Choudhary, M., Crosfill, F., Deb, S., Duncan, W., Ewer, A., Hinshaw, K., Holland, T., Izzat, F., Johns, J., Kriedt, K., Lumsden, M., Manda, P., Norman, J., Nunes, N., Overton, C., Quenby, S., Rao, S., Ross, J., Shahid, A., Underwood, M., Vaithilingam, N., Watkins, L., Wykes, C., Horne, A. and Jurkovic, D., 2019. A Randomized Trial of Progesterone in Women with Bleeding in Early Pregnancy. New England Journal of Medicine, [online] 380(19), pp.1815-1824. Available at: <https://www.nejm.org/doi/full/10.1056/NEJMoa1813730> [Accessed 4 January 2022].
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
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
Thangaratinam, S., Tan, A., Knox, E., Kilby, M., Franklyn, J. and Coomarasamy, A., 2012. Association Between Thyroid Autoantibodies and Miscarriage and Preterm Birth. Obstetric Anesthesia Digest, [online] 32(2), pp.87-88. Available at: <https://www.bmj.com/content/342/bmj.d2616>.
Tian, L., Shen, H., Lu, Q., Norman, R. and Wang, J., 2007. Insulin Resistance Increases the Risk of Spontaneous Abortion after Assisted Reproduction Technology Treatment. The Journal of Clinical Endocrinology & Metabolism, [online] 92(4), pp.1430-1433. Available at: <https://academic.oup.com/jcem/article/92/4/1430/2597532>.
Palomba, S., Russo, T., Falbo, A., Di Cello, A., Amendola, G., Mazza, R., Tolino, A., Zullo, F., Tucci, L. and Battista La Sala, G., 2012. Decidual Endovascular Trophoblast Invasion in Women With Polycystic Ovary Syndrome. Obstetrical & Gynecological Survey, [online] 67(12), pp.788-789. Available at: <https://pubmed.ncbi.nlm.nih.gov/22508703/>.
Gonçalves, D., Braga, A., Braga, J., & Marinho, A. (2018). Recurrent pregnancy loss and vitamin D: A review of the literature. American Journal Of Reproductive Immunology, 80(5), e13022. doi: 10.1111/aji.13022
Mumford, S., Garbose, R., Kim, K., Kissell, K., Kuhr, D., & Omosigho, U. et al. (2018). Association of preconception serum 25-hydroxyvitamin D concentrations with livebirth and pregnancy loss: a prospective cohort study. The Lancet Diabetes & Endocrinology, 6(9), 725-732. doi: 10.1016/s2213-8587(18)30153-0