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Progesterone for Pregnancy: Miscarriage Prevention Hope for Women with a History of Miscarriage

Updated: Jan 10


It’s an open secret. Miscarriage is a relatively common occurrence for women, affecting up to 20% of known pregnancies. Recurrent miscarriage, (3 or more consecutive pregnancy losses) affects about 1% of couples trying to conceive [1] (Quenby et al, 2021)


The Ongoing Debate Over Miscarriage Prevention Using Progesterone Support in Pregnancy

Let's face it, right now in Canada there are limited care options for miscarriage prevention during pregnancy. Why?


For decades, progestens (progesterone-like hormones) have been used to try to prevent miscarriage in women with high risk pregnancies, specifically those with recurrent miscarriage or threatened miscarriage (vaginal bleeding in early pregnancy). However, evidence on the effectiveness of progestogen treatments has been unclear and inconsistent in previous studies for preventing miscarriage. This meta-analysis is interesting as it reviews multiple studies using various progestogen treatments. It also agrees with the findings of the ground breaking PRISM study [2] (Coomarasamy et al, 2020) in assessment that certain treatments are effective for specific target groups at higher risk.


Meta-Analysis of Prevention of Miscarriage with Progesterone Support

"Progestogens for preventing miscarriage: a network meta-analysis", a published meta-analysis, looked at 7 randomized controlled trials involving 5,682 women. [3] (Devall et al., 2021) The underlying studies assessed different types of progestogens for treating threatened or recurrent miscarriage. Underlying studies evaluated progestogen treatments, including vaginal micronized progesterone, oral micronized progesterone, 17-a-hyroxyprogesterone and dydrogesterone. Of these routes, vaginal progesterone was effective at preventing miscarriage and increasing live birth rates in women with threatened or recurrent miscarriage. The key findings have important implications for guiding treatment to support healthy pregnancies in higher risk women. It also explains some of the confounding factors of previous studies that considered progesterone of any type to be providing equivalent progesterone support for pregnancy maintenance. Clearly the route of administration is important.


Why a Meta-Analysis ? Notes on the Study Methodology


By pooling data from multiple studies, this meta-analysis was able to analyze results from a large sample size of 5,682 women, increasing statistical power and helping provide more definitive conclusions about the efficacy of progestogens.


All of the studies included were randomized controlled trials (RCTs), which are considered the gold standard for evaluating the efficacy of medical treatments. RCTs randomly assign patients to receive either the treatment being studied or a placebo, helping ensure the results are due to the treatment itself and not confounding factors.[3]


Key Findings


  • Overall, progestogens dydrogesterone do not appear to increase live birth rates for most women with threatened or recurrent miscarriage compared to placebo

  • Oral micronized progesterone and 17-a-hyroxyprogesterone studies did not provide conclusive evidence and more research is required of higher quality to make an assessment.

IMPORTANTLY:


  • Vaginal micronized progesterone did increase live birth rates for women with threatened miscarriage who had a history of one or more previous miscarriages, compared to placebo.

  • For these higher risk women, vaginal progesterone had no difference in side effects or birth defects compared to placebo. Overall, progestogens appeared safe, with no increase in side effects or birth defects compared to placebo. [2].



Implications for Clinical Practices


Overall, this analysis suggests micronized vaginal progesterone does appear to be effective for women with threatened miscarriage who have a history miscarriage [3].


For 30 years in Canada, physicians trained in Restorative Reproductive Medicine (RRM) have offered this exact treatment, bio-identical progesterone using micronized vaginal capsules for support in pregnancy. My Fertility Labs is making this treatment accessible to patients with high-risk pregnancy through our Progesterone & Thyroid Support in Pregnancy Program (ProSPr). Treatment, paired with ongoing lab monitoring throughout pregnancy, is started as early as possible in high risk pregnancies.


Remaining questions

& need for more research

This meta study identified the need for more studies on different types of progestogens, dosages, and delivery methods to determine if certain regimens may be effective for broader groups of women. And that:


  • Research should further evaluate whether progestogen treatment improves live birth rates for women with recurrent pregnancy loss or specific miscarriage risk factors beyond just a history of previous miscarriage.

  • Additional investigation is warranted on combining progestogens with other treatments like thyroid hormone, anticoagulants, or immunotherapy to improve efficacy.

  • Larger randomized trials over multiple centers are required to provide more definitive evidence on efficacy and safety of progestogens. Thanks to the UK research efforts through Tommys.org , the PRISM trial [2] has responded verifying this meta-analysis findings.



Progesterone & Thyroid Support in Pregnancy (ProSPr)

My Fertility Labs ProSPr is one example of a restorative reproductive medicine program that has aligned treatment with these study findings. This program provides lab monitoring of progesterone and thyroid levels throughout pregnancy, along with bioidentical progesterone and thyroid supplementation when needed, monitored by one of our clinicians.


The goal of the program is to optimize progesterone and thyroid function for women with indicators of high risk pregnancies, to help prevent miscarriage and support a healthy pregnancy. This is especially relevant for women at higher risk due to a history of infertility, recurrent pregnancy loss, or low progesterone. As the study showed, progesterone can be an effective treatment.


Key benefits of the My Fertility Labs program for high-risk pregnancies include:


- Personalized care and treatment based on the patient's lab results and medical history

- Ongoing lab monitoring of hormone levels

- Prescription bio-identical hormones to help sustain pregnancy

- Pre-conception care to correct underlying dysfunction supporting a healthier pregnancy and healthy baby


By taking a proactive, preventive approach, the program aims to identify and treat issues early that could otherwise threaten the pregnancy. This represents a more progressive, functional medicine model of care compared to simply waiting for problems to occur before intervening.



Written by Carolyn Plican, Creighton Model FertilityCare Practitioner

Reviewed by Dr. Mary Ellen Haggerty, Restorative Reproductive Medicine Clinician



[1]Quenby S, Gallos ID, Dhillon-Smith RK, Podesek M, Stephenson MD, Fisher J, Brosens JJ, Brewin J, Ramhorst R, Lucas ES, McCoy RC, Anderson R, Daher S, Regan L, Al-Memar M, Bourne T, MacIntyre DA, Rai R, Christiansen OB, Sugiura-Ogasawara M, Odendaal J, Devall AJ, Bennett PR, Petrou S, Coomarasamy A. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss. Lancet. 2021 May 1;397(10285):1658-1667. doi: 10.1016/S0140-6736(21)00682-6. Epub 2021 Apr 27. PMID: 33915094.


[2] Coomarasamy, A., Harb, H. M., Devall, A. J., Cheed, V., Roberts, T. E., Goranitis, I., Ogwulu, C. B., Williams, H. M., Gallos, I. D., Eapen, A., Daniels, J. P., Ahmed, A., Bender-Atik, R., Bhatia, K., Bottomley, C., Brewin, J., Choudhary, M., Crosfill, F., Deb, S., Duncan, W. C., … Middleton, L. J. (2020). Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT. Health technology assessment (Winchester, England), 24(33), 1–70. https://doi.org/10.3310/hta24330


[3] Devall AJ, Papadopoulou A, Podesek M, Haas DM, Price MJ, Coomarasamy A, Gallos ID. Progestogens for preventing miscarriage: a network meta‐analysis. Cochrane Database of Systematic Reviews 2021, Issue 4. Art. No.: CD013792. DOI: 10.1002/14651858.CD013792.pub2





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