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Stopping Preterm Birth in Its Tracks: The Promise of Progesterone

Preterm birth (birth before 37 weeks) is a major global health problem associated with high risks of infant mortality and morbidity. Even in high-income countries with good prenatal care, babies born very preterm (before 32 weeks) have a higher risk of death and increased risk of long term health problems. Increasing maternal age of first pregnancy and the use of ARTs like IVF that increase odds of preterm birth 4 times [1] (Sanders et al., 2022) make reducing preterm birth through interventions like Progesterone Thyroid Support in Pregnancy (ProSPr), in at-risk women a priority to improve pregnancy outcomes.

Fetus cocooned with progesterone therapy during pregnancy preventing preterm birth

Preterm Birth Guideline Summary:

The two main risk factors for PTB :

  1. Prior preterm birth

  2. Short cervix of less than 25 mm before 24 weeks gestation

Recommendations for treatment:

For women with major risk factors, moderate to strong evidence exist that interventions such as progesterone therapy may help reduce their risk of another preterm birth with therapy starting as early as 16 weeks and carried through to 34-36 weeks gestation.[2]

Special Note: Normally we review recent studies in our discussion, however here we review an important Guidance document “Progesterone for Prevention of Spontaneous Preterm Birth”[2] (Jain et al., 2020), produced by the Maternal–Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). It’s an excellent resource that helps evaluate the evidence that underlies pregnancy monitoring & support programs like ProSPr. 

The objectives of the guidance document were first to assess benefits and risks of progesterone therapy for women at high risk of preterm birth based on abstraction of current evidence and then to make recommendations for use of progesterone therapy to reduce preterm birth risk and improve outcomes. 

Who is at High Risk?

Some women are at higher risk for preterm birth (PTB) than others with two main risk factors being:

- Prior preterm birth: Women who have had a prior preterm birth are at increased risk in subsequent pregnancies. 

- Short cervix: A cervix length of less than 25 mm before 24 weeks gestation indicates a shortened cervix and increased risk. Having reviewed much research, I note that the length of cervix determined as “short” is not consistent between studies ranging from < 20 to <30 mm, however these authors hoped to produce an abstraction of the evidence. 

There are other risk factors that can increase a woman's chances of preterm birth (multiple pregnancy, infections, chronic health conditions such as diabetes or high blood pressure, smoking etc) however, a history of prior preterm birth or a short cervix are the two strongest predictors.[2]

Progesterone Therapy Recommendations

For women with either of these two major risk factors, moderate to strong evidence exists that progesterone therapy may help reduce their risk of another preterm birth.

What is Progesterone Therapy?

Progesterone plays an important role through out pregnancy,  helping prepare the lining of the uterus for implantation of the embryo, maintains the pregnancy once it's established, and helps prevent preterm labor. In terms of preventing PTB, progesterone maintaining a relaxed state of the smooth muscle in the uterus, preventing contractions.

For women at high risk of preterm birth, progesterone is typically given as a vaginal suppository. Vaginal administration results in higher concentrations to the target organ, the uterus (in oral routes, it needs to be metabolized first by the liver). 

The recommended daily dosing suggested by SOGC is:

- 200 mg vaginal progesterone daily for singleton pregnancy

- 400 mg vaginal progesterone daily for twin or multiple pregnancy

In terms of preventing preterm birth only, progesterone supplementation is recommended to be started between 16-24 weeks gestation, after an ultrasound confirms a cervix <25mm or other risk factors, and continued until 34-36 weeks. 

If we note back to an early study review of the large PRISM study findings [3] (Coomarasamy et al., 2020) that investigated progesterone for the prevention of early miscarriage, progesterone supplementation started at 12 weeks gestation reduced the risks of early miscarriage in certain high risk pregnancies by 15%. Subsequent research found the progesterone supplementation from 12 - 16 weeks gestation reduced hypertensive disorders of pregnancy and preeclampsia risks, which lead to PTB, by 29% and 39% respectively [4] (Melo et al, 2023). Evidence mounts for progesterone support throughout pregnancy for higher risk patients. 

Other SOGC Recommendations To Be Excited About 

  • Progesterone supplementation was preferred over cerclage placement for women with a prior preterm birth or short cervix. This is a relief as cerclage requires an invasive procedure to place a suture around the cervix, whereas progesterone can be administered vaginally at home. 

  • Avoiding bed rest or activity restriction in favor of vaginal progesterone support. Light activity and work can be continued while taking progesterone.

  • Lastly, progesterone therapy has not demonstrated any harms or side effects in pregnancy to mother or baby.

Progesterone & Thyroid Support in Pregnancy (ProSPr)

My Fertility Labs ProSPr is one example of a restorative reproductive medicine program with treatment that aligns with these recommendations. ProSPr provides lab monitoring of hormonal levels, including progesterone, 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 levels for women with indicators of high risk pregnancies, to help prevent miscarriage and support a healthy full term pregnancy. This is especially relevant for women at higher risk due to a history of infertility and have utilized ARTs, who’ve suffered recurrent pregnancy loss, or who have had previous preterm birth and previous pregnancy complications. For those at risk, progesterone supplementation can be an effective treatment preventing another preterm birth or another miscarriage.

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

ProSPr's proactive, preventive approach 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, FertilityCare Practitioner

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

[1] Sanders, J.N., Simonsen, S.E., Porucznik, C.A. et al. Fertility treatments and the risk of preterm birth among women with subfertility: a linked-data retrospective cohort study. Reprod Health 19, 83 (2022).

[2]Jain, V., McDonald, S. D., Mundle, W. R., & Farine, D. (2020). Guideline No. 398: Progesterone for prevention of spontaneous preterm birth. SOGC Clinical Practice Guideline, 42(6), 806-812.

[3] 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.

[4] Melo, P.; Devall, A.; Shennan A.H.; Vatish, M.; Becker, C.M.; Granne, I.; Papageorghiou, A.T.; Mol, B. & Coomarasamy, A. (2023) Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta-analysis, BJOG,

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