Luteal Start Vaginal Micronized Progesterone ups the rate of ongoing pregnancy in RPL.

vaginal micronized progesterone

Recurrent pregnancy loss (RPL) is one of the most traumatic and frustrating experience for patients and consulting obstetricians. It is an area of obstetrics lacking in evidence based diagnostic and treatment strategies. As per data by American Society for Reproductive Medicine(ASRM) it affects 15-25% of all pregnancies and in nearly 50% of cases the cause is not known.

Courtesy:Dr.Malpani Blog

Therapeutic interventions are generally based on the cause of RPL and data from observational studies and clinical experiences of the treating obstetrician. Treatment options range from active interventions in the form of hormonal supplementation to masterly inactivity (= reassurance).[i]

Progesterone (P) has long been used in the treatment of infertility because of its immunomodulator action on endometrium but it’s use is largely empirical along with other treatment regimen.  Cochrane review and meta-analysis concluded that P supplementation could improve the reproductive outcome in women with 3 or more pregnancy loss.

But, in none of these studies P was started after LH surge (luteal start) and varied route and dosing of P administration was used. [ii]

A new study published on line on January 9, 2017 in Fertility & Sterility international journal of the American Society for Reproductive Medicine assessed the effectiveness of luteal start vaginal micronized P in a recurrent pregnancy loss (RPL) cohort.

In this observational, cohort study 116 women with a history of RPL were recruited and followed prospectively. Vaginal micronized progesterone was supplemented in dose of 100–200 mg every 12 hours starting 3 days after LH surge (luteal start corresponding to day 13 of the cycle) with or without >20% increase in levels of nuclear cyclin E (nCyclinE) expression. The controls did not receive P and had normal nCyclinE (≤20%). P was continued till 10 weeks of pregnancy.

The research team lead by Dr. Mary D. Stephenson tested Nuclear cyclin E (nCyclinE) levels to assess the state of endometrium. It is an endometrial molecular marker(EFT) and a cell cycle regulator, levels more than 20% after day 20 of the menstrual cycle correlates with a history of infertility. NCyclinE expression was determined by an EB was performed 9–11 days after the LH surge in previous cycle.

Of 116 women tested, 59 had high levels of nCyclinE and 57 had normal levels.

The results of the test were very promising with 68% pregnancy rate in study group as compared to women who did not take P. The chances of successful pregnancy increased from 6% to 69% in treatment group.

Six women needs to be treated with P to achieve one additional successful pregnancy.( Number need to treat). 

This observational study cannot establish causality, the researchers believe that P is beneficial in changing the endometrial milieu and benefitting the developing embryo.   

Dr. Stephenson said “The positive results show us that next we need to study progesterone as a treatment for recurrent pregnancy loss with a prospective randomized trial to validate the findings." 

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[i] http://blog.drmalpani.com/2016/08/pgs-for-recurrent-pregnancy-loss-forget.html

[ii] Haas, M.D. and Ramsey, P.S. Progestogen for preventing miscarriage. Cochrane Database Syst Rev. 2013;: CD003511