Women with recurrent pregnancy loss, and higher levels of a certain hormone, who were treated with progesterone prior to their next attempt to conceive seemed to have a higher percentage of pregnancy success, a prospective study found.
Among women who had multiple miscarriages and abnormal levels of nuclear cyclin E, there was a significant increase in pregnancy success (an ongoing pregnancy for more than 10 weeks) after being treated with micronized progesterone (6% versus 69%, P<0.001), reported Mary D. Stephenson, MD, of University of Illinois at Chicago, and colleagues, in Fertility and Sterility.
They cited prior research that found higher than normal expression of nuclear cyclin E (nCyclinE), a hormone released during a woman's luteal phase, may have an impact on her fertility and ability to conceive. They hypothesized that since progesterone is prescribed during assisted reproduction to improve endometrial development, administering it to women with abnormal levels of nCyclinE and recurrent pregnancy loss may improve their subsequent pregnancy outcomes.
"We propose that luteal start vaginal micronized [progesterone] leads to improved endometrial gland development, which optimizes the local environment for early maintenance of pregnancy," they wrote.
Overall, 116 women were recruited -- 59 with elevated levels of nCyclinE and 57 with normal levels of the hormone. Mean age of participants was 33-35, and participants were mostly of white race with a normal mean BMI of 25.
The 59 women with elevated levels of nCyclinE were treated with 100 mg of progesterone, and then given the option of repeating the endometrial biopsy or attempting pregnancy. If their nCyclinE levels were still abnormal, the dose of progesterone was increased to 200 mg. All women were monitored in the university's Recurrent Pregnancy Loss Program, which provides support to women who have suffered a miscarriage.
The authors also noted a "step-wise progression" in pregnancy success, as nCyclinE levels normalized. Women whose hormone levels decreased had a greater portion of successful ongoing pregnancies compared with women who saw a reduction, but not a normalization in nCyclinE, and women who saw no change (80% versus 71% and 63%, respectively).
The sample was also comprised of 57 women who had normal levels of nuclear cyclin E. A subset of 29 women within this group requested vaginal micronized progesterone anyway, but there was a nonsignificant difference in the portion of successful pregnancies compared to women in this group who did not receive progesterone (68% versus 51%, P=0.14).
Stephenson's group noted that of the women who had abnormal nCyclinE levels, treatment with progesterone either normalized or decreased the expression of this hormone in 84% of these women.
"We recommend a repeat [endometrial biopsy] in the first treatment cycle of luteal start vaginal micronized [progesterone], with a dosing adjustment if nCyclinE is persistently elevated," they wrote, arguing that micronized progesterone "appears to be safe and is relatively inexpensive" for use in women with recurrent pregnancy loss.
They also said a randomized trial to a placebo-matched control group is "urgently needed" to see if progesterone can improve the live birth rate among women with multiple miscarriages.
Disclosures
Stephenson disclosed no relevant relationships with industry. One co-author disclosed a owning patent related to the monitoring of endometrial glandular development.
Primary Source
Fertility and Sterility
Source Reference: Stephenson MD, et al "Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss" Fertil Steril 2017; DOI:10.1016/j.fertnstert.2016.11.029.