Pre-Pregnancy Progesterone May Cut Risk of Loss After Recurrent Miscarriages

By Marilynn Larkin

January 19, 2017

NEW YORK (Reuters Health) - Use of luteal start vaginal micronized progesterone is associated with improved pregnancy success in women with recurrent pregnancy loss, researchers say.

Dr. Mary Stephenson of the University of Illinois Hospital and Health Sciences System in Chicago told Reuters Health by email, "Recurrent pregnancy loss affects about 5% of couples trying to have a child. Unfortunately, there are very few evidence-based treatments available."

"I am very encouraged by the findings of our study, which provide promising early evidence that progesterone treatment, started in the luteal phase of the menstrual cycle, can help women with a history of multiple, unexplained pregnancy losses of less than 10 weeks have a healthy baby," she said.

As reported in Fertility and Sterility, online January 9, Dr. Stephenson and colleagues recruited 116 women (average age, 34) between 2004 and 2012 with a history of two or more unexplained pregnancy losses (less than 10 weeks); an endometrial biopsy performed 9 to 11 days after the luteinizing hormone (LH) surge; and one or more subsequent pregnancy(ies).

Nuclear cyclin E (nCyclinE) was used as a molecular marker of endometrial development, based on a previous study showing that abnormal nCyclinE expression in the endometrial glands - defined as greater than 20% after day 20 of the menstrual cycle - correlates with a history of infertility.

A total of 59 participants had elevated nCyclinE and 57 had normal nCyclinE.

Women in whom nCyclinE expression was elevated in the endometrial glands received vaginal micronized progesterone at a dose of 100 mg to 200 mg every 12 hours starting three days after the LH surge. In addition, according to the authors, some women with normal nCyclinE "insisted on using" the medication, and they received it at the same dose.

Women with normal nCyclinE who did not receive progesterone were used as controls.

In the 59 women with elevated nCyclinE, pregnancy success - defined as an ongoing pregnancy greater than 10 weeks - improved significantly after the intervention, from 6% (16/255) in prior pregnancies to 69% (57/83) in subsequent pregnancies.

Pregnancy success in subsequent pregnancies was higher overall in women prescribed vaginal micronized P compared with controls: 68% (86/126) versus 51% (19/37); odds ratio, 2.1.

"We propose that luteal start vaginal micronized progesterone leads to improved endometrial gland development, which optimizes the local environment for early maintenance of pregnancy," the authors suggest.

"Although the use of the molecular marker, nCyclinE, is exploratory, and there is no control group of women without recurring pregnancy loss, vaginal micronized progesterone resulted in decreased or normalization of nCyclinE expression in 84% of women with initially elevated expression of this molecular marker," they add.

Dr. Stephenson said she plans on validating the study findings in a randomized control clinical trial.

Dr. Sherry Ross, a women's health expert at Providence Saint John's Health Center in Santa Monica, California, told Reuters Health, "Recurrent miscarriages . . . can be emotionally devastating. Trying to find the magic treatment remedy can be challenging."

"This is a very small but hopeful study for women experiencing recurrent miscarriages," she said by email. "The use of vaginal progesterone immediately after ovulation may be a step in the right direction towards having a healthy pregnancy. Vaginal progesterone during this sensitive time of the reproductive cycle helps make the environment inside the uterus a welcoming one for the embryo."

"Even though more studies are needed," she concluded, "women experiencing recurrent miscarriages may have another safe and inexpensive treatment option to allow them to carry a full term pregnancy."

One coauthor is the inventor of the patented test for nCyclinE levels used in the study.


Fertil Steril 2017.