New research suggests that progesterone treatment may prevent recurrent miscarriage.
Recurrent pregnancy loss (RPL) is a clinical condition that occurs when a woman has two or more failed pregnancies within the first 4-6 weeks of pregnancy.
According to the American Society for Reproductive Medicine (ASRM), between 15-25 percent of all pregnancies are affected by RPL. Potential causes include genetics, age, hormonal disorders, lifestyle choices, and a variety of uterine disorders.
However, the ASRM estimate that nearly 50 percent of all RPL cases have unknown causes.
New research from the Yale School of Medicine in New Haven, CT, in collaboration with the University of Illinois at Chicago, examines the role of progesterone in helping mothers to carry a pregnancy successfully to term.
The findings were published in the international journal of the ASRM, Fertility & Sterility.
Researchers were led by Dr. Mary D. Stephenson, who is the Dr. Theresa S. Falcon-Cullinan Professor of Obstetrics and Gynecology at the University of Illinois at Chicago and director of the University of Illinois Recurrent Pregnancy Loss Program.
Studying progesterone in women with poor endometrial health
Dr. Stephenson and team examined women who inexplicably lost two or more pregnancies between 2004-2012, at more than 10 weeks into their pregnancies.
Researchers used an endometrial biopsy to exclude women who presented other conditions, such as endometritis, glandular-stromal dyssynchrony, or maturation delay. After the biopsy, 116 women were included in the study.
Using an endometrial function test specially designed by study co-author Dr. Harvey J. Kliman, researchers assessed the endometrium of these participants to see if it was healthy enough to keep an embryo.
The endometrium is the tissue lining the inside of the uterus, where the embryo implantation usually takes place. It plays a crucial role in providing nutrients for the fetus and supporting the pregnancy.
In their tests, the team examined a molecular marker for endometrium health called nCyclinE, which is a glandular epithelial nuclear cyclin. Abnormally high levels of the marker indicate that the pregnancy is likely to fail, while normal levels suggest that it is likely to succeed.
Of the 116 women, 59 had high levels of nCyclinE and 57 had normal levels.
The women with high nCyclinE levels received treatment with natural micronized progesterone, administered vaginally, whereas those with normal levels made up the control group.
The women were administered 100-200 milligrams of progesterone every 12 hours, and the treatment was initiated 3 days after a surge in the luteinizing hormone indicated that ovulation was due to begin.
Progesterone improves pregnancy success rates
The results were promising. In the group that received the treatment, the pregnancy success rate improved significantly.
Before receiving the treatment, the group had a 6 percent success rate. This jumped to 69 percent after progesterone administration.
Overall, the pregnancy success rate was also higher among women who were treated with progesterone, compared with the control group.
Women who took progesterone had a 68 percent pregnancy success rate, compared with 51 percent in the control group.
Although this is an observational study and cannot therefore establish causality, the researchers hypothesize that the progesterone stimulated endometrial secretions, which in turn fed the embryo.
"The endometrium feeds the baby up until the eighth week of pregnancy. Then at 9 to 10 weeks the mother's blood takes over to feed the embryo. In this subset of women experiencing multiple early miscarriages, we assume that their embryos were literally starving to death. They attached, but they were not getting enough food. When we give progesterone back to these women, the endometrium makes more nutrients and prevents their pregnancy loss."
Dr. Harvey J. Kliman
"We are very pleased to find that these results reinforce the evidence that progesterone could be a very beneficial, inexpensive, and safe treatment for many women with a history of recurrent pregnancy loss," adds Dr. Stephenson. "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."