In my field, progesterone is frequently given to prevent miscarriages. Two theories about the relationship between progesterone and miscarriages exist: low progesterone may lead to miscarriages; and unhealthy pregnancies not destined to continue produce lower-than-normal progesterone. The latter explanation is probably more logical, given that most miscarriages occur due to genetic abnormalities in the fetus. Nevertheless, given lack of evidence for harmful effect of progesterone, it is often given when progesterone blood levels are low in early pregnancy. The following study is a sobering view on progesterone supplementation role in preventing miscarriages. But will it change the practice of liberally prescribing progesterone for pregnancies at risk? Doubtfully, absent other treatment for such pregnancies.
Researchers had hoped that pregnant women who were given supplemental progesterone early in their first trimester would be less likely to miscarry than women who did not have it. Previous studies suggested that progesterone could lower the risk among women with a history of recurrent miscarriages.
But the results of the new trial, published in The New England Journal of Medicine, show that 65.8 percent of the women given progesterone gave birth to a baby, compared with 63.3 percent of the control group — not a significant difference.
More than 800 women participated in the trial at 36 sites in Britain and nine in the Netherlands. Neither they nor their doctors knew whether they were receiving progesterone or a placebo, provided via vaginal suppositories.
“There’s always disappointment whenever you find out that a magic bullet isn’t a magic bullet,” she added.
About 5 percent of women experience two consecutive miscarriages in the first trimester, and 1 percent go through three or more losses. Progesterone, a hormone that is crucial to bringing about and maintaining pregnancy, is often a first-line treatment for unexplained recurrent miscarriages.
The negative result is sure to dismay patients, but it comes with a silver lining, experts said. Couples should take solace in the “impressive” result that “more than half of these women had a live birth,” Dr. Pfeifer said.
The study also suggested that supplemental progesterone did not lead to an increase in congenital abnormalities. “Progesterone doesn’t cause harm,” said Dr. Arri Coomarasamy, the trial’s lead author and a professor of gynecology at the University of Birmingham.
Some experts wondered if progesterone should have been given to the study subjects earlier — perhaps after ovulation, and not only after confirmation of the pregnancy.
“My big concern is they are starting the progesterone too late,” said Dr. Mary D. Stephenson, chief of obstetrics and gynecology at the University of Illinois at Chicago, who was not involved in the new research. “You have to start it before they are pregnant.”
Miscarriage is often caused by chromosomal errors that happen by chance. This kind of genetic fluke becomes more likely as a woman ages, which is why enrollment age in the study was capped at 39.
Some specialists suggested that the study should have included only women with at least one miscarriage clearly unrelated to chromosomal errors.
“No amount of progesterone or any medication can fix a situation where the fetus doesn’t have the right number of chromosomes,” said Dr. Zev Williams, the director of the program for early and recurrent pregnancy loss at Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx.
“It would be quite a different study if they recruited patients with miscarriages that had normal chromosomal results,” Dr. Stephenson said. “If progesterone was effective, we’d be much more likely to see a difference.”
Dr. Pfeifer disagreed, saying, “It would have been nice to have that information, but I’m not so sure that it is a make-or-break deal.”
The study did exclude women with known causes of miscarriage, like structural problems with the uterus, clotting disorders or thyroid dysfunction.
Some doctors may still choose to give progesterone to women with a history of miscarriage in the first six weeks of pregnancy, if they ask for it. “I don’t think people will read this paper and stop,” Dr. Coomarasamy said. But “it will plant seeds of doubt,” he added.
Still unknown is whether progesterone works as a rescue therapy, preventing miscarriage in women who have early-pregnancy bleeding, Dr. Coomarasamy said. Researchers plan to recruit thousands of women for a trial to find out.