By Gene Emery

(Reuters Health) – Giving progesterone to women with bleeding early in pregnancy doesn’t prevent pregnancy loss, except among women who have had a previous miscarriage, according to a study of 4,153 women treated at 48 hospitals in the UK.

“It’s great news for patients,” lead author Dr. Arri Coomarasamy, a professor of gynecology at the University of Birmingham, told Reuters Health in a telephone interview. It will prevent unnecessary progesterone treatment for most women, and give extra hope to women facing a second, third or fourth miscarriage.

“The live birth rate is 5 percentage points higher in the progesterone group in a pregnant woman who has had a previous miscarriage and is now bleeding,” he said. “If she’s had three or more previous miscarriages, it’s 15 percentage points higher.”

The bleeding that might signify trouble in the first few months of pregnancy occurs in about 25 percent of all pregnancies. In perhaps 10 percent to 20 percent of cases, the bleeding can be a harbinger of a lost pregnancy.

For years, doctors have used progesterone preparations off-label to treat a threatened miscarriage based in part on a decline in hormone levels just before a miscarriage. That led to a long-practiced treatment of giving progesterone even though it was not backed up by good evidence.

The new study, published in the New England Journal of Medicine, provides evidence of when the hormone does or does not work.

“In retrospect, it is likely that the initial rationale for hormonal therapy – that is, the observed fall in pregnancy hormone levels before pregnancy loss – was, in fact, a consequence rather than a cause of pregnancy failure,” Dr. Michael Green of Massachusetts General Hospital in Boston writes in an accompanying editorial.

For the 2,238 women who did not have a history of miscarriage, the rate of live birth after 34 weeks of gestation was 75 percent among women with bleeding treated with 400 milligrams of micronized progesterone twice daily versus 72 percent among women treated with matching placebo. Statistically, that difference is too small to rule out the possibility it was due to chance.

“There was no benefit of any kind,” Coomarasamy said.

But among women who had experienced one or more miscarriages, 75 percent in the progesterone group gave birth compared with 70 percent who got vaginal placebo suppositories, suggesting that the hormone helped.

Women in the ultra-high risk group, who had experienced three or more miscarriages, had a successful pregnancy 72 percent of the time if they were given progesterone versus 57 percent with placebo.

The findings are expected to increase progesterone use in the UK, where a 2012 survey showed that it was only given in 4.5 percent of cases of bleeding in early pregnancy, and to lower use of the hormone in some countries where up to 90 percent of women get progesterone if they have bleeding.

“Right now, if a patient starts bleeding, they will go to their local hospital and doctors will do an ultrasound to see if the pregnancy is okay,” Coomarasamy said. “The doctors would tell the patient you have two-thirds chance that everything is okay and a one-third chance of miscarriage. If the patient asks what can be done about that, right now the answer is nothing. Now, for the first time, we might be able to say there is a treatment that might help you if you have had a miscarriage before.”

A woman who has never lost a pregnancy may wish to be treated anyway, but “this is where the doctor will need to share the evidence and show there is no benefit to be had” for her from progesterone therapy.

The researchers found no evidence that the treatment, which used a natural version of progesterone, was harmful.

SOURCE: The New England Journal of Medicine, online May 8, 2019.