In the USA, the most common fertility treatment given to women is progesterone. In many cases,
progesterone is given if a blood test for progesterone is low or more commonly because of
bleeding early in pregnancy. Does this treatment help? In other words, does the chance for having a
live birth improve by giving women progesterone? New studies over the last few years have helped
us to answer this question. Stay tuned to the end for my Infertility TV Bottom Line recommendations
Progesterone is a hormone produced by the ovaries in high amounts after ovulation.
It is necessary to prepare the uterine lining so that an embryo can implant
and is necessary for maintaining the uterine lining after implantation.
Measuring progesterone with a blood test has limited usefulness because
the levels jump around a lot and are dramatically different based
on the timing of the test. Urine tests for progesterone metabolites have also
not been shown to be useful. I talk about both of these concepts in this playlist.
Just because we are unable to measure progesterone accurately, does not necessarily
mean that it is not important, however. As a result, in the last several years,
a number of studies have been performed looking at whether taking extra progesterone after ovulation
or in early pregnancy increases the chance for having a live birth. What did these studies find?
The first study is known as PROMISE trial or PROgesterone in recurrent MIScarriagE. The PROMISE
trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands. In order to
be included in this study, participants must have had 3 or more miscarriages either consecutively
or non-consecutively. This was considered a very high quality study because of its large
size and because the patients were split into two treatment groups. Group one received real
progesterone and group two received a placebo. Neither the participants or their doctors knew
who got what. Statistical analysis found that the tiny difference in the chance for live
birth between the two groups was likely due to chance and not because of the treatment given
A second study is known as the PRISM trial or PRogesterone In Spontaneous Miscarriage.
The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom. In this study,
participants were enrolled if they had bleeding early in the pregnancy. This is known as
threatened miscarriage. Like the PROMISE trial, participants were split into two groups with some
receiving progesterone and some getting placebo. Again, there was no difference in the live birth
rate between the two groups. Researchers tried to determine if there were any subgroups that
might have been helped by taking progesterone. The study population was split into 3 subgroups:
women without a history of miscarriage; women with 1 or 2 previous miscarriages;
and women with 3 or more previous miscarriages. In this analysis,
they found a mild benefit in participants with three or more miscarriages. There was a 14%
increase in the chance for live birth. Stated another way, we would need to give progesterone
to 8 patients with a history of three or more miscarriages and who were bleeding
in the current pregnancy in order to get one more live birth. Not dramatic but something.
The most recent study comes from Australia. It is known as the STOP trial. This study ended up being
smaller than planned, with only 278 participants. I’ll tell you why in a minute. Otherwise,
this was just like the PRISM trial looking at people who were having early pregnancy
bleeding. Midway through the study, they did an analysis and found no difference in live births
between the progesterone group and the placebo group. Because the outcomes were so similar,
the study monitors calculated that continuing the study would not be able to show any benefit
to progesterone so the study was stopped at that point. In the smaller group analysis,
there were no benefits found even if the progesterone level
was low or if the participants had a number of previous miscarriages.
Our InfertilityTV Bottom Line is this. We have adequate data now to say with a high degree
of certainty that for patients who are having bleeding in early pregnancy, giving them extra
progesterone will not improve their chances for having a live birth. A possible exception is for
those couples who in addition to having bleeding, have also had three or more previous miscarriages