Written by Dr Sarah Merritt
Progesterone is an important hormone. It is produced by the corpus luteum in the ovary during the menstrual cycle regardless of whether a woman becomes pregnant or not and then continues to be released if a woman does become pregnant. It helps thicken the lining of the womb in order for a pregnancy to implant and helps to support and maintain a pregnancy. In women undergoing IVF progesterone is given to help prepare the lining of the womb for embryo implantation.
Progesterone has previously been given to women with a history of recurrent miscarriage (3 or more miscarriages in a row) without adequate evidence from studies to support its use and there has been an ongoing debate whether it should be given or not. Only in the last 10 years have larger studies looked at the potential benefits of using progesterone with women with recurrent miscarriage. Recurrent miscarriage affects bout 1% of couples and often after investigation, most couples have no reason as to why they have had so many losses.
The PROMISE Trial
The PROMISE trial was a large trial which was designed to examine if women with 3 or more unexplained miscarriages had any benefit- i.e. a live birth after 24 weeks from taking with progesterone. The 836 women who were recruited to the trial and then conceived naturally within a year were randomized to either take a progesterone pessary (a tablet inserted into the vagina) twice a day or a placebo from the time when they knew they were pregnant and before 6 weeks of pregnancy through to 12 weeks.
- Randomised: a computer made the selection randomly as to which women were given the treatment (in this case progesterone) or a placebo
- A placebo is a substance that is made to look like a real drug/ medication but contains an inactive or ‘dummy’ substance.
The women did not know who had had the progesterone and who had had the placebo until after the trial was over. The study took place at multiple hospitals over the UK and the Netherlands.
A successful outcome was judged to be a live birth after 24 weeks of gestation.
- For those who received progesterone 65.8% of women had a livebirth after 24 weeks
- For those who got the placebo 63.3% had a livebirth after 24 weeks
The difference between the two groups (3.5%) was not statistically significant, meaning that the difference could have been due to chance. The results showed that progesterone did not help reduce the risk of another miscarriage in women with recurrent miscarriages.
This was extremely disappointing news for both doctors, nurses and researchers, however it did show that in both groups the majority of women had babies. No harmful affect were seen from use of progesterone and for those that did miscarry, progesterone did not delay the miscarriage process. The study also meant that the same group of researchers focused on further studies including possible benefits of progesterone treatments in women with bleeding in early pregnancy.
The PRISM trial
This trial involved 4153 women from 48 hospitals across the UK. It examined whether progesterone given to women with bleeding in early pregnancy increased the chances of having a live birth by preventing miscarriage. Bleeding can affect 20% of women in early pregnancy. For 2 out of 3 women the pregnancy will continue and the bleeding is not a sign of a problem. For 1 out of 3 the pregnancy will sadly miscarry. PRISM was a very large randomized, double blinded, placebo controlled trial.
- Double blind: Neither the women who participated in the study or the doctors and nurses knew who was having the placebo and who had the progesterone.
- Placebo controlled- half the women had the active or treatment medication and the other half (the controls) had the placebo.
For those women taking part in the study approximately half were randomized to take progesterone and half to take a placebo if they had bleeding in the first 12 weeks of pregnancy and an ultrasound scan showed a baby with a heart beat. The overall live birth rate for:
- Women who took progesterone the live birth rate was 75%
- For women who took the placebo it was 72%
The difference of 3% between the two groups was again not statistically significant meaning that this difference could have happened by chance.
However when the results where further examined and spilt by the number of previous miscarriages that a participant had previously suffered:
- No previous miscarriages: the live birth rate was 74% in the progesterone group and 75% in the placebo group- this shows no benefit of taking progesterone
- 1-2 previous miscarriages: the live birth rate was 76% in the progesterone group and 72% in the placebo group- this shows some benefit.
- 3 or more recurrent miscarriages: the live birth rate was 72% in the progesterone group and 57% in the placebo group- this shows significant benefit, which means that the difference between the two groups did not happen by chance alone.
The overall conclusion is that women who have bleeding in early pregnancy and a previous history of miscarriage could benefit from progesterone.
Not every GP or clinician may have heard of the results and if you do have bleeding in early pregnancy and have had previous miscarriages you should discuss the results from PRISM with your GP or early pregnancy unit. Taking progesterone cannot guarantee a live birth but particularly for women with a history of recurrent miscarriage and bleeding in pregnancy, there is a significant chance of progesterone pessaries stopping a miscarriage.
For further information please see the link below from Tommy’s