Key messages

• In women with polycystic ovary syndrome (PCOS), there may be little or no difference in live birth, multiple pregnancy (twins or triplets), pregnancy, or miscarriage rates between urinary-derived gonadotropins (derived from urine from menopausal women) and recombinant follicle-stimulating hormone (developed with recombinant DNA technology).

• For human menopausal gonadotropin (also derived from the urine of menopausal women) versus purified urinary follicle stimulating hormone, we are uncertain whether one or the other improves or reduces the chance of a live birth, multiple pregnancy, pregnancy, or miscarriage.

• In women who do not conceive after taking clomiphene citrate, gonadotropins probably result in more live births and pregnancies compared to continuing treatment with clomiphene citrate, without increasing the risk of having twins or triplets. Gonadotropins may increase the risk of a miscarriage.

What is the problem?

One in seven couples worldwide may experience infertility, defined as having trouble getting pregnant after one year of trying. Infertility due to problems with the release of an egg (ovulation) during the menstrual cycle is the most common reason for women to seek counselling or treatment. These women are treated by stimulating the release of an egg from the ovaries with medication, so-called 'ovulation induction'. This is usually done with pills containing clomiphene citrate, as the first choice of treatment. If women do not respond to clomiphene, the most common second choice of treatment is stimulation of egg release with gonadotropins, which are injectable drugs.

What are the available treatments?

Various types of gonadotropins have been developed by processing urine from menopausal women. These gonadotropins include human menopausal gonadotropin, available in purified and highly purified form, and purified and highly purified follicle-stimulating hormone. Finally, recombinant follicle-stimulating hormone was developed artificially to obtain even higher purity. Women who do ovulate, but do not get pregnant within six cycles of treatment with clomiphene citrate, may continue with clomiphene citrate or switch to gonadotropins. Gonadotropins can result in the development of multiple follicles. To prevent multiple pregnancy and ovarian hyperstimulation syndrome (OHSS), which is a serious condition, the cycle needs to be cancelled.

It is important to know which medication works best to enable doctors and women to make informed decisions about the course of treatment.

What did we want to find out?

We wanted to find out which gonadotropin is the best choice to trigger egg release in women with PCOS who do not ovulate or get pregnant after taking clomiphene citrate pills.

What did we do?

We searched for studies comparing different gonadotropins to stimulate ovulation in women with PCOS. We summarised the results of the included studies and rated our confidence in the evidence by evaluating factors such as study methods and study size.

What did we find?

The review includes 15 studies with 2348 women with PCOS. Ten trials compared recombinant FSH with urinary-derived gonadotropins. Three trials compared human menopausal gonadotropin with purified urinary follicle-stimulating hormone and one trial compared gonadotropins with continued clomiphene citrate.

Main results

There may be little or no difference in live birth, multiple pregnancy, clinical pregnancy, or miscarriage rate between purified urinary-derived gonadotropins and recombinant follicle-stimulating hormone. We are uncertain whether human menopausal gonadotropin improves pregnancy outcomes in women with PCOS compared to urinary follicle-stimulating hormone. We are uncertain whether any of the treatments reduce the risk of OHSS or ectopic pregnancy.

When compared to continued treatment with clomiphene citrate, gonadotropins probably result in more live births and pregnancies without increasing the rate of multiple pregnancies. Gonadotropins may result in more miscarriages than clomiphene citrate, while there were no cases of OHSS.

What are the limitations of the evidence?

Our confidence in the evidence ranged from very low to moderate. Many studies had small sample sizes and were conducted a long time ago, meaning important information about study methods was missing. Ten of the 15 studies included in this review reported a commercial sponsor. We did not take costs and convenience into account; we do encourage patients to discuss costs, convenience and unwanted effects with their healthcare provider.

How up to date is the evidence?

This is a review update. The evidence is current to March 2024.