An overview of treatment options for inducing ovulation in polycystic ovary syndrome

This review analyzed current evidence on the most effective approach to achieve mono-ovulation (one egg released) or ovulation in general in women with polycystic ovary syndrome (PCOS). Authors reported good safety and effectiveness for a number of treatment options for PCOS. These should be individualized wherever possible. 

PCOS affects about 5 to 10% of women. PCOS is associated with a number of cysts growing on the ovaries. Women with PCOS produce an excess of androgens (male hormones like testosterone). This can cause irregular ovulation (release of eggs), or even a lack of ovulation, and therefore infertility.

Treatment approaches for PCOS vary in effectiveness, duration, and tolerability. Clomiphene citrate (Clomid) is a type of drug used to stimulate ovulation. It is often the first-line treatment for infertility due to PCOS. Gonadotrophins are hormones that can be administered to release eggs resting in the ovary. Metformin (Glucophage) is a treatment used in diabetes to lower insulin levels (hormone that regulates blood sugar). It is believed to help restore ovulation in women with PCOS. Letrozole (Femara) can also be used for ovarian stimulation. Other treatment options include lifestyle interventions and minimally invasive ovary surgery. Some treatments can lead to multiple eggs being released during a single cycle, increasing the chance of a multiple pregnancy (such as twins).

The aim of this study was to analyze high-quality evidence on the most effective approach to achieve ovulation in women with PCOS.

Clomiphene citrate is inexpensive and usually administered daily for 5 days after menstruation. The risk of multiple pregnancies (such as twins) is low. One large study reported ovulation rates of 46% for 50 mg, 70% for 100 mg, and 85 to 90% for more than 150 mg of clomiphene citrate. Another study involving 5,268 women showed an ovulation rate of 73% and a pregnancy rate of 36%. A high body mass index (BMI; excess weight according to height), very high levels of androgens, absence of menstruation, and large ovarian volume have been associated with a poorer response to clomiphene citrate. Clomiphene citrate has also been found to be effective when used in combination with gonadotrophins (birth rate of 71%, multiple pregancy rate of 3% in one study).

Gonadotrophin stimulation has been associated with a risk of ovarian hyperstimulation syndrome (painful, swollen ovaries, considered a serious complication) and multiple pregnancies. However, this risk is reduced if the dose is started low and steadily increased. One study of 343 women and 945 treatment cycles found a single ovulation rate of 61.3%, and a pregnancy rate of 53.1%. Another study found a higher pregnancy rate and live birth rate following gonadotrophin stimulation when compared to clomiphene citrate. The live birth rate was 36.9% with clomiphene citrate and 47.4% with gonadotrophin stimulation.

Metformin has been reported to increase pregnancy rates 2.3-fold when compared to placebo (control substance with no active effect). A number of trials found increased pregnancy rates when metformin was combined with clomiphene citrate compared to each treatment alone. However, clomiphene citrate has been associated with higher live birth rates compared to metformin (by about 52%). Overweight and obese women may particularly benefit from treatment with metformin.

The most important lifestyle intervention believed to improve ovulation in overweight women is weight loss. The ovulation rate for women with a healthy BMI was noted to be 79%, then steadily decreased up to 12% in women with an obese BMI. A bodyweight loss of 5 to 10% can induce spontaneous ovulation and has been found to increase the response to clomiphene citrate.

One large study involving 5,560 women with PCOS reported 34% more live birth rates with letrozole than with clomiphene citrate. The risk of multiple pregnancies was also reduced by 62%. However, more high-quality evidence on the safety and effectiveness of letrozole is needed.

Ovary surgery involves a minimally invasive laparoscopic surgery that destroys parts of the ovaries. Significant differences in live birth rates have not been found between surgery and treatment with clomiphene citrate or gonadotrophin stimulation. Further studies on the safety and effectiveness of ovary surgery are needed.

Authors reported good safety and effectiveness for a number of treatment options for PCOS. The authors advised that ovulation induction in women with PCOS should ideally be individualized (e.g. according to weight).

Discuss with your doctor the most suitable treatment plan for you.