What is the Best Drug for PCOS Patients?

Polycystic ovary syndrome (PCOS) is a common cause of infertility. Women with PCOS often have irregular or absent periods and therefore ovulate infrequently or do not ovulate.

In PCOS patients with obesity, weight loss is a very effective treatment. Weight loss will often lead to resumption of ovulation and spontaneous pregnancy. Even in patients that do not conceive spontaneously, weight loss will increase the chances of the patient responding to fertility drugs. Even a weight loss of 15 – 20 lb can make a huge impact in success rates.

Drugs used for ovulation induction include clomiphene citrate (e.g. Clomid, Serophene), letrozole (Femara) and follicle stimulating hormone (FSH) injections. FSH injections are associated with an uncontrolled and unacceptably high incidence of high-order multiple pregnancy (triplets or higher). At InVia Fertility Specialists, we generally avoid the use of FSH injection for ovulation induction in PCOS patients. This is especially so in young patients with PCOS.

A recent blog discussed the use of letrozole versus clomiphene citrate for ovulation induction in PCOS patients. A large prospective randomized trial (Legro et al. NEJM, 2014) confirmed that Letrozole had a significantly higher pregnancy rate than clomiphene citrate in PCOS patients.

This study was a potential game-changer where a relatively new drug (Letrozole) was shown to be superior to a well-established drug that had been used for several decades (clomiphene citrate). Of interest is the fact that the FDA has not even approved the use of Letrozole for ovulation induction!

A soon to be published summary of a Cochrane review (the best available evidence-based medicine) confirmed the superiority of Letrozole. Franik et al. (Fertil Steril, 2015 In Press) reviewed the literature and analyzed all randomized controlled trials (RCTs) of aromatase inhibitors used for ovulation induction in PCOS patients.

They analyzed a total of 26 RCTs. These were their conclusions:

• The live birth rate was higher with Letrozole when compared with clomiphene citrate (OR 1.64, 95% CI 1.32 – 2.04). This superiority was maintained in both intercourse and intrauterine insemination (IUI) cycles.
• The incidence of ovarian hyperstimulation syndrome (OHSS) was similar in both groups and quite low
• The incidence of multiple pregnancy was not discussed in this paper. It has previously reported to be about 8%. The overwhelming majority of multiple pregnancy are twins. There, however, is a recent case report of a sextuplet pregnancy with the use of letrozole.
• The study also compared the use letrozole with laparoscopic ovarian drilling. There were only two studies that compared these two treatments and they reported similar pregnancy rates. At InVia, we hardly ever use ovarian drilling as it involves laparoscopy and is therefore more invasive.

In conclusion, the literature now seems to suggest that Letrozole (Femara) is now the drug of choice for ovulation induction in PCOS patients.

To see a fertility specialist who will answer your questions about PCOS and IVF, make an appointment at one of InVia Fertility’s four Chicagoland locations.