Letrozole may help induce ovulation in PCOS patients with infertility

Delhi: Letrozole can be recommended as the preferred first line of treatment for women with polycystic ovary syndrome (PCOS) and infertility, suggests a recent study published in the journal Human Reproduction Update. According to the study, treatment with letrozole improved live birth, clinical pregnancy rates and reduced time-to-pregnancy compared to clomiphene citrate (CC) -- currently used medication for the treatment of infertility in women who do not ovulate.

According to the Mayo Clinic, PCOS is the hormonal disorder common among women of reproductive age. Women affected by the disorder have infrequent or prolonged menstrual periods. The ovaries may develop numerous small collections of fluid (follicles) and fail to regularly release eggs, making it the most frequent cause of anovulatory (non-occurrence of ovulation) infertility. Thus, in women with PCOS effective ovulation induction serves as an important first-line treatment for anovulatory infertility,

Rui Wang, University of Adelaide, North Adelaide, SA, Australia, and colleagues aimed to evaluate the effectiveness of ovulation induction agents, in particular, letrozole alone and clomiphene citrate plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility. And, to explore interactions between treatment and participant-level baseline characteristics.

The researchers searched online databases up to 20 December 2018. It included randomized controlled trials that compared the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. Studies on treatment-resistant women were excluded.

The primary outcome was live birth. Individual participant data (IPD) of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women.

Key findings include:

• Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72).


• Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29).


• Eight RCTs compared CC plus metformin to CC alone in 1039 women.


• Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08).


• Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC.

"Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS," wrote the authors.

More Information: "First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis" published in the journal Human Reproduction Update.

DOI: https://doi.org/10.1093/humupd/dmz029

Journal Information: Human Reproduction Update