From the Guidelines
Letrozole is not shown to be more effective than clomiphene citrate for treating Polycystic Ovary Syndrome (PCOS) related infertility, according to the most recent and highest quality evidence available 1. When considering treatment options for PCOS-related infertility, the goal is to achieve the best possible outcomes in terms of morbidity, mortality, and quality of life. The available evidence suggests that both clomiphene citrate and letrozole can be effective, but the choice between them should be based on the most current and reliable research.
Key Considerations
- The American College of Obstetricians and Gynecologists (ACOG) recommends clomiphene citrate as a first-line treatment for ovulation induction in women with PCOS, citing its effectiveness and the availability of good and consistent scientific evidence 1.
- A more recent study published in 2018 found no significant benefit of letrozole over clomiphene citrate in terms of pregnancy rates, based on moderate quality evidence 1.
- The 2018 study also highlights the importance of using low-dose gonadotropins (75 IU or lower) to minimize the risk of multiple pregnancies and ovarian hyperstimulation syndrome (OHSS) 1.
Treatment Recommendations
- Clomiphene citrate (50-150 mg daily for 5 days, starting on day 3-5 of the cycle) is a reasonable first-line treatment option for PCOS-related infertility, given its established efficacy and safety profile 1.
- Letrozole may be considered as an alternative, but its use should be based on individual patient factors and preferences, rather than a presumed superiority over clomiphene citrate.
- Treatment should be monitored with ultrasound to track follicular development and minimize the risk of multiple pregnancies.
- Patients should be counseled on the importance of timing intercourse appropriately during the fertile window to maximize the chances of conception.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Comparative Efficacy of Clomiphene and Letrozole
- The efficacy of Clomiphene (Clomid) versus Letrozole for treating Polycystic Ovary Syndrome (PCOS) related infertility has been compared in several studies 2, 3, 4, 5, 6.
- A retrospective cohort study found that combination treatment of Clomiphene citrate with Letrozole may potentially improve fertility outcomes in PCOS subfertility in terms of the likelihood of ovulation and higher post-ovulatory progesterone levels 2.
- A clinical trial comparing the efficacy of Letrozole with Clomiphene citrate for ovulation induction in patients with PCOS found that the pregnancy rate in the Letrozole group was higher than that in the Clomiphene group, although the difference was not significant 3.
- A cohort study found that Letrozole was associated with significantly higher clinical pregnancy and live birth rates compared to Clomiphene in treatment-naïve infertile women with PCOS 4.
- A systematic review and meta-analysis found that the probability of ovulation was significantly higher in Letrozole as compared to Clomiphene citrate cycles 5.
- An individual participant data meta-analysis found that Letrozole improved live birth and clinical pregnancy rates and reduced time-to-pregnancy compared to Clomiphene citrate, and can be recommended as the preferred first-line treatment for women with PCOS and infertility 6.
Ovulation Induction and Pregnancy Rates
- The studies suggest that Letrozole may be a more effective ovulation induction agent than Clomiphene citrate, with higher ovulation rates and pregnancy rates 3, 4, 5, 6.
- The combination of Clomiphene citrate and Letrozole may also improve fertility outcomes in PCOS subfertility 2.
- The treatment effects of Letrozole are influenced by baseline serum levels of total testosterone, while those of Clomiphene citrate plus metformin are affected by baseline serum levels of insulin 6.
Treatment Recommendations
- Based on the available evidence, Letrozole can be recommended as the preferred first-line treatment for women with PCOS and infertility 6.
- Clomiphene citrate plus metformin may also be considered as a treatment option, although the evidence is less strong 6.
- The combination of Clomiphene citrate and Letrozole may be considered for women who do not respond to Letrozole alone 2.