A big NICHD-funded trial of 900 couples looked at three common fertility treatments: letrozole, clomiphene, and injectable gonadotropins. If you’re weighing options after a diagnosis of unexplained infertility — or managing PCOS while trying to conceive — this study gives clear, usable info. Here are the key takeaways and what they mean for real people.
Researchers compared success rates and risks across the three drugs. Letrozole — originally developed for breast cancer but widely used for fertility, especially with PCOS — led to better outcomes than clomiphene for many women. Gonadotropins produced the highest pregnancy rates overall, but they also came with more downsides: more monitoring, higher cost, and a bigger chance of multiple pregnancies. The trial’s sample size (about 900 couples) gives weight to these findings, so they’re worth discussing with your provider.
Why does that matter? If you have PCOS or irregular ovulation, letrozole often boosts ovulation quality and timing compared with clomiphene. That can translate into higher chances of conception with fewer side effects. On the other hand, gonadotropins push the ovaries harder and can produce more eggs — good for some couples, risky for others because of twins or triplets.
Thinking practically: clomiphene has been a longtime go-to because it’s oral, cheap, and familiar. But this study suggests letrozole should be the preferred first step for many women, especially those with PCOS. Gonadotropins make sense when oral meds fail or when a clinic is aiming for faster results, but they require injections, frequent scans, and a willingness to accept higher multiple-pregnancy risk.
Cost and monitoring matter. Gonadotropins typically need more clinic visits and blood tests. If your budget, schedule, or tolerance for frequent monitoring is tight, letrozole may be a more comfortable choice. If you’re okay with intensive treatment and your team can closely monitor your cycle, gonadotropins could raise your odds — but plan for the possibility of multiples and the extra care that brings.
Side effects are different, too. Letrozole and clomiphene are oral and usually have milder immediate side effects than injectables. Gonadotropins carry higher risks of ovarian hyperstimulation and multiples, so clinics usually track hormone levels and follicle growth closely.
So what should you do? Talk it through with your fertility provider. Mention this NICHD trial and your personal priorities: cost, convenience, desire to avoid multiples, and whether you have PCOS. If you want a straightforward, lower-risk first step, ask about letrozole. If previous oral treatments didn’t work, discuss whether the higher success rate of gonadotropins justifies the extra monitoring and risk.
Want the full article from our August 2024 archive? Read the complete post on MarleyDrug to see more details, or bring the study summary to your next clinic visit to get personalized advice.
A significant study funded by NICHD compared the effectiveness of letrozole, clomiphene, and gonadotropins in treating unexplained infertility among 900 couples. The findings indicated that letrozole, often a breast cancer drug, outperformed clomiphene, especially for women with polycystic ovary syndrome (PCOS). Conception rates with gonadotropins were higher but had greater risks, including multiple pregnancies.
© 2025. All rights reserved.
