Alternatives to Clomiphene: What Works When Clomiphene Doesn't

When Clomiphene, a selective estrogen receptor modulator used to trigger ovulation in women with infertility. Also known as Clomid, it has been a first-line treatment for ovulation disorders for decades. doesn’t work—or causes side effects like mood swings, hot flashes, or thinning of the uterine lining—many women and doctors turn to other options. Clomiphene isn’t the only path to ovulation, and in some cases, it’s not even the best one. Research shows that for women with PCOS, letrozole, an aromatase inhibitor originally developed for breast cancer. Also known as Femara, it often leads to higher live birth rates than Clomiphene. It’s not a hormone replacement. It doesn’t mimic estrogen. Instead, it gently lowers estrogen levels, which tells the brain to produce more FSH and kickstart ovulation. Many clinics now use letrozole as the default for PCOS patients because it works better and has fewer side effects.

Then there’s gonadotropins, injectable hormones like FSH and LH that directly stimulate the ovaries. Also known as fertility shots, they are the next step up when pills fail. These aren’t casual treatments—they require close monitoring with blood tests and ultrasounds to avoid overstimulation and multiple pregnancies. But for women who don’t respond to oral meds, they’re often the only way to get pregnant. Some also explore metformin, an insulin-sensitizing drug used for type 2 diabetes. Also known as Glucophage, it when insulin resistance is the root cause of anovulation. It doesn’t directly trigger ovulation, but by improving how the body handles sugar, it can restore natural cycles over time. Lifestyle changes—weight loss, reducing stress, better sleep—also play a bigger role than most realize. A 5-10% drop in body weight can restart ovulation in overweight women, sometimes without any medication at all.

What’s clear from the real-world data is that Clomiphene is just one tool in a much larger toolbox. The right alternative depends on your diagnosis, your body’s response, your age, and your goals. Some women find success with letrozole alone. Others need a combo of metformin and lifestyle shifts. A few require injections. There’s no one-size-fits-all, but there are proven paths forward—even if Clomiphene didn’t work for you. Below, you’ll find detailed comparisons of the most common alternatives, real patient experiences, and practical advice on how to choose the next step in your fertility journey.