Clomid Treatment For Infertility: How It Works, Uses And Side Effects

Clomid is a brand name for clomiphene citrate, a nonsteroidal powder approved in 1967 by the Food and Drug Administration (FDA) for use as a fertility medication. It belongs to a class of medications known as ovulatory stimulants. For consumption, the powder is pressed into small tablets, typically dosed at 50 milligrams per tablet.

While many other fertility treatments require an appointment with a reproductive endocrinologist at a specialized fertility clinic, Clomid can be prescribed by a gynecologist.

In short, taking Clomid prompts your body to release hormones that increase the chances of your ovaries releasing a mature and ready-to-be-fertilized egg. Some patients take Clomid as part of fertility treatment, such as an IUI (intrauterine insemination) or IVF (in vitro fertilization) cycle, but many start simply by taking Clomid and having sex.

The idea is to “try to increase the odds of sperm and egg meeting,” says Kenan Omurtag, M.D., division director of the reproductive endocrinology and infertility department at the Washington University School of Medicine in St. Louis.

Clomid works by binding to the receptors in your brain that would typically bind with estrogen. As a result, your brain thinks your estrogen levels are low and compensates by producing more FSH, or follicle-stimulating hormone, which can boost estrogen. FSH’s primary function is fertility-related—as the name implies, the hormone stimulates your ovarian follicles, encouraging them to grow. An ovarian follicle is a tiny fluid sac in your ovaries that holds an immature egg, called an oocyte. Most women are born with a reserve of millions of oocytes that gradually depletes throughout a lifetime.

By triggering follicle growth, FSH helps oocytes grow into mature eggs. Ideally, while on Clomid, at least one of those eggs will mature enough to release from the follicle and be swept into the fallopian tubes, where it can meet with sperm to be fertilized into an embryo.

If you have been trying to get pregnant through sex for at least a year (or for six months if you’re older than 34), you may be a candidate for Clomid. Clomid is often prescribed for patients with:

• Unexplained infertility. It can be frustrating to hear that there isn’t a clear explanation for your inability to get pregnant. However, you’ll likely receive this diagnosis if you have regular menstrual cycles and at least one working fallopian tube, and your partner’s sperm tests don’t reveal any problems with count or motility. Up to 30% of couples seeking fertility treatment are diagnosed with unexplained fertility^[1]Evidence-based treatments for couples with unexplained infertility: a guideline. American Society for Reproductive Medicine. Accessed 07/28/2021. . Since there’s no identified problem to target, your doctor will likely prescribe an oral medication like Clomid because it’s non-invasive and relatively inexpensive compared to other fertility treatments.

• Irregular menstrual cycles. If you don’t ovulate on a typical monthly schedule or don’t ovulate at all, your doctor may prescribe Clomid to help induce ovulation.
• Polycystic ovary syndrome (PCOS). Patients with PCOS often experience either infrequent periods or no periods at all and may be prescribed Clomid. However, U.S. guidelines now recommend letrozole, another oral medication, as the first-line fertility treatment for women with anovulatory (which refers to the absence of ovulation) PCOS who are trying to conceive, as success rates in recent studies have been slightly higher with letrozole versus clomiphene citrate^[2]LeFevre N. Aromatase inhibitors such as letrozole (Femara) vs. clomiphene (Clomid) for subfertile women with PCOS. Am Fam Physician. 2019;99(9):545-546. .

Clomid comes in 50-milligram tablets. The most common starting dose is one tablet a day for five days, beginning on the third, fourth or fifth day of your menstrual cycle. From there (unless you’re using Clomid with a IUI or IVF cycle), you need to have sex timed to your fertile window, which is the six-or-so-day time period during your menstrual cycle that you’re able to get pregnant.

If you don’t get pregnant during your first month of taking Clomid, your doctor may increase your dose to two or three tablets a day during your next menstrual cycle. Never take Clomid without a prescription.

Hot flashes, mood swings and pelvic pain are the most common side effects in patients taking Clomid, says Abigail Mancuso, M.D., a reproductive endocrinologist with University of Iowa Health Care in Des Moines, Iowa.

Other potential side effects include:

• Ovarian enlargement
• Nausea and vomiting
• Breast discomfort
• Visual symptoms, including blurred vision or floaters (small dark spots, lines or other shapes that seem to be floating in your line of vision)
• Headaches
• Spotting

Clomid and Chance of Multiples

Taking Clomid increases the chance of carrying multiple babies. In one review of 42 randomized controlled trials, which, in sum, looked at 7,935 women with PCOS ages 18 to 40 taking either clomiphene citrate or letrozole, 1.7% of clomiphene-assisted pregnancies resulted in twins or higher-order multiples^[2]LeFevre N. Aromatase inhibitors such as letrozole (Femara) vs. clomiphene (Clomid) for subfertile women with PCOS. Am Fam Physician. 2019;99(9):545-546. .

In another major study funded by the National Institutes of Health, 750 women with PCOS ages 18 to 40 were assigned to take either clomiphene citrate or letrozole, and 7.4% of patients taking clomiphene citrate became pregnant with twins^[3]Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-129. .

Success rates are hard to predict and often decline with age. In the 2014 NIH-funded study in the New England Journal of Medicine, 19.1% of patients taking clomiphene citrate achieved a successful pregnancy resulting in a live birth^[3]Legro RS, Brzyski RG, Diamond MP, et al. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-129. . Meanwhile, in the 2019 review of 42 trials in American Family Physician, 21.4% of patients taking clomiphene citrate achieved a successful pregnancy resulting in a live birth^[4]LeFevre N. Aromatase inhibitors such as letrozole (Femara) vs. clomiphene (Clomid) for subfertile women with PCOS. Am Fam Physician. 2019;99(9):545-546. .

The FDA recommends taking no more than six cycles of Clomid. If Clomid hasn’t worked for you, there are many other fertility treatments you can explore.

One cycle of Clomid typically costs less than $10 if covered by insurance, and about $20 to $50 if not covered. It’s common for insurance to cover Clomid, but always check with your doctor and insurance provider so you know what to expect.