Gonadotropin Side Effects for Fertility

Before starting treatment with gonadotropins—sometimes referred to as injectables or GNDs—your doctor should explain the potential side effects and risks of treatment. Gonadotropins may be used during fertility treatment, for women donating their eggs, and for egg freezing procedures. Most gonadotropin side effects are mild, but in rare cases, some can be serious and even life-threatening.

Important note: Not all possible side effects and risks are listed below. If you are experiencing severe side effects, unusual symptoms, or are concerned for any reason, contact your doctor. The information in this article does not replace consultation with a medical professional.

What Medications Are Considered Gonadotropins?

Gonadotropins are fertility drugs containing FSH, LH, or a combination of the two (which is called human menopausal gonadotropins, or hMG). They also include the hormone hCG, which is biochemically similar to LH. These hormones are taken via injection.

Gonadotropins can be produced either in a lab using recombinant DNA technology, or they can be extracted and purified from the urine of postmenopausal or pregnant women. In either situation, the goal is for your body to react to the hormones in the same way as if they came from your body.

Brand names of gonadotropins created using recombinant DNA technology include Gonal-F (rFSH), Follistim (rFSH), Puregon (rFSH), Luveris (rLH), and Ovidrel (rHCG).

Bravelle, Metrodin, and Fertinex are brand names for urinary extracted FSH. Novarel, Pregnyl, and Profasi are urinary extracted hCG.

Brand names of urinary extracted human menopausal gonadotropins (a combination of FSH and LH) include Humegon, Menogon, Pergonal, Repronex, and Menopur.

When Are Gonadotropins Used?

Gonadotropins are used to stimulate follicles in the ovaries. During fertility treatment, they may be used alone or in combination with other fertility drugs and medications. Some possible reasons your doctor may prescribe gonadotropins include:

• As part of a Clomid cycle: A single injection of hCG or LH may be added to a Clomid cycle, specifically just before ovulation. In this context, it's sometimes called a "trigger shot."
• Alone as the primary ovulatory stimulation: FSH along with LH may be used to stimulate ovulation. In a cycle like this, you may expect to give yourself an injection of hormones every day at the start of your cycle.
• As part of an IUI treatment cycle: Gonadotropins may also be used during an intrauterine insemination cycle.
• As part of IVF treatment: Gonadotropins may be used during IVF. You may expect to give yourself multiple injections a day, and you may be more likely to experience side effects.
• As part of egg donation: If you've chosen to donate your eggs, you'll be giving yourself gonadotropins.
• As part of egg freezing: If you've decided to freeze your eggs (oocyte preservation), you'll likely be giving yourself gonadotropin injections over many days.

Side Effects of Gonadotropins

The percentages below refer to research comparing Gonal-F—which is rFSH, created in a lab using recombinant DNA technology—and urofollitropin, or uFSH, which is purified FSH extracted from the urine of postmenopausal women. Rates may vary slightly from drug to drug, but gonadotropin treatment side effects are generally similar.

Possible side effects of gonadotropins include:

• Headache (rFSH: 22%, uFSH: 20.2%)
• Nausea (rFSH: 13.6%, uFSH: 3.5%)
• Upper respiratory tract infection (rFSH: 11.9%, uFSH: 7.9%)
• Abdominal tenderness (rFSH: 9.3%, uFSH: 12.3%)
• Bloating and gas (rFSH: 6.8%, uFSH: 8.8%)
• Sinus congestion (rFSH: 5.1%, uFSH: 5.3%)
• General achiness (rFSH: 5.9%, uFSH: 6.1%)
• Mood swings (rFSH: 5.1%, uFSH: 2.6%)
• Acne (rFSH: 4.2%, uFSH: 2.6%)
• Breast tenderness (rFSH: 4.2%, uFSH: 6.1%)
• Weight gain (rFSH: 3.6%, uFSH: 0.0%)
• Pelvic discomfort (rFSH: 2.5%, uFSH: 6.1%)
• Abnormal bleeding or spotting (rFSH: 2.5%, uFSH: 0.9%)
• Vomiting (rFSH: 2.5%, uFSH: 2.6%)
• Injection site pain, redness (rFSH: 2.5%, uFSH: 0.9%)
• Dizziness (rFSH: 2.5%, uFSH: 0.0%)

Risks of Gonadotropins

Ovarian Hyperstimulation Syndrome (OHSS): OHSS occurs when the ovaries and abdomen become swollen with fluid. Up to 10% to 20% of women will develop a mild form of OHSS, which will usually resolve on its own. It is important to report even mild symptoms to your doctor. Your physicians monitor you frequently to adjust your doses to prevent OHSS.

If you have PCOS, you are at a higher risk of developing OHSS. Severe OHSS occurs in about 1% of patients. Contact your doctor immediately if you experience vomiting, severe abdominal or pelvic pain, rapid weight gain, or severe bloating.

Multiple pregnancy: Depending on which study you look at, the rate of multiples with gonadotropin treatment is anywhere from 2% to 30%, with up to 5% triplet or higher order pregnancies.

Clinical trials found that multiple pregnancies occurred 12% to 14% of the time when using rFSH or uFSH respectively. Careful monitoring and using the lowest effective dose can reduce the risk.

When using gonadotropins during IUI or alone, it’s much harder to control the risk of multiples than when used during IVF. During IVF, your doctor can transfer a single embryo.

If you are concerned about the risk of multiples, and you are using injectables as part of an IUI cycle, you may want to ask your doctor about mini-IVF.

Ovarian cysts: Ovarian cysts occur commonly with gonadotropins. With rFSH, they occur about 15% of the time, and with uFSH they occur about 29% of the time. Usually, they resolve on their own. In rare cases, may require surgical intervention.

Injection site infection: Some redness and tenderness are normal, but in rare cases, the injection site may become infected. Contact your doctor if you notice at the injection site increasing redness, constant warmth, swelling, puss, odor, or severe pain. Also, if you get a fever over 101 degrees F, contact your doctor.

Adnexal torsion (or ovarian twisting): In rare cases (less than 2% of the time), the ovary may twist, rupture, or bleed, requiring surgical intervention. This occurs because the ovary becomes heavy and enlarged from the stimulation. Possible symptoms include severe pelvic pain or lower abdominal pain, nausea, and vomiting.

This is a medical emergency and may be life-threatening if not treated quickly. But ovarian torsion is very rare, especially if you are observing the precautions recommended by your clinic (such as no running, jumping, or other high-impact activities).

Ectopic pregnancy: The risk of ectopic pregnancy is slightly increased when taking gonadotropins. Ectopic pregnancies can be life-threatening or may require surgical intervention.

Blood clots: Clots are extremely rare (4.2 per 1,000), but can be life-threatening. The increased blood clot risk is not just during treatment. If you conceive, the risk continues to be higher during the pregnancy.

If you experience symptoms of a possible blood clot—swelling or pain one leg, warmth in the affected area, change in skin color (redness, bluish, or pale)—contact your doctor immediately.

If you develop symptoms of a pulmonary embolism—sudden onset of shortness of breath, chest pain that worsens when you try to take a deep breath or when you cough, feeling lightheaded or faint, rapid pulse, sweating, coughing up blood, a sense of impending doom—get medical help immediately.