Fertility Drugs 101: Possible Side Effects & Use Cases

During a natural menstrual cycle, only one egg is usually produced. Powerful hormones are used in both ovulation induction (OI) and in vitro fertilization (IVF) cycles to stimulate the ovaries to produce multiple follicles, tiny fluid-filled sacs in which multiple mature eggs can develop. Other medications may also be prescribed to the female or her partner to improve the chances for conception.
To best limit possible side effects of stimulation medications, cycles are monitored carefully by our medical team. Blood tests and ultrasound are done in order to track follicular development and allow us to adjust medication dosages, if necessary.

What Infertility Medications May Be Prescribed

1. Antibiotics (Doxycycline, Z-pack) – prescribed during an IVF cycle for the cycling partner, to control bacteria that may affect implantation in the uterus.
Method of Administration: Oral.
Timing: Antibiotics are taken by the female two times a day for four days, beginning the day of retrieval. A Z-Pack (Zithromax) may be prescribed in some cases, depending on individual needs/allergies.
Possible Side Effects: Sensitivity to sunlight, gastrointestinal distress. Take with food and a full glass of water.

2. Birth Control Pills – may be used in an IVF cycle to suppress a woman’s natural cycle, preventing ovulation in preparation for ovarian stimulation and cycle synchronization.
Method of Administration: Oral.
Timing: For approximately 1-2 or more weeks prior to the start of a stimulation cycle for IVF.
Possible Side Effects: Although oral contraceptives can have serious long-term effects for some women, the short-term effect of using oral contraceptives should be minimal. These may include nausea, headache, dizziness, and visual disturbances.

3. Bromocriptine (Parlodel) – reduces the amount of prolactin released by the pituitary gland. This medication is prescribed in cases where infertility is linked to irregular ovulation resulting from over-production of prolactin.
Method of Administration: Oral or vaginal.
Timing: Introduced gradually over several weeks and continued until the prolactin level becomes normal. It is usually discontinued following a positive pregnancy test.
Possible Side Effects: Nasal stuffiness, nausea, vomiting, fainting, dizziness and high blood pressure.

4. Clomid – used to stimulate the development of follicles and eggs in women with infrequent periods and long menstrual cycles. Clomid causes the hypothalamus gland to detect an estrogen deficiency in the blood and react by secreting more follicle stimulating hormone (FSH) and luteinizing hormone (LH) into the bloodstream. The high hormone levels stimulate production of a follicles and eggs.
Method of Administration: Oral.
Timing: Starting on the third, fourth or fifth day of a cycle and continuing for five consecutive days. If ovulation does not occur, the dose may be increased or the drug may be combined with injectable medications, in subsequent cycles.
Possible Side Effects: Hot flashes, mood swings, visual disturbances and depression while taking clomiphene; nausea and breast tenderness later in the cycle. If visual disturbances occur, contact IRMS. Women taking this medication have approximately a 5% to 10% chance of having twins, and less than a 1% chance of higher order multiples.

5. Dexamethasone – taken with ovulation stimulation drugs, it helps the ovaries be more receptive to treatment by decreasing male hormones (androgens) produced by the adrenal gland.
Method of Administration: Oral.
Timing: One pill a day beginning day two of the menstrual cycle and ending with ovulation.
Possible Side Effects: None, based on the low doses prescribed.

6. Estradiol – pills/patches/injections for cryo synthetic cycles, recipient cycles.

7. Human Chorionic Gonadotropin (HCG: Ovidrel, Pregnyl, Novarel) – like the surge of luteinizing hormone (LH) in a natural cycle, HCG prepares the eggs for ovulation/ retrieval by prompting their release from the follicle wall. Floating free in the follicular fluid, the eggs are aspirated during oocyte retrieval for IVF or are ovulated for insemination/intercourse cycles. HCG, produced by the placenta during pregnancy, is extracted from the urine of pregnant women. This drug may not be required, or the dosage reduced, depending on how the ovaries respond to stimulation medications.
Method of Administration: Subcutaneous Ovidrel only or Intramuscular injection.
Timing: When follicles are mature. HCG may be given at any time 1-2 days prior to insemination or intercourse. For IVF patients, HCG is given at a prescribed time 35 hours prior to the retrieval.
Possible Side Effects: Headache, bloating, irritability, pain at the injection site, ovarian hyperstimulation syndrome (in less than 1% of cases).

8. Human Menopausal Gonadotropins (hMG: Menopur) – made from equal parts of FSH and LH that are derived from the urine of post-menopausal women, HMG works directly on the ovaries to stimulate follicle development. These medications come in powder form and must be mixed with a diluent prior to administration.
Method of Administration: Intramuscular injection or subcutaneous injection.
Timing: Given daily starting the second, third, fourth or fifth day of the cycle, and continuing for 7 to 12 days or longer if the ovary responds slowly.
Possible Side Effects: Breast tenderness, swelling or rash at the injection site, abdominal bloating, mood swings and slight abdominal pain. Use of gonadotropins is linked to a slight increase in the risk of ectopic pregnancies and a risk of ovarian hyperstimulation syndrome (OHSS) in 1 to 5% of cycles, a risk that is increased in women with polycystic ovarian syndrome. When severe, OHSS can result in blood clots, kidney damage, chest and abdominal fluid, or ovarian twisting (adnexal torsion) that cuts off the blood supply to the ovary and requires surgery. Severe OHSS is rare. Hospitalization may be required for monitoring of OHSS; however, the condition usually lasts only about a week. Gonadotropins have been suggested as a possible link to an increased risk of breast and ovarian cancer, but no statistical significance has been established. Multiple pregnancies (two-thirds twins and one-third triplets) occur in approximately 15-25% of hMG cycles.

9. Follicle Stimulating Hormones (Gonal F, Follistim) – consisting primarily of FSH, with little or no LH, they bypass the hypothalamus and pituitary glands to stimulate growth of multiple follicles. These medications are most often administered via a redi-inject pen device.
Method of Administration: Subcutaneous injection. These medications may be mixed with the HMG medications, but must then be given intramuscularly.
Timing: Generally started on the second, third, fourth or fifth day of the cycle, and continued for 7 to 12 days or longer if the ovary responds slowly.
Possible Side Effects: Breast tenderness, swelling or rash at the injection site, abdominal bloating, mood swings and slight abdominal pain. Use of gonadotropins is linked to a slight increase in the risk of ectopic pregnancies and a risk of ovarian hyperstimulation syndrome (OHSS) in 1 to 5% of cycles, a risk that is increased in women with polycystic ovarian syndrome. When severe, OHSS can result in blood clots, kidney damage, chest and abdominal fluid, or ovarian twisting (adnexal torsion) that cuts off the blood supply and requires surgery. Severe OHSS is rare. Hospitalization may be required for monitoring of OHSS; however, the condition usually lasts only about a week. Gonadotropins have been suggested as a possible link to an increased risk of breast and ovarian cancer, but no statistical significance has been established. Multiple pregnancies (two-thirds twins and one-third triplets) occur in approximately 15-25% of hMG cycles.

10. Leuprolide Acetate (Lupron) – initially accelerates the pituitary gland and then stops it from producing LH and FSH, allowing for a controlled stimulation cycle prior to IVF. A synthetic hormone, Lupron prevents ovulation and produces a drop in estrogen level, which may cause the patient to experience symptoms of menopause.
Method of Administration: Subcutaneous injection. Vial premixed and patient draws up dosage from a vial.
Timing: Five, ten or twenty units given daily as prescribed during the cycle. It may be overlapped with birth control pills for 3-7 days.
Possible Side Effects: Bloating, bruising at the injection site, hot flashes, insomnia and night sweats, headache, mood swings, and vaginal dryness. Many symptoms are relieved by two Tylenol every four hours and usually disappear with the start of stimulation drugs. Symptoms may not occur when Lupron and birth control pills overlap.

11. Pre-Natal Vitamins – contain folic acid (folate), which may reduce the risk of certain birth defects such as spina bifida and other neural tube defects.
Method of Administration: Oral.
Timing: Taken daily, starting before attempting pregnancy, if possible.
Possible Side Effects: Constipation, nausea, bloating.

12. Methotrexate – used as a first step for treating ectopic pregnancies, this drug destroys pregnancy tissue and allows it to be reabsorbed by the body. If methotrexate therapy fails, as evidenced by continued elevated beta HCG levels, the medication may be repeated or surgery may be required.
Method of Administration: Intramuscular injection.
Timing: Prescribed after diagnosis of ectopic pregnancy and review of baseline bloodwork by a physician.
Possible Side Effects: Short-term/temporary symptoms include ulcers in the mouth and gastrointestinal system, liver function problems, sensitivity to sunlight and adverse effects from alcohol consumption.

13. Methylprednisolone (Medrol) – a steroid used for its anti-inflammatory effect after IVF oocyte retrieval.
Method of Administration: Oral.
Timing: One pill daily beginning the day of retrieval and take for 4 days prior to embryo transfer.
Possible Side Effects: None, based on the low dose prescribed.

14. Progesterone – administered to support the uterine lining during early pregnancy.
Method of Administration: Oral capsules, vaginal suppositories/capsules/gel, or intramuscular injection.
Timing: Used daily starting day of IVF retrieval and continuing until the pregnancy test, and an additional four to six weeks if the pregnancy test is positive.
Possible Side Effects: Cramping, headaches, nausea, diarrhea, breast tenderness, swelling or soreness at the intramuscular injection site, mood swings or (if using a gel) vaginal irritation. Allergic reaction (rash, itching, redness) to the oil base used in the intramuscular injection preparation.

Taking Your Medications

It is important that you fill your prescriptions several weeks prior to needing them in order to be sure you have the required medications on hand. Once your protocol has been determined by your MD, you will take an online medication class. Your medication protocol and instructions on self-administration of your meds will be reviewed. In this Orientation the Nurse will provide you with important information about your treatment cycle and the role you play in its success.

IMPORTANT: Never take a medication unless a Nurse or Physician has specifically told you to do so. Also, never stop a medication unless told to do so. All instructions must be followed carefully and timing is extremely important to the success of your cycle. In some cases, failure to follow instructions may result in cancellation of treatment.

Over the counter medications, health food remedies, herbal and nutritional supplements should not be taken during the cycle unless cleared by your nurse or physician. Some of these substances may have adverse effects on the cycle or during pregnancy.