Ovulation Induction

Ovulation is the release of a mature egg from the ovary. Normally this occurs approximately every 28 days. The time from the start of the period to ovulation is variable, however it is usually 14 days from ovulation to the next period. Anovulation is the absence of ovulation. Anovulation is frequently corrected with fertility drugs and called ovulation induction. Ovulation induction is also performed in patients who are ovulatory to increase the chance of pregnancy.

Female Reproductive Anatomy

Vagina

The canal (birth canal) that leads from the uterus to outside the body.

Uterus

The female organ in which the unborn baby develops; also called the womb.

Fallopian tubes

Tubes that transport the egg from the ovary to the uterus.

Ovaries

Two glands that make eggs and hormones.

Follicle

A sac where an egg may develop. Follicles can be seen by a vaginal ultrasound.

Physiology of Ovulation and the Menstrual Cycle

Medications Used to Induce Ovulation

Medications that stimulate follicle development:

• Clomiphene citrate (Clomid, Serophene™)
• Gonadotropins (HMG, Humegon™, Pergonal™, Repronex™)
• Recombinant FSH (Follistim™, Gonal-F™)

Medication that induces ovulation:

• Human chorionic gonadotropin (hCG, Pregnyl™, Ovidrel™)

Medications that help support the luteal phase:

• Human chorionic gonadotropin (hCG)
• Progesterone

Each medication has possible side effects and risks. Refer to Side Effects and Risks of Your Medications.

Clomiphene citrate (CC)
This drug is often used to correct ovulatory disturbances. Approximately 80 percent of individuals will ovulate and approximately 40 percent will achieve a pregnancy using CC. The per cycle fecundity is approximately 12 percent. Clomiphene is usually started at a dose of 50 mg daily on day three to five of the cycle for five days. Documentation of ovulation may be confirmed with a day 21 progesterone, BBT or ovulation predictor kit. If ovulation is not achieved in any cycle the dose is increased by 50 mg increments to a maximum of 150 mg daily for five days. The side effects of CC include:

• Hot flashes (10 percent)
• Abdominal discomfort (five percent)
• Nausea and vomiting (2.2 percent)
• Headache (1.3 percent)
• Visual symptoms (1.5 percent)
• Dryness or loss of hair (0.3 percent)
• Mood swings
• Dysmenorrhea

The risks of CC include multiple pregnancy, ovarian cysts, and possibly borderline ovarian cancer although several studies suggest no increased risk of cancer. Baseline ultrasound or pelvic exam should be performed in consecutive cycles to avoid large cyst formation. Visual symptoms usually resolve within two weeks. Clomiphene citrate should be discontinued if visual symptoms occur and an alternative therapy utilized. The multiple pregnancy rate is approximately five percent, almost entirely twins: however rare cases of higher order multiples have been reported. Once ovulation has been achieved, higher doses of CC do not appear have any beneficial effect. One should reassess therapy after three ovulatory cycles if no conception occurs. The pregnancy rate with additional cycles is low, although the ovulatory rate remains high.

Gonadotropins
Human chorionic gonadotropin (hCG) is often added to clomiphene or FSH cycles. hCG causes the ovary to release an egg and help time inseminations. Ovulation usually occurs 36-72 hours after hCG is given. HCG will cause pregnancy tests to be falsely positive.

Follicle stimulating hormone (FSH) and gonadotropins (e.g., HMG) stimulates eggs to mature in the ovary. FSH may be used in women who can not make their own FSH, failed clomiphene or to increase the chance of pregnancy in ovulatory women. FSH treatment requires careful monitoring. Risks include a multiple pregnancy rate of 20-30 percent and ovarian hyperstimulation syndrome. An increased risk of ovarian cancer has been debated and the data are conflicting, however it is recommended to minimize the number of cycles to those necessary. Most pregnancies occur in three cycles of a particular therapy.