Ovulation Induction

Ovulation induction uses hormonal therapy to stimulate egg development and release.

Historically, the use of agents to induce ovulation (egg development and release) were designed to induce ovulation in women, who themselves, did not ovulate. These were women with irregular menstrual cycles. The goal of this treatment was to produce a single, healthy egg and started with the simplest agents (typically oral).

The second use of ovulation induction was to increase the number of eggs reaching maturity in a single cycle to increase chances for conception. The initial agents for this treatment (used first for IVF and only later for simpler treatments) were injectable medications. These agents carry an increased risk of multiple gestation, ovarian hyperstimulation, and increased cost and time commitment.

More recently, in the mid-90s, evidence developed to suggest there may be an advantage to the oral agents in ovulatory women. These women with "unexplained infertility" may have subtle defects in ovulation AND the use of oral agents may induce the maturity of 2-3 eggs versus only one. This treatment therefore improves the quality AND quantity of the ovulation, thus enhancing pregnancy rates.

Ovulation induction, in ovulatory women, is always combined with intrauterine insemination. Ovulation induction should only progress after a complete and thorough evaluation. All underlying hormonal disorders (such as thyroid dysfunction) should be treated prior to resorting to ovulation induction with fertility drugs.

This page discusses the following common fertility drugs used for ovulation induction:

• Clomiphene Citrate (Seraphene, Clomid)
• HMG: LH/FSH (Pergonal, Humegon, Repronex) Human Menopausal Gonadotropin (hMG)
• FSH (Follistim/Gonal F)
• HCG (Profasi or Pregnyl) Human Chorionic Gonadotropin
• Leuprolide (Lupron) Synthetic Gonadotropin (FSH/LH) Inhibitor

Clomiphene citrate induces ovulation by blocking estrogen receptors. This artificial estrogen effect causes your body to believe estrogen is low and therefore cause the production of more FSH and LH. Clomiphene citrate acts as a fertility agent in women by inducing superovulation, i.e. the release of multiple eggs in a given menstrual cycle.

Clomiphene citrate is available as 50 mg tablets. It is used to induce ovulation in select women. The dosage range is 25 mg (½ tablet) to 150 mg (3 tablets) once a day for five days early in a woman's menstrual cycle. The dosage and the days the drug is taken are determined by your physician based on your diagnosis.

Some form of monitoring is necessary while you are taking clomiphene citrate. This monitoring may include ultrasounds, blood estrogen levels, and/or urinary LH testing. Clomiphene citrate is typically prescribed with intrauterine insemination (IUI).

Side effects may include: hot flashes, ovarian enlargement, breast tenderness, nausea, vomiting, visual disturbances, headache, and multiple pregnancy.

HMG is a medication that is composed of FSH, with or without LH, and is used for stimulation of egg development in women who do not ovulate spontaneously, who ovulate extremely irregularly, or to increase the number of eggs developed in a single cycle. Due to the variability in response from patient to patient no fixed dosage regimen can be recommended. Each patient and cycle must be individualized. However, it is generally thought to be a stronger superovulation agent than clomiphene citrate.

Some form of monitoring of the ovarian response is necessary; a combination of blood estrogen measurement (E2) and ultrasound is the best approach at the present time. This fertility medication can be used with both intrauterine insemination (IUI) and in vitro fertilization (IVF).

HMG is available only in an injectable form. Therefore, you or your partner will be taught self-administered injection techniques through a special injection instruction class given by the nursing staff at the UCSF Center for Reproductive Health. This injection should be given between 6 and 10 pm each evening.

Side effects may include: ovarian enlargement, hyperstimulation syndrome, and multiple gestation, abdominal pain and headache. Discomfort and bruising may occur at the injection site. Monitoring, with ultrasounds and estradiol levels, minimizes the risk of complications.

These two FSH medications (Follistim/Gonal-F) are genetically engineered (recombinant) forms of FSH (Follicle Stimulating Hormone) which are used to stimulate the recruitment and development of multiple eggs in women during an ovulation induction cycle. FSH products may be used alone or in combination with hMG to induce superovulation.

Due to the variability in response from patient to patient, no fixed dosage regimen can be recommended. Each patient cycle must be individualized. This will require ultrasound exams and blood estrogen levels to assess ovarian response.

FSH is available only in an injectable form. You will need to learn injection techniques. FSH is administered by subcutaneous (SQ) injection techniques. If FSH and hMG are used together, a single injection is possible. As above, this injection should be given between 6 and 10 pm each evening.

Side effects may include: ovarian enlargement, hyperstimulation syndrome, multiple gestation, abdominal pain, and headache. Discomfort and bruising may occur at the injection site. Monitoring with ultrasounds and estradiol minimizes the risk of complications.

HCG is a natural hormone that helps with the final maturation of the eggs and triggers the ovaries to release the mature eggs (ovulation). It also stimulates the corpus luteum to secrete progesterone to prepare the lining of the uterus for implantation of the fertilized egg. Ovulation (follicle rupture) usually occurs about 36 hours after the hCG is given. It is self-administered as an injection.

Side effects may include: headaches, irritability, restlessness, depression, fatigue, edema, and ovarian hyperstimulation.

Lupron suppresses the brain's secretion of LH and FSH; therefore, it is used in preparation for cycles of treatment with ovulation induction drugs (exogenous hMG-LH/FSH and or FSH). It improves the recruitment of follicles by preventing the recruitment of a dominant follicle for the next menstrual cycle. Lupron enables the ovaries to respond with the recruitment of multiple follicles since in most cases we are able to override the selection of a single dominant follicle. It will also prevent premature ovulation (release of eggs) by preventing LH release.

To confirm the effectiveness of the Lupron treatment, an ultrasound will be performed before the ovarian stimulation is begun and a blood estrogen level (E2) may be required.

Lupron may also be utilized to stimulate FSH if it is used early in the menstrual cycle. This property of the drug is helpful in patients expected to respond poorly.

Lupron is available in an injectable form. Therefore, you and your partner will be taught subcutaneous (SQ) injection technique. The multidose vial should be kept cool (< 75%F) - refrigeration is OK. This drug should be given at the same time everyday (1 hour leeway). If you are starting Lupron after a spontaneous menstrual cycle (no oral contraceptive pills) you should use barrier contraception for the preparatory cycle.

Side effects may include: hot flushes, vaginal dryness, and skin rash. Side effects of long-term treatment (greater than six weeks) include hot flushes, vaginal dryness, and bone loss. These side effects are extremely rare after short-term use associated with standard IVF. No long-term side effects after treatment occur.