Ovulation Induction

Using fertility medications to enhance your fertility.

What is Ovulation Induction

Ovulation Induction is the use of specialized fertility medication to stimulate the development and release of eggs in a woman's body.

Fertility medications, such as FSH to stimulate the recruitment and development of one or more mature follicles in the ovaries. Women with ovulatory dysfunction (irregular or even absent menstrual cycles) will benefit from the use of fertility drugs to induce ovulation. Furthermore, couples with unexplained infertility may undergo treatment with a form of ovulation induction called ‘controlled ovarian hyperstimulation in conjunction with either intrauterine insemination (IUI) or in vitro fertilization (IVF). Ovulation induction cycles should be administered and monitored by a trained fertility specialist.

Controlled ovarian hyperstimulation involves the use of fertility drugs to intentionally stimulate the development of multiple mature follicles and eggs in order to increase the chances of pregnancy because there will be ‘more eggs’ available for possible conception. In IVF and donor egg cycles, the recruitment and maturation of multiple eggs is desired so there will be multiple embryos made for possible embryo transfer. Even in fertile women, not every egg is capable of fertilizing normally, and not every embryo will continue to grow and divide normally.

Fertility drugs used include oral drugs such as Clomid or letrozole (Femara) as well as injectable gonadotropins (FSH). In some patients, both Clomid and injectable medications are used. Gonadotropins are hormones that are naturally synthesized and released by the pituitary gland, a small gland located at the base of the brain. The pituitary gland produces two different types of gonadotropins known as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), both acting in a synchronized pattern to recruit follicles and lead to the development of mature eggs.

There are several commercially prepared fertility drugs (Gonal-F, Follistim, Menopur, Bravelle, Repronex) that are collectively known as “gonadotropins” because they contain human FSH with or without LH. Monitoring response from fertility medications will depend on the type of medications used, and if ovulation induction is being given in the context of an IUI or IVF cycle. This includes ultrasound as well as blood testing for estradiol and/or progesterone levels.

One of the risks from ovulation induction and controlled ovarian hyperstimulation is that of multiple gestations. Even in carefully monitored cycles, there is incomplete control over how many eggs are ovulated. Our goal is to balance the benefit of an increased chance of pregnancy with the risk of multiples (twins, triplets, etc.). The degree of risk depends on the type of medications used, a woman’s response to the fertility medications, as well as the type of fertility treatment used (IUI, IVF). When gonadotropins (given by injection) are used, the risk of twins is increased to approximately 15-20%. These drugs should always be administered by a trained fertility specialist.

Medications Used for Ovulation Induction

Fertility drugs exist for a variety of reasons, but most work to correct, stimulate, or regulate ovulation. Clomid is one of the oldest fertility drugs and enjoys widespread use. It works at the hypothalamus to compete for estrogen-binding sites. The hypothalamus thus “reads” lower estrogen levels and signals the pituitary to produce FSH, which stimulates the ovaries.

Fertility drugs can produce side effects if not properly administered.

Clomid

Clomid’s major drawback is that non-fertility specialists often prescribe it for too many cycles. Studies show that Clomid is most likely to work in the first three ovulatory cycles, and treatment beyond six cycles is rarely recommended. Extended treatment with Clomid can produce unwanted side effects.

Dependent upon patient-specific variables, Clomid is usually started on Cycle Day 3 at 50 milligrams for five days. There is no need to increase the dose if ovulation occurs at 50 milligrams. If ovulation does not occur, many specialists will increase the dosage in 50-milligram increments.

Gonadotropin, hMG

Gonadotropins (hMG) are hormones that function by stimulating the ovaries to produce follicles, each of which contains an egg. The name gonadotropin stems from “gonad,” the name for an ovary or testicle, and “tropin.” meaning to stimulate. Gonadotropins are synthesized and released by the pituitary gland, a small gland located at the base of the brain. The pituitary gland produces two types of gonadotropins: luteinizing hormone (LH) and follicle stimulating hormone (FSH), both of which act on the ovaries in a coordinated fashion to recruit and develop ovarian follicles.

Today, gonadotropins are obtained either as a highly purified product from human urinary sources (hMG), or are the products of genetic engineering and biotechnology (recombinant FSH). Fertility drugs such as Bravelle, Repronex, and Menopur are examples of hMG, and contain FSH with variations in the amount of LH. Gonal-F and Follistim (rFSH) are types of genetically engineered gonadotropins. Production of these proteins involves incorporating the human FSH gene into a controlled cell-line, which then produces pure FSH, identical to that produced by the human pituitary gland.

Fertility drugs are given by injection to stimulate the development of follicles when ovulation is not occurring naturally, when many eggs are needed for in vitro fertilization (IVF), or when ovulation is being timed. FSH should be administered by a trained fertility specialist to minimize potential side effects.

Fertility Drugs – The Treatment Cycle

Fertility drugs are employed in a treatment cycle. A treatment cycle includes ovulation induction, cycle monitoring, triggering ovulation, and the determination of pregnancy with a blood test. Two types of cycles are intrauterine insemination (IUI) and in vitro fertilization (IVF).

Intrauterine Insemination Cycle (IUI) – (This is a general discussion and does not replace the physician and nurses patient specific instructions. The text is for information only.)

With the onset of menses, the first day of full flow, a baseline sonogram and blood test should be scheduled on Cycle Day 2 or 3. If the baseline tests are normal, ovarian stimulation with gonadotropin begins. The stimulation phase of the treatment cycle typically lasts seven to 14 days. During stimulation, patients must come to our office about every two or three days for additional sonograms and/or estradiol blood tests. These tests allow the physician to evaluate the effects of stimulation on the ovaries.

Different women respond to FSH at different rates, and even the same woman may respond differently in subsequent cycles. The dosage can be increased or decreased during the cycle. It is essential that treatment be monitored closely to ensure proper dosing and to time the triggering of ovulation with human chorionic gonadotropin (hCG). hCG is given to mimic the LH surge and stimulate ovulation 36 hours after the FSH injection, at which time insemination(s) or intercourse can be scheduled. Lupron or birth control pills may be employed prior to the stimulation phase.

The fertility drugs Gonal-F and Follistim are injected subcutaneously into the abdomen or thigh and are usually self-administered. Both fertility drugs can be conveniently administered using a pen injection system supplied by the manufacturers.

The fertility drugs Repronex, Menopur, and Bravelle can be safely given subcutaneously, although the original hMG preparations were typically given intramuscularly. We encourage employing the subcutaneous route to ease administration. The injections should be given at the same time each day (within 2 hours), usually between 7:00 and 9:00 p.m. Some patients have their husband or a friend administer these products. All patients meet with our nurses for “medication injection training.”

Pregnancy rates using IUI vary from couple-to-couple, depending upon many factors. Typical pregnancy rates with IUI range from 15 to 20 percent per cycle.

Fertility Drugs – Risks and Side Effects

Fertility drugs are associated with several side effects, including ovarian hyperstimulation syndrome (1-5%), multiple gestation (15%), ectopic (tubal) pregnancies (1-3%), ovarian torsion (<1%), and possibly an increased risk of ovarian cancer (controversial). Since these products are injectable, there is a risk of infection at the injection site, a condition referred to as cellulitis.

Ovarian hyperstimulation syndrome (OHSS) is a condition in which there is excessive ovarian response to fertility drugs, usually associated with elevated levels of estradiol. OHSS is triggered by ovarian enlargement and changes in vascular permeability, which leads to ascites, the abnormal presence of fluid in the abdominal cavity. Other consequences include electrolyte disturbances and, rarely, blood clots. Severe OHSS usually occurs only after hCG is given.

You should call us if you have any problems with medications during the cycle, particularly if you experience dizziness, decreased urination or weight gain of more than five pounds. These cysts usually recede after four to seven days, but on rare occasions can cause serious problems and lead to hospitalization.

If pregnancy occurs, OHSS may persist for two or three weeks because the pregnancy hormone (hCG) exacerbates hyperstimulation. Under rare circumstances, these cysts may rupture, or the ovary may twist, possibly requiring surgery and loss of the involved ovary. Other side effects of hMG are breast tenderness, mood swings, and fatigue.