Gonadotropins (Ovarian Hyperstimulation)

Gonadotropins (Ovarian Hyperstimulation)

Ovulation induction is a term that refers to the administration of medication to stimulate ovulation. These medications range from clomiphene to gonadotropins to combinations of the two. Gonadotropins are injectable ovulation stimulating hormones that are identical to the hormones secreted by the body. With the administration of these injectable medications, the circulating levels of these hormones are increased, resulting in the stimulation and growth of multiple eggs. In addition to increasing the number of eggs with the use of gonadotropins, timing factors are controlled, such as when ovulation occurs, to maximize the chance of becoming pregnant.

Why do I need it?

This treatment does not really correct any specific cause of infertility. Instead it is a "shotgun" approach to get multiple eggs and sperm together at the time of ovulation. This type of treatment has been shown to increase the monthly chances for a pregnancy as compared to timed intercourse alone. Ovarian stimulation with insemination should not be used with very low sperm concentration or very poor sperm motility, blocked fallopian tubes, or age of the female partner over 43. This treatment is very unlikely to be effective in these situations. Controlled ovarian hyperstimulation is also used to develop multiple mature follicles for in vitro fertilization cycles.

What is it?

Gonadotropin releasing hormone agonists (GnRHa) such as lupreulide acetate (Lupron), administered 8 to 10 days prior to spontaneous or induced menstruation, elicit an initial and rapid, out-pouring of pituitary gonadotropins. This causes blood FSH and LH to fall to negligible concentrations within a few days which is followed by a synchronous drop in blood estrogen (estradiol) levels. This elicits uterine withdrawal bleeding or menstruation.

What Kinds are There?

There are multiple types of gonadotropins available for ovulation induction. These products include Gonal-F, Follistim, Repronex, Humegon and Pergonal. The most commonly used gonadotropin is a man-made form of follicle stimulating hormone (FSH) which is identical to the hormone secreted from the pituitary gland. Because this formulation is man-made it contains very few impurities and accordingly can be injected directly under the skin with very few local reactions. Other injectable medications include human menopausal gonadotropin (hMG) which contains both FSH and LH. Because of the formulation, the majority of these medications require injections into the muscle.

Does it Work?

Success rates for controlled ovarian hyperstimulation with intrauterine insemination vary considerably and depend on the age of the woman, the total motile sperm count, the quality of the sperm, how long the couple has been trying to get pregnant, what the infertility factors are in the couple, etc. Ovarian stimulation with gonadotropins ( injectable FSH products like Pergonal or Follistim) plus intrauterine insemination gives pregnancy rates of about 5-12% per cycle (women 36 and younger) for unexplained infertility, as demonstrated in several published studies. Success rates are lower if the woman is over age 36 or if
there is a sperm problem - male factor infertility. For women 40 and older, success rates with this form of infertility treatment
are very low, and IVF should be considered as an option relatively soon. In general, this type of treatment is considered reasonable for about 3-6 cycles (in women under 37), after which IVF is usually considered as the next step.

How Much Does it Cost?

The costs associated with controlled ovarian hyperstimulation depend on the type and dose of medication required and the number of ultrasound and blood tests required to adequately monitor the cycle.Intrauterine insemination increases the chances for a pregnancy, as well as the cost of the cycle.

What Are the Risks?

There are side effects and risks associated with gonadotropin use. The most common side effects of these medications include discomfort or "fullness" in the lower abdomen, bloating, headache or fatigue. Patients can also experience discomfort in the area of injection. Massaging the area or applying heat is often helpful. Perhaps the most significant risks of using injectable gonadotropins are multiple gestation and ovarian hyperstimulation. Ovulation induction can have up to a 20% incidence of multiple gestation (more than one fetus). The majority of these pregnancies are twins, however, more than two fetuses can sometimes develop.

The ovaries of some women tend to over-respond to the initial GnRHa-induced pituitary gonadotropin surge (i.e., the flare effect), often leading to rapid over development of one or more ovarian follicles (i.e., functional ovarian cysts). Functional ovarian cysts are literally nothing more than ovarian follicles that have become enlarged, dilated and distended with fluid.

However, they acquire special relevance when detected in women about to undergo controlled ovarian hyperstimulation (COH) with gonadotropins where they can literally, "throw a spanner in the works," causing a slight delay, postponement and sometimes even a cancellation of the cycle of treatment.

Functional ovarian cysts do not present as serious health hazard, even when they are present during pregnancy. Almost without exception functional ovarian cysts spontaneously resolve within 4 to 6 weeks. Tumors will not. Accordingly, the persistence of any ovarian cyst for longer than 6 weeks should raise suspicion with regard to it being a tumor. Since ovarian tumors may undergo malignant change, all ovarian cysts that persist for longer than 6 weeks (whether in non-pregnant or pregnant women), should be treated by surgical removal and the specimen, submitted for pathological diagnosis.

How Will I Know if I Have it?

Aside from causing menstrual dysfunction such as a delay in the onset of menstruation or irregular cycles, they are usually non-symptomatic. In some cases, these cysts will undergo rapid distention (often as a result of a minor degree of bleeding inside the cyst itself) and the woman will experience a sharp or aching pain on one or other side of her lower abdomen and/or deep seated pain during intercourse. Rarely, these functional cysts rupture, causing sudden onset of severe lower abdominal pain, which may simulate an attack of acute appendicitis or even a ruptured ectopic (tubular) pregnancy. While very unpleasant, a ruptured functional cyst hardly ever produces a degree of internal bleeding that warrants surgical intervention. The pain, which is worse on movement, almost always subsides progressively over a period of four to five days.


Your doctor's office should closely monitor all cycles involving gonadotropins. A patient's response can be monitored in two ways:

For more information:

"Success Rates of Patients who have Undergone Coasting: Withholding gonadotropins ('coasting') to minimize the risk of ovarian hyperstimulation syndrome during superovulation and in vitro fertilization-embryo transfer cycles"Margo R. Fluker,
Wendy M. Hooper, A. Albert Yuzpe; Genesis Fertility Centre, Vancouver, British Columbia, Canada. Fertility and Sterility, Volume 71, Number 2, pp.294-301.

"Comparison of intrauterine insemination with timed intercourse in superovulated cycles with gonadotropins: a meta-analysis." Zeyneloglu HB, Arici A, Olive DL, Duleba AJ Fertil Steril 1998; 69:486-91.

"Randomized comparison of ovulation induction with and without intrauterine insemination in the treatment of unexplained infertility." Chung CC, Fleming R, Jamieson ME, Yates RWS, Coutts JRT. Hum Reprod 1995; 10:3139-41

"The total dose of gonadotropins used during controlled ovarian hyperstimulation as a predictor of pregnancy outcome "Galal A. Abdo, Tarek I. Abozaid, Ziad Massaad, Elizabeth Formentini, Sheryl Benford-loyer. Middle East Fertility Society Journal
The Official Journal of the Middle East Fertility Society; 2001; 6:3

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