Super Ovulation with Injectable Fertility Medications
Gonadotropins (hMG) are hormones that function by stimulating the ovaries to produce follicles, each of which contains an egg. The name gonadotropin stems from the term “gonad,” which is 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 produces two different types of gonadotropins: luteinizing hormone (LH) and follicle stimulating hormone (FSH). Both of these hormones 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). 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 and contain FSH only. 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.
These medications are given by injection to stimulate the development of follicles if ovulation is not occurring naturally, if many eggs are needed for IVF, or if no success has been met with lesser therapies. FSH should be administered by a trained fertility specialist to minimize potential side effects.
Gonadotropin Treatment Cycle
A gonadotropin treatment cycle refers to the entire process of ovulation induction or superovulation with fertility drugs, cycle monitoring, ovulation triggering, and the determination of pregnancy with a blood test. Two common types of cycles used in conjunction with gonadotropin administration are intrauterine insemination (IUI) and in vitro fertilization (IVF).
Intrauterine Insemination Cycle (IUI) – (This is a general discussion and does not replace the physician’s and nurse’s patient-specific instructions. The following text is for information only.) With the onset of menses a baseline sonogram and blood tests maybe scheduled. These are usually performed on cycle days 2, 3, or 4, where the first day of full menstrual flow is considered cycle day 1. If the baseline tests are normal, ovarian stimulation with gonadotropins 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 gonadotropin stimulation on the ovaries.
Different women respond to gonadotropins at different rates, and even the same woman may respond differently in multiple cycles. Therefore, the gonadotropin dosage may 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). This medication is given to mimic the LH surge and stimulate ovulation, which occurs approximately 36-40 hours later, at which time insemination(s) or intercourse can be scheduled. Additional medications, such as Lupron or birth control pills, may be employed prior to the stimulation phase.
Gonal-F and Follistim are injected subcutaneously into the abdomen or thigh, and are usually self-administered. Both products can be conveniently administered using a pen injection system supplied by the manufacturers. Repronex, Menopur, and Bravelle can also be safely administered subcutaneously, although the original hMG preparations were typically given intramuscularly. We encourage employing the subcutaneous route to ease administration.
Gonadotropin injections should be given at about the same time every day, usually between 7:00 and 9:00 p.m. Most patients are able to administer their own injections but some patients have their spouse or a friend perform the injections for them. All patients meet with our nurses for medication injection training prior to initiating a cycle.
Pregnancy rates using IUI vary from couple-to-couple depending upon many factors, such as age and sperm quality. Typical pregnancy rates with IUI range from 15 to 20 percent per cycle and the incidence of multiple births is approximately 15 percent. High order (equal to or more than three) multiple births are more common with IUI than IVF. This is because the number of embryos placed into the uterus is controlled in IVF, whereas the number of eggs ovulated, fertilized and implanted cannot be exactly determined during IUI cycles.
Risks and Side Effects
Gonadotropins are associated with several side effects including:
- ovarian hyperstimulation syndrome (1 to 5 percent)
- multiple gestation (15 percent)
- pregnancies (1 to 3 percent)
- ovarian torsion (less than 1 percent)
- possibly an increased risk of ovarian cancer (this potential side effect is controversial)
Also since these medications are injectable, there is a risk of infection at the injection site, called cellulitis. Ovarian hyperstimulation syndrome (OHSS) is a condition in which there is an excessive ovarian response to the fertility medication, usually associated with elevated levels of estradiol. OHSS is comprised of ovarian enlargement (multicystic) and changes in vascular permeability leading 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 our office if you have any medication problems 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 if fluid accumulates in the abdomen. This usually requires hospitalization or drainage of the fluid in the office. If pregnancy occurs, this condition may persist for two or three weeks, as the pregnancy hormone (hCG) exacerbates hyperstimulation. In rare circumstances, these cysts may rupture or the ovary may twist, possibly requiring surgery and loss of the involved ovary. Other side effects of gonadotropins are breast tenderness, mood swings, and fatigue.