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Controlled Ovarian Hyperstimulation

A woman's eggs develop inside fluid-filled cysts (sacs) inside the ovaries called follicles. During a natural menstrual cycle in which no fertility drugs are taken, several follicles begin to enlarge around the time when the woman is having her period.


However, over the course of the next few weeks, only one of these follicles develops to maturity, ruptures, and releases its egg during the process of ovulation. The other follicles that had begun to develop stop growing and degenerate (dissolve), therefore, only a small percentage of eggs present in the ovaries are ever ovulated during the woman's reproductive life span. We can "rescue" follicles and eggs that would otherwise degenerate by giving shots of fertility drugs which contain FSH (follicle stimulating hormone). This is the same hormone that the pituitary gland produces to cause one egg to develop. By increasing the woman's blood level of FSH, several follicles may grow at approximately the same rate allowing us to collect more than one mature egg.

The first fertility drug that most women use is Lupron (Leuprolide acetate). Lupron causes the pituitary gland to release high amounts of FSH and LH (luteinizing hormone) for several days until its stores are depleted. Since continued use of Lupron prevents the pituitary gland from producing new supplies of FSH and LH, the amount of these hormones being released per day becomes very low after 7 to 10 days. The goal of Lupron is to ensure that blood levels of LH are low during the last few days of follicle growth.  High levels of LH can lead to poor egg quality, premature ovulation, and stimulate progesterone production by the ovaries. A premature rise in progesterone may cause inappropriate maturation of the uterine lining and lead to lower chances of embryo implantation.

Some women will be placed on a Lupron "flare" medication schedule. This involves starting Lupron early in the menstrual cycle after suppressing pituitary and ovarian function for up to one month of birth control pills. The Lupron causes a rapid increase in FSH and LH release by the pituitary gland and initiates follicular growth. On the third day after the Lupron starts, the woman begins shots of FSH or FSH+LH (brand names include Repronex, Follistim, Menopur and Gonal-F). This stimulates the continued growth of the follicles as the pituitary's release of FSH begins to decline. Women over age 39 and those with elevated day 3 FSH blood levels, as determined prior to enrollment, are typically treated with a Lupron "flare" schedule in order to maximally stimulate the ovaries. Our program has published its success with this medication regimen in the medical journal Fertility and Sterility. Repronex, Follistim, Menopur, and Gonal-F are administered as subcutaneous injections (small needle placed just underneath the skin).

Younger women or those with polycystic ovaries are usually treated with Lupron for approximately 10 days prior to beginning the shots of FSH. With this "long Lupron" schedule, the pituitary is no longer releasing large amounts of LH and FSH when Repronex, Follistim, Menopur, or Gonal-F is started. Hence, the best treatment schedule is determined by the unique circumstances of the individual patient. The average number of follicles that develop is from 8 to 25, although some women will have more or less than that amount.

Another class of drugs called Gonadotropin releasing horomone (GnRH) antagonists (brand name Antagon & Cetrotide) may be used in some patients over a shorter time course to prevent a spontaneous LH surge and ovulation without overly suppressing ovarian function.

With either the "Lupron flare", "long Lupron", or GNRH Antoginist schedule, Repronex, Menopurs, Follistim, or Gonal-F shots are taken twice daily for 8 to 11 days, depending on how quickly the follicles mature. We can assess the ovarian response to these fertility drugs by measuring the follicle sizes with vaginal ultrasound and by following the increase in production of estradiol (estrogen) and progesterone by the cells inside the follicles. When the largest follicles reach approximately 18 mm in diameter, the woman takes a shot of hCG (human chorionic gonadotropin - brand name Novarel, Profasi and Pregnyl). This hormone stimulates the final steps of maturation of the eggs and stimulates the LH surge. The egg collection occurs 35 hours after the hCG injection.