In a normal menstrual cycle, an egg grows, develops, and matures to the point of its release (called “ovulation”) in the attempt to achieve pregnancy. This process depends on a delicate balance of hormones and other factors that, if not produced in the right way, can lead to infertility.
In ovulation induction, patients are treated with hormone medications or fertility drugs to increase the chances of ovulation. These medications stimulate inactive or under-producing ovaries to produce a mature egg and release it, so it may be fertilized. Ovulation induction medications are used to help women who do not normally ovulate to produce a single, healthy egg, and women who ovulate but where the quality or number of eggs produced may not be sufficient to achieve a successful pregnancy. In these cases, gentle ovulation induction may be used to make 2-3 eggs and is often used with Intrauterine Insertion (IUI). Where many more eggs are needed (as in IVF requiring the retrieval of multiple eggs so that following fertilization in vitro, the best embryo can be selected for transfer), more than one ovulation induction medication is generally used and at higher doses than for IUI. The process of creating more than one mature egg is called “superovulation.”
Because fertility drugs can cause mood swings and can increase the chance of multiple pregnancy (twins, triplets, or more), they are best prescribed by Infertility Specialists that are board certified by the American Board of Obstetrics and Gynecology in the specialty of Reproductive Endocrinology and Infertility. We closely monitor laboratory blood tests and ultrasounds to minimize potential risks. Rarely, superovulation may be associated with ovarian hyperstimulation, which is a painful condition of ovarian enlargement. In the past, it was reported that ovulation induction medications may increase the subsequent risk for ovarian cancer but these findings were later invalidated by larger and better controlled studies.
Common fertility drugs used for ovulation induction include:
Clomiphene Citrate is an ovulation induction medication that can be taken orally in a pill form. It works by blocking estrogen receptors. This artificial anti-estrogen effect causes your body to produce more FSH. Because of its anti-estrogen effects, Clomiphene Citrate is associated with hot flashes, mood swings, and rarely may make the uterine lining too thin for successful implantation. Clomiphene Citrate should not be used for more than 4 cycles, and monitoring should be done to minimize risks. Clomiphene Citrate may be very effective in women under age 35 who do not ovulate. More effective medications (HMG, FSH) are available for ovulatory women over age 35 with infertility, where better and more eggs are required.
FSH medications are available only as an injection, generally subcutaneous. They are used to stimulate egg production and maturation during an ovulation induction cycle. The dose chosen is dependent on multiple factors, including the woman’s age, weight, and previous response, if any. Each cycle, whether for timed intercourse, IUI or IVF, must be individualized and closely followed using blood estrogen levels and ultrasounds to minimize potential risks and to determine the precise time for ovulation.
GnRH releasing hormone antagonists involve subcutaneous injections that immediately suppress ovulation and are given as part of an Antagonist protocol for IVF. This medication is given once ovulation induction has begun and an ovarian follicle has reached 13-14mm in size. As with all ovulation induction medications, it should be given only under the supervision of infertility specialists who are able to closely monitor your cycle.
HCG is a natural hormone given by self-administered injection, either subcutaneous or intramuscularly, that achieves the final maturation of the eggs and triggers the ovaries to release the mature egg (ovulate). HCG also stimulates the corpus luteum in the ovary to secret progesterone to prepare the lining of the uterus for embryo implantation. Ovulation (follicle rupture) usually occurs 36 hours after HCG is given.
HMG is a medication that is given by injection under the skin (subcutaneous) and is composed of FSH and LH. This medication is used for women who do not ovulate on their own, who ovulate irregularly, and for women whose the number of ovulated eggs needs to be increased as in superovulation. No fixed dosage regimen is suggested due to the variability in response, but the lowest dose possible is recommended. Women taking this medication must be closely monitored with laboratory blood tests and ultrasounds to minimize the risks of hyperstimulation and multiple pregnancy because it is a much stronger inducer of ovulation than oral medications. This medication is used both with IUI and with IVF.
Most recently, letrozole, an aromatase-inhibitor has gained favor for ovulation induction. It enhances FSH release by acting at the level of the ovary and inhibits estradiol synthesis. Originally approved in 1997 for treatment in breast cancer, it has been used successfully as an off-label means of ovulation induction. Its distinct advantage over other oral ovulation modulators is that it does not have a negative effect on the endometrium, tends to generate one dominant follicle (lower chances of multiple gestations) and its half-life is only 45 hours. It is prescribed as a short course to be taken early in the menstrual cycle, usually for 5 days. With such a shortened half-life, it is unlikely that there is any association between significant negative effects on pregnancy.
Lupron is a subcutaneous injection that initially stimulates then suppresses the brain’s secretion of FSH and LH and is used in IVF cycles to improve the recruitment of follicles by preventing a dominant follicle from being developed. Lupron is also used to prevent premature ovulation by preventing LH release during ovulation induction with either HMG or FSH. Lupron treatment usually begins during the later half of the cycle before ovulation induction for IVF as part of a Long Cycle or Luteal Lupron protocol. An ultrasound and blood estrogen level is usually performed at the start of ovulation induction. In cases where a not as vigorous response is anticipated, Lupron is given in much smaller doses than in a Long cycle protocol to take advantage of its follicle stimulating effect on the ovaries. This low dose Lupron ovulation induction protocol is referred to as a MicroFlare protocol.