Fertility Drugs: Injectable Gonadotropins

Please define estradiol, progesterone, follicle size and endomentrial thickness.
Estradiol is the most important hormone in the estrogen family of sex steroid hormones. It does many things to prepare the reproductive system for pregnancy. It rises in a predictable way in a natural cycle, and provides important information about egg development in a gonadotropin cycle. Progesterone provides support for the second half of the menstrual cycle, after ovulation, supportin and stabilizing the uterine lining.

Prior to ovulation, progesterone slowly rises, providing information that the more mature eggs are approaching readiness for release.

Follicle size refers to the appearance of the egg- containing areas of the ovaries in the days leading up to ovulation. The eggs themselves are too small to see on an ultrasound, but the small, fluid-filled follicles that contain the eggs are easy to see and measure. Typically, follicles start at less than 10 millimeters and increase to at least 18 millimeters just prior to the LH surge. In addition, the appearance of the lining amy change from a homogeneous white line to a characteristic three-lined (also known as a Type 1 or trilaminar appearance) prior to ovulation. The subsequent release of progesterone further changes the appearance of the lining.

Does the Lh trigger come naturally during gonadotropin cycles?
Since the normal communication between the brain and the ovary is affected by the use of HMG or FSH, we trigger the LH surge ourselves. Since pure LH is difficult to prepare and rapidly loses its effectiveness after injection, we use human chorionic gonadotropin, a naturally occurring hormone that looks and acts very much like LH in this situation. Other names for human chorionic gonadotropin are HCG (generic name), Profasi, Pregnyl, Novarel and Ovidrel (commercial names).

What are the risks of injectable gonadotropins?
The principal risks are multiple pregnancy and ovarian hyperstimulation syndrome.

Gonadotropins constitute the family of medications most associated with multiple pregnancy. News reports of high-order multiple pregnancy - quadruplets, quintuplets or even higher - are almost always related to the use of injectable gonadotropins. Since gonadotropins bypass the body's usual mechanism for limiting the number of mature eggs available in any given cycle, the possiblility of multiple pregnancy is always a foremost consideration in managing a gonadotropin cycle.

Ovarian hyprestimulation syndrome (OHSS) refers to a combination of symptoms created after ovulation by the very stimulated ovaries. The principal problem is a release of large amounts of fluid by the ovaries coupled with a leaking of fluid from the blood vessels into the abdomen. Symptoms include bloating, decreased output of urine, nausea and vomiting. Serious cases can include fluid around the lungs and imbalances in electrolytes (principally sodium and potassium). The most serious cases can require intensive care and be life-threatening.

Are these risks preventable?
They can be minimized, but not completely prevented. Thankfully, a small number of eggs will fertilize and develop in any gonadtropin cycle, usually one or two. The risk of a higher level multile can be decreased by adjusting the medication dose to provide fewer eggs, withholding the HCG and abstaining from intercourse to prevent pregnancy completely in a cycle with too many mature eggs, or performing an in vitro fertilization procedure, removing the eggs and limiting the number of resulting embryos returned. As a last resort, high level multiple pregnancies can be reduced after the pregnancy has been established.

Do these medications increase the risk of ovarian cancer?
The honest answer is we do not know yet. Because these medications bypass the body's normal mechanism for controlling egg development, one can theorize that they may stimulate abnormal as well as normal development. No study has definitely implicated injectable gonadotropins in higher rates of ovarian cancer, but research has not disproved a potential link either. For this reason we try to limit HMG use to a reasonable number of cycles.

Is there an increase in birth defects or pregnancy complications?
None other than those associated with the higher multiple pregnancy rate.

Edited by:David Sable, M.D. and Owen Davis, M.D.

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