Clomiphene citrate (Clomid), one of the oldest and most basic of the fertility drugs, is supposed to be indicated only for those women with ovulatory dysfunction. Its manufacturer, Aventis Pharma, does not recommend its use in more than three cycles (Medicines Compendium, Pharmaceutical Press, 2003). Despite this guidance, it is common practice to prescribe it as a first-line therapy, regardless of whether a woman is ovulating regularly, and to extend its use to six cycles.
Taken orally, clomiphene works by blocking oestrogen, which tricks the pituitary gland into producing follicle-stimulating hormone (FSH) and luteinising hormone (LH), boosting follicle growth and the release of the egg. Side-effects include a reduced amount and quality of cervical mucus, and thinning of the womb lining, in which case, yet more hormonal agents may be given to restore thickness. Women may also develop ovarian cysts, hot flushes, nausea, weight gain and fatigue.
Down-regulating your cycle
If this approach fails, the woman is then moved onto even more potent fertility drugs. These are the ‘superovulation’ drugs that force a woman’s body to pump out multiple eggs. Many of these are either hormones taken from natural sources, such as the urine of pregnant or postmenopausal women, or are recombinant - genetically developed - versions (see box, p 3).
In February this year, the Committee on Safety of Medicines advised that Metrodin, one of the older superovulation drugs, should no longer be used in the UK. This is a precautionary measure following a case of confirmed variant Creutzfeldt-Jakob disease (vCJD) in Italy from where the human urine used to make the drug is sourced.
Most women undergoing fertility treatment are likely to be bombarded with three types of drugs: a GnRHa (gonadotropin-releasing hormone agonist) to suppress the release of LH from the pituitary gland (the LH surge) and to prevent ovulation until the follicles are mature; an FSH product to stimulate production of multiple follicles; and hCG (human chorionic gonadotropin) to bring about final maturation of the eggs in the follicles.
In addition, gonadotropins such as LH and FSH are given directly every day for four to eight days of the treatment.
During ‘pituitary down-regulation’ - as this phase of the treatment is known - when ovulation is postponed, one GnRHa drug given is goserelin acetate, which can be 100 times more potent than the natural hormone for ovarian stimulation. This and other GnRHa drugs are usually given together with human menopausal gonadotropin (hMG) during the superovulation stage of IVF, and there have been reports of potentially life-threatening ovarian hyperstimulation in women given the two drugs in combination (Medicines Compendium, Pharmaceutical Press, 2003).
The hCG stage is a delicate balancing act, in which at least three follicles have to be of a particular size and blood levels of oestradiol, an oestrogen, have to be at a certain level, before hCG can be given, warns Organon, one of the manufacturers. About 36 hours later, the eggs are then ready to be harvested.
If ovarian hyperstimulation does arise, the hMG must be stopped immediately and the hCG held back (Medicines Compendium, Pharmaceutical Press, 2003).
Throughout this entire procedure, where science and chemistry have basically taken over - and drastically altered - the entire female cycle, oestrogen levels and ovary size must be carefully monitored, preferably by ultrasound, to avoid the risk of high dosages causing oestrogen levels to rise too rapidly.