Gonadotropins in ovarian stimulation

Follicle-stimulating hormone (FSH)-containing gonadotropin preparations have been commercially available since the 1960s. Their first use was in ovulation induction in women with anovulatory disorders. Since 1978, however, after the first IVF baby was born, they have been used increasingly in assisted reproductive technologies (ART) such as IVF or ICSI but also in intra uterine insemination (IUI). Now, in many countries, ovulation induction comprises only 10% of gonadotropin usage, while 90% is used for ovarian hyperstimulation in ART, of which about half of the gonadotropin usage is for IVF and the other half is used for stimulated IUI cycles. In the follicular phase of a normal menstrual cycle, a cohort of 10–20 antral follicles develops. Of this cohort only one follicle obtains dominance over the others and shows continued growth until ovulation takes place. In patients with hypogonadotropic anovulation (WHO type I), the aim of ovarian stimulation with a FSH-containing gonadotropin is to induce the growth of preferably no more than one dominant follicle – i.e. mimicking the natural cycle – in order to prevent multiple pregnancies. In IVF however, ovarian stimulation with FSH-containing gonadotropins is aimed to achieve the maturation of a much larger part of the antral follicle cohort, achieved by increasing the dosage. These large numbers of domininant follicles are accompanied with high serum estrogen levels, which can lead to a premature endogenous LH surge. In order to prevent this premature LH surge, pituitary desensitization is accomplished by the co-administration of either a GnRH agonist or antagonist.