Recombinant or urinary human chorionic gonadotropin in ovulation induction?

The onset of the spontaneous LH surge in women is relatively abrupt with concentrations doubling within 2 h to between 100 and 200 IU/l being sustained for 12–14 h over a mean duration of 50 h [1]. This mid-cycle surge, in addition to follicular rupture [2], promotes several periovulatory events including disruption of the oocyte– cumulus oophorus cell contact and induction of the resumption of the oocyte’s meiotic maturation [3], cumulus oophorus mucification, luteinization of the follicular granulosa cells [4] and secretion of progesterone. These events are also induced by an injection of human chorionic gonadotropin (hCG) through exactly the same sequence, the only difference being in the pharmacokinetic profile where the mean duration of the ‘surge’ after an IM injection of 5,000 IU u-hCG is longer than for LH (*96 h) and maximum concentrations may be less [5]. Current practice is that C5,000 IU u-hCG is an acceptable ovulatory dose and that lesser concentrations can lead to reduced oocyte recovery and a lower fertilization rate in assisted reproductive treatments [6]. The first preparations of hCG were investigated in the late 1930 s [7]. Subsequent studies and improved preparation of hCG from the urine of pregnant women (u-hCG), where its abundance allowed ease of extraction, meant that for almost 40 years it has been the sole hormonal preparation commercially marketed for induction of ovulation in anovulatory women. For the last three decades patients undergoing assisted reproductive treatments have also used u-hCG to induce the final maturation of follicles and oocytes before their collection and additionally to support the luteal phase of the cycle. The history of gonadotropin use when derived from either animal or human tissues has, however, not always been without clinical danger (e.g. antibody formation from pregnant mare serum gonadotropin; Creutzfeld–Jacob disease from human pituitary gonadotropin) so, as recombinant technology evolved, the logic of increasing both a compound’s purity and safety could not be ignored. Such a uniform, specific product would mean that drug production would no longer be dependent on the vagaries of urine collection and hormone extraction, allowing commercial production to be adjusted according to market requirements. In addition all urinary contaminants would also be removed. Furthermore this would allow the safe subcutaneous administration of a compound with less batch-tobatch variation than has been demonstrated for urinary menopausal gonadotropins preparations [8]. Allahbadia G. (&), Medical Director Rotunda Blue Fertility Clinic & Keyhole Surgery Center, Shivaji Park, Mumbai, India e-mail: [email protected]