Endocrinology of Ovarian Stimulation for In Vitro Fertilization

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Abstract
Summary: Understanding of the endocrinology of in vitro fertilization has advanced rapidly in the past 5 years. Despite a multitude of ovarian stimulation regimens a particular regimen has not demonstrated a marked superiority. In principle the achievement of high FSH levels during the early follicular phase to recruit a maximum number of follicles with a tolerable degree of asynchrony for final maturation is confined to a limited time span or ‘FSH window’ of about 3 to 4 days before negative E2 feedback induces below‐threshold FSH levels, thereby condemning all subsequent follicles in that cycle to atresia. It appears that one can widen and/or amplify the ‘FSH window’ too far from gross hyperstimulation resulting in the recruitment of many follicles with an intolerable degree of asynchrony. This may lead to a defective endocrine environment for the oocytes contained within these follicles or an abnormal luteal environment and an increased frequency of fertilization, cleavage and implantation failure. Whichever regimen is used, the stimulation should ideally be sufficient to promote the development of at least 3 follicles beyond 18mm diameter at the time of OPU. This can be expected to result in at least 2 embryos to be available for transfer. Monitoring of follicular response by a combination of E2 and ultrasonic parameters is recommended so that the administration of HCG is given close to the anticipated endogenous rise of LH. This can be achieved by detecting a reduction in the rate of E2 rise (to plateau). A plateau in E2 in the absence of follicles of preovular diameter (e.g. < 18mm) may be followed by a secondary acceleration phase and associated follicle growth. Timing of OPU from the start of the LH surge tends to result in embryos which give rise to a higher pregnancy rate. This natural timing of OPU may give the recruited follicles time to achieve their maximum potential by correction of asynchrony and development of better oocytes. Permitting the natural mid‐cycle events to occur may also minimize disruption of the critical follicular to luteal phase transition period. Luteal phase deficiencies as detected hormonally do not appear to be a feature of either moderate Clomid or Clomid+HMG stimulation regimens, provided women with disordered follicular phase endocrine responses are identified and not subjected to laparoscopy. Luteal phase plasma progesterone concentrations in the conceptual cycles begin to diverge from the nonconceptual groups by day +5 after OPU and become significantly higher by day +10. This difference is likely to be a result of successful implantation rather than an intrinsic luteal defect in the nonconceptual cycles.