Manipulation of Human Ovarian Function: Physiological Concepts and Clinical Consequences*

Abstract

IN RECENT years much new information related to regulation of human follicle development has become available. Recent techniques for the investigation of human ovarian tissue include direct visualization of proteins in tissue), or in situ hybridization for the in situ detection of DNA or RNA. New tools such as pelvic ultrasound have been developed allowing the longitudinal monitoring of follicle growth dynamics in a given patient. In addition, assays of steroids and peptides in serum and follicle fluid, together with in vitro cultures of human ovarian cells, have generated additional information regarding endocrine and para-/autocrine factors regulating follicle growth. New insight in the interplay between systemic and intraovarian factors regulating development and atresia of follicles may have significant implications. Relevant clinical conditions include ovarian ageing as well as chronic anovulation in patients presenting with serum FSH and estradiol (E2 hormone levels within the normal range, frequently diagnosed as polycystic ovary syndrome (PCOS). More effective and safe protocols for stimulation of ovarian function for infertility therapy may be developed. This involves both gonadotropin induction of ovulation (aiming at single dominant follicle growth in anovulatory patients) and so-called controlled ovarian hyperstimulation for in vitro fertilization (IVF) (aiming at interfering with single dominant follicle selection to induce ongoing multiple follicle development in ovulatory women). Due to ongoing concern regarding the potential for side effects and long-term health hazards, doses of combined estrogen/progestin steroid contraceptive pills have been decreased continuously since their introduction in the 1960s. It has been noticed subsequently that tolerance for omission of pill intake, especially around the pill-free interval, has diminished substantially in women using regimens presently on the market. Modest suppression of pituitary gonadotropin secretion during pill intake and recovery of FSH release during the pill-free week creates a situation resembling the early follicular phase of the normal menstrual cycle and allows for substantial residual ovarian activity Concepts involved in regulation of follicle growth during gonadotropin induction of ovulation (attempting to enhance fertility) as well as during steroid contraception (aiming at inhibiting fertility) are derived from recent findings regarding regulation of ovarian function under…