The physiology of follicle selection

Abstract

During the follicular phase of the primate menstrual cycle, a single follicle usually matures to the preovulatory stage and releases its oocyte for fertilization and the potential establishment of pregnancy. In assisted reproductive technology procedures, it is desirable to override the natural process of follicle selection to produce many oocytes that are capable of being fertilized and undergoing normal embryo development. The goal of this chapter is to summarize the current views regarding the natural process of follicle selection in primates and to discuss how this process may be amplified to produce a greater number of oocytes.

Figure 1

Gonadotropic requirements for follicular development. The early stages of follicular development do not appear to require cyclic fluctuations in the secretion of FSH and LH. The role of FSH is to stimulate the formation of a large preovulatory follicle which, because of its FSH-dependent maturation, is capable of ovulation and forming a corpus luteum in response to the midcycle surge of LH.

Figure 2

Schematic diagram of the "FSH threshold" model for the selection of the preovulatory follicle in primates. During the luteal phase of the menstrual cycle circulating FSH concentrations are held below the FSH threshold by secretions of the corpus luteum. As a result, growing follicles do not advance beyond the preantral stage and undergo atresia. Upon the regression of the corpus luteum at the end of the nonfertile menstrual cycle, the negative feedback suppression of FSH secretion is released and FSH concentrations rise above threshold levels. One (or occasionally more) of the maturing preantral follicles is stimulated in response to the elevation of FSH and develops both the aromatase enzyme and LH receptors. The acquisition of aromatase results in a rise in systemic levels of estradiol which result in the suppression of FSH secretion, which, in turn, prevents the maturation of less mature follicles. The FSH-stimulated induction of LH receptors and the acquisition of LH responsiveness of granulosa cells of the stimulated follicle permit it to mature in the presence of FSH concentrations which are insufficient to stimulate the maturation of other less mature follicles.

Figure 3

Physiological basis of ovarian hyperstimulation. Panel A illustrates the conventional mechanism of ovarian hyperstimulation in which concentrations of circulating FSH are elevated above threshold levels either by direct administration of exogenous FSH or by interfering with the negative feedback actions of estrogen on FSH secretion either by the administration of anti-estrogens or aromatase inhibitors. The number of preovulatory follicles increases but in an asynchronous manner owing to the asynchronous nature of preantral follicular development. Panel B illustrates a hypothetical way to provide a more synchronous population of preovulatory follicles by increasing the number of preantral follicles prior to elevating FSH concentrations and substituting FSH with LH when an appropriate number of follicles are selected.