Application of the concept of follicular waves in human assisted reproduction
Bianchi, Paulo Homem de Mello
Background: Ovulation induction (OI) is one of the cornerstones in human assisted reproduction treatments. OI is based on the understanding of ovarian follicular physiology. Current knowledge of human follicular dynamics relies on hystologic observations of ovaries in distinct moments during one menstrual cycle (interval between two menses). According to this data follicles in different stages of maturation are seen at any time during a menstrual cycle. Initial recruitment and grow of the primordial follicles is still a poorly understood process, but continued development of antral follicles, selection of the dominant follicle and ovulation depends on follicle stimulating hormone (FSH) and luteinizing hormone (LH) serum levels, which are influenced by estradiol and progesterone concentrations. With the degeneration of the corpus luteum at the end of the luteal phase, serum estradiol and progesterone concentrations fall, leading to menstruation and an increase in FSH levels. All this observations have led to the formulation of the current theory of human follicular dynamics by which follicles continuously grow from the primordial pool randomicaly, but only those which happen to be at the antral stage (FSH sensitive) during menses (FSH elevation) may continue to develop until the pre ovulatory stage and ovulate. Accordingly, in current OI protocols for human in vitro fertilization (IVF) stimulation usually beggins 2 to 5 days after the first day of menstruation. Review: Recently a new model of human folliculogenesis, based on the occurence of follicular waves, has been described. Major development of medical ultrasound technology has allowed for the precise detection of small antral follicles in the transvaginal route. Using this technology and shifting the landmark for observations from menses to ovulation, synchronic grow of a group of antral follicles (follicular wave) has been observed two or three times in an inter ovulatory interval. Emergence of a wave is preceeded by an elevation in FSH levels. The first wave emerges around ovulation and the last is the ovulatory follicular wave. This is in accordance with previous observations in other mono ovulatory animals like the cows and mares, but in contrast with the current model of human folliculogenesis, Application of follicular wave knowledge has proved to be very usefull to the development of more effective OI protocols used in Veterinary Medicine. It has been shown that synchronization of OI with wave emergence results in more oocytes and embryos with better quality in cows. Protocols to control wave emergence are currently standart of practice for in vitro production of some animals' embryos. The description of the follicular waves in humans gives the opportunity to develop new OI protocols for IVF. Synchronization of OI with wave emergence could be achieved through mechanical (aspiration of the dominant follicle folowed by ovarian stimulation) or chemical interventions (initiate ovulation or using high doses of estradiol and progesterone in any phase of the cycle, followed by ovulation induction). However some differences between in vitro production of animal embryos and Human IVF should be enfasized and could challenge the application of this knowledge. For instance, Human embryos are usually obtained and transfered to the same subject, therefore a synchronization of embryo and endometrial development is a major concern. Conclusions: Description of follicular waves in Human ovaries could have profound implications in OI for IVF, but some challenges should be expected to transpose the animal model to the Human setting.
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