פרופ' ג'וני יונס

The Mechanisms of Ovarian Aging

Johnny S. Younis, BMSc, MD

Assisted Reproductive Medicine Unit, Department of Obstetrics and Gynecology, Poriya Medical Center, Tiberias and Faculty of Medicine, Galilee, Bar-Ilan University.

Aim: To study the mechanisms of ovarian aging in infertile women undergoing assisted reproductive technologies (ART) treatment.

Background: Ovarian aging is a continuous process governed by a gradual decrease in the quantity and quality of the oocytes, contained within the ovarian follicles, starting in-utero and extending through the menopausal transition. Commonly, woman’s fecundity begins gradually decreasing at about age 31 and around 37-38 years of age a significant decline in fertility begins. Nevertheless, there is a wide variability in the ovarian follicle pool reserve among women of the same age group with a distribution range of almost twenty years. A significant part of women in the reproductive age will exhibit follicular apoptosis, depletion of ovarian reserve and a significant decline in fertility at a much earlier age. In the last few decades pregnancy is being intentionally delayed and ovarian aging has become a major detrimental factor of pregnancy achievement and maintenance. Moreover, it is now clear that ovarian aging is closely related to other issues of women’s health. In general, the exact mechanisms that dictate ovarian aging are still not identified. Yet, many risk factors have been established including medical, lifestyle, autoimmune, genetic and idiopathic. Our group has been engaged in the clinical investigation of this enigmatic topic in the last fifteen years and this will be presented during the talk.

Materials and Methods: The ART setting is an optimal tool for infertility treatment as well as ovarian aging investigation. A significant part of infertile women in need of ART treatment, whatever the basic etiology of their infertility, do show clear manifestations of reduced ovarian reserve and ovarian aging. Well designed prospective controlled targeted studies may uncover whether the patho-physiology underlying ovarian aging is related to one of the three suggested theories; possible differences in germ cell formation during fetal life, changes in the quality of the granulosa cells surrounding the oocyte or accumulated damage to the oocytes during female childhood and reproductive life. This may be accomplished by meticulous studying of the environment surrounding or within the follicle, including serum, follicular fluid and granulosa cells evaluation during ART treatment. Several investigational approaches could be employed including endocrine and growth factors evaluation, insulin/IGF-1 signaling, environmental stress, oxidative free radicals or apoptosis markers analyzing as well as luteinized granulosa cells extended culture assessment.

Significance: Ovarian aging studying in an ART setting may uncover novel mechanisms of its development. As well, it may assist to design improved treatment methods for these patients related to infertility or other issues of women’s health.