Folliculogenesis resumption after ovarian cortex transplantation: what is the earliest hormonal indicator?

Introduction: Ovarian tissue cryopreservation (OTC) is recommended by scientific societies for women undergoing highly gonadotoxic cancer treatments. Following transplantation, the restoration of ovarian function is typically characterised by the resumption of spontaneous menstruation. Yet, a few studies have looked at the longitudinal hormonal variations following transplantation. This study aims to investigate the fluctuation of gonadotropins and granulosa/theca cells secretions during the interval between ovarian transplantation and the recovery of menstrual function in two young women with no residual ovarian activity.

Method: We selected two patients diagnosed with Hodgkin's lymphoma, initially referred for OTC at the ages of 19 and 15, respectively, and who had both undergone two consecutive stem cell transplants due to recurrent disease episodes. Both patients presented with premature ovarian failure and returned at ages 29 and 26, respectively, for ovarian cortex transplantation. Hormonal secretions and menstrual function were closely monitored both prior and in the months following the ovarian transplantation.

Results: Menstruation resumed at 7 and 5 months post-transplantation, respectively. FSH and LH levels significantly decreased as early as 1 and 3 months before the first menstruation. As for ovarian hormonal secretion, AMH, measured with an ultra-sensitive assay ("pico AMH"), and Inhibin B were the first to increase, starting 1 month before the resumption of menstruation. Subsequently, AMH levels consistently remained very low throughout the follow-up, as did androgens, which showed a slight increase after the graft but remained at postmenopausal levels.

Conclusion: Pico AMH, measured by an ultra-sensitive assay, Inhibin B and estradiol are the first ovarian hormones to be secreted following an ovarian graft, with levels rising 1 month prior the return of menstruation. However, the earliest hormonal indicators of graft success are the significant drops in FSH and LH levels, accompanied by a rise in estradiol levels, which occur 1-3 months before menstruation resumes.