IVM Treatment in Patients With Low Ovarian Response. Does it Improve IVF Outcome or May it Cause Activation of Ovarian Follicles and Increase the Chances of Success in the Following IVF Cycle?

IVM treatment in patients with low ovarian response. Does it improve IVF outcome or may it cause activation of ovarian follicles and increase the chances of success in the following IVF cycle?

Scientific background:

Poor ovarian response (POR) is one of the major therapeutic challenges in in vitro fertilization. The prevalence of poor responders patients varies in the literature between 9 and 24%, however due to the increase in childbearing age it is expected to be one of the main infertility cause. Failure to respond adequately to standard protocols and to recruit adequate follicles results in decreased oocyte production, cycle cancellation and, overall, it is associated with a significantly diminished probability of pregnancy Several therapeutic approaches for POR have been explored; yet, a single effective strategy has not yet been established. Previously it was shown that mechanical manipulation on ovarian cortex such as ovarian wedge resection or ovarian "drilling" by diathermy or laser, induced follicle growth in polycystic ovarian syndrome (PCOS) patient.

Recently, a live birth was reported after ovarian cortex fragmentation and in vitro disruption of the Hippo signaling pathway and activation of Akt signaling. The treated ovarian fragments were grafted back to the patient and after follicle growth, retrieval of mature eggs, in vitro fertilization and embryo transfer; a healthy baby was delivered. The Hippo signaling pathway is essential to maintain optimal organ size and is conserved in all metazoan animals [6-8]. In this study it was shown that ovarian fragmentation increased actin polymerization and disrupted Hippo signaling by decreasing phosphorylated Yes-associated protein (pYAP) levels together with increased nuclear localization of YAP, leading to increased expression of CCN growth factors genes and BIRC apoptosis inhibitors. Secreted CCN2 and related factors promoted follicle growth

Genes involved in ovarian fragmentation, Hippo signaling, and follicle growth is important for ovarian physiology and pathophysiology. Ovarian fragmentation led to changes in intercellular tension and facilitated the conversion of G-actin to F-actin. Subsequent disruption of Hippo signaling decreased pYAP to total YAP ratios, leading to increased expression of downstream CCN growth factors and BIRC apoptosis inhibitors