Drug-free in-vitro activation of follicles for infertility treatment in poor ovarian response patients with decreased ovarian reserve

作者：Kazuhiro Kawamura, Bunpei Ishizuka, Aaron J.W. Hsueh · 发表于：Reproductive BioMedicine Online · 年份：2019 · DOI：10.1016/j.rbmo.2019.09.007 · 被引用次数：120 · 研究领域：Reproductive Biology and Fertility、Ovarian function and disorders、Assisted Reproductive Technology and Twin Pregnancy

RESEARCH QUESTION: The recently developed in-vitro activation (IVA) approach provides a promising infertility treatment for patients with premature ovarian insufficiency. The IVA method promotes growth of residual ovarian follicles following ovarian tissue fragmentation leading to Hippo signalling disruption, together with in-vitro incubation with Akt stimulators. As poor ovarian response (POR) patients with decreased ovarian reserve (DOR) have multiple secondary follicles, this study tested whether Hippo signalling disruption alone using in-vitro ovarian cortical fragmentation, followed by autologous grafting, was sufficient to promote follicle growth. DESIGN: A case series study. RESULTS: In 9 out of 11 POR patients with DOR treated with a simplified IVA procedure, increases in antral follicle numbers in multiple growth waves were detected following FSH treatment. Subsequent injection with human chorionic gonadotrophin allowed retrieval of more mature oocytes for IVF (median antral follicle counts before and after IVA per ovarian stimulation: 1.0 versus 2.6) with 68.7% fertilization rates and 56.9% showing high-quality embryonic development. One natural conception and 16 embryo transfers in five patients resulted in one live birth, two ongoing pregnancies and one miscarriage. Three additional patients and the miscarriage patient have cryopreserved embryos for future transfer. CONCLUSIONS: The present drug-free IVA approach may be suitable for POR patients with DOR, as it in...