Drug-free In Situ Activation of Follicle through Laparoscopic Ovarian Cortical Incisions in Patients with Premature Ovarian Insufficiency

Background Individuals with premature ovarian insufficiency (POI) face significant challenges in attaining favorable reproductive outcomes. To date, no effective interventions have been established to substantially improve this complex clinical scenario. Methods We conducted a clinical trial in a tertiary university-affiliated hospital to study a protocol of Drug-free In Situ Activation (Df-ISA) of ovarian follicles for treatment of POI patients in improving reproductive outcomes. Five women were enrolled and accepted the Df-ISA procedure through longitudinal and transverse mechanical cutting on one ovary. The contralateral ovary remained intact as control. Changes in antral follicle count (AFC), oocyte retrieval rates, embryo cryopreservation, clinical pregnancy and live birth outcomes were clinical observational indicators. Results Antral follicle development was observed in all five patients by ultrasound monitoring after Df-ISA. A total of 21 echo-free antral follicle-like structures were identified and one viable cleavage embryo were obtained in the 6-month follow-up. In the longer follow-up, a total of seven cleavage embryos were obtained from two patients, and one live birth was achieved. Paired t-test revealed a statistically significant difference of follicle-like structures observed between the Df-ISA ovaries and the contralateral control ovaries. Conclusions The "Longitudinal and Latitudinal cutting in situ" Df-ISA procedure represents a novel infertility treatment for patients with POI. This procedure promotes the growth of residual antral ovarian follicles through dense mechanical disruption, yielding encouraging results that warrant further investigation. The study adhered to the principles outlined in the Declaration of Helsinki and was granted ethical approval by the Ethics Research Committee of the University of Hong Kong-Shenzhen Hospital and has been registered in the National Medical Research Registration and Filing Information System, with the registration number ChiCTR2400086676.Every participant has provided informed consent.