Abstract

Abstract Study question Is there a relationship between the biomechanical characteristics of ovarian cortex of POI patients and the resumption ovarian function after Drug-Free IVA? Summary answer Physical properties of ovarian cortex in POI are different. A significant ovarian stiffness increase was observed when resumption of ovarian function occurred after Drug-Free IVA. What is known already There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. Primordial follicles are localized at the collagen-rich ovarian cortex, which offers a rigid physical environment that supports follicular architecture and increases survival. Therefore, premature loss of ovarian function would be associated with a physically less rigid ovarian cortex. Study design, size, duration Prospective observational cohort study at a tertiary-care university hospital including POI patients according ESHRE criteria who underwent Drug-Free IVA by laparoscopy between January 2018 and December 2019 and were follow-up for a year after intervention. Participants/materials, setting, methods Nineteen patients were included. Resumption of ovarian function was defined as resumption of menstrual cycles (at least three consecutive episodes of menstrual bleeding) and/or the presence of follicles > 10 mm on ultrasound. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure mechanical properties at the nanometer scale (Young’s elastic modulus, E). Main results and the role of chance Median data at intervention were: age = 35 years (28–39); length of amenorrhea = 2 years (1–10); FSH level = 104.4 mIU/ml (38.9–176); and AMH = 0.02 ng/ml (0.01–0.1). Resumption of ovarian function was observed in 10 patients (52.6 %), achieving 2 pregnancies (one spontaneous and one after an IVF cycle). Median stiffness (E) measured by AFM was 2583 Pa (999–11296). There were no differences in clinical and hormonal parameters as a function of resumption of ovarian activity. Remarkably, ovarian cortex stiffness was significantly increased in patients with ovarian activity after Dug-Free VIA: 5519 (2260–11296] vs 1501 [999–3474], p value <0.001. Limitations, reasons for caution The main limitations of the study are the unavailability of ovarian tissue samples from a control group of patients without POI and the inability to perform histological studies on the same samples in which the biomechanical study was carried out. Wider implications of the findings These findings show the high variability of ovarian cortex stiffness in POI and that the increase of this stiffness entails a more favorable status after Drug-Free IVA. This may be related to an ovary with more residual follicles, which would explain a greater chances of ovarian follicular reactivations after treatment. Trial registration number not applicable

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