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Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA

  • Fertility Preservation
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Abstract

Purpose

There is increasing evidence that the ovarian extracellular matrix (ECM) plays a critical role in follicle development. The rigidity of the cortical ECM limits expansion of the follicle and consequently oocyte maturation, maintaining the follicle in its quiescent state. Quiescent primordial, primary, and secondary follicles still exist in primary ovarian insufficiency (POI) patients, and techniques as in vitro activation (IVA) and drug-free IVA have recently been developed aiming to activate these follicles based on the Hippo signaling disruption that is essential in mechanotransduction. In this context, we analyze the effect of drug-free IVA in POI patients, comparing the relationship between possible resumption ovarian function and biomechanical properties of ovarian tissue.

Methods

Nineteen POI patients according to ESHRE criteria who underwent drug-free IVA by laparoscopy between January 2018 and December 2019 and were followed up for a year after the intervention. A sample of ovarian cortex taken during the intervention was analyzed by atomic force microscopy (AFM) in order to quantitatively measure tissue stiffness (Young’s elastic modulus, E) at the micrometer scale. Functional outcomes after drug-free were analyzed.

Results

Resumption of ovarian function was observed in 10 patients (52.6%) and two of them became pregnant with live births. There were no differences in clinical characteristics (age and duration of amenorrhea) and basal hormone parameters (FSH and AMH) depending on whether or not there was activation after surgery. However, ovarian cortex stiffness was significantly greater in patients with ovarian activity after drug-free IVA: median E = 5519 Pa (2260–11,296) vs 1501 (999–3474); p-value < 0.001.

Conclusions

Biomechanical properties of ovarian cortex in POI patients have a great variability, and higher ovarian tissue stiffness entails a more favorable status when drug-free IVA is applied in their treatment. This status is probably related to an ovary with more residual follicles, which would explain a greater possibility of ovarian follicular reactivations after treatment.

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Funding

This study was supported in part by the grant “Premi Fi de Residencia Emili Letang 2017” from the Hospital Clinic of Barcelona: 398–37-250,777 PFR 2017.

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Authors and Affiliations

  1. Institute of Gynaecology Obstetrics and Neonatology (ICGON), Hospital Clínic de Barcelona, Barcelona, Spain

    M. Méndez, F. Fabregues, J. Ferreri, J. M. Calafell & F. Carmona

  2. August Pi Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain

    F. Fabregues, R. Farre & F. Carmona

  3. Biophysics and Bioengineering Unit, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

    A. Villarino, J. Otero & R. Farre

  4. CIBER of Respiratory Diseases, Madrid, Spain

    J. Otero & R. Farre

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  1. M. Méndez
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Contributions

All authors contributed to the study conception and design. Marta Méndez and Francesc Fabregues conceived, structured, and wrote the text. Material preparation and biomechanical analysis of tissue stiffness by AFM were performed by Alvaro Villarino, Jordi Otero, and Ramon Farre. Data collection and analysis were performed by Marta Méndez, Janisse Ferreri, and Josep Maria Calafell. Drug-free IVA by laparoscopy was performed by Francesc Fabregues, Janisse Ferreri, and Josep Maria Calafell. The study supervision was performed by Francesc Fabregues and Francisco Carmona. All authors commented on previous versions of the manuscript and approved the final version submitted.

Corresponding author

Correspondence to M. Méndez.

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Ethics approval and consent to participate

It was conducted according to the Declaration of Helsinki for Medical Research involving Human Subjects [20]. The study protocol was approved by Ethics Committee of the Hospital Clinic of Barcelona (registry number 2017/08569) in 2017. All patients provided written, informed consent to participate in the study.

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The authors declare no competing interests.

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Méndez, M., Fabregues, F., Ferreri, J. et al. Biomechanical characteristics of the ovarian cortex in POI patients and functional outcomes after drug-free IVA. J Assist Reprod Genet 39, 1759–1767 (2022). https://doi.org/10.1007/s10815-022-02579-w

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