Institute of Gynaecology Obstetrics and Neonatology (ICGON), Hospital Clínic de Barcelona, Barcelona, Spain.
August Pi Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
J Assist Reprod Genet. 2022 Aug;39(8):1759-1767. doi: 10.1007/s10815-022-02579-w. Epub 2022 Jul 29.
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.
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.
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.
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.
越来越多的证据表明，卵巢细胞外基质（ECM）在卵泡发育中起着关键作用。皮质 ECM 的刚性限制了卵泡的扩张，进而限制了卵母细胞的成熟，使卵泡保持静止状态。在原发性卵巢功能不全（POI）患者中仍然存在静止的原始卵泡、初级卵泡和次级卵泡，最近已经开发出体外激活（IVA）和无药物 IVA 等技术，旨在基于对机械转导至关重要的 Hippo 信号中断来激活这些卵泡。在这种情况下，我们分析了无药物 IVA 在 POI 患者中的作用，比较了可能恢复卵巢功能与卵巢组织生物力学特性之间的关系。
根据 ESHRE 标准，19 名 POI 患者于 2018 年 1 月至 2019 年 12 月期间接受腹腔镜下无药物 IVA，并在干预后一年进行随访。在干预过程中取卵巢皮质样本，通过原子力显微镜（AFM）进行分析，以定量测量微米级组织硬度（杨氏弹性模量，E）。分析无药物 IVA 后的功能结果。
10 名患者（52.6%）观察到卵巢功能恢复，其中 2 名患者怀孕并分娩。术后是否激活，患者的临床特征（年龄和闭经时间）和基础激素参数（FSH 和 AMH）无差异。然而，无药物 IVA 后卵巢活动患者的卵巢皮质硬度明显更高：中位数 E=5519 Pa（2260-11296）比 1501（999-3474）；p 值<0.001。
POI 患者卵巢皮质的生物力学特性具有很大的可变性，无药物 IVA 治疗时，卵巢组织硬度越高，状态越有利。这种状态可能与卵巢中保留更多卵泡有关，这可以解释治疗后卵巢卵泡重新激活的可能性更大。
