Johnson Joshua, Emerson John W, Smith Annika, Medina Kayla, Telfer Evelyn E, Anderson Richard A, Lawley Sean D
Division of Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Colorado Denver (AMC), Aurora, CO, USA.
Department of Statistics and Data Science, Yale University, New Haven, CT, USA.
Hum Reprod Update. 2025 May 5. doi: 10.1093/humupd/dmaf009.
Women are increasingly choosing to delay childbirth, and those with low ovarian reserves indicative of primary ovarian insufficiency are at risk for sub- and infertility and also the early onset of menopause. Experimental strategies that promise to extend the duration of ovarian function in women are currently being developed. One strategy is to slow the rate of loss of existing primordial follicles (PFs), and a second is to increase, or 'boost', the number of autologous PFs in the human ovary. In both cases, the duration of ovarian function would be expected to be lengthened, and menopause would be delayed. This might be accompanied by an extended production of mature oocytes of sufficient quality to extend the fertile lifespan.
In this work, we consider how slowing physiological ovarian aging might improve the health and well-being of patients, and summarize the current state-of-the-art of approaches being developed. We then use mathematical modeling to determine how interventions are likely to influence the duration of ovarian function quantitatively. Finally, we consider efficacy benchmarks that should be achieved so that individuals will benefit, and propose criteria that could be used to monitor ongoing efficacy in different patients as these strategies are being validated.
Current methods to estimate the size of the ovarian reserve and its relationship to the timing of the menopausal transition and menopause were compiled, and publications establishing methods designed to slow loss of the ovarian reserve or to deliver additional ovarian PFs to patients were identified.
We review our current understanding of the consequences of reproductive aging in women, and compare different approaches that may extend ovarian function in women at risk for POI. We also provide modeling of primordial reserve decay in the presence of therapies that slow PF loss or boost PF numbers. An interactive online tool is provided that estimates how different interventions would impact the duration of ovarian function across the natural population. Modeling output shows that treatments that slow PF loss would need to be applied as early as possible and for many years to achieve significant delay of menopause. In contrast, treatments that add additional PFs should occur as late as possible relative to the onset of menopause. Combined approaches slowing ovarian reserve loss while also boosting numbers of (new) PFs would likely offer some additional benefits in delaying menopause.
Extending ovarian function, and perhaps the fertile lifespan, is on the horizon for at least some patients. Modeling ovarian aging with and without such interventions complements and helps guide the clinical approaches that will achieve this goal.
Not applicable.
越来越多的女性选择推迟生育，而那些卵巢储备低提示原发性卵巢功能不全的女性存在生育力低下和不育的风险，并且还会过早绝经。目前正在研发有望延长女性卵巢功能持续时间的实验性策略。一种策略是减缓现有原始卵泡（PFs）的丢失速度，另一种是增加或“提升”人卵巢中自体PFs的数量。在这两种情况下，预计卵巢功能的持续时间会延长，绝经会延迟。这可能伴随着足够质量的成熟卵母细胞产量的延长，从而延长生育寿命。
在这项工作中，我们考虑减缓生理性卵巢衰老如何改善患者的健康和福祉，并总结正在研发的方法的当前技术水平。然后，我们使用数学建模来定量确定干预措施可能如何影响卵巢功能的持续时间。最后，我们考虑应该实现的疗效基准，以便个体能够受益，并提出在验证这些策略时可用于监测不同患者持续疗效的标准。
汇编了当前估计卵巢储备大小及其与绝经过渡和绝经时间关系的方法，并确定了建立旨在减缓卵巢储备丢失或为患者提供额外卵巢PFs的方法的出版物。
我们回顾了目前对女性生殖衰老后果的理解，并比较了可能延长有原发性卵巢功能不全风险女性卵巢功能的不同方法。我们还提供了在存在减缓PF丢失或增加PF数量的治疗情况下原始储备衰减的模型。提供了一个交互式在线工具，可估计不同干预措施将如何影响自然人群中卵巢功能的持续时间。模型输出表明，减缓PF丢失的治疗需要尽早应用并持续多年，以实现绝经的显著延迟。相比之下，添加额外PFs的治疗应相对于绝经开始尽可能晚进行。减缓卵巢储备丢失同时增加（新的）PF数量的联合方法可能在延迟绝经方面提供一些额外益处。
至少对一些患者来说，延长卵巢功能乃至生育寿命即将成为现实。对有无此类干预措施情况下的卵巢衰老进行建模，补充并有助于指导实现这一目标的临床方法。
不适用。
