An old mattress stops bouncing back: the filling clumps up, and the springs lose their resilience. The ovary changes with age in much the same way, except that instead of filling, stiff connective tissue grows inside it, and the role of springs is played by the cells that support the eggs. For the first time, scientists have managed to measure this stiffness in living women and link it to the chances of successful IVF.
The study included 32 women under 33 and over 37 years old who were undergoing IVF or fertility preservation, as well as 100 women aged 24 to 45 for independent validation. Ovarian stiffness was measured on days 2–3 of the menstrual cycle using transvaginal shear wave elastography, an ultrasound method that assesses tissue elasticity by sending vibrations through it. In parallel, molecular fragments of collagen reflecting its formation and breakdown were measured in follicular fluid and blood, and RNA was extracted from follicular fluid cells to see which cell types change their activity with age.
Molecular analysis showed that type VIII collagen accumulates in follicular fluid and the breakdown of type VI collagen decreases. Single-cell sequencing revealed that stromal cells, the connective tissue cells of the ovary that activate fibrosis and inflammation programs, change the most with age. Increased stiffness turned out to be associated with a lower number of retrieved eggs and reduced follicle efficiency, independent of age and AMH level (a hormone reflecting the egg supply).
Before this work, human ovarian fibrosis could not be measured in vivo: histology provides only a static picture, and mouse models did not translate to women. Here, three methods were combined in the same patients: ultrasound elastography, collagen neoepitope analysis, and single-cell RNA sequencing. This made it possible to link biomechanical, molecular, and cellular changes into a single picture.
An old mattress cannot be fixed, but you can learn to predict when it will stop bouncing. The same goes for the ovary: by measuring its stiffness, a doctor can assess a woman's reproductive age in advance and choose a suitable treatment strategy. In the future, anti-fibrotic drugs tested in animals may slow this process, and stiffness will become a quantitative criterion for their effectiveness.
Ovarian stiffness in women over 37 reaches values comparable to those of a cirrhotic liver (up to 40 kPa), even though the ovary is far smaller. What is more, the spread of stiffness within a single ovary is wider in older women than in younger ones, reflecting the patchy nature of fibrosis.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.