Women who are over 40 have a notoriously hard time getting pregnant by in-vitro fertilization (IVF), and it’s long been assumed that their problem stems from “old eggs”. But a preprint now available online at the Journal of Endocrinology suggests that the real problem might be the aging of the cells that surround the eggs.
Eggs aren’t packed in the ovary by themselves: each oocyte is surrounded by a layer of granulosa cells that help it mature and develop, wrapped in a structure called a follicle. The granulosa cells mediate a complex hormonal conversation inside the ovary between follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone that controls egg maturation and ovulation. Center for Human Reproduction biologist Yan-Guang Wu and colleagues found that in women in their forties, this conversation can go awry.
The group collected granulosa cells from 64 women in their thirties and 41 women in their mid-to-late forties who were undergoing IVF, and compared the cells’ gene expression and growth in culture to granulosa cells taken from 31 healthy egg donors in their twenties. They found that the cells’ profile of hormone receptors changes in women over the age of 43: specifically, gene expression for FSH receptors drops, and expression for LH and progesterone receptors increases.
These results suggest that the profile of hormone-detecting receptors on the granulosa cells shifts in older women, making the cells less sensitive to FSH–which normally stimulates egg development–and more sensitive to LH and progesterone, which mediate ovulation and pregnancy. One possible effect? The follicle can start its post-ovulation conversations too early, before ovulation has occurred, and damage the immature egg.
The team is now testing whether retrieving eggs from older women earlier in their menstrual cycles could improve their fertilization rates and produce fewer abnormal embryos.
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