Age-related changes to cells that support egg development – not changes to the eggs themselves – are the key factors that reduce the likelihood of successful conception via in vitro fertilization (IVF) among older women. Early oocyte retrieval could neutralize those changes and improve fertility.

“We used to think that ageing eggs were responsible for poor IVF success rates in older women, but here we show that it is more due to the ageing of the egg’s environment”, said Dr. Yanguang Wu, embryologist and associate scientist at the Center for Reproductive Medicine in New York, New York, US. “The chances of reversing damage to an egg are practically zero and so these findings are exciting because it’s much more hopeful to therapeutically target the egg’s supporting environment.”

A comparison of granulosa cells (GCs), which surround oocytes and help them grow, showed that among young women (n=31, 21-29 years, oocyte donors in the study), GCs more commonly expressed follicle-stimulating hormone (FSH) receptors and, as they aged, the number of these receptors fell while the number of luteinising hormone (LH) and progesterone receptors increased among the middle aged (n=64, 3037 years) and particularly the older (n=41, 43-47 years) infertile women included in the study. [J Endocrinol 2015;JOE-15-0246]

The result of these changes in receptor expression likely explain why the chance of conception from IVF declines from 23.6 percent in women aged 38-39 to 1.3 percent among women aged 44 and older, the researchers note.

Premature luteinisation, which can happen if GCs are sensitised to LH with more LH receptors, arrests egg maturation in the process of preparing the uterus for pregnancy before the egg has left the ovary, which reduces the chance of pregnancy.

FSH response, which included cell proliferation, reduced apoptosis and some inhibited luteinisation, also seemed to decline as women aged.

To prevent premature luteinisation, the researchers conducted a pilot oocyte retrieval study in women over 43 (mean age 44.8±0.3 years) to collect follicles when they reached 16 mm rather than waiting until the normal 19-21 mm.

Compared to a group of 91 women over age 43 (n=91, mean age 44.3±0.15 years) who underwent normal retrieval, early retrieval of immature eggs produced more and better quality embryos and better IVF success rates.

Subsequent trials need to be powered to prove that early retrieval results in improved clinical pregnancy and live birth rates, the researchers said. However, “this study… with considerable certainty established non-inferiority for this new treatment and, with a reasonable level of likelihood suggest that early oocyte retrieval may improve IVF outcomes.”