The likelihood of conceiving through in vitro fertilization reduces dramatically once women reach their early 40s. Now, researchers believe they may have shed light on why this is - opening the door to more effective fertility treatment for older women.
Dr. Yanguang Wu, embryologist and associate scientist at the Centre for Human Reproduction in New York, NY, and colleagues publish their findings in the Journal of Endocrinology.
In vitro fertilization (IVF) is a form of assisted reproductive technology (ART). First, fertility medication is administered to stimulate a woman's egg, or oocyte, production. The eggs are then retrieved from the ovaries and combined with sperm in a laboratory dish for fertilization. The embryos are then transferred into the woman's uterus.
It is well established that IVF is more likely to be successful for women under the age of 40. According to Dr. Wu and colleagues, recent studies have shown women aged 38-39 have an IVF success rate of 23.6%, while those aged 44 and older have a success rate of only 1.3%.
Previous research has shown that the quality of oocytes declines as a woman ages, reducing the likelihood of older women conceiving through IVF. However, the mechanisms behind this are unclear, which Dr. Wu puts down to lack of resources in clinical laboratories.
However, with the resources available at the Centre for Human Reproduction, the team was able to take a closer look at what drives reduced oocyte quality in older women.
Aging of the eggs' environment is the problem, not aging of the eggs themselves
The researchers compared the reproductive tissue of egg donors aged 21-29, 30-37 and 43-47 years.
Compared with egg donors aged 21-29 and 30-37, those aged 43-47 had reduced growth and multiplication of granulosa cells - the cells that support the oocytes inside a woman's ovary and aid their growth.
Further investigation revealed that the granulosa cells of the older women produced fewer cell receptors for follicle-stimulating hormone (FSH), but produced more receptors for luteinizing hormone (LH) and progesterone.
According to the authors, these changes in hormone sensitivity mean older women are significantly more likely to experience early luteinization, which prevents the ovaries from maturing oocytes and preparing the womb for pregnancy.
The team explains that the process of luteinization normally happens after ovulation, in which increasing LH levels cause a fall in FSH levels and a rise in progesterone levels. However, if luteinization occurs prior to the oocyte leaving the ovary, the chance of conception is reduced.
Dr. Wu says these findings show that is it not the aging eggs themselves that are responsible for lower IVF success among older women, but the aging of the eggs' environment that is to blame.
"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," adds Dr. Wu.
These results got the team thinking; could retrieving oocytes earlier in the IVF process - before premature luteinization - increase success?
Harvesting oocytes earlier resulted in better IVF success rates
At present, doctors performing IVF normally wait until oocyte follicles reach 19-21 mm before administering the hormone human chorionic gonadotropin (hCG) to "ripen" the oocytes, preparing them for removal.
In this study, however, Dr. Wu and colleagues adopted an IVF approach in which they administered hCG when the oocyte follicles were 16 mm - at a point when the risk of early luteinization is lower - allowing them to retrieve the oocytes when they were more immature.
Comparing outcomes from conventional IVF with those of their new approach, the team found earlier retrieval of oocytes led to increased production of good quality embryos and higher success rates.
Dr. Wu told Medical News Today that the team is hopeful their findings will improve pregnancy success in older women receiving IVF:
"We do believe our study would benefit IVF outcome in older women because from our study, by retrieving oocytes earlier from smaller follicles, the negative effects of early luteinization were reduced, which results in a significant increase of oocyte/embryo quality and pregnancy rate."
Dr. Wu added that the efficacy of the new IVF approach needs to be tested in larger studies, and the team also hopes to test whether it could improve IVF success rates in younger women.
Last month, MNT reported on a study that found many adolescents and young adults who are undergoing cancer therapy - which can negatively impact fertility - are unaware of their fertility preservation options.