High doses of follicle-stimulating hormone (FSH) during ovarian stimulation may disrupt follicular function leading to reduced egg quality.
During a cycle of IVF FSH is administered to stimulate the ovaries and induce the growth of egg-containing follicles, allowing multiple eggs to be collected during one round of treatment compared with one egg in a natural cycle. However, too much FSH may be detrimental. A new study published in Endocrinology may help explain how it can reduce ovarian function and compromise oocyte viability.
'After analysing half a million assisted reproductive technology cycle records for women, we saw that, as the clinics added more and more FSH, the live birth rates went down almost 50 percent,' explained author James Ireland, professor of animal science at Michigan State University (MSU) in East Lansing. 'For the last 15 to 20 years, the FSH doses used on many women is way too high.'
To understand why this is the case, the researchers used heifers (female cows who have not yet birthed a calf) with small ovarian reserves as models. The heifers either received the industry standard dose or an excessive dose of FSH. Cattle treated with excessive FSH showed a range of abnormal follicles compared to those treated with a standard dose.
The researchers used RNA sequencing to study the gene expression of the oocytes and the cumulus cells (CCs) and granulosa cells (GCs) surrounding them within the follicles. They found that when heifers were administered with high-dose FSH, the CCs and GCs exhibited abnormal gene expression patterns compared to those administered with standard doses, reflecting a disruption to key molecular and cellular processes. Although less severe, the oocytes also displayed changes in gene expression, which the researchers suggested reflect significant alterations to essential processes that may compromise egg quality.
They found that these changes in gene expression affected the typical sequence of development during follicular maturation, with ovulation and luteinisation occurring at the same time rather than sequentially.
'This indicates that the follicles are "confused" and do not develop along any previously described or expected pathway,' said Keith Latham, professor of animal science and research professor in the Department of Obstetrics, Gynaecology and Reproductive Biology at MSU.
Overall, these data indicate that excessive FSH doses during ovarian stimulation result in varying degrees of follicular abnormalities and reduced oocyte viability. This research could help to refine IVF practices by avoiding excess FSH administration and could have implications in both human medicine and agriculture.
Leave a Reply
You must be logged in to post a comment.