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Genetic Test to Predict IVF Egg Production in Older Women

by Leigh Ann Woodruff, March 19, 2012

A specific gene may have a lot to do with your chances of IVF success, particularly if you are undergoing treatment at an older age.

According to an ovarian aging study published in March 2012 in the medical journal PLoS One, a genotype (the genetic make-up of a trait) of the FMR1 gene preserves a woman's ability to produce eggs well into the 40s. Conducted by the Center for Human Reproduction in New York, the study compared egg yields during in vitro fertilization (IVF) in women above age 40 with varying FMR1 genotypes and sub-genotypes.

The FMR1 gene is located on the X chromosome and contains DNA segments called CGG trinucleotides. For the majority of people, the CGG segment is repeated in the gene approximately five to 44 times. If there is an abnormally high number of CGG repeats on the FMR1 gene, it can be associated with impaired cognitive and reproductive functions. If a person has 45-54 repeats this is considered borderline risk, while 55 to 200 repeats is called a premutation, and more than 200 repeats is considered a full mutation of the FMR1 gene. In cases where there is a full mutation of the gene, it is expressed as the fragile X mental retardation syndrome.

In previous work, the researchers had defined new CGG repeat ranges, which specifically appeared to relate to ovarian function, and they called them "ovarian genotypes" of the FMR1 gene. In the new paper, they found that in women with very poor ovarian reserve, the FMR1 sub-genotype het-norm/high, which means normal CGG repeat count (in range of 26-34 CGG repeats) on one allele (one of two or more forms of a gene), and an abnormally high count on the other allele, produced significantly more eggs than other genotypes and sub-genotypes. The observation suggests that the het-norm/high FMR1 sub-genotype preserves a woman's ability to produce a good number of eggs into older ages even if her ovarian reserve is severely reduced.

"We got interested in this gene a few years ago because the premutation genotype for decades also has been associated with premature ovarian failure (POF)," says study author Norbert Gleicher, M.D., medical director of the Center for Human Reproduction. "This made me suspicious that this gene may also play an important role in regards to ovarian function."

In previous research, the team demonstrated that different ovarian genotypes are associated with distinct ovarian aging patterns, determining how slowly or quickly a woman uses up her eggs. They had found that the het-norm/high sub-genotype was responsible for slow recruitment of eggs into the maturation process at younger ages and theorized that more eggs would be left for older age. In the most recent paper, "We demonstrated that women with a het-norm/high sub-genotype appear to preserve eggs into older age," Dr. Gleicher says. Because the number of eggs produced in IVF cycles usually correlates with pregnancy chances, older women with extremely low ovarian reserve appear to have better chances of success if their FMR1 sub-genotype is het-norm/high. The study found that women with this sub-genotype performed better in IVF cycles than even women with a normal FMR1 genotype.

Dr. Gleicher says researchers are gaining more understanding regarding the involvement of genetics in the process of ovarian aging and that the FMR1 gene is of increasing importance. "The FMR1 gene, at least to a degree, controls ovarian aging," he says. "The ovarian FMR1 genotype of a woman, at least to a degree, determines her ovarian aging pattern, and also determines her pregnancy chances with IVF. Older women with extremely low ovarian reserve, therefore, appear to have better chances of success if their FMR1 sub-genotype is het-norm/high."

The knowledge will help fertility doctors predict success in older women undergoing IVF and design more individualized treatment protocols. "We are predicting that in the future we will treat women with different IVF protocols, based on their ovarian FMR1 genotype," Dr. Gleicher says.


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