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Genetic Technique Dramatically Improves Pregnancy Rates of Older Women

Tue, 01/21/2014 - 9:36am
Cynthia Fox

Using preimplantation genetic diagnosis (PGD), a research group achieved the same pregnancy rates for 42-year-old as 35-year-old women. (Source: NYU Langone Medical Center/NYU Fertility Center)A large global team of reproduction experts has found a way to even the score for older women seeking pregnancy.

Via a process called preimplantation genetic diagnosis (PGD), the group achieved the same pregnancy rates for 42-year-old as 35-year-old women.

“You can wipe out the age effect by just implanting chromosomally normal embryos” isolated via new PGD techniques, New York University Fertility Center Program Director Jamie Grifo tells Bioscience.

Only 5 percent of embryos created from eggs of 42-year-old women normally implant in the uterus using typical IVF methods, says Grifo. That number increased to nearly 50 percent with new PGD methods, a number nearly equal to the 55 percent implantation rate of 35-year-old women undergoing the new techniques. (Using typical IVF methods, 35-year-olds see success rates of 35 percent.)

The new data were published in a December 2013 Fertility and Sterility by a multi-center team led by globally recognized fertility pioneers, including Santiago Munne of Reprogenetics in New Jersey, Dagan Wells of Oxford University in the U.K., and Grifo.

PGD is a process, first used in a successful pregnancy in 1989, by which clinicians can biopsy, and analyze, cells from embryos. (Generally, the phrase PGS, or preimplantation genetic screening, is used to refer to the process of PGD for aneuploidy, or chromosomal abnormalities.) During PGD/PGS, a single cell— or a small number of cells— is removed from embryos at a very early stage for genetic analysis.

Embryos found to be without those abnormalities are then inserted into uteruses.

It is an IVF process that is increasingly being used by parents hoping to spare their children severe, inherited genetic or chromosomal abnormalities. Lately, it has also been used to winnow out embryos that have accumulated non-inherited chromosomal abnormalities caused by maternal aging.

But in the past, the process has been more successful winnowing out embryos with single gene mutations, those that cause diseases like Fanconi’s anemia, than embryos with multiple chromosomal abnormalities due to age.

The new technique has improved those success rates. It has improved them to the point where the teams report in the recent paper they may have “finally” proven that “the bulk of implantation failure and pregnancy loss with advancing maternal age is due to chromosome abnormalities and can be prevented by replacing euploid (chromosomally normal) embryos.”

More important to patients, the study showed the new approach “was able to mitigate the maternal age effect in all but the oldest category of IVF patients”– that is, those older than 42 who can’t generate multiple embryos of any quality.

The group reported that three advances have converged to create this new, successful, “second generation PGS,” PGD technology. New “complete chromosome screening” via a process called comparative genomic hybridization (CGH) is one such advance. An earlier chromosome screening method, fluorescent in situ hybridization (FISH), only allowed a handful of chromosomes to be tested at a time due to limited numbers of tagging colors involved.

Also, FISH can be technician-dependent, leading to variable results, with reported error rates ranging from 50 percent to 3.7 percent. The more complete method of CGH has been used in IVF since the late 1990’s, but there was a problem: the analysis took a full three days. Since PGD/PGS deals with living embryos, time is of the essence.

But a second advance— improvement in embryo freezing techniques— gave CGH the time it needed. This advance allowed the team to freeze the embryos whose cells were being analyzed, keeping them from inappropriately developing in vitro.

Finally, the teams reported they were aided by a newly refined ability to biopsy embryos at a later day (five), not the more common day three, when embryos are less damaged by biopsy. This advance came about in part due to work by Robert Jansen’s group at the University of Wales.

The recent PGD study was comparatively large, involving dozens of clinics on both sides of the Atlantic. A total of 451 IVF cycles of cleavage stage (day three) biopsy and 462 IVF cycles of blastocyst (day five) biopsy were included, with 3,412 and 2,467 embryos analyzed, respectively.

The recent study “pretty clearly demonstrates” the increasing efficacy of PGD, which is becoming “more and more popular,” concludes Grifo.

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