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PGD May Ease Miscarriage Risk After IVF in Older Patients

Women over age 35 who've experienced repeat miscarriage may be able to ease their risk of having another pregnancy loss following in vitro fertilization (IVF) by having their embryos tested for genetic abnormalities before they're transferred to begin a pregnancy.That's the conclusion of a group of reproductive endocrinologists and geneticists who studied the value of using a procedure known as preimplantation genetic diagnosis, or PGD, before embryo transfer. Their study is published in the August issue of the journal Fertility and Sterility.1

Several years ago, the same group of researchers published research claiming that PGD may help ease the risk of having a miscarriage,2 but this was the first study to examine the effect of PGD on the risk of recurrent miscarriage, explained Santiago Munne, PhD, director of Reprogenetics, a genetics testing lab in West Orange, New Jersey, and this study's chief investigator.

PGD: Reducing Miscarriage Risk?
Preimplantation genetic diagnosis involves removing one or two cells from an embryo three days after fertilization, then performing a genetic test on them to look for any possible chromosomal abnormalities. Any such abnormality could prevent implantation, or predict either birth defects or a possible miscarriage. "I would say almost every IVF clinic now offers it, usually through a reference lab like ours," Munne explained, in a telephone interview. "We serve about 150 clinics."

A less common technique involves genetic testing of cells known as polar body cells that are tossed away by the egg as it matures and is fertilized. Embryos without such abnormalities are then transferred to the mother's uterus for pregnancy in hopes of boosting the likelihood of success.3

While other experts have suggested that repeat pregnancy loss—defined clinically as a minimum of three miscarriages occurring consecutively—may occur due to hormonal, anatomic, or immunologic causes, the exact reasons haven't been uncovered in 50% of cases, wrote Munne and his fellow researchers. Still, the possibility that genetics may play a role is "large", they added. "At least 50% to 60% of early losses show a number of genetic abnormalities," Munne and his associates wrote. "Conversely, 90% of chromosomally abnormal pregnancies abort, compared with 7% of the chromosomally normal."

There is also evidence that an overwhelming 90% of miscarriages are due to chromosomal disorders, the study team maintained. And it appears that this occurs more often in older women. In younger women, these chromosomal abnormalities occur in about half of all embryos derived from younger women, but that climbs to an overwhelming 90% in women who are older, Munne explained.

As such, the risk of such abnormalities may extend to embryos created through IVF or other forms of assisted reproductive technologies (ART), stated Munne and his colleagues. "Given this, recurrent miscarriage patients should benefit from preimplantation genetic diagnosis (PGD) because selection can allow transfer only of chromosomally normal embryos." The result, they maintained, should be increased rates of embryo implantation, reduced miscarriage, and eventually, an increase in the number of births resulting from ART.

Could PGD Reduce Repeat Miscarriages?
To test that theory, Munne's group collected information on 58 women who had experienced repeat miscarriage after seeking treatment at two 
fertility clinics, one in New Jersey and the second in Colorado, between 2001 and 2003. On average, the women had had nearly four previous miscarriages.

To determine whether PGD would decrease the risk of a subsequent miscarriage in those who experience repeat pregnancy loss, Munne's team evaluated results from PGD tests performed on the patients' embryos created using IVF. Up to four embryos found to be chromosomally normal were transferred up to five days after fertilization. Five embryos were transferred in rare instances where patients were of advanced age or when embryos had poor structure.

The effects of PGD on the risk of repeat miscarriage were analyzed by comparing the actual pregnancy loss experienced by a patient with the expected rate of miscarriage on the basis of the patient's history, the researchers wrote.

A second analysis was undertaken in a group of women over age 35.

The investigators found that the actual rate of miscarriages after PGD was about 16%, overall, compared to an expected pregnancy loss rate of approximately 36% in the group of women they studied.  Among those older than 35, the expected rate of miscarriage was about 44%, whereas the actual rate after PGD was just 12%, the study team reported. In those younger than age 35, the researchers found that PGD did not make much of a difference between observed and expected miscarriage rates.

This is likely because the numbers of miscarriages in women below age 35 are too infrequent, Munne said.

Study: Older Women May Benefit
"The key finding was that for women aged 35 years and older, PGD significantly reduced losses and increased number of viable pregnancies, benefiting 46 percent of patients aged equal to or greater than 35 years, per cycle," wrote Munne and his colleagues.

It's also reasonable to conclude that repeat miscarriage of unknown causes in older women "is mostly a problem of recurrent chromosomally abnormal embryos," they stated.

Thus, doctors can recommend PGD to their older patients undergoing ART, prior to embryo transfer. "After PGD, preimplantation rates are higher and embryonic loss rates lower," they concluded, adding that further clinical trials should be carried out to verify their findings, and to identify the patients who are mostly likely to benefit from this technique.

1. Munne S, Chen S, Fischer J et al. Preimplantation genetic diagnosis reduces pregnancy loss in women aged 35 years and older with a history of recurrent miscarriages. Fertil Steril 2005 Aug;84(2):331-5.
2. Munne S, Magli C, Cohen J et al. Positive outcome after preimplantation diagnosis of aneuploidy in human embryos. Hum Reprod 1999 Sep;14(9):2191-9.
3. Genetics and Public Policy Center. Preimplantation Genetic Diagnosis (PGD). Available at: http://www.dnapolicy.org/genetics/pgd.jhtml.html

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.



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