Prenatal genetic screening (PGS) and prenatal genetic diagnosis (PGD).

Prenatal genetic screening (PGS) and prenatal genetic diagnosis (PGD).

prenatal genetic screening (PGS) genetic screening of embryos for chromosome abnormalities reduces the success rate of in vitro fertilization (IVF) by nearly a third in older women, according to a European study.

The study looked at the rates of ongoing pregnancies and live births in a total of 408 women aged 35 to 41 years undergoing a total of 862 cycles of in vitro fertilization. Half of the women (206) were randomized to undergo preimplantation genetic screening, and thePrenatal genetic screening (PGS) other half Prenatal genetic screening (PGS) were a control group and were not screened. Screening involved taking a biopsy of one cell at three days and testing chromosomes to detect trisomies or other abnormalities in chromosome number.

Sebastiaan Mastenbroek, from the Center for (PGS/PGD) Reproductive Medicine at the University of Amsterdam, the Netherlands, and the lead author of the study, explained the rationale, “Pregnancy rates in women of advanced maternal age undergoing IVF are disappointingly low. A potential cause is the increased incidence of chromosomal abnormalities. It has been suggested that use of preimplantation screening of cleavage stage embryos for aneuploidies may improve the effectiveness of IVF in these women.”

The results showed a significantly lower rate of pregnancies in the women who underwent genetic screening, however. Only 25% achieved ongoing pregnancies, compared with 37% of women who were not screened (rate ratio 0.69, 95% confidence interval 0.51 to 0.93).

The women randomised to preimplantation genetic screening also had a significantly lower rate of live births, at 24%, compared with 35% in women who were not screened (0.68, 0.50 to 0.92).

Dr Mastenbroek reported, “The study showed that preimplantation genetic screening did not increase, but instead significantly reduced, the ongoing pregnancy and live births after IVF in women of advanced maternal age.”

He concluded (PGS/PGD), “These results argue strongly against routinely performing preimplantation genetic screening as an adjunct to IVF in this group of women.” Because the study looked at screening in only older women, however, he said that they may not apply to younger women with other indications for preimplantation genetic screening.

“The results suggest that for every nine women who are 35 to 41 years of age who plan three cycles of IVF or IVF and intracytoplasmic sperm injection, there will be one more live birth if the preimplantation genetic diagnosis for aneuploidy screening is not performed,” said John Collins, from the Faculty of Health Sciences, McMaster University, Hamilton, Canada, in an editorial in the same issue (p 61).

These results should be broadly generalisable to women of similar age, he considered. “Given the findings, preimplantation genetic diagnosis should not be performed solely because of advanced maternal age.”

Preimplantation genetic diagnosis may reduce the potential for a successful pregnancy for several reasons, Dr Mastenbroek said. The biopsy of a blastomere may reduce the potential of an embryo to successfully implant into the uterus wall. Limitations in the numbers of chromosomes that can be analysed with the technique used in the study may mean that embryos labelled as normal were, in reality, aneuploid for one or more chromosomes not tested.

Prenatal genetic screening (PGS) and prenatal genetic diagnosis (PGD).

Finally, human embryos resulting from in vitro fertilization may be mosaic, so that the chromosomal make-up shown by analysing the blastomere may not reflect that of the entire embryo.

Peter Braude, head of the department of women’s health, at King’s College, London, and director of the centre for preimplantation genetic diagnosis, at Guy’s and St Thomas’ Foundation Trust, London, thought it was important to distinguish between prenatal genetic screening (PGS) and prenatal genetic diagnosis (PGD).

“Prenatal genetic diagnosis was developed to help couples who had recurrent known genetic disease that would put their offspring at risk of being affected by the disorder,” he explained. These patients are usually fertile and are choosing prenatal genetic diagnosis as a way of avoiding having to confront termination of pregnancy or an affected child.

“This is in sharp contrast with screening for sporadic risk of aneuploidy in order to try to improve success of IVF in older, infertile patients,” Professor Braude said. “These patients have no prior genetic risk but are trying to screen out any embryos that have a sufficient aneuploidy to result in failure of implantation, miscarriage, or a survivable single aneuploidy more commonly seen in older women, such as Down’s syndrome [trisomy 21]. Hence the use of the term ‘preimplantation genetic screening.’”

Prenatal genetic screening has been widely used, especially in the United States, in the belief that it must improve the odds in women who have a reduced chance of conception because of age.

Sjoerd Repping, associate professor in reproductive biology and director of the in vitro fertilization laboratory of the Center for Reproductive Medicine, Academic Medical Center, Amsterdam, and one of the researchers, said, “PGS is an expensive technique that is very frequently offered to women of advanced maternal age under the statement that it will increase pregnancy rates. The fact that the data shows that it does not—on the contrary, it decreases pregnancy rates—should be included in the counseling of these patients undergoing IVF treatment.”

Professor Braude agreed, “The key here is that the evidence just does not support the continued use of prenatal genetic screening for advanced maternal age.”

He added, “Despite the fact that we are the largest and most successful PGD unit in the country, having done over 400 collections with over 100 babies born healthy after testing for a variety of genetic conditions, we have never undertaken PGS as we have always had grave doubts over its efficacy.”

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