Pre-implantation genetic screening reduces both ongoing pregnancy and live birth rates in over 35s

The research is published simultaneously in the New England Journal of Medicine*. Sebastiaan Mastenbroek, M.Sc, from the Centre for Reproductive Medicine of the Academic Medical Centre of the University of Amsterdam, The Netherlands, said that the results of his team’s research suggested that PGS should not be carried out routinely in women of advanced maternal age.

In a randomised double-blind trial, the team compared three cycles of IVF with and without PGS in women from35 to 41 years of age. Of the 408 women, 206 of whom were given PGS and 202 were not, the ongoing pregnancy rate was considerably lower in the PGS group than in those who did not have PGS. “We found that, at 12 weeks, 52 or 25% of the women in the PGS group were pregnant, whereas 74 or 37% of the control group had an ongoing pregnancy”, said Mr. Mastenbroek. “And the women in the PGS group also had a significantly lower live birth rate – 49 or 24% as opposed to 71 or 35% of the controls.”

The investigators believe that there may be a number of explanations for the failure of PGS to improve IVF outcomes in older women. “It is possible that the biopsy of a cell from an early embryo on day 3 after conception hampers the potential of an embryo to successfully implant”, said Mr. Mastenbroek, “though the effect of biopsy alone on pregnancy rates has not been studied.”

Furthermore, say the investigators, the limitation on the number of chromosomes that can be analysed could lead to the transfer of embryos that appear normal but are in fact abnormal for one or more chromosomes not tested. Finally, many embryos resulting from IVF may be mosaic, where a single cell does not properly reflect the chromosomal composition of the whole, so that chromosomal analysis may not be representative of the entire embryo.

PGS is a relatively new technique that is in increasing use in IVF centres around the world. In 2003, more than 1700 IVF cycles with PGS for various indications were reported to the ESHRE preimplantation genetic diagnosis (ESHRE-PGD) consortium. This figure under-estimates the total number of IVF/PGD cycles, since only 50 centres worldwide reported their data to the consortium. “In a recent survey of 415 assisted reproductive technology clinics in the US, 186 respondents (45%) reported that they had performed a total of 2197 cycles of PGS in 2005”, said Mr. Mastenbroek.

The investigators are currently following up their work by investigating why PGS does not work. Even though evidence underpinning the effectiveness of PGS was lacking until now, patients as well as doctors were attracted to this technique. The idea of screening embryos for chromosomal abnormalities to increase live birth rates in IVF is very plausible, and women of advanced maternal age are willing to undergo any technique that may provide them with a baby”, said Mr. Mastenbroek.

“Our study was limited to older women undergoing PGS. We believe that our findings imply that the efficacy of the technique also needs to be investigated in other groups of women who are offered PGS, such as those who suffer recurrent miscarriage or repeated failure of IVF, since evidence for a benefit of PGS in these groups of women is currently still lacking”, he said.