What next for preimplantation genetic screening (PGS)? A position statement from the ESHRE PGD Consortium steering committee 

Abstract

Since 2004, there have been 11 randomized controlled trials (RCTs) mainly for advanced maternal age (AMA), which have shown no benefit of performing preimplantation genetic screening (PGS). Ten of the RCTs have been performed at the cleavage stage and one at the blastocyst stage. It is probable that the high levels of chromosomal mosaicism at cleavage stages, which may result in the tested cell not being representative of the embryo, and the inability to examine all of the chromosomes using fluorescence in situ hybridization, have contributed to the lack of positive outcome from the RCTs. We suggest that future RCTs should examine alternative biopsy timing (polar body and/or trophectoderm biopsy), and should apply technologies that allow more comprehensive testing to include all chromosomes (microarray-based testing) to determine if PGS shows an improvement in delivery rate. Currently there is no evidence that routine PGS is beneficial for patients with AMA and conclusive data (RCTs) on repeated miscarriage, implantation failure and severe male factor are missing. To evaluate benefits of PGS, an ESHRE trial has recently been started on patients with AMA using polar body biopsy and array-comparative genomic hybridization, which should bring more information on this patient group in the near future.

A review of, and commentary on, the ongoing second clinical introduction of preimplantation genetic screening (PGS) to routine IVF practice

“…Other studies later reaffirmed the results reported by Mastenbroek et al [3][4][5][6]. Professional organizations followed by unequivocally concluding that PGS, at current practice levels, did not improve clinical IVF outcomes [7][8][9].…”

“…Published reviews in the literature are confirmatory [6,33,34]. PGS utilization to improve pregnancy and miscarriage rates, based on currently available data [1,2,7,9,29,30,35,36] should, therefore, only occur under study conditions, and with appropriate informed consents.…”

“…Following publication of the study by Mastenbroek et al [2], PGS#1 was, however, widely reassessed, resulting in authoritative statements that PGS#1 neither improved IVF pregnancy rates nor reduced miscarriages [7][8][9]. Astutely, those, however, were not blanket condemnations of the concept of PGS but left open the possibility that PGS might be improved, leading to better outcomes and, therefore, different conclusions about the utility of PGS.…”

“…An obvious first argument against current routine clinical utilization of PGS#2 is that authoritative bodies, at present, see no clinical value in PGS [7][8][9]. ESHRE's previously noted effort to set up a prospectively randomized multicenter study also suggests a healthy level of skepticism, and confirms PGS as an experimental procedure of no proven clinical effectiveness, yet.…”

Preimplantation genetic testing for aneuploidy: what technology should you use and what are the differences?

“…Following this report, other studies followed failing to demonstrate a benefit of PGS in terms of pregnancy outcome. Subsequently, multiple major professional societies including the American Society for Reproductive Medicine (ASRM), the American College of Obstetrics and Gynecology (ACOG), and the European Society of Human Reproduction and Embryology (ESHRE) all released formal opinions discouraging the general use of PGS [12][13][14].…”