A short summary of CHR’S involvement in PGS history


Verlinsky et al propose PGS via polar body biopsy [Preimplantation diagnosis of common aneuploidies by the first and second polar body FISH analysis. J Assist Reprod Genet 1998;15:285-289]. CHR, at that time located in Chicago, establishes a PGS laboratory.

Instead, laboratories introduce PGS 1.0, involving cleavage-stage blastomere biopsy and analysis by FISH of selected number (6-8) chromosomes. CHR starts questioning underlying hypothesis for PGS, and closes its PGS laboratory.


RCTs by Belgian investigators fail to demonstrate outcome benefits from PGS 1.0 [Staessen et al., Comparison of blastocyst transfer with and without genetic diagnosis for aneuploid screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod 2004;19(12)2849-2858].


Reanalysis of above noted Belgian data in 2005, suggested to CHR investigator that PGS, not only does not improve IVF outcomes, but may actually have adverse effects on PGS outcomes in older patients but a manuscript, authored by Drs. Gleicher and Barad, is repeatedly rejected by medical journals.


Investigators from the Netherlands fail to demonstrate outcome benefits in IVF from PGS 1.0 [Twisk et al., Preimplantation genetic screening for abnormal number of chromosomes (aneuploidies) in in vitro fertilization or intracytoplasmic sperm injection. Cochrane Database Syst Rev 2006;21(1):3-21].


Same Dutch investigators report in prestigious New England Journal of Medicine that PGS, indeed, negatively affects IVF outcomes in older women. [Mastenbroek et al., In vitro fertilization with preimplantation genetic screening 2007 Jul 5;357(1):9-17].

The Dutch paper gets aggressively attacked by proponent of PGS. [Cohen J et al., Removal of 2 cells from cleavage stage embryos is likely to reduce the efficacy of chromosomal tests that are used to enhance implantation rates. Fertil Steril 2007;87(3):496-503].


After publication of the Dutch paper by the prestigious New England Journal of Medicine, Fertility & Sterility recalls and publishes the above noted CHR paper [Gleicher et al., Preimplantation genetic screening: “established” and ready for prime time. 2008;89(4):780-788], which had suggested the same negative outcome effects from PGS on IVF as the Dutch study.

ASRM declares PG 1.0 clinically ineffective in improving IVF outcomes. [Practice Committee of the American Society for Reproductive Medicine, Preimplantation genetic testing: a Practice Committee opinion. Fertil Steril 2008; 90:S136-143]

The first recommendation for use of comprehensive chromosome screening with microarray and CGH in place of PGS 1.0. The concept of the new PG2.0 is born [Wells et al. Use of comprehensive chromosomal screening for embryo assessment: microarray and CGH. Mol Hum Reprod 2008; 14(12):703-710]

PGS 2.0 takes over, offering 23-chromosome screening through a variety of platforms, all utilizing trophectoderm biopsy at blastocyst stage (5-7 cells on average). By 2016, ca. 20% of all U.S. IVF cycles utilized PGS 2.0.


CHR for the first time transfers an embryo, after PGS reported to be aneuploid.


The patient delivers chromosomally healthy child. CHR from this moment on attempts to publish this experience; but manuscripts are being rejected by multiple journals, even as healthy births multiply.


CHR publicly announces a voluntary new transfer policy for women with no euploid embryos (as an experimental procedure with an appropriate informed consent) for embryos judged “aneuploid” after 2nd healthy birth, and forms public reporting consortium with 2 other IVF programs in New York City. An updated manuscript, including both cases, continues to be rejected by multiple medical journals.


OCTOBER First public acceptances in print of Consortium data as abstract at the Annual ASRM Meeting in Baltimore, Maryland, including 3 healthy pregnancies after 7 transfers. By time of oral presentation at meeting itself, Norbert Gleicher, MD, CHR’s Medical Director and Chief Scientist, reports 5 healthy pregnancies in 8 transfer attempts and 1 chemical pregnancy. Abstract is published by Fertility & Sterility in October.

NOVEMBER Italian group from Rome reports 6 healthy births after 18 transfers of what they described as “mosaic” embryos as research letter in the New England Journal of Medicine.


Other groups around the world start reporting normal births after transfers of aneuploid/mosaic embryos.

Still, not a single properly conducted study has been able to demonstrate IVF outcome benefits from PGS. A number of CHR studies and papers from other prominent centers in the U.S., indeed, demonstrate the opposite [Kushnir et al. Effectiveness of in vitro fertilization with preimplantation genetic screening: a reanalysis of United States assisted reproductive technology data 2011-2012, Fertil Steril 2016;106(1):75-79; Barad et al. Preimplantation genetic screening effects on donor egg-recipient cycles. Am J Obstet Gynecol; in press; Murugappan et al., Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss. Hum Reprod 2016; 31(8):1668-1674]. At least in poor prognosis patients, PGS 2.0, like PGS 1.0 before, appears to harm IVF outcomes.

JULY PGDIS suddenly issues new guidelines for PGS reporting, switching from bi-nominal reporting of euploid-normal and aneuploid-abnormal to tri-phasic reporting of euploid-normal, mosaic and aneuploid-abnormal, acknowledging that at least selected “mosaic” embryos may be transferred. Concomitantly, PGS receives a new name, preimplantation genetic testing from aneuploidy (PGT-A).


The CURRENT STATUS of the debate is still unresolved, though even most proponents of PGS no longer claim that PGS/PGT-A improves clinical pregnancy and live birth rates in IVF. The new rationale for the procedure given is that “it shortens time to pregnancy and reduces miscarriages.” In the opinion of CHR, both of these new claims lack any evidentiary support and are just as misleading as earlier claims by proponents of PGS.

OCTOBER The GOOD NEWS is that close to 100 healthy babies have so far been born worldwide from transfers of embryos, which until July 2016, likely, would have been discarded. The BAD NEWS, however, is that, based on the new PGDIS guidelines, many IVF centers still dispose of perfectly normal embryos in large numbers and/or simply refuse to transfer them.

It, therefore, appears high time for the ASRM to, finally, forcefully speak out against utilization of PGS/PGT-A as an add-on to routine IVF, and for the Food and Drug Administration (FDA) to intervene on a regulatory level.

This is a part of the October 2017 VOICE.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.