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      Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review

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          Abstract

          Only a few years ago the American Society of Assisted Reproductive Medicine (ASRM), the European Society for Human Reproduction and Embryology (ESHRE) and the British Fertility Society declared preimplantation genetic screening (PGS#1) ineffective in improving in vitro fertilization (IVF) pregnancy rates and in reducing miscarriage rates. A presumably upgraded form of the procedure (PGS#2) has recently been reintroduced, and is here assessed in a systematic review. PGS#2 in comparison to PGS#1 is characterized by: (i) trophectoderm biopsy on day 5/6 embryos in place of day-3 embryo biopsy; and (ii) fluorescence in-situ hybridization (FISH) of limited chromosome numbers is replaced by techniques, allowing aneuploidy assessments of all 24 chromosome pairs. Reviewing the literature, we were unable to identify properly conducted prospective clinical trials in which IVF outcomes were assessed based on “intent to treat”. Whether PGS#2 improves IVF outcomes can, therefore, not be determined. Reassessments of data, alleged to support the efficacy of PGS#2, indeed, suggest the opposite. Like with PGS#1, the introduction of PGS#2 into unrestricted IVF practice again appears premature, and threatens to repeat the PGS#1 experience, when thousands of women experienced reductions in IVF pregnancy chances, while expecting improvements. PGS#2 is an unproven and still experimental procedure, which, until evidence suggests otherwise, should only be offered under study conditions, and with appropriate informed consents.

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          Diminished effect of maternal age on implantation after preimplantation genetic diagnosis with array comparative genomic hybridization.

          Brian Kaplan, Mark Surrey, Jamie A. Grifo … (2013)
          To assess the relationship between maternal age, chromosome abnormality, implantation, and pregnancy loss. Multicenter retrospective study. IVF centers in the United States. IVF patients undergoing chromosome screening. Embryo biopsy on day 3 or day 5/6 with preimplantation genetic diagnosis (PGD) by array comparative genomic hybridization. Aneuploidy, implantation, pregnancy, and loss rates. Aneuploidy rates increased with maternal age from 53% to 93% for day 3 biopsies and from 32% to 85% for blastocyst biopsies. Implantation rates for euploid embryos for ages 42 years old had implantation rates of 23.3% (day 3), 27.7% (day 5/6), and the pregnancy rate with day 3 biopsy was 9.3% and with day 5 biopsy 10.3%. Selective transfer of euploid embryos showed that implantation and pregnancy rates were not significantly different between reproductively younger and older patients up to age 42 years. Some patients who start an IVF cycle planning to have chromosome screening do not have euploid embryos available for transfer, a situation that increases with advancing maternal age. Mounting data suggests that the dramatic decline in IVF treatment success rates with female age is primarily caused by aneuploidy. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
          Article 0 comments Cited 80 times – based on 0 reviews     Review now
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            Single blastocyst transfer: a prospective randomized trial.

            Joanne Gardner, Eric Surrey, William B. Schoolcraft … (2004)
            To determine the efficacy of single blastocyst transfer. Prospective randomized trial. Private assisted reproductive technology unit. Forty-eight women undergoing IVF-embryo transfer with day 3 FSH 12 mm in diameter on day of hCG administration. Embryo culture to the blastocyst stage in sequential media G1/G2 followed by transfer of either one or two blastocysts. Implantation rate, ongoing pregnancy rate, and twinning. The transfer of a single blastocyst resulted in an implantation and ongoing pregnancy rate of 60.9% with no twins. The transfer of two blastocysts resulted in an implantation rate of 56%, an ongoing pregnancy rate of 76% with a 47.4% incidence of twins. Single blastocyst transfer is an effective method of eliminating multiple births while maintaining high pregnancy rates in this selected group of patients.
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              The ESHRE PGD Consortium: 10 years of data collection.

              J Harper, L Wilton, J Traeger-Synodinos … (2015)
              Since it was established in 1997, the ESHRE PGD Consortium has been collecting data from international preimplantation genetic diagnosis (PGD) centres. Ten papers have been published, including data from January 1997 to December 2007. The data collection originally used a hard-copy format, then an excel database and finally a FileMaker Pro database. The indications are divided into five categories: PGD for chromosome abnormalities, sexing for X-linked disease, PGD for single gene defects, preimplantation genetic screening (PGS) and PGD for social sexing. The main end-points are pregnancy outcome and follow-up of deliveries. In data collection I, 16 centres contributed data, which increased to 57 centres by data X (average of 39 centres per data collection). These centres contributed data on over 27 000 cycles that reached oocyte retrieval. Of these cycles, 61% were for aneuploidy screening, 17% for single gene disorders, 16% for chromosomal abnormalities, 4% for sexing of X-linked disease and 2% for social sexing. Cumulatively, 5187 clinical pregnancies gave rise to 4140 deliveries and 5135 newborns (singletons: 3182, twins: 921, triplets: 37). In this paper, we present an overview of the first 10 years of PGD data, highlighting trends. These include the introduction of laser-assisted biopsy, an increase in polar body and trophectoderm biopsy, new strategies, methodologies and technologies for diagnosis, including recently arrays, and the more frequent use of freezing biopsied embryos. The Consortium data reports represent a valuable resource for information about the practice of PGD.
              Article 0 comments Cited 63 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Norbert Gleicher
                Vitaly A Kushnir
                David H Barad
                Journal
                Journal ID (nlm-ta): Reprod Biol Endocrinol
                Journal ID (iso-abbrev): Reprod. Biol. Endocrinol
                Title: Reproductive Biology and Endocrinology : RB&E
                Publisher: BioMed Central
                ISSN (Electronic): 1477-7827
                Publication date Collection: 2014
                Publication date (Electronic): 15 March 2014
                Volume: 12
                Page: 22
                Affiliations
                [1 ]The Center for Human Reproduction (CHR), New York, USA
                [2 ]The Foundation for Reproductive Medicine, New York, USA
                Article
                Publisher ID: 1477-7827-12-22
                DOI: 10.1186/1477-7827-12-22
                PMC ID: 3986466
                PubMed ID: 24628895
                SO-VID: 22ee3944-70c1-4e24-8497-3ef83abcf436
                Copyright © Copyright © 2014 Gleicher et al.; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 17 January 2014
                Date accepted : 9 March 2014
                Categories
                Subject: Review

                ScienceOpen disciplines: Human biology
                Keywords: preimplantation genetic diagnosis (pgs),assisted reproduction (art),in vitro fertilization (ivf),trophectoderm biopsy,blastocyst stage embryo transfer
                Data availability:
                ScienceOpen disciplines: Human biology
                Keywords: preimplantation genetic diagnosis (pgs), assisted reproduction (art), in vitro fertilization (ivf), trophectoderm biopsy, blastocyst stage embryo transfer

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