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

Gleicher, Norbert; Barad, David H.

doi:10.1007/s10815-012-9871-2

Cited by 38 publications

(32 citation statements)

References 41 publications

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“…These observations may at least partially explain why embryo morphology is only relatively poorly associated with embryo ploidy [16], and why the procedure of PGS so far has failed to improve IVF outcomes [17].…”

Section: Discussionmentioning

confidence: 99%

Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization

Kushnir

Barad

et al. 2014

PLoS ONE

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ContextMutations of the fragile X mental retardation 1 (FMR1) gene are associated with distinct ovarian aging patterns.ObjectiveTo confirm in human in vitro fertilization (IVF) that FMR1 affects outcomes, and to determine whether this reflects differences in ovarian aging between FMR1 mutations, egg/embryo quality or an effect on implantation.Design, Setting, PatientsIVF outcomes were investigated in a private infertility center in reference to patients' FMR1 mutations based on a normal range of CGGn = 26–34 and sub-genotypes high (CGGn>34) and low (CGG<26). The study included 3 distinct sections and study populations: (i) A generalized mixed-effects model of morphology (777 embryos, 168 IVF cycles, 125 infertile women at all ages) investigated whether embryo quality is associated with FMR1; (ii) 1041 embryos in 149 IVF cycles in presumed fertile women assessed whether the FMR1 gene is associated with aneuploidy; (iii) 352 infertile patients (< age 38; in 1st IVF cycles) and 179 donor-recipient cycles, assessed whether the FMR1 gene affects IVF pregnancy chances via oocyte/embryo quality or non-oocyte maternal factors.InterventionsStandardized IVF protocols.Main Outcome MeasuresMorphologic embryo quality, ploidy and pregnancy rates.Results(i) Embryo morphology was reduced in presence of a low FMR1 allele (P = 0.032). In absence of a low allele, the odds ratio (OR) of chance of good (vs. fair/poor) embryos was 1.637. (ii) FMR1 was not associated with aneuploidy, though aneuploidy increased with female age. (iii) Recipient pregnancy rates were neither associated with donor age or donor FMR1. In absence of a low FMR1 allele, OR of clinical pregnancy (vs. chemical or no pregnancy) was 2.244 in middle-aged infertility patients.ConclusionsA low FMR1 allele (CGG<26) is associated with significantly poorer morphologic embryo quality and pregnancy chance. As women age, low FMR1 alleles affect IVF pregnancy chances by reducing egg/embryo quality by mechanisms other than embryo aneuploidy.

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Section: Discussionmentioning

confidence: 99%

Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization

Kushnir

Barad

et al. 2014

PLoS ONE

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“…Although the newest PGS methodologies improve the accuracy of aneuploidy diagnosis when compared with older methods, investigations that examine how these new variables affect the target population of patients who would most benefit from PGS are lacking (Gleicher and Barad 2012).…”

Section: Karyotype the Couple Experiencing Rplmentioning

confidence: 99%

Genetic Considerations in Recurrent Pregnancy Loss

Hyde

Schust

2015

Cold Spring Harbor Perspectives in Medicine

116

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“…We, therefore, cautioned from uncritically accepting the notion that improvements in PGS#1 techniques and technologies, alone, would improve IVF outcomes [12]. …”

Section: Introductionmentioning

confidence: 99%

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

Gleicher

Kushnir

Barad

2014

Reprod Biol Endocrinol

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

Cited by 38 publications

References 41 publications

Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization

Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization

Genetic Considerations in Recurrent Pregnancy Loss

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

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