Worldwide live births following the transfer of chromosomally “Abnormal” embryos after PGT/A: results of a worldwide web-based survey

Patrizio, Pasquale; Shoham, Gon; Shoham, Zeev; Leong, Milton; Barad, David H.; Gleicher, Norbert

doi:10.1007/s10815-019-01510-0

Cited by 70 publications

(57 citation statements)

References 19 publications

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“…Overall, PGT‐A has very limited use in the Nordic countries when viewed as a proportion of the national ART activities: in 2014 the total number of in vitro fertilization and frozen/thawed embryo transfer cycles in these countries was 54 653 . This is in striking contrast to the situation in many other countries, where a large proportion of in vitro fertilization cycles are performed with PGT‐A . The development of the diagnostic techniques such as complete genome sequencing, enables more genetic information to be uncovered than the specific genetic problem requiring PGT .…”

Section: Discussionmentioning

confidence: 84%

Preimplantation genetic testing legislation and accessibility in the Nordic countries

Hreinsson¹,

Lundin

Iwarsson

et al. 2020

Acta Obstet Gynecol Scand

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Introduction:Assisted reproduction technologies are being rapidly developed and implementation of preimplantation genetic testing (PGT) has allowed patients with genetic disorders to initiate pregnancies while minimizing or eliminating the risk of transmitting these disorders to their offspring. Testing for numeric chromosomal anomalies has been proposed as a way to increase efficacy in assisted reproduction; however, this remains disputed. Legislation is lagging behind the rapid developments in this field. Material and methods:We conducted a structured online survey of legislation and accessibility to preimplantation genetic testing in the Nordic countries to compare the regulation and uptake of this technique. The survey was designed and answered by the authors. Results: Key elements in the regulation of preimplantation testing for monogenic disorders and structural rearrangements are similar in the Nordic countries, although accessibility varies since only Denmark, Finland, and Sweden have national clinics offering treatment. In addition, Denmark and Finland have private clinics offering PGT. Regulation is the most stringent in Norway where a national board evaluates all couples seeking treatment. Treatment volumes vary between the Nordic countries, with Norway and Finland having lowest treatment numbers. Preimplantation genetic testing for aneuploidy in the embryo varies between the Nordic countries: Finland and Iceland allow this form of treatment, Denmark and Sweden offer it only in the form of a research protocol, and Norway does not allow it at all. Therefore the number of treatment cycles involving testing for embryo aneuploidy are lower in the Nordic countries than in other countries where this treatment option is more common. Conclusions: Science needs to inform politics regarding the rapidly evolving field of reproductive medicine and we recommend harmonization of legislation and accessibility between the Nordic countries. | 717 HREINSSON Et al.

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Section: Discussionmentioning

confidence: 84%

Preimplantation genetic testing legislation and accessibility in the Nordic countries

Hreinsson¹,

Lundin

Iwarsson

et al. 2020

Acta Obstet Gynecol Scand

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“…Loss of false-positively diagnosed embryos is more significant in poorer-prognosis patients with small embryo numbers. (iii) Hundreds of chromosomally healthy births following transfer of, by PGT-A reported to be chromosomal-abnormal embryos ("mosaic" and "aneuploid"), have been reported [12], confirming the discarding of embryos with considerable normal pregnancy potential after false-positive PGT-A diagnoses, recently also pointed out by Paulson [5]. (iv) Demonstration that aneuploid embryos have the capacity to self-correct downstream from the blastocyst stage, was first reported in the mouse [13] and, recently confirmed in the human embryonic cell lineage and in human gastruloids [14].…”

Section: Summarizing the Argumentmentioning

confidence: 99%

“…compared to euploid transfers, transfer of mosaic or mosaic segmental embryos do give rise to healthy pregnancies but may be associated with reduced implantation and higher miscarriage rates," is unreferenced and in view of recent publications, likely, inaccurate. Unexpectedly high pregnancy/live births of approximately 50% and equally unexpected low miscarriage rates have been reported worldwide following transfers of allegedly chromosomal-abnormal embryos, designated by PGT-A as mosaic or aneuploid-abnormal [12,[20][21][22][23][24][25][26]. Moreover, over 400 chromosomal-healthy offspring have so-far been delivered worldwide following such transfers [12].…”

Section: Transfer Outcomes From Mosaic Embryosmentioning

confidence: 99%

“…Unexpectedly high pregnancy/live births of approximately 50% and equally unexpected low miscarriage rates have been reported worldwide following transfers of allegedly chromosomal-abnormal embryos, designated by PGT-A as mosaic or aneuploid-abnormal [12,[20][21][22][23][24][25][26]. Moreover, over 400 chromosomal-healthy offspring have so-far been delivered worldwide following such transfers [12]. Whether transfer of (under PGDIS -definition) "mosaic" embryos, is at all associated with reduced implantation and/or increased miscarriage rates, therefore, deserves further study and currently available data clearly dispute these propositions.…”

Section: Transfer Outcomes From Mosaic Embryosmentioning

confidence: 99%

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The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A

Gleicher

Albertini

Barad

et al. 2020

Reprod Biol Endocrinol

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Background: A recently published Position Statement (PS) by the Preimplantation Genetics Diagnosis International Society (PGDIS) regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF) contained inaccuracies and misrepresentations. Because opinions issued by the PGDIS have since 2016 determined worldwide IVF practice, corrections appear of importance. Methods: The International Do No Harm Group in IVF (IDNHG-IVF) is a spontaneously coalesced body of international investigators, concerned with increasing utilization of add-ons to IVF. It is responsible for the presented consensus statement, which as a final document was reached after review of the pertinent literature and again revised after the recent publication of the STAR trial and related commentaries. Results: In contrast to the PGDIA-PS, we recommend restrictions to the increasing, and by IVF centers now often even mandated, utilization of PGT-A in IVF cycles. While PGT-A has been proposed as a tool for achieving enhanced singleton livebirth outcomes through embryo selection, continued false-positive rates and increasing evidence for embryonic self-correction downstream from the testing stage, has led IDNHG-IVF to conclude that currently available data are insufficient to impose overreaching recommendations for PGT-A utilization. Discussion: Here presented consensus offers an alternative to the 2019 PGDIS position statement regarding utilization of preimplantation genetic testing for aneuploidy (PGT-A) in association with in vitro fertilization (IVF). Mindful of what appears to offer best outcomes for patients, and in full consideration of patient autonomy, here presented opinion is based on best available evidence, with the goal of improving safety and efficacy of IVF and minimizing wastage of embryos with potential for healthy births. Conclusions: As the PGDIS never suggested restrictions on clinical utilization of PGT-A in IVF, here presented rebuttal represents an act of self-regulation by parts of the IVF community in attempts to control increasing utilization of different unproven recent add-ons to IVF.

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“…Comprehensive chromosome screening can be highly predictive of the reproductive potential of human embryos . However, the true impact on the cumulative pregnancy rate is not yet fully known, as some discarded aneuploid embryos do have the potential to give rise to healthy babies . Routine use of PGT‐A in infertility treatment is therefore questioned and a subject of intense discussion …”

Section: Introductionmentioning

confidence: 99%

Preimplantation genetic testing practices in the Nordic countries

Hreinsson¹,

Iwarsson

Hanson

et al. 2020

Acta Obstet Gynecol Scand

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Introduction: Preimplantation genetic testing (PGT) is growing in importance and volume internationally. International societies such as the European Society for Human Reproduction and Embryology compile international results and these data are published in scientific journals. We present the first compilation of practices, quality measuress and outcome data from Nordic clinics performing PGT. Material and methods: We conducted a structured online survey of PGT practices in the Nordic countries to compare clinical and laboratory techniques, outcomes and quality measures applied in Nordic clinics. The survey was designed by the authors and answered by the authors and members of the study group. The outcome data represents results from 2018. Results and details were clarified through iteration with responding clinics while maintaining anonymity. Response rate in the study was 80%, with 8 of 10 clinics performing PGT responding. Results: Most of the PGT cycles in the Nordic countries are funded through the public healthcare system with University Hospitals performing the majority of treatments, 716/848, or 84.4%, of oocyte retrievals in this dataset. The genetic analyses are in five cases performed by the affiliated local genetic laboratory, and the remaining three consult with large international private enterprise laboratories. Genetic counseling is widely used. Results in the Nordic clinics compare well with international data. Systematic quality control procedures are in place and the larger clinics and laboratories utilize ISO certification or accreditation in the quality management. Automatic witnessing with detailed electronic documentation of laboratory processes is not utilized in the responding clinics, although a majority uses manual witnessing procedures in the laboratory. The outcome after PGT in terms of clinical pregnancy per transfer is around 40% per embryo transfer and compares well with international data. Treatments offered FET PGT-M OP for PGT-M OPRs (95% CI) for PGT-M FET PGT-SR OP for PGT-SR OPRs (95% CI) for PGT-SR FET PGT-A OP for PGT-A OPRs (95% CI) for PGT-A Clinic 1 PGT-M/SR/A 5 3 60% (22-88) 4 3 75% (28-95) 25 12 48% (30-67) Clinic 2 PGT-M/SR 32 10 31% (18-49) 8 4 50% (21-79) 0 Clinic 3 PGT-M/SR a a a 163 57 35% (28-43) 0 Clinic 4 PGT-M/SR/A 5 2 40% (12-78) 5 2 40% (12-78) 27 8 30% (16-49) Clinic 5 PGT-M/SR 107 41 38% (30-48) 19 8 42% (23-64) 0 Clinic 6 PGT-M/SR/A 20 8 40% (22-62) 18 8 44% (24-67) 4 0 0 Clinic 7 PGT-A 0 0 18 12 67% (43-84) Clinic 8 PGT-M/SR 56 18 32% (21-45) 52 14 27% (17-40) 0Note: In PGT-SR chromosomal status is taken into account when selecting embryos for transfer even if the clinic otherwise does not offer PGT-A.

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Worldwide live births following the transfer of chromosomally “Abnormal” embryos after PGT/A: results of a worldwide web-based survey

Cited by 70 publications

References 19 publications

Preimplantation genetic testing legislation and accessibility in the Nordic countries

Preimplantation genetic testing legislation and accessibility in the Nordic countries

The 2019 PGDIS position statement on transfer of mosaic embryos within a context of new information on PGT-A

Preimplantation genetic testing practices in the Nordic countries

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