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      Lower chromosomal abnormality frequencies in miscarried conceptuses from frozen blastocyst transfers in ART

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          Abstract

          STUDY QUESTION

          Are blastocyst culture and cryopreservation in ART associated with chromosomal abnormalities in miscarried products of conception (POC)?

          SUMMARY ANSWER

          Frozen blastocyst transfer in women aged 35 years or older and frozen embryo transfer (ET) (including both cleavage-stage embryo and blastocyst) in women aged <35 years are associated with decreased frequencies of embryonic chromosomal abnormalities in miscarried POC.

          WHAT IS KNOWN ALREADY

          Blastocyst culture and embryo cryopreservation have been previously associated with favorable ART treatment outcomes and widely applied in clinical practice. However, the association between these embryo manipulation procedures and embryonic chromosomal abnormalities has not been evaluated to the best of our knowledge.

          STUDY DESIGN, SIZE, DURATION

          This retrospective study included a total of 720 patients who underwent IVF/ICSI, and the retained POC were obtained. A single-nucleotide polymorphism (SNP)-based chromosomal microarray analysis (CMA) of all miscarried conceptuses was performed.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          This study was based on the Clinical Reproductive Medicine Management System/Electronic Medical Record Cohort Database (CCRM/EMRCD) at our center. In total, 720 miscarried POCs were collected from patients undergoing ART (including fresh cleavage-stage ET, fresh blastocyst transfer, frozen cleavage-stage ET and frozen blastocyst transfer), and the incidences and profiles of cytogenetic abnormalities in the miscarried conceptuses were measured via SNP-based CMA.

          MAIN RESULTS AND THE ROLE OF CHANCE

          The chromosomal abnormality rate in POC varied from 33.7% to 66.7% among the different ET strategies. In the patients aged ≥35 years, frozen blastocyst transfer was significantly associated with a lower incidence of chromosomal aberrations in the POCs (adjusted odds ratio (aOR): 0.171 (95% CI: 0.040–0.738); P = 0.018) than fresh blastocyst transfer. In the patients aged <35 years, frozen ET was significantly associated with a lower incidence of chromosomal aberrations than fresh ET in both cleavage-stage ET cycles and blastocyst transfers cycles (aOR: 0.545 (0.338–0.879), P = 0.013; and aOR: 0.357 (0.175–0.730), P = 0.005, respectively). Trisomy was the most frequent abnormal embryonic karyotype in the different ET strategies, and its frequency significantly differed among strategies (P < 0.05).

          LIMITATIONS, REASONS FOR CAUTION

          This study was retrospectively designed, and we cannot draw any definite conclusions from our results regarding the adequate safety of embryo cryopreservation in ongoing pregnancy.

          WIDER IMPLICATIONS OF THE FINDINGS

          To our knowledge, this is the first study assessing the associations of ET strategies with the probability of miscarriage associated with embryonic chromosomal abnormalities. However, the underlying mechanism of these associations is unknown; this study may promote research concerning ET strategies and promote comprehensive consultations and recommendations for patients.

          STUDY FUNDING/COMPETING INTEREST(S)

          This work was supported by the Natural Science Foundation of China (Grant No.81571409), Science and Technology Research Project of Henan (Grant No. 172102310009) and Medical Science and Technology Research Project of Henan (Grant No. 201701005). The authors declare no competing interests.

          TRIAL REGISTRATION NUMBER

          N/A

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          Most cited references41

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          Chromosome instability is common in human cleavage-stage embryos.

          Chromosome instability is a hallmark of tumorigenesis. This study establishes that chromosome instability is also common during early human embryogenesis. A new array-based method allowed screening of genome-wide copy number and loss of heterozygosity in single cells. This revealed not only mosaicism for whole-chromosome aneuploidies and uniparental disomies in most cleavage-stage embryos but also frequent segmental deletions, duplications and amplifications that were reciprocal in sister blastomeres, implying the occurrence of breakage-fusion-bridge cycles. This explains the low human fecundity and identifies post-zygotic chromosome instability as a leading cause of constitutional chromosomal disorders.
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            Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome.

            The transfer of fresh embryos is generally preferred over the transfer of frozen embryos for in vitro fertilization (IVF), but some evidence suggests that frozen-embryo transfer may improve the live-birth rate and lower the rates of the ovarian hyperstimulation syndrome and pregnancy complications in women with the polycystic ovary syndrome.
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              • Record: found
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              Frozen versus fresh single blastocyst transfer in ovulatory women: a multicentre, randomised controlled trial

              Elective single embryo transfer (eSET) has been increasingly advocated, but concerns about the lower pregnancy rate after reducing the number of embryos transferred have encouraged transfer of multiple embryos. Extended embryo culture combined with electively freezing all embryos and undertaking a deferred frozen embryo transfer might increase pregnancy rate after eSET. We aimed to establish whether elective frozen single blastocyst transfer improved singleton livebirth rate compared with fresh single blastocyst transfer.
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                Author and article information

                Journal
                Human Reproduction
                Oxford University Press (OUP)
                0268-1161
                1460-2350
                April 01 2021
                March 18 2021
                December 30 2020
                April 01 2021
                March 18 2021
                December 30 2020
                : 36
                : 4
                : 1146-1156
                Affiliations
                [1 ]Center for Reproductive Medicine, Henan Province Key Laboratory of Reproduction and Genetics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
                [2 ]Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, 450052, China
                Article
                10.1093/humrep/deaa352
                d5ec35e5-fd30-4b21-b4b2-58a38f347fe9
                © 2020

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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