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      Definition, diagnostic and therapeutic options in recurrent implantation failure: an international survey of clinicians and embryologists

      1 , 2 , 3 , 4 , 4
      Human Reproduction
      Oxford University Press (OUP)

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          Abstract

          STUDY QUESTION

          What is the global variability in recurrent implantation failure (RIF) definition, investigation and therapy, currently offered to patients undergoing IVF?

          SUMAMRY ANSWER

          Definitions, diagnostic investigations and treatments offered to RIF patients differ widely amongst assisted reproduction healthcare professionals and clinical guidelines on RIF are urgently needed.

          WHAT IS KNOWN ALREADY

          RIF affects around 10% of patients undergoing IVF worldwide. There is no consensus on the definition of RIF, its diagnostic investigations or the therapeutic options, which leads to inconsistencies in clinical practice.

          STUDY DESIGN, SIZE, DURATION

          A cross-sectional study of clinicians and embryologists was conducted between May and June 2020. The survey included 43 questions aimed at understanding participants’ background and their current practice with regards to defining, investigating and managing RIF. The questions were designed by the European Society of Human Reproduction and Embryology (ESHRE) Special Interest Group (SIG) on implantation and early pregnancy following three consensus meetings.

          PARTICIPANTS/MATERIALS, SETTING, METHODS

          A total of 8579 ESHRE members from 6916 IVF centers were invited to participate using two global email calls based on their pre-specified interest in implantation and early pregnancy. SurveyMonkey and SPSS were used for data collection and analysis, respectively. Furthermore, differences were reported in the answers of European and non-European professionals, as well as between public and private settings and among clinicians clustered according to the average number of RIF patients treated per year.

          MAIN RESULTS AND THE ROLE OF CHANCE

          The final data set included 735 clinicians and 300 embryologist or IVF-biologists. The majority defines RIF based on the number of failed embryo transfers (ETs) with the most common threshold adopted being three ETs both fresh and frozen. More than two-thirds take lifestyle factors into account, mainly drugs, smoking and BMI. The highest consensus on which diagnostic investigations should be performed was reached for anatomical malformations and gynecological aspects focusing on hydrosalpinx, Asherman’s syndrome, endometrial thickness and endometriosis. Concerning treatment of RIF patients, the highest consensus was reached for preconceptional therapies, including BMI adjustment, smoking and endometritis followed by therapies during IVF procedures.

          LIMITATIONS, REASONS FOR CAUTION

          The response rate was relatively low, but comparable to other surveys.

          WIDER IMPLICATIONS OF THE FINDINGS

          A consensus on definition, diagnosis and treatment of RIF would help to reduce costly, time-consuming and poorly validated approaches.

          STUDY FUNDING/COMPETING INTEREST(S)

          No external funding was used. B.T. received support from Bayer for Clinical trials concerning endometriosis and Ferring for clinical trials concerning ovarian stimulation. She received reimbursement for travel expenses from Astropharm, Ferring. Dr Kade and is a shareholder of Reprognostics. She is a board member of the Austrian Society for Obstetrics and Gynecology (OEGGG), the associate head of the ‘Reproduktionsmedizinische Zentren Baden-Württemberg’ (RZBW), a member of guideline group of the German Society for Obstetrics and Gynecology (DGGG) and an editorial board member of the following journals: American Journal of Reproductive Immunology (AJRI), Archives of Gynecology and Obstetrics. All the other authors declare no conflict of interest.

          TRIAL REGISTRATION NUMBER

          N/A.

          Related collections

          Most cited references46

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          The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.

          Many variations in oocyte and embryo grading make inter-laboratory comparisons extremely difficult. This paper reports the proceedings of an international consensus meeting on oocyte and embryo morphology assessment. Background presentations about current practice were given. The expert panel developed a set of consensus points to define the minimum criteria for oocyte and embryo morphology assessment. It is expected that the definition of common terminology and standardization of laboratory practice related to embryo morphology assessment will result in more effective comparisons of treatment outcomes. This document is intended to be referenced as a global consensus to allow standardized reporting of the minimum data set required for the accurate description of embryo development.
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            The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening.

            To determine the relationship between the age of the female partner and the prevalence and nature of human embryonic aneuploidy. Retrospective. Academic. Trophectoderm biopsies. Comprehensive chromosomal screening performed on patients with blastocysts available for biopsy. Evaluation of the impact of maternal age on the prevalence of aneuploidy, the probability of having no euploid embryos within a cohort, the complexity of aneuploidy as gauged by the number of aneuploid chromosomes, and the trisomy/monosomy ratio. Aneuploidy increased predictably after 26 years of age. A slightly increased prevalence was noted at younger ages, with >40% aneuploidy in women 23 years and under. The no euploid embryo rate was lowest (2% to 6%) in women aged 26 to 37, was 33% at age 42, and was 53% at age 44. Among the biopsies with aneuploidy, 64% involved a single chromosome, 20% two chromosomes, and 16% three chromosomes, with the proportion of more complex aneuploidy increasing with age. Finally, the trisomy/monosomy ratio approximated 1 and increased minimally with age. The lowest risk for embryonic aneuploidy was between ages 26 and 30. Both younger and older age groups had higher rates of aneuploidy and an increased risk for more complex aneuploidies. The overall risk did not measurably change after age 43. Trisomies and monosomies are equally prevalent. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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              Culture and transfer of human blastocysts.

              The transfer of the human embryo at the blastocyst stage during an in-vitro fertilization procedure is a way of increasing implantation rates. This, in turn, means that significantly fewer embryos are required to be transferred in order to establish a successful pregnancy. The result of this is that high order multiple gestations are eliminated, while maintaining high pregnancy rates, in in-vitro fertilization.
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                Author and article information

                Journal
                Human Reproduction
                Oxford University Press (OUP)
                0268-1161
                1460-2350
                February 01 2021
                January 25 2021
                December 12 2020
                February 01 2021
                January 25 2021
                December 12 2020
                : 36
                : 2
                : 305-317
                Affiliations
                [1 ]Clinica Valle Giulia, Genera Center for Reproductive Medicine, Rome, Italy
                [2 ]Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
                [3 ]ESHRE Central Office, Grimbergen, Belgium
                [4 ]Department of Gynecological Endocrinology and Reproductive Medicine, Medical University Innsbruck, Innsbruck, Austria
                Article
                10.1093/humrep/deaa317
                b6adbc24-a0a6-4198-886b-6aa26bc42533
                © 2020

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

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