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      Does time-lapse imaging have favorable results for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization? A meta-analysis and systematic review of randomized controlled trials

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          Abstract

          Objective

          The present study aimed to undertake a review of available evidence assessing whether time-lapse imaging (TLI) has favorable outcomes for embryo incubation and selection compared with conventional methods in clinical in vitro fertilization (IVF).

          Methods

          Using PubMed, EMBASE, Cochrane library and ClinicalTrial.gov up to February 2017 to search for randomized controlled trials (RCTs) comparing TLI versus conventional methods. Both studies randomized women and oocytes were included. For studies randomized women, the primary outcomes were live birth and ongoing pregnancy, the secondary outcomes were clinical pregnancy and miscarriage; for studies randomized oocytes, the primary outcome was blastocyst rate, the secondary outcome was good quality embryo on Day 2/3. Subgroup analysis was conducted based on different incubation and embryo selection between groups.

          Results

          Ten RCTs were included, four randomized oocytes and six randomized women. For oocyte-based review, the pool-analysis observed no significant difference between TLI group and control group for blastocyst rate [relative risk (RR) 1.08, 95% CI 0.94–1.25, I2 = 0%, two studies, including 1154 embryos]. The quality of evidence was moderate for all outcomes in oocyte-based review. For woman-based review, only one study provided live birth rate (RR 1,23, 95% CI 1.06–1.44,I2 N/A, one study, including 842 women), the pooled result showed no significant difference in ongoing pregnancy rate (RR 1.04, 95% CI 0.80–1.36, I2 = 59%, four studies, including 1403 women) between two groups. The quality of the evidence was low or very low for all outcomes in woman-based review.

          Conclusions

          Currently there is insufficient evidence to support that TLI is superior to conventional methods for human embryo incubation and selection. In consideration of the limitations and flaws of included studies, more well designed RCTs are still in need to comprehensively evaluate the effectiveness of clinical TLI use.

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          Most cited references44

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          Non-invasive imaging of human embryos before embryonic genome activation predicts development to the blastocyst stage.

          Connie Wong, Kevin E. Loewke, Nancy L. Bossert … (2010)
          We report studies of preimplantation human embryo development that correlate time-lapse image analysis and gene expression profiling. By examining a large set of zygotes from in vitro fertilization (IVF), we find that success in progression to the blastocyst stage can be predicted with >93% sensitivity and specificity by measuring three dynamic, noninvasive imaging parameters by day 2 after fertilization, before embryonic genome activation (EGA). These parameters can be reliably monitored by automated image analysis, confirming that successful development follows a set of carefully orchestrated and predictable events. Moreover, we show that imaging phenotypes reflect molecular programs of the embryo and of individual blastomeres. Single-cell gene expression analysis reveals that blastomeres develop cell autonomously, with some cells advancing to EGA and others arresting. These studies indicate that success and failure in human embryo development is largely determined before EGA. Our methods and algorithms may provide an approach for early diagnosis of embryo potential in assisted reproduction.
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            Assisted reproductive technology in Europe, 2009: results generated from European registers by ESHRE.

            Marianne Andersen, J Castilla, V Goossens … (2013)
            The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.
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              Embryo incubation and selection in a time-lapse monitoring system improves pregnancy outcome compared with a standard incubator: a retrospective cohort study.

              Marcos Meseguer, Irene Rubio, Maria Eduarda Cruz … (2012)
              To quantify the effect on reproductive outcome of culturing and selecting embryos using a novel time-lapse monitoring system (TMS). Retrospective observational cohort study. University-affiliated private center. Donation and autologous intracytoplasmic sperm injection (ICSI) cycles from ten IVF clinics using similar procedures, cultured in TMS (n = 1,390) or in a standard incubator (SI; n = 5,915). None. Clinical pregnancy rate confirmed by ultrasound in week 7. A logistic regression analysis, which included all significant confounding factors, was used to evaluate the effect of culturing and selecting embryos with the use of TMS. Comparing clinical pregnancy rates per oocyte retrieval with TMS and SI treatments gave a crude effect of odds ratio [OR] 1.190 (95% confidence interval [CI] 1.058-1.337). Oocyte source, maternal age, day of transfer, and number of retrieved oocytes were identified as significant confounding factors. After accounting for confounding factors, the effect of TMS culture was OR 1.201 (95% CI 1.059-1.363). Limiting analysis to treatments with embryo transfer and including number of transferred embryos as a confounding factor likewise gave a significant effect of TMS with OR 1.157 (95% CI 1.018-1.315). Analysis of retrospective data indicated that culturing and selecting embryos by TMS significantly improved the relative probability of clinical pregnancy (+20.1% per oocyte retrieval, +15.7% per embryo transfer). The elevated clinical pregnancy rate was attributed to a combination of stable culture conditions and the use of morphokinetic parameters for embryo selection. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Joël R. Drevet: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 1 June 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 6
                Electronic Location Identifier: e0178720
                Affiliations
                [1 ]Reproductive Center, Guangdong Women and Children Hospital, Guangzhou, China
                [2 ]Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China
                [3 ]Department of Emergency, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
                [4 ]School of Traditional Chinese Medicine, Jinan University, Guangzhou, China
                Universite Blaise Pascal, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MC FL.

                • Data curation: MC SW.

                • Formal analysis: MC SW JH.

                • Investigation: MC SW.

                • Methodology: MC SW JH.

                • Project administration: FL.

                • Resources: MC SW JH JY.

                • Software: SW JH.

                • Supervision: MC SW.

                • Validation: JH JY.

                • Visualization: MC SW JH JY.

                • Writing – original draft: MC SW JH JY.

                • Writing – review & editing: FL.

                Article
                Publisher ID: PONE-D-16-45976
                DOI: 10.1371/journal.pone.0178720
                PMC ID: 5453598
                PubMed ID: 28570713
                SO-VID: 4b5771f8-116c-4987-9b54-f25165909f28
                Copyright © © 2017 Chen et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 19 November 2016
                Date accepted : 17 May 2017
                Page count
                Figures: 3, Tables: 3, Pages: 18
                Funding
                The authors received no specific funding for this work.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Embryology
                Subject: Embryos
                Subject: Medicine and Health Sciences
                Subject: Women's Health
                Subject: Maternal Health
                Subject: Pregnancy
                Subject: Medicine and Health Sciences
                Subject: Women's Health
                Subject: Obstetrics and Gynecology
                Subject: Pregnancy
                Subject: Biology and Life Sciences
                Subject: Cell Biology
                Subject: Cellular Types
                Subject: Animal Cells
                Subject: Germ Cells
                Subject: OVA
                Subject: Oocytes
                Subject: Biology and Life Sciences
                Subject: Developmental Biology
                Subject: Embryology
                Subject: Blastocysts
                Subject: Medicine and Health Sciences
                Subject: Women's Health
                Subject: Maternal Health
                Subject: Pregnancy
                Subject: Pregnancy Complications
                Subject: Miscarriage
                Subject: Medicine and Health Sciences
                Subject: Women's Health
                Subject: Obstetrics and Gynecology
                Subject: Pregnancy
                Subject: Pregnancy Complications
                Subject: Miscarriage
                Subject: People and Places
                Subject: Population Groupings
                Subject: Professions
                Subject: Technicians
                Subject: Research and Analysis Methods
                Subject: Mathematical and Statistical Techniques
                Subject: Statistical Methods
                Subject: Meta-Analysis
                Subject: Physical Sciences
                Subject: Mathematics
                Subject: Statistics (Mathematics)
                Subject: Statistical Methods
                Subject: Meta-Analysis
                Subject: Research and Analysis Methods
                Subject: Research Assessment
                Subject: Systematic Reviews
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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                ScienceOpen disciplines: Uncategorized

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