Evelyn Lee1, Peter Illingworth2, Leeanda Wilton3, Georgina Mary Chambers4. 1. National Perinatal Epidemiology and Statistics Unit, School of Women's and Children's Health, University of New South Wales (UNSW), Level 2, McNevin Dickson Building, Randwick Hospitals Campus, Sydney 2031, Australia evelyn.lee@unsw.edu.au. 2. IVF Australia Pty Ltd, 176 Pacific Highway, Greenwich, Sydney 2065, Australia. 3. Melbourne IVF, Victoria Parade, East Melbourne, VIC 3002, Australia. 4. National Perinatal Epidemiology and Statistics Unit, School of Women's and Children's Health, University of New South Wales (UNSW), Level 2, McNevin Dickson Building, Randwick Hospitals Campus, Sydney 2031, Australia.
Abstract
STUDY QUESTION: Is preimplantation genetic diagnosis for aneuploidy (PGD-A) with analysis of all chromosomes during assisted reproductive technology (ART) clinically and cost effective? SUMMARY ANSWER: The majority of published studies comparing a strategy of PGD-A with morphologically assessed embryos have reported a higher implantation rate per embryo using PGD-A, but insufficient data has been presented to evaluate the clinical and cost-effectiveness of PGD-A in the clinical setting. WHAT IS KNOWN ALREADY: Aneuploidy is a leading cause of implantation failure, miscarriage and congenital abnormalities in humans, and a significant cause of ART failure. Preclinical evidence of PGD-A indicates that the selection and transfer of euploid embryos during ART should improve clinical outcomes. STUDY DESIGN, SIZE AND DURATION: A systematic review of the literature was performed for full text English language articles using MEDLINE, EMBASE, SCOPUS, Cochrane Library databases, NHS Economic Evaluation Database and EconLit. The Downs and Black scoring checklist was used to assess the quality of studies. Clinical effectiveness was measured in terms of pregnancy, live birth and miscarriage rates. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Nineteen articles meeting the inclusion criteria, comprising three RCTs in young and good prognosis patients and 16 observation studies were identified. Five of the observational studies included a control group of patients where embryos were selected based on morphological criteria (matched cohort studies). MAIN RESULTS AND ROLE OF CHANCE: Of the five studies that included a control group and reported implantation rates, four studies (including two RCTs) demonstrated improved implantation rates in the PGD-A group. Of the eight studies that included a control group, six studies (including two RCTs) reported significantly higher pregnancy rates in the PGD-A group, and in the remaining two studies, equivalent pregnancies rates were reported despite fewer embryos being transferred in the PGD-A group. The three RCTs demonstrated benefit in young and good prognosis patients in terms of clinical pregnancy rates and the use of single embryo transfer. However, studies relating to patients of advanced maternal age, recurrent miscarriage and implantation failure were restricted to matched cohort studies, limiting the ability to draw meaningful conclusions. LIMITATIONS, REASONS FOR CAUTION: Relevant studies may have been missed and findings from RCTs currently being undertaken could not be included. WIDER IMPLICATIONS OF THE FINDINGS: Given the uncertain role of PGD-A techniques, high-quality experimental studies using intention-to-treat analysis and cumulative live birth rates including the comparative outcomes from remaining cryopreserved embryos are needed to evaluate the overall role of PGD-A in the clinical setting. It is only in this way that the true contribution of PGD-A to ART can be understood.
STUDY QUESTION: Is preimplantation genetic diagnosis for aneuploidy (PGD-A) with analysis of all chromosomes during assisted reproductive technology (ART) clinically and cost effective? SUMMARY ANSWER: The majority of published studies comparing a strategy of PGD-A with morphologically assessed embryos have reported a higher implantation rate per embryo using PGD-A, but insufficient data has been presented to evaluate the clinical and cost-effectiveness of PGD-A in the clinical setting. WHAT IS KNOWN ALREADY: Aneuploidy is a leading cause of implantation failure, miscarriage and congenital abnormalities in humans, and a significant cause of ART failure. Preclinical evidence of PGD-A indicates that the selection and transfer of euploid embryos during ART should improve clinical outcomes. STUDY DESIGN, SIZE AND DURATION: A systematic review of the literature was performed for full text English language articles using MEDLINE, EMBASE, SCOPUS, Cochrane Library databases, NHS Economic Evaluation Database and EconLit. The Downs and Black scoring checklist was used to assess the quality of studies. Clinical effectiveness was measured in terms of pregnancy, live birth and miscarriage rates. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Nineteen articles meeting the inclusion criteria, comprising three RCTs in young and good prognosis patients and 16 observation studies were identified. Five of the observational studies included a control group of patients where embryos were selected based on morphological criteria (matched cohort studies). MAIN RESULTS AND ROLE OF CHANCE: Of the five studies that included a control group and reported implantation rates, four studies (including two RCTs) demonstrated improved implantation rates in the PGD-A group. Of the eight studies that included a control group, six studies (including two RCTs) reported significantly higher pregnancy rates in the PGD-A group, and in the remaining two studies, equivalent pregnancies rates were reported despite fewer embryos being transferred in the PGD-A group. The three RCTs demonstrated benefit in young and good prognosis patients in terms of clinical pregnancy rates and the use of single embryo transfer. However, studies relating to patients of advanced maternal age, recurrent miscarriage and implantation failure were restricted to matched cohort studies, limiting the ability to draw meaningful conclusions. LIMITATIONS, REASONS FOR CAUTION: Relevant studies may have been missed and findings from RCTs currently being undertaken could not be included. WIDER IMPLICATIONS OF THE FINDINGS: Given the uncertain role of PGD-A techniques, high-quality experimental studies using intention-to-treat analysis and cumulative live birth rates including the comparative outcomes from remaining cryopreserved embryos are needed to evaluate the overall role of PGD-A in the clinical setting. It is only in this way that the true contribution of PGD-A to ART can be understood.
Authors: Antonio Capalbo; Valeria Romanelli; Danilo Cimadomo; Laura Girardi; Marta Stoppa; Lisa Dovere; Domenico Dell'Edera; Filippo Maria Ubaldi; Laura Rienzi Journal: J Assist Reprod Genet Date: 2016-07-16 Impact factor: 3.412
Authors: Karen Sermon; Antonio Capalbo; Jacques Cohen; Edith Coonen; Martine De Rycke; Anick De Vos; Joy Delhanty; Francesco Fiorentino; Norbert Gleicher; Georg Griesinger; Jamie Grifo; Alan Handyside; Joyce Harper; Georgia Kokkali; Sebastiaan Mastenbroek; David Meldrum; Marcos Meseguer; Markus Montag; Santiago Munné; Laura Rienzi; Carmen Rubio; Katherine Scott; Richard Scott; Carlos Simon; Jason Swain; Nathan Treff; Filippo Ubaldi; Rita Vassena; Joris Robert Vermeesch; Willem Verpoest; Dagan Wells; Joep Geraedts Journal: Mol Hum Reprod Date: 2016-06-02 Impact factor: 4.025