Preimplantation genetic testing for aneuploidy by microarray analysis of polar bodies in advanced maternal age: A randomized clinical trial
| Autor: | Maryse Bonduelle, Willem Verpoest, M.C. Magli, Georgia Kokkali, Luca Gianaroli, Katrin van der Ven, Monica Tobler, Veerle Goossens, Karen Sermon, Martha Devesa, Jana Liebenthron, Patrick M. M. Bossuyt, Catherine Staessen, Georgia Kakourou, Mònica Parriego, Joep P.M. Geraedts, Talia Eldar-Geva, Andreas G. Schmutzler, Georg Griesinger, Gheona Altarescu |
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| Přispěvatelé: | Epidemiology and Data Science, APH - Methodology, APH - Personalized Medicine, 10 Public Health & Methodologie, RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, Reproduction and Genetics, Surgical clinical sciences, Centre for Reproductive Medicine - Gynaecology, Vrije Universiteit Brussel, Clinical sciences, Medical Genetics, Basic (bio-) Medical Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Polar Bodies BLASTOCYST BIOPSY comprehensive chromosome screening law.invention Miscarriage 0302 clinical medicine Randomized controlled trial STAGE Pregnancy Risk Factors law Obstetrics and Gynaecology Birth Rate PGD Comparative Genomic Hybridization 030219 obstetrics & reproductive medicine medicine.diagnostic_test Obstetrics Rehabilitation BODY ARRAY CGH Obstetrics and Gynecology General Medicine Embryo transfer Intention to Treat Analysis polar body biopsy TROPHECTODERM BIOPSY array comparative genomic hybridization PGS Female Live birth Live Birth PGT-A Adult medicine.medical_specialty MOSAICISM EMBRYO-TRANSFER DIAGNOSIS 03 medical and health sciences Double-Blind Method medicine Humans Polar body biopsy Sperm Injections Intracytoplasmic Advanced maternal age Ovarian reserve Genetic testing In vitro fertilisation Intention-to-treat analysis business.industry Aneuploidy Embryo Transfer medicine.disease randomized clinical trial 030104 developmental biology Reproductive Medicine Infertility Relative risk IMPLANTATION business IN-VITRO FERTILIZATION |
| Zdroj: | Human reproduction (Oxford, England), 33(9), 1767-1776. Oxford University Press Human Reproduction, 33(9), 1767-1776. Oxford University Press Obstetrical and Gynecological Survey, 74(10), 597-598. Lippincott Williams and Wilkins |
| ISSN: | 0268-1161 0029-7828 |
| Popis: | STUDY QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) by comprehensive chromosome screening (CCS) of the first and second polar body to select embryos for transfer increase the likelihood of a live birth within 1 year in advanced maternal age women aged 36-40 years planning an ICSI cycle, compared to ICSI without chromosome analysis? SUMMARY ANSWER: PGT-A by CCS in the first and second polar body to select euploid embryos for transfer does not substantially increase the live birth rate in women aged 36-40 years. WHAT IS KNOWN ALREADY: PGT-A has been used widely to select embryos for transfer in ICSI treatment, with the aim of improving treatment effectiveness. Whether PGT-A improves ICSI outcomes and is beneficial to the patients has remained controversial. STUDY DESIGN, SIZE, DURATION: This is a multinational, multicentre, pragmatic, randomized clinical trial with intention-to-treat analysis. Of 396 women enroled between June 2012 and December 2016, 205 were allocated to CCS of the first and second polar body (study group) as part of their ICSI treatment cycle and 191 were allocated to ICSI treatment without chromosome screening (control group). Block randomization was performed stratified for centre and age group. Participants and clinicians were blinded at the time of enrolment until the day after intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertile couples in which the female partner was 36-40 years old and who were scheduled to undergo ICSI treatment were eligible. In those assigned to PGT-A, array comparative genomic hybridization (aCGH) analysis of the first and second polar bodies of the fertilized oocytes was performed using the 24sure array of Illumina. If in the first treatment cycle all oocytes were aneuploid, a second treatment with PB array CGH was offered. Participants in the control arm were planned for ICSI without PGT-A. Main exclusion criteria were three or more previous unsuccessful IVF or ICSI cycles, three or more clinical miscarriages, poor response or low ovarian reserve. The primary outcome was the cumulative live birth rate after fresh or frozen embryo transfer recorded over 1 year after the start of the intervention. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 205 participants in the chromosome screening group, 50 (24%) had a live birth with intervention within 1 year, compared to 45 of the 191 in the group without intervention (24%), a difference of 0.83% (95% CI: -7.60 to 9.18%). There were significantly fewer participants in the chromosome screening group with a transfer (relative risk (RR) = 0.81; 95% CI: 0.74-0.89) and fewer with a miscarriage (RR = 0.48; 95% CI: 0.26-0.90). LIMITATIONS, REASONS FOR CAUTION: The targeted sample size was not reached because of suboptimal recruitment; however, the included sample allowed a 90% power to detect the targeted increase. Cumulative outcome data were limited to 1 year. Only 11 patients out of 32 with exclusively aneuploid results underwent a second treatment cycle in the chromosome screening group. WIDER IMPLICATIONS OF THE FINDINGS: The observation that the similarity in birth rates was achieved with fewer transfers, less cryopreservation and fewer miscarriages points to a clinical benefit of PGT-A, and this form of embryo selection may, therefore, be considered to minimize the number of interventions while producing comparable outcomes. Whether these benefits outweigh drawbacks such as the cost for the patient, the higher workload for the IVF lab and the potential effect on the children born after prolonged culture and/or cryopreservation remains to be shown. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the European Society of Human Reproduction and Embryology. Illumina provided microarrays and other consumables necessary for aCGH testing of polar bodies. M.B.'s institution (UZBrussel) has received educational grants from IBSA, Ferring, Organon, Schering-Plough, Merck and Merck Belgium. M.B. has received consultancy and speakers' fees from Organon, Serono Symposia and Merck. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott and Gedeon-Richter as well as personal fees from VitroLife, NMC Healthcare, ReprodWissen, BioSilu and ZIVA. W.V., C.S., P.M.B., V.G., G.A., M.D.,T.E.G., L.G., G.Ka., G.Ko., J. L., M.C.M., M.P., A. S., M. T., K.V., J.G. and K.S. declare no conflict of interest. TRIAL REGISTRATION NUMBER: NCT01532284. TRIAL REGISTRATION DATE: 7 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 25 June 2012. |
| Databáze: | OpenAIRE |
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