Christos A Venetis1,2,3, Liza Tilia4, Erin Panlilio4, Andrew Kan2,3. 1. Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. 2. School of Women's and Children's Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia. 3. IVF Australia Southern Sydney, St George Private Hospital, Kogarah, New South Wales, Australia. 4. IVF Australia Eastern Suburbs, Maroubra, New South Wales, Australia.
Abstract
STUDY QUESTION: Is the number of oocytes retrieved after ovarian stimulation for ICSI independently associated with the number of day-3 euploid embryos (EE)? SUMMARY ANSWER: A larger oocyte yield is independently associated with more day-3 EE, although the expected benefit decreases significantly with advancing age. WHAT IS KNOWN ALREADY: Although traditionally ovarian stimulation aims at collecting more than one oocyte in order to increase the chance of pregnancy, there is evidence suggesting that excessive ovarian response leads to lower live birth rates. Whether a larger oocyte yield after ovarian stimulation is associated with the genetic composition of the resulting embryos and therefore with their reproductive potential is still largely unknown. STUDY DESIGN, SIZE, DURATION: This is a multi-centered retrospective cohort study analyzing 724 cycles of preimplantation genetic testing for aneuploidy (PGT-A) cycles using day-3 biopsy and array-comparative genomic hybridization between March 2011 and December 2016 in three laboratories. PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome measure was the number of EE on day-3. Statistical analysis was performed using the generalized estimating equations (GEE) framework and multivariate regression models to control for the clustered nature of the data while adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: A multivariate regression GEE model including all significant population and stimulation characteristics as covariates as well as an interaction term between female age and number of oocytes revealed that the number of oocytes retrieved was still positively associated with the number of EE (coeff: +0.40, 95% CI: 0.24-0.56). The interaction term was highly significant (coeff: -0.01, P < 0.001) indicating an effect modifying role of female age on the association of oocytes retrieved with the number of EE. The number of oocytes retrieved was also positively associated with cumulative live birth rates (odds ratio: 1.07, 95% CI: 1.03-1.12). LIMITATIONS, REASONS FOR CAUTION: This study is retrospective and the presence of residual unknown bias cannot be excluded. Furthermore, the population analyzed in this study might not be completely representative of the general population undergoing ICSI. WIDER IMPLICATIONS OF THE FINDINGS: These results provide an explanatory mechanism for the recently published positive association between the number of oocytes retrieved and cumulative live birth rates. STUDY FUNDING/COMPETING INTEREST(S): CAV is supported by a NHMRC Early Career Fellowship (GNT1147154)/ No competing interests to declare.
STUDY QUESTION: Is the number of oocytes retrieved after ovarian stimulation for ICSI independently associated with the number of day-3 euploid embryos (EE)? SUMMARY ANSWER: A larger oocyte yield is independently associated with more day-3 EE, although the expected benefit decreases significantly with advancing age. WHAT IS KNOWN ALREADY: Although traditionally ovarian stimulation aims at collecting more than one oocyte in order to increase the chance of pregnancy, there is evidence suggesting that excessive ovarian response leads to lower live birth rates. Whether a larger oocyte yield after ovarian stimulation is associated with the genetic composition of the resulting embryos and therefore with their reproductive potential is still largely unknown. STUDY DESIGN, SIZE, DURATION: This is a multi-centered retrospective cohort study analyzing 724 cycles of preimplantation genetic testing for aneuploidy (PGT-A) cycles using day-3 biopsy and array-comparative genomic hybridization between March 2011 and December 2016 in three laboratories. PARTICIPANTS/MATERIALS, SETTING, METHODS: The primary outcome measure was the number of EE on day-3. Statistical analysis was performed using the generalized estimating equations (GEE) framework and multivariate regression models to control for the clustered nature of the data while adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: A multivariate regression GEE model including all significant population and stimulation characteristics as covariates as well as an interaction term between female age and number of oocytes revealed that the number of oocytes retrieved was still positively associated with the number of EE (coeff: +0.40, 95% CI: 0.24-0.56). The interaction term was highly significant (coeff: -0.01, P < 0.001) indicating an effect modifying role of female age on the association of oocytes retrieved with the number of EE. The number of oocytes retrieved was also positively associated with cumulative live birth rates (odds ratio: 1.07, 95% CI: 1.03-1.12). LIMITATIONS, REASONS FOR CAUTION: This study is retrospective and the presence of residual unknown bias cannot be excluded. Furthermore, the population analyzed in this study might not be completely representative of the general population undergoing ICSI. WIDER IMPLICATIONS OF THE FINDINGS: These results provide an explanatory mechanism for the recently published positive association between the number of oocytes retrieved and cumulative live birth rates. STUDY FUNDING/COMPETING INTEREST(S): CAV is supported by a NHMRC Early Career Fellowship (GNT1147154)/ No competing interests to declare.
Authors: Glykeria I Karatasiou; J K Bosdou; C A Venetis; L Zepiridis; K Chatzimeletiou; T B Tarlatzi; G Lainas; B C Tarlatzis; G Grimbizis; E M Kolibianakis Journal: J Assist Reprod Genet Date: 2020-05-29 Impact factor: 3.412
Authors: Jori A Leijdekkers; Helen L Torrance; Nienke E Schouten; Theodora C van Tilborg; Simone C Oudshoorn; Ben Willem J Mol; Marinus J C Eijkemans; Frank J M Broekmans Journal: Hum Reprod Date: 2020-09-01 Impact factor: 6.918