Miriam J Haviland1, Lauren A Murphy2, Anna M Modest2, Matthew P Fox1, Lauren A Wise1, Yael I Nillni3, Denny Sakkas4, Michele R Hacker2. 1. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA. 2. Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. 3. Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA. 4. Boston IVF, Waltham, MA 02451, USA.
Abstract
STUDY QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos? SUMMARY ANSWER: PGT-A is associated with a greater probability of live birth among women 35 years old and older who are undergoing IVF. WHAT IS KNOWN ALREADY: Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A. LIMITATIONS, REASONS FOR CAUTION: We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles. WIDER IMPLICATIONS OF THE FINDINGS: Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
STUDY QUESTION: Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos? SUMMARY ANSWER: PGT-A is associated with a greater probability of live birth among women 35 years old and older who are undergoing IVF. WHAT IS KNOWN ALREADY: Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A. LIMITATIONS, REASONS FOR CAUTION: We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles. WIDER IMPLICATIONS OF THE FINDINGS:Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.