Despite recent advancements in assisted reproductive technology (ART), the rate of live birth in advanced-age women remains suboptimal. Although many factors likely contribute, age-related embryo aneuploidy is considered the most significant determinant of cycle outcomes and has the lowest rate among women in their middle to late 20s but rises steadily from age 31 through 43 years. Preimplantation genetic testing for aneuploidies is routinely conducted to genetically evaluate embryos before transfer; however, the benefits are uncertain, and it has become a contested procedure in the field of reproductive medicine. Research on factors other than embryo chromosome segregation errors that may affect reproductive outcomes is needed.This systematic review and meta-analysis aimed to investigate whether increasing maternal age may limit ART success independent of ploidy status. Studies that evaluated the impact of maternal age on ART outcomes after the transfer of euploid embryos and included assessment of ongoing pregnancy rate (OPR) or live birth rate (LBR) were included. Ongoing pregnancy was defined as pregnancy beyond 12 weeks' gestation. The primary study outcome was comparison of OPR or LBR in women younger than 35 years compared with those 35 years or older. Additional analyses included evaluation of implantation rate and miscarriage rate (MR), as well as comparison between different age groups (ie, <35 vs 35-37, 38-40, 41-42, >42 years; <38 vs >= 38 years). The body of evidence was assessed by 2 investigators using the GRADE methodology. Meta-analysis of binary outcomes was performed with a random-effects model, and study outcomes were expressed using odds ratio (OR) with 95% confidence intervals (CIs).A total of 7 studies were included in this meta-analysis including 2 multicenter randomized controlled trials and 5 retrospective trials comprising a total of 11,335 embryo transfer cycles. Aneuploidy rate in biopsied blastocysts was reported in 4 studies and ranged between 28.9% and 54.2%. Meta-analysis revealed a significantly higher OPR/LBR (OR, 1.29; 95% CI, 1.07-1.54; P = 0.006; RD, 0.06; 95% CI, 0.02-0.09) among women younger than 35 years compared with those 35 years or older. In addition, the implantation rate was significantly higher in the youngest group (OR, 1.22; 95% CI, 1.12-1.32; P < 0.00001; RD, 0.04; 95% CI, 0.02-0.06), and there was a trend toward a lower MR (OR, 0.084; 95% CI, 0.71-1.00; P = 0.05; RD, -0.02; 95% CI, -0.03 to 0.00).The results of this study suggest that the increase in maternal age is associated with a lower OPR/LBR even after the transfer of euploid blastocysts. Notably, this gradient relationship between age and OPR/LBR remained when sensitivity analysis was conducted restricting analysis to only studies with low risk of bias.
Does Maternal Age Affect Assisted Reproduction Technology Success Rates After Euploid Embryo Transfer? A Systematic Review and Meta-analysis
Vitagliano, Amerigo;
2023-01-01
Abstract
Despite recent advancements in assisted reproductive technology (ART), the rate of live birth in advanced-age women remains suboptimal. Although many factors likely contribute, age-related embryo aneuploidy is considered the most significant determinant of cycle outcomes and has the lowest rate among women in their middle to late 20s but rises steadily from age 31 through 43 years. Preimplantation genetic testing for aneuploidies is routinely conducted to genetically evaluate embryos before transfer; however, the benefits are uncertain, and it has become a contested procedure in the field of reproductive medicine. Research on factors other than embryo chromosome segregation errors that may affect reproductive outcomes is needed.This systematic review and meta-analysis aimed to investigate whether increasing maternal age may limit ART success independent of ploidy status. Studies that evaluated the impact of maternal age on ART outcomes after the transfer of euploid embryos and included assessment of ongoing pregnancy rate (OPR) or live birth rate (LBR) were included. Ongoing pregnancy was defined as pregnancy beyond 12 weeks' gestation. The primary study outcome was comparison of OPR or LBR in women younger than 35 years compared with those 35 years or older. Additional analyses included evaluation of implantation rate and miscarriage rate (MR), as well as comparison between different age groups (ie, <35 vs 35-37, 38-40, 41-42, >42 years; <38 vs >= 38 years). The body of evidence was assessed by 2 investigators using the GRADE methodology. Meta-analysis of binary outcomes was performed with a random-effects model, and study outcomes were expressed using odds ratio (OR) with 95% confidence intervals (CIs).A total of 7 studies were included in this meta-analysis including 2 multicenter randomized controlled trials and 5 retrospective trials comprising a total of 11,335 embryo transfer cycles. Aneuploidy rate in biopsied blastocysts was reported in 4 studies and ranged between 28.9% and 54.2%. Meta-analysis revealed a significantly higher OPR/LBR (OR, 1.29; 95% CI, 1.07-1.54; P = 0.006; RD, 0.06; 95% CI, 0.02-0.09) among women younger than 35 years compared with those 35 years or older. In addition, the implantation rate was significantly higher in the youngest group (OR, 1.22; 95% CI, 1.12-1.32; P < 0.00001; RD, 0.04; 95% CI, 0.02-0.06), and there was a trend toward a lower MR (OR, 0.084; 95% CI, 0.71-1.00; P = 0.05; RD, -0.02; 95% CI, -0.03 to 0.00).The results of this study suggest that the increase in maternal age is associated with a lower OPR/LBR even after the transfer of euploid blastocysts. Notably, this gradient relationship between age and OPR/LBR remained when sensitivity analysis was conducted restricting analysis to only studies with low risk of bias.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
