Discussion
ANEUPLOIDY
In this retrospective cohort study with PSM, GH supplementation was associated with higher proportion of cycles with euploid blastocysts, euploidy blastocyst rate per cohort, and mean euploid blastocyst rate per cycle in women with AMA. Moreover, GH supplementation was an independent factor in improving the acquisition of euploid blastocysts in this population, and the effect was age-dependent, with greater benefits in patients aged 38–40 years. However, for patients aged ≥ 41 years, GH supplementation had no significant effect on increasing the acquisition of euploid embryos during OS. Euploid blastocysts obtained with or without GH supplementation did not differ significantly in clinical outcomes after embryo transfer.To the best of our knowledge, this is the first study to investigate the effect of GH in IVF from the perspective of the ploidy status of embryos in patients with AMA. Currently, only one study has evaluated the effect of GH supplementation during PGT-A cycles in 41 patients without a priori suspicion of poor outcomes based on their clinical parameters [As the aneuploidy rate of oocytes increases with age, we stratified the patients by age to investigate whether the effect of GH treatment was age dependent. We found that GH supplementation benefitted the acquisition of euploid embryos in women aged 38–40 years, but the effect was not significant in patients aged ≥ 41 years. These results are consistent with those of a previous study by Keane et al. [We compared the implantation, clinical pregnancy, ongoing pregnancy and live birth rates of euploid embryos obtained with or without GH supplementation, and the results showed no differences. Meanwhile, the gestational age at delivery and birth weight of newborns were similar between the two groups (Table There were no significant differences between the two groups in the proportion of patients with mosaic embryos (9/140, 6.43% vs.18/272, 6.62%) and the rate of mosaic embryos per biopsy (9/231, 3.89% vs. 30/492, 6.10%, Table Our study has some limitations. First, this study was observational and retrospective in nature, which can only provide correlation instead of causation of the benefit of GH on embryo euploidy status. Second, there was a potential selection bias as patients in the two groups were not randomized. Although all the first PGT-A cycles during the study period were reviewed and were 1-to-2 matched using propensity scoring, some potential unknown or unmeasured covariates may have led to incomplete matching. For example, affordability may also have been a confounder since patients were required to pay for GH, and it was not possible to be evaluated in our study. Third, this was a single center study which limited the sample size. Although the dataset was relatively large and sufficient patients were included in the two groups, caution need to be made to interpret the age group analyses due to the reduced case number per subgroup, especially for patients with ultra-advanced ages (≥ 44 years). Patients in this age group seeking IVF do not account for a high proportion of patients in IVF centers but were clinically challenging, with an extremely low chance of live birth [