Abstract:

Objective To analyze the cumulative assisted reproductive outcomes and influencing factors of different assisted reproductive protocols in female patients aged 38 years or older who are undergoing their first fertility treatment with available embryos on day 3 after oocyte retrieval. Methods This study was a retrospective cohort study. It included elderly women （aged ≥ 38 years） who underwent their first cycle of either preimplantation genetic testing for aneuploidy （PGT-A） or in vitro fertilization/intracytoplasmic sperm injection （IVF/ICSI） for assisted reproduction at the Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University between January 2019 and June 2023， and had usable embryos available on the third day after oocyte retrieval. The participants were divided into two groups according to the protocol they selected： the PGT-A group and the IVF/ICSI group. A 1∶1 propensity score matching was performed to match the two groups （PGT-A group vs. IVF/ICSI group）. The primary observation indicator was the cumulative live-birth rate per oocyte retrieval cycle， and the influencing factors of cumulative live birth were further investigated through Cox regression. Results After PSM， there were 192 cases in both the PGT-A group and the IVF/ICSI group. The PGT-A group experienced a greater number of miscarriages （2 vs. 1， P < 0.001）， and the proportion of non-transplantable cycles was relatively high （24.48%）. The PGT-A group also showed higher clinical pregnancy rates and live birth rates per embryo transfer cycle （59.42% vs. 32.96%， P < 0.001； 44.93% vs. 19.63%， P < 0.001）. In comparison with the PGT-A group， the optimistically-estimated cumulative pregnancy rate for each oocyte retrieval cycle in the IVF/ICSI group was higher （65.62% vs. 51.56%， P = 0.005）. Subsequently， subgroup analyses were carried out according to age （categorized as 38 - 40， 41 - 42， and ≥ 43 years）， AMH level （< 1.2 ng/mL vs. ≥ 1.2 ng/mL）， and number of prior miscarriages （< 2 vs. ≥ 2）， as indicated by the Cox regression findings. Among these three subgroups， the PGT-A group presented significantly higher clinical pregnancy and live birth rates compared to the IVF/ICSI group in all subgroups （P < 0.05）， except for patients aged ≥ 43 years. In the subgroup of women aged ≥ 43 years， the IVF/ICSI group had a significantly higher early miscarriage rate （77.78% vs. 18.18%， P = 0.012）. Additionally， in this subgroup， the proportion of cycles with no transplantable embryos in the PGT-A group reached as high as 56.76%. Among patients with AMH < 1.2 ng/mL or ≥ 2 prior miscarriages， the optimistically estimated cumulative pregnancy rate per oocyte retrieval cycle was significantly higher in the IVF/ICSI group compared to the PGT-A group （47.22% vs. 30.56%， P = 0.040； 65.17% vs. 51.54%， P = 0.045， respectively）. Among women aged 41 to 42 years， the optimistically estimated cumulative live birth rate per oocyte retrieval cycle was significantly higher in the PGT-A group （47.50% vs. 23.40%， P = 0.018）. Conclusions For infertile women aged 41 - 42 years， the cumulative live birth rate per oocyte retrieval cycle is significantly higher with PGT-A-assisted reproduction compared to IVF/ICSI. Consequently， PGT-A is more strongly recommended for this population.

Key words: advanced age, cumulative live birth rate, infertility, in vitro fertilization embryo transfer, preimplantation genetic testing for aneuploidy