Abstract

Studies have shown that early-follicular phase long-acting gonadotropin-releasing hormone (GnRH) agonist long protocol (EFLL), a popular controlled ovarian hyperstimulation protocol widely used in China, leads to higher rates of implantation and clinical pregnancy, as well as lower rates of spontaneous abortion and ectopic pregnancy in patients undergoing in vitro fertilization treatment. However, the impact of EFLL on euploid embryos and its underlying mechanisms remain unclear. To address these gaps of knowledge, we conducted a retrospective comparative study of 310 preimplantation genetic testing (PGT) cycles with a total of 1,541 embryos using the EFLL protocol or midluteal short-acting GnRH agonist long protocol (MLSL). Patients were matched by PGT subtype [aneuploidies (PGT-A) vs. PGT for chromosomal structural rearrangements (PGT-SR)], age (±2 years), and body mass index (±1 kg/m2). For PGT-A, there was no significant difference in the number of euploid embryos (1.80 ± 1.47 for EFLL vs. 1.84 ± 2.03 for MLSL, p > 0.05) or the rate of euploidy (44.6 vs. 36.9%, p > 0.05). For PGT-SR, the number of euploid embryos in the EFLL group was significantly higher than that in the MLSL group (1.76 ± 1.54 vs. 1.21 ± 1.24, p < 0.05). A higher euploidy rate was also observed with the EFLL protocol compared with that obtained in MLSL (31.9 vs. 25.7%), although the difference was not statistically significant (p > 0.05). Compared with the MLSL protocol, more euploid embryos were achieved when using the EFLL protocol in PGT-SR, demonstrating the value in PGT-SR. To the best of our knowledge, this study is the first one to compare embryonic outcomes between EFLL and MLSL, providing key insights into the clinical application of EFLL in PGT cycles. In the light of the limited sample size of our study, we recommend that these questions be explored using a larger prospective study.

Highlights

  • For patients who have undergone preimplantation genetic testing (PGT) cycles, euploid embryos may be precious, especially for those with advanced maternal age, unexplained recurrent miscarriage, recurrent in vitro fertilization (IVF) failure, or chromosomal abnormalities

  • The influence of controlled ovarian stimulation is of paramount importance, and three protocols are currently used for PGT: the midluteal short-acting gonadotropin-releasing hormone (GnRH) agonist long protocol (MLSL), the GnRH antagonist protocol, and the microstimulation protocol

  • A suitable controlled ovarian stimulation protocol is used for obtaining a relatively maximum ovarian response in PGT cycles to ensure that at least one euploid embryo is available for transfer

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Summary

Introduction

For patients who have undergone PGT cycles, euploid embryos may be precious, especially for those with advanced maternal age, unexplained recurrent miscarriage, recurrent in vitro fertilization (IVF) failure, or chromosomal abnormalities. Some studies have found that moderate ovarian stimulation does not significantly decrease the rate of embryo euploidy [11], the optimal protocol remains to be identified. It has been suggested that the GnRH antagonist protocol results in a higher number of euploid embryos compared with the GnRH agonist (GnRH-a) protocol [12]. Data from our center on 5,197 IVF/ICSI cycles from May 2015 to 2016 showed better outcomes with the EFLL protocol than that with the MLSL protocol: higher implantation rate (45.34 vs 37.68%) and clinical pregnancy rate (63.72 vs 52.67%), lower miscarriage rate (8.41 vs 11.55%), and lower ectopic pregnancy rate (1.52 vs 3.30%) [14]. Ron-El et al [15] have suggested that the metaphase II (MII) oocyte rate and successful embryo rate are significantly enhanced with the EFLL protocol compared with that obtained with MLSL. The impact of EFLL on the rate of euploid embryos remains unclear

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