Abstract

Abstract Study question Does growth hormone (GH) supplementation during ovarian stimulation affect the euploid rate and morphokinetic characteristics of euploid embryos in patients with advanced maternal age (AMA)? Summary answer GH supplementation improved the probability of obtaining euploid blastocysts in women with AMA, while did not affect the morphokinetic parameters of the euploid embryos. What is known already Studies have demonstrated that supplementation with GH during ovarian stimulation (OS) has positive impact on the clinical outcomes of in vitro fertilization (IVF). However, few studies have investigated the association of GH supplementation with the ploidy status of embryos. Meanwhile, it is unclear whether GH supplementation affects the morphokinetic signatures and the transfer outcomes of euploid blastocysts. Therefore, the underlying reason for the effect of GH on IVF outcomes remains largely unknown. Study design, size, duration This is a single centre open-labelled randomized controlled trial conducted at single IVF center from August 2022 to August 2023. A total of 441 patients were screened for eligibility and 309 patients were enrolled and allocated. The primary outcome was the proportion of cycles which obtained euploid blastocysts. Secondary outcomes included euploid blastocyst rate per cohort, euploid blastocyst rate per cycle and morphokinetic parameters of euploid embryos obtained with or without GH supplementation. Participants/materials, setting, methods A total of 309 patients aged 38–46 years who underwent their first preimplantation genetic testing for aneuploidy (PGT-A) cycle using antagonist protocol were randomized into the GH group or the control group at 1:1 ratio, with all embryos cultured in the time-lapse monitoring system. Patients in the GH group received 2 IU/day subcutaneous GH from the 2nd day of the previous menstrual period until the day of trigger, for a total of approximately 6 weeks. Main results and the role of chance The baseline and cycle characteristics between the two groups were similar. The proportion of cycles which obtained euploid blastocysts was significantly higher in the GH group (44.74% vs 31.85%, p = 0.02). The GH group had a significantly higher euploid blastocyst rate per cohort (38.46% vs 28.01%, p = 0.01) and mean euploid blastocyst rate per cycle (per biopsy cycle 0.38±0.43 vs. 0.26±0.39, p = 0.02; per OS cycle 0.29±0.41 vs. 0.19±0.36, p = 0.03). Multivariate logistic regression indicated GH supplement was an independent factor for acquisition of euploid embryos (adjusted risk ratio=1.79, 95%CI [1.06-2.99], p = 0.03). We did not observe a statistically significant difference in the morphokinetic parameters and transfer outcomes of the euploid embryos acquired with or without GH supplemented. Limitations, reasons for caution This was a single center study which limited the sample size, further limiting the number of patients with euploid blastocysts analyzed for the morphokinetic parameters and transfer outcomes. Meanwhile, affordability may also introduce selection bias since patients were required to pay for GH. Wider implications of the findings Our research presents new evidence that GH supplementation AMA patients increased the probability of obtaining euploid blastocysts, and explains the underlying reason for the positive effect of GH on IVF outcomes in existing studies. The effect of GH on morphokinetic parameters and transfer outcomes of euploid embryos warrants further investigation. Trial registration number NCT05447208, www.clinicaltrials.gov.

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