Personalized growth hormone pretreatment for oocyte retrieval and embryo quality in women with diminished ovarian reserve: A prospective cohort study.

Abstract

Objective: We evaluated the effects of growth hormone (GH) pretreatment on oocyte retrieval and embryo quality in patients undergoing assisted reproductive technology (ART) for diminished ovarian reserve (DOR).

Methods: In this prospective cohort study, conducted at Shahida Islam Medical Complex from October 2023 to June 2025, 2,000 women aged ≤40 years with DOR were recruited before starting ART. DOR diagnosis was based on the 2017 criteria and the 2011 Bologna criteria. Participants were nonrandomly allocated to four equal groups: G1 (1 month of GH before ovulation induction+standard ART), G2 (2 months of GH pretreatment+ART), G3 (GH supplementation during the ovulation induction phase+ART), and G4 (control; standard ART). Hormonal and metabolic profiling was performed before, during, and after GH treatment. Accordingly, secondary stratification was applied to enable personalized treatment. Based on early response to GH pretreatment, participants underwent dynamic regrouping into good and poor responders. Key outcomes included oocyte retrieval, embryo quality, and maternal-fetal outcomes.

Results: GH pretreatment improved ART results, with the G2 group achieving the best estradiol levels, follicular growth, and oocyte retrieval, albeit with increased insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]). The G1 and G3 groups also outperformed controls (G4). GH dose and anti-Müllerian hormone (AMH) level strongly predicted successful oocyte retrieval. Testosterone was negatively associated with retrieval; interleukin 6 and dehydroepiandrosterone sulfate (DHEA-S) had weaker effects. G2 embryos exhibited the best development and blastocyst formation outcomes, with the most advanced development by day 5. A nomogram was developed to predict oocyte retrieval outcomes from GH dose, AMH, HOMA-IR, and testosterone.

Conclusion: In patients with DOR, GH pretreatment improves treatment outcomes. Over 1 month of pretreatment can increase the oocytes retrieved but confers higher insulin resistance. Thus, when using GH for more than 4 weeks, clinicians should closely monitor HOMA-IR and perform continuous glucose monitoring; otherwise, 1-month GH pretreatment is preferred when initiating ART.