Improved Pregnancy Outcomes with Granulocyte Colony Stimulating Factor and Human Chorionic Gonadotropin Co-Treatment in Recurrent Intracytoplasmic Sperm Injection Failure: A Randomized Clinical Trial

Why clinicians should know about it

• Picked for Reproductive Medicine (paper of the day, 10 August 2026).

Abstract

OBJECTIVE: Despite notable advances in assisted reproductive technologies (ART), pregnancy rates remain suboptimal, and improving endometrial receptivity continues to be a clinical challenge. Emerging evidence suggests that granulocyte colony stimulating factor (G-CSF) and human chorionic gonadotropin (HCG) may enhance endometrial implantation. This study aimed to evaluate the combined therapeutic effect of G-CSF and HCG on reproductive outcomes in women with prior unsuccessful intracytoplasmic sperm injection (ICSI) cycles. MATERIALS AND METHODS: In this randomized clinical trial conducted at Reyhana Infertility Treatment Center (Qom University of Medical Sciences), 150 infertile women aged 20-40 years with ≥2 previous ICSI failures using good-quality embryos were enrolled. After applying exclusion criteria, 120 participants were randomized into either a treatment group (n=60, receiving 300 μg subcutaneous G-CSF and 2,500 IU intramuscular HCG 1 hour before frozen-thawed embryo transfer (FET)), or a control group (n=60, receiving no intervention). Hormonal profiles, ovarian stimulation outcomes, implantation rates (IRs), and the primary outcome (clinical pregnancy rate) as well as secondary outcomes (chemical pregnancy rate, implantation rate, and endometrial thickness) were compared between the groups. RESULTS: Baseline demographic and hormonal characteristics, including age (P=0.652), BMI (P=0.574), follicle- stimulating hormone (FSH, P=0.051), luteinizing hormone (LH, P=0.421), anti-Müllerian hormone (AMH, P=0.229), prolactin (PRL, P=0.154), and thyroid-stimulating hormone (TSH, P=0.861), were comparable between the groups. Similarly, ICSI cycle parameters, including the number of previous ICSI cycles (P=0.099), retrieved oocytes (P=0.528), metaphase II oocytes (P=0.323), embryos transferred (P=0.648), embryo quality (P=0.572), and endometrial thickness on the transfer day (P=0.440), did not differ significantly. The treatment group demonstrated significantly higher chemical and clinical pregnancy rates compared with the control group: 53.3% vs. 30.0% (P=0.041) and 48.3% vs. 28.3% (P=0.050), respectively. CONCLUSION: Adjunctive administration of G-CSF and HCG significantly improves pregnancy outcomes in women with recurrent ICSI failure, suggesting a promising therapeutic approach for this challenging patient population (Registration number: IRCT20220921056008N2).

Abstract as published, via PubMed.