Cytokines hold promise for human embryo culture in vitro: results of a randomized clinical trial

Objective To evaluate the effects of cytokine enrichment of culture medium on embryological and clinical outcomes after intracytoplasmic sperm injection (ICSI). Design A randomized clinical trial. Setting In vitro fertilization centers. Patient(s) This trial included 443 ICSI cycles randomized into two groups. Intervention(s) This study evaluated the influence of integration of granulocyte-macrophage colony-stimulating factor, heparin-binding epidermal growth factor-like growth factor, and leukemia inhibitory factor into culture media on human embryo development after ICSI. Main Outcome Measure(s) Ongoing pregnancy rate per a randomized participant. Result(s) Cytokine enrichment of culture medium showed improvement in ongoing pregnancy rate compared with no cytokines (106/224 [47%] vs. 78/219 [36%]; absolute rate difference [ARD] = 12; 95% confidence interval [CI], 2.5–21). This integration of cytokines also showed better rates of live birth (101/224 [45%] vs. 71/219 [33%]; ARD=13; 95% CI, 4–21) and cumulative live birth (132/224 [60%] vs. 97/219 [44%]; ARD=12; 95% CI, 4–20) and lower rate of pregnancy loss (27/124 [22%] vs. 37/103 [36%]; ARD=–14; 95% CI, –26 to –2) than conventional medium. Embryos developed in the cytokine-supplemented medium showed better blastocyst formation, quality, cryopreservation, and use than control medium. Conclusion(s) Integration of cytokines into human embryo culture media showed improvement in embryological and clinical outcomes after ICSI. However, the long-term effect of cytokine enrichment of a medium is still unclear and warrants further studies with longitudinal follow-up. Clinical Trial Registration Number NCT02420886 at ClinicalTrials.gov.