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

Cytokine enrichment of medium with granulocyte-macrophage colony-stimulating factor, heparin-binding epidermal growth factor-like growth factor, and leukemia inhibitory factor improves ongoing pregnancy and live birth rates after intracytoplasmic sperm injection.

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Volume 112, Issue 5, Pages 849–857.e1


Mohamed Fawzy, M.D., Mai Emad, B.Sc., Mohamed A. Elsuity, M.D., Ali Mahran, M.D., Mohamed Y. Abdelrahman, M.D., Ahmed N. Fetih, M.D., Hazem Abdelghafar, M.D., Mohamed Sabry, M.D., Mohamed Nour, M.D., Salah M. Rasheed, M.D.



To evaluate the effects of cytokine enrichment of culture medium on embryological and clinical outcomes after intracytoplasmic sperm injection (ICSI).


A randomized clinical trial.


In vitro fertilization centers.


This trial included 443 ICSI cycles randomized into two groups.


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.


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.


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

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.