The impact of IVF culture medium on post-implantation embryonic growth and development with emphasis on sex specificity: the Rotterdam Periconceptional Cohort

Research question: Are there (sex-specific) differences in first-trimester embryonic growth and morphological development between two culture media used for IVF and intracytoplasmic sperm injection (ICSI) treatment? Design: A total of 835 singleton pregnancies from a prospective hospital-based cohort study were included, of which 153 conceived after IVF/ICSI treatment with Vitrolife G-1™ PLUS culture medium, 252 after culture in SAGE 1-Step™ and 430 were naturally conceived. Longitudinal three-dimensional ultrasound examinations were performed at 7, 9 and 11 weeks of gestation for offline biometric (crown rump length, CRL), volumetric (embryonic volume) and morphological (Carnegie stage) measurements. Results: Embryos cultured in SAGE 1-Step grew faster than those cultured in Vitrolife G-1 PLUS (beta_EV 0.030 3√ml [95% CI 0.008–0.052], P = 0.007). After stratification for fetal sex, male embryos cultured in SAGE 1-Step demonstrated faster growth than those cultured in Vitrolife G-1 PLUS (beta_EV 0.048 3√ml [95% CI 0.015–0.081], P = 0.005). When compared with naturally conceived embryos, those cultured in SAGE 1-Step grew faster (beta_EV 0.040 3√ml [95% CI 0.012–0.069], P = 0.005). This association was most pronounced in male embryos (beta_EV 0.078 3√ml [95% CI 0.035–0.120], P < 0.001). Conclusions: This study shows that SAGE 1-Step culture medium accelerates embryonic growth trajectories compared with Vitrolife G-1 PLUS and naturally conceived pregnancies, especially in male embryos. Further research should focus on the impact of culture media on postnatal development and the susceptibility to non-communicable diseases.