Sperm very long-chain polyunsaturated fatty acids: relation to semen parameters and live birth outcome in a multicenter trial

Objective: To determine whether the levels of sperm very long-chain polyunsaturated fatty acids (VLC-PUFAs) are correlated with sperm parameters and the outcome of live birth after conventional therapy for unexplained infertility.Design: Cohort analysis of the Reproductive Medicine Network's Assessment of Multiple Intrauterine Gestations from Ovarian Stim-ulation randomized controlled trial.Setting: Multicenter randomized controlled trial.Patients: Male partners from 185 couples with unexplained infertility who provided baseline semen samples for analysis.Intervention: We determined the levels of VLC-PUFAs in total lipid isolated from sperm membranes using liquid chromatography -mass spectrometry/mass spectrometry analyses.Main Outcome Measures: Sperm concentration, motility, morphology, total motile count (TMC), and live birth after standard treatment for unexplained infertility.Results: Total VLC-PUFA percentage was positively correlated with sperm concentration (Spearman's rank correlation (rs) 0.56, P<.0001), TMC (rs = 0.40, P<.0001), and morphology (rs = 0.26, P=.0005). After adjustment for male body mass index, age, and race, a one-standard-deviation increase in the percentage of total VLC-PUFA was associated with a 62% increase in the geometric mean (GM) of sperm concentration (GM Ratio: 1.62 [95% confidence intervals {CI}: 1.45, 1.82]) and a 43% increase in the geometric mean of TMC (GM Ratio: 1.43 [95% CI; 1.24, 1.63]). Although no evidence of association was observed for sperm motility, a positive relationship was also observed between the percentage of total VLC-PUFA and sperm morphology [adjusted incidence rate ratio (IRR) for one-standard-deviation increase in total VLC-PUFA: 1.18 (95% CI; 1.02, 1.36)]. After adjustment for female age and treatment group, the probability of a live birth outcome was 72% more likely among those in the third tertile of hydroxylated VLC-PUFA percentage than in the first tertile (RR 1.72 [95% CI; 1.01, 2.94]).Conclusions: The positive correlation between sperm VLC-PUFAs percentage and sperm parameters, as well as the significant association between hydroxylated VLC-PUFA percentage and the outcome of live birth, strongly suggest that this class of fatty liquid chromatography-mass spectrometry/mass spectrometry acids is essential for normal sperm structure and function. (Fertil Sterile 2023;119:753-60. (c) 2023 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo.