Folic acid and zinc supplementation does not improve semen quality or increase live birth rate

Reference

Schisterman EF, Sjaarda LA, Clemons T, et al. Effect of folic acid and zinc supplementation in men on semen quality and live birth among couples undergoing infertility treatment. A randomized trial. JAMA 2020;323(1):35-48.

Synopsis

Although most supplements marketed for male infertility contain folic acid and zinc, evidence of their effectiveness is uncertain. These investigators identified the male partners of couples seeking infertility treatment from 4 US reproductive endocrinology and infertility centers. Consenting patients (N = 2370) randomly received (concealed allocation assignment) daily folic acid (5 mg) and elemental zinc (30 mg) or matched placebo for 6 months. Treatment began a minimum of 4.5 weeks to 6 weeks before the ovulatory phase of the first infertility treatment cycle. Individuals masked to treatment group assignment ascertained pregnancy outcomes by medical record review. Complete follow-up occurred for 75% of patients at 6 months. Using intention-to-treat analysis, no significant difference in live birth rates occurred between the intervention and control groups (34% vs 35%, respectively). Similarly, no significant differences occurred between the 2 groups in semen quality parameters. The study was 90% powered to detect a clinically significant group difference of 7% in live birth rates. No significant differences occurred in stillbirth, neonatal morbidity/mortality, or maternal complications.