Folic Acid and Zinc Supplementation Trial (FAZST)

Summary

The overarching goal of this trial is to determine if an intervention comprising folic acid and zinc dietary supplementation improves semen quality and indirectly fertility outcomes (i.e., live birth rate) among couples trying to conceive and seeking assisted reproduction. The following study objectives underlie successful attainment of the overarching research goal: 1. To estimate the effect of folic acid and zinc dietary supplementation on semen quality parameters, including but not limited to concentration, motility, morphology, and sperm DNA integrity, relative to the placebo group. 2. To estimate the effect of folic acid and zinc dietary supplementation on fertility treatment outcomes \[fertilization, embryo quality, implantation/human Chorionic Gonadotropin (hCG) confirmed pregnancy, clinical pregnancy, live birth\], relative to the placebo group. 3. To estimate the association between semen quality parameters, sperm DNA integrity and fertility treatment outcomes (fertilization, embryo quality, clinical pregnancy, live birth) and to identify the best combination of semen quality parameters for prediction of clinical pregnancy and live birth. 4. To estimate the effect of folic acid and zinc dietary supplementation on fertilization rates among couples undergoing assisted reproductive technology procedures, relative to the placebo group. 5. To estimate the effect of folic acid and zinc dietary supplementation on embryonic quality among couples undergoing assisted reproductive technology procedures, relative to the placebo group.

Timeline

Start

2013-06

Primary completion

2019-06

Completion

2019-06

Publications

• Nobles C, Canty TP, Mendola P, Russo LM, Rabeya K, Schliep KC, Shaaban M, Singh A, Ring AM, Hemmert R, Perkins NJ, Oluwayiose OA, Peterson CM, Nowak K, Pilsner JR. Heat exposure during susceptible windows of spermatogenesis and sperm epigenetic age. Hum Reprod. 2026 Jun 1;41(6):969-980. doi: 10.1093/humrep/deag048.
• DiTosto JD, Caniglia EC, Hinkle SN, Sealy N, Schisterman EF, Johnstone E, Mendola P, Mills J, Hotaling J, Ryan G, Mumford SL. Target trial emulation of preconception serum vitamin D status on fertility outcomes: a couples-based approach. Fertil Steril. 2025 Feb;123(2):300-312. doi: 10.1016/j.fertnstert.2024.08.332. Epub 2024 Aug 20.
• DeVilbiss EA, Sjaarda LA, Peterson CM, Hotaling JM, Mills JL, Mendola P, Carrell DT, Johnstone E, Chen Z, Perkins NJ, Ryan G, Schisterman EF, Mumford SL. Longitudinal semen parameter assessments and live birth: variability and implications for treatment strategies. Fertil Steril. 2022 Nov;118(5):852-863. doi: 10.1016/j.fertnstert.2022.08.012. Epub 2022 Oct 1.
• Jenkins T, Aston K, Carrell D, DeVilbiss E, Sjaarda L, Perkins N, Mills JL, Chen Z, Sparks A, Clemons T, Chaney K, Peterson CM, Emery B, Hotaling J, Johnstone E, Schisterman E, Mumford SL. The impact of zinc and folic acid supplementation on sperm DNA methylation: results from the folic acid and zinc supplementation randomized clinical trial (FAZST). Fertil Steril. 2022 Jan;117(1):75-85. doi: 10.1016/j.fertnstert.2021.09.009. Epub 2021 Oct 14.
• Schisterman EF, Sjaarda LA, Clemons T, Carrell DT, Perkins NJ, Johnstone E, Lamb D, Chaney K, Van Voorhis BJ, Ryan G, Summers K, Hotaling J, Robins J, Mills JL, Mendola P, Chen Z, DeVilbiss EA, Peterson CM, Mumford SL. Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial. JAMA. 2020 Jan 7;323(1):35-48. doi: 10.1001/jama.2019.18714.

Drugs

Indications