High-Dose Supplementation of Folic Acid in Infertile Men Improves IVF-ICSI Outcomes: A Randomized Controlled Trial (FOLFIV Trial).

Emmanuelle Mathieu D’Argent,Karine Morcel,Alexandra Rousseau,Kamila Kolanska,Nathalie Massin,Tabassome Simon,Julie Sussfeld,Emile Daraï,Celia Ravel,Jacqueline Mandelbaume,Jean-Marie Antoine

doi:10.3390/jcm10091876

Abstract

Dietary supplementation is commonly used in men with male infertility but its exact role is poorly understood. The aim of this multicenter, randomized, double-blind, placebo-controlled trial was to evaluate the impact of high-dose folic acid supplementation on IVF-ICSI outcomes. 162 couples with male infertility and an indication for IVF-ICSI were included for one IVF-ICSI cycle. Male partners of couples wishing to conceive, aged 18–60 years old, with at least one abnormal spermatic criterion were randomized in a 1:1 ratio to receive daily supplements containing 15 mg of folic acid or a placebo for 3 months from Day 0 until semen collection for IVF-ICSI. Sperm parameters and DNA fragmentation before and after the treatment and the biochemical and clinical pregnancy rates after the fresh embryo transfer were analyzed. We observed an increase in the biochemical pregnancy rate and a trend for a higher clinical pregnancy rate in the folic acid group compared to placebo (44.1% versus 22.4%, p = 0.01 and 35.6% versus 20.4%, p = 0.082, respectively). Even if no changes in sperm characteristics were observed, a decrease in DNA fragmentation in the folic acid group was noted (8.5 ± 4.5 vs. 6.4 ± 4.6, p < 0.0001). High-dose folic acid supplementation in men requiring IVF-ICSI for male infertility improves IVF-ICSI outcomes.

Highlights

Licensee MDPI, Basel, Switzerland.The prevalence of infertility is estimated at almost 15% in couples of reproductive age [1] and a male factor can be identified in around half of the cases [2]
Participants were enrolled between November 2011 and September 2015 in six participating centers: Tenon Hospital, Rennes University Hospital, Intercommunal Center of Creteil Hospital, Pitié-Salpétrière Hospital, Monsouris Mutualist Institute, and Jean Verdier
Testicular ultrasonography performed before inclusion in the study showed a higher rate of varicocele grade 1 to 3 in the folic acid group as compared to the placebo group (33% versus 49%, respectively)

Summary

Introduction

The prevalence of infertility is estimated at almost 15% in couples of reproductive age [1] and a male factor can be identified in around half of the cases [2]. Male infertility can have multiple origins such as genetic and environmental, or it can be associated with lifestyle [1]. In most cases the exact etiology remains unknown. Some authors have reported that oxidative stress affects sperm parameters and live birth chances [3].

Results

Discussion

Conclusion