Impact of a nutritional supplement (Impryl) on male fertility: study protocol of a multicentre, randomised, double-blind, placebo-controlled clinical trial (SUppleMent Male fERtility, SUMMER trial)

INTRODUCTION: Infertility is a worldwide problem and about 10%-15% of all couples will be affected by the inability to have children. In approximately 50% of infertile couples, a male factor is involved. Most of the male infertile cases are characterised as 'idiopathic', except for a small percentage of cases which are causative by a genetic aetiology. In the past decade, the role of oxidative stress related to sperm quality has been researched thoroughly and estimated to be the problem in 25%-87% of male infertility cases. Impryl is a nutritional supplement which works on the metabolic system and the regulation of oxidative stress by activating the 1-carbon cycle and therefore recycling of homocysteine. We hypothesise that the nutritional supplement Impryl in men of infertile couples might improve the ongoing pregnancy rate. METHODS AND ANALYSIS: We designed a multicentre, randomised, double-blind, placebo-controlled clinical trial. We aimed to include 1200 male adults aged 18-50 years, part of a couple that is diagnosed with infertility. The couple will either start or has already been started with fertility treatment, that is, expectative management (duration of 6 months), intrauterine insemination (IUI) with or without mild ovarian stimulation or ovulation induction, either in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Male participants will be randomised in either the Impryl or the placebo group, with identical appearance of the tablets to be distributed (doses: one tablet each day), for a total duration of maximal 6 months. Patients can start directly with fertility treatment and/or natural conception. The primary outcome is the number of ongoing pregnancies confirmed by ultrasound at ≥10 to 12 weeks, and conceived in the time window between randomisation up to and including month 6 of intervention use. Secondary outcomes are change in semen parameters between baseline and after 3 months of intervention in the IUI/IVF/ICSI group, based on (prewash) total motile sperm count. Furthermore the number of pregnancies conceived in the optimal intervention time window (after full spermatogenesis of 72 days), overall number of pregnancies, time to pregnancy, embryo fertilisation rate in IVF/ICSI, embryo-utilisation rate in IVF/ICSI, number of miscarriages, live birth rate and adverse events are documented within the study period of 15 months. ETHICS AND DISSEMINATION: The protocol is approved by the local medical ethical review committee at the Radboud University Medical Centre and by the national Central Committee on Research Involving Human Subjects. Findings will be shared with the academic and medical community, funding and patient organisations in order to contribute to optimisation of medical care and quality of life for patients with infertility. TRIAL REGISTRATION NUMBERS: NCT03337360 and NTR6551