The impact of a nutritional supplement (Impryl®) on male fertility

Infertility is a worldwide problem and about 10% of all couples will be
affected by the inability to have children. In approximately 50% of infertile
couples a male factor is involved. In the past decade, the role of oxidative
stress on sperm has been researched thoroughly and found to be the problem in
30% to 80% of male subfertility cases. Oxidative stress in the sperm cells can
be measured with DNA fragmentation assays, these assay measure the level of DNA
damage in the sperm cells. Impryl® is a nutritional supplement which works on
the metabolic system and regulation of oxidative stress by activating the one
carbon cycle and therefore recycling of homocysteine.

To determine the effectiveness of nutritional supplement Impryl® in men of
infertile couples on ongoing pregnancy rate, with or without assisted
reproduction technology (ART).

Multicentre, randomised double blind placebo controlled clinical
trial/superiority study.

Impryl® or placebo, with identical appearance one tablet each day for a total
duration of 6 months. Patients can start directly to conceive or start with
fertility treatment.

Couples with infertility will receive standard fertility treatment, i.e. EM or
ART. The risks of participating in the trial are small. After a complete
diagnostic work-up for infertility, the males will be randomised for use of
either Impryl® or placebo. Impryl® is a food supplement already free available
throughout Europe. Males need to take study medication one tablet each day for
6 months in total. For this study, we want to measure improvement of semen
parameters after at least 3 months use of study medication. Performing a
pre-wash TMSC is in Radboudumc standard procedure when semen is used for IUI or
IVF/ICSI. However, at some sites there is only a post-wash TMSC available.
Furthermore, in couples with EM performing a TMSC after 3 months is not
standard care. We decided not to perform a semen analysis in the EM group due
to the fact that improvement in fertility treatment from expectative management
is not possible. Participants are required to collect study medication directly
at their local hospital or at Radboudumc. At the start of taking study
medication the couple is asked to fill in a questionnaire about their baseline
characteristics. To asses lifestyle changes during intervention and amount of
used study medication, every male will be asked each month (6 times in total)
to fill in an online questionnaire. Every couple will receive a final
questionnaire, 15 months after inclusion, about the outcome of fertility
treatment and occurrence of pregnancy.

Patients included in the Jeroen Bosch hospital will have two extra visits to
the hospital - upon inclusion and after 3 months - to hand over a semen sample
for the assessment of DNA fragmentation. The riks of participation for these
patients is low and the burden of participation for these patients is moderate.

The risks and burden associated with participation in this trial for all other
patients (except Jeroen Bosch hospital) can be considered negligible.