The Impact of a Nutritional Supplement (Impryl®) on Male Fertility
- Conditions
- Male Subfertility
- Interventions
- Other: PlaceboDietary Supplement: Impryl
- Registration Number
- NCT03337360
- Lead Sponsor
- Radboud University Medical Center
- Brief Summary
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. Male infertility is of multifactorial origin. 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 infertility cases.
Impryl® is a nutritional supplement mainly consisting of vitamin B, which works on the metabolic system by activating the one carbon cycle and recycling of homocysteine without the use of any direct strong antioxidants.
In this study the investigators want to determine the effectiveness of nutritional supplement Impryl® in men of infertile couples on ongoing pregnancy rate, with or without assisted reproduction technology (ART).
- Detailed Description
Rationale: 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. 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 infertility cases. Impryl® is a nutritional supplement which works on the metabolic system and regulation of oxidative stress by activating the 1-Carbon cycle and therefore recycling of homocysteine.
Objective: To determine the effectiveness of nutritional supplement Impryl® in men of infertile couples on ongoing pregnancy rate, with or without assisted reproduction technology (ART).
Study design: Multicentre, randomised double blind placebo controlled clinical trial/superiority study.
Study population: All participants in this study are male adults, age 18-50 years, part of a couple that is diagnosed with infertility, regardless the outcome of semen analysis. The couple will either start or is already started with fertility treatment, i.e. expectative management (EM, duration 6 months), intra-uterine insemination (IUI) with or without ovarian stimulation (mild ovarian hyperstimulation (MOH) or ovulation induction (OI)), either in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.
Intervention: Impryl® or placebo, with identical appearance one tablet each day for a total duration of maximal 6 months. Patients can start directly with study medication and fertility treatment (or to conceive spontaneously).
Main study parameters/endpoints: The primary outcome is the number of ongoing pregnancies confirmed by ultrasound at ≥ 10-12 weeks. Secondary outcomes are change in semen parameters between baseline and 3 months intervention in IUI/IVF/ICSI group, based on (pre-wash) total motile sperm count (TMSC), leading to a change in treatment category Furthermore the occurrence of pregnancy, time to pregnancy, embryo fertilization rate in IVF/ICSI, embryo-utilization rate in IVF/ICSI, number of miscarriages and live birth rate are documented within the study period. The occurrence of adverse events will be reported.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 1200
Couples with failure to conceive for at least 12 months and starting with EM or Couples starting with 1st/ 2nd/3rd cycle of IUI (with/without ovarian stimulation) or Couples starting with 1st/ 2nd/3rd cycle of IVF/ICSI
Furthermore:
- Male with age 18-50 years
- Female partner with age 18-43 years
- Willing and able to give informed consent
- Planned or performed diagnostic testicular biopsy (TESE) or percutaneous epididymal sperm aspiration (PESA)
- Use of donor-, cryopreserved- or electro-ejaculated semen
- Ovulation induction (OI) without IUI
- IVF for an absolute tubal factor
- Embryo-transfers after cryopreservation
- Embryo-transfer after pre-implantation genetic diagnosis
- Known genetic abnormalities related to infertility
- Known urological abnormality such as a varicocele or bilateral cryptorchism
- Use of other vitamin supplements
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo One tablet daily for 6 months Impryl Impryl One tablet daily for 6 months
- Primary Outcome Measures
Name Time Method Ongoing pregnancy rate 15 months Ongoing pregnancy ≥10-12 weeks of gestation
- Secondary Outcome Measures
Name Time Method Number of miscarriages 15 months Defined as a non-vital intra-uterine pregnancy before 16 weeks of gestation
Time to pregnancy 1 - start intervention 15 months The time between start of intervention and reaching ongoing pregnancy
Overall pregnancy rate 15 months All pregnancies confirmed with a positive pregnancy (HCG) test
Time to pregnancy 1 - start fertility treatment 15 months The time between start of fertility treatment and reaching ongoing pregnancy
Change in semen parameters leading to change in treatment category 15 months Between baseline and 3 months intervention, based on pre-wash total motile sperm count (TMSC) from the subpopulation from Radboudumc and sites that deliver a pre-wash TMSC before IUI/IVF/ICSI
Live birth rate 15 months All live births
Embryo fertilization rate 15 months Relative improvement. Fertilization rate is the percentage of oocytes with \>=2 PN after insemination (IVF) of injection (ICSI).
Adverse effects 15 months Gastro-intestinal problems such as reflux, obstipation, diarrhea, nausea or vomiting, furthermore loss of appetite, headache, dizziness, pruritus or skin rash.
Embryo-utilization rate 15 months Relative improvement of the embryo-utilization rate (EUR), defined as the number of high quality embryos obtained, embryo's used at transfer plus the number of embryos frozen, divided by the number of zygotes obtained in a cycle
Trial Locations
- Locations (21)
Gelre Ziekenhuizen
🇳🇱Apeldoorn, Netherlands
Amphia ziekenhuis
🇳🇱Breda, Netherlands
Slingeland Ziekenhuis
🇳🇱Doetinchem, Netherlands
Albert Schweitzer ziekenhuis
🇳🇱Dordrecht, Netherlands
Maasziekenhuis Pantein
🇳🇱Boxmeer, Netherlands
Nij Linge
🇳🇱Gorinchem, Netherlands
Rijnstate
🇳🇱Arnhem, Netherlands
Catharina Ziekenhuis Eindhoven
🇳🇱Eindhoven, Netherlands
Nij Geertgen
🇳🇱Elsendorp, Netherlands
Radboudumc
🇳🇱Nijmegen, Netherlands
Bernhoven Ziekenhuis
🇳🇱Uden, Netherlands
Medisch Centrum Kinderwens
🇳🇱Leiderdorp, Netherlands
Jeroen Bosch Ziekenhuis
🇳🇱's-Hertogenbosch, Netherlands
Treant ziekenhuis Scheper
🇳🇱Emmen, Netherlands
Máxima Medisch Centrum
🇳🇱Veldhoven, Netherlands
Nij Barrahus
🇳🇱Wolvega, Netherlands
Bravis Ziekenhuis
🇳🇱Roosendaal, Netherlands
Franciscus Gasthuis en Vlietland
🇳🇱Rotterdam, Netherlands
Elisabeth-TweeSteden Ziekenhuis
🇳🇱Tilburg, Netherlands
Fertiliteitscentrum Voorburg
🇳🇱Voorburg, Gelderland, Netherlands
Maasstad ziekenhuis
🇳🇱Rotterdam, Netherlands