The Impact of a Nutritional Supplement (Impryl®) on Male Fertility

Male Subfertility Clinical Trial

— SUMMER  

Official title:

The Impact of a Nutritional Supplement (Impryl®) on Male Fertility

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03337360
• Other study ID #: NL61414.091.17
• Secondary ID: NTR6551
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 23, 2018
• Est. completion date: April 30, 2026

Study information

• Verified date: February 2024
• Source: Radboud University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: April 30, 2026
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Infertility
• Infertility, Male
• Male Subfertility

Intervention

Dietary Supplement:
• Impryl
Food supplement with betaine, cystine, zinc, niacin, folic acid (5MTHF-glucosamine), Vitamin B12 (cobalamin), Vitamin B6, Vitamin B2 (riboflavin)

Other:
• Placebo
Inactive ingredients, placebo

Locations

Country	Name	City	State
Netherlands	Jeroen Bosch Ziekenhuis	's-Hertogenbosch
Netherlands	Gelre Ziekenhuizen	Apeldoorn
Netherlands	Rijnstate	Arnhem
Netherlands	Maasziekenhuis Pantein	Boxmeer
Netherlands	Amphia ziekenhuis	Breda
Netherlands	Slingeland Ziekenhuis	Doetinchem
Netherlands	Albert Schweitzer ziekenhuis	Dordrecht
Netherlands	Catharina Ziekenhuis Eindhoven	Eindhoven
Netherlands	Nij Geertgen	Elsendorp
Netherlands	Treant ziekenhuis Scheper	Emmen
Netherlands	Nij Linge	Gorinchem
Netherlands	Medisch Centrum Kinderwens	Leiderdorp
Netherlands	Radboudumc	Nijmegen
Netherlands	Bravis Ziekenhuis	Roosendaal
Netherlands	Franciscus Gasthuis en Vlietland	Rotterdam
Netherlands	Maasstad ziekenhuis	Rotterdam
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Netherlands	Bernhoven Ziekenhuis	Uden
Netherlands	Máxima Medisch Centrum	Veldhoven
Netherlands	Fertiliteitscentrum Voorburg	Voorburg	Gelderland
Netherlands	Nij Barrahus	Wolvega

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	Goodlife Fertility B.V.

Country where clinical trial is conducted

Netherlands, 

References & Publications (8)

Agarwal A, Prabakaran S, Allamaneni S. What an andrologist/urologist should know about free radicals and why. Urology. 2006 Jan;67(1):2-8. doi: 10.1016/j.urology.2005.07.012. No abstract available. — View Citation

Dattilo M, Cornet D, Amar E, Cohen M, Menezo Y. The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report. Reprod Biol Endocrinol. 2014 Jul 29;12:71. doi: 10.1186/1477-7827-12-71. — View Citation

Dattilo M, D'Amato G, Caroppo E, Menezo Y. Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet. J Assist Reprod Genet. 2016 Dec;33(12):1633-1648. doi: 10.1007/s10815-016-0767-4. Epub 2016 Jul 16. Erratum In: J Assist Reprod Genet. 2017 Jan;34(1):155. — View Citation

Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992 Feb;57(2):409-16. doi: 10.1016/s0015-0282(16)54855-9. — View Citation

Shekarriz M, Thomas AJ Jr, Agarwal A. Incidence and level of seminal reactive oxygen species in normal men. Urology. 1995 Jan;45(1):103-7. doi: 10.1016/s0090-4295(95)97088-6. — View Citation

Showell MG, Mackenzie-Proctor R, Brown J, Yazdani A, Stankiewicz MT, Hart RJ. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2014;(12):CD007411. doi: 10.1002/14651858.CD007411.pub3. Epub 2014 Dec 15. — View Citation

Tremellen K. Oxidative stress and male infertility--a clinical perspective. Hum Reprod Update. 2008 May-Jun;14(3):243-58. doi: 10.1093/humupd/dmn004. Epub 2008 Feb 14. — View Citation

Zini A, de Lamirande E, Gagnon C. Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa. Int J Androl. 1993 Jun;16(3):183-8. doi: 10.1111/j.1365-2605.1993.tb01177.x. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ongoing pregnancy rate	Ongoing pregnancy =10-12 weeks of gestation	15 months
Secondary	Overall pregnancy rate	All pregnancies confirmed with a positive pregnancy (HCG) test	15 months
Secondary	Time to pregnancy 1 - start intervention	The time between start of intervention and reaching ongoing pregnancy	15 months
Secondary	Time to pregnancy 1 - start fertility treatment	The time between start of fertility treatment and reaching ongoing pregnancy	15 months
Secondary	Change in semen parameters leading to change in treatment category	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	15 months
Secondary	Number of miscarriages	Defined as a non-vital intra-uterine pregnancy before 16 weeks of gestation	15 months
Secondary	Live birth rate	Live birth rate defined as beyond 24 weeks of gestation, the birth of a living child.	15 months
Secondary	Adverse effects	Gastro-intestinal problems such as reflux, obstipation, diarrhea, nausea or vomiting, furthermore loss of appetite, headache, dizziness, pruritus or skin rash.	15 months
Secondary	Embryo fertilization rate	Relative improvement. Fertilization rate is the percentage of oocytes with >=2 PN after insemination (IVF) of injection (ICSI).	15 months
Secondary	Embryo-utilization rate	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	15 months
Secondary	Live birth rate	All live births	15 months

External Links

•   Website Impryl