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

NCT ID: NCT03337360

Last Updated: 2025-04-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-23

Study Completion Date

2026-04-30

Brief Summary

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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

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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.

Conditions

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Male Subfertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Impryl

One tablet daily for 6 months

Group Type ACTIVE_COMPARATOR

Impryl

Intervention Type DIETARY_SUPPLEMENT

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

Placebo

One tablet daily for 6 months

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Inactive ingredients, placebo

Interventions

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Impryl

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

Intervention Type DIETARY_SUPPLEMENT

Placebo

Inactive ingredients, placebo

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Goodlife Fertility B.V.

UNKNOWN

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Annemiek Nap, Prof.dr.

Role: STUDY_DIRECTOR

Gynecologist, head of department of Obstetrics and Gynaecology

Annemiek Nap, Prof MD PhD

Role: PRINCIPAL_INVESTIGATOR

Gynecologist, head of department of Obstetrics and Gynecology

Locations

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Fertiliteitscentrum Voorburg

Voorburg, Gelderland, Netherlands

Site Status

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, , Netherlands

Site Status

Gelre Ziekenhuizen

Apeldoorn, , Netherlands

Site Status

Rijnstate

Arnhem, , Netherlands

Site Status

Maasziekenhuis Pantein

Boxmeer, , Netherlands

Site Status

Amphia ziekenhuis

Breda, , Netherlands

Site Status

Slingeland Ziekenhuis

Doetinchem, , Netherlands

Site Status

Albert Schweitzer ziekenhuis

Dordrecht, , Netherlands

Site Status

Catharina Ziekenhuis Eindhoven

Eindhoven, , Netherlands

Site Status

Nij Geertgen

Elsendorp, , Netherlands

Site Status

Treant ziekenhuis Scheper

Emmen, , Netherlands

Site Status

Nij Linge

Gorinchem, , Netherlands

Site Status

Medisch Centrum Kinderwens

Leiderdorp, , Netherlands

Site Status

Radboudumc

Nijmegen, , Netherlands

Site Status

Bravis Ziekenhuis

Roosendaal, , Netherlands

Site Status

Franciscus Gasthuis en Vlietland

Rotterdam, , Netherlands

Site Status

Maasstad ziekenhuis

Rotterdam, , Netherlands

Site Status

Elisabeth-TweeSteden Ziekenhuis

Tilburg, , Netherlands

Site Status

Bernhoven Ziekenhuis

Uden, , Netherlands

Site Status

Máxima Medisch Centrum

Veldhoven, , Netherlands

Site Status

Nij Barrahus

Wolvega, , Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type BACKGROUND
PMID: 1735495 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8359932 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7817460 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16413322 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18281241 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25504418 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25073983 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27423667 (View on PubMed)

de Ligny WR, de Bruin JP, Smits RM, Goovaerts IGF, Peeters K, Nap AW, Boxmeer JC, Donker RB, Schoonenberg M, Koks CAM, van Rumste MME, Visser J, Gielen SCJP, Boomsma CM, Smeenk JMJ, van Oppenraaij RHF, Cox T, Janse F, Muller LT, Brink-van der Vlugt JJ, Braat DDM, Fleischer K. Antioxidant Treatment and the Chance to Conceive in Men Seeking Fertility Care: The SUMMER Randomized Clinical Trial. JAMA Netw Open. 2025 Sep 2;8(9):e2532405. doi: 10.1001/jamanetworkopen.2025.32405.

Reference Type DERIVED
PMID: 40996763 (View on PubMed)

Smits R, D'Hauwers K, IntHout J, Braat D, Fleischer K. 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). BMJ Open. 2020 Jul 2;10(7):e035069. doi: 10.1136/bmjopen-2019-035069.

Reference Type DERIVED
PMID: 32616489 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://impryl.com/

Website Impryl

Other Identifiers

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NTR6551

Identifier Type: REGISTRY

Identifier Source: secondary_id

NL61414.091.17

Identifier Type: -

Identifier Source: org_study_id

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