NCT03337360

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).

Trial Health

55
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
1,200

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2018

Longer than P75 for not_applicable

Geographic Reach
1 country

21 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 6, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

November 9, 2017

Completed
6 months until next milestone

Study Start

First participant enrolled

April 23, 2018

Completed
6.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 30, 2025

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2026

Completed
Last Updated

April 4, 2025

Status Verified

April 1, 2025

Enrollment Period

6.8 years

First QC Date

November 6, 2017

Last Update Submit

April 3, 2025

Conditions

Male Subfertility

Keywords

fertilitymale subfertilityfoodsupplementoxidative stress

Outcome Measures

Primary Outcomes (1)

  • Ongoing pregnancy rate

    Ongoing pregnancy ≥10-12 weeks of gestation

    15 months

Secondary Outcomes (10)

  • Overall pregnancy rate

    15 months

  • Time to pregnancy 1 - start intervention

    15 months

  • Time to pregnancy 1 - start fertility treatment

    15 months

  • Change in semen parameters leading to change in treatment category

    15 months

  • Number of miscarriages

    15 months

  • +5 more secondary outcomes

Study Arms (2)

Impryl

ACTIVE COMPARATOR

One tablet daily for 6 months

Dietary Supplement: Impryl

Placebo

PLACEBO COMPARATOR

One tablet daily for 6 months

Other: Placebo

Interventions

ImprylDIETARY_SUPPLEMENT

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

Impryl
PlaceboOTHER

Inactive ingredients, placebo

Placebo

Eligibility Criteria

Age18 Years - 50 Years
Sexmale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (21)

Fertiliteitscentrum Voorburg

Voorburg, Gelderland, Netherlands

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5200ME, Netherlands

Location

Gelre Ziekenhuizen

Apeldoorn, 7334DZ, Netherlands

Location

Rijnstate

Arnhem, 6815AD, Netherlands

Location

Maasziekenhuis Pantein

Boxmeer, 5835DV, Netherlands

Location

Amphia ziekenhuis

Breda, 4818CK, Netherlands

Location

Slingeland Ziekenhuis

Doetinchem, 7002BL, Netherlands

Location

Albert Schweitzer ziekenhuis

Dordrecht, 3318AT, Netherlands

Location

Catharina Ziekenhuis Eindhoven

Eindhoven, 5623EJ, Netherlands

Location

Nij Geertgen

Elsendorp, 5424SM, Netherlands

Location

Treant ziekenhuis Scheper

Emmen, 7824AA, Netherlands

Location

Nij Linge

Gorinchem, 4207HG, Netherlands

Location

Medisch Centrum Kinderwens

Leiderdorp, Netherlands

Location

Radboudumc

Nijmegen, 6500HB, Netherlands

Location

Bravis Ziekenhuis

Roosendaal, 4708AE, Netherlands

Location

Franciscus Gasthuis en Vlietland

Rotterdam, 3045PM, Netherlands

Location

Maasstad ziekenhuis

Rotterdam, 3079DZ, Netherlands

Location

Elisabeth-TweeSteden Ziekenhuis

Tilburg, 5022GC, Netherlands

Location

Bernhoven Ziekenhuis

Uden, 5400AS, Netherlands

Location

Máxima Medisch Centrum

Veldhoven, 5504DB, Netherlands

Location

Nij Barrahus

Wolvega, Netherlands

Location

Related Publications (10)

  • 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.

    PMID: 1735495BACKGROUND

  • 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.

    PMID: 8359932BACKGROUND

  • 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.

    PMID: 7817460BACKGROUND

  • 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.

    PMID: 16413322BACKGROUND

  • 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.

    PMID: 18281241BACKGROUND

  • 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.

    PMID: 25504418BACKGROUND

  • 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.

    PMID: 25073983BACKGROUND

  • 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.

    PMID: 27423667BACKGROUND

  • 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.

    PMID: 40996763DERIVED

  • 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.

    PMID: 32616489DERIVED

Related Links

MeSH Terms

Conditions

Infertility, Male

Condition Hierarchy (Ancestors)

Genital Diseases, MaleGenital DiseasesUrogenital DiseasesInfertilityMale Urogenital Diseases

Study Officials

  • Annemiek Nap, Prof.dr.

    Gynecologist, head of department of Obstetrics and Gynaecology

    STUDY DIRECTOR

  • Annemiek Nap, Prof MD PhD

    Gynecologist, head of department of Obstetrics and Gynecology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Multicentre, randomised double blind placebo controlled clinical trial/superiority study.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 6, 2017

First Posted

November 9, 2017

Study Start

April 23, 2018

Primary Completion

January 30, 2025

Study Completion

April 30, 2026

Last Updated

April 4, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Locations

NL(21)