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Male SubfertilitySUMMERNCT03337360

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

A study testing Impryl in people with Male Subfertility, run by Radboud University Medical Center at 21 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 50 years, men onlyHealthy volunteers can take part
Conditions the study is for
Male Subfertility
What is being tested?
Impryl
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,200 participants
Where
21 sitesNetherlands
Study dates
23 Apr 2018to 1 Jun 2025
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • Known genetic abnormalities related to infertility
  • Known urological abnormality such as a varicocele or bilateral cryptorchism
  • Use of other vitamin supplements

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

Netherlands21 sites
  • Jeroen Bosch Ziekenhuis

    's-Hertogenbosch, 5200ME

  • Gelre Ziekenhuizen

    Apeldoorn, 7334DZ

  • Rijnstate

    Arnhem, 6815AD

  • Maasziekenhuis Pantein

    Boxmeer, 5835DV

  • Amphia ziekenhuis

    Breda, 4818CK

  • Slingeland Ziekenhuis

    Doetinchem, 7002BL

  • Albert Schweitzer ziekenhuis

    Dordrecht, 3318AT

  • Catharina Ziekenhuis Eindhoven

    Eindhoven, 5623EJ

  • Nij Geertgen

    Elsendorp, 5424SM

  • Treant ziekenhuis Scheper

    Emmen, 7824AA

  • Nij Linge

    Gorinchem, 4207HG

  • Medisch Centrum Kinderwens

    Leiderdorp

  • Radboudumc

    Nijmegen, 6500HB

  • Bravis Ziekenhuis

    Roosendaal, 4708AE

  • Franciscus Gasthuis en Vlietland

    Rotterdam, 3045PM

  • Maasstad ziekenhuis

    Rotterdam, 3079DZ

  • Elisabeth-TweeSteden Ziekenhuis

    Tilburg, 5022GC

  • Bernhoven Ziekenhuis

    Uden, 5400AS

  • Máxima Medisch Centrum

    Veldhoven, 5504DB

  • Fertiliteitscentrum Voorburg

    Voorburg, Gelderland

  • Nij Barrahus

    Wolvega

Other trials in Netherlands

About this study

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).

Read the 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.

Being tested
Impryl, Placebo
Keywords
fertility, male subfertility, foodsupplement, oxidative stress
Medical subject headings
Infertility, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ImprylDietary supplement

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

  • PlaceboOther

    Inactive ingredients, placebo

Study groups in NCT03337360
Study groupRoleWhat they receive
ImprylActive comparatorOne tablet daily for 6 months
Receives: Dietary Supplement: Impryl
PlaceboPlacebo comparatorOne tablet daily for 6 months
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ongoing pregnancy rate

    Ongoing pregnancy ≥10-12 weeks of gestation

    Measured: 15 months

Secondary outcomes (10)
  1. Overall pregnancy rate

    All pregnancies confirmed with a positive pregnancy (HCG) test

    Measured: 15 months

  2. Time to pregnancy 1 - start intervention

    The time between start of intervention and reaching ongoing pregnancy

    Measured: 15 months

  3. Time to pregnancy 1 - start fertility treatment

    The time between start of fertility treatment and reaching ongoing pregnancy

    Measured: 15 months

  4. 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

    Measured: 15 months

  5. Number of miscarriages

    Defined as a non-vital intra-uterine pregnancy before 16 weeks of gestation

    Measured: 15 months

  6. Live birth rate

    Live birth rate defined as beyond 24 weeks of gestation, the birth of a living child.

    Measured: 15 months

  7. Adverse effects

    Gastro-intestinal problems such as reflux, obstipation, diarrhea, nausea or vomiting, furthermore loss of appetite, headache, dizziness, pruritus or skin rash.

    Measured: 15 months

  8. Embryo fertilization rate

    Relative improvement. Fertilization rate is the percentage of oocytes with >=2 PN after insemination (IVF) of injection (ICSI).

    Measured: 15 months

  9. 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

    Measured: 15 months

  10. Live birth rate

    All live births

    Measured: 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2017
  2. Study start23 Apr 2018
  3. Primary completion1 Dec 2024
  4. Study completion1 Jun 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Multicentre, randomised double blind placebo controlled clinical trial/superiority study.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
1,200 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03337360
Sponsor's protocol ID
NL61414.091.17
Other IDs
NTR6551
Acronym
SUMMER
Status last verified
Jun 2025
First submitted
6 Nov 2017
Last updated
28 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 1735495
  • 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.

    PubMed 8359932
  • 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.

    PubMed 7817460
  • 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.

    PubMed 16413322
  • 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.

    PubMed 18281241
  • 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.

    PubMed 25504418
  • 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.

    PubMed 25073983
  • 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.

    PubMed 27423667
  • 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.

    PubMed 40996763
  • 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.

    PubMed 32616489

Questions about this trial

What is this clinical trial studying?

A study testing Impryl in people with Male Subfertility, run by Radboud University Medical Center at 21 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ongoing pregnancy rate (time frame: 15 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03337360, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2026.

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