AzTrials
AzTrials

Male InfertilityNCT07330869

Warfarin Effects on Male Fertility After Cardiac Surgery

An observational study of Male Infertility and Heart Valve Disease, run by Città di Lecce Hospital, GVM Care & Research at 1 site in Italy.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Young male patients undergoing cardiac surgery may require oral anticoagulation with warfarin either lifelong, such as after mechanical valve replacement, or for a limited postoperative period, for example following valve repair or bioprosthetic valve implantation. Read more about this study

Who is it for?
Ages 18 to 50 years, men only
Conditions the study is for
Male Infertility, Heart Valve Disease
What is being tested?
Semen analysis, sperm DNA fragmentation and hormonal evaluation
Type of treatment
Pill or oral medicine
How many people
90 participants
Where
1 siteItaly
Study dates
Feb 2026to Jun 2028
Phase
Observational
Are there results?
Not yet: the study is under way

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
  • No healthy volunteers
  • Adult

Study population: This study will enroll male patients aged 18 to 50 years undergoing elective cardiac surgery at a high-volume cardiac surgery center. Participants will include individuals requiring either lifelong Warfarin therapy (mechanical heart valve replacement), short-term postoperative Warfarin therapy (e.g., mitral valve repair or bioprosthetic valve implantation), or no long-term anticoagulation beyond routine perioperative prophylaxis. Eligible patients must have no previous diagnosis of male infertility, must be able and willing to provide semen samples at scheduled follow-up timepoints, and must provide written informed consent. Patients with severe testicular disease, prior chemotherapy or radiotherapy, endocrine disorders affecting spermatogenesis, active genitourinary infection, or current/recent use of anabolic steroids or medications known to impair spermatogenesis will be excluded.

Who may be able to join

  • Male sex, age between 18 and 50 years;
  • Scheduled for elective cardiac surgery (valve replacement, valve repair, or other cardiac procedures) with or without indication to Warfarin therapy;
  • Ability and willingness to provide semen samples at scheduled timepoints;
  • No previous diagnosis of male infertility documented in medical records;
  • Signed informed consent.

Who cannot join

  • Known severe testicular pathology (for example, untreated high-grade varicocele, history of cryptorchidism, orchiectomy, testicular tumors);
  • Prior chemotherapy or pelvic radiotherapy;
  • Current or recent use of anabolic steroids or other drugs known to strongly impair spermatogenesis;
  • Known endocrine disorders affecting spermatogenesis (for example, untreated hypogonadism, hyperprolactinaemia, severe thyroid disease);
  • Active genitourinary infection at the time of evaluation;
  • Life expectancy less than 12 months or clinical conditions preventing adherence to follow-up.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Giuseppe Santarpino, MD, PhD contact

+393246940566

gsantarpino@gvmnet.it

Veronica D'Anna, MSc contact

+39 3891437634

veronicadanna21@gmail.com

Italy1 site

  • Città di Lecce Hospital - Department of Cardiac Surgery

    Lecce, LE, 73100

    Giuseppe Santarpino MD, PhD, Cardiac Surgeon, +39 3246940566, gsantarpino@gvmnet.it

    Veronica D'Anna, MSc, +393891437634, veronicadanna21@gmail.com

Other trials in Italy

About this study

Official title: Effects of Warfarin Therapy on Semen Quality, DNA Integrity, Hormonal Profile and Molecular Alterations in Male Patients Undergoing Cardiac Surgery: A Prospective Comparative Pilot Study

Young male patients undergoing cardiac surgery may require oral anticoagulation with warfarin either lifelong, such as after mechanical valve replacement, or for a limited postoperative period, for example following valve repair or bioprosthetic valve implantation. Although the teratogenic effects of warfarin during pregnancy are well established, prospective clinical data on the potential impact of warfarin therapy on male reproductive health are scarce. This gap is particularly relevant for patients of reproductive age who may have a present or future desire for fatherhood.

Warfarin acts as a vitamin K antagonist by inhibiting the vitamin K epoxide reductase complex, thereby reducing the availability of functional vitamin K. Beyond its role in coagulation, vitamin K is increasingly recognized as an important regulator of spermatogenesis, mitochondrial function, oxidative balance, and steroid hormone synthesis. Experimental and translational evidence suggests that disruption of vitamin K-dependent pathways may impair sperm quality, DNA integrity, mitochondrial bioenergetics, and reproductive hormone homeostasis. In addition, warfarin exposure has been associated with increased oxidative stress and inflammatory responses, both of which are known contributors to male infertility.

Read more

Despite these biologically plausible mechanisms, no prospective observational studies have systematically evaluated semen parameters, sperm DNA fragmentation, hormonal profiles, inflammatory markers, and advanced molecular sperm alterations in men exposed to warfarin after cardiac surgery. Consequently, structured andrological assessment is rarely incorporated into routine preoperative counseling or postoperative follow-up in this population.

This prospective pilot observational study aims to investigate the association between warfarin therapy and male reproductive health in patients undergoing elective cardiac surgery. Male patients aged 18 to 50 years will be enrolled and observed in three cohorts based on clinical indication for anticoagulation: (1) long-term warfarin therapy following mechanical valve replacement; (2) short-term warfarin therapy (approximately three months) after selected cardiac procedures; and (3) a control cohort undergoing cardiac surgery without an indication for long-term oral anticoagulation beyond standard perioperative prophylaxis.

Participants will undergo comprehensive andrological assessments at baseline and during follow-up up to 12 months after surgery. Evaluations will include semen analysis according to World Health Organization guidelines, assessment of sperm DNA fragmentation, reproductive hormonal profiles, and seminal inflammatory markers. Exploratory analyses will assess mitochondrial function, oxidative stress, and molecular alterations in spermatozoa. Detailed warfarin exposure data, including dose, cumulative exposure, international normalized ratio values, and time in therapeutic range, will be collected to explore potential exposure-response relationships.

As a pilot study, the primary aims are to assess feasibility and generate preliminary clinical evidence to inform future larger studies. The findings may contribute to improved clinical counseling, fertility preservation strategies, and integration of reproductive health considerations into the multidisciplinary management of young male cardiac surgery patients.

Read the detailed description

This prospective, comparative, pilot observational study is designed to investigate the effects of warfarin therapy on male reproductive health in patients undergoing elective cardiac surgery, integrating conventional andrological assessment with inflammatory, hormonal, and exploratory molecular analyses.

Young male patients undergoing cardiac surgery may require oral anticoagulation with warfarin either lifelong, most commonly after mechanical heart valve replacement, or for a limited postoperative period following selected procedures such as valve repair or bioprosthetic valve implantation. Although the teratogenic effects of warfarin during pregnancy are well established, prospective clinical data addressing its potential impact on male reproductive health are scarce. This knowledge gap is particularly relevant for patients of reproductive age who may have a present or future desire for fatherhood and for whom fertility-related counseling is increasingly important.

Warfarin exerts its anticoagulant effect through inhibition of the vitamin K epoxide reductase (VKOR) complex, resulting in reduced availability of biologically active vitamin K. Beyond its role in coagulation, vitamin K-dependent pathways are involved in key aspects of male reproductive physiology, including spermatogenesis, mitochondrial bioenergetics, oxidative stress regulation, inflammatory signaling, and steroid hormone synthesis. Experimental and translational evidence suggests that disruption of these pathways may impair semen quality, sperm DNA integrity, mitochondrial function, and endocrine homeostasis, while promoting oxidative stress and inflammatory responses known to contribute to male infertility. However, these mechanisms have not been systematically explored in prospective clinical studies involving men exposed to warfarin after cardiac surgery.

The study adopts a prospective cohort design with a comparative approach and includes three groups of male patients stratified according to clinical indication for anticoagulation: (1) patients receiving long-term warfarin therapy following mechanical valve replacement; (2) patients receiving short-term postoperative warfarin therapy, typically for approximately three months, after selected cardiac surgical procedures; and (3) a control group undergoing cardiac surgery without indication for long-term oral anticoagulation beyond standard perioperative prophylaxis. This design allows evaluation of different exposure patterns, including chronic exposure, transient exposure, and non-exposure, and supports exploratory assessment of exposure-response relationships and reversibility after treatment discontinuation.

Participants undergo structured and standardized andrological evaluations at baseline (preoperative) and during longitudinal follow-up up to 12 months after surgery. Conventional semen analysis is performed according to World Health Organization (WHO) guidelines and includes assessment of sperm concentration, progressive motility, morphology, and related semen parameters. Sperm DNA integrity is evaluated through measurement of the sperm DNA fragmentation index (DFI) using the sperm chromatin dispersion (SCD) assay.

Reproductive endocrine function is assessed through serial measurement of serum reproductive hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, sex hormone-binding globulin (SHBG), prolactin, and thyroid-stimulating hormone (TSH), using standardized laboratory immunoassay methods.

Local inflammatory processes within the male reproductive tract are investigated through assessment of seminal inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), and prostaglandin F2α (PGF2α). These biomarkers are measured using standardized enzyme-linked immunosorbent assay (ELISA) techniques and evaluated in relation to semen quality parameters.

To provide mechanistic insight beyond conventional clinical and laboratory assessments, exploratory molecular analyses are performed on spermatozoa. These analyses include evaluation of mitochondrial function and bioenergetics, assessment of oxidative stress-related parameters, and analysis of selected proteins involved in sperm energy metabolism and motility, using validated laboratory techniques. These exploratory investigations are intended to characterize molecular alterations potentially associated with warfarin exposure and to generate hypotheses for future mechanistic studies.

Detailed warfarin exposure data are collected prospectively from clinical records and anticoagulation monitoring systems, including daily and cumulative dosing information, international normalized ratio (INR) measurements, and quality of anticoagulation control over time as reflected by time in therapeutic range (TTR). These exposure variables are used to support exploratory correlation analyses with reproductive, inflammatory, and molecular outcomes, as well as evaluation of potential reversibility of observed alterations in patients receiving short-term warfarin therapy after treatment discontinuation.

Sexual and reproductive function is further characterized through validated questionnaires assessing sexual function, including the International Index of Erectile Function-5 (IIEF-5), and through collection of exploratory reproductive outcomes, such as desire for paternity and occurrence of partner pregnancies during follow-up.

As a pilot study, the primary objectives are to assess feasibility, characterize longitudinal changes in male reproductive parameters, and generate preliminary clinical and mechanistic data to inform the design of future larger-scale studies. The findings are expected to contribute to improved fertility-related counseling, consideration of fertility preservation strategies, and integration of reproductive health assessment into the multidisciplinary management of young male patients undergoing cardiac surgery.

Being tested
Semen analysis, sperm DNA fragmentation and hormonal evaluation
Keywords
warfarin, male infertility, Semen quality, Sperm DNA fragmentation, Mitochondrial function, Inflammation, Mechanical heart valve, Cardiac surgery, Oral anticoagulation, Vitamin K antagonists, Reproductive hormones, anticoagulation
Medical subject headings
Infertility, Male, Heart Valve Diseases, Inflammation

What participants receive

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

  • Semen analysis, sperm DNA fragmentation and hormonal evaluationOther

    Participants undergo standardized study assessments including semen analysis according to WHO criteria, sperm DNA fragmentation assessment, hormonal blood tests, andrological ultrasound, and exploratory molecular analyses of spermatozoa (mitochondrial function, oxidative stress markers, inflammatory mediators, and protein expression). All assessments are performed for observational and research purposes only and do not guide or modify clinical treatment.

Study groups in NCT07330869
Study groupRoleWhat they receive
Long-term Warfarin GroupMale patients undergoing cardiac surgery with an indication for lifelong oral anticoagulation with warfarin, typically after mechanical heart valve replacement. Warfarin therapy is prescribed as part of standard clinical care and is not assigned by the study.
Receives: Other: Semen analysis, sperm DNA fragmentation and hormonal evaluation
Short-term Warfarin GroupMale patients undergoing cardiac surgery with an indication for short-term postoperative warfarin therapy (approximately three months), such as after valve repair or bioprosthetic valve implantation. Anticoagulation is administered according to standard clinical practice and not determined by the study protocol.
Receives: Other: Semen analysis, sperm DNA fragmentation and hormonal evaluation
Control Group (No Long-term Anticoagulation)Male patients undergoing cardiac surgery without an indication for long-term oral anticoagulation beyond routine perioperative prophylaxis. These patients serve as a comparison group and do not receive chronic warfarin therapy.
Receives: Other: Semen analysis, sperm DNA fragmentation and hormonal evaluation

What is being measured

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

  1. Change in sperm concentration over time

    Change in sperm concentration expressed as millions of spermatozoa per milliliter (millions/mL), assessed by standard semen analysis performed according to World Health Organization (WHO) guidelines. Correlation between warfarin exposure status (long-term exposure, short-term exposure, or no exposure) and changes in sperm concentration over time will be evaluated.

    Measured: Baseline (T0) to 6 months (T2) and 12 months (T3)

  2. Change in progressive sperm motility over time

    Change in progressive sperm motility expressed as percentage (%), assessed by standard semen analysis according to World Health Organization (WHO) guidelines. Correlation between warfarin exposure status (long-term exposure, short-term exposure, or no exposure) and changes in progressive sperm motility over time will be evaluated.

    Measured: Baseline (T0) to 6 months (T2) and 12 months (T3)

  3. Change in sperm morphology over time

    Change in the percentage (%) of spermatozoa with normal morphology, assessed using strict criteria as part of standard semen analysis according to World Health Organization (WHO) guidelines. Correlation between warfarin exposure status (long-term exposure, short-term exposure, or no exposure) and changes in sperm morphology over time will be evaluated.

    Measured: Baseline (T0) to 6 months (T2) and 12 months (T3)

Secondary outcomes (23)

  1. Change in sperm DNA fragmentation index (DFI)

    Change in sperm DNA fragmentation index (DFI), assessed using a validated assay (sperm chromatin dispersion method), between baseline and follow-up timepoints in warfarin-exposed and control groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  2. Change in serum follicle-stimulating hormone (FSH) levels

    Change in serum follicle-stimulating hormone (FSH) levels, measured in international units per liter (IU/L) using standard immunoassay methods, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  3. Change in serum luteinizing hormone (LH) levels

    Change in serum luteinizing hormone (LH) levels, measured in international units per liter (IU/L) using standard immunoassay methods, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  4. Change in serum total testosterone levels

    Change in serum total testosterone levels, measured in nanograms per deciliter (ng/dL) using standard immunoassay methods, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  5. Change in serum sex hormone-binding globulin (SHBG) levels

    Change in serum sex hormone-binding globulin (SHBG) levels, measured in nanomoles per liter (nmol/L) using standard immunoassay methods, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  6. Change in serum prolactin levels

    Change in serum prolactin levels, measured in nanograms per milliliter (ng/mL) using standard immunoassay methods, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  7. Change in serum thyroid-stimulating hormone (TSH) levels

    Change in serum thyroid-stimulating hormone (TSH) levels, measured in milli-international units per liter (mIU/L) using standard immunoassay methods, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  8. Correlation between mean daily warfarin dose and changes in semen parameters

    Correlation between mean daily warfarin dose, expressed in milligrams per day (mg/day), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines, in warfarin-exposed patients.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  9. Correlation between cumulative warfarin dose and changes in semen parameters

    Correlation between cumulative warfarin dose, expressed in milligrams (mg), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines, in warfarin-exposed patients.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  10. Correlation between time in therapeutic range and changes in semen parameters

    Correlation between time in therapeutic range (TTR), expressed as percentage (%), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines, in warfarin-exposed patients.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  11. Correlation between warfarin exposure and changes in sperm DNA fragmentation index

    Correlation between warfarin exposure variables (mean daily dose [mg/day], cumulative dose [mg], and time in therapeutic range [%]) and changes from baseline in sperm DNA fragmentation index (DFI), expressed as percentage (%), assessed using the sperm chromatin dispersion (SCD) assay.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  12. Reversibility of changes in semen parameters after short-term warfarin discontinuation

    Evaluation of reversibility of changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines, between 3 and 6 months after surgery (T1 to T2), in patients receiving short-term warfarin therapy.

    Measured: From 3 to 6 months after surgery (T1 to T2)

  13. Reversibility of changes in sperm DNA fragmentation index after short-term warfarin discontinuation

    Evaluation of reversibility of changes from baseline in sperm DNA fragmentation index (DFI), expressed as percentage (%), assessed using the sperm chromatin dispersion (SCD) assay, between 3 and 6 months after surgery (T1 to T2), in patients receiving short-term warfarin therapy.

    Measured: From 3 months (T1) to 6 months (T2) after surgery

  14. Correlation between seminal interleukin-6 (IL-6) levels and semen parameters

    Correlation between seminal interleukin-6 (IL-6) concentration, measured using a standardized enzyme-linked immunosorbent assay (ELISA), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  15. Correlation between seminal tumor necrosis factor-alpha (TNF-α) levels and semen parameters

    Correlation between seminal tumor necrosis factor-alpha (TNF-α) concentration, measured using a standardized enzyme-linked immunosorbent assay (ELISA), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  16. Correlation between seminal prostaglandin E2 (PGE2) levels and semen parameters

    Correlation between seminal prostaglandin E2 (PGE2) concentration, measured using a standardized enzyme-linked immunosorbent assay (ELISA), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  17. Correlation between seminal prostaglandin F2α (PGF2α) levels and semen parameters

    Correlation between seminal prostaglandin F2α (PGF2α) concentration, measured using a standardized enzyme-linked immunosorbent assay (ELISA), and changes from baseline in semen parameters assessed by standard semen analysis according to World Health Organization (WHO) guidelines.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  18. Exploratory assessment of mitochondrial function in spermatozoa

    Exploratory evaluation of mitochondrial function in spermatozoa, assessed using validated bioenergetic assays evaluating mitochondrial respiratory activity and related functional parameters.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  19. Exploratory assessment of oxidative stress markers in spermatozoa

    Exploratory evaluation of oxidative stress-related parameters in spermatozoa, assessed using validated assays measuring reactive oxygen species production and lipid peroxidation markers.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  20. Exploratory assessment of sperm protein expression involved in bioenergetics and motility

    Exploratory evaluation of the expression of selected sperm proteins involved in bioenergetics and motility, assessed using validated protein analysis techniques.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  21. Change in sexual function assessed by the International Index of Erectile Function-5 (IIEF-5)

    Change in sexual function assessed using the International Index of Erectile Function-5 (IIEF-5) questionnaire, expressed as total score on a validated scale, evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  22. Desire for paternity over time

    Assessment of desire for paternity, recorded as a categorical variable (presence or absence of desire for fatherhood), evaluated over time and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

  23. Occurrence of partner pregnancies during follow-up

    Occurrence of partner pregnancies during the follow-up period, assessed as incidence of pregnancies reported by participants and compared between study groups.

    Measured: Baseline (T0), 3 months (T1), 6 months (T2), and 12 months (T3)

Timeline

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

  1. First posted9 Jan 2026
  2. Study startFeb 2026 (estimated)
  3. Primary completionFeb 2027 (estimated)
  4. Study completionJun 2028 (estimated)

Resources

More details

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

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
90 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07330869
Sponsor's protocol ID
WARF-SEMIN-2025-01
Status last verified
Dec 2025
First submitted
15 Dec 2025
Last updated
9 Jan 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Popov A, Belij S, Subota V, Zolotarevski L, Mirkov I, Kataranovski D, Kataranovski M. Oral warfarin affects peripheral blood leukocyte IL-6 and TNFalpha production in rats. J Immunotoxicol. 2013 Jan-Mar;10(1):17-24. doi: 10.3109/1547691X.2012.684159. Epub 2012 Jul 13.

    PubMed 22793260

  • Azenabor A, Ekun AO, Akinloye O. Impact of Inflammation on Male Reproductive Tract. J Reprod Infertil. 2015 Jul-Sep;16(3):123-9.

    PubMed 26913230

  • Ma H, Zhang BL, Liu BY, Shi S, Gao DY, Zhang TC, Shi HJ, Li Z, Shum WW. Vitamin K2-Dependent GGCX and MGP Are Required for Homeostatic Calcium Regulation of Sperm Maturation. iScience. 2019 Apr 26;14:210-225. doi: 10.1016/j.isci.2019.03.030. Epub 2019 Mar 29.

    PubMed 30981116

  • Shiba S, Ikeda K, Horie-Inoue K, Azuma K, Hasegawa T, Amizuka N, Tanaka T, Takeiwa T, Shibata Y, Koji T, Inoue S. Vitamin K-Dependent gamma-Glutamyl Carboxylase in Sertoli Cells Is Essential for Male Fertility in Mice. Mol Cell Biol. 2021 Mar 24;41(4):e00404-20. doi: 10.1128/MCB.00404-20. Print 2021 Mar 24.

    PubMed 33526452

  • Alfano M, Pederzoli F, Locatelli I, Ippolito S, Longhi E, Zerbi P, Ferrari M, Brendolan A, Montorsi F, Drago D, Andolfo A, Nebuloni M, Salonia A. Impaired testicular signaling of vitamin A and vitamin K contributes to the aberrant composition of the extracellular matrix in idiopathic germ cell aplasia. Fertil Steril. 2019 Apr;111(4):687-698. doi: 10.1016/j.fertnstert.2018.12.002.

    PubMed 30929729

  • Shirakawa H, Ohsaki Y, Minegishi Y, Takumi N, Ohinata K, Furukawa Y, Mizutani T, Komai M. Vitamin K deficiency reduces testosterone production in the testis through down-regulation of the Cyp11a a cholesterol side chain cleavage enzyme in rats. Biochim Biophys Acta. 2006 Oct;1760(10):1482-8. doi: 10.1016/j.bbagen.2006.05.008. Epub 2006 Jun 6.

    PubMed 16844298

  • Sanyaolu AO, Oremosu AA, Osinubi AA, Vermeer C, Daramola AO. Warfarin-induced vitamin K deficiency affects spermatogenesis in Sprague-Dawley rats. Andrologia. 2019 Nov;51(10):e13416. doi: 10.1111/and.13416. Epub 2019 Oct 1.

    PubMed 31576592

  • Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomstrom-Lundqvist C, Cifkova R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA; ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018 Sep 7;39(34):3165-3241. doi: 10.1093/eurheartj/ehy340. No abstract available.

    PubMed 30165544

  • Chan WS, Anand S, Ginsberg JS. Anticoagulation of pregnant women with mechanical heart valves: a systematic review of the literature. Arch Intern Med. 2000 Jan 24;160(2):191-6. doi: 10.1001/archinte.160.2.191.

    PubMed 10647757

  • Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med. 1980 Jan;68(1):122-40. doi: 10.1016/0002-9343(80)90181-3.

    PubMed 6985765

Questions about this trial

What is this clinical trial studying?

An observational study of Male Infertility and Heart Valve Disease, run by Città di Lecce Hospital, GVM Care & Research at 1 site in Italy.

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 6 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: opening soon, as of the sponsor's last update on 9 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. 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. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Giuseppe Santarpino, MD, PhD (+393246940566, gsantarpino@gvmnet.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in sperm concentration over time (time frame: Baseline (T0) to 6 months (T2) and 12 months (T3)). The study lists 3 primary outcomes in all. 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 NCT07330869, 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 9 Jan 2026.

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