Clinical Thresholds of Double-strand Breaks in Sperm's DNA in ART

A Prospective Trial Assessing the Impact of Double-strand Breaks on ART Outcomes and Predicting Its Clinical Thresholds

Status

Not yet recruiting

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT07621991

Acronym

DSBs

Enrollment

484

Registered

2026-06-02

Start date

2026-06-01

Completion date

2027-12-01

Last updated

2026-06-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Sperm DNA Fragmentation, Sperm DNA Impact on ART Outcomes

Keywords

Sperm DNA fragmentation, Double-strand sperm DNA fragmentation, LensHooke® X12, ntracytoplasmic sperm injection, Live birth

Brief summary

The goal of this prospective observational study is to learn about the impact of double-strand sperm DNA fragmentation (dsSDF) on assisted reproductive technology (ART) outcomes and to derive clinically relevant threshold values for dsSDF and global sperm DNA fragmentation (SDF) in couples undergoing intracytoplasmic sperm injection (ICSI). The main questions it aims to answer are: * Can clinically relevant threshold values of dsSDF and global SDF predict live birth rates following ICSI? * Does elevated dsSDF reduce live birth rates following ICSI? Participants undergoing ICSI as part of their routine fertility treatment will provide semen samples for global SDF and dsSDF assessment using the R10 Plus and R11 Plus kits, respectively, analysed using the LensHooke® X12 platform before and after sperm preparation. SDF and dsSDF assessments will be performed both prior to and following sperm washing for each participant. Embryos will be assessed from fertilization through embryo development, and following embryo transfer, participants will be prospectively followed for clinical outcomes ranging from biochemical pregnancy to live birth.

Detailed description

This prospective, two-centre observational study is designed to evaluate the impact of double-strand sperm DNA fragmentation (dsSDF) on assisted reproductive technology (ART) outcomes and to derive clinically relevant threshold values for dsSDF and global sperm DNA fragmentation (SDF) in couples undergoing intracytoplasmic sperm injection (ICSI). Although conventional sperm DNA fragmentation assays assess overall DNA damage, they do not differentiate between single- and double-strand DNA breaks. Emerging evidence suggests that dsSDF represents a more severe form of genomic damage with limited oocyte repair potential and may therefore have a greater impact on embryological and reproductive outcomes, particularly live birth. A total of 484 infertile couples undergoing ICSI treatment at two tertiary IVF centres in India will be prospectively recruited based on predefined eligibility criteria. Semen samples will be collected on the day of ICSI following 2-3 days of sexual abstinence. Global SDF and dsSDF assessments will be performed using the LensHooke® X12 platform with the R10 Plus and R11 Plus kits, respectively. SDF testing will be conducted both before and after sperm preparation to evaluate the impact of sperm washing on DNA fragmentation parameters. Embryos derived from enrolled participants will be prospectively assessed from fertilization through embryo development. Following embryo transfer, participants will be prospectively followed for clinical outcomes including biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, and live birth. Receiver operating characteristic (ROC) curve analysis will be used to derive clinically relevant threshold values for dsSDF and global SDF. Multivariable regression analyses will additionally be performed to evaluate the predictive value of dsSDF and global SDF for ART outcomes while adjusting for potential confounding factors. The findings of this study are expected to improve the clinical interpretation of sperm DNA damage assessment and support the integration of dsSDF into individualized reproductive care.

Interventions

DEVICELensHooke X12 Device

The LensHooke® X12 device is an automated sperm DNA fragmentation assessment platform based on the sperm chromatin dispersion (SCD) principle. In this study, the device will be used to assess global sperm DNA fragmentation (SDF) and double-strand sperm DNA fragmentation (dsSDF) using the R10 Plus and R11 Plus kits, respectively. The platform incorporates automated image acquisition and analysis to minimize operator-dependent variability and standardize sperm DNA fragmentation assessment. Semen samples collected from participants undergoing intracytoplasmic sperm injection (ICSI) will be analysed before and after sperm preparation to evaluate the association between sperm DNA damage parameters and assisted reproductive technology (ART) outcomes.

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

21 Years to 55 Years

Healthy volunteers

Yes

Inclusion criteria

* Males aged 21-55 years undergoing ICSI treatment for male factor infertility. * Women with age 21-35 for self-oocyte pickup cycles * Oocyte donor cycles with recipient age of 21-35 years of age * Sperm with a minimum total motile sperm count of 2.0 million/mL and a minimum volume of 1.2 mL * Patients not underwent sperm DNA fragmentation testing * 2-3 days of abstinence prior to intracytoplasmic sperm injection (ICSI).

Exclusion criteria

* Severe male factor infertility (azoospermia or severe oligozoospermia; for this study defined as no sperm present or sample with \<2 million/ml sperm count) * Known systemic diseases (e.g., diabetes mellitus). * Surgically retrieved sperms using testicular sperm aspiration, testicular sperm extraction and percutaneous epididymal sperm aspiration. * Untreated endometrial or uterine factors or adnexal pathology * Embryos underwent preimplantation genetic testing for aneuploidy testing. * Patients with thin endometrium (\<7mm) * Patients opted or underwent donor sperms as the male gamete source. * Patients underwent antioxidant treatment in last 6 months prior to ICSI treatment.

Design outcomes

Primary

Measure	Time frame	Description
Live Birth rate	24 weeks post embryo transfer	Live birth will be defined as the delivery of one or more live infants at or beyond 24 weeks of gestation following embryo transfer. Live birth rate will be calculated as the proportion of embryo transfer cycles resulting in at least one live birth.

Secondary

Measure	Time frame	Description
Clinical Threshold Values for dsSDF and Global SDF	From fertilization assessment following intracytoplasmic sperm injection (ICSI) until live birth, approximately 18 months after participant enrolment.	Clinically relevant threshold values for double-strand sperm DNA fragmentation (dsSDF) and global sperm DNA fragmentation (SDF) will be derived using receiver operating characteristic (ROC) curve analysis based on their predictive ability for live birth and other assisted reproductive technology (ART) outcomes. Thresholds will be identified as the values associated with a significant reduction in reproductive outcomes following intracytoplasmic sperm injection (ICSI).

Countries

India