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

Indira IVF Hospital Pvt Ltd

Status: Not yet enrolling

Conditions: Sperm DNA Fragmentation; Sperm DNA Impact on ART Outcomes

Treatments: Device: LensHooke X12 Device

Study type: Observational

Funder types: Other

Identifiers

NCT07621991

IIHL/EMB/PRS_001_2026

Details and patient eligibility

About

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.

Full 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.

Enrollment: 484 estimated patients

Sex: All

Ages: 21 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

484 participants in 1 patient group

ICSI Couples Undergoing SDF and dsSDF Assessment

Description:

Infertile couples undergoing intracytoplasmic sperm injection (ICSI) at participating tertiary IVF centres will be prospectively enrolled based on predefined eligibility criteria. Semen samples collected on the day of ICSI will undergo assessment of global sperm DNA fragmentation (SDF) and double-strand sperm DNA fragmentation (dsSDF) using the LensHooke® X12 platform with the R10 Plus and R11 Plus kits, respectively. SDF assessments will be performed before and after sperm preparation.

Treatment:

Device: LensHooke X12 Device