Impact of DNA Fragmentation in Sperm on Pregnancy Outcome After Intra-uterine Insemination in a Spontaneous Cycle

Infertility affects about 10% of all couples and is defined by a failure to achieve a clinical pregnancy within a year of regular unprotected sexual intercourse. Up to one third of these couples will not have an identifiable cause after routine investigation, id est idiopathic infertility. The current diagnosis of male infertility relies on the World Health Organization (WHO) 2010 criteria which focus on concentration, motility and morphology in comparison to cut-off values of a fertile population. Alas, the relevance of the conventional semen analysis for the choice of treatment and the predictive value for an infertile couple with idiopathic or mild male infertility embarking on medically assisted reproduction (MAR) remains questionable. In other words, there is a strong clinical need to distinguish fertile from infertile men through new sperm function testing and to be able to select both the patient population who will benefit from MAR as well as the type of treatment.

Numerous studies utilizing different techniques for assessing sperm DNA fragmentation support the existence of a significant association between sperm DNA damage and pregnancy outcomes.

In this prospective cohort study the investigators aim to study the role of sperm DNA fragmentation analysis in selecting the patient who will benefit from intra-uterine insemination (IUI) therapy since IUI is still considered the first step in MAR and is performed at a large scale in Belgium and worldwide.

Study Overview

• Status: Completed
• Conditions: DNA Damage; Infertility, Male; Infertility Unexplained
• Intervention / Treatment: Diagnostic test: DNA fragmentation by TUNEL assay

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Couples seeking fertility treatment after at least 12 months of unprotected intercourse are eligible. All couples underwent basic fertility investigations which included semen analysis, evaluation of menstrual cycle, and tubal patency testing.

Exclusion Criteria:

Double sided tubal disease, severe endometriosis (classified as revised American Society for Reproductive Medicine stage III or IV), premature ovarian failure, and known endocrine disorders (such as Cushing's syndrome or adrenal hyperplasia), azoö- or necrozoospermia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spontaneous cycle IUI; DNA fragmentation by TUNEL assay DNA fragmentation will be measured both at the time of the diagnostic work-up as at the time of insemination.	Diagnostic test: DNA fragmentation by TUNEL assay; Direct DNA fragmentation testing with terminal deoxyuridine nick end labeling (TUNEL) assay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA Fragmentation as a Predictor of Live Birth Rate	The odds ratio on live birth per unit increase in % total Sperm DNA Fragmentation of the diagnostic sample.	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% SDF in the Total Fraction After Density Gradient in the Diagnostic Sample (Pre-IUI)	% of spermatozoa with DNA fragmentation in the total fraction after density gradient in the diagnostic sample (pre-IUI)	up to 3 months
% SDF in the Vital Fraction After Density Gradient in the Diagnostic Sample (Pre-IUI)	% of spermatozoa with DNA fragmentation in the vital fraction after density gradient in the diagnostic sample (pre-IUI)	up to 3 months
% SDF in the Total Fraction in the Ejaculate of the IUI- Sample	% of spermatozoa with DNA fragmentation in the total fraction in the ejaculate (before density gradient) of the IUI-sample	36 months
% SDF in the Vital Fraction in the Ejaculate of the IUI- Sample	% of spermatozoa with DNA fragmentation in the vital fraction in the ejaculate (before density gradient) of the IUI-sample	36 months
% SDF in the Total Fraction After Density Gradient in the IUI Sample	% of spermatozoa with DNA fragmentation in the total fraction after density gradient in the IUI sample	36 months
% SDF in the Vital Fraction After Density Gradient in the IUI Sample	% of spermatozoa with DNA fragmentation in the vital fraction after density gradient in the IUI sample	36 months

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Collaborators: Universiteit Antwerpen
• Investigators: Principal Investigator: Alessa N Sugihara, MD, University Hospital, Antwerp

Publications and helpful links

General Publications

• Sugihara A, Punjabi U, Roelant E, De Neubourg D. Is There a Relationship between Sperm DNA Fragmentation and Intra-Uterine Insemination Outcome in Couples with Unexplained or Mild Male Infertility? Results from the ID-Trial. Life (Basel). 2022 Dec 20;13(1):11. doi: 10.3390/life13010011.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2017
• Primary Completion (Actual): May 31, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: September 15, 2017
• First Submitted That Met QC Criteria: October 23, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: September 11, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: DNA damage; Insemination; DNA fragmentation; Unexplained Infertility; Idiopathic Infertility
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Diseases, Male; Male Urogenital Diseases; Infertility; Infertility, Male
• Other Study ID Numbers: UZA TBM -DNA IUI 2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No