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
• Genders Eligible for Study: All

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: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

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 clinical pregnancy and live birth rate	DNA fragmentation as evaluated by TUNEL assay.	up to 36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNA fragmentation in the total and vital fraction before and after density gradient in the diagnostic sample (pre-IUI)	DNA fragmentation as evaluated by TUNEL assay	up to 36 months
DNA fragmentation in the total and vital fraction before and after density gradient in the therapeutic sample (IUI sample)	DNA fragmentation as evaluated by TUNEL assay	up to 36 months
DNA fragmentation in relation to the cumulative clinical pregnancy and cumulative live birth rate	DNA fragmentation as evaluated by TUNEL assay.	up to 36 months

Collaborators and Investigators

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

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): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: DNA damage; Insemination; DNA fragmentation; Unexplained Infertility; Idiopathic Infertility
• Additional Relevant MeSH Terms: 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