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

Sponsor

University Hospital, Antwerp (Other)

Overall Status

Completed

CT.gov ID

NCT03319654

Collaborator

Universiteit Antwerpen (Other)

120

Enrollment

Location

Arm

44.8

Actual Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Infertility Unexplained Infertility, Male DNA Damage	Diagnostic Test: DNA fragmentation by TUNEL assay	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single center, university setting, no commercial affiliationSingle center, university setting, no commercial affiliation

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

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

Actual Study Start Date :

Oct 5, 2017

Actual Primary Completion Date :

May 31, 2021

Actual Study Completion Date :

Jun 30, 2021

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

DNA fragmentation as a predictor of clinical pregnancy and live birth rate [up to 36 months]
DNA fragmentation as evaluated by TUNEL assay.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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