Prednisolone Improves IVF Outcomes in Men With Anti-sperm Antibodies

Sponsor
Barz IVF Center for Infertility Treatment and Embryo Research (Other)
Overall Status
Completed
CT.gov ID
NCT02935738
Collaborator
University of Baghdad (Other)
241
4
19

Study Details

Study Description

Brief Summary

Corticosteroids have been indicated to treat men with ASAs. Although many studies have confirmed the clinical therapeutic significance of corticosteroids in the treatment of men with ASAs, other studies have not found a therapeutic significance for corticosteroids in the treatment of men with ASAs. Moreover, although some reports have shown high fertilization and conception rates in couples when husbands did not have ASAs, other reports have shown that ASAs do not have a negative effect on fertilization and conception rates. These contradictory results have left the therapeutic effect of corticosteroids in men with ASA in continuing controversy. This controversy is also extended to include the usefulness of assisted reproductive technology (ART) in the treatment of patients with ASAs. In this regard, although some studies have shown that the pregnancy rate following in vitro fertilization (IVF) or intracellular sperm injection (ICSI) were similar in men with or without ASA or did not associate with ASA, others reported the superiority of ICSI over IVF and intrauterine insemination over natural intercourse in men with ASAs. It is possible that some patients with ASAs also have an additional problem(s) related to sperm binding to the oolemma and fusion into the ovum as well as sperm head decondensation. The latter condition may negatively influence or mask the clinical significance of corticosteroids on pregnancy rates in patients with ASAs. Some patients might not have benefited from corticosteroids and conventional IVF treatments due to the impaired sperm fusogenic capacity in addition to ASAs. Human sperm penetration assay (SPA), of the hamster oocyte free from zona pellucida, is a sensitive tool that can address such potential impairment of sperm binding with the oolemma and fusion into the oocyte as well as sperm head decondensation. Males with poor SPA results benefit from ICSI whereas those with good SPA results can still benefit from conventional IVF.

The present study was therefore conducted to address the therapeutic usefulness of a corticosteroid named prednisolone in the treatment of immunologically infertile men undergoing IVF or ICSI determined by SPA.

Condition or Disease Intervention/Treatment Phase
  • Drug: Prednisolone treatment
N/A

Detailed Description

This prospective study was conducted at the Barz IVF Center for Infertility Treatment and Embryo Research, Erbil, Kurdistan Region, Iraq and the Baghdad University Teaching Hospital of the College of Medicine, University of Baghdad, Baghdad, Iraq between October 2014 and May 2016. In all cases, the wife's ova were inseminated with the husband's semen samples. Identified men with positive ASAs were randomly assigned for treatment with or without prednisolone for three cycles. Infertile men were treated with prednisolone tablet, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles

Treated men that recovered from ASAs and control patients underwent SPA. Patients with positive or negative SPA results were then admitted to conventional IVF or ICSI cycles, respectively. Only the first embryo transfer cycle following IVF or ICSI was included in this analysis.

Study Design

Study Type:
Interventional
Actual Enrollment :
241 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Improvement in Pregnancy Outcomes in Immunologically Infertile Male Patients Undergoing Prednisolone Treatment and Conventional IVF Preceded by Sperm Penetration Assay: A Randomized Controlled Trial
Study Start Date :
Oct 1, 2014
Actual Primary Completion Date :
Mar 1, 2016
Actual Study Completion Date :
May 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Prednisolone treated men / positive SPA / IVF

Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (greater than five) were admitted to conventional in vitro fertilization (IVF) cycles.

Drug: Prednisolone treatment
Infertile men were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles.
Other Names:
  • Experimental
  • Experimental: Prednisolone treated men / negative SPA / ICSI

    Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were admitted to intracytoplasmic sperm injection (ICSI) cycles.

    Drug: Prednisolone treatment
    Infertile men were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles.
    Other Names:
  • Experimental
  • No Intervention: Control men / positive SPA / IVF

    Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (more than five) were then admitted to in vitro fertilization (IVF) cycle.

    No Intervention: Control men / negative SPA / ICSI

    Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were then admitted to intracytoplasmic sperm injection (ICSI) cycles.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Control and Treated Participants With Successful Live Births Following Conventional IVF or ICSI Cycles [Nine months (pregnancy term) after the in vitro fertilization.]

      Live birth rates in treated and control patients undergoing conventional IVF or ICSI cycles as determined by the sperm penetration assay (SPA) of hamster zone free ova

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    25 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Female partners had complete or partial tubal patency

    • Male partners with anti-sperm antibodies

    • Male partners with sperm count > 35 million/ml.

    Exclusion Criteria:
    • Female partners with polycystic ovary

    • Female partners with endometriosis

    • Female partners with abnormal profile of reproductive hormones

    • Female partners with abnormal profile of thyroid hormones

    • Male partners with seminal fluid infections (e.g. leukospermia)

    • Male partners with abnormal profile of reproductive hormones

    • Male partners with abnormal profile of thyroid hormones

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Barz IVF Center for Infertility Treatment and Embryo Research
    • University of Baghdad

    Investigators

    • Principal Investigator: Saeeda A. Muhsen, DVM, PhD, Barz IVF Center for Infertility Treatment and Embryo Research

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Barz IVF Center for Infertility Treatment and Embryo Research
    ClinicalTrials.gov Identifier:
    NCT02935738
    Other Study ID Numbers:
    • Prednisolone-SPA-IVF
    First Posted:
    Oct 17, 2016
    Last Update Posted:
    Nov 16, 2020
    Last Verified:
    Oct 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Keywords provided by Barz IVF Center for Infertility Treatment and Embryo Research
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Prednisolone Treated Men / Positive SPA / IVF Prednisolone Treated Men / Negative SPA / ICSI Control Men / Positive SPA / IVF Control Men / Negative SPA / ICSI
    Arm/Group Description Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (greater than five) were admitted to conventional in vitro fertilization (IVF) cycles. Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were admitted to intracytoplasmic sperm injection (ICSI) cycles. Prednisolone treatment: Infertile men were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (more than five) were then admitted to in vitro fertilization (IVF) cycle. Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were then admitted to intracytoplasmic sperm injection (ICSI) cycles.
    Period Title: Overall Study
    STARTED 67 74 47 53
    COMPLETED 50 53 46 48
    NOT COMPLETED 17 21 1 5

    Baseline Characteristics

    Arm/Group Title The Clinical Data of Control Men Underwent IVF The Clinical Data of Treated Men Underwent IVF The Clinical Data of Control Men Underwent ICSI The Clinical Data of Treated Men Underwent ICSI Total
    Arm/Group Description Total of all reporting groups
    Overall Participants 46 50 48 53 197
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    46
    100%
    50
    100%
    48
    100%
    53
    100%
    197
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Age
    36.2
    (7.8)
    37.9
    (5.8)
    34.5
    (3.8)
    34.2
    (2.9)
    35.7
    (5.1)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    46
    100%
    50
    100%
    48
    100%
    53
    100%
    197
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    46
    100%
    50
    100%
    48
    100%
    53
    100%
    197
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    46
    100%
    50
    100%
    48
    100%
    53
    100%
    197
    100%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Iraq
    46
    100%
    50
    100%
    48
    100%
    53
    100%
    197
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Control and Treated Participants With Successful Live Births Following Conventional IVF or ICSI Cycles
    Description Live birth rates in treated and control patients undergoing conventional IVF or ICSI cycles as determined by the sperm penetration assay (SPA) of hamster zone free ova
    Time Frame Nine months (pregnancy term) after the in vitro fertilization.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Prednisolone Treated Men / Positive SPA / IVF Prednisolone Treated Men / Negative SPA / ICSI Control Men / Positive SPA / IVF Control Men / Negative SPA / ICSI
    Arm/Group Description Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (greater than five) were admitted to conventional in vitro fertilization (IVF) cycles. Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were admitted to intracytoplasmic sperm injection (ICSI) cycles. Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (more than five) were then admitted to in vitro fertilization (IVF) cycle. Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were then admitted to intracytoplasmic sperm injection (ICSI) cycles.
    Measure Participants 50 53 46 48
    Number [participants]
    18
    39.1%
    13
    26%
    8
    16.7%
    9
    17%

    Adverse Events

    Time Frame Infertile men with positive titer of ASA were treated with prednisolone tablet for 21 days of their wife's menstrual cycles and for three cycles. This made the total duration of treatment for each individual three months throughout an experiment duration window of 15 months, starting from October 2014 till March 2016.
    Adverse Event Reporting Description Adverse effects included infection, nausea, vomiting, diarrhea, headache, and hypertension.
    Arm/Group Title Prednisolone Treated Men / Positive SPA / IVF Prednisolone Treated Men / Negative SPA / ICSI Control Men / Positive SPA / IVF Control Men / Negative SPA / ICSI
    Arm/Group Description Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (greater than five) were admitted to conventional in vitro fertilization (IVF) cycles. Infertile men, with anti-sperm antibodies, were treated with prednisolone tablet, which is an intermediate acting corticosteroid, po, for 21 days of their wife's menstrual cycles. Briefly, the prednisolone regimen was started with a dose of 5mg, tid, for two weeks followed by 5mg bid for five days. This was further tapered to one tablet of 5mg/day for two days. Patients were then given one week of rest from the treatment, before this prednisolone regimen was repeated for another two cycles. Prednisolone treated men, who recovered from anti-sperm antibodies, underwent then sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were admitted to intracytoplasmic sperm injection (ICSI) cycles. Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having positive SPA results (more than five) were then admitted to in vitro fertilization (IVF) cycle. Infertile men with anti-sperm antibodies who were not treated with prednisolone, which is an intermediate acting corticosteroid, underwent sperm penetration assay (SPA) using zona-free hamster ova. Couples with male partners having negative SPA results (equal or less than five) were then admitted to intracytoplasmic sperm injection (ICSI) cycles.
    All Cause Mortality
    Prednisolone Treated Men / Positive SPA / IVF Prednisolone Treated Men / Negative SPA / ICSI Control Men / Positive SPA / IVF Control Men / Negative SPA / ICSI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/50 (0%) 0/53 (0%) 0/46 (0%) 0/48 (0%)
    Serious Adverse Events
    Prednisolone Treated Men / Positive SPA / IVF Prednisolone Treated Men / Negative SPA / ICSI Control Men / Positive SPA / IVF Control Men / Negative SPA / ICSI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/50 (0%) 0/53 (0%) 0/46 (0%) 0/48 (0%)
    Other (Not Including Serious) Adverse Events
    Prednisolone Treated Men / Positive SPA / IVF Prednisolone Treated Men / Negative SPA / ICSI Control Men / Positive SPA / IVF Control Men / Negative SPA / ICSI
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/50 (0%) 0/53 (0%) 0/46 (0%) 0/48 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Saeeda A. Muhsen-Alanssari
    Organization Barz IVF Center for Embryo Research and Infertility Treatment
    Phone 9798201303
    Email barzivfcenter@gmail.com
    Responsible Party:
    Barz IVF Center for Infertility Treatment and Embryo Research
    ClinicalTrials.gov Identifier:
    NCT02935738
    Other Study ID Numbers:
    • Prednisolone-SPA-IVF
    First Posted:
    Oct 17, 2016
    Last Update Posted:
    Nov 16, 2020
    Last Verified:
    Oct 1, 2020