Prednisolone Improves IVF Outcomes in Men With Anti-sperm Antibodies

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Improvement in Pregnancy Outcomes in Immunologically Infertile Male Patients Undergoing Prednisolone Treatment and Conventional IVF Preceded by Sperm Penetration Assay: A Randomized Controlled Trial

Conditions
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Reproductive Sterility

Intervention / Treatment
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* Drug: Prednisolone treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prednisolone treated men / positive SPA / IVF<br>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<br>* 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.<br>* Other names: Experimental;|
| Experimental: Prednisolone treated men / negative SPA / ICSI<br>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<br>* 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.<br>* Other names: Experimental;|
| No Intervention: Control men / positive SPA / IVF<br>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<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Control and Treated Participants With Successful Live Births Following Conventional IVF or ICSI Cycles | 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 | Nine months (pregnancy term) after the in vitro fertilization. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prednisolone, anti-sperm antibodies, sperm penetration assay