Prednisolone Improves IVF Outcomes in Men With Anti-sperm Antibodies

NCT ID: NCT02935738

Last Updated: 2020-11-16

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

241 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2016-05-31

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.

Conditions

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Reproductive Sterility

Keywords

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prednisolone anti-sperm antibodies sperm penetration assay

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Prednisolone treatment

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

Prednisolone treatment

Intervention Type DRUG

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.

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Experimental

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
Minimum Eligible Age

25 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Baghdad

OTHER

Sponsor Role collaborator

Barz IVF Center for Infertility Treatment and Embryo Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Saeeda A. Muhsen, DVM, PhD

Role: PRINCIPAL_INVESTIGATOR

Barz IVF Center for Infertility Treatment and Embryo Research

References

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Omu AE, al-Qattan F, Abdul Hamada B. Effect of low dose continuous corticosteroid therapy in men with antisperm antibodies on spermatozoal quality and conception rate. Eur J Obstet Gynecol Reprod Biol. 1996 Nov;69(2):129-34. doi: 10.1016/0301-2115(95)02539-1.

Reference Type BACKGROUND
PMID: 8902446 (View on PubMed)

Hendry WF, Treehuba K, Hughes L, Stedronska J, Parslow JM, Wass JA, Besser GM. Cyclic prednisolone therapy for male infertility associated with autoantibodies to spermatozoa. Fertil Steril. 1986 Feb;45(2):249-54. doi: 10.1016/s0015-0282(16)49163-6.

Reference Type BACKGROUND
PMID: 3949025 (View on PubMed)

Hendry WF, Hughes L, Scammell G, Pryor JP, Hargreave TB. Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa. Lancet. 1990 Jan 13;335(8681):85-8. doi: 10.1016/0140-6736(90)90548-j.

Reference Type BACKGROUND
PMID: 1967425 (View on PubMed)

Keane D, Jenkins DM, Higgins T, O'Neill M, Mulcahy MF, Ferriss JB. The effect of intermittent steroid therapy on anti-sperm antibody levels. Eur J Obstet Gynecol Reprod Biol. 1995 Nov;63(1):75-9. doi: 10.1016/0301-2115(95)02217-u.

Reference Type BACKGROUND
PMID: 8674571 (View on PubMed)

Bals-Pratsch M, Doren M, Karbowski B, Schneider HP, Nieschlag E. Cyclic corticosteroid immunosuppression is unsuccessful in the treatment of sperm antibody-related male infertility: a controlled study. Hum Reprod. 1992 Jan;7(1):99-104. doi: 10.1093/oxfordjournals.humrep.a137568.

Reference Type BACKGROUND
PMID: 1551969 (View on PubMed)

De Almeida M, Feneux D, Rigaud C, Jouannet P. Steroid therapy for male infertility associated with antisperm antibodies. Results of a small randomized clinical trial. Int J Androl. 1985 Apr;8(2):111-7. doi: 10.1111/j.1365-2605.1985.tb00824.x.

Reference Type BACKGROUND
PMID: 3894245 (View on PubMed)

Haas GG Jr, Manganiello P. A double-blind, placebo-controlled study of the use of methylprednisolone in infertile men with sperm-associated immunoglobulins. Fertil Steril. 1987 Feb;47(2):295-301.

Reference Type BACKGROUND
PMID: 3545909 (View on PubMed)

Vazquez-Levin MH, Notrica JA, Polak de Fried E. Male immunologic infertility: sperm performance on in vitro fertilization. Fertil Steril. 1997 Oct;68(4):675-81. doi: 10.1016/s0015-0282(97)00255-0.

Reference Type BACKGROUND
PMID: 9341610 (View on PubMed)

Ayvaliotis B, Bronson R, Rosenfeld D, Cooper G. Conception rates in couples where autoimmunity to sperm is detected. Fertil Steril. 1985 May;43(5):739-42. doi: 10.1016/s0015-0282(16)48557-2.

Reference Type BACKGROUND
PMID: 3996618 (View on PubMed)

Pagidas K, Hemmings R, Falcone T, Miron P. The effect of antisperm autoantibodies in male or female partners undergoing in vitro fertilization-embryo transfer. Fertil Steril. 1994 Aug;62(2):363-9. doi: 10.1016/s0015-0282(16)56892-7.

Reference Type BACKGROUND
PMID: 8034086 (View on PubMed)

Zini A, Lefebvre J, Kornitzer G, Bissonnette F, Kadoch IJ, Dean N, Phillips S. Anti-sperm antibody levels are not related to fertilization or pregnancy rates after IVF or IVF/ICSI. J Reprod Immunol. 2011 Jan;88(1):80-4. doi: 10.1016/j.jri.2010.09.002. Epub 2010 Dec 15.

Reference Type BACKGROUND
PMID: 21111486 (View on PubMed)

Zini A, Fahmy N, Belzile E, Ciampi A, Al-Hathal N, Kotb A. Antisperm antibodies are not associated with pregnancy rates after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2011 Jun;26(6):1288-95. doi: 10.1093/humrep/der074. Epub 2011 Mar 23.

Reference Type BACKGROUND
PMID: 21429953 (View on PubMed)

Lahteenmaki A, Reima I, Hovatta O. Treatment of severe male immunological infertility by intracytoplasmic sperm injection. Hum Reprod. 1995 Nov;10(11):2824-8. doi: 10.1093/oxfordjournals.humrep.a135800.

Reference Type BACKGROUND
PMID: 8747025 (View on PubMed)

Robinson JN, Forman RG, Nicholson SC, Maciocia LR, Barlow DH. A comparison of intrauterine insemination in superovulated cycles to intercourse in couples where the male is receiving steroids for the treatment of autoimmune infertility. Fertil Steril. 1995 Jun;63(6):1260-6. doi: 10.1016/s0015-0282(16)57608-0.

Reference Type BACKGROUND
PMID: 7750598 (View on PubMed)

Other Identifiers

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Prednisolone-SPA-IVF

Identifier Type: -

Identifier Source: org_study_id