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Prevalence of anti-sperm antibodies and relationship of degree of sperm auto-immunization to semen parameters and post-coital test outcome: a retrospective analysis of over 10 000 men.

STUDY QUESTION
What is the prevalence and the relationship of anti-sperm antibodies (ASA), screened by means of IgG-mixed anti-globulin reaction (MAR) test, to semen quality and post-coital test (PCT) outcome?


SUMMARY ANSWER
A 100% positive IgG-MAR test, detected in 2% of the study population, was associated with lower sperm output and progressive motility, and was the sole determinant of higher prevalence of a negative PCT outcome.


WHAT IS KNOWN ALREADY
Although ASA may affect sperm fertilizing ability and the IgG-MAR test is recommended by the World Health Organization (WHO) as an integral part of semen analysis for screening the occurrence of ASA, the prevalence and clinical relevance of positive MAR test results remain controversial.


STUDY DESIGN, SIZE, DURATION
A retrospective analysis of 12 296 consecutive men who attended a university/hospital andrology clinic for the evaluation of fertility potential was carried out.


PARTICIPANTS/MATERIALS, SETTING, METHODS
Immunological screening with the IgG-MAR test was performed on all ejaculates as an integral part of semen analysis. Positive samples (≥10%) were further tested for IgA-ASA. The prevalence of positive IgG-MAR tests results, along with the relationship of the degree of sperm auto-immunization to semen parameters and PCT outcome, were analyzed.


MAIN RESULTS AND THE ROLE OF CHANCE
After excluding semen samples showing azoospermia or severe oligo-asthenozoospermia, the prevalence of a positive IgG-MAR test in the remaining 10 025 men was 4%, 3.4% and 2%, with 10%, 50% and 100% thresholds, respectively. The 100%-positive MAR tests exhibited significantly higher consistency over time, and were significantly associated with higher prevalence of a mixed pattern (i.e. when the majority of sperm exhibited beads attached on both the head and along the tail) of positivity as well as with the concomitant occurrence of IgA-ASA. Additionally, the 100%-positive MAR tests were significantly associated with a lower median value of the total number of spermatozoa and progressive motility, compared to samples with a lower degree of positivity or negative samples. In the PCT performed in 120 couples, where ASA were detected in the male partner, the 100%-positive MAR tests were significantly associated with a higher prevalence of negative PCT outcome, in comparison to the lower degree of positivity, independent of, and without any significant contribution from, other determinants (semen and cervical mucus quality).


LIMITATIONS, REASONS FOR CAUTION
Only surrogate infertility-related end-points were analyzed in the present study. However, since the impairment of sperm penetration through the cervical mucus represents the primary mechanism of ASA-interference with fertility, PCT outcome may represent a suitable clinical end-point.


WIDER IMPLICATIONS OF THE FINDINGS
The present study, being the largest reported to date, provides a reliable estimate of ASA prevalence. Moreover, it indicates that a 50%-positive MAR test, which is suggested by WHO as the clinically-relevant threshold, also includes patients with a degree of sperm auto-immunization that contributes to couple infertility only in the presence of other causal factors; conversely, the 100%-positive MAR test can represent the sole determinant of couple infertility, as it was the sole significant predictor of the highly prevalent negative PCT outcome.


STUDY FUNDING/COMPETING INTEREST(S)
The study was supported by the University of L'Aquila, Italy. The authors declare no competing interests.


TRIAL REGISTRATION NUMBER
N/A.