During the gathering of demographic data for the Buerger’s Disease biobank, we found that infertility after disease diagnosis is one of the problems that BD patients face. They usually tried to conceal it from their spouses, and those patients without children were concerned about it. Notably, we do not know how reliable the self-reporting on impotency and libido is, because infertility is a source of stigma for men in Iranian culture. This stigma is demonstrated by the fact that only three patients collaborated in the spermogram test. For two patients, the infertility had led to getting divorced and re-marrying, believing that their first wives were the infertile partners.
Owing to the fact that we did not have access to semen samples of more than three patients, in order to evaluate for secondary infertility in Buerger’s Disease, we first tested the serum levels of testosterone, LH, and FSH because, in disturbed genital circulation such as arteriosclerosis, the levels of these hormones are typically abnormal [4]. However, there was no statistically significant difference in the serum levels of gonadal and sexual hormones between the patients and healthy controls. Yet, approximately 15% of the patients complained of erectile dysfunction without favorable response to Sildenafil, which may have been due to impaired genital circulation. Also, 9.5% of the patients complained of orgasmic dysfunction early after disease diagnosis which may have been due to autonomic dysfunction in BD patients [5].
There are a few case reports involving spermatic arteries in Buerger’s Disease [6–8]. In these reports, the occlusion of a spermatic artery led to genital lesions. However, we do not yet know whether BD leads to impaired circulation of genitalia that does not involve thrombotic or ischemic lesions.
Immunological infertility was also evaluated in the patients. Because cultural concerns prevented most of the patients from cooperating in a spermogram test, we therefore conducted only the study on serum samples.
According to our findings, ASA was positive in approximately 25% of the patients. The prevalence of anti-sperm antibodies in the general population has been reported to be between 0 and 2.5% [9, 10], which aligns with the results of our control group. Therefore, it appears that ASA may play a role in the secondary infertility of the patients. However, the origin of ASA in the serum of patients is still unknown, and we do not know if this type of autoantibody formation is due to an infectious pathogen and cross-reactions with auto-antigens, or because of an inflammation as a result of autoimmunity in Buerger’s Disease. The prevalence of ASA in various conditions is summarised in [Table 1].
Table 1
The prevalence of ASA in various conditions or diseases.
Condition | Anti Sperm Antibody Percentage | Secondary infertility? |
Unexplained infertility [18] | 7% (male) | Primary and secondary |
Infection [19] | 16.3% | Secondary |
Systemic autoimmune diseases [20] | 7.1% | Secondary |
Vasectomy [21] | 50–70% | Secondary |
Cystic fibrosis [22] | 75% | Primary and secondary |
Varicoceles [23] | 32% | Primary and secondary |
Dysfunctional seminal vesicles [24] | 38.3% | Primary and secondary |
Several studies that evaluated ASA in both sperm and serum appear to indicate that the ASA serum level is about half of the ASA sperm [9]. Therefore, if we consider that even half of the patients suffered from immunological infertility, and approximately 15% suffered from impotency due to impaired genitalia circulation, the question regarding underlying cause of infertility would remain in terms of the rest of the study subjects.
Impaired sperm motility was the only finding in the spermograms of the three ASA-negative patients. Various causes explain low sperm motility, such as varicocele, disturbed sex hormones, genetic disorders, and lifestyle and environmental factors, such as smoking.
Genetic disorders [11] and varicocele [12] are usually responsible for primary infertility, yet, the gonadal and sexual hormones of the patients were in a normal range. Therefore, these two causes may not be responsible for the secondary infertility of the patients. In addition, many factors associated with lifestyle, such as nutrition, psychological stress, environmental and occupational exposures [13], and addiction to smoking [14] or illegal drugs [15] may influence fertility. Notably, the majority of patients with Buerger’s Disease are heavy smokers [16]. Some studies show the negative effects of smoking on sperm count, motility, and morphology [17], whilst others claim that there is no significant relationship between smoking and infertility [18]. However, the BD patients began smoking many years before disease onset, and many had children who were born whilst the patients were smokers, before illness manifestation.
Notably, thrombogenicity and high oxidative stress, independent from smoking, has been demonstrated in BD patients [19, 20]. Interestingly, semen contains clotting and fibrinolysis factors which have a significant role in male reproductive physiology including the motility and function of sperms [21]. Besides, high oxidative stress in semen could lead to male infertility by influencing on DNA, lipids and proteins of sperms [22].
It is still unknown, if the serum level changes in coagulation and oxidative stress of BD patients also happened in the semen of these patients. But, such changes might be responsible for secondary infertility of the ASA negative patients.