Summary
Background
Oligo‐astheno‐teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute ...to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options.
Materials and Methods
PubMed was searched for papers in English for articles with search terms: male infertility and oligo‐astheno‐teratozoospermia. For evidence‐based recommendations, the GRADE system was applied. Issues related to urogenital infections/inflammations have not been included in this document as they will be covered by separate guidelines.
Results
For men with oligo‐astheno‐teratozoospermia, the European Academy of Andrology recommends:
A general physical examination to assess signs of hypogonadism.
A scrotal physical examination to assess (i) the testes and epididymes for volume and consistency, (ii) deferent ducts for total or partial absence, and (iii) occurrence of varicocoele.
Performing two semen analyses, according to World Health Organization guidelines to define an oligo‐astheno‐teratozoospermia.
An endocrine evaluation.
A scrotal ultrasound as part of routine investigation.
Karyotype analysis and assessment of Yq microdeletions in infertile men with a sperm concentration ≤5 × 106/mL.
Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for incomplete congenital obstruction of the genital tract.
Against quitting physical activity to improve the chance of achieving pregnancy.
Against androgen replacement therapy to improve the chance of achieving pregnancy.
Assisted reproduction techniques to improve the chance of achieving pregnancy, in case other treatment options are not available or not efficient.
Androgen replacement therapy in patients with biochemical/clinical signs of hypogonadism, after completion of the fertility treatment.
Conclusion
These guidelines can be applied in clinical work and indicate future research needs.
Summary
Infection and inflammation of the male reproductive tract are accepted as important aetiological factors of infertility. With regard to their impact on male reproductive function, orchitis ...and epididymo‐orchitis due to local or systemic infection as well as noninfectious aetiological factors are of particular concern. There is clinical and pathological evidence that chronic inflammatory conditions of the testes can disrupt spermatogenesis and irreversibly alter both sperm number and quality. In the majority of patients, however, diagnosis is hampered by an asymptomatic course of the disease and unspecific clinical signs. Hence, respective epidemiological data are scarce. On the other hand, systematic histopathological work‐up of testicular biopsies from infertile men indicates a high prevalence of inflammatory reactions. A characteristic pattern of inflammatory lesions with focal or multifocal, predominantly peritubular lymphocyte infiltration and concomitant damage of seminiferous tubules is seen in chronic orchitis of various origins. This supports the concept that induction of testicular inflammation is associated with a T‐cell‐mediated autoimmune response, i.e. disruption of the immune privilege. Moreover, despite the patchy distribution of the lesions, testicular volume and score counts for spermatogenesis may be significantly reduced. In conclusion, asymptomatic inflammatory reactions in the testis should not be neglected as an underlying cause or co‐factor of male infertility. However, definitive diagnosis of chronic asymptomatic orchitis still requires testicular biopsy and guidelines for the therapeutic management are not yet available.
Summary
Definition of chronic male genital tract inflammation and its impact on male infertility is still a matter of debate. In particular, DNA integrity has been reported to be disturbed in ...subfertile men. Thus, the aim of this study was to investigate an association of DNA integrity to altered standard semen parameters as well as inflammatory parameters such as peroxidase‐positive cells, macrophages and seminal interleukin‐6 concentration. Macrophages were detected by CD18/HLA‐Dr staining, and DNA integrity was analysed by acridine orange staining using flow cytometry. Interleukin‐6 was detected by ELISA. Normal DNA integrity showed a significant correlation to sperm number and progressive motility. Moreover, a significant inverse correlation of DNA integrity to Interleukin‐6 and macrophages could be demonstrated. Further on, seminal interleukin‐6 also significantly correlated to macrophages. No association has been observed between the number of peroxidase‐positive cells and normal DNA integrity. As disturbed DNA integrity has been reported to negatively influence spermatozoon–egg interaction and even fertilisation rates following ICSI, and as early miscarriages have been associated with sperm DNA damage, it should be screened very carefully for male genital tract inflammations in couples undergoing infertility treatment. Measuring Interleukin‐6 seems superior to assessment of the number of leucocytes alone and additional assessment of DNA integrity into the diagnostic work‐up should be considered.
Summary
Chronic inflammatory conditions of the genital tract are frequently encountered in male fertility problems. The diagnosis, however, is hampered by a mostly asymptomatic course of the disease ...as well as inappropriate definitions and unspecific diagnostic criteria. With regard to their impact on male reproductive function, epididymitis seems to be more relevant than inflammation/infection of the prostate and/or seminal vesicles. Chronic epididymitis may result in reduced sperm count and motility. Impaired sperm motility because of epididymal dysfunction is frequently associated with an atypical staining behaviour of sperm tails. In many cases of chronic epididymitis, the number of leukocytes in the ejaculate is below the threshold of 106 per ml; therefore, consideration of additional markers of inflammation such as granulocyte elastase, pro‐inflammatory cytokines (e.g. interleukin‐6 or 8) or reactive oxygen species is helpful for establishing the diagnosis. Besides changes in the conventional sperm parameters, alterations in DNA integrity have been observed. Positive effects of antiphlogistic/antibiotic treatment on semen quality have been reported; however, controlled prospective studies are still lacking.
The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate ...that human sperm–oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8–11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm–oocyte interaction. Graphical Abstract Summary Sentence The chemokine CCL20 is produced by human oocytes as well as surrounding cumulus granulosa cells and induces chemotaxis of CCR6+ sperm. Infertile male donors demonstrate increased levels of CCL20 in testis and seminal fluid, which may negatively influence sperm–oocyte interaction.
Zusammenfassung
Die Pharmakotherapie stellt neben Maßnahmen der assistierten Reproduktion und operativen Eingriffen eine wichtige Säule in der Behandlung männlicher Fertilitätsstörungen dar. Eine ...pathophysiologisch begründete Therapie ist nicht nur bei verschiedenen Formen des hypogonadotropen Hypogonadismus oder der Hyperprolaktinämie etabliert, sondern auch bei Infektionen und Entzündungen des männlichen Genitaltrakts möglich. Neben dem erreger- und resistenzgerechten Einsatz von Antibiotika liegen Daten für nichtsteroidale Antiphlogistika, Glukokortikosteroide, Mastzellblocker und Antioxidanzien vor. Ejakulations- und Emissionsstörungen können mit α‑Sympathomimetika, Imipramin oder Brompheniramin behandelt werden; als wirksame Medikation bei Erektionsstörungen sind Phosphodiesterase-5-Inhibitoren verfügbar. Wesentlich problematischer ist dagegen die Frage nach Therapieoptionen bei Patienten mit Einschränkungen der Ejakulatqualität ohne erkennbare Ursache. Für verschiedenste Medikamente liegen Studiendaten mit nicht ausreichendem Evidenzgrad vor. Neuere Metaanalysen sprechen für eine begrenzte Wirksamkeit von Antiöstrogenen wie Tamoxifen oder Clomifen; vielversprechende Ergebnisse fanden sich nach Behandlung mit follikelstimulierendem Hormon. Zunehmende Aufmerksamkeit erlangen Antioxidanzien und Spurenelemente. Für die als Nahrungsergänzungsmittel vertriebenen Kombinationspräparate liegen jedoch keine adäquat kontrollierten klinischen Studien vor.
Background There is evidence that chronic idiopathic urticaria (CIU) and psoriasis are associated with personality based difficulties in emotional regulation particularly with regard to the feeling ...of anger. This deficit in emotional awareness could lead to the phenomenon that emotions are rather experienced in bodily symptoms such as pruritus.
Aim We investigated whether there is a relationship between pruritus as major symptoms in CIU and psoriasis and the experience of negative emotions.
Setting Forty‐one CIU patients and 44 psoriasis patients treated at Bonn University Hospital and 49 healthy controls were included.
Method Patients and controls were compared on questionnaires measuring alexithymia (TAS‐20), emotional distress (SCL‐90‐R) and anger (STAXI). In skin‐disordered patients, separate stepwise regressions with pruritus severity as dependent variable and questionnaires, skin status, duration, sex and age as independent variables were calculated.
Results CIU and psoriasis patients showed higher alexithymia, emotional distress, depression, anxiety and state anger compared with controls. State anger was the only significant predictor of pruritus severity in CIU explaining 19% of variance. Depression was the only significant predictor of pruritus severity in psoriasis explaining 12% of variance.
Conclusions Our findings suggest a relationship between pruritus severity and anger in CIU. Furthermore, our results indicate a relationship between pruritus severity and depression in psoriasis.
Summary
Chronic testicular inflammation and infection have been regarded as important factors in the pathogenesis of azoospermia. As key effector cells in innate and adaptive immune system, mast ...cells (MCs) were observed in inflammation and autoimmune disease. Furthermore, increased expression of tryptase‐positive MCs has been reported in testicular disorders associated with male infertility/subfertility. However, little is known about the potential relationship between MCs and chronic testicular inflammation in azoospermic patients. Moreover, the preferential expression of MCs' subtypes in testis of these patients is still far from being understood. Thus, this study aimed to investigate characteristics of testicular MCs as well as their subtypes in azoospermic men with chronic testicular inflammation (AZI, n = 5) by immunohistochemical techniques. Our results showed significant increase of MCs in AZI, and more importantly, considerable numbers of tryptase‐positive/chymase‐positive MCs could also be demonstrated in AZI, when compared to control groups representing azoospermia without chronic testicular inflammation (AZW, n = 5) and normal spermatogenesis (NT, n = 5) respectively. Most interestingly, immunofluorescence staining revealed autoimmune‐associated interleukin (IL)‐17‐producing MCs in AZI, whereas co‐expression of MC markers with tumour necrosis factor (TNF)‐α, IL‐10 and IL‐1β could not be detected. In conclusion, AZI is associated with significant increase of tryptase‐positive/chymase‐positive MCs expressing IL‐17, and these MCs might contribute to the pathogenesis of AZI.
Summary
Genital tract inflammation is considered as a major cause of male infertility with leucocytospermia as widely used diagnostic marker. However, threshold of 106 leucocytes ml−1 recommended by ...the WHO is a matter of debate. Moreover, leucocyte subpopulations and their impact cannot be identified by the routine peroxidase method (POM). Ejaculates of subfertile men (n = 47) were analysed by flow cytometry (FACS) using a bead‐based method. Leucocytes were identified by CD18 and further divided into macrophages (HLA‐Dr+/CD66abce‐) and neutrophils (HLA‐Dr‐/CD66abce+). IL‐1β, TNF‐α and IL‐6 production was investigated in these subpopulations. It was found that CD18‐positive cells correlated significantly with POM. However, only in samples with POM below 106 per millilitre, FACS detected significantly higher leucocyte numbers. Moreover, in 31% of these samples, FACS leucocyte detection reached threshold values greater than 1 × 106 ml−1, fulfilling the criteria for diagnosis of leucocytospermia. Neutrophils were the predominating leucocyte population. Nevertheless, in 24% of samples, macrophages encountered more than 50% of leucocytes. Most interestingly, only macrophages produced significant amounts of IL‐1β, TNF‐α and IL‐6. It is concluded that FACS improves detection and functional differentiation of seminal leucocytes as one of the diagnostic hallmarks of male genital tract inflammation.
PDF
