Severe sperm DNA fragmentation may persist for up to 3 years after cytotoxic therapy in patients affected by Hodgkin lymphoma and non-Hodgkin lymphoma.

STUDY QUESTION: Does sperm DNA recover from damage in all men after 2 years from the end of cytotoxic treatments? SUMMARY ANSWER: The current indication of 2 years waiting time for seeking natural pregnancy after cytotoxic treatment may not be adequate for all men, since severe sperm DNA damage is present in a proportion of subjects even after this timeframe. WHAT IS KNOWN ALREADY: Data in the literature on sperm DNA fragmentation (SDF) in lymphoma patients after cytotoxic treatments are scarce. The largest longitudinal study evaluated paired pre- and post-therapy (up to 24 months) semen samples from 34 patients while one study performed a longer follow-up (36 months) in 10 patients. The median/mean SDF values >24 months after therapy did not show significant differences but the studies did not explore the proportion of patients with severe DNA damage and the analysis was done on frozen-thawed samples. STUDY DESIGN, SIZE, DURATION: In this study, 53 Hodgkin lymphoma (HL) and 25 non-Hodgkin lymphoma (NHL) post-pubertal patients were included over a recruitment period of 10 years (2012-2022). Among them, 18 subjects provided paired semen samples for SDF analysis at the three time points. SDF was evaluated in patients before (T0) and after 2 (T2) and 3 years (T3) from the end of, cytotoxic treatments (chemotherapy alone or in combination with radiotherapy). A cohort of 79 healthy, fertile, and normozoospermic men >18 years old served as controls (recruited between 2016 and 2019). PARTICIPANTS/MATERIALS, SETTING, METHODS: SDF was evaluated on fresh semen samples (i.e. spermatozoa potentially involved in natural conception) from patients and controls using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay coupled with flow cytometry. SDF median values were compared between groups: (i) HL and NHL patients versus controls at the three time points; (ii) HL versus NHL patients at baseline; and (iii) patients at T0 versus T2 and T3. Severe DNA damage (SDD) was defined for SDF levels above the 95th percentile of controls (50%) and the proportion of patients with SDD at all time points was established. MAIN RESULTS AND THE ROLE OF CHANCE: At T0, patients displayed higher median SDF than controls, reaching statistical significance in the NHL group: 40.5% [IQR: 31.3-52.6%] versus 28% [IQR: 22-38%], P < 0.05. Comparing SDF pre-treatment to that post-treatment, HL patients exhibited similar median values at the three time points, whereas NHL showed significantly lower values at T3 compared to T0: 29.2% [IQR: 22-38%] versus 40.5% [IQR: 31.3-52.6%], P < 0.05. The proportion with SDD in the entire cohort at T2 was 11.6% and 13.3% among HL and NHL patients, respectively. At T3, only one in 16 NHL patients presented SDD. LIMITATIONS, REASONS FOR CAUTION: TUNEL assay requires at least 5 million spermatozoa to be performed; hence, severe oligozoospermic men were not included in the study. Although our cohort represents the largest one in the literature, the relatively small number of patients does not allow us to establish precisely the frequency of SDD at T2 which in our study reached 11-13% of patients. WIDER IMPLICATIONS OF THE FINDINGS: Our data provide further insights into the long-term effects of cytotoxic treatments on the sperm genome. The persistent severe DNA damage after 2 years post-treatment observed in some patients suggests that there is an interindividual variation in restoring DNA integrity. We propose the use of SDF as a biomarker to monitor the treatment-induced genotoxic effects on sperm DNA in order to better personalize pre-conceptional counseling on whether to use fresh or cryopreserved spermatozoa. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Istituto Toscano Tumori (ITT), Fondazione Ente Cassa di Risparmio di Firenze, the European Commission-Reproductive Biology Early Research Training (REPROTRAIN). C.K., G.F., V.R., and A.R.-E. belong to COST Action CA20119 (ANDRONET) which is supported by the European Cooperation in Science and Technology (www.cost.eu). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Psychobiological Correlates of Vaginismus: An Exploratory Analysis.

BACKGROUND: Evidence concerning the determinants of vaginismus (V), in particular medical conditions, is inconclusive. AIM: To investigate, in a cohort of subjects consulting for female sexual dysfunction, whether there is a difference in medical and psychosocial parameters between women with V and women with other sexual complaints. METHODS: A series of 255 women attending our clinic for female sexual dysfunction was consecutively recruited. V was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Lifelong and acquired V cases were included. OUTCOMES: Patients underwent a structured interview and physical, gynecologic, laboratory, and clitoral ultrasound examinations; they completed the Female Sexual Function Index (FSFI), the Middlesex Hospital Questionnaire, the Female Sexual Distress Scale-Revised (FSDS), and the Body Uneasiness Test. RESULTS: V was diagnosed in 20 patients (7.8%). Women with V were significantly younger than the rest of the sample (P < .05). No differences were found for traditional risk factors such as a history of sexual abuse, relational parameters, or gynecologic diseases or for newly investigated parameters (ie, neurologic, hormonal, and metabolic alterations). Women with V showed significantly higher histrionic-hysterical symptoms and traits (as detected by MHQ-H score; P < .05) compared with subjects with other sexual complaints. When the scores of all MHQ subscales were simultaneously introduced in a logistic model, the association between V and MHQ-H score was confirmed (P = .013). Women with V also showed higher FSFI pain and FSDS total scores, even after adjusting for age (P < .05). In an age-adjusted model, FSDS total score increased as a function of the years of duration of V (P = .032) but not as a function of its severity. All observations were confirmed in a case-control study (ratio = 1:3). CLINICAL IMPLICATIONS: Our data demonstrate that some novel contributors of V should be investigated, namely histrionic-hysterical traits. This psychological comorbidity could offer valuable insights for intervention and managing complications. STRENGTHS AND LIMITATIONS: This is the first study to assess the role of many metabolic and hormonal parameters as potential determinants of V. The main limitation is its exploratory and cross-sectional nature; our data need to be confirmed in larger, more systematic analyses. CONCLUSION: V was associated with histrionic-hysterical traits, FSFI pain domain, and sex-related distress. A history of abuse, relational parameters, gynecologic diseases, and hormonal and metabolic alterations do not seem to play a role in the development of V. Maseroli E, Scavello I, Cipriani S, et al. Psychobiological Correlates of Vaginismus: An Exploratory Analysis. J Sex Med 2017;14:1392-1402.