Civello, Daniel

Abstract Introduction Male masturbation is a scarcely discussed topic in male sexual health. In the context of trying to conceive, male masturbation may impact overall sexual function and ultimately fertility outcomes. Objective To evaluate the relationship between masturbation frequency and sexual function amongst men undergoing fertility testing. Methods We performed a review of a prospectively maintained database of men utilizing a mail-in semen analysis test system developed by Fellow Health, Inc. Men ≥18 years were included if they consented to participate in research and completed survey questionnaires on both their quality of life and sexual function. Men reported their typical weekly masturbation frequency (0, 1-2, 3-4, 5-6, or ≥ 7 times per week) as part of the sexual function questionnaire. Descriptive statistics were reported and chi-squared tests were used to determine statistical significance at the 0.05 alpha level. Results Of the 2,034 men included, most reported masturbating one to two times per week (41.2%). Nearly one-fourth (21.6%) reported never masturbating, and only 14.2% reported a frequency of more than four times per week. Mean semen volume did not differ significantly by masturbation frequency (p = 0.07). Of note, patients were instructed to abstain from ejaculation for 48 hours prior to sample collection. Men who reported masturbating most frequently (≥7 times per week) were least likely to report ejaculatory dysfunction (12.0% vs. 21.0% for all others combined; p = 0.04), but most likely to report orgasmic dysfunction (12.0% vs. 5.7% for all others combined; p = 0.02). Interestingly, men who reported masturbating most often (≥7 times per week) were both most likely to report having sex less than once per week and most likely to report having sex ≥7 times per week when compared to other strata of masturbation frequency. Conclusions Those with higher masturbation frequency also had better ejaculatory function, but worse orgasmic function. Men who masturbate most frequently (>7 times per week) were most likely to report having sex less than one time per week and also most likely to report having sex >7 times per week, which may be reflective of differences in libido in this group. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Fellow Health.

Abstract Introduction Undergoing fertility testing can be a stressful event in a couple's life. This can impact multiple aspects of life, including sex. Objective To evaluate the relationship between stress and sexual function in men undergoing fertility testing. Methods We performed a review of a prospectively maintained database of men utilizing a mail-in semen analysis test system developed by Fellow Health, Inc. Those included consented to participate in research, were 18 or older, and completed survey questionnaires on both their quality of life and sexual function. Stress level (low, moderate, or high stress) was determined using the validated Perceived Stress Scale (PSS) 10-question survey. The sexual function survey assessed libido, orgasmic and ejaculatory dysfunction, intercourse frequency, Erection Hardness Score, and IIEF-5 score. Descriptive statistics were reported and chi-squared and t-tests were used to determine statistical significance at the 0.05 alpha level. Results A total of 2077 men undergoing fertility testing were included in this study. 50.2% reported moderate stress levels and 2.6% reported high stress levels. Those with low stress were older than those with moderate or high stress (average 35.4 vs. 34.3 and 34.0 years, respectively; p < 0.01). Men with high stress levels were more likely to report a “poor” or “terrible” libido (31.4%) compared to those with moderate or low stress, 17.2% and 9.5%, respectively (p < 0.01). Stress was highly associated with weekly intercourse frequency (p < 0.01): among men with high levels of stress, 25.5% reported having sex less than once a week compared to 6.0% of men with low stress. Likewise, no highly stressed men reported having sex more than six times per week compared to 2.8% of men with low stress. Whereas 80.4% of men with low stress were evaluated to have “No signs of ED” by the IIEF-5, the same was true for only 62.3% of moderately stressed men and 56.0% of highly stressed men (p < 0.01). Conclusions More than half of men undergoing fertility testing report increased levels of stress, which is negatively associated with libido and erectile function. In men seeking fertility evaluation, lifestyle factors such as stress levels should be assessed to identify patients who may benefit from stress management strategies. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Fellow Health.

Abstract Introduction Depression is a common mental health disorder affecting men of reproductive age. Depression or depressive symptoms may impact a variety of health factors, including sexual function. Trying to conceive may contribute to additional stress and negative emotions for the couple. Objective To determine the rate of sexual dysfunction in men with depression who are undergoing fertility testing. Methods A review was performed of a prospectively maintained database of men utilizing a mail-in semen analysis test system developed by Fellow Health, Inc. Men ≥18 years were included if they consented to participate in research and completed survey questionnaires on both their quality of life and sexual function. Depression level (normal, mild, moderate, or severe) was derived via the short-form depression assessment developed by the Patient Reported Outcomes Measurement Information System (PROMIS). The sexual function survey assessed libido, orgasmic and ejaculatory dysfunction, intercourse frequency, Erection Hardness Score, and IIEF-5 score. Descriptive statistics were reported and chi-squared tests were used to determine statistical significance at the 0.05 alpha level. Results Of the 2125 men included, 15.2% reported mild depression and 12.8% moderate or severe depression. The presence of depression was negatively associated with libido, with 11.2% of men with normal levels of depression reporting terrible or poor libido compared to 18.7% with mild depression and 22.2% with moderate or severe depression, p < 0.001. Compared to men without depression, those with moderate or severe depression were nearly twice as likely to report ejaculatory dysfunction (17.2% vs. 29.7%) and three times as likely to report orgasmic dysfunction (3.9% vs. 13.0%), p < 0.001 for all. Severity of depression was also predictive of an erection sufficient for penetration: whereas 96.8% of those with normal levels of depression reported an erection sufficient for penetration, the same could be said for only 94.5% of those with mild depression and 92.5% of those with moderate or severe depression (p < 0.001). Only 53.1% of men with moderate or severe depression had an IIEF-5 score greater than 21 (i.e., “No signs of ED”), compared to 60.9% with mild depression and 75.8% without depression, p < 0.001. Importantly, men with moderate to severe depression were more than twice as likely to report intercourse frequency less than once weekly (18.0%) as opposed to men without depression (7.4%), p < 0.001. Conclusions The presence of depression in men undergoing fertility testing is negatively associated with libido, ejaculatory, orgasmic, and erectile function. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Fellow Health.

Abstract Introduction Sleep disorders can negatively impact multiple facets of health including sexual function. In men undergoing fertility testing, optimization of general health is of utmost importance to maximize fertility outcomes. Objective To determine the relationship between sleep disturbance and sexual function in men undergoing fertility testing. Methods This study evaluated men undergoing fertility testing who completed an at-home semen analysis kit developed by Fellow Health, Inc. Men ≥18 years were included if they consented to participate in research and completed survey questionnaires on both their quality of life and sexual function. Sleep disturbance level (normal, mild, moderate, or severe) was derived using a validated survey assessment, developed by the Patient-Reported Outcomes Measurement Information System (PROMIS), which queried sleep quality, sleep depth, and restoration associated with sleep. The sexual function survey assessed libido, orgasmic and ejaculatory dysfunction, Erection Hardness Score, and IIEF-5 score. Descriptive statistics were reported and chi squared tests were used to test for independence of categorical variables with statistical significance reported at the 0.05 alpha level. Results Of the 1919 men included in this analysis, 7.7% were assessed to have a mild level of sleep disturbance and 4.4% had moderate to severe sleep disturbance. Compared to those with “normal” levels of sleep disturbance, those with mild to severe levels more often reported low libido (20.7% vs. 13.8%; p = 0.01), ejaculatory dysfunction (31.3% vs. 19.9%; p < 0.01), and orgasmic dysfunction (15.3% vs. 5.1%; p < 0.01). Of men with mild to severe sleep disturbance, 28.3% reported pursuing treatment for erectile dysfunction compared to those with normal levels of sleep disturbance (17.8%; p < 0.01). Further, only 57.2% of men with mild to severe sleep disturbance were assessed to have “No signs of ED” compared to 71.0% of men without elevated levels of sleep disturbance (p < 0.01). Conclusions Sleep disturbance is associated with reduced libido, ejaculatory, orgasmic, and erectile function in men undergoing fertility testing. Providers should assess for sleep-related symptoms during initial evaluation to optimize fertility potential. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Fellow Health.

Abstract CCGA [NCT02889978] is the largest study of cfDNA-based early cancer detection; the first CCGA learnings from multiple cfDNA assays are reported here. This prospective, multi-center, observational study has enrolled 10,012 of 15,000 demographically-balanced participants at 141 sites. Blood was collected from participants with newly diagnosed therapy-naive cancer (C, case) and participants without a diagnosis of cancer (noncancer [NC], control) as defined at enrollment. This preplanned substudy included 878 cases, 580 controls, and 169 assay controls (n=1627) across 20 tumor types and all clinical stages. All samples were analyzed by: 1) Paired cfDNA and white blood cell (WBC)-targeted sequencing (60,000X, 507 gene panel); a joint caller removed WBC-derived somatic variants and residual technical noise; 2) Paired cfDNA and WBC whole-genome sequencing (WGS; 35X); a novel machine learning algorithm generated cancer-related signal scores; joint analysis identified shared events; and 3) cfDNA whole-genome bisulfite sequencing (WGBS; 34X); normalized scores were generated using abnormally methylated fragments. In the targeted assay, non-tumor WBC-matched cfDNA somatic variants (SNVs/indels) accounted for 76% of all variants in NC and 65% in C. Consistent with somatic mosaicism (i.e., clonal hematopoiesis), WBC-matched variants increased with age; several were non-canonical loss-of-function mutations not previously reported. After WBC variant removal, canonical driver somatic variants were highly specific to C (e.g., in EGFR and PIK3CA, 0 NC had variants vs 11 and 30, respectively, of C). Similarly, of 8 NC with somatic copy number alterations (SCNAs) detected with WGS, 4 were derived from WBCs. WGBS data revealed informative hyper- and hypo-fragment level CpGs (1:2 ratio); a subset was used to calculate methylation scores. A consistent “cancer-like” signal was observed in <1% of NC participants across all assays (representing potential undiagnosed cancers). An increasing trend was observed in NC vs stages I-III vs stage IV (nonsyn. SNVs/indels per Mb [Mean±SD] NC: 1.01±0.86, stages I-III: 2.43±3.98; stage IV: 6.45±6.79; WGS score NC: 0.00±0.08, I-III: 0.27±0.98; IV: 1.95± 2.33; methylation score NC: 0±0.50; I-III: 1.02±1.77; IV: 3.94±1.70). These data demonstrate the feasibility of achieving >99% specificity for invasive cancer, and support the promise of cfDNA assay for early cancer detection. Additional data will be presented on detected plasma:tissue variant concordance and on multi-assay modeling. Citation Format: Alexander A. Aravanis, Geoffrey R. Oxnard, Tara Maddala, Earl Hubbell, Oliver Venn, Arash Jamshidi, Ling Shen, Hamed Amini, John A. Beausang, Craig Betts, Daniel Civello, Konstantin Davydov, Saniya Fazullina, Darya Filippova, Sante Gnerre, Samuel Gross, Chenlu Hou, Roger Jiang, Byoungsok Jung, Kathryn Kurtzman, Collin Melton, Shivani Nautiyal, Jonathan Newman, Joshua Newman, Cosmos Nicolaou, Richard Rava, Onur Sakarya, Ravi Vijaya Satya, Seyedmehdi Shojaee, Kristan Steffen, Anton Valouev, Hui Xu, Jeanne Yue, Nan Zhang, Jose Baselga, Rosanna Lapham, Daron G. Davis, David Smith, Donald Richards, Michael V. Seiden, Charles Swanton, Timothy J. Yeatman, Robert Tibshirani, Christina Curtis, Sylvia K. Plevritis, Richard Williams, Eric Klein, Anne-Renee Hartman, Minetta C. Liu. Development of plasma cell-free DNA (cfDNA) assays for early cancer detection: first insights from the Circulating Cell-Free Genome Atlas Study (CCGA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-343.