Are they functional hypogonadal men? Testosterone serum levels unravel male idiopathic infertility subgroups.

PURPOSE: To evaluate total testosterone distribution in male idiopathic infertility. METHODS: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL). RESULTS: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020). CONCLUSION: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile.

The chronic alcohol consumption influences the gonadal axis in men: Results from a meta-analysis.

BACKGROUND: Low testosterone concentrations affect 2-13% of adult males, with a direct association between reduction in testosterone (T) concentrations and cardiovascular events. Lifestyle habits have been linked to visceral fat accumulation and endocrine disorders like secondary hypogonadism. Alcohol intake has also been a topic of debate, with studies showing a detrimental effect on sperm production and underlying mechanisms. This meta-analysis aims to comprehensively evaluate the effect of alcohol consumption on T serum concentrations in adult men. METHODS: The literature search included only controlled clinical trials comparing men who drink alcohol to men who do not, or who assumed placebo or nonalcoholic beverages. The primary outcome was the comparison of total testosterone serum concentrations between the study and control groups. The publications were examined for publication bias using Egger's test. RESULTS: Twenty-one studies were included in the analysis for a total of 30 trials that examined the effects of alcohol consumption on testosterone level in 10,199 subjects. The meta-analysis showed that alcohol consumption overall is related to significant reduction in circulating concentrations of total testosterone (mean difference [MD] = -4.02; 95% CI -6.30, -1.73), free T (MD = -0.17; 95% CI -0.23, -0.12), sex hormone binding globulin (SHBG) (MD = -1.94; 95% CI -3.37, -0.48), an increase in estradiol (E2) (MD = 7.65; 95% CI 1.06, 14.23) and neutral effect on luteinizing hormone (LH) (MD = -0.15; 95% CI -0.36, 0.06), independently by age, body mass index (BMI), E2, and LH serum concentrations and alcohol intake. However, these results are evident only in healthy men exposed to chronic alcohol consumption and not in those with a recognized diagnosis of alcohol use disorder or after acute alcohol intake. CONCLUSION: This study suggests how chronic alcohol consumption may inhibit the gonadal axis in healthy men, although the exact pathophysiological mechanisms connecting alcohol exposure and steroidogenesis are still not completely clarified.

Alterations in the Menstrual Cycle as a Peculiar Sign of Type 1 Diabetes Mellitus: A Meta-analytic Approach.

BACKGROUND: Menstrual irregularities are present in >30% of women with type 1 diabetes mellitus (T1DM). These abnormalities will likely lead to reduced fertility and earlier menopause. T1DM management has changed over time, with even more emphasis on stringent levels of glycemic management. Thus, we investigated whether therapeutic T1DM changes have an influence on the proportion of menstrual disorders in women with T1DM. METHODS: A meta-analysis was performed that included clinical trials in which menstrual abnormalities in women with T1DM were studied. The literature was checked for studies in which women with T1DM were compared with healthy, age-matched controls. Case-control, cohort, and cross-sectional studies were included. The primary endpoint was rate of menstrual dysfunction. RESULTS: Menstrual dysfunction was higher in women with T1DM compared with controls (odds ratio 2.08, 95% confidence interval [CI] 1.43 to 3.03, p<0.001), even when sensitivity analysis was performed, considering only studies published after 2000. The age at menarche was higher for women with T1DM compared with controls (mean difference 0.53, 95% CI 0.32 to 0.74 years, p<0.001). The proportion of menstrual abnormalities in T1DM was inversely related to diabetes duration, but was unrelated to both body mass index and glycated hemoglobin. CONCLUSIONS: The meta-analytic approach used confirmed the correlation between T1DM and menstrual irregularities. T1DM menstrual dysfunction seemed unrelated to change in therapeutic management across years, as well as to glycemic management and body weight. The underlying pathogenetic mechanisms are not fully understood.

Gonadotropins in the Management of Couple Infertility: Toward the Rational Use of an Empirical Therapy.

Although epidemiology shows that both men and woman can experience infertility, the female partner usually experiences most of the diagnostic and therapeutic burden. Thus, management of couple infertility is a unique example of gender inequality. The use of exogenous gonadotropins in assisted reproductive technology (ART) to induce multifollicular growth is well consolidated in women, but the same is not done with the same level of confidence and purpose in infertile men. Indeed, the treatment of idiopathic male infertility is based on an empirical approach that involves administration of the follicle-stimulating hormone (FSH) in dosages within the replacement therapy range. This treatment has so far been attempted when the endogenous FSH serum levels are within the reference ranges. According to the most recent evidence, a "substitutive" FSH administration may not be effective enough, while a stimulatory approach could boost spermatogenesis over its basal levels without adverse extragonadal effects. This article aims to describe the rationale behind the empirical application of gonadotropins in couple infertility, highlighting the need for a change in the therapeutic approach, especially for the male partner.

Microbiota Composition and Probiotics Supplementations on Sleep Quality-A Systematic Review and Meta-Analysis.

The gut microbiota (GM) plays a crucial role in human health. The bidirectional interaction between GM and the central nervous system may occur via the microbiota-gut-brain axis, possibly regulating the sleep/wake cycle. Recent reports highlight associations between intestinal dysbiosis and sleep disorders, suggesting that probiotics could ameliorate this condition. However, data are poor and inconsistent. The aim of this quantitative metanalytic study is to assess the GM composition in sleep disturbances and evaluate probiotics' effectiveness for managing sleep disorders. A systematic review was carried out until July 2022 in online databases, limiting the literature research to human studies and English language articles. No significant GM diversity between patients with sleep disturbances versus healthy controls was found, revealed by α-diversity, while ß-diversity is missing due to lack of proper reporting. However, probiotics supplementation significantly reduced the self-assessed parameter of sleep quality and disturbances Pittsburgh Sleep Quality Index (PSQI) score compared with the placebo. No difference in the Epworth Sleepiness Scale (ESS) score was found. While available data suggest that GM diversity is not related to sleep disturbances, probiotics administration strongly improves sleep quality as a subjective perception. However, heterogeneity of data reporting in the scientific literature should be considered as a limitation.

Sperm Concentration Improvement May Be a Parameter Predicting Efficacy of FSH Therapy of Male Idiopathic Infertility.

Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. A real-world study was conducted, enrolling idiopathic infertile men treated with FSH 150IU three times weekly. Patients were treated until pregnancy achievement or for a maximum of two years and two visits were considered: V0 (baseline) and V1 (end of FSH treatment). Primary endpoints were the V1-V0 percentage change in sperm concentration, total sperm count, and total motile sperm number. In total, 48 pregnancies were recorded (27.7%) among 173 men (age 37.9 ± 6.2 years). All three endpoints increased after FSH administration, and only the V1-V0 percentage of sperm concentration significantly predicted pregnancy (p = 0.007). A V1-V0 sperm concentration of 30.8% predicted pregnancy, and the sperm concentration V1-V0 percentage (Y) required to obtain a pregnancy was predicted according to its baseline values (x): Y = 9.8433x2 - 203.67x + 958.29. A higher number of pregnancies was reached in men with baseline sperm concentration below 7.3 million/mL. Thus, the percentage of sperm concentration increasing after FSH administration could predict the treatment efficacy in terms of pregnancy. At the dosage used, the efficacy was significantly higher in patients with a starting sperm concentration < 7.3 mill/mL. Mathematical analyses identified a function able to predict the sperm concentration increase required to obtain a pregnancy in relation to the baseline sperm number.

Prolactin and spermatogenesis: new lights on the interplay between prolactin and sperm parameters.

PURPOSE: To clarify the relationship between one the most gender-specific hormone, i.e. prolactin (PRL), and semen parameters in men. METHODS: A retrospective, observational, cohort, real-world study was carried out, enrolling all men performing a semen analysis and PRL examination from 2010 to 2022. For each patient, the first semen analys was extracted, associated to PRL, total testosterone (TT), follicle stimulating hormone (FSH) and luteinizing hormone (LH). Hyperprolactinaemia (>35 ng/mL) was excluded. RESULTS: 1211 subjects were included. PRL serum levels were lower in normozoospermia compared to azoospermia (p = 0.002) and altered semen parameters (p = 0.048) groups. TT serum levels were not different among groups (p = 0.122). Excluding azoospermic men, PRL serum levels were lower in normozoospermic patients, when compared to other groups of semen alterations. An inverse correlation was detected between PRL and sperm concentration. Considering normozospermic subjects, PRL was directly related to both non-progressive sperm motility (p = 0.014) and normal sperm morphology (p = 0.040). Subdiving the cohort in quartiles according to PRL distribution, the highest motilities were observed in the second PRL quartile (8.30-11.10 ng/mL) and asthenozoospermia was significantly predicted by FSH (p < 0.001) and second PRL quartile (p = 0.045). CONCLUSION: The PRL-spermatogenesis connection seems to be mild, although low-normal PRL levels are associated with the best spermatogenetic profile. PRL serum levels could mirror the immunoregulatory status within the testis, suggesting that there is a sort of 'PRL optimal window' reflecting an efficent spermatogenesis. Alternatively, men with good semen parameters might have a higher central dopaminergic tone resulting in low PRL levels.

Talking about sex: erectile dysfunction in the oncology patient.

Cancer-related diagnosis and treatments can profoundly affect every aspect of an individual's life. The negative impact on the sexual sphere can manifest with onset or worsening of the most frequent male form of sexual dysfunction, that is the erectile dysfunction (ED), with an estimated incidence ranging from 40 to 100% in patients living with cancer. Cancer and ED are strictly related for many reasons. First, the psychological distress, the so-called 'Damocles syndrome', afflicting cancer patients contributes to ED onset. Second, all cancer therapies can variably lead to sexual dysfunction, even more than the disease itself, having both direct or indirect effects on sexual life. Indeed, alongside pelvic surgery and treatments directly impairing the hypothalamus-pituitary-gonadal axis, the altered personal-body-image frequently experienced by people living with cancer may represent a source of distress contributing to sexual dysfunction. It is undeniable that sexual issues are currently neglected or at least under-considered in the oncological setting, mainly due to the subjective lack of preparation experienced by healthcare professionals and to scant information provided to oncological patients on this topic. To overcome these management problems, a new multidisciplinary medical branch called 'oncosexology' was set up. The aim of this review is to comprehensively evaluate ED as an oncology-related morbidity, giving new light to sexual dysfunction management in the oncological setting.

Systematic review and meta-analysis of long-term reintervention following thoracic endovascular repair for blunt traumatic aortic injury.

OBJECTIVE: To investigate the long-term reinterventions of thoracic endovascular repair (TEVAR) after blunt traumatic aortic injury. METHODS: MEDLINE, EMBASE, and Cochrane databases were interrogated until June 2021. Inclusion criteria were blunt traumatic aortic injury treated with TEVAR and mean follow-up of more than 60 months. A systematic review was conducted and data were pooled using a random effects model of proportions applying the Freeman-Tukey transformation. Late reintervention was the primary outcome. Secondary outcomes were procedure-related complications (endoleak, in-stent thrombosis, occlusion, infolding/collapse, bird-beak, migration, and left arm claudication), overall and aortic-related mortality, and aortic diameter changes. RESULTS: Eleven studies with a low quality assessment were included. Four hundred eight patients were collected and the 389 surviving more than 30 days were included. The mean follow-up was 8.2 years (95% confidence interval [CI], 5.7-10.8; I2 = 40.2%). Late reintervention was 2.1% (95% CI, 0.6-3.9; I2 = 0.0%; 11/389 cases) with 0.1% (95% CI, 0.0-1.2; I2 = 0.0%; 3/389) occurring after 5 years. Bird-beak was identified in 38.7% (95% CI, 16.4-63.6; I2 = 86.6%). Left arm claudication occurring after 30 days was 3.1% (95% CI, 0.1-8.6; I2 = 26.9%; 11/140 cases). In-stent thrombosis was 1.9% (95% CI, 0.1-5.2; I2 = 51.8%; 11/389 cases). Endoleak was 0.5% (95% CI, 0.0-1.9; I2 = 0.0%; 5/389 cases). Infolding, occlusion, and migration were reported in 2 of 389, 1 of 389, and 0 of 389 patients, respectively. Overall late survival was 95.6% (95% CI, 88.1-99.8; I2 = 84.7%; 358/389 patients) and only one patient accounted for aortic related mortality. The increase in proximal and distal aortic diameters was estimated at 2.7 mm (95% CI, 1.2-4.3; I2 = 0.0%) and 2.5 mm (95% CI, 1.1-3.9; I2 = 0.0%), respectively. CONCLUSIONS: TEVAR demonstrates remarkably good long-term results and reinterventions are rarely required. Aortic reinterventions tend to occur within the first and after the fifth year.

Which sperm parameter limits could really guide the clinical decision in assisted reproduction?

BACKGROUND: The predictive role of sperm motility and morphology was recently detected in a large sample of more than 20000 assisted reproductive technology (ART) fresh cycles. However, the complete ART procedure consisted of both fresh and frozen-embryos transfers and only a comprehensive evaluation of the entire process could really confirm if these parameters really predict the ART success. The aim of the study was to evaluate which sperm parameter could predict the success of ART. METHODS: A retrospective, real-world data analysis was performed, enrolling all couples attending ART from 2008 to 2021, including both fresh and frozen cycles and both in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) procedures. RESULTS: Fresh cycles success (considering live birth rate) was predicted by female age (1.04 [1.02-1.06]), injected oocytes (0.96 [0.93-0.99]), embryo number (0.79 [0.75-0.83]) and progressive sperm motility (0.98 [0.97-0.99]). On the contrary, frozen cycle outcomes were predicted only by sperm motility (0.97 [0.95-0.99]). This prediction was confirmed in IVF but not in ICSI cycles. CONCLUSION: Both female and male parameters predicted the ART success considering the entire path. However, frozen cycle success was predicted only by progressive sperm motility in IVF cycles, suggesting that the potential amelioration of this male parameter is relevant to improve ART success. Those couples expected to obtain the highest embryos after fertilization (low female age and better semen parameters) will have more attempts with frozen cycles and thus would benefit from a potential treatment focused to improve sperm parameters.

Follicle-stimulating hormone effectiveness in male idiopathic infertility: What happens in daily practice?

OBJECTIVES: To assess the effectiveness of follicle-stimulating hormone (FSH) administration in male idiopathic infertility in a clinical setting. METHODS: A retrospective real-world study was carried out, including all consecutive FSH-treated infertile men attending the Andrology Unit of Modena (Italy) from June 2015 to May 2022. Medical history, physical and andrological examinations, hormonal and seminal parameters, therapeutic management and pregnancy data were collected. The primary endpoint was the number of pregnancies obtained after FSH administration, whereas semen parameters change was the secondary outcome. RESULTS: A total of 194 of 362 (53.6%) infertile men, eligible according to the Italian Health System regulations, were treated with FSH (mean age 37.9 ± 6.1 years). Following FSH administration (mean therapy duration 9.1 ± 7.1 months), 43 pregnancies were recorded (27.6%), of which 22 occurred naturally and 21 after assisted reproduction. A significant increase in sperm concentration (9.9 ± 12.2 vs. 18.9 ± 38.9 million/mL, p = 0.045) was detected after treatment, together with a significant increase in normozoospermia (from 1.0% to 5.1%, p = .044) and a reduction in azoospermia rate (from 9.8% to 7%, p = 0.044). Dividing the cohort in FSH-responders and non-responders, in terms of pregnancy achieved, higher sperm concentrations (15.7 ± 26.6 vs. 22.2 ± 25.7 million/mL, p = 0.033) and progressive sperm motility (18.0 ± 18.2 vs. 27.3 ± 11.3, p = 0.044) were found in pregnancy group. CONCLUSION: Our experience suggests that FSH, empirically administered to men with idiopathic infertility, leads to pregnancy in one out of four patients and increases sperm concentration. Although the expected limits because of a real-world data study, the number of FSH-treated patients required to achieve one pregnancy seems to be lower in clinical setting if compared to previously published data.

Semen cryopreservation in men undergoing cancer treatment: a ten-year study.

BACKGROUND: The advancement of Assisted Reproductive Technologies and the improvement in sperm freezing made male fertility preservation widely available. This study aims to evaluate the impact of cancer diseases on semen parameters before cryopreservation and the reproductive outcomes of patients who have thawed their semen samples. METHODS: An observational, cohort study was conducted on cancer patients submitted to fertility preservation in AUSL-IRCCS of Reggio Emilia between 2007 and 2018. Semen samples were collected before cancer treatments, analyzed and frozen by rapid freezing. On request, these samples were thawed for Assisted Reproductive Technologies procedures. Semen parameters were compared between testicular versus other cancers. RESULTS: We included 329 patients with a successful cryopreservation in 94.5% of cases. Testicular cancer was associated with lower sperm volumes (P=0.041) and lower total sperm concentration (P=0.009) compared to other cancers. No difference was observed about sperm motility and morphology, while oligozoospermia was significantly more frequent in men with testicular cancer (P<0.001). In our cohort, the 8.4% of patients thawed their samples; the usage rate and the embryo transfer rate were significantly higher (P<0.05) among those with a testicular cancer, while pregnancy and livebirth rates did not differ. CONCLUSIONS: Male fertility preservation is feasible, easy to be performed, non-invasive and does not delay cancer treatments. Men affected by testicular cancer had worse semen parameters at cryopreservation but pregnancy and livebirth rates were similar to those achieved by men with other cancers and similar to those achieved with fresh sperm.

Ketogenic state improves testosterone serum levels-results from a systematic review and meta-analysis.

BACKGROUND: It is widely demonstrated that obesity and hypogonadism are bi-directionally correlated, since the hypogonadism prevalence is higher in obese population, while weight loss increases testosterone serum levels. Several approaches are available to contrast weight excess, from simple dietary regimens to more complex surgical procedures. Ketogenic diets (KD) fit in this context and their application is growing year after year, aiming to improve the metabolic and weight patterns in obese patients. However, KD influence on testosterone levels is still poorly investigated. OBJECTIVES: To systematically evaluate the potential effect of KD on testosterone levels. METHODS: A systematic literature search was performed until April 2022 including studies investigating testosterone levels before and after KD. Secondary endpoints were body weight, estradiol and sex-hormone binding globulin serum levels. Any kind of KD was considered eligible, and no specific criteria for study populations were provided. RESULTS: Seven studies (including eight trials) were included in the analysis for a total of 230 patients, five using normocaloric KD and three very low calories KD (VLCKD). Only three studies enrolled overweight/obese men. A significant total testosterone increase was recorded after any kind of KD considering 111 patients (2.86 [0.95, 4.77], p = 0.003). This increase was more evident considering VLCKD compared to normocaloric KD (6.75 [3.31, 10.20], p < 0.001, versus 0.98 [0.08, 1.88], p = 0.030). Meta-regression analyses highlighted significant correlations between the post-KD testosterone raise with patients' age (R-squared 36.4, p < 0.001) and weight loss (R-squared 73.6, p < 0.001). CONCLUSIONS: Comprehensively, KD improved testosterone levels depending on both patients' age and KD-induced weight loss. However, the lack of information in included studies on hormones of the hypothalamic-pituitary-gonadal axis prevents an exhaustive comprehension about mechanisms connecting ketosis and testosterone homeostasis.

Testosterone Serum Levels Are Related to Sperm DNA Fragmentation Index Reduction after FSH Administration in Males with Idiopathic Infertility.

Purpose: Although a robust physiological rationale supports follicle stimulating hormone (FSH) use in male idiopathic infertility, useful biomarkers to evaluate its efficacy are not available. Thus, the primary aim of the study was to evaluate if testosterone serum levels are related to sperm DNA fragmentation (sDF) index change after FSH administration. The secondary aim was to confirm sDF index validity as a biomarker of FSH administration effectiveness in male idiopathic infertility. Methods: A retrospective, post-hoc re-analysis was performed on prospectively collected raw data of clinical trials in which idiopathic infertile men were treated with FSH and both testosterone serum levels and sDF were reported. Results: Three trials were included, accounting for 251 patients. The comprehensive analysis confirmed FSH's beneficial effect on spermatogenesis detected in each trial. Indeed, an overall significant sDF decrease (p < 0.001) of 20.2% of baseline value was detected. Although sDF resulted to be unrelated to testosterone serum levels at baseline, a significant correlation was highlighted after three months of FSH treatment (p = 0.002). Moreover, testosterone serum levels and patients' age significantly correlated with sDF (p = 0.006). Dividing the cohort into responders/not responders to FSH treatment according to sDF change, the FSH effectiveness in terms of sDF improvement was related to testosterone and male age (p = 0.003). Conclusion: Exogenous FSH administration in male idiopathic infertility is efficient in reducing sDF basal levels by about 20%. In terms of sDF reduction, 59.2% of the patients treated were FSH-responders. After three months of FSH administration, a significant inverse correlation between sDF and testosterone was detected, suggesting an association between the FSH-administration-related sDF improvement and testosterone serum levels increase. These observations lead to the hypothesis that FSH may promote communications or interactions between Sertoli cells and Leydig cells.

Qualitative and quantitative analysis of doctor-patient interactions during andrological consultations.

INTRODUCTION: Although a trustworthy connection between doctor and patient is crucial in clinical practice, it could be hindered by different cultural and linguistic backgrounds. Moreover, an effective doctor-patient interaction could be even more challenging in andrological fields, in which psychological and social components are predominant. AIM: To analyse the doctor-patient relationship in the andrological field, applying both qualitative and quantitative analyses. METHODS: monocentric, cross-sectional, observational study was performed between May and December 2018. During the study, all patients aged >18 years attending the Modena Andrology Unit for couple infertility or erectile dysfunction were enrolled and the doctor-patients interaction recorded. Patients were divided into two groups depending on their medical seeking and were further divided between native and non-native speakers of Italian. All patients underwent a routine andrological examination. Every first medical consultation was audio-recorded and transcribed using "ELAN" software for socio-linguistic analysis. Transcriptions underwent qualitative analysis through conversation analysis. Then, quantitative analyses were performed, and interaction parameters underwent correlation analyses. RESULTS: Twenty-five patients were enrolled. The analysis of the andrological interview allowed to recognise five consecutive phases, following a semi-standardized pattern. Patients without linguistic barriers and with infertility problems showed more autonomous contribution during the consultation. No difference arose in the sexual dysfunctions group. Doctor's explanations were frequent, but when linguistic barrier was present or Italian patients seemed less talkative, explanations were shorter, and doctors tried to use other conversational mechanisms to promote understanding. Patient's variables were significantly lower compared to the doctor, considering the number of turns (p = 0.025) and their minimum (p = 0.032), maximum (p < 0.001), and average durations (p < 0.001). Only patient's latency was significantly higher than the doctor's (p = 0.001). CONCLUSION: This is the first attempt to analyse the doctor-patient relationship in andrology using authentic audio-recorded consultations. The results confirmed that a patient-centred communication must be applied also in andrological consultations. However, the topics discussed may require more "medical formulation" to be acceptable to the participants in this context.

Human fertility and sleep disturbances: A narrative review.

INTRODUCTION: Many factors may be hidden behind the global fertility decline observed in Western countries. Alongside the progressively increased age of infertile couples, environmental and behavioural factors, including non-optimal lifestyle habits, should be considered. Among these, sleep disorders have been suggested to be linked to human fertility. METHODS: This is a narrative review, describing first sleep physiology, its disturbances, and the tools able to quantify sleep dysfunction. Then, we consider all available studies aimed at investigating the connection between sleep disorders and human fertility, providing a comprehensive view on this topic. RESULTS: Forty-two studies investigating the relationship between sleep habits and human reproduction were included. All the published evidence was grouped according to the aspect of human fertility considered, i.e. i) female reproductive functions, ii) male reproductive functions, iii) natural conception and iv) assisted reproduction. For each of the sub-groups considered, the connection between sleep dysregulation and human fertility was classified according to specific sleep characteristics, such as sleep duration, quality, and habits. In addition, possible physio-pathological mechanisms proposed to support the link between sleep and fertility were summarized. CONCLUSION: This review summarizes the most relevant findings about the intricate and still largely unknown network of molecular pathways involved in the regulation of circadian homeostasis, to which sleep contributes, essential for reproductive physiology. Thus, many mechanisms seem correlate sleep disorders to reproductive health, such as adrenal activation, circadian dysregulation, and genetic influences. This review highlights the need to properly designed trials on the topic.

Real-world evidence analysis of the follicle-stimulating hormone use in male idiopathic infertility.

Male idiopathic infertility remains a therapeutic challenge in the couple infertility management. In this setting, an empirical treatment with follicle-stimulating hormone (FSH) is allowed, although not recommended. Twenty-one clinical trials and four meta-analyses highlighted an overall increased pregnancy rate in case of FSH administration, but the indiscriminate FSH prescription is still unsupported by clinical evidence in idiopathic infertility. This context could represent an example in which real-world data (RWD) could add useful information. From a nationwide clinical practice survey performed in Italy, emerged the clinicians' attitude to prescribe FSH in the case of impaired semen with a significant improvement of semen parameters, identifying FSH treatment as a therapeutic card in the real-life management. Although more robust data are still needed to optimize FSH treatment in male idiopathic infertility, RWD should be included in the body of evidence considered in healthcare decision-making.

Accurate and time-saving, two-step intracavernosal injection procedure to diagnose psychological erectile dysfunction.

BACKGROUND: The recognition of the erectile dysfunction pathogenesis is essential to identify the appropriate erectile dysfunction management. As vascular erectile dysfunction could be a manifestation of a systemic arterial damage, the watershed in the erectile dysfunction diagnostic framework is the discrimination between psychological erectile dysfunction and vascular erectile dysfunction. However, reliable tools to directly diagnose psychological erectile dysfunction are currently lacking. OBJECTIVE: To identify which parameters could predict psychological erectile dysfunction. Moreover, we suggest a new intracavernosal injection procedure to optimize the erectile dysfunction diagnostic workup. MATERIALS AND METHODS: A retrospective, real-world analysis was carried out including all men who underwent intracavernosal injection procedure at the Modena Andrology Unit from 2018 to 2021. A first intracavernosal injection procedure with 5 µg of prostaglandin E-1 (PGE-1) was performed. In the absence of a full drug-induced erection (immediate or delayed), an echo-color Doppler penile evaluation after administration of PGE-1 10 µg was conducted, measuring intracavernosal blood flows, to document a possible vascular etiology. Hormonal evaluations were performed. RESULTS: Out of 179 enrolled patients, 70.4% showed psychological erectile dysfunction, 21.7% vascular erectile dysfunction, and 7.8% hormonal genesis. Multinomial logistic regression analysis identified absence of cardiovascular disease (p = 0.017), presence of spontaneous morning erections (p = 0.018), and normal penile erections with masturbation (p = 0.035) as predictors of psychological erectile dysfunction. Clinically, normal intracavernosal injection test response was detected in 86 patients and abnormal response in 93 subjects. Among the latter, 54 patients experienced a delayed response. The combination of intracavernosal injection test with late penile erections evaluation was able to diagnose psychological erectile dysfunction (sensitivity 97%, specificity 100%), avoiding unnecessary retesting. DISCUSSION: We propose a two-step intracavernosal injection procedure that allows to recognize psychological erectile dysfunction with a high sensitivity/specificity, saving costs and time, and limiting adverse events. Moreover, the presence of spontaneous morning erections and valid penile erections after masturbation could guide the diagnostic workup, indirectly identifying those patients deserving of a deeper evaluation of vascular health.

The (decision) tree of fertility: an innovative decision-making algorithm in assisted reproduction technique.

PURPOSE: Several mathematical models have been developed to estimate individualized chances of assisted reproduction techniques (ART) success, although with limited clinical application. Our study aimed to develop a decisional algorithm able to predict pregnancy and live birth rates after controlled ovarian stimulation (COS) phase, helping the physician to decide whether to perform oocytes pick-up continuing the ongoing ART path. METHODS: A single-center retrospective analysis of real-world data was carried out including all fresh ART cycles performed in 1998-2020. Baseline characteristics, ART parameters and biochemical/clinical pregnancies and live birth rates were collected. A seven-steps systematic approach for model development, combining linear regression analyses and decision trees (DT), was applied for biochemical, clinical pregnancy, and live birth rates. RESULTS: Of fresh ART cycles, 12,275 were included. Linear regression analyses highlighted a relationship between number of ovarian follicles > 17 mm detected at ultrasound before pick-up (OF17), embryos number and fertilization rate, and biochemical and clinical pregnancy rates (p < 0.001), but not live birth rate. DT were created for biochemical pregnancy (statistical power-SP:80.8%), clinical pregnancy (SP:85.4%), and live birth (SP:87.2%). Thresholds for OF17 entered in all DT, while sperm motility entered the biochemical pregnancy's model, and female age entered the clinical pregnancy and live birth DT. In case of OF17 < 3, the chance of conceiving was < 6% for all DT. CONCLUSION: A systematic approach allows to identify OF17, female age, and sperm motility as pre-retrieval predictors of ART outcome, possibly reducing the socio-economic burden of ART failure, allowing the clinician to perform or not the oocytes pick-up.

Are sperm parameters able to predict the success of assisted reproductive technology? A retrospective analysis of over 22,000 assisted reproductive technology cycles.

BACKGROUND: An explosive increase in couples attending assisted reproductive technology has been recently observed, despite an overall success rate of about 20%-30%. Considering the assisted reproductive technology-related economic and psycho-social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of assisted reproductive technology success, male parameters are largely underestimated so far. STUDY DESIGN: Retrospective, observational study. OBJECTIVES: To evaluate whether conventional semen parameters could predict assisted reproductive technology success. MATERIALS AND METHODS: All couples attending a single third-level fertility center from 1992 to 2020 were retrospectively enrolled, collecting all semen and assisted reproductive technology parameters of fresh cycles. Fertilization rate was the primary end-point, representing a parameter immediately dependent on male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to the World Health Organization manual editions used for semen analysis. RESULTS: Note that, 22,013 in vitro fertilization and intracytoplasmic sperm injection cycles were considered. Overall, fertilization rate was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective of the World Health Organization manual edition. In the in vitro fertilization setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted the fertilization rate (statistical accuracy = 71.1%). Sperm motilities also predicted pregnancy (p < 0.001) and live birth (p = 0.001) rates. In intracytoplasmic sperm injection cycles, sperm morphology predicted fertilization rate (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p < 0.001) and live birth (p < 0.001) rates and a cut-off of 5.5% was identified as a threshold to predict clinical pregnancy (area under the curve = 0.811, p < 0.001). DISCUSSION: Interestingly, sperm motility plays a role in predicting in vitro fertilization success, while sperm morphology is the relevant parameter in intracytoplasmic sperm injection cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples.