Hyperbaric oxygen therapy has emerged as a potential adjunctive treatment for male infertility, as it targets various sperm abnormalities and improves fertility outcomes. This systematic review and meta-analysis synthesized data from randomized controlled trials to evaluate the efficacy of hyperbaric oxygen therapy in treating male infertility. A comprehensive literature search identified nine eligible studies, which were assessed for quality using the Jadad scale and analyzed for heterogeneity. The meta-analysis revealed significant improvements in sperm survival, density, morphology, normal sperm rates, and motility following hyperbaric oxygen therapy, with an increased clinical pregnancy rate. Subgroup analyses based on infertility etiology and treatment duration further elucidated the heterogeneity of male infertility stemming from the etiology of infertility. Despite the high robustness of the meta-analysis results, the study is limited by the small number of included trials and potential publication bias. In conclusion, when combined with conventional treatments, hyperbaric oxygen therapy significantly enhances sperm parameters and fertility, underscoring its role as an effective adjunctive therapy for male infertility.

Atorvastatin and fenofibrate are well-known lipid-lowering drugs. Atorvastatin acts by reducing the production of cholesterol through the inhibition of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG Co-A reductase) enzyme, whereas fenofibrate is a PPAR-α agonist. Piperine is an alkaloid mostly found in black pepper fruits. The present study was planned to evaluate the activities of atorvastatin, fenofibrate, and piperine on the male reproductive system. A total of 35 male Wistar rats were obtained for the experiment. Rats were randomly divided into 7 groups, each group with 5 rats. The experiment was run for 28 days. Group I rat got normal meals for 28 days; Group II received atorvastatin (08 mg/kg/day); Group III received piperine (10 mg/kg/day); and Group IV received fenofibrate (20 mg/kg/day). Group V received atorvastatin (8 mg/kg/day) and piperine (10 mg/kg/day); Group VI received piperine (10 mg/kg/day) and fenofibrate (20 mg/kg/day). VII received fenofibrate (20 mg/kg bw/day) and atorvastatin (8 mg/kg/day). After sacrifice, serum and testicular cholesterol and testosterone levels assessed by ELISA, ROS generation analysed by using flow cytometry, MDA, SOD, and catalase were measured. Histological, sperm-parameter analysis, and spermatogenic evaluations were also done. Activities of atorvastatin and piperine revealed reproductive toxicity upon treatment. Fenofibrate treatment, along with atorvastatin and piperine, showed protective effects. In conclusion, atorvastatin and piperine affected reproductive potential, whereas fenofibrate might have protective efficacy against atorvastatin and piperine-induced reproductive toxicity.

Olanzapine (OLZ) is one of atypical antipsychotic drugs (second generation) used for treating schizophrenia, manic, and mixed episodes of bipolar disorder. Continuous evaluation of its effects is necessary, and there is a need to explore alternative natural products as G-CSF and UMB to manage potential side effects. This research designed to mitigate the atypical antipsychotic drugs' adverse effects through biochemical analyses, light and electron microscopic studies. Fifty-six rats were divided into five groups: Control, OLZ, G-CSF, UMB, and Recovery groups. End body and testicular weights, serum testosterone, testicular MDA levels, and seminal analysis were recorded. Testicular specimens were processed to evaluate histological structure, PCNA, and CD34 immune expression. Morphometric and statistical analyses were also performed. OLZ group exhibited a distorted testicular structure, a significant increase in end body and a decline in testicular weight, a significant decline in the serum level of testosterone level, testicular MDA, and seminal analysis parameters. Furthermore, disturbed histoarchitecture, reduction in PCNA, and elevation in CD34 immunoreaction were observed. These alterations were partially attenuated by G-CSF therapy, whereas UMB significantly improved all parameters. In conclusion, UMB, and to a lesser degree G-CSF, appeared to be superior therapeutic options by attenuating oxidative stress and restoring intact histological structure and biochemical parameters.

Background/Objectives: Inflammatory bowel disease significantly impairs the patient's quality of life. In young individuals, both the disease and the drugs used for the treatment may impact fertility. Our study aimed to assess the action of new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone on the rat testes in a model of TNBS-induced colitis in rats. Methods: In the current study, testes from eight randomly chosen rats were taken from each of the following groups: the control group (K), the colitis group (C), and the groups receiving compounds 7b, 10b, and 13b in higher doses (20 mg/kg). Results: Colitis did not affect the testicular index (expressed as a percentage of the body weight), but in group 13b, this parameter was significantly higher than in group K. No significant differences between groups were noticed in malondialdehyde, superoxide dismutase, interleukin-1, or metalloproteinase 9 levels. In the colitis group, lactate dehydrogenase activity in the testes was not increased; however, the administration of compound 10b significantly increased this parameter when compared to both groups K and C. Histological evaluation also did not reveal abnormalities, and the morphology of the testicular tissues was comparable in all groups. Conclusions: The results may suggest that the new 1,3,4-oxadiazole derivatives of pyrrolo[3,4-d]pyridazinone did not exert significant testicular toxicity.

This study investigated the effects of dietary vitamin E (VE) and selenium (Se) supplementation on body weight changes, blood profile, and semen quality in Dexamethasone (DEX)-stressed Japanese quails. One hundred and five 10-week-old quail cocks were acclimated and divided into five treatment groups: negative control - G1, DEX-treated (20 mgL-1 of drinking water) - G2, DEX + VE (180 mg kg diet-1) - G3; DEX + Se (0.3 mg kg diet-1) - G4; and DEX + VE (180 mg kg diet-1) + Se (0.3 mg kg diet-1) - G5. The birds received their respective treatments over 21 days, and various performance, hematological, and semen quality parameters were measured. Results indicated that DEX treatment significantly reduced weight gain (WG) and feed intake (P < 0.05). Supplementation with VE and Se, individually and combined, ameliorated these effects, with groups G3, G4, and G5 showing similar WG to the control. Hematological analysis revealed significant increases (P < 0.05) in packed cell volume, hemoglobin, and white blood cell count in DEX-treated groups compared to G1. Treatment did not affect blood glucose and cholesterol levels (P ≥ 0.05). Plasma antioxidant assays showed elevated superoxide dismutase and catalase functions and reduced malondialdehyde levels in G3, G4, and G5 compared to G2, indicating reduced oxidative stress. No marked differences were seen in the plasma glutathione peroxidase activities across groups. Sperm motility was impaired in the DEX-only group but improved (P < 0.05) with antioxidant supplementation. In conclusion, dietary VE and Se effectively mitigated the negative impacts of DEX-induced stress on growth, antioxidant status, and spermatozoa motility in Japanese quail cocks. VE and Se supplementation could be beneficial in enhancing the welfare and productivity of poultry under stress.

Prostate cancer (PCa) accounts for roughly 15% of diagnosed cancers among men, with disease incidence increasing worldwide. Age, family history and ethnicity, diet, physical activity, and chemoprevention all play a role in reducing PCa risk. The prostate is an exocrine gland that is characterized by its multi-functionality, being involved in reproductive aspects such as male ejaculation and orgasmic ecstasy, as well as playing key roles in the regulation of local and systemic concentrations of 5α-dihydrotestosterone. The increase in androgen receptors at the ventral prostate is the first elevated response induced by copulation. The regulation of prostate growth and function is mediated by an androgen-dependent mechanism. Binding 5-DHT to androgen receptors (AR) results in the formation of a 5α-DHT:AR complex. The interaction of the 5α-DHT:AR complex with the specific DNA enhancer element of androgen-regulated genes leads to the regulation of androgen-specific target genes to maintain prostate homeostasis. Consequently, ejaculation may play a significant role in the reduction of PCa risk. Thus, frequent ejaculation in the absence of risky sexual behavior is a possible approach for the prevention of PCa. In this review, we provide an insight into possible mechanisms regulating the impact of frequent ejaculation on reducing PCa risk.

Background/Objectives: Male infertility is a complex, multifactorial condition influenced by infectious, inflammatory, and autoimmune components. Immunological factors, though implicated in reproduction, remain poorly understood. This study aims to deepen the understanding of infections, inflammation, and autoimmune factors in male infertility, with a focus on immune-related disorders affecting the testes and epididymis-immunologically privileged but vulnerable sites. These factors can impair sperm quality through oxidative stress (ROS) and antisperm antibodies (ASA), further compromising fertility. Methods: A narrative review was conducted by analyzing scientific literature from the past 10 years conducted on PubMed using keywords such as "male infertility", "autoimmunity", and "inflammatory disease". Studies focusing on testicular and epididymal disorders, immunological impacts, and therapeutic approaches were included. Results: Our research highlights that conditions like epididymitis, vasectomy, testicular trauma, and previous surgeries can trigger inflammatory responses, leading to ASA formation and oxidative stress. ASA, particularly sperm-immobilizing antibodies, inhibits sperm motility and migration in the female reproductive tract. Infections caused by sexually transmitted bacteria or urinary pathogens frequently induce epididymo-orchitis, a primary contributor to male infertility. While standardized methodologies for ASA testing remain elusive, assisted reproductive treatments such as intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and intrauterine insemination (IUI) show promise in overcoming immune-mediated infertility. Conclusions: This review underscores the critical role of infection, inflammation, and autoimmune responses in male infertility. It highlights the necessity of improving diagnostic methods, understanding immune-pathological mechanisms, and addressing medicolegal issues associated with male infertility. This knowledge could pave the way for innovative therapies, ultimately enhancing fertility outcomes, and mitigating the societal and legal repercussions of infertility.

Real-world big data studies on drug-reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a limited number of pre-market clinical trials.

This study aimed to identify culprit drugs that reduced male semen quality based on the United States Food and Drug Administration adverse event reporting system. The Medical Dictionary for Regulatory Activities preferred terms and standardized Medical Dictionary for Regulatory Activities queries were used to define reduced male semen quality. Adverse events related to drug-reduced male semen quality were then analyzed by disproportionality analysis using the United States Food and Drug Administration adverse event reporting system data between 2004 and 2023.

At the preferred term level, 59 drugs with risk signals were detected to be associated with drug-reduced male semen quality, with the three most frequently reported second-level Anatomical Therapeutic Chemical groups being antineoplastic agents (n = 16, 27.12%), psychoanaleptics (n = 9, 15.25%), and psycholeptics (n = 6, 10.17%). At the standardized Medical Dictionary for Regulatory Activities queries level, the five drugs with the greatest number of cases were finasteride (845 cases, IC025 = 7.72), dutasteride (163 cases, IC025 = 7.22), tamsulosin (148 cases, IC025 = 5.99), testosterone (101 cases, IC025 = 4.08), and valproic acid (54 cases, IC025 = 2.44). Additionally, clinical information about drug-reduced male semen quality is absent from the Summary of Product Characteristics of 41 drugs in our study.

Using the United States Food and Drug Administration adverse event reporting system database, we offer a list of drugs with risk signals for reducing male semen quality. In the future, there is still a need for more studies on drugs whose effects on male semen quality are not fully understood.

Increasing numbers of adolescents with gender dysphoria start gonadotropin-releasing hormone agonists to halt puberty, minimizing psychological distress. The uncertainty of long-term effects of this medication, and the subsequent likelihood of accessing gender-affirming hormone treatment, highlights the importance of fertility preservation before starting hormone treatment. We investigated the take-up, hormonal profile, and sperm quality in adolescents undergoing fertility preservation via cryopreservation by masturbation or surgical sperm retrieval, before starting hormonal therapy.

Data were prospectively maintained from a tertiary UK-based hospital. A total of 122 people <19 years, mean age 15.2 ± 1.7 years, referred by gender clinics and general practitioners, were included in this cohort study.

Participants were counseled for fertility preservation, and serum testosterone, follicle-stimulating hormone, and luteinizing hormone levels were recorded before providing semen samples.

Masturbation semen samples were classified as normal (>15 mil/mL), oligozoospermia (1-15 mil/mL), cryptozoospermia (<1 mil/mL), or azoospermia. If the sample was insufficient or the person was unwilling to masturbate, surgical sperm retrieval was offered in a stepwise manner using electroejaculation, testicular sperm extraction (TESE) ± microdissection testicular sperm extraction (mTESE).

Quality of semen produced by participants, via masturbation or surgical sperm retrieval, was analyzed to determine if it was good enough to cryopreserve for future fertility use.

Of 122 participants, 23 (19%) declined sample storage. In the masturbation group (average age, 16.3 years), 78 people produced 106 samples. Of 106 samples, 86 were stored-43.7% were normospermic, 35.9% oligozoospermic, 8.7% cryptozoospermic, and 11.7% azoospermic. Overall, semen parameters varied but were generally abnormal, illustrated by only 43.7% of the masturbation samples produced being normospermic. For surgical sperm retrieval subjects (average age, 15.2 years), electroejaculation was successful in 4 of 21 people, whereas the rest proceeded with TESE/mTESE. Encouragingly, 16 of 21 subjects had an average of 5 vials stored, and all participants had a testosterone level >8 nmol/L. Semen parameters in this subcohort were poor but possibly adequate for intracytoplasmic sperm injection.

In this large database of transgender girls referred for fertility preservation in the United Kingdom, fertility preservation is possible, even with those unwilling to masturbate. Long-term data are required to check the health of these gametes, observing live birth rates using these preserved gametes.

Infertility has become a serious health and socio-economic-psychological problem globally. The harmful role of trace metals in male infertility is recognized but still not sufficiently explained. Herein, a comprehensive review was conducted to elucidate the detrimental role of cadmium (Cd) on male infertility, particularly on infertility with unknown (idiopathic) causes. Peer-reviewed studies from 2000 to 2024 dealing with seminal plasma and blood Cd levels of fertile and infertile men were retrieved were interrogated with regard to strict inclusion/exclusion criteria, and then were thoroughly reviewed and analyzed. Another aim of this review was to indicate the potential effects of Cd on changes in seminogram findings. A median range of seminal plasma Cd levels from 0.2 to 1.5 µg/L can be considered safe for men's fertility. This review strongly implies that Cd levels were notably higher in seminal plasma of infertile cases than controls. The review's data also indicate that exposure to tobacco smoke is a major source of elevated seminal and blood Cd levels in infertile men. Newer research points to the importance of Cd in lower levels from the environment on changes in seminogram findings, primarily count, motility of spermatozoa, and their morphology. Overall, this review implies that seminal plasma Cd levels could be a good indicator of semen quality. However, new, in-depth studies are needed to confirm or reject the causal relationship of Cd with male infertility.

Paternal use of analgesics during the time of conception and adverse birth outcomes are poorly studied. We investigated the association between paternal exposure to non-steroid anti-inflammatory drugs and opioids within 3 months before the date of conception and the risk of adverse birth outcomes (preterm birth, small for gestational age, low Apgar score, and major congenital malformations).

We used nationwide data from the Danish health registers. We included information on all singleton live births, and their fathers and mothers from 1997 to 2018. We created two exposed cohorts, children with preconception paternal exposure to (1) non-steroid anti-inflammatory drugs and (2) opioids. The unexposed cohort was children without preconception paternal exposure to non-steroid anti-inflammatory drugs or opioids, and we performed a sub-analysis against paternal use of acetaminophen (paracetamol). We used logistic regression models to estimate the odds ratios of adverse birth outcomes including 95% confidence intervals.

We identified 1,260,934 children, 45,667 children with paternal exposure to non-steroid anti-inflammatory drugs, 10,086 children with paternal exposure to opioids, and 1,205,181 unexposed children. The adjusted odds ratio for preterm birth was 1.08 (95% confidence interval, 1.03-1.13) after paternal exposure to non-steroid anti-inflammatory drugs and 1.21 (95% confidence interval, 1.08-1.35) after paternal exposure to opioids. The adjusted odds ratio for small for gestational age was 1.09 (95% confidence interval, 1.03-1.17) after paternal exposure to non-steroid anti-inflammatory drugs, and 1.03 (95% confidence interval, 0.88-1.21) after paternal exposure to opioids. We found null-associations for a low Apgar score and major congenital malformations. Estimates were attenuated when compared against paternal paracetamol exposure.

Overall, we found null-associations across the comparisons made. Weak associations were found for paternal exposure to non-steroid anti-inflammatory drugs or opioids and preterm birth and small for gestational age, but not with low Apgar score or major congenital malformation. All associations were attenuated when compared against an active comparator of paternal paracetamol exposure. The effect sizes were small and less likely to be of clinical relevance.

Based on real data from the FDA Adverse Event Reporting System (FAERS), we explored and evaluated the adverse reactions (ADRs) of sulfasalazine (SSZ) in the first quarter of 2004-2023 to provide a reference basis and early warning for the safe use of SSZ in the clinic.

The reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the empirical Bayesian geometric mean (EBGM) were used as measures of SSZ-associated adverse events (AEs) signals, mining for potential positive signals between SSZ and AE.

In this study, a total of 5327 case reports related to SSZ in the last 20 years involving 25 system organ classes (SOCs) were collected in FAERS. The AEs of SSZ were mainly focused on Immune system disorders (n = 1621, IC025 = 2.86), Blood and lymphatic system disorders (n = 638, IC025 = 2.4), and others. In addition, we found 41 adverse reactions not mentioned in the specification, including oculomucocutaneous syndrome (n = 12, IC025 = 4.86), wegener's granulomatosis(n = 6, IC025 = 4.05) and reproductive system aspects.

Significant new AEs signals were observed in this study and may provide important support for clinical monitoring and risk identification in SSZ.

Ketoprofen and meloxicam, non-steroidal anti-inflammatory drugs widely used in clinical practice, lack comprehensive investigation regarding their impact on male reproductive health, particularly on epididymal duct contractions and sperm parameters. Therefore, this study investigated the negative effects of ketoprofen or meloxicam on the contractions of the epididymal duct, sperm parameters, and serum testosterone levels in rats. Firstly, we assessed the in vitro effects of ketoprofen or meloxicam (1-100 μM) on the contractions of the epididymal duct elicited by noradrenaline. Rats were also orally treated with 5 mg/kg ketoprofen or 1 mg/kg meloxicam for 15 days following evaluation of epididymal duct contractions, sperm parameters, and serum testosterone levels. In vitro exposure to meloxicam (100 μM), but not ketoprofen, significantly reduced the maximum effect of noradrenaline in epididymal duct. Moreover, in vivo administration of ketoprofen and meloxicam decreased testosterone levels, sperm production, and sperm count in the caput/corpus region of the rat epididymis. Conversely, the sperm count in the cauda epididymis remained unchanged in animals treated with both ketoprofen and meloxicam. Meloxicam, but not ketoprofen, caused a delay in sperm transit time in the cauda region of the epididymis. In vivo treatment with both ketoprofen or meloxicam hindered the noradrenaline-induced contractions in the epididymal duct. In conclusion, ketoprofen and meloxicam can modify sperm parameters by decreasing testosterone levels and the contractions of the epididymal duct isolated from the distal cauda region of the rat epididymis.

Carnitine is a vital molecule in human metabolism, prominently involved in fatty acid β-oxidation within mitochondria. Predominantly sourced from dietary intake, carnitine also derives from endogenous synthesis. This review delves into the complex network of carnitine transport and distribution, emphasizing its pivotal role in human fertility. Together with its role in fatty acid oxidation, carnitine modulates the acety-CoA/CoA ratio, influencing carbohydrate metabolism, lipid biosynthesis, and gene expression. The intricate regulation of carnitine homeostasis involves a network of membrane transporters, notably OCTN2, which is central in its absorption, reabsorption, and distribution. OCTN2 dysfunction, results in Primary Carnitine Deficiency (PCD), characterized by systemic carnitine depletion and severe clinical manifestations, including fertility issues. In the male reproductive system, carnitine is crucial for sperm maturation and motility. In the female reproductive system, carnitine supports mitochondrial function necessary for oocyte quality, folliculogenesis, and embryonic development. Indeed, deficiencies in carnitine or its transporters have been linked to asthenozoospermia, reduced sperm quality, and suboptimal fertility outcomes in couples. Moreover, the antioxidant properties of carnitine protect spermatozoa from oxidative stress and help in managing conditions like polycystic ovary syndrome (PCOS) and endometriosis, enhancing sperm viability and fertilization potential of oocytes. This review summarizes the key role of membrane transporters in guaranteeing carnitine homeostasis with a special focus on the implications in fertility and possible treatments of infertility and other related disorders.

Infertility, defined as the inability to achieve pregnancy after one year of unprotected, frequent sexual intercourse, is a global burden that affects approximately 15% of couples, or 190-230 million people worldwide, who are trying to start a family. The male contributes significantly, directly accounting for 30-35% and up to 52% of total couple infertility, affecting approximately 7-8% of all men. This work aims to present, in a didactic and objective way, a standardization of the initial steps toward a thorough evaluation of subfertile and infertile men. We have focused on the evaluation of initial management, emphasizing the need for a comprehensive evaluation that includes a detailed history, physical examination, and semen analysis as the golden triple helix of basic evaluation of the infertile male. General and genital physical examinations are highly valuable due to the wealth of information they provide, from potential diagnoses to pregnancy prognoses. Comprehensive and quality-controlled semen analysis provides reliable information as a baseline test to evaluate the patency of the reproductive tract and to evaluate basic sperm parameters and fertility potential. However, it is not a fertility determinant and should preferentially be complemented with sperm functional tests. like biomarkers of oxidative stress, sperm immaturity and DNA fragmentation. Most cases of infertility require evaluation by a specialist in andrology, nonetheless the understanding and rationale of the initial assessment of the infertile male can be undertaken by non-specialists, thus improving the care and counseling of couples facing this troubling issue and avoiding unnecessary use of assisted reproductive technologies (ART) since most cases of male infertility can be treated and reversed by medical or surgical interventions, and the fertility status can be restored. The ultimate goal is to achieve natural pregnancy, the use of ART should not be the initial offered resource.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) have been extensively utilized for the treatment of depression and anxiety disorders. Clinical trials and real-world data suggest that SNRIs may cause reproductive toxicity. To comprehensively assess this association, we conducted a pharmacovigilance study.

We utilized various disproportionality analysis algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multi-item gamma poisson shrinker (MGPS), to assess the significance of reproductive toxicity-related adverse events (AEs) reported to FDA Adverse Event Reporting System (FAERS) from January 2004 to December 2023, with subgroup analysis conducted by sex and age.

Duloxetine and venlafaxine were associated with 14 and 25 AE signals related to reproductive toxicity, respectively, with erectile dysfunction (ED) and retrograde ejaculation identified as shared important medical events (IMEs). ED had the highest reporting frequency, strongest in venlafaxine-treated patients under 45 years (ROR 4.34, PRR 4.33, IC 2.09, EBGM 4.25). Retrograde ejaculation was newly identified. With decreasing incidence, venlafaxine's median ED onset was 122.5 days and duloxetine's 38 days.

Our study provides evidence through an extensive analysis of the large-scale real-world FAERS database, aiding healthcare professionals in mitigating, and prioritizing SNRI-related reproductive toxicity AEs.

Fluoxetine (FLX) is a Selective Serotonin Re-uptake Inhibitor (SSRI) commonly used as a first-line treatment for depression, anxiety, and mood disorders. It can cause infertility in the male reproductive system through the release of Reactive Oxygen Species (ROS). This study aimed to evaluate the testiculo-protective potential of ascorbic acid against fluoxetine-induced spermatotoxicity in male Wistar rats.

This study assessed Vitamin C's effect on male fertility in fluoxetine-treated Wistar rats. Thirty rats (130 ± 40 g) were divided into six groups (n=5): Control (distilled water), fluoxetine 20 mg/kg, Vitamin C 100 mg/kg, fluoxetine 20 mg/kg + Vitamin C 50 mg/kg, fluoxetine 20 mg/kg + Vitamin C 100 mg/kg, and fluoxetine 20 mg/kg + Vitamin C 150 mg/kg. Treatments were administered daily via oral gavage for 60 days, followed by assessments of testicular weight, semen analysis, oxidative stress biomarkers (CAT and GPx), and histomorphology. The data was analyzed using one-way ANOVA and Turkey's post-hoc multiple comparison test, reporting as mean±SEM using The GraphPad Prism version 6.0 for Windows, with significance set at p<0.05.

Vitamin C, administered particularly at higher doses, significantly increased body weight, testicular weight, and antioxidant enzyme levels (glutathione peroxidase and catalase) while improving fertility parameters such as sperm count, motility, and viability in treated rats (P<0.05). Fluoxetine alone led to a significant reduction (P<0.05) in these parameters, but the combination with Vitamin C mitigated these effects. Histological analysis showed improved testicular structure in Vitamin C-treated groups, highlighting its protective role against fluoxetine-induced testicular damage.

Ascorbic acid has testiculoprotective potential in fluoxetine-induced spermatotoxicity, mainly owing to its antioxidant properties.

The human immunodeficiency virus continues to pose a significant global public health challenge, affecting millions of individuals. The current treatment strategy has incorporated the utilization of combinations of antiretroviral drugs. The administration of these drugs is associated with many deleterious consequences on several physiological systems, notably the reproductive system. This study aimed to assess the toxic effects of abacavir sulfate, ritonavir, nevirapine, and zidovudine, as well as their combinations, on TM3 Leydig and TM4 Sertoli cells. The cell viability was gauged using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays. Reactive oxygen species (ROS) production was assessed via the 2',7'-dichlorofluorescein diacetate (DCFDA) test, and DNA damage was determined using the comet assay. Results indicated cytotoxic effects at low drug concentrations, both individually and combined. The administration of drugs, individually and in combination, resulted in the production of ROS and caused damage to the DNA at the tested concentrations. In conclusion, the results of this study suggest that the administration of antiretroviral drugs can lead to testicular toxicity by promoting the generation of ROS and DNA damage. Furthermore, it should be noted that the toxicity of antiretroviral drug combinations was shown to be higher compared to that of individual drugs.

Male factor infertility is a multifaceted problem that affects approximately 50% of couples suffering from infertility. Causes of male infertility include endocrine disturbances, gonadotoxins, genetic abnormalities, varicocele, malignancies, infections, congenital or acquired urogenital abnormalities, iatrogenic factors, immunological factors, and idiopathic reasons. There are a variety of treatment options for male infertility, depending on the underlying cause(s). These can include surgical treatments, medical/hormonal therapies, and assisted reproductive techniques (ART), which can be combined with surgical sperm retrieval (SSR) if necessary. In this review article, the pharmacological therapies for male infertility are grouped by their underlying causes. Some of these therapies are targeted and specific, while others are used empirically to treat idiopathic male infertility. This will include treatments to optimize infertility in patients who have hypogonadism, ejaculatory dysfunction, infections, or idiopathic male infertility. Finally, we will provide an overview of the future directions of pharmacological therapies for male infertility. Significance Statement Male infertility is a significant worldwide problem. Detailed knowledge of the pharmacological therapies available will ensure the prescription of appropriate therapy and avoid the use of unnecessary or harmful treatments.

Exogenous substances, including drugs and chemicals, can transfer into human seminal fluid and influence male fertility and reproduction. In addition, substances relevant in the context of sports drug testing programs, can be transferred into the urine of a female athlete (after unprotected sexual intercourse) and trigger a so-called adverse analytical finding. Here, the question arises as to whether it is possible to distinguish analytically between intentional doping offenses and unintentional contamination of urine by seminal fluid. To this end, 480 seminal fluids from nonathletes were analyzed to identify concentration ranges and metabolite profiles of therapeutic drugs that are also classified as doping agents. Therefore, a screening procedure was developed using liquid chromatography connected to a triple quadrupole mass spectrometer, and suspect samples (i.e., samples indicating the presence of relevant compounds) were further subjected to liquid chromatography-high-resolution accurate mass (tandem) mass spectrometry. The screening method yielded 90 findings (including aromatase inhibitors, selective estrogen receptor modulators, diuretics, stimulants, glucocorticoids, beta-blockers, antidepressants, and the nonapproved proliferator-activated receptor delta agonist GW1516) in a total of 81 samples, with 91% of these suspected cases being verified by the confirmation method. In addition to the intact drug, phase-I and -II metabolites were also occasionally observed in the seminal fluid. This study demonstrated that various drugs including those categorized as doping agents partition into seminal fluid. Monitoring substances and metabolites may contribute to a better understanding of the distribution and metabolism of exogenous substances in seminal fluid that may be responsible for the impairment of male fertility. SIGNIFICANCE STATEMENT: This study demonstrates that doping agents as well as clinically relevant substances are transferred/eliminated into seminal fluid to a substantial extent and that knowledge about drug levels (and potential consequences for the male fertility and female exposure) is limited. The herein generated new dataset provides new insights into an important and yet little explored area of drug deposition and elimination, and hereby a basis for the assessment of contamination cases by seminal fluid in sports drug testing.

Inflammatory rheumatic diseases (IRDs) refer to a range of persistent disorders that have a major influence on several physiological systems. Although there is much evidence connecting IRDs to sexual dysfunction and fertility problems, research specifically focusing on male infertility in relation to these diseases is sparse. This review addresses the complicated connection between IRDs and male infertility, emphasising the physiological, psychological, and pharmacological aspects that influence reproductive health outcomes in men with rheumatic conditions. We explore the effects of IRDs and their treatments on many facets of male reproductive well-being, encompassing sexual functionality, semen characteristics, and hormonal balance. Additionally, we present a comprehensive analysis of the present knowledge on the impact of several categories of anti-rheumatic drugs on male reproductive function. Although there is an increasing awareness of the need of addressing reproductive concerns in individuals IRDs, there is a noticeable lack of research especially dedicated to male infertility. Moving forward, more comprehensive research is needed to determine the prevalence, risk factors, and mechanisms driving reproductive difficulties in males with IRDs. We can better assist the reproductive health requirements of male IRD patients by expanding our understanding of male infertility in the setting of rheumatic disorders and implementing holistic methods to care.

Quetiapine (QET) abuse has increased due to its anxiolytic and hedonic effects, necessitating protective adjunct treatments. Acacia saligna (A. saligna) flowers, used in traditional medicine, have potential health benefits.

To investigate the protective role of A. saligna flower extract against QET-induced sexual toxicity, and to elucidate the possible underlying mechanisms through metabolomic and physiological studies.

A. saligna extract was subjected to metabolite profiling via High-Resolution Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI-qTOF-MS). Forty-eight adult male albino rats were assigned into six groups for 30 days. The intracavernosal pressure (ICP), semen, biochemical, hormonal, histological, genetic and Western blot (WB) analyses were determined.

A. saligna extract is rich in phenolic compounds, flavonoids, tannins, and unsaturated fatty acids. QET significantly decreased ICP and negatively affected semen parameters. A. saligna mitigated decreased sperm motility and ameliorated overexpressed proinflammatory genes in QET-55 group. A. saligna ameliorated the reduction of the antioxidant biomarkers, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), concurrent with downregulation of the nuclear factor kappa B (NF-κB) protein. A. saligna counteracted the disrupted testicular and prostatic structures revealed by histological examination.

The extract from A. saligna, which contains a high concentration of antioxidants and anti-inflammatory chemicals, effectively mitigates sexual toxicity caused by QET. This study provided the first known explanation of the hypothesized processes behind the protective properties of A. saligna through biological, biochemical, and histological parameters. The results emphasize the potential of A. saligna as a safeguarding agent against drug-induced sexual toxicity.

Most males with cystic fibrosis (MwCF) have congenital bilateral absence of the vas deferens and require assisted reproductive technology to conceive, yet many have limited knowledge about how CF affects sexual and reproductive health (SRH). This study evaluates the feasibility, acceptability, and potential effectiveness of telehealth fertility preservation (FP) counseling for MwCF.

Pre-lung transplant MwCF ≥18 years, recruited from U.S. CF centers, social media, and via snowball sampling, received individualized telehealth counseling. Participants completed intervention feasibility/acceptability one week post-counseling and FP knowledge, care satisfaction, and self-efficacy assessments at baseline and two months post-counseling. We completed acceptability interviews one-week post-counseling and audio-recorded, transcribed, and thematically analyzed results. We descriptively analyzed survey results and conducted pre/post comparisons using paired t-tests.

Thirty MwCF (ages 22-49 years) completed counseling. Most were in a relationship (70 %) and White (86.7 %). Telehealth FP counseling was acceptable (M = 4.38/5 ± 0.60), appropriate (M = 4.37/5 ± 0.60), and feasible (M = 4.60/5 ± 0.45) to MwCF. FP knowledge (9.53 vs. 10.40/12; p = .010), care satisfaction (20.23 vs 26.67/32; p<.001), and self-efficacy (22.87 vs 25.20/30; p = .016) improved at two months post-counseling. Despite desiring provider-initiated SRH, wanting children (81 %), and perceiving the CF team as their primary care provider (97 %), 44 % report not receiving information about infertility by the CF team.

Integrating FP counseling into CF care is feasible and acceptable to MwCF and can improve FP knowledge, self-efficacy, and care satisfaction. MwCF desire early and regular provider-initiated SRH education.

Background: The use of selective serotonin reuptake inhibitors (SSRIs) has been associated with potential effects on male fertility, although the exact mechanisms are not fully understood. The aim of this study was to understand the relationship between SSRIs and male infertility; Methods: A retrospective chart review of Saudi males who were treated with SSRIs and attended an infertility clinic in KSMC was undertaken. The medical records of men from an infertility clinic were reviewed to screen the quality of the sperm parameters in patients taking SSRIs; Results: In total, 299 men were identified, of whom 29 (9.6%) were exposed to SSRIs, while 270 (90.4%) did not receive SSRIs, defined as the control infertile group. When comparing the mean ages, a notable disparity was observed between the control group of infertile men (34.2 ± 6.9 years) and the infertile group using SSRIs (41.5 ± 3.2 years) (p < 0.001). Regarding the sperm analysis and the use of SSRIs, the impact of SSRIs use showed no significant differences in sperm liquefaction (p = 0.1), motility (p = 0.17), viscosity (p = 0.16), or count (p = 0.069) with escitalopram, fluoxetine, or paroxetine use; Conclusions: Our study showed no significant difference in the sperm analysis between the SSRI and non-SSRI cohorts. However, the relationship between SSRI use and sperm count warrants further investigation and consideration in clinical practice.

For several years, fertility disorders have been on the increase worldwide. These disorders affect both sexes, but are more pronounced in men; and in half of cases the etiology is unknown. The role of drugs in male infertility has been little studied to date. Most of the available data comes from experimental animal studies, with all their limitations. With the exception of a few drugs, such as certain anticancer agents, human data are rare. This article describes the mainly drugs known to have deleterious effects on male fertility, the mechanisms leading to these effects and methods used to assess the risk of drug-induced male infertility. It underlines the need for further work in experimental research, clinical trials and post-marketing surveillance to improve our knowledge of drugs that induce male infertility. Although these adverse effects are not life-threatening, they can have a significant impact on patients' lives.

Obesogens have been identified as a significant factor associated with increasing obesity rates, particularly in developed countries. Substances with obesogenic traits are prevalent in consumer products, including certain pharmaceuticals. Specific classes of pharmaceuticals have been recognized for their ability to induce weight gain, often accompanied by hormonal alterations that can adversely impact male fertility. Indeed, research has supplied evidence underscoring the crucial role of obesogens and therapeutic agents in the normal functioning of the male reproductive system. Notably, sperm count and various semen parameters have been closely linked to a range of environmental and nutritional factors, including chemicals and pharmacological agents exhibiting obesogenic properties. This review aimed to explore studies focused on analyzing male fertility parameters, delving into the intricacies of sperm quality, and elucidating the direct and adverse effects that pharmacological agents may have on these aspects.

Lifestyle factors such as sedentary behavior and consumption of certain medications can disturb the function of the male reproductive system. In the present study, we investigated the potential co-treatment effects of low-volume high-intensity interval training (HIIT) on markers of reproductive function in adult male Wistar rats under aspirin (ASA) treatment. Eighteen adult male Wistar rats were randomized into three groups: control (C), aspirin treatment (AT), and aspirin treatment + exercise (ATE). Animals in the AT and ATE groups received an oral subchronic dose of aspirin (12.5 mg/kg body mass). The exercise was performed three times per week for 6 weeks (4-6 reps of 10-s sprints). Serum testosterone level, sperm parameters (sperm count, viability, maturity, and DNA fragmentation), histomorphometric (Leydig cell, tubule diameter, thickness of tubular epithelium, and indices of spermatogenesis and spermiogenesis), and histochemical parameter (testicular fat density) were assessed. Results revealed that compared to the C group, ASA consumption led to a negative alteration in serum testosterone levels, sperm parameters, and histomorphometric and histochemical parameters (P < 0.05). However, there were no significant differences between the C and ATE groups in terms of serum testosterone level, number of Leydig cells, epididymal fat density, tubule diameter, epithelium height, immature-to-mature sperm ratio, and DNA breakage (P > 0.05). These findings suggest that ASA treatment is associated with deleterious changes in male reproductive parameters. However, low-volume HIIT may prevent ASA-induced male reproductive impairments and could be considered a potential prophylactic measure in subjects under ASA treatment.

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision-making on systemic anti-inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti-inflammatory treatment in men and women of reproductive age. Twenty-one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two-round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first-choice long-term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short-course prednisolone for flare management. No consensus was reached on second-choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication-specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3-month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared-care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.

Non-steroidal anti-inflammatory drugs (NSAIDs) and 17α-ethinylestradiol (EE2) are extensively used in human and veterinary medicine. Due to their partial removal by wastewater treatment plants, they are frequent environmental contaminants, particularly in drinking water. Here, we investigated the adverse outcomes of chronic exposure to mixtures of NSAIDs (ibuprofen, 2hydroxy-ibuprofen, diclofenac) and EE2 at two environmentally relevant doses in drinking water, on the reproductive organ development and fertility in F1-exposed male and female mice and in their F2 offspring. In male and female F1 mice, which were exposed to these mixtures, reproductive organ maturation, estrous cyclicity, and spermiogenesis were altered. These defects were observed also in F2 animals, in addition to some specific sperm parameter alterations in F2 males. Transcriptomic analysis revealed significant changes in gene expression patterns and associated pathways implicated in testis and ovarian physiology. Chronic exposure of mice to NSAID and EE2 mixtures at environmental doses intergenerationally affected male and female fertility (i.e. total number of pups and time between litters). Our study provides new insights into the adverse effects of these pharmaceuticals on the reproductive health and will facilitate the implementation of a future regulatory environmental risk assessment of NSAIDs and EE2 for human health.

Tramadol is one of the most commonly abused substances in the Middle East. Furthermore, smoking is extremely common among the population.

An experimental study was performed on Sprague-Dawley rats to explore the effects of both nicotine and tramadol on the liver and testes. The tramadol was administered at 10 and 20 mg/kg, respectively, while the nicotine was administered at 125 mg/kg. Histological examination and androgen receptor ELISA assay showed mild effects on the liver and proofed safety on the testis. Western blot analysis of BIP (immunoglobulin heavy-chain binding protein) and CHOP (CCAAT-enhancer-binding protein homologous protein) revealed that fewer problems were induced by adding nicotine to tramadol. Autophagy marker LCIII and apoptosis marker caspase-8 showed similar effects to CHOP and BIP on liver samples. The real-time PCR of BIP expression showed similar but not identical results.

The results showed mild endoplasmic reticulum stress, autophagy, and apoptosis in the liver samples. Histological examination revealed stable spermatogenesis with average androgen receptor blood levels in the different groups.

Paternal medication use around the time of conception is common, but information about its effects on pregnancy outcome and the health of the child is generally limited. The aim of this study is to examine the feasibility of studying paternal exposure in the Dutch Pregnancy Drug Register by using immunosuppressants as a proof of concept. In 113 of 15,959 pregnancies, long-term paternal immunosuppressant use was reported 3 months before conception. In total, 134 immunosuppressants were used. Pregnancy outcome was known for 54 cases and was in accordance with previous findings. Two spontaneous abortions, two premature births, six small for gestational age babies, and two major congenital malformations were reported. Time to pregnancy (TTP) was known for 9548 pregnancies, including 89 with paternal immunosuppressant use. TTP analysis did not show a difference in pregnancies with paternal immunosuppressant use compared to the control group. Moreover, the number of fertility treatments in the paternal immunosuppressant group was similar to the control group. In our opinion, it is feasible to use the Dutch Pregnancy Drug Register to study the effects of paternal exposure on pregnancy outcome. However, to study the potential effects on fertility, more information is needed, particularly since the beginning of pregnancy attempts.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting patients of reproductive age. Although HS shares risk factors with male infertility, only 1 epidemiological study has evaluated this association. To further evaluate this potential association, findings on semen and hormonal analysis, testicular ultrasound, and the International Index of Erectile Function (IIEF-15) were compared between 28 men attending a tertiary HS clinic during the period April 2019 to April 2021, and 44 healthy controls, spouses of infertile women undergoing semen evaluation before in vitro fertilization. Patients with HS were divided based on the absence or presence of gluteal and genital lesions. Patients with HS were younger than controls (median 27 vs 34 years, p < 0.0004) and had a higher proportion of smokers (86% vs 33%, p < 0.0001). Semen parameters in patients with gluteal-genital lesions, specifically those with severe scrotal involvement necessitating surgery, were lower than the WHO reference values and significantly lower than in patients without gluteal-genital lesions and controls. Erectile dysfunction was reported by 93% of patients with HS. These findings suggest that spermatogenesis and sexual function may be impaired in young men with HS. Therefore, multidisciplinary management of HS should include their evaluation to identify patients who might benefit from semen cryopreservation and sexual treatment.

Over the past 30 years, progress has been made in increasing women's representation in clinical research. However, women continue to be underrepresented in phase I clinical trials-those trials that test the safety and tolerability of investigational drugs, often on healthy individuals. As sex-based differences in adverse drug reactions are often linked to drug dose, pivotal safety information in phase I trials is often insufficiently-and inequitably-captured for females. Yet there has been little attention to how clinical investigators and those charged with overseeing the ethical conduct of these trials perceive the barriers to women's inclusion in phase I trials. To address this gap, we report on 22 interviews with U.S. phase I investigators and institutional review board (IRB) members. Our findings indicate that although these investigators and IRB members acknowledged the importance of including women in clinical trials, they justified women's exclusion from phase I trials by citing the need to manage their reproductive potential. In particular, we identified four key themes that informants used to warrant women's exclusion from phase I trials: the structure of the drug-development system itself, fears about risks to potential fetuses, distrust of women to prevent pregnancy, and concerns about risks and burdens to institutions from resulting pregnancies. We argue that these rationales reflect structural and cultural barriers to women's inclusion in clinical research that ultimately fail to respect female research participants as persons, highlighting the need for broad-based solutions.

Finasteride and minoxidil are medicaments commonly prescribed for treating benign prostatic hyperplasia (BPA), hypertension, and/or androgenetic alopecia (AGA). The mechanism of action of finasteride is based on the interference in androgenic pathways, which may lead to fertility-related disorders in men. Minoxidil, however, can act in multiple ways, and there is no consensus that its use can adversely affect male fertility. Since finasteride and minoxidil could be risk factors for male fertility, we aimed to compare their impact on the two reproductive organs testis and epididymis of adult murine models, besides testis/epididymis-related cells, and describe the mechanism of action involved. For such, we used the PRISMA guideline. We included 31 original studies from a structured search on PubMed/MEDLINE, Scopus, and Web of Science databases. For in vivo studies, the bias analysis and the quality of the studies were assessed as described by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). We concluded that finasteride and minoxidil act as hormone disruptors, causing oxidative stress and morphological changes mainly in the testis. Our results also revealed that finasteride treatment could be more harmful to male reproductive health because it was more associated with reproductive injuries, including damage to the epididymis, erectile dysfunction, decreased libido, and reduced semen volume. Thus, this study contributes to the global understanding of the mechanisms by which medicaments used for alopecia might lead to male reproductive disorders. We hope that our critical analysis expedites clinical research and reduces methodological bias. The registration number on the Prospero platform is CRD42022313347.

Pregabalin is an anticonvulsant drug with analgesic activity for the treatment of neuropathic pain.

To valuate the toxicity of pregabalin in reproductive parameters, spermatogenesis, and teratogenicity in the offspring of mice.

Twenty male mice were randomly distributed into two groups: PGB group and group C (n =10 per group). The animals in the PGB group received, via gavage, 200mg/kg of pregabalin diluted in distilled water daily, for a period of 45days. Group C received distilled water under the same experimental design.

In the paternal parameters of the PGB group, there was a significant increase in the size of the testicles, morphological alterations in the spermatozoa, a decrease in the Johnsen score, an increase in the Leydig cells, and a decrease in the serum level of testosterone. In the intrauterine development parameters of females mated with males from the PGB group, a significant decrease in placental weight, weight and length of fetuses, and fetal viability rate was observed. There was a significant increase in the number of resorptions and post-implantation losses. The significant anomalies observed in the offspring were alteration in the size of the kidneys, absent metacarpals and phalanges, alteration in the sternum, and supernumerary thoracic vertebrae.

Results suggest that pregabalin had toxic effects on the reproductive function of male mice and teratogenic potential.

The findings of this study may provide new hypotheses, taking into account the risk-benefit ratio for male reproduction and offspring health.

Biologically active and nanoscale extracellular vesicles (EVs) participate in a variety of cellular physiological and pathological processes in a cell-free manner. Unlike cells, EVs not only do not cause acute immune rejection, but are much smaller and have a low risk of tumorigenicity or embolization. Because of their unique advantages, EVs show promise in applications in the diagnosis and treatment of reproductive disorders. As research broadens, engineering strategies for EVs have been developed, and engineering strategies for EVs have substantially improved their application potential while circumventing the defects of natural EVs, driving EVs toward clinical applications. In this paper, we will review the engineering strategies of EVs, as well as their regulatory effects and mechanisms on reproductive disorders (including premature ovarian insufficiency (POI), polycystic ovarian syndrome (PCOS), recurrent spontaneous abortion (RSA), intrauterine adhesion (IUA), and endometriosis (EMS)) and their application prospects. This work provides new ideas for the treatment of female reproductive disorders by engineering EVs.

Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures and ageing, among others. The evaluation of male infertility includes detailed history taking, focused physical examination and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.

Although testosterone has a pivotal role in bone health, its correlation with bone mineral density (BMD) is understudied in kidney transplant recipients who are at high risk of osteoporosis. This study aimed to elucidate if there is any correlation between serum free testosterone and BMD in this population.

Sixty male kidney transplant recipients were enrolled in this cross-sectional study, and they were subjected to history taking, clinical examination, and laboratory investigations (including total and free testosterone). BMD was assessed in three regions (forearm, hip, and lumbar spine) using DEXA scan.

The mean age of the included patients was 45.55 ± 13.58 years. Serum total and free testosterone had mean values of 5.17 ± 1.4 ng/ml and 95.46 ± 28.24 pg/ml, respectively, with all levels within the normal range. DEXA scan detected osteoporosis and osteopenia in 9 (15%) and 30 (50%) patients in the lumbar region, 3 (5%) and 36 (60%) in the hip region, as well as 21 (35%) and 33 (55%) in the forearm region, respectively. BMD of the lumbar region had a significant positive correlation with free testosterone, phosphorus, and eGFR, while it had a significant negative correlation with platelets and patient age. BMD of the hip region was positively correlated with serum phosphorus, parathyroid hormone, and duration since the transplant, whereas it was negatively correlated with platelets and total testosterone level. BMD of the forearm had a significant positive correlation with eGFR, whereas it had a significant negative correlation with age and duration since transplantation. In addition, forearm BMD was significantly lower in patients with a radiocephalic AVF.

Even within the normal range, free testosterone has a significant positive correlation with lumbar spine BMD with no significant association with the forearm or hip BMD.

The application of fertility preservation, initially intended for oncological patients prior to gonadotoxic treatment, has extended in recent years to transgender and gender-non-conforming individuals undergoing therapy for gender compatibility.

To examine semen quality and survival in transgender women pursuing semen cryopreservation in the presence or absence of gender-affirming hormonal medication.

In this retrospective cohort study, we reviewed data of 74 consecutive transgender women presenting for semen cryopreservation at a single center between 2000 and 2019. Semen parameters before and after cryopreservation were compared to a control group composed of 100 consecutive sperm bank donor candidates. A subgroup analysis of subjects who had used gender-affirming hormonal treatment was also performed.

Compared to the control group, transgender women had lower total sperm count (144.0 vs. 54.5 million, respectively, p < 0.001), lower sperm motility percentage (65.0% vs. 51.0%, respectively, p < 0.001), and lower total motile sperm count (94.0 vs. 27.0 million, respectively, p < 0.001). Values were further decreased in transgender women who had received hormonal treatment before sperm cryopreservation. Post-thawing motility rate remained lower in the transgender group compared to the control group (20.0% vs. 45.0%, respectively, p < 0.001), and the total motile count remained lower as well (2.7 vs. 9.0 million, respectively, p < 0.001). Following sperm cryopreservation, the post-thaw decreases in total motile sperm count were higher in the transgender group compared with the control group (91.5% vs. 90.0%). Further subdivision in the transgender group showed that the decrease in total motile sperm count was lower for transgender women who did not use gender-affirming hormonal treatment compared to those who did (-89.7% vs. -92.6%, respectively, p < 0.01).

Sperm parameters in transgender women are poor compared to candidates for sperm donation representing the general population. Specimens collected after discontinuation of gender-affirming hormone treatments were further impaired. Moreover, post-thawing sperm total motile count, motility, and overall sperm survival were reduced in transgender women.