Chapter

Causes of Male Infertility

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Abstract

It is estimated that 12%–15% of sexually active couples are infertile. When broken down by gender, a male component can be identified approximately 50% of the time either in isolation or in combination with a female factor. Previous research in a US male fertility clinic analyzing 1430 patients identified causes of infertility from most to least common: varicocele, idiopathic, obstruction, female factor, cryptorchidism, immunologic, ejaculatory dysfunction, testicular failure, drug effects/radiation, endocrinology, and all others. However, despite recent technologic and diagnostic advances, idiopathic infertility remains a common diagnosis, with approximately 25% of patients not having an identifiable cause of infertility. Regardless, many recognizable causes of male infertility are treatable or preventable; thus, a keen understanding of these conditions is paramount. This chapter comprises an overview of etiologies of male infertility, divided into pre-testicular, testicular, and post-testicular causes.

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... It is not a surprise if we consider ejaculate as a final product obtained from testes and male accessory glands and after being released from the genital tract. The abstinence time, ejaculatory frequency, general health status, scrotal conditions, surgery, genital or urinary tract infections, lifestyle or medications are only a few factors that may have an impact on the sperm quality [10,11]. ...
... Lastly, it is essential to highlight that the ejaculatory abstinence period is just one of the several factors contributing to the final semen specimen and fertilization of the oocyte. While analyzing semen quality or counseling couples regarding the impact of male contribution on natural fertility or assisted reproduction, one should always bear in mind often forgotten or underestimated factors such as general health status [10], male age [43], body mass index [44] or socio-psycho-behavioral [45] factors. Furthermore, the duration of sexual arousal before masturbation [46], specific sexual stimuli [47] or obtaining ejaculate via intercourse [48] could also modulate semen and sperm quality. ...
Article
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Since the publication of the first edition of the WHO (World Health Organization) Laboratory Manual for the examination of Human Semen in 1980, the reference values of sperm parameters have been updated on four occasions. Currently and globally, most of the laboratories analyzing semen samples use the latest, 5th edition of the manual that recommends ejaculatory abstinence from two to seven days before producing the sample for examination. While this standardized interval of time facilitates the interpretation of the results and research, no solid evidence exists to support the WHO-recommended abstinence time for a semen analysis in order to optimize clinical outcomes after assisted reproduction. Most of the studies refer to different clinical outcomes, different groups of patients and different editions of the WHO Laboratory Manual, including heterogeneous intervals of abstinence or sperm parameters. The aim of the current systematic review was to evaluate available evidence correlating ejaculatory abstinence time with clinical outcomes and sperm parameters analyzed according to the last edition of the World Health Organization Laboratory Manual reference values in different male populations. The results from the included studies indicate that WHO abstinence recommendations may need revision, given that a shorter ejaculatory abstinence interval appears to be associated with improved sperm parameters, such as sperm DNA fragmentation, progressive motility or morphology, while evidence suggests a potential increase in embryo euploidy rates and pregnancy outcomes.
... Azoospermia, oligozoospermia, asthenospermia, and teratospermia are the four main types of MI (Huynh et al., 2002). Other studies showed that MI is caused by idiopathic blockage, varicocele, immunologic, ejaculatory dysfunction, cryptorchidism, drug/ radiation, testicular failure side effects, endocrinology, and other factors (Machen and Sandlow, 2020). Furthermore, a recent study found that testicular-borne may have an impact on sperm quality (Kiyozumi et al., 2020;Lord and Oatley, 2020). ...
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Male infertility is a major and growing health problem with an estimated global prevalence of 4.2%. The current therapy is limited by the unknown etiology of MI, emphasizing the critical requirement forward to a more efficient method or medication. Through thousands of years, Traditional Chinese Medicine (TCM) has been shown to be effective in treating MI effectively. However, the components, mechanisms and functions of TCM prescriptions on MI are still obscure, severely limiting its clinical application. In order to discover the molecular mechanism of TCM against MI, our study presents a comprehensive approach integrated data mining, network pharmacology, molecular docking, UHPLC-Q-Orbitrap HRMS, and experimental validation. Here, we begin to acquire 289 clinical TCM prescriptions for MI from a TCM hospital’s outpatient department. Then, Core Chinese Materia Medica (CCMM) was then retrieved from the TCM Inheritance Support System (TCMISS), which was utilized to discover the underlying rules and connections in clinical prescriptions. After that, 98 CCMM components and 816 MI targets were obtained from ten distinct databases. Additionally, the network pharmacology methods, including network construction, GO and KEGG pathway enrichment, PPI analysis, were utilized to reveal that kaempferol, quercetin, isorhamnetin, and beta-sitosterol are the core components of CCMM in treating MI. The mechanisms and functions of CCMM against MI are hormone regulation, anti-apoptosis, anti-oxidant stress, and anti-inflammatory. Furthermore, the strong connections between four core components and six key targets were verified using a molecular docking method. Following that, the core components of the CCMM extract were identified using UHPLC-Q-Orbitrap HRMS analysis. Finally, in vivo experiments demonstrated that CCMM and four core components could improve the density, motility, viability of sperm, lecithin corpuscle density, decrease the rate of sperm malformation and testis tissue damage, and regulate the protein expressions of AKT1, MAPK3/1, EGFR, and TNF-α in a mouse model of MI. UHPLC-Q-Orbitrap HRMS analysis and in vivo experiments further validated the results of data mining, network pharmacology, and molecular docking. Our study could uncover the components, mechanisms, and functions of TCM prescriptions against MI and develop a new integrative approach to demonstrate TCM’s multi-component, multi-target, and multi-pathway approach to disease treatment.
... It is therefore important to determine whether SARS-CoV-2 infection can affect male fertility as an immediate or long-term consequence of the disease (Dutta and Sengupta, 2021) because SARS-CoV-1 was able to affect the testicles (Khali et al., 2020) It is known that some viruses such as HIV as well as mumps and viral hepatitis, can enter the testicle and cause viral orchitis, and in some cases may cause male infertility and testicular tumor (Xu et al., 2006) Infertility is defined as a disease characterized by the failure to conceive after approximately 12 months of regular sexual intercourse and is an important factor in the occurrence of pregnancy (Zegers-Hochschild et al., 2017). That between 12% to 15% of sexually active couples suffer from infertility, and men contribute about 50% of cases in general at the present time (Machen and Sandlow, 2020). The most common causes of infertility are cases in which the patient suffers from low sperm count, oligospermia, which accounts for 35%, and the other case is asthenospermia, which accounts for 30% of infertility cases, in addition to the presence of other cases (Patki et al., 2008). ...
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The current study aimed to know the effect of some physiological and hormonal variables in the blood serum of 60 samples of recovered men from COVID-19, their ages range from 20 to 49 years old, some of them were infected once and some of them were infected more than once, while the control group included 30 samples of healthy men, The samples were collected in Fallujah Teaching Hospital and from some private laboratories in the city of Fallujah. The sample collection period was from 10/15/2021 to 7/2/2022, during which semen samples were collected and the characteristics of semen were known, in addition to knowing the concentration of fructose sugar in semen
... In 70% of cases of male infertility the underlying etiology remains unclear, while the recognizable underlying causes can be genetic, epigenetic modifications caused by environmental toxins or drugs, lifestyle choices, medical illnesses or medications, and nutritional state [8][9][10]. Many of these causes of male infertility may be treatable or preventable and require an accurate assessment of the condition and identification of the cause to prevent further impairment in fertility [11]. Numerous testicular factors, gonadotoxins, and lifestyle factors have been studied as preventable factors of male infertility and the health care providers and educators tend to inform the general public and the vulnerable groups about the reproductive risks associated with such factors, e.g., smoking, alcohol, etc. ...
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Male contribution towards couple infertility is increasing but is less discussed. We aimed to assess the knowledge about iron deficiency anemia (IDA) as a contributor to male infertility in students at health colleges of Jazan University. A multicentric, cross-sectional survey included 910 participants and 768 participants qualified as per our inclusion criteria. The questions were categorized as: Model 1—knowledge about IDA-induced male infertility; Model 2—knowledge about IDA. The average knowledge of IDA causing male infertility is very low among students. The 18–20 years age group had a lesser score for either knowledge of IDA (M2; p-value = 0.047) or total (p-value < 0.0001) compared to the older group. In addition, female students were significantly more likely to be better in achieving higher total scores (p-value = 0.023) as well as M2 scores (p-value < 0.0001) when compared to the respective male category. On the other hand, males were significantly better in scoring for M1 (p-value = 0.004) compared to females. Awareness about iron deficiency anemia as a factor in male infertility may reduce the infertility burden, arising from a preventable factor, in the Jazan region.
... Due to the protracted period of replication and cell division along the continuous cycles of mitosis and meiosis in adult males spermatogenesis, it is thought that the accumulation of environmentally induced epigenetic are much greater in males than in females [106]. In addition to studies that highlighted dynamical reaction of sperm epigenome to a wide range of environmental and lifestyle stressors [105,107]. Sperm epigenome is believed to be affected by a large number of biological factors (including aging, obesity, diet, endocrine disruptors and disease), environmental exposures (such as smoking, alcohol, medications, air pollutions, toxic waste socioeconomic stress) and life style (i.e. exercise intervention). ...
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Male infertility is a complex medical condition, in which epigenetic factors play an important role. Epigenetics has recently gained significant scientific attention since it has added a new dimension to genomic and proteomic research. As a mechanism for maintaining genomic integrity and controlling gene expression, epigenetic modifications hold a great promise in capturing the subtle, yet very important, regulatory elements that might drive normal and abnormal sperm functions. The sperm's epigenome is known to be marked by constant changing over spermatogenesis, which is highly susceptible to be influenced by a wide spectrum of environmental stimuli. Recently, epigenetic aberrations have been recognized as one of the causes of idiopathic male infertility. Recent advances in technology have enabled humans to study epigenetics role in male infertility.
... Infertility affects nearly 60 to 80 million couples worldwide, which is defined as the inability to conceive after 12 months of regular unprotected intercourse. 1 Male infertility accounts for almost half of the infertility cases. 2 Oligoasthenozoospermia (OA) is clearly amongst the most common forms of male infertility, which arises under circumstances that the total sperm number or sperm concentration of gradually mobile sperm are below the lower reference limits (total number < 39×10 6 per ejaculate; concentration < 15×10 6 per mL; progressively motile < 32%). 3,4 Earlier studies have shown that a significant range of factors affect sperm production, including varicocele, idiopathic, obstruction, cryptorchidism, immunological, ejaculatory, testicular insufficient, medicinal/ radioactive, endocrinological, etc., which may further prompt the occurrence of OA. 5 Moreover, the aetiology remains unknown in one-third of all OA patients. 6 To be noted, recent studies have demonstrated that sperm concentration and motility decreased for 72-90 days following Coronavirus Disease 2019 (COVID-19) infection. ...
Article
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Purpose: One of the most common types of male infertility is recognized as oligoasthenozoospermia (OA), characterized by low sperm count and quality in males. As a traditional Chinese medicine (TCM), Cuscutae Semen-Mori Fructus coupled-herbs (CSMFCH) has been known to act a curative effect on OA for thousands of years. Nevertheless, the substantial basis and molecular mechanism of CSMFCH in treating OA remain elusive. Methods: Herein, an integrated approach, including network pharmacology, molecular docking, and experiment validation, was utilized to reveal the new candidate active component and mechanism of CSMFCH in treating OA. Results: The results show that kaempferol is the most significant bioactive component of CSMFCH on OA. The mechanism and targets of CSMFCH against OA are relevant to hormone regulation, oxidant stress, and reproductive promotion. In order to validate network pharmacology results, molecular docking and experiment validation were conducted. In detail, molecular docking was employed to verify the strong binding interactions between kaempferol and the core targets. UHPLC-Q-Orbitrap-MS was used to identify kaempferol in the CSMFCH extract. In vitro and in vivo experiments further proved CSMFCH and kaempferol could enhance the mouse Leydig (TM3) and mouse Sertoli (TM4) cell viability, improve the male reproductive organ weights, sperm quality, and decrease testis tissue damage in the OA mouse model induced by CP. Conclusion: Our results not only identify the new candidate active component of CSMFCH in treating OA but also provide new insights into the mechanisms of CSMFCH against OA.
... Male infertility (MI), characterized by the abnormal semen quality or defective sperm transport [1], has become a disease with high incidence, and 75% of these cases are unexplained idiopathic [2]. The main types of MI are azoospermia, oligozoospermia, asthenospermia and teratospermia [3], which is considered to be caused by varicocele, idiopathic, obstruction, cryptorchidism, immunologic, ejaculatory dysfunction, testicular failure, drug effects/radiation, endocrinology, and all others [4]. Besides, a most recent study showed that sperm fertility could be affected by the testicular-borne factors [5,6]. ...
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Background: Male infertility (MI) affects almost 5% adult men worldwide, and 75% of these cases are unexplained idiopathic. There are limitations in the current treatment due to the unclear mechanism of MI, which highlight the urgent need for a more effective strategy or drug. Traditional Chinese Medicine (TCM) prescriptions have been used to treat MI for thousands of years, but their molecular mechanism is not well defined. Methods: Aiming at revealing the molecular mechanism of TCM prescriptions on MI, a comprehensive strategy integrating data mining, network pharmacology, and molecular docking verification was performed. Firstly, we collected 289 TCM prescriptions for treating MI from National Institute of TCM Constitution and Preventive Medicine for 6 years. Then, Core Chinese Materia Medica (CCMM), the crucial combination of TCM prescriptions, was obtained by the TCM Inheritance Support System from China Academy of Chinese Medical Sciences. Next, the components and targets of CCMM in TCM prescriptions and MI-related targets were collected and analyzed through network pharmacology approach. Results: The results showed that the molecular mechanism of TCM prescriptions for treating MI are regulating hormone, inhibiting apoptosis, oxidant stress and inflammatory. Estrogen signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway are the most important signaling pathways. Molecular docking experiments were used to further validate network pharmacology results. Conclusions: This study not only discovers CCMM and the molecular mechanism of TCM prescriptions for treating MI, but may be helpful for the popularization and application of TCM treatment.
... Infertility is a disease that fails to establish a pregnancy after 12 months of regular, unprotected sexual intercourse, or because a person's ability to reproduce is impaired (Zegers-Hochschild et al., 2017). Between 12% and 15% of couples are infertile of all Sexually active couples, 50% can be determined from the male component at present (Machen and Sandlow, 2020). ...
Article
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The present study is designed to investigate some variables in some types of trace elements such as zinc and magnesium in some different cases of infertility and lack of fertility in men in the northern governorates of Iraq. The study included (75) samples with ages ranging between (25-50) years, of which (60) samples suffered from infertility and lack of fertility, depending on the medical diagnosis made by infertility specialist consultants in Azadi Teaching Hospital in Kirkuk Governorate. The samples were distributed into five groups, each group included (15) sample agencies: the Azoospermia group), the Teratozospermia group, the Oligozoospermia group, the Asthenozoospermia group and the fifth group, which included (15) able healthy people On procreation, which is considered a control group. The study included measuring some biochemical variables for the study samples represented by measuring the level of zinc and magnesium in the blood serum. The results indicated a significant decrease in the levels of trace elements zinc (Zn) and magnesium (Mg) in the experimental groups: Azoospermia group, Teratozospermia group, Oligozoospermia group, Asthenozoospermia group compared to Control group. Hasan MF, Raddam QN (2020) The relationship of zinc and magnesium in different male infertility cases. Eurasia J Biosci 14: 4347-4351.
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Abstract This study was conducted at Azadi Teaching Hospital in the city of Kirkuk from (November 2019 to February 2020) for people suffering from infertility and low fertility diagnosed by doctors, as 75 samples were collected at ages ranging between (50-25) years, including (60) Sample suffers from infertility and lack of fertility. The samples were distributed into five groups, each the group contained (15) samples and agencies: Azoospermia group, Teratozospermia group, Oligozoospermia group, Asthenozoospermia group and the fifth group which includes fifteen 15 healthy individuals able to give birth are considered as a control group. The study included measuring some biochemical parameters in the serum and plasma samples, represented by measuring the levels of vitamin D, Zinc, Magnesium and some sex hormones such as Testosterone, Follicle stimulating hormone (FSH), and the Luteinizing hormone (LH), in addition to measuring some of the oxidant-antioxidant parameters, which included Mallon dialdehyde (MDA), Glutathione (GSH), Glutathione Peroxidase (GPx) and Super Oxide Dismutase (SOD) The results of the current study, which are analyzed statistically according to an Anova One Way program by SPSS application at a significant level P< 0.05 indicated a significant decrease in Vitamin D levels in the experimental groups: The Azoospermia group, Teratozospermia group, Oligozoospermia group and Asthenozoospermia group compared to the control group, The results also showed a significant decrease in testosterone levels In Oligozoospermia group, and Asthenozoospermia Compared to a control group. while there were no significant differences in Testosterone hormone levels for the Azoospermia and Teratozospermia group as compared to control group. The results also showed a significant increase in the levels of B follicle stimulating hormone (FSH) in the experimental groups: Azoospermia group, Oligozoospermia group and Asthenozoospermia group as compared to control group. Compared to the control group, there was a significant decrease in FSH levels in the experimental group Teratozospermia group as compared to the control group. The results showed a significant decrease in the LH levels in experimental groups: Teratozospermia group, Oligozoospermia group and Asthenozoospermia group, while there is no significant difference in Azoospermia group as compared with the control group. The study determined a positive correlation (direct) between Vitamin D level and Testosterone hormone where was the correlation coefficient (r=0.4434), also there was a negative correlation (indirect) between Vitamin D levels and FSH levels where was the correlation coefficient (r=0.6894). In addition positive correlation (direct) determined between Vitamin levels and LH levels where was the correlation coefficient between them (r=0.3331). The study reported a significant increase in MDA levels as an antioxidant indicator in the Asthenozoospermia group, Teratozospermia group, Oligozoospermia group and Azoospermia group with a significant decrease in the SOD levels, GPx and GSH in the experimental groups as compared to the control group. The study results showed a negative correlation between Vitamin D levels and MDA levels where was the correlation coefficient between them (r=- 0.5863), also a positive direct correlation between Vitamin levels and antioxidant enzymes GSH The correlation coefficients were (r=0.5154), GPx (r=0.8507) and SOD (r=0.7254) respectively. The study results revealed a significant decrease in trace elements levels Zn and Mg in the experimental groups: Azoospermia group, Teratozospermia C group, Oligozoospermia group and Asthenozoospermia group compared to the control group. The results also showed a positive direct correlation between Vitamin D levels with Zn levels The correlation coefficients were (r=0.7049) and Mg (r=0.5548). By presenting the results, we conclude that the level of vitamin D has a vital and essential role in the case of infertility and decreased fertility and is directly related to the state of oxidative stress and the lack of micronutrients necessary for the work of many effective enzymes such as Zinc and Magnesium in addition to its direct effect on sex hormones such as Testosterone and FSH and LH.
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The objective was to reveal predictors for fertility recovery after varicocelectomy in subfertile men. This retrospective study recruited 93 men with clinical varicocele and pathozoospermia who underwent microsurgical varicocelectomy. Stepwise discriminant analysis was performed to identify predictors of spontaneous pregnancy (SP) after surgery. ‘Clinically significant improvement’ (CSI) following varicocelectomy was defined as an increase in total progressively motile sperm count (TPMSC) by at least 12.5 million (calculated from WHO-2010 reference values). 52% of patients showed CSI, and 28% reported SP after surgery. Patients who reported SP (group II), compared to that remained infertile (group I), were younger (27.3 ± 2.9 versus 30.2 ± 4.2 years; p < .01), had less infertility period (24.1 ± 14.0 versus 44.4 ± 32.9 months; p < .05) and had initially higher TPMSC (median (25% −75%) = 34 (11–67) versus 9.5 (0–33) mln; p < .05). The stepwise discriminant analysis showed that male age (coefficient value = −0.157), total sperm motility (0.024) and postoperative increase in TPMSC (0.010) were the significant predictors of SP. The predictive ability, sensitivity, and specificity of the discriminant function were 84%, 87%, 76% respectively. This algorithm can be recommended after varicocelectomy in decision-making on natural conception or the ART protocols usage.
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Oligoasthenozoospermia (OA) is one of the most common types of male infertility affecting sperm count and sperm motility. Unfortunately, it is difficult for existing drugs to fundamentally improve the sperm quality of OA patients, because the pathological mechanism of OA has not been fully elucidated yet. Morinda officinalis–Lycium barbarum coupled-herbs (MOLBCH), as traditional Chinese Medicines, has been widely used for treating OA over thousands of years, but its molecular mechanism is still unclear. For this purpose, we adopted a comprehensive approach integrated network pharmacology and molecular docking to reveal the bioactive components and potential targets of MOLBCH against OA. The results showed that MOLBCH alleviated apoptosis, promoted male reproductive function, and reduced oxidant stress in the treatment of OA. Ohioensin-A, quercetin, beta-sitosterol and sitosterol were the key bioactive components. Androgen receptor (AR), Estrogen receptor (ESR1), Mitogen-activated protein kinase 3 (MAPK3), RAC-alpha serine/threonine-protein kinase (AKT1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were the core potential targets. PI3K/Akt signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications were the most representative pathways. Moreover, molecular docking was performed to validate the strong binding interactions between the obtained core components and targets. These observations provide deeper insight into the pathogenesis of OA and can be used to design new drugs and develop new therapeutic instructions to treat OA.
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Study question: What are the primary causes of severe male factor infertility? Summary answer: Although 40% of all patients showed primary causes of infertility, which could be subdivided into three groups based on the severity of their effect, ~75% of oligozoospermia cases remained idiopathic. What is known already: There are few large-scale epidemiological studies analyzing the causes of male factor infertility. Study design, size, duration: A prospective clinical-epidemiological study was conducted at the Andrology Centre, Tartu University Hospital between 2005 and 2013, recruiting male partners of couples failing to conceive a child for over ≥12 months. Among 8518 patients, 1737 (20.4%) were diagnosed with severe male factor infertility. A reference group of fertile controls was comprised of 325 partners of pregnant women. Participants/materials, setting, methods: The mean age of infertility patients and fertile controls was 33.2 ± 7.3 and 31.7 ± 6.3 years, respectively. All participants were examined using a standardized andrology workup, accompanied by a structured medical interview. Hormonal analysis included serum FSH, LH and testosterone. Semen quality was determined in accordance to the World Health Organization recommendations. Cases with spermatozoa concentrations of ≤5 million/ml were screened for chromosomal aberrations and Y-chromosomal microdeletions. Main results and the role of chance: The primary cause of infertility was defined for 695 of 1737 patients (~40%). The analyzed causal factors could be divided into absolute (secondary hypogonadism, genetic causes, seminal tract obstruction), severe (oncological diseases, severe sexual dysfunction) and plausible causal factors (congenital anomalies in uro-genital tract, acquired or secondary testicular damage). The latter were also detected for 11 (3.4%) men with proven fertility (diagnoses: unilateral cryptorchidism, testis cancer, orchitis, mumps orchitis). The causal factors behind the most severe forms of impaired spermatogenesis were relatively well understood; causes were assigned: for aspermia in 46/46 cases (100%), for azoospermia in 321/388 cases (82.7%), and for cryptozoospermia in 54/130 cases (41.5%). In contrast, 75% of oligozoospermia cases remained unexplained. The main cause of aspermia was severe sexual dysfunction (71.7% of aspermia patients). Azoospermia patients accounted for 86.4% of all cases diagnosed with secondary hypogonadism and 97.1% of patients with seminal tract obstruction. Of patients with a known genetic factor, 87.4% had extreme infertility (azoo-, crypto- or aspermia). The prevalence of congenital anomalies in the uro-genital tract was not clearly correlated with the severity of impaired sperm production. Previously defined 'potential contributing factors' varicocele and leukocytospermia were excluded as the primary causes of male infertility. However, their incidence was >2-fold higher (31.0 vs 13.5% and 16.1 vs 7.4%; P < 0.001) in the idiopathic infertility group compared to controls. In addition, the proportions of overweight (or obese) patients and patients suffering from a chronic disease were significantly increased in almost all of the patient subgroups. Limitations reasons for caution: The study included only subjects with reduced total spermatozoa counts. Thus, these findings cannot be automatically applied to all male factor infertility cases. Wider implications of the findings: The novel insights and improved clarity achieved in the comprehensive analysis regarding the absolute, causative and plausible factors behind male infertility, as well as the 'potential contributing factors', will be valuable tools in updating the current clinical guidelines. The study highlights knowledge gaps and reiterates an urgent need to uncover the causes and mechanisms behind, and potential treatments of, oligozoospermic cases, representing the majority of idiopathic infertility patients (86.3%). Study funding/competing interests: The project was financed by the EU through the ERDF, project HAPPY PREGNANCY, no. 3.2.0701.12-004 (M.P., M.L.) and the Estonian Research Council: grants PUT181 (M.P.) and IUT34-12 (M.L.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. Trail registration number: Not applicable.
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Couples with a spinal cord injured male partner require assisted ejaculation techniques to collect semen that can then be further used in various assisted reproductive technology methods to achieve a pregnancy. The majority of men sustaining a spinal cord injury regardless of the cause or the level of injury cannot ejaculate during sexual intercourse. Only a small minority can ejaculate by masturbation. Penile vibratory stimulation and electroejaculation are the two most common methods used to retrieve sperm. Other techniques such as prostatic massage and the adjunct application of other medications can be used, but the results are inconsistent. Surgical sperm retrieval should be considered as a last resort if all other methods fail. Special attention must be paid to patients with T6 and rostral levels of injury due to the risk of autonomic dysreflexia resulting from stimulation below the level of injury. Bladder preparation should be performed before stimulation if retrograde ejaculation is anticipated. Erectile dysfunction is ubiquitous in the spinal cord injured population but is usually easily managed and does not pose a barrier to semen retrieval in these men. Semen analysis parameters of men with spinal cord injury are unique for this population regardless of the method of retrieval, generally presenting as normal sperm concentration but abnormally low sperm motility and viability. When sperm retrieval is desired in this population, emphasis should be placed on initially trying the simple methods of penile vibratory stimulation or electroejaculation before resorting to more advanced and invasive surgical procedures.
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This hospital-based, prospective study was conducted to evaluate the relationship between body mass index (BMI) and various semen parameters in infertile men. A total of 439 men presented for infertility evaluation were assessed by basic infertility evaluation measures including semen analysis and BMI calculation. The main outcome measure was the relationship between BMI groups [BMI: 18.5-24.9 kg/m(2) (normal weight), 25-29.9 kg/m(2) (overweight) and ≥30 kg/m(2) (obese)] and different semen parameters [volume, concentration, motility and morphology]. The mean BMI was 29.67 ± 5.89. Most of patients (82.91%) were overweight or obese. The 3 BMI groups were comparable in semen parameters (P > 0.05). BMI had a negative correlation with various semen parameters. However, this correlation was significant only with sperm concentration (P = 0.035). We concluded that sperm concentration was the only semen parameter which showed significant reduction with higher BMI in infertile men.
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The use of testosterone replacement therapy (TRT) for hypogonadism continues to rise, particularly in younger men who may wish to remain fertile. Concurrently, awareness of a more pervasive use of anabolic-androgenic steroids (AAS) within the general population has been appreciated. Both TRT and AAS can suppress the hypothalamic-pituitary-gonadal (HPG) axis resulting in diminution of spermatogenesis. Therefore, it is important that clinicians recognize previous TRT or AAS use in patients presenting for infertility treatment. Cessation of TRT or AAS use may result in spontaneous recovery of normal spermatogenesis in a reasonable number of patients if allowed sufficient time for recovery. However, some patients may not recover normal spermatogenesis or tolerate waiting for spontaneous recovery. In such cases, clinicians must be aware of the pathophysiologic derangements of the HPG axis related to TRT or AAS use and the pharmacologic agents available to reverse them. The available agents include injectable gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors, but their off-label use is poorly described in the literature, potentially creating a knowledge gap for the clinician. Reviewing their use clinically for the treatment of hypogonadotropic hypogonadism and other HPG axis abnormalities can familiarize the clinician with the manner in which they can be used to recover spermatogenesis after TRT or AAS use.
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In the past, the indications for varicocelectomy are primarily for infertility with abnormal semen parameters, testicular hypotrophy/atrophy in adolescents, and/or pain. The surgical treatment of varicocele for hypogonadism is controversial and debated. Recently, multiple reports in the literature have suggested that varicocele is associated with hypogonadism and varicocele repair can increase testosterone levels. Men with hypogonadal symptoms should have at least two serum testosterone levels. Microsurgical varicocelectomy may be beneficial for men with clinically palpable varicoceles with documented hypogonadism. In this review, we summarize the most recent literature linking varicocele to hypogonadism and sexual dysfunction and the impact of repair on serum testosterone levels. We performed a search of the published English literature. The key words used were "varicocele and hypogonadism" and "varicocele surgery and testosterone." We included published studies after 1998. We, also, evaluated the effect of surgery on the changes in the serum testosterone level regardless of the indication for the varicocele repair.
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Introduction: We aim to predict results of varicocelectomy on sperm density and progressive motility using preoperative clinical, laboratory and radiological data and to propose cut-off values for significant parameters. Methods: This prospective study was carried out between July 2011 and June 2014. We included 123 patients in our study. They were diagnosed with primary infertility with varicocele, were scheduled for varicocelectomy, and completed their follow-up. We excluded patients with azoospermia, total necrospermia, recurrent varicocele, and pituitary hormonal abnormalities. Varicocele was diagnosed and graded by physical examination and colour Doppler ultrasound. Semen analyses were completed preoperatively and 6 months postoperatively. Microscopic subinguinal varicocelectomy was done in all cases. Patient demographics, pre- and postoperative clinical data (varicocele grade and semen parameters) were statistically analyzed. Results: The mean ± standard deviation of age, body mass index, and subfertility duration was 28.3 ± 7.4 years, 29.1 ± 2.7 kg/m(2), and 21.9 ± 7.1 months, respectively. About 53% of our patients (n = 66) had bilateral varicocele, and unilateral disease was found in the other 57 (46.3%) cases. Varicocele grade I was diagnosed in 42 (34.1%) patients, while the other 81 (65.9%) patients had grade II or III. Higher grades of varicocele, preoperative total testosterone level, sperm density, and progressive motility had a statistically significant impact on the outcome of varicocelectomy in univariate testing. Multivariate logistic analysis revealed that grade of preoperative varicocele (95% confidence interval [CI] 5.6-6.3, p = 0.007) and sperm density (95% CI 2.7-1.6, p = 0.0035), and progressive motility (95% CI 1.1-2.3, p = 0.0123) are independent predictors of semen parameters improvement after varicocelectomy. Conclusion: The grade of the varicocele, sperm density, and progressive motility are major predictors of outcome in varicocelectomy. Cut-off values of >8 million/mL and >18% for sperm density and progressive motility, respectively, in men with varicocele grade II or III, indicate a successful outcome.
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Background Antipsychotic drugs are associated with sexual dysfunction but the mechanisms are poorly understood. Aims To ascertain the frequency of sexual dysfunction in patients taking conventional antipsychotics and to determine the possible underlying mechanisms. Method Sexual dysfunction was assessed in 101 patients receiving conventional antipsychotic medication, 57 normal controls and 55 controls attending a sexual dysfunction clinic. Results Sexual dysfunction occurred in 45% of patients taking antipsychotic medication, 17% of normal controls and 61% of controls attending a sexual dysfunction clinic. Sexual dysfunction was associated with autonomic side-effects in normoprolactinaemic males, but the presence of hyperprolactinaemia overrode other causes of sexual dysfunction. For women, hyperprolactinaemia was the main cause of sexual dysfunction. Conclusions Conventional anti-psychotic medications cause significant levels of sexual dysfunction. Clinicians should routinely enquire about sexual symptoms prior to the prescription of antipsychotics and on follow-up.
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Objective To examine the hypotheses that clinical varicoceles affect baseline serum total testosterone levels (T) and varicocelectomy improves T. Materials and Methods This prospective, nonrandomized, controlled study involved 4 groups of adult men. Varicocele-infertile treatment group (VIT) included 66 men who underwent varicocelectomy. Thirty-three varicocele-infertile control men (VIC) and 33 varicocele-fertile control men (VFC) were only observed. Normal-control (NC) group included 33 fertile men without varicocele. Varicocele groups were stratified into baseline hypogonadal (T <300 ng/dL) or eugonadal (T ≥300 ng/dL) subgroups. Main outcome measurements were between-group baseline T differences; and within-group T changes at 6- and 12-month follow-ups of men with varicocele. P <.05 was considered significant. Results Means (standard deviations) of baseline T in VIT, VIC, VFC, and NC were 347.4 (132.1), 339.7 (125.8), 396.6 (164.9), and 504.8 (149.7) ng/dL, respectively. The baseline T levels of varicocele groups were comparable, whereas they were significantly low compared with NC group. At 6-month follow-up, VIT demonstrated significant T improvements (mean change = 44.7 ng/dL; 12.9%; P <.0001). T changes were more remarkable among baseline hypogonadals (mean change = 93.7 ng/dL; 40.1%; P <.0001) compared with eugonadals (mean change = 8.6 ng/dL; 2.01%; P = .1223). These improvements were persistent at 12-month follow-up. Contrariwise, VIC and VFC exhibited nonsignificant T changes. Postvaricocelectomy T changes correlated significantly and inversely with baseline T (r = −0.689; P <.0001). This correlation was stronger and more significant among hypogonadals (r = −0.528; P = .004) than eugonadals (r = −0.400; P = .013). T improvements also exhibited significant positive correlations with preoperative and postoperative sperm concentrations. Conclusion Baseline T was significantly low in men with varicocele compared with normal men. Varicocelectomy yielded significant T improvements among hypogonadal men but insignificant changes in eugonadals. T changes correlated strongly and significantly with baseline T and sperm concentrations.
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Patients with non-obstructive azoospermia (NOA) were once considered to be infertile with few treatment options due to the absence of sperm in the ejaculate. In the last two decades, the advent of intracytoplasmic sperm injection (ICSI), and the application of various testicular sperm retrieval techniques, including fine needle aspiration (FNA), conventional testicular sperm extraction (TESE) and microdissection testicular sperm extraction (micro-TESE) have revolutionized treatment in this group of men. Because most men with NOA will have isolated regions of spermatogenesis within the testis, studies have illustrated that sperm can be retrieved in most men with NOA, including Klinefelter's syndrome (KS), prior history of chemotherapy and cryptorchidism. Micro-TESE, when compared with conventional TESE has a higher sperm retrieval rate (SRR) with fewer postoperative complications and negative effects on testicular function. In this article, we will compare the efficacy of the different procedures of sperm extraction, discuss the medical treatment and the role of testosterone optimization in men with NOA and describe the micro-TESE surgical technique. Furthermore, we will update our overall experience to allow counseling on the prognosis of sperm retrieval for the specific subsets of NOA.Asian Journal of Andrology advance online publication, 17 December 2012; doi:10.1038/aja.2012.141.
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To assess the incidence and the type of chromosomal aberrations in males with infertility we reviewed cytogenetic results in 76 Tunisian infertile men (54 nonobstructive azoospermia and 22 oligo-asthenospermia). Karyotyping was performed on peripheral blood lymphocytes according to the standard methods. Molecular diagnosis of classical and partial Y-chromosomal microdeletions was performed by amplifying Y-specific STSs markers. Various numerical and structural chromosome abnormalities were identified in 15 patients (19.48%). The occurrence of chromosomal abnormality in the azoospermics and severe oligo-asthnospermic was 21.7% and 13.5%, respectively. The most common was Klinefelter syndrome, accounting for 10 of the 15 cytogenetic defects. The total frequency of Y chromosomal microdeletions was 17.1%, with respective frequencies in azoospermic and severe oligospermic groups, 11.1% and 31.8%. The most frequent of Y chromosomal deletions were the partial ones (11.1% in azoospermic and 27.2% in oligospermic). The occurrence of chromosomal abnormalities among infertile males strongly suggests the need for routine genetic testing and counseling prior to the employment of assisted reproduction techniques.
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To the Editors: Young's syndrome (YS) is a triad of bronchiectasis, chronic rhinosinusitis and infertility due to vas deferens obstruction, in which case cystic fibrosis (CF) and primary ciliary diskinesia are excluded. One assumed aetiology of YS is mercury exposure during childhood. During the 20th Century, mercury use was discouraged, thus reducing exposure. Hendry et al. 1 postulated that this was the reason for the declining prevalence of YS. They observed a rate of 50% of YS in males with obstructive azoospermia who …
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Introduction: Over the last several decades, the opioid epidemic has become a national crisis, largely spurred by the spike in the use of prescription painkillers. With the epidemic came a concomitant rise in the incidence of opioid-induced androgen deficiency (OPIAD). Although OPIAD can significantly impact male sexual function and quality of life, it is an overlooked and poorly understood clinical entity that requires more attention from healthcare providers. Aim: The objectives of the current review are to highlight the increasing incidence of OPIAD and the importance of an integrated, multidisciplinary approach to identify and treat patients with the condition. Methods: This review presents the epidemiology surrounding the current opioid epidemic, with a focus on its origin, followed by a literature review surrounding the pathophysiology, diagnosis, and treatment of OPIAD. Main outcome measure: Single-center studies were used to determine the safety and efficacy of various opioid and testosterone formulations on analgesia, sexual function, and quality of life. Results: There should be a low threshold for obtaining laboratory studies (testosterone, luteinizing hormone [LH], follicle-stimulating hormone [FSH]) on symptomatic patients who have a history of chronic opioid use. Treatment options include opioid cessation, short-acting opioids, and testosterone replacement therapy (TRT). The patient and physician should weigh the risks and benefits of TRT against more conservative approaches. Options such as clomiphene and anastrozole are available for patients who wish to preserve fertility. Conclusion: Because OPIAD is an underappreciated and underdiagnosed consequence of chronic opioid abuse, healthcare providers should be particularly vigilant for signs of hypogonadism in this patient population. It is reasonable for pain specialists, urologists, and primary care physicians to closely monitor patients on prescription opioids and discuss available options for treatment of hypogonadism. Hsieh A, DiGiorgio L, Fakunle M, et al. Management strategies in opioid abuse and sexual dysfunction: A review of opioid-induced androgen deficiency. Sex Med Rev 2018;XX:XXX-XXX.
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To evaluate the success rate in sperm retrieval (SR) through microdissection testicular sperm extraction (micro‐TESE) in infertile azoospermia factor c (AZFc)‐deleted men and determining their reproductive outcomes following ICSI, medical records of couples with AZFc‐deleted male partners were reviewed on patient's age, serum hormone levels, karyotype, testicular pathology and pregnancy outcomes. A comparison on age and serum hormone level was conducted between groups with positive and negative sperm retrieval in both azoospermic and oligozoospermic AZFc‐deleted men. Of 225 who had AZFc deletion, 195 cases followed clinical treatments. From 195 cases, 116 were azoospermic, 79 were oligozoospermic. Pathology profile was available in 103 of 195 subjects which the predominant trait was SCOS and was seen in 66.9% of cases (69 of 103). Success rate of sperm retrieval in azoospermic patients who underwent micro‐TESE was 36.3% (28/77). Forty‐three oligozoospermic and 17 azoospermic patients started ART cycle. Pregnancy rate in oligozoospermic group was 35.4% (17 cases), whilst there was no clinical pregnancy in azoospermic group. In conclusion, the pregnancy and delivery in oligozoospermic patients with AZFc deletion are comparable with other studies, but despite of sperm retrieval in azoospermic patients with AZFc deletion, the chance of pregnancy or delivery in these patients was very low.
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Although the incidence of mumps orchitis has dramatically declined since the introduction of the childhood vaccination programme, a sharp increase in reported cases of both mumps and mumps orchitis has been seen recently in the UK. There are great concerns about mumps outbreaks and the associated risk of infertility; it remains an important clinical condition. Immunization is the best policy to avoid this viral disease.
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Obesity is a growing epidemic and a common problem among reproductive-age men that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the fidelity and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and nonhuman animal data support these findings. Recent works in the burgeoning field of epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, and perhaps more importantly, conveying the impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Reproductive urologists and endocrinologists must learn to assimilate these new findings to better counsel men about the importance of paternal preconception health, a topic recently being championed by the Centers for Disease Control and Prevention.
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Background In light of the worldwide increase in childhood obesity, we examined the association between body-mass index (BMI) in late adolescence and death from cardiovascular causes in adulthood. Methods We grouped data on BMI, as measured from 1967 through 2010 in 2.3 million Israeli adolescents (mean age, 17.3±0.4 years), according to age- and sex-specific percentiles from the U.S. Centers for Disease Control and Prevention. Primary outcomes were the number of deaths attributed to coronary heart disease, stroke, sudden death from an unknown cause, or a combination of all three categories (total cardiovascular causes) by mid-2011. Cox proportional-hazards models were used. Results During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death. On multivariable analysis, there was a graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range). Hazard ratios in the obese group (≥95th percentile for BMI), as compared with the reference group in the 5th to 24th percentiles, were 4.9 (95% confidence interval [CI], 3.9 to 6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7 to 4.1) for death from stroke, 2.1 (95% CI, 1.5 to 2.9) for sudden death, and 3.5 (95% CI, 2.9 to 4.1) for death from total cardiovascular causes, after adjustment for sex, age, birth year, sociodemographic characteristics, and height. Hazard ratios for death from cardiovascular causes in the same percentile groups increased from 2.0 (95% CI, 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI, 3.1 to 5.4) during follow-up for 30 to 40 years; during both periods, hazard ratios were consistently high for death from coronary heart disease. Findings persisted in extensive sensitivity analyses. Conclusions A BMI in the 50th to 74th percentiles, within the accepted normal range, during adolescence was associated with increased cardiovascular and all-cause mortality during 40 years of follow-up. Overweight and obesity were strongly associated with increased cardiovascular mortality in adulthood. (Funded by the Environment and Health Fund.)
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Varicocele is defined as an excessive dilation of the pampiniform plexus. The association between varicocele and infertility has been well-established as evidenced by negative effects on spermatogenesis. Accumulating evidence now suggests that varicocele presents a pantesticular insult, with resultant impairment of Leydig cell function. The presence of a varicocele has been linked to lower serum testosterone levels and varicocelectomy may reverse some of the adverse effects on androgen production. In this review, the evidence linking varicoceles to impaired steroidogenesis and which cohorts of men may benefit most from varicocele repair are discussed.
Article
The relationship between obesity and hypogonadism is complicated. The relationship is bidirectional and there are numerous causative and correlative factors on both sides of the equation. Obesity is increasing in prevalence in epidemic proportions. Likewise, we are beginning to see the rapid increase in the incidence of male hypogonadism. It is only recently that we are learning the ways in which these 2 conditions exacerbate each other, and we are only beginning to understand how by treating one of these conditions, we can help to treat the other as well.
Conference Paper
Purpose: Our aim was to determine whether the deleterious effect of varicocele on spermatogenesis, as reflected by semen analysis, occurs in boys as young as 17 to 19 years. Data analysis was done of semen variables of select, boys attending randomly chosen schools. Materials and Methods: A total of 36 healthy boys without a pathological condition detected by history, physical examination and scrotal ultrasound served as controls, and 38 with profound varicocele who were otherwise healthy served as an experimental group. All boys were followed as outpatients 2 times during the last year, We performed semen and clinical examinations, Doppler ultrasound assessment of venous reflux, and ultrasound measurement of testicular and pampiniform vein diameters. Results: No significant differences were found in sperm concentration, volume,presence of spontaneus agglutination and pH between the 2 groups,There were significant; differences in total and progressive sperm motility and vitality, which were lower in boys with varicocele, as were the number of normal sperm forms. There was a statistically and clinically significant linear negative relationship between sperm motility, and maximal and basal blood flow velocities as well as pampiniform vein diameter. Conclusions: Varicocele can affect spermatogenesis in boys as young as 17 to 19 years, as shown by the decrease in motility, vitality and number of normal forms of spermatozoons. The clinically significant correlations between semen analysis parameters and ultrasound findings allow the prediction of testicular function using ultrasound alone.
Article
We summarize and comment on the topics discussed by the contributors to this Special Issue of Asian Journal of Andrology. The scope of varicocele covers a wide spectrum, including proteomics and metabolomics, hormonal control, interventional therapy, and assisted reproductive technology (ART). The selection of topics demonstrates the exciting breadth of this thematic area and the opportunity research holds for both increasing the understanding and improving the reproductive health of males with varicocele.
Article
Spinal cord injury (SCI) occurs most often in young men at the peak of their reproductive health. The majority of men with SCI cannot father children naturally. Three major complications contribute to infertility in men with SCI: erectile dysfunction, ejaculatory dysfunction, and abnormal semen quality. Erectile dysfunction can be managed by regimens available to the general population, including oral administration of phosphodiesterase-5 (PDE-5) inhibitors, intracavernosal injections, vacuum devices, and penile prostheses. Semen may be obtained from anejaculatory men with SCI via the medically assisted ejaculation methods of penile vibratory stimulation (PVS) or electroejaculation (EEJ). Sperm retrieval is also possible via prostate massage or surgical sperm retrieval. Most men with SCI have abnormal semen quality characterized by normal sperm concentrations but abnormally low sperm motility and viability. Accessory gland dysfunction has been proposed as the cause of these abnormalities. Leukocytospermia is evident in most SCI patients. Additionally, elevated concentrations of pro-inflammatory cytokines and elevated concentrations of inflammasome components are found in their semen. Neutralization of these constituents has resulted in improved sperm motility. There is a recent and alarming trend in the management of infertility in couples with SCI male partners. Although many men with SCI have sufficient motile sperm in their ejaculates for attempting intrauterine insemination (IUI) or even intravaginal insemination, surgical sperm retrieval is often introduced as the first and only sperm retrieval method for these couples. Surgical sperm retrieval commits the couple to the most advanced, expensive, and invasive method of assisted conception: in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI). Couples should be informed of all options, including semen retrieval by PVS or EEJ. Intravaginal insemination or IUI should be considered when indicated.
Article
An assumption in case-control studies is that forces of selection are the same for cases and controls. This may not be true for studies of male infertility among infertility clients. Earlier reproductive outcomes may introduce modification of risk behavior or differential referral. Selection bias might also occur when infertile males are compared with fertile males. Partners of sterile men are more likely to have normal fertility, while partners of a reference group of normozoospermic men tend to have a lower fertility potential. The latter may lead to overrepresentation of causes of reduced female fertility and introduce bias into estimates of risk factors shared by couples. The relation between cigarette smoking and semen quality was studied in a population of infertility clients from the Netherlands during 1995-1996. To reduce the potential for bias, this relation was studied first in a restricted population less aware of the type of infertility involved. The odds ratio of infertility with smoking was elevated in the restricted population as compared with the total population. Adjustment for smoking by the female partner increased the odds ratios for male smoking as well. These results indicate that bias may occur in clinic-based fertility studies because of different forms of selection.
Article
Identifying the correct cause of hyperprolactinemia is crucial for treatment. Prolactinoma is the most common pathologic cause of hyperprolactinemia. Dopamine agonists are efficacious in about 80% to 90% of patients with prolactinoma, leading to reduction of serum prolactin levels and tumor dimensions. Neurosurgery, mainly by the transsphenoidal route, is indicated in cases of intolerant and resistant dopamine agonists. Radiotherapy is rarely used because of its side effects and low efficacy. The alkylating agent temozolomide showed efficacy for treatment of aggressive and resistant prolactinomas. Other approaches, such as thyrosine kinase inhibitors, are currently being tested and could be an additional tool for these troublesome tumors. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
In a prospective manner, we studied the effect of varicocelectomy on premature ejaculation and testicular hormonal function in patients with varicocele. Microsurgical subinguinal varicocelectomy was carried out in 73 patients with clinical varicocele associated with premature ejaculation (group 1) and compared with 56 patients without operative intervention (group 2; control). The primary efficacy variable was the mean change in the Premature Ejaculation Diagnostic Tool. The changes in International Index of Erectile Function questionnaire, total serum testosterone and testicular size were also assessed. In group 1, the Premature Ejaculation Diagnostic Tool decreased significantly after varicocelectomy, from 15.56 to 11.37 (P < 0.001), indicating improvement of premature ejaculation. Thirty patients (41.1%) showed improvement of premature ejaculation compared to 5.3% in the control group (P < 0.001). In group I, but not in group II, testosterone levels and International Index of Erectile Function values increased significantly when compared with pre-operative values (P < 0.001 and 0.040 respectively). Testicular size increased after varicocelectomy, but this increase was nonsignificant till the end of study (P = 0.054). We concluded that varicocelectomy is clearly related to improvement of premature ejaculation and testicular hormonal function in varicocele patients.
Article
Varicoceles are an abnormal dilation of the pampiniform plexus of veins within the scrotum. Varicoceles are highly prevalent and can result in a myriad of deleterious effects on male reproduction. Numerous therapeutic options are available for correcting varicoceles, including surgical varicocelectomy and radiographic venous embolization. Varicocele correction is a more cost-effective therapeutic modality than both intrauterine insemination (IUI) and in vitro fertilization (IVF) for affected couples. In summary, varicoceles contribute significantly to male reproductive pathology, and varicocele correction is an important option for both clinicians and patients to consider in this era of assisted reproductive techniques.
Article
This article summarizes the current literature regarding azoospermia caused by spermatogenic failure. The causes and genetic contributions to spermatogenic failure are reviewed. Medical therapies including use of hormonal manipulation, whether guided by a specific abnormality or empiric, to induce spermatogenesis are discussed. The role of surgical therapy, including a discussion of varicocelectomy in men with spermatogenic failure, as well as an in-depth review of surgical sperm retrieval with testicular sperm extraction and microdissection testicular sperm extraction, is provided. Finally, future directions of treatment for men with spermatogenic failure are discussed, namely, stem cell and gene therapy.
Article
To analyze how frequently and why men presenting with infertility take testosterone (T) and if negative effects of T on semen parameters are reversed following cessation. Analysis of a prospectively collected database. Male Infertility clinic. Men presenting for fertility evaluation from 2008 to 2012. None. The frequency and reason for T use in the infertile male population, and semen and hormonal parameters while on T and following discontinuation. A total of 59/4,400 men (1.3%) reported taking T. T was prescribed by a variety of physicians, including endocrinologists (24%), general practitioners (17%), urologists (15%), gynecologists (5%), and reproductive endocrinologists (3%). Only one of the men admitted that he had obtained T from an illicit source. More than 82% of men were prescribed T for the treatment of hypogonadism, but surprisingly, 12% (7/59) were prescribed T to treat their infertility. While on T, 88.4% of men were azoospermic, but by 6 months after T cessation, 65% of the men without other known causes for azoospermia recovered spermatogenesis. In Canada, T was not commonly used by men presenting for fertility investigation (1.3%). Close to 2/3 of infertile men using T recovered spermatogenesis within 6 months of T discontinuation.
Article
Treatment of cancer with chemo- or radiotherapy causes reduction of sperm counts often to azoospermic levels that may persist for several years or be permanent. The time course of declines in sperm count can be predicted by the sensitivity of germ cells, with differentiating spermatogonia being most sensitive, and the known kinetics of recovery. Recovery from oligo- or azoospermia is more variable and depends on whether there is killing of stem cells and alteration of the somatic environment that normally supports differentiation of stem cells. Of the cytotoxic therapeutic agents, radiation and most alkylating drugs are the most potent at producing long-term azoospermia. Most of the newer biologic targeted therapies, except those used to target radioisotopes or toxins to cells, seem to have only modest effects, mostly on the endocrine aspects of the male reproductive system; however, their effects when used in combination with cytotoxic agents have not been well studied.
Article
Gunshot injuries to the testicles are rare and usually result in testicular atrophy. In the case of severe bilateral testicular injuries, this could cause not only infertility but also the need for lifetime testosterone-substitution. We report an 18-year-old patient with bilateral testicular gunshot injury. During the surgical exploration an orchiectomy of the complete ruptured left testicle was necessary. Debridement of the damaged tissue and a partial orchiectomy was performed on the right side. After the operation, the patient developed an incretory hypogonadism and oligozoospermia. During follow-up, an improvement in the sperm count and of the hormonal status occurred. These finally reached normal levels. After genital traumata, immediate surgical exploration should be performed. Based on the above results, the patient benefits from conservative debridement and primary repair of the injured testicle, if possible. An improvement in hormonal status and sperm parameters after testicular injury and consecutive testicular malfunction can occur. Regeneration of the testicular tissue seems possible.
Article
With the increasing number of patients surviving cancer, there is increasing interest in long-term quality of life, especially with respect to cancer-related infertility. Although infertility most commonly occurs as the result of treatment with gonadotoxic agents, it can also manifest before treatment has commenced. Current fertility preservation strategies for the postpubertal male patient with cancer focus on sperm cryopreservation before therapy. Sperm acquisition techniques should be discussed with the patient as early as possible, by either an oncologist or a specialist in male reproduction. For patients rendered infertile by cancer treatment who did not cryopreserve sperm beforehand, there are no techniques currently available to restore fertility. For the prepubertal male patient, cryopreservation of sperm is impossible. However, emerging research-primarily in animal models-into promising fertility preservation and restoration strategies might provide a clinical solution in the future. Advances in the protection and cryopreservation of spermatogonial stem cells (SSCs) might translate into clinical options for fertility preservation before treatment. Restoring fertility after treatment might also be possible via SSC autotransplantation or in vitro maturation of SSCs. Before any of these techniques become clinically viable, a number of scientific, logistical and ethical issues will need to be resolved.
Article
Les effets secondaires sexuels des antipsychotiques atypiques sont fréquents, en général sous-estimés par les cliniciens et subjectivement mal tolérés par les patients. Ils contribuent à l’importante non-compliance rapportée chez les patients traités. La plupart des antipsychotiques atypiques sont non sélectifs et ont des actions sur une multitude de récepteurs tant centraux que périphériques. Parmi celles-ci, l’action antidopaminergique pourrait avoir un effet délétère direct et indirect sur la fonction sexuelle en général. Pour certaines substances (neuroleptiques conventionnels, rispéridone et amisulpiride), l’antagonisme dopaminergique peut induire une hyperprolactinémie, qui contribue aux dysfonctions sexuelles et pourrait provoquer, particulièrement chez les femmes, un hypogonadisme. Les conséquences à long terme de cet hypogonadisme, qui équivaut à une ménopause précoce, sont encore débattues mais potentiellement -sévères. Par ailleurs, les actions adrénolytiques, antihistaminiques, anticholinergiques et modulatrices de la fonction -sérotoninergique de certains antipsychotiques atypiques contribuent également à induire des troubles sexuels. Afin d’illustrer les conséquences de ces dysfonctions sexuelles sur les patients et de discuter les solutions possibles, 5 cas de dysfonction sexuelle ou de la fonction reproductive apparus sous traitement par rispéridone sont présentés: 2 cas de troubles éjaculatoires, 1 cas de galactorrhée et 2 cas d’aménorrhée. L’impact subjectif de ces troubles ainsi que leurs effets sur la compliance et les solutions possibles sont discutés.
Objective: To determine the appropriate methods for the diagnosis and management of gunshot injuries to the external genitalia. Design: Retrospective analysis. Materials and Methods: Fifty-six patients with gunshot wounds (GSWs) to the external genitalia were seen over the last 10 years. All patients underwent physical examination, radiographic staging, and surgical exploration, according to protocol. Results: There were 25 testicular, 19 scrotal soft tissue, 14 penile, 4 epididymal, 4 urethral, 4 vasal, and 3 superficial scrotal skin injuries. When possible, all injuries, except for the vasal and 1 urethral injury, were primarily repaired with excellent long-term results. Orchiectomy was required in half of testes struck by gunshots. Associated injuries with single GSWs were mostly to the proximity soft tissue and were amenable to conservative management. Major associated injuries were present in patients with multiple GSWs. In the absence of a suspected major associated injury, genital GSWs required only two diagnostic studies, a retrograde urethrogram for suspected urethral injury and a routine abdominal radiograph. Gunshot injuries to the penis or perineum, blood at the penile meatus, or gross hematuria were highly suggestive of urethral injury. Conclusions: Successful management of genital GSWs is dependent upon prompt surgical exploration, conservative debridement, and primary repair.
Article
There has been a growing interest over the past few years in the impact of male nutrition on fertility. Infertility has been linked to male overweight or obesity, and conventional semen parameter values seem to be altered in case of high body mass index (BMI). A few studies assessing the impact of BMI on sperm DNA integrity have been published, but they did not lead to a strong consensus. Our objective was to explore further the relationship between sperm DNA integrity and BMI, through a 3-year multicentre study. Three hundred and thirty male partners in subfertile couples were included. Using the terminal uridine nick-end labelling (TUNEL) assay, we observed an increased rate of sperm DNA damage in obese men (odds ratio (95% confidence interval): 2.5 (1.2-5.1)).Asian Journal of Andrology advance online publication, 24 June 2013; doi:10.1038/aja.2013.65.
Article
Objective To examine the incidence of cystic fibrosis transmembrane-conductance regulator (CFTR) gene mutations in Scottish patients with congenital bilateral absence of the vas deferens (CBAVD). Patients and methods Thirty patients with CBAVD presenting consecutively to the Edinburgh infertility clinic were examined for CFTR gene mutations. All patients were assessed clinically and tested for 15 gene mutations using a single-tube polymerase chain-reaction multiplex system. Results All patients were in good health and without clinical evidence of cystic fibrosis. CFTR gene mutations were found in 70% of patients with CBAVD. Conclusion CFTR gene-testing and genetic counselling are important in all men with CBAVD.
Article
Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive azoospermia and accounts for 1%–2% of male infertility. A high incidence of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has recently been reported in males with CAVD. We have investigated a cohort of 106 German patients with congenital bilateral or unilateral absence of the vas deferens for mutations in the coding region, flanking intron regions and promotor sequences of the CFTR gene. Of the CAVD patients, 75% carried CFTR mutations or disease-associated CFTR variants, such as the “5T” allele, on both chromosomes. The distribution of mutation genotypes clearly differed from that observed in cystic fibrosis. None of the CAVD patients was homozygous for ΔF508 and none was compound heterozygous for ΔF508 and a nonsense or frameshift mutation. Instead, homozygosity was found for a few mild missense or splicing mutations, and the majority of CAVD mutations were missense substitutions. Twenty-one German CAVD patients were compound heterozygous for ΔF508 and R117H, which was the most frequent CAVD genotype in our study group. Haplotype analysis indicated a common origin for R117H in our population, whereas another frequent CAVD mutation, viz. the “5T allele” was a recurrent mutation on different intragenic haplotypes and multiple ethnic backgrounds. We identified a total of 46 different mutations and variants, of which 15 mutations have not previously been reported. Thirteen novel missense mutations and one unique amino-acid insertion may be confined to the CAVD phenotype. A few splice or missense variants, such as F508C or 1716 G→A, are proposed here as possible candidate CAVD mutations with an apparently reduced penetrance. Clinical examination of patients with CFTR mutations on both chromosomes revealed elevated sweat chloride concentrations and discrete symptoms of respiratory disease in a subset of patients. Thus, our collaborative study shows that CAVD without renal malformation is a primary genital form of cystic fibrosis in the vast majority of German patients and links the particular expression of clinical symptoms in CAVD with a distinct subset of CFTR mutation genotypes.
Article
To determine the effect of surgical varicocele repair in improving testicular Leydig cell function as shown by increased testosterone production. Eligible studies were searched in Medline and the Pubmed database, and cross-referenced as of 31 May 2011 using the terms "varicocele,"testosterone" and "surgery." The database search, quality assessment and data extraction were independently carried out by two reviewers. Only studies including patients with testosterone evaluation before and after surgery were considered for the analysis. A systematic review and meta-analysis was carried out for continues variables using random effect models. Out of 125 studies, a total of nine were selected, including 814 patients. The combined analysis showed that mean serum testosterone levels after surgical treatment increased by 97.48 ng/dL (95% confidence interval 43.73-151.22, P=0.0004) compared with preoperative levels. Surgical treatment of varicocele significantly increases testosterone production and improves testicular Leydig cell function.
Article
1745 patients at the Department of Urology of Tenon Hospital (Paris, France) from 1990 to 2006 and at the department of urology of Tbilisi State Medical University (Georgia) during last several months have been examined and counseled on male infertility. Leydig cell tumor was found in 4 patients, among them 3 by palpation and testicle echography, fourth patient (at the age of 33) with bilateral varicocele (III stage at the left, II stage at the right) was more interesting for us. Leydig cell tumor was found out at the scrotum exploration. Oligoteratozoospermia (OATS) has been distinguished from his spermogram. Microsurgical bilateral correction of varicocele and scrotum exploration, and double-sided double biopsy of testicle have been carried out. During examination of the left testis the hardly palpable node has been found out in the lower pole. We became compelled to make enlarged incision of tunica alba of the testicle lower pole. After that it was found out the solid, well encapsulated and yellow-brown node (8 mm in diameter). The node enucleation away from tumor by 0.5 cm has been carried out. Exact histological investigation confirmed the presence of Leydig cell tumor. In 6 years after surgical operation the tumor node 1.8 mm in diameter has been found out in right (contra lateral) testis. The patient was urgently operated, ex-tempo investigation confirmed the presence of Leydig cell tumor in right testicle--high orchidectomy at the right has been carried out. Now, patient has not any symptoms of disease during 3.5 years of observation. Given case shows that the enucleation of Leydig cell tumor proves to be equivalent alternative of orchidectomy, which is suggested by many authors. Taking into account the presence of encapsulation and tumor benignity it is important to have opportunity of the testicle preservation due to infertility problems. However, this tactics must be carried out under strong observation due to the opportunity of relapse even in several days after surgical operation.
Article
Marihuana and alcohol consumption affect adversely reproduction by inhibiting the hypothalamic-pituitary-gonadal axis. The endocannabinoid system, present in the central nervous system and in peripheral tissues, participates in the regulation of hormones involved in the reproductive physiology such as luteinizing hormone, prolactin and oxytocin. This system is activated in response to pathophysiological conditions such as stress and inflammatory/infectious states as well as alcoholism and drug consumption acting as a negative modulator of reproductive function. The secretion of luteinizing hormone from the adenohypophysis is reduced, mainly through hypothalamic inhibitory action of cannabinoids and alcohol on luteinizing hormone releasing hormone release from its nervous terminals in the median eminence. This inhibitory effect is mediated, at least in part, by the activation of cannabinoid type 1 receptors. Cannabinoids also inhibit prolactin release from the lactotropes in the adenohypophysis acting locally and by increasing the release of hypothalamic dopamine mainly from tuberoinfundibular dopaminergic neurons in the external layer of the median eminence. On the contrary, ethanol stimulates prolactin release from the adenohypophysis as well as oxytocin from the neurohypophysis. Besides, endocannabinoids modulate oxytocin synthesis and release from the hypothalamic magnocellular neurons and neurohypophysis. In summary, all the results exposed in the present review suggest that there is interplay between the endocannabinoid system, hormones and neuropeptides in the control of reproduction and that this system mediates, at least in part, ethanol adverse effects on reproductive function.
Article
Cryptorchidism has been on the rise for several decades and can be observed with frequency of 1-2% of males within the first year of age. It may appear as an isolated disorder or can be a consequence of genetic and endocrine abnormalities connected with somatic anomalies. Its genetic background still seems to be unclear although a range of genes can be responsible for the development of this syndrome. Cryptorchidism can be associated with serum testosterone level although the often co-existing hypogonadotropic hypogonadism may also indicate the involvement of pituitary hormones. Recently, environmental factors have been blamed for cryptorchidism induction. Autoimmune reactions in conjunction with steroid hormones regulating immune response can be also partly responsible for cryptorchidism etiology. The appearance of antisperm antibodies can be considered as a marker or a serious side-effect of uncorrected cryptorchidism. If so, it could be implied that early surgery (orchidopexy) should be beneficial since it may prevent antisperm antibodies induction or at least eliminate them in the post-operative period.
Article
In 2001, when the testicular dysgenesis syndrome (TDS) concept was proposed, it suggested that impaired development of foetal testes could lead to increased risks of cryptorchidism, hypospadias, decreased spermatogenesis or testis cancer. The TDS concept links the pathogenesis of the four disorders together, but does not imply that all affected men develop all four symptoms. The least affected men may merely have a slightly reduced spermatogenic capacity, and only the most severely affected may present all symptoms. A majority of cases of testicular germ cell cancers (TGCC) and cryptorchidism are most likely caused by TDS. However, the frequency of the syndrome in the general population and to what extent poor semen quality and hypospadias are actually biologically related through a foetal mechanism remain unresolved. Hypospadias and impaired spermatogenesis can be classified as TDS if combined with cryptorchidism or TGCC. By contrast, recent studies demonstrated that among men with isolated hypospadias, only a fraction of cases are linked to TDS. There is no doubt that TDS contributes to impaired semen quality. This is most obvious for cases with visible dysgenetic features in testis histology, but in the majority of men with impaired semen quality as the only symptom, an association with TDS is less clear. Such cases have a very heterogeneous aetiology and may be caused by a host of other - often post-natal-factors. In conclusion, the TDS as a holistic concept has inspired new research activities and led to a better understanding of the early origin of male reproductive problems, but it clearly encompasses only a fraction of cases of hypospadias and impaired spermatogenesis.
Article
Significantly higher levels of oxidants (malonaldehyde and nitric oxide) and reduced levels of antioxidants (superoxide dismutase, glutathione peroxidase, catalase, and ascorbic acid) are seen in semen of infertile men with varicocele. Seminal oxidative stress (OS) seen in men with varicocele is associated with sperm motility and grade of varicocele.