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Non-surgical Management of Oligozoospermia
Abstract
Male infertility secondary to oligozoospermia is surprisingly common. Although a majority of cases are idiopathic, oligozoospermia can be caused by endocrine dysfunction, anatomic abnormalities, medications, or environmental exposures. The work-up includes excluding reversible factors such as hormonal deficiency, medication effects, and retrograde ejaculation and identifying any underlying genetic syndrome and treating reversible medical causes. If no reversible cause is found, appropriate referrals to urology and assisted reproductive technology should be initiated. Lastly, clinicians should be aware of and respond to the psychological and general health ramifications of a diagnosis of oligozoospermia as part of the comprehensive care of men and couples struggling with a diagnosis of infertility.
... Male infertility factors have been recognised in around 40 %-50 % of infertile couples; more than 90% of cases in male infertility are due to low sperm counts, poor sperm quality or both. Other factors involve anatomical disorders, hormonal imbalances and genetic defects [1] (Leaver, 2016). Moreover, male factors can include ejaculatory problems such as retrograde ejaculation, premature ejaculation or anejaculation, defects in sperm count, mobility, or abnormalities [1] (Leaver, 2016). ...
... Other factors involve anatomical disorders, hormonal imbalances and genetic defects [1] (Leaver, 2016). Moreover, male factors can include ejaculatory problems such as retrograde ejaculation, premature ejaculation or anejaculation, defects in sperm count, mobility, or abnormalities [1] (Leaver, 2016). Some of the most common factors that correlate to irregularities in sperm are listed in (Table 1) . ...
... ICSI requires injecting one sperm directly into an oocyte prior to transferring to the uterus. ICSI has the advantage of using few viable sperm to fertilise an egg and can bypass natural barriers that prevent fertilisation [1] (Leaver, 2016). ...
Assisted reproductive technology has been developed significantly throughout the past few years, particularly diagnosing and treating male infertility. Many studies have been performed showing that Intracytoplasmic Sperm Injection (ICSI) is a successful method to attain clinical pregnancy and live birth through impaired spermatozoa characteristics or low sperm count, such as severe oligospermia. Severe oligospermia indicates low sperm count, which in some cases leads to azoospermia. Severe oligospermia can be caused by several factors such as genetics or medication. In search of efficient treatment for couples with Severe oligospermia, numerous retrospective and prospective researches have reported high pregnancy and live birth rates through testicular sperm for men with severe oligospermia and cryptozoospermia with or without high sperm DNA damage. The research showed that the use of testicular sperm in combination with ICSI yielded a high pregnancy rate and live births over another source of sperm, such as ejaculated sperms. Moreover, the use of ICSI in severe oligospermia has shown successful fertilization and pregnancy.
... Men who are diagnosed with azoospermia are generally offered a testicular biopsy for testicular sperm extraction (TESE). Overall, sperm retrieval rates are highly variable, up to 50-60% in specialized centres 32,43 , and depend on different surgical approaches, for example, conventional TESE or the microsurgery variant [43][44][45] . NOA resulting from a lack of gonadotropins is identifiable as hypogonadotropic hypogonadism, which can commonly be treated through gonadotropin substitution and, therefore, does not require TESE. ...
... The term is 28 defined as the detection of spermatozoa in the semen sample only after centrifugation. A semen 29 sample with an extremely low concentration of spermatozoa can be described by two different 30 terms solely based on the chance of detecting a spermatozoa: 1) if spermatozoa are observed 31 prior to centrifugation, the condition is labelled as "Oligozoospermia", 2) if spermatozoa are only 32 observed after centrifugation, the condition is labelled as "Cryptozoospermia". Since using two 33 different terms for the same condition (very low numbers of spermatozoa in the ejaculate) is 34 unnecessary complicated, we propose to use the term "Oligozoospermia" in combination with a 35 defined set of adjectives: extreme, severe, moderate and mild. ...
An increasing number of genes are being described in the context of non-syndromic male infertility. Linking the underlying genetic causes of non-syndromic male infertility with clinical data from patients is important to establish new genotype-phenotype correlations. This process can be facilitated by using universal nomenclature, but no standardized vocabulary is available in the field of non-syndromic male infertility. The International Male Infertility Genomics Consortium aimed at filling this gap, providing a standardized vocabulary containing nomenclature based on the Human Phenotype Ontology (HPO). The "HPO tree" was substantially revised compared with the previous version and is based on the clinical work-up of infertile men, including physical examination and hormonal assessment. Some causes of male infertility can already be suspected based on the patient's clinical history, whereas in other instances, a testicular biopsy is needed for diagnosis. We assembled 49 HPO terms that are linked in a logical hierarchy and showed examples of morphological features of spermatozoa and testicular histology of infertile men with identified genetic diagnoses to describe the phenotypes. This work will help to record patients' phenotypes systematically and facilitate communication between geneticists and andrologists. Collaboration across institutions will improve the identification of patients with the same phenotypes, which will promote the discovery of novel genetic causes for non-syndromic male infertility.
... Infertility is a significant global health issue that affects approximately 9% to 20% of couples, with over 50% of cases attributed to male-related factors [1,2]. Abnormalities in spermatogenesis, influenced by factors such as genetics, hormonal disorders, psychological stress, sexual issues, obesity, environmental pollutants, and medication, are often the cause [3][4][5]. Chemotherapies, particularly those involving alkylating agents like busulfan (BSF), are associated with reversible or irreversible fertility disorders [6]. ...
Cancer treatments, including cytotoxic therapy, often result in male infertility, necessitating the development of safe and effective strategies to preserve male reproductive potential during chemotherapy. Notably, our study uncovers the potential of repurposing riluzole, an FDA-approved drug for amyotrophic lateral sclerosis (ALS), in enhancing spermatogenesis. Hence, this research aims to explore the feasibility of utilizing riluzole to alleviate male infertility induced by busulfan (BSF), a commonly used chemotherapy drug. We established a BSF-induced oligospermia model in 4-week-old male mice and found that riluzole could effectively counter the detrimental effects of BSF on sperm production in mice with oligospermia. By restoring blood–testis barrier (BTB) functionality, riluzole improves sperm quality and reduces testicular atrophy. Through transcriptomic and molecular docking analyses, we identify transient receptor potential canonical subfamily member 5 (TRPC5) as a potential target for riluzole-mediated regulation of blood–testis barrier function. These findings propose riluzole as a promising therapeutic option for chemotherapy-induced male infertility, thereby addressing the fertility challenges associated with cancer treatments. Moreover, repurposing riluzole could streamline the drug development process, providing a cost-effective approach with reduced risk compared to developing entirely new drugs.
... 17 Oligozoospermia is a common cause of male infertility, with over 60% of cases being idiopathic and genetic causes accounting for less than 10%. 18 Male infertility has been scarcely documented as a component of Carney complex and it is generally connected to the presence of LCCSC tumours, as these tumours are present in 40% to 50% of patients with CNC. 3 Moreover, there have been just a small number of reports on infertility tied with oligozoospermia and CNC. Burton et al, 8 showed that in CNC mice PRKAR1A haploinsufficiency can cause oligozoospermia alongside impaired semen motility and morphology, in the absence of LCCSCT. ...
Plain Language Summary
Male infertility associated with a novel PRKAR1A mutation in carney complex
Carney Complex (CNC) is a rare genetic disorder that leads to the development of various tumours, including in the heart and endocrine glands. Most cases are linked to mutations in a gene called PRKAR1A and are inherited in an autosomal dominant manner. This case report presents a detailed examination of a patient diagnosed with Carney Complex (CNC), followed over nearly 10 years. The patient initially consulted due to infertility, which led to extensive investigations and diagnosis of several type of tumours: Primary pigmented nodular adrenocortical disease (PPNAD) in the adrenal glands, a cardiac myxoma, and Large cell calcifying Sertoli cell tumours (LCCSCT) in the testes - all tumours are characteristic features of CNC. Notably, genetic testing revealed a novel mutation in the PRKAR1A gene. Through this case, we highlight how this genetic mutation might cause PRKAR1A haploinsufficiency and be solely responsible for infertility in CNC irrespective of testicular tumours, providing valuable insights into a condition where male infertility is rarely documented. This report contributes important new information to the limited existing research on the connection between CNC and male infertility.
... This study also show that most of the urea based herbicides, branch chain amino acid inhibiting herbicides, synthetic auxin herbicides, acetyl-CoA carboxylase inhibiting herbicides and photosynthesis inhibiting herbicides were positively correlated with the development of oligospermia. Some of the causes of oligospermia as documented in literature includes endocrine dysfunctions, enviromental toxins, and anatomic abnormalities 42 . Hypogonadism and hormonal imbalance has been shown to lead to partial spermatogenic arrest, low levels of testosterone and increased estrogen in the male all of which are contributing factors towards the pathogenesis of oligospermia 43 . ...
Background Reports from various countries have consistently demonstrated a correlation between herbicide exposure, arising from agricultural practices, and a decline in semen quality, leading to male infertility. This study was conducted at Ekiti State University Teaching Hospital in Ado-Ekiti, a rural community characterized by a predominantly agrarian population to determine the relationship between semen quality and herbicides residues. Methods The study focused on males whose spouses were seeking assistance at infertility clinics. Routine semen analyses were performed according to the World Health Organization (WHO) criteria, categorizing samples into normospermic, asthenospermic, oligospermic, and azoospermic groups. Seminal plasma samples from each group (twenty samples per group) were subjected to analysis for the presence and concentration of herbicides using High-Performance Liquid Chromatography (HPLC). The following herbicides were investigated: halosulfurum, linuron, fluometuron, chlo-rimuron, imaxamox, cloransulam, dicamba, fluroxypor, trichlopyr, propanil, cloclinafop, clethodim, quizalofop, fluazifop, pinoxaden, bentazon, atrazine, and bromoxynil. The obtained results were subjected to statistical analysis using SPSS version 24. Results The analysis revealed significantly higher concentrations of most herbicides in the asthenospermia, oligospermia, and azoospermia groups compared to the normospermic group (P<0.05). These findings suggest a strong association between herbicide exposure and poor semen quality in the studied population.Conclusion This study provides compelling evidence supporting the hypothesis that herbicides exposure could be a contributory factor to diminished semen quality in the investigated rural com-munity. The results underscore the importance of considering seminal herbicide determination as a routine component in male infertility testing. Additionally, the study advocates for the implementation of relevant legislation to mitigate potential risks associated with herbicide exposure.
... Năm 2010, Tổ chức Y tế Thế giới đã công bố cẩm nang phiên bản thứ V đánh giá các thông số trong tinh dịch ở nam giới hiếm muộn [2]. Trong phiên bản này, hội chứng tinh trùng ít -yếu -dị dạng (OAT: Oligo-Astheno-Teratozoospermie) được định nghĩa là trường hợp tinh dịch đồ có tổng số (hoặc mật độ, tùy thuộc vào kết quả báo cáo) tinh trùng, tỷ lệ di động tiến tới và hình dạng bình thường của tinh trùng thấp hơn ngưỡng tham khảo [3]. Nguyên nhân của hội chứng OAT có thể do bất thường nhiễm sắc thể, tinh hoàn lạc chỗ, giãn tĩnh mạch thừng tinh, rối loạn nội tiết,viêm sinh dục, thoát vị bẹn, đái tháo đường, thừa cân, suy dinh dưỡng hoặc trường hợp bệnh nhân nghiện rượu, thuốc lá, ma túy… Khả năng sinh sản tự nhiên giảm nhiều ở nhóm bệnh nhân OAT [4]. ...
Mục tiêu: Đánh giá kết quả điều trị tiêm tinh trùng vào bào tương noãn (ICSI) trên bệnh nhân vô sinh nam do hội chứng tinh trùng ít-yếu-dị dạng (OAT) và xác định một số yếu tố liên quan đến kết quả phương pháp tiêm tinh trùng vào bào tương noãn. Phương pháp nghiên cứu: Nghiên cứu mô tả cắt ngang được thực hiện trên 160 cặp vợ chồng điều trị IVF/ICSI tại Bệnh viện Phụ sản – Nhi Đà Nẵng từ tháng 01/2020 đến tháng 12/2020 có kết quả tinh dịch đồ OAT đã được chuyển phôi. Kết quả: Phương pháp ICSI điều trị các trường hợp vô sinh nam do OAT có tỷ lệ thụ tinh trung bình là 72,1 ± 19,0% và tỷ lệ tạo phôi trung bình là 79,5 ± 20,0%, tỷ lệ thai lâm sàng, tỷ lệ thai sinh sống và tỷ lệ sẩy thai lần lượt là 52,5%, 45%, 7,5%. Mật độ tinh trùng, sự hiện diện của tinh trùng di động tiến tới và sự có mặt của tinh trùng có hình thái bình thường không ảnh hưởng đến tỷ lệ thụ tinh, tỷ lệ phôi tốt, tỷ lệ thai lâm sàng, tỷ lệ thai sinh sống và tỷ lệ sẩy thai. Kết luận: Điều trị phương pháp (ICSI) trên nhóm bệnh nhân vô sinh nam do OAT có hiệu quả cao. Kết quả ICSI chưa thấy bị ảnh hưởng bởi một số chỉ số của tinh dịch đồ bệnh nhân OAT. Sperm concentration, progressive rate and normal morphology sperm rate had no significantly effected to fertilization rate, good – embryo rate, clinical pregnancy rate, live birth rate and misscariage rate. Conclusions: ICSI increased the IVF success rates in the patients with OAT syndrome. There were no correlations between the sperm concentration, progressive rate and normal morphology rate with ICSI’s results
... Azoospermia is defined by the total absence of sperm in the ejaculate and is identified in 15% of infertile men [4], while severe oligozoospermia is characterized by markedly low sperm concentrations (less than 5 million sperm/mL) [5]. These conditions not only reflect severe impairments in spermatogenesis but also raise complex diagnostic and therapeutic challenges [4,6]. The causes of azoospermia and severe oligozoospermia are multifaceted, involving a complex interplay of genetic, environmental, and lifestyle factors, making their management particularly challenging [7]. ...
Citation: Chatziparasidou, A.; Kyrgiafini, M.-A.; Sarafidou, T.; Moutou, K.A.; Mamuris, Z. Genetic Insights into Azoospermia and Severe Oligozoospermia: Discovering Seven SNPs through GWAS and In Silico Analysis. Curr. Issues Mol. Biol. 2024, 46, 6522-6532. https://doi. These authors contributed equally to this work. Abstract: Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood , with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms (SNPs) linked to both azoospermia and severe oligozoospermia. We conducted a genome-wide association study (GWAS) involving 280 Greek males with normal semen parameters and 85 Greek males diagnosed with either azoospermia or severe oligozoospermia. Following rigorous quality control measures, our analysis identified seven SNPs associated with azoospermia/severe oligozoospermia. An in silico functional annotation was subsequently used to further investigate their role. These SNPs, found in regions not previously associated with male reproductive disorders, suggest novel genetic pathways that may contribute to these forms of infertility and pave the way for future studies. Additionally, this study sheds light on the significant role of noncoding RNAs in the pathogenesis of male infertility, with three of the identified SNPs situated in long intergenic non-coding RNAs (lincRNAs). Our findings highlight the intricate genetic landscape of azoospermia and severe oligozoospermia, underlining the necessity for more detailed studies to fully grasp the underlying mechanisms and their potential for informing diagnostic and therapeutic strategies.
... RE, the process where seminal fluid is forced into the bladder instead of being expelled through the penis, is a unique condition that disrupts the regular ejaculatory system. The intricate coordination of smooth and striated muscles in the posterior urethra plays a crucial role in the ejaculation process [8]. The malfunctions of this system can result from congenital or acquired anomalies of the bladder, neck, and urethra, as well as interference with the neurologic control of ejaculation, especially in conditions like diabetes. ...
Infertility, a complicated reproductive health issue that affects both men and women, can have a variety of causes, from anatomical abnormalities to hormone imbalances. This research addresses a couple who have been struggling with infertility for the past four years: a 31-year-old woman with bilateral tubal blockage and her 34-year-old spouse who suffered from primary infertility due to retrograde ejaculation (RE) for the same period. Analyzing the male’s semen sample, it was discovered that there were dead sperm and urine, indicating RE. A hysterosalpingography indicated bilateral tubal obstruction in the female partner. Pelvic factors were examined via laparoscopy, which played a crucial role in addressing further issues. The procedure of treatment included testicular sperm aspiration for sperm extraction and intracytoplasmic sperm injection. Hormonal support was involved in the follow-up, and on the 14th day, the β-hCG test came back positive. The intricate procedures of RE and cornual block are discussed, with a focus on how they affect reproductive health.
... Male infertility secondary to oligozoospermia is surprisingly common. Although some cases are idiopathic, oligozoospermia can be caused by endocrine dysfunction, anatomical abnormalities, medications, or environmental exposures [20]. Azoospermia, which is an absence of sperm in the semen, has several etiologies. ...
... Many risk factors, ranging from the patient's genetic background [5], maternal exposure [6], environmental pollutants [7], metabolic syndrome (MetS) [8], and obesity [9] to the patient's lifestyle [10], have been recognized to affect sperm count. Sperm count is further associated with sperm quality and could determine male fertility [11]. However, the extent of the influence of these factors on semen quality remains to be clearly determined due to the inability to design an experiment to account for all possible confounding factors. ...
In many countries, especially developed nations, the fertility rate and birth rate have continually declined. Taiwan’s fertility rate has paralleled this trend and reached its nadir in 2022. Therefore, the government uses many strategies to encourage more married couples to have children. However, couples marrying at an older age may have declining physical status, as well as hypertension and other metabolic syndrome symptoms, in addition to possibly being overweight, which have been the focus of the studies for their influences on male and female gamete quality. Many previous studies based on infertile people are not truly representative of the general population. This study proposed a framework using five machine learning (ML) predictive algorithms—random forest, stochastic gradient boosting, least absolute shrinkage and selection operator regression, ridge regression, and extreme gradient boosting—to identify the major risk factors affecting male sperm count based on a major health screening database in Taiwan. Unlike traditional multiple linear regression, ML algorithms do not need statistical assumptions and can capture non-linear relationships or complex interactions between dependent and independent variables to generate promising performance. We analyzed annual health screening data of 1375 males from 2010 to 2017, including data on health screening indicators, sourced from the MJ Group, a major health screening center in Taiwan. The symmetric mean absolute percentage error, relative absolute error, root relative squared error, and root mean squared error were used as performance evaluation metrics. Our results show that sleep time (ST), alpha-fetoprotein (AFP), body fat (BF), systolic blood pressure (SBP), and blood urea nitrogen (BUN) are the top five risk factors associated with sperm count. ST is a known risk factor influencing reproductive hormone balance, which can affect spermatogenesis and final sperm count. BF and SBP are risk factors associated with metabolic syndrome, another known risk factor of altered male reproductive hormone systems. However, AFP has not been the focus of previous studies on male fertility or semen quality. BUN, the index for kidney function, is also identified as a risk factor by our established ML model. Our results support previous findings that metabolic syndrome has negative impacts on sperm count and semen quality. Sleep duration also has an impact on sperm generation in the testes. AFP and BUN are two novel risk factors linked to sperm counts. These findings could help healthcare personnel and law makers create strategies for creating environments to increase the country’s fertility rate. This study should also be of value to follow-up research.
... While these results are in agreement with a previous study that recruited 5000 (non-infertile) military draftees, they are in contrast with another study that observed a reduction of sperm count in southern Europe between 2001 and 2011 [8]. It is worth mentioning that whereas these two studies involved healthy, young individuals, the data of the present work were collected from infertile patients, which are known to present lower sperm count than healthy males [45]. One may, therefore, reasonably suggest that the differences in the effects of time on sperm quality between the two groups could come from the distinct condition of patients compared to healthy donors. ...
Semen quality has a direct relation to male fertility. Whether sperm variables in humans have decreased over the last years is still uncertain, with some studies showing a decline and others reporting no changes. In this regard, previous research has suggested that lifestyle and environmental conditions may contribute to this variability, calling for regional studies. The present work is a retrospective, unicentric study that includes semen samples analyzed between 1997 and 2017 at the Parc Taulí Hospital (Barcelona metropolitan area). First, a multivariate analysis including the age as a confounding factor showed a statistically significant decrease in semen volume, pH, progressive motility, morphology and total motile sperm over time. Contrarily, no significant variation in sperm count or concentration was observed. Mean reductions per year were −0.02 mL for volume, −0.57% for progressively motile sperm and −0.72% for sperm with normal morphology. Interestingly, the average annual temperature registered by the Spanish Meteorology Agency negatively correlated to sperm morphology and sperm count (Rs = −0.642; p = 0.002 and Rs = −0.435; p = 0.049, respectively). In conclusion, the present study based on infertile patients from the Barcelona area found a decline in sperm motility and morphology, without effects on sperm count. Changes in temperature appeared to be associated to this decline, but further studies are needed to address the mechanisms linked to the observed variations.
... Oligozoospermia and severe oligozoospermia are clinically defined as sperm concentrations <15 and 5 million/ml of ejaculate, respectively (Choy and Amory, 2020). The low sperm number might result from a wide variety of genetic alterations. ...
Proper assembly of the synaptonemal complex is essential for successful meiosis, and impairments in the process lead to infertility. Meiotic transverse filament proteins encoded by the SYCP1 (synaptonemal complex protein 1) gene are one of the main components of the synaptonemal complex and play an important role in correct synapsis and recombination. Family-based whole exome sequencing revealed a rare homozygous SYCP1 frameshift mutation (c.2892delA: p.K967Nfs*1) in two men with severe oligozoospermia, followed by validation and segregation through Sanger sequencing. This single nucleotide deletion not only changes lysine 967 (K) into asparagine (N) but also causes a premature stop codon, which leads to deletion of 968-976 residues from the end of the C-tail region of the SYCP1 protein. Although, sycp1 knockout male mice are reported to be sterile with a complete lack of spermatids and spermatozoa, to date no SYCP1 variant has been associated with human oligozoospermia. HADDOCK analysis indicated that this mutation decreases the ability of the truncated SYCP1 protein to bind DNA. Immunodetection of ϒH2AX signal, in SYCP1 mutant semen cells and a 40% DNA fragmentation index might indicate that a small number of DNA double-strand breaks, which require SYCP1 and/or synapsis to be repaired, are not efficiently repaired, resulting in defects in differentiation of germline cells and appearance of the oligozoospermia phenotype. To our knowledge, this is the first report of homozygous SYCP1 mutation that decreases sperm count. Further studies are required to determine the function of the SYCP1 mutation, which is potentially associated with human oligozoospermia.
... Oligozoospermia is sperm cell count below the threshold of 15 million/ml in the male ejaculate, categorized as mild, moderate and severe oligozoospermia (Choy & Amory, 2020). A recent cohort study showed a significant reduction in the expression levels of miR-34b-5p, miR-34b-3p and miR-34c-3p in semen samples of oligozoospermic patients compared with normozoospermic men. ...
Infertility is a multiplex disorder in the reproductive system, and men are responsible for more than half of the cases. Nowadays, semen analysis has been considered the critical assessment test to diagnose infertile men; however, it has limitations so that the cause behind infertility in 40% of infertile men is unrevealed. Weaknesses of semen assessment indicate a global need for novel and better diagnostic tools and biomarkers. MicroRNAs are short (about 18–22 nucleotide length) non‐coding RNAs that control most (>60%) of our protein‐coding genes post‐transcriptionally. These molecules are aberrant in the body fluids, and abnormal alterations in their expression level can signify a specific disease such as infertility. Therefore, microRNAs can be novel candidate biomarkers that can diagnose different types of male infertility, including azoospermia, oligozoospermia, asthenozoospermia and teratozoospermia. This narrative review aimed to collect and sum up new papers published about the significant role of microRNAs in different male infertility categories.
... Isolated teratozoospermia, sperm DNA fragmentation and systemic inflammation in infertile men and LH were higher, while inhibin B was lower in infertile men presenting with iOZS compared to those in all other groups. These data further corroborate previous findings supporting a link between oligozoospermia and endocrine dysfunctions [26]. The correlations between sperm morphology, sperm DNA integrity and oxidative balance have been recently investigated [13,27,28]. ...
Aim
To assess the prevalence of isolated teratozoospermia (iTZS) in a cohort of infertile and fertile men; explore the relationship between iTZS, inflammatory parameters and sperm DNA fragmentation index (SDF) in the same cohort.
Materials and methods
1824 infertile men and 103 fertile controls. Semen analysis, the neutrophil-to-lymphocyte ratio (NLR) and serum hormones were investigated. DFI was tested in infertile men only. According to 2010 WHO semen analysis, patients were categorized in 3 sub-groups of isolated sperm defects: isolated oligozoospermia (iOZS), isolated asthenozoospermia (iAZS) and iTZS. Descriptive statistics and linear regression models tested the association between clinical variables and inflammatory markers.
Results
Among infertile men, iAZS, iTZS, and iOZS were found in 13.9%, 11.9% and 4.1% participants, respectively. iTZS was found in 37 (35.9%) fertile men. Infertile men with iTZS had higher NLR values than those with iOZS, iAZS and men with normal semen parameters (all p<0.001). FSH and LH were higher and inhibin B lower in iOZS infertile men compared to all other groups (p≤0.001). Hormonal characteristics were similar between iTZS infertile and fertile men. Similarly, iTZS infertile men had higher SDF than all other groups (all p<0.001). Infertile men with iTZS had higher NLR values than fertile men with iTZS (p<0.01). Linear regression analysis showed that, in infertile men, iTZS was associated with SDF and NLR (all p≤0.01).
Conclusions
iTZS was found in 11.9% of infertile men but it was even more prevalent in fertile controls. Infertile men with iTZS had higher NLR than fertile controls and increased SDF values than infertile participant with iAZS, iOZS, or normal semen parameters. No differences in hormonal characteristics were found between infertile and fertile men with iTZS.
Infertility is defined as inability to conceive after 1 year of regular, unprotected intercourse. Approximately about 10–15% of couples suffer from infertility all over the world. Male fertility may be impaired by abnormal sperm parameters and contributes to 50% of all cases of infertility. The causes of male infertility are widely varied and are best evaluated by an expert in male reproductive health. Some causes of male infertility can be identified and reversed (or improved) with specific surgery or medication, while other causes can be identified but not reversed. The main cause is low quality and quantity of sperm. In more than 90% of cases, male infertility is due to either low sperm count or poor semen quality or both. Semen analysis remains the single most useful and fundamental investigation in the search for the cause of male infertility. It is a simple test that assesses the formation and maturity of sperm as well as how the sperm interacts with the seminal fluid so it provides insight not only on sperm production (count), but sperm quality (motility, morphology) as well. Nonetheless, conventional semen analysis may provide inadequate information regarding the etiology of infertility. To overcome the limitations of routine seminal evaluation, several invasive and non-invasive approaches have been developed for the management of male factor infertility. While today we are more successful in treating male infertility, pregnancy is still not always achieved likely due to factors that remain poorly understood. Clinicians treating infertility should advocate for couple-based therapy and require that both partners have a thorough evaluation and an informed discussion before undergoing specific therapies/treatments. The current chapter addresses the methodology of sperm concentration and total sperm count testing and its usefulness to diagnose male infertility; etiology of male reproductive dysfunction; possible causes implied in low sperm count; non-ART management of patient with low sperm count and concentration; and ART management of patient with low sperm count and concentration.
Pyrethroids (PYRs) may act as endocrine disrupters and lead to infertility. The aim of the study was to analyze the levels of anti-androgenic PYRs (cypermethrin, deltamethrin, and permethrin) and 3-phenoxy benzoic acid (3-PBA), a general metabolite of PYRs, in both semen and urine samples of men with oligozoospermia. The PYRs and 3-PBA metabolite levels in the semen and urine samples of the men were analyzed through GC-MS. The results indicated that the levels of PYRs in the semen samples of the infertile group were significantly higher than those of the fertile group. It was determined that cypermethrin exposure was associated with changes in sperm count and total sperm motility, while permethrin, deltamethrin, and 3-PBA levels were associated with changes in sperm morphology. It was determined that there was a significant negative correlation between semen deltamethrin levels and sperm morphology and sperm count. In addition, exposure of these patients to deltamethrin (range; 1.53–8.02 µg/l) and having farmer parents were determined to increase the risk of infertility. In conclusion, the findings of this study showed that exposure to environmental PYRs may adversely affect semen quality, especially in terms of sperm morphology, in men with oligozoospermia.
Introduction and importance
The most common causes of infertility are idiopathic spermatogenetic disorders; occurring in multiple reproductive or systemic diseases. The underlying genetic disorders influence the treatment, and transmission of the disease to the offspring.
Case presentation
A 32-year-old Syrian male, married for 6 years, presented with primary infertility. The patient had a history of muscle dystrophy for 12 years. He had no previous medical, drug addiction, or family history. He had gynaecomastia. Semen analysis revealed: oligospermia in the patient. FSH was elevated. Gene analysis could not be done due to funding issues.The Percutaneous testicular biopsy revealed hypospermatogenesis, atrophy, and marked hyalization of the seminiferous tubules.Electromyography of the upper extremities demonstrated myotonic discharges, with a waxing–waning frequency, amplitude and a characteristic ‘engine revving’ sound.
Clinical discussion
Myotonic dystrophy is an autosomal dominant inheritance disease, with adult-onset. Muscle weakness is the predominant presenting feature, with early involvement of the distal limbs and neck muscles, and a characteristic facial appearance.
Systemic clinical manifestations may include cardiac conduction defects, cataracts, insulin resistance and diabetes, testicular atrophy with impaired spermatogenesis, and others. Testicular biopsy findings are specific. To our knowledge, this is the first case of male infertility associated with MD in Syria. Although there are no data on the prevalence of MD1 in Syria.
Conclusion
The practicing physician should keep in mind the frequent association between MD, and infertility.
Background
Around 15% of couples of childbearing age suffer from infertility; in 50% of these cases, the male factor is present. In this study, we investigated the association between anti-ODF2 autoantibody existence and the DNA fragmentation and apoptosis of sperm in oligozoospermia men.
Material and Methods
35 fertile men and 57 oligozoospermia men are enrolled in this study as control and case groups, respectively. After the identification of ODF2 as a possible target of anti-sperm antibodies in sera of oligozoospermia men using two-dimensional gel electrophoresis followed by western blotting and mass spectrometry, the case group serums were screened for anti-ODF2 autoantibodies and divided into anti-ODF2 negative (N=24) and positive (N=33) subgroups to follow assays. The mRNA expression levels of ODF2, Caspases 3, 8, 9, BAX, and BCL-2 were evaluated via qRT-PCR in spermatozoa samples of mentioned groups. DNA fragmentation and apoptosis rate of spermatozoa in studied groups were assessed using an SDF kit and flow cytometry, respectively.
Results
Mass spectrometry showed that ODF2 is one of the anti-sperm antibodies targeted in oligozoospermia patients. 33 of 57 oligozoospermia men had anti-ODF2 autoantibody in their sera. An elevated expression of ODF2 mRNA was observed in spermatozoa of anti-ODF2+ patients compared to anti-ODF2- patients and controls. There was an increased expression level of Caspase 3, 8, 9, and BAX and decreased expression of BCL-2 in spermatozoa of anti-ODF2+ patients compared to anti-ODF2- patients and controls. Noticeable increases in DNA fragmentation and apoptosis rate of anti-ODF2+ patients' spermatozoa were observed compared to anti-ODF2- patients and healthy controls spermatozoa. A positive correlation was observed between ODF-2 expression and DNF fragmentation and apoptosis rate of anti-ODF2+ patients' spermatozoa.
Conclusion
Our results revealed that ODF2 is one of the main spermatozoa structural proteins, which is one of the anti-sperm antibodies targets, and its dysregulated expression may result in an increased rate of sperm DNA fragmentation and apoptosis.
Background:
There is a strong within-subject alteration of semen parameters in men with infertility. However, it remains unknown in which subgroup variations are likely to occur and which semen parameters are affected.
Objective:
To evaluate parameters associated with spontaneous alterations in semen analysis.
Patients and methods:
We retrospectively selected 3456 men with infertility without known causes affecting spermatogenesis or sperm output for analysis of repeated ejaculate samples. Exclusion criteria comprised: sperm concentration <1 million/ml, abnormal FSH or low testosterone, low bitesticular volume (bTV, <10ml). Grouped linear 2-level nested mixed-effect models were applied. Analyzed parameters included: abstinence time, bTV, age, accessory gland markers, FSH, FSHB c.-211 variants.
Results:
Groups: A (n = 397): ≥1.0 to <5.0 mill/ml, B (n = 708): ≥5.0 to <15.0 mill/ml, C (n = 2351): ≥15.0 mill/ml. A, B and C: changes in ejaculate volume were associated with alterations in total sperm count and motility (p<0.003). Changes were, controlled for abstinence time (p<0.001), related to alpha-glucosidase, fructose or zinc (p = 0.005-0.02). A+B: fluctuations in FSH level influenced sperm concentration/count (p = 0.004-0.02), albeit only in men with FSHB c.-211 GG (p = 0.007-0.02). T-allele carriers did not show changes in FSH level (p>0.1). B: age <50 years (p = 0.007-0.01) and normal bTV (p = 0.008-0.02) were associated with spontaneous increases of sperm concentration, count and motility.
Conclusion:
Semen parameters exhibit intra-individual alterations associated with organic, hormonal and genetic variables. Changes are pronounced in younger men with normal bTV and oligo- to almost normozoospermia. The effect is modulated by abstinence time, accessory gland function and fluctuations in FSH level, which is bound to FSHB c.-211G>T variant. Judgement of semen analysis should be based on two semen samples, with abstinence time between 4-5 days respectively. As a future perspective, it might be investigated whether younger men with normal bTV and unable to elicit increases in serum FSH (FSHB c.-211 genotype of GT/TT) benefit from improving accessory gland function and increasing FSH. This article is protected by copyright. All rights reserved.
Background
Shizi Sanhua Decoction, a traditional Chinese medicine (TCM) prescription, shows a treatment advantage on male oligospermia. While due to the complexity of the compatibility (multiple herbs composition), the underlying mechanism remains to be deciphered.
Methods
Herbs-ingredients-target genes were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SWISSADME database, intersecting with oligospermia-related derived from DisGeNET to obtain co-target genes. The protein-protein interaction (PPI) network of co-target genes was constructed based on the STRING database, and highly condensed sub-networks and top 10 Hub genes were identified with the CytoHubba plug-in. Herbs, ingredients and KEGG enrichment information were projected onto the identified highly condensed subnetwork to build Herbs-ingredients and disease co-target genes sub-network.
Results
After integration of herbs-ingredients-target genes (n=453) with disease genes (n=329), 29 cotarget genes were obtained. Among them, PARP1, AR, CYP17A1, ESR1, ABCB1, STS, CFTR, SOAT1, NR5A1, and HIF1A were related to male infertility (WP4673-WikiPathways). Sub-network analysis further revealed the top 10 Hub genes, and the relation with the herbs and ingredients was demonstrated in the sub-network of herbs-ingredients and disease co-target genes. As expected, reproductive- related biological processes (mammary gland epithelium development, GO:0061180; Oocyte meiosis, hsa04114; Progesterone-mediated oocyte maturation, hsa04914) were enriched. Thyroid hormone signaling pathway (hsa04919), Serotonergic synapse (hsa04726), Chemical carcinogenesisreactive oxygen species (hsa05208), and Endocrine resistance (hsa01522) may contribute to the development of male oligospermia.
Conclusion
Constructed herbs-ingredients and disease co-target genes sub-network discloses specific bioprocesses and molecular targets of Shizi Sanhua Decoction in oligospermia treatment.
This review summarizes ten years experience with male abusers of anabolic androgenic steroids (AAS). The typical user of AAS is male, aged between 20 and 40 and lifting weights. Illegal AAS are cheap and easily obtained via internet or local suppliers. AAS are mostly used in cycles with a duration between 6 and 18 weeks. Most AAS cycles contain multiple agents, used simultaneously in a dose vastly exceeding a substitution dose. A variety of other performance and image-enhancing drugs are commonly used, including human growth hormone, thyroid hormone, tamoxifen, clomiphene citrate and human chorionic gonadotrophin. Short term clinical and biochemical side effects are well established. Long term side effects are uncertain, but may include heart failure, mood-and anxiety disorders, hypogonadism and subfertility. We share our views on the management of common health problems associated with AAS abuse.
A genetic basis of congenital isolated hypogonadotropic hypogonadism (CHH) can be deined in almost 50% of cases, albeit not necessarily the complete genetic basis. Next-generation sequencing (NGS) techniques have led to the discovery of a great number of loci, each of which has illuminated our understanding of human gonadotropin-releasing hormone (GnRH) neurons, either in respect of their embryonic development or their neuroendocrine regulation as the "pilot light" of human reproduction. However, because each new gene linked to CHH only seems to underpin another small percentage of total patient cases, we are still far from achieving a comprehensive understanding of the genetic basis of CHH. Patients have generally not beneited from advances in genetics in respect of novel therapies. In most cases, even genetic counselling is limited by issues of apparent variability in expressivity and penetrance that are likely underpinned by oligogenicity in respect of known and unknown genes. Robust genotype-phenotype relationships can generally only be established for individuals who are homozygous, hemizygous or compound heterozygotes for the same gene of variant alleles that are predicted to be deleterious. While certain genes are purely associated with normosmic CHH (nCHH) some purely with the anosmic form (Kallmann syndrome-KS), other genes can be associated with both nCHH and KS-sometimes even within the same kindred. Even though the anticipated genetic overlap between CHH and constitutional delay in growth and puberty (CDGP) has not materialised, previously unanticipated genetic relationships have emerged, comprising conditions of combined (or multiple) pituitary hormone deiciency (CPHD), hypothalamic amenorrhea (HA) and CHARGE syndrome. In this review, we report the current evidence in relation to phenotype and genetic peculiarities regarding 60 genes whose loss-of-function variants can disrupt the central regulation of reproduction at many levels: impairing GnRH neurons migration, diferentiation or activation; disrupting neuroendocrine control of GnRH secretion; preventing GnRH neuron migration or function and/ or gonadotropin secretion and action.
Context:
Androgen abuse impairs male reproductive and cardiac function but the rate, extent and determinants of recovery are not understood.
Objective:
To investigate recovery of male reproductive and cardiac function after ceasing androgen intake in current and past androgen abusers compared with healthy non-users.
Methods:
Cross-sectional, observational study recruited via social media 41 current and 31 past users (≥3 months since last use, median 300 days since last use) with 21 healthy, eugonadal non-users. Each provided a history, examination, serum and semen sample and underwent testicular ultrasound, body composition analysis and cardiac function evaluation.
Results:
Current abusers had suppressed reproductive function, impaired cardiac systolic function and lipoprotein parameters compared with non or past users. Past users did not differ from non-users suggesting full recovery of suppressed reproductive and cardiac functions after ceasing androgen abuse, other than residual reduced testicular volume. Mean time to recovery was faster for reproductive hormones (AMH, 7.3 months; LH, 10.7 months) than for sperm variables (output, 14.1 months) whereas spermatogenesis (serum FSH, inhibin B, inhibin) took longer. The duration of androgen abuse was the only other variable associated with slower recovery of sperm output (but not hormones).
Conclusion:
Suppressed testicular and cardiac function due to androgen abuse is effectively fully reversible (apart from testis volume and serum SHBG) with recovery taking between 6 to 18 months after ceasing androgen intake with possible cumulative effects on spermatogenesis. Suppressed serum AMH, LH and FSH represent convenient, useful and underutilized markers of recovery from androgen abuse.
For decades researchers have reported men who engaged in intensive exercise training can develop low resting testosterone levels, alterations in their hypothalamic-pituitary-gonadal (HPG) axis, and display hypogonadism. Recently there is renewed interest in this topic since the International Olympic Committee (IOC) Medical Commission coined the term "Relative Energy Deficiency in Sports" (RED-S) as clinical terminology to address both the female-male occurrences of reproductive system health disruptions associated with exercise. This IOC Commission action attempted to move beyond the sex-specific terminology of the "Female Athlete Triad" (Triad) and heighten awareness/realization that some athletic men do have reproductive related physiologic disturbances such as lowered sex hormone levels, HPG regulatory axis alterations, and low bone mineral density similar to Triad women. There are elements in the development and symptomology of exercise-related male hypogonadism that mirror closely that of women experiencing the Triad/RED-S, but evidence also exists that dissimilarities exist between the sexes on this issue. Our research group postulates that the inconsistency and differences in the male findings in relation to women with Triad/RED-S are not just due to sex dimorphism, but that there are varying forms of exercise-related reproductive disruptions existing in athletic men resulting in them displaying a relative hypogonadism condition. Specifically, such conditions in men may derive acutely and be associated with low energy availability (Triad/RED-S) or excessive training load (overtraining) and appear transient in nature, and resolve with appropriate clinical interventions. However, manifestations of a more chronic based hypogonadism that persists on a more permanent basis (years) exist and is termed the "Exercise Hypogonadal Male Condition." This article presents an up-to-date overview of the various types of acute and chronic relative hypogonadism found in athletic, exercising men and proposes mechanistic models of how these various forms of exercise relative hypogonadism develop.
Hyperprolactinaemia is one of the most common problems in clinical endocrinology. It relates with various aetiologies (physiological, pharmacological, pathological), the clarification of which requires careful history taking and clinical assessment. Analytical issues (presence of macroprolactin or of the hook effect) need to be taken into account when interpreting the prolactin values. Medications and sellar/parasellar masses (prolactin secreting or acting through "stalk effect") are the most common causes of pathological hyperprolactinaemia. Hypogonadism and galactorrhoea are well-recognized manifestations of prolactin excess, although its implications on bone health, metabolism and immune system are also expanding. Treatment mainly aims at restoration and maintenance of normal gonadal function/fertility, and prevention of osteoporosis; further specific management strategies depend on the underlying cause. In this review, we provide an update on the diagnostic and management approaches for the patient with hyperprolactinaemia and on the current data looking at the impact of high prolactin on metabolism, cardiovascular and immune systems.
Aromatase activity has commonly been associated with male infertility characterized by testicular dysfunction with low serum testosterone and/or testosterone to estradiol ratio. In this subset of patients, and particularly in those with hypogonadism, elevated levels of circulating estradiol may establish a negative feedback on the hypothalamic-pituitary-testicular axis by suppressing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) production and impaired spermatogenesis. Hormonal manipulation via different agents such as selective estrogen modulators or aromatase inhibitors to increase endogenous testosterone production and improve spermatogenesis in the setting of infertility is an off-label option for treatment. We carried out a systematic review and meta-analysis of the literature of the past 30 years in order to evaluate the benefits of the use of aromatase inhibitors in the medical management of infertile/hypoandrogenic males. Overall, eight original articles were included and critically evaluated. Either steroidal (Testolactone) or nonsteroidal (Anastrozole and Letrozole) aromatase inhibitors were found to statistically improve all the evaluated hormonal and seminal outcomes with a safe tolerability profile. While the evidence is promising, future prospective randomized placebo-controlled multicenter trials are necessary to better define the efficacy of these medications.
Context
The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear.
Objective
The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.
Methods
Eight electronic databases were searched for articles published up to May 8, 2018. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals. This study is reported following the PRISMA- and MOOSE-guidelines.
Data Synthesis
52 studies (22 low risk of bias) were included describing 18,428 subjects, consisting of patients with chronic pain (n=21 studies), or on maintenance treatment for opioid addiction (n=9) and healthy volunteers (n=4). The most frequently used opioid was methadone (n=13 studies), followed by morphine (n=12). Prevalence of hypogonadism was 63% (95% CI: 55-70%, 15 studies, 3,250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and non-dynamic testing was 15% (95% CI: 6-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16-33%, 2 studies, n=97 patients). In 5 out of 7 studies hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described.
Conclusions
Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately a fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.
The single most significant risk factor for testosterone deficiency in men is obesity. The pathophysiological mechanisms involved in male obesity-related secondary hypogonadism are highly complex. Obesity-induced increase in levels of leptin, insulin, proinflammatory cytokines and oestrogen can cause a functional hypogonadotrophic hypogonadism with the defect present at the level of the hypothalamic gonadotrophin-releasing hormone (GnRH) neurons. The resulting hypogonadism by itself can worsen obesity, creating a self-perpetuating cycle. Obesity-induced hypogonadism is reversible with substantial weight loss. Lifestyle-measures form the cornerstone of management as they can potentially improve androgen deficiency symptoms irrespective of their effect on testosterone levels. In selected patients, bariatric surgery can reverse the obesity-induced hypogonadism. If these measures fail to relieve symptoms and to normalise testosterone levels, in appropriately selected men, testosterone replacement therapy could be started. Aromatase inhibitors and selective oestrogen receptor modulators are not recommended due to lack of consistent clinical trial-based evidence.
Men with hypogonadotropic hypogonadism (HH) are typically azoospermic, and yet HH is one of the few treatable forms of male infertility. Sperm induction protocols using gonadotrophins aim to replicate the natural endocrine control of spermatogenesis. Previously virilised men with adult‐onset HH and normal testicular volume respond well to monotherapy in which human chorionic gonadotrophin (hCG) acts as a long‐acting LH‐analogue stimulating spermatogenesis. However, this approach is rarely successful for men with congenital HH (CHH) (e.g. Kallmann syndrome), for whom combined gonadotrophin therapy (hCG + follicle stimulating hormone [FSH]) is an absolute requirement to maximize fertility potential. Key baseline predictors of successful spermatogenesis‐induction include prior spontaneous testicular development (i.e. testicular volume [TV] >4ml), serum inhibin B (IB) concentration >60pg/ml and no history of maldescended testes (cryptorchidism).
This article is protected by copyright. All rights reserved.
Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype – phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.
Keywords
Androgen insensitivity syndrome; androgen receptor; disorders of sex development; 46,XY DSD
Purpose:
Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. This review summarises the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population.
Methods:
We searched PubMed, Web of Science, and Scopus for manuscripts published prior to November 2017 using key words "Klinefelter syndrome" AND "insulin resistance" OR "metabolic syndrome" OR "diabetes mellitus" OR "cardiovascular disease" OR "testosterone". Manuscripts were collated, studied and carried forward for discussion where appropriate.
Results:
Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system.
Conclusion:
Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS.
Context:
Current knowledge on gonadal function in Congenital Adrenal Hyperplasia (CAH) is mostly limited to single center/country studies enrolling small patient numbers. Overall data indicate that gonadal function can be compromised in men with CAH.
Objective:
To determine gonadal function in men with CAH within the European "dsd-LIFE" cohort.
Design:
Cross-sectional clinical outcome study, including retrospective data from medical records.
Methods:
Fourteen academic hospitals included 121 men with CAH aged 16-68 years. Main outcome measures were serum hormone concentrations, semen parameters, and imaging data of the testes.
Results:
At the time of assessment, 14/69 patients had a serum testosterone concentration below the reference range; 7 of those were hypogonadotropic, 6 normogonadotropic, and 1 hypergonadotropic. In contrast, among the patients with normal serum testosterone (55/69), 4 were hypogonadotropic, 44 normogonadotropic, and 7hypergonadotropic. The association of decreased testosterone with reduced gonadotropin concentrations (Odds Ratio (OR)=12.8 [2.9-57.3]) was weaker than the association between serum androstenedione/testosterone ratio≥1 and reduced gonadotropin concentrations (OR=39.3 [2.1-732.4]). Evaluation of sperm quality revealed decreased sperm concentrations (15/39), motility (13/37), and abnormal morphology (4/28). Testicular adrenal rest tumor (TART)s were present in 39/80 patients, with a higher prevalence in patients with the most severe genotype (14/18), and in patients with increased current 17-hydroxyprogesterone (20/35) or androstenedione (12/18) serum concentrations. Forty-three children were fathered by 26/113 patients.
Conclusions:
Men with CAH have a high risk of developing hypothalamic-pituitary-gonadal disturbances and spermatogenic abnormalities. Regular assessment of endocrine gonadal function and imaging for TART development are recommended, in addition to measures for fertility protection.
Background:
Herein, we describe the consensus guideline methodology, summarize the evidence-based recommendations we provided to the World Health Organization (WHO) for their consideration in the development of global guidance and present a narrative review of the diagnosis of male infertility as related to the eight prioritized (problem or population (P), intervention (I), comparison (C) and outcome(s) (O) (PICO)) questions. Additionally, we discuss the challenges and research gaps identified during the synthesis of this evidence.
Objective and rationale:
The aim of this paper is to present an evidence-based approach for the diagnosis of male infertility as related to the eight prioritized PICO questions.
Search methods:
Collating the evidence to support providing recommendations involved a collaborative process as developed by WHO, namely: identification of priority questions and critical outcomes; retrieval of up-to-date evidence and existing guidelines; assessment and synthesis of the evidence; and the formulation of draft recommendations to be used for reaching consensus with a wide range of global stakeholders. For each draft recommendation the quality of the supporting evidence was then graded and assessed for consideration during a WHO consensus.
Outcomes:
Evidence was synthesized and recommendations were drafted to address the diagnosis of male infertility specifically encompassing the following: What is the prevalence of male infertility and what proportion of infertility is attributable to the male? Is it necessary for all infertile men to undergo a thorough evaluation? What is the clinical (ART/non ART) value of traditional semen parameters? What key male lifestyle factors impact on fertility (focusing on obesity, heat and tobacco smoking)? Do supplementary oral antioxidants or herbal therapies significantly influence fertility outcomes for infertile men? What are the evidence-based criteria for genetic screening of infertile men? How does a history of neoplasia and related treatments in the male impact on (his and his partner's) reproductive health and fertility options? And lastly, what is the impact of varicocele on male fertility and does correction of varicocele improve semen parameters and/or fertility?
Wider implications:
This evidence synthesis analysis has been conducted in a manner to be considered for global applicability for the diagnosis of male infertility.
Background:
Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality.
Objective and rationale:
To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group.
Search methods:
PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981-2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973-2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group ('Unselected by fertility' versus 'Fertile'), geographic group ('Western', including North America, Europe Australia and New Zealand versus 'Other', including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models.
Outcomes:
SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models -0.70 million/ml/year; 95% CI: -0.72 to -0.69; P < 0.001; slope in adjusted meta-regression models = -0.64; -1.06 to -0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (-1.38; -2.02 to -0.74; P < 0.001) and among Fertile Western (-0.68; -1.31 to -0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (-5.33 million/year, -7.56 to -3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (-2.06 million/ml, -3.38 to -0.74; P = 0.004 and -8.12 million, -13.73 to -2.51, P = 0.006, respectively).
Wider implications:
This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50-60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.
The Y chromosome harbors a number of genes essential for testis development and function. Its highly repetitive structure predisposes this chromosome to deletion/duplication events and is responsible for Y-linked copy-number variations (CNVs) with clinical relevance. The AZF deletions remove genes with predicted spermatogenic function en block and are the most frequent known molecular causes of impaired spermatogenesis (5-10% of azoospermic and 2-5% of severe oligozoospermic men). Testing for this deletion has both diagnostic and prognostic value for testicular sperm retrieval in azoospermic men. The most dynamic region on the Yq is the AZFc region, presenting numerous NAHR hotspots leading to partial losses or gains of the AZFc genes. The gr/gr deletion (a partial AZFc deletion) negatively affects spermatogenic efficiency and it is a validated, population-dependent risk factor for oligozoospermia. In certain populations, the Y background may play a role in the phenotypic expression of partial AZFc rearrangements and similarly it may affect the predisposition to specific deletions/duplication events. Also, the Yp contains a gene array, TSPY1, with potential effect on germ cell proliferation. Despite intensive investigations during the last 20 years on the role of this sex chromosome in spermatogenesis, a number of clinical and basic questions remain to be answered. This review is aimed at providing an overview of the role of Y chromosome-linked genes, CNVs, and Y background in spermatogenesis.
Introduction:
Testis was considered unresponsive to thyroid hormone for a long time. However, like in animals, the presence of thyroid hormone receptors in different testicular cell types was demonstrated also in humans. Accordingly, thyrotoxicosis and hypothyroidism have remarkable effects on testicular function and more extensively on fertility.
Review:
Thyrotoxicosis and hypothyroidism are associated with changes affecting the endocrine, sexual, or reproductive functions. Particularly, compared with controls, hyperthyroid patients have higher serum SHBG and lower free and bioavailable testosterone concentrations, a higher rate of astheno-zoospermia, oligo-zoospermia, and terato-zoospermia, and a higher prevalence of sexual disturbances, such as premature ejaculation. In hypothyroid patients, hormonal changes are in the opposite direction compared with hyperthyroid patients. Thyroid hormone regulates a number of functions in the testis, such as proliferation and differentiations of non-germ cells, steroidogenesis, and sperm motility. Furthermore, thyroid hormone regulates testicular redox status. Consequently, thyroid hormone excess or deficiency can affect testicular function at different levels.
Conclusions:
In view of the high prevalence of thyrotoxicosis and hypothyroidism, a considerable part of infertile patients may harbor overt or subclinical thyroid disease. Identification and management of thyrotoxicosis/hypothyroidism associated infertility needs the collaboration of andrologists, endocrinologists, gynecologists, and general practitioners.
Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6–3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4–17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9–17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.
Background
Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system. Objective
This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users. Methods
An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation. ResultsThirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) −3.37 IU/L, 95% confidence interval (CI) −5.05 to −1.70, p < 0.001], follicle-stimulating hormone (WMD −1.73 IU/L, 95% CI −2.67 to −0.79, p < 0.001), and endogenous testosterone levels (WMD −10.75 nmol/L, 95% CI −15.01 to −6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13–24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD −9.40 nmol/L, 95% CI −14.38 to −4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility. Conclusion
The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.
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.
Both pulsatile gonadotropin-releasing hormone (GnRH) infusion and combined gonadotropin therapy (human chorionic gonadotropin and human menopausal gonadotropin [HCG/HMG]) are effective to induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism (CHH). However, evidence is lacking as to which treatment strategy is better. This retrospective cohort study included 202 patients with CHH: twenty had received pulsatile GnRH and 182 had received HCG/HMG. Patients had received therapy for at least 12 months. The total follow-up time was 15.6 ± 5.0 months (range: 12-27 months) for the GnRH group and 28.7 ± 13.0 months (range: 12-66 months) for the HCG/HMG group. The median time to first sperm appearance was 6 months (95% confidence interval [CI]: 1.6-10.4) in the GnRH group versus 18 months (95% CI: 16.4-20.0) in the HCG/HMG group (P < 0.001). The median time to achieve sperm concentrations ≥5 × 10 6 ml-1 was 14 months (95% CI: 5.8-22.2) in the GnRH group versus 27 months (95% CI: 18.9-35.1) in the HCG/HMG group (P < 0.001), and the median time to concentrations ≥10 × 10 6 ml-1 was 18 months (95% CI: 10.0-26.0) in the GnRH group versus 39 months (95% CI unknown) in the HCG/HMG group. Compared to the GnRH group, the HCG/HMG group required longer treatment periods to achieve testicular sizes of ≥4 ml, ≥8 ml, ≥12 ml, and ≥16 ml. Sperm motility (a + b + c percentage) evaluated in semen samples with concentrations >1 × 10 6 ml-1 was 43.7% ± 20.4% (16 samples) in the GnRH group versus 43.2% ± 18.1% (153 samples) in the HCG/HMG group (P = 0.921). Notably, during follow-up, the GnRH group had lower serum testosterone levels than the HCG/HMG group (8.3 ± 4.6 vs 16.2 ± 8.2 nmol l-1 , P < 0.001). Our study found that pulsatile GnRH therapy was associated with earlier spermatogenesis and larger testicular size compared to combined gonadotropin therapy. Additional prospective randomized studies would be required to confirm these findings.
BACKGROUND
A varicocele is a meshwork of distended blood vessels in the scrotum, usually left-sided, due to dilatation of the spermatic vein. Although the concept that a varicocele causes male subfertility has been around for more than 50 years now, the mechanisms by which a varicocele would affect fertility have not yet been satisfactorily explained. Neither is there sufficient evidence to explain the mechanisms by which varicocelectomy would restore fertility. Furthermore, it has been questioned whether a causal relation exists at all between the distension of the pampiniform plexus (a network of many small veins found in the human male spermatic cord) and impairment of fertility.
OBJECTIVES
To evaluate the effect of varicocele treatment on live birth and pregnancy rate in subfertile couples where the male has a varicocele.
METHODS
Search
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (12 September 2003 to January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 1, 2012), Medline (January 1966 to January 2012), Embase (January 1985 to January 2012), PsycINFO (to Week 1 2012) and reference lists of articles. In addition, we handsearched specialist journals in the field from their first issue until 2012. We also checked cross-references, references from review articles and contacted researchers in the field.
Selection criteria
Randomized controlled trials (RCTs) were included if they were relevant to the clinical question posed. If they reported pregnancy rates or live birth rates as an outcome measure, and if they reported data in treated (surgical ligation or radiological embolization of the internal spermatic vein) compared to untreated or placebo groups. Two authors independently screened potentially relevant trials. Any differences of opinion were resolved by consensus (none occurred for this review).
Data collection and analysis
Ten studies met the inclusion criteria for the review. For one study we had only data from a published abstract. All ten studies only included men from couples with subfertility problems; one excluded men with sperm counts less than 5 million per mL and one excluded men with sperm counts less than 2 million per mL, with or without progressive motility of less than 10%. Two trials involving clinical varicoceles included some men with normal semen analysis. Three studies specifically addressed only men with subclinical varicoceles. Studies were excluded from meta-analysis if they made comparisons other than those specified above.
Search
We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (12 September 2003 to January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 1, 2012), Medline (January 1966 to January 2012), Embase (January 1985 to January 2012), PsycINFO (to Week 1 2012) and reference lists of articles. In addition, we handsearched specialist journals in the field from their first issue until 2012. We also checked cross-references, references from review articles and contacted researchers in the field.
Selection criteria
Randomized controlled trials (RCTs) were included if they were relevant to the clinical question posed. If they reported pregnancy rates or live birth rates as an outcome measure, and if they reported data in treated (surgical ligation or radiological embolization of the internal spermatic vein) compared to untreated or placebo groups. Two authors independently screened potentially relevant trials. Any differences of opinion were resolved by consensus (none occurred for this review).
Data collection and analysis
Ten studies met the inclusion criteria for the review. For one study we had only data from a published abstract. All ten studies only included men from couples with subfertility problems; one excluded men with sperm counts less than 5 million per mL and one excluded men with sperm counts less than 2 million per mL, with or without progressive motility of less than 10%. Two trials involving clinical varicoceles included some men with normal semen analysis. Three studies specifically addressed only men with subclinical varicoceles. Studies were excluded from meta-analysis if they made comparisons other than those specified above.
MAIN RESULTS
The meta-analysis included 894 men. No studies reported live birth. The combined fixed-effect odds ratio (OR) of the 10 studies for the outcome of pregnancy was 1.47 (95% confidence interval (CI) 1.05 to 2.05, very low quality evidence), favouring the intervention. The number needed to treat for an additional beneficial outcome was 17, suggesting benefit of varicocele treatment over expectant management for pregnancy rate in subfertile couples in whom varicocele in the man was the only abnormal finding. Omission of the studies including men with normal semen analysis and subclinical varicocele, some of which had semen analysis improvement as the primary outcome rather than live birth or pregnancy rate, was the subject of a planned subgroup analysis. The outcome of the subgroup analysis (five studies) also favoured treatment, with a combined OR 2.39 (95% CI 1.56 to 3.66). The number needed to treat for an additional beneficial outcome was 7. The evidence was suggestive rather than conclusive, as the main analysis was subject to fairly high statistical heterogeneity (I2 = 67%) and findings were no longer significant when a random-effects model was used or when analysis was restricted to higher quality studies.
AUTHOR' CONCLUSIONS
There is evidence suggesting that treatment of a varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy. However, findings are inconclusive as the quality of the available evidence is very low and more research is needed with live birth or pregnancy rate as the primary outcome.
The purpose of this study is to evaluate whether follicle-stimulating hormone treatment improves sperm DNA parameters and pregnancy outcome in infertile male candidates to in-vitro fertilization.
Observational study in 166 infertile male partners of couples undergoing in-vitro fertilization. Eighty-four patients were receiving follicle-stimulating hormone treatment (cases) and 82 refused treatment (controls). Semen parameters, sexual hormones, and sperm nucleus (fluorescence in-situ hybridization, acridine orange, TUNEL, and γH2AX) were evaluated at baseline (T0) and after 3 months (T1), when all subjects underwent assisted reproduction techniques. Statistical analysis was performed by analysis of variance.
Compared to baseline, cases showed significant improvements in seminal parameters and DNA fragmentation indexes after follicle-stimulating hormone therapy (all P < 0.05), whereas no changes were observed in controls. Within cases, follicle-stimulating hormone treatment allowed to perform intrauterine insemination in 35 patients with a pregnancy rate of 23.2 %. Intracytoplasmic sperm injection was performed in all controls and in 49 patients from cases, with pregnancy rates of 23.2 and 40.8 %, respectively (P < 0.05). After 3 months (T0 vs. T1) of follicle-stimulating hormone therapy, cases with positive outcome had reduced DNA fragmentation index and lower double strand breaks (P < 0.05 and P < 0.001 vs. negative outcome, respectively).
In this observational study, we showed that follicle-stimulating hormone treatment improves sperm DNA fragmentation, which in turn leads to increased pregnancy rates in infertile males undergoing in-vitro fertilization. In particular, double strand breaks (measured with γH2AX test) emerged as the most sensible parameter to follicle-stimulating hormone treatment in predicting reproductive outcome.
Secondary pituitary enlargement due to primary hypothyroidism is not a common manifestation. The loss of thyroxin feedback inhibition in primary hypothyroidism causes overproduction of thyrotropin-releasing-hormone (TRH), which results in secondary pituitary enlargement. TRH has a weak stimulatory effect on the lactotroph cells of the pituitary, so a mild to moderate increase in prolactin (PRL) levels is expected. We report the case of a 67-year-old female who presented with a large pituitary mass and a very high level of TSH in association with a significant rise in PRL level. In this case, diagnosing a sellar mass was challenging; it was difficult to distinguish between pituitary prolactinoma and primary hypothyroidism with secondary pituitary hyperplasia. Thyroid hormone replacement proved that this patient’s hyperprolactinemia was due to hyperplasia of the pituitary gland. As such, making the correct diagnosis and initiating thyroid hormone therapy can prevent unnecessary treatment with dopamine agonists.
In this, our Second Edition of Reproduction in Mammals, we are responding to numerous requests for a more up-to-date and rather more detailed treatment of the subject. The First Edition was accorded an excellent reception, but the first five books were written ten years ago and inevitably there have been advances on many fronts since then. As before, the manner of presentation is intended to make the subject matter interesting to read and readily comprehensible to undergraduates in the biological sciences, and yet with sufficient depth to provide a valued source of information to graduates engaged in both teaching and research. Our authors have been selected from among the best known in their respective fields. This volume discusses the manifold ways in which hormones control the reproductive processes in male and female mammals. The hypothalamus regulates both the anterior and posterior pituitary glands, whilst the pineal can exert a modulating influence on the hypothalamus. The pituitary gonadotrophins regulate the endocrine and gametogenic activities of the gonads, and there are important local feedback effects of hormones within the gonads themselves. Non-pregnant females display many different types of oestrous or menstrual cycles, and there are likewise great species differences in the endocrinology of pregnancy. But the hallmark of mammals is lactation, and this also exerts a major control on subsequent reproductive activity.
Somatic health is associated with male infertility; potential links between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible connections between male infertility and oncologic, cardiovascular, metabolic, chronic, and autoimmune diseases. Male infertility also may be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health.
Objective
To assess whether paternal health is associated with maternal peripartum and neonatal outcomes.
Design
Retrospective cohort study.
Setting
University research departments.
Patient(s)
Analytic sample of children born to paired fathers and mothers covering live births within the United States between 2009–2016.
Intervention(s)
Paternal health status (e.g., metabolic syndrome diagnoses, individual chronic disease diagnoses).
Main Outcome Measure(s)
Primary outcome of preterm birth (i.e., live birth before 37 weeks), and secondary outcomes of low birth weight, neonatal intensive care unit (NICU) stay, gestational diabetes, preeclampsia, eclampsia, and length of maternal stay.
Result(s)
The IBM Marketscan Research database covers reimbursed health care claims data on inpatient and outpatient encounters who are privately insured through employment-sponsored health insurance. We assessed 785,809 singleton live births, with 6.6% born preterm. The presence of paternal comorbidities was associated with higher odds of preterm birth, low birth weight (LBW), and NICU stay. After adjusting for maternal factors, fathers with most or all components of the metabolic syndrome had 19% higher odds of having a child born preterm (95% CI 1.11–1.28), 23% higher odds of LBW (95% CI 1.01–1.51), and 28% higher odds of NICU stay (95% CI 1.08–1.52). Maternal morbidity (e.g., gestational diabetes or preeclampsia) was also positively associated with preconception paternal health.
Conclusion(s)
Increased preconception paternal comorbidity may be associated with negative infant and maternal outcomes. Although the paternal effect remains modest, these findings highlight the importance of the health of both parents, particularly the mother, on healthy pregnancy.
Male reproduction is a complex process, and numerous medical conditions have the potential to alter spermatogenesis. In addition, male factor infertility may be a biomarker for future health. In the present review, we discuss the current literature regarding the association between systemic diseases and fertility, which may impact clinical outcomes or semen parameters. A number of conditions that have systemic consequences were identified, including genetic (e.g., cystic fibrosis, DNA mismatch repair alterations), obesity, psychological stress, exogenous testosterone, and a variety of common medications. As such, the infertility evaluation may offer an opportunity for health counseling beyond the discussion of reproductive goals. Moreover, male infertility has been suggested as a marker of future health, given that poor semen parameters and a diagnosis of male infertility are associated with an increased risk of hypogonadism, cardiometabolic disease, cancer, and even mortality. Therefore, male fertility requires multidisciplinary expertise for evaluation, treatment, and counseling.
Importance
Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.
Objective
To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.
Design, Setting, and Participants
The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.
Interventions
Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.
Main Outcomes and Measures
The co–primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization.
Results
Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).
Conclusions and Relevance
Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples’ live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.
Trial Registration
ClinicalTrials.gov Identifier: NCT01857310
Opioids are pivotal therapeutics in the management of escalated chronic pain (moderate‐severe). In the last two decades, the increased prescription rate and the prolonged usage of opioids shed light on opioid‐induced endocrinopathy. Opioid‐induced hypogonadism (OHG) results upon long‐term opioid therapy. Clinically, patients with OHG are presented mainly by sexual dysfunction and infertility. Opioid clinical use in pain therapy is indispensable. However, the resultant sexual endocrinopathy cannot be overlooked and hence hormonal replacement therapy with regular monitoring of the patients represents a potential therapeutic strategy while avoiding opioids in patients with guaranteed long therapeutic exposure and switching to using low dose naltrexone as alternative represents a possible prophylactic measure to ensure therapeutic compliance and secure a good life quality of patients.
Context
The increased use of opioids has resulted in an unprecedented opioid epidemic. Chronic opioid use causes hypogonadism, but its frequency, as well as the effects of opioids on other hypothalamo-pituitary-end organ hormone axes, remains unclear.
Objective
The aim of this systematic review and meta-analysis was to assess the effects of opioid use on pituitary function.
Methods
Eight electronic databases were searched for articles published up to May 8, 2018. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions with 95% confidence intervals. This study is reported following the PRISMA- and MOOSE-guidelines.
Data Synthesis
52 studies (22 low risk of bias) were included describing 18,428 subjects, consisting of patients with chronic pain (n=21 studies), or on maintenance treatment for opioid addiction (n=9) and healthy volunteers (n=4). The most frequently used opioid was methadone (n=13 studies), followed by morphine (n=12). Prevalence of hypogonadism was 63% (95% CI: 55-70%, 15 studies, 3,250 patients, 99.5% males). Prevalence of hypocortisolism relying on dynamic and non-dynamic testing was 15% (95% CI: 6-28%, 5 studies, 205 patients, 57.5% males) and including only studies using the insulin tolerance tests 24% (95% CI 16-33%, 2 studies, n=97 patients). In 5 out of 7 studies hyperprolactinemia was present. No clear effects on the somatotropic and hypothalamo-pituitary-thyroid axes were described.
Conclusions
Hypogonadism occurs in more than half of male opioid users, and hypocortisolism in approximately a fifth of all patients. Periodical evaluation of at least the gonadal and adrenal axes is therefore advisable.
Background: Selective estrogen receptor modulators (SERMs) represent a poorly investigated class of drugs for the treatment of male infertility. The aim of this study was to assess the effects of SERMs on conventional sperm parameters, serum gonadotropin and testosterone levels, and pregnancy rate in patients with idiopathic infertility.
Methods: The authors performed a comprehensive systematic review with meta-analysis of all available controlled and not-controlled studies of the literature reporting sperm conventional parameters, gonadotropin and testosterone levels, and/or the pregnancy rate following SERM administration in normogonadotropic patients with idiopathic oligozoospermia.
Results: From the 418 papers retrieved, 16 controlled and not-controlled trials were lastly included. SERM administration increased significantly sperm concentration, total sperm count, and serum luteinizing hormone, follicle-stimulating hormone, and total testosterone levels compared with baseline values. In contrast, SERMs did not have any significant effect on sperm concentration and progressive and total motility, but improved total sperm count, sperm morphology, and increased the pregnancy rate compared to the control group, which included studies done with placebo or other treatments.
Conclusions: The results of this meta-analysis suggest that SERMs may be effective in the treatment of infertile patients with idiopathic infertility. However, the paucity of data does not allow to draw a definitive conclusion.
Study question:
What is the natural history of outcomes of sperm cryostorage at an Australian tertiary academic centre?
Summary answer:
Cryostorage is feasible in virtually all men facing gonadotoxic therapy but the timing of sperm disposal varies according to the reason for it.
What is known already:
Gonadotoxic treatment for cancer or non-cancer diseases damages spermatogenesis and impairs male fertility. Sperm cryopreservation is an established technique to preserve male fertility prior to gonadotoxic treatment.
Study design, size, duration:
A retrospective review of clinical, anthropometric, semen analysis and hormonal data from 1978 to 2017 involving 2717 men comprising 2085 men with cancer, 234 non-cancer disease and 398 healthy controls, in a single tertiary academic centre with the same clinic and laboratory staff.
Participants/materials, setting and methods:
Sperm output was analysed according to diseases, the feasibility of sperm cryostorage notably for adolescents, regional access to an urban cryostorage facility, the determinants of sperm output and time-dependent disposal of cryostored sperm. Semen samples were assessed by contemporaneous WHO methods.
Main results and the role of chance:
Of 2085 men with cancer, 904 (43%) had haematological malignancies, 680 (33%) testicular cancers and 136 (6.5%) were adolescents. Most men (89%) and adolescents (80%) could collect sperm. Sperm output for all cancers and non-cancer diseases was lower than controls. Sperm output correlated positively with total testicular volume (r = 0.44, P < 0.0001) and negatively with serum FSH and LH (r = -0.24, -0.12, respectively, both P < 0.0001) but not testosterone. For all stored samples, the median time in cryostorage was 8.5 years, 7% were transferred for use to induce pregnancy (median time 2.5 years) and 62.2% were discarded as no longer needed (return of fertility, 35.9% median 3.5 years; death, 26.3%, median 6.5 years), the high disposal rate reflecting regular annual follow-up to establish ongoing need for continued cryostorage. Cryostorage facilities are not available in remote and rural areas of the State and the proportion of outer regional and remote area residents cryostoring sperm was only about half that compared with urban residents.
Limitations, reasons for caution:
This study does not report the pregnancy outcomes of the patients who used the cryostored sperm, due to recent limitations on health data privacy.
Wider implications of the findings:
Sperm cryostorage is feasible for virtually all men, including sufficiently mature adolescents, who can collect semen to insure future paternity as well as making positive psychological preparation for the patient's survival. Disposal of cryostored material when no longer required is efficient with regular follow-up. Sperm cryopreservation should be an integral part of comprehensive treatment plan in men receiving gonadotoxic treatment but remains underutilized.
Study funding/competing interest(s):
There was no external funding for this study and there were no relevant conflicts of interest.
Serum testosterone values vary considerably with little correlation to intratesticular testosterone (ITT). ITT is approximately ~100 times that of serum testosterone and is critical for spermatogenesis. Unfortunately, the only method to accurately measure ITT is invasive testicular aspiration and therefore is not performed routinely. The identification of a serum biomarker for ITT would allow serial monitoring during hormonal manipulation and the ability to assess the effectiveness of a male contraceptive agent. Prior studies have evaluated several serum biomarkers for their ability to accurately reflect ITT with data supporting 17-hydroxyprogesterone (17-OHP) and insulin-like factor 3 (INSL3) as a potential marker. Because evaluation of serum 17-OHP is readily available through commercial laboratories, in this review, we present the evidence for 17-OHP and how it can play a pivotal role in the management of male infertility.
Ejaculatory duct obstruction is an uncommon but surgically correctable cause of male infertility. With the advent and increased use of high-resolution transrectal ultrasonography, anomalies of the ejaculatory ducts related to infertility have been well documented. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, the diagnosis should be suspected in an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes, and hormonal profile, and dilated seminal vesicles, midline cyst, or calcifications on transrectal ultrasound (TRUS). Although additional larger prospective and comparative studies are needed, it appears that TRUS with aspiration is the most effective method for diagnosis. While intrusive, it is less invasive than vasography. The most robust and published evidence for treatment involves transurethral resection of ejaculatory duct (TURED). More recent experience with antegrade endoscopic approaches are promising and may also be considered. An alternative to surgeries for reversal of obstruction is sperm retrieval for in vitro fertilization/intracytoplasmic sperm injection. A thorough discussion of all alternatives, including risks and benefits, should be held with couples facing this uncommon condition to allow them to make informed decisions regarding management.
The initiation and maintenance of reproductive capacity in humans is dependent upon pulsatile secretion of the hypothalamic hormone gonadtropin-releasing hormone, GnRH. Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder that results from the failure of the normal episodic GnRH secretion, leading to delayed puberty and infertility. CHH can be associated with an absent sense of smell, also termed Kallmann syndrome, or with other anomalies. CHH is characterized by rich genetic heterogeneity, with mutations in more than 30 genes identified to date acting either alone or in combination. CHH can be challenging to diagnose, particularly in early adolescence where the clinical picture mirrors that of constitutional delay of growth and puberty. Timely diagnosis and treatment will induce puberty, leading to improved sexual, bone, metabolic and psychological health. In most cases, patients require lifelong treatment yet a significant portion of male patients (around 10-20%) exhibit a spontaneous recovery of their reproductive function. Finally, fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in a majority of patients. In summary, this review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management and genetic foundations of congenital hypogonadotropic hypogonadism relative to normal reproductive development.
Oxidative stress (OS), defined as an overabundance of reactive oxygen species (ROS) or a deficiency of antioxidants, has been linked to sperm damage and male infertility. There are many sources of OS and inflammation including varicocele, tobacco usage, alcohol, obesity/metabolic syndrome, leukocytospermia, sexually transmitted disease (i.e., Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum), bacterial prostatitis, microorganism mutations leading to more OS, and viral infections (i.e., human immunodeficiency virus, hepatitis). This review is focusing on infection and inflammation‐mediated OS, the inflammatory markers underlying pathology, clinical significance in male infertility, and a brief description of the recommended treatment modalities.
Introduction: Infertility is one of the great challenges of modern healthcare. It afflicts about 8–12% of reproductive-aged couples worldwide, but the prevalence is even higher in industrialized countries. In 50% of cases, a male factor of infertility underlies the problem, but in about 30% of these cases the etiology of male infertility remains unknown. This eventuality, called idiopathic infertility, requires empirical medical therapy and/or assisted reproductive techniques.
Areas covered: This article reviews the literature about the medical treatments available for idiopathic male infertility. These treatments can be divided into two main categories: hormonal therapies and non-hormonal therapies. The compounds with the strongest evidence of efficacy and the most used in clinical practice for the treatment of idiopathic male infertility are follicle-stimulating hormone (FSH) and estrogen receptor selective modulators (SERMs). Non-hormonal treatments include a series of compounds with antioxidant and prokinetic properties, supported by variable degrees of evidence of clinical efficacy.
Expert opinion: Patients with idiopathic infertility have peculiar clinical features that differentiate them from each other. Therapy must, therefore, be personalized to each patient. Furthermore, scientific research must investigate the pathophysiological mechanisms that underlie infertility; only in this way, new targeted therapies can be developed.
There is an emerging body of evidence suggesting that male infertility may be a harbinger of future health. Potential associations between infertility and health may arise from genetic, developmental, and lifestyle factors. Studies have explored possible links between male infertility and oncologic, cardiovascular, metabolic, and autoimmune diseases. Male infertility may also be a predictor of hospitalization and mortality. Additional research is required to elucidate the mechanisms by which male infertility affects overall health.
Delivering serious, bad, or life-altering news to a patient is one of the most difficult tasks physicians encounter. Broadly defined as information that may alter a patient’s view of his or her future, bad news may include information related to a chronic disease (e.g., diabetes mellitus), a life-altering illness (e.g., multiple sclerosis), or an injury leading to significant change (e.g., a season-ending knee injury). Patients prefer to receive such news in person, with the physician’s full attention, and in clear, easy-to-understand language with adequate time for questions. Most patients prefer to know their diagnosis, but the amount of desired details varies among different cultures and by education level, age, and sex. The physician should respect the patient’s unique preferences for receiving bad news. Physicians may experience stress related to providing bad news that extends beyond the actual conversation. For example, physicians are afraid of eliciting an emotional reaction, being blamed for the bad news, and expressing their emotions during the process. Physicians often withhold information or are overly optimistic regarding prognosis, but this can lead to confusion for patients regarding their condition. There are several algorithms available to help guide the physician in the delivery of bad news, including the SPIKES protocol (setting, perception, invitation, knowledge, emotion, and strategy and summary). Skillful delivery of bad news can provide comfort for the patient and family.
Background
Oligo‐astheno‐teratozoospermia is frequently reported in men from infertile couples. Its etiology remains, in the majority of cases, unknown with a variety of factors to contribute to its pathogenesis. The aim of this European Academy of Andrology guideline was to provide an overview of these factors and to discuss available management options.
Materials and Methods
PubMed was searched for papers in English for articles with search terms: male infertility and oligo‐astheno‐teratozoospermia. For evidence‐based recommendations, the GRADE system was applied. Issues related to urogenital infections/inflammations have not been included in this document as they will be covered by separate guidelines.
Results
For men with oligo‐astheno‐teratozoospermia, the European Academy of Andrology recommends:
• A general physical examination to assess signs of hypogonadism.
• A scrotal physical examination to assess (i) the testes and epididymes for volume and consistency, (ii) deferent ducts for total or partial absence, and (iii) occurrence of varicocoele.
• Performing two semen analyses, according to World Health Organization guidelines to define an oligo‐astheno‐teratozoospermia.
• An endocrine evaluation.
• A scrotal ultrasound as part of routine investigation.
• Karyotype analysis and assessment of Yq microdeletions in infertile men with a sperm concentration ≤5 × 10⁶/mL.
• Cystic fibrosis transmembrane conductance regulator gene evaluation in case of suspicion for incomplete congenital obstruction of the genital tract.
• Against quitting physical activity to improve the chance of achieving pregnancy.
• Against androgen replacement therapy to improve the chance of achieving pregnancy.
• Assisted reproduction techniques to improve the chance of achieving pregnancy, in case other treatment options are not available or not efficient.
• Androgen replacement therapy in patients with biochemical/clinical signs of hypogonadism, after completion of the fertility treatment.
Conclusion
These guidelines can be applied in clinical work and indicate future research needs.
Reproductive health is a common concern and often a source of distress for male childhood, adolescent, and young adult cancer survivors. Clinical and epidemiologic research in survivor populations has identified alkylating agent chemotherapy, testicular radiation, and surgery or radiation to the genitourinary organs, lower spine, or the hypothalamic-pituitary region as risk factors for adverse reproductive outcomes, including impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction. Much of the research on male survivors has focused on the outcome of fertility, using spermatogenesis, serum gonadotropins, and paternity as the measures. However, these studies often fail to account for the clinically relevant but difficult-to-quantify aspects of fertility such as sexual function, cancer-related delayed psychosocial development, medical comorbidities, and socioeconomic concerns. Clinical and basic science research has made significant contributions to improving reproductive outcomes for survivors, with recent advancements in the areas of fertility preservation, clinical assessment of reproductive function, and treatment of adverse reproductive outcomes. Furthermore, there is an emerging qualitative literature addressing the psychosexual aspects of male reproductive health, the clinical application of which will improve quality of life for survivors. This review summarizes the current survivorship literature on reproductive health outcomes for male survivors, including the epidemiology of impaired spermatogenesis, testosterone insufficiency, and sexual dysfunction; clinical and laboratory assessment of reproductive function; and established and investigational interventions to preserve reproductive function for patients newly diagnosed and survivors. Although survivorship research has made significant contributions to improving reproductive outcomes, additional scientific progress is needed in the areas of fertility preservation, risk assessment, and psychosexual support with the aim of optimizing reproductive health for current and future survivors.
Male infertility is a multifactorial pathological condition affecting approximately 7% of the male population. The genetic landscape of male infertility is highly complex as semen and testis histological phenotypes are extremely heterogeneous, and at least 2,000 genes are involved in spermatogenesis. The highest frequency of known genetic factors contributing to male infertility (25%) is in azoospermia, but the number of identified genetic anomalies in other semen and aetiological categories is constantly growing. Genetic screening is relevant for its diagnostic value, clinical decision making, and appropriate genetic counselling. Anomalies in sex chromosomes have major roles in severe spermatogenic impairment. Autosome-linked gene mutations are mainly involved in central hypogonadism, monomorphic teratozoospermia or asthenozoospermia, congenital obstructive azoospermia, and familial cases of quantitative spermatogenic disturbances. Results from whole-genome association studies suggest a marginal role for common variants as causative factors; however, some of these variants can be important for pharmacogenetic purposes. Results of studies on copy number variations (CNVs) demonstrate a considerably higher CNV load in infertile patients than in normozoospermic men, whereas whole-exome analysis has proved to be a highly successful diagnostic tool in familial cases of male infertility. Despite such efforts, the aetiology of infertility remains unknown in about 40% of patients, and the discovery of novel genetic factors in idiopathic infertility is a major challenge for the field of androgenetics. Large, international, and consortium-based whole-exome and whole-genome studies are the most promising approach for the discovery of the missing genetic aetiology of idiopathic male infertility.
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.
The use of pseudoephedrine, an alpha agonist, for the treatment of retrograde ejaculation is well-known, however, there is no clear consensus from the literature regarding its efficacy and treatment protocol. We evaluated the efficacy of pseudoephedrine treatment in patients with retrograde ejaculation, utilizing a yet undescribed short-period treatment protocol. Twenty men were medically treated with pseudoephedrine for retrograde ejaculation between January 2010 and May 2016 (12 with complete retrograde ejaculation and 8 with partial retrograde ejaculation). All patients had a semen analysis and post-ejaculatory urinalysis before and after treatment. The treatment protocol consisted of 60 mg of pseudoephedrine every 6 h on the day before semen analysis and two more 60 mg doses on the day of the semen analysis. Diabetes was the most common etiology for complete retrograde ejaculation (60%), whereas an idiopathic cause was the most common etiology for partial retrograde ejaculation (82%). Of the 12 complete retrograde ejaculation patients treated with pseudoephedrine prior to semen analysis, 7 (58.3%) recovered spermatozoa in the antegrade ejaculate, with a mean total sperm count of 273.5 ± 172.5 million. Of the eight patients with partial retrograde ejaculation, five (62.5%) had a ≥50% increase in the antegrade total sperm count. In this group, the mean total sperm count increased from 26.9 ± 8.5 million before treatment to 84.2 ± 24.6 million after treatment, whereas the percentage of spermatozoa in the urine declined from 43.2 ± 9% to 17 ± 10%, respectively (both p < 0.05). Overall, in men with retrograde ejaculation treated with a pseudoephedrine regimen prior to ejaculation, some improvement in seminal parameters occurred in 14 (70%) patients, with 10 patients (38.5% of all patients) achieving antegrade total sperm counts over 39 million.
The name “pituitary” for the hormone-secreting gland beneath the brain originates from ideas of Aristotle that the brain secretes phlegm or pituita which cools the body. This fluid was thought to pass from the brain via the pituitary body and into the nasal passages. In the nineteenth century ideas about the function of the pituitary began to change when it was realized that certain pathological conditions were associated with tumors of the pituitary: for example, acromegaly, which is excessive growth of parts of the skeleton in adults. From a mixture of clinical observations and experiments on laboratory mammals, the relationships between the pituitary and other endocrine organs were established. Comparative studies have also made significant contributions to our understanding of pituitary hormone physiology. Early studies on tadpoles established the pituitary as an important controlling organ in development and function of the adrenals, gonads, and thyroid, and, moreover, that the pituitary was important for skin color changes in amphibia. The proliferative response of pigeon crop sac mucosa to prolactins from all tetrapods became a standard bioassay and hastened the isolation and characterization of this pituitary hormone. Because of the position of the pituitary beneath the brain, and its connections with it, it was realized that the pituitary must be a coordinating center for stimuli from the brain and, moreover, is probably dependent on signals from the brain for its function.
Objective:
To determine whether the change in sperm parameters in subfertile hypoandrogenic men treated with anastrozole is correlated to the magnitude of increase in testosterone (T) to estrogen ratio in men responding to treatment.
Design:
Retrospective study.
Setting:
Male fertility clinic.
Patient(s):
The study group consisted of 86 subfertile hypoandrogenic men with low T/estradiol (E2) ratio (n = 78) or a prior aversive reaction to clomiphene citrate (n = 8).
Intervention(s):
All patients were treated with 1 mg anastrozole daily, administered orally.
Main outcome measure(s):
Hormone analysis and semen analysis before and after treatment were performed. Hormone analysis included measurements of total T, E2, sex-hormone binding globulin, albumin, FSH, and LH, and bioavailable T was calculated. Total motile sperm count was calculated from the semen analysis.
Result(s):
In all, 95.3% of patients had an increased serum T and decreased serum E2 after treatment with anastrozole. Sperm concentration and total motile counts improved in 18 of 21 subfertile hypoandrogenic oligozoospermic men treated with anastrozole. In these men the magnitude of total motile count increase was significantly correlated with the change in the T/E2 ratio. No improvement was seen in semen parameters of men with azoospermia, cryptozoospermia, or normozoospermia at presentation.
Conclusion(s):
Approximately 95% of men with hypoandrogenism responded with improved endocrine parameters, and a subset of oligozoospermic men (approximately 25% of all patients) displayed significantly improved sperm parameters. In that subset, increase in sperm parameters was correlated with the change in the T/E2 ratio, which argues for a physiologic effect of treatment.
Interactions between infertility and sexuality are numerous and complex. Infertile men may suffer from sexual dysfunctions (SD) when undergoing an assisted reproductive technology programme. We undertook a review both in French and English of the available data on male SD when being diagnosed with a fertility problem with a specific focus on azoospermic men. The review was performed over a 30-year time period using PubMed/Medline. The sexual concerns and needs of infertile/sterile men for whom potential parenting can be compromised were evaluated. When diagnosed with infertility, men usually go through a crisis that can have a deleterious effect on their sexuality with sometimes a feeling of sexual inadequacy. Infertile men will feel stigmatized because they are perceived as being deficient in a specific component of their masculinity. Hence, subsequent SD may occur that can impact the couple sexuality and the infertility management. However, little is known on how the announcement of azoospermia may affect male on a sexual and psychological point of view. The present review suggests that a global management through a healthcare network (biologist, andrologist, sexologist and psychologist) is required which will allow to consider infertility and its subsequent sexual disorders as a whole and not as dichotomized issues.
Clinical review of the present data on the effects of selective serotonin reuptake inhibitors (SSRIs) on male fertility was the objective of the study. PubMed and Scopus were searched for publications in English or Danish and reviewed. Human trials, animal studies and in vitro studies were included. Use of SSRIs negatively affects semen parameters in most studies. In some studies, SSRIs are also shown to reduce DNA integrity. SSRIs can also delay ejaculation. Depression and anxiety can cause reduced libido, erectile dysfunction and delayed ejaculation as well. The use of SSRIs seems to reduce male fertility by affecting semen parameters, although most studies have a degree of confounding by indication caused by the underlying depression.