BACKGROUND Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. METHODS Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of < or =12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. RESULTS The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP < or = 12 months: semen volume, 1.5 ml (1.4-1.7); total sperm number, 39 million per ejaculate (33-46); sperm concentration, 15 million per ml (12-16); vitality, 58% live (55-63); progressive motility, 32% (31-34); total (progressive + non-progressive) motility, 40% (38-42); morphologically normal forms, 4.0% (3.0-4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. CONCLUSIONS The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.

/pdf/world-health-organization-reference-values-for-human-semen-3qu21s6tqf.pdf

World Health Organization reference values for human semen characteristics

WHO laboratory manual for the examination and processing of human semen

Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men to participate in contraception and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost one third of contraceptive use in the United States and other countries. Recent international clinical research efforts have demonstrated high efficacy rates (90-95%) for hormonally based male contraceptives. Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such nonhormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade.

Advances in male contraception.

Background Infertility is estimated to affect as many as 186 million people worldwide. Although male infertility contributes to more than half of all cases of global childlessness, infertility remains a woman's social burden. Unfortunately, areas of the world with the highest rates of infertility are often those with poor access to assisted reproductive techniques (ARTs). In such settings, women may be abandoned to their childless destinies. However, emerging data suggest that making ART accessible and affordable is an important gender intervention. To that end, this article presents an overview of what we know about global infertility, ART and changing gender relations, posing five key questions: (i) why is infertility an ongoing global reproductive health problem? (ii) What are the gender effects of infertility, and are they changing over time? (iii) What do we know about the globalization of ART to resource-poor settings? (iv) How are new global initiatives attempting to improve access to IVF? (v) Finally, what can be done to overcome infertility, help the infertile and enhance low-cost IVF (LCIVF) activism? Methods An exhaustive literature review using MEDLINE, Google Scholar and the keyword search function provided through the Yale University Library (i.e. which scans multiple databases simultaneously) identified 103 peer-reviewed journal articles and 37 monographs, chapters and reports from the years 2000-2014 in the areas of: (i) infertility demography, (ii) ART in low-resource settings, (iii) gender and infertility in low-resource settings and (iv) the rise of LCIVF initiatives. International Federation of Fertility Societies Surveillance reports were particularly helpful in identifying important global trends in IVF clinic distribution between 2002 and 2010. Additionally, a series of articles published by scholars who are tracking global cross-border reproductive care (CBRC) trends, as well as others who are involved in the growing LCIVF movement, were invaluable. Results Recent global demographic surveys indicate that infertility remains an ongoing reproductive problem, with six key demographic features. Despite the massive global expansion of ART services over the past decade (2005-2015), ART remains inaccessible in many parts of the world, particularly in sub-Saharan Africa, where IVF clinics are still absent in most countries. For women living in such ART-poor settings, the gender effects of infertility may be devastating. In contrast, in ART-rich regions such as the Middle East, the negative gender effects of infertility are diminishing over time, especially with state subsidization of ART. Furthermore, men are increasingly acknowledging their male infertility and seeking ICSI. Thus, access to ART may ameliorate gender discrimination, especially in the Global South. To that end, a number of clinician-led, LCIVF initiatives are in development to provide affordable ART, particularly in Africa. Without access to LCIVF, many infertile couples must incur catastrophic expenditures to fund their IVF, or engage in CBRC to seek lower-cost IVF elsewhere. Conclusions Given the present realities, three future directions for research and intervention are suggested: (i) address the preventable causes of infertility, (ii) provide support and alternatives for the infertile and (iii) encourage new LCIVF initiatives to improve availability, affordability and acceptability of ART around the globe.

http://fertility.com.br/wp-content/uploads/2015/03/reuniao-fevereiro-16-edson.pdf

Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century

Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between “substitutive” and “pharmacological” androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of th...

https://www.hormonebalance.org/images/documents/Kauffman%2005%20TDS%20REVIEW%20ER.pdf

The decline of androgen levels in elderly men and its clinical and therapeutic implications.

Klinefelter's syndrome

https://www.fertstert.org/article/S0015-0282(97)80083-0/pdf

Screening for deletions of the y chromosome involving the daz (deleted in azoospermia) gene in azoospermia and severe oligozoospermia

In a search for pathophysiological causes of idiopathic male infertility we investigated the occurrence of mutations of the FSH receptor in 48 men with this disorder. The entire FSH receptor gene was analyzed by single stranded conformation polymorphism analysis (SSCP). A heterozygous point mutation without functional consequences, exchanging Val to Ala in codon 341, was found in one patient. SSCP analysis led to the identification of 2 polymorphisms in exon 10 associated in 2 discrete FSH receptor allelic variants, i.e. Thr307-Asn680 and Ala307-Ser680. The frequency and distribution of the two allelic variants was further analyzed in 86 proven fathers and 75 infertile men by SSCP (codon 307) and restriction fragment length polymorphism (codon 680). The 2 receptor isoforms showed similar Mendelian distribution in proven fathers and in infertile men. Serum FSH, inhibin B, and combined testicular volume did not differ between subjects with different receptor isoforms. Binding studies in transiently transfected COS-7 cells showed similar binding affinity for the two receptor variants. Moreover, the Ala307-Ser680 and the Thr307-Asn680 FSH receptors responded in vitro to FSH with comparable cAMP production. These data suggest that different isoforms of the FSH receptor with similar functional properties exist in normal and infertile men. We conclude that mutations of the FSH receptor or the FSH receptor genotype do not play a pathogenic role in male idiopathic infertility. The possibility that different FSH isoforms might interact differently with the 2 receptor variants remains to be investigated.

Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms.

Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.

https://erj.ersjournals.com/content/erj/11/1/41.full.pdf

Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy.

Androgens are essential for the maintenance of normal spermatogenesis. Androgen action is mediated by the androgen receptor (AR), which in the testis is expressed by Leydig, peritubular, and Sertoli cells. The fact that sperm numbers range from 20 up to 300 million/mL in normal men without any indication of changed endocrine parameters led us to assume that genetic variability of transduction of androgen signaling could be important. We therefore compared the variable number of CAG repeats in the AR with sperm concentrations in men with normal ejaculate parameters (62 fathers and 69 volunteers participating in clinical trials). In multivariate analysis CAG repeat length did not differ between the volunteers (19.4 ± 3.1) and the fathers (20.6 ± 3.0), but was significantly correlated to sperm concentrations with a coefficient of −0.25. When compared with a group of infertile men with (n = 14) or without (n = 30) a family history of infertility, no such correlation was found. These results indicate that men ...

Axel Kamischke

Papers

Klinefelter's syndrome

Screening for deletions of the y chromosome involving the daz (deleted in azoospermia) gene in azoospermia and severe oligozoospermia

Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms.

Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy.

Inverse correlation between sperm concentration and number of androgen receptor CAG repeats in normal men.