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The summary presented herein represents Part II of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part II outlines the appropriate management of the male in an infertile couple. Medical therapies, surgical techniques, as well as use of intrauterine insemination (IUI)/in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) are covered to allow for optimal patient management. Please refer to Part I for discussion on evaluation of the infertile male and discussion of relevant health conditions that are associated with male infertility.The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January 2000 through May 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table[Table: see text]). This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology.This Guideline provides updated, evidence-based recommendations regarding management of male infertility. Such recommendations are summarized in the associated algorithm (figure[Figure: see text]).Male contributions to infertility are prevalent, and specific treatment as well as assisted reproductive techniques are effective at managing male infertility. This document will undergo additional literature reviews and updating as the knowledge regarding current treatments and future treatment options continues to expand.

Context Progress has been made in determining the fertility timeline and potential in adolescents with Klinefelter syndrome; however, medical professionals are currently without protocols to guide treatment. Objective To evaluate the current practices regarding fertility and andrology care in adolescent males with Klinefelter syndrome. Design A 24-question survey was developed to elicit practitioner background/expertise and management practices. This was distributed to members of the Society for the Study of Male Reproduction, the Pediatric Endocrine Society, and the Endocrine Society. Setting N/A. Patients Adolescent males with Klinefelter syndrome. Intervention None. Main Outcome Measured Current practices regarding fertility and andrology care. Results 232 responses were received from 133 (57%) adult endocrinologists, 60 (26%) pediatric endocrinologists, and 39 (17%) urologists. Among these, 69% of respondents were in academics, 62% practiced for > 10 years, and 65% received formal training in Klinefelter syndrome. All specialties encouraged sperm banking in late puberty, however most disagreed with the practice in early puberty. Seventy-eight percent agreed that testicular biopsy should be offered if no sperm was found in the ejaculate. The perceived optimal age for testicular biopsy varied among specialists. Clinical symptoms of hypogonadism (28%), rising gonadotropin levels (15%), and testosterone levels (15%) were the most commonly cited reasons for initiation of testosterone replacement therapy. Conclusion Fertility preservation practices in adolescents with Klinefelter syndrome vary greatly within and among the specialties caring for these patients. These findings should guide future research and highlight the importance of establishing clinical practice guidelines.

Purpose The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceed from obtaining an appropriate history and physical exam ( Appendix I ), as well as diagnostic testing, where indicated. Materials/Methods The Emergency Care Research Institute Evidence-based Practice Center team searched PubMed®, Embase®, and Medline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. ( Table 1 ) This summary is being simultaneously published in Fertility and Sterility and The Journal of Urology. Results This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as the association of male infertility with other important health conditions. The detection of male infertility increases the risk of subsequent development of health problems for men. In addition, specific medical conditions are associated with some causes for male infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. ( Figure 1 ) Conclusion The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare of society. This document will undergo updating as the knowledge regarding current treatments and future treatment options continues to expand.

Patient requests for transfer of embryos with genetic anomalies linked to serious health-affecting disorders detected in preimplantation testing are rare but do exist. This Opinion sets out the possible rationales for a provider's decision to assist or decline to assist in such transfers. The Committee concludes in most clinical cases it is ethically permissible to assist or decline to assist in transferring such embryos. In circumstances in which a child is highly likely to be born with a life-threatening condition that causes severe and early debility with no possibility of reasonable function, provider transfer of such embryos is ethically problematic and highly discouraged.

This opinion addresses the ethics of providing fertility treatment to women at elevated risk from fertility treatment or pregnancy. Providers ethically may treat women at elevated risk provided that they are carefully assessed; that specialists in their medical condition are consulted as appropriate; and that patients are fully informed about risks, benefits, and alternatives, including oocyte and embryo donation, use of a gestational surrogate, not undergoing fertility care, and adoption. Providers also may conclude that the risks are too high for them to treat particular patients ethically; such determinations must be made in a medically objective and unbiased manner and patients must be fully informed of the decision. Counseling of women who wish to initiate fertility treatment with underlying medical conditions that confer increased risk during treatment or pregnancy should incorporate the most current knowledge available, being cognizant of the woman's personal determinants in relation to her reproductive desires. In such a way, both physician and patient will optimize decision making in an ethically sound, patient-supportive context.

A normal functioning reproductive endocrine system is a prerequisite for normal male fertility. Any disruption of the delicately coordinated interaction between the components of the hypothalamic-pituitary-testicular axis may lead to hypogonadism and/or infertility. The goal of the clinical evaluation is to determine if the patient has an abnormality of testosterone production or action, the etiology of the abnormality, and if hormone therapy will correct the infertility. Based on a careful history, physical examination, and evaluation of the hormones of the reproductive axis, the physician will ascertain if the patient's hypogonadism is (1) prepubertal or postpubertal in onset; (2) the result of an abnormality in the hypothalamic-pituitary axis, the testes, or the androgen receptor; or (3) associated with another underlying medical condition. This information will place the patient into one of four diagnostic categories: hypogonadotropic hypogonadism, testicular failure, 5alpha-reductase deficiency, or androgen resistance. Within each category are disorders with identifiable pathogenic mechanisms. Recent studies have added to these lists and have provided insights into the molecular basis and inheritance patterns of several of these endocrinopathies.

Many studies have investigated the association between male infertility and trinucleotide repeat polymorphisms in the androgen receptor (AR) gene, but no comprehensive meta-analysis of all published studies has been conducted.Our goals were to summarize published data on associations between AR CAG and GGC repeat lengths and male infertility and investigate sources of variation between study results.We searched for reports published before October 2006 using Medline, PubMed, and Web of Science.All selected studies included the following: a case group with infertility as measured by semen parameters, a control group of known or presumed fertile men, and measurement of CAG and/or GGC repeat lengths among cases and controls. Thirty-nine reports were selected based on these criteria, and 33 were ultimately included in the meta-analysis.One investigator extracted data on sample size, mean and sd of trinucleotide repeat length, and study characteristics.Estimates of the standardized mean difference (95% confidence interval) were 0.19 (0.09-0.29) for the 33 studies and 0.31 (0.14-0.47) for a subset of 13 studies that used more stringent case and control selection criteria. Thus, in both groups, cases had statistically significantly longer CAG repeat length than controls. Publication date appeared to be a significant source of variation between studies.This meta-analysis provides support for an association between increased androgen receptor CAG length and idiopathic male infertility, suggesting that even subtle disruptions in the androgen axis may compromise male fertility.

This document presents arguments that conclude that it is unethical to use somatic cell nuclear transfer (SCNT) for infertility treatment due to concerns about safety; the unknown impact of SCNT on children, families, and society; and the availability of other ethically acceptable means of assisted reproduction. This document replaces the ASRM Ethics Committee report titled, "Human somatic cell nuclear transfer and cloning," last published in Fertil Steril 2012;98:804–7.

Idiopathic male infertility may be due to exposure to environmental toxicants that alter spermatogenesis or sperm function. We studied the relationship between air pollutant levels and semen quality over a 2-year period in Los Angeles, California, by analyzing repeated semen samples collected by sperm donors. Semen analysis data derived from 5,134 semen samples from a sperm donor bank were correlated with air pollutant levels (ozone, nitrogen dioxide, carbon monoxide, and particulate matter < 10 microm in aerodynamic diameter) measured 0-9, 10-14, and 70-90 days before semen collection dates in Los Angeles between January 1996 and December 1998. A linear mixed-effects model was used to model average sperm concentration and total motile sperm count for the donation from each subject. Changes were analyzed in relationship to biologically relevant time points during spermatogenesis, 0-9, 10-14, and 70-90 days before the day of semen collection. We estimated temperature and seasonality effects after adjusting for a base model, which included donor's date of birth and age at donation. Forty-eight donors from Los Angeles were included as subjects. Donors were included if they collected repeated semen samples over a 12-month period between January 1996 and December 1998. There was a significant negative correlation between ozone levels at 0-9, 10-14, and 70-90 days before donation and average sperm concentration, which was maintained after correction for donor's birth date, age at donation, temperature, and seasonality (p < 0.01). No other pollutant measures were significantly associated with sperm quality outcomes. Exposure to ambient ozone levels adversely affects semen quality.

BACKGROUND: Bladder exstrophy is an uncommon anomaly rarely associated with uterus didelphys. Fertility is limited by associated vaginal malformations, which have traditionally required surgical reconstruction. CASE: A woman with a history of bladder exstrophy and hypoplastic vagina presented complaining of painful intercourse. The patient underwent vaginal dilator treatment after corrective surgery for the bladder defect. Without any further fertility therapy she subsequently conceived twins, with one implantation in each horn of a didelphic uterus. CONCLUSION: Bladder exstrophy, uterus didelphys, and vaginal hypoplasia share a common embryological devel-opment, and the finding of one anomaly can alert to the presence of another. Vaginal dilators may be used in place of surgical reconstruction to allow conception.

The majority of men with cystic fibrosis (CF) have associated congenital bilateral absence of the vas deferens (CBVAD). This congenital defect results in the absence of the anatomic ducts through which spermatozoa pass from the testes to the urethra. No spermatozoa are found in the semen, a condition referred to as obstructive azoospermia. This abnormality of the genital-urinary system is associated with the same genetic mutation in the cystic fibrosis transmembrane conductance regulator gene (CFTR ), which leads to the classic presentation of a patient with CF. However, patients may have CBVAD and CFTR mutations without symptoms of CF. Screening for the common mutations may miss a milder rare gene alteration: a DNA variant in the 5T allele. With the advent of assisted reproductive technologies, fertility is now possible for these men. The National Institutes of Health recommend genetic counseling for any couple attempting assisted reproductive techniques when the man has CF or presents with obstructive azoospermia and is positive for a CF mutation.

Objective: This study was undertaken to determine the effect of male aging on sperm quality as determined by semen analysis, the fertilization rate of human oocytes in vitro, and live birth rates. Study Design: Retrospective analysis correlating outcome measures with male age was performed for 558 oocyte donation cycles in 441 couples. The oocyte donation model was chosen because it controls for oocyte quality and endometrial receptivity, which allows variations in sperm quality as a function of male age to be the only dependent variable. Outcome measures analyzed were semen analysis, fertilization rates in vitro, pregnancy rates, live birth rates, and cumulative live birth rates by life-table analysis. Results: There was a negative correlation between male age and total sperm count, but there was no correlation between male age and any of the other parameters in the semen analysis. There was no association between male age and the fertilization rate of donated oocytes in vitro, pregnancy rates, or live birth rates. Recipient couples were grouped by quartiles of male age, and cumulative live birth rates were the same in the 4 groups. Conclusion: Whereas male aging is associated with a significant decline in total sperm count, this change is not reflected in a decreased fertilization rate or a decreased live birth rate in the oocyte donation model. (Am J Obstet Gynecol 2001;184:818-24.)

Important medical conditions associated with Klinefelter syndrome (KS) are categorized as: 1) motor, cognitive, and behavioral dysfunction; 2) tumors; 3) vascular disease; and 4) endocrine/metabolic and autoimmune diseases. Earlier diagnosis of KS may lead to earlier intervention with effective treatment.

Sprague-Dawley dams from Harlan Ind. (Indianapolis, IN) were administered a fortified ethanol liquid diet containing 35% ethanol derived calories for two weeks (E-2) beginning on day 7 or one week (E-1) beginning on day 13 of gestation and continuing through parturition. Control dams were pair-fed an isocaloric liquid diet containing no ethanol during these periods or remained on lab chow and water. E-2 dams consumed an average of 13.52 g ethanol/kg bwt during the first week of exposure (days 8-14) and 12.50 g ethanol/kg bwt the second week (days 14-20). E-1 dams consumed significantly less than E-2 dams during the second week (9.75 g/kg; p < 0.0001). Although the lower consumption in E-1 dams led to a significant decrease in maternal weight gained during the few days of pregnancy compared to E-2 dams, birthweights of E-1 offspring were significantly heavier than those of E-2 offspring (p < 0.05). No effect of ethanol was detected on anogenital distance at birth in either sex. Puberty was delayed in female offspring of both E-1 and E-2 dams (p < 0.01) as measured by age of vaginal opening. These data suggest that the primary teratogenic actions of ethanol in the rat on fetal growth, as well as delayed puberty in females, occur in the last week of gestation. In adult E-2 males, testis weight was significantly heavier than all other groups when indexed to body weight. No effect of prenatal ethanol exposure was observed on the indexed weights of prostate, epididymis, or seminal vesicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Sprague-Dawley dams were administered lead acetate (0.1%) in their drinking water from Day 14 of gestation to parturition to determine whether exposure of the fetus to elevated lead (Pb) levels during a period of rapid differentiation of the hypothalamic-pituitary-gonadal (HPG) axis would disrupt HPG function in adulthood. At birth, offspring from 20 Pb-treated and 10 control dams were weighed and 2 litter representatives from each sex were fostered to untreated dams. Animals were weaned at 26 days of age and subsequently group housed by sex and treatment. Blood Pb levels in prenatally exposed pups were below the limits of detectability at weaning. Female offspring from Pb-treated dams were found to have a significant delay in the day of vaginal opening. In a sample of lead exposed females, 50% were found to exhibit prolonged and irregular periods of diestrous which was accompanied by an absence of observable corpora lutea when they were euthanized at 83 days of age. Male offspring from these dams were found to have decreased sperm counts at 70 and 160 days of age and to exhibit significantly less territorial scent marking and masculine sex behavior in adulthood compared to controls. Azoospermia was observed in 1 lead exposed animal at 70 days of age and 2 animals at 160 days. Enlarged prostates were observed in Pb-exposed males measured at 160 days, but other sex organ weights were normal. Volume of the sexually dimorphic nucleus of the preoptic area of the hypothalamus in adulthood was significantly reduced by approximately 35% in Pb-exposed males. Pulsatile release of gonadotropins, measured in castrated adult animals of both sexes, revealed irregular release patterns of both FSH and LH in some Pb animals which were not observed in controls. The overall pattern of results suggests that multiple levels of the HPG axis can be affected by exposure to Pb during a period of gestation when structures related to the HPG axis are undergoing rapid proliferation. These data indicate that lead exposure during this period places the exposed animal at significant risk for reduced reproductive capacity in adulthood.

In the field of reproductive environmental health there remain many unanswered questions regarding the impact of the environment on male reproductive health. Suggested needs include studies that target populations with high exposure to chemicals, including phthalates and bisphenol A. We also need to identify susceptibility factors and critical exposure windows (life stages) that may increase a man's risk of infertility. Finally, we need to develop methods to better study mixtures of chemicals and develop methods to assess clinical reproductive outcomes of human exposure to the ever-growing list of chemicals.

BackgroundMale-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.Methodology/principal findingWe determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.ConclusionsThis is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.

A higher proportion of nonobstructive than obstructive azoospermia, as well as an increased prevalence of hypogonadotropic hypogonadism were documented in a retrospective study characterizing azoospermia in a population of predominantly Latino, inner-city male partners of infertile couples, as compared to previous reports from relatively affluent socioeconomic status male populations.

To evaluate the signs and symptoms associated with hyperprolactinemia and establish guidelines for a minimal serum PRL level for which pituitary imaging is indicated.Retrospective study.Reproductive endocrinology clinic in a university hospital.One hundred four consecutive patients with hyperprolactinemia, mean age 30 +/- 6.5 (range 19-44) years.Classification of clinical symptoms, serum hormone measurements, and pituitary magnetic resonance imaging (MRI).Incidence of presenting symptoms, serum PRL levels, and pituitary tumor size.Median (range) PRL value was 82.6 ng/mL (25-1,342). Reported symptoms from most to least common were infertility (48%), headaches (39%), oligoamenorrhea (29%), galactorrhea (24%), and visual changes (13%). Hypothyroidism was diagnosed in 2 of 104 (1.9%) patients. Of 86 patients who had pituitary imaging, 23 (26%) had normal findings and 63 (74%) had pituitary tumor; of these, 47 (55% of total imaged) had microadenomas and 16 (19% of total imaged) had macroadenomas. There was a statistically significant association between the tumor size and the PRL level. However, 11% of the patients with microadenomas had PRL levels200 ng/mL, and 44% of the patients with macroadenomas had PRL levels between 25 and 200 ng/mL.The most common symptoms in the population studied were infertility and headaches. Coexisting thyroid disease was an uncommon finding. Most patients had a pituitary tumor on MRI. Although tumor size correlated with the serum PRL level, some macroadenomas were detected in women with only moderately elevated PRL values. On the basis of these findings, pituitary imaging should be obtained to identify pituitary tumors in all patients with persistently elevated PRL levels.

To determine whether inhibin B levels are reflective of the etiology of gonadal dysfunction.Institutional study.A tertiary care university-affiliated infertility clinic.Forty-four men: 16 with primary testicular failure, 10 with partial idiopathic hypogonadotropic hypogonadism (IHH), 8 with primary germ cell failure, one with iatrogenic hypogonadotropic hypogonadism, one with untreated Kallmann's syndrome, and 8 healthy fertile controls.Three individuals (one each with IHH, hypogonadotropic hypogonadism [HH], and Kallmann's syndrome) underwent treatment with human chorionic gonadotropin.Baseline serum inhibin B, FSH, LH, total testosterone and estradiol levels, and sperm concentrations were measured.Serum inhibin B concentrations were significantly higher in fertile controls (255 +/- 59 pg/mL) than in men presenting with primary testicular failure (75 +/- 46 pg/mL, P.0001) or in those presenting with primary germ cell failure (73 +/- 31 pg/mL, P.0001). Inhibin B levels were also lower in males with partial IHH (187 +/- 112 pg/mL, P.05). The patient with iatrogenic HH had a level of 184 pg/mL, whereas the patient with Kallmann's syndrome had nondetectable levels (10 pg/mL). Serum inhibin B levels correlated positively with sperm concentration (P=.0001), and negatively with FSH levels (P=.01) and LH levels (P.05). Human chorionic gonadotropin therapy altered inhibin B levels.Inhibin B plays an important role as an endocrine regulator of FSH secretion, whereas gonadotropins are involved in the regulation of inhibin B secretion.

Objective: To determine: [1] what percentage of men in an infertile relationship will have a semen abnormality, [2] the average value for each semen parameter in this group of men, [3] the distribution of abnormal semen parameters in this group, and [4] if our data support the hypothesis that sperm concentration is declining. Design: Retrospective cohort study. Setting: County hospital university-based infertility clinic. Patient(s): Male partners of women presenting for an infertility evaluation. Intervention(s): Semen specimens were collected after 2–5 days of abstinence. Main Outcome Measure(s): Sperm concentration, motility, and morphology. Result(s): Fifty-two percent of samples had at least one sperm abnormality based on World Health Organization criteria. Fifty-one percent had an abnormality in sperm motility, 18% in sperm concentration, and 14% in sperm morphology. Four percent of the patients were azoospermic. Conclusion(s): No decline in sperm density was revealed in semen collected by men presenting for an initial screening semen analysis.

Objective: To determine the accuracy of both the hemocytometer and the MicroCell, to evaluate which method is the most reliable, and to confirm the accuracy of latex beads as an internal standard. Design: Prospective procedural assessment. Setting: University-based infertility clinic. Patient(s): One hundred sixty-five male sexual partners of women undergoing screening for infertility. Intervention(s): Semen analysis. Main Outcome Measurement(s): Sperm and latex bead concentrations. Result(s): Sperm concentration values obtained with the hemocytometer were highly correlated with those obtained from the MicroCell (r = 0.88). The mean value of the latex beads concentration was closer to the standard value using the hemocytometer than the MicroCell. Conclusion(s): Both the hemocytometer and the MicroCell are suitable as screening techniques to measure sperm concentration. Fixed suspensions of latex beads serve as reliable internal quality control standards.

The differential diagnosis of male factor infertility can be subdivided into four major diagnostic categories: (1) irreversible germ cell failure, (2) hypogonadotropic hypogonadism, (3) anatomic defects, and (4) idiopathic infertility. Therapies for germ cell failure and hypogonadotropic hypogonadism are clearly delineated. Anatomic defects are surgically corrected. A specific therapy for idiopathic infertility has yet to be defined, but a number of medical therapies have been proposed for its treatment. Because of the heterogeneity of the disorders that fall into this category, specific etiologic factors for each are not yet defined, which prevents identification of specific therapies. No single empiric medical therapy proposed has proven efficacious when studied in a controlled, prospective fashion. Placebo-controlled trials are necessary because the treatment-independent pregnancy rate is 30% in 1 year.1 A 30% improvement in pregnancy rate in a noncontrolled study is therefore meaningless.

Male factor infertility is a heterogeneous disorder, a factor that precludes the development of either a single laboratory test to predict sperm fertility potential or a single therapy to improve fertility. A better understanding of the pathophysiology of the disorder will ultimately lead to more clearly defined diagnostic categories and specific treatment regimens.

The effects of a combined GnRH antagonist and testosterone (T) replacement regimen on gonadotropins and spermatogenesis were examined to assess its potential as a male contraceptive regimen. The potent Nal-Glu GnRH antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5, D4-p-methoxybenzoyl-2-amino butyric acid6,D-Ala10]GnRH) was administered daily (7.5 mg, sc) to eight normal men for 16 weeks. T enanthate was given im starting at week 2 and every 2 weeks thereafter through week 14 of the treatment phase. Serum LH, FSH, T, and estradiol concentrations were measured frequently during the 5-week control period, the 16-week treatment phase, and the 14-week recovery phase. Semen analyses were performed every week during the control phase and every 2 weeks during the treatment and recovery phases. Seven of eight subjects became azoospermic by 6-10 weeks of treatment; the eighth subject, who failed to achieve azoospermia, suppressed his sperm count to 7 million/mL by week 14 (from a mean baseline of 42 million/mL) before treatment was prematurely terminated because of localized swelling at each of his injection sites. Sperm counts returned to baseline 10-14 weeks after the end of Nal-Glu administration. Seven of the eight subjects showed suppression of LH to the limit of assay detection (less than 0.2 U/L), whereas the eighth subject showed incomplete suppression. Serum bioactive and immunoreactive LH concentrations showed concordant responses. Mean serum FSH concentrations were also markedly suppressed. Serum T and estradiol concentrations declined dramatically during the first 2 weeks of Nal-Glu GnRH treatment, but returned to the normal physiological range after T enanthate replacement was initiated. Libido and sexual potency were maintained. No systemic side-effects, other than erythema and induration at injection sites, were observed. These data demonstrate that combined GnRH antagonist plus T treatment can predictably and reversibly induce azoospermia in most men and has potential as a male contraceptive regimen.This study examined the hypothesis that a gonadotropin-releasing hormone (GnRH) antagonist, given at a dose that will suppress gonadotropin secretion and combined with a replacement dose of androgen, will induce reversible azoospermia in normal men while maintaining sexual function. About 8 normal men aged 24-48 years participated in the study. Sperm concentration in all 8 subjects decreased during the treatment; 7 became azoospermic by 6-10 weeks of treatment. In the 8th subject, who failed to achieve azoospermia, the sperm count declined to 7 million/ml by week 14, when treatment was prematurely terminated because of localized inflammation and induration at each of the injection sites. Sperm count returned to baseline following the end of Nal-Glu administration. No statistically significant change was observed in the sperm function during the oligospermic phase of treatment from baseline. 7 subjects showed suppression of luteinizing hormone, while the 8th experienced edema and discomfort at the injection sites. Mean serum follicle stimulating hormone concentrations were suppressed. Serum testosterone and estradiol concentrations declined during the treatment but returned to normal following T enanthate replacement initiation. Main side effects of Nal-Glu GnRh treatment were local erythema and induration at the injection sites due to local histamine release. In conclusion, the combined GnHR antagonist and T treatment can induce azoospermia in most men and has potential as a male contraceptive regimen.

Pregnant Sprague-Dawley dams were exposed to a low-level, low-frequency pulsed electromagnetic (EM) field (15 Hz, 0.3 msec duration, peak intensity 8 gauss) for 15 min twice a day from day 15 through day 20 of gestation, a period in development that is critical for sexual differentiation of the male rat brain. No differences in litter size, number of stillborns, or body weight were observed in offspring from field-exposed dams. At 120 days of age, field-exposed male offspring exhibited significantly less scent marking behavior than controls. Accessory sex organ weights, including epididymis, seminal vesicles, and prostate, were significantly higher in field-exposed subjects at this age. However, circulating levels of testosterone, luteinizing hormone, and follicle-stimulating hormone, as well as epididymal sperm counts, were normal. These data indicate that brief, intermittent exposure to low-frequency EM fields during the critical prenatal period for neurobehavioral sex differentiation can demasculinize male scent marking behavior and increase accessory sex organ weights in adulthood.

Objective To describe the clinical symptoms associated with the diagnosis of pituitary gonadotroph adenoma in premenopausal women. Design Report of three separate cases. Setting University medical center. Patient(s) Three patients: a 31-year-old woman with primary infertility, recurrent adnexal masses, and highly elevated estradiol level; a 30-year-old woman with recurrent multicystic ovaries following multiple cystectomies and transvaginal cyst aspirations, and elevated estradiol level; a 43-year-old woman with bilateral complex cystic adnexal masses and an elevated estradiol level, who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a suspected granulosa cell tumor. Intervention(s) Transsphenoidal resection of a pituitary mass. Main Outcome Measure(s) Serum estradiol, FSH, and LH levels; transvaginal ultrasonography of the ovaries; histologic examination of pituitary tumors. Result(s) Transsphenoidal resection of pituitary adenomas resulted in normalization of serum estradiol and FSH levels and resolution of adnexal masses in two of the women. Conclusion(s) Pituitary gonadotroph adenoma must be considered in the differential diagnosis in reproductive-aged women presenting with the clinical symptom triad of new onset oligomenorrhea, bilateral cystic adnexal masses, and elevated estradiol and FSH levels with suppressed levels of LH; timely diagnosis may prevent unnecessary and potentially damaging surgical procedures.

Male reproductive function requires the integrated functioning of the hypothalamus, pituitary, and testis. The disturbance of endocrine function at any of these levels may result in hypogonadism and infertility. The clinical and laboratory evaluation of these disorders is reviewed here.

In this study we report on a successful pregnancy in the spouse of a man who, on repeated occasions, spaced over 3 years, presented with a mean sperm concentration of less than 200,000 sperm/ml. Serum was drawn from the father, mother, and daughter for polymorphic gene marker analysis. The calculation of relative probability of paternity with the use of gene frequencies for whites gave a figure of 99.9% that our patient is the father of the child.

A 15-yr-old male with the diagnosis of Kallmann's syndrome manifested secondary gonadal resistance during a third treatment course of hCG. A serum sample obtained 6 months after failure of the patient to respond to hCG bound [125I]hCG 60% at a 1:2 dilution of serum; 50% at 1.5; 28% at 1:50; 21% at 1:100; and less than 5% at a 1:500 dilution. Serial sampling of the patient's serum over a 22-month period demonstrated a progressive decline in binding capacity, decreasing to 32% binding of [125I]hCG at a 1:2 dilution of serum. The data demonstrated that the patient produced a low affinity, high capacity binding substance with a Ka of 5 x 10(7) liters/M and a R0 of 1.8 x 10(16) sites/g gamma-globulin. The binding substance appeared to be a gamma-globulin of the immunoglobulin G class, which bound labeled hCG and human LH (hLH) more avidly than it bound hFSH and interfered with the biological response to hCG therapy. These data further indicated that antibodies produced against hCG may bind other endogenous glycoproteins such as hLH, hFSH, and hTSH. Although binding to hTSH did not occur in this patient, the presence of a common beta-chain in the molecular structures of hLH, hFSH, hCG, and TSH makes such a potential occurrence not implausible. Despite the apparent infrequency of the development of clinically observable interference with the biological activity of hLH/hCG in hCG-treated patients, this report indicates that a potential hazard exists. The possibility should be considered in the decision to treat a patient with normal gonadotropin secretion with exogenous gonadotropins.

To determine whether clomiphene citrate (CC) improves fertility in oligospermic men, 23 men with sperm concentrations between 0.5 and 20 million sperm per milliliter; normal serum gonadotropins and testosterone; and a presumptively fertile partner were enrolled in the study. After a 3-month control period, patients were randomly prescribed CC, 25 mg/day; or placebo, 1 tablet/day, for 12 months. The pregnancy rates for the CC group and the placebo group were 9.09% and 44.44%, respectively (not significant). During the treatment phase, the CC group had significantly higher levels of luteinizing hormone (LH) serum, follicle-stimulating hormone (FSH), testosterone (T), and estradiol than the placebo group. CC treatment also resulted in greater LH, FSH, and T responses to gonadotropin-releasing hormone (GnRH). There were no differences between the placebo and CC groups for the sperm penetration assay or semen parameters. The authors conclude that CC is not a useful drug in the treatment of male infertility.

Zinc is necessary for growth, sexual maturation and reproduction. Because high concentrations of zinc are found in the male reproductive system, a relationship between zinc and male infertility has been suggested. We studied 11 unselected men who presented to a Reproductive Endocrinology Clinic with histories of infertility and low sperm counts. Reproductive hormones and semen and serum zinc levels were measured. All men had semen analyses performed on at least three separate occasions. A similar set of laboratory evaluations were performed on 11 other men who had normal semen analyses and no history of infertility. No abnormalities of reproductive hormones were found in either group. Mean serum zinc levels were significantly lower in the infertile men (p less than 0.05). Mean semen zinc levels were not significantly different. There was no correlation between serum and semen zinc levels in either group. A significant correlation was found between sperm count and semen zinc (r = 0.66, p less than 0.05) in the volunteers with normal counts, but not in the oligozoospermic men. The results obtained in this study suggest that lowered serum zinc is more common than formerly appreciated in unselected patients with infertility. The high level of zinc found in semen is due primarily to the secretions of the prostate gland and reflects prostatic stores. Serum zinc is thought to be a reasonable indicator of zinc status. The lack of correlation between serum zinc and semen zinc found in our study suggests that mild zinc deficiency may lower serum zinc while the larger prostatic zinc stores remain unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

The first and most important rule in the evaluation of infertility is to consider the couple as a unit in the evaluation and treatment of infertility. Too often a woman is investigated extendsively only to discover later that her husband is azoospermic; likewise, a man may undergo lengthy treatmnet for oligospermia while his wife has an undiagnosed tubal obstruction or anovulatory cycles. The evaluation of both the man and woman should proceed in parallel until a significant problem is uncovered. Ideal management is best achieved when the couple is seen together by a team of physicians. When the man is under teh care of either an endocrinologist or a urologist and the woman is under the care of a gynecologist, communication between physicians must be ongoing.