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Progestin-only long-acting reversible contraceptives (LARCs) are increasingly popular among women seeking contraception; however, recent epidemiological studies suggest that systemically administered medroxyprogesterone acetate (MPA) may increase HIV acquisition. In order to determine the exact mechanisms underlying increases in transmission specific to MPA use and to test safer, alternative contraceptive progestin types and delivery methods, in vitro modeling studies must be performed. To achieve this, it is imperative that accurate hormone concentrations be utilized when modeling progestin-mediated outcomes, as the down-stream effects are dose-dependent. The local concentrations of progestins to which the lower female genital tract tissues are exposed after initiation of LARCs are unknown, but they likely differ from peripheral concentrations, dependent upon the progestin type and delivery method. Here, we measured in vivo endocervical and plasma concentrations of (1) systemically-delivered depo MPA (DMPA), (2) levonorgestrel (LNG) delivered via intrauterine system (IUS) and (3) etonogestrel (ETG) delivered via vaginal ring in women who recently initiated contraception treatment. Levels of ETG and LNG in cervical secretions were 100–200 fold higher than plasma levels. In contrast, measurable MPA levels were approximately 10-fold higher in plasma compared to cervical secretions. These results will inform the design of accurate in vitro studies on the influence of progestins on epithelial cells, tissue explants, and peripheral blood cells, to be able to better predict in vivo outcomes. Subsequent observations will aid in determining how MPA might influence HIV acquisition and may facilitate identification of optimal progestin-containing LARC alternatives for women at high risk for HIV infection. [ABSTRACT FROM AUTHOR]

Although varicoceles are a widely accepted identifiable male factor in infertile couples, the benefit of varicocele repair in improving pregnancy and live birth rates remains uncertain. The Study for Future Families obtained semen and reproductive hormone samples from US men whose partners were currently pregnant. In our analysis cohort of 709 men, a varicocele was detected by clinical examination in 56 (8%) of men. Men with varicocele had smaller left testis, and lower total and total motile sperm counts than men without varicocele. Gonadotropin levels were higher as well in men with varicocele. Interestingly, testosterone levels were also slightly higher in men with varicocele. Despite these differences, there was no difference between the groups in the time to achieve the study pregnancy or percentage of men with a previous pregnancy. We conclude that even in fertile men, varicoceles are associated with some degree of testicular hypofunction. This would support current recommendations to consider varicocele repair in male partners in infertile couples who demonstrate both a varicocele and abnormal semen parameters and after evaluation for treatable female factors. [ABSTRACT FROM AUTHOR]

A response to the Commentary ‘Should sperm DNA fragmentation testing be included in the male infertility work-up?’ by Professor Sheena Lewis. [ABSTRACT FROM AUTHOR]

The authors comment on the clinical significance of DNA fragmentation (DNA-F) testing of spermatozoa. According to the authors, there is a need for valid diagnostic tests to examine male fertility. Particular focus is given to existing clinical tests that assess semen quality. Topics discussed include weaknesses of studies on the use of DNA-F testing in the diagnosis of infertility, sensitivity and specificity of semen analysis, and advantage of DNA-F testing.

A letter to the editor is presented in response to the article "Adherence and Acceptability of the Contraceptive Ring Compared With the Pill Among Students: A Randomized Controlled Trial," by Melissa L. Gilliam and colleagues, as well as a reply from the authors of the article.

Surgical site infections (SSI) are the most common surgical complication. Perioperative antibiotics can reduce SSI when used properly. Despite guidelines from The American College of Obstetrics and Gynecology, non-indicated antibiotic use is widespread which exposes women to unnecessary risks. This study represents a quality improvement analysis assessing surgeon compliance with established guidelines regarding antibiotic use in gynaecological surgery. This is a single centre, retrospective study examining gynaecological procedures over two years. Cases were identified using Current Procedure Terminology codes. Perioperative antibiotics were used contrary to published guidelines in 199 of 1046 cases. Three variables were independently associated with inappropriate administration of perioperative antibiotics: entrance into abdominal cavity, higher EBL, and longer procedures. Impact statement Overuse of antibiotics has unintended consequences including allergic sequelae, extended length of hospital stay, increased healthcare costs, and the formation of antibiotic-resistant organisms. Antibiotic stewardship programmes have been shown to reduce the number of resistant pathogens, decrease incidence of Clostridium difficile colitis, and decrease length of hospital stay without increasing infection rates. Further outcomes-based research is needed regarding the use of antibiotic stewardship programmes in gynaecological surgery. [ABSTRACT FROM AUTHOR]

Concentrations of the hormone leptin, which is produced by adipose tissue, increase with increasing BMI, whereas leptin sensitivity often declines with higher BMI. Thus, altered leptin signaling may play a role in reproductive health risks observed with increasing BMI, which include later onset and slow progression of labor. Conflicting evidence from clinical, animal and in vitro studies have suggested that leptin either promotes or inhibits labor. We hypothesized that serum leptin concentrations or serum leptin: body mass index (BMI) ratios in women may be associated with the initiation and progression of labor. Following informed consent, serum samples were collected from 90 women with singleton pregnancies at the time of routine glucose-challenge testing, for measurement of leptin. The potential influence of leptin on gestation length and cervical dilation timing were examined by multiple linear regression. Data were analyzed from 63 participants who met exclusion and inclusion criteria. Leptin concentrations (log-transformed) at 24–28 weeks gestation were not significantly correlated with first trimester BMI. Log serum leptin and leptin: BMI ratio each were significantly associated with shorter total gestation length in uncomplicated, term pregnancies. In contrast, the mid-pregnancy leptin concentrations were not associated with progression of labor, assessed by cervical dilation over time. The association between higher serum leptin and shorter gestation length is consistent with the hypothesis that leptin promotes, or is permissive for, the onset of labor. [ABSTRACT FROM AUTHOR]

Human sperm lack major histocompatibility class I molecules, making them susceptible to lysis by natural killer (NK) cells. Major histocompatibility class I negative tumor cells block NK cell lysis by expressing sufficient amounts of bisecting type N-glycans on their surfaces. Therefore, sperm could employ the same strategy to evade NK cell lysis. The total N-glycans derived from sperm were sequenced using ultrasensitive mass spectrometric and conventional approaches. Three major classes of N-glycans were detected, (i) high mannose, (ii) biantennary bisecting type, and (iii) biantennary, triantennary, and tetraantennary oligosaccharides terminated with Lewisx and Lewisy sequences. Immunostaining of normal sperm showed that glycoproteins bearing Lewisy sequences are localized to the acrosome and not the plasma membrane. In contrast, defective sperm showed distinct surface labeling with anti-Lewisy antibody. The substantial expression of high mannose and complex type N-glycans terminated with Lewisx and Lewisy sequences suggests that sperm glycoproteins are highly decorated with ligands for DC-SIGN. Based on previous studies, the addition of such carbohydrate signals should inhibit antigen-specific responses directed against sperm glycoproteins in both the male and female reproductive systems. Thus, the major N-glycans of human sperm are associated with the inhibition of both innate and adaptive immune responses. These results provide more support for the eutherian fetoembryonic defense system hypothesis that links the expression of carbohydrate functional groups to the protection of gametes and the developing human in utero. This study also highlights the usefulness of glycomic profiling for revealing potential physiological functions of glycans expressed in specific cell types. [ABSTRACT FROM AUTHOR]

Although geographic variation in semen quality has been reported, this is the first study in the United States to compare semen quality among study centers using standardized methods and strict quality control. We evaluated semen specimens from partners of 512 pregnant women recruited through prenatal clinics in four U.S. cities during 1999-2001; 91% of men provided two specimens. Sperm concentration, semen volume, and motility were determined at the centers, and morphology was assessed at a central laboratory. Study protocols were identical across centers, and quality control was rigorously maintained. Sperm concentration was significantly lower in Columbia, Missouri, than in New York, New York; Minneapolis, Minnesota; and Los Angeles, California. Mean counts were 58.7, 102.9, 98.6, and 80.8 × 10[sup 6]/mL (medians 53.5, 88.5, 81.8, and 64.8 × 10[sup 6]/mL) in Missouri, New York, Minnesota, and California, respectively. The total number of motile sperm was also lower in Missouri than in other centers: 113, 196, 201, and 162 × 10[sup 6] in Missouri, New York, Minnesota, and California, respectively. Semen volume and the percent morphologically normal sperm did not differ appreciably among centers. These between-center differences remained significant in multivariate models that controlled for abstinence time, semen analysis time, age, race, smoking, history of sexually transmitted disease, and recent fever (all p-values < 0.01). Confounding factors and differences in study methods are unlikely to account for the lower semen quality seen in this mid-Missouri population. These data suggest that sperm concentration and motility may be reduced in semirural and agricultural areas relative to more urban and less agriculturally exposed areas. [ABSTRACT FROM AUTHOR]

According to the Americans with Disabilities Act (1990), couples with blood-borne viruses that lead to infectious disease cannot be denied fertility treatment as long as the direct threat to the health and safety of others can be reduced or eliminated by a modification of policies or procedures. Three types of infectious patients are commonly discussed in the context of fertility treatment: those with human immunodeficiency virus (HIV), hepatitis C or hepatitis B. Seventy-five per cent of hepatitis C or HIV positive men and women are in their reproductive years, and these couples look to assisted reproductive techniques for risk reduction in conceiving a pregnancy. In many cases, only one partner is infected. Legal and ethical questions about treatment of infectious patients aside, the question most asked by clinical embryologists and andrologists is: “What are the laboratory protocols for working with gametes and embryos from patients with infectious disease?” The serostatus of each patient is the key that informs appropriate treatments. This guidance document describes protocols for handling gametes from seroconcordant and serodiscordant couples with infectious disease. With minor modifications, infectious patients with stable disease status and undetectable or low viral load can be accommodated in the IVF laboratory. [ABSTRACT FROM AUTHOR]

Phthalates, a ubiquitous class of environmental chemicals, may interfere with typical reproductive hormone production both in utero and in adulthood. Although they are best known as anti-androgens, increasingly, evidence suggests that phthalates, particularly di-2-ethylhexyl phthalate (DEHP), may also suppress estrogen production. Given that both androgens and estrogens are essential for sexual function, particularly sexual interest, it is plausible that adult exposure to phthalates alters sexual function. To this end, we used data from 360 women participating in a pregnancy cohort study (the Study for Future Families) to examine whether urinary phthalate metabolite concentrations were associated with two dimensions of self-reported sexual dysfunction in the months prior to conception: lack of sexual interest and vaginal dryness. Women in the highest quartile of urinary concentrations of mono-2-ethyl-5-hydroxyhexyl phthalate, a DEHP metabolite, had 2.58 (95% CI 1.33, 5.00) times the adjusted odds of reporting that they almost always or often lacked interest in sexual activity, and results were similar for mono-2-ethyl-5-oxohexyl phthalate (aOR: 2.56, 95% CI 1.32, 4.95), another DEHP metabolite. Self-reported vaginal dryness was not associated with any phthalate metabolite concentration. This study is novel in its focus on sexual function in relation to environmentally relevant (rather than occupational) exposure to phthalates in adult women and these preliminary findings merit replication in a large, prospective study. Better understanding how adult exposure to phthalates may affect reproductive health, including sexual function, is of public health interest given that virtually all Westerners are exposed to phthalates. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Is there an association between alcohol intake and semen quality and serum reproductive hormones among healthy men from the USA and Europe? SUMMARY ANSWER Moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels. WHAT IS KNOWN ALREADY High alcohol intake has been associated with a wide range of diseases. However, few studies have examined the correlation between alcohol and reproductive function and most have been conducted in selected populations of infertile men or have a small sample size and the results have been contradictory. STUDY DESIGN, SIZE, DURATION A coordinated international cross-sectional study among 8344 healthy men. A total of 1872 fertile men aged 18–45 years (with pregnant partners) from four European cities and four US states, and 6472 young men (most with unknown fertility) aged 18–28 years from the general population in six European countries were recruited. PARTICIPANTS/MATERIALS, SETTING, METHODS The men were recruited using standardized protocols. A semen analysis was performed and men completed a questionnaire on health and lifestyle, including their intake of beer, wine and liquor during the week prior to their visit. Semen quality (semen volume, sperm concentration, percentage motile and morphologically normal sperm) and serum reproductive hormones (FSH, LH, testosterone, sex hormone-binding globulin, and inhibin B and free testosterone) were examined. MAIN RESULTS AND THE ROLE OF CHANCE The participation rate for our populations was 20–30%. We found no consistent association between any semen variable and alcohol consumption, which was low/moderate in this group (median weekly intake 8 units), either for total consumption or consumption by type of alcohol. However, we found a linear association between total alcohol consumption and total or free testosterone in both groups of men. Young and fertile men who consumed >20 units of alcohol per week had, respectively, 24.6 pmol/l (95% confidence interval 16.3–32.9) and 19.7 pmol/l (7.1–32.2) higher free testosterone than men with a weekly intake between 1 and 10 units. Alcohol intake was not significantly associated with serum inhibin B, FSH or LH levels in either group of men. The study is the largest of its kind and has sufficient power to detect changes in semen quality and reproductive hormones. LIMITATIONS, REASONS FOR CAUTION The participation rate was low, but higher than in most previous semen quality studies. In addition, the study was cross-sectional and the men were asked to recall their alcohol intake in the previous week, which was used as a marker of intake up to 3 months before. If consumption in that week differed from the typical weekly intake and the intake 3 months earlier, misclassification of exposure may have occurred. However, the men were unaware of their semen quality when they responded to the questions about alcohol intake. Furthermore, we cannot exclude that our findings are due to unmeasured confounders, including diet, exercise, stress, occupation and risk-taking behavior. WIDER IMPLICATIONS OF THE FINDINGS Our study suggests that moderate alcohol intake is not adversely associated with semen quality in healthy men, whereas it was associated with higher serum testosterone levels which may be due to a changed metabolism of testosterone in the liver. Healthy men may therefore be advised that occasional moderate alcohol intake may not harm their reproductive health; we cannot address the risk of high alcohol consumption of longer duration or binge drinking on semen quality and male reproductive hormones. STUDY FUNDING/COMPETING INTEREST(S) All funding sources were non-profitable and sponsors of this study played no role in ... [ABSTRACT FROM PUBLISHER]

Background/ Aims: During arrest of descent, maternal tissues conform to the fetal head, resulting in a suction-cup like effect during cesarean delivery. We hypothesize that breaking this suction might ease delivery. A novel device was designed for this purpose and tested in this series of 23 patients. Methods: University-based retrospective cohort feasibility study. Term pregnant women with second-stage labor arrest (n = 23) provided written consent for use of the experimental device, inserted vaginally prior to cesarean delivery. Delivering obstetricians rated device effectiveness. Following case collection, the presence of hysterotomy extensions in study patients was retrospectively compared with controls (n = 49) from the same study period. Results: On a 7-point Likert scale, consultant obstetricians rated overall device effectiveness as 6.0, and resident obstetricians rated it 6.3, consistent with a moderate improvement in ease of delivery. The device performed optimally at mid-pelvic stations (0 to +1), with no hysterotomy extensions (n = 0/17), which was significantly better than controls (n = 14/41, 34%, p < 0.01). Conclusion: A simple device prevented hysterotomy extension during second-stage cesarean delivery at 0 and +1 station. Obstetricians perceived that the device afforded a moderate improvement in delivery compared with previous deliveries in which the device was not used. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To describe associations between serum inhibin-b and sperm counts, adjusted for effect of time of blood sampling, in larger cohorts than have been previously reported.Design: Cross-sectional studies of spermatogenesis markers.Setting: Four European and four US centers.Patient(s): Fertile men (1,797) were included and examined from October 1996-February 2005.Intervention(s): The study was observational and therefore without any intervention.Main Outcome Measure(s): Associations between inhibin-b and semen variables controlled for time of blood sampling and other covariates.Result(s): Inhibin-b decreased about 2.00% per hour from 8 am-12 pm and then about 3.25% per hour from 12 pm-4 pm. There was a strong positive association between inhibin-b levels less than 150 pg/mL and both sperm concentration and total sperm count (slopes of the regression lines were β=0.011 and β=0.013 for natural logarithm-transformed sperm concentration and total sperm count, respectively). For inhibin-b levels of 150-300 pg/mL the associations were not as steep (β=0.002), but still significant. For inhibin-b levels more than 300 pg/mL there was little association to the sperm counts. Neither sperm motility nor morphology was significantly related to inhibin-b level in any group.Conclusion(s): Serum inhibin-b levels decrease nonlinearly during the daytime, and are positively correlated with sperm counts, but the predictive power is best when inhibin-b is low. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rodent and in vitro studies have demonstrated the estrogenicity of bisphenol A (BPA). However, few studies have examined the relationship between human exposure to BPA and male reproductive function. OBJECTIVES: We investigated the relationships between environmental BPA exposure and reproductive parameters, including semen quality and male reproductive hormones, in prospectively recruited fertile men. METHODS: Participants (n = 375) were partners of pregnant women who participated in the Study for Future Families in four U.S. cities, and all of the men provided blood, semen, and urine samples. BPA was measured in urine. Serum samples were analyzed for reproductive hormones, including follicle-stimulating hormone, luteinizing hormone (LH), testosterone, inhibin B, estradiol, and sex hormone--binding globulin (SHBG), as well as the free androgen index (FAI). Semen analyses were performed according to World Health Organization criteria. Pearson correlations were used for unadjusted analyses, and multiple linear regression analyses were used to examine associations controlling for age, body mass index, smoking, ethnicity, urinary creatinine concentration, time of sample collection, and duration of abstinence. RESULTS: After multivariate adjustment, we observed no significant associations between any semen parameter and urinary BPA concentration. However, a significant inverse association was found between urinary BPA concentration and FAI levels and the FAI/LH ratio, as well as a significant positive association between BPA and SHBG. CONCLUSIONS: Our results suggest that, in fertile men, exposure to low environmental levels of BPA may be associated with a modest reduction in markers of free testosterone, but any effects on reproductive function are likely to be small, and of uncertain clinical significance. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between stressful life events and semen parameters. Design: Cross-sectional analysis in a pregnancy cohort study. Setting: Prenatal clinics in five U.S. cities. Patient(s): Fertile men (n = 744) in the Study for Future Families, a cohort study of pregnant women and their partners. Intervention(s): None. Main Outcome Measure(s): Sperm concentration, percent motile, and percent normal morphology and classification above/below World Health Organization (WHO) cutoffs for semen quality. Result(s): After adjusting for confounders, men reporting 2+ recent stressful life events had an increased risk of being classified below WHO thresholds for “normal” defined by concentration, motility, and morphology criteria compared with men reporting <2 stressful life events (odds ratio [OR] = 2.06; 95% confidence interval [CI], 1.18, 3.61; OR = 1.54; 95% CI, 1.04, 2.29; OR = 1.93; 95% CI, 1.02, 3.66 for concentration, motility and morphology, respectively). Men experiencing 2+ stressful life events had lower sperm concentration (log scale, β = −0.25; 95% CI, −0.38, −0.11) and lower percent motile sperm (β = −1.95; 95% CI, −3.98, 0.07), but percent normal morphology was less affected. Conclusion(s): These results suggest that stressful life events may be associated with decreased semen quality in fertile men. The experience of psychosocial stress may be a modifiable factor in the development of idiopathic infertility. [Copyright &y& Elsevier]

Addresses the hypothesis that pesticides currently used in Missouri contributed to the differences in semen quality in fertile men. Examination of the relationship between environmental pesticide exposure and semen quality in infertile and fertile men; Association of the herbicides 2,4-D(2,4-dichlorophenoxyacetic acid) and metolachor with poor semen quality.

Building on our recent discovery of the zinc signature phenomenon present in boar, bull, and human spermatozoa, we have further characterized the role of zinc ions in the spermatozoa's pathway to fertilization. In boar, the zinc signature differed between the three major boar ejaculate fractions, the initial pre-rich, the sperm-rich, and the post-sperm-rich fraction. These differences set in the sperm ejaculatory sequence establish two major sperm cohorts with marked differences in their sperm capacitation progress. On the subcellular level, we show that the capacitation-induced Zn-ion efflux allows for sperm release from oviductal glycans as analyzed with the oviductal epithelium mimicking glycan binding assay. Sperm zinc efflux also activates zinc-containing enzymes and proteases involved in sperm penetration of the zona pellucida, such as the inner acrosomal membrane matrix metalloproteinase 2 (MMP2). Both MMP2 and the 26S proteasome showed severely reduced activity in the presence of zinc ions, through studies using by gel zymography and the fluorogenic substrates, respectively. In the context of the fertilization-induced oocyte zinc spark and the ensuing oocyte-issued polyspermy-blocking zinc shield, the inhibitory effect of zinc on sperm-borne enzymes may contribute to the fast block of polyspermy. Altogether, our findings establish a new paradigm on the role of zinc ions in sperm function and pave the way for the optimization of animal semen analysis, artificial insemination (AI), and human male-factor infertility diagnostics. [ABSTRACT FROM AUTHOR]

Background: Hormonal contraceptives, particularly depot medroxyprogesterone acetate (DMPA), have been reported to be associated with substantially enhanced HIV acquisition; however, the biological mechanisms of this risk remain poorly understood. We aimed to investigate the effects of different hormonal contraceptives on the expression of the HIV co-receptors, CXCR4 and CCR5, on female endocervical and peripheral blood T cells. Methods: A total of 59 HIV-negative women were enrolled, including 15 initiating DMPA, 28 initiating a levonorgestrel-releasing intrauterine device (LNG-IUD) and 16 initiating an etonogestrel (ETG)-delivering vaginal ring. Peripheral blood and endocervical cytobrush specimens were collected at enrollment and 3–4 weeks after contraception initiation to analyze the expression of CXCR4 and CCR5, on CD4+ and CD8+ T cells using flow cytometry. Results: Administration of DMPA increased the percentages of CD4+ and CD8+ T cells expressing CCR5 in the endocervix but not in the peripheral blood. Administration of the LNG-IUD or the ETG vaginal ring did not affect the percentages of T lymphocytes expressing CXCR4 or CCR5 in the female cervix or peripheral blood. Conclusions: Increase in the percentage of endocervical T cells expressing CCR5 upon DMPA exposure provides a plausible biological explanation for the association between DMPA use and an elevated risk of HIV infection. [ABSTRACT FROM AUTHOR]