Ahmad O. Hammoud

Male obesity and alteration in sperm parameters

OBJECTIVE To study the effect of male obesity on sperm parameters and erectile dysfunction. DESIGN Retrospective analysis. SETTING Referral fertility center. PATIENT(S) Couples presenting for infertility treatment. INTERVENTION(S) On presentation, all men reported their weight and height and filled out an intake form that includes questions regarding factors that affect male infertility, including presence of erectile dysfunction. Body mass index (BMI) was divided into three groups: normal (BMI <25 kg/m(2)), overweight (25 kg/m(2) <or= BMI < 30 kg/m(2)), and obese (BMI >or=30 kg/m(2)). Sperm parameters reviewed included sperm concentration and progressively motile sperm count. MAIN OUTCOME MEASURE(S) Oligozoospermia, low progressively motile sperm count, and self-reported erectile dysfunction. RESULT(S) The mean age of the study population was 32.8 +/- 0.3 years. Among the 526 patients, 10.2% (54 of 526) were excluded because of the presence of a male factor known to affect fertility. The incidence of oligozoospermia increased with increasing BMI: normal weight = 5.32%, overweight = 9.52%, and obese = 15.62%. The prevalence of a low progressively motile sperm count was also greater with increasing BMI: normal weight = 4.52%, overweight = 8.93%, and obese = 13.28%. The incidence of erectile dysfunction did not vary across BMI categories when corrected for potential contributing factors. CONCLUSION(S) Male obesity is associated with increased incidence of low sperm concentration and low progressively motile sperm count.

Impact of male obesity on infertility: a critical review of the current literature

OBJECTIVE To evaluate the current understanding of the effects and potential mechanisms of obesity on male fertility. DESIGN Literature review of articles pertaining to obesity and male infertility. RESULT(S) Recent population-based studies suggest an elevated risk for subfertility among couples in which the male partner is obese and an increased likelihood of abnormal semen parameters among heavier men. Male factor infertility is associated with a higher incidence of obesity in the male partner. Obese men exhibit reduced androgen and SHBG levels accompanied by elevated estrogen levels. Reduced inhibin B levels correlate with degree of obesity and are not accompanied by compensatory increases in FSH. This complexly altered reproductive hormonal profile suggests that endocrine dysregulation in obese men may explain the increased risk of altered semen parameters and infertility. Additional features of male obesity that may contribute to an increased risk for infertility are altered retention and metabolism of environmental toxins, altered lifestyle factors, and increased risks for sexual dysfunction. Neither reversibility of obesity-associated male infertility with weight loss nor effective therapeutic interventions have been studied yet. CONCLUSION(S) The increasing prevalence of obesity calls for greater clinician awareness of its effects on fertility, better understanding of underlying mechanisms, and eventually avenues for mitigation or treatment.

Genome-wide analysis identifies changes in histone retention and epigenetic modifications at developmental and imprinted gene loci in the sperm of infertile men

BACKGROUND The sperm chromatin of fertile men retains a small number of nucleosomes that are enriched at developmental gene promoters and imprinted gene loci. This unique chromatin packaging at certain gene promoters provides these genomic loci the ability to convey instructive epigenetic information to the zygote, potentially expanding the role and significance of the sperm epigenome in embryogenesis. We hypothesize that changes in chromatin packaging may be associated with poor reproductive outcome. METHODS Seven patients with reproductive dysfunction were recruited: three had unexplained poor embryogenesis during IVF and four were diagnosed with male infertility and previously shown to have altered protamination. Genome-wide analysis of the location of histones and histone modifications was analyzed by isolation and purification of DNA bound to histones and protamines. The histone-bound fraction of DNA was analyzed using high-throughput sequencing, both initially and following chromatin immunoprecipitation. The protamine-bound fraction was hybridized to agilent arrays. DNA methylation was examined using bisulfite sequencing. RESULTS Unlike fertile men, five of seven infertile men had non-programmatic (randomly distributed) histone retention genome-wide. Interestingly, in contrast to the total histone pool, the localization of H3 Lysine 4 methylation (H3K4me) or H3 Lysine 27 methylation (H3K27me) was highly similar in the gametes of infertile men compared with fertile men. However, there was a reduction in the amount of H3K4me or H3K27me retained at developmental transcription factors and certain imprinted genes. Finally, the methylation status of candidate developmental promoters and imprinted loci were altered in a subset of the infertile men. CONCLUSIONS This initial genome-wide analysis of epigenetic markings in the sperm of infertile men demonstrates differences in composition and epigenetic markings compared with fertile men, especially at certain imprinted and developmental loci. Although no single locus displays a complete change in chromatin packaging or DNA modification, the data suggest that moderate changes throughout the genome exist and may have a cumulative detrimental effect on fecundity.

Effect of Roux-en-Y Gastric Bypass Surgery on the Sex Steroids and Quality of Life in Obese Men

CONTEXT The effect of bariatric surgery on the reproductive function of obese men is not entirely elucidated. OBJECTIVE The aim of the study was to define the effect of Roux-En-Y gastric bypass surgery on the reproductive hormones and sexual function in obese men. DESIGN AND SETTING The cohort was followed for 2 yr at a clinical research center. PATIENTS Sixty-four severely obese men (22 who had gastric bypass surgery and 42 controls) participated in the study. INTERVENTION(S) Anthropometrics [weight, body mass index (BMI), and percentage body fat] and reproductive hormones were measured. The sexual quality of life was assessed using the Impact of Weight on the Quality Of Life-Lite questionnaire. MAIN OUTCOME MEASURE(S) Reproductive hormones and sexual quality of life were measured. RESULTS The mean age was 48.9 +/- 1.2 yr. At baseline, mean weight was 333.0 +/- 7.1 lb, BMI was 46.2 +/- 0.9 kg/m(2), and total testosterone was 339.9 +/- 21.32 ng/dl. BMI correlated positively with estradiol and negatively with total and free testosterone. Indices of dissatisfaction with sexual quality of life correlated positively with measures of obesity. Difficult sexual performance and low sexual desire correlated negatively with free and total testosterone (r = -0.273, P = 0.038; and r = -0.267, P = 0.042, respectively). After 2 yr, the gastric bypass surgery group had a significant decrease in BMI (-16.6 +/- 1.2 vs. -0.46 +/- 0.51 kg/m(2)) and estradiol (-8.1 +/- 2.4 vs. 1.6 +/- 1.4 pg/ml) and had an increase in total testosterone (310.8 +/- 47.6 vs. 14.2 +/- 15.3 ng/dl) and free testosterone (45.2 +/- 5.1 vs. -0.4 +/- 3.0 pg/ml). Sexual quality of life was improved after gastric bypass surgery. CONCLUSION Hormonal alterations and diminished sexual quality of life among obese men are related to degree of obesity, and both are improved after gastric bypass surgery.

In vitro fertilization availability and utilization in the United States: a study of demographic, social, and economic factors

OBJECTIVE To characterize the demographic correlates of IVF availability and utilization. DESIGN Demographic analysis of public data. SETTING Each of the 50 states in the United States was used as a unit of analysis. PATIENT(S) Patients undergoing IVF, as demographically estimated. INTERVENTION(S) Publicly available data were collected through the Society for Assisted Reproductive Technology and the Centers for Disease Control. The US Census Bureau data were collected by using software available from the Centers for Disease Control. MAIN OUTCOME MEASURE(S) The number of physicians performing IVF and the number of IVF cycles per 100,000 reproductive-age women were used to estimate IVF availability and utilization. RESULT(S) In 2005, 1,031 providers performed 98,242 fresh IVF cycles in 430 centers. Overall availability was 2.5 IVF physicians per 100,000, and utilization was 236 IVF cycles per 100,000. Availability and utilization of IVF were highly correlated. Mean IVF availability and utilization were significantly higher in states with IVF insurance coverage. In adjusted analyses, IVF availability correlated positively with mandated insurance coverage, percentage of single persons, and median income. Utilization of IVF correlated with IVF availability, percentage urbanization, and percentage of individuals >or=25 years of age who had a bachelors degree. CONCLUSION(S) Lower rates of IVF utilization in some states are correlated with a lack of insurance coverage and decreased availability of physicians providing this service.

Obesity and Male Infertility: A Practical Approach

Obesity in men is associated with infertility in numerous studies, and the temporal trend for a decline in semen parameters parallels the increasing prevalence of obesity in the developed world. In addition to impaired semen quality, fertility among obese men may be affected by decreased libido and erectile dysfunction. This spectrum of expression of hypogonadism among obese men originates from multiple interacting factors including reduced levels of gonadotropins and testosterone, altered androgen-to-estrogen ratios, insulin resistance, and sleep apnea. No evidence-based treatment that increases the likelihood of pregnancy for the infertility associated with male obesity has been demonstrated to date. Interventions associated with improvement of intermediate outcomes that include the endocrine profile, semen parameters, and sexual function may be appropriately selected based on history, physical findings, as well as endocrine and metabolic evaluation. Among these interventions are weight loss through lifestyle change, relief from sleep apnea, use of aromatase inhibitors, gonadotropin administration, phosphodiesterase inhibitors, and insulin-sensitizing agents.

Effect of male and female body mass index on pregnancy and live birth success after in vitro fertilization

OBJECTIVE To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes. DESIGN Prospective cohort study. SETTING University fertility center. PATIENT(S) All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Embryologic parameters, clinical pregnancy, and live birth incidence. RESULT(S) The average male BMI among the study population was 27.5 ± 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (≥35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success. CONCLUSION(S) Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.

Sleep apnea, reproductive hormones and quality of sexual life in severely obese men.

The effect of sleep apnea on the reproductive function of obese men is not entirely elucidated. The objective of this study was to define the effect of sleep apnea on the reproductive hormones and sexual function in obese men. This study included 89 severely obese men with BMI ≥35 kg/m2 considering gastric bypass surgery. Anthropometrics (weight, and BMI), reproductive hormones, and sleep studies were measured. The sexual quality of life was assessed using the Impact of Weight on Quality of Life‐Lite questionnaire (IWQOL‐Lite). The mean age of our patients was 46.9 ± 11.0 years, the mean BMI was 47.8 ± 8.7 kg/m2 and the mean weight was 337.7 ± 62.4 lb. After correction for age and BMI, means of free testosterone per severity group of sleep apnea were as follows: no or mild sleep apnea 74.4 ± 3.8 pg/ml, moderate sleep apnea 68.6 ± 4.2 pg/ml, and severe sleep apnea 60.2 ± 2.92 pg/ml, P = 0.014. All other parameters of sleep apnea including hypopnea index, percent time below a SpO2 of 90%, and percent time below a SpO2 of 80% were also negatively correlated with testosterone levels after correction for age and BMI. BMI and presence of coronary artery disease decreased the sexual quality of life. Sleep apnea was associated with reduced sexual quality of life. In summary, sleep apnea negatively affects testosterone levels independent of BMI. Severely obese men had decreased sexual quality of life.

Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study

OBJECTIVE We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study. STUDY DESIGN In this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort. RESULTS The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57-3.76) and population (AOR, 7.91; 95% CI, 1.69-37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28-4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44-5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32-0.75), parity (AOR, 0.42; 95% CI, 0.28-0.64), and body mass index (AOR, 0.95; 95% CI, 0.93-0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor. CONCLUSION An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.

The effect of gestational age on trial of labor after Cesarean section

Objectives: To evaluate the effect of gestational age on the rate of successful vaginal delivery and the rate of uterine rupture in patients undergoing a trial of labor (TOL) after a prior Cesarean delivery.Study design: This was a cohort study including patients with a live singleton fetus undergoing a TOL after a previous low transverse Cesarean delivery between 1988 and 2002. Patients were divided into three groups according to gestational age: 24–36 weeks 6 days, 37–40 weeks 6 days and ≥41 weeks. Obstetric outcomes, including the rates of successful vaginal delivery and symptomatic uterine rupture, were compared between the groups. Multivariate logistic regression analysis was performed to adjust for potential confounding factors.Results: There were 253, 1911 and 329 patients in each group, respectively. In patients with advanced gestational age (≥41 weeks) the rate of uterine rupture was significantly higher (0% vs. 1.0% vs. 2.7%, p=0.006) and the rate of successful vaginal deliveries was significantly lower (83% vs. 76.9% vs. 62.6%, p<0.001). After adjusting for confounding variables, advanced gestational age was associated with a lower rate of successful vaginal delivery (odds ratio 0.68, 95% CI 0.51–0.89), and a higher rate of uterine rupture (odds ratio 2.85, 95% CI 1.27–6.42) when compared to 37–40 weeks 6 days.Conclusion: Advanced gestational age is associated with higher rates of failed TOL and uterine rupture.