Jorge E. Chavarro

Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic

OBJECTIVE To examine the association between body weight and measures of male reproductive potential. DESIGN Cross-sectional study. SETTING Fertility clinic in an academic medical center. PATIENT(S) Four hundred eighty-three male partners of subfertile couples. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Standard semen analysis, sperm DNA fragmentation, and serum levels of reproductive hormones. RESULT(S) As expected, body mass index (BMI) was positively related to estradiol levels and inversely related to total testosterone and sex hormone-binding glogulin (SHBG) levels. There was also a strong inverse relation between BMI and inhibin B levels and a lower testosterone:LH ratio among men with a BMI > or = 35 kg/m(2). Body mass index was unrelated to sperm concentration, motility, or morphology. Ejaculate volume decreased steadily with increasing BMI levels. Further, men with BMI > or = 35 kg/m(2) had a lower total sperm count (concentration x volume) than normal weight men (adjusted difference in the median [95% confidence interval] = -86 x 10(6) sperm [-134, -37]). Sperm with high DNA damage were significantly more numerous in obese men than in normal-weight men. CONCLUSION(S) These data suggest that despite major differences in reproductive hormone levels with increasing body weight, only extreme levels of obesity may negatively influence male reproductive potential.

BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis

BACKGROUND The global obesity epidemic has paralleled a decrease in semen quality. Yet, the association between obesity and sperm parameters remains controversial. The purpose of this report was to update the evidence on the association between BMI and sperm count through a systematic review with meta-analysis. METHODS A systematic review of available literature (with no language restriction) was performed to investigate the impact of BMI on sperm count. Relevant studies published until June 2012 were identified from a Pubmed and EMBASE search. We also included unpublished data (n = 717 men) obtained from the Infertility Center of Bondy, France. Abstracts of relevant articles were examined and studies that could be included in this review were retrieved. Authors of relevant studies for the meta-analysis were contacted by email and asked to provide standardized data. RESULTS A total of 21 studies were included in the meta-analysis, resulting in a sample of 13 077 men from the general population and attending fertility clinics. Data were stratified according to the total sperm count as normozoospermia, oligozoospermia and azoospermia. Standardized weighted mean differences in sperm concentration did not differ significantly across BMI categories. There was a J-shaped relationship between BMI categories and risk of oligozoospermia or azoospermia. Compared with men of normal weight, the odds ratio (95% confidence interval) for oligozoospermia or azoospermia was 1.15 (0.93-1.43) for underweight, 1.11 (1.01-1.21) for overweight, 1.28 (1.06-1.55) for obese and 2.04 (1.59-2.62) for morbidly obese men. CONCLUSIONS Overweight and obesity were associated with an increased prevalence of azoospermia or oligozoospermia. The main limitation of this report is that studied populations varied, with men recruited from both the general population and infertile couples. Whether weight normalization could improve sperm parameters should be evaluated further.

Diet and lifestyle in the prevention of ovulatory disorder infertility.

OBJECTIVE: To evaluate the relation of a dietary pattern and other lifestyle practices to risk of ovulatory disorder infertility. METHODS: We followed a cohort of 17,544 women without a history of infertility for 8 years as they tried to become pregnant or became pregnant. A dietary score based on factors previously related to lower ovulatory disorder infertility (higher consumption of monounsaturated rather than trans fats, vegetable rather than animal protein sources, low glycemic carbohydrates, high fat dairy, multivitamins, and iron from plants and supplements) and other lifestyle information was prospectively related to the incidence of infertility. RESULTS: Increasing adherence to a “fertility diet” pattern was associated with a lower risk of ovulatory disorder infertility. The multivariable-adjusted relative risk of ovulatory disorder infertility comparing women in the highest with women in the lowest quintile of the “fertility diet” pattern score was 0.34 (95% confidence interval 0.23–0.48; P for trend<.001). This inverse relation was similar in subgroups defined by women’s age, parity, and body weight. A combination of five or more low-risk lifestyle factors, including diet, weight control, and physical activity was associated with a 69% lower risk of ovulatory disorder infertility and an estimated population attributable risk of 66% (95% confidence interval 29–86%). CONCLUSION: Following a “fertility diet” pattern may favorably influence fertility in otherwise healthy women. Further, the majority of infertility cases due to ovulation disorders may be preventable through modifications of diet and lifestyle. LEVEL OF EVIDENCE: II

A Prospective Study of Polyunsaturated Fatty Acid Levels in Blood and Prostate Cancer Risk

Background: Animal models suggest that n-3 fatty acids inhibit prostate cancer proliferation, whereas n-6 fatty acids promote it, but epidemiologic studies do not uniformly support these findings. Methods: A nested case-control study was conducted among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Conditional logistic regression was used to estimate the relative risks (RR) and 95% confidence intervals (95% CI) of total, non-aggressive (stage A/B and Gleason < 7) and aggressive (stage C/D, Gleason ≥ 7, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific fatty acids expressed as percentages of total fatty acids. Results: Whole blood levels of all long-chain n-3 fatty acids examined and of linoleic acid were inversely related to overall prostate cancer risk (RRQ5vs.Q1, 0.59; 95% CI, 0.38-0.93; Ptrend = 0.01 for total long-chain n-3 fatty acids and RRQ5vs.Q1, 0.62; 95% CI, 0.41-0.95; Ptrend = 0.03 for linoleic). Blood levels of γ-linolenic and dihomo-γ-linolenic acids, fatty acids resulting from the metabolism of linoleic acid, were directly associated with prostate cancer (RR, 1.41; 95% CI, 0.94-2.12; Ptrend = 0.05 for γ-linolenic and RR, 1.54; 95% CI, 1.03-2.30; Ptrend = 0.02 for dihomo-γ-linolenic acid). Levels of arachidonic and α-linolenic acids were unrelated to prostate cancer. Conclusions: Higher blood levels of long-chain n-3 fatty acids, mainly found in marine foods, and of linoleic acid, mainly found in non-hydrogenated vegetable oils, are associated with a reduced risk of prostate cancer. The direct associations of linoleic acid metabolites with prostate cancer risk deserve further investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1364–70)

Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic

BACKGROUND High isoflavone intake has been related to decreased fertility in animal studies, but data in humans are scarce. Thus, we examined the association of soy foods and isoflavones intake with semen quality parameters. METHODS The intake of 15 soy-based foods in the previous 3 months was assessed for 99 male partners of subfertile couples who presented for semen analyses to the Massachusetts General Hospital Fertility Center. Linear and quantile regression were used to determine the association of soy foods and isoflavones intake with semen quality parameters while adjusting for personal characteristics. RESULTS There was an inverse association between soy food intake and sperm concentration that remained significant after accounting for age, abstinence time, body mass index, caffeine and alcohol intake and smoking. In the multivariate-adjusted analyses, men in the highest category of soy food intake had 41 million sperm/ml less than men who did not consume soy foods (95% confidence interval = -74, -8; P, trend = 0.02). Results for individual soy isoflavones were similar to the results for soy foods and were strongest for glycitein, but did not reach statistical significance. The inverse relation between soy food intake and sperm concentration was more pronounced in the high end of the distribution (90th and 75th percentile) and among overweight or obese men. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume. CONCLUSIONS These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration.

Dietary fat and semen quality among men attending a fertility clinic

BACKGROUND The objective of this study was to examine the relation between dietary fats and semen quality parameters. METHODS Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders. RESULTS Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62-14%) lower total sperm count and 38% (95% CI: 58-10%) lower sperm concentration than men in the lowest third (P(trend) = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= -0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4-3.5%) higher normal morphology than men in the lowest third (P(trend) = 0.02). CONCLUSIONS In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.

Fatty Acid Synthase Polymorphisms, Tumor Expression, Body Mass Index, Prostate Cancer Risk, and Survival

PURPOSE Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI). METHODS In a prospective nested case-control study of 1,331 white patients with PCa and 1,267 age-matched controls, we examined associations of five common SNPs within FASN (and 5 kb upstream/downstream, R(2) > 0.8) with PCa incidence and, among patients, PCa-specific death and tested for an interaction with BMI. Survival analyses were repeated for tumor FASN expression (n = 909). RESULTS Four of the five SNPs were associated with lethal PCa. SNP rs1127678 was significantly related to higher BMI and interacted with BMI for both PCa risk (P(interaction) = .004) and PCa mortality (P(interaction) = .056). Among overweight men (BMI > or = 25 kg/m(2)), but not leaner men, the homozygous variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to 6.23) compared with lean men with the wild type. Overweight patients carrying the variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa mortality. Similarly, overweight patients with elevated tumor FASN expression had a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (P(interaction) = .02). CONCLUSION FASN germline polymorphisms were significantly associated with risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and FASN tumor expression suggest FASN as a potential link between obesity and poor PCa outcome and raise the possibility that FASN inhibition could reduce PCa-specific mortality, particularly in overweight men.

Protein intake and ovulatory infertility.

OBJECTIVE The objective of the study was to evaluate whether intake of protein from animal and vegetable origin is associated with ovulatory infertility. STUDY DESIGN A total of 18,555 married women without a history of infertility were followed up as they attempted a pregnancy or became pregnant during an 8 year period. Dietary assessments were related to the incidence of ovulatory infertility. RESULTS During follow-up, 438 women reported ovulatory infertility. The multivariate-adjusted relative risk (RR) (95% confidence interval [CI]; P for trend) of ovulatory infertility comparing the highest to the lowest quintile of animal protein intake was 1.39 (1.01 to 1.90; 0.03). The corresponding RR (95% CI; P for trend) for vegetable protein intake was 0.78 (0.54 to 1.12; 0.07). Furthermore, consuming 5% of total energy intake as vegetable protein rather than as animal protein was associated with a more than 50% lower risk of ovulatory infertility (P =.007). CONCLUSION Replacing animal sources of protein with vegetable sources of protein may reduce ovulatory infertility risk.

A Prospective Study of Trans-Fatty Acid Levels in Blood and Risk of Prostate Cancer

Background: Previous studies suggest a positive association between markers of trans-fatty acid intake and prostate cancer. We therefore prospectively evaluated the association between blood trans-fatty acid levels and risk of prostate cancer. Methods: We conducted a nested case-control study among 14,916 apparently healthy men who provided blood samples in 1982. Blood fatty acid levels were determined for 476 men diagnosed with prostate cancer during a 13-year follow-up and their matched controls. Controls were individually matched to cases according to age and smoking status at baseline. Conditional logistic regression was used to estimate the relative risk and 95% confidence interval of total, nonaggressive (stage A/B and low grade), and aggressive (stage C/D, high grade, subsequent distant metastasis or death) prostate cancer associated with blood levels of specific trans-fatty acids. Results: Blood levels of all the trans-fatty acids examined were unrelated to total prostate cancer risk. When results were divided according to tumor aggressiveness, blood levels of 18:1n-9t, all the 18:2t examined, and total trans-fatty acids were positively associated to nonaggressive tumors. The relative risks (95% confidence intervals; P trend) comparing top with bottom quintile trans-fatty acid levels were 2.16 (1.12-4.17; 0.11) for 18:1n-9t, 1.97 (1.03-3.75; 0.01) for total 18:2t, and 2.21 (1.14-4.29; 0.06) for total trans-fatty acids. None of the trans fats examined was associated with aggressive prostate tumors. Conclusion: Blood levels of trans isomers of oleic and linoleic acids are associated with an increased risk of nonaggressive prostate tumors. As this type of tumors represents a large proportion of prostate cancer detected using prostate-specific antigen screening, these findings may have implications for the prevention of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(1):95–101)

Iron intake and risk of ovulatory infertility

OBJECTIVE: To evaluate whether iron supplement use or greater intake of total, heme and nonheme iron is associated with lower risk of ovulatory infertility. METHODS: We conducted a prospective cohort study among 18,555 married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999 (mean baseline age±standard deviation 32.6±3.6). Diet was assessed twice during follow-up and prospectively related to the incidence of infertility due to ovulatory disorder. RESULTS: During the 8 years of follow-up, 438 women reported infertility due to ovulatory disorder. Women who consumed iron supplements had a significantly lower risk of ovulatory infertility than women who did not use iron supplements (relative risk 0.60, 95% confidence interval 0.39–0.92), after adjusting for potential confounders. Total nonheme iron intake, primarily consumed as multivitamins and iron supplements, was inversely associated with the risk of infertility (relative risk Quintile 1 compared with 5, 95% confidence interval 0.39–0.92; P, trend .005.) Heme iron intake was unrelated to ovulatory infertility in multivariable adjusted analyses. CONCLUSION: Consumption of iron supplements and nonheme iron from other sources may decrease the risk of ovulatory infertility. LEVEL OF EVIDENCE: II-2