Abstract
The global obesity epidemic parallels a decrease in male fertility. Yet, the association between body mass index (BMI) and sperm parameters remains controversial. A negative correlation between BMI and sperm concentration or total sperm count (TSC) was shown by several reports,1, 2 but not documented by others.3, 4 The purpose of this report was to update the level of evidence on the association between body mass index (BMI) and sperm count through a systematic review and meta-analysis.
Keywords: obesity, BMI, sperm concentration, total sperm count, meta-analysis
METHODS
A systematic review of available literature was conducted to investigate the impact of BMI on sperm count in human males according to the PRISMA statement. A Pubmed and EMBASE search identified relevant studies published until October 2010. Authors of relevant studies were contacted by email and asked to complete a standardized data form regarding total sperm counts according to BMI categories. Unpublished data obtained from patients followed at the Infertility Center of Jean Verdier Hospital, Bondy, France, between January 2007 and December 2010 were also included.
The following BMI categories were used for analyses: <18.5, 18.5-24.9, 25.0-29.9 and ≥ 30.0 kg/m2. Data were stratified according to TSC as having normozoospermia (≥ 40 × 106 spermatozoa per ejaculate), oligozoospermia (< 40 × 106 but > 0 spermatozoa per ejaculate), and azoospermia (absence of spermatozoa), as in WHO guidelines.5 We performed random effects models to obtain summary estimates in order to account for inter-study variation. Studies were weighted according to an estimate of statistical size defined as the inverse of the variance of the log odds-ratio (OR). Prevalent ORs and 95% confidence intervals (95% CI) are presented. We calculated the ORs of overweight and obese men to present with oligozoospermia or azoospermia in comparison with normal weight men.
RESULTS
A total of 8,873 articles were identified. In total, 31 articles were potentially appropriate to be included in the meta-analysis because investigating the relationship between BMI and sperm parameters. A total of 14 eligible studies were included in the present meta-analysis, corresponding to a total study sample of 9,779 individuals. Overweight men were at significantly increased odds of presenting with oligozoospermia (OR, 1.11; 95% CI, 1.01-1.20) or azoospermia (OR, 1.39; 95% CI, 0.98-1.97) compared to men of normal weight (Figure). Likewise, obese men were at increased risk of oligozoospermia (1.42; 95% CI, 1.12-1.79) or azoospermia (1.81; 95% CI, 1.23-2.66), compared to men of normal weight (Figure).
Figure.
Association between oligozoospermia and azoospermia stratified by BMI categories.
COMMENT
This meta-analysis based on 9,779 men showed an inverse association between overweight or obesity and abnormal sperm count. This relationship may be explained by different pathophysiological hypotheses: (i) hypogonadotropic hyperestrogenic hypogonadism due to aromatization of steroids in estrogens in peripheral tissues,6 (ii) direct alterations of spermatogenesis and Sertoli cell function,7 (iii) hip, abdominal and scrotal fat tissue accumulation leading to the increase of scrotal temperature,8 (iv) accumulation of toxic substances and liposoluble endocrine disruptors in fatty tissue.2
Our strategy based on individual patient data and analysis of dichotomized sperm count made it possible to have a more homogeneous meta-analysis of the available evidence. Limitations of our study are the exclusion of 15 studies because of incomplete data or lack of response from authors, and the variations in the study populations. Yet, this variability suggests that our findings may be generalizable to both infertile and general population. We were also reliant on BMI and conventional semen parameters as relevant measure of body fat content and assessment of fertility potential. However, even if they may not be the best indicators, they remain the gold standard for clinical evaluation of adiposity and male fertility, respectively, and allow a clear application of our findings. On the other hand, the strengths of our meta-analysis are a large sample size based on a collection of individual level data. In conclusion, overweight and obesity are associated with an increased risk of azoospermia or oligozoospermia. These data strongly suggest that excess body weight affects sperm production.
ACKNOWLEDGMENTS
Niels Jorgensen, Rigshospitalet, Copenhagen, Denmark; Yafei Li, Third Military Medical University, Chongqing, China; Zhihong Cui, Third Military Medical University, Chongqing, China; Rosa Molina, Laboratorio de Andrologia y Reproduccion, Cordoba, Argentina; Ruben Daniel Ruiz, Facultad de Ciencias Medicas, Universidad Nacional de Cordoba, Argentina; Thomas L. Toth, Harvard Medical School, Boston MA, USA; Russ Hauser, Harvard School of Public Health, Boston MA, USA; Janos Szollosi, University of Szeged, Hungary; Ane Marie Thulstrup, Aarhus University Hospital, Aarhus, Denmark; Joop Laven, Erasmus University Medical Center, Rotterdam, The Netherlands; Marijana Vujkovic, Erasmus University Medical Center, Rotterdam, The Netherlands; Fatima Hammiche, Erasmus University Medical Center, Rotterdam, The Netherlands; Gregor Majdic, Center for animal genomics, Veterinary faculty, University of Ljubljana, Slovenia; Rosana Hernandez Weldon, UC Berkeley School of Public Health, Berkeley CA, USA; Andrew J. Wyrobek, Lawrence Berkeley National Laboratory, Berkeley CA, USA; Department of Assisted Reproduction, Landspitali University Hospital, Iceland; Zoltan Zavaczki, Landstinget Gavleborg, Hudiksvall, Sweden.
Funding/Support: Dr. Chavarro was supported in part by grant 5P30DK46200-18. Dr. Eskenazi was supported in part by grant P42ES04705.
Footnotes
The Obesity-Fertility Collaborative Group consists of:
Nathalie Sermondade (Hôpital Jean Verdier, Bondy, France & Université Paris 13, Bobigny, France), Céline Faure (Hôpital Jean Verdier, Bondy, France & Université Paris 13, Bobigny, France), Léopold Fezeu (Université Paris 13, Bobigny, France), Rachel Lévy (Hôpital Jean Verdier, Bondy, France & Université Paris 13, Bobigny, France), Sébastien Czernichow (Ambroise Paré Hospital & University of Versailles Saint Quentin en Yvelines, Boulogne-Billancourt, France), Tina Kold Jensen (Rigshospitalet, Copenhagen, Denmark), Madelon Van Wely (Academic Medical Centre, Amsterdam, The Netherlands), Jia Cao (Third Military Medical University, Chongqing, China), Ana Carolina Martini (Universidad Nacional de Cordoba, Cordoba, Argentina), Jorge Chavarro (Brigham and Women's Hospital & Harvard Medical School, Boston, USA), Sandor Koloszar (University of Szeged, Szeged, Hungary), Cecilia H. Ramlau-Hansen (Aarhus University, Aarhus C, Denmark), Régine P.M. Steegers-Theunissen (Erasmus University Medical Center, Rotterdam, The Netherlands), Branko Zorn (University Medical Center, Ljubljana, Slovenia), Alex J. Polotsky (University of Colorado Denver, Aurora, USA), Brenda Eskenazi (UC Berkeley School of Public Health, Berkeley, USA), Elin V. Magnusdottir (University of Iceland, Reykjavik, Iceland), Imre Fejes (University of Szeged, Szeged, Hungary), Serge Hercberg (Hôpital Avicenne, Bobigny, France & Université Paris 13, Bobigny, France)
Conflicts of interest statement: none.
Author Contributions:
Sermondade, Fezeu and Czernichow have full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analyses.
Study concept and design: Lévy, Czernichow, Sermondade, Fezeu
Acquisition of data: Sermondade, Faure, Jensen, Van Wely, Cao, Martini, Chavarro, Koloszar, Ramlau-Hansen, Steegers-Theunissen, Zorn, Polotsky, Eskenazi, Magnusdottir, Fejes, Hercberg
Analysis and interpretation of data: Lévy, Czernichow, Sermondade, Faure, Fezeu
Drafting of the manuscript: Sermondade, Czernichow, Fezeu
Critical revision of the manuscript for important intellectual content: Sermondade, Faure, Fezeu, Jensen, Van Wely, Cao, Martini, Chavarro, Koloszar, Ramlau-Hansen, Steegers-Theunissen, Zorn, Polotsky, Eskenazi, Magnusdottir, Fejes, Hercberg, Lévy, Czernichow
Statistical analyses: Fezeu
Study supervision: Czernichow
Financial Disclosures: none reported.
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