Alexander W Pastuszak1, Amin S Herati2, Michael L Eisenberg3, Cenk Cengiz4,5, Peter H Langlois6, Taylor P Kohn7, Dolores J Lamb8, Larry I Lipshultz4,5. 1. Division of Urology, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA. 2. The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 3. Department of Urology, Stanford University School of Medicine, Palo Alto, CA, USA. 4. Center for Reproductive Medicine, Baylor College of Medicine, Houston, TX, USA. 5. Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA. 6. Texas Department of State Health Services, Birth Defects Epidemiology and Surveillance Branch, Austin, TX, USA. 7. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 8. Department of Urology, Weill Cornell Medical College, New York, NY, USA.
Abstract
STUDY QUESTION: What is the relationship between semen parameters and birth defect (BD) rates in offspring of men evaluated for infertility? SUMMARY ANSWER: Among men undergoing infertility evaluation, there is no significant relationship between semen parameters and defect rates in live or still births, even when considering mode of conception. WHAT IS KNOWN ALREADY: Approximately 15% of couples have fertility difficulties, with up to a 50% male factor contribution. An increased risk of BDs exists in couples using ART, particularly IVF and ICSI, but it is unknown if this related to the ART procedures or an underlying male factor. STUDY DESIGN, SIZE, DURATION: To determine if the severity of male factor infertilty, as assessed via sperm quality and mode of conception, is associated with BD rates, we performed a retrospective cohort study. Fathers with semen analysis data in the Baylor College of Medicine Semen Database (BCMSD) were linked with their offspring using Texas Birth Defects Registry (TBDFR) data between 1999 and 2009. In this 10-year period, a total of 1382 men were identified in linkage between the BCMSD and TBDFR. A total of 109 infants with and 2115 infants without BDs were identified. PARTICIPANTS/MATERIALS, SETTING, METHODS: To determine the association between BDs and semen parameters, we used hierarchical linear modeling to determine odds ratios between BD rates, semen parameters, and mode of conception before and after adjustment for paternal, maternal and birth covariates. Semen parameters were stratified based on thresholds defined by the WHO fifth edition laboratory manual for the examination and processing of human semen. MAIN RESULTS AND THE ROLE OF CHANCE: In total 4.9% of 2224 infants were identified with a BD. No statistically significant association was observed between BD rates and semen parameters, before or after adjustment for covariates. The association between sperm concentration and BDs demonstrated an odds ratio (OR) of 1.07 (95% confidence interval: 0.63-1.83); motility: OR 0.91 (0.52-2.22); and total motile count: OR 1.21 (0.70-2.08). Likewise, mode of conception, including infertility treatment and ART, did not affect BD rates (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: BDs recorded in the TBDFR only include live born infants or still births after 20 weeks, our study did not evaluate the effect of impaired semen parameters on developmental defects prior to 20 weeks of gestation. With 109 BDs, our statistical analysis was powered to detect moderate differences associated with particular semen parameters. Additionally, data about mode of conception was not available for 1053 of 2224 births. WIDER IMPLICATIONS OF THE FINDINGS: BD rates are not associated with semen quality or mode of conception. The current study suggests that the severity of male factor infertility does not impact the rate of congenital anomalies. This information is important when counseling couples concerned about the relationship between impaired semen quality and BDs. STUDY FUNDING/COMPETING INTEREST(S): Supported in part by the NIH Men's Reproductive Health Research (MRHR) K12 HD073917 (D.J.L.), the Multidisciplinary K12 Urologic Research (KURe) Career Development Program (D.J.L.), P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, NIH (D.J.L.), and by U01DD000494 from the Centers for Disease Control and Prevention and the Title V Block Grant to the Texas Department of State Health Services. A.W.P. is a National Institutes of Health K08 Scholar supported by a Mentored Career Development Award (K08DK115835-01) from the from the National Institute of Diabetes and Digestive and Kidney Diseases. This work is also supported in part through a Urology Care Foundation Rising Stars in Urology Award (to A.W.P.) None of the authors has a conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.
STUDY QUESTION: What is the relationship between semen parameters and birth defect (BD) rates in offspring of men evaluated for infertility? SUMMARY ANSWER: Among men undergoing infertility evaluation, there is no significant relationship between semen parameters and defect rates in live or still births, even when considering mode of conception. WHAT IS KNOWN ALREADY: Approximately 15% of couples have fertility difficulties, with up to a 50% male factor contribution. An increased risk of BDs exists in couples using ART, particularly IVF and ICSI, but it is unknown if this related to the ART procedures or an underlying male factor. STUDY DESIGN, SIZE, DURATION: To determine if the severity of male factor infertilty, as assessed via sperm quality and mode of conception, is associated with BD rates, we performed a retrospective cohort study. Fathers with semen analysis data in the Baylor College of Medicine Semen Database (BCMSD) were linked with their offspring using Texas Birth Defects Registry (TBDFR) data between 1999 and 2009. In this 10-year period, a total of 1382 men were identified in linkage between the BCMSD and TBDFR. A total of 109 infants with and 2115 infants without BDs were identified. PARTICIPANTS/MATERIALS, SETTING, METHODS: To determine the association between BDs and semen parameters, we used hierarchical linear modeling to determine odds ratios between BD rates, semen parameters, and mode of conception before and after adjustment for paternal, maternal and birth covariates. Semen parameters were stratified based on thresholds defined by the WHO fifth edition laboratory manual for the examination and processing of human semen. MAIN RESULTS AND THE ROLE OF CHANCE: In total 4.9% of 2224 infants were identified with a BD. No statistically significant association was observed between BD rates and semen parameters, before or after adjustment for covariates. The association between sperm concentration and BDs demonstrated an odds ratio (OR) of 1.07 (95% confidence interval: 0.63-1.83); motility: OR 0.91 (0.52-2.22); and total motile count: OR 1.21 (0.70-2.08). Likewise, mode of conception, including infertility treatment and ART, did not affect BD rates (P > 0.05). LIMITATIONS, REASONS FOR CAUTION: BDs recorded in the TBDFR only include live born infants or still births after 20 weeks, our study did not evaluate the effect of impaired semen parameters on developmental defects prior to 20 weeks of gestation. With 109 BDs, our statistical analysis was powered to detect moderate differences associated with particular semen parameters. Additionally, data about mode of conception was not available for 1053 of 2224 births. WIDER IMPLICATIONS OF THE FINDINGS: BD rates are not associated with semen quality or mode of conception. The current study suggests that the severity of male factor infertility does not impact the rate of congenital anomalies. This information is important when counseling couples concerned about the relationship between impaired semen quality and BDs. STUDY FUNDING/COMPETING INTEREST(S): Supported in part by the NIH Men's Reproductive Health Research (MRHR) K12 HD073917 (D.J.L.), the Multidisciplinary K12 Urologic Research (KURe) Career Development Program (D.J.L.), P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, NIH (D.J.L.), and by U01DD000494 from the Centers for Disease Control and Prevention and the Title V Block Grant to the Texas Department of State Health Services. A.W.P. is a National Institutes of Health K08 Scholar supported by a Mentored Career Development Award (K08DK115835-01) from the from the National Institute of Diabetes and Digestive and Kidney Diseases. This work is also supported in part through a Urology Care Foundation Rising Stars in Urology Award (to A.W.P.) None of the authors has a conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.
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