Abstract
Objective: To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays. Design: Secondary analysis. Setting: Nine US-based fertility centers. Patient(s): Infertile men (N = 147) with sperm concentration ≤15 × 106/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency. Intervention(s): At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months. Main Outcome Measure(s): The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ2 test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations. Result(s): The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19). Conclusion(s): Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 282-288 |
| Number of pages | 7 |
| Journal | F and S Reports |
| Volume | 2 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2021 |
All Science Journal Classification (ASJC) codes
- Embryology
- Obstetrics and Gynecology
- Reproductive Medicine
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Sperm deoxyribonucleic acid fragmentation : predictors, fertility outcomes, and assays among infertile males. / Rios, Julie S.; Coward, R. Matthew; Hansen, Karl R.; Barnhart, Kurt T.; Cedars, Marcelle I.; Legro, Richard S.; Diamond, Michael P.; Krawetz, Stephen A.; Usadi, Rebecca; Baker, Valerie L.; Sun, Fangbai; Wild, Robert; Smith, James F.; Santoro, Nanette; Zhang, Heping; Steiner, Anne Z.
In: F and S Reports, Vol. 2, No. 3, 09.2021, p. 282-288.Research output: Contribution to journal › Article › peer-review
TY - JOUR
T1 - Sperm deoxyribonucleic acid fragmentation
T2 - predictors, fertility outcomes, and assays among infertile males
AU - Rios, Julie S.
AU - Coward, R. Matthew
AU - Hansen, Karl R.
AU - Barnhart, Kurt T.
AU - Cedars, Marcelle I.
AU - Legro, Richard S.
AU - Diamond, Michael P.
AU - Krawetz, Stephen A.
AU - Usadi, Rebecca
AU - Baker, Valerie L.
AU - Sun, Fangbai
AU - Wild, Robert
AU - Smith, James F.
AU - Santoro, Nanette
AU - Zhang, Heping
AU - Steiner, Anne Z.
N1 - Funding Information: J.S.R. has nothing to disclose. R.M.C. has nothing to disclose. K.R.H. reports grants from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, Yale University, during the conduct of the study; grants from Roche Diagnostics and Ferring International Pharmascience Center US, outside the submitted work. K.T.B. has nothing to disclose. M.I.C. has nothing to disclose. R.S.L. is a consultant for Bayer, Kindex, Fractyl, Ferring, AbbVie, and Insud Pharma and reports grants from Guerbet and the Hass Avocado Board, outside the submitted work. M.P.D. reports grants from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, Yale University RMN subcontracts, during the conduct of the study; Stockholder, Board of Directors for Advanced Reproductive Care. S.A.K. reports grants from EMD Serono and Grant for Fertility Innovations and honorarium from Taylor and Francis and Kansas Idea Network of Biomedical Research Excellence, outside the submitted work. R.U. has nothing to disclose. V.L.B. has nothing to disclose. F.S. has nothing to disclose. R.W. reports grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, during the conduct of the study. J.F.S. has nothing to disclose. N.S. has nothing to disclose. H.Z. reports grants from the National Institutes of Health, during the conduct of the study. A.Z.S. reports grants from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, during the conduct of the study; consultant for Prima-Temp and Seikagaku Corporation, outside the submitted work. Funding Information: Supported by grants National Insitutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (Bethesda, MD) including R25 HD 0757375 (N.S.); U10HD077844 (A.Z.S.), U10HD077680 (K.R.H.), U10 HD077841 (M.I.C.), U10HD027049 (K.T.B.); U10HD038992 (R.S.L.); U10HD039005 (M.P.D.); and U10HD055925 (H.Z). Funding Information: J.S.R. has nothing to disclose. R.M.C. has nothing to disclose. K.R.H. reports grants from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, Yale University, during the conduct of the study; grants from Roche Diagnostics and Ferring International Pharmascience Center US, outside the submitted work. K.T.B. has nothing to disclose. M.I.C. has nothing to disclose. R.S.L. is a consultant for Bayer, Kindex, Fractyl, Ferring, AbbVie, and Insud Pharma and reports grants from Guerbet and the Hass Avocado Board, outside the submitted work. M.P.D. reports grants from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, Yale University RMN subcontracts, during the conduct of the study; Stockholder, Board of Directors for Advanced Reproductive Care. S.A.K. reports grants from EMD Serono and Grant for Fertility Innovations and honorarium from Taylor and Francis and Kansas Idea Network of Biomedical Research Excellence, outside the submitted work. R.U. has nothing to disclose. V.L.B. has nothing to disclose. F.S. has nothing to disclose. R.W. reports grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, during the conduct of the study. J.F.S. has nothing to disclose. N.S. has nothing to disclose. H.Z. reports grants from the National Institutes of Health, during the conduct of the study. A.Z.S. reports grants from the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development, during the conduct of the study; consultant for Prima-Temp and Seikagaku Corporation, outside the submitted work. Supported by grants National Insitutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development (Bethesda, MD) including R25 HD 0757375 (N.S.); U10HD077844 (A.Z.S.), U10HD077680 (K.R.H.), U10 HD077841 (M.I.C.), U10HD027049 (K.T.B.); U10HD038992 (R.S.L.); U10HD039005 (M.P.D.); and U10HD055925 (H.Z). Publisher Copyright: © 2021 The Authors
PY - 2021/9
Y1 - 2021/9
N2 - Objective: To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays. Design: Secondary analysis. Setting: Nine US-based fertility centers. Patient(s): Infertile men (N = 147) with sperm concentration ≤15 × 106/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency. Intervention(s): At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months. Main Outcome Measure(s): The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ2 test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations. Result(s): The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19). Conclusion(s): Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.
AB - Objective: To examine the factors associated with increased deoxyribonucleic acid fragmentation index (DFI), evaluate the pregnancy outcomes of men with increased DFI, and compare three independent DFI assays. Design: Secondary analysis. Setting: Nine US-based fertility centers. Patient(s): Infertile men (N = 147) with sperm concentration ≤15 × 106/mL, motility ≤40%, or normal morphology ≤4% were enrolled. The female partners were ovulatory, ≤40 years old, and had documented tubal patency. Intervention(s): At a baseline visit, the men provided a semen sample. The couples attempted conception without assistance for 3 months and with ovarian stimulation and intrauterine insemination in the subsequent 3 months. Main Outcome Measure(s): The DFI was analyzed using the sperm chromatin structure assay (SCSA) with increased DFI defined as >30%. The predictors of increased DFI were determined by a multivariable linear regression model. The pregnancy outcomes were compared using the χ2 test. The independent DFI assays (SCSA, deoxynucleotidyl transferase-mediated dUTP nick end labeling, and Comet) were compared with Pearson and Spearman correlations. Result(s): The 19% of men with increased DFI were older (36.0 vs. 33.0 years) and had lower total sperm motility (38.2% ± 20.5% vs. 45.2% ± 15.6%). Increased male age was found to be a significant predictor of DFI (0.75, 95% confidence interval [0.06, 1.45]). Increased DFI was not associated with conception or live birth. There was a modest correlation of the deoxynucleotidyl transferase-mediated dUTP nick end labeling assay with the SCSA (r = 0.34) and Comet assay (r = 0.19). Conclusion(s): Older age was associated with increased DFI among infertile men. The DFI assays were only weakly correlated, indicating a standard definition of DFI is needed to truly interrogate how sperm deoxyribonucleic acid fragmentation impacts male fertility.
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UR - http://www.scopus.com/inward/citedby.url?scp=85117302688&partnerID=8YFLogxK
U2 - 10.1016/j.xfre.2021.06.003
DO - 10.1016/j.xfre.2021.06.003
M3 - Article
AN - SCOPUS:85117302688
VL - 2
SP - 282
EP - 288
JO - F and S Reports
JF - F and S Reports
SN - 2666-3341
IS - 3
ER -