Letter to the Editor: “Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility”

Letter to the Editor: “Higher TSH Levels Within the Normal Range Are Associated With... Orouji Jokar et al. (1) recently reported that among infertile women with normal TSH levels, those with unexplained infertility [(UI); n = 187] had significantly higher TSH levels than couples with severe male factor (n = 52; mean, 1.95 vs. 1.66 mIU/L, respectively; P = 0.003) and that the relationship remained significant after controlling for age, body mass index, and smoking. Furthermore, they identified that those with UI were nearly twice as likely as those with severe male factor to have a TSH level ≥2.5 mIU/L (26.9% vs. 13.5%; P < 0.05). Their report over 13 years used more than eight TSH assays (1). We have completed the Assessing Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) study, a 900-couple study of UI in whom all women had normal preconceptual TSH levels (using a single, centralized laboratory assay) (2). Furthermore, a post hoc analysis revealed that conception, clinical pregnancy, miscarriage, and live birth rates did not differ as a function of preconceptual TSH levels equal to, higher than, or lower than 2.5 mIU/L (although antithyroid peroxidase antibodies were associated with an increased risk of miscarriage and a lower live birth probability) (3). To further examine the possible significance of TSH levels in the upper normal range, we assessed conception and live birth rates in couples from the AMIGOS study in which the female partner had a normal TSH level (within the normal range of the assay and ≤5 mIU/L) and the male partner had a total motile sperm count of >15 million (n = 758). We identified that in the AMIGOS UI subpopulation treated with ovarian stimulation and intrauterine insemination, there was no significant difference in conception and live birth rates as a function of the female partner’s TSH levels lower or higher than 2.5 mIU/L [conception: 234 of 591 women (39.6%) vs. 57 of 167 women (34.1%), respectively; P = 0.200; live birth: 157 of 591 women (26.6%) vs. 37 or 167 women (22.2%), respectively; P = 0.249]. When adjusted by study treatment and female age, the OR for conception was 0.76 (95% CI, 0.53 to 1.09) and for live birth, the OR was 0.77 (95% CI, 0.51 to 1.16; P = 0.206) when those with TSH levels <2.5 mIU/L were set as the reference group. Furthermore, for women in the AMIGOS study who had UI and whose male partner’s total motile sperm count was ≥15 million (n = 758), the median (interquartile range) TSH level was 1.75 mIU/L (1.24 to 2.37) vs. either 1.74 mIU/L (0.98 to 2.24) in those couples with mean motile sperm <15 million (n = 91; P = 0.143) or 1.72 mIU/L (0.98 to 2.25) for those with <10 million sperm (n = 42; P = 0.282). Thus, in this population that was fourfold larger than that reported by Orouji Jokar et al. (1), we were unable to identify a significant impact of female TSH levels in women with unexplained infertility. Abbreviations: Abbreviations: AMIGOS Assessing Multiple Intrauterine Gestations from Ovarian Stimulation UI unexplained infertility Acknowledgments We acknowledge the contributions of the members of the Reproductive Medicine Network. Financial Support: This work was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development Grants U10 HD39005 (to M.P.D.) U10HD055925 (to H.Z.), U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, and U10 HD055936, and by the American Recovery and Reinvestment Act. Disclosure Summary: The authors have nothing to disclose. References 1. Orouji Jokar T , Fourman LT , Lee H , Mentzinger K , Fazeli PK . Higher TSH levels within the normal range are associated with unexpected infertility . J Clin Endocrinol Metab . 2018 ; 103 ( 2 ): 632 – 639 . Google Scholar CrossRef Search ADS PubMed 2. Diamond MP , Legro RS , Coutifaris C , Alvero R , Robinson RD , Casson P , Christman GM , Ager J , Huang H , Hansen KR , Baker V , Usadi R , Seungdamrong A , Bates GW , Rosen RM , Haisenleder D , Krawetz SA , Barnhart K , Trussell JC , Ohl D , Jin Y , Santoro N , Eisenberg E , Zhang H ; NICHD Reproductive Medicine Network . Letrozole, gonadotropin, or clomiphene for unexplained infertility . N Engl J Med . 2015 ; 373 ( 13 ): 1230 – 1240 . Google Scholar CrossRef Search ADS PubMed 3. Seungdamrong A , Steiner AZ , Gracia CR , Legro RS , Diamond MP , Coutifaris C , Schlaff WD , Casson P , Christman GM , Robinson RD , Huang H , Alvero R , Hansen KR , Jin S , Eisenberg E , Zhang H , Santoro N ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Reproductive Medicine Network . Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women . Fertil Steril . 2017 ; 108 ( 5 ): 843 – 850 . Google Scholar CrossRef Search ADS Copyright © 2018 Endocrine Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Clinical Endocrinology and Metabolism Oxford University Press

Letter to the Editor: “Higher TSH Levels Within the Normal Range Are Associated With Unexplained Infertility”

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Publisher
Oxford University Press
Copyright
Copyright © 2018 Endocrine Society
ISSN
0021-972X
eISSN
1945-7197
D.O.I.
10.1210/jc.2018-00704
Publisher site
See Article on Publisher Site

Abstract

Orouji Jokar et al. (1) recently reported that among infertile women with normal TSH levels, those with unexplained infertility [(UI); n = 187] had significantly higher TSH levels than couples with severe male factor (n = 52; mean, 1.95 vs. 1.66 mIU/L, respectively; P = 0.003) and that the relationship remained significant after controlling for age, body mass index, and smoking. Furthermore, they identified that those with UI were nearly twice as likely as those with severe male factor to have a TSH level ≥2.5 mIU/L (26.9% vs. 13.5%; P < 0.05). Their report over 13 years used more than eight TSH assays (1). We have completed the Assessing Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) study, a 900-couple study of UI in whom all women had normal preconceptual TSH levels (using a single, centralized laboratory assay) (2). Furthermore, a post hoc analysis revealed that conception, clinical pregnancy, miscarriage, and live birth rates did not differ as a function of preconceptual TSH levels equal to, higher than, or lower than 2.5 mIU/L (although antithyroid peroxidase antibodies were associated with an increased risk of miscarriage and a lower live birth probability) (3). To further examine the possible significance of TSH levels in the upper normal range, we assessed conception and live birth rates in couples from the AMIGOS study in which the female partner had a normal TSH level (within the normal range of the assay and ≤5 mIU/L) and the male partner had a total motile sperm count of >15 million (n = 758). We identified that in the AMIGOS UI subpopulation treated with ovarian stimulation and intrauterine insemination, there was no significant difference in conception and live birth rates as a function of the female partner’s TSH levels lower or higher than 2.5 mIU/L [conception: 234 of 591 women (39.6%) vs. 57 of 167 women (34.1%), respectively; P = 0.200; live birth: 157 of 591 women (26.6%) vs. 37 or 167 women (22.2%), respectively; P = 0.249]. When adjusted by study treatment and female age, the OR for conception was 0.76 (95% CI, 0.53 to 1.09) and for live birth, the OR was 0.77 (95% CI, 0.51 to 1.16; P = 0.206) when those with TSH levels <2.5 mIU/L were set as the reference group. Furthermore, for women in the AMIGOS study who had UI and whose male partner’s total motile sperm count was ≥15 million (n = 758), the median (interquartile range) TSH level was 1.75 mIU/L (1.24 to 2.37) vs. either 1.74 mIU/L (0.98 to 2.24) in those couples with mean motile sperm <15 million (n = 91; P = 0.143) or 1.72 mIU/L (0.98 to 2.25) for those with <10 million sperm (n = 42; P = 0.282). Thus, in this population that was fourfold larger than that reported by Orouji Jokar et al. (1), we were unable to identify a significant impact of female TSH levels in women with unexplained infertility. Abbreviations: Abbreviations: AMIGOS Assessing Multiple Intrauterine Gestations from Ovarian Stimulation UI unexplained infertility Acknowledgments We acknowledge the contributions of the members of the Reproductive Medicine Network. Financial Support: This work was supported by the National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development Grants U10 HD39005 (to M.P.D.) U10HD055925 (to H.Z.), U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, and U10 HD055936, and by the American Recovery and Reinvestment Act. Disclosure Summary: The authors have nothing to disclose. References 1. Orouji Jokar T , Fourman LT , Lee H , Mentzinger K , Fazeli PK . Higher TSH levels within the normal range are associated with unexpected infertility . J Clin Endocrinol Metab . 2018 ; 103 ( 2 ): 632 – 639 . Google Scholar CrossRef Search ADS PubMed 2. Diamond MP , Legro RS , Coutifaris C , Alvero R , Robinson RD , Casson P , Christman GM , Ager J , Huang H , Hansen KR , Baker V , Usadi R , Seungdamrong A , Bates GW , Rosen RM , Haisenleder D , Krawetz SA , Barnhart K , Trussell JC , Ohl D , Jin Y , Santoro N , Eisenberg E , Zhang H ; NICHD Reproductive Medicine Network . Letrozole, gonadotropin, or clomiphene for unexplained infertility . N Engl J Med . 2015 ; 373 ( 13 ): 1230 – 1240 . Google Scholar CrossRef Search ADS PubMed 3. Seungdamrong A , Steiner AZ , Gracia CR , Legro RS , Diamond MP , Coutifaris C , Schlaff WD , Casson P , Christman GM , Robinson RD , Huang H , Alvero R , Hansen KR , Jin S , Eisenberg E , Zhang H , Santoro N ; Eunice Kennedy Shriver National Institute of Child Health and Human Development Reproductive Medicine Network . Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women . Fertil Steril . 2017 ; 108 ( 5 ): 843 – 850 . Google Scholar CrossRef Search ADS Copyright © 2018 Endocrine Society

Journal

Journal of Clinical Endocrinology and MetabolismOxford University Press

Published: Aug 1, 2018

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