Gayathree Murugappan1, Shufeng Li2, Ruben J Alvero3, Barbara Luke4, Michael L Eisenberg2. 1. Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA. Electronic address: gm807@stanford.edu. 2. Department of Urology, Stanford University Medical Center, Stanford, CA. 3. Department of Obstetrics and Gynecology, Stanford University Medical Center, Stanford, CA. 4. Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI.
Abstract
BACKGROUND: The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease. OBJECTIVE: This study aimed to examine the association between female infertility and all-cause mortality. STUDY DESIGN: This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race. RESULTS: Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18-1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of <35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Women with infertility who delivered a child during the follow-up period faced a similar increased risk for mortality than the overall infertile group. Finally, receiving fertility treatment was not associated with a higher risk for death than receiving an infertility diagnosis or testing alone. CONCLUSION: Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae.
BACKGROUND: The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease. OBJECTIVE: This study aimed to examine the association between female infertility and all-cause mortality. STUDY DESIGN: This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race. RESULTS: Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18-1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of <35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Women with infertility who delivered a child during the follow-up period faced a similar increased risk for mortality than the overall infertile group. Finally, receiving fertility treatment was not associated with a higher risk for death than receiving an infertility diagnosis or testing alone. CONCLUSION: Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae.
Authors: Clara Helene Glazer; Jens Peter Bonde; Michael L Eisenberg; Aleksander Giwercman; Katia Keglberg Hærvig; Susie Rimborg; Ditte Vassard; Anja Pinborg; Lone Schmidt; Elvira Vaclavik Bräuner Journal: Semin Reprod Med Date: 2017-06-28 Impact factor: 1.303
Authors: Gayathree Murugappan; Shufeng Li; Ruth B Lathi; Valerie L Baker; Michael L Eisenberg Journal: Am J Obstet Gynecol Date: 2019-01-30 Impact factor: 8.661
Authors: Barbara Luke; Judy E Stern; Mark D Hornstein; Milton Kotelchuck; Hafsatou Diop; Howard Cabral; Eugene R Declercq Journal: J Assist Reprod Genet Date: 2015-12-03 Impact factor: 3.412
Authors: Gayathree Murugappan; Stephanie A Leonard; Leslie V Farland; Emily S Lau; Aladdin H Shadyab; Robert A Wild; Peter Schnatz; Suzan L Carmichael; Marcia L Stefanick; Nisha I Parikh Journal: Fertil Steril Date: 2022-03-16 Impact factor: 7.490