Infertility and mortality.

BACKGROUND: Infertility affects 1 in 10 American reproductive-age women. The impact of this disease beyond the reproductive years is largely unknown. OBJECTIVE: The objective of the study was to determine the association of infertility history with all-cause and cause-specific mortality. STUDY DESIGN: This secondary analysis of a multicenter randomized clinical trial included 75,784 women (aged 55-74 years) prospectively enrolled in the Prostate, Lung, Colorectal, and Ovarian cancer-screening trial from 1992 through 2001 and followed up a minimum of 10 years for health-related outcomes and death (856,935 person-years). We examined the association of infertility history (inability to conceive for 1 year or greater) of all-cause and cause-specific mortality using disease risk score-adjusted Cox-proportional hazard regression models. RESULTS: Infertile women had a 10% increased risk of death (from any cause) during the study period compared with the unexposed (adjusted hazard risk, 1.10, 95% confidence interval, 1.02-1.18, P = .010). This effect was predominantly noted in women at an otherwise low risk of mortality who had a 26% increased risk of death (adjusted hazard risk, 1.26, 95% confidence interval, 1.12-1.42, P < .001). No differences in cardiovascular or diabetic mortality were noted. The risk of cancer death at any time over the study period was increased by 23% in infertile women compared with the unexposed (adjusted hazard risk, 1.23, 95% confidence interval, 1.10-1.37, P < .001). This effect was predominantly noted in women at an otherwise low risk of cancer mortality who had a 47% increased risk of cancer death (adjusted hazard risk, 1.47, 95% confidence interval, 1.25-1.73, P < .001). While no differences are seen in the risk of death from endometrial or ovarian cancer, the risk of death from breast cancer was more than doubled in infertile women at an otherwise low risk of breast cancer death compared with the unexposed (adjusted hazard risk, 2.64, 95% confidence interval, 1.71-4.08, P < .001). CONCLUSION: Infertility is a harbinger of future morbidity and mortality. Infertile women are at an increased risk of all-cause and cancer-related mortality. Consideration of infertility history in health care maintenance presents an opportunity for screening and early intervention for long-term health outcomes.

Reproduction as a window to future health in women.

Cultivating awareness for reproduction as a window to future health presents an opportunity for early identification and modification of risk factors that can affect both individual and population-level morbidity and mortality. Infertility could serve as both a window into future health as well as a pathway to future pathology. The underlying mechanisms of infertility may share common pathways with long-term risk for health and well-being. Making this identification early in the disease process may improve opportunities for intervention, and deepen our understanding of long-term risk. Additionally, fertility treatments may increase individual risk. Only by making these associations and designing studies to understand how disease and treatment risk impact health can we truly fulfill our goal of building healthy families. The aim of this review is to discuss the short-term impact of fertility challenges and treatment, long-term associations of infertility with morbidity and mortality, and the role of parity in modifying these risk associations.

Mature Follicle Count and Multiple Gestation Risk Based on Patient Age in Intrauterine Insemination Cycles With Ovarian Stimulation.

OBJECTIVE: To estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number. METHODS: We conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation. RESULTS: We identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P<.01 and 0.2-10.6%, P<.01, respectively) when comparing one with five mature follicles present at the time of IUI (P<.01). In women younger than age 38 years with more than three follicles present, more than one quarter of all pregnancies were multiples. Similar findings occurred in women aged 38-40 years. In women older than age 40 years, up to four follicles tripled the odds of pregnancy (aOR 3.1, 95% CI 2.1-4.5) while maintaining a less than 12% risk of multiple gestation per pregnancy and a 1.0% absolute risk of multiples. CONCLUSION: Caution should be used in proceeding with IUI after ovarian stimulation when there are more than two mature follicles in women younger than age 40 years owing to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.

Association of Patient Race With Surgical Practice and Perioperative Morbidity After Myomectomy.

OBJECTIVE: To compare surgical approach, operative time, and perioperative morbidity after myomectomy by patient race. METHODS: In this retrospective cohort study, data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program database on 8,438 women undergoing myomectomy between January 1, 2012, and December 31, 2015. Myoma burden and approach to myomectomy were determined based on Current Procedural Terminology coding. Surgical approach and perioperative morbidity were examined in African American, Asian American, and Hispanic American women using non-Hispanic Caucasian women as the referent population. Adjusted means and odds ratios (ORs) with 95% CI were calculated using propensity score matching accounting for age, ethnicity, body mass index (BMI), myoma burden, preoperative anemia, hypertension, smoking, and operative time. RESULTS: Data were available for 2,533 Caucasian, 3,359 African American, 664 Asian American, and 700 Hispanic American women. Smoking, BMI, hypertension, myoma burden, and anemia varied by race (P<.001, all comparisons). In adjusted analysis, African American women were twice as likely to undergo abdominal myomectomy (adjusted OR 1.9, 95% CI 1.7-2.0), Asian American women were more than twice as likely (adjusted OR 2.3, 95% CI 1.8-2.8), and Hispanic American women were 50% more likely to undergo abdominal myomectomy (adjusted OR 1.5, 95% CI 1.2-1.9) when compared with Caucasian women. African American women were 50% more likely to experience composite morbidity after abdominal myomectomy (adjusted OR 1.5, 95% CI 1.2-1.7) and Asian American women were more than three times as likely to experience composite morbidity after laparoscopic myomectomy (adjusted OR 3.7, 95% CI 1.7-8.1) compared with Caucasian women. There were no differences in composite morbidity in other racial groups. CONCLUSION: Minority women are substantially more likely to undergo abdominal myomectomy when compared with Caucasian women. African American women had 50% increased odds of morbidity after abdominal myomectomy, and Asian American women were more than three times as likely to experience morbidity after laparoscopic myomectomy. Further examination into the etiology and prevention of these racial disparities is needed.

Changes in Myomectomy Practice After the U.S. Food and Drug Administration Safety Communication on Power Morcellation.

OBJECTIVE: To examine the association between the 2014 U.S. Food and Drug Administration (FDA) safety communication on power morcellation and surgical approach and morbidity after myomectomy. METHODS: In this retrospective cohort study, data were abstracted from the American College of Surgeons National Surgical Quality Improvement Program database on 3,160 myomectomies between April 2012 and December 2013 (pre-FDA) and 4,378 between April 2014 and December 2015 (post-FDA). Aims were to 1) compare rates of abdominal and laparoscopic myomectomy pre-FDA and post-FDA (primary outcome), 2) directly compare the morbidity of abdominal and laparoscopic myomectomy during each time period (secondary outcome 1), and 3) compare the morbidity after all myomectomies performed pre-FDA and post-FDA (secondary outcome 2). Adjusted means, odds ratios, and rate ratios with 95% confidence intervals were calculated using linear, logistic, and Poisson regression, respectively, adjusting for age, race, ethnicity, body mass index, and myoma burden. RESULTS: Myomectomies performed post-FDA were more likely to be abdominal (60.0%, 95% confidence interval [CI] 58.6-61.5%) than laparoscopic (40.0%, 95% CI 38.5-41.4%) as compared with myomectomies pre-FDA, which were equally divided between surgical approaches (49.1% abdominal, 95% CI 47.4-50.9% compared with 50.9% laparoscopic, 95% CI 49.1-52.6%; P<.001). When directly compared with laparoscopic myomectomy, abdominal myomectomy was associated with longer hospitalizations, higher readmission rates, and greater morbidity both pre-FDA and post-FDA (P<.05, all comparisons). Adjusted models demonstrated shorter operative times post-FDA for all myomectomies (P<.001), although composite morbidity was similar between myomectomies performed pre-FDA and post-FDA (P=.809). CONCLUSIONS: The FDA safety communication on power morcellation was associated with an 11% absolute increase in the use of abdominal myomectomy. Although morbidity is consistently higher after abdominal as compared with laparoscopic myomectomy, the increased reliance on abdominal myomectomy post-FDA did not result in clinically significant changes in morbidity in this cohort.