Stanford JB et al., 2026·Frontiers in Reproductive Health·
Open Access
Background The total fertility rate (TFR) in most developed countries has been declining for decades. In the United States (U.S.), the total fertility rate has remained below replacement level since 2007. Subfertility affects at least 15% of women or couples over their reproductive lifespan and contributes to reduced TFR. Restorative reproductive medicine (RRM) is a medically based approach to subfertility care that can be delivered in primary care settings to increase live birth rates. Objective To estimate the theoretical impact of use of RRM among subfertile couples in the United States. Methods We conducted a simulation study. Model inputs included the number of women of reproductive age in the United States by 5-year age groups; current age-specific and total fertility rates; the proportion of women in each age group with subfertility; estimated spontaneous live birth rates among women with subfertility; and age-specific crude live birth rates with RRM treatment. We evaluated fifteen scenarios including sensitivity analyses: two different varying assumptions for spontaneous conception (25% vs. 50%), two levels of RRM utilization among subfertile women (20% vs. 50%), three different estimates of the number of subfertile women who would be potentially eligible for RRM treatment, and 4 different levels of effectiveness (live birth) from RRM treatment. Results The baseline TFR in the United States was 1.77 during 2015-2019, and 13.5% of women ages 20-44 were estimated to have subfertility. In a conservative scenario (50% spontaneous births; 20% RRM utilization; married women trying to conceive for at least 12 months, 20.7% RRM live births), the TFR increased to 1.79, representing a 1.0% relative increase (absolute +0.02). In an optimistic scenario (25% spontaneous births; 50% RRM utilization; all subfertile women), the TFR increased to 2.02, a 14.5% relative increase (absolute +0.26), approaching replacement-level fertility. Conclusion Simulation results suggest that expanding access to RRM within primary care settings could meaningfully increase the U.S. TFR, by reducing unresolved subfertility. Realizing this potential would require policy and health system changes to address workforce capacity, insurance coverage, and equitable access. These findings underscore the potential contribution of non-IVF fertility care pathways in addressing population-level fertility decline.
Treatment for gynecologic cancer is associated with sexual dysfunction, which may present during and/or after treatment. The aim of this study was to investigate the risk of sexual dysfunction among gynecologic cancer survivors compared to cancer-free women in a population-based cohort study. We identified a cohort of 4863 endometrial, ovarian, and cervical cancer survivors diagnosed between 1997 and 2012 in the Utah Cancer Registry. Up to five cancer-free women were matched to cancer survivors (N = 22,693). We used ICD-9 codes to identify sexual dysfunction. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for sexual dysfunction with adjustment for potential confounders. Approximately 6.6% of gynecologic cancer survivors had sexual dysfunction diagnoses 1-5 years after cancer diagnosis. Gynecologic cancer survivors had higher risks of overall sexual dysfunction (HR: 2.51, 95% CI: 2.16, 2.93), dyspareunia (HR: 3.27, 95% CI: 2.63, 4.06), and vaginal dryness (HR: 2.63, 95% CI: 2.21, 3.12) compared to a general population of women, 1-5 years after cancer diagnosis. Sexual dysfunction was associated with advance cancer stage (HR(Regional vs. Localized): 1.61, 95% CI: 1.19, 2.31), radiation therapy (HR: 1.73, 95% CI: 1.29, 2.31), and chemotherapy (HR: 1.80, 95% CI: 1.30, 2.50). This large cohort study confirms that there is an increased risk of sexual dysfunction among gynecologic cancer survivors when compared to the general population. Further investigation is needed to address the risk factors for sexual dysfunction and to improve patient-provider communication, diagnosis, documentation, and treatment of sexual dysfunction among gynecologic cancer survivors.
Sanders JN et al., 2022·Reprod Health·
Open Access
In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women. The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth. A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment. IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.
Breast cancer is the leading cause of cancer death among Hispanic women. The aim of our study was to estimate cardiovascular disease (CVD) risk among Hispanic and non-Hispanic White (NHW) breast cancer survivors compared with their respective general population cohorts. Cohorts of 17 469 breast cancer survivors (1774 Hispanic and 15 695 NHW) in the Utah Cancer Registry diagnosed between 1997 and 2016, and 65 866 women (6209 Hispanic and 59 657 NHW) from the general population in the Utah Population Database were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CVD. The risk of diseases of the circulatory system was higher in Hispanic than NHW breast cancer survivors 1-5 years after cancer diagnosis, in comparison with their respective general population cohorts (HR(Hispanic) = 1.94, 99% confidence interval [CI] = 1.49 to 2.53; H(NHW) = 1.38, 99% CI = 1.33 to 1.43; 2-sided P (heterogeneity) = .01, respectively). Increased risks were observed for both Hispanic and NHW breast cancer survivors for diseases of the heart and the veins and lymphatics, compared with the general population cohorts. More than 5 years after cancer diagnosis, elevated risk of diseases of the veins and lymphatics persisted in both ethnicities. The CVD risk due to chemotherapy and hormone therapy was higher in Hispanic than NHW breast cancer survivors but did not differ for distant stage, higher baseline comorbidities, or baseline smoking. We observed a risk difference for diseases of the circulatory system between Hispanic and NHW breast cancer survivors compared with their respective general population cohorts but only within the first 5 years of cancer diagnosis.
While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.
Prior research has collectively shown that endometriosis is inversely related to women's adiposity. The aim of this study was to assess whether this inverse relationship holds true by disease severity and typology.
Cross-sectional study among women with no prior diagnosis of endometriosis.
Fourteen clinical centers in Salt Lake City, UT, and San Francisco, CA. A total of 495 women (of which 473 were analyzed), aged 18-44 years, were enrolled in the operative cohort of the Endometriosis, Natural History, Diagnosis, and Outcomes (ENDO) Study. Gynecologic laparoscopy/laparotomy regardless of clinical indication. MAIN Participants underwent anthropometric assessments, body composition measurements, and evaluations of body fat distribution ratios before surgery. Surgeons completed a standardized operative report immediately after surgery to capture revised American Society for Reproductive Medicine staging (I-IV) and typology of disease (superficial endometriosis [SE], ovarian endometrioma [OE], and deep infiltrating endometriosis [DIE]). Linear mixed models, taking into account within-clinical-center correlation, were used to generate least square means (95% confidence intervals) to assess differences in adiposity measures by endometriosis stage (no endometriosis, I-IV) and typology (no endometriosis, SE, DIE, OE, OE + DIE) adjusting for age, race/ethnicity, and parity. Although most confidence intervals were wide and overlapping, 3 general impressions emerged: (1) women with incident endometriosis had the lowest anthropometric/body composition indicators compared with those without incident endometriosis, (2) women with stage I or IV endometriosis had lower indicators compared with women with stage II or III, and (3) women with OE and/or DIE tended to have the lowest indicators, whereas women with SE had the highest indicators. Our research highlights that the relationship between women's adiposity and endometriosis severity and typology may be more complicated than prior research indicates.
Hemmert R et al., 2018·Paediatr Perinat Epidemiol·
Caffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone-dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis. Four hundred and seventy three women, ages 18-44 years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007-2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors. There were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10 ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk. This study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.
Sanders JN et al., 2016·Paediatr Perinat Epidemiol·
Most cohort-based research for subfertility has been conducted in clinic-based cohorts, which may differ from population-based cohorts. We retrospectively recruited parallel cohorts of subfertile women: one by sampling two specialty fertility clinics in Utah, and one by population-based sampling based on marriage and birth records. The index date (of first clinic visit or subfertility status) was between 2000 and 2009, and we linked the women recruited to subsequent birth certificate records through December 2010. We enrolled 459 women through clinic-based sampling and 501 women through population-based sampling. Clinic-based women were older, had higher annual household income and more likely to have had a most intensive treatment of intrauterine insemination (31%) or in vitro fertilisation (46%) than women from population recruitment (19% and 14% respectively). Conversely, they were less likely to have received no medical treatment (9%) compared to women from population recruitment (41%). For both types of sampling, prior to eligibility screening, non-responders were less likely to link to a live birth than responders: 51% vs. 58% for clinic-based, and 69% vs. 76% for the population-based with an index date in 2004. Population-based sampling for subfertility cohort research identifies women who were more likely to have had less intensive treatment or no treatment. However, in both clinic-based and population-based sampling, women who have had a live birth are more likely to respond to retrospective recruitment.
The Creighton Model FertilityCare System (CrMS) teaches women to identify days when intercourse is likely to result in pregnancy. We sought to assess the impact of the CrMS on time to pregnancy (TTP), via per-cycle pregnancy rates (fecundability). We conducted a parallel randomised trial at the University of Utah School of Medicine, 2003-06. Women ages 18-35 years, in a relationship of proven fertility, who desired to conceive, were block-randomised and stratified for age, with allocation concealment by opaque sequentially numbered sealed envelopes. The control group received the advice to have intercourse 2-3 times per week, and the intervention group received CrMS instruction. All women were asked to begin trying to conceive starting the second cycle in the study and were followed actively up to seven cycles, without blinding of research personnel. We calculated descriptive statistics and fecundability, and estimated Cox models for TTP. (Clinicaltrials.gov NCT00161395). There were 143 women randomised: 71 to the control group (all analysed) and 72 to the CrMS group (69 analysed). The adjusted hazard ratio for the influence of CrMS on TTP was 0.86 [95% confidence interval (CI): 0.53, 1.38]. Fecundability in cycles with intent to conceive was 31% in controls and 36% with CrMS (P = 0.32). By the first cycle, fecundability was 17% in controls, and 4% with CrMS (P = 0.02). No adverse events were reported. We found no significant impact of CrMS on TTP or fecundability, but fewer of the women receiving CrMS conceived by the first cycle.
Utah has the highest total fertility of any state in the United States and also the highest proportion of population affiliated with the Church of Jesus Christ of Latter-day Saints (the LDS or Mormon Church). Data were used from the 1996 Utah Health Status Survey to investigate how annual household income, education and affiliation with the LDS Church affect fertility (children ever born) for married women in Utah. Younger age and higher education were negatively correlated with fertility in the sample as a whole and among non-LDS respondents. Income was negatively associated with fertility among non-LDS respondents. However, income was positively correlated with fertility among LDS respondents. This association persisted when instrumental variables were used to address the potential simultaneous equations bias arising from the potential endogeneity of income and fertility. The LDS religion's pronatalist stance probably encourages childbearing among those with higher income.
To assess the day-specific and cycle-specific probabilities of conception leading to clinical pregnancy, in relation to the timing of intercourse and vulvar mucus observations. This was a retrospective cohort study of women beginning use of the Creighton Model Fertility Care System in Missouri, Nebraska, Kansas, and California. Data were abstracted from Creighton Model Fertility Care System records, including women's daily standardized vulvar observations of cervical mucus discharge, days of intercourse, and clinically evident pregnancy (conception). Established statistical models were used to estimate day-specific probabilities of conception. Data were analyzed from 1681 cycles with 81 conceptions from 309 normally fertile couples (initially seeking to avoid pregnancy) and from 373 cycles with 30 conceptions from 117 subfertile couples (who were initially trying to achieve pregnancy). The highest probability of pregnancy occurred on the peak day of vulvar mucus observation (.38 for normally fertile couples and.14 for subfertile couples). The probability of pregnancy was greater than.05 for normally fertile couples from 3 days before to 2 days after the peak, and for subfertile couples from 1 day before to 1 day after the peak. The cycle-specific probability of conception correlated with the quality of mucus discharge in normally fertile couples but not in subfertile couples. Standardized vulvar observations of vaginal mucus discharge identify the days with the greatest likelihood of conception from intercourse in normal fertility and subfertility and provide an indicator of the overall potential for conception in a given menstrual cycle in normal fertility.
Effective use of natural family planning is strongly dependent upon adequate instruction. The Creighton Model Fertility Care System (CrMS) has a standardized protocol for instruction of new users that includes individual follow-up visits in the first year of use. This study evaluated the number of follow-up visits completed by new CrMS users from eight CrMS centers in the United States. Four follow-up visits were completed by 75.7% of women. Women who continued instruction were more likely to be educated, Catholic, and white, and to have a more challenging reproductive status (discontinuing oral contraceptives, or breastfeeding). These results suggest that the number of follow-up visits needed varies among new CrMS users. Future research should address the optimal length of instruction for adequate use of the CrMS by women with different characteristics and needs.