Consumer wearables and personal devices for tracking the fertile window.

The market for technology that tracks ovulation to promote conception is rapidly expanding in the United States, targeting the growing audience of technologically proficient, reproductive-age female consumers. In this narrative review, twenty-three different, non-prescription wearables and devices designed to help women track their fertile window were identified as currently, commercially available in the United States. The majority of these utilize measurements of basal body temperature or combinations of various urinary hormones. This clinical opinion characterizes the scant available research validating the accuracy of these technologies. It further examines research oversight, discusses the utility of these wearables and devices to consumers, and considers these technologies through an equity lens. The discussion concludes with a call for innovation, describing promising new technologies that not only harness unique physiologic parameters to predict ovulation, but also focus on cost-effectiveness with the hope of increasing access to these currently costly devices and wearables.

In Vitro Fertilization Practice in Patients with Absolute Uterine Factor Undergoing Uterus Transplant in the United States.

OBJECTIVE: Report detailed, pooled multicenter experiences and outcomes after IVF among patients undergoing uterus transplantation in the United States. DESIGN: Cohort study SUBJECTS: Patients undergoing uterus transplant from the three longest running uterus transplant clinical trials in the United States. INTERVENTION: In vitro fertilization among uterus transplant patients MAIN OUTCOME MEASURES: Reproductive outcomes pre- and post-transplant ovarian stimulation RESULTS: 31 uterus transplant recipients were included in this cohort (mean age at transplant was 31 years, standard deviation 4.7). Prior to transplant, recipients completed a mean of 2 oocyte retrievals (range 1-4), banking a mean of 8 untested embryos (range 3-24) or 6 euploid embryos (range 2-10). Post-transplant retrieval cycles were required in 19% of recipients (n=6/31): a total of 16 cycles (range 2-4 cycles per recipient). All post-transplant retrievals were performed vaginally without complication. Preimplantation genetic testing was used by 74% of subjects (n=23/31). 72 autologous single embryo transfers occurred in 23 patients who completed at least one embryo transfer. Two embryo transfers followed a fresh IVF cycle and the remainder were frozen embryo transfers (n=70). Endometrial preparation during was more commonly performed with programmed protocols (n=61) (exogenous administration of estrogen/progesterone) compared to natural cycle protocols (n=9). The overall live birth rate for this cohort was 35% (n=25/72) per embryo transfer. Among those patients who had an embryo transfer leading to a live birth (n=21), a mean of 2.2 embryo transfers was performed. The overall live birth rate after the first embryo transfer was 57% (n=13/23) and rose to 74% after a second embryo transfer (n=17/23). There was no difference in rate of preeclampsia, live birth, neonatal birth, or placental weights among programmed versus natural cycle frozen embryo transfers. There were no differences in the live birth rate between living or deceased donor uteri (37% versus 32%, p=0.6). CONCLUSIONS: Post-transplant ovarian stimulation was required in 26% (n=6/23) of recipients undergoing at least one embryo transfer despite high rates of preimplantation genetic testing and pre-transplant embryo cryopreservation. Post-transplant retrievals were performed transvaginally, without complication. Future reporting of IVF experience will be essential to optimize reproductive outcomes after uterus transplant.

Use of artificial intelligence to develop predictive algorithms of cough and PCR-confirmed COVID-19 infections based on inputs from clinical-grade wearable sensors.

There have been over 769 million cases of COVID-19, and up to 50% of infected individuals are asymptomatic. The purpose of this study aimed to assess the use of a clinical-grade physiological wearable monitoring system, ANNE One, to develop an artificial intelligence algorithm for (1) cough detection and (2) early detection of COVID-19, through the retrospective analysis of prospectively collected physiological data from longitudinal wear of ANNE sensors in a multicenter single arm study of subjects at high risk for COVID-19 due to occupational or home exposures. The study employed a two-fold approach: cough detection algorithm development and COVID-19 detection algorithm development. For cough detection, healthy individuals wore an ANNE One chest sensor during scripted activity. The final performance of the algorithm achieved an F-1 score of 83.3% in twenty-seven healthy subjects during biomarker validation. In the COVID-19 detection algorithm, individuals at high-risk for developing COVID-19 because of recent exposures received ANNE One sensors and completed daily symptom surveys. An algorithm analyzing vital parameters (heart rate, respiratory rate, cough count, etc.) for early COVID-19 detection was developed. The COVID-19 detection algorithm exhibited a sensitivity of 0.47 and specificity of 0.72 for detecting COVID-19 in 325 individuals with recent exposures. Participants demonstrated high adherence (≥ 4 days of wear per week). ANNE One shows promise for detection of COVID-19. Inclusion of respiratory biomarkers (e.g., cough count) enhanced the algorithm's predictive ability. These findings highlight the potential value of wearable devices in early disease detection and monitoring.

Classification and treatment of vaginal strictures at the donor-recipient anastomosis after uterus transplant.

OBJECTIVE: To describe the incidence and management of vaginal stricture after uterus transplantation (UTx) in the US, to propose a grading system to classify stricture severity, and to identify risk factors for stricture formation. DESIGN: Prospective cohort study. SETTING: University Hospital. PATIENTS: Recipients undergoing UTx from 2016-2023 at Baylor University Medical Center in Dallas, Cleveland Clinic, the University of Pennsylvania, and the University of Alabama at Birmingham were monitored postoperatively with regular pelvic examinations. Stricture was defined as vaginal narrowing of <3 cm in patients with graft survival of at least 7 days. INTERVENTION: Demographic and surgery characteristics. MAIN OUTCOME MEASURES: Stricture development and severity (grade 1 for diameter 2-<3 cm, grade 2 for 1-<2 cm, or grade 3 for <1 cm). RESULTS: Of the 45 UTx from 2016-2023 (16 deceased donors and 29 living donors), 3 were excluded from the analysis because of graft loss within 7 days. Of the 42 remaining recipients, 39 (92.9%) had Mayer-Rokitansky-Küster-Hauser syndrome and 3 (7.1%) had a prior hysterectomy. Twenty-eight (66.7%) UTx recipients developed postoperative vaginal strictures with a median time to stricture of 33 days (interquartile range 19-53 days). Most strictures were of moderate severity, with 4 (14.3%) strictures categorized as grade 1, 19 (67.9%) as grade 2, and 5 (17.9%) as grade 3. History of Mayer-Rokitansky-Küster-Hauser syndrome and preoperative recipient vaginal length were significant risk factors for stricture, after adjustment for donor and recipient age and body mass index, anastomosis technique, total ischemia time, center, and year. Patients with longer preoperative vaginal length had a lower risk of stricture (hazard ratio 0.45, 0.29-0.70). The severity grading of the stricture was associated with the effectiveness of a nonoperative treatment approach (grade 1 vs. grade 3). No patients with grade 3 strictures improved with self-dilation alone; all required surgical repair and/or dilation under anesthesia. Conversely, for grade 1 or 2 strictures, self-dilation alone was successful in 47.8% (11/23), and no grade 1 strictures required surgical repair. CONCLUSIONS: Vaginal stricture is a common postoperative complication after UTx, affecting >65% of recipients. Short preoperative vaginal length and history of müllerian agenesis in the recipient are significant risk factors. Vaginal self-dilation was effective for some mild to moderate strictures, although dilation under anesthesia or surgical repair was required in most cases. CLINICAL TRIAL REGISTRATION NUMBERS: Dallas UtErus Transplant Study (DUETS) at Baylor University Medical Center (NCT02656550), Uterine transplantation for the treatment of uterine factor infertility at the Cleveland Clinic (NCT02573415), The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial (UNTIL) (NCT03307356).

Cost-effectiveness analysis of expectant vs active management for treatment of persistent pregnancies of unknown location.

BACKGROUND: Persistent pregnancies of unknown location are defined by abnormally trending serum human chorionic gonadotropin with nondiagnostic ultrasound. There is no consensus on optimal management. OBJECTIVE: This study aimed to assess the cost-effectiveness of 3 primary management strategies for persistent pregnancies of unknown location: (1) expectant management, (2) empirical 2-dose methotrexate, and (3) uterine evacuation followed by methotrexate, if indicated. STUDY DESIGN: This was a prospective economic evaluation performed concurrently with the Expectant versus Active Management for Treatment of Persistent Pregnancies of Unknown Location multicenter randomized trial that was conducted from July 2014 to June 2019. Participants were randomized 1:1:1 to expectant management, 2-dose methotrexate, or uterine evacuation. The analysis was from the healthcare sector perspective with a 6-week time horizon after randomization. Costs were expressed in 2018 US dollars. Effectiveness was measured in quality-adjusted life years and the rate of salpingectomy. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were generated. Sensitivity analyses were performed to assess the robustness of the analysis. RESULTS: Methotrexate had the lowest mean cost ($875), followed by expectant management ($1085) and uterine evacuation ($1902) (P=.001). Expectant management had the highest mean quality-adjusted life years (0.1043), followed by methotrexate (0.1031) and uterine evacuation (0.0992) (P=.0001). The salpingectomy rate was higher for expectant management than for methotrexate (9.4% vs 1.2%, respectively; P=.02) and for expectant management than for uterine evacuation (9.4% vs 8.1%, respectively; P=.04). Uterine evacuation, with the highest costs and the lowest quality-adjusted life years, was dominated by both expectant management and methotrexate. In the base case analysis, expectant management was not cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year given an incremental cost-effectiveness ratio of $175,083 per quality-adjusted life year gained (95% confidence interval, -$1,666,825 to $2,676,375). Threshold analysis demonstrated that methotrexate administration would have to cost $214 (an increase of $16 or 8%) to favor expectant management. Moreover, expectant management would be favorable in lower-risk patient populations with rates of laparoscopic surgical management for ectopic pregnancy not exceeding 4% of pregnancies of unknown location. Based on the cost-effectiveness acceptability curves, the probability of expectant management being cost-effective compared with methotrexate at a willingness to pay of $150,000 per quality-adjusted life year gained was 50%. The results were dependent on the cost of surgical intervention and the expected rate of methotrexate failure. CONCLUSION: The management of pregnancies of unknown location with a 2-dose methotrexate protocol may be cost-effective compared with expectant management and uterine evacuation. Although uterine evacuation was dominated, expectant management vs methotrexate results were sensitive to modest changes in treatment costs of both methotrexate and surgical management.

Embryo transfers performed during daylight savings time led to reduced live birth rates in older patients.

PURPOSE: To study the impact of undergoing an embryo transfer during the week of daylight savings time transition on live birth rates. METHODS: We performed a retrospective observational cohort study of patients undergoing embryo transfer at an academic infertility practice during the week of spring or fall daylight savings time transition (cases), or the 2 weeks preceding and following the daylight savings transition (controls) between 2015 and 2021. The primary exposure was completion of an embryo transfer during the week of daylight savings time transition. The primary outcome was a comparison of live birth rate per embryo transfer among individuals undergoing an embryo transfer during the week of daylight savings time (DST) transition and those who did not. RESULTS: A total of 309 embryo transfers occurred during the week of daylight savings transition and 1242 embryo transfers occurred in the control group outside of the daylight savings transition week. The live birth rate after embryo transfer during DST transition weeks was 39.2% (121/309) compared to 40.8% (507/1242) (p = 0.59). When restricting the analysis to individuals (age > 37 years), the live birth rate after embryo transfer during DST transition week was 23.5% (24/102) compared to 34.8% (149/429) (p = 0.03). This difference persisted in the mixed-effects regression model demonstrating that after adjusting for relevant covariates, embryo transfer during DST transition weeks resulted in a 45% decrease in the odds of achieving a live birth. CONCLUSION: Daylight savings time transition may be associated with less favorable outcomes after embryo transfer among an older infertile patient population. Future work is needed to prospectively examine the influence of circadian rhythm disruption on reproductive outcomes.

A comprehensive wireless neurological and cardiopulmonary monitoring platform for pediatrics.

Neurodevelopment in the first 10 years of life is a critical time window during which milestones that define an individual's functional potential are achieved. Comprehensive multimodal neurodevelopmental monitoring is particularly crucial for socioeconomically disadvantaged, marginalized, historically underserved and underrepresented communities as well as medically underserved areas. Solutions designed for use outside the traditional clinical environment represent an opportunity for addressing such health inequalities. In this work, we present an experimental platform, ANNE EEG, which adds 16-channel cerebral activity monitoring to the existing, USA FDA-cleared ANNE wireless monitoring platform which provides continuous electrocardiography, respiratory rate, pulse oximetry, motion, and temperature measurements. The system features low-cost consumables, real-time control and streaming with widely available mobile devices, and fully wearable operation to allow a child to remain in their naturalistic environment. This multi-center pilot study successfully collected ANNE EEG recordings from 91 neonatal and pediatric patients at academic quaternary pediatric care centers and in LMIC settings. We demonstrate the practicality and feasibility to conduct electroencephalography studies with high levels of accuracy, validated via both quantitative and qualitative metrics, compared against gold standard systems. An overwhelming majority of parents surveyed during studies indicated not only an overall preference for the wireless system, but also that its use would improve their children's physical and emotional health. Our findings demonstrate the potential for the ANNE system to perform multimodal monitoring to screen for a variety of neurologic diseases that have the potential to negatively impact neurodevelopment.

Awareness and Interest in Uterus Transplantation over Time: Analysis of Those Seeking Surgical Correction for Uterine-Factor Infertility in the US.

This study describes the characteristics of women who contacted an active program performing uterus transplantation (UTx) in the US, expressing interest in becoming a uterus transplant recipient or a living donor. Basic demographic and self-reported clinical information was collected from women who contacted any of the three US UTx programs from 2015 to July 2022. The three centers received 5194 inquiries about becoming a UTx recipient during the study timeframe. Among those reporting a cause of infertility, almost all of the reports (4066/4331, 94%) were absence of a uterus, either congenitally (794/4066, 20%) or secondary to hysterectomy (3272/4066, 80%). The mean age was 34 years, and 49% (2545/5194) had at least one child at the time of application. The two centers using living donors received 2217 inquiries about becoming living donors. The mean age was 34 years, and 60% (1330/2217) had given birth to ≥1 child. While most of the UTx clinical trial evidence has focused on young women with congenital absence of the uterus, these results show interest from a much broader patient population in terms of age, cause of infertility, and parity. These results raise questions about whether and to what extent the indications and eligibility criteria for UTx should be expanded as the procedure transitions from the experimental phase to being offered as a clinical treatment.

Advanced wireless monitoring for children in the cardiac perioperative setting.

INTRODUCTION: More than 40,000 children undergo surgical interventions annually for the treatment of congenital heart defects. Intraoperative and postoperative vital sign monitoring is a cornerstone of pediatric care. METHODS: A single-arm prospective observational study was performed. Pediatric patients undergoing a procedure with a planned admission to the Cardiac Intensive Care Unit at Lurie Children's Hospital (Chicago, IL) were eligible for enrollment. Participant vital signs were monitored using standard equipment and an FDA-cleared experimental device (ANNE® ) consisting of a wireless patch positioned at the suprasternal notch and index finger or foot. The primary goal of the study was to assess real-world feasibility of wireless sensors in pediatric patients with congenital cardiac defects. RESULTS: A total of 13 patients were enrolled, ranging in age from 4 months to 16 years with a median age of 4 years. Overall, 54% (n = 7) were female and the most common anomaly in the cohort was an atrial septal defect (n = 6). The mean admission length was 3 days (range 2-6), resulting in more than 1000 h of vital sign monitoring (⟩60,000 data points). Bland-Altman plots were generated for heart rate and respiratory rate to assess beat-to-beast differences between the standard equipment and the experimental sensors. CONCLUSIONS: Novel, wireless, flexible sensors demonstrated comparable performance to standard monitoring equipment in a cohort of pediatric patients with congenital cardiac heart defects undergoing surgery.

Neighborhood disadvantage is associated with decreased ovarian reserve in women with overweight and obesity.

OBJECTIVE(S): To evaluate the association between neighborhood disadvantage and ovarian reserve stratified by body mass index (BMI). DESIGN: Cross-sectional cohort study. SETTING: Single academic medical center. PATIENT(S): A total of 193 healthy reproductive-age women with regular menstrual cycles in the St. Louis, Missouri metropolitan area. INTERVENTION(S): Residence in a disadvantaged neighborhood. MAIN OUTCOME MEASURE(S): Ovarian reserve as assessed by ovarian antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) concentration. RESULT(S): Women (n = 193) ranged from 20 to 44 years. The majority had overweight or obesity (59%, n = 117) with mean BMI of 28±7 kg/m2. Forty-eight women lived in the most disadvantaged neighborhood quartile, of which 75% had overweight or obesity, compared with 54% of the 145 women living in the 3 less disadvantaged neighborhood quartiles. When controlling for age, race, and smoking status, women with overweight or obesity living in the most disadvantaged neighborhoods had significantly lower AMH compared with those living in the less disadvantaged neighborhoods. Antral follicle count did not differ among women with overweight or obesity by neighborhood of residence. Neighborhood disadvantage was not associated with ovarian reserve by AFC or AMH in women with normal weight or underweight status. CONCLUSION(S): Living in a socioeconomically deprived area is associated with lower markers of ovarian reserve among women with an elevated BMI.

Assessment of Blue Light Phototherapy for Grover Disease: A Nonrandomized Controlled Trial.

This nonrandomized clinical trial assesses treatment of patients diagnosed with Grover disease with blue light phytotherapy for several weeks.

Pregnancy outcomes in infertility patients diagnosed with sleep disordered breathing with wireless wearable sensors.

OBJECTIVE: To study the feasibility of home-based assessment of sleep disordered breathing (SDB) on early pregnancy success after in vitro fertilization with novel wearable sensors. DESIGN: Prospective observational study. SETTING: Patients 18 to 45 years old undergoing autologous IVF at an academic infertility center. PATIENTS: 30 women (24-44 years old) INTERVENTION: Participants provided medical history, completed sleep surveys, and a single night of home sleep monitoring prior to IVF with a novel, FDA-cleared wireless sensor system (ANNE® Sleep, Sibel Health), to collect continuous measurements of heart rate, respiratory rate, pulse oxygenation, respiratory effort/snoring, peripheral arterial tonometry, pulse arrival time, and pulse transit time, an accepted surrogate of continuous blood pressure generated by pulse arrival time and pulse transit time. Sleep nights were reviewed to derive the apnea hypopnea index (AHI), defined as the average number of apnea or hypopnea events per hour. An AHI of greater than or equal to 5 events/hour was considered abnormal. MAIN OUTCOME MEASURE: Rate of clinical pregnancy (defined as intrauterine gestational sac with a yolk sac) after IVF. Logistic regression models were used to estimate the unadjusted and adjusted odds ratio. RESULTS: The overall rate of sleep disordered breathing of any severity was 57%. Participants with SDB had a mean AHI of 13.4 compared to 2.7 events/hr (p<0.01), were younger, and more likely to have polycystic ovary syndrome. Of the 29 patients undergoing an embryo transfer, clinical pregnancy and livebirth occurred in 35% of women with SDB compared to 58% without SDB (p = 0.22). After adjusting for age, SDB reduced pregnancy rates but was not statistically significant (aOR 0.23, 95% CI: 0.04-1.5, p = 0.12). Though polycystic ovary syndrome was associated with higher rates of SDB it was not independently associated with lower pregnancy rates. CONCLUSION: Screening for sleep disordered breathing using home-based wireless, wearable sensors was well accepted and easily performed by infertile patients in this cohort. Sleep disordered breathing of any severity was associated with an 77% (95% CI: 0.08-1.8) lower likelihood of clinical pregnancy and live birth independent of underlying diagnosis. Future larger studies will be needed to understand the role of sleep disordered breathing and IVF outcomes.

Translational gaps and opportunities for medical wearables in digital health.

A confluence of advances in biosensor technologies, enhancements in health care delivery mechanisms, and improvements in machine learning, together with an increased awareness of remote patient monitoring, has accelerated the impact of digital health across nearly every medical discipline. Medical grade wearables-noninvasive, on-body sensors operating with clinical accuracy-will play an increasingly central role in medicine by providing continuous, cost-effective measurement and interpretation of physiological data relevant to patient status and disease trajectory, both inside and outside of established health care settings. Here, we review current digital health technologies and highlight critical gaps to clinical translation and adoption.

Reproductive Technology Considerations in Uterus Transplant.

Uterus transplantation (UTx) provides a new pathway to parenthood for patients with absolute uterine factor infertility. The application of reproductive technologies, such as in vitro fertilization, embryo cryopreservation, and frozen embryo transfers, for this unique population, is particularly nuanced and continually evolving. There are important pretransplant and posttransplant reproductive considerations for physicians and patients anticipating UTx. As with any rapidly evolving medical innovation, efforts to consolidate experiences and knowledge by centers offering UTx is paramount.

Racial disparities in frozen embryo transfer success.

PURPOSE: To compare pregnancy and birth outcomes after frozen embryo transfers (FETs) among White, Black, and Asian women and evaluate the effect of patient, protocol, and cycle characteristics on success. METHODS: A retrospective chart review identified women who underwent an autologous FET at an academic fertility center between January 2013 and March 2020. RESULTS: White, Black, and Asian women completed 1,181 (71.7%), 230 (14.0%), and 235 (14.3%) cycles, respectively. Black women were significantly less likely to achieve a positive hCG level (AOR 0.66, 95% CI 0.49-0.90), clinical pregnancy (AOR 0.71, 95% CI 0.53-0.97), and live birth (AOR 0.65, 95% CI 0.47-0.89) compared to White women after adjusting for possible confounders. There were no differences in the aforementioned outcomes when looking at cycles completed by Asian versus White women. When comparing outcomes by endometrial preparation protocol, significant differences were seen amongst the three groups for live birth rates following natural cycle FETs (52.36%, 25.81%, and 44.19% for White, Black, and Asian women, respectively, p = 0.02), a difference not appreciated after programmed FETs. CONCLUSION: Black race is associated with significantly worse pregnancy and live birth rates following FET when compared to White race. Additionally, significant differences in live birth rates among White, Black, and Asian women exist following natural cycle FET versus programmed FET. These disparities in success are not only important for patient counseling, but also when determining management strategies to improve fertility rates among minority women.