Telemedicine Follow-up After Medication Management of Early Pregnancy Loss.

Objective: Our objective was to evaluate the feasibility of a new protocol for telemedicine follow-up after medication management of early pregnancy loss. Study Design: The study was designed to assess the feasibility of planned telemedicine follow-up after medication management of early pregnancy loss. We compared these follow-up rates with those after planned in-person follow-up of medication management of early pregnancy loss and planned telemedicine follow-up after medication abortion. We conducted a retrospective cohort study, including patients initiating medication management of early pregnancy loss <13w0d gestation and medication abortion ≤10w0d with a combination of mifepristone and misoprostol between April 1, 2020, and March 28, 2021. As part of a new clinical protocol, patients could opt for telemedicine follow-up one week after treatment and a home urine pregnancy test 4 weeks after treatment. Our primary outcome was completed follow-up as per clinical protocol. We also examined outcomes related to complications across telemedicine and in-person follow-up groups. Results: Of patients reviewed, 181 were eligible for inclusion; 75 had medication management of early pregnancy loss, and 106 had medication abortion. Thirty-six out of 75 patients elected for telemedicine follow-up after early pregnancy loss. Of patients scheduled for telemedicine follow-up, 29/36 (81%, 95% CI: 64-92) with early pregnancy loss and 64/69 (93%, 95% CI: 84-98) undergoing medication abortion completed follow-up as per protocol (p = 0.06). Completed follow-up was also similar among patients undergoing medication management of early pregnancy loss who planned for in-person follow-up (p = 0.135). Complications were rare and did not differ across early pregnancy loss and medication abortion groups. Conclusions: Telemedicine follow-up is a feasible alternative to in-person assessment after medication management of early pregnancy loss.

Exploring Reasons for Loss to Follow-up in Pregnancy of Unknown Location: A Mixed-Methods Study.

Objective: To quantify proportions of loss to follow-up in patients presenting with a pregnancy of unknown location and explore patients' perspectives on follow-up for pregnancy of unknown location. A pregnancy of unknown location is a scenario in which a patient has a positive pregnancy test but the pregnancy is not visualized on transvaginal ultrasound. Study Design: We conducted a retrospective cohort study of patients with pregnancy of unknown location who presented to an urban academic emergency department or complex family planning outpatient office. We sought to calculate the proportion of patients lost to follow-up, defined as inability to contact the patient within 2 weeks. We then conducted focus groups of patients diagnosed with a pregnancy of unknown location. We used thematic analysis to identify themes related to follow-up. Results: We reviewed 464 charts of patients diagnosed with pregnancy of unknown location. The median age in this cohort was 27 with most patients identifying as Black (80%, n = 370) and using public insurance (67%, n = 315). When looking at loss to follow-up rates, Black patients experienced loss to follow-up (20%, n = 72) more often than White patients (4%, n = 2; p = 0.003). Focus group participants had a mean age of 31.8+/-4.8, and the majority were of Black race (n = 16, 72.7%). Participants identified barriers to follow-up including the long duration of management, general inconvenience, and poor communication with their health care team. Participants felt a burden of responsibility to learn about their condition and to self-advocate for their follow-up and communication of results. Conclusions: These data indicate that Black patients are more likely to experience loss to follow-up compared with White patients during monitoring for pregnancy of unknown location. Patients identified many barriers to follow-up and felt that successful follow-up required substantial self-efficacy.

High-Volume Surgeons and Reducing Racial Disparities in Route of Hysterectomy.

STUDY OBJECTIVE: To examine racial disparities in route of hysterectomy and perioperative outcomes before and after expansion of high-volume minimally invasive surgeons (>10 minimally invasive hysterectomies (MIH)/year) DESIGN: Retrospective cohort study SETTING: Multi-center academic teaching institution PATIENTS: All patients who underwent a scheduled hysterectomy for benign indications during 2018 (pre-intervention) and 2022 (post-intervention) INTERVENTIONS: Recruitment of Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS)- trained faculty and increased surgical training for academic specialists in obstetrics and gynecology occurred in 2020. MEASUREMENTS AND MAIN RESULTS: Patients in the pre-intervention cohort (n=171) were older (median age 45 years vs. 43 years, p=0.003) while patients in the post-intervention cohort (n=234) had a higher burden of comorbidities (26% ASA class III vs. 19%, p=0.03). Uterine weight was not significantly different between cohorts (p=0.328). Between the pre-intervention and post-intervention cohorts, high-volume minimally invasive surgeons increased from 27% (n=4) to 44% (n=7) of those performing hysterectomies within the division and percentage of hysterectomies performed via minimally invasive route increased (63% vs. 82%, p<0.001). In the pre-intervention cohort, Black patients had a lower percentage of hysterectomies performed via minimally invasive route compared to White patients (Black = 56% MIH vs. White = 76% MIH, p=0.014). In the post-intervention cohort, differences by race were no longer significant (Black = 78% MIH vs. White = 87% MIH, p= 0.127). There was a significant increase (22%) in MIH for Black patients between cohorts (p<0.001). After adjusting for age, BMI, ASA class, prior surgery, and uterine weight, disparities by race were no longer present in the post-intervention cohort. Perioperative outcomes including length of stay (p<0.001), infection rates (p=0.002) and blood loss (p=0.01) improved post-intervention. CONCLUSION: Increasing FMIGs-trained gynecologic surgeons and providing more opportunities in robotic/laparoscopic training for academic specialists may improve access to MIH for Black patients and reduce disparities.

Multiplexed serum biomarkers to discriminate nonviable and ectopic pregnancy.

OBJECTIVE: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies. DESIGN: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location. SETTING: Three university hospitals. PATIENTS: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages. INTERVENTIONS: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage). MAIN OUTCOME MEASURES: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated. RESULTS: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers. CONCLUSION: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location.

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.

Outcomes After Induction of Labor Compared With Dilation and Evacuation for the Management of Rupture of Membranes in the Second Trimester.

Previable and periviable rupture of membranes is associated with significant morbidity for the pregnant patient. For those who have a choice of options and undergo active management, it is not known how the risks of induction of labor compare with those for dilation and evacuation (D&E). We performed a retrospective cohort study of patients with rupture of membranes between 14 0/7 and 23 6/7 weeks of gestation who opted for active management. Adverse events (52.2% vs 16.9%, P <.01) and time to uterine evacuation greater than 24 hours (26.7% vs 9.6%, P =.01) were more common among patients undergoing induction of labor. In a multivariable regression, induction of labor was an independent risk factor for complications (odds ratio 5.70, 95% CI, 2.35-13.82) compared with D&E. Severe complications were rare across both groups (4.4% for patients undergoing induction vs 2.6% for D&E, P =.63). Given the differing risks by termination method, access to D&E is an important treatment option for this patient population.

Impact of coronavirus disease 2019 vaccination on live birth rates after in vitro fertilization.

OBJECTIVE: To investigate coronavirus disease 2019 (COVID-19) vaccination on the live birth rates in patients who underwent in vitro fertilization. DESIGN: Retrospective cohort study. SETTING: Academic fertility practice. PATIENT(S): Patients who underwent fresh or frozen embryo transfer cycles at an academic center between January 1, 2020, and December 31, 2021. INTERVENTION(S): Coronavirus disease 2019 vaccination, defined as completing a 2-dose regimen (Pfizer or Moderna) or 1-dose regimen (Johnson & Johnson/Janssen) before cycle initiation. MAIN OUTCOME MEASURE(S): The primary outcome was the live birth rate per embryo transfer. The secondary outcomes included positive human chorionic gonadotropin (hCG) and clinical pregnancy rates per embryo transfer. The outcomes from cycles among vaccinated and unvaccinated patients were compared. Descriptive statistics were used to analyze demographic and cycle characteristics using the Student t test and Wilcoxon rank sum, Pearson chi-square, and Fisher exact tests as appropriate for univariate analysis. Generalized estimating equation models were used to examine the strength of the relationship between vaccination status and pregnancy outcomes. RESULT(S): Among 709 unvaccinated and 648 vaccinated fresh cycles, no statistically significant differences were observed between the number of oocytes retrieved, oocyte maturity, fertilization, and blastocyst utilization rates. In the adjusted multivariate analysis, no statistically significant differences were noted between fresh cycles among vaccinated patients compared with those among unvaccinated patients with the rates of positive hCG (adjusted odds ratio [aOR], 1.37; 95% confidence interval [CI], 0.84-2.25), clinical pregnancy (aOR, 1.22; 95% CI, 0.73-2.03), or live birth (aOR, 1.37; 95% CI, 0.79-2.25) per embryo transfer. Among 264 unvaccinated and 423 vaccinated frozen embryo transfer (FET) cycles, vaccinated patients had higher odds of positive hCG (aOR, 1.54; 95% CI, 1.08-2.20), clinical pregnancy (aOR, 1.80; 95% CI, 1.27-2.56), and live birth (aOR, 2.31; 95% CI, 1.60-3.32) per embryo transfer than unvaccinated patients. CONCLUSION(S): Patients who were COVID-19 vaccinated before FET had higher rates of biochemical pregnancy, clinical pregnancy, and live birth. Vaccination was not associated with the pregnancy or live birth rates after fresh cycles. This study contributes to evidence supporting COVID-19 vaccination for patients attempting pregnancy.

Evaluation of novel biomarkers for early pregnancy outcome prediction†.

OBJECTIVE: To assess performance and discriminatory capacity of commercially available enzyme-linked immunosorbent assays of biomarkers for predicting first trimester pregnancy outcome in a multi-center cohort. DESIGN: In a case-control study at three academic centers of women with pain and bleeding in early pregnancy, enzyme-linked immunosorbent assays of biomarkers were screened for assay performance. Performance was assessed via functional sensitivity, assay reportable range, recovery/linearity, and intra-assay precision (%Coefficient of Variation). Top candidates were analyzed for discriminatory capacity for viability and location among 210 women with tubal ectopic pregnancy, viable intrauterine pregnancy, or miscarriage. Assay discrimination was assessed by visual plots, area under the curve with 95% confidence intervals, and measures of central tendency with two-sample t-tests. RESULTS: Of 25 biomarkers evaluated, 22 demonstrated good or acceptable assay performance. Transgelin-2, oviductal glycoprotein, and integrin-linked kinase were rejected due to poor performance. The best biomarkers for discrimination of pregnancy location were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 1, insulin-like growth factor binding protein 1, kisspeptin (KISS1), pregnancy-specific beta-1-glycoprotein 3, and beta parvin (PARVB). The best biomarkers for discrimination of pregnancy viability were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 3, EH domain-containing protein 3, KISS1, WAP four-disulfide core domain protein 2 (HE4), quiescin sulfhydryl oxidase 2, and pregnancy-specific beta-1-glycoprotein 1. CONCLUSION: Performance of commercially available enzyme-linked immunosorbent assays was acceptable for a panel of novel biomarkers to predict early pregnancy outcome. Of these, six and seven candidates demonstrated good discriminatory capacity of pregnancy location and viability, respectively, when validated in a distinct external population. Four markers demonstrated good discrimination for both location and viability.

Telehealth utilization in gynecologic oncology clinical trials.

OBJECTIVE: Prior to the COVID-19 pandemic, telehealth visits and remote clinical trial operations (such as local collection of laboratory tests or imaging studies) were underutilized in gynecologic oncology clinical trials. Current literature on these operational changes provides anecdotal experience and expert opinion with few studies describing patient-level safety data. We aimed to evaluate the safety and feasibility of telehealth and remote clinical trial operations during the COVID-19 Pandemic. METHODS: Gynecologic oncology patients enrolled and actively receiving treatment on a clinical trial at a single, academic institution during the designated pre-Telehealth and Telehealth periods were identified. Patients with at least 1 provider or research coordinator telehealth visit were included. Patient demographics, health system encounters, adverse events, and protocol deviations were collected. Pairwise comparisons were performed between the pre-Telehealth and Telehealth period with each patient serving as their own control. RESULTS: Thirty-one patients met inclusion criteria. Virtual provider visits and off-site laboratory testing increased during the Telehealth period. Delays in provider visits, imaging, and laboratory testing did not differ between time periods. Total and minor protocol deviations increased in incidence during the Telehealth period and were due to documentation of telehealth and deferment of non-therapeutic testing. Major protocol deviations, emergency department visits, admissions, and severe adverse events were of low incidence and did not differ between time periods. CONCLUSIONS: Telehealth and remote clinical trial operations appeared safe and did not compromise clinical trial protocols in a small, single institutional study. Larger scale evaluations of such trial adaptations should be performed to determine continued utility following the Pandemic.

Induced Abortion and the Risk of Rh Sensitization.

Importance: While population-level data suggest Rh immunoglobulin is unnecessary before 12 weeks' gestation, clinical evidence is limited. Thus, guidelines vary, creating confusion surrounding risks and benefits of Rh testing and treatment. As abortion care in traditional clinical settings becomes harder to access, many people are choosing to self-manage and need to know if ancillary blood type testing is necessary. Objective: To determine how frequently maternal exposure to fetal red blood cells (fRBCs) exceeds the most conservative published threshold for Rh sensitization in induced first-trimester abortion. Design, Setting, and Participants: Multicenter, observational, prospective cohort study using high-throughput flow cytometry to detect circulating fRBCs in paired maternal blood samples before and after induced first-trimester abortion (medication or procedural). Individuals undergoing induced first-trimester abortion before 12 weeks 0 days' gestation were included. Paired blood samples were available from 506 participants who underwent either medical (n = 319 [63.0%]) or procedural (n = 187 [37.0%]) abortion. Exposure: Induced first-trimester abortion. Main Outcomes and Measures: The primary outcome was the proportion of participants with fRBC counts above the sensitization threshold (125 fRBCs/5 million total RBCs) after induced first-trimester abortion. Results: Among the 506 participants, the mean (SD) age was 27.4 (5.5) years, 313 (61.9%) were Black, and 123 (24.3%) were White. Three of the 506 participants had elevated fRBC counts at baseline; 1 of these patients had an elevated fRBC count following the abortion (0.2% [95% CI, 0%-0.93%]). No other participants had elevated fRBC counts above the sensitization threshold after induced first-trimester abortion. The median change from baseline was 0 fRBCs, with upper 95th and 99th percentiles of 24 and 35.6 fRBCs, respectively. Although there was a strong association between the preabortion and postabortion fRBC counts, no other baseline characteristic was significantly associated with postabortion fRBC count. Conclusions and Relevance: Induced first-trimester abortion is not a risk factor for Rh sensitization, indicating that Rh testing and treatment are unnecessary before 12 weeks' gestation. This evidence may be used to inform international guidelines for Rh immunoglobulin administration following first-trimester induced abortion.

Telephone-Based Intervention to Improve Family Planning Care in Pregnancies of Unknown Location: Retrospective Pre-Post Study.

BACKGROUND: Patients followed for a pregnancy of unknown location are generally followed by a team of clinicians through telephone calls, and their contraceptive needs at the time of pregnancy resolution may not be addressed. OBJECTIVE: This study aimed to assess contraceptive counseling and contraceptive uptake before and after a telephone-based intervention. METHODS: This was a retrospective pre-post study assessing pregnancy intendedness in patients with a pregnancy of unknown location and the proportion of patients who received contraceptive counseling and a contraceptive prescription before and after the initiation of a telephone-based intervention. We reviewed medical records 1 year before and 1 year after implementation of our intervention for demographic characteristics, pregnancy intendedness, pregnancy outcome, contraceptive counseling documentation, receipt of contraception, and repeat pregnancy within 6 months. We assessed the effects of an implementation strategy to address family planning needs once pregnancy was resolved by comparing the proportions of patients who were counseled and received contraception before and after our intervention was implemented. We performed logistic regression to identify associations between covariates and the outcomes of contraceptive counseling documentation and receipt of contraception. RESULTS: Of the 220 patients in the combined cohort, the majority were Black (161/220, 73%) and ultimately had a resolved pregnancy of unknown location (162/220, 74%), and the proportion of pregnancies documented as unintended was 60% (132/220). Before our intervention, 27 of 100 (27%) patients received contraceptive counseling, compared with 94 of 120 (78%) patients after the intervention (odds ratio [OR] 9.77, 95% CI 5.26-18.16). Before the intervention, 17 of 90 (19%) patients who did not desire repeat pregnancy received contraception, compared with 32 of 86 (37%) patients after the intervention (OR 2.54, 95% CI 1.28-5.05). Our postintervention cohort had an increased odds of receiving contraceptive counseling (OR 9.77, 95% CI 5.26-18.16) and of receiving a contraceptive prescription (OR 2.54, 95% CI 1.28-5.05) compared with our preintervention cohort. CONCLUSIONS: We found that over half of patients with a pregnancy of unknown location have an unintended pregnancy, and standardization of care through a telephone-based intervention improves contraceptive counseling and prescribing in patients with a resolved pregnancy of unknown location. This intervention could be used at any institution that follows patients with a pregnancy of unknown location remotely to improve care.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously been implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Race, ovarian responsiveness, and live birth after in vitro fertilization.

OBJECTIVE: To determine if ovarian responsiveness to gonadotropin stimulation differs by race/ethnicity and whether this predicts live birth rates (LBRs) in non-White patients undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Academic infertility center. PATIENT(S): White, Asian, Black, and Hispanic patients undergoing ovarian stimulation for IVF. INTERVENTION(S): Self-reported race and ethnicity. MAIN OUTCOME MEASURE(S): The primary outcome was ovarian sensitivity index (OSI), defined as (the number of oocytes retrieved ÷ total gonadotropin dose) × 1,000 as a measure of ovarian responsiveness, adjusting for age, body mass index, infertility diagnosis, and cycle number. Secondary outcomes included live birth and clinical pregnancy after first retrievals, adjusting for age, infertility diagnosis, and history of fibroids, as well as miscarriage rate per clinical pregnancy, adjusting for age, body mass index, infertility diagnosis, duration of infertility, history of fibroids, and use of preimplantation genetic testing for aneuploidy. RESULT(S): The primary analysis of OSI included 3,360 (70.2%) retrievals from White patients, 704 (14.7%) retrievals from Asian patients, 553 (11.6%) retrievals from Black patients, and 168 (3.5%) retrievals from Hispanic patients. Black and Hispanic patients had higher OSIs than White patients after accounting for those with multiple retrievals and adjusting for confounders (6.08 in Black and 6.27 in Hispanic, compared with 5.25 in White). There was no difference in OSI between Asian and White patients. The pregnancy outcomes analyses included 2,299 retrievals. Despite greater ovarian responsiveness, Black and Hispanic patients had lower LBRs compared with White patients, although these differences were not statistically significant after adjusting for confounders (adjusted odds ratio, 0.83; 95% confidence interval [CI], 0.63-1.09, for Black; adjusted odds ratio, 0.93; 95% CI, 0.61-1.43, for Hispanic). Ovarian sensitivity index was modestly predictive of live birth in White and Asian patients but not in Black (area under the curve, 0.51; 95% CI, 0.38-0.64) and Hispanic (area under the curve, 0.50; 95% CI, 0.37-0.63) patients. CONCLUSION(S): Black and Hispanic patients have higher ovarian responsiveness to stimulation during IVF but do not experience a consequent increase in LBR. Factors beyond differences in responsiveness to ovarian stimulation need to be explored to address the racial/ethnic disparity established in prior literature.

Elevated antimüllerian hormone levels are not associated with preterm delivery after in vitro fertilization or ovulation induction.

OBJECTIVE: To investigate the association between antimüllerian hormone (AMH) and preterm birth risk in a larger cohort of patients who underwent either in vitro fertilization or ovulation induction with intrauterine insemination at a US academic fertility center. DESIGN: Retrospective cohort study. SETTING: Single academic fertility center. PATIENT(S): Live singleton births from patients who underwent in vitro fertilization or ovulation induction between 2016 and 2020 at a single academic fertility center were included in this study. Patients were excluded if they had a missing prepregnancy AMH level, a pregnancy using donor oocytes or a gestational carrier, multiple gestations, a delivery before 20 weeks gestation, or a cerclage in place. INTERVENTION(S): AMH level. MAIN OUTCOME MEASURE(S): The primary outcome was the proportion of preterm delivery. Secondary outcomes included the rate of pregnancy-induced hypertension, gestational diabetes, and small for gestational age. RESULT(S): In the entire cohort (n = 875), 8.4% of deliveries were preterm. The mean AMH values were similar between those with term and preterm births (3.9 vs. 4.2 ng/mL). Similar proportions of patients with term and preterm deliveries had AMH levels greater than the 75th percentile (25% vs. 21%). The odds of preterm birth were similar by AMH quartile after adjusting for the history of preterm birth. Similarly, in the polycystic ovary syndrome (PCOS) cohort, there was no difference between mean AMH values of term and preterm births (n = 139, 9.6 vs. 10.0 ng/mL). The proportions of patients with PCOS with AMH levels greater than the 75th percentile were similar between those with term and preterm deliveries (25% vs. 22%). The odds of preterm birth were similar by the AMH quartile after adjusting for the history of preterm birth. CONCLUSION(S): Elevated AMH levels were not associated with an increased risk of preterm birth in patients who conceived after in vitro fertilization and ovulation induction, including patients with PCOS. Although studies suggest that AMH levels may help stratify the risk of preterm birth in this population, our findings indicate that further studies are needed before clinical application.

Evaluation of a decision aid for early pregnancy loss: A pilot randomized controlled trial in Philadelphia, Pennsylvania.

OBJECTIVES: To evaluate the effect of a decision aid on decisional conflict scale in patients choosing management for early pregnancy loss. STUDY DESIGN: We conducted a pilot randomized control trial to assess the effect of the Healthwise patient decision aid on decisional conflict scale in patients with early pregnancy loss as compared with a control website. Patients 18years and older were eligible if they had an early pregnancy loss between 5 and 12 completed weeks of gestation. Participants completed surveys at baseline, poststudy intervention, after consultation, and 1week postconsultation. Surveys assessed participant scores on the decisional conflict scale (scale 0-100), knowledge, assessment of shared decision-making, satisfaction, and decision regret. Our primary outcome was the poststudy-intervention decisional conflict scale score. RESULTS: From July 2020 through March 2021 we randomized 60 participants. After the intervention, the median decisional conflict scale score for the control group was 10 [0-30] and 0 [0-20] for the intervention group (p = 0.17). When assessing the decisional conflict scale subscales postintervention, the informed subscale for the control group was 16.7 [0-33.3] as opposed to 0 [0] for the patient decision aid group (p = 0.003). Knowledge remained significantly higher in the experimental arm from the postintervention to the 1-week follow-up. We found no differences between groups when assessing our other metrics. CONCLUSIONS: Use of a validated decision aid did not result in statistically significant differences in the total decisional conflict scale scores as compared with the control. Participants allocated to the intervention were more informed postintervention and had consistently higher knowledge scores. IMPLICATIONS: Use of a validated decision aid prior to early pregnancy loss management consultation did not affect overall decisional conflict but resulted in improved knowledge.

Outcomes of assisted reproductive technology procedures performed on weekdays versus weekends: a retrospective cohort study.

PURPOSE: To evaluate if assisted reproductive technology (ART) outcomes are different based on whether procedures - oocyte retrieval, insemination, embryo biopsy, or embryo transfer - are performed on a weekday versus weekend/holiday. METHODS: Retrospective cohort study of all patients ≥ 18 years old who underwent oocyte retrieval for in vitro fertilization or oocyte banking (n = 3,197 cycles), fresh or natural-cycle frozen embryo transfers (n = 1,739 transfers), or had embryos biopsied for pre-implantation genetic testing (n = 4,568 embryos) in a large academic practice from 2015-2020. The primary outcomes were as follows: oocyte maturity for oocyte retrievals; fertilization rate for insemination; rate of no result on pre-implantation genetic testing for embryo biopsy; and live birth rate for embryo transfers. RESULTS: The average number of procedures performed per embryologist per day was higher on weekends/holidays than weekdays. For oocyte retrievals performed on weekdays vs. weekends/holidays, there was no difference in oocyte maturity rate (88% vs 88%). There was no difference in the fertilization rate (82% vs 80%) in cycles that had intracytoplasmic sperm injection performed on weekdays vs. weekends/holidays. No difference was found in the no result rate for embryos biopsied on weekdays vs. weekends/holidays (2.5% vs 1.8%). Finally, there was no difference by weekday vs. weekend/holiday in the live birth rate per transfer among all transfers (39.6% vs 36.1%), or when stratified by fresh (35.1% vs 34.9%) or frozen embryo transfer (49.7% vs. 39.6%). CONCLUSION: We found no differences in ART outcomes among women who had their oocyte retrievals, inseminations, embryo biopsies, or embryo transfers performed on weekdays versus weekends/holidays.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high through-put technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥ 0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥ 0.80: lutropin subunit beta and serpin B8. While some of the markers were previously identified as implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high through-put platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Exploring technology-based interventions to improve oral contraceptive pill adherence: a cross-sectional survey.

PURPOSE: To assess the resources that oral contraceptive pill (OCP) users currently use and wish to use after missing pills. MATERIALS AND METHODS: People 18-44 years old with a OCP prescription were emailed a cross-sectional survey to assess how they obtain information about managing missed pills, what information they would prefer to access, and whether they would use additional information if it were available. We performed a logistic regression and a dominance analysis to compare independent predictors of desire for a technological resource at the time of missed pills. RESULTS: We received 166 completed surveys. Nearly half of participants (47%, n = 76, 95% CI 39.0-54.4%) did not seek information about managing their missed pills. When missing a pill, more patients preferred non-technology-based information (57.1%, n = 93, 95% CI 49.3-64.5%) over technology-based information (43%, n = 70, 95% CI 35.5-50.7%). Most reported they would appreciate more information at the time of missed pills (76%, n = 124, 95% CI 68.9-82.0%). The strongest predictors for desire for technology-based information were: current use of technology, lower parity, white race, and higher educational attainment. CONCLUSIONS: This study indicates that most OCP users would utilise additional information at the time of a missed pill if they had access to it and that they desire information in varying formats.

Patients desire more educational information at the time of missed oral contraceptive pills, and preferences are varied regarding the format of patient information. Implementation of high-quality counseling with oral contraceptive pills requires a broad range of educational materials as well as provider education.

Cell-free DNA screening for trisomy 21 in twin pregnancy: a large multicenter cohort study.

BACKGROUND: Analysis of cell-free DNA from maternal blood provides effective screening for trisomy 21 in singleton pregnancies. Data on cell-free DNA screening in twin gestations are promising although limited. In previous twin studies, cell-free DNA screening was primarily performed in the second trimester and many studies did not report chorionicity. OBJECTIVE: This study aimed to evaluate the screening performance of cell-free DNA for trisomy 21 in twin pregnancies in a large, diverse cohort. A secondary aim was to evaluate screening performance for trisomy 18 and trisomy 13. STUDY DESIGN: This was a retrospective cohort study of twin pregnancies from 17 centers for which cell-free DNA screening was performed from December 2011 to February 2020 by one laboratory using massively parallel sequencing technology. Medical record review was conducted for all newborns and data on the birth outcome, the presence of any congenital abnormalities, phenotypic appearance at birth, and any chromosomal testing that was undertaken in the antenatal or postnatal period were extracted. Cases with a possible fetal chromosomal abnormality with no genetic test results were reviewed by a committee of maternal-fetal medicine geneticists. Cases with a vanishing twin and inadequate follow-up information were excluded. A minimum of 35 confirmed cases of trisomy 21 was required to capture a sensitivity of at least 90% with a prevalence of at least 1.9% with 80% power. Test characteristics were calculated for each outcome. RESULTS: A total of 1764 samples were sent for twin cell-free DNA screening. Of those, 78 cases with a vanishing twin and 239 cases with inadequate follow-up were excluded, leaving a total of 1447 cases for inclusion in the analysis. The median maternal age was 35 years and the median gestational age at cell-free DNA testing was 12.3 weeks. In total, 81% of the twins were dichorionic. The median fetal fraction was 12.4%. Trisomy 21 was detected in 41 of 42 pregnancies, yielding a detection rate of 97.6% (95% confidence interval, 83.8-99.7). There was 1 false negative and no false positive cases. Trisomy 21 was detected in 38 out of 39 dichorionic twin pregnancies, yielding a detection rate of 97.4% (95% confidence interval, 82.6-99.7). Trisomy 18 was detected in 10 of the 10 affected pregnancies. There was 1 false positive case. Trisomy 13 was detected in 4 of the 5 cases, yielding a detection rate of 80% (95% confidence interval, 11.1-99.2). There was one false negative and no false positive cases. The nonreportable rate was low at 3.9 %. CONCLUSION: Cell-free DNA testing is effective in screening for trisomy 21 in twin gestations from the first trimester of pregnancy. Detection of trisomy 21 was high in dichorionic and monochorionic twins, and the nonreportable result rates were low. This study included high numbers of cases of trisomy 18 and 13 when compared with the current literature. Although screening for these conditions in twins seems to be promising, the numbers were too small to make definitive conclusions regarding the screening efficacy for these conditions. It is possible that cell-free DNA testing performance may differ among laboratories and vary with screening methodologies.