Association of HCG Level with Ultrasound Visualization of the Gestational Sac in Early Viable Pregnancies.

Our primary objective is to verify or refute a 2013 study by Connolly et al. which showed that in early pregnancy, a gestational sac was visualized 99% of the time on transvaginal ultrasound when the HCG level reached 3510 mIU/mL. Our secondary objective was to make clinical correlations by assessing the relationship between human chorionic gonadotropin (HCG) level in early pregnancy when a gestational sac is not seen and pregnancy outcomes of live birth, spontaneous abortion, and ectopic pregnancy. This retrospective study includes 144 pregnancies with an outcome of live birth, 87 pregnancies with an outcome of spontaneous abortion, and 59 ectopic pregnancies. Logistic regression is used to determine the probability of visualizing a gestational sac and/or yolk sac based on the HCG level. A gestational sac is predicted to be visualized 50% of the time at an HCG level of 979 mIU/mL, 90% at 2421 mIU/mL, and 99% of the time at 3994 mIU/mL. A yolk sac was predicted to be visualized 50% of the time at an HCG level of 4626 mIU/mL, 90% at 12,892 mIU/mL, and 99% at 39,454 mIU/mL. A total of 90% of ectopic pregnancies presented with an HCG level below 3994 mIU/mL. These results are in agreement with the study by Connolly et al. Since most early ectopic pregnancies had an HCG value below the discriminatory level for gestational sac visualization, other methods for the evaluation of pregnancy of unknown location such as repeat HCG values are clinically important.

Effects of parity on preterm delivery in twin gestations conceived with in vitro fertilization.

Objective: To determine the relationship between prior obstetrical history and gestational age at delivery in a twin pregnancy. Design: Retrospective cohort study using the United States Society for Assisted Reproductive Technology Clinic Outcomes Reporting System database. Setting: Clinic-based data. Patients: Patients undergoing in vitro fertilization (IVF) in the United States with live delivery of twins. Interventions: None. Main outcome measures: The main outcome measures are median gestational age at delivery and rate of preterm delivery (before 37 weeks). Results: The median gestational age at delivery of IVF-conceived twins was 36.3 (interquartile rate 34.4, 37.6) weeks for nulliparous women, 35.9 (34.0, 37.1) weeks for parous women with a prior preterm birth, and 36.7 (35.1, 37.7) weeks for parous women without a prior preterm birth. The rate of preterm delivery was 61% for nulliparous women, 70% for parous women with a prior preterm birth, and 55% for parous women without a prior preterm birth. Conclusions: Parous women without a history of preterm delivery had lower rates of preterm delivery in a subsequent twin pregnancy than nulliparous women. Nulliparous women had lower rates of preterm delivery compared with parous women with a history of preterm delivery.

Implementing pharmacists' medication safety recommendations is associated with reduced health care resource utilization and mortality in high-risk older Americans.

BACKGROUND: A medication safety review (MSR) is a novel, pharmacist-driven, technology-supported intervention that prioritizes adverse drug event risk mitigation. Previous research has shown that Medicare Part D beneficiaries who received MSRs in an enhanced medication therapy management (EMTM) model realized improvements in total Medicare spending, hospitalizations, emergency department (ED) visits, and mortality compared to control. However, it is unknown whether beneficiaries implemented pharmacists' MSR recommendations. OBJECTIVE: The objective of the study was to evaluate whether MSR recommendation implementation is associated with improvements in these same outcomes for Part D beneficiaries enrolled in EMTM compared to a control group. METHODS: This retrospective, pre-post, cohort study evaluated outcomes for beneficiaries who were targeted for MSR services in 2018 and 2019. The "validated implementation MSR (viMSR)" cohort included those who received their first-ever MSR in 2018, received another MSR in 2019, and validated implementation of ≥1 recommendation in their 2018 MSR. The "failed to engage" (FTE) cohort included beneficiaries who were targeted for MSR services in both 2018 and 2019 but did not engage in an MSR at any point through the end of 2019. For both cohorts, we calculated the 2018-to-2019 change for each outcome and then determined whether year-over-year changes differed significantly between cohorts. For mortality, we relaxed the requirement for continuous enrollment in 2019, permitting us to compare the proportion of beneficiaries that died in each group in 2019. Analyses were adjusted for baseline multimorbidity. RESULTS: Of 4384 beneficiaries who completed MSRs, 602 (13.7%) implemented ≥1 recommendation. The viMSR cohort (N = 602) outperformed the FTE cohort (N = 7052) in total Medicare costs ($2162/y lower; P = 0.020), Part A Medicare costs ($1855/y; P = 0.024), hospitalizations (9.1 fewer admissions/100 beneficiaries/y, P = 0.020), ED visits (10.8 fewer visits/100 beneficiaries/y, P = 0.014), and mortality (3.8% fewer died in 2019; P < 0.001). CONCLUSION: Implementing pharmacists' recommendations in MSRs was associated with improved health care resource utilization and mortality for MSR-eligible beneficiaries.

Embryo morphology and live birth in the United States.

Objective: To determine the best-fit live birth rate per embryo based on maternal age, embryo stage, and embryo morphology. Design: Retrospective data analysis. Setting: Fertility clinics. Patients: The patients included were treated with in vitro fertilization in the United States at clinics reporting data to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. We analyzed live birth data of unbiopsied autologous cleavage and blastocyst stage embryos for cycles started from 2016 through 2018. The analysis included 223,377 embryo transfers with a total of 336,888 embryos. Interventions: None. Main Outcome Measures: Live birth rate per embryo and rate of multiple gestations per pregnancy. Results: At the mean maternal age of 34 years, fresh embryos produced live birth rates of 19%, 38%, 26%, and 27% for embryos aged 3, 5, 6, and 7 days, respectively. At the age 34 years, live birth rates for day 5 fresh embryos by overall morphology grade were 43% for good, 30% for fair, and 21% for poor. For the transfer of 2 fresh day 5 blastocysts, the rate of multiple gestations per pregnancy was 47% at 25 years old, 44% at 30 years old, 35% at 35 years old, and 23% at 40 years old. Conclusions: The analysis of pregnancy data in the Society for Assisted Reproductive Technology database can be used to calculate live birth rates per embryo based on maternal age, embryo age, and morphology. This information can be used for evidence-based decision making, quality control, and planning multicenter studies.

Effect of trophectoderm biopsy for PGT-A on live birth rate per embryo in good prognosis patients.

PURPOSE: To determine if blastocyst trophectoderm biopsy for PGT-A is associated with an increased rate of live birth per embryo in good prognosis IVF patients at a single center. METHODS: We performed a retrospective cohort study of good prognosis embryo transfer cycles at a single center from 1/1/2017 to 12/31/2019. We evaluated the rate of live birth per embryo with and without PGT-A for transfer of embryos in two groups of good prognosis patients: embryos from donor oocytes and embryos from autologous oocytes with maternal age less than 35 years at oocyte retrieval. Two-sided Fisher's exact tests were used for comparisons between groups. RESULTS: After transfer of embryos created from donor oocytes the live birth rate per euploid embryo was 70.6% (24/34) compared to 34.3% (35/102) for untested embryos for a rate difference of 36.3% (95% CI 18.4-54.1%, p < 0.01). After transfer of embryos created from autologous oocytes with maternal age less than 35 years at oocyte retrieval the live birth rate per euploid embryo was 70.0% (49/70) compared to 52.5% (53/101) for untested embryos for a rate difference of 17.5% (95% CI 3.0-32.0%, p = 0.03). CONCLUSIONS: In good prognosis patients at our center the live birth rate per euploid blastocyst was higher than for untested blastocysts.

Medication-related problems identified by pharmacists in an enhanced medication therapy management model.

OBJECTIVES: To describe the types of clinically actionable medication-related problems (MRPs) identified and the types of resolving recommendations issued by pharmacists using an advanced clinical decision support system (CDSS) for Medicare Part D beneficiaries. STUDY DESIGN: Retrospective cross-sectional study. METHODS: We examined frequencies of MRPs and recommendations for beneficiaries who received a first-ever medication safety review (MSR) during plan years 2018-2019. MRPs were considered clinically actionable if implementation of a recommendation would alter the medication regimen. RESULTS: Pharmacists identified ≥ 1 clinically actionable MRP for 82.4% (18,703/22,696) beneficiaries receiving an MSR. Among these beneficiaries, 36,455 MRPs were identified (mean [SD] number of MRPs: 1.9 [1.0]). "Adverse drug reaction" (n = 14,788; 40.6%), "drug interaction" (n = 9716; 26.7%), and "medication use without indication" (n = 6496; 17.8%) represented 85.0% of all MRPs. "Start alternative therapy" was most frequently recommended to resolve "adverse drug reactions" (6724/14,788; 45.5%), followed by "change time of administration" to resolve "drug interactions" (5189/9716; 53.4%) and "discontinue medication" to resolve "drug use without indication" (5718/6496; 88.0%). Overall, "start alternative therapy" (n = 12,219) and "discontinue medication" (n = 12,059) made up 66.6% of all recommendations. CONCLUSIONS: In Medicare Part D beneficiaries, pharmacists using an advanced CDSS identified a substantial number of MRPs pertaining to medication safety and issued recommendations to decrease the risk of adverse drug events.

Health outcomes from an innovative enhanced medication therapy management model.

OBJECTIVE: To evaluate the impact of pharmacist-delivered medication safety reviews (MSRs) on total medical expenditures, hospitalizations, emergency department (ED) visits, and mortality in Medicare Part D beneficiaries, whose plan was a participant of the Enhanced Medication Therapy Management model. STUDY DESIGN: Retrospective, pre-post, cohort study. METHODS: We evaluated the aforementioned outcomes for beneficiaries who were targeted, according to their MedWise Risk Scores (MRS), for MSR services in both 2018 and 2019. The "MSR" cohort included those who received their first-ever MSR in 2018 and received another MSR in 2019. The "failed to engage" (FTE) cohort included beneficiaries who were targeted in both 2018 and 2019 but did not engage in an MSR at any point through the end of 2019. For both cohorts, we calculated the change from 2018 to 2019 for each outcome and then determined whether unadjusted year-over-year changes differed significantly between cohorts. Additionally, these difference-in-differences (DiD) analyses were adjusted for baseline MRS and multimorbidity. RESULTS: A total of 11,436 beneficiaries were targeted for MSRs in both 2018 and 2019. Beneficiaries were, on average, aged 76.6 ±â€…10.0 years. The MSR cohort (N = 4384) outperformed the FTE cohort (N = 7052) in total medical costs (DiD = $958/y [7.5% savings]; P = .042), hospitalizations (DiD = 3.9 admissions/100 beneficiaries/y [10% reduction]; P = .032), ED visits (DiD = 6.2 visits/100 beneficiaries/y [10% reduction]; P = .014), and mortality (2.1% fewer died in 2019; P < .001). Each outcome remained significant after adjusting for baseline MRS and multimorbidity. CONCLUSION: MSRs were effective at improving annual health care costs, hospitalizations, ED visits, and mortality in Medicare beneficiaries targeted according to MRS.

Effect of age and morphology on sustained implantation rate after euploid blastocyst transfer.

RESEARCH QUESTION: What impact does maternal age and embryo morphology have on sustained implantation rates of euploid blastocysts? DESIGN: This was a retrospective analysis of sustained implantation rates of euploid blastocysts stratified by maternal age and morphology. The primary analysis included 208 embryo transfers with a total of 229 embryos transferred from January 2017 through August 2020. RESULTS: For all ages the sustained implantation rates for day 5 good quality blastocysts were higher than for day 5 fair, day 5 poor and day 6 blastocysts. At a maternal age of 36 years the best-fit sustained implantation rates were 86% for day 5 good quality blastocysts, 64% for day 5 fair, 63% for day 5 poor, and 51% for all day 6 blastocysts analysed as one group. When controlling for morphology and day of biopsy, there were higher sustained implantation rates for euploid embryos of younger patients compared with older patients. The best-fit sustained implantation rates for age 33 compared to age 39 years were 86% versus 80% for day 5 good, 71% versus 62% for day 5 fair, 59% versus 55% for day 5 poor, and 81% versus 46% for all day 6. CONCLUSIONS: There was a clinically significant higher sustained implantation rate at all ages for euploid day 5 good quality embryos compared with day 5 fair, day 5 poor and day 6 embryos.

Successful Vaginal Delivery after External Cephalic Version in a Woman with a Large Partial Uterine Septum.

Septate uteri have been associated with adverse pregnancy outcomes including spontaneous abortion, preterm delivery, and malpresentation. It is unclear if uterine septa are associated with infertility. Although some studies have shown improved pregnancy outcomes after septum resection, indications for resection are not well established. We describe a case of a woman with a large partial uterine septum diagnosed during workup for infertility who conceived without septum resection. Both of her subsequent pregnancies were initially breech presentations for which the patient underwent external cephalic version followed by full-term vaginal deliveries. This case adds evidence that an unresected uterine septum should not be considered a contraindication to external cephalic version.

Developmental potential of immature human oocytes aspirated after controlled ovarian stimulation.

PURPOSE: Intracytoplasmic sperm injection (ICSI) for initially immature oocytes that mature in vitro is controversial and practice varies widely. While it may increase the number of usable embryos, it may also be time-intensive and potentially low-yield. This study sought to elucidate which patients may benefit from ICSI of initially immature oocytes that matured in vitro. METHODS: A retrospective study comparing fertilization, cleavage, blastulation, and embryo usage rates between sibling initially immature and mature oocytes that underwent ICSI between 2015 and 2019 was performed. Outcomes of initially immature oocytes were stratified by initial maturation stage, timing of progression to metaphase II (MII) in vitro, percentage of mature oocytes in the cycle, and female age. RESULTS: Ten thousand eight hundred seventeen oocytes from 889 cycles were included. Of 3137 (29.0%) initially immature oocytes, 418 (13.3%) reached MII later on the day of retrieval (day 0) and 1493 (47.6%) on day 1. Overall, embryos originating from initially immature oocytes had lower cleavage and blastulation rates compared to those from initially mature oocytes (P<0.05, all groups). However, embryos from oocytes that matured later on day 0 comprised a unique subset that had clinically similar cleavage (75% vs 80%, RR 0.93, P=0.047) and blastulation rates (41% vs 50%, RR 0.81, P=0.024) compared to initially mature oocytes. Women with low percentages of mature oocytes in the cycle overall and women ≥40 in cleavage cycles derived the highest relative benefit from the use of immature oocytes. CONCLUSION: ICSI of immature oocytes, particularly those that mature later on the day of retrieval, may improve numbers of usable embryos. This study supports routine reassessment of immature oocytes for progression to MII and ICSI on day 0. An additional reassessment on day 1 may also be of use in older women or those with low percentage of mature oocytes.

A validated model for predicting live birth after embryo transfer.

Accurately predicting the probability of live birth and multiple gestations is important for determining a safe number of embryos to transfer after in vitro fertilization. We developed a model that can be fit to individual clinic data for predicting singleton, twin, and total live birth rates after human embryo transfer. The predicted and observed rates of singleton and twin deliveries were compared in a tenfold cross-validation study using data from a single clinic. The model presented accounts for patient age, embryo stage (cleavage or blastocyst), type of transfer cycle (fresh or frozen) and uterine/universal factors. The standardized errors for rates of singleton and twin deliveries were normally distributed and the mean errors were not significantly different from zero (all p > 0.05). The live birth rates per embryo varied from as high as 43% for fresh blastocysts in the 35-year-old age group to as low as 1% for frozen cleavage stage embryos in the 43-year-old age group. This quantitative model or a simplified version can be used for clinics to generate and analyze their own data to guide the number of embryos to transfer to limit the risk of multiple gestations.

Influence of Trophectoderm Biopsy Prior to Frozen Blastocyst Transfer on Obstetrical Outcomes.

The purpose of this study is to determine if trophectoderm biopsy prior to autologous frozen blastocyst transfer in programmed cycles is associated with gestational age at delivery, birth weight, or cesarean rate in viable singleton gestations. We conducted a retrospective cohort study of patients at a university-affiliated center that had viable singleton gestations after autologous frozen blastocyst transfer in programmed cycles. Obstetrical outcomes of 67 pregnancies after blastocyst trophectoderm biopsy for preimplantation genetic testing were compared to 78 pregnancies from unbiopsied blastocysts. There were no significant differences between the two cohorts in terms of maternal age, BMI, or ethnicity. There were no differences in the preimplantation genetic testing cohort compared to the reference cohort for median gestational age at delivery (39.4 vs 39.4 weeks, p = 0.80), median birth weight (3420 vs 3430 g, p = 0.97), cesarean rate (51% vs 44%, p = 0.41), preterm delivery rate (12% vs 8%, p = 0.41), rate of low birth weight (12% vs 9%, p = 0.59), or rate of birth weight over 4000 g (13% vs 8%, p = 0.29). There were no differences in the primary outcomes with subgroup analysis based on fetal sex, single embryo transfer, gravidity, history of prior term birth, and maternal age < or ≥ 35 years. Trophectoderm biopsy prior to frozen blastocyst transfer in programmed cycles was not associated with adverse obstetrical outcomes related to gestational age at delivery, birth weight, or cesarean rate.

Design and validation of a model for quality control monitoring of dichotomous in vitro fertilization outcomes.

OBJECTIVE: To develop and validate a practical model for quality control monitoring of dichotomous in vitro fertilization (IVF) outcomes such as pregnancy resulting from the transfer of euploid blastocysts. DESIGN: We designed and validated a model for quality control monitoring of dichotomous IVF outcomes. We demonstrate use of this model for assessment of euploid blastocyst transfer quality control based on fetal heartbeat rate per embryo. The model uses 3 weighted moving averages with window sizes of 21, 51, and 101 embryo transfers to detect short and long-term shifts in success rates. The quality warning limit was set to have a 2-sided type I error rate of 0.30 per 100 embryo transfers and the control limit was set to have a type I error rate of 0.05 per 100 embryo transfers. Simulation studies were performed to validate the model through assessment of type I and type II errors using custom computer programs. SETTING: Not applicable. PATIENT(S): Patients undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Type I and type II error rates and statistical power analysis. RESULT(S): Validated quality warning and control limits are presented for a range of expected outcome rates. The power to detect a 20% decrease from an expected fetal heartbeat rate of 50%, when the decrease persisted for 50 embryo transfers, was 86% for the warning limit and 57% for the control limit. CONCLUSION(S): This model can be used for continuous quality control assessment of dichotomous IVF outcomes such as pregnancy rates.

Transfer the best and biopsy the rest? Blastocyst euploidy rates differ by morphology and day of biopsy.

PURPOSE: To determine if blastocyst euploidy rates differ by embryo morphology or day of biopsy. METHODS: We performed a retrospective analysis of euploidy rates based on patient age, overall embryo morphology grade (good, fair, or poor), and day of biopsy (days 5, 6, or 7) for blastocysts undergoing preimplantation genetic testing for aneuploidy (PGT-A). Our primary analysis included 904 embryos from oocytes age 33-39 years at retrieval. RESULTS: In our primary analysis, euploidy rates were higher for good quality embryos than poor (64% vs. 48%, p < 0.01) and for fair quality embryos than poor (61% vs. 48%, p < 0.01). There was no significant difference in the euploidy rate between good and fair quality embryos (64% vs. 61%, p = 0.56). Embryos biopsied on day 5 were more likely to be euploid than embryos biopsied on day 6 (59% vs. 50%, p < 0.01) or day 7 (59% vs. 37%, p < 0.01). There was no significant difference in the euploidy rate between day 6 and day 7 embryos (50% vs. 37%, p = 0.07). CONCLUSION: PGT-A may be more useful in cycles where a lower euploidy rate is expected based on age at oocyte retrieval, embryo morphology, and day of biopsy. There may be little benefit to biopsy of embryos with a high euploidy rate. Young patients with one or more good quality day 5 embryos may benefit from a "transfer the best fresh and biopsy the rest" strategy.

Medication-related problems encountered in the Program of All-Inclusive Care for the Elderly: An observational study.

OBJECTIVE: To evaluate pharmacist-encountered medication-related problems (MRPs) among the participants of the Program of All-Inclusive Care for the Elderly (PACE). DESIGN: This was a retrospective analysis of proprietary pharmacy records detailing pharmacist encounters with PACE clinical staff. SETTING AND PARTICIPANTS: A national provider of pharmacy services to more than 75 PACE organizations. In total, 1057 PACE participants at 69 PACE sites across the United States with documented pharmacist encounters between March and May 2018. OUTCOME MEASURES: MRPs were classified using the Hepler-Strand taxonomy, and pharmacists' recommendations made to prescribers to resolve these MRPs were classified using a modified Hoth taxonomy. In addition, pharmacists' communication methods and prescribers' responses were analyzed. RESULTS: Overall, 2004 MRPs were encountered. The most frequent MRPs identified were related to medication safety concerns, including drug interactions (720, 35.9%), adverse drug reactions (ADRs, 356, 17.8%), high doses (270, 13.5%), and unindicated drugs (252, 12.6%). Drug interactions frequently involved competitive inhibition, 3 or more drugs, opioids, anticoagulants, antiplatelets, and antidepressants. Deprescribe medication (561, 24.8%), start alternative therapy (553, 24.4%), change doses (457, 20.2%), and monitor (243, 10.7%) were the top 4 types of recommendations made by pharmacists. Among 1730 responses obtained from PACE prescribers, 78.1% (n = 1351) of pharmacists' recommendations were accepted. Compared with electronic communication, telephonic communication was associated with more acceptance and less prescriber nonresponse (χ2 = 78.5, P < 0.001). CONCLUSION: Pharmacists identified a substantial number of MRPs in PACE, especially those related to medication safety such as drug interactions and ADRs. In this practice setting, significant collaboration occured between pharmacists and PACE prescribers, as evidenced by the rate of prescribers' acceptance of pharmacists' recommendations. Further research is needed to fully evaluate the economic, clinical, and humanistic outcomes associated with pharmacists' encounters in PACE.