Examining reasons that patients discard cryopreserved oocytes.

PURPOSE: Assess the rate, rationale, and characteristics of patients who cryopreserved and subsequently discarded their oocytes, and compare their characteristics to patients with continued cryopreservation of oocytes. METHODS: All patients who disposed of cryopreserved oocytes between 2009 and 2022 reported their reason for discarding their oocytes. This was a retrospective cohort study. RESULTS: Of 5,010 patients who underwent oocyte cryopreservation (OC) cycles, 201 (4%) patients elected to discard their oocytes and 751 (15%) thawed oocytes for clinical use. The average ages of OC and disposal were 35 and 39 years old, respectively. Of the 201 patients who discarded their oocytes, 71 patients (35%) requested disposal after having a child. Twenty-six (13%) discarded oocytes because of worsening cancer and three (1.4%) discarded because of death. 16 (8%) discarded oocytes due to cost of cryopreservation and eight (4%) due to low oocyte yield. Ten (5%) patients underwent new IVF cycles and discarded previously stored oocytes. Sixty-seven patients (33%) discarded oocytes for unspecified reasons. When comparing patients who discarded oocytes with those who did not, the former had lower AMH (2.7 vs 3.5 ng/ml, p < 0.001) but otherwise comparable age and number of cryopreserved oocytes. The mean age for those with continued cryopreservation was 35.4 years at time of OC and 40 years at time of data collection in June 2023. CONCLUSION: Childbirth was the most common reason to dispose of oocytes followed by unspecified reasons. Larger studies of oocyte disposal may better define clinical characteristics of patients most likely to use, maintain or discard their oocytes.

Gestational carrier pregnancy outcomes from frozen embryo transfer depending on the number of embryos transferred and preimplantation genetic testing: a retrospective analysis.

OBJECTIVE: To compare gestational age, birth weight (BW), and live birth rates in gestational carriers (GC) after the transfer of 1 or 2 frozen embryo(s) with or without preimplantation genetic testing for aneuploidy (PGT-A), with the understanding that several social and economic factors may motivate intended parents to request the transfer of 2 embryos and/or PGT-A when using a GC. DESIGN: Retrospective cohort study SETTING: An assisted reproductive technology practice. PATIENT(S): All frozen blastocyst transfers with GCs from 2009-2018. INTERVENTION(S): One or 2 embryo frozen embryo transfers with and without PGT-A. MAIN OUTCOME MEASURE(S): Live birth, preterm birth, and low BW. RESULTS: A total of 583 frozen embryo transfer cycles with vitrified high-grade blastocysts (grade BB or higher) to GCs were analyzed. Although the live birth rate was significantly greater in frozen embryo transfers with 2 embryos, after single embryo transfer (SET), the mean gestational age and BW of live births were statistically significantly greater than those of double embryo transfer (DET). The rate of multiple births was 1.9% for SET compared to 20.0% for DET per transfer. Only 3.8% of live births from SET experienced low BW and 0.6% had very low or extremely low BW. By comparison, 12.5% of DET live births were low BW and 5% were very low BW. After SET, 13.4% of live births were preterm, compared with 40% in DET. The analysis also included a total of 194 transfers with PGT-A compared to 389 cycles without. Overall, live births per transfer were not significantly different between these latter 2 subgroups. CONCLUSION: Frozen embryo transfer cycles in GCs with DET were associated with more preterm births and lower birth weights compared with those of SET. Intended parents and GCs should be counseled that DET is associated with greater risks of adverse pregnancy and perinatal outcomes, which mitigates higher live birth rates. The use of PGT-A did not appear to improve the live birth rate.

Subchorionic Hematomas and Adverse Pregnancy Outcomes among Twin Pregnancies.

OBJECTIVE: This study estimates the association of a first trimester finding of subchorionic hematoma (SCH) with third trimester adverse pregnancy outcomes in women with twin pregnancies. STUDY DESIGN: Retrospective cohort study of twin pregnancies prior to 14 weeks at a single institution from 2005 to 2019, all of whom had a first trimester ultrasound. We excluded monoamniotic twins, fetal anomalies, history of fetal reduction or spontaneous reduction, and twin-to-twin transfusion syndrome. Ultrasound data were reviewed, and we compared pregnancy outcomes after 24 weeks in women with and without a SCH at their initial ultrasound 60/7 to 136/7 weeks. Regression analysis was used to control for any differences in baseline characteristics. RESULTS: A total of 760 women with twin pregnancies met inclusion criteria for the study, 68 (8.9%) of whom had a SCH. Women with SCH were more likely to have vaginal bleeding and had their initial ultrasound at earlier gestational ages. On univariate analysis, SCH was not significantly associated with gestational age at delivery, preterm birth, birthweight of either twin, low birthweight percentiles of either twin, fetal demise, or preeclampsia. SCH was associated with placental abruption on univariate analysis, but not after controlling for vaginal bleeding and gestational age at the time of the initial ultrasound (adjusted odds ratio: 2.00, 95% confidence interval: 0.63-6.42). Among women with SCH, SCH size was not associated with adverse pregnancy outcomes. CONCLUSION: In women with twin pregnancies, the finding of a first trimester SCH is not associated with adverse pregnancy outcomes >24 weeks.

Cervical length, cervical dilation, and gestational age at cerclage placement and the risk of preterm birth in women undergoing ultrasound or exam indicated Shirodkar cerclage.

Background: Preterm birth is a major cause of neonatal morbidity and mortality in the USA. In many patients at risk for preterm birth, cervical length (CL) screening is used to guide decisions regarding cerclage placement. Quality evidence shows that cerclage prolongs pregnancy in high-risk women with a short CL in women with a history of preterm birth and in women with painless cervical dilation in the second trimester, though the degree of cervical shortening, dilation, or gestational age at cerclage placement are not consistently associated with the subsequent rate of preterm birth. Our objective was to determine if cervical length (CL), cervical dilation or gestational age (GA) at the time of cerclage placement are associated with preterm birth among women undergoing ultrasound-indicated or exam-indicated cerclage.Study design: This was a retrospective cohort study of all patients with a singleton pregnancy who underwent ultrasound-indicated or exam-indicated Shirodkar cerclage placement at a single maternal-fetal medicine practice in New York City between November 2005 and May 2017. All patients included in the study had previously undergone CL screening for an increased risk of preterm birth (for example, prior spontaneous preterm birth or mid-trimester loss, prior cervical excision). The cervical length or dilation and GA at the time of cerclage placement were collected, as were demographic and obstetric outcome data for the current pregnancy. The primary outcome was delivery <36 or ≥36 weeks. Planned subgroup analyses of the primary outcome were performed based on CL at the time of ultrasound-indicated cerclage (0-9 mm, 10-19 mm, ≥20 mm), cervical dilation at the time of physical exam-indicated cerclage (<2 cm vs. ≥2 cm), and gestational age at cerclage placement (<20 weeks vs. ≥20 weeks). Data were analyzed using the Student's t-test and chi-square test for trend.Results: There were 123 and 39 patients in the ultrasound- and exam-indicated cerclage groups, respectively. Twenty six (21.2%) patients in the ultrasound-indicated subgroup and 24 patients (61.5%) in the exam-indicated subgroup delivered <36 weeks. CL (16.4 versus 17.6 mm, p = .28) and GA (19.7 versus 20.0 weeks, p = .58) at the time of ultrasound-indicated cerclage placement were not significantly different in patients who delivered <36 and ≥36 weeks' gestation, respectively. Women with cervical dilation ≥2 cm prior to exam-indicated cerclage placement were significantly more likely to deliver <36 weeks when compared to women with cervical dilation <2 cm (77.8 versus 47.6%, p = .05); however, there were no significant differences in rates of preterm birth <28 and <32 weeks between these two groups (38.9 versus 23.8%, p = .31 and 50.0% versus 28.6%, p = .17, respectively).Conclusions: Cervical length and GA at the time of ultrasound-indicated Shirodkar cerclage placement do not appear to impact the likelihood of preterm birth <36 weeks, while cervical dilation ≥2 cm at the time of exam-indicated Shirodkar cerclage is associated with an increased rate of preterm birth <36 weeks, but not earlier gestational ages at delivery.

The impact of non-medical reading on clinician burnout: a national survey of palliative care providers.

BACKGROUND: Clinician burnout in hospice and palliative care (HPC) has potentially widespread negative consequences including increased clinical errors, decreased professionalism, decreased staff retention, and decreased empathy. Reading non-medical literature has been associated with increased empathy, but no studies on the effect of reading on burnout have previously been conducted. We wished to assess reading patterns of practicing HPC clinicians and determine associations between non-medical reading and burnout. METHODS: Sixteen-item electronic survey regarding reading practices, exposure to non-medical literature, fatigue, quality of life, and burnout symptoms was administered to members of the American Academy of Hospice and Palliative Medicine. Burnout measures of emotional exhaustion and depersonalization were assessed by the validated 2-item Maslach Burnout Inventory. Data were analyzed using descriptive statistics and multivariate regression. RESULTS: Seven hundred nine members responded (15.2% response rate), of which 129 (18.2%) met the criteria for burnout, with 117 (16.6%) meeting the criteria for high emotional exhaustion and 45 (7.9%) meeting the criteria for high depersonalization. On univariate analysis, burnout was associated with age, reading habits, and fatigue, but not years in practice. On multivariable logistic regression consistent readers had decreased odds of overall burnout compared to inconsistent readers (OR 0.61; 95% CI, 0.39-0.97, P=0.036). This was true across the depersonalization (OR 0.58; 95% CI, 0.36-0.93, P=0.025), but not the emotional exhaustion domain. CONCLUSIONS: Reading non-medical literature on a consistent basis may be associated with a significantly decreased likelihood of burnout, specifically across the depersonalization domain.

Vaginal birth after a cesarean delivery for arrest of descent.

OBJECTIVE: The objective of this study is to determine vaginal birth after cesarean (VBAC) success rates for patients with a prior cesarean delivery (CD) for arrest of descent, as well as determine any predictors for success. STUDY DESIGN: This was a retrospective cohort study of all patients delivered by a single MFM practice from 2005 to 2017 with a singleton pregnancy and one prior CD for arrest of descent. We estimated the rate and associated risk factors for successful VBAC. RESULTS: We included 208 patients with one prior CD for arrest of descent, 100 (48.1%) of whom attempted a trial of labor after cesarean (TOLAC) with a VBAC success rate was 84/100 (84%, 95% CI 76-90%). Among the women who attempted TOLAC, women with a prior vaginal delivery >24 weeks' had a significantly higher VBAC success rate (91.8% versus 71.8%, p = .01). Maternal age, body mass index, estimated fetal weight, induction of labor, and cervical dilation were not associated with a higher VBAC success rate. CONCLUSIONS: For women with a prior CD for arrest of descent, VBAC success rates are high. This suggests that arrest of descent is mostly dependent on factors unique to each pregnancy and not due to an inadequate pelvis or recurring conditions. Women with a prior CD for arrest of descent should not be discouraged from attempting TOLAC in a subsequent pregnancy due to concerns about the likelihood of success.

Practical Pharmacogenomic Approaches to Heart Failure Therapeutics.

OPINION STATEMENT: The major challenge in applying pharmacogenomics to everyday clinical practice in heart failure (HF) is based on (1) a lack of robust clinical evidence for the differential utilization of neurohormonal antagonists in the management of HF in different subgroups, (2) inconsistent results regarding appropriate subgroups that may potentially benefit from an alternative strategy based on pharmacogenomic analyses, and (3) a lack of clinical trials that focused on testing gene-guided treatment in HF. To date, all pharmacogenomic analyses in HF have been conducted as post hoc retrospective analyses of clinical trial data or of observational patient series studies. This is in direct contrast with the guideline-directed HF therapies that have demonstrated their safety and efficacy in the absence of pharmacogenomic guidance. Therefore, the future of clinical applications of pharmacogenomic testing will largely depend on our ability to incorporate gene-drug interactions into the prescribing process, requiring that preemptive and cost-effective testing be paired with decision-support tools in a value-based care approach.

Spherical Harmonics Reveal Standing EEG Waves and Long-Range Neural Synchronization during Non-REM Sleep.

Previous work from our lab has demonstrated how the connectivity of brain circuits constrains the repertoire of activity patterns that those circuits can display. Specifically, we have shown that the principal components of spontaneous neural activity are uniquely determined by the underlying circuit connections, and that although the principal components do not uniquely resolve the circuit structure, they do reveal important features about it. Expanding upon this framework on a larger scale of neural dynamics, we have analyzed EEG data recorded with the standard 10-20 electrode system from 41 neurologically normal children and adolescents during stage 2, non-REM sleep. We show that the principal components of EEG spindles, or sigma waves (10-16 Hz), reveal non-propagating, standing waves in the form of spherical harmonics. We mathematically demonstrate that standing EEG waves exist when the spatial covariance and the Laplacian operator on the head's surface commute. This in turn implies that the covariance between two EEG channels decreases as the inverse of their relative distance; a relationship that we corroborate with empirical data. Using volume conduction theory, we then demonstrate that superficial current sources are more synchronized at larger distances, and determine the characteristic length of large-scale neural synchronization as 1.31 times the head radius, on average. Moreover, consistent with the hypothesis that EEG spindles are driven by thalamo-cortical rather than cortico-cortical loops, we also show that 8 additional patients with hypoplasia or complete agenesis of the corpus callosum, i.e., with deficient or no connectivity between cortical hemispheres, similarly exhibit standing EEG waves in the form of spherical harmonics. We conclude that spherical harmonics are a hallmark of spontaneous, large-scale synchronization of neural activity in the brain, which are associated with unconscious, light sleep. The analogy with spherical harmonics in quantum mechanics suggests that the variances (eigenvalues) of the principal components follow a Boltzmann distribution, or equivalently, that standing waves are in a sort of "thermodynamic" equilibrium during non-REM sleep. By extension, we speculate that consciousness emerges as the brain dynamics deviate from such equilibrium.

Decreased heart rate and enhanced sinus arrhythmia during interictal sleep demonstrate autonomic imbalance in generalized epilepsy.

We hypothesized that epilepsy affects the activity of the autonomic nervous system even in the absence of seizures, which should manifest as differences in heart rate variability (HRV) and cardiac cycle. To test this hypothesis, we investigated ECG traces of 91 children and adolescents with generalized epilepsy and 25 neurologically normal controls during 30 min of stage 2 sleep with interictal or normal EEG. Mean heart rate (HR) and high-frequency HRV corresponding to respiratory sinus arrhythmia (RSA) were quantified and compared. Blood pressure (BP) measurements from physical exams of all subjects were also collected and analyzed. RSA was on average significantly stronger in patients with epilepsy, whereas their mean HR was significantly lower after adjusting for age, body mass index, and sex, consistent with increased parasympathetic tone in these patients. In contrast, diastolic (and systolic) BP at rest was not significantly different, indicating that the sympathetic tone is similar. Remarkably, five additional subjects, initially diagnosed as neurologically normal but with enhanced RSA and lower HR, eventually developed epilepsy, suggesting that increased parasympathetic tone precedes the onset of epilepsy in children. ECG waveforms in epilepsy also displayed significantly longer TP intervals (ventricular diastole) relative to the RR interval. The relative TP interval correlated positively with RSA and negatively with HR, suggesting that these parameters are linked through a common mechanism, which we discuss. Altogether, our results provide evidence for imbalanced autonomic function in generalized epilepsy, which may be a key contributing factor to sudden unexpected death in epilepsy.