Management and Recommendations for Future Pregnancy in Patients with Early-Stage Endometrial Cancer: A Survey of Gynecologic Oncologists and Reproductive Endocrinology and Infertility Specialists.

Purpose: To determine how young patients with early-stage endometrial cancer are counseled regarding fertility preserving therapy and pregnancy options by gynecologic oncology and reproductive endocrinology and infertility (REI) providers. Methods: Anonymous online survey of Society of Gynecology Oncology (SGO) and the Society for Reproductive Endocrinology and Infertility (SREI) members; data were analyzed using chi-square and t-tests. Results: Twelve percent (169/1433) of SGO and 6.5% (60/927) of SREI members responded to the survey request. Most providers manage fewer than 10 fertility preservation patients annually. All gynecologic oncologists offer conservative management to patients with grade 1 endometrial cancer without evidence of invasion, and 40% would offer it to patients with grade 2 or <50% invasion. Magnetic resonance imaging was the most common method of assessing invasion, and the progesterone intrauterine device was the preferred first-line treatment. Two-thirds of providers would recommend hysterectomy if no endometrial response was noted by 12 months, two-thirds would continue conservative management for more than a year if a partial response was noted, and 70% would recommend hysterectomy after a patient completes childbearing. Comparatively, 60% of REI providers would recommend hysterectomy after childbearing. More gynecologic oncologists than REI providers recommend attempting spontaneous conception and for longer durations before initiating fertility treatments. Conclusion: Heterogeneous management styles exist among and between gynecologic oncology and REI providers for patients with early-stage endometrial cancer desiring future pregnancy. Improved guidelines are needed regarding treatment and monitoring surrounding trials of conception and pregnancy.

Circulating Cell-Free DNA Methylation Profiles in the Early Detection of Ovarian Cancer: A Scoping Review of the Literature.

Epithelial ovarian cancer is the most lethal gynecologic malignancy and has few reliable non-invasive tests for early detection or diagnosis. Recent advances in genomic techniques have bolstered the utility of cell-free DNA (cfDNA) evaluation from peripheral blood as a viable cancer biomarker. For multiple reasons, comparing alterations in DNA methylation is particularly advantageous over other molecular assays. We performed a literature review for studies exploring cfDNA methylation in serum and plasma for the early diagnosis of ovarian cancer. The data suggest that serum/plasma cfDNA methylation tests have strong diagnostic accuracies for ovarian cancer (median 85%, range 40-91%). Moreover, there is improved diagnostic performance if multiple genes are used and if the assays are designed to compare detection of ovarian cancer with benign pelvic masses. We further highlight the vast array of possible gene targets and techniques, and a need to include more earlier-stage ovarian cancer samples in test development. Overall, we show the promise of cfDNA methylation analysis in the development of a viable diagnostic biomarker for ovarian cancer.

Discrepancies between author- and industry-reported disclosures of financial relationships at an annual gynecologic oncology research meeting.

OBJECTIVE: Trillions of dollars pass to physicians from industry-related businesses annually, leading to many opportunities for financial conflicts of interest. The Open Payments Database (OPD) was created to ensure transparency. We describe the industry relationships as reported in the OPD for presenters at the 2019 Society of Gynecologic Oncology (SGO) Annual Meeting and evaluate concordance between author disclosures of their financial interests and information provided by the OPD. METHODS: This is an observational, cross-sectional study. Disclosure data were collected from authors with oral and featured abstract presentations in the 2019 SGO annual conference. These disclosures were compared to data available for each author in the 2018 OPD, which included the amount and nature of industry payments. RESULTS: We examined the disclosures of 301 authors who met inclusion criteria. Of 161 authors who had disclosure statements on their presentations,147 reported "no disclosures," and 14 disclosed industry relationships. The remaining 140 did not list any disclosure information. Sixty percent (184/301) of authors had industry relationships in the 2018 OPD, including 173 of 287 (60.3%) of authors who either reported no disclosures or did not have disclosure data available in their presentations. These transactions totaled over 43 million USD from 122 different companies, with most payments (46%) categorized as "Research or Associated Research." Accurate disclosure reporting was associated with receiving higher payments or research payments, and being a presenting author. CONCLUSIONS: Most authors at the SGO annual conference did not correctly disclose their industry relationships when compared with their entries in the OPD.

Ovarian Stimulation Is Safe and Effective for Patients with Gynecologic Cancer.

Purpose: To compare long-term outcomes of gynecologic cancer patients who pursued controlled ovarian hyperstimulation (COH) for fertility preservation (FP) with those who did not. Methods: Retrospective cohort, COH, and health outcomes in gynecologic cancer patients; data were analyzed by chi-square test, t-tests, and logistic regression. Results: Ninety patients with a gynecologic malignancy contacted the FP patient navigator: 45.6% (n = 41) had ovarian cancer, 25.6% (n = 23) endometrial cancer, 18.9% (n = 17) cervical cancer, 5.6% (n = 5) uterine cancer, and 4.4% (n = 4) multiple gynecologic cancers. From this cohort, 32 underwent COH, 43 did not, and 18 pursued ovarian tissue cryopreservation (OTC; 3 patients had both COH and OTC). Median age and type of cancer were not significantly different between the groups. COH patients had a range of 1-35 oocytes retrieved. Days to next cancer treatment in the COH group was 36 days; for those who declined COH, it was 22 days (not significant [NS], p > 0.05). There were two recurrences reported in the stimulation group and four in the no stimulation group (NS). Five deaths were reported, two in the stimulation group, none in the no stimulation group, and three in the OTC group (NS); 34% (n = 11) COH patients returned to use cryopreserved specimens, of which 45% (n = 5) had a live birth. Conclusion: Although time to next treatment was longer in the group of patients who underwent COH, this did not reach statistical significance. It appears that in selected patients with GYN malignancies, COH for oocyte or embryo cryopreservation is safe, with reasonable stimulation outcomes and no difference in long-term outcomes.

Intranasal oxytocin decreases cross-frequency coupling of neural oscillations at rest.

Recent research has suggested a role for the hormone oxytocin in social cognition and behavior. Administration of intranasal oxytocin modulates multiple brain regions during experimental tasks; however, the neural mechanisms that underscore the changes associated with oxytocin administration are yet to be fully elucidated. In a double-blind placebo controlled design using electroencephalography, the effects of intranasal oxytocin on neural oscillations (delta, theta, alpha, beta) and their coupling during the resting state were examined. Prior work suggested that coupling of slow and fast waves are indicative of the integration of motivational and cognitive processes. While neural oscillations were unaffected by oxytocin relative to placebo administration; oxytocin decreased delta-beta, delta-alpha, theta-alpha, and theta-beta coupling. These findings suggest that one mechanism through which intranasal oxytocin may modulate brain and behavior is through affecting the cross-frequency coupling of neural oscillations, a phenomenon that has been associated with specific cognitive and motivational states.

Intranasal oxytocin and the neural correlates of infant face processing in non-parent women.

Event-related potentials (ERPs) have been widely employed to identify different stages of face processing, with recent research probing the neural dynamics of adult's processing of infant faces. Infant faces represent a salient category of visual stimuli, especially in parents, likely prioritized for processing through activity of the oxytocinergic system. Here we employed a randomized, double-blind, and within-subject crossover study of 24 non-parent women to examine the impact of intranasal oxytocin administration, relative to placebo, on processing infant and adult faces. Our main finding was that, relative to placebo, the P300 ERP elicited by infant faces was greater than the P300 elicited by adult faces in the oxytocin condition. Therefore, oxytocin administration may enhance the allocation of attention towards infant cues, even in non-parent women.

Implantation rates subsequent to the transfer of embryos produced at different phases during double stimulation of poor ovarian responders.

To compare the implantation capacity of embryos obtained at different phases of double stimulation (DS) of poor ovarian responders, 153 DS cycles were analysed retrospectively. As part of the DS protocol, antral follicles were stimulated continuously during both the follicular and luteal phases. Fresh embryos obtained in both phases were cryopreserved and transferred in the next artificial cycle. The mean number of oocytes retrieved, MII oocytes and zygotes with two pronuclei was significantly higher for collections during luteal-phase stimulation. Furthermore, the dose of exogenous gonadotropin administered was higher during the luteal phase. The rate of clinical pregnancy and embryo implantation increased progressively from pure follicular phase embryos to mixed embryos to pure luteal phase embryos. Embryos produced during the luteal phase resulted in higher implantation rates.

Inpatient Laparoscopic Hysterectomy in the United States: Trends and Factors Associated With Approach Selection.

STUDY OBJECTIVE: To examine utilization patterns of different laparoscopic approaches in inpatient hysterectomy and identify patient and hospital characteristics associated with the selection of specific laparoscopic approaches. DESIGN: Using data from the 2007 to 2012 National (Nationwide) Inpatient Sample (NIS), we identified adult women undergoing inpatient laparoscopic hysterectomy for nonobstetric indications based on International Classification of Diseases, Ninth Revision, Clinical Modification codes. Benign cases were categorized based on laparoscopic approach, classified as total laparoscopic hysterectomy (TLH), laparoscopic-assisted vaginal hysterectomy (LAVH), or laparoscopic supracervical hysterectomy (LSH). We assessed changes in the use of these approaches during 2007 to 2012, and used multinomial logistic regression to examine the association of patient and hospital characteristics with the choice of laparoscopic approach in 2012. The NIS sample weights were applied to generate nationally representative estimates. DESIGN CLASSIFICATION: Retrospective study (Canadian Task Force classification III). SETTING: Hospital inpatient care nationwide. PATIENTS: Female adult patients in the NIS database who underwent an inpatient laparoscopic hysterectomy between 2007 and 2012. INTERVENTION: Inpatient laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS: Of the inpatient laparoscopic hysterectomies performed in 2012, 83.2% were for benign indications. The TLH approach accounted for 48.3% of all laparoscopic hysterectomies, followed by LAVH at 37.3% and LSH at 14.4%. Robotic assistance was reported in 45.0% of all cases and 72.3% of malignant hysterectomies. An examination of temporal trends during 2007 to 2012 demonstrates a shift in the laparoscopic approach from LAVH toward TLH, with a slight decrease in LSH. Patient race/ethnicity, income, indication for hysterectomy, and comorbid conditions, as well as hospital teaching status, urban/rural location, bed size, type of ownership, and geographic region, were significantly associated with the choice of laparoscopic approach. CONCLUSION: Benign laparoscopic hysterectomy is increasingly performed as TLH rather than LAVH. In addition to clinical factors, the selection of laparoscopic approach is influenced by patient socioeconomic and hospital characteristics.

Hindbrain regional growth in preterm newborns and its impairment in relation to brain injury.

Premature birth globally affects about 11.1% of all newborns and is a risk factor for neurodevelopmental disability in surviving infants. Histology has suggested that hindbrain subdivisions grow differentially, especially in the third trimester. Prematurity-related brain injuries occurring in this period may selectively affect more rapidly developing areas of hindbrain, thus accompanying region-specific impairments in growth and ultimately neurodevelopmental deficits. The current study aimed to quantify regional growth of the cerebellum and the brainstem in preterm neonates (n = 65 with individually multiple scans). We probed associations of the regional volumes with severity of brain injury. In neonates with no imaging evidence of injury, our analysis using a mixed-effect linear model showed faster growth in the pons and the lateral convexity of anterior/posterior cerebellar lobes. Different patterns of growth impairment were found in relation to early cerebral intraventricular hemorrhage and cerebellar hemorrhage (P < 0.05), likely explaining different mechanisms through which neurogenesis is disrupted. The pattern of cerebellar growth identified in our study agreed excellently with details of cerebellar morphogenesis in perinatal development, which has only been observed in histological data. Our proposed analytic framework may provide predictive imaging biomarkers for neurodevelopmental outcome, enabling early identification and treatment of high-risk patients. Hum Brain Mapp 37:678-688, 2016. © 2015 Wiley Periodicals, Inc.

Optimal polar bodies angle for higher subsequent embryo viability: a pilot study.

OBJECTIVE: To determine the optimal polar bodies (PB) angle for higher subsequent embryo implantation potential. DESIGN: Prospective study. SETTING: Academic fertility center. PATIENT(S): From January to July 2015, 116 patients were recruited in their first IVF-ET cycles. INTERVENTION(S): At the pronuclear stage, PB angle was measured with the use of E-ruler 1.1. MAIN OUTCOME MEASURE(S): The primary outcome measure was good-quality embryo rate. Secondary measures were clinical pregnancy rate (CPR) and embryo implantation rate (IR). RESULT(S): A total of 1,103 oocytes were retrieved. PB angle was measured in 454 zygotes, and 164 of their subsequent embryos were transferred into the uterus. All-or-none implantation took place in 129 embryos, and 89 patients accepted fresh embryo(s) transfer with known PB angle. By means of receiver operating characteristic analysis, the optimal PB angle for subsequent embryo implantation was 24.25°. Based on this cutoff value, 454 zygotes were divided into two groups: small-angle and large-angle. A higher percentage of small-angle zygotes developed into good-quality embryos (70.97% vs. 58.58%). CPR and IR both decreased progressively from purely small-angle embryos to mixed embryos to purely large-angle embryos (CPR: 72.41% vs. 38.46% vs. 26.47%, respectively; IR: 63.27% vs. 26.92% vs. 16.67%, respectively). CONCLUSION(S): Noninvasive assessment of PB angle is a viable technique for zygote selection and should be included in embryo selection parameters. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-OOC-15005882.

Carbon Monoxide Exposure During Pregnancy.

IMPORTANCE: Carbon monoxide (CO) is the leading cause of poisoning in the United States and is associated with high maternal and fetal mortality rates. Given the nonspecific signs and symptoms of toxicity, cases may go unsuspected or attributed to other etiologies. As CO adversely affects both mother and fetus, it is important for practitioners to recognize and treat poisoning in a timely manner. OBJECTIVE: We seek to assist practitioners with understanding the physiology and recognizing the presentations of both acute and chronic CO poisoning, as well as provide information on diagnosis and treatment options. We also conducted a review of cases described in the literature during the past half century to show varying presentations and treatment methodologies. EVIDENCE ACQUISITION: A qualitative literature search was conducted using PubMed and Google Scholar for articles published between 1970 and 2014 that assessed cases of CO poisoning during pregnancy. Excluded studies were not in English or contained nonhuman subjects. RESULTS: Nineteen published reports of CO poisoning during pregnancy described in varying levels of detail were found in the literature from 1971 to 2010. CONCLUSIONS AND RELEVANCE: Carbon monoxide poisoning requires a high degree of suspicion. Diagnosis is made based on initial history and physical evaluation and assessment of environmental CO levels; presenting carboxyhemoglobin levels may be poor indicators of severity of disease. Oxygen therapy should be initiated promptly in all possible cases with consideration of hyperbaric oxygen therapy in cases of significant maternal exposure. Treatment requires a longer duration for fetal CO elimination than in the nonpregnant patients. Importantly, practitioners should educate pregnant patients on prevention.

Gender in facial representations: a contrast-based study of adaptation within and between the sexes.

Face aftereffects are proving to be an effective means of examining the properties of face-specific processes in the human visual system. We examined the role of gender in the neural representation of faces using a contrast-based adaptation method. If faces of different genders share the same representational face space, then adaptation to a face of one gender should affect both same- and different-gender faces. Further, if these aftereffects differ in magnitude, this may indicate distinct gender-related factors in the organization of this face space. To control for a potential confound between physical similarity and gender, we used a Bayesian ideal observer and human discrimination data to construct a stimulus set in which pairs of different-gender faces were equally dissimilar as same-gender pairs. We found that the recognition of both same-gender and different-gender faces was suppressed following a brief exposure of 100 ms. Moreover, recognition was more suppressed for test faces of a different-gender than those of the same-gender as the adaptor, despite the equivalence in physical and psychophysical similarity. Our results suggest that male and female faces likely occupy the same face space, allowing transfer of aftereffects between the genders, but that there are special properties that emerge along gender-defining dimensions of this space.

Cross-orientation transfer of adaptation for facial identity is asymmetric: a study using contrast-based recognition thresholds.

Recent studies suggest that adaptation effects for face shape and gender transfer from upright to inverted faces more than the reverse. We investigated whether a similar asymmetry occurred for face identity, using a recently developed adaptation method based on contrast-recognition thresholds. When adapting and test stimuli shared the same orientation, aftereffects were similar for upright and inverted faces. When orientation differed, there was significant transfer of aftereffects from upright adapting to inverted test faces, but none from inverted to upright faces. We show that asymmetric cross-orientation transfer of face aftereffects generalize across two distinct face adaptation paradigms: the previously used perceptual-bias methodology and the recently introduced contrast-threshold based adaptation paradigm. These results also represent a generalization from aftereffects for face shape and gender to aftereffects for face identity. While these results are consistent with the dual-mode hypothesis, they can also be accounted for by a single population of units of varying orientation selectivity.