Case Series of Reproductive Outcomes after Surgical Correction of Obstructed Hemivagina in OHVIRA.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) is a rare congenital developmental syndrome manifested by uterine duplication, lower genital tract obstruction, and unilateral renal anomaly. Literature on reproductive outcomes in this patient population is limited. The aim of this study is to describe obstetric outcomes after surgical correction of obstructed hemivagina in a longitudinal cohort of patients with a diagnosis of OHVIRA. All cases of OHVIRA presenting to a single tertiary care children's hospital from 1990 to 2021 were retrospectively reviewed. Three cases demonstrating a variety of clinically important reproductive outcomes are described in detail including risks such as retained products, endometritis, preterm labor, and malpresentation. Understanding the reproductive outcomes associated with this diagnosis is important for practitioners seeking to counsel and care for patients with this diagnosis. This case series demonstrates a wide array of potential gynecologic and obstetric risks, though ultimately with successful term and near-term pregnancies.

Risk factors for delayed termination of pregnancy following increased nuchal translucency.

OBJECTIVES: Termination of pregnancy after increased nuchal translucency (NT) is a common occurrence. This study aimed to identify characteristics of a cohort with a NT ≥3.0 mm who underwent a pregnancy termination ≥15 weeks compared with those who terminated <15 weeks. METHODS: All NT ≥3.0 mm identified within our department over an 11-year period (2010-2021) (n = 689) were retrospectively examined and characteristics of the cohort of increased NTs ending in termination were further categorized. RESULTS: There were 221 (32.1%) individuals with an increased NT (≥3 mm) who underwent a termination of pregnancy within our study period (2010-2021). Pregnancy termination occurred at a gestational age <15 weeks in 162 (73.3%) and ≥15 weeks in 59 individuals. Pregnant individuals without positive NIPT for aneuploidy were at a higher risk for a ≥15-week termination (p = 0.004). In 29% (17/59) of late terminations, there were additional imaging findings after the NT scan (ultrasound, echocardiogram, magnetic resonance imaging) that ultimately triggered the decision to pursue termination. CONCLUSIONS: As the options for workup of an increased NT expand, potential delays in decision-making surrounding termination increase. This study identifies multiple reasons for delayed termination and proposes several approaches to care aimed at maximizing diagnostic information by imaging and diagnostic testing in an expedited manner.

Increased use of diagnostic testing after increased nuchal translucency: The influence of non-invasive prenatal testing and chromosomal microarray.

OBJECTIVE: The utilization of non-invasive prenatal testing (NIPT) and chromosomal microarray (CMA) has significantly altered the options for testing following the diagnosis of an increased nuchal translucency (NT). This study defines the rates of utilization of diagnostic testing in the pre-NIPT, pre-CMA, and post-CMA eras. METHODS: We retrospectively examined NT scans performed in our department from January 2010 to December 2020 and identified all NTs ≥3.0 mm for analysis. We divided our data into three distinct periods (2010-2012, 2013-2016, and 2017-2020) corresponding to our institutional practice shifts in recommending and offering use of NIPT (2013) and CMA (2016), respectively. RESULTS: 689 patients with NT ≥ 3.0 mm met inclusion criteria in our study, of which 355 (51.5%) individuals underwent diagnostic testing and 334 (48.5%) did not. There was a significant decline in rates of diagnostic testing with NIPT (2013), which has returned to pre-NIPT levels with the availability of microarray. CONCLUSIONS: Since the routine use of CMA (2016), the rates of diagnostic testing for increased NT have returned to pre-NIPT levels. This study validates data suggesting an initial decline in the rates of diagnostic testing following abnormal NT but suggests that the decline may be reversing in the post-CMA era due to a rise in rates of chorionic villus sampling.

Use of preimplantation genetic testing for monogenic disorders and subsequent prenatal care and diagnostic testing.

OBJECTIVE: The goal of preimplantation genetic testing for monogenic or single gene defects (PGT-M) is to identify inherited pathogenic variants in the embryo prior to embryo transfer, increasing the likelihood of an unaffected child. Prenatal diagnostic testing is recommended to confirm the results of PGT-M. The purpose of this study was to characterize the population undergoing PGT-M over time. METHODS: This retrospective study examined patients who had a positive pregnancy test after PGT-M from 2012 to 2019. A query of the internal assisted reproductive technology database and chart review were used. RESULTS: One hundred and 42 patients completed IVF cycles for PGT-M during this time period and progressed past 10 weeks gestation. There were more PGT-M cycles over time with 46 cycles between 2012 and 2015 and 96 cycles between 2016 and 2019. Patients varied on the decision to pursue prenatal diagnostic testing after PGT-M. For those with known follow-up (130/142), 16 patients underwent diagnostic testing (12%) and 114 did not. CONCLUSION: As PGT-M is increasingly utilized prior to pregnancy, it is important for genetic counselors and OB/GYNs to understand the characteristics and outcomes of the population of patients undergoing PGT-M, including how to counsel about the residual risk of an affected pregnancy after PGT-M.

Third trimester stillbirth during the first wave of the SARS-CoV-2 pandemic: Similar rates with increase in placental vasculopathic pathology.

Whether early SARS-CoV-2 definitively increases the risk of stillbirth is unknown, though studies have suggested possible trends of stillbirth increase during the pandemic. This study of third trimester stillbirth does not identify an increase in rates during the first wave of the pandemic period, however investigation of the placental pathology demonstrates trends towards more vascular placental abnormalities.

Preimplantation genetic testing as a component of root cause analysis of errors and reassignment of embryos in IVF.

The risks of embryo/gamete mix-up are a threat to the integrity of the IVF process, with significant implications for affected families. The use of preimplantation genetic testing through single-nucleotide polymorphism array or next-generation sequencing technology can help to identify, characterize and ultimately help, in some cases, to find the root cause, and to mitigate the extent of these errors for a given patient or laboratory.

Female adnexal tumor of probable Wolffian Origin - A report of two cases at one institution.

•FATWOs are rare gynecologic neoplasms of low malignant potential derived from mesonephric (Wolffian) duct remnants.•FATWOs have diverse presentations from vague abdominal symptoms to incidental diagnosis.•In general, FATWOs require no additional management beyond initial surgical intervention.

The Dartmouth Dementia Directive: Experience with a Community-Based Workshop Pilot of a Novel Dementia-Specific Advance Directive.

Dementia is a growing issue at the end of life that presents unique challenges for advance care planning. Advance directives are a useful and important component of end-of-life planning, but standard advance directives have less utility in cases of loss of capacity due to dementia. An advance directive designed to specifically address end-of-life issues in the setting of dementia can provide patients with increased autonomy and caregivers with improved information about the desires of the individual in question. The Dartmouth Dementia Directive is a dementia-specific advance directive, available online, that seeks to address common concerns of individuals who are planning for dementia-related end-of-life care. This directive was piloted in a community-based workshop, which provided important details and perspective on the best use of dementia-specific advance directives in the greater population.

Biobank participant support of newborn screening for disorders with variable treatment and intervention options.

We aimed to better understand biobank participant opinions of the benefits of newborn screening (NBS) for certain disorder types and how terminology used in NBS discourse might impact stakeholder opinion. We conducted a between-subjects randomized survey of 5840 members of the Northwestern University Biobank. The survey contained 12 scenarios, each describing a disorder and its treatment. For each scenario, we varied the terminology used to describe treatment options. One survey version used the term intervention and the other treatment. The outcome measured for each scenario was perceived benefit (for the infant) and importance of testing (for participants). Comparisons were made between participants and between scenarios. Ratings of benefit and importance were not influenced by the use of the term intervention versus treatment within scenarios. Nuances existed in ratings of benefit to the infant and importance to participants amongst scenarios. Participants were most likely to perceive benefit and importance in screening for a disorder if treatment/intervention offered a high chance of improved outcomes. While participants perceived benefit to the infant and importance to themselves in screening for most disorders, nuances in inter-scenario ratings suggest participants weighed availability and type of treatment/intervention in consideration of the benefits of NBS.

Competitive control of cognition in rhesus monkeys.

The brain has evolved different approaches to solve problems, but the mechanisms that determine which approach to take remain unclear. One possibility is that control progresses from simpler processes, such as associative learning, to more complex ones, such as relational reasoning, when the simpler ones prove inadequate. Alternatively, control could be based on competition between the processes. To test between these possibilities, we posed the support problem to rhesus monkeys using a tool-use paradigm, in which subjects could pull an object (the tool) toward themselves to obtain an otherwise out-of-reach goal item. We initially provided one problem exemplar as a choice: for the correct option, a food item placed on the support tool; for the incorrect option, the food item placed off the tool. Perceptual cues were also correlated with outcome: e.g., red, triangular tool correct, blue, rectangular tool incorrect. Although the monkeys simply needed to touch the tool to register a response, they immediately pulled it, reflecting a relational reasoning process between themselves and another object (Rself-other), rather than an associative one between the arbitrary touch response and reward (Aresp-reward). Probe testing then showed that all four monkeys used a conjunction of perceptual features to select the correct option, reflecting an associative process between stimuli and reward (Astim-reward). We then added a second problem exemplar and subsequent testing revealed that the monkeys switched to using the on/off relationship, reflecting a relational reasoning process between two objects (Rother-other). Because behavior appeared to reflect Rself-other rather than Aresp-reward, and Astim-reward prior to Rother-other, our results suggest that cognitive processes are selected via competitive control dynamics.

Human embryo mosaicism: did we drop the ball on chromosomal testing?

There are newly recognized challenges presented by the occurrence of mosaicism in the context of trophectoderm (TE) biopsy for pre-implantation genetic screening (PGS) in in vitro fertilization (IVF) embryos. Chromosomal mosaicism, known to be significantly higher in IVF embryos than in later prenatal samples, may contribute to errors in diagnosis. In particular, PGS may result in discarding embryos diagnosed as aneuploid but in which the inner cell mass may be completely or mainly euploid, thus representing a false positive diagnosis. Although less likely, some embryos diagnosed as euploid could be mosaic and contain some aneuploid cells, possibly impacting their implantation potential. The ability of current diagnostic techniques to detect mosaicism is limited by the number and location of TE cells in the biopsy and by the methodology used for chromosomal assessment. The clinical consequences of mosaicism are dependent on the chromosome(s) involved, the developmental stage at which the mosaicism evolved, and whether TE biopsy accurately reflects the status of the inner cell mass that forms the fetus. Consequently, in patients with no euploid embryos identified on PGS, it may be appropriate to consider the transfer of diagnosed aneuploid embryos if the TE biopsy result is a non-viable chromosomal monosomy or triploidy that could not result in a birth. It should be acknowledged in consent forms that mosaicism has the potential to impact test results and that its detection may be below the resolution of the genetic tests being used. This concept represents a major shift in current IVF practice and ought to be considered given the data, or lack thereof, of the impact of mosaicism on IVF/PGS outcomes.