Thyroid Peroxidase Antibodies in Infertile Women with Polycystic Ovary Syndrome.

To compare the rate of positive thyroid peroxidase antibodies (TPO Ab) between women with different polycystic ovary syndrome (PCOS) phenotypes and women without PCOS. This is a retrospective cohort study. Women with PCOS at My Duc Hospital between June 1, 2020, and March 27, 2021, were matched with non-PCOS women by age. TPO Ab (cut-off: 34 IU/mL) and thyroid-stimulating hormone (TSH) levels were measured as markers of Hashimoto thyroiditis and thyroid function, respectively. One thousand eight hundred eight infertile women were included, 904 with PCOS (mean age 29.0 ± 3.58 years) and 904 without PCOS (29.1 ± 3.4 years; controls). Women with PCOS had a higher body mass index (22.8 ± 3.84 vs. 19.9 ± 2.23 kg/m2, p < 0.001), but most were not overweight/obese. Rates of positive TPO Ab in women with versus without PCOS were 8.2% and 8.4%, respectively (p = 0.932). Rates of positive TPO Ab in patients with PCOS phenotype A, B, C, or D were not statistically different (7.5%, 2.9%, 20.0%, and 7.8%, respectively). Median TSH concentrations were similar in the PCOS and control groups (1.84 mIU/L vs. 1.78 mIU/L, respectively; p = 0.194). Based on a linear regression model, there was no correlation between either BMI or the estradiol to progesterone ratio and TPO Ab status. In a large population of infertile women with PCOS who were mostly lean patients, rates of positive TPO Ab across all four PCOS phenotypes did not differ significantly from those in women without PCOS. These findings did not support the hypothesis that PCOS is a risk factor for Hashimoto thyroiditis.

Development of children born to women with twin pregnancies treated with cervical pessary or vaginal progesterone: Follow-up of a randomized controlled trial.

INTRODUCTION: Preterm birth is the most common cause of neonatal morbidity and mortality. Women with twin pregnancies and a short cervical length are at high risk for preterm birth. Vaginal progesterone and cervical pessary have been proposed as potential strategies to reduce preterm birth in this high-risk population. Therefore, we aimed to compare the effectiveness of cervical pessary and vaginal progesterone in improving developmental outcomes of children born to women with twin pregnancies and mid-trimester short cervical length. MATERIAL AND METHODS: This was a follow-up study (NCT04295187) of all children at 24 months of age, born from women treated with cervical pessary or progesterone to prevent preterm birth in a randomized controlled trial (NCT02623881). We used a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ-3) and a red flag questionnaire. In surviving children, we compared the mean ASQ-3 scores, abnormal ASQ-3 scores, the number of children with any abnormal ASQ-3 scores and red flag signs between the two groups. We reported the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in offspring. These outcomes were also calculated in a subgroup of women with a cervical length ≤28 mm (<25th percentile). RESULTS: In the original randomized controlled trial, we randomized 300 women to pessary or progesterone. After counting the number of perinatal deaths and lost to follow-up, 82.8% parents in the pessary group and 82.5% parents in progesterone group returned the questionnaire. The mean ASQ-3 scores of the five skills and red flag signs did not differ significantly between the two groups. However, the percentage of children having abnormal ASQ-3 scores in fine motor skills was significantly lower in the progesterone group (6.1% vs 1.3%, P = 0.01). There were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in unselected women and in those with cervical length ≤28 mm. CONCLUSIONS: Cervical pessary and vaginal progesterone may have comparable effects on developmental outcomes in children at ≥24 months of age, born to women with twin pregnancies and short cervical length. However, this finding could be likely due to a lack of study power.

Electrical status epilepticus during sleep in a child with Prader-Willi syndrome: a case report.

Prader-Willi syndrome (PWS) is a rare and complex genomic imprinting disorder caused by an absence of expression of paternal genes from chromosome 15q11.2-q13. Clinical manifestations of PWS depends on age. In early infancy, PWS patients is characterized by hypotonia and failure to thrive. Later in life, they can also exhibit hyperphagia, obesity, short stature, hypogonadism, behavioral issues and cognitive disability. Multiple sleep abnormalities including obstructive and/or central sleep apnea, daytime hypersomnolence, and impaired responses to hypercapnia and hypoxia have been described in patients with PWS. Recent studies also demonstrated an increased risk of seizures in PWS patients. Electrical status epilepticus in sleep (ESES) is an age-limited epilepsy with various seizure types, neurophysiological and motor impairment. The classic electroencephalogram (EEG) pattern of ESES involves continuous epileptic activity at 2-3 Hz occupying greater than 85% of non-rapid eye movement (REM) sleep. Treatment of the ESES syndrome consists of anti-epileptic drugs in routine cases, and corticosteroids, gamma globulins, the ketogenic diet, and surgery in refractory cases. In this project, we describe ESES during polysomnography in a 5-year-old female with PWS and no history of seizure disorder. To the best of our knowledge, this is the first case report on ESES in a PWS patient.

Bartonella endocarditis in patients with right ventricle-to-pulmonary artery conduit: 2 case reports and literature review.

Bartonella species are Gram-negative bacilli and fastidious bacteria that can cause a number of clinical syndromes, including blood culture-negative infective endocarditis (IE). The two most commonly isolated species in humans are Bartonella quintana, the agent of trench fever, and Bartonella henselae, mostly known for causing cat scratch disease (Edouard et al., 2015 [1]; Edouard and Raoult, 2010 [2]). Both species also cause bacillary angiomatosis, primarily in immunocompromised patients (Edouard et al., 2015 [1]; Fournier et al., 2001 [3]). The risk of B. henselae IE is increased in patients with cardiac valvular disease and congenital heart disease (CHD) (Edouard and Raoult, 2010 [2]; Das et al., 2009 [4]; Abandeh et al., 2012 [5]; Ouellette et al., 2016 [6]; Hoffman et al., 2007 [7]; Georgievskaya et al., 2014 [8]). In this article, we detail two cases of Bartonella IE in patients with right ventricle-to-pulmonary artery (RV-PA) conduits who presented to our institution. We also perform a literature review on Bartonella IE in patients with a history of RV-PA conduit or pulmonary valve replacement.

Positive effects of amphiregulin on human oocyte maturation and its molecular drivers in patients with polycystic ovary syndrome.

STUDY QUESTION: Does use of medium containing amphiregulin improve meiotic maturation efficiency in oocytes of women with polycystic ovary syndrome (PCOS) undergoing in vitro maturation (IVM) preceded by a capacitation culture step capacitation IVM (CAPA-IVM)? SUMMARY ANSWER: Use of medium containing amphiregulin significantly increased the maturation rate from oocytes retrieved from follicles with diameters <6 or ≥6 mm pre-cultured in capacitation medium. WHAT IS KNOWN ALREADY: Amphiregulin concentration in follicular fluid is correlated with human oocyte developmental competence. Amphiregulin added to the meiotic trigger has been shown to improve outcomes of IVM in a range of mammalian species. STUDY DESIGN, SIZE, DURATION: This prospective, randomized cohort study included 30 patients and was conducted at an academic infertility centre in Vietnam from April to December 2019. Patients with PCOS were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the first stage, sibling oocytes from each patient (671 in total) were allocated in equal numbers to maturation in medium with (CAPA-AREG) or without (CAPA-Control) amphiregulin 100 ng/ml. After a maturation check and fertilization using intracytoplasmic sperm injection (ICSI), all good quality Day 3 embryos were vitrified. Cumulus cells (CCs) from both groups were collected at the moment of ICSI denudation and underwent a molecular analysis to quantify key transcripts of oocyte maturation and to relate these to early embryo development. On return for frozen embryo transfer (second stage), patients were randomized to have either CAPA-AREG or CAPA-Control embryo(s) implanted. Where no embryo(s) from the randomized group were available, embryo(s) from the other group were transferred. The primary endpoint of the study was meiotic maturation efficiency (proportion of metaphase II [MII] oocytes; maturation rate). MAIN RESULTS AND THE ROLE OF CHANCE: In the per-patient analysis, the number of MII oocytes was significantly higher in the CAPA-AREG group versus the CAPA-Control group (median [interquartile range] 7.0 [5.3, 8.0] versus 6.0 [4.0, 7.0]; P = 0.01). When each oocyte was evaluated, the maturation rate was also significantly higher in the CAPA-AREG group versus the CAPA-Control group (67.6% versus 55.2%; relative risk [RR] 1.22 [95% confidence interval (CI) 1.08-1.38]; P = 0.001). No other IVM or embryology outcomes differed significantly between the two groups. Rates of clinical pregnancy (66.7% versus 42.9%; RR 1.56 [95% CI 0.77-3.14]), ongoing pregnancy (53.3% versus 28.6%; RR 1.87 [95% CI 0.72-4.85]) and live birth (46.7% versus 28.6%; RR 1.63 [95% CI 0.61-4.39]) were numerically higher in the patients who had CAPA-AREG versus CAPA-Control embryos implanted, but each fertility and obstetric outcome did not differ significantly between the groups. In the CAPA-AREG group, there were significant shifts in CC expression of genes involved in steroidogenesis (STAR, 3BHSD), the ovulatory cascade (DUSP16, EGFR, HAS2, PTGR2, PTGS2, RPS6KA2), redox and glucose metabolism (CAT, GPX1, SOD2, SLC2A1, LDHA) and transcription (NRF2). The expression of three genes (TRPM7, VCAN and JUN) in CCs showed a significant correlation with embryo quality. LIMITATIONS, REASONS FOR CAUTION: This study included only Vietnamese women with PCOS, limiting the generalizability. Although 100 ng/ml amphiregulin addition to the maturation culture step significantly improved the MII rate, the sample size in this study was small, meaning that these findings should be considered as exploratory. Therefore, a larger patient cohort is needed to confirm whether the positive effects of amphiregulin translate into improved fertility outcomes in patients undergoing IVM. WIDER IMPLICATIONS OF THE FINDINGS: Data from this study confirm the beneficial effects of amphiregulin during IVM with respect to the trigger of oocyte maturation. The gene expression findings in cumulus indicate that multiple pathways might contribute to these beneficial effects and confirm the key role of the epidermal growth factor system in the stepwise acquisition of human oocyte competence. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED; grant number FWO.106-YS.2017.02) and by the Fund for Research Flanders (FWO; grant number G.OD97.18N). L.N.V. has received speaker and conference fees from Merck, grants, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring. T.M.H. has received speaker fees from Merck, Merck Sharp and Dohme and Ferring. J.S. reports speaker fees from Ferring Pharmaceuticals and Biomérieux Diagnostics and grants from FWO Flanders, is co-inventor on granted patents on CAPA-IVM methodologies in USA (US10392601B2), Europe (EP3234112B1) and Japan (JP 6806683 registered 08-12-2020) and is a co-shareholder of Lavima Fertility Inc., a spin-off company of the Vrije Universiteit Brussel (VUB, Brussels, Belgium). NA, TDP, AHL, MNHN, SR, FS, EA and UDTH report no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: NCT03915054.