A prenatally diagnosed case of Donnai-Barrow syndrome: Highlighting the importance of whole exome sequencing in cases of consanguinity.

Donnai-Barrow syndrome (DBS) is an autosomal recessive disorder characterized by typical craniofacial features, vision and hearing loss, intellectual disability, agenesis of the corpus callosum (ACC), congenital diaphragmatic hernia (CDH), and omphalocele. This condition is associated with loss-of-function mutations in the LRP2 gene. Few cases have been described in the literature. In our case, CDH and ACC were prenatally diagnosed by ultrasound, and the fetus was the product of a first-degree union. Single-nucleotide polymorphism-microarray showed large regions of homozygosity. Whole exome sequencing (WES) was performed and revealed a homozygous frameshift pathogenic variant in LRP2 (c.6978dupG). Here, we present a case of DBS, which diagnosed prenatally via WES in a fetus with CDH and ACC.

Exposure of the developing heart to diabetic environment and early cardiac assessment: A review.

Hyperglycemia during organogenesis is associated with an increased risk of congenital cardiac defects (CHDs). The pathophysiology leading to CHDs is not completely uncovered. However, elevated oxidative stress is considered to be the primary trigger that causes CHDs in fetuses of diabetic mothers. Maternal diabetes has been found to increase the risk for all types of CHDs. Diabetes may also impact the fetal cardiac performance at all gestational ages. Early detection of CHDs has certain advantages, such as making early decision about termination of pregnancy, enabling early genetic testing, and early reassurance if scan is normal. Combined transabdominal and transvaginal approach at 13-14 weeks of gestation is a reasonable strategy to assess fetal heart in diabetic women. Diagnostic accuracy of early fetal echocardiography has reached to above a reasonable cutoff when it is done in the late first trimester or early second trimester in the hands of expert sonographers. However, the literature is less certain to provide a firm conclusion about functional heart assessment in fetuses of diabetic mothers.

Marginal placental cord insertion: the need for follow up?

OBJECTIVE: The objectives of this study were (1) to estimate the association between marginal placental cord insertion (PCI) and small for gestational age (SGA) and other adverse perinatal outcomes and (2) to determine if pregnancy-associated plasma protein A (PAPP-A) levels was altered in these patients. METHODS: It was a retrospective cohort study of singleton pregnancies undergoing ultrasound between 2016 and 2018. Marginal PCI was defined as a distance of ≤2 cm from placental edge to PCI site, visualized in both sagittal and transverse planes, and diagnosed between 16 and 32 weeks. Velamentous PCI were excluded. The primary outcome was SGA, defined as birthweight below 10th percentile for gestational age. Pregnancies with marginal PCI were compared to those with normal PCI with respect to maternal characteristics, PAPP-A levels and adverse perinatal and delivery outcomes. RESULTS: The incidence of marginal PCI was 4.2% (76/1819). Compared to those with a normal PCI, patients with a marginal PCI were more likely to be nulliparous and less likely to be African American or morbidly obese (p < .05). SGA rate was similar between the groups (17.6% vs. 18.1%). There was a trend toward an increased incidence of oligohydramnios, polyhydramnios and breech presentation in patients with marginal PCI; however, these did not reach statistical significance. The incidence of low PAPP-A level was comparable between the groups (18.4% vs. 14.3%, p > .05). CONCLUSION: Our study did not demonstrate any increase in adverse pregnancy outcomes in the presence of marginal PCI. These findings may provide reassurance for counseling patients with this sonographic finding.

Effects of single vaginal incision technique on quality of life in women with stress urinary incontinence.

STUDY OBJECTIVE: To estimate the short-term effects of a minimally invasive single vaginal incision technique without passing through the abdomen or groin (ContaSure Needleless System) on the quality of life in women with incontinence. DESIGN: Prospective cohort study (Canadian Task Force classification II-2). SETTING: Tertiary referral urogynecology clinic. PATIENTS: 50 consecutive patients with urodynamically proved stress urinary incontinence from October 2008 to March 2009. INTERVENTIONS: Preoperative and postoperative scores on the short forms of the IIQ-7 (Incontinence Impact Questionnaire, UDI-6 (Urinary Distress Inventory) PISQ-12 (Pelvic Organ Prolapse/Urinary Incontinence Sexual Function), and long form of the P-QOL (Prolapse Quality of Life) were evaluated in 50 patients with urodynamically proved stress urinary incontinence. Scores were compared with postoperative urodynamic findings. MEASUREMENTS AND MAIN RESULTS: Mean (SD) follow-up was 433.5 (44.1) days (95% CI, 420.1-445.1). Patients showed statistically significant improvement insofar as preoperative and postoperative scores on the IIQ-7, P-QOL, and PISQ-12 and the irritative and stress subgroups of UDI-6. Obstructive score of UDI-6 worsened, consistent with the findings of pressure-flow studies. Postoperatively, 40 patients (80%) were urodynamically continent. Eight patients (16%) were still incontinent; however, their quality of life scores (IIQ-7 and UDI-6 stress) improved. Two patients (4%) continued to experience leakage, with equal or worsened quality-of-life scores. CONCLUSION: Early clinical results of the present trial demonstrate that the ContaSure Needleless System seems to be capable of improving significantly all aspects of quality of life in women with incontinence. To improve the willingness for treatment of women with stress incontinence, this minimally invasive technique should be encouraged after confirming its efficacy in larger prospective, randomized, comparative trials.

A novel approach to reduce blood loss in patients with placenta accreta spectrum disorder.

OBJECTIVE: Cesarean hysterectomy for the treatment of placenta accreta spectrum (PAS) disorders has the potential to be associated with significant blood loss, massive transfusion, and operative morbidity. Two major contributors to blood loss are the hysterotomy and the bladder dissection. We introduce a new surgical technique and hypothesize that developing the hysterotomy with a linear cutter and mobilization of the bladder using a vessel sealing system (VSS) before clamping uterine arteries will lead to a total reduction in blood loss and transfusion rates. MATERIALS AND METHODS: This was a case series, which presents clinical outcomes according to our described surgical technique. The following surgical outcomes were collected: operation time (minutes), estimated blood loss (EBL), intraoperative complications, need for reoperation before discharge, and transfusion rates. Our surgical technique utilizes a linear cutter to create a bloodless hysterotomy and a VSS to dissect the vesicouterine tissue. The VSS cauterizes and transects the small vesicouterine and placental-vesical vascular anastomoses that are prone to bleeding. Once the bladder is mobilized below the level of the cervix, the uterine arteries are ligated to complete the key components of the hysterectomy. RESULTS: Of the 23 cases, the median EBL was 1500 cubic centimeters and patients received a median of 1 unit of packed red blood cells. Eleven of the 23 cases did not require any blood transfusion and no patients required massive transfusion. The EBL did not differ between procedures that were performed emergently versus scheduled and it also did not differ between patients that had placenta increta versus placenta percreta, as diagnosed by histopathology. CONCLUSION: Use of a linear cutter and closure of the lower anastomosis with VSS prior to clamping uterine artery during cesarean hysterectomy can significantly reduce blood loss and transfusion rates. This technique is applicable in emergent and nonemergent settings as well as for the most challenging procedures complicated by placenta percreta.

Estrogen Receptors and Signaling in Fibroids: Role in Pathobiology and Therapeutic Implications.

Uterine fibroids are the most common gynecologic tumors with a significant medical and financial burden. Several genetic, hormonal, and biological factors have been shown to contribute to the development and growth of fibroid tumors. Of these factors, estrogen is particularly critical since fibroids are considered estrogen dependent because no prepubertal cases have been described in the literature and tumors tend to regress after menopause. Understanding the role of estrogen in fibroids is not only important for understanding the pathobiology of fibroids but also for the development of successful therapeutics. In this review, we discuss the types and structure of estrogen receptors (nuclear and membrane bound, including α and ß receptors and G protein-coupled estrogen receptor 1 GPER1). Estrogen-signaling pathways in fibroids include genomic (direct and indirect) and nongenomic including Ras-Raf-MEK (MAPK/Erk Kinase)-mitogen-activated protein kinase (MAPK) and phosphatidylinositide 3-kinase (PI3K)-phosphatidylinositol-3,4,5-trisphosphate (PIP3)-Akt (Protein kinase B)-mammalian target of rapamycin (mTOR) pathways; shortly Ras-Raf-MEK-MAPK and PI3K-PIP3-Akt-mTOR pathways. Several aberrations in estrogen receptors and signaling pathways are implicated in fibroid pathobiology. Current therapeutic and research agents targeting ERs/signaling include gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists, aromatase inhibitors, selective ER modulators, gene therapy, and others. Future research can identify potential targets for the development of novel treatments. In particular, epigenomics of estrogen activity and individualized (precision) medicine appear to be attractive areas for future research.

Incidence of occult leiomyosarcoma in presumed morcellation cases: a database study.

OBJECTIVE: Our objective was to estimate the incidence of uterine leiomyosarcoma in patients with leiomyomas following laparoscopic supracervical hysterectomy and myomectomy procedures. STUDY DESIGN: For this study, we analyzed records of 13,964 women aged 25-64 years who underwent laparoscopic supracervical hysterectomies or myomectomies for leiomyomas from 2002 to 2011 using Clinformatics DataMart. Patient records were divided into two groups: history of laparoscopic supracervical hysterectomy and history of myomectomy. Subjects were tracked to identify diagnosis of leiomyosarcoma within 1 year of the procedure. We analyzed data from the 25-39, 40-49, and 50-64 age brackets. Evidence was obtained from a cohort study from national private insurance claims in the US. RESULTS: Our results showed the incidence of occult leiomyosarcoma developing within 1 year following supracervical hysterectomy using a laparoscopic-assisted approach are 9.8, 10.7, and 33.4 per 10,000 for the 25-39, 40-49, and 50-64 age brackets, respectively; the overall incidence rate is 13.1 per 10,000. The incidence rate of occult leiomyosarcoma developing within 1 year following myomectomy using a laparoscopic-assisted approach are 0.0, 33.8, and 90.1 per 10,000 for the 25-39, 40-49, and 50-64 age brackets, respectively; the overall incidence rate is 17.3 per 10,000. CONCLUSION: Our analysis shows the overall risk of being diagnosed with occult leiomyosarcoma is 12.9 per 10,000 in laparoscopic-assisted supracervical hysterectomy and myomectomy for patients younger than 49. There is no evidence of occult leiomyosarcoma 1 year after operation for patients younger than 40 who underwent laparoscopic myomectomy.