Sonographic Diagnosis and Management With Delayed Hysterectomy of Two Cesarean Scar Pregnancies That Developed Into Placenta Percreta: Two Case Reports.

Approximately two-thirds of the patients with a cesarean scar pregnancy (CSP) will develop placenta accreta spectrum (PAS). PAS occurs when the placenta attaches too deeply to the uterine wall, and sometimes, the placenta can extend beyond the uterus, invading surrounding organs. PAS is commonly managed with a cesarean hysterectomy, and these deliveries are often complicated by maternal and fetal morbidity and mortality. However, delaying hysterectomy and using chemotherapeutic agents may be a safe and beneficial alternative. We describe the case of a 32 -year-old G3P2002 with a history of two prior cesarean sections (CS) who was referred to our Maternal Fetal Medicine department due to the concern of a gestational sac embedded in the anterior uterine wall in the cesarean scar. Magnetic resonance imaging (MRI) findings at 33 weeks confirmed that the patient had developed placenta percreta extending into the sigmoid colon. We also describe the case of a 30-year-old G6P4104 with a history of four prior CS who was referred to our department for concern of a pregnancy complicated by CSP. This patient had an MRI performed at 23 weeks that showed placenta percreta invading the bladder. Patients one and two were managed with a staged procedure, with CS followed by a delayed laparoscopic and abdominal hysterectomy, respectively, to minimize bowel and bladder injury. After the CS, the patients subsequently received a five-day course of intravenous (IV) etoposide 100mg/m2, and at six weeks postpartum, the patients had a hysterectomy, both showing resolution of the placenta invasion into the surrounding organs on postpartum MRI and confirmed by tissue pathology reports. Our cases present the challenge in diagnosis and management of the most severe presentation of PAS that varies from the generally accepted management recommendations. Delayed hysterectomy with chemotherapy can be a reasonable, conservative surgical approach in the most severe types of PAS. As in our cases, this management could improve maternal and fetal morbidity and mortality.

Disparities in Emergency Department Utilization Among Women with Postpartum Mood Disorders (2006-2016).

INTRODUCTION: Postpartum mood disorders are associated with adverse outcomes for newborns and mothers and may require urgent evaluation. The emergency department is often a healthcare entry point, but factors associated with these emergency department visits are unknown. METHODS: A longitudinal retrospective analysis using the Nationwide Emergency Department Sample to assess national estimates of emergency department visits by women ages 15-49 with primary diagnosis of a postpartum mood disorder between 2006 and 2016. Emergency department visit rates for postpartum mood disorders per 100,000 live births were calculated. RESULTS: Emergency department visits related to postpartum mood disorders remained stable from 2006 to 2016 (5153 to 5390 respectively). Two-thirds of visits were by patients younger than 30. Approximately half of visits for postpartum mood disorders were funded by Medicaid (42.4-56.7%) compared to 27.4-41.2% funded by Medicaid for all other age-matched women. Of postpartum mood disorder visits 30.3% were by women from the lowest income quartile. The highest rate of emergency department visits occurred in the youngest patients (ages 15-19: 231 visits versus ages 35-49: 105 visits). Postpartum mood disorder admissions were higher than those for age-matched women with all other diagnoses (19.8% vs. 6.5%). DISCUSSION: The high rate of women that are young and with public insurance visiting the emergency department for postpartum mood disorders demonstrates an increased risk for these disorders in these populations and an opportunity for targeted intervention by policymakers and providers. Higher admission rates for postpartum mood disorders compared to all other diagnoses reveals a chance to optimize outpatient screening and treatment.

Emergency Department Utilization for Substance Use Disorder During Pregnancy and Postpartum in the United States (2006-2016).

OBJECTIVES: We aimed to better understand emergency department (ED) use, admission patterns, and demographics for substance use disorder in pregnancy and postpartum (SUDPP). METHODS: In this longitudinal study, the United States Nationwide Emergency Department Sample was queried for all ED visits by 15- to 50-year-old women with a primary diagnosis defined by International Classification of Diseases, 9th or 10th edition Clinical Modification, codes of SUDPP between 2006 and 2016. Patterns of ED visit counts, rates, admissions, and ED charges were analyzed. RESULTS: Annual national estimated ED visits for SUDPP increased from 2,919 to 9,497 between 2006 and 2016 (a 12.4% annual average percentage change), whereas admission rates decreased (from 41.9% to 32.0%). ED visits were more frequent among women who were 20-29 years old, using Medicaid insurance, in the lowest income quartile, living in the South, and in metropolitan areas. Compared with the proportion of ED visits, 15- to 19-year-olds had significantly lower admission rates, whereas women with Medicaid and in the lowest income quartile had higher admission rates (p < .001). Opioid use, tobacco use, and mental health disorders were most commonly associated with SUDPP. The ED average inflation-adjusted charges for SUDPP increased from $1,486 to $3,085 between 2006 and 2016 (7.1% annual average percentage change; p < .001), yielding total annual charges of $4.02 million and $28.53 million. CONCLUSIONS: Despite the decrease in admissions, the number and charges for ED visits for SUDPP increased substantially between 2006 and 2016. These increasing numbers suggest a continuous need to implement preventive public health measures and provide adequate outpatient care for this condition in this population specifically.

Obesity-induced follicular phase endometrial proteome dysregulation in a well-phenotyped population.

OBJECTIVE: Despite obesity's significant impact on reproduction, its influence on the physiology of the human endometrium is largely understudied. We hypothesized that endometrial proteomic differences exist between obese (OW; body mass index [BMI] ≥30 kg/m2) and normal-weight women (NWW; BMI, 18.5-24.9 kg/m2). DESIGN: Clinical cross-sectional study. SETTING: Academic Medical Center. PATIENT(S): Healthy, normally-cycling, 18 to 40-year-old women (n = 6 OW and n = 6 NWW). MAIN OUTCOME MEASURE(S): Participants underwent screening and midfollicular phase visits. Demographic and anthropometric characteristics, blood samples, ultrasounds, and follicular phase endometrial biopsies were collected. Proteomic analyses of endometrial samples (liquid chromatography-mass spectrometry) were performed. Proteins with ≥2-fold difference and a false discovery rate of <0.1 were considered statistically significant (Benjamini-Hochberg adjustment). RESULT(S): Reproductive hormone levels did not differ between the two groups. Mean BMI, serum leptin concentration, and bioelectrical impedance analysis indices of adiposity were higher in OW than in NWW. Histological examination of the endometrial samples confirmed normal-appearing endometrium in both OW and NWW. A total of 2,930 proteins were detected across all samples, with an average number of proteins per sample of 2,059 ± 482 in NWW and 2,437 ± 187 in OW. A total of 17 proteins were differentially expressed in OW vs. NWW; 2 were more abundant, whereas 15 were underexpressed in OW, including the progesterone receptor. CONCLUSION(S): In this well-phenotyped population of healthy women, obesity was associated with significant endometrial proliferative phase proteomic differences affecting the hormonal and immunologic pathways. These could contribute to an increased risk of menstrual bleeding abnormalities and create an altered environment for future luteinization.

Antenatal Three-Dimensional Printing for Ex Utero Intrapartum Treatment Procedures.

BACKGROUND: Prenatal ultrasonography allows for timely identification of fetal abnormalities that can have an effect on securing the neonatal airway at delivery. We illustrate the role of antenatal three-dimensional printing in cases with fetal airway obstruction. CASE: We present two cases that highlight the utility of a three-dimensional printing technique to aid in ex utero intrapartum treatment procedures during cesarean delivery. CONCLUSION: Three-dimensional printing plays a complementary role to standard imaging options in optimizing presurgical planning, prenatal parental counseling, personalized patient care, and education of the multidisciplinary team in cases of fetal congenital airway obstruction.

Trends in Emergency Department Visits among Adolescents with Abnormal Uterine Bleeding.

STUDY OBJECTIVE: To explore trends over time in the utilization of the Emergency Department (ED) for adolescents with abnormal uterine bleeding (AUB). DESIGN: Retrospective cross-sectional study. SETTING: Nationwide Emergency Department Sample database (Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, Rockville, MD). PARTICIPANTS: Subset of adolescents aged 10-19 years from overall cohort of women aged 10-49 years. INTERVENTIONS: All ED visits from 2010-2014 for which International Classification of Diseases, ninth revision codes for AUB were listed as the principal diagnosis were compared. Health insurance coverage, demographic factors, hospital characteristics, comorbid anemia, and comorbid bleeding disorders were explored. MAIN OUTCOME MEASURES: Number of visits, ED disposition, blood transfusions, and billing for pelvic ultrasound. RESULTS: There were an estimated 262,939 ED visits nationally for women aged 10-49 years for AUB in 2014. Of these, 12.7% (33,511/262,939) were from adolescents aged 10-19 years. The number of adolescent visits with an AUB diagnosis declined by 11% from 2010-2014 (37,642 vs 33,511; P = .026), while visits by patients aged 20-49 did not change significantly (215,309 vs 229,428; P = .19). The number of adolescent visits for which Medicaid was the primary payer increased slightly, from 17,283 to 18,785, from 2010 to 2014 (P = .152), while the number using self-pay decreased from 8769 (23.4%) in 2010 to 5146 (15.4%) in 2014 (P < .0001). CONCLUSION: ED visits among adolescents with AUB decreased from 2010 to 2014. There was a sharp reduction in the number of visits funded by self-pay and a slight increase in visits funded by Medicaid.

Epidemiology and management of uterine fibroids.

Uterine leiomyomas are one of the most common and yet understudied diseases in women. These tumors, commonly known as fibroids, affect women mainly during their reproductive years and are diagnosed in up to 70% of white women and more than 80% of women of African ancestry during their lifetime. This disease has a profound impact on health care delivery and costs worldwide. Though most women with fibroids are asymptomatic, approximately 30% of them will present with severe symptoms which can include abnormal uterine bleeding, anemia, pelvic pain and pressure, back pain, urinary frequency, constipation, or infertility, and will require intervention. Furthermore, fibroids have been associated with poor obstetrical outcomes. The current options for symptomatic fibroid treatment include expectant, medical, and surgical management, and interventional radiology procedures. This article reviews the recent progress and available management strategies for uterine fibroids and highlights areas where further research is needed to find new therapeutic targets and better personalize treatments.

Secondary Prevention of Intrauterine Adhesions Following Hysteroscopic Surgery in Women With Asherman Syndrome: Is Something Better Than Nothing?

Asherman syndrome is a reproductive disorder characterized by intrauterine adhesions and amenorrhea, infertility, abnormal placentation, or pregnancy loss. Treatment of Asherman syndrome involves hysteroscopic lysis of adhesions. Many surgeons utilize postoperative measures such as hormone therapy, solid mechanical devices, or barrier gels to prevent recurrent adhesions in this setting. However, there is limited high-quality evidence to support their use. Additional research is needed on the safety and efficacy of these commonly used methods to guide patient care.

The dynamic changes in the number of uterine natural killer cells are specific to the eutopic but not to the ectopic endometrium in women and in a baboon model of endometriosis.

BACKGROUND: Endometriosis is a common condition associated with growth of endometrial-like tissue beyond the uterine cavity. Previous reports have suggested a role for uNK cells in the pathogenesis of endometriosis postulating that survival and accumulation of menstrual endometrial tissue in the peritoneal cavity may relate to a reduction in the cytotoxic activity of peripheral blood NK cells. We aimed to assess the differences in percentage of uNK cells and their phenotypical characterization in eutopic and ectopic endometrial samples from women with and without endometriosis and baboons with induced endometriosis. METHODS: Eutopic and ectopic endometrial samples from 82 women across the menstrual cycle with/without endometriosis and from 8 baboons before and after induction of endometriosis were examined for CD56 and NKp30 expression with immunohistochemistry, quantified using computer assisted image analysis. Curated secretory phase endometrial microarray datasets were interrogated for NK cell receptors and their ligands. In silico data was validated by examining the secretory phase eutopic endometrium of women with and without endometriosis (n = 8/group) for the immuno-expression of BAG6 protein. RESULTS: The percentage of uNK cells increased progressively from the proliferative phase with the highest levels in the late secretory phase in the eutopic endometrium of women with and without endometriosis. The percentage of uNK cells in ectopic lesions remained significantly low throughout the cycle. In baboons, induction of endometriosis increased the percentage of uNK in the ectopic lesions but not NKp30. Published eutopic endometrial microarray datasets demonstrated significant upregulation of NKp30 and its ligand BAG6 in women with endometriosis compared with controls. Immunohistochemical staining scores for BAG6 was also significantly higher in secretory phase eutopic endometrium from women with endometriosis compared with the endometrium of healthy women (n = 8/group). CONCLUSIONS: The dynamic increase in the percentage of uNK cells in the secretory phase is preserved in the endometrium of women with endometriosis. The low number of uNK cells in human and baboon ectopic lesions may be due to their exaggerated reduction in hormonal responsiveness (progesterone resistance).

Mice deficient in AKAP13 (BRX) develop compulsive-like behavior and increased body weight.

OBJECTIVE: Hormonal contributions to the sex-dependent development of both obsessive-compulsive disorder (OCD) and obesity have been described, but the underlying mechanisms are incompletely understood. A-kinase anchoring protein 13 (AKAP13) significantly augments ligand-dependent activation of estrogen receptors alpha and beta. The hypothalamus and pituitary gland are implicated in the development and exacerbation of OCD and obesity and have strong AKAP13 expression. The AKAP13 localization pattern observed in these key brain regions together with its effects on sex steroid action suggest a potential role for AKAP13 in compulsive-like behaviors. Here we tested the role of AKAP13 in compulsive-like behavior and body weight using an Akap13 haploinsufficient murine model. MATERIALS AND METHODS: Targeted deletion of the Akap13 gene generated haploinsufficient (Akap13+/-) mice in a C57BL6/J genetic background. Established behavioral assays were conducted, video recorded, and scored blindly to assess compulsive-like behavior based on genotype and gender. Tests included: marble-burying, grooming, open- field and elevated plus-maze. Brain and body weights were also obtained. Mean levels of test outcomes were compared using multi-way ANOVA to test for genotype, sex, genotype*sex, and genotype*sex*age interaction effects with Bonferroni adjustment for multiple comparisons, to further explain any significant interactions. RESULTS: The marble-burying and grooming assays revealed significant sex-dependent increases in perseverative, compulsive-like behaviors in female Akap13 haploinsufficient mice compared to female wild type (WT) mice by demonstrating increased marble-burying activity (p = .0025) and a trend towards increased grooming behavior (p = .06). Male Akap13 haploinsufficient mice exhibited no behavioral changes (p > 0.05). Elevated plus-maze and open-field test results showed no overt anxiety-like behavior in Akap13 haploinsufficient mice irrespective of sex (p > 0.05, both). No differences in brain weight were found in Akap13 haploinsufficient mice compared to WT mice (p > 0.05). However, female Akap13 haploinsufficient mice weighed more than female WT mice in the 4 to <7 months age range (p = .0051). Male Akap13 haploinsufficient mice showed no differences in weight compared to male WT mice (p = >0.05) at any age range examined. CONCLUSION: Akap13 haploinsufficiency led to sex-dependent, compulsive-like behavioral changes in a murine model. Interestingly, Akap13 haploinsufficiency also led to a sex-dependent increase in body weight. These results revealed a requirement for AKAP13 in murine behavior, particularly in female mice, and is the first report of AKAP13 involvement in murine behavior. Future studies may examine the involvement of AKAP13 in the pathophysiology of OCD in female humans and may contribute to a better understanding of the role of AKAP13 and sex hormones in the development and exacerbation of OCD.

Gestational age of pregnancy loss in women with unexplained recurrent miscarriage.

AIM: The aim of this study was to investigate the gestational age (GA) of pregnancy loss in women with unexplained recurrent miscarriage (RM) and to determine whether the miscarriages occur at similar GA in RM women. MATERIAL AND METHODS: This retrospective study was carried out in a university hospital and included 288 women with unexplained RM. The GA at which each miscarriage occurred was carefully determined. Overall, 739 miscarriages were analyzed. RESULTS: RM women had miscarriages at a median GA of 7 weeks (range: 3-20). In RM women, 47.2% (n = 136) experienced miscarriages within a 1-week range of GA and 53.4% (n = 154) had miscarriages in the same period of fetal development (pre-embryonic, embryonic or fetal). CONCLUSION: Women with unexplained RM tend to have miscarriages at the same GA, which is characteristic for each patient.

Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis.

PROBLEM: Uterine natural killer cells (uNK) have been thought to play a key role in endometriosis and infertility. We investigated the expression of CD56, CD16, and NKp46 in endometrial tissues from 61 women with unexplained recurrent pregnancy loss (uRPL) or infertility (UI) and correlated this with the presence or absence of endometriosis. The results from the patients with subfertility were compared with those from 10 fertile patients. METHOD OF STUDY: Mid-secretory phase endometrial biopsies were obtained, and the endometrial expression of CD56, CD16, or NKp46 was identified by immunohistochemistry and quantified (ImageJ Software). RESULTS: The percentage of CD16(+) cells was higher in women with uRPL (7.9 ± 3.2) and UI (9.0 ± 5.5), even when these conditions were associated with endometriosis (8.9 ± 5.3), compared with fertile patients (5.6 ± 2.4, P < 0.05). Likewise, the ratio of NKp46(+) :CD56(+) cells was higher in women with uRPL (0.28 ± 0.25) and UI (0.21 ± 0.2), even when these conditions were associated with endometriosis (0.19 ± 0.14), compared with fertile patients (0.1 ± 0.1, P < 0.05). No differences were observed when comparing CD56. CONCLUSIONS: Women, with or without endometriosis, who have larger populations of cytotoxic CD16(+) uNK cells and/or higher populations of NKp46(+) CD56(+) cells may be at greater risk of infertility disorders resulting from an inflammatory environment occurring during implantation or later during decidualization.

Thyroid autoimmunity and recurrent miscarriage.

PROBLEM: To investigate the role of antithyroid autoantibodies (ATA) in recurrent miscarriage (RM). METHODS: In this case-control study, a total of 160 women with RM and 100 healthy women were investigated for the presence of serum ATA directed against thyreoglobulin (TG-Ab), thyroid peroxidase (TPO-Ab) and TSH receptor (TSHr-Ab), which were determined by either chemiluminescence or radioimmunoassay. RESULTS: Antithyroid autoantibodies were detected in 46 (28.75%) women with RM and in 13 (13%) women of the control group (P < 0.05). The frequencies for TG-Ab and TPO-Ab were higher in RM than in control women. Among the women of RM group, 91.3% of ATA+ women were positive also for other autoantibodies. The majority of study women were euthyroid. CONCLUSIONS: Antithyroid autoantibodies, particularly TG-Ab, are associated with RM and could be an expression of a more general maternal immune system abnormality leading to RM. ATA could have a role in RM irrespective of thyroid hormone status.