Updates in emergency medicine: Ectopic pregnancy.

INTRODUCTION: Ectopic pregnancy is a serious condition that can have significant morbidity and mortality. OBJECTIVE: This review highlights the pearls and pitfalls of ectopic pregnancy, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Ectopic pregnancy is a pregnancy that implants outside the normal uterine cavity. It most commonly presents with vaginal bleeding, abdominal or pelvic pain, and amenorrhea. Risk factors for ectopic pregnancy include abnormalities of the fallopian tube, prior ectopic pregnancy, and age over 35 years, but a significant number of patients with confirmed ectopic pregnancy will not have an identifiable risk factor. In patients with suspected ectopic pregnancy, evaluation includes quantitative serum hCG, blood type, and ultrasound. Ultrasound is necessary regardless of the hCG level. If the patient is hemodynamically unstable, resuscitation with blood products and early consultation of obstetrics/gynecology is necessary. Patients with confirmed ectopic pregnancy but who are otherwise stable may be managed medically or surgically. If a yolk sac or fetal pole is not seen in the uterus on ultrasound, this is considered a pregnancy of unknown location (PUL), which may represent an early, failed, or ectopic pregnancy. Stable patients with a PUL who can reliably follow up are managed with close specialist follow up and repeat 48 h HCG level. These patients need to have an hCG level repeated every 48 h until diagnosed with a viable pregnancy, failed pregnancy, or ectopic pregnancy. CONCLUSIONS: Knowledge of the latest advances in managing ectopic pregnancy will help clinicians more quickly and accurately diagnose patients presenting with this potentially fatal condition.

Vaginoscopy to investigate vaginal bleeding and discharge in prepubertal girls.

STUDY OBJECTIVE: To investigate the aetiology of vaginal bleeding and discharge in prepubescent girls, and the utility of vaginoscopy for making a diagnosis. DESIGN: Retrospective observational study over 14 years. SETTING: Two major tertiary referral paediatric hospitals in Sydney, Australia. PARTICIPANTS: All prepubescent girls (n = 104) who presented with vaginal bleeding and/or discharge and subsequently underwent a vaginoscopy. A total of 120 procedures were performed. MAIN OUTCOME MEASURES: Surgical findings at vaginoscopy; number needed to investigate (NNI) to establish a diagnosis and to exclude malignancy. RESULTS: There were 52/120 (43.3%) vaginoscopies which provided a positive diagnosis, including 36/86 (41.8%) performed for bleeding and 16/34 (47.0%) for vaginal discharge. In the vaginal bleeding group, the causes found were a foreign body in 11/86 (12.7%), vulvovaginitis in 6/86 (6.9%), benign Mullerian papilloma in 5/86 (5.8%), trauma in 4/86 (4.6%), and malignant tumours in 2/86 (2.3%). To establish a diagnosis in girls presenting with vaginal bleeding, the NNI was 2.4; to detect a malignancy the NNI was 43.0. In girls presenting with vaginal discharge, vulvovaginitis was noted intraoperatively in 7/34 (20.6%) and a foreign body was found in 7/34 (20.6%). No malignant tumours were identified in the vaginal discharge group. To establish a diagnosis in girls presenting with vaginal discharge, the NNI was 2.1. CONCLUSIONS: Vaginoscopy is an important diagnostic tool in the setting of vaginal bleeding in prepubescent girls, allowing the ability to confirm a diagnosis, and importantly, to exclude malignancy.

Assessing the Clinical Significance of Third-Trimester Post-Coital Bleeding.

INTRODUCTION: This study aimed to evaluate the impact of third-trimester post-coital bleeding (PCB) on pregnancy outcomes. METHODS: A retrospective cohort study was conducted at two tertiary medical centers, including all pregnant women between 24 and 34 weeks of gestation referred due to vaginal bleeding over an 11-year period. The study population includes all singleton deliveries; within this population, women were further classified into three groups: those admitted due to vaginal bleeding related to PCB, those admitted due to vaginal bleeding not related to PCB, and those who did not report vaginal bleeding. The primary outcome measure was delivery prior to 37 weeks of gestation, while secondary outcome measures included maternal and neonatal complications. Baseline characteristics of the two groups were compared. RESULTS: During the study period, there were a total of 51,698 deliveries. Among these, 230 cases involved bleeding between 24 and 34 weeks of gestation, 34 (14.8%) were identified as PCB, and 196 as bleeding unrelated to intercourse. In addition, 51,468 pregnancies without bleeding were analyzed as the general population for comparison. The incidence of preterm labor before 37 weeks of gestation was notably higher in both women with PCB (14.7%) and those with bleeding unrelated to coitus (20.9%) compared to the general population (5.6%); however, there was no statistically significant difference between the two bleeding groups (p = 0.403) while both were significantly different from the general population (p < 0.001). The odds ratio for preterm birth before 37 weeks of gestation after PCB was 3.29 (95% CI: 1.26-8.56, p = 0.0149). There were no significant differences between the PCB and bleeding unrelated to intercourse groups in terms of maternal and neonatal complications. CONCLUSION: This study found that third-trimester PCB is a risk factor for preterm delivery, with rates similar to other causes of third-trimester bleeding but significantly higher than the general population without bleeding. These findings challenge the assumption that PCB is benign.

Vaginal bleeding in pregnancy and adverse clinical outcomes: a systematic review and meta-analysis.

Background: Vaginal bleeding during pregnancy has been recognised as a significant risk factor for adverse pregnancy outcomes. This study aimed to investigate the association between vaginal bleeding during the first trimester of pregnancy and clinical adverse effects using a systematic review and meta-analysis.Methods: Databases of Scopus, Web of Science, PubMed (including Medline), Cochrane Library and Science Direct were searched until June of 2023. Data analysis using statistical test fixed- and random-effects models in the meta-analysis, Cochran and meta-regression. The quality of the eligible studies was assessed by using the Newcastle-Ottawa Scale checklist (NOS).Results: A total of 46 relevant studies, with a sample size of 1,554,141 were entered into the meta-analysis. Vaginal bleeding during the first trimester of pregnancy increases the risk of preterm birth (OR: 1.8, CI 95%: 1.6-2.0), low birth weight (LBW; OR: 2.0, CI 95%: 1.5-2.6), premature rupture of membranes (PROMs; OR: 2.3, CI 95%: 1.8-3.0), abortion (OR: 4.3, CI 95%: 2.0-9.0), stillbirth (OR: 2.5, CI 95%: 1.2-5.0), placental abruption (OR: 2.2, CI 95%: 1.4-3.3) and placenta previa (OR: 1.9, CI 95%: 1.5-2.4).Conclusions: Vaginal bleeding in the first trimester of pregnancy is associated with preterm birth, LBW, PROMs, miscarriage, stillbirth, placental abruption and placenta previa. Therefore, physicians or midwives need to be aware of the possibility of these consequences and manage them when they occur.

Vaginal bleeding in the first trimester of pregnancy increases the relative risk of preterm birth, low birth weight, premature rupture of membranes, abortion, stillbirth, placental abruption and placenta previa.

Association between Antenatal Vaginal Bleeding and Adverse Perinatal Outcomes in Placenta Accreta Spectrum.

Background and Objectives: Placenta accreta spectrum (PAS) disorders are placental conditions associated with significant maternal morbidity and mortality. While antenatal vaginal bleeding in the setting of PAS is common, the implications of this on overall outcomes remain unknown. Our primary objective was to identify the implications of antenatal vaginal bleeding in the setting of suspected PAS on both maternal and fetal outcomes. Materials and Methods: We performed a case-control study of patients referred to our PAS center of excellence delivered by cesarean hysterectomy from 2012 to 2022. Subsequently, antenatal vaginal bleeding episodes were quantified, and components of maternal morbidity were assessed. A maternal composite of surgical morbidity was utilized, comprised of blood loss ≥ 2 L, transfusion ≥ 4 units of blood, intensive care unit (ICU) admission, and post-operative length of stay ≥ 4 days. Results: During the time period, 135 cases of confirmed PAS were managed by cesarean hysterectomy. A total of 61/135 (45.2%) had at least one episode of bleeding antenatally, and 36 (59%) of these had two or more bleeding episodes. Increasing episodes of antenatal vaginal bleeding were associated with emergent delivery (p < 0.01), delivery at an earlier gestational age (35 vs. 34 vs. 33 weeks, p < 0.01), and increased composite maternal morbidity (76, 84, and 94%, p = 0.03). Conclusions: Antenatal vaginal bleeding in the setting of PAS is associated with increased emergent deliveries, earlier gestational ages, and maternal composite morbidity. This important antenatal event may aid in not only counseling patients but also in the coordination of multidisciplinary teams caring for these complex patients.

A comparison of the clinical features of molar pregnancy in adolescents and adults.

Objective: To compare the age-specific clinical features of molar pregnancy and to describe the risk factors associated with this situation. Method: This retrospective case-control study was conducted at the Department of Obstetrics and Gynecology. Tepecik Education and Research Hospital, Izmir, Turkey. The participants included both adolescents (≤ 19 years) and adults with histologically confirmed hydatidiform moles in our institution between January 2015 and January 2022. The interventions and main outcome measures of this study involved evaluating the clinical and ultrasonographic features, as well as the risk factors, associated with molar pregnancies in adolescents. Results: This study of 137 patients with molar pregnancy found that adults had a higher incidence of partial molar pregnancy (20 patients versus seven patients) and lower beta-hCG levels than adolescents (176.890.71 mIU/ml versus 253.734.47 mIU/ml). Adolescents had a higher likelihood of hyperthyroidism (25.4% versus 9.2%). bleeding on admission (4.2% versus 1.51%),. longer hospital stays (5.44 ± 2.73 days versus 3.59 ± 3.08 days). Higher rates of uterine enlargement and postoperative bleeding (15.5% versus 1.5%). Adolescents also required more analgesia (97% versus 89.4%). Conclusions: Adolescents with Gestational trophoblastic diseases (GTD) may present with more severe symptoms compared to adults, which can lead to delayed diagnosis and treatment. Further research is needed to better understand the underlying mechanisms and risk factors for GTDs in this population. Increased awareness and education can help improve recognition and management of GTDs in adolescents and improve their overall health outcomes.

Uterine Arteriovenous Malformations.

Uterine arteriovenous malformations (AVMs) are an abnormal presence of shunts between myometrial arteries and veins within the myometrium that usually occurs after a traumatic event on the uterus and it is often diagnosed after a miscarriage. In this case report, we propone the case of a woman, gravida 3 para 2, admitted at the emergency department presenting deep vaginal bleeding and suspicion of incomplete miscarriage at 11 weeks of pregnancy. The suspect of AVM was made with noninvasive procedure; transvaginal ultrasound examination with the advantage of color Doppler showed a myometrial hypervascular lesion of the posterior wall. Pulsed Doppler permitted the waveform analysis of uterine arteries and three-dimensional sonography with color Doppler and reconstructions clearly showed dilated ad tortuous blood vessels within the contest of the myometrium. Magnetic resonance angiography showed multiple tubular structures with tortuous appearance that confirmed the suspicion of AVM. Uterine artery embolization was performed of the right uterine artery. One month after uterine embolization, the ultrasound control confirmed the complete resolution of the AVM.

Uterine Artery Pseudoaneurysm after Total Abdominal Hysterectomy Managed by Ultrasound-guided Percutaneous Glue Injection.

Uterine artery pseudoaneurysm (UAP) following abdominal hysterectomy is an uncommon complication. However, it can cause life-threatening bleeding, necessitating early diagnosis and intervention. Imaging is vital in its prompt diagnosis and aids in planning interventions. Here, we describe a case of recurrent massive per-vaginal bleeding from a left UAP developed following total abdominal hysterectomy and bilateral salpingo-oophorectomy. Bleeding was successfully managed with percutaneous ultrasound-guided glue (N-butyl cyanoacrylate) injection into the aneurysmal sac. The patient is doing well without any recurrent bleeding.

The WID-qEC test: Performance in a hospital-based cohort and feasibility to detect endometrial and cervical cancers.

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.

Combining early pregnancy bleeding with ultrasound measurements to assess spontaneous abortion risk among infertile patients.

BACKGROUND: Approximately 15% of all clinically recognized pregnancies in patients with infertility result in spontaneous abortion. However, despite its potential to have a profound and lasting effect on physical and emotional well-being, the natural history of spontaneous abortion in women with infertility has not been described. Although vaginal bleeding is a common symptom in pregnancies conceived via reproductive technologies, its prognostic value is not well understood. OBJECTIVE: This study aimed to evaluate the combination of early pregnancy bleeding and first-trimester ultrasound measurements to determine spontaneous abortion risk. STUDY DESIGN: This was a retrospective cohort study of patients with infertility who underwent autologous embryo transfer resulting in singleton intrauterine pregnancy confirmed by ultrasound from January 1, 2017, to December 31, 2019. Early pregnancy symptoms of bleeding occurring before gestational week 8 and measurements of crown-rump length and fetal heart rate from ultrasounds performed during gestational week 6 (6 0/7 to 6 6/7 weeks of gestation) and gestational week 7 (7 0/7 to 7 6/7 weeks of gestation) were recorded. Modified Poisson regression with robust error variance was adjusted a priori for patient age, embryo transfer day, and transfer of a preimplantation genetic-tested embryo to estimate the relative risk and 95% confidence interval of spontaneous abortion for dichotomous variables. The relative risks and positive predictive values for early pregnancy bleeding combined with ultrasound measurements on the occurrence of spontaneous abortion were calculated for patients who had an ultrasound performed during gestational week 6 and separately for patients who had an ultrasound performed during gestational week 7. The primary outcome was spontaneous abortion in the setting of vaginal bleeding with normal ultrasound parameters. The secondary outcomes were spontaneous abortion with vaginal bleeding and (1) abnormal crown-rump length, (2) abnormal fetal heart rate, and (3) both abnormal crown-rump length and abnormal fetal heart rate. RESULTS: Of the 1858 patients who were included (359 cases resulted in abortions and 1499 resulted in live births), 315 patients (17.0%) reported vaginal bleeding. When combined with ultrasound measurements from gestational week 6, bleeding was significantly associated with increased spontaneous abortion only when accompanied by absent fetal heart rate (relative risk, 5.36; 95% confidence interval, 3.36-8.55) or both absent fetal heart rate and absent fetal pole (relative risk, 9.67; 95% confidence interval, 7.45-12.56). Similarly, when combined with ultrasound measurements from gestational week 7, bleeding was significantly associated with increased spontaneous abortion only when accompanied by an abnormal assessment of fetal heart rate or crown-rump length (relative risk, 5.09; 95% confidence interval, 1.83-14.19) or both fetal heart rate and crown-rump length (relative risk, 14.82; 95% confidence interval, 10.54-20.83). With normal ultrasound measurements, bleeding was not associated with increased spontaneous abortion risk (relative risk: 1.05 [95% confidence interval, 0.61-1.78] in gestational week 6 and 0.80 [95% confidence interval, 0.36-1.74] in gestational week 7), and the live birth rate was comparable with that in patients with normal ultrasound measurements and no bleeding. CONCLUSION: Patients with a history of infertility who present after embryo transfer with symptoms of vaginal bleeding should be evaluated with a pregnancy ultrasound to accurately assess spontaneous abortion risk. In the setting of normal ultrasound measurements, patients can be reassured that their risk of spontaneous abortion is not increased and that their live birth rate is not decreased.

Abnormal uterine bleeding in anticoagulated patients by drug class: outcomes and management.

BACKGROUND: Although abnormal uterine bleeding is a known adverse effect of anticoagulant drugs, true rates have not been widely studied. Society-backed recommendations and guidelines do not yet exist for prevention and management of abnormal uterine bleeding among anticoagulated patients. OBJECTIVE: This study aimed to describe the incidence of new-onset abnormal uterine bleeding among patients receiving therapeutic anticoagulation by anticoagulant class, and to evaluate gynecologic treatment patterns. STUDY DESIGN: We conducted an institutional review board-waived retrospective chart review of female patients aged 18 to 55 years and prescribed therapeutic anticoagulants, including vitamin-K antagonists, low-molecular-weight heparins, and direct oral anticoagulants, in an urban hospital network from January 2015 through January 2020. We excluded patients with antecedent abnormal uterine bleeding and menopause. Associations between abnormal uterine bleeding, anticoagulant class, and other covariates were evaluated with Pearson chi-square and analysis-of-variance tests. The primary outcome, abnormal uterine bleeding odds by anticoagulant class, was modeled with logistic regression. Age, antiplatelet therapy, body mass index, and race were included in our multivariable model. Secondary outcomes included emergency department visits and treatment patterns. RESULTS: Of the 2479 patients who met the inclusion criteria, 645 were diagnosed with abnormal uterine bleeding after initiating therapeutic anticoagulation. After adjusting for age, race, body mass index, and concurrent use of antiplatelet therapy, those receiving all 3 classes of anticoagulants had higher odds of experiencing abnormal uterine bleeding (adjusted odds ratio, 2.63; confidence interval, 1.70-4.08; P<.001), whereas those taking only direct oral anticoagulants had the lowest odds (adjusted odds ratio, 0.70; confidence interval, 0.51-0.97; P=.032), with vitamin-K antagonists as the reference group. Race other than White was associated with higher odds of abnormal uterine bleeding, as was lower age. The most common hormone therapies used among patients with abnormal uterine bleeding were levonorgestrel intrauterine devices (7.6%; 49/645) and oral progestins (7.6%; 49/645). Sixty-eight patients (10.5%; 68/645) had an emergency department visit for abnormal uterine bleeding; 29.5% (190/645) of patients received a blood transfusion; 12.2% (79/645) began any pharmacologic therapy for bleeding; and 18.8% (121/645) underwent any gynecologic procedure. CONCLUSION: Abnormal uterine bleeding occurs frequently among patients on therapeutic anticoagulation. Incidence in this sample varied considerably by anticoagulant class and race; use of single-agent direct oral anticoagulation carried the lowest risk. Important sequelae such as bleeding-related emergency department visits, blood transfusions, and gynecologic procedures were common. Balancing bleeding and clotting risk in patients on therapeutic anticoagulation requires a nuanced approach and should involve collaborative management between hematologists and gynecologists.

Association between vaginal bleeding in pregnancy that resulted in delivery and risk of cancer: A Danish registry-based cohort study.

BACKGROUND: Vaginal bleeding (VB) before 20 gestational weeks of a viable pregnancy is a manifestation of a threatened miscarriage. VB is associated with increased levels of pro-inflammatory cytokines such as interferon-gamma, tumour necrosis factor-alpha and interleukin-6. Increased levels of these cytokines and oxidative stress are risk factors for cancer. The risk of cancer following a VB-affected pregnancy that ended in childbirth is unknown. OBJECTIVES: To investigate the associations between VB in pregnancy that resulted in delivery and risk of incident cancer. METHODS: We conducted a cohort study (1995-2018) in Denmark using administrative and healthcare registries. We included 37,082 VB-affected deliveries, 1,363,614 VB-unaffected deliveries, 324,328 pregnancies ending in terminations, and 137,104 miscarriages. We computed the absolute risk of cancer and hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, morbidities, and socio-economic factors using Cox proportional hazards regression. Multiple pregnancies to the same woman were accounted for in the analysis. RESULTS: The median (25th-75th percentile) follow-up in the study was 12.6 (6.9, 18.2) years. The prevalence of VB in the present study was 3%. At the end of the follow-up, there were 1320 cancer cases among the VB-affected delivery cohort, 40,420 among the VB-unaffected delivery cohort, 10,300 among the termination cohort and 4790 among the miscarriage cohort. HRs for any cancer among VB-affected deliveries were 1.03 (95% CI 0.97, 1.08) compared with VB-unaffected deliveries, 1.03 (95% CI 0.97, 1.09) compared with terminations and 0.90 (95% CI 0.84, 0.95) compared with miscarriages. There were no increased risks of premenopausal breast cancer, cervical cancer, ovary and fallopian tube cancer or uterine cancer following VB-affected deliveries vs. comparison cohorts. CONCLUSIONS: We found no evidence of an association between vaginal bleeding in pregnancy and an increased risk of cancer.

The predictive value of common symptoms in early pregnancy for complications later in pregnancy and at birth.

INTRODUCTION: The aim was to investigate whether common pregnancy-related symptoms-nausea, vomiting, back pain, pelvic girdle pain, pelvic cavity pain, vaginal bleeding, itching of vulva, pregnancy itching, leg cramps, uterine contractions and varicose veins-in the first trimester of pregnancy add to the identification of women at high risk of future pregnancy and birth complications. MATERIAL AND METHODS: Survey data linked to national register data. All women booking an appointment for a first prenatal visit in one of 192 randomly selected General Practices in East Denmark in the period April 2015-August 2016. The General Practices included 1491 women to this prospective study. Two outcomes, pregnancy complications and birth complications, were collected from the Danish Medical Birth Register. RESULTS: Among the 1413 included women, 199 (14%) experienced complications in later pregnancy. The most serious complication, miscarriage, was experienced by 65 women (4.6%). Other common pregnancy complications were gestational diabetes mellitus (n = 11, 0.8%), gestational hypertension without proteinuria (n = 34, 2.4%), mild to moderate preeclampsia (n = 34, 2.4%) and gestational itching with effect on liver (n = 17, 1.2%). Women who experienced pelvic girdle pain, pelvic cavity pain or vaginal bleeding in the first trimester of pregnancy had a higher risk of pregnancy complications later on in later pregnancy. None of the other examined symptoms showed associations to pregnancy complications. No associations were found between pregnancy-related physical symptoms in first trimester and birth complications. CONCLUSIONS: Symptoms in early pregnancy do not add much information about the risk of pregnancy or birth complications, although pain and bleeding may give reason for some concern. This is an important message to women experiencing these common symptoms and to their caregivers.

Vaginal bleeding in children: A retrospective audit at a tertiary paediatric gynaecology service.

AIM: The aim of this study was to describe the clinical features and investigations of vaginal bleeding in prepubertal children. METHODS: We performed a retrospective case series of children under the age of 10 who presented with vaginal bleeding to our institution between 2018 and 2019. RESULTS: There were 32 cases identified during the timeframe, with a mean age of 5.5 years (standard deviation 3.2 years, range 5.5 days to 9.6 years). Vulvovaginitis was the most common diagnosis (n = 12, 37.5%), followed by precocious puberty (n = 5, 15.6%). Uncommon but serious causes were vaginal rhabdomyosarcoma (n = 1), and sexual abuse (one patient presenting with gonorrhoea and one with a non-accidental injury). Vaginoscopy was performed in nine patients (28.1%) for various reasons, and a vaginal foreign body was identified in two patients (6.3%). All the patients who had a serious cause of bleeding (neoplasm or sexual assault) or who required specific treatment (precocious puberty, lichen sclerosus, urethral prolapse) presented with red flags on history and/or examination: recurrent episodes of vaginal bleeding, heavy bleeding, associated general symptoms (poor feeding and growth), presence of thelarche, abdominal mass, associated profuse vaginal discharge and abnormal genital examination (skin changes, urethral prolapse or protruding mass from the vagina). CONCLUSIONS: A thorough history-taking and clinical examination aiming at identifying red flags may help to discriminate between benign causes of vaginal bleeding, where no further investigations are indicated, and alternative diagnoses with a poor outcome and/or requiring specific treatment and additional investigations.

McCune-Albright Syndrome: A Case Report and Review of Literature.

McCune-Albright syndrome (MAS) is a rare sporadic condition defined by the classic triad of fibrous dysplasia of bone, café au lait skin macules, and hyperfunctioning endocrinopathies. The molecular basis of MAS has been ascribed to the post-zygotic somatic gain-of-function mutations in the GNAS gene, which encodes the alpha subunit of G proteins, leading to constitutive activation of several G Protein-Coupled Receptors (GPCRs). The co-occurrence of two of the above-mentioned cardinal clinical manifestations sets the diagnosis at the clinical level. In this case report, we describe a 27-month-old girl who presented with gonadotropin-independent precocious puberty secondary to an estrogen-secreting ovarian cyst, a café au lait skin macule and growth hormone, and prolactin excess, and we provide an updated review of the scientific literature on the clinical features, diagnostic work-up, and therapeutic management of MAS.

First-Trimester Pregnancy: Considerations for Wilderness and Remote Travel.

Women increasingly participate in outdoor activities in wilderness and remote environments. We performed a literature review to address diagnostic and therapeutic considerations during first-trimester pregnancy for remote multiday travel. Pretrip planning for pregnant patients traveling outside access to advanced medical care should include performing a transvaginal ultrasound to confirm pregnancy location and checking D rhesus status. We discuss the risk of potential travel-related infections and recommended vaccinations prior to departure based on destination. Immediate evacuation to definitive medical care is required for patients with a pregnancy of unknown location and vaginal bleeding. We propose algorithms for determining the need for evacuation and present therapeutic options for nausea and vomiting, urinary tract infections, and candidiasis in the field.

Rare (uro-)genital pathologies in young girls mimicking sexual abuse.

Examinations of young children for suspicions of sexual abuse are challenging for the involved medical specialists because the consequences of the interpretation of the findings can be severe and dramatic. A broad knowledge of differential diagnoses including rare pathologies like urethral prolapse and failure of the midline fusion of the perineum, known as perineal groove, is essential in order to avoid unnecessary diagnostics and treatment, prejudgment, and to reduce patient family's anxiety. We report two independent cases of girls aged 7 months and 5 years suffering from these rare pathologies, one presenting with painless lower genital tract bleeding, the other showing a lesion of the perineum as random finding during a neuropediatrician's consultation. In both cases, the pathologies were initially misdiagnosed as injuries due to sexual assault, and judicial investigation procedures were initiated. In this paper, the characteristic symptoms and morphology of urethral prolapse and perineal groove are presented to enhance the awareness of these pathologies among forensic experts and help to establish the correct diagnosis.

Use of aromatase inhibitors in menopausal deep endometriosis: a case report and literature review.

We report and review the clinical effectiveness of aromatase inhibitors in a patient with refractory, recurrent and infiltrating endometriosis. We demonstrate excellent clinical, radiological and endoscopic responses after failure of multiple other modalities. Our case and the literature show that single-agent letrozole is capable to treat deep infiltrative endometriosis involving the rectum and the urinary tract. The use of aromatase inhibitor treatment of endometriosis in postmenopausal women makes sense, is safe and is well tolerated. Difficult cases of deep infiltrative endometriosis might require use of combined surgical and medical treatment modalities. Multidisciplinary involvement of the gynecologist, bowel surgeon, urologist and invasive radiologist might be needed. Aromatase inhibitors should be considered to be an integral part of the armamentarium in the management of women with endometriosis, especially in refractory cases that have failed conventional therapeutic modalities.

The association of maternal vaginal bleeding and progesterone supplementation in early pregnancy with offspring outcomes: a prospective cohort study.

BACKGROUND: Progesterone is widely used to improve the adverse pregnancy outcomes related to vaginal bleeding during early pregnancy. However, the evidence of its effectiveness is equivocal. METHODS: Six thousand six hundred fifteen mother-infant pairs from Tongji Maternal and Child Health Cohort (TMCHC) were involved in the study. Information on vaginal bleeding, progesterone administration in early pregnancy were obtained at enrolment. Birth outcomes were obtained from the hospital notes. Body weight of the infants at 12 months of age was collected by telephone interview. Multivariable logistic regression was conducted to estimate the effect of vaginal bleeding and progesterone administration in early pregnancy on birth outcomes and weight status of infants at 12 months of age. RESULTS: 21.4% (1418/6615) participants experienced bleeding in early pregnancy, and 47.5% (674/1418) of them were treated with progesterone. There were no significant associations between progesterone supplementation in early pregnancy and offspring outcomes. Compared to women without bleeding or any therapy, women with bleeding and progesterone therapy experienced increased risk of preterm (OR 1.74, 95% CI 1.21-2.52), and delivering a small-for-gestational-age (SGA) (OR 1.46, 95% CI 1.07-1.98) or low birth weight (LBW) (OR 2.10, 95% CI 1.25-3.51) neonate, and offspring of them had an increased risk of weight for age z-score (WAZ) < -1 at 12 months of age (OR 1.79, 95%CI 1.01-3.19). CONCLUSIONS: Offspring of mothers with bleeding and progesterone therapy were more likely to be a premature, SGA or LBW neonate, and had lower weight at 12 months of age. Progesterone supplementation may have no beneficial effect on improving adverse offspring outcomes related to early vaginal bleeding. TRIAL REGISTRATION: TMCHC was registered at clinicaltrials.gov as NCT03099837 on 4 April 2017.

Association between first-trimester subchorionic hematoma detected at 6-8 weeks of gestation and pregnancy outcomes after fresh embryo transfers: a propensity score-matching cohort study.

PURPOSE: This study aimed to investigate the association between first-trimester subchorionic hematoma (SCH) detected at 6-8 weeks of gestation after fresh embryo transfers and adverse pregnancy outcomes. METHODS: We performed a retrospective cohort involving 3074 patients. All of them acquired singleton pregnancies after fresh embryo transfers in the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. According to first-trimester ultrasound examinations at 6-8 weeks of gestation, we divided patients into SCH and non-SCH groups and compared their perinatal outcomes. Symptomatic patients with vaginal bleeding and asymptomatic patients were analyzed separately, and propensity score matching (PSM) and multivariable regression were adopted to control potential confounding factors. RESULTS: The incidence of SCH was 17.1% in 3074 women, and vaginal bleeding occurred in 92 SCH patients and 215 control patients. In the asymptomatic cohort, 415 women with SCH and 807 women without SCH were finally included after PSM. No significant differences were observed in livebirth rate (91.3% vs 92.9%, P = 0.314), miscarriage rate (8.4% vs 6.7%, P = 0.267), and preterm birth rate (4.8% vs 5.7%, P = 0.519) between two groups. Secondary outcomes including gestational hypertension or preeclampsia, gestational diabetes mellitus (GDM), gestational age (GA) at delivery, mode of delivery, sex of newborns and birthweight of newborns were comparable. For symptomatic patients, both univariable and multivariable regression analysis showed no significant association between SCH and pregnancy outcomes. A subgroup analysis including patients with SCH illustrated the symptom of vaginal bleeding rather than hematoma size was associated with livebirth. CONCLUSION: First-trimester SCH detected at 6-8 weeks of gestation was not associated with adverse pregnancy outcomes in singleton pregnancies after fresh embryo transfers. Vaginal bleeding was the risk factor of pregnancy loss for patients with SCH.