Physical resolution of tubal ectopic pregnancy on ultrasound imaging following successful expectant management.

RESEARCH QUESTION: What is the time required for complete physical resolution of tubal ectopic pregnancies diagnosed on ultrasound imaging in women undergoing successful expectant management? DESIGN: A prospective observational cohort study of 177 women who had successful expectant management of tubal ectopic pregnancy, who attended a single Early Pregnancy Unit between January 2014 and December 2018. All participants were monitored until their serum beta-human chorionic gonadotrophin (beta-HCG) dropped to non-pregnant concentrations and with 2-weekly follow-up ultrasound scans until resolution of the pregnancy. RESULTS: A total of 112/177 (63.3%, 95% confidence interval [CI] 55.7-70.4) of tubal ectopic pregnancies were indiscernible on ultrasound 2 weeks after serum beta-HCG had returned to non-pregnant concentrations. In 8/177 (4.5%, 95% CI 2.0-8.7), physical resolution took longer than 78 days. There was a positive correlation between biochemical and physical resolution of tubal ectopic pregnancy (r = 0.21, P = 0.006). CONCLUSIONS: Physical resolution of tubal ectopic pregnancy is often prolonged and is positively correlated with initial and maximum beta-HCG concentrations. Results of this study indicate that beta-HCG resolution cannot be used as the end-point of expectant management of tubal ectopic pregnancy, which should be considered when counselling women and planning for future pregnancies.

Intertwin estimated fetal weight or crown rump length discordance and adverse perinatal outcome.

AIM: In the current review study, we present recent data regarding the importance of intertwin estimated fetal weight (EFW) and crown rump length (CRL) discordance for the prediction of adverse perinatal outcome both in monochorionic and in dichorionic diamniotic gestations. RESULTS: Twins with significant weight disparity are associated with higher rates of perinatal morbidity and mortality, regardless of gestational age at delivery. However, there is no agreement regarding as to the cut off value above which the perinatal outcome is unfavorably affected and the threshold range from 10 to 30%. On the other hand, CRL discrepancy has proved to be a weak predictor of adverse outcomes, such as fetal or neonatal death in fetuses without chromosomal and structural abnormalities. In clinical practice, decisions about obstetric surveillance of discordant twin gestations, frequency of fetal sonographic monitoring and time of delivery are usually based on amniotic fluid volume and Doppler assessments on a weekly basis. CONCLUSION: Significant EFW discordance leads to adverse perinatal outcome, although the cut-off value has not yet been estimated. CRL discrepancy is not correlated well with adverse perinatal outcome. However, increased monitoring of women with EFW and CRL discrepancy is suggested.

Obstetric outcomes in women with pelvic endometriosis: a prospective cohort study.

OBJECTIVE: To determine whether obstetric outcomes differ between women with endometriosis and those without, where all women undergo first-trimester screening for endometriosis. DESIGN: A prospective observational cohort study. SETTING: The Early Pregnancy Unit at University College London Hospital, United Kingdom. PATIENTS: Women with a live pregnancy progressing beyond 12 weeks' gestation and concurrent endometriosis (n = 110) or no endometriosis (n = 393). INTERVENTION: All women underwent a pelvic ultrasound examination in early pregnancy to examine for the presence of endometriosis and uterine abnormalities. MAIN OUTCOME MEASURES: The primary outcome of interest was preterm birth, defined as delivery before 37 completed weeks' gestation. Secondary outcomes included late miscarriage, antepartum hemorrhage, placental site disorders, gestational diabetes, hypertensive disorders of pregnancy, neonates small for gestational age, mode of delivery, intrapartum sepsis, postpartum hemorrhage, and admission to the neonatal unit. RESULTS: Women with a diagnosis of endometriosis did not have statistically significantly higher odds of preterm delivery (adjusted odds ratio [aOR] 1.85 [95% confidence interval {CI} 0.50-6.90]), but they did have higher odds of postpartum hemorrhage during cesarean section (aOR 3.64 [95% CI 2.07-6.35]) and admission of their newborn infant to the neonatal unit (aOR 3.24 [95% CI 1.08-9.73]). Women with persistent or recurrent deep endometriosis after surgery also had higher odds of placental site disorders (aOR 8.65 [95% CI 1.17-63.71]) and intrapartum sepsis (aOR 3.47 [95% CI 1.02-11.75]). CONCLUSION: We observed that women with endometriosis do not have higher odds of preterm delivery, irrespective of their disease subtype. However, they do have higher odds of postpartum hemorrhage during the cesarean section and newborn admission to the neonatal unit.

A prospective comparison of the diagnostic accuracies of ultrasound and magnetic resonance imaging in preoperative staging of endometrial cancer.

OBJECTIVE: To compare the diagnostic accuracies of ultrasound and magnetic resonance imaging (MRI) for deep (≥50%) myometrial invasion (DMI) and cervical stromal invasion (CSI) in women with endometrial cancer. METHODS: This was a prospective study at a gynecology clinic for women with postmenopausal bleeding. Between October 2015-October 2018, consecutive women with suspected endometrial cancer based on ultrasound subjective pattern recognition were simultaneously assessed for DMI and CSI on ultrasound. Subsequently, they also underwent preoperative MRI. We compared the diagnostic accuracies of ultrasound and MRI in predicting DMI and CSI with the final histology as the gold standard. RESULTS: We included 51 women. The prevalence of DMI and CSI were 22/51 (43%) and 7/51 (14%), respectively. The majority of malignancies were of endometrioid histological subtype (38/51, 75%) and FIGO stage 1 or 2 (40/51, 78%). Ultrasound diagnosed more cases of DMI compared to MRI (19/22 vs. 17/22), however, the difference was not statistically significant. The sensitivities and specificities of ultrasound and MRI for DMI were 86% vs. 77% and 66% vs. 76%, respectively. For CSI, ultrasound and MRI correctly diagnosed the same number of cases (5/7, 71%); their respective false-positive rates were low, 0/44 (0%) and 1/44 (2%). Ultrasound and MRI had a moderate agreement for DMI (ƙ=0.49; 95% confidence interval [CI]=0.26-0.73), whereas the agreement for CSI was substantial (ƙ=0.69; 95% CI=0.36-1.00). CONCLUSION: Endometrial cancer can be simultaneously diagnosed and staged at women's initial ultrasound assessment. The accuracies of ultrasound for DMI and CSI are comparable to MRI. TRIAL REGISTRATION: ISRCTN Identifier: ISRCTN24363390.

Risk of Pre-Malignancy or Malignancy in Postmenopausal Endometrial Polyps: A CHAID Decision Tree Analysis.

BACKGROUND AND AIMS: Postmenopausal endometrial polyps are commonly managed by surgical resection; however, expectant management may be considered for some women due to the presence of medical co-morbidities, failed hysteroscopies or patient's preference. This study aimed to identify patient characteristics and ultrasound morphological features of polyps that could aid in the prediction of underlying pre-malignancy or malignancy in postmenopausal polyps. METHODS: Women with consecutive postmenopausal polyps diagnosed on ultrasound and removed surgically were recruited between October 2015 to October 2018 prospectively. Polyps were defined on ultrasound as focal lesions with a regular outline, surrounded by normal endometrium. On Doppler examination, there was either a single feeder vessel or no detectable vascularity. Polyps were classified histologically as benign (including hyperplasia without atypia), pre-malignant (atypical hyperplasia), or malignant. A Chi-squared automatic interaction detection (CHAID) decision tree analysis was performed with a range of demographic, clinical, and ultrasound variables as independent, and the presence of pre-malignancy or malignancy in polyps as dependent variables. A 10-fold cross-validation method was used to estimate the model's misclassification risk. RESULTS: There were 240 women included, 181 of whom presented with postmenopausal bleeding. Their median age was 60 (range of 45-94); 18/240 (7.5%) women were diagnosed with pre-malignant or malignant polyps. In our decision tree model, the polyp mean diameter (≤13 mm or >13 mm) on ultrasound was the most important predictor of pre-malignancy or malignancy. If the tree was allowed to grow, the patient's body mass index (BMI) and cystic/solid appearance of the polyp classified women further into low-risk (≤5%), intermediate-risk (>5%-≤20%), or high-risk (>20%) groups. CONCLUSIONS: Our decision tree model may serve as a guide to counsel women on the benefits and risks of surgery for postmenopausal endometrial polyps. It may also assist clinicians in prioritizing women for surgery according to their risk of malignancy.

Risk prediction of major haemorrhage with surgical treatment of live cesarean scar pregnancies.

OBJECTIVE: To evaluate the association between demographic and ultrasound variables and major intra-operative blood loss during surgical transcervical evacuation of live caesarean scar pregnancies. STUDY DESIGN: This was a retrospective cohort study conducted in a tertiary referral center between 2008 and 2019. We included all women diagnosed with a live caesarean scar ectopic pregnancy who chose to have surgical management in the study center. A preoperative ultrasound was performed in each patient. All women underwent transcervical suction curettage under ultrasound guidance. Our primary outcome was the rate of postoperative blood transfusion. The secondary outcomes were estimated intra-operative blood loss (ml), rate of retained products of conception, need for repeat surgery, need for uterine artery embolization and hysterectomy rate. Descriptive statistics were used to describe the variables. Univariate and multivariable logistic regression models were constructed using the relevant covariates to identify the significant predictors for severe blood loss. RESULTS: During the study period, 80 women were diagnosed with a live caesarean scar pregnancy, of whom 62 (78%) opted for surgical management at our center. The median crown-rump length was 9.3 mm (range 1.4-85.7). Median blood loss at the time of surgery was 100 ml (range, 10-2300), and six women (10%; 95%CI 3.6-20) required blood transfusion. Crown-rump length and presence of placental lacunae were significant predictive factors for the need for blood transfusion and blood loss > 500 ml at univariate analysis (p < .01); on multivariate analysis, only crown-rump length was a significant predictor for need for blood transfusion (OR = 1.072; 95% CI 1.02-1.11). Blood transfusion was required in 6/18 (33%) cases with the crown-rump length ≥ 23 mm (≥9+0 weeks of gestation), but in none of 44 women presenting with a crown-rump length < 23 mm (p < .01). CONCLUSION: The risk of severe intraoperative bleeding and need for blood transfusion during or after surgical evacuation of live caesarean scar pregnancies increases with gestational age and is higher in the presence of placental lacunae. One third of women presenting at ≥ 9 weeks of gestation required blood transfusion and their treatment should be ideally arranged in specialized tertiary centers.

The Effect of Novel Medical Nonhormonal Treatments on the Angiogenesis of Endometriotic Lesions.

IMPORTANCE: Irrespective of the precise mechanisms leading to endometriosis, angiogenesis is essential for the establishment and long-term proliferation of the disease. As current surgical and medical management options for women with endometriosis have substantial drawbacks and limitations, novel agents are needed and molecules targeting the angiogenic cascade could serve as potential candidates. OBJECTIVE: Our aim was to review current data about the role of angiogenesis in the pathophysiology of endometriosis and summarize the novel antiangiogenic agents that could be potentially used in clinical management of patients with endometriosis. EVIDENCE ACQUISITION: Original research and review articles were retrieved through a computerized literature search. RESULTS: Loss of balance between angiogenic activators and suppressors triggers the nonphysiological angiogenesis observed in endometriotic lesions. Several proangiogenic mediators have been identified and most of them have demonstrated increased concentrations in the peritoneal fluid and/or serum of women with endometriosis. Among the antiangiogenic molecules, anti-vascular endothelial growth factor agents, dopamine agonists, romidepsin, and statins have shown the most promising results so far. CONCLUSIONS AND RELEVANCE: Given the limitations of current treatments of endometriosis, there is a need for novel, more efficient agents. Antiangiogenic molecules could be used potentially in clinical management of women with endometriosis; however, their safety and efficiency should be carefully assessed prior to that. Further large prospective trials in humans are needed before any treatment is introduced into daily clinical practice.

Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency.

PURPOSE: Previous studies have suggested that deletion of Foxo3a, FoxL2, PTEN, p27, and AMH leads to early exhaustion of the primordial follicle pool and premature ovarian insufficiency (POI) in transgenic mice. Our aim was to assess for the first time, to our knowledge, messenger RNA (mRNA) expression of these genes and AMHR2 in human ovarian tissue from women with POI. We hypothesized that these genes would be underexpressed in POI women compared with healthy controls. METHODS: mRNA levels were evaluated by quantitative reverse transcription-polymerase chain reaction and real-time polymerase chain reaction in cortical ovarian tissue obtained by laparoscopy from Caucasian Greek women with POI (n = 5) and healthy women with normal menstruation (n = 6). Morphological analysis of the ovarian biopsies was also performed to assess the presence of primordial or other types of growing follicles. RESULTS: Ovarian tissue from POI patients showed lower Foxo3a, FoxL2, and p27 mRNA expression compared with controls (p = 0.017, p = 0.017, and p = 0.030, respectively). mRNA expression of AMH, PTEN, and AMHR2 was reduced in ovarian biopsies from POI patients as well. However, these differences were not statistically significant (p = 0.143, p = 0.247, and p = 0.662, respectively). Morphological analysis showed complete lack of follicular structures in all POI biopsies. CONCLUSIONS: Our findings suggest a possible role of Foxo3a, FoxL2, and p27 in the pathogenesis of human POI, which may prove to be of great diagnostic-therapeutic value. Further larger studies are needed to identify a similar pattern for AMH, PTEN, and AMHR2 and to investigate gene expression at a protein level.

Correction to: Reduced Foxo3a, FoxL2, and p27 mRNA expression in human ovarian tissue in premature ovarian insufficiency.

The original version of this article, published 21 October 2019, unfortunately contained a mistake. The presentation of Fig. 1 was incorrect. The corrected figure is given below.