Accuracy of the sonographic determination of estimated fetal weight in anhydramnios.

OBJECTIVE: To determine whether the presence of anhydramnios significantly influences the sonographic estimated fetal weight (EFW) compared to a matched cohort with normal amniotic fluid volume. METHODS: The study sample of this retrospective case-control study consisted of 114 pregnant women who presented to a Tertiary Perinatal Clinic between 2015 and 2020. 57 of them presented with an anhydramnios and a matched cohort of 57 women with normal amniotic fluid volume. At time of admission, gestational age varied between 22 + 4 and 42 + 6 weeks of pregnancy. All women underwent detailed ultrasound assessment for EFW and amniotic fluid index. To determine EFW Hadlock's estimation formula I was used which is based on measurements of biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur length (FL). The EFW was compared with the weight at delivery. The maximum time interval between measurement and delivery was 5 days. RESULTS: There was neither a significant difference between the case and control group with regard to gestational age at ultrasound in days (median 249 days and 246 days, p = 0.97), nor to gestational age at birth (median 249 days and 247 days, p = 0.98). Concerning the newborns parameters, the body length at birth was not significantly different between the case and control group in centimeters (cm) (median 47 cm and 47 cm, p = 0.79). EFW in gram (g) was lower than birth weight in both groups and did not differ significantly between case and control group (estimated weight median 2247 g and 2421 g, p = 0.46; birth weight median 2440 g and 2475 g, p = 0.47). The difference between EFW and birth weight in percent (%) did not differ between the case and control group (median - 3.9% and - 5.6%, p = 0.70). The maternal parameters showed that the patients in the case group were younger (median 31 years and 38 years p = 0.20) and had a significantly higher body mass index (BMI) (median 27.3 kg/m2 vs 22.0 kg/m2, < 0.001) compared to the control group. CONCLUSION: Our study shows for the first time that EFW in women with anhydramnios can be determined sonographically just as accurately as in a matched cohort with normal amniotic fluid volume. A reliable estimation of fetal weight is crucial for optimal assessment of the newborns prognosis and counseling of the parents especially when advising women in the early weeks of pregnancy at the limit of viability.

Soluble endoglin versus sFlt-1/PlGF ratio: detection of preeclampsia, HELLP syndrome, and FGR in a high-risk cohort.

The angiogenic factors sFlt-1 and PlGF play an established role in the detection of preeclampsia (PE). Recent data suggest that sEng might contribute to the pathogenesis of PE. However, only a few studies so far have addressed its role.This monocentric cross-sectional study of high-risk pregnancies aims to compare the levels of sFlt-1/PlGF ratio and sEng depending on different placental-related adverse pregnancy outcomes. The statistical analysis takes into account Pearson's correlation coefficient between angiogenic factors, the area under the curve estimates (AUCs) for detection, and adjusted odds ratios (aOR) with 95% confidence intervals (95%-CIs). The analysis included 206 patients: 60 controls, 90 PE (59 EOPE, 35 LOPE), 94 FGR, and 35 HELLP cases. Some outcomes overlapped because FGR commonly complicated PE and HELLP syndrome. Serum levels of sFlt-1/PlGF and sEng correlated with each other. Higher levels were observed in HELLP syndrome and EOPE cases. AUCs for sFlt-1/PlGF ratio and sEng were, respectively, 0.915 (95%-Cl 0.87-0.96) and 0.872 (95%-Cl 0.81-0.93) in PE, 0.895 (95%-Cl 0.83-0.96) and 0.878 (95%-Cl 0.81-0.95) in HELLP syndrome, 0.891 (95%-Cl 0.84-0.94), and 0.856 (95%-Cl 0.79-0.92) in FGR.aORsfor sFlt-1/PlGF ratio and sEng were, respectively: 2.69 (95%-Cl 1.86-3.9) and 2.33 (95%-Cl 1.59-3.48) in PE, 2.38 (95%-Cl 1.64-3.44) and 2.28 (95%-Cl 1.55-3.4) in FGR, and 2.10 (95%-Cl 1.45-3.05) and 1.88 (95%-Cl 1.31-2.69) in HELLP syndrome. In addition, the aORs between sFlt-1/PlGF and sEng were very similar but higher for PE and FGR than HELLP syndrome.In conclusion,sEng performed similarly to sFlt-1/PlGF to detect placental dysfunctions.

Course of the sFlt-1/PlGF ratio in fetal growth restriction and correlation with biometric measurements, feto-maternal Doppler parameters and time to delivery.

PURPOSE: The study aimed to assess the course of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in pregnant women with fetal growth restriction (FGR) and to evaluate potential associations between the sFlt-1/PlGF ratio and feto-maternal Doppler parameters, fetal biometric measurements and the time between study inclusion and birth ("time to delivery"). METHODS: This was a retrospective longitudinal single center study including 52 FGR cases. The serum levels of sFlt-1 and PlGF were measured by using the BRAHMS Kryptor Compact PLUS. Fetal biometric and Doppler parameters, as well as the sFlt-1/PlGF ratio, were obtained both upon study inclusion and upon birth. RESULTS: Various associations between the levels of the biomarkers in maternal blood upon study inclusion and upon birth and sonographic parameters were observed in FGR cases: umbilical artery (p < 0.01), uterine arteries (p < 0.01), ductus venosus (p < 0.05), cerebroplacental ratio (CPR) (p < 0.01), femur length (p < 0.01) and birth weight (p < 0.01). The higher the sFlt-1/PlGF ratio upon study inclusion, the shorter the "time to delivery" (p < 0.01). The multivariate regression analysis showed that the greater the daily percentage increase of the angiogenic markers, the shorter the "time to delivery" (p < 0.01). CONCLUSION: The fetal well-being, as measured by feto-maternal Doppler parameters such as CPR and the severity of the placental dysfunction, as measured by the urgency of birth and birth weight, is reflected by the level of the sFlt-1/PlGF ratio in the maternal serum. A rapid daily increase of the sFlt-1/PlGF ratio is significantly associated with the clinical progression of the disease.

MR-proANP, a cardiovascular biomarker to predict late-onset preeclampsia and intrauterine growth restricted fetuses.

OBJECTIVES: Midregional pro-atrial natriuretic peptide (MR-proANP) is a cardiac biomarker and the maternal serum levels could predict late-onset preeclampsia (PE) or intrauterine growth restriction (IUGR) at third trimester of pregnancy. METHODS: We measured MR-proANP between 32 and 37 weeks of pregnancy prospectively: 32 patients suffered from PE and 22 developed IUGR. 676 patients exhibited no pregnancy complications. RESULTS: The median MR-proANP showed significantly higher results in PE (64.9 pmol/l (interquartile range (IQR) 36.3-105.2) and IUGR (59.7 pmol/l (IQR 39.7-163.0) groups compared to controls (38.7 pmol/l (IQR 29.7-49.2). Linear regression analysis showed association between PE and MR-proANP levels (Exp(ß) = 1.56; 95% CI: 1.34-1.81). AUC showed a predictive value for PE (AUC: 0.72) and IUGR (AUC: 0.71). CONCLUSIONS: Measuring MR-proANP in maternal serum between 32 and 37 weeks of pregnancy could help predicting IUGR and PE diagnosed after 34 week in pregnancy. Thus, we assume that MR-proANP may be an additional biomarker which mirrors the maternal cardiosvascular status next to sFlt-1/PLGF representing the angiogenic status.

Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy.

OBJECTIVES: The aim of this study was to investigate, whether maternal serum levels of sFlt-1, PlGF and PAPP-A at third trimester of pregnancy are associated with late-onset PE and intrauterine growth retardation (IUGR) after 34 weeks of pregnancy. METHODS: This was a prospective study measuring the maternal serum levels of soluble tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 32-37 weeks of pregnancy: 730 patients were enrolled and 676 had neither intrauterine growth restriction (IUGR) nor preeclampsia (PE) or pregnancy induced hypertension (PIH) throughout the pregnancy. 22 patients developed IUGR, 32 PE and 24 PIH. RESULTS: Linear regression analyses after adjusting for maternal age, gestational age at the blood sampling and maternal BMI showed associations between PE and serum sFlt-1 levels (Exp(ß) = 3.29; 95% CI: 2.69-4.04), serum PlGF levels (Exp(ß) = 0.18; 95% CI: 0.13-0.24), sFlt-1/PlGF ratio (Exp(ß) = 15.59; 95% CI: 10.64-22.84) and serum PAPP-A (Exp(ß) = 1.48; 95% CI 1.15-1.89). sFlt-1, PlGF and sFlt-1/PlGF-Ratio showed comparable area under the curve (AUC) estimates with a predictive ability to discriminate pregnancies developing PE and IUGR from controls. The predictive ability of PAPP-A for PE was only slightly better than chance. CONCLUSIONS: This study supported the ability of a single measurement of sFlt-1/PlGF ratio at third trimester to predict PE and IUGR occurring after 34 weeks of pregnancy. However, larger multicentre studies are needed to replicate our results.

Anti-Mullerian-Hormone during pregnancy and peripartum using the new Beckman Coulter AMH Gen II Assay.

BACKGROUND: AMH levels determined by the conventional AMH assay declined during pregnancy and postpartum. A new Beckman Coulter AMH Gen II assay removes the potentially assay-interfering complement which is activated in pregnancy. The aim of this study was to evaluate if the decline of AMH levels in the serum of pregnant women during the course of pregnancy and peripartum was assay-dependent and thus artificial. METHODS: In this cross-sectional study prepartal blood samples were collected from 62 patients (median age 30.6 years [interquartile range: 25.6 - 34.5]) in the third trimester of pregnancy and again 1-4 days after delivery between 2011 and 2012. In another cohort of 11 patients (median age 34.1 years [interquartile range: 32.6 - 37.8]) blood samples were taken in different trimesters of pregnancy between 1995 and 2001. The conventional and the modified AMH assay were performed in the same patient serum samples. We used the conventional and the modified AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. The Wilcoxon signed rank test was used for determining differences between AMH levels pre- and postpartum. The method of Bland and Altman was applied for analyzing the agreement of both methods for determining AMH levels. RESULTS: AMH values peripartum were lower than those expected in fertile non-pregnant women of comparable age. An overall mean difference of 0.44 ng/ml was observed between the conventional and the modified assay. Measurements with the modified assay showed a significant decline of postpartal levels compared with prepartal levels which is consistent with values obtained using the conventional assay (both p < 0.00001). Compared to the longitudinal measurements of AMH levels determined using the conventional assay, AMH levels obtained using the modified assay suggest a steeper decline of values during the course of pregnancy. CONCLUSION: By comparing the conventional assay for AMH determination with the modified assay the present study confirmed that AMH levels decline during the course of pregnancy and early after delivery.

Change of anti-Mullerian-hormone levels during follicular phase in PCOS patients.

Anti-Mullerian-hormone (AMH) does not seem to fluctuate significantly during the menstrual cycle in healthy women. However, little is known about cycle fluctuations of AMH levels in patients with polycystic ovarian syndrome (PCOS). The purpose of this study was to examine AMH fluctuations during the follicular phase in PCOS patients receiving antiestrogens or recombinant follicle-stimulating hormone (FSH). About 40 PCOS patients diagnosed according to Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2003 and 19 controls were prospectively enrolled. PCOS patients received either antiestrogens or recombinant FSH for monoovulation induction and controls received antiestrogens. AMH levels were determined (1) between the 2nd and the 5th day of follicular phase and (2) when a single large dominant follicle ≥18 mm had appeared. Our study shows that AMH levels do not change during follicular development in controls as well as in PCOS patients with AMH levels < 5 ng/ml, irrespective of antiestrogen or FSH therapy. However, in PCOS patients with AMH levels ≥5 ng/ml, AMH declines significantly during follicular development (p < 0.01). We conclude that AMH levels should be determined in the early follicular phase in PCOS patients without the influence of antiestrogens or exogenous FSH, because these interventions may lower AMH values in patients with high levels.

Predictive markers for the FSH sensitivity of women with polycystic ovarian syndrome.

STUDY QUESTION: Do parameters which are involved in pathogenesis of polycystic ovarian syndrome (PCOS) predict the dosage of recombinant FSH required to achieve monofollicular development for ovulation induction? SUMMARY ANSWER: Anti-Mullerian hormone (AMH) appeared to be an independent predictor of the required dosage of FSH to achieve monofollicular development for ovulation induction in a study sample of clomiphene-resistant PCOS patients. WHAT IS KNOWN ALREADY: AMH plays a key role in the pathogenesis of PCOS. This is the first study that has evaluated the association between AMH and the required FSH dosage to achieve the development of a large follicle of at least 18 mm, in the presence of additional predictors of ovarian responsiveness. In the few studies to date which have evaluated predictors of ovarian responsiveness in PCOS patients, fasting insulin has been shown to be a significant predictor. STUDY DESIGN, SIZE, DURATION: A total of 48 infertile PCOS patients aged 18-43 years were enrolled in this prospective, observational study between 2009 and 2013. Study participants received between one and six cycles of ovarian stimulation with recombinant FSH using a step-up protocol. The mean total FSH dosage per cycle for reaching a monofollicular development for ovulation induction was evaluated to investigate its association with AMH, LH, FSH, LH/FSH-ratio, sex hormone-binding globulin (SHBG), androstendione, testosterone, free testosterone index, antral follicle count, ovarian volume, body mass index (BMI) and the age of patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, TX, USA) for the assessment of AMH levels. Crude and multiple linear regression models were fitted to explore potential predictors of the required FSH dosage. MAIN RESULTS AND THE ROLE OF CHANCE: An interquartile range (IQR) increase in AMH was associated with a 51.4% [95% confidence interval (CI): 24.7-79.0%; P = 0.0003] increase in the mean total FSH dosage per cycle (in IU) in a crude regression model, corresponding to a 7.2% increase in the mean total FSH dosage per cycle per ng/ml AMH. Adjustment for BMI augmented the effect of AMH, with a 58.3% (95% CI: 33.2-84.2%; P = 1.8 × 10(-5)) increase in FSH dosage per IQR AMH (corresponding to an 8.2% increase per ng/ml AMH) and a 46.2% (95% CI: 16.5-76.6%; P = 0.003) increase per IQR BMI (corresponding to a 3.7% increase per kg/m(2)). AMH was the only independent variable for which the effect on FSH dosage was statistically significant in the crude regression model as well as after adjustment for other promising predictors. The association of BMI with FSH dosage was statistically significant while adjusted for AMH, but not in the crude model. LIMITATIONS, REASONS FOR CAUTION: The impact of metabolic parameters such as insulin resistance on the reported association between AMH and FSH dosage was not assessed. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about the predictors of ovarian sensitivity to FSH can facilitate a physician's decision-making in providing the optimal infertility therapy for PCOS patients. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by the University Hospital of Essen.

Early detection of maternal risk for preeclampsia.

Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. New molecular insights offer new possibilities of early diagnosis of elevated maternal risk. Maternal risk factors, biophysical parameters like Doppler examination of the uterine arteries and biochemical parameters allow early risk calculation. Preventive and effective therapeutic agents like acetylsalicylacid can be started in the early second trimester. This article reviews the diagnostic possibilities of early risk calculation to detect women having high risk for preeclampsia and the potential benefits for them, the offspring and health care systems. We provide risk calculation for preeclampsia as an important and sensible part of first trimester screening.

[The female external genitalia : pathologic findings and first steps in treatment]. / Das äußere Genitale der Frau : Pathologische Befunde und initiale Behandlungsschritte.

Symptoms of diseases of the female external genitalia are often expressed in pruritus and burning pain. To accomplish a targeted differential diagnosis an exact knowledge of anatomy is essential. An accurate anamnesis, a detailed inspection, and conducting a biopsy or microbiological smear lead to the correct diagnosis. Lichen sclerosus et atrophicus is the most common non-neoplastic disease of the vulva. This should be distinguished from amongst others lichen ruber planus, psoriasis, contact dermatitis of the vulva, or infectious diseases like condylomata acuminata, herpes genitalis, or mycosis.Preinvasive dysplastic alterations commonly cause symptoms comparable to benign diseases. Their appearance can be very heterogeneous. To avoid missing these conditions, it is often necessary to obtain a biopsy.Vulvar carcinoma occurs most frequently in the 8th decade. Nonetheless it should be included in differential diagnostic considerations in younger women since the incidence of the HP-positive variant is increasing in the younger age group.

[Detection of microcalcifications by high-resolution B-mode sonography in patients with BI-RADS 4a lesions]. / Nachweis von Mikrokalk durch hochauflösende B-Mode-Sonographie bei BI-RADS-4a-Patientinnen.

OBJECTIVE: Evaluation of the diagnostic quality of high-resolution B-mode sonography for the detection of microcalcifications and calcification-associated focal findings in patients with BI-RADS lesions of subtype 4a. PATIENTS AND METHODS: 40 patients underwent X-ray mammography and 13-MHz B-mode sonography. The following parameters were examined: with X-ray mammography: extent of microcalcification and visibility of associated focal areas; with ultrasound: sensitivity of microcalcification findings, quality of presentation, extent of microcalcification, visibility of associated focal areas and feasibility of ultrasound-assisted biopsy. RESULTS: X-ray mammography showed a mean extent of microcalcification of 28 8 21 mm. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and accuracy of microcalcification-associated focal findings were 61.5, 57.9, 50, 45.8 and 47.5%. B-mode sonography achieved a sensitivity of 100%. Sonographically, the mean extent of microcalcification was 7 +/- 3 mm and thus significantly smaller (p < 0.01). Sensitivity, specificity, PPV, NPV and accuracy were 14.3, 84.2, 50, 47.1 and 47.5%. Ultrasound-assisted biopsy appeared feasible in 22 patients (55%). CONCLUSION: High-frequency B-mode sonography allows a highly sensitive confirmation of microcalcifications in the case of BI-RADS 4a lesions and seems to allow ultrasound-assisted biopsy in about half the patients.

[Imatinib--a possible therapeutic option for cervical carcinoma: results of a preclinical phase I study]. / Imatinib - eine mogliche Therapieoption beim Zervixkarzinom: Ergebnisse einer praklinischen Phase-I-Studie.

BACKGROUND: In the last few years, the therapy of cervical carcinoma has progressed substantially due to the use of simultaneous platinum- containing radiochemotherapy. However, there are no data which evaluate an individualized treatment adapted to tumor biology, in spite of the fact that patients show remarkably different responses to chemotherapy. Therefore this preclinical phase I study aims at finding therapeutic alternatives to the current cytostatic drugs to treat cervical carcinoma. MATERIAL AND METHODS: In a tumor chemosensitivity assay, 8 drugs were tested on freshly isolated tumor cells of 16 patients [carbo- and cisplatin, topotecan, paclitaxel as well as the 2 tyrosine kinase inhibitors imatinib (Glivec) and gefitinib (Iressa (R) ) and the 2 monoclonal antibodies cetuximab (Erbitux) and trastuzumab (Herceptin (R) )]. RESULTS: Overall the test was evaluable for 16 specimens (100%). Ten of 15 tumor samples (66.6%) were sensitive to imatinib. A sensitive therapeutic response could be demonstrated in all tested FIGO stages. An interindividual comparison could establish sensitivity to cetuximab in 12.5% of cases, to gefitinib in 6.25%, to trastuzumab in 6.6%, to cisplatin in 13.3%, to carboplatin in 7.6%, to paclitaxel in 93.8% and to topotecan in 25%. CONCLUSION: Imatinib seems to be an efficacious therapeutic option for patients with cervical carcinoma, independently of tumor subtype.