Biomarkers for predicting spontaneous preterm birth: an umbrella systematic review.

OBJECTIVE: To identify all systematic reviews investigating the role of maternal and fetal biomarkers for predicting spontaneous preterm birth (SPTB). METHODS: Medline and Web of Sciences databases were searched electronically. Studies exploring the association between maternal biomarkers and spontaneous delivery were considered suitable for inclusion. A synthesis of the systematic reviews was performed with the umbrella methodology. Statistical measures of association (Odd ratio, OR, relative risk, RR) and predictive accuracy (sensitivity, specificity, positive and negative likelihood ratios were used to synthesize results of the included studies. RESULTS: 21,614 articles were identified, 542 were assessed with respect to their eligibility for inclusion and 14 systematic reviews included. Cervical fibronectin was the biomarkers which showed the highest strength of association with the occurrence of SPTB (delivery within 24 h OR 7, 95%CI 3-17; delivery <7 days (OR 12, 95%CI 8-16). Maternal serum alpha fetoprotein, was associated with an OR of 4 and 3 for early and late SPTB. C-reactive protein had an OR of 2 (95%CI 1-2) and 8 (95%CI 4-16) when detected in maternal plasma and amniotic fluid, respectively. Among cytokines, interleukin-6 had an OR and an LR + for SPTB of 2 and 12 when detected in maternal serum. CONCLUSIONS: Cervical fetal fibronectin, alpha fetoprotein, C- reactive protein and interleukin 6 can have an overall good diagnostic accuracy in identifying pregnancies at risk of SPTB. Large prospective studies in different sub-set of women are needed to ascertain whether the combination of different serological and imaging marker can improve antenatal prediction of this condition.

Satisfactory rate of postprocessing visualization of standard fetal cardiac views from 4-dimensional cardiac volumes acquired during routine ultrasound practice by experienced sonographers in peripheral centers.

The aim of this study was to evaluate the feasibility of visualizing standard cardiac views from 4-dimensional (4D) cardiac volumes obtained at ultrasound facilities with no specific experience in fetal echocardiography. Five sonographers prospectively recorded 4D cardiac volumes starting from the 4-chamber view on 500 consecutive pregnancies at 19 to 24 weeks' gestation undergoing routine ultrasound examinations (100 pregnancies for each sonographer). Volumes were sent to the referral center, and 2 independent reviewers with experience in 4D fetal echocardiography assessed their quality in the display of the abdominal view, 4-chamber view, left and right ventricular outflow tracts, and 3-vessel and trachea view. Cardiac volumes were acquired in 474 of 500 pregnancies (94.8%). The 2 reviewers respectively acknowledged the presence of satisfactory images in 92.4% and 93.6% of abdominal views, 91.5% and 93.0% of 4-chamber views, in 85.0% and 86.2% of left ventricular outflow tracts, 83.9% and 84.5% of right ventricular outflow tracts, and 85.2% and 84.5% of 3-vessel and trachea views. The presence of a maternal body mass index of greater than 30 altered the probability of achieving satisfactory cardiac views, whereas previous maternal lower abdominal surgery did not affect the quality of reconstructed cardiac views. In conclusion, cardiac volumes acquired by 4D sonography in peripheral centers showed high enough quality to allow satisfactory diagnostic cardiac views.

Satisfactory rate of post-processing visualization of fetal cerebral axial, sagittal, and coronal planes from three-dimensional volumes acquired in routine second trimester ultrasound practice by sonographers of peripheral centers.

OBJECTIVE: The aim of this study was to evaluate the feasibility to visualize central nervous system (CNS) diagnostic planes from three-dimensional (3D) brain volumes obtained in ultrasound facilities with no specific experience in fetal neurosonography. METHODS: Five sonographers prospectively recorded transabdominal 3D CNS volumes starting from an axial approach on 500 consecutive pregnancies at 19-24 weeks of gestation undergoing routine ultrasound examination. Volumes were sent to the referral center (Department of Obstetrics and Gynecology, Università Roma Tor Vergata, Italy) and two independent reviewers with experience in 3D ultrasound assessed their quality in the display of axial, coronal, and sagittal planes. RESULTS: CNS volumes were acquired in 491/500 pregnancies (98.2%). The two reviewers acknowledged the presence of satisfactory images with a visualization rate ranging respectively between 95.1% and 97.14% for axial planes, 73.72% and 87.16% for coronal planes, and 78.41% and 94.29% for sagittal planes. The agreement rate between the two reviewers as expressed by Cohen's kappa coefficient was >0.87 for axial planes, >0.89 for coronal planes, and >0.94 for sagittal planes. The presence of a maternal body mass index >30 alters the probability of achieving satisfactory CNS views, while existence of previous maternal lower abdomen surgery does not affect the quality of the reconstructed planes. CONCLUSIONS: CNS volumes acquired by 3D ultrasonography in peripheral centers showed a quality high enough to allow a detailed fetal neurosonogram.

Histomorphometric characteristics of first trimester chorionic villi in pregnancies with low serum pregnancy-associated plasma protein-A levels: relationship with placental three-dimensional power doppler ultrasonographic vascularization.

OBJECTIVE: To evaluate histomorphometric vascular characteristics from samples obtained by chorionic villus sampling (CVS) in pregnancies with low serum pregnancy-associated plasma protein-A (PAPP-A) levels and to relate these findings to three-dimensional (3D) placental volume and power Doppler vascularization. METHODS: Immediately before CVS, placental 3D-power Doppler ultrasonography was performed at 11 + 0 to 13 + 6 weeks in 12 pregnancies with PAPP-A concentrations <0.3 multiples of median (MoM) as well as in 11 control women. Using a standardized setting placental volume, vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured. Histomorphometric parameters of villi were blindly evaluated with a video-computerized-image-analysis system. RESULTS: Pregnancies with low PAPP-A showed a significantly reduced number of capillary vessels per villus cross-section (p = 0.005) and a smaller capillary diameter (p = 0.041). Placental vascular indices were significantly related to the number of fetal capillary vessels per villus (VI: r = 0.51, p = 0.03; FI: r = 0.48, p = 0.04; VFI: r = 0.56, p = 0.01). CONCLUSIONS: Differences in placental vascularization are present in first trimester in pregnancies with low PAPP-A and they are associated to altered 3D placental Doppler indices.

Effects of maternal cigarette smoking on placental volume and vascularization measured by 3-dimensional power Doppler ultrasonography at 11+0 to 13+6 weeks of gestation.

OBJECTIVE: We sought to establish the effect of maternal smoking on placental volume and vascularization in early gestation. STUDY DESIGN: Three-dimensional power Doppler ultrasonography of the placenta was performed at 11+0 to 13+6 weeks in 80 pregnancies categorized according to cigarette consumption: group A never smoked, B smoking < 10 cigarettes/day, C smoking 10-20 cigarettes/day, and D smoking > 20 cigarettes/day. Using a standardized setting, placental volume and vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were calculated. RESULTS: No differences were found in placental volume among groups. In groups C and D lower values were found for VI (group C: t = 4.52, P = .0002; group D: t = 3.72, P = .0014), FI (group C: t = 5.06, P = .0001; group D: t = 4.59, P = .0002), and VFI (group C: t = 3.49, P = .0024; group D: t = 2.88, P = .0095). Placental vascular indices were significantly related to birthweight (VI r = 0.563, FI r = 0.580, VFI r = 0.601; P < .001). CONCLUSION: Maternal smoking is associated with altered 3-dimensional placental Doppler indices and these changes are related to birth weight.

Can gray-scale and color Doppler sonography differentiate between uterine leiomyosarcoma and leiomyoma?

PURPOSE: To evaluate the role of gray-scale and color Doppler sonography to distinguish uterine leiomyosarcoma (LMS) from leiomyoma (LM). METHODS: We analyzed the preoperative gray-scale and color Doppler sonographic findings of 8 patients with LMS, 21 patients with cellular leiomyomas, and 3 patients with smooth muscle tumors of uncertain malignant potential and compared these findings to 225 patients with benign LM. All patients underwent myomectomy or hysterectomy. Number, size, echotexture, degenerative changes, and vascularity (central or peripheral; absent, mild, moderate, or marked) were recorded and correlated to the histologic findings RESULTS: LMSs were significantly larger than other uterine smooth muscle tumors. They were all solitary, and 7/8 lesions had a diameter >or=8 cm. Degenerative cystic changes were observed in 4 lesions, and increased peripheral and central vascularity was demonstrated in 7 lesions. Sensitivity, specificity, and positive predictive value of increased central and peripheral vascularity in the diagnosis of LMS were 100%, 86%, and 19%, respectively. Combining other sonographic findings with marked central vascularity, positive predictive value increased to 60%, but sensitivity decreased to 75%. CONCLUSION: The findings of the present study suggest that the detection of hypervascularity in combination with other sonographic findings can identify suspicious uterine smooth muscle tumors that will require additional diagnostic evaluation before treatment.

Recurrence of endometriomas after laparoscopic removal: sonographic and clinical follow-up and indication for second surgery.

STUDY OBJECTIVE: This study involved patients who, after laparoscopic surgery, had recurrence of endometriomas detected by sonography. The aim of this study was to evaluate the role of transvaginal sonography (TVS) in the management of recurrent endometriomas and to establish ultrasonographic criteria that would direct the therapy toward additional surgery versus medical or expectant management. DESIGN: Retrospective analysis of 62 reproductive-age women who showed recurrence of endometriomas on TVS after laparoscopic removal of an ovarian endometrioma by the stripping technique (Canadian Task Force classification II-1). SETTING: Obstetrics and Gynecology Department, University of Rome Tor Vergata. PATIENTS: Sixty-two patients with recurrent endometriomas after first-line treatment with laparoscopy. INTERVENTIONS: Ultrasonographic follow-up and/or second surgery. MEASUREMENTS AND MAIN RESULTS: Recurrence of an ovarian endometrioma was defined as the presence of ovarian cysts with the typical sonographic criteria of endometriomas and a diameter of more than 10 mm. The clinical and sonographic postoperative follow-up period lasted from 6 to 97 months (median 24.6) after the first procedure. Of 62 patients with recurrent endometriomas, 50 had recurrence on the treated ovary, 7 on the contralateral untreated ovary, and 5 on both the treated and untreated ovaries. Recurrence of endometriomas was associated with symptoms (pain or infertility) in 47 patients (76%), while the remaining 15 (24%) were asymptomatic. Of the 47 symptomatic patients with recurrence detected by TVS, a second procedure was performed in 15. Second surgery in these patients was indicated by the larger size of the recurrent cysts, a poor response to medical treatment, the presence on TVS of pelvic adhesions and nodules of deep endometriosis, and overall progression of the disease. Symptomatic patients who did not undergo a second procedure (32) had smaller recurrent endometriomas. However of the 31 symptomatic patients with large recurrent endometriomas (>3 cm), only 45% had repeat surgery. CONCLUSION: Recurrent endometriomas, as detected by TVS, can remain asymptomatic and do not necessarily progress in size with or without medical treatment. The decision to reoperate depends less on the endometrioma's size than on symptoms, in particular severe pain, and failure of medical treatment. However such patients are also more likely to have signs of deep nodules and adnexal/bowel adhesions and larger endometriomas on TVS scan, thus predisposing them to require a second procedure.

The use of contrasted transvaginal sonography in the diagnosis of gynecologic diseases: a preliminary study.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of a new contrast-dedicated ultrasound technology, contrast-tuned imaging (CnTI), implemented on an endovaginal probe and using the second-generation contrast agent SonoVue (Bracco International BV, Amsterdam, the Netherlands), compared with the standard ultrasound examination in different gynecologic diseases. METHODS: Eighty-nine patients were enrolled in the study in 4 different clinical centers. The study included 40 patients with uncertain pelvic adnexal masses, 10 patients with pelvic masses indicative of recurrences of gynecologic tumors, 26 patients with uterine pathologic features, and 13 patients with cervical lesions. RESULTS: Application of CnTI technology after the SonoVue injection gave a picture of the intralesional microvascularization dramatically different from that obtained during color Doppler examination. Of the 40 pelvic masses, 15 (37.5%) were considered benign and 25 (62.5%) were considered malignant at B-mode and color Doppler examinations. Contrast-enhanced sonography showed no intralesional contrast perfusion in 11 (73%) of 15 cases, and all these were benign at final diagnosis. Of the 4 (27%) cases that had perfusion, 2 were malignant. Conversely, of the 25 cases with positive findings at color Doppler examination and therefore expected to show the appearance of contrast tissue-filling morphologic characteristics, 13 (52%) were malignant at final diagnosis. For evaluation of uterine pathologic features, the CnTI-SonoVue technology did not appear to be superior to the B-mode and color Doppler examinations; however, for the evaluation of cervical cancer, CnTI-SonoVue technology revealed a better definition of the margins of the neoplastic lesions in 4 (40%) of 10 cases. CONCLUSIONS: In the evaluation of uncertain pelvic masses, the CnTI technology led to an improvement in the ability of the practitioner to differentiate benign from malignant adnexal lesions.

Laparoscopic removal of endometriomas: sonographic evaluation of residual functioning ovarian tissue.

OBJECTIVE: The aim of this study was to determine whether and to what extent laparoscopic removal of ovarian endometriotic cysts is a tissue-sparing procedure. STUDY DESIGN: At the University Hospital, 77 women of reproductive age with endometriomas and 55 with dermoid cysts underwent laparoscopic removal of the ovarian disease by stripping. Within 1 month before and within 36 months after surgery all patients underwent transvaginal sonographic evaluation of ovarian volume of the endometriomas or dermoid cysts and measurement of the residual ovarian tissue. RESULTS: The residual ovarian volume after surgery was significantly less for the endometrioma group than for the dermoid group. Comparison of the volume of the treated ovary with that of the untreated contralateral ovary showed a significant difference (4.3+/-2.3 cm(3) vs 9.7+/-3.9 cm(3)) only in the endometrioma group. CONCLUSION: Ovarian stripping of endometriomas, but not of ovarian dermoids, is associated with a significant decrease in residual ovarian volume which may result in diminished ovarian reserve and function.

Directed laparoscopic cryomyolysis: a possible alternative to myomectomy and/or hysterectomy for symptomatic leiomyomas.

OBJECTIVE: The purpose of this study was to develop a minimally invasive, safe, and effective technique for managing symptomatic uterine myomas. STUDY DESIGN: Twenty patients with symptomatic uterine fibroids were treated. All had complaints of abnormal bleeding and/or pelvic pain/pressure and/or urinary frequency. Myoma diameters were 4 to 8 cm. Power color Doppler imaging was performed preoperatively and postoperatively to determine the effectiveness of cryomyolysis in reducing or eliminating the primary blood supply, as well as regression of the myomas. Laparoscopic cryomyolysis was performed with use of the Her Option Cryoablation System (American Medical Systems Gynecology, San Diego, Calif). Patients were evaluated at 1, 3, and 6 months postoperatively. RESULTS: All patients were discharged within 24 hours of treatment. No intraoperative or postoperative complications occurred. Of the 20 patients treated, 19 had complete resolution of their complaints. Myomas regressed up to 80%, and major blood supply to the myomas was eliminated. CONCLUSION: Directed laparoscopic cryomyolysis is an effective and safe technique for symptom relief from leiomyomas.

Hysterosalpingo-contrast sonography compared with hysterosalpingography and laparoscopic dye pertubation to evaluate tubal patency.

STUDY OBJECTIVE: To evaluate the advantages and accuracy of hysterosalpingo-contrast sonography (HyCoSy) in assessing tubal patency compared with hysterosalpingogram (HSG) and laparoscopic dye pertubation. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: Obstetrics and Gynecology Department, University of Rome Tor Vergata. PATIENTS: Twenty-three women with at least 1 year of infertility, and 15 women with a history of chronic pelvic pain, suspected endometriosis, or pelvic inflammatory disease (PID), or with sonographic markers of adhesions. INTERVENTIONS: HyCoSy, HSG, and laparoscopic dye pertubation. MEASUREMENTS AND MAIN RESULTS: All patients underwent HyCoSy during the proliferative phase using air with saline as contrast medium, and HSG within 1 month of HyCoSy. Laparoscopy and dye pertubation were performed only in women with chronic pelvic pain, suspected endometriosis, PID, and sonographic markers of adhesions. In women undergoing all three procedures, HSG and HyCoSy had the same high concordance as laparoscopy, 86.7% and 86.7%, respectively. Three women in the infertility group became pregnant immediately after HyCoSy and dropped out of the study. In one woman, HyCoSy could not be performed because of cervical stenosis. Considering the total number of tubes (67), concordance between HyCoSy and HSG was 89.6%. CONCLUSION: Transvaginal HyCoSy using a combination of air and saline appears to be an inexpensive, fast, and well-tolerated method of determining tubal patency. One of the most important advantages of this technique is, in our opinion, the possibility of obtaining information on tubal status and the uterine cavity at the same time as conventional ultrasound scan is performed.

Staging of pelvic endometriosis: role of sonographic appearance in determining extension of disease and modulating surgical approach.

STUDY OBJECTIVE: To estimate whether laparoscopic staging of endometriosis can be predicted by ultrasound findings. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: Obstetrics and Gynecology Department, University of Rome Tor Vergata. PATIENTS: One hundred twenty-one women with histologically confirmed sonographic diagnosis of endometriomas. INTERVENTIONS: Ultrasonographic staging and laparoscopic assessment. MEASUREMENTS AND MAIN RESULTS: All patients underwent transvaginal and/or transrectal sonographic evaluation of ovarian endometriomas and other sonographic markers (anatomic sites and their relation to abdominovaginal palpation, adhesions, deep or infiltrating nodules) to stage the disease before surgery. These results were compared with laparoscopic staging. Concordance between methods was 83.5%. Specificity and sensitivity of ultrasonographic staging of stages 3 and 4 disease were 86% and 82% and 76% and 91%, respectively. CONCLUSION: Ultrasonographic findings can predict pelvic extension and stage of endometriosis.

Laparoscopic approach to dermoid cysts: combined surgical technique and ultrasonographic evaluation of residual functioning ovarian tissue.

STUDY OBJECTIVE: To estimate how and if laparoscopic removal of ovarian dermoid cysts is a tissue-sparing procedure. DESIGN: Prospective study (Canadian Task Force classification II-2). SETTING: University-associated hospital. PATIENTS: Fifty-five women. INTERVENTION: Laparoscopic removal of ovarian dermoid cysts by a combination of hydrodissection and blunt dissection, and transvaginal sonographic (TVS) evaluation of residual ovarian tissue. MEASUREMENTS AND MAIN RESULTS: Within 1 week before surgery all recruited patients underwent TVS evaluation of ovarian volume, size, and morphology of dermoid cysts and measurement of surrounding ovarian cortex. Mean cyst diameter was 5.5 +/- 2.2 cm (range 2.1-15.0 cm). Within 6 to 12 months after laparoscopic excision, TVS measurements of residual ovarian tissues were obtained. Ovarian residual cortex surrounding the cyst was not visible at TVS in 24 ovaries, whereas in 56 ovaries residual tissue volume was greater than 3 cm3 after laparoscopic excision. CONCLUSION: We propose laparoscopic removal of dermoid cysts by combining hydrodissection and blunt dissection with maximum tissue sparing, even when the cyst seems to fill the ovary and no surrounding ovarian cortex can be seen on ultrasound.

C-peptide and insulin levels at 24-30 weeks' gestation: an increased risk of adverse pregnancy outcomes?

OBJECTIVE: The hypothesis was that fasting C-peptide and insulin values, during an oral glucose tolerance test (OGTT), might allow an estimation of the increased risk for gestational hypertension (GH) and fetal macrosomia. STUDY DESIGN: Two-hundred and six consecutive patients were submitted to an OGTT. Thirty-five developed gestational hypertension and 29 delivered large-for-gestational-age (LGA) newborns. Plasma glucose levels (mg/dl) and insulin levels (microU/ml) were measured fasting and after 60, 120 and 180 min C-peptide fasting levels (ng/ml) were also measured. RESULTS: Twenty-five patients were excluded, 181 were enrolled. According to the OGTT, 143 patients were classified as normal, 26 were found affected by gestational diabetes (GD) mellitus, and 12 had impaired gestational glucose tolerance (IGGT). Hypertensive women exhibited higher 60 and 120 min insulin values than the normotensive group (128.3+/-69.9 microU/ml versus 86.2+/-58.3 microU/ml, P<0.05; 104.9+/-66.4 microU/ml versus 78.7+/-56.5 microU/ml, P<0.05).C-peptide cut-off at 2.9 ng/ml resulted predictive for patients delivering large-for-gestational-age newborns (OR=3.42, 95% CI=1.59-7.39). CONCLUSIONS: C-peptide and insulin may be used as indicators of risk for the development of complications in late pregnancy.