Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. OBJECTIVE: The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. SEARCH STRATEGY: Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. SELECTION CRITERIA: Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. DATA COLLECTION AND ANALYSIS: The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. MAIN RESULTS: Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. CONCLUSION: Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. TWEETABLE ABSTRACT: Pituitary block with GnRH antagonists does not improve the success of IUI cycles.

Innovative clinical pathways for obese pregnant women: design and feasibility of the Padua project (North-Eastern Italy).

BACKGROUND: Obesity during pregnancy can adversely affect the wellbeing of the mother and the newborn, as well as the latter's long-term health. Preconception counseling, careful prenatal management, and strict follow-up during pregnancy are, therefore, essential for obese fertile women in order to prevent the negative effects of obesity. METHODS: In this setting, we developed a project that consisted in creating an integrated network of primary, secondary, and tertiary care providers and designing new clinical pathways for managing pregnancy in obese women. RESULTS: Two distinct pathways were devised: a Pre-Gestational Pathway for programming a pregnancy in obese women; and a Gestational Pathway for the clinical management of their pregnancy. DISCUSSION: Judging from the preliminary results of our study, the latter (Gestational) pathway seems to be successful, since there has been a gradual increase in the number of women using it, and these women have reported having no difficulty in accessing the services involved. It is noteworthy that immigrant women (who accounted for 60% of the women using the pathway) also reported no access issues. The pre-gestational pathway was very little used, however, accounting for only 2% of the appointments made with the services involved. In conclusion, the key to success in managing pregnancy in obese women lies in sharing the various different health care competences required and taking the local resources into account. The prevention of obesity in women of fertile age remains the main problem, however, and further efforts are needed in this setting.

Four cases of fetal intra-abdominal umbilical vein varix: a single centre's approach to management.

Fetal intra-abdominal umbilical vein (FIUV) varix is a rare prenatal abnormality characterised by a focal intrahepatic or extrahepatic dilatation of the intra-abdominal portion of the umbilical vein. Usually, it is an isolated finding, but in some cases it can be associated to other fetal anomalies. Thrombosis is a possible complication of FIUV varix and it can lead to poor fetal or neonatal outcome. We describe four consecutive cases of FIUV varix diagnosed in our Unit and managed with low-dose aspirin (LDA) prophylaxis until the 35th week of gestation. None of the fetuses developed thrombosis of the varix and the neonatal outcomes were good in all the cases.

The trend of VEGF-A and PlGF in pregnant patients: a perspective case-control study on 214 women.

OBJECTIVE: The aim of this study was to measure plasmatic concentrations of vascular endothelial growth factor-A (VEGF-A) and placental growth factor (PIGF) in pregnant women, and to evaluate their relationship with age, hormonal status, gestational age, and different diseases of pregnancy. METHODS: We selected a control group of 163 patients (96 fertile and 67 in menopause) and a group of 214 pregnant patients during the whole gestational period. VEGF-A and PlGF were assayed by ELISA and EIA methods, respectively. Statistical analysis was performed using the Mann-Whitney test. RESULTS: The control group showed mean VEGF-A and PlGF values of 89.87 pg/ml and 10.22 pg/ml, respectively; PlGF showed the highest values in menopausal patients. The group of pregnant patients showed VEGF-A values of 27.05 pg/ml and PlGF values of 231.36 pg/ml respectively, with lower (for the VEGF-A) and higher (for the PlGF) statistical significance. These values were not influenced by biological age, but were related to gestational age: VEGF-A showed a decrease and PlGF an increase particularly after the 20th gestational week. PlGF showed a statistically significant decrease compared to physiological gestation in spontaneous and threatened abortions (p < 0.0001) and in ectopic pregnancies (p < 0.0001), an increase in ultrasound and CTG alterations (p < 0.05), and threatened premature delivery and uterine hypercontractility (p < 0.01); on the other hand VEGF-A showed a statistically significant increase in ectopic pregnancies (p < 0.05). CONCLUSIONS: VEGF-A and PlGF may play a diagnostic and prognostic role in pregnancy. Further studies are required to better understand the meaning of variability of their values.

Correlation between fetal movement revealed in actography and fetal-neonatal well-being: observational study on 3,805 pregnancies followed in a Northern Italy tertiary care hospital.

PURPOSE OF INVESTIGATION: To evaluate the correlation between fetal movement revealed in cardiotocography and fetal-neonatal well-being as well as to assess the value of cardiotocography in our clinical practice. METHODS: Retrospective analysis of 3,805 pregnancies followed at Parma General Hospital. Exclusion criteria were cesarean section, preterm delivery, and stillbirth. We analyzed the predictive power of actography during the dilating and expulsive phases of labor by establishing a correlation between number of fetal movements and our neonatal indexes of well being, i.e., cardiotocographic score, Apgar index and neonatal pH value. Statistical tests used were Fisher's test, chi-square test (X2), Pearson correlation and Spearman Rho; p value was considered significant if it was less than 0.05. RESULTS: We considered 2,389 vaginal deliveries. Analyzing the correlation between fetal movement and cardiotocographic score in the two different phases of labor, the comparison among subpopulations identified by different cardiotocograph scores revealed no statistical difference. CONCLUSION: Cardiotocography is reconfirmed as a good instrument to evaluate neonatal outcome, while actigraphy cannot be used alone to define fetal well-being, mainly due to the inability to standardize assessment of the actographic study.

Incidence of port-site metastasis after laparoscopic management of borderline ovarian tumors: a series of 22 patients.

PURPOSE: The aim of this work was to evaluate the incidence of port-site metastasis in patients undergoing laparoscopy for borderline ovarian carcinoma (BOT). METHODS: Twenty-two patients who underwent laparoscopy from 2004 to 2008 for BOT were evaluated retrospectively. RESULTS: In 15 patients an ultraconservative procedure with enucleation of the annexal neoplasia was carried out, while in five (23%) unilateral salpingo-oophorectomy was performed and in two cases (9%) bilateral salpingo-oophorectomy was done. CONCLUSION: The literature data report few cases of port-site metastasis in BOT patients. Residual cutaneous metastases have been reported to occur within 12 months from the first surgery, generally in association with serous histology. In our analysis, we found 17 out of 22 cases of serous BOT, three mucinous and two endometriod. In no case was cutaneous metastasis revealed after an average of 30 months of follow-up.

Pelvic lymphadenectomy in endometrial cancer: our current experience.

OBJECTIVE: Lymph node involvement is the single most important factor in the prognosis of endometrial cancer, because it is predictive of locoregional and distant metastases. The purpose of our study was to determine whether lymphadenectomy is useful in the surgical staging of endometrial cancer and if it may help establish a more accurate prognosis and reduce the need for postoperative therapy in patients without surgical complications. STUDY DESIGN: We conducted a retrospective study on 55 patients with diagnosis of endometrial cancer. RESULTS: Surgical staging of patients undergoing pelvic lymphadenectomy (47/55) showed that 59.6% of cases (n = 28) had Stage I cancer (IA in 4, IB in 16, IC in 8), 17.02% (n = 8) Stage II (IIA in 3, IIB in 5), 21.2% (n = 10) Stage III (IIIB in 5, IIIC in 5), and 2.1% (n = 1) Stage IVA. In the remaining eight patients with a very high anesthesiologic risk (ASA 4), surgical staging was incomplete because they underwent only node palpation. CONCLUSION: In conclusion, as we wait for the sentinel lymph node technique to demonstrate satisfactory results and be standardized also for endometrial cancer, we believe that surgical lymph node dissection plays a crucial role in debulking this type of cancer. When performed by a good surgical oncology team, it does not entail a significantly increased operative risk.

A perspective study on correlation between HPV DNA and lymph nodes in surgically treated cervical carcinoma patients. Preliminary data.

UNLABELLED: The purpose of this study was to analyze the presence of HPV DNA in lymph nodes in patients with cervical cancer. STUDY DESIGN: A prespective study was performed on a total of 18 patients with cervical cancer in FIGO Stage I-II. The surgical procedure consisted of systematic pelvic lymphadenectomy with removal of the common/external/internal (obturator) iliac lymph node chains, followed by radical hysterectomy depending on the clinical stage, or by Piver's type II radical laparohysterectomy for Stage IA2 carcinoma and Piver's type-III laparohysterectomy for Stage IB or Stage II carcinoma. After removal by a technique not yet described in the literature, the lymph nodes were processed directly in the operating room. HPV DNA testing was done using a cytobrush device. At the end of this operation, the lymph nodes were sent to the hospital's pathologist for metastasis detection. RESULTS: The correlation between a positive HPV DNA test in the cervix and lymph node metastasis was non significant (p < 0.63). By contrast, the correlation between a positive HPV DNA test in the lymph nodes and lymph node metastasis was highly significant (p < 0.005), as was the correlation between positive HPV DNA tests in the cervix and lymph nodes (p < 0.005). Finally, the correlation between disease stage and positive HPV DNA testing in the lymph nodes was also significant (p < 0.05). CONCLUSIONS: In conclusion, the technique that we used for HPV DNA extraction appears safe and reproducible. The results are comparable with, if not better, than those obtained with other techniques reported in the literature. The presence of HPV DNA in the lymph nodes is probably an early indicator of metastasis and as such it could be used as a predictor of relapse. Normally untreated patients who have this marker could then receive adjuvant therapy.

Uterine smooth muscle tumor of uncertain malignant potential: a three-case report.

Based on the degree of cytologic atypia, mitotic activity, and other features, uterine smooth muscle tumors have historically been grouped into two classes: benign leiomyomas and malignant leiomyosarcomas. However, this separation holds true more in principle than in practice because the tumor's biological potential may not always be determined with certainty, complicating diagnosis, and therapy. We report three cases of patients with uterine smooth muscle tumors of uncertain malignant potential. Surgery was radical in two and conservative in one. During the follow-up, one patient developed diffuse lung metastases. The two other patients have not shown any signs of relapse to date. Uterine smooth muscle tumors of uncertain malignant potential may have an unpredictable clinical course and may metastasize to seemingly low-grade neoplasms in distant sites even after several years and even in the absence of important negative prognostic predictors, such as coagulative tumor cell necrosis. At present, no final consensus has been reached on the choice of the best strategy for surgery and adjuvant therapy.

Vaginal versus abdominal hysterectomy in endometrial cancer: a retrospective study in a selective population.

The purpose of this study was to analyze the outcome of vaginal and abdominal hysterectomy for the treatment of early-stage endometrial cancer in a selected group of elder patients. This retrospective study analyzed a total of 154 patients: 113 (group I) underwent vaginal surgery and 41 (group II) underwent laparotomy. In both groups, we investigated the following parameters: intra- and postoperative complications, mean operative time, mean hospital stay, disease-free survival (DFS), overall survival (OS), and time of local or retroperitoneal recurrence. Medically compromised patients were significantly more frequent in the vaginal surgery group (P = 0.005), and the operative duration in this group was significantly shorter (P = 0.01). Intra- and postoperative complications, along with local and distant recurrence, did not show a statistically significant difference in the two groups. Total survival in the two populations, 85% at 5 years, did not reach statistically significant difference either in terms of DFS or in terms of OS. Vaginal surgery compared to traditional abdominal approach is feasible also in patients with high surgical risk; it does not require general anesthesia, abolishes abdominal trauma correlated to laparotomy, and allows a quicker reprise of the bladder and rectal function; therefore, it achieves high eradication rates and low intra- and postoperative morbidity rates.

Preterm delivery and premature rupture of membranes after conization in 80 women. Preliminary data.

AIM: Cervical intraepithelial neoplasia is most frequently in young women in reproductive age. Cold knife conization, laser ablation, laser conization and large loop excision are conservative methods of treatment to remove the transformation zone and preserve the cervical function. Previous studies have shown conflicting results on the outcomes of pregnancy following these therapies that might increase the risk of preterm delivery. The purpose of this study was to evaluate the outcome of pregnancy after conization and its role as predictive risk factor. METHODS: A retrospective study was performed. The study group comprised 80 women who had a conization and that had a subsequent singleton pregnancy. Variables considered includes maternal excision date, surgery procedure, previous surgery treatments, time interval between excisional procedure and subsequent pregnancy; duration and week of pregnancy, mode of delivery, histological grading (no cervical intraepithelial neoplasia [CIN], CIN 1, CIN 2-3) and cone excised depth. RESULTS: In group study 45 women underwent loop electrosurgical excision procedure (LEEP) conization, 32 cold knife conization and 3 laser CO2. The authors found 11 cases of cone tissue depth<1 cm, and remaining one>1 cm. Eight preterm delivery have been reported to data: 5 between 28 and 34 weeks, 2 lower than 28 weeks and 1 between 34 and 37 weeks. CONCLUSION: In these preliminary data the percentage of preterm birth appears as 10% and in range 6-15% evaluated for women not submitted to excisional procedures.

Clinical practice evaluation of combination of atosiban, ritodrine and ketoprofen for inhibiting preterm labor.

AIM: The aim of this study was to compare the efficacy and tolerability of atosiban vs ritodrine administered as single-drug or as combination therapy with the COX inhibitor ketoprofen in the treatment of preterm labor and to investigate how frequent is the need for combination therapy with ketoprofen. METHODS: Ninety-one women with diagnosis of threatened preterm delivery at 24-33 weeks' gestation were enrolled in an observational case-control study. Forty-seven received IV atosiban (6.75 mg initial dose, 300 microg/min loading dose for 3 hours, 100 microg/min maintenance dose for 48-96 hours) and 44 IV ritodrine (0.05-0.3 mg/min). When response to the first drug in the first 2-4 hours was unsatisfactory, ketoprofen was added (100 mg loading dose IV and 100-150 mg maintenance dose every 12 hours) for a maximum of 48 hours. RESULTS: Ketoprofen was added in 51.1% of the atosiban group and 47.7% of the ritodrine group (P 0.75, not statistically significant). The percentages of women non delivered in the two groups were 85.1% vs 81.8% at 48 hours (P=0.44) and 59.6% vs 54.5% at 7 days (P=0.39). One woman treated with atosiban reported transient dyspnea at the administration of the bolus dose; 20.5% of women who received ritodrine developed tachycardia and 4.5% dyspnea (P=0.001). Neonatal mortality and morbidity were comparable in both groups and unrelated to ketoprofen exposure. CONCLUSION: Atosiban efficacy was comparable to ritodrine, but with a superior safety profile. A large proportion of women in both groups required second-line ketoprofen therapy, with comparable neonatal outcomes.

Sertoli cell tumor: a rare case in an elderly patient.

Sertoli-Leydig cell tumors constitute < 1% of ovarian tumors, mostly in young women with virilization; however, not all present endocrine manifestations. A 72-year-old female presented with an abdominal mass and no signs of virilization. Total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy and selective pelvic lymphadenectomy was performed. The pathologic diagnosis was poorly-differentiated sex cord-stromal tumor with Sertoli cells. No adjuvant chemotherapy or radiation was administered. At 12-month follow-up the patient showed no evidence of disease.

Determining the best catheter for sonohysterography.

OBJECTIVE: To compare the characteristics of six different catheters for performing sonohysterography (SHG) to identify those that offer the best compromise between reliability, tolerability, and cost. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Six hundred ten women undergoing SHG. INTERVENTION(S): We performed SHG with six different types of catheters: Foleycath (Wembley Rubber Products, Sepang, Malaysia), Hysca Hysterosalpingography Catheter (GTA International Medical Devices S.A., La Caleta D.N., Dominican Republic), H/S Catheter Set (Ackrad Laboratories, Cranford, NJ), PBN Balloon Hystero-Salpingography Catheter (PBN Medicals, Stenloese, Denmark), ZUI-2.0 Catheter (Zinnanti Uterine Injection; BEI Medical System International, Gembloux, Belgium), and Goldstein Catheter (Cook, Spencer, IN). MAIN OUTCOME MEASURE(S): We assessed the reliability, the physician's ease of use, the time requested for the insertion of the catheter, the volume of contrast medium used, the tolerability for the patients, and the cost of the catheters. RESULT(S): In 568 (93%) correctly performed procedures, no statistically significant differences were found among the catheters. The Foleycath was the most difficult for the physician to use and required significantly more time to position correctly. The Goldstein catheter was the best tolerated by the patients. The Foleycath was the cheapest whereas the PBN Balloon was the most expensive. CONCLUSION(S): The choice of the catheter must be targeted to achieving a good balance between tolerability for the patients, efficacy, cost, and the personal preference of the operator.

A prospective study of fifty-three consecutive calcium heparin treated pregnancies in patients with antiphospholipid antibody-related fetal loss.

OBJECTIVE: In this study the efficacy and safety of calcium heparin administered alone for the prevention of fetal loss related to antiphospholipid antibodies (aPL) were evaluated. METHODS: Fifty-three consecutively ascertained pregnancies were followed in 53 patients who had a history of at least 2 consecutive miscarriages during the first trimester and/or 1 fetal death during the second or third trimesters. In addition, all patients had at least 2 positive aPL tests more than 8 weeks apart before pregnancy, or a positive aPL test at the beginning of pregnancy. They were treated with calcium heparin alone, self-administered subcutaneously 3 times daily at dosages varying between 15,000 and 37,500 units. Treatment was started soon after a sonogram demonstrated a live embryo and was continued throughout pregnancy until the end of puerperium. RESULTS: All pregnancies terminated favourably between the 25th and 40th weeks (mean +/- SD: 36.69 +/- 2.91) with planned caesarean section in 27 cases and vaginal delivery in 26. Delivery was brought forward due to maternal and/or fetal complications in 18 cases (33.96%). Calcium heparin was associated with intravenous immunoglobulin therapy in 2 patients with fetal problems unresponsive to anticoagulant treatment alone. The newborns, 30 females and 25 males, had a mean birth weight of 2,828.3 g +/- 706.5 and a mean Apgar score at 5 minutes of 9.60 +/- 0.68. No malformations were observed. Thirty of the 37 examined placentas (81.08%) showed signs of thrombotic events. Only minor side effects of calcium heparin were observed during treatment. CONCLUSION: Our study suggests that calcium heparin administered alone using the dosages and timing described here is effective in achieving the delivery of viable infants, and that it is well tolerated.

Placental and fetal pulsatility indices in gestational diabetes mellitus.

OBJECTIVE: To assess the usefulness of placental and fetal Doppler velocimetry in the surveillance of gestational diabetes mellitus (GDM). STUDY DESIGN: We studied 89 patients with GDM. All fetuses underwent umbilical, fetal descending thoracic aorta and fetal middle cerebral artery pulsatility index (PI) assessment. Doppler results were not used for management. We correlated PI with route of delivery and with the following perinatal complications: small size for gestational age, cesarean section (CS) for acute fetal distress (AFD), respiratory distress syndrome, hyperbilirubinemia, hypocalcemia, hypoglycemia, macrosomia and stay in a neonatal intensive care unit. RESULTS: Seventy-seven patients (87%) had normal Doppler measurements, while 12 (13%) showed one or more abnormal measurements. The greatest incidence of CS for AFD (42% vs. 16%, P < .001), as well as neonatal hyperbilirubinemia (25% vs. 10%, P < .001) and hypoglycemia (25% vs. 5%, P < .001) was reported among the women with abnormal Doppler measurements. CONCLUSION: Fetal placental hemodynamics are normal in most cases of GDM. In a small percentage of cases we observed abnormal fetal placental PI associated with a higher incidence of perinatal complications. Hence, the finding of abnormal PI must induce the physician to carry out more intensive obstetric care of women with GDM.

ER-D5 antigen immune radiometric assay in breast cancer research.

A trial of 185 breast cancer tissues has been developed to characterize receptor negative tumors. We observed the ER-D5-Ag availability to recognize the hormone sensitivity inside the receptor-negative patient groups. In Pre-M ER--ve patients, we observed 26.9%-29.4% of D5+ve cases and in PgR--ve 50% of D5+ve cases. In Post-M ER--ve patients, we observed 31.2%-36.5% of D5+ve cases and in PgR--ve 53.2% of D5+ve cases. The reproducibility of our results suggests the relevance of an additional investigation to characterize the hormonal sensitivity of receptor-negative breast cancer tissues.

Original technique in mammary echotomography.

The Authors report a new technique of employing mammary echotomography. The patient, in prone position, is tested with her breasts immersed in water, using a linear array of 2.8 MHz.

Estrogen and progesterone receptors status in the prediction of response of breast cancer to endocrine therapy (preliminary report).

The authors selected 263 ER cases and 224 ER/PgR cases for receptor status analysis from 1548 breast cancer tissues assayed. 30 Operating-theatres address their breast frozen specimens at our laboratory and thanks to this wide cooperation, we can perform the statistical analysis and relationship with very good reliability. In our experience we observed that the response to hormonal therapy is present in 50% of the cases containing ER concentrations up to 100 fmol/mg of proteins, and in 74% of the cases with ER concentrations more of 100 fmol/mg of proteins. Considering the presence of both receptors (ER+/PgR+) we observed the response rate to hormonal treatment in 76% of the cases while in 9% of the cases the status is ER/PgR negative. The cases classified ER negative and PgR positive demonstrated a response rate of 28%, 7 out of 26 cases ER+/PgR- responded to hormonal therapy. In this last situation, in addition to experienced hypotheses, the authors believe it is important to examine sonographically the ovaries, because the presence of a functional ovarian cyst could influence the saturation of receptorial sites.