Search

Study Objective: Several studies have been published on hysteroscopic treatment of cesarean scar defect using the 26 Fr resectoscope. This study compared the effects of the 26 Fr resectoscope with those of the 16 Fr mini-resectoscope in terms of efficacy, safety profile, and peri- and postoperative complications. Design: A prospective cohort study. Setting: Tertiary care university hospital (S. Orsola–Malpighi, Bologna, Italy). Patients: Three hundred and nine women having symptoms and with a cesarean scar defect diagnosis were divided into 2 groups according to a temporal criterion: from March 2012 to March 2015, 155 consecutive women (control group) underwent isthmoplasty with the 26 Fr resectoscope (Karl Storz, Tuttlingen, Germany), whereas from April 2015 to March 2018, 154 consecutive women (study group) underwent isthmoplasty with the 16 Fr mini-resectoscope (Gubbini system, Tontarra Medizintechnik, Tuttlingen, Germany). Interventions: One hundred and fifty-five women (control group) underwent isthmoplasty with the 26 Fr resectoscope, and 154 women (study group) underwent isthmoplasty with the 16 Fr mini-resectoscope. The so-called “channel-like” 360° endocervical resection technique was applied. Measurements and Main Results: The isthmoplasty time with the 2 resectoscopes, excluding cervical dilatation, was similar (p =. 25), whereas the overall surgical time was shorter in the case of the mini-resectoscope. The use of the 16 Fr mini-resectoscope was significantly associated with a reduced volume of distension medium used (p

Study Objective To compare the costs of hysteroscopic polypectomy using mechanical and electrosurgical systems in the hospital operating room and an office-based setting. Design Retrospective cohort study (Canadian Task Force classification II-2). Setting Tertiary referral hospital and center for gynecologic care. Patients Seven hundred and fifty-four women who underwent endometrial polypectomy between January 20, 2015, and April 27, 2016. Interventions Hysteroscopic endometrial polypectomy performed in the same-day hospital setting or office setting using one of the following: bipolar electrode, loop electrode, mechanical device, or hysteroscopic tissue removal system. Measurements and Main Results The various costs associated with the 2 clinical settings at Palagi Hospital, Florence, Italy were compiled, and a direct cost comparison was made using an activity-based cost-management system. The costs for using reusable loop electrode resection-16 or loop electrode resection-26 were significantly less expensive than using disposable loop electrode resection-27, the tissue removal system, or bipolar electrode resection (p = .0002). Total hospital costs for polypectomy with all systems were significantly less expensive in an office setting compared with same-day surgery in the hospital setting (p = .0001). Office-based hysteroscopic tissue removal was associated with shorter operative time compared with the other procedures (p = .0002) Conclusion The total cost of hysteroscopic polypectomy is markedly higher when using disposable equipment compared with reusable equipment, both in the hospital operating room and the office setting. Same-day hospital or office-based surgery with reusable loop electrode resection is the most cost-effective approach in each settings, but requires experienced surgeons. Finally, the shorter surgical time should be taken into consideration for patients undergoing vaginal polypectomy in the office setting, owing more to patient comfort than to cost savings.

STUDY OBJECTIVE To compare the effectiveness and safety of different techniques of hysteroscopic polypectomy. DESIGN Multicenter, prospective observational trial (Canadian Task Force classification II-2). SETTING Nineteen Italian gynecologic departments (university-affiliated or public hospitals). PATIENTS Consecutive patients suffering from endometrial polyps (EPs). INTERVENTIONS Hysteroscopic polypectomy, as performed through different techniques. MEASUREMENTS AND MAIN RESULTS Included in the study were 1404 patients (with 1825 EPs). The setting was an ambulatory care unit in 40.38% of the cases (567 women), of whom 97.7% (554) did not require analgesia/anesthesia. In the remaining 59.62% of women (837 women), the procedures were performed in an operating room under mild sedation, local or general anesthesia. Minor complications occurred in 32 patients (2.27%), without significant differences between the techniques used (p = ns). Uterine perforation occurred in 14 cases, all performed in the operating room with some kind of anesthesia, only 1 with a vaginoscopic technique and the remaining during blind dilatation (odds ratio [OR], 19.98; 95% confidence interval [CI], 1.19-335.79; p = .04). An incomplete removal of EPs was documented in 39 patients. Logistic regression analysis showed that a higher risk of residual EPs was associated with the use of a fiber-based 3.5-mm hysteroscope (OR, 6.78; 95% CI, 2.97-15.52; p

Study Objective To estimate the incidence of infection after diagnostic and operative hysteroscopic procedures performed in an in-office setting with different distension media (saline solution or CO2). Design Prospective, multicenter, observational study (Canadian Task Force classification II-2). Setting Tertiary women's health centers. Patients A total of 42,934 women who underwent hysteroscopy between 2015 and 2017. Interventions Of the 42,934 patients evaluated, 34,248 underwent a diagnostic intervention and 8686 underwent an operative intervention; 17,973 procedures used CO2 and 24,961 used saline solution as a distension medium. Patients were contacted after the procedure to record postprocedure symptoms suggestive of infection, including 2 or more of the following signs occurring within the 3 weeks after hysteroscopy: fever; lower abdominal pain; uterine, adnexal, or cervical motion tenderness; purulent leukorrhea; vaginal discharge or itchiness; and dysuria. Vaginal culture, clinical evaluation, transvaginal ultrasound, and histological evaluation were completed to evaluate symptoms. Measurements and Main Results Operative hysteroscopies comprised polypectomies (n = 7125; 82.0%), metroplasty (n = 731; 15.0%), myomectomy (n = 378; 7.8%), and tubal sterilization (n = 194; 4.0%). Twenty-five of the 42,934 patients (0.06%) exhibited symptoms of infection, including 24 patients (96%) with fever, 11 (45.8%) with fever as a single symptom, 7 (29.2%) with fever with pelvic pain, and 10 (41.7%) with fever with dysuria. In 5 patients with fever and pelvic pain, clinical examination and transvaginal ultrasound revealed monolateral or bilateral tubo-ovarian abscess. In these patients, histological examination from surgical specimens revealed the presence of endometriotic lesions. Conclusion The present study suggests that routine antibiotic prophylaxis is not necessary before hysteroscopy because the prevalence of infections following in-office hysteroscopy is low (0.06%).

Objective Polypectomy under hysteroscopic guidance is the treatment of choice for most endometrial polyps, but mechanical or electrical effects at the time of surgery may result in artifactual displacement of tissue with obvious resultant diagnostic problems. The purpose of this study was to record qualitative and quantitative histopathological artifacts and to assess differences between artifacts found in specimens obtained by different surgical polypectomy techniques. Study design During the period from November 2012 to March 2013, 90 retrospective consecutive polyp histopathological slides and their reports were identified for this study. Initially reported slides were reviewed blind by two histopathologists, who were not provided with any surgical details. The issued reports and those of the reviewing pathologists were then compared. Results Of the 90 reviewed polyp slides, there was complete agreement on the initial issued report in all cases. Conclusions Removal of endometrial polyps in an office setting using mechanical instruments, bipolar electrode or a hysteroscopic morcellator provides adequate tissue for histological diagnosis, and there is no difference between these three techniques for adequacy of histological examination, despite the effects of thermal injury or tissue fragmentation.

S100B protein has been recently proposed as a consolidated marker of brain damage and death in adult, children and newborn patients. The present study evaluates whether the longitudinal measurement of S100B at different perioperative time-points may be a useful tool to identify the occurrence of perioperative early death in congenital heart disease (CHD) newborns. We conducted a case-control study in 88 CHD infants, without pre-existing neurological disorders or other co-morbidities, of whom 22 were complicated by perioperative death in the first week from surgery. Control group was composed by 66 uncomplicated CHD infants matched for age at surgical procedure. Blood samples were drawn at five predetermined timepoints before during and after surgery. In all CHD children, S100B levels showed a pattern characterized by a significant increase in protein's concentration from hospital admission up to 24-h after procedure reaching their maximum peak (P

We did a double-blind, randomized, placebo-controlled study to assess the incidence of infectious complications and the protective effect of antibiotic administration during operative hysteroscopic procedures in an office setting. A total of 1046 consecutively enrolled women with intrauterine lesions were randomly allocated to the reference group (523 patients administered with 1 g of cefazolin intramuscularly) and the study group (523 patients administered with 10 mL of isotonic sodium chloride solution), and treated in office setting by operative hysteroscopy for endometrial polypectomy, uterine septa, submucosal myomas, and intrauterine adhesions. The primary outcome measure was the computation of difference between groups in postsurgical infectious complications occurring in the 5 days after the procedures. The time spent in performing the various procedures did not differ significantly (P > .05) between the groups. With respect to the overall rate of postsurgical infection, we found that 12 (1.15%) of 1046 patients referred with symptoms related to infective complications, 7 (1.3% of 523 women) in the study--untreated--group and 5 (1.0% of 523 women) in the reference group. Such incidences did not differ significantly between the groups (P > .05). Antibiotics were prescribed in all cases of postsurgical infection and the infective process resolved in few days. None of these patients developed serious infections with adnexal involvement, as confirmed by clinical and ultrasounds evaluation. The results of the current study would support the American College of Obstetricians and Gynecologists recommendation not to prescribe routine antibiotic administration in the case of hysteroscopic surgery.

background: Activin A is a growth factor, produced by the endometrium, whose actions are modulated by the binding protein follistatin. Both proteins are detectable in the peripheral serum and their concentrations may be increased in women with endometriosis. The present study was designed to evaluate whether serum levels of activin A and follistatin are altered, and therefore have a potential diagnostic value, in women with peritoneal, ovarian and deep infiltrating endometriosis. methods: We performed a multicenter controlled study evaluating simultaneously serum activin A and follistatin concentrations in women with and without endometriosis. Women with endometriosis (n ¼ 139) were subdivided into three groups: peritoneal endometriosis (n ¼ 28); ovarian endometrioma (n ¼ 61) and deep infiltrating endometriosis (n ¼ 50). The control group (n ¼ 75) consisted of healthy women with regular menstrual cycles. Blood samples were collected from a peripheral vein and assayed for activin A and follistatin using commercially available enzyme immunoassay kits. results: The ovarian endometrioma group had serum activin A levels significantly higher than healthy controls (0.22+ 0.01 ng/ml versus 0.17+ 0.01 ng/ml, P , 0.01). None of the endometriosis groups had serum follistatin levels which were significantly altered compared with healthy controls; however, levels found in the endometrioma group (2.34+ 0.32 ng/ml) were higher than that in the deep endometriosis group (1.50+ 0.17 ng/ml, P , 0.05). The area under the receiver operating characteristic curve of activin A was 0.700 (95% confidence interval: 0.605 –0.794), while that of follistatin was 0.620 (95% confidence interval: 0.510–0.730) for the diagnosis of ovarian endometrioma. The combination of both markers into a duo marker index did not improve significantly their diagnostic accuracy. conclusions: The present study demonstrated that serum activin A and follistatin are not significantly altered in peritoneal or deep infiltrating endometriosis and have limited diagnostic accuracy in the diagnosis of ovarian endometrioma.

Women with endometriosis have altered endometrial function. CRH and urocortin (Ucn) are neuropeptides produced by human endometrium and modulate endometrial decidualization.To evaluate endometrial mRNA expression of CRH and Ucn, their role in in vitro decidualization of cultured human endometrial stromal cells (HESCs) in patients with endometriosis, and the role of CRH receptors (CHR-Rs).Obstetrics and Gynecology, University of Siena.Endometrial specimens were obtained from patients with and without endometriosis.Endometrial biopsy obtained at both phases of menstrual cycle. In vitro decidualization of HESCs collected from endometriosis or control was done in the presence of CRH, Ucn, or CRH receptor type 1 (CRH-R1, antalarmin) or type 2 (CRH-R2, astressin 2b) antagonists.Endometrial mRNA expression of CRH and Ucn during endometrial cycle; prolactin, CRH-R1, and CRH-R2 mRNA expression during in vitro decidualization.In healthy women CRH and Ucn expression were significantly higher (P0.05) in secretory than in proliferative phase; no differences were observed in endometriotic women. During in vitro decidualization, prolactin mRNA expression and release in endometriosis was lower than in control (P0.001). CRH and Ucn were able to significantly increase (P0.01) prolactin release only in control group; moreover, in this group antalarmin reduced prolactin release (P0.01). CRH-R1 mRNA expression increased during in vitro decidualization of HESCs in control (P0.01) but not in endometriosis.Women with endometriosis show an impaired endometrial expression of CRH and Ucn mRNA, and these neuropeptides are no more active in modulating the in vitro decidualization of HESCs, associated with a reduced expression of CRH-R1 mRNA.

To measure serum activin A levels together with progesterone and hCG, in women with overt clinical signs and symptoms of ectopic pregnancy (EP) and, in gestational age-matched intrauterine pregnancy (IUP).Retrospective case-control study.Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy.The study group was composed by 30 women with an EP; the control group was composed by 30 women with a sonographic evidence of a single spontaneous IUP.Clinical examination; transvaginal ultrasound scan; hCG, progesterone and activin-A measurements; laparoscopy; uterine curettage; histological examination.Pregnancy outcome; sensitivity and specificity of hCG, progesterone, and activin A for EP.Serum hCG levels did not differ significantly between tubal EP and IUP, while P concentrations were significantly (P0.001) lower in tubal EP than IUP. Serum levels of activin A were significantly (P0.0001) lower in tubal EP than in IUP and, at the cutoff 0.43 ng/mL achieved a sensitivity of 96.7% and a specificity of 100% for EP.Activin A secretion in EP is reduced and measurement of its serum levels may have the potential clinical advantage to signal the presence of EP.

Objective: To compare two distension media, carbon dioxide (CO2) and saline, with regards to patient discomfort and the adequacy of the panoramic view in diagnostic hysteroscopy by the vaginoscopic approach. Design: Randomized prospective study. Setting: Tertiary referral centers for gynecologic care. Patient(s): 264 patients randomly allocated to two groups: CO2(132 women) and normal saline (132 women). Intervention(s): Office hysteroscopy performed with a forward-oblique 30° telescope (total diameter 5.1 mm) and CO2as the distension medium or with a forward-oblique 30° telescope (final diameter 5.1 mm) and saline solution as the distension medium. Main Outcome Measure(s): Global operative time, pain experienced by patients using a visual analogue scale (VAS), severity of the pain (VAS), incidence of collateral effects (shoulder-tip pain, nausea, or dizziness), degree of difficulty, and view (VAS). Result(s): Pelvic discomfort was comparable between groups, without statistically significant differences in intensity or degree of difficulty. However, the visual quality was statistically significantly higher when hysteroscopy was performed with CO2as the distension medium. Conclusion(s): No relevant difference in pain or technical difficulty was found between the two distension media, but CO2was associated with better quality visualization. Copyright © 2010 American Society for Reproductive Medicine, Published by Elsevier Inc.

Cerebral monitoring constitutes an emerging issue in perinatal medicine. Near Infrared Spectroscopy (NIRS) monitors brain oxygenation status in sick infants although data in healthy infants are lacking. The present study investigates whether NIRS parameters change according to gestational age and correlate with S100B protein. We recruited 64 healthy newborns (weeks' gestation: 30-42 wks) in which we performed in the first 6-hours after birth routine clinical, radiological and laboratory variables, cerebral oxygen saturation (rSO2), fractional cerebral tissue oxygen extraction (FTOE) values and S100B urine assessment. rSO2 and FTOE correlated (R=-0.73; R=0.51; P less than 0.01, for both) with gestational age. Highest rSO2 and the lowest FTOE peaks (P less than 0.001) were found at 30-33 wks. From 34 wks onwards, rSO2 progressively decreased and FTOE increased reaching their lower dip/peak (P less than 0.001) at 38-39 weeks. A significant correlation between S100B and NIRS parameters (rSO2: r=0.77; FTOE: r=-0.69; P less than 0.01) has been found. The present study shows that NIRS parameters and S100B protein correlation may be of help in brain function monitoring.

The clinical relevance of antibodies anti-protein C and anti-protein S in pregnancy remains controversial. We evaluate whether, in the absence of thrombophilic diseases, maternal plasma levels of antibodies (IgM and IgG) change during pregnancy and in preeclampsia (PE), with and without superimposed fetal growth restriction (FGR).A retrospective cohort of 50 women with PE (n = 30) and PE + FGR (n = 20) and 70 controls [first trimester (n = 20); second trimester (n = 20); third trimester (n = 30)] were enrolled in the study.In healthy pregnant women, plasma levels of anti-protein C antibodies decreased from first to third trimester and were below the range of positivity. IgM anti-protein-C and anti-protein-S were significantly higher (P0.001) in both PE (23.88 +/- 10.65 MoM and 43.90 +/- 20.45 MoM, respectively) and PE + FGR group (15.95 +/- 12.62 MoM and 36.02 +/- 27.43 MoM, respectively) than in control group (2.23 +/- 3.23 MoM and 1.68 +/- 4.075 MoM, respectively), in the presence of unchanged levels of IgG isotype.In this study, we first found that the production of anti-protein C and anti-protein S antibodies decreases throughout healthy pregnancies, while they circulate in high levels in women with PE and PE/FGR.

Near Infrared Spectroscopy (NIRS) is an emerging technique for brain oxygenation monitoring in newborns complicated by acute and chronic hypoxia. However, data regarding cerebral oxygenation normal values are still lacking and matter of debate. Therefore, we investigate whether NIRS parameters in healthy preterm/term infants are gestational age and delivery modalities dependent and correlate with standard monitoring parameters. From January to December 2007, 100 healthy newborns with gestational age from 30 to 42 weeks' gestation were evaluated. Routine laboratory variables, daily clinical and neurological evaluation and ultrasound imaging were performed. The regional cerebral oxygen saturation (rSO2) and fractional cerebral tissue oxygen extraction (FTOE) were measured by NIRS in the first 6-hours after birth. Data were recorded by MetaVision ICU X-Edition software and analyzed by SPSS statistical package. rSO2 and FTOE correlated (R=-0.77; R=0.41; P

Activin A is a dimeric protein that regulates endometrial functions by signaling at its receptors, namely type I (ActRI) and type II (ActRII). Nodal is an activin competitor that requires the coreceptor cripto to assemble its signaling pathway through ActRI and ActRII. In the current study, we evaluated the expression of activin A, ActRII, nodal, and cripto in eutopic and ectopic endometrium collected from women with ovarian endometrioma (n = 15) and in eutopic endometrium of healthy participants (n = 15). Eutopic endometrial samples were evaluated according to the stage of menstrual cycle. Total RNA was extracted from tissue homogenates and analyzed by real-time polymerase chain reaction (PCR). Activin A messenger RNA (mRNA) expression in eutopic endometrium of patients with endometriosis was significantly higher than in controls (P < .001) with a 10.2-fold and 7.3-fold increase in the proliferative and secretory phases, respectively. ActRII and nodal mRNA expression were found to be similar in patients with and without endometriosis, while cripto mRNA was markedly lower in eutopic (fold change = 0.03 at proliferative phase, P < .001) and ectopic endometrium (fold change = 0.14, P < .001) of women with endometriosis compared with eutopic endometrium from healthy controls. In conclusion, the altered endometrial expression of activin A and cripto during the menstrual cycle and the differences observed in the endometriotic tissue support the involvement of the activin system in endometrial changes of women with endometriosis.

Follistatin is an activin-binding protein produced by several tissues, including endometrium and endometriotic implants. We aimed to quantify follistatin in patients with ovarian endometriosis and investigate its value as a diagnostic marker.Women undergoing laparoscopic excision of ovarian endometrioma (n = 52) or other benign ovarian cysts (n = 52) were studied, plus women with non-ovarian endometriosis (n = 11) and healthy controls (n = 27). Serum was collected from all subjects, and peritoneal and cystic fluid from a subset with endometrioma. Follistatin was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of follistatin to detect endometrioma was evaluated by receiver operating characteristic (ROC) curve and compared with cancer antigen (CA)-125.Serum follistatin was increased in women with ovarian endometrioma (2080 +/- 94 pg/ml) compared with controls (545 +/- 49 pg/ml, P0.001), other benign ovarian cysts (795 +/- 60 pg/ml, P0.001) or non-ovarian endometriosis (1271 +/- 115 pg/ml, P0.001). Cystic fluid showed a higher concentration of follistatin (9850 +/- 4461 pg/ml) than peritoneal fluid (1885 +/- 261 pg/ml, P0.001) and serum (P0.001). Follistatin levels detected 48/52 cases of endometrioma (92% sensitivity) at 1433 pg/ml cut-off, corresponding to 92% specificity. CA-125 detected only 44% of endometriomas with 90% specificity. ROC curve comparison showed follistatin was more accurate than CA-125 to discriminate women with endometrioma either from controls or women with other benign ovarian cysts (P0.0001).Serum follistatin is increased in women with endometriosis and allows clear distinction between endometrioma and other benign ovarian cysts. Follistatin has the sensitivity and specificity to become a useful clinical marker of ovarian endometrioma.

OBJECTIVE: The pathogenesis of hot flushes involves several brain neurotransmitter systems, and changes in serotonin turnover have been hypothesized. Veralipride is an anti-dopaminergic agent that relieves hot flushes and putatively also modulates serotonergic neurons. To further elucidate this relationship, in the present study we evaluated whether administration of veralipride for relief of hot flushes is able to affect serum levels of the serotonin precursor tryptophan in postmenopausal women.METHODS: Twenty-four postmenopausal women were randomly assigned to receive veralipride (100 mg/day) or similar placebo tablets for 3 months (n = 12 per group). Free tryptophan and total tryptophan (free + protein-bound) levels were assayed before and monthly by high pressure liquid chromatography. Data were analyzed with repeated measures ANOVA and Student-Newman-Keuls post hoc test.RESULTS: Relief of hot-flushes was achieved with complete suppression of symptoms after veralipride, but not placebo, treatment. In the veralipride group, total tryptophan levels significantly (p < 0.05) decreased from baseline (11.2 +/- 0.4 microg/ml) to 3 months (8.0 +/- 0.3 microg/ml), as well as free tryptophan concentrations (baseline 2.1 +/- 0.1 microg/ml; after 3 months 1.3 +/- 0.1 microg/ml; p < 0.05). No changes were recorded in the placebo group.CONCLUSION: Women treated with veralipride for relief of menopausal symptoms show a decrease in serum levels of serotonin precursors, suggesting that the brain serotonergic system may be involved in the pathogenesis of postmenopausal vasomotor symptoms.

Kisspeptin, a placental polypeptide secreted throughout pregnancy, is suggested to play a role at parturition. Here we evaluated whether its placental mRNA expression and maternal/fetal plasma levels change at term and preterm delivery, and its effect on oxytocin secretion from placental explants. Samples were collected from 40 women with singleton pregnancies who underwent elective cesarean section at term (TNL), term vaginal delivery (TD), and preterm vaginal delivery (PTD). Plasma Kisspeptin and oxytocin levels were assessed by ELISA; placental mRNA expression by Real-time quantitative RT-PCR analysis. Placental expression was significantly (P < 0.0001) higher in PTD than TNL and TD and significantly (P < 0.001) higher in TD than TNL. Maternal/fetal plasma concentrations did not differ among the groups, and maternal were significantly higher than fetal levels (P < 0.05). In placental explants increasing doses of kisspeptin did not modify oxytocin secretion. In conclusion, labor is associated with increased placental KiSS-1 expression without changes in maternal/fetal circulation.

Neurokinin B (NKB) is a neuropeptide belonging to the family of tachykinins-related peptides that elicits contractility of human myometrial strips in vitro. The present study evaluates whether placental mRNA and peptide expression of NKB change in women at preterm labor.A group of 26 women with singleton pregnancies were enrolled in the study. Placental tissue specimens were collected from pregnant women delivering after elective cesarean section, after labor at term, or after preterm labor. Changes in placental NKB mRNA and protein expression were evaluated by real-time quantitative RT-PCR analysis and by immunofluorescence respectively.Placental mRNA expression of NKB was significantly higher after term and preterm labor (P0.001) than cesarean section, and highest after preterm labor. Immunofluorescent staining in placentas from preterm or term labor was more intense than after cesarean section (P0.001). In particular, NKB protein expression was higher in placentas collected after preterm labor than those collected after term labor.Neurokinin B mRNA and protein are highly expressed in placenta at term and preterm labor; thus, the involvement of this neuropeptide in the events cascade leading to parturition may be suggested.

OBJECTIVE: Urocortin is a neuropeptide, member of the corticotropin-releasing hormone family, that is produced by the human endometrium. Ovarian endometrioma is a prevalent gynecologic disorder still lacking specific serum markers. In the present study we measured systemic levels of urocortin to assess the diagnostic performance of its determination in distinguishing endometriomas from other benign ovarian cysts. METHODS: Plasma urocortin was measured by radioimmunoassay in women with ovarian endometrioma (n40) and in women with benign, nonendometriotic ovarian cysts (n40). The diagnostic accuracy of urocortin measurement was evaluated by receiver operating characteristic curve and compared with the standard marker, CA 125. To support the local origin of the peptide, we also evaluated its localization in endometriomas by immunohistochemistry and its concentrations in cyst fluid and peritoneal fluid of 12 women with endometrioma. RESULTS: Plasma urocortin levels were twice as high in women with endometrioma (median 49 pg/mL, interquartile range 41–63 pg/mL) than in the control group (19 [15–23] pg/mL, P

Objective: Placental corticotropin-releasing factor (CRF) affects myometrial contractility and the secretion of several uterotonins such as prostaglandins (PGs); however, the activity of CRF is counteracted by CRF-binding protein (CRF-BP). At term and pre-term labor, CRF levels in maternal plasma are highest whereas those of CRF-BP are falling, and the cause of this fall is unknown. Thus, in this study, we investigated the effect of PG administration for labor induction on maternal plasma CRF and CRF-BP concentrations. Design: Maternal plasma CRF and CRF-BP levels were assayed before and after (2 h later) induction of labor by intracervical administration of prostaglandin E2 (PGE2), and at delivery in a group of healthy post-term pregnancies (n=18). Controls were women at term out of labor (n=22), who subsequently progressed to deliver a healthy singleton baby. Methods: CRF was measured by two-site immunoradiometric assay, and CRF-BP was assayed by radioimmunoassay. Results: Maternal plasma CRF levels were significantly (PP2 were sufficient to increase maternal plasma CRF levels at delivery (P2 significantly decreased maternal plasma CRF-BP levels at delivery (P2 significantly reduced CRF-BP concentrations both after 2 h (PP Conclusions: In the light of the well-known stimulation of prostaglandin release by CRF, these data suggest a positive feedback effect of PGE2 on maternal CRF release during induced labor.

Objective To evaluate the messenger RNA (mRNA) expression and peptide localization of follistatin and follistatin-like protein (FLRG) in ovarian endometriosis, compared to healthy human endometrium. Design Samples of ovarian endometriotic and healthy endometrial tissues were processed by semiquantitative reverse transcript ase-polymerase chain reaction and immunohistochemistry. Setting Academic health centers in Siena, Italy, and Belo Horizonte, Brazil. Patient(s) Women with endometrioma who underwent laparoscopic excision of ovarian endometriotic cysts (n = 16), and healthy, nonpregnant women (n = 18, control group). Main Outcome Measure(s) Immunostaining and relative quantification of follistatin and FLRG mRNA in ovarian endometriosis and eutopic endometrium. Result(s) Both ovarian endometriosis and healthy endometrium expressed and localized follistatin and FLRG. In endometriotic glands, follistatin immunostaining was homogeneously distributed throughout the cytoplasm of the epithelial cells, contrasting with normal eutopic endometrium, where follistatin expression was focal, irregular, and confined to the basal side of the glands. Follistatin-like protein was immunolocalized in the nuclei of both glandular epithelial cells and stromal cells, with less intense staining in endometriotic samples. The relative intensity of follistatin and FLRG immunostaining was significantly higher and lower, respectively, in endometriosis than in controls. The expression of follistatin mRNA was higher, while that of FLRG mRNA was lower, in ovarian endometriosis than in healthy eutopic endometrium. Conclusion(s) Ovarian endometriotic lesions show a deranged expression of FLRG and follistatin, which are activin A-binding proteins. This may result in an altered effect of activin A on angiogenesis and/or endometrial differentiation.

Background The vaginoscopic approach for hysteroscopy allows detailed endoscopic evaluation of the vaginal walls, fornices, and exocervix. Objectives To review the feasibility and efficacy of vaginohysteroscopy in the diagnosis and treatment of vaginal lesions. Search strategy A systematic review was performed of PubMed/Medline, Embase, Google Scholar, and the Cochrane Database to identify papers published in English. The search terms were “hysteroscopy,” “vaginoscopy,” “vagino-hysteroscopy,” and “vaginal lesion.” The last review was performed on January 31, 2015. Selection criteria Studies in which the diagnosis and treatment of vaginal lesions used the vaginoscopic approach and hysteroscopic instrumentation were reviewed. Data collection and analysis Data were extracted from the identified studies and then analyzed. Main results Thirteen studies were reviewed. Eleven described one case; one reported observations from two patients, and one study reported a case series. All vaginohysteroscopies reported were performed successfully and without significant complications. Conclusions Vaginohysteroscopy is an easy way to gain access to the cervical canal and an important tool with which to diagnose and treat vaginal lesions.

We aimed to evaluate whether nerve fibers are present in the endometrial layer of patients submitted to office hysteroscopy and their potential contribution to the pathogenesis of pain during that procedure. Through a prospective case-control study performed in tertiary centers for women's health, endometrium samples were collected during operative office hysteroscopy from 198 cycling women who previously underwent laparoscopy and/or magnetic resonance imaging investigation for infertility assessment. Samples were classified according to the degree of the pain patients experienced and scored from values ranging from 0 (absence of discomfort/pain) to 10 (intolerable pain) on a 10-cm visual analog scale (VAS). The presence of nerve fiber markers (S100, NSE, SP, VIP, NPY, NKA, NKB, NKR1, NKR2, and NKR3) in the endometrium was also evaluated by morphologic and immunohistochemical analyses. We found that S-100, NSE, NKR1, NK-A, NK-B, VIP, and NPY, were immunolocalized in samples of endometrium, in significantly (P < .01, for all) higher levels in samples collected from patients with VAS score > 5 (group A) than ≤ 5 (group B) and significantly (P < .0001 for all) positively correlated with VAS levels. A statistically significant (P = .018) higher prevalence of endometriosis and/or adenomyosis was depicted in patients of group A than group B. Data from the present study led us to conclude that nerve fibers are expressed at the level of the functional layer of the endometrium and may contribute to pain generation during office hysteroscopy, mainly in women affected by endometriosis and adenomyosis.

Urocortin II and urocortin III are recently identified corticotropin-releasing factor-related neuropeptides, and their endometrial expression throughout the menstrual cycle and in early pregnancy was evaluated in the present study by semiquantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. The endometrial expression of urocortin II mRNA was significantly (P.01) higher in the early proliferative phase of the menstrual cycle than in other phases and maternal decidua (MD), whereas that of urocortin III mRNA was higher (P.01) in MD than in all other endometrial samples. Both peptides were immunolocalized in epithelial, stromal, and endothelial cells.

OBJECTIVE We evaluated maternal and fetal plasma levels and placental mRNA expression of urocortin, a placental vasoactive neuropeptide, in singleton pregnancies (n = 70) complicated by hypertensive disorders classified as gestational hypertension (n = 36), pre-eclampsia (n = 19), and pre-eclampsia complicated by intrauterine growth restriction (PE/IUGR, n = 15), and in 70 healthy normotensive singleton pregnancies. METHODS Plasma levels were assayed by radioimmunoassay, fetal biometry by ultrasound scans, utero-placental and fetal perfusion by Doppler velocimetry, and placental urocortin mRNA expression by quantitative real time reverse transcriptase-polymerase chain reaction. The main outcome measures were the correlation of urocortin concentrations with patterns of the utero-placental and fetal circulation, and the early prediction of a poor neonatal outcome such as the occurrence of perinatal death and intraventricular hemorrhage. RESULTS Maternal and fetal urocortin levels were significantly (both P < 0.001) higher in gestational hypertension, pre-eclampsia and PE/IUGR women than in controls, and correlated with Doppler velocimetry patterns. Fetal concentrations were significantly (P < 0.0001) higher than and significantly (P < 0.0001) correlated to maternal levels. Placental mRNA expression did not change. Ten out of 140 newborns had a poor neonatal outcome, with an overall prevalence of 7.14% (pretest probability). Using the receiver operator characteristics curve analysis cut-off values, the probability of a poor neonatal outcome was 66.7% when urocortin was used, and was 0% if levels were unaltered. CONCLUSIONS Maternal and fetal urocortin levels are increased in hypertensive disorders of pregnancy. Since urocortin has vasoactive properties, the evidence of increased urocortin levels in hypertensive disorders may represent an adaptive fetal response.

BACKGROUND: Urocortin (UCN) gene expression and synthesis have been reported in epithelial and stromal cells of the human endometrium. In this study we evaluated (i) UCN messenger RNA (mRNA) expression and peptide production in uterine specimens collected throughout the endometrial cycle, (ii) UCN secretion after decidualization of cultured human endometrial stromal cells (HESCs) and (iii) the effect of UCN on endometrial decidualization. METHODS: HESCs were isolated from samples of human endometrium collected from healthy patients with normal menstrual cycle and cultured in presence of cAMP, 17-beta-estradiol (E 2 ) + medroxyprogesterone acetate (MPA) and UCN. UCN levels were measured in endometrial extracts by an enzyme immunoassay, and changes of endometrial UCN mRNA expression were measured by RT-PCR analysis. RESULTS: UCN peptide concentrations and mRNA expression were highest in the secretory phase of the menstrual cycle (P < 0.001, late secretory versus early and late proliferative phase) and higher in the late than the early secretory phase (P < 0.01). After decidualization of HESC with cAMP or E 2 + MPA, UCN levels rose in parallel with prolactin concentrations by days 6 (P < 0.01, for all). Finally, the addition of UCN to HESCs, with or without E 2 + MPA, induced the release of prolactin. CONCLUSIONS: The evidence that (i) UCN is highly expressed in the secretory phase of the endometrial cycle; (ii) cAMP and E 2 + MPA modulate secretion of UCN and (iii) UCN induces HESCs decidualization together suggest a possible role for UCN in endometrial physiology.

Objective[s] Activin A and inhibin A are growth factors expressed by human endometrium involved in the control of endometrial functions. In the present study we investigated the effects of activin A and inhibin A in modulating the tumor necrosis factor (TNF)-α/intercellular adhesion molecule (ICAM)-1 system in cultured human endometrial stromal cells. Study design Endometrial samples were obtained from 34 reproductive age women undergoing laparoscopy for benign ovarian cysts or infertility. Endometrial stromal cells were cultured and soluble ICAM-1 and TNF-α were measured in cell-free supernatants following treatment with or without activin A or inhibin A. Cell surface ICAM-1 was assayed by flow cytometry by staining endometrial cells with specific monoclonal antibodies. Results Activin A and inhibin A did not influence either the expression of cell surface ICAM-1 or soluble ICAM-1 shedding by cultured endometrial cells. On the other hand, TNF-α secretion significantly increased in presence of activin A but not of inhibin A. Conclusions Since TNF-α modulates several endometrial processes such as menstruation, proliferation, apoptosis, implantation and decidualization, an effect of activin A in the physiological control of endometrium is further supported by the present data.

Placental urocortin has a role in the cascade of events leading to parturition by stimulating myometrial contractility and placental uterotonins secretion.The objective of this study was to evaluate urocortin levels in maternal and fetal [umbilical cord artery (UCA) and vein (UCV)] plasma at term and preterm labor.The study design was a controlled cross-sectional study performed from November 2003 to June 2004.This study was performed at the Division of Obstetrics and Gynecology, University of Siena (Siena, Italy).Plasma samples were collected at term in the absence of labor (TNL; n = 27; 39.3 +/- 0.1 gestational weeks), at term spontaneous vaginal delivery (TL; n = 24; 40.1 +/- 0.2 gestational weeks), and at preterm labor (PTL; n = 19; 32.4 +/- 0.4 gestational weeks). Changes in urocortin mRNA expression were also evaluated in placentas collected from TNL (n = 11), TL (n = 11), and PTL (n = 10).Urocortin levels were measured by specific RIA. Changes in placental mRNA expression were determined by real-time quantitative RT-PCR analysis.Maternal and UCA plasma urocortin levels were significantly (P0.0001 for all) higher in TL and PTL than in TNL. Furthermore, UCA concentrations were significantly (P0.0001 for all) higher than and correlated with maternal concentrations (TNL: r = 0.45; P0.05; TL: r = 0.959; P0.0001; PTL: r = 0.7719; P0.0001). UCV levels were significantly (P0.001) higher in TL and PTL than in TNL and were significantly (P0.0001 for all) higher than and significantly (P0.0001 for all) correlated with maternal values, but were significantly (P0.0001 for all) lower than and correlated with UCA values (TNL: r = 0.9548; P0.0001; TL: r = 0.927; P0.0001; PTL: r = 0.838; P0.0001). Placental urocortin mRNA expression did not differ among TNL, TL, and PTL samples.Fetal urocortin secretion is increased in term and preterm labor. Whether these changes are a consequence rather than a cause of human parturition remains to be addressed.

Background: Preeclampsia (PE) is a disorder that occurs in at least 5% of pregnancies and affects both the mother and the unborn baby. A dramatic increase of maternal serum inhibin A concentration in the second and third trimester of pregnancy is a common feature of PE and inhibin A measurement may add significant prognostic information for predicting PE in pregnant women. Design: We evaluated the presence and prevalence of gene polymorphisms for inhibin a subunit (INHα) in patients affected by PE (no.=50; study group), and in the general population (control group composed of 103 women and 42 men). Methods: DNA extraction, single strand conformation polymorphism analysis, DNA sequencing, restriction fragment length polymorphism analysis, and Fisher’s exact test were used. Results: A 769G→A transition was found in INHα1, but not in INHα2 or INHα3 fragment. This variant was found in 10/145 normal controls (7,6%), and in 1/50 preeclamptic patients (2%), without significant difference between the two groups (p=0.29). Conclusions: The prevalence of INHα gene variants is not increased in PE. Due to its frequency, the 769G→A transition may be considered a polymorphism present in the general Italian population.

Hypoxic ischemic encephalopathy (HIE) is an important cause of mortality and morbidity in full-term newborns, and neurologic handicaps develop in ∼25–28% of these infants (1)(2). The postasphyxia period is crucial because brain damage may be at a subclinical stage or its symptoms may be hidden by the effects of sedation, and radiologic assessment may still be unrevealing (3)(4). Because activin A is a growth factor produced in the central nervous system (CNS) (5)(6), mainly after brain injury to modulate neuronal survival against toxicity (7)(8)(9)(10)(11)(12)(13)(14), in the present study we investigated whether its concentrations in cerebrospinal fluid (CSF) collected from asphyxiated full-term newborns were higher in those developing HIE and whether this measurement could be useful for the early detection of postasphyxia HIE. We conducted a longitudinal cohort study, recruiting any infants consecutively admitted (April 1998 through June 2002) to our Neonatal Intensive Care Units (NICUs), who underwent a lumbar puncture in the first 24-h from birth for clinical indications. We expected approximately one third of asphyxiated infants to exhibit moderate/severe HIE; we therefore planned to enroll 30 infants in the asphyxiated group (full-term infants with a gestational age >36 weeks), with at least 8 of them in the HIE subgroup, which would assure a statistical power of 90% to detect differences ≥10% between group means with a significance level of 95%. Considering that

Human placenta, decidua, and fetal membranes are the major sites of production and secretion of inhibin A and activin A in maternal serum, amniotic fluid, and umbilical cord blood. These tissues also express follistatin-related gene and betaglycan, the binding proteins of activin A and inhibin A, respectively, recently identified. They show a different expression throughout pregnancy, suggesting new functional roles into gestational tissues. The availability of suitable assays for measuring inhibin A and activin A lead us the possibility to investigate their secretion in healthy pregnancy. In addition, several evidences underline the potential role and the clinical usefulness of their measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as: threatened abortion, placental tumors, hypertensive disorders of pregnancy, intrauterine growth restriction, fetal hypoxia. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future further possibilities in early diagnosis, prediction, and monitoring pregnancy diseases.

OBJECTIVE: From early gestation the human trophoblast secretes large amounts of inhibin A and activin A, and their measurement provides a value for predicting the outcome in women who become pregnant after assisted reproductive techniques. The aim of the study was to investigate the putative role of maternal serum inhibin A and activin A levels as markers of a viable trophoblast in women who miscarry. DESIGN: Controlled cross-sectional study. METHODS: One group consisted of 65 healthy pregnant women (controls), progressing to deliver a healthy singleton baby and another group consisted of 54 miscarriages (38 incomplete (27 non-viable, 11 anembryonic pregnancies) and 16 complete). Maternal blood samples were collected between 5 and 12 weeks of gestation. RESULTS: Serum human chorionic gonadotrophin concentrations in women with incomplete or complete miscarriages were significantly (both P

Activin A and inhibins (A and B) are growth factors expressed during pregnancy by the human placenta, decidua and fetal membranes, and by several fetal organs. They are secreted in both the maternal and the fetal circulations, but the net contribution of the fetus to inhibins/activin A production is still unclear. In the present study we determined whether there was a difference in the serum concentration of activin A, inhibin A and inhibin B between the artery and vein of the umbilical cord. Arterial and venous umbilical cord blood was obtained immediately before elective Cesarean section of 16 term infants from uncomplicated pregnancies. Inhibins and activin A levels were assayed by specific enzyme-linked immunosorbent assays. The paired t-test and linear regression analysis were used to calculate statistical significance. Inhibin A levels did not differ between the artery and vein of the umbilical cord. In contrast, arterial inhibin B levels were significantly (p0.001) lower, and activin A concentrations significantly (p0.05) higher than the respective venous concentrations. A significant correlation between arterial and venous levels of inhibin A (r = 0.591; p0.05), inhibin B (r = 0.749; p0.0001) and activin A (r = 0.571; p0.05) was found. The present findings suggest that the human placenta is the main source of inhibin B, and the fetus of activin A, in the umbilical cord. In light of the possible roles played by inhibin and activin in erythroid differentiation, protection of neurons against brain injury and modulation of adrenal and pancreatic hormone release, the present data may be of help in evaluating their changes in the umbilical cord when gestational diseases occur.

Activin A is a dimeric protein member of the transforming growth factor-beta (TGF-beta) family: it is synthesized by a variety of organs and follistatin is an activin-binding protein. A sensitive and specific assays for bioactive dimeric activin A and follistatin have recently allowed to measure these proteins in blood and other biological fluids, giving a new insights into their possible physiological role. Since human breast is able to produce activin A, the aim of the present study was to evaluate whether it and follistatin are measurable in breast milk of women during lactation. Concentrations of activin A and follistatin were measured in milk samples collected at 3, 5 and 30 days after delivery by using specific and sensitive two-site ELISAs. For the first time the presence of immunoreactive activin A and follistatin in human milk has been shown; no significant different concentration between the third and the fifth day after delivery was found. Furthermore, no difference of activin A and follistatin concentration between the whole and the skim milk or between spontaneous delivery and cesarean section was found. Milk activin A and follistatin concentrations after 1 month of lactation were significantly decreased (P < 0.01). Activin A and follistatin are present in human milk in high concentrations in the first week of lactation, while decrease after a month suggesting a possible role as growth factors in human milk.

Several findings suggest a role of placental hormones in the regulation of maternal and fetal physiology during pregnancy. The placenta and its accessory membranes, amnion and chorion, although of fetal origin, actually undertake the role of intermediary barriers and active messengers in the maternal-fetal dialogue. They synthesize, metabolize and serve as targets for numerous hormones and cytokines which control all aspects of pregnancy and parturition. Among these, corticotropin-releasing factor (CRF) has been one of the most investigated in the last decade. The secretion of placental CRF is autonomous, but increasing evidence indicates that maternal or fetal physiological and pathological conditions may influence such secretion. In the event of acute or chronic metabolic, physical or infection stress, the placenta takes part in a stress syndrome by releasing CRF, which may contribute to restore local blood flow, and to influence the timing of delivery. Placental CRF and cytokines produced in case of intrauterine infection may activate labour, thereby helping the fetus to escape from a hostile environment.On the background of maternal and/or fetal stress elicited by a number of pathological conditions, CRF appears to play a role in coordinating adaptive changes in uterine perfusion,maternal metabolism, fluid balance and possibly uterine contractility.

Our studies demonstrate significantly lower expression of relaxin and its receptor in ectopic endometriotic tissues than their expression in eutopic endometrium and in endometrium from normal controls. These data suggest that in normal and eutopic endometrium, relaxin may exert a protective effect against endometriosis.

Human placenta is a major source of corticotropin-releasing factor (CRF), and local effects of CRF in fetal membranes and placenta have been shown, i.e., adrenocorticotropic hormone (ACTH) and oxytocin release from cultured placental cells, as well as prostaglandin release from amnion, chorion and decidua. Two distinct CRF receptors (CRF-R1 and CRF-R2) have been characterized: CRF-R1 consists of two isoforms (CRF-R1alpha and CRF-R1beta) while CRF-R2 has at least three different splice variants (CRF-R2alpha, CRF-R2beta and CRF-R2gamma). To date, CRF-R1 receptor has been identified in human placenta and in pregnant myometrium, while no evidence for placental CRF-R2 receptor isoforms has been provided. The present study investigated whether the different isoforms of CRF-R1 and CRF-R2 receptor mRNA are expressed in fetal membranes and placenta. Tissues were collected after spontaneous vaginal delivery (38-40 weeks) or elective caesarean section (39-41 weeks). The gene expression of CRF receptors was first studied by reverse transcriptase-polymerase chain reaction (RT-PCR), and the presence of CRF-R1alpha, but not of CRF-R1beta, in human placental trophoblast, amnion/chorion and decidua was shown. In addition, among the three CRF-R2 splice variants, only CRF-R2beta mRNA was expressed by trophoblast and fetal membranes. By using in situ hybridization, CRF-R1 and CRF-R2 probes positively hybridized trophoblast and related membranes. CRF-R1 was localized in the syncytiotrophoblast cells, chorionic trophoblast and decidua with a small amount in the amnion. CRF-R2 probe mainly hybridized syncytiotrophoblast cells, but cytotrophoblast also contained discreet amounts of CRF-R2 mRNA signal. The CRF-R2 hybridization signal was also observed within the structure of the villi (blood vessels), chorionic trophoblast and decidual cells, but it was faint or absent in the amniotic epithelium. There was no significant difference in the distribution of CRF-R1 or CRF-R2 mRNA signal between placentas collected from vaginal delivery or caesarean section. The evidence that intrauterine tissues differently express CRF-R1alpha and CRF-R2beta supports possible different local roles of CRF and related peptides into intrauterine tissues during pregnancy.

Background: Hypoxic ischemic encephalopathy (HIE) is a major cause of permanent neurological disabilities in full-term newborns. We measured activin A in urine collected immediately after birth in asphyxiated full-term newborns, and assessed the ability of the measurements to predict the occurrence of perinatal encephalopathy.Methods: We studied 30 infants with perinatal asphyxia and 30 healthy term neonates at the same gestational age. We recorded routine laboratory variables, cranial assessments by standard cerebral ultrasound, and the presence or absence of neurological abnormalities during the first 7 days after birth. Urinary activin A concentrations were measured at first urination and 12, 24, 48, and 72 h after birth.Results: Asphyxiated infants were subdivided as follows: group A (n = 18): no or mild HIE with good prognosis and group B (n = 12): moderate or severe HIE with a greater risk of neurological handicap. Activin A concentrations in urine collected at birth (median collection time at first urination 0.08 μg/L at first urination in 10 of 12 patients with moderate or severe HIE but in none of 18 patients with no or mild HIE.Conclusions: Activin A measurements in urine soon after birth may be a promising tool to identify which asphyxiated infants are at risk of neurological sequelae.

Corticotropin-releasing factor (CRF) is a 41-amino acid neurohormone involved in the neuroendocrine response to stress, also playing a role in cell-mediated immune functions and in inflammation. In the light of recent evidence showing an association between endometriosis and altered cellular immunity factors, the present study investigates immunoreactive (ir) CRF in the peritoneal fluid of healthy women, and in patients with pelvic adhesions and endometriosis. In addition, peritoneal fluid concentrations of CRF-binding protein (CRF-BP), a 37-kDA protein of 322 amino acids able to modulate central and peripheral CRF functions, were evaluated. Peritoneal fluid samples (n = 35) were collected from healthy women (n = 12), from patients with intrapelvic adhesions (n = 8), and from women with endometriosis (n = 15). In the control group a specimen of blood was collected. Peritoneal fluid and plasma CRF levels were measured by a two-site immunoradiometric assay (IRMA), and CRF-BP levels were measured by a specific radioimmunoassay (RIA). CRF and CRF-BP levels in peritoneal fluid were lower than plasma values, and independent of the phase of the menstrual cycle: in particular, in healthy women there was no significant difference between peritoneal fluid and plasma CRF-BP levels during two phases of the menstrual cycle. Peritoneal fluid levels of CRF and CRF-BP were similar in healthy patients and women with pelvic adhesions or with endometriosis, and when patients with adhesions or with endometriosis were considered as single group, no difference in CRF and CRF-BP levels was noted in comparison to the control group. In patients with endometriosis, no significant differences in peritoneal fluid CRF or CRF-BP levels were recorded, although in patients with stage 2 and stage 3 of the disease peritoneal fluid CRF-BP levels were higher than in healthy patients or in those with a lower grade of the disease. These results suggest that the peritoneal concentration of these hormones may reflect the circulating levels: the absence of any significative variations in peritoneal fluid CRF levels according to the degree of the endometriosis, suggests a limited role of CRF in the immunological changes related to the disease

This study was designed to determine whether basic fibroblast growth factor (bFGF) gene expression in human placenta varies as a function of gestational age and to evaluate whether bFGF synthesis might be altered in pathological pregnancies. Moreover, we also investigated whether human placental cells express the bFGF receptor gene. The presence of mRNA for bFGF and its receptor was demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) performed on total RNA derived from human placental cells at different times of culture. Levels of bFGF mRNA were determined by competitive RT-PCR in human placental tissues collected at the beginning and at the end of pregnancy. Competitive RT-PCR was also employed to evaluate bFGF synthesis in term placentas derived from pregnancies complicated by diabetes. mRNA for both bFGF and its receptor were demonstrated in human placenta starting as early as 8 weeks of pregnancy. Values of bFGF mRNA were significantly higher in first trimester compared with term placentas. Term placentas derived from pregnancies associated with type I diabetes expressed levels of bFGF mRNA higher than those present in normal term placentas. These data demonstrate that bFGF and its receptor are synthesized in human placental cells throughout gestation. Moreover, bFGF gene expression is developmentally regulated. Finally, bFGF might also be partially responsible for the placental alterations observed in pregnancies complicated by diabetes.

Aim Intraventricular haemorrhage (IVH) is the most common variety of cerebral haemorrhage and cause of neurological disabilities in preterm newborns. We evaluated the usefulness of urine Activin A concentrations for the early detection of perinatal IVH. Methods We conducted a case–control study on 100 preterm newborns (20 with IVH and 80 without IVH) in whom urine Activin A was measured at five predetermined time-points in the first 72 h after birth. IVH diagnosis and the extension of the lesion were performed by ultrasound scanning within the first 72 h and at 1 week after birth, respectively. Results Urine Activin A in infants who developed IVH was significantly higher than in controls at all monitoring time-points (p

Study Objective To show and evaluate outcomes of a modified laparoscopic hysterectomy technique (total reverse laparoscopic hysterectomy). Design Observational study (Canadian Task Force classification II-2). Setting Department of Women's and Children's Health, Obstetrics and Gynecology Clinic, University of Padova, Padova, Italy. Patients One hundred one women underwent total reverse laparoscopic hysterectomy for benign disease. Indications for surgery, patient characteristics, surgical data, complications, and patient satisfaction were recorded. Interventions Total reverse laparoscopic hysterectomy. Measurements and Main Results The modified procedure was performed starting with the incision of the vesicouterine fold and the pubocervical fascia followed by the dissection of only the anterior layer of the broad ligament, thus preserving the integrity of the posterior leaf (retrograde hysterectomy). This technique permits identification of the ureter until the cross with the uterine artery, creating a “safe triangle” for closure of the uterine vessels. The remaining surgical time did not differ from the standard technique. The average operating time was 112.1 ± 35.6 minutes, and the average intraoperative mean blood loss was 79.5 ± 138.4 mL. Ninety-one (90%) patients were very satisfied after surgery. No injuries to the ureter or bladder occurred in any patients. No other major complications were recorded. Conclusion Reverse hysterectomy is another technique for performing laparoscopic hysterectomy, and it has been proven to be safe and efficient.

Recently a new member of the corticotropin-releasing factor (CRF) family has been cloned and named urocortin. It has been localized in rat brain and to human chromosome 2. The present study investigated whether human placenta and related tissues express mRNA and immunoreactive urocortin. Using specific oligonucleotide primers, reverse transcriptase-polymerase chain reaction experiments were performed on total RNA isolated from human placenta and decidua collected both at early stage of gestation (8-11 weeks) and at term (39-40 weeks). In addition, experiments were also done on specimens of amnion and chorion collected at term. Independently from the gestational age, placental and decidual cells expressed urocortin mRNA, with a 145 bp DNA band corresponding to the expected length. The expression of urocortin mRNA was also found in amnion and chorion. Using specific antiserum and an immunoperoxidase technique, immunoreactive urocortin was then localized in syncytiotrophoblast cells and in some extent in cytotrophoblast cells of placental villi at term, as well as in fetal membranes and maternal decidua. The present findings revealed that human placenta and gestational related tissues express human urocortin gene and localize immunoreactive urocortin, supporting the concept that these tissues are capable of expressing a large number of neuroendocrine peptides.

The aim of the present study was to investigate the presence of the immunoreactive oxytocin in human placental extracts and putative factors regulating the release of immunoreactive oxytocin from cultured human placental cells. Fresh placental tissue was collected from pregnant women at term and dissected of membranes (n = 5). Presence of immunoreactive oxytocin in trophoblast tissue was evaluated by a specific radio-immunoassay after acidic extraction and high-pressure liquid chromatography. In a second set of experiments, primary cultures of placental cells were performed and, 48-72 h after dissociation, the effect of arginine vasopressin, corticotropin-releasing factor, neuropeptide Y, activin A, inhibin A, noradrenaline or prostaglandins on immunoreactive oxytocin level in culture medium was investigated. The presence of immunoreactive oxytocin was shown in the acidic extract of trophoblast at term, and in the culture medium of human placental cells, and it was identical to the native peptide. The addition of corticotropin-releasing factor or arginine vasopressin, but not of neuropeptide Y, increased the release of immunoreactive oxytocin three- to fourfold from placental cells, with a dose-dependent effect (P < 0.01). A significantly increased release of immunoreactive oxytocin was shown in presence of noradrenaline (P < 0.01), which was reversed by prazosin, an antagonist of alpha-adrenergic receptors. Recombinant human activin A (P < 0.01), but not inhibin A, stimulated the release of immunoreactive oxytocin three- to fourfold from placental cells. Prostaglandin F2 alpha was a potent secretagogue of immunoreactive oxytocin, whereas a partial or no effect was observed when prostaglandin E2 or prostaglandin I2 was added. Thus, the present findings showed that human placenta contains immunoreactive oxytocin, and that its release from cultured placental cells is regulated by neurohormones, growth factors or prostaglandins.

OBJECTIVE: The primary objective of this investigation was to evaluate whether maternal serum corticotropin-releasing factor levels during pregnancy were predictive of spontaneous preterm delivery. STUDY DESIGN: Maternal serum levels of corticotropin-releasing factor and its binding protein were measured from 20 weeks of gestation in a cross-sectional study of 396 asymptomatic women at high risk for preterm delivery. RESULTS: Gestational age–specific corticotropin-releasing factor levels were not consistently or substantially increased for preterm compared with term deliveries, whether preterm delivery was due to preterm labor or preterm premature rupture of membranes. The binding protein for corticotropin-releasing factor did not vary according to gestational age until term, when it dropped substantially. CONCLUSION: Serum corticotropin-releasing factor levels do not appear to be an important predictor of preterm birth in asymptomatic patients who subsequently have either preterm labor or preterm premature rupture of membranes. Nevertheless, the drop in the corticotropin-releasing factor binding protein level at term suggests that the bioavailability of corticotropin-releasing factor increases as parturition approaches. (AM J OBSTET GYNECOL 1996;174:1477-83.)

I. Introduction During the last 15 years our concepts of the role and functioning of intrauterine tissues during human pregnancy have been changing. While initially considered solely for their role in the exchange of gas and transfer of nutrients and waste, recent studies emphasize the contribution of placenta, decidua, and amnion-chorion to gestational development. Indeed, starting in the 1970s, evidence that human placenta is able to produce hormones, cytokines, and growth factors greatly expanded our knowledge of the functioning of intrauterine tissues and their putative roles in the physiology of pregnancy. A growing number of studies has provided strong evidence that fetal membranes (amnion, chorion) and maternal decidua are capable of hormone production and metabolism and, when containing hormonal receptors, serve as endocrine organs (Fig. 1). Intrauterine tissues are a source of brain, pituitary, gonadal, and adrenocortical peptide and steroid hormones, chemically identical to and biologically acti...

Fetal death in the mid-trimester of pregnancy is unexplained and no reliable markers are available to identify at-risk women. We aimed to assess use of alpha fetoprotein and S100B concentrations in amniotic fluid as markers. We did a case-control study in 758 healthy women undergoing amniocentesis at mid-gestation, of whom 12 had a spontaneous intrauterine fetal death before 28 weeks, and 746 matched controls. Concentrations were corrected for gestational age by conversion to multiples of median (MoM) of healthy controls of the same gestational age. Concentrations of S100B, but not alpha fetoprotein, were significantly higher (p0.0001) in women who later had spontaneous fetal death (median 4.431 MoM [95%CI 3.605-6.197]) than in controls (1.000 MoM [1.062-1.121]). Sensitivity, specificity, and positive and negative predictive values of S100B as a diagnostic test were 100%, suggesting that measurement of this protein at amniocentesis could be useful to identify at-risk women.

Human placenta is the major source of activin A in maternal circulation. The aim of the present study was to evaluate maternal activin A serum concentration in pregnant women with chronic hypertension (n = 14), pregnancy-induced hypertension (n = 10) or pre-eclampsia (n = 16). In the group of pregnant women with chronic hypertension and of healthy pregnant women (n = 10) activin A was measured in samples collected longitudinally throughout gestation. Using a specific two-site enzyme-linked immunosorbent assay, it has been possible to measure maternal serum activin A concentration. In addition, the effect of recombinant human activin A administration on mean arterial pressure and heart rate in female rats have been also investigated. Mean +/- SEM of maternal serum activin A concentration in pre-eclamptic women (57.4 +/- 28.3 ng/ml), was significantly higher than in women with pregnancy-induced hypertension (14.8 +/- 10.5 ng/ml), chronic hypertension (10.3 +/- 5.4 ng/ml) or healthy control women (9.2 +/- 9.4 ng/ml) (P0.01). Serum activin A levels evaluated 2 weeks after anti-hypertensive treatment were not significantly different in pre-eclamptic women. Moreover, when exogenous recombinant human activin A was administered in female rats arterial pressure or frequency of heart rate did not change. The present study showed that maternal serum activin A concentration is abnormally high in patients with pre-eclampsia. Thus, since the patients with chronic hypertension or pregnancy-induced hypertension have activin A concentration in the normal range of values, activin A may be a prognostic marker of hypertension in pregnancy.

Human placenta produces a large variety of bioactive substances with endocrine and neural competence: pituitary and gonadal hormones, hypothalamic-like releasing or inhibiting hormones, growth factors, cytokines and neuropeptides. The most recent findings indicate that locally produced hormones regulate the secretion of other placental hormones supporting a paracrine/autocrine regulation. In placental endocrinology, a particular relevance is played by steroid hormones. In fact, a specific gonadotropin-releasing hormone (GnRH)-human chorionic gonadotropin (hCG) regulation of placental steroidogenesis has been proposed as a placental internal regulatory system acting on steroids production from human placenta. In addition, activin and inhibin have been proposed as further regulatory substances of the synthesis and secretion of steroids; the addition of activin A to placental culture augments GnRH, hCG and progesterone, and this effect can be significantly reduced by the addition of inhibins. Finally, a steroid-steroid interaction is suggested by the evidence that placental estrogen has a positive role in the regulation of progesterone biosynthesis. Other steroid-protein interactions have been observed in human placenta. In fact, recent data indicate that progesterone inhibits placental corticotropin-releasing factor (CRF) and estrogens act on placental conversion of cortisol to cortisone, activating cortisol secretion by the fetal adrenal and enhancing fetal adrenal function with advancing gestation.