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Background Smith-Lemli-Opitz syndrome (SLOS) is a rare genetic neurodevelopmental disorder caused by the defect in the 7-dehydrocholesterol reductase. This defect leads to the deficiency of cholesterol biosynthesis with accumulation of 7-dehydrocholesterol. Inhibitory factor 1 (IF1) is a well-known mitochondrial protein. Recently, it has been discovered in the human serum where it is reported to be involved in the HDL-cholesterol intake. Here we report the IF1 presence in the serum of two paediatric SLOS dizygotic twins treated with dietary cholesterol supplementation. Case presentation The patients showed a typical phenotype. They started dietary supplementation with cholesterol when 2 months old. The cholesterol intake was periodically titrated on the basis of weight increase and the twin 1 required a larger supplementation than the twin 2 during the follow-up. When 6.4-year-old, they underwent IF1 assay that was 7-fold increased in twin 2 compared to twin 1 (93.0 pg/ml vs 13.0 pg/ml, respectively). Conclusions We report, for the first time, the presence of circulating IF1 in the serum of SLOS patients, showing different levels among them. Our findings confirm that IF1 could be a novel research target in cholesterol-related disorders and also in SLOS, and could contribute to the general debate on IF1 as a new modulator of cholesterol levels.

Background: Normal morphometry of the vermis and its relation to the posterior fossa (PF) rule out most major anomalies of the cerebellum. However, accurate categorization of the position and size of the fetal vermis remains a challenge. Objective: Our aim was to test a new method to assess the position and size of fetal vermis on 3-dimensional ultrasound (3D-US). Methods: We measured the vermian-crest angle (VCA) in normal fetuses using multiplanar 3D-US. We also assessed the diameters (superoinferior, anteroposterior, and horizontal) and volume of the vermis. The Spearman rank test and linear and polynomial regression analyses were used for statistical purposes. Results: We included 126 fetuses. Mean ± SD gestational age (GA) was 26.3 ± 4.6 (range 17–35.5) weeks. Mean ± SD superoinferior, anteroposterior, and horizontal diameters were 16.2 ± 4.9, 11.2 ± 3.6, and 5.6 ± 1.6 mm, respectively. Median (range) vermian volume was 0.50 (0.05–2.9) cm3. The VCA was 64.49° ± 11.45. We found no correlation between GA and VCA (r = 0.15; p = 0.13), a linear correlation between GA and vermian diameters, and a quadratic correlation between GA and vermian volume. Conclusions: We provide a new method to assess vermian position and size within the PF using 3D-US. The combined information may be of value for screening purposes, particularly to differentiate between the various pathological situations encountered within the PF.

In recent years, substantive attention has been drawn to the relationship between oral microbiome homeostatic equilibrium disruption and systemic health, demonstrating the negative impacts of this reciprocal biological interplay. Increasingly, there is a concern over the potential noxious effect of oral microbiome dysbiosis on obstetric poor outcomes, focusing on preterm birth. This epidemiological observation remains unexplained, although biologically plausible mechanism has been proposed. Intrauterine infection has long been associated with adverse pregnancy, when the elicitation of an immune response is determinant. There is evidence that Fusobacterium nucleatum (FN), a Gram-negative anaerobe ubiquitous in the oral cavity, infects the mouse placenta originating in the decidua basalis. Based on the current data in literature, we performed a review to provide resources for the explanation of the potential impact of microbiome dysbiosis on poor obstetric outcomes, focusing on the role of FN.

Background Advanced laparoscopic procedures have been shown to be safe in patients with high Body Mass Index (BMI), but conversion rates remain high. This analysis aimed to evaluate the feasibility and clinical outcomes in terms of long- and short-term complications, pain relief of robotic surgery in morbidly obese patients. Methods Patients with BMI class I-II-III with endometrial cancer or hyperplasia were treated with robotic hysterectomy (RH). Patients' characteristics, operating room time (OT), type of surgery, length of hospital stay, and incidence of complications were recorded. Records were reviewed for demographic data, medical/surgical history and comorbidities, perioperative findings and outcomes, as well as long-term complications and recurrences. Regarding stage, according to 2009 FIGO, 26 of cases were IA, while eight and five of cases were, respectively, IB, II stage. Results A total of 87 consecutive RH were analyzed. The more frequent comorbidity was hypertension. Twenty percent of the patients had multiple comorbidities (>2). The mean age was 63±10 years, with a mean BMI of 36±8.2 kg/m2. The more frequent BMI group treated was II class. The median OT was 114 minutes (range: 49-270). According to the Dindo Classification, there were no differences in major or minor complications between the 3 BMI classes. This series had a median follow-up of 60 months (range: 8-96) with an overall survival rate of 100%. The RRH+PLH was feasible and pathology confirmed the adequacy of the surgical specimen, with a median count of 20 nodes. Conclusions Our data support the adoption of the surgical management of the morbidly obese patient. Although short term complication rates are higher with increasing obesity (II-III class), a majority of procedures can still be completed with minimally invasive approach.

BACKGROUND: Physiological changes that occur during pregnancy involve, as a natural consequence, also modifications of oral microbiome. However, the addition with microbial imbalance due to pre-existing periodontal infection might impair a pathological alteration in the phylogenetic community structure and composition in the oral cavity, exacerbating an inflammatory status, and becoming a potential risk factor for preterm birth. From the empirical findings about the relationship between periodontal pathogens and systemic diseases, a clear interest focused on the potential impact of some periodontal pathogens on the preterm birth risk has emerged. AIM: Exploration of the potential interdependence existing between dysbiosis of oral microbiome and changes in maternal-fetal barrier in premature rupture of membranes. MATERIALS AND METHODS: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a Medline search was performed for studies focusing on oral microbioma and its association with pre-term birth, and completed by additional hand searching. Two reviewers independently selected studies and extracted data. The search was restricted to only reports written in English. RESULTS: The electronic search produced 66 items. Six duplicates were found. Among the collected studies, 56 were discarded because they met the exclusion criteria. The articles and reports in our review showed a connection between preterm birth and altered oral microbiome, suggesting a potential key role of Fusobacterium nucleatum, a notable periodontal pathogen involved in several pathological periodontal conditions, in increasing the risk of premature birth. CONCLUSIONS: Since F. nucleatum is frequently associated with preterm birth, it is coherent to hypothesize a potential role for the oral microbiota for preterm birth risk. Further studies should be carried out to determine the changes of the oral microflora in pregnancy and to provide comprehensive knowledge of the diversity of oral bacteria involved in preterm birth.

The purpose of our study was to explore maternal and fetal outcomes in the second and third trimester in women with bicornuate uterus.A total of 280,106 pregnancies met the inclusion criteria and were divided in two study groups: (1) pregnancies in women with bicornuate uterus (n = 444); and (2) controls (n = 279,662). The diagnosis of bicornuate uterus was performed in all patients during the workup for infertility or recurrent pregnancy loss, during pregnancy, or at the time of cesarean delivery. Multivariate logistic regression models were performed in order to assess the risk factors for cervical insufficiency in women with bicornuate uterus.The rate of women with a bicornuate uterus in our population was 0.15%. Women with bicornuate uterus had lower parity (2.93 ± 1.90 vs. 3.42 ± 2.51, p 0.001) and a higher rate of previous cesarean deliveries (54.1% vs. 12.3%, p 0.001). In addition, these patients were more prone to conceive with assisted reproductive techniques (5.6% vs. 1.9%, p 0.001) and had a significantly higher rate of recurrent abortions (12.4% vs. 5.1%, p 0.001) compared to controls.Bicornuate uterus is an independent risk factor for cervical os insufficiency. This is an important finding due to the burden of the risk for midtrimester periviable birth associated with cervical incompetence.

Ultrasounds are known since about 170 years. Firstly, echo sounding has been used in the First World War to fix the position of submarines, now we apply the echo sounding method in medical imaging to study organs and tissue structures, to learn about the body’s function, and to recognize the malfunction. That requires good knowledge about both physical and technological properties in ultrasonic and the tissue interaction with ultrasound waves (Fig. 4.1) [1].

(1) Background: Menopause is a physiological condition typified by drastic hormonal changes, and the effects of this transition have long-term significant clinical implications on the general health, including symptoms or physical changes. In menopausal women, the periodontium can be affected directly or through neural mechanism by oestrogen (E2) deficiency. The majority of the biological effects of E2 are modulated via both oestrogen receptor-α (ERα) and oestrogen receptor- β (ERβ). There is evidence that hypoestrogenism has a substantial impact on the aetiology, manifestation and severity of periodontitis, via the regulation of the expression of osteoprogesterin and RANKL in human periodontal ligament cells through ERβ. However, the mechanistic understanding of oestrogen in periodontal status has been partially clarified. The aim of this paper was to synopsize the recent scientific evidence concerning the link between the menopause and periodontitis, through the investigation of physio-pathological impact of the oestrogen deficiency on osteogenic differentiation of PDLSCs and PDLSC, as well as the dynamic change of ERα and ERβ. (2) Methods: Search was conducted for significant studies by exploring electronic PubMed and EMBASE databases, and it was independently performed by two researchers. All studies on the impact of oestrogen level on alveolar bone resorption were searched from 2005 to July 2020. Data selection was in concordance with PRISMA guidelines. (3) Results: Eight studies met the criteria and were included in this systematic review. All studies reported that oestrogen deficiency impairs the osteogenic and osteoblastic differentiation of PDL cells and oestrogen affects the bone formation capacity of cells. Seven studies were conducted on animal samples, divided into two groups: the OVX animals and animals who received the sham operation. (4) Conclusions: There is a multitude of data available showing the influence of menopause on periodontal status. However, the evidence of this line to investigation needs more research and could help explain the physiological linkage between menopause state and periodontal disease.

Preterm parturition is a syndrome that may result from many underlying mechanisms. Infection and inflammation are the prominent ones. Intrauterine infection and inflammation have an effect akin to sepsis, and that is similar to systemic inflammatory response in adults. Indeed, there is evidence to support the association of a fetal inflammatory response syndrome (FIRS) to systemic infection and inflammation. The utilization of invasive procedures for the prenatal diagnosis of FIRS is associated with a risk for complications resulting from the invasive method. The progress in the imaging quality of obstetrical ultrasound and the development of novel methods for functional anatomical assessment of the fetal organs may help to identify, noninvasively, fetuses at risk for FIRS in patients presenting with preterm labor. We review the studies describing advanced sonographic modalities and the imaging findings in the heart, thymus, kidney, adrenal glands, and spleen of these fetuses.

Endometrial cancer is the most common cancer of the female genital tract in Western Countries, with an incidence of 150.000 new cases/year. Despite high incidence, little is known about the molecular pathogenesis of this tumor. Phospholipids including lysophosphatidic acid (LPA) are involved in proliferation and dissemination of cancer. LPA is a potent bioactive phospholipid synthesized by autotaxin (ATX) through its lysophospholipase D activity. Recent evidence suggests that the ATX/LPA signaling axis plays a role in endometrial cancer. We carried out a prospective study involving two groups of patients classified in accordance to hysteroscopic-guided biopsy. Patients with histological diagnosis of endometrial cancer were enrolled into group one, whereas control patients with pelvic organ prolapse were assigned group two. Both groups underwent hysterectomy, with either open or laparoscopic surgery. After uterine extraction, a second endometrial biopsy was performed to collect tissues. Real-Time PCR was performed to evaluate ATX gene expression in collected tissues. Statistical analysis including unpaired two-way or one-way Student’s t test and ANOVA was performed. We found ATX gene expression significantly higher in neoplastic endometrium compared with normal tissue (P value = 0.0002). In particular, the expression of ATX was significantly elevated in type I endometrial cancer (i.e., endometrioid histotype) compared to type II, in premenopausal women and in patients affected either by obesity (BMI > 30) or diabetes. We propose ATX as a novel potential biomarker particularly implicated in the pathobiology of type I endometrial cancer. Also, we propose ATX as a useful theranostic target in endometrial cancer.

Uterine myomas are the most common benign growths affecting female reproductive system, occurring in 20–40% of women, whereas the incidence rate in pregnancy is estimated from 0.1 to 3.9%. The lower incidence in pregnancy is due to the association with infertility and low pregnancy rates and implantation rates after in vitro fertilization treatment. Uterine myomas, usually, are asymptomatic during pregnancy. However, occasionally, pedunculated fibroids torsion or other superimposed complications may cause acute abdominal pain. There are many controversies in performing myomectomy during cesarean section because of the risk of hemorrhage. Nevertheless, the majority of indication arises before labor and delivery due to acute symptoms leading to a discussion regarding the need for intervention during pregnancy. Therefore, we present a case of successful multiple laparotomic myomectomy at 17 + 2 weeks of gestational age and a systematic review of the literature in order to clarify the approach to this pathologic condition and its effect on pregnancy outcome.

To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

This article aimed to determine sexual behaviors among female and male adolescents in northern Italy. An anonymous self-administered questionnaire evaluating sexual attitudes was distributed in middle and high schools in northern Italy. Adolescents between 13 and 19 years of age were asked to participate at the survey. The study group included 664 participants. Overall, 164 (25%) adolescents had had at least one sexual intercourse. Among adolescents who have had sexual intercourse, 90 (55%) use condoms, 25 (15%) use hormonal contraception, and 49 (30%) do not use any contraception method. A total of 559 adolescents (84%) participated in school-based sexual education programs. This group had better knowledge on sexually transmitted diseases and contraception methods in comparison with adolescents who have never participated in such educational programs (p.05), and no difference in high-risk sexual behaviors was observed (p = 1.0). School-based sexual education programs improve knowledge of sexual transmitted diseases and contraception methods. However, this knowledge does not correlate to high-risk sexual behaviors reduction.

Background Identification of peri-operative variables predicting postoperative morbidity may improve postoperative patients' care. We aimed to identify patients' characteristics and operative factors predictive of early (≤30-day) and late (≤6-month) morbidity in cervical cancer patients undergoing surgery plus external beam radiotherapy (EBRT). Methods We studied 45 propensity-matched patient pairs (90 patients) undergoing laparoscopic radical hysterectomy (LRH) plus EBRT vs. abdominal radical hysterectomy (RAH) plus EBRT. Basic descriptive, multivariable and artificial neuronal network analyses (ANN) were used to design predicting models influencing outcomes. Results Baseline characteristics of the study populations were similar. Patients undergoing LRH experienced lower blood loss (200 (range, 10–700) vs. 400 (range, 100–2000) ml; P

Vaginal cuff dehiscence is a rare, but potentially morbid, complication of total hysterectomy and refers to separation of the vaginal cuff closure. The term vaginal cuff dehiscence is frequently interchanged with the terms of cuff separation or cuff rupture. All denote the separation of a vaginal incision that was previously closed at time of total hysterectomy. After dehiscence of the vaginal cuff, abdominal or pelvic contents may prolapse through the vaginal opening. Bowel evisceration, outside the vulvar introitus, can lead to serious sequelae, including peritonitis, bowel injury and necrosis, or sepsis. Therefore, although prompt surgical and medical intervention is required to replace prolapsed structures, the main problem remains the reconstruction of vaginal vault. In case of recent hysterectomy, vaginal reparation only requires the approximation of vaginal walls, including their fascia, while if dehiscence occurs after a long time from hysterectomy, the adequate suspension of the vaginal vault has to be taken into consideration. In this report we describe the case of a postmenopausal patient, undergoing surgical emergency because of the evisceration of an intestinal loop through a dehiscence of vaginal vault, after numerous reconstructive vaginal surgeries for vaginal prolapse. This paper analyzes clinical circumstances, risk factors, comorbidity, and clinical and surgical management of this complication.

Midwives and nurses have a key role in monitoring postpartum period. They represent the first line professional figure in quantifying blood loss, initiating early diagnosis of obstetric hemorrhage, and mobilizing a team response, if needed. These actions are crucial in determining maternal outcome in postpartum hemorrhage (PPH). In our review we aimed to: (1) Provide a picture of PPH including its pathophysiology, epidemiology, and associated complications; (2) Discuss diagnosis of this dangerous postpartum event; and, (3) Especially evaluate the efficiency of the employment of visual blood loss estimation as a rapid way to suspect PPH and activate the patient assessment.

Objectives Detectable human papillomavirus (HPV) DNA is the most common sexually transmitted infection. Reports on the prevalence of detectable HPV DNA among transsexuals (not sex workers) are scarce. The objective of the study was to determine the prevalence of detectable HPV DNA in a clinic sample of transsexuals and to assess the relationship between detectable HPV DNA and cytological outcomes. Methods Clinical samples (oral, anal, vaginal, cervicovaginal and penile scraped cells) from 35 transsexuals (surgically treated and surgically untreated) who attended the outpatient Clinic of Gender Identity Dysphoria of the Department of Obstetrics and Gynecology of Policlinico Hospital (Bari, Italy) were collected for cytological analysis and HPV DNA detection and typing. All enrolled subjects answered an anonymous structured questionnaire about their sexual habits. Serological status for other sexually transmitted diseases (hepatitis B virus (HBV), hepatitis C virus (HCV), HIV and syphilis) was also evaluated. Results HPV DNA was detected in 14 of 35 patients (40.0%). The prevalence of detectable HPV DNA was 38.2% (13/34) in tested anal samples, 9.1% (2/22) in vaginal samples and 8.3% (1/12) in penile samples. Oncogenic HPV genotypes have been detected in 93% of HPV-positive transsexuals. More than one-third (35.7%) of HPV-positive transsexuals were infected with at least one of the four vaccine-preventable genotypes, 6, 11, 16 and 18. Conclusions The high rate of detectable HPV DNA by oncogenic types suggests that periodic cytological screening and clinical evaluation may be necessary since transsexuals are at high risk of anogenital cancer. Also promoting HPV vaccination in younger subjects may be advisable.

Rationale: PNETs (primitive neuroectodermal tumors) are a family of highly malignant neoplasms characterized by small round cells of neuroepithelial origin. They usually involve bone and soft tissues, and have a higher incidence in childhood. Patient concerns: In this case report, we describe the obstetric and oncological outcome of a huge mass diagnosed as a leiomyoma in a 39-year-old pregnant woman who complained of low back pain, dysuria, and urinary frequency at 22 weeks of gestation. Diagnoses: During the 25th week of pregnancy, the patient was referred to our hospital at night with severe anemia and suspected hemoperitoneum. She underwent an emergency caesarean section, delivering a female fetus weighing 400 g, with an Apgar score of 7 at 1 minute and 9 at 5 minutes. Intervention: During surgery, we found a huge uterine sarcoma-like metastatic tumor, invading the pelvic peritoneum and parametria bilaterally; the adnexae seemed disease-free. We performed a type B radical hysterectomy, bilateral salpingo-oophorectomy, pelvic peritonectomy, omentectomy, appendectomy, and excision of a bulky lymph node. Seven days after delivery, staging computed tomography (CT) scan demonstrated a large lombo-aortic lymph node compressing the left renal vein and we completed debulking with a second surgery, including diaphragmatic peritonectomy and excision of a huge lymph node by lombo-aortic lymphadenectomy, requiring partial reconstruction of an infiltrated renal vein. Outcome: Ten days after the second surgery, echo-color Doppler showed a regular microcirculation in the left kidney. The patient was discharged after 10 days, and the baby after 1 month, both in good health. Histological examination revealed a uterine body cPNET (central primitive neuroectodermal tumor) orienting the clinical management toward chemotherapy with cisplatin and etoposide. Lessons: PNETs are aggressive neoplasms, usually diagnosed at an advanced stage. Due to their low incidence, universally accepted guidelines are still unavailable. Radical surgery leaving no macroscopic residual disease is mandatory in advanced stages. A good fertility-sparing procedure can be performed only in young women at early stages of disease, when the wish for childbearing is not yet fulfilled.

PURPOSE The aim of this present study was to evaluate the sonographic correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer, in order to establish a new potential marker to monitor treatment response. METHODS This was a retrospective cohort study of 25 patients who underwent a sonographic evaluation of Doppler flow characteristics of the uterine arteries before surgery or radiochemotherapy for early and locally advanced/advanced cervical cancer, respectively, was analyzed. The primary outcome was the correlation between Doppler flow characteristics of the uterine arteries and tumor size in patients with cervical cancer. RESULTS Median age was 49 (range 26-85) years, and mean tumor size was 40.8 ± 17 mm. A significant positive correlation was found between tumor diameter and the uterine artery end-diastolic velocity (r = 0.47, p

Objective To evaluate surgery-related outcomes of laparoscopic (LH) and vaginal hysterectomy (VH) in patients with a history of previous cesarean section (CS). Study design Data on 289 consecutive patients with a history of CS undergoing VH (n = 49, 17%) and LH (n = 219, 76%) were collected. Basic descriptive statistics, univariate and multivariate analyses were performed to evaluate surgery-related outcomes. A propensity-matched algorithm was applied in order to reduce allocation biases between groups. Results Patients undergoing LH were more likely to have a history of multiple cesarean sections (44% vs. 18%; p = 0.001). Additionally, uterine weight was greater among patients undergoing LH than VH (median weight: 235 (range, 45–2830) vs. 150 (range, 40–710) g; p

ObjectiveThis study aimed to evaluate the impact on perioperative and medium-term oncologic outcomes of the implementation of laparoscopy into a preexisting oncologic setting.MethodsData from consecutive 736 patients undergoing surgery for apparent early stage gynecological malignancies (endometrial, cervical, and adnexal cancers) between 2000 and 2011 were reviewed. Complications were graded per the Accordion classification. Survival outcomes within the first 5 years were analyzed using Kaplan-Meier method.ResultsOverall, 493 (67%), 162 (22%), and 81 (11%) had surgery for apparent early stage endometrial, cervical, and adnexal cancer. We assisted at an increase of the number of patients undergoing surgery via laparoscopy through the years (from 10% in the years 2000-2003 to 82% in years 2008-2011; P < 0.001 for trend); while the need to perform open surgery decreased dramatically (from 83% to 10%; P < 0.001). Vaginal approach was nearly stable over the years (from 7% to 8%; P = 0.76). A marked reduction in estimated blood loss, length of hospital stay, blood transfusions as well as grade greater than or equal to 3 postoperative complications over the years was observed (P < 0.001). Surgical radicality assessed lymph nodes count was not influenced by the introduction of laparoscopic approach (P > 0.05). The introduction of laparoscopy did not adversely affect medium-term (within 5 years) survival outcomes of patients undergoing surgery for apparent early stage cancers of the endometrium, uterine cervix, and adnexa (P > 0.05 log-rank test).ConclusionsThe introduction of laparoscopy into a preexisting oncologic service allows an improvement of standard of care due to a gain in perioperative results, without detriments of medium-term oncologic outcomes.

Ewing sarcoma-primitive neuroectodermal tumors (ES/PNETs) constitute a family of neoplasms characterized by a continuum of neuroectodermal differentiations. ES/PNET of the uterus is rare. There are 48 cases of ES/PNET of the uterus published in the literature as far as we know. We describe a case of Ewing sarcoma of the uterus occurring in a 17-year-old woman presenting with a two-month history of pelvic pain. After surgical excision and microscopic, immunohistochemical, and electron microscopy examination, the diagnosis of Ewing sarcoma of the uterus was suggested. This report will discuss the diagnosis and surgical and clinical management of Ewing uterine sarcoma in young women, according to the available literature. In spite of the rarity of ES/PNETs, they should be taken into account in the differential diagnosis of uterine neoplasms in young women.

The aim of the study was to compare surgery-related outcomes between laparoscopic (LH) and vaginal (VH) hysterectomy, performed for benign uterine disease (other than pelvic organs prolapse) in obese women.Data of consecutive obese (BMI≥30) patients undergoing LH and VH, between 2000 and 2013, were compared using a propensity-matched analysis. One hundred propensity-matched patient pairs (200 patients) undergoing LH (n=100) and VH (n=100) represented the study group.Baseline demographic characteristics were similar between groups. Patients undergoing LH experienced similar operative time (87.5 (25-360) vs. 85 (25-240)min; p=0.28), slightly lower blood loss (100 (10-3200) vs. 150 (10-800)ml; p=0.006) and shorter length of hospital stay (1 (1-5) vs. 2 (1-5) days; p0.001) than women undergoing VH. There was no statistically significant difference between LH and VH in complication rate (3% for VH vs. 10% for LH; OR: 3.4; 95%CI: 0.95-13.5; p=0.08). At multivariable analysis complication rates increased as BMI increase (OR: 1.01 (1.00-1.02) for 1-unit increase in BMI; p=0.05). Independently, LH correlated with reduced hospital stay (OR: 0.63 (95%CI: 0.49-0.82); p=0.001) and complication rates (OR: 0.91 (95%CI: 0.85-0.97); p=0.01).In obese women affected by benign uterine disease LH and VH should not be denied on the basis of the mere BMI, per se. In this setting, LH upholds effectiveness of VH, improving postoperative outcomes. However, complication rate increases as BMI increase, regardless surgical route.

ObjectiveThe objective of this study was to evaluate how the administration of different adjuvant therapies influences the risk for developing recurrences in the para-aortic area in endometrial cancer (EC) with positive pelvic and unknown para-aortic nodes.MethodsWe retrospectively evaluated the data of 58 patients with EC affected by stage IIIC1 who had undergone pelvic but not para-aortic lymphadenectomy from January 1, 1990 to December 31, 2011. Survival outcomes within the first 5 years after surgery were assessed using the Kaplan-Meier model.ResultsChemotherapy plus radiotherapy, chemotherapy only, and external radiotherapy only were administered in 12 (23%), 18 (34%), and 23 (43%) patients, respectively. Five (9%) patients, who were selected to forego adjuvant therapy due to poor performance status, were excluded from the analysis. Disease-free and overall survivals assessed at 5 years were 54%, and 61%, respectively. All para-aortic recurrences were observed among the patients with endometrioid EC, whereas no cases of para-aortic recurrences were found in patients with nonendometrioid histology (5/36 (14%) vs 0/17 (0%); P = 0.16); the latter were more likely to develop distant (hematogenous, peritoneal, and distant lymphatic) recurrences (P = 0.09). Type of adjuvant therapy was the only factor influencing para-aortic failure: chemotherapy (± radiotherapy) reduced the rate of para-aortic node recurrence in comparison with pelvic radiotherapy as a sole modality (P = 0.01). However, adjuvant therapy did not influence the 5-year survival outcomes (P > 0.05).ConclusionsIn the absence of local treatment (ie, para-aortic lymphadenectomy and radiotherapy), the administration of chemotherapy seems effective in reducing recurrences in the para-aortic area among patients with stage IIIC1 endometrioid EC.

According to some reports in the literature, the hormonal fluctuations which occur during the menstrual cycle may affect the clinical expression of contact allergy to a greater or lesser degree. In clinical practice, too, patient history often shows exacerbation of the contact dermatitis during the days immediately preceding menstruation. On the contrary, the follicular phase of the cycle seems to have a temporary protective role in inhibiting the eliciting phase of allergic contact dermatitis. One possible explanation for this phenomenon is of immunological type: it has been demonstrated that oestradiol induces inhibition of delayed hypersensitivity type reactions, probably by acting indirectly on cells having a regulatory function in cell-mediated immunity. To investigate any inhibitory effect of the ovulatory phase of the menstrual cycle on contact sensitization, 30 selected fertile women, allergic to nickel sulfate and with a regular menstrual cycle lasting between 25 and 32 days, were enrolled. Patch tests were performed with a series of 10 serial aqueous dilutions of nickel sulfate, from 5% to 0.0013%. The 30 women were tested at 2 different times, in the ovulatory phase (demonstrated by transvaginal ultrasound) and the progestinic phase; they were subdivided into 2 groups of 15 women: in one group, the tests were made first in the ovulatory phase, and in the other, first in the progestinic phase of the menstrual cycle. There was a minimum interval of 5 weeks between the 2 test phases. The study shows that during ovulation the patch tests elicited significantly less intense responses than in the progestinic phase. These data therefore suggest that the ovulatory phase of the cycle has a significant inhibitory role on delayed hypersensitivity type reactions. For this reason, negative responses to patch tests executed in this phase could likely be false-negatives, and after careful evaluation of the phenomenon and of the clinical condition and patient history, it may be considered advisable to repeat the tests during the progestinic phase of the menstrual cycle.

Objective Monochorionic twins with twin–twin transfusion syndrome (TTTS) provide an ideal model in which to evaluate the influence of differing hemodynamic stress on umbilical cord (UC) morphology. The purpose of this study was to investigate the UC morphometry and UC coiling pattern at ultrasound in monochorionic twin pregnancies with TTTS. Methods A targeted sonographic evaluation of the UC was performed in 21 consecutive twin pregnancies with untreated TTTS. The cross-sectional area of the UC and of its vessels was measured. The Wharton's jelly area was computed by subtracting the vessels area from the area of the UC. The umbilical coiling index (UCI) was calculated as the reciprocal of the sonographic length of one complete vascular coil. The UCs were classified as uncoiled, normally coiled, hypocoiled, hypercoiled and atypically coiled (UCI not valuable). Results The UCs of recipient twins were invariably larger than those of donors, and this difference was mainly attributable to both a larger amount of Wharton's jelly and a larger umbilical vein diameter. The proportion of lean UCs was higher in the donor than in the recipient fetuses (18/21 vs 1/21, p < 0.0001), while large UCs were significantly more frequent in the recipient than in the donor twins (13/21 vs 1/21, p = 0.0002). In all twin pairs, a discordant umbilical coiling pattern was observed between the donor and the recipient twin. The prevalence of uncoiled and hypocoiled cords was higher in the donor group, while hypercoiling and atypical coiling were more frequently detected in the recipient group. Conclusions A discordant UC morphometry represents an additional phenotypic feature of twins with TTTS. The discordant intertwin coiling pattern in TTTS argues against an exclusively genetic origin of UC twists, and further supports a key role of hemodynamic forces in coiling development. Copyright © 2005 John Wiley & Sons, Ltd.

Acta Obstet Gynecol Scand 2002; 81: 1040-1046. © Acta Obstet Gynecol Scand 2002 Objective. To evaluate whether the technique to open the abdomen might influence the operative time and the maternal and neonatal outcome. Methods. All consecutive women who underwent a cesarean section at a gestational age greater than or equal to 32 weeks were randomly allocated to have either the Joel-Cohen or the Pfannenstiel incision. Exclusion criteria were two or more previous cesarean sections and previous longitudinal abdominal incision. During the study period 366 patients underwent a cesarean delivery. Of these patients, 56 did not meet the inclusion criteria. The remaining patients were allocated to the Joel-Cohen ( n = 152) group and to the Pfannenstiel ( n = 158) group. Extraction time was defined as the time interval from skin incision to the clamping of the umbilical cord. Results. The total operative time was similar in both groups [Joel-Cohen 32 min (12-60) vs. Pfannenstiel 33 min (18-70)]. The extraction tim...

Acta Obstet Gynecol Scand 2002; 81: 527-533. © Acta Obstet Gynecol Scand 2002 Objective. To explore whether the umbilical vein blood flow of growth-retarded fetuses with normal Doppler parameters changes over time differently to that of normally grown fetuses. Methods. Fifteen consecutive women whose fetus was diagnosed to be growth restricted were compared with 30 women whose fetus was normally grown. Two ultrasonographic evaluations were conducted at 2-weekly intervals (± 2 days) in all cases. At each sonographic evaluation, umbilical vein blood flow parameters were obtained by digital color Doppler velocity profile integration. To allow comparisons among fetuses, the umbilical vein blood flow per minute was normalized for abdominal circumference. Results. The absolute vein blood flow was lower in growth-retarded than in normally grown fetuses (209 ml/min ± 73 vs. 313 ml/min ± 72, p < 0.01). The median (range) umbilical vein blood flow normalized for abdominal circumference was significantly lower in gr...

A pre-existing intrauterine inflammation in the first half of gestation has been proposed as a possible condition that leads to preterm delivery. Indeed, elevated levels of inflammatory mediators (eg, interleukin-6, tumor necrosis factor) in midtrimester amniotic fluid have been found in cases of preterm delivery and/or spontaneous abortion. The objective of this study was to investigate whether the amniotic fluid C-reactive protein level at the time of genetic amniocentesis is a marker for spontaneous preterm delivery before 34 and 37 weeks of gestation.Women who underwent genetic amniocentesis between 15 and 18 weeks of gestation with (1) singleton gestation, (2) uneventful pregnancy course before the amniocentesis, and (3) absence of fetal abnormalities were included in the study. Patients with abnormal karyotype were excluded. C-reactive protein concentration was measured in amniotic fluid and in maternal blood immediately after genetic amniocentesis. All patients were followed until delivery for the occurrence of pregnancy complications. Nonparametric tests and receiver-operating characteristic curve analysis were used for statistical purposes.The prevalence of spontaneous preterm delivery before 34 and 37 weeks was 3.3% (10 of 306 pregnancies) and 8.5% (26 of 306 pregnancies), respectively. Women with preterm delivery at37 weeks had a higher median (range) of amniotic fluid C-reactive protein concentration than those women who delivered at term (median, 113.3 ng/mL [range, 16-623 ng/mL] vs median, 57.8 ng/mL [range, 0-808.9 ng/mL]; P.005). Women with preterm delivery at34 weeks had a higher median (range) amniotic fluid C-reactive protein concentration than those women who delivered at term (median, 183.8 ng/mL [range, 46.5-447 ng/mL] vs median, 57.8 ng/mL [range, 0-808.9 ng/mL]; P.005]. No correlation was found between amniotic fluid C-reactive protein and maternal blood C-reactive protein concentrations. No relationship was found between maternal blood C-reactive protein concentration and preterm delivery before either 34 or 37 weeks. Amniotic fluid C-reactive protein concentration of110 ng/mL had a sensitivity of 80.8% and a specificity of 69.5% in the prediction of spontaneous preterm delivery at34 weeks.This study supports the theory that a subclinical intrauterine/fetal inflammatory process early in gestation may be important for the occurrence of preterm delivery in the second half of gestation.

ObjectivesThe aim of this study was to analyze perioperative and long-term survival outcomes after either laparoscopic or open abdominal staging for apparent early-stage ovarian cancer.MethodsData of consecutive women with early-stage ovarian cancer undergoing comprehensive laparoscopic staging between 2003 and 2010 were matched with a historical cohort of patients undergoing open surgery. Five-year survival outcomes were analyzed using the Kaplan-Meier method. In addition, a systematic review of the literature and meta-analysis of comparative studies was performedResultsA total of 35 women undergoing staging via laparoscopy were compared with a cohort of 32 patients undergoing open surgery. Baseline characteristics were similar between groups. Spillage occurred in 6 and 4 patients in laparoscopic and open group, respectively (P = 0.59). Patients undergoing laparoscopy experienced longer operative time (P < 0.001), shorter hospital stay (P = 0.03), and lower postoperative complication rate (3% vs 28%; P = 0.005) than patients undergoing staging via open surgery. The median (range) follow-up period was 64 (37–106) and 100 (61–278) months for case and control, respectively (P < 0.001). Five-year disease-free survival (P = 0.12, log-rank test) and overall survival (P = 0.26, log-rank test) were not influenced by surgical approach. Pooled analyses of the literature results corroborate our results suggesting an improvement of perioperative results in the laparoscopic group in comparison with the open abdominal one. In comparison with open surgery, laparoscopy did not influenced spillage (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.35–1.73) and upstaging rate (OR, 0.7; 95% CI, 0.38–1.27). No between-group differences in survival were observed (OR, 0.5; 95% CI, 0.21–1.21).ConclusionsLaparoscopy upholds open surgery in long-term oncologic control, reducing morbidity.

Introduction Although growing evidence suggests the beneficial effects of a nerve‐sparing (NS) approach to surgery in cervical cancer patients, only limited data on NS laparoscopic radical hysterectomy (LRH) are available, and no studies have investigated the effects of NS‐LRH on sexual function. Aim This study aims to determine whether the implementation of NS‐LRH impacts on sexual function in cervical cancer patients. Methods Sexually active cervical cancer patients undergoing type C (class III) LRH between 2004 and 2013 were enrolled in this prospective study. Main Outcome Measures Preoperative and postoperative sexual function were assessed using a validated questionnaire, the Female Sexual Function Index (FSFI). The FSFI evaluates desire, arousal, lubrication, orgasm, satisfaction, and pain. Results Forty patients undergoing radical hysterectomy (20 conventional LRH vs. 20 NS‐LRH) represented the study group. Baseline characteristics were similar between groups ( P > 0.05). No differences in preoperative FSFI scores were recorded ( P > 0.05). We observed that both LRH and NS‐LRH worsened postoperative FSFI scores ( P P = 0.04). Considering postoperative domain scores, we observed that desire, arousal, orgasm, and pain scores were similar between groups ( P > 0.05), while patients undergoing NS‐LRH experienced higher lubrication (3.4 ± 2.3 vs. 1.7 ± 2.2; P = 0.02) and satisfaction (4.6 ± 3.9 vs. 2.8 ± 2.2; P = 0.004) scores in comparison with patients undergoing conventional LRH. No between‐group differences in survival outcomes were found. Conclusions Both conventional LRH and NS‐LRH impact negatively on patients' sexual function. However, the NS approach impairs sexual function less, minimizing the effects of radical surgery. Bogani G, Serati M, Nappi R, Cromi A, di Naro E, and Ghezzi F. Nerve-sparing approach reduces sexual dysfunction in patients undergoing laparoscopic radical hysterectomy. J Sex Med 2014;11:3012–3020.

This study evaluated the efficacy of intravaginal prostaglandin E(2) gel in comparison with that of a Foley catheter for cervical ripening and induction of labor.Consecutive patients with unfavorable cervix requiring preinduction cervical ripening and induction of labor at term gestation were asked to participate in the study. One hundred and two patients were assigned to treatment with intravaginal prostaglandin E(2) gel (group 1) and 122 patients underwent the placement of an intracervical Foley catheter (group 2). After a maximum of three applications of intravaginal prostaglandin E(2) gel (18h) or after 18h from Foley catheter insertion oxytocin was administered to patients not in active labor. Labor profiles and pregnancy and neonatal outcome were compared between groups.The groups were comparable in term of demographic characteristics, indications for induction of labor, Bishop score at admission. The induction to labor time and the induction to delivery time were similar between groups. The cesarean sections rate was higher in group 1 than in group 2 (26.5 versus 14.7%, P0.05). This remained significant when the analysis was restricted to nulliparous patients (32.3 versus 14.2%). The incidence of urinary tract infections, chorioamnionitis, and febrile morbidity was similar between groups.For preinduction cervical ripening, the Foley catheter is a valid alternative to the application of intravaginal prostaglandin E(2) gel and it is associated with a lower cesarean rate in nulliparous women.

The presence of a communicating vessel, the Hyrtl anastomosis, between the umbilical arteries is well described in pathological studies. Using different injection techniques, it has been speculated that this vessel acts as a pressure-equalizing mechanism between the different lobes of the placenta. However, its detection during fetal life has never been reported. We report on two cases of ultrasonographic detection and Doppler assessment of the Hyrtl anastomosis during pregnancy. A pulsatile blood flow from the umbilical artery with higher resistance to that with lower resistance has been demonstrated at the level of the Hyrtl anastomosis, which was confirmed after delivery. In addition, this report supports the hypothesis that the anastomosis plays an important role in regulating the blood pressure in the placental lobes and in equalizing the blood pressure between umbilical arteries.

Objectives: Megacystis (MC) is rare and often associated with other structural and chromosomal anomalies. In euploid cases with early oligohydramnios, prognosis is poor mainly due to pulmonary hypoplasia and renal damage. We report our experience of the past 20 years. Methods: A retrospective review of cases with prenatally diagnosed MC was performed. Complete prenatal as well as postnatal medical records from 1989 to 2009 were reviewed focusing on diagnostic precision, fetal interventions [vesicocentesis (VC), vesicoamniotic shunt (VAS)], short- and long-term outcome, and potential prognostic factors. Results: 68 cases were included. Follow-up was available in 54 cases (9 girls and 45 boys including 3 cases with aneuploidy). We found 39 isolated MC at sonography (5 girls and 34 boys). 24 fetuses with isolated MC underwent VC and VAS at 19.6 ± 6.3 and 20 ± 4.9 weeks of gestation, respectively. Survival rate was higher in male than in female fetuses (51 vs. 33%). Renal problems occurred in 4/14 prenatally treated fetuses and in 1/10 when cases with prune belly syndrome (PBS) were excluded from the analysis. Conclusions: Our study shows that a careful selection of cases with MC excluding fetuses with PBS and early treatment has still the potential to improve outcome.

Objective The aim of this study was to achieve pregnancy in a woman with premature ovarian insufficiency (POI) by means of estrogen pretreatment, a combination of estrogen therapy and gonadotropin ovarian stimulation, and intracytoplasmic sperm injection (ICSI). Methods A 34-year-old woman with POI who failed to achieve follicular growth in two previous ovarian stimulation protocols using high doses of gonadotropins alone underwent an ICSI trial after estrogen pretreatment (ethinyl estradiol 0.05 mg three times a day for 10 d) followed by estrogens (at the same dose) and recombinant β-follicle-stimulating hormone (250 IU/d for 12 d). Results Delivery of a healthy female baby was achieved. Conclusions Stimulation with gonadotropins plus estrogens after pretreatment with estrogen can be considered a useful intervention in women with POI trying to conceive.

Background To verify the feasibility of ovarian stromal evaluation and correlate ovarian parameteres (echogenicity and volume) with hyperandrogenism, and both cardiovascular and metabolic risk factors in PCOS. Methods Twenty four young PCOS patients and twelve age-matched control women were enrolled. Diagnosis of PCOS was based on the Rotterdam criteria. Ultrasound ovarian study included ovarian volume, stromal volume, stromal area and stromal area/total ovarian area ratio (S/A). Concerning hormones, insulin, LH, FSH, estradiol, androstenedione, testosterone, DHEAS, 17-hydroxy-progesterone, and SHBG were measured during the early follicular phase (days 2-5). Cardiovascular risk factors were represented by fasting plasma levels of glucose, lipids (total and HDL-cholesterol), plasminogen activator inhibitor 1 (PAI-1), von-Willebrand factor (vWF), and adiponectin. Carotid intima-media thickness (C-IMT) was measured as a parameter of cardiovascular risk. Results A positive correlation between the S/A ratio and plasma levels of testosterone (p < 0.05) and androstenedione (p < 0.05) was found. The stromal volume, stromal area and S/A ratio were also significantly and positively correlated with PAI-1, and vWF levels, and with IMT in PCOS women (P < 0.05). Conclusions This study shows that the ultrasound measurement of ovarian stroma is a predicting factor of hyperandrogenism degree, prothrombotic factors and cardiovascular risk in patients with PCOS.

Introduction: Ovarian cancer is highly sensitive to chemotherapy but also shows a high rate of recurrence and drug resistance. These negative outcomes mostly depend on altered apoptotic pathways, making the design of new therapeutic strategies based on the induction of other types of cell death highly desirable. Several lines of research are now addressing cancer-specific features to specifically target tumor cells, thus reducing adverse effects. In this light, a great deal of attention has been devoted to the metabolic reprogramming occurring in cancer cells, which display increased levels of glycolysis compared with their normal counterparts. We recently showed that inhibition of p38α impairs key metabolic functions of colorectal cancer cells, inducing growth arrest, autophagy, and cell death both in vivo and in vitro. These effects are mediated by a switch from hypoxia-inducible factor 1α (HIF1α) to forkhead transcription factor O (FoxO)-dependent transcription. Methods: We first characterized p38 expression in OVCAR-3, A2780, and SKOV-3 ovarian cancer cell lines. Then, we treated these cells with the p38α/p38β-specific inhibitor SB202190 and performed a morphological, proliferation, and survival analyses. Finally, we studied HIF1α and FoxO3A expressions and signaling pathways to evaluate their role in SB202190-induced effects. Results: p38α blockade induces the formation of intracellular autophagic vacuoles and reduces growth and viability of ovarian cancer cells. As in colorectal cancer, the underlying molecular mechanism seems to rely on a shift from HIF1α- to FoxO3A-dependent transcription, which is promoted by the activation of the adenosine monophosphate-activated protein kinase pathway. Conclusions: These data corroborate the hypothesis that pharmacological modulation of genes involved in cancer-specific homeostasis, such as p38α, might be exploited to design new therapeutic approaches to cancer treatment.

Objective: To describe a technique for treating hematocolpos and hematometra in patients with uterus didelphys and unilateral imperforate vagina involving the use of resectoscopy under ultrasonographic control. Design: Case report. Setting: University hospital. Patient(s): A 13-year-old girl with uterus didelphys with unilateral hematometra, hematocolpos, and ipsilateral renal agenesis. The girl complained of severe abdominal pain, which appeared with each of her menses. Intervention(s): The intervention was performed by a vaginoscopic approach to preserve the integrity of the hymen. The first incision on the vaginal wall was performed in correspondence with the hematocolpos under continuous ultrasonographic guidance with the use of a straight resectoscopic loop. Resection of the vaginal septum was continued with the use of an angled resectoscopic loop until almost complete excision of the septum was achieved. Main Outcome Measure(s): Clinical, echographic, and vaginoscopic findings before the operation and 2 and 6 months after the operation. Result(s): The surgical procedure was easy to perform. Almost complete excision of the septum was achieved with just a few passages of the resectoscope. Complete drainage of both the hematocolpos and the hematometra was confirmed by ultrasonography. The postoperative period was completely uneventful. Clinical and vaginoscopic evaluations 6 months after the operation confirmed the integrity of the hymen, the complete resolution of clinical symptoms, and the persistence of a large communication between the two vaginas. Conclusion(s): Resectoscopic excision under ultrasonographic guidance of the vaginal septum in a girl with uterus didelphys with unilateral hematometra and hematocolpos was effective and easy to perform, and it fully respected the integrity of the reproductive system.

Objective To evaluate whether the addition of finasteride (a 5〈-reductase inhibitor) to conventional protocol of ovarian stimulation with gonadotropin can improve ovarian follicular growth in polycystic ovary syndrome (PCOS) women who did not respond to previous stimulation with gonadotropin alone. Design Double-blind randomized study. Setting Outpatient in an academic research environment. Patient(s) Thirty-six PCOS patients in whom the previous multifollicular stimulation protocols with gonadotropin failed. Intervention(s) The patients were randomly assigned to two treatment groups: group 1 underwent ovarian stimulation with recombinant FSH (rFSH) plus finasteride, and group 2 received rFSH alone. When the dominant follicle reached a mean diameter of 18 mm, hCG was administered and finasteride withdrawn. Main Outcome Measure(s) Ovulation rate in women with PCOS. Result(s) Follicular growth and ovulation occurred in eight patients in group 1, whereas no cases were detected in group 2. Conclusion(s) This study confirms that hyperandrogenism interferes with follicular growth and suggests that administration of finasteride during ovarian stimulation with rFSH improves ovulation rate in selected hyperandrogenic anovulatory women.

Objective The purpose of this study was to compare 2 methods of expansion of the uterine incision at the time of cesarean delivery. Study Design Women who underwent a low-segment transverse cesarean delivery were assigned randomly to have the blunt expansion of the uterine incision by the physician separating the fingers either in a transversal direction or in a cephalad-caudad direction. The primary outcome measure was the incidence of unintended extensions. Results The transversal (n = 406) and cephalad-caudad (n = 405) expansion groups were similar with regard to patient characteristics, indication to surgery, type of anesthesia, and proportion of emergency procedures. No difference in the need for transfusions (0.7% vs 0.7%; P = 1.0) or estimated blood loss (440 ± 341 vs 398 ± 242 mL; P = .09) was noted. The incidence of unintended extension (7.4% vs 3.7%; P = .03) and blood loss of >1500 mL (2.0% vs 0.2%; P = .04) was significantly higher in the transversal expansion group, compared with the cephalad-caudad group. Transversal expansion was an independent contributor to unintended extension and blood loss of >1500 mL. Conclusion Because it is associated with less risk of unintended extension and excessive blood loss, expansion of the uterine incision with a cephalad-caudad traction should be preferred to transversal expansion when a cesarean delivery is performed.

Currently, fetal point mutations cannot be reliably analyzed from circulatory fetal DNA in maternal plasma, due to the predominance of maternal DNA sequences. However, analysis of circulatory fetal DNA sequences in maternal plasma have been shown to selectively enrich for fetal DNA molecules on the basis of a smaller molecular size than maternal DNA.To examine the prenatal analysis of 4 common beta-thalassemia point mutations: IVSI-1, IVSI-6, IVSI-110, and codon 39.A total of 32 maternal blood samples were collected at 10 to 12 weeks of gestation (mean, 10.7 weeks) between February 15, 2003, and February 25, 2004, in Bari, Italy, from women with risk for beta-thalassemia in their newborns immediately prior to chorionic villous sampling. Samples in which the father and mother did not carry the same mutation were examined. Circulatory DNA was size-fractionated by gel electrophoresis and polymerase chain reaction (PCR) amplified with a peptide-nucleic-acid clamp, which suppresses amplification of the normal maternal allele. Presence of the paternal mutant allele was detected by allele-specific real-time PCR.Detection of paternally inherited beta-globin gene point mutations.Presence or absence of the paternal mutant allele was correctly determined in 6 (86%) of 7 cases with the IVSI-1 mutation, 4 (100%) of 4 with the IVSI-6 mutation, 5 (100%) of 5 with the IVSI-110 mutation, and 13 (81%) of 16 with the codon 39 mutation. One false-positive test result was scored for the IVSI-1 mutation. Two cases with the codon 39 mutation were classified as uncertain and 1 case was excluded due to lack of a diagnostic test result at the time of analysis. These results yielded an overall sensitivity of 100% and specificity of 93.8%, with classified cases removed.Our recently described technique of the size-fractionation of circulatory DNA in maternal plasma may be potentially useful for the noninvasive prenatal determination of fetal point mutations.

Objective. To compare prenatal morphometric changes of umbilical cord components in intrauterine growth-restricted fetuses with and without abnormal umbilical artery Doppler parameters. Methods. Consecutive singleton intrauterine growth-restricted fetuses at a gestational age of older than 20 weeks were compared with matched appropriate-for-gestational-age fetuses. Intrauterine growth restriction was defined in the presence of a sonographic abdominal circumference below the 5th percentile for gestational age at the time of sonography and a birth weight below the 10th percentile. The sonographic examination included pulsed Doppler measurements of the umbilical artery resistance index and measurements of the umbilical cord cross-sectional area and the umbilical cord vessel area. Results. A total of 84 intrauterine growth-restricted fetuses and 168 appropriate-for-gestational-age fetuses were included in the study. All umbilical cord components (umbilical cord cross-sectional area, vein area, artery area, and Wharton jelly area) were smaller in the intrauterine growth-restricted fetuses. The prevalence of lean umbilical cords (cross-sectional area

To assess whether C-reactive protein (CRP) concentrations in cervical amniotic fluid reflect the condition of the intrauterine environment in patients with preterm premature rupture of membranes (PROM) before 35 weeks of gestation.Amniotic fluid was obtained in 29 consecutive patients admitted with the diagnosis of preterm PROM earlier than 35 weeks of gestation either by amniocentesis or by collecting cervical fluid. CRP was measured in maternal blood, amniotic fluid, vaginal fluid and in cord blood obtained at delivery. Intraamniotic infection was defined as a positive amniotic fluid for aerobic or anaerobic bacteria, or Mycoplasma. The placentas and umbilical cords were examined for the presence of chorioamnionitis and funisitis.A significant correlation was found between vaginal fluid CRP concentrations and both amniotic fluid (r = 0.95, p0.001) and umbilical cord levels (r = 0.47, p0.05). No correlation was found between maternal blood and vaginal fluid CRP concentrations. The proportion of patients with intraamniotic infection was 37.9% (11/29). The median (range) vaginal fluid CRP concentration was higher in patients with intraamniotic infection than in those with sterile amniotic fluid [901 (0-1354) vs. 507 (0-798) ng/mL, p0.001]. The median (range) vaginal fluid CRP concentration was higher in fetuses with (n = 12) than in those without funisitis (n = 17) [901 (598-1354) vs. 487 (0-1115) ng/mL, p0.01]. After adjustment for gestational age, vaginal fluid CRP concentration800 ng/mL remained a predictor of intraamniotic infection and funisitis.Increased vaginal fluid CRP concentration is associated with intraamniotic infection and funisitis. As CRP is produced by hepatocytes and does not cross the placenta, its measurement in vaginal fluid might be an additional parameter for the assessment of fetal well-being in patients with premature PROM.

The purpose of this study was to investigate whether the effects of 17beta-estradiol tablets that are designed for the treatment of postmenopausal urovaginal atrophy are influenced by the site of placement into the vagina.In this controlled crossover trial, 10 postmenopausal women received a single 17beta-estradiol tablet in the outer or inner one third of the vagina. Before and 3 hours after treatment, the pulsatility index, resistance index, and blood flow were evaluated in the uterine and periurethral vessels by Doppler examination. Parallel 17beta-estradiol serum evaluations were performed.Comparable and significant increases in 17beta-estradiol were observed. After inner administration, the pulsatility index and resistance index of both uterine arteries decreased; uterine artery blood flow increased significantly (P.0001) but decreased in periurethral vessels (P.02). After outer administration, the uterine artery pulsatility index, resistance index, and blood flow did not change, and the periurethral blood flow significantly increased (P.0001).For optimizing the efficacy while minimizing the risk of endometrial hyperplasia, 17beta-estradiol tablets must be placed in the outer one third of the vagina.

Objective This study was conducted to assess if the delivery of a previous growth-retarded (IUGR) fetus increases the risk of having an IUGR fetus in subsequent pregnancies and to explore if a familial pattern of transmission is involved. Methods Seventy consecutive multiparous women whose fetus was IUGR (group 1) and 70 controls (group 2) were enrolled in this study. Results The proportion of women who developed preeclampsia (9 versus 2, p = 0.05) and who had delivered an IUGR fetus in a previous pregnancy (20 versus 4, p < 0.05) were higher in group 1 than in group 2. There was no difference in the incidence of chronic hypertension, diabetes, smoking, substance or alcohol abuse, and HIV infection between the groups. After adjustment for preeclampsia, the delivery of a previous IUGR fetus remained a risk factor for having a subsequent IUGR fetus [Odds ratio = 6.7 (CI 2.15–21.22), p < 0.01]. Pedigree analysis conducted in 15 families revealed a familial cluster of IUGR infants in all families that were investigated. In 9 out of 15 families, a dominant pattern of inheritance of IUGR was observed while the remaining families were more heterogeneous. In one family, a balanced carrier of chromosome 7 inversion generated a malformed fetus and two IUGR infants. Conclusions This study clarifies that IUGR may be an inherited genetic condition and emphasizes that a knowledge of the family history and of the parental karyotype may be helpful in the prevention of both fetal malformations and adverse neonatal morbidity in subsequent low birth weight infants. Copyright © 2003 John Wiley & Sons, Ltd.

OBJECTIVE: To determine whether the sonographic morphometry of the umbilical cord components is different in preeclamptic compared with healthy pregnant women. METHODS: Consecutive women admitted after 20 weeks’ gestation with the diagnosis of preeclampsia and whose fetus was normally grown (cases) were included in the study. Each case was matched to a healthy pregnant woman (controls) who had ultrasonography at the same gestational age (± 3 days). The sonographic cross-sectional areas of the umbilical cord and umbilical vessels were obtained in all patients and plotted on reference ranges. The umbilical artery resistance index was measured in all patients with preeclampsia. RESULTS: Twenty-five preeclamptic women were enrolled. The proportion of cases with a lean (below the tenth centile) umbilical cord was higher in cases than in controls (12 of 25 versus 1 of 25, P < .001). The Wharton’s jelly area was lower in cases than in controls (median 105.8 mm2 [range 49.6–212.9 mm2] versus 138.7 mm2 [79.7–226.6 mm2], P = .024). The umbilical vein area was less in cases than in controls (median 29.2 mm2 [range 8.0–52.8 mm2] versus 37.4 mm2 [13.8–70.8 mm2], P = .032). The proportion of patients with a lean umbilical cord was higher among those with early-onset preeclampsia than in those with late-onset preeclampsia (12 of 19 versus 0 of 6, P = .014). CONCLUSION: Early-onset preeclampsia frequently is associated with reduced Wharton’s jelly area and umbilical vein area compared with normal pregnancy. Sonographic umbilical cord morphometry might have clinical value for prompt identification of women at risk for preeclampsia.

Traditionally, the prenatal assessment of the umbilical cord (UC) is limited to the assessment of the number of vessels and to the evaluation of umbilical artery blood flow parameters. Morphologic aspects of the UC have usually been studies by pathologists and retrospectively correlated with the perinatal outcome. The introduction of more sophisticated imaging techniques have offered the possibility to investigate the UC characteristics during fetal life from early to late gestation. A number of investigations have demonstrated that an altered structure of the UC can be associated with pathologic conditions (i.e. Preeclampsia, fetal growth restriction, diabetes, fetal demise). Nomograms of the various UC components have been generated and allow the identification of lean or large umbilical cords, entities frequently associated with fetal growth abnormalities and diabetes. A Wharton's jelly reduction has also been invoked as a possible cause of fetal death in the presence of single umbilical artery. Prenatal morphometric UC characteristics as well as arterial and venous blood flow parameters in normal and pathologic conditions will be discussed.

Objective: To determine reference ranges for the diameter and the cross-sectional area of the umbilical cord during pregnancy and to determine if umbilical cord morphometry is related to fetal size. Methods: A prospective cross-sectional study was designed to assess the sonographic cross-sectional diameter and area of the umbilical cord. The sonographic umbilical cord measurements were obtained in a plane adjacent to the insertion of the cord into the fetal abdomen. Nomograms for the umbilical cord diameter and area were computed. Fetal biometry included: biparietal diameter, abdominal circumference, and femur length. Polynomial regression analysis was conducted. Results: Five hundred and fifty seven patients were included into the study. The regression equation for the umbilical cord diameter (y) according to gestational age (x) was y=−10.0563+1.4265x+0.0194x2 and for the umbilical cord area (y′) was y′=91.6−3.3x+0.03x2−0.00007x3. A significant relationship was found between umbilical cord measurements and fetal anthropometric parameters. Conclusion: Reference ranges for umbilical cord diameter and area have been generated. The sonographic diameter and cross-sectional area of the umbilical cord increase as a function of gestational age and both diameter and area correlate with fetal size.