Nutraceuticals in fibroid management after ulipristal acetate administration: An observational study on patients' compliance.

OBJECTIVE: On May 13, 2020, the Italian government Pharmaceutical Agency (AIFA) stopped ulipristal acetate (UPA) treatments for uterine fibroids (UFs), so patients shifted to other natural treatments. The authors tested the patients' compliance with UF natural treatments. METHODS: Thirty patients of reproductive age (30-45 years) affected by UFs stopped UPA intake and started epigallocatechin gallate (EGCG) plus vitamin D3 treatment. Patients were asked to complete the Uterine Fibroid symptoms and Quality of Life (UFS-QOL) questionnaire, divided into symptoms severity (SS) and health-related quality of life (HRQL), after UPA suspension and to repeat it after 3 months of natural treatment. Collected data were analyzed using paired Student's t test, considering a P value less than 0.05 to be significant. RESULTS: The SS score was significantly lower (-12.19%) for natural treatment when compared with UPA administration. The HRQL score significantly improved (+11.79%) after shifting treatment from UPA to natural therapy. All the investigated parameters appeared improved by 10% after the natural treatment. No adverse effects were reported following the natural treatment. CONCLUSION: Natural treatments showed positive compliance in patients with UFs, based on HRQL score, representing an alternative therapeutic opportunity for patients forced to stop UPA therapy.

Diagnostic Accuracy of Doppler Ultrasound in Predicting Perinatal Outcome in Appropriate for Gestational Age Fetuses: A Prospective Study.

OBJECTIVE: To elucidate the role of Doppler ultrasound in predicting perinatal outcome in appropriate for gestational age (AGA) fetuses at term. MATERIAL AND METHODS: Prospective study carried out in a dedicated research ultrasound clinic. The inclusion criterion was AGA fetuses, defined as those with an estimated fetal weight between the 10th and 90th percentile, at 36 + 0-37 + 6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome including either adverse intrapartum events or abnormal acid-base status at birth. Secondary outcomes were the individual components of the primary outcome. The Doppler parameters explored were umbilical artery (UA) PI, middle cerebral artery (MCA) PI, uterine arteries (UtA) PI and cerebroplacental ratio (CPR). Attending clinicians were blinded to Doppler findings. Logistic regression and ROC curve analyses were used to analyze the data. RESULTS: 553 AGA fetuses were included. There was no difference in mean UA PI (p = 0.486), MCA PI (p = 0.621), CPR (p = 0.832) and UtA PI (p = 0.611) between pregnancies complicated by composite perinatal morbidity compared to those not complicated by composite perinatal morbidity. In pregnancies complicated by adverse intrapartum outcome, the mean MCA PI (1.47 ±â€Š0.4 vs 1.61 ±â€Š0.4, p = 0.0039) was lower compared to the control group, while there was no difference in UA PI (p = 0.758), CPR (p = 0.108), and UtA PI (p = 0.177). Finally, there was no difference in any of the Doppler parameters explored between AGA fetuses with abnormal acid-base status at birth compared to those without abnormal acid-base status at birth. In the logistic regression analysis, UA PI, MCA PI, CPR, UtA PI, EFW and AC percentiles were not independently associated with composite adverse outcome, adverse intrapartum outcome or abnormal acid-base status at birth in non-SGA fetuses. The diagnostic performance of all of these Doppler parameters for predicting composite adverse outcome, adverse intrapartum outcome and abnormal acid-base status was poor. CONCLUSION: Cerebroplacental and maternal Doppler is not associated with or predictive of adverse pregnancy outcome in AGA fetuses close to term.

Hemorrhagic corpus luteum: Clinical management update.

Hemorrhagic corpus luteum (HCL) is an ovarian cyst formed after ovulation and caused by spontaneous bleeding into a corpus luteum (CL) cyst. When HCL rupture happens, a hemoperitoneum results. Clinical symptoms are mainly due to peritoneal irritation by the blood effusion. The differential diagnosis is extensive and standard management is not defined. The authors elaborated a comparison of the differential diagnosis and therapeutic modalities from the laparoscopic approach to nonsurgical, medical options because hemorrhage from HCL is often self-limiting. The authors reviewed all data implicated with the development of HCL, trying to give homogeneity to literature data. The authors analyzed extensive literature data and subdivided the medical approach into many topics. The wait-and-see attitude avoids unnecessary laparoscopic surgery using supportive therapies (antifibrinolytic, analgesics, liquid infusion, transfusions and antibiotic prophylaxis). Surgical therapy: operative management should be laparoscopic, with surgical options such as luteumectomy, ovarian wedge-shaped excision or oophorectomy. Prevention: the possibility to preserve fertility is essential, mainly in patients with bleeding disorders or undergoing anticoagulant therapy; therefore, they need estro-progestinics or GnRH analogues to prevent ovulation and avoid further episodes of HCL. This review will aid physicians in making an early diagnosis of HCL, to avoid unnecessary surgery, and use the most effective treatment.

Diagnostic accuracy of Doppler ultrasound in predicting perinatal outcome in pregnancies at term: A prospective longitudinal study.

INTRODUCTION: To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term. MATERIAL AND METHODS: Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36+0 and 37+6  weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data. RESULTS: In all, 600 consecutive singleton pregnancies from 36 weeks of gestation were included in the study. Mean MCA PI (1.1 ± 0.2 vs 1.5 ± 0.4, P < 0.001) and cerebroplacental ratio (1.4 ± 0.4 vs 1.9 ± 0.6, P < 0.001) were lower, whereas uterine arteries PI (0.8 ±0.2 vs 0.7 ±0.3, P = 0.001) was higher in pregnancies experiencing than in those not experiencing composite adverse outcome. Conversely, there was no difference in either UA PI (P = 0.399) or estimated fetal weight centile (P = 0.712) between the two groups, but AC centile was lower in fetuses experiencing composite adverse outcome (45.4 vs 53.2, P = 0.040). At logistic regression analysis, MCA PI (odds ratio [OR] 0.1, 95% CI 0.01-.2, P = 0.001), uterine arteries PI (OR 1.4, 95% CI 1.2-1.6, P = 0.001), abdominal circumference centile (OR 1.12, 95% CI 1.1-1.4, P = 0.001) and gestational age at birth (OR 1.6, 95% CI 1.2-2.1, P = 0.004) were independently associated with composite adverse outcome. Despite this, the diagnostic accuracy of Doppler in predicting adverse pregnancy outcome at term was poor. CONCLUSIONS: MCA PI and cerebroplacental ratio are associated with adverse perinatal outcome at term. However, their predictive accuracy for perinatal compromise is poor, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.

Laminin and Collagen IV: Two Polypeptides as Marker of Dystocic Labor.

Collagen IV and Laminin are localized in cells and tissue of numerous human organs including the uterus, where these polypeptides control either age changes, or uterus growth in pregnancy, or ripening and dilatation in labor. Authors examined the polypeptides distribution of collagen IV and Laminin in the human pregnant uterus, in normal and dystocic labor, to clarify their physiologic role, by distribution and/or their changes in prolonged dystocic labor. We collected lower uterine segment (LUS) fragments during cesarean section (CS); these biopsies were treated with basic morphological staining for the observation of microscopic- anatomic details. Other samples were processed with immunohistochemical staining for collagen IV and for membrane bound Laminin. All morphological and immunochemical results were analyzed with quantitative analysis of images and statistical analysis of data. Both Collagen IV and Laminin show changes in the pregnant uterus before 4 hours of full cervical dilatation in patients after 4 hours. All the three types of the human uterine cells, mucosal, submucosal and smooth muscular cells, are more reduced in LUS after 4 hours of cervical dilatation in dystocic labor. The connective tissues (including fibroblast) show the most evident changes in the dystocic LUS, collagen IV and laminin changes during cervical dilatation in prolonged dystocic labor, with a decreased elasticity with increased roughness and dryness. The LUS anatomical modifications during labor can be the cause of pathological changes in protracted dystocic labor. In the dystocic labor that lasts more than 4 hours from the complete cervical ripening and dilatation, the laminin and collagen IV concentration reduces in the LUS tissue. In dystocic labor, delivery should be completed before the 3 hours of full dilation, to avoid a reduction of laminin and collagen IV and a worsening of LUS healing for the next pregnancy.

Neurotransmitters and Neuropeptides Expression in the Uterine Scar After Cesarean Section.

Peptides and neuropeptides influence the uterine disorders of healing or cicatrization, chronic pelvic pain and disorder of pregnancy, labor and puerperium. They also promote changes in the lower uterine segment (LUS) during pregnancy, labor and delivery. We investigated the tissue quantity of neurotensin (NT), neuropeptide tyrosin (NPY) and Protein Gene Product 9.5 (PGP 9.5) in women submitted to elective cesarean section (CS) and urgent CS. During surgery, authors biopsied tissue samples of vesico-uterine space (VUS) to detect nerve fibers, and compared them. VUS samples from 106 patients have been evaluated with light microscopy, immunochemistry and Immunohistochemistry, and finally by Quantimet Leica analyzer software. Significantly higher amount of nerve fibers, containing NT, NPY and PGP 9.5 have been found in VUS tissue samples obtained during the first elective CS and during the first urgent CS were respectively 5±0.7, 7±0.6 and 5±0.9 CU and 2.5±0.5, 3.6±0.4 and 3.5±0.9 CU (p<0.05). This neurotransmitter reduction should indicate the inflammatory damage of cervical tissue for LUS over distension in dystocic-prolonged labor before CS. These results may be correlated with the decrease of NT, NPY and PGP 9.5, responsible for an optimal healing and LUS functions. In our opinion, the presence of neuropeptides reduction in uterine samples of women undergoing urgent CS may be due to a prolonged fetal head station in LUS, with a tissue denervation, in consequence of both overdistension and inflammatory process of the dystocic LUS.

Outcome of fetal gastro-intestinal cysts: a systematic review and meta-analysis.

OBJECTIVES: To explore the outcome of fetal gastrointestinal (GI) cysts and to ascertain the detection rate of prenatal ultrasound in identifying these anomalies. METHODS: Medline and Embase databases were searched. The outcomes explored were: resolution of the cyst, additional GI anomalies detected only at birth, clinical symptoms, need for surgery, post-surgical complications and diagnostic accuracy. Meta-analyses of proportions and hierarchical summary receiver operating characteristics (HSROC) model were used to analyse the data. RESULTS: Ten studies were included; 27.0% (95% CI 2.6-64.4) of the cysts resolved either pre or post-natally. Additional GI anomalies were detected in 6.0% (95% CI 1.1-14.7). Clinical symptoms occurred in 31.1% (95% CI 14.9-50.2), while 50.6% (95% CI 10.0-90.8) had surgery. Post-surgical complications occurred in 6.1% (95% CI 0.2-19.6). Overall detection rate of prenatal ultrasound in correctly identifying GI cysts was good (sensitivity: 94.5%, 95% CI: 39.1-99.8; specificity: 97.7%, 95% CI 89.9-99.5). CONCLUSION: GI cysts are usually benign. Clinical symptoms occur in approximately one third of children. About one third of the cysts resolves, while the rate of complications after surgery is low. Prenatal ultrasound has an overall good diagnostic accuracy in identifying these anomalies. © 2016 John Wiley & Sons, Ltd.

Intrapartum sonographic signs: new diagnostic tools in malposition and malrotation.

In the past years, numerous studies have been published on the use of ultrasound during labor, showing this is an effective, accurate and objective tool for the assessment of the fetal head position and station. Literature affirmed that traditional transvaginal digital examination is highly subjective and dependent on the operator's experience. On the contrary, the use of intrapartum suprapubic transabdominal ultrasound can improve accuracy in determination of fetal head position and the precise knowledge of the location of specific fetal head landmarks in relationship to maternal pelvis. Intrapartum ultrasound will assist obstetricians in the diagnosis of normal labor progression, suggesting when medical and or operative intervention should be taken in case of complications. During each fetal head movement, there is a very specific relationship between fetal head landmarks and well-identified maternal structures, so the ultrasound diagnosis is performed step by step. In this review, we summarized the clinical situation of the fetal head in the pelvis and the relative ultrasonographic signs. Moreover, we collected all the ultrasonographic measures to diagnose the fetal head progression and rotations in the birth canal.

Molecular alterations in endometrial archived liquid-based cytology.

Endometrial cancer is one of the most common gynecological malignancy worldwide and its prevalence is increasing. The introduction of liquid-based cytology (LBC) and endoflower dispositive in routine practice gives the possibility to examine endometrial cells by cytological diagnosis and may also release the opportunity to study molecular alterations, in endometrioid type cancer in which carcinogenesis is well known. We gathered 72 cases of endometrial LBC samples and corresponding formalin-fixed paraffin-embedded (FFPE) blocks, collected from 2004 to 2010. DNA was isolated from both samples using standard protocols. DNA quality and quantity were assessed using Nanodrop and BIOMED2 multiplex PCR. Mutations in exon 5 of PTEN and exon 20 of PI3K were studied using Sanger sequencing. DNA with good quality and amount was isolated from 67/72 FFPE cases. In these samples, two cases were found to harbor mutations in exon 5 of PTEN. No PI3K mutations were identified. LBC samples were then assessed to verify the concordance with the FFPE DNA results. The results obtained were concordant, that is the wild type cases in FFPE were also wild type in LBC and vice versa for the mutated case. Unfortunately, the second case of mutation in PTEN could not be confirmed in LBC due to low amount of DNA obtained. Detection of molecular alterations in LBC will open a new era for the detection in asymptomatic women of precursor lesions that could evolve into cancer and for endometrial cancer diagnosis and screening in selected high-risk women.

Detection of residual/recurrent cervical disease after successful LEEP conization: the possible role of mRNA-HPV test.

BACKGROUND: Loop Electrosurgical Excision Procedure (LEEP) represents the mainstay technique for CIN2+ removal. The major concern in conservative treatment is to verify whether CIN eradication was complete, since incomplete excision is associated with an increased risk of cervical cancer. The histopathologic evaluation of resection margins status is far from perfect, since cervical lesions may recur in 5-15% of patients who had conisation specimens with clean margins. Current follow-up protocol of patients treated by conisation for high grade CIN is manly based on the combination of cytology-plus- HPV-DNA testing. This approach showed high sensitivity but low specificity level in detecting recurrence. The consequence were overdiagnosis and overtreatment, especially in youngest women, in which spontaneous regression rate of CIN is substantial. In this longitudinal study we investigated whether patient's age, cone depth and pre-conisation HPV-load level, may be used as predictive markers for residual/recurrent CIN after conisation. Then we aimed to examined the role of E6/E7 mRNA testing during post-conization follow-up. METHODS: The study, focused on the outcome of 116 patients treated for CIN by LEEP, included three consecutive steps. Firstly, the authors analysed the prevalence of residual/recurrence disease after conization; then, they investigated which factors may influence treatment failure even when resection margins were clean; finally, they evaluated the diagnostic accuracy of E6/E7 mRNA test as predictive marker of recurrence. RESULTS: HPV infection was detected in 31% of patients at 6-month follow-up and in 11.2% of patients, at 24-month follow-up. Younger women showed higher rate of recurrence than older ones. The risk of residual/recurrent infection did not correlate with cone-depth. Recurrence is higher in patients with low viral load level than in those having high load levels. mRNA test showed higher specificity and positive predictive value than the combination cytology-plus-HPV-DNA test. CONCLUSION: The inclusion of mRNA test within the current protocol of follow-up would efficiently and earlier predict the risk of residual/ recurrent cervical abnormalities after conisation. This molecular strategy would also reduce overtreatment, particularly in patients above 30 years of age.

Surgical management of neurovascular bundle in uterine fibroid pseudocapsule.

The uterine fibroid pseudocapsule is a fibro-neurovascular structure surrounding a leiomyoma, separating it from normal peripheral myometrium. The fibroid pseudocapsule is composed of a neurovascular network rich in neurofibers similar to the neurovascular bundle surrounding a prostate. The nerve-sparing radical prostatectomy has several intriguing parallels to myomectomy. It may serve either as a useful model in modern fibroid surgical removal, or it may accelerate our understanding of the role of the fibrovascular bundle and neurotransmitters in the healing and restoration of reproductive potential after intracapsular myomectomy. Surgical innovations, such as laparoscopic or robotic myomectomy applied to the intracapsular technique with magnification of the fibroid pseudocapsule surrounding a leiomyoma, originated from the radical prostatectomy method that highlighted a careful dissection of the neurovascular bundle to preserve sexual functioning after prostatectomy. Gentle uterine leiomyoma detachment from the pseudocapsule neurovascular bundle has allowed a reduction in uterine bleeding and uterine musculature trauma with sparing of the pseudocapsule neuropeptide fibers. This technique has had a favorable impact on functionality in reproduction and has improved fertility outcomes. Further research should determine the role of the myoma pseudocapsule neurovascular bundle in the formation, growth, and pathophysiological consequences of fibroids, including pain, infertility, and reproductive outcomes.

Robotic assisted surgery in gynecology: current insights and future perspectives.

To focus on the recent adoption, patents, experience, and future of Robotic assisted surgery (RAS) applications in gynecologic surgery, a computer aided and manual search for clinical and systematic reviews, randomized controlled trials, prospective observational studies, retrospective studies and case reports published between 1970 and January of 2011 has been performed. The use of RAS in gynecologic patients includes hysterectomy, myomectomy, tubal reanastomoses, radical hysterectomy, lymph node dissection, and sacrocolpopexies. Although individual studies vary, gynecological RAS is often associated with longer operating room time but similar clinical outcomes, decreased blood loss, and shorter hospital stay. RAS procedures on women have, however, their own limitations: the patented equipment is very large, bulky, and expensive, the staff must be trained specifically on draping and docking the instruments, the lack of surgical haptic feedback, a limited vaginal access, a limited specific instrumentation, and the need for larger port incisions requiring fascial closure. The RAS significantly facilitates gynecologic surgery, even if well-designed, prospective studies are needed to fully assess the value of this equipments in particular studies with well-defined clinical and long-term outcomes, including complications, cost, pain, return to normal activity, and quality of life. The future of robotic surgery in gynecology may be bright, but currently, caution is advisable and clinically meaningful long-term outcomes are needed. These recent patents, however, has exciting potential for future applications, especially in long-distance telesurgery and might change the paradigm of gynecologic surgery in the future.