Approximately 70-80% of endometrial carcinomas, type I carcinomas, are associated with endometrial hyperplasia, hyperestrogenism, and expression of estrogen receptor (ER). The aim of this review was to clarify the role of ER in endometrial diseases carcinoma. The estrogens exert their effect via two estrogen receptor: α and β. The ERs modulate transcriptional process by binding directly to the estrogen response elements (ERE) located in the target gene, or in non classical mode through protein-protein tethering with other transcription factors. There are also orphan receptors (their natural ligands have not been identified). Among this group, estrogen receptor-related receptors (ERRs) were identified by their sequences similar to those of ERs. Since the ERRs have shown a high similarity in DNA binding domain with ERs can interfere with estrogen signalling strengthening the hypothesis of an estrogen-ER-ERR crosstalk. Recently, the ERs and estrogen enzymes emerge as pharmacological targets in different disorders, as well as ERRs, and they may represent the reliable biomarkers in endometrial disease.

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.

BACKGROUND: Incarceration of the fallopian tube is a rare condition. Symptoms are often misleading, making proper diagnosis difficult because of nonspecific clinical presentations. We report a case of cornual pregnancy occurring 7 months after the treatment of an incarcerated fallopian tube. We believe that the abnormal cornual implantation of the gestational sac was due to myometrial reconstruction of the uterine wall. CASE: A primigravid woman treated for the incarceration of a fallopian tube was subsequently found to have a cornual pregnancy in a septate uterus. The cornual pregnancy was successfully aborted after laparoscopic myometrial reconstruction, and a metroplasty allowed a subsequent pregnancy. CONCLUSION: This hazardous type of ectopic pregnancy can be managed with systemic administration of methotrexate. If the cornual pregnancy is correctly identified at an early stage, this medical management can be attempted and offers the potential advantage of avoiding surgery and increasing the likelihood of preserving fertility.

With infertility populations rapidly aging, treatments improving pregnancy chances assume increasing clinical importance. Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy rates and lower miscarriage rates in women with diminished ovarian function. This study was planned to evaluate whether pretreatment with DHEA may improve in vitro fertilization (IVF) parameters and pregnancy outcomes in infertile women with advanced reproductive age and normal ovarian reserve. Methods: In this double-blind, randomized, placebo-controlled study, 109 infertile patients aging 36-40 years old were selected to undergo the long protocol IVF. Eight weeks before starting the IVF cycle and during treatment, patients in Group 1 received 75 mg of DHEA once a day; patients in control group (Group 2) received placebo. The primary endpoint of the study was number of clinical pregnancy, live birth and miscarriage rates; secondary endpoint was modification of standard IVF parameters, including stimulation duration (days of rhFSH administration), E2 on HCG-day, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, number of transferred embryos and score of leading embryos transferred. Results: Patients in the DHEA group had a significantly higher live birth rate compared with controls (P < 0.05). Conversely, miscarriage rate was higher for patients in the control group (P < 0.05). Conclusions: DHEA supplementation may significantly improve IVF outcomes in infertile women with advanced reproductive age and normal ovarian reserve. © Tartagni et al.; licensee BioMed Central.

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. (Fertil Steril (R) 2010; 94: 247-9. (C) 2010 by American Society for Reproductive Medicine.)

STUDY OBJECTIVE: Hirsutism has negative impact on adolescent psychosocial development for both cosmetic and endocrine reasons. This study evaluated the effectiveness of a new intermittent, low-dose finasteride regimen consisting of 2.5 mg of drug given every 3 days (1 day of treatment, 2 days of drug withdrawal) for 6 months in girls with hirsutism by polycystic ovarian syndrome (PCOS) or idiopathic hirsutism (IH). DESIGN AND PARTICIPANTS: Twenty-eight girls (15-19 y old) with hirsutism were randomly assigned to 2 treatment groups and treated for 6 months. Fourteen patients (7 with IH, 7 with PCOS) received finasteride; fourteen patients (7 with IH, 7 with PCOS) received placebo. Hirsutism score (HS), clinical, and hormonal effects were compared between the 2 groups. RESULTS: In patients treated with finasteride, the HS value at 6 months was 52.9% lower than that observed at baseline in girls with IH, and 52.8% lower in girls with PCOS (P < .0001 for both). Similarly, the 3α-17 β-androstenediol glucuronide serum levels were decreased by 34.8% in patients with IH, and by 47.5% in patients with PCOS (P < .0001, respectively). Finasteride treatment was well tolerated and did not alter values of BMI, serum levels of sexual hormones, metabolic parameters related to liver and kidney function as well as glycemic and lipidic asset. CONCLUSIONS: A low-dose of finasteride, given every 3 days, reduces the HS in young patients affected by PCOS or IH. Compared with conventional continuous finasteride administration, the intermittent low-dose regimen has similar efficacy with the advantage to be safer and less expensive

Objective: To determine whether decreased estrogen receptor alpha (ER-alpha) expression in endometriotic lesions could be balanced by an increased expression of estrogen receptor-related receptors (ERRs). To evaluate whether ERR-alpha expression is influenced by hormonal change in fertile and menopausal women. Design: Prospective controlled study. Setting: University Hospital, Department of Gynecology. Patient(s): Twenty-five women: 20 women of reproductive age with (n = 10) and without (control; n = 10) endometriosis and 5 menopausal women. Intervention(s): Real-time polymerase chain reaction (qPCR). Immunohistochemistry. Main Outcome Measure(s): The ER and ERR expression levels were studied by reverse transcriptase-qPCR, ELISA, and immunohistochemistry using endometriotic and normal endometrial tissues. The ERR-alpha protein distribution was performed by immunohistochemistry in fertile and menopausal women. Result(s): Increased levels of ER-beta were associated with ER-alpha, ERR-alpha, and ERR-gamma reductions in ectopic tissue but not in eutopic and normal endometria. Similar levels of ERR-beta were found in women with and without endometriosis. The ERR-alpha expression was similar in proliferative and secretory endometrial samples, whereas a down-regulation of this receptor was found in atrophic tissue. Conclusion(s): Our data confirm the up-regulation of ER-beta as the principal receptor involved in the progression of human endometriosis. In addition, we found that ERR-alpha seems to be unresponsive to hormonal changes during the menstrual cycle. (Fertil Steril (R) 2011;96:102-6. (C)2011 by American Society for Reproductive Medicine.)

OBJECTIVE: The purpose of this study was to assess myocardial function of fetuses who were exposed to intraamniotic infection compared with fetuses of uncomplicated pregnancies by the application of tissue Doppler and strain rate (SR) imaging. STUDY DESIGN: We evaluated the right ventricular function of fetuses with preterm premature rupture of membranes and proven intraamniotic infection (n = 12 fetuses) and healthy fetuses (n = 27). Tissue Doppler velocities during early diastolic relaxation (E(m)) and atrial contraction (A(m)) and early diastolic SR were measured as indices of diastolic function, whereas the peak systolic strain and SR were used as parameters of systolic function. RESULTS: Fetuses with intraamniotic infection exhibit impairment in both diastolic and systolic performance, which was characterized by increased diastolic compliance (increased E(m)/A(m) ratio, increased early diastolic SR compared with the control fetuses), decreased systolic contractile function (reduced systolic strain and SR), and longitudinal myocardial dyskinesia. CONCLUSION: New echocardiographic tools suggest that fetal heart is a target organ in the context of intraamniotic infection.

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 p38 alpha 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 1 alpha (HIF1 alpha) to forkhead transcription factor O (Fox)-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 p38 alpha/p38A-specific inhibitor SB202190 and performed a morphological, proliferation, and survival analyses. Finally, we studied HIF1 alpha and FoxO3A expressions and signaling pathways to evaluate their role in SB202190-induced effects. Results: p38 alpha 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 HIF1 alpha- 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 p38 alpha, might be exploited to design new therapeutic approaches to cancer treatment.

Abstract Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e., infection, inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic systemduring normal and complicated pregnancy in maternal blood, maternal-fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes. © 2014 Mastrolia et al.

To evaluate the hypothesis that pretreatment with dehydroepiandrosterone(DEHA) may improve the result on in vitro fertilization (IVF) and the pregnancy outcome among infertile women with normal ovarian reserve STUDY DESIGN: Double-blind, randomized, placebo-controlled study. 52 infertile patients received the long protocol IVF. Patients in Group 1, received 75 mg of DHEA once a day , 8 weeks before starting the IVF cycle and during treatment; control group (Group 2) received placebo. The primary endpoint was pregnancy, live birth and miscarriage rates, secondary endpoint was standard IVF parameters such us stimulation duration (hCG day ), E2 on HCGday, endometrial thickness, number of retrieved oocytes, metaphase II oocytes, embryos transferred and score of leading embryos transferred. RESULT(S): Patients in the DHEA group had a significantly higher live birth rate compared with controls ( P< 0.05). Miscarriage rate was higher in control group ( P< 0.05) CONCLUSION: DHEA supplementation could have a beneficial effect on IVF outcome in infertile women with normal ovarian reserve.

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.

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 A-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.

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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.

Abstract 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