Quality of sex life in endometriosis patients with deep dyspareunia before and after laparoscopic treatment.

PURPOSE: The present work aims at showing how dyspareunia linked to endometriosis can affect the life of fertile age women and how surgical treatment of endometriosis can relieve painful symptoms and consequently improve sex and social life. METHODS: From a cohort of 320 women with a clinical and instrumental diagnosis of pelvic endometriosis, 67 patients were selected. These patients had deep dyspareunia that underwent laparoscopic surgical treatment. All the patients had filled out a pre- and post-surgery questionnaire. RESULTS: Six months after laparoscopic treatment, a significant reduction of dyspareunia was recorded, per VAS scores. A statistically significant improvement in sex life was observed between the pre- and post-surgical condition: in particular, an increased number of coituses and of non-difficult coituses, a higher number of patients who declared that pain did not negatively affect sexual pleasure and of patients achieving orgasm. CONCLUSIONS: The quality of the sex life in patients with endometriosis and dyspareunia showed significant improvement 6 months after laparoscopic treatment. In view of the diagnostic delay characterizing this disease and confirmed by our results, it is essential to involve a multidisciplinary team to assess all the signs and symptoms of endometriosis that may appear in a women of fertile age. This clinical approach is able to ensure a treatment that is as personalized as possible and an appropriate follow-up also with the objective of preserving reproductive performance.

Endometriosis allergic or autoimmune disease: pathogenetic aspects--a case control study.

PURPOSE OF INVESTIGATION: The aim of this study was to evaluate the correlation between endometriosis and pathologies on an immune basis for the possible involvement of the immune system in the pathogenesis of endometriosis. MATERIALS AND METHODS: In this retrospective study, data of 304 patients with endometriosis and 318 without endometriosis were collected in a uniform manner for both groups and inserted into two databases, respectively, for patients with and without endometriosis. The authors calculated the percentages of patients with allergies, autoimmune diseases, asthma in both groups, and later statistical analysis were performed with two different chi-square tests. RESULTS: The results obtained have shown that patients with endometriosis have a higher prevalence of allergies (p = 0.0003) and coexistence of both allergies and autoimmune diseases (p = 0.0274), compared to those without. CONCLUSIONS: The present study seems to support the possible association between endometriosis and allergic diseases.

Pulmonary embolism in pregnancy.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery, remaining a diagnostic and therapeutic challenge in both states. The absolute incidence of pregnancy-associated VTE has been reported as 1 in 1,000 to 1 in 2,000 deliveries. With 5-6 million new births computed in Europe in 2010, the potential clinical relevance of diagnosing and treating gravidic VTE is immediately evident. Fivefold higher in a pregnant as compared with a non-pregnant woman, VTE risk is also higher in postpartum than antepartum period. Ranked absolute and relative thrombotic risk may be described in the several thrombophilic conditions experienced by women at risk, according to which specific prophylactic and therapeutic recommendations have been formulated by recent guidelines. The main purpose of the present review article was to emphasize the most recent findings and recommendations in diagnostic strategies, discussing thrombophilic risk evaluation, as well as risks and benefits of various diagnostic techniques for both mother and fetus.

A 29-year-old woman with complex atypical hyperplasia and polycystic ovary syndrome: a challenging issue.

BACKGROUND: The standard treatment for complex atypical hyperplasia is hysterectomy and bilateral salpingo-oophorectomy. Although radical surgery offers high survival prospects, it also eliminates any chance of further fertility, thus in young nulliparous women who wish to preserve their childbearing potential, a conservative progestin therapy is preferable. CASE REPORT: The authors report a case of complex atypical hyperplasia in a 29-year-old nulliparous woman with polycystic ovary syndrome treated with norethisterone acetate in order to preserve her childbearing potential. The specimens sampled during the follow-up demonstrated inactive endometrium with pseudodecidual changes and no ultrasonographic images exhibited abnormal endometrial thickness. CONCLUSION: According to literature and to the authors' experience, they can affirm that progestin treatment is the most reasonable option for young nulliparous women affected by complex atypical hyperplasia who desire to maintain their fertility potential, showing its efficacy also in patients with an associated polycystic ovary syndrome.

Premature ovarian failure in a 17-year-old woman.

INTRODUCTION: Premature ovarian failure (POF) in a healthy adolescent is a rare event. It is diagnosed by the presence of amenorrhea, hypoestrogenism, and elevated follicle-stimulating hormone (FSH) levels before the age of 40. CASE: The patient presented with amenorrhoea at 17 years after identifying a change from her regular to irregular and metrorrhagic cycles. No positive medical history was noted regarding smoking, chemotherapy, radiation or autoimmune diseases and the physical examination was normal. Her family history revealed that both her maternal aunt and grandmother were affected by POF, but the karyotype test was normal and the FMR1 screening premutation test was negative. The patient underwent an ovarian biopsy which revealed the absence of functional follicles. She began a replacement therapy with estroprogestogens and she was informed about the most successful means to start a family, including adoption and oocyte donation. CONCLUSION: POF is a heterogeneous, multifactorial, and poorly understood condition that involves medical concerns, psychological sphere, and sexuality of the affected patients. Management should be directed at symptoms resolution, bone protection, and psychosocial support for women facing this unexpected and devastating diagnosis.

Celiac disease and endometriosis: an insidious and worrisome association hard to diagnose: a case report.

BACKGROUND: Primary infertility is an unusual presentation of celiac disease (CD). When non-classical symptoms are present, the diagnosis is not easy and it becomes even more difficult when CD is associated with endometriosis, representing a diagnostic challenge for medical practitioners and gynecologists. CASE REPORT: A 34-year-old patient presented to the authors' observation with primary infertility. Formerly she was treated for endometriosis and the diagnosis of CD was delayed. A favorable clinical and serological response following a gluten-free-diet (GFD) was achieved and a successful pregnancy was obtained. DISCUSSION: This case report emphasizes the role of the CD in women's infertility and the possible association between CD and endometriosis. Even if the relationship between these two diseases is still unclear and further studies to address this issue are required, more attention from gynecologists is needed, considering that the later this association is diagnosed, the greater the probability of adverse outcomes of health developing.

In vitro fertilization stimulation protocol for normal responder patients.

The aim of this prospective observational study is to determine the different outcomes of IVF/ICSI treatments after using antagonists or agonists of gonadotrophin-releasing hormone (GnRH) for controlled ovarian hyperstimulation (COH) in normal responder patients. Two hundred forty-seven patients undergoing IVF treatment at the Centre of Reproductive Medicine, Rome (CERMER), from January 2005 to December 2008, were included in the study. Patients were stimulated either with a standard long protocol with GnRH agonists (n = 156) or with GnRH antagonists (n = 91). The use of GnRH antagonists resulted in a significant reduction in the duration of the stimulation (Agonist Group 14.10 ± 2.25 vs Antagonist Group 11.34 ± 2.11; p < 0.001) and in the amount of gonadotrophin (IU of r-FSH) needed (Agonist Group 1878 ± 1109 vs Antagonist Group 1331 ± 1049; p = 0.0014). Moreover a lower number of cycles were cancelled with the antagonist protocol (4.39 vs 6.41%). The GnRH antagonist protocol, when compared to the GnRH agonist one, is associated with a similar clinical pregnancy rate, similar implantation rate, significantly lower gonadotrophin requirement and shorter duration of stimulation. For this reason, GnRH antagonists might be a good treatment even for normal responder patients undergoing IVF.

Heavy metals and placental fetal-maternal barrier: a mini-review on the major concerns.

BACKGROUND: Heavy metals (HMs) are environmental contaminants with toxic properties for wildlife and humans. The placenta is a privileged organ that, along with the fetal membranes and amniotic fluid, enables growth and development of the fetus during the physiological pregnancy. It also acts as a filter reducing the passage of harmful substances, protecting the embryo and then the fetus from exposure to pollutants. The placental barrier is not completely impermeable to the passage of harmful substances; indeed, HMs were detected not only in placental tissues, but also in amniotic fluid and umbilical cord blood. The amniotic fluid can be considered as a valuable marker of prenatal exposure to exogenous factors, and as an indicator of the integrity of placental barrier. The effect of an intrauterine exposure to heavy metals has been amply evaluated during the last decades. Several studies investigated the exposure to HMs in order to evaluate the mechanism of placental transfer and the impact on fetuses and later children's health. In particular,  the early exposure to Pb, Hg, and Cd was correlated to infant health effects, such as neurological, developmental, and endocrine disorders. The aim of this mini-review is to summarise the current state of knowledge about the interaction between HMs and placental barrier, considering possible implications on fetal health.

GnRH antagonists in assisted reproductive techniques: a review on the Italian experience.

Current Controlled Ovarian Stimulation (COH) for Assisted Reproductive Techniques (ART) pursues three main objectives: hypophyseal activity suppression, multiple follicle growth stimulation, and ovulation induction. By suppressing hypophyseal activity, it is possible to prevent untimely LH surge and allow the appropriate development of the leading follicle. The classical GnRH agonist long protocol is the most widely used in COH for ART. However, an alternative regimen based on GnRH antagonist has been recently introduced in clinical practice. As competitive antagonists, these drugs display an immediate and quickly reversible effect and they avoid hormonal withdrawal side effects. Moreover, this protocol shows undeniable advantages, including the shorter duration of the treatment, the lower amount of gonadotropin required, the shorter hormonal and ultrasound monitoring of patients, milder physical and emotional stress, and a lower risk of Ovarian Hyperstimulation Syndrome (OHSS). The use of GnRH antagonists was traditionally restricted to selected patients, as "poor responders" and women at high-risk of developing OHSS such as Polycystic Ovary Syndrome (PCOS) and patients who had previously experienced OHSS. These findings could prompt a trend to change from the standard agonist protocol to the antagonist protocol in all categories of patients. This review provides a comprehensive overview of the use of GnRH antagonist protocols applied both to IVF techniques and to IUI procedures in the Italian experience.

Imiquimod 5% cream versus cold knife excision for treatment of VIN 2/3: a five-year follow-up.

BACKGROUND: Vulvar intraepithelial neoplasia (VIN) is a premalingnant condition. For long time, surgery was considered the first-line therapy in the treatment of high grade VIN. Imiquimod was recently introduced as an alternative to surgery. AIM: To compare the overall complete response, the recurrence rate and the risk factors for relapse among patients with VIN 2/3 treated with Imiquimod or surgical excision. PATIENTS AND METHODS: Eighty women who had histological diagnosis of VIN 2 and VIN 3 were enrolled in this prospective study. Patients immunocompromised, with recurrent VIN, with well differentiated type VIN or VIN 1 and women treated more than once were excluded from the study. Patients were divided into two groups: group A was treated with Imiquimod, group B underwent surgical excision. Patients' characteristics analyzed were: age, smoking, degree of the primary lesion, state of margins, multifocal disease. We have evaluated the recurrence rate, the relapse rate, and the overall complete response, considering as recurrence the onset of a lesion after an initial complete response to Imiquimod and/or after the surgical treatment and as relapse all patients who had a recurrence plus those with medical treatment failure. RESULTS: Multifocal lesions (p = 0.03) and VIN 3 (p = 0.002) were associated with a higher risk of relapse. The recurrence rate was higher in the group B (p = 0.009), but the relapse rate was higher in the group A (p = 0.04). The overall complete response was better in the group B (p = 0.04). CONCLUSIONS: Although the advent of new medical options can decrease the morbidity associated with invasive surgical procedures, surgical treatments remain the best treatment modality for VIN with regard to relapse and overall complete response.

Endometrial adenocarcinoma in a young woman.

BACKGROUND: Endometrial carcinoma usually occurs in post-menopausal women, but in three to five percent of cases, it affects patients under 40 years of age, who wish to preserve their fertility. Patients with polycystic ovarian syndrome (PCOS) and the features of this syndrome (including obesity, hyperinsulinemia, and hyperandrogenism) are at great risk of developing endometrial carcinoma. CASE REPORT: The authors report a case of endometrial adenocarcinoma at Stage I in a 37-year-old obese woman with PCOS who underwent surgical staging. DISCUSSION: In young women with obesity and PCOS, a periodic evaluation of the endometrium and implementation of risk-reducing measures for the development of endometrial cancer are needed.

An unusual clinical presentation of a pure yolk sac tumor of the ovary: case report.

INTRODUCTION: Yolk sac tumor (YST) of the ovary is a rare neoplasm, which belongs to the group of ovarian germ cell tumors. It most commonly occurs in children and young women and it is characterized by high malignancy given its premature metastasis. An early diagnosis is important but not easy. CASE: An 18-year-old girl came to the authors' observation for amenorrhea lasting approximately 16 weeks. Abdominal examination revealed a painless palpable mass in the right lower abdomen. At admission ultrasonography (US) and magnetic resonance imaging (MRI) showed a complex mass of the right adnexa with a diameter of about 15 cm. The alpha-fetoprotein (AFP) serum level was elevated to 960 UI/ml. Fertility-sparing surgery was undertaken and the histopathology revealed a Stage IA pure YST. Chemotherapy was avoided and an intensive 36 months follow-up was performed without clinical and radiological evidence of recurrence. CONCLUSION: This is the first case report of a pure YST of the ovary presented with amenorrhea. It is also a very interesting case for its Stage IA despite prolonged duration of symptoms and AFP high levels.

Gynecologic sarcoma: a clinico-pathological review.

Most of the cases showing good prognosis in literature are probably intermediate tumors between benign and malignant of undetermined malignant potential (UMP) and other tumors with intermediate features which are currently not considered among sarcomas. Misdiagnosis of a malignant lesion as a benign one has a tragic outcome for the patient. Best therapic choice for sarcomas remains surgery, while chemotherapy (CTX) and radiation therapy (RT) could be used in adjuvant settings. A major effort should be played in the understanding of biological features and behavior of the disease to address a better clinical practice. Uterine sarcomas are rare gynecological tumors; their incidence has been increasing during the last few years.

[Venous thromboembolism in pregnancy: current state of the art]. / Tromboembolismo venoso in gravidanza: attuale stato dell'arte.

Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality during pregnancy or early after delivery and it remains a diagnostic and therapeutic challenge. The latest Confidential Enquiry into Maternal Deaths (2006-2008) showed that VTE is now the third leading cause of direct maternal mortality, beside sepsis and hypertension. In particular the prevalence of VTE has been estimated to be 1 per 1000-2000 pregnancies. The risk of VTE is five times higher in a pregnant woman than in non-pregnant woman of similar age and postpartum VTE is more common than antepartum VTE. A literature search was carried out on Pubmed using the following key words: "venous thromboembolism", "pregnancy", "risk factors", "prophylaxis", "anticoagulants". Studies from 1999 onwards were analyzed. This review aimed to provide an update of whole current literature on VTE in pregnancy highlighting the most recent findings in diagnostic and therapeutic strategies, considering in detail risks and benefits of various techniques and drug classes, for both mother and fetus. Large trials of anticoagulants administration in pregnancy are lacking and recommendations are mainly based on case series and on expert opinions. Nonetheless, anticoagulants are believed to improve the outcome of pregnancy for women with current or previous VTE.

External-beam radiotherapy and/or HDR brachytherapy in postoperative endometrial cancer patients: clinical outcomes and toxicity rates.

PURPOSE: The objectives of this study were to evaluate local disease control, overall survival (OS), disease-free survival (DFS) and local relapse-free survival (LRFS) in patients with endometrial cancer undergoing adjuvant vaginal brachytherapy (VBT )± external-beam radiotherapy (EBRT). MATERIALS AND METHODS: From September 2007 to February 2011, 40 patients with endometrial cancer were retrospectively analysed. Surgery consisted of total hysterectomy and bilateral salpingo-oophorectomy without node dissection (16 patients) or with bilateral pelvic node dissection (24 patients). The stage distribution was as follows: two IA, nine IB, 12 IC, five IIA, eight IIB, two IIIA and two IIIC. Thirty-four patients underwent EBRT and VBT. Six patients received VBT alone. RESULTS: Median follow-up was 26 months. The 5-year OS and DFS were 96.4% and 86.9%, respectively. No local recurrence was observed. Four patients presented distant disease (three had lung metastases and one had hepatic node metastases). Acute EBRT-related toxicities were seen in 15 (38%) patients. We recorded late toxicities in 14 patients (35%). There was no evidence of grade 3-4 toxicity. CONCLUSIONS: Adjuvant EBRT and/or VBT in patients with endometrial cancer showed good outcomes in terms of local disease control, with an acceptable toxicity profile.

Colostrum in menopause effects on vaginal cytology/symptoms.

The aim of this study was to assess the effects of three weeks of daily colostrum cream on vaginal cytology and local symptoms related to menopause. Genito-urinary symptoms and cell morphology were analyzed at time 0 (T0) and after three weeks (16 +/- days since the end of treatment) at time 1 (T1). Dyspareunia, vaginal dryness, and maturation index (MI) reached a statistically significant difference between T0 and T1. The results proved to be an alternative treatment for vaginal distress caused by lack of hormones in patients in which hormonal treatment is contraindicated.

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

Fertility-sparing treatment of endometrial cancer precursors among young women: a reproductive point of view.

BACKGROUND: Early-stage endometrial cancer and complex atypical hyperplasia are treated with hysterectomy and bilateral salpingo-oophorectomy. An emerging issue among younger women affected is the possibility of a fertility-sparing treatment with progestative therapy and close follow-up. AIM: To assess the possibility of conceiving after a diagnosis of atypical endometrial hyperplasia among women younger than 40 years old, in term of delaying definitive treatment and achieving pregnancy. MATERIALS AND METHODS: 15 women younger than 40 years old with complex CAH or early carcinoma of the endometrium and a wish to preserve fertility. Progestins were administered orally for at least a 12 weeks period. Endometrial biopsies were used at follow-up. RESULTS: In 11 women, a complete pathological remission of the disease was observed. 4 pregnancies were attained in 4 women. 3 showed progression and underwent definitive surgery at 18 months. 1 showed no response at 24 months and 3 cycles and was counseled to receive a hysterectomy. CONCLUSIONS: A conservative approach in patients younger than 40 years appears a valid option, and a progestative therapy trial should be attempted whether a valid consensus is attained. Considering the risk to find AEH at biopsies and eventually a carcinoma at hysterectomy (25% of cases) a careful management is strictly required.

Evaluation of E6 and E7 mRNA expression in HPV DNA positive breast cancer.

Several studies have suggested a possible role for HPV in the pathogenesis of the breast cancer. We investigated the presence of the HPV DNA in breast cancers and non malignant disease breast tissues by the use of a standard HPV detection method (INNO-Lipa HPV), in order to detect HPV DNA in metastatic nodes, to investigate a possible cervical HPV co-infection, and to evaluate the E6/E7 mRNA expression in HPV DNA positive breast cancer tissues. The rate of HPV infection was significantly higher in the cancer group than in controls (9/31 vs. 0/12, p = 0.04). One out of eight metastatic axillary nodes was positive for HPV infection; 2/3 of the positive HPV breast cancer patients were co-infected at the cervical site. The role of the virus in breast oncogenesis is still unclear, since our analysis failed in demonstrating the expression of viral E6 and E7 in positive HPV positive breast tumor tissues.

Prognostic implication of high risk human papillomavirus E6 and E7 mRNA in patients with intraepithelial lesions of the cervix in relationship to age.

Since the introduction of the cytological screening programs, a significant reduction in the incidence of cervical cancer has been achieved. Almost all of these cancers are related to high-risk (HR) Human Papillomavirus (HPV) cervical infections. However, the natural history of HPV infection seems to be different in younger patients, resulting in a higher rate of regression. There is, therefore, the need to identify HPV-related biomarkers in order to enhance the effectiveness of screening of high-risk cytological lesions, in particular in women over 35 years of age. This study aims to evaluate the prognostic value of the HR HPV E6 and E7 mRNA expression in women with intraepithelial lesions of the cervix, older or younger than 35 years of age. One hundred and eighty-four HR HPV DNA positive patients with a low squamous intraepithelial lesion (LSIL) were tested for mRNA expressions, included in an observational study, and evaluated at follow-up with standard cytology up to 24 months from the mRNA test. The frequency of HSIL/LSIL cytology in the older cohort of mRNA positive patients was significantly higher compared to mRNA-negative patients, both at 1 and 2 years of follow-up (Chi-square: p 0.007 and p 0.009), but this difference was not found in the younger cohort. According to our results, the E6/E7 mRNA test could be a biomarker for viral activity, useful in identifying patients at higher risk of abnormal cytology, and in implementing the management of HR HPV DNA-positive women over 35 years of age.