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.

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.

Combined oral contraceptives: health benefits beyond contraception.

It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

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.

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.

Fertility preservation in female cancer patients: an emerging challenge for physicians.

Fertility preservation has become an issue of great importance in female cancer patients due to increasing survival rates and delayed childbearing. It is an emerging challenge for physicians, cause of several related issues (multidisciplinary approach, doctor-patient communication, ethical, religious and legal problems) and many unresolved questions. This review aims to update the latest literature data, summarizing the effects of cancer treatments on female fertility and the various options currently available to offer cancer patients the opportunity of future pregnancies. Many strategies exist for fertility preservation in young women and they should be assessed according to the patient's age, type of cancer, partner status and time available. Some techniques are well established, others are still experimental. The established methods include embryo cryopreservation, transposition of ovaries prior to radiation therapy, radiation shielding of gonads and conservative surgical approaches. The experimental methods include oocyte cryopreservation, in vitro maturation of oocytes, ovarian tissue cryopreservation and transplantation, and ovarian suppression. Improvement of these techniques as well as better characterization of their success rates and risks, await further investigation. Oocytes donation and gestational surrogacy represent the last options. Thus, the care of these patients is challenging, complex and requires a multidisciplinary approach. A close collaboration between Oncologists, Specialists in Reproductive Medicine, Gynecologic Oncologists and Endocrinologists is crucial for always offering the best possible option.

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.

Borderline ovarian tumors, fertility-sparing surgery and pregnancy outcome.

BACKGROUND: Borderline ovarian tumors (BOTs) represent a type of epithelial tumors having a biologic intermediate behavior between clearly malignant and straight benign tumors. Most of BOTs interest women during fertile age, for which it is necessary to consider a fertility sparing surgery. AIM: To evaluate the clinical aspects and pregnancy rate of women affected by borderline ovarian tumors who have undergone fertility sparing surgery. PATIENTS AND METHODS: A study of 22 patients affected by BOTs who have been treated with a fertility sparing surgery was conducted between January 2005 and October 2011 at Sant'Andrea Hospital, "Sapienza" University of Rome. The patients' characteristics analyzed were: age, histological type, tumor size, adnexal surgery, pre-operative serum CA-125, diagnostic circumstances, number of patients who became pregnant and number of overall pregnancies. RESULTS: Among the 22 patients treated with a fertility sparing surgery, only sixteen wanted to get pregnant. Eleven patents out of 16 accomplished it. The pregnancy rate was 68.7%. CONCLUSIONS: Fertility sparing surgery can be considered a safe procedure for young women affected by borderline ovarian tumors.

Maternal and perinatal outcomes in spontaneous versus assisted conception twin pregnancies.

OBJECTIVE: To compare maternal and perinatal outcomes in twin pregnancies conceived via assisted reproductive techniques (ART) compared with spontaneous twin pregnancies. STUDY DESIGN: This retrospective study examined 345 dichorionic, di-amniotic twin pregnancies (207 conceived spontaneously and 138 conceived via ART), delivered between January 2007 and June 2011 at the San Pietro Fatebenefratelli Hospital, Rome, a tertiary medical centre. Maternal and perinatal outcomes were compared. A multiple logistic regression analysis was performed to calculate risk estimates as odds ratios (OR) adjusted for maternal age, parity and systemic diseases. Patient data were obtained from a computerized database and analyzed using Statistical Package for the Social Sciences Version 17. RESULTS: Gestational age and birth weight were lower in the ART group, and preterm delivery, gestational diabetes and placental abruption were higher in the ART group compared with the spontaneous conception group. The incidence rates of respiratory complications, patent ductus arteriosus and admission to the neonatal intensive care unit were higher among ART newborns. Length of hospital stay for mothers and newborns was longer in the ART group. No differences in mode of delivery, Apgar score at 5min, congenital anomalies, perinatal mortality, and other considered pregnancy and neonatal complications were found between the two groups. Multivariate analysis adjusted for maternal age, parity and systemic diseases revealed that only the rates of placental abruption [OR 7.45, 95% confidence interval (CI) 2.05-26.98] and patent ductus arteriosus (OR 3.39, 95% CI 1.01-11.46) were significantly higher for the ART group. CONCLUSIONS: Twin pregnancies conceived via ART are at greater risk of poorer outcomes than spontaneous twin pregnancies. This may be related to the type of conception and specific negative features of subfertile patients undergoing infertility treatment.

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.

[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.

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.

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.

Growth factors in preeclampsia: a vascular disease model. A failed vasodilation and angiogenic challenge from pregnancy onwards?

Preeclampsia is the major cause of maternofetal and neonatal morbi-mortality including intrauterine growth retardation, miscarriages and stillbirths. Inadequate vascular dilation and angiogenesis represent the crucial underlying defect of gravidic hypertension, denoting a failed response to the vasodilatory and pro-angiogenic challenge imposed by pregnancy, especially if multifetal. A similar pathogenesis appears involved in gestational diabetes. In this review we aimed to provide a hint on understanding the deeply involved angiogenic disorders which eventually culminate in utero-placental failure. The key players in these complex processes may be found in an intricate network of growth factors (GFs) and GF inhibitors, controlled by several vascular risk factors modulated by environment and genes, which eventually impact on early and late cardiovascular outcomes of mother and fetus.

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.

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.

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.

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.

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.