Serena Pinzauti

Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.

Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.

Preoperative and postoperative clinical and transvaginal ultrasound findings of adenomyosis in patients with deep infiltrating endometriosis

Objectives: Deep infiltrating endometriosis (DIE) represents the most complex form of endometriosis and its treatment is still challenging. The coexistence of DIE with other appearances of endometriosis stimulates new studies to improve the preoperative diagnosis. Adenomyosis is a clinical form that shares several symptoms with DIE. The present study investigated the possible presence of adenomyosis in a group of women with DIE and its impact on pre- and postoperative symptoms. Materials and Methods: A group of women (n = 121) undergoing laparoscopic treatment for DIE were enrolled. Clinical and ultrasound evaluations were performed as preoperative assessment. The ultrasonographical appearances of DIE and of adenomyosis were recorded by 2-dimensional ultrasound. The following symptoms were considered: dysmenorrhea, dyspareunia, abnormal uterine bleeding, bowel, and urinary symptoms. Pain was evaluated by the visual analog scale system and menstrual bleeding was assessed by the use of the pictorial blood assessment chart. In a subgroup of women (n = 55), a follow-up evaluation (3-6 months after surgery) was done. Results: A relevant number of patients with DIE showed adenomyosis (n = 59; 48.7%); in this group, dysmenorrhea (P = .0019), dyspareunia (P = .0004), and abnormal uterine bleeding (P < .001) were statistically higher than that in the group with only DIE. After surgery, painful symptoms improved in the whole group but remained significantly higher (P < .001) in the group with adenomyosis. Conclusions: Deep infiltrating endometriosis is frequently associated with adenomyosis, significantly affecting pre- and postoperative symptoms and thus influencing the follow-up management.

Activins and Related Proteins in the Establishment of Pregnancy

Activin A and related proteins (inhibins, follistatin [FS], follistatin-related gene [FLRG], endometrial bleeding associated factors [ebaf]) are involved in the complex mechanisms allowing the establishment and the maintenance of pregnancy. As a consequence of ovarian progesterone stimuli, activin A is expressed and secreted by the stromal endometrial cells, which locally induces the decidualization process, a prerequisite for implantation. Moreover, activin A does influence the implantation phase, also enhancing cytotrophoblast differentiation, indirectly, by increasing the expression of other molecules involved in embryo implantation, such as matrix metalloproteinases (MMPs) and leukemia inhibitory factor (LIF). The local derangement of activin A pathway in some pregnancy disorders (incomplete and complete miscarriages, recurrent abortion, and ectopic pregnancy [EP]) further sustains the hypothesis that activin A and its related proteins play a relevant role in the establishment of pregnancy.

Transvaginal sonographic features of diffuse adenomyosis in 18–30‐year‐old nulligravid women without endometriosis: association with symptoms

To investigate whether there are sonographic features of diffuse adenomyosis in 18–30‐year‐old nulligravid women without endometriosis and to examine their association with symptoms of dysmenorrhea and abnormal uterine bleeding.

How to Manage Bowel Endometriosis: The ETIC Approach

A panel of experts in the field of endometriosis expressed their opinions on management options in a 35-year-old patient desiring pregnancy with a history of previous surgery for endometrioma and bowel obstruction symptoms. Many questions that this paradigmatic patient may pose to the clinician are addressed, and various clinical scenarios are discussed. A decision algorithm derived from this discussion is proposed as well.

Adenomyosis by transvaginal ultrasonographic features in nulligravid women without endometriosis aged 18–30 years: correlation with symptoms

To investigate whether there are sonographic features of diffuse adenomyosis in 18–30‐year‐old nulligravid women without endometriosis and to examine their association with symptoms of dysmenorrhea and abnormal uterine bleeding.

Uterine fibroids affect pregnancy outcome in women over 30 years old: role of other risk factors

Objective: To evaluate the pregnancy outcome in women >30 years old with uterine fibroids also considering other possible concomitant risk factors. Methods: A multicentric, observational and retrospective study was conducted. All women were asked to complete a questionnaire while they were in hospital and the outcome of pregnancy was investigated. Results: Women with uterine fibroids before pregnancy were more frequently >35 years old and in their clinical history before pregnancy showed more pelvic pain, polliachiuria, previous pelvic surgery, hypermenorrhea and dysmenorrhea, than control women (p < 0.0001). During pregnancy patients with uterine fibroids showed significantly more threatened preterm birth (PTB) and PTB, weight gain, hyperemesis, gestational hypertension and post-partum bleeding and showed more often requirement for emergency cesarean section (p < 0.0001). The multivariate logistic regression model used for evaluating the effect of clinical parameters on outcome of pregnancy showed that age >35 years, pelvic pain, work, weight gain, hyperemesis, threatened miscarriage and threatened PTB were significantly correlated with unfavorable pregnancy outcome , independently of the presence of uterine fibroids (p < 0.0001). Conclusions: The present study confirming a more frequent negative pregnancy outcome in presence of uterine fibroids, showed that other risk factors may affect pregnancy and delivery outcome in women aging >30 years old.

Endometriosis and Perceived Stress: Impact of Surgical and Medical Treatment

Background: The aim of the study was to investigate the levels of perceived stress in a group of women with a long-term history of endometriosis in conjunction with surgical and/or medical treatments. Methods: A clinical trial was conducted at the Department of Molecular and Developmental Medicine, University of Siena, in collaboration with a non-profit association of women with endometriosis, A.P.E. Onlus. Patients (n = 204) with a previous diagnosis of endometriosis (for at least 3 years) were included in this study. Each patient completed a semi-structured questionnaire and a validated scale to assess perceived stress, the Perceived Stress Scale (PSS) by e-mail. Results: The study showed that in women with a long-term history of endometriosis, the level of perceived stress was increased by repeated surgical treatments and reduced by some medical treatments. The median PSS value was 23 (range 9-36) and 30.6% of the study population were included in the highest stress category (>26). The highest levels were found in patients who had undergone the most surgery. The use of progestins was associated with a lower perceived stress (p = 0.004) than in the patients treated with gonadotropin-releasing hormones. Conclusions: Long-term endometriosis has a relevant impact on perceived stress, in particular in those undergoing repeated surgery.

Twin pregnancies after assisted reproductive technologies: the role of maternal age on pregnancy outcome

OBJECTIVES Our aim was to investigate whether advanced maternal age (≥40years) still impairs the outcome of twin pregnancies after assisted reproductive techniques (ART). STUDY DESIGN The retrospective observational study evaluated 430 nulliparous dichorionic diamniotic twin pregnancies conceived with ART. The population was divided into women <40 years old (Group A, n=265) and ≥40 years old (Group B, n=165). RESULTS Gestational diabetes mellitus and gestational hypertension/preeclampsia were significantly more frequent in nulliparous twin pregnancies after ART ≥40years compared to <40years (p=0.021 and p<0.001, respectively). In univariate analysis of twin pregnancies after ART, there was only a trend of higher incidence of total preterm birth (PB) rate within mother aged ≥40 years old (p=0.104). However, Group A showed higher rate of spontaneous preterm birth (SPB) <37 weeks, whereas Group B showed significantly higher rate of iatrogenic PB <37 weeks of gestation (p=0.023 and p=0.001, respectively). For delivery <32 weeks of gestation, the rate of SPB in Group A was significantly higher (p=0.002). A higher incidence of PB was observed in Group B after heterologous treatment (p<0.001). Despite this, the absolute prevalence of PB in the entire population is higher in Group A, both after autologous (22.5%) and heterologous (25%) ART treatment, than in Group B (10.1% vs 21.4%). CONCLUSIONS Our data indicate that nulliparous twin pregnancies conceived with ART in mothers ≥40 years old did not show significantly higher incidence of PB, even if an increased rate of iatrogenic PB <37 weeks is showed.

Serum markers for the noninvasive diagnosis of endometriosis

Endometriosis is a disease that affects millions of women worldwide and its diagnosis is still challenging. Medical history, symptoms together with imaging data may address the correct diagnosis, but the gold standard remains laparoscopic assessment with histological confirmation. The development of serum markers as diagnostic tools for endometriosis may allow a prompt and noninvasive diagnosis. Several serum biomarkers have been investigated over the years, but none of these have shown a clinical utility and nowadays the more realistic diagnostic biomarker consists in a panel of biomarkers. The recent introduction of new technologies such as genomics and proteomics may represent the future perspective of endometriosis diagnosis.