Giuseppe De Placido

Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity.

Hysteroscopic resection of the septum improves the pregnancy rate of women with unexplained infertility: a prospective controlled trial.

OBJECTIVE To assess fecundity of infertile women after surgical correction of uterine septum. DESIGN Prospective controlled trial. SETTING Three academic infertility clinics. PATIENT(S) Forty-four women affected by septate uterus and otherwise unexplained infertility represented the study group (group A), and 132 women with unexplained infertility were enrolled as control subjects (group B). INTERVENTION(S) Hysteroscopic metroplasty was performed in group A, and group B was managed expectantly. All women were followed-up for 1 year without any other intervention. MAIN OUTCOME MEASURE(S) Fecundity rate was calculated as the number of pregnancies per 100 person-months. RESULT(S) Pregnancy rate (38.6% vs. 20.4%) and live birth rate (34.1% and 18.9%) were significantly higher in group A than in group B. The survival analysis showed that the probability of a pregnancy in the twelve-months follow up was significantly higher in patients who had undergone metroplasty than in women with unexplained infertility. The corresponding fecundity (10-week pregnancy) rates were 4.27 and 1.92 person-months in women who had undergone metroplasty and in women with unexplained infertility, respectively. CONCLUSION(S) Hysteroscopic resection of the septum improves fecundity of women with septate uterus and otherwise unexplained infertility. Patients with septate uterus and no other cause of sterility have a significantly higher probability of conceiving after removal of the septum than patients affected by idiopathic sterility.

Laparoscopic approach to acute abdomen from the Consensus Development Conference of the Società Italiana di Chirurgia Endoscopica e nuove tecnologie (SICE), Associazione Chirurghi Ospedalieri Italiani (ACOI), Società Italiana di Chirurgia (SIC), Società Italiana di Chirurgia d’Urgenza e del Trauma (SICUT), Società Italiana di Chirurgia nell’Ospedalità Privata (SICOP), and the European Association for Endoscopic Surgery (EAES)

BackgroundIn January 2010, the SICE (Italian Society of Endoscopic Surgery), under the auspices of the EAES, decided to revisit the clinical recommendations for the role of laparoscopy in abdominal emergencies in adults, with the primary intent being to update the 2006 EAES indications and supplement the existing guidelines on specific diseases.MethodsOther Italian surgical societies were invited into the Consensus to form a panel of 12 expert surgeons. In order to get a multidisciplinary panel, other stakeholders involved in abdominal emergencies were invited along with a patient’s association. In November 2010, the panel met in Rome to discuss each chapter according to the Delphi method, producing key statements with a grade of recommendations followed by commentary to explain the rationale and the level of evidence behind the statements. Thereafter, the statements were presented to the Annual Congress of the EAES in June 2011.ResultsA thorough literature review was necessary to assess whether the recommendations issued in 2006 are still current. In many cases new studies allowed us to better clarify some issues (such as for diverticulitis, small bowel obstruction, pancreatitis, hernias, trauma), to confirm the key role of laparoscopy (such as for cholecystitis, gynecological disorders, nonspecific abdominal pain, appendicitis), but occasionally previous strong recommendations have to be challenged after review of recent research (such as for perforated peptic ulcer).ConclusionsEvery surgeon has to develop his or her own approach, taking into account the clinical situation, her/his proficiency (and the experience of the team) with the various techniques, and the specific organizational setting in which she/he is working. This guideline has been developed bearing in mind that every surgeon could use the data reported to support her/his judgment.

Chaotic mosaicism in human preimplantation embryos is correlated with a low mitochondrial membrane potential.

OBJECTIVE To determine the relationship between the intrinsic mitochondrial deltapsi of human embryos and the embryo karyotype. DESIGN Analysis of mitochondrial deltapsi of living embryos followed by chromosomal enumeration with fluorescence in situ hybridization. A tertiary center for assisted reproduction technology. PATIENT(S) Fifty-two patients attending the fertility center for assisted reproduction. INTERVENTION(S) Donated embryos were loaded with a mitochondrial deltapsi-sensitive fluorescence dye. MAIN OUTCOME MEASURE(S) Mitochondrial deltapsi was measured by confocal microscopy. Subsequently, embryos were fixed and fluorescence in situ hybridization analysis was used to denote embryo karyotype. MAIN OUTCOME MEASURE(S) Mitochondrial deltapsi and embryo karyotype. RESULT(S) An association was observed between low mitochondrial deltapsi and the detection of chaotic mosaicism. Analysis of oocytes suggested that this was due to the effect of low mitochondrial deltapsi on the morphology of the meiotic apparatus. CONCLUSION(S) The data suggest that the intrinsic mitochondrial deltapsi of human oocytes programs the developmental fate of embryos through an effect on the ability of oocytes to form a normal meiotic apparatus and not through nondisjunction.

A new more detailed stratification of low responders to ovarian stimulation: from a poor ovarian response to a low prognosis concept

The management of patients with impaired or poor ovarian response (POR) remains a controversial and complex clinical issue. A systematic review of 47 randomized controlled trials revealed 41 different definitions of POR (1). Notably, the number of oocytes retrieved was adopted as a criterion of POR in 40% of the trials, although the threshold number differed considerably among studies (1). To standardize the definition of POR, Ferraretti et al. (2) proposed new criteria, known as the ‘‘Bologna criteria,’’ based on three conditions: 1) advanced maternal age (R40 years) or any other POR risk factor; 2) a previous incident of POR; and 3) a low ovarian reserve test in terms of antim€ ullerian hormone (AMH) and antral follicle count (AFC). Two of these three criteria are required for a POR diagnosis. In addition, two cycles with POR after maximal stimulation are sufficient to classify a patient as a poor responder even in the absence of the other criteria mentioned. Although the Bologna criteria were found to be useful in predicting the outcome of IVF and for counseling purposes, their use in clinical trials has been questioned because they entail the risk of grouping together women who differ significantly in biologic characteristics (3). For example, according to the Bologna criteria, young women with a low ovarian reserve associated with a previous episode of POR, young women with a normal ovarian reserve and two POR episodes, and older women (R40 years) with a normal ovarian reserve and a previous episode of POR would be included in the same category even though the clinical management of these patients requires different strategies. In clinical terms, apart from the number of oocytes retrieved, various features that may affect treatment outcomes must be considered in the management of patients, namely: 1) the age-related embryo/blastocyst aneuploidy rate, which could dramatically change the prognosis in women that have the same oocyte yield; and 2) ovarian ‘‘sensitivity’’ to exogenous gonadotropins, which could be related to a specific genetic profile. To introduce a more nuanced picture of POR, we here propose clinically relevant criteria that can help to guide the physician in the management of patients. In detail, we suggest a more specific new definition of ‘‘low prognosis’’ patients that:

The management of Asherman syndrome: a review of literature

Asherman syndrome is a debatable topic in gynaecological field and there is no clear consensus about management and treatment. It is characterized by variable scarring inside the uterine cavity and it is also cause of menstrual disturbances, infertility and placental abnormalities. The advent of hysteroscopy has revolutionized its diagnosis and management and is therefore considered the most valuable tool in diagnosis and management. The aim of this review is to explore the most recent evidence related to this condition with regards to aetiology, diagnosis management and follow up strategies.

Hyperhomocysteinemia in women with unexplained sterility or recurrent early pregnancy loss from Southern Italy: a preliminary report

BackgroundHyperhomocysteinemia has been described as a risk factor for unexplained recurrent pregnancy loss. Increased levels of homocysteine may be due to inadequate dietary intake of folate and vitamin B12 and inherited defects within the methionine-homocysteine pathway such as MTHFR C677T gene polymorphism. However, the association between hyperhomocysteinemia and sterility problems have been underlined only for recurrent pregnancy loss while a relationship between hyperhomocysteinemia and female sterility is still matter of discussion.AimThis study sought to find out a possible relationship between sterility (primary sterility or secondary sterility due to recurrent pregnancy loss) and homocysteine metabolism.Patients and MethodsWe selected 20 patients with recurrent pregnancy loss, 20 patients with unexplained female sterility and 20 healthy women as control group. Several whole blood samples were collected by venipuncture. Firstly homocysteinemia and other related variables were tested (i.e. folate and vitamin B12 levels); thereafter DNA was extracted by a further whole blood sample collected in EDTA in order to screen MTHFR C677T gene polymorphism. Statistical analysis was performed by chi square test; differences were considered to be significant if p < 0.05.ResultsThe median fasting total plasma homocysteine concentration was 19.2 ± 6.14 μM for patients with recurrent pregnancy loss, while was 21.05 ± 8.78 μM for patients with unexplained sterility, vs 7.85 ± 3.31 μM of control group (p < 0.05). Fifteen patients with unexplained female sterility showed MTHFR C677T homozigosity vs 17 with recurrent pregnancy loss and 3 in the control group (p < 0.05). On the other hand no significant differences were found in the levels of vitamin B 12 in the three groups, while reduced folate concentrations were found in women with unexplained female sterility and recurrent pregnancy loss (p < 0.05 vs control group.DiscussionMTHFR C677T gene polymorphism is frequent in the studied populations. These data raise questions on the role of the homocysteine metabolism in sterility problems. Even though increased homocysteine (i.e. > 15 μM) and MTHFR C677T homozigosity have already been described as risk factors for recurrent pregnancy loss, few studies evaluated their role in women with unexplained sterility. Further studies on larger series are needed to better understand the role of homocysteine metabolism, including folate metabolism, in this clinical setting.

Laparoscopic nerve-sparing transperitoneal approach for endometriosis infiltrating the pelvic wall and somatic nerves: anatomical considerations and surgical technique

PurposeEndometriotic or fibrotic involvement of sacral plexus and pudendal and sciatic nerves may be quite frequently the endopelvic cause of ano-genital and pelvic pain. Feasibility of a laparoscopic transperitoneal approach to the somatic nerves of the pelvis was determined and showed by Possover et al. for diagnosis and treatment of ano-genital pain caused by pudendal and/or sacral nerve roots lesions and adopted at our institution. In this paper we report our experience and anatomo-surgical consideration regarding this technique.MethodsConfidence with this technique was obtained after several laparoscopic and laparotomic dissections on fresh, embalmed and formalin-fixed female cadavers and is now routinely performed at our institution in all cases of extensive endometriosis of the pelvic wall, involving the somatic nerves.ResultsWe describe two different laparoscopic transperitoneal approaches to the lateral pelvic wall in case of: (A) deep pelvic endometriosis with rectal and/or parametrial involvement extending to pelvic wall and somatic nerves; (B) isolated endometriosis of pelvic wall and somatic nerves.ConclusionsLaparoscopic transperitoneal retroperitoneal nerve-sparing approach to the pelvic wall proved to be a feasible and useful procedure even if limited to referred laparoscopic centers and anatomically experienced and skilled surgeons.

Recurrent pregnancy loss and thrombophilia.

Emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). First studies which focused on the association between thrombophilia and RPL underlined the role of reduced clotting inhibitors and RPL, and subsequent studies underlined a pathogenetic role of gene variant associated to hypercoagulable state in the occurrence of RPL. On the other hand, acquired thrombophilic abnormalities as antiphipsholipid syndrome are a well known cause of RPL and should be considered for a screening. These data are relevant because recent studies suggested a role of an extensive thromprophilaxis in women with RPL that should be addressed only in case of known thrombophilia and high risk of venous thromboembolism. Keywords Thrombophilia; Recurrent pregnancy loss; Factor V Leiden; Hyperhomocysteinemia; Antiphospholipid antibodies; PAI 4G\4G

In vitro fertilization following laparoscopic ovarian diathermy in patients with polycystic ovarian syndrome

Background. To evaluate the in vitro fertilization outcome in patients with polycystic ovarian syndrome previously treated by laparoscopic ovarian diathermy.