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Cervical squamous cell carcinoma of the uterus associated with pelvic organ prolapse is very rare and usually occurs in elderly women. We hereby present an 81-year-old postmenopausal woman presented to the outpatient department with an ulcerated irreducible uterine procidentia. The prolapse was reduced under general anesthesia and biopsy of the lesions confirmed a cervical squamous cell carcinoma. Pretreatment clinical staging revealed a 16 cm enlarged uterus and mild to moderate unilateral hydroureteronephrosis, secondary to periureteric infiltration, clinical stage IIIB. The patient was disqualified from surgery, and palliative chemotherapy plus radiotherapy was recommended. Patient’s general condition was rapidly deteriorated, and three months after the diagnosis, the patient passed away. Therapeutic management of cervical cancer associated with uterovaginal prolapse is not well established. Hence, this article presents the clinical concerns that arise in such rare and neglected cases.

We present a case of a large interstitial pregnancy which was intraoperatively ruptured, but was eventually laparoscopically treated. The patient experienced 9 weeks of amenorrhea, and a right cornual pregnancy measuring 6 cm was diagnosed. The patient consented on having a minimal surgical treatment, and a laparoscopic right cornuotomy was decided. During surgery, and prior to any manipulation to the uterus, there was a spontaneous rupture of the ectopic which resulted in excessive bleeding. Temporal pressure at the bleeding site and ligation of the superior branches of the right uterine artery allowed for a careful dissection of the right uterine cornua and achieved hemostasis. The surgery proceeded uneventfully thereafter. Although surgical intervention in such cases entails a high risk of hemorrhage, successful completion of the laparoscopy lies on the meticulous preoperative planning and the controlled precise surgical steps during the procedure.

Adenomyosis has generally been considered as a disease of adult life; however, it is rarely encountered in young girls, especially when severe dysmenorrhea and chronic pelvic pain are present. The variant of adenomyosis that is specific to adolescent women is the so-called cystic adenomyosis which represent cystic formations within the myometrium with hemorrhagic content resembling that of an endometriotic cyst. Recent advances in imaging techniques and improved awareness of the disease led to the emergence of several articles investigating the pathophysiology and implications on diagnosis of adenomyosis in younger patients.

Fetal growth restriction (FGR) is a gynecological disorder of varying etiology. In the present study, an expression analysis of pregnancy-associated plasma protein A (PAPPA), pregnancy-associated plasma protein A2 (PAPPA2) and placenta-specific-1 (PLAC-1) was conducted in pregnancies with FGR and control pregnancies. Placental tissues were collected from pregnancies with FGR (n=16) and control pregnancies (n=16) and the expression of the genes of interest was examined by qPCR. The mean expression levels of PAPPA and PAPPA2 were significantly lower (P

Ovarian cancer is the most lethal gynecologic malignancy. Lack of early detection markers and the development of drug resistance following chemotherapy are the main obstacles to effective treatment strategies. Despite advances in cancer research and treatment, survival statistics have remained largely unchanged for many years. Genetic alterations alone cannot account for the complexity of ovarian cancer. The potential reversibility of epigenetic mechanisms makes them attractive candidates for the prevention and treatment of ovarian carcinoma. Detection of the epigenetic signature of each cancer cell may be useful in the identification of candidate biomarkers for disease detection, classification, and monitoring and may also facilitate personalized cancer treatment. Herein we summarize the current developments in epigenetic research in ovarian cancer and evaluate the potential role of epigenetic markers as diagnostic and prognostic tools. Furthermore, novel epigenetic therapies that target cancer cells, reactivate tumor-suppressor genes, and resensitize tumor cells to chemotherapy, will be discussed.

Endometriosis is defined by the presence and growth of functional endometrial tissue, outside the uterine cavity, primarily in the ovaries, pelvic peritoneum and rectovaginal septum. Although it is a benign disease, it presents with malignant characteristics, such as invasion to surrounding tissues, metastasis to distant locations and recurrence following treatment. Accumulating evidence suggests that various epigenetic aberrations may play an essential role in the pathogenesis of endometriosis. Aberrant DNA methylation represents a possible mechanism repsonsible for this disease, linking gene expression alterations observed in endometriosis with hormonal and environmental factors. Several lines of evidence indicate that endometriosis may partially be due to selective epigenetic deregulations influenced by extrinsic factors. Previous studies have shed light into the epigenetic component of endometriosis, reporting variations in the epigenetic patterns of genes known to be involved in the aberrant hormonal, immunologic and inflammatory status of endometriosis. Although recent studies, utilizing advanced molecular techniques, have allowed us to further elucidate the possible association of DNA methylation with altered gene expression, whether these molecular changes represent the cause or merely the consequence of the disease is a question which remains to be answered. This review provides an overview of the current literature on the role of DNA methylation in the pathophysiology and malignant evolution of endometriosis. We also provide insight into the mechanisms through which DNA methylation-modifying agents may be the next step in the research of the pharmaceutical treatment of endometriosis.

Herein we present two cases of pregnant women with placenta percreta and severe hematuria during the 24th and 35th weeks of pregnancy, respectively. A timely sonographic diagnosis was feasible in the first case and cesarean section was performed during the 29th week. During the operation, the placenta was invading the bladder wall and concomitant hysterectomy with cystotomy and bladder wall reconstruction was performed. The second case presented in our emergency department with vaginal bleeding during the 35th weeks of pregnancy. She underwent an emergency cesarean section with uterine preservation, cystotomy, and bladder reconstruction.

Extrapelvic endometriosis is a rare entity that presents serious challenges to researchers and clinicians. Endometriotic lesions have been reported in every part of the female human body and in some instances in males. Organs that are close to the uterus are more often affected than distant locations. Extrapelvic endometriosis affects a slightly older population of women than pelvic endometriosis. This might lead to the assumption that it takes several years for pelvic endometriosis to “metastasize” outside the pelvis. All current theories of the pathophysiology of endometriosis apply to some extent to the different types of extrapelvic endometriosis. The gastrointestinal tract is the most common location of extrapelvic endometriosis with the urinary system being the second one. However, since sigmoid colon, rectum, and bladder are pelvic organs, extragenital pelvic endometriosis may be a more suitable definition for endometriotic implants related to these organs than extrapelvic endometriosis. The sigmoid colon is the most commonly involved, followed by the rectum, ileum, appendix, and caecum. Most lesions are confined in the serosal layer; however, deeper lesion can alter bowel function and cause symptoms. Bladder and ureteral involvement are the most common sites concerning the urinary system. Unfortunately, ureteral endometriosis is often asymptomatic leading to silent obstructive uropathy and renal failure. Surgical excision of the endometriotic tissue is the ideal treatment for all types of extrapelvic endometriosis. Adjunctive treatment might be useful in selected cases.

Subcutaneous emphysema to the neck represents a rare entity mainly derived from iatrogenic and traumatic origin. We report a case of a subcutaneous emphysema resulted from an intraoral injury aiming to emphasise the significance of precise medical history to identify an unlikely mechanism. A 40-year-old female patient was presented with subcutaneous emphysema extending from the region underneath the left eye up to the submandibular area of the neck. The patient complained of painful, swollen neck. The patient mentioned that the symptoms began after an intraoral injury accidentally caused by the use of a high-pressure water jet device meant for car wash. The patient was managed conservatively and was discharged after 2 days. This case highlights the urgency for clinical suspicion for unlikely mechanisms. Moreover, the manufacturer companies should alert and give official warning for the contingency of injury due to incorrect or careless usage.

Spontaneous hematoma of the umbilical cord due to rupture of an umbilical cord vessel is a rare obstetrical complication which represents a severe cause of fetal distress with a 50% of reported fetal demise. Although several risk factors have been suggested, the cause of this disorder remains unknown. Herein we describe two cases of term deliveries with spontaneous umbilical cord hematomas which resulted in live births. In both cases the diagnosis was made intrapartum and was confirmed by a histopathologic examination.

Genetic alterations alone cannot account for the complexity of ovarian cancer. The potential reversibility of epigenetic mechanisms makes them attractive candidates for the prevention and/or treatment of ovarian carcinoma. Detection of the epigenetic signature of each cancer cell may be useful in the identification of candidate biomarkers for disease detection, classification and monitoring and may also facilitate personalized cancer treatment. In ovarian cancer, in addition to other non‑gynaecological cancers, two opposite epigenetic phenomena occur. The first involves an overall global decrease in DNA methylation of heterochromatin leading to demethylation of several oncogenes, while the second involves specific CpG island hypermethylation associated with the promoters of tumor suppressor genes. Early studies focused on the methylation patterns of single genes associated with tumorigenesis. However, newer genome-wide methods have identified a group of genes whose regulation is altered by DNA methylation during ovarian cancer progression.

Purpose To analyze laparoscopically treated cases of adenomyosis based on intraoperative and histopathology findings and to correlate different types with patients' presenting symptoms and characteristics, as well as with the surgical approach. Materials and methods Sixty-eight women who underwent laparoscopic treatment of adenomyosis at a referral center for gynecological laparoscopy. Results Four distinct types of adenomyosis could be identified: diffuse, sclerotic, nodular, and cystic (54.5%, 13%, 28%, and 4.5% of cases, respectively). Menorrhagia as the main presenting symptom was significantly more frequent in patients with the diffuse type (84%) compared to those with sclerotic (44%) and nodular (37%) types (p = 0.025 andp = 0.001, respectively). All cases of cystic and nodular adenomyosis were treated by laparoscopic excision of the lesion. Eighty-nine percent of patients with sclerotic adenomyosis were treated with wide laparoscopic excision of the abnormal tissue. Eighty-one percent of patients with diffuse adenomyosis were treated with laparoscopic hysterectomy. Conclusions Adenomyosis can be classified in four distinct types with differences in the presenting symptoms, as well as in the ideal surgical approach.

The aim of this study was to assess the relationship between long term quality of life (QoL), patient satisfaction, and Pelvic Organ Prolapse Quantification (POPQ) scores following anterior vaginal repair with mesh.This cross-sectional study included 127 patients who underwent anterior pelvic floor repair with mesh and were assessed 1.03-2.69 years post surgery. One hundred and four women completed the King's Health Questionnaire (KHQ), the Sheffield Prolapse Symptoms Questionnaire, the EurolQoL EQ-5D, and the Patient Satisfaction Index. POPQ scores were recorded for up to 1 year.Patients reported good current QoL and high patient satisfaction. POPQ Aa and Ba scores showed significant improvements from a pre-surgery median of +1 to a median of -3 at 12-month follow-up (P.001). Patient satisfaction was inversely correlated with Aa scores at 12 months (r(s) = -.360, n = 49, P.011). There were high QoL scores at an average 2 years after anterior compartment mesh repair.QoL outcomes were good. There was a significant relationship between Aa scores and patient satisfaction, suggesting that this outcome is a key to patient satisfaction.

Throughout in utero development, the placenta plays a key role in controlling growth and development. The placenta acts not only as a gatekeeper of nutrient and waste exchange between mother and developing fetus, but also as a regulator of the intrauterine environment. Its functions can be influenced by the environment encountered throughout pregnancy, thereby altering the appropriate genetic programming needed to allow for appropriate fetal growth. Epigenetic alterations related to environmental exposures have been linked to aberrant fetal growth. DNA methylation, which is the best known DNA epigenetic modification, may provide an attractive mechanism linking environmental cues to placental pathology, with consequences for fetal growth and adult life. Alteration of the methylation patterns of genes expressed in the placenta has recently been found to modify gene expression and subsequently impair function of the placenta. Although there is strong evidence to demonstrate that the environment can affect the pattern of DNA methylation of the placenta during fetal development, a direct association between environmental conditions, methylation alterations and gene expression is difficult to confirm. DNA methylation in the placenta has mainly been investigated in the context of imprinted and non-imprinted genes transcription. Several environmental factors have also been assessed in regard to their association with changes to the epigenetic motives of embryonic and extraembryonic tissues and their impact on pregnancy outcome. In this review, we briefly present the available evidence regarding the role of DNA methylation patterns of the placenta on aberrant fetal growth.

Please cite this paper as: Gourvas V, Sifakis S, Dalpa E, Soulitzis N, Koukoura O, Spandidos D. Reduced placental prolyl hydroxylase 3 mRNA expression in pregnancies affected by fetal growth restriction. BJOG 2010;117:1635–1642. Objective To investigate the role of the hypoxia-inducible factor (HIF) pathway in fetal growth restriction (FGR). Design A case–control study. Setting Research laboratory and gynaecology clinic. Sample Twenty placentas from normal pregnancies and 20 from FGR pregnancies. Methods RNA extraction, cDNA synthesis, quantitative real-time polymerase chain reaction (qRT-PCR) assay, statistical analysis. Main outcome measures mRNA expression of HIF-1α, HIF-2α and HIF-β (ARNT), along with prolyl hydroxylase domain 3 (PHD3), which leads to proteasomal degradation of HIF-α subunits. Results No statistically significant differences in the transcription levels of ARNT and HIF-2α were found between FGR and normal placentas. By contrast, PHD3 and HIF-1α mRNA were downregulated in FGR placentas. PHD3 mRNA expression was associated with gestational age at delivery (P = 0.008), birthweight centile (P = 0.029) and abnormal umbilical artery (UA) Doppler measurements (P = 0.034). Conclusions As PHD3 regulates the HIF-mediated hypoxic response in FGR, we deduce that fetal adaptation to hypoxia ranges from impaired to adequate, as observed by the gradient of PHD3 downregulation in relation to the severity of FGR.

Background The placental anticoagulant protein Annexin A5 (ANXA5) is highly expressed on the apical surfaces of syncytiotrophoblasts and plays an important role in maintaining blood fluidity in the placental circulation. We investigated the mRNA and protein expression of ANXA5 in placentas from pregnancies complicated by fetal growth restriction (FGR) compared with uncomplicated pregnancies. Materials and Methods Placental tissue was collected from 18 pregnancies complicated by FGR and 16 pregnancies with a normal outcome. ANXA5 mRNA expression was quantified by Real-Time PCR (RT-PCR), and protein concentrations were measured by an enzyme-linked immunosorbent assay (ELISA). Results A decreased ANXA5 mRNA expression was observed in placenta samples from FGR-affected pregnancies compared to those from uncomplicated pregnancies. However, similar ANXA5 protein levels were measured in both specimen groups. No correlation was observed between ANXA5 mRNA and protein levels. Conclusions Transcriptional ANXA5 down-regulation was demonstrated in FGR-affected pregnancies, although protein levels were similar in FGR-related placentas and controls. We can speculate that either recruitment of the protein from the bloodstream or increased apoptosis or post-transcriptional modifications occur, which affect ANXA5 protein levels in FGR-related placentas. Further studies are required to reveal the role of ANXA5 in FGR pathology.

BACKGROUND: Asplenia or polysplenia and complex cardiovascular defects, in association with disturbed body symmetry and malposition of internal organs, constitute the main corpus of malformations in the heterogeneous group of heterotaxy disorders. In affected pregnancies, prenatal diagnosis is possible by ultrasonography, while prognosis and counseling largely depend upon the severity of the cardiac defect. CASE: We present a 25 week gestation fetus with typical findings of asplenia–cardiovascular defect–heterotaxy (Ivemark syndrome) and aplasia of the pancreas. CONCLUSIONS: Pancreatic aplasia emerges as an additional phenotypic feature in Ivemark syndrome and raises the possibility of total pancreatic insufficiency of the affected neonate as an additional, although rare, clinical consideration. Birth Defects Research (Part A) 2008. © 2008 Wiley-Liss, Inc.

Amniotic band syndrome is an uncommon, congenital fetal abnormality with multiple disfiguring and disabling manifestations. A wide spectrum of clinical deformities are encountered and range from simple ring constrictions to major craniofacial and visceral defects. We report a case of constriction amniotic bands involving upper extremities and intrauterine fetal death due to strangulation of umbilical cord. Abnormally elevated levels of α-fetoprotein and β-chorionic gonadotropin were detected at 17 weeks’ gestation. They were probably caused by the loss of cutaneous integrity of the fetus (α-fetoprotein), and by the placental attempt to counteract the fetal growth restriction and hypoxia, due to the strangulation of umbilical cord by the amniotic bands (β-chorionic gonadotropin).

Dilatation of the fetal umbilical vein is a rare, most commonly isolated finding. Approximately 100 cases have been reported in the literature that describe different management approaches, especially regarding the time of delivery. We present a new case of umbilical vein dilatation diagnosed at 23 weeks’ gestation as an isolated sonographic finding, in a fetus with short umbilical cord, delivered at 38 weeks’ gestation. The clinical and sonographic features as well as the management options of this uncommon condition are shortly discussed.

Inflammatory myofibroblastic tumour (IMT) of the bladder is a rare tumour of indeterminate malignant potential with myofibroblastic differentiation, with a generally benign but rarely aggressive behaviour. Vesical IMT is usually treated by transurethral resection or partial cystectomy. Herein we describe a case of a woman who underwent laparoscopic excision of an IMT of the bladder, initially diagnosed as deep infiltrating endometriosis.

ΕΙΣΑΓΩΓΗ Η ενδομήτρια υπολειπόμενη ανάπτυξη (ΕΥΑ) (intrauterine growth restriction IUGR) περιγράφει μία κατάσταση κατά την οποία το έμβρυο δεν μπορεί να αναπτυχθεί όσο του υπαγορεύει η γενετική του προδιάθεση. Τα νεογνά που γεννιούνται με ΕΥΑ είναι μικρότερα για τη δεδομένη ηλικία κύησης (μικρά για την ηλικία κύησης, small for gestational age SGA), και το βάρος τους είναι κάτω από την 10η ή 5η ή 3η εκατοστιαία θέση για την ηλικία κύησης, σύμφωνα με διαφορετικούς ορισμούς. Είναι πολύ σημαντικό να είμαστε σε θέση να διαγνώσουμε τα νεογνά που είναι μικρά για την ηλικία κύησης επειδή είχαν υπολειπόμενη ανάπτυξη κατά τη διάρκεια της ενδομήτριας ζωής τους, σε σχέση με αυτά που είναι «προγραμματισμένα» για να γεννηθούν μικρά. Τα νεογνά της πρώτης κατηγορίας, εμφανίζουν βραχυπρόθεσμες και μακροπρόθεσμες επιπτώσεις στην ανάπτυξη και υγεία τους γιατί ουσιαστικά κάποιος βλαπτικός παράγοντας επέδρασε στην ομαλή αύξηση τους κατά τη διάρκεια της εμβρυϊκής ζωής τους με αποτέλεσμα να μην αναπτυχθούν όσο θα μπορούσαν με βάση τη γενετική τους προδιάθεση. Οι αιτιολογικοί παράγοντες που έχουν συσχετιστεί με την παθοφυσιολογία της ΕΥΑ έχουν παραδοσιακά χωριστεί σε 3 κατηγορίες: μητρικοί, εμβρυικοί και μητροπλακουντιακοί παράγοντες. Η πλακουντιακή ανεπάρκεια όμως αφορά την πλειοψηφία των περιπτώσεων ΕΥΑ. Η συνεχιζόμενη έρευνα για την ανεύρεση των παθογενετικών μηχανισμών της ΕΥΑ έχει συσχετίσει διαφορετικά γενετικά αίτια με την εμφάνιση της παθολογικής αυτής οντότητας. Παρόλα αυτά δεν έχει βρεθεί κάποιος παράγοντας ο οποίος μπορεί να προβλέψει την εμφάνιση ΕΥΑ από τα αρχικά στάδια της κύησης, ή να μπορεί να εξηγήσει την παθοφυσιολογία της νόσου. Οι έρευνες σε μοριακό επίπεδο θα μπορούσαν να βοηθήσουν στη διαλεύκανση των διεργασιών που αφορούν την ΕΥΑ, η οποία είναι ξεκάθαρο πλέον ότι δεν αποτελεί μία μεμονωμένη νόσο, αλλά ένα σύμπτωμα πολλών διαφορετικών επιπλοκών της κύησης. Τα γονίδια αποτύπωσης αποτελούν μία κατηγορία γονιδίων που σχετίζονται με την αύξηση και τη λειτουργία του πλακούντα, και κατά συνέπεια αποτελούν ιδανικούς υποψηφίους για τη μελέτη γενετικών μηχανισμών που σχετίζονται με διαταραχές στην πλακουντιακή λειτουργία που συνεπάγονται καθυστέρηση της ανάπτυξης του εμβρύου. Η αποτύπωση αποτελεί ένα μοριακό μηχανισμό κατά τον οποίο μόνο το ένα αλληλόμορφο από ένα ζεύγος γονιδίων εκφράζεται, και εξαρτάται από την προέλευση του χρωμοσώματος του (μητρική ή πατρική) το κατά πόσο θα εκφραστεί ή όχι. Αυτή η ελεγχόμενη έκφραση, ρυθμίζεται από επιγενετικούς μηχανισμούς όπως η μεθυλίωση του DNA. Η μεθυλίωση της κυτοσίνης μπλοκάρει τον μηχανισμό μεταγραφής ενός γονιδίου. Η μεθυλίωση στους εκκινητές των γονιδίων έχει σαν αποτέλεσμα την μη αναγνώριση τους από τους παράγοντες μεταγραφής και την RNA πολυμεράση, αφού οι μεθυλιωμένες κυτοσίνες προτιμούν να συνδέονται με μία πρωτείνη η οποία ονομάζεται μεθυλ- κυτοσίνη συνδετική πρωτείνη ή MeCP. Όταν η περιοχή ενός εκκινητή αναγνωριστεί από έναν παράγοντα μεταγραφής ως μεθυλιωμένη, τότε η μεταγραφή θα ανασταλεί. Πολλά γονίδια αποτύπωσης εκφράζονται σε σημαντικό βαθμό στον πλακούντα και επηρεάζουν τη λειτουργία και τη μορφολογία του. Τα πατρικής προέλευσης εκφραζόμενα γονίδια ευνοούν την ανάπτυξη του εμβρύου, ενώ αντίθετα τα μητρικής προέλευσης εκφραζόμενα γονίδια «φρενάρουν» την ανεξέλεγκτη παροχή συστατικών προς το έμβρυο με στόχο την εξοικονόμηση πόρων προς όφελος της μητέρας και των επόμενων κυήσεων. Τα γονίδια IGF2 και Η19 αποτελούν δύο γονίδια αποτύπωσης που μοιράζονται κοινούς μεταγραφικούς μηχανισμούς αλλά με αντίθετο τρόπο και παίζουν σημαντικό ρόλο στην ανάπτυξη του εμβρύου. Το γονίδιο IGF2 εκφράζεται από το πατρικό αλληλόμορφο και ευνοεί την ανάπτυξη του εμβρύου ενώ το μητρικό αλληλόμορφο δεν μεταγράφεται. Αντίθετα το μητρικό αλληλόμορφο του γονιδίου Η19 είναι εκείνο που εκφράζεται και αν και δεν κωδικοποιεί μια πρωτεΐνη, θεωρείται πως έχει ιδιότητες που καταστέλλουν την ανάπτυξη. Ερευνητικές μελέτες έχουν καταδείξει συγκεκριμένες περιοχές των δύο γονιδίων που έχουν διαφορετικό προφίλ μεθυλίωσης σε κάθε αλληλόμορφο με αποτέλεσμα να ελέγχουν την έκφραση τους. Πιο συγκεκριμένα, μία περιοχή με διαφορετικό προφίλ μεθυλίωσης (Differentially Methylated Region DMR) που εδράζεται μεταξύ των δύο γονιδίων, είναι υπεύθυνη για την αντίθετη αποτύπωση των δύο γονιδίων. Αν η περιοχή αυτή είναι υπομεθυλιωμένη, τότε επιτρέπεται η σύνδεση της με τον παράγοντα CTC Factor (CTCF) ο οποίος εμποδίζει την δράση διεγερτών στους εκκινητές του IGF2 με αποτέλεσμα το IGF2 να μη μεταγράφεται και να μεταγράφεται το Η19. Αντίθετα αν η συγκεκριμένη περιοχή είναι μεθυλιωμένη η πρόσδεση του παράγοντα CTCF δεν επιτρέπεται με αποτέλεσμα οι διεγέρτες να επιδρούν στους εκκινητές του IGF2 και να μεταγράφεται το IGF2 και να μην εκφράζεται το Η19. Συνεπώς υπό φυσιολογικές συνθήκες το μητρικό αλληλόμορφο είναι υπομεθυλιωμένο και το IGF2 δεν μεταγράφεται σε αυτό ενώ μεταγράφεται το Η19...

Unfamiliar cystic formations may develop in the anterior vaginal wall. In view of the close proximity of the anterior vagina to the urethra and bladder, it is important that management of such masses is carefully planned after detailed examination and investigation. Herein, we present the case of an unusual painful swelling in the anterior vaginal wall that was first diagnosed as vaginal wall prolapse. Despite thorough preoperative investigations, the origin of the mass as a urethral diverticulum was confirmed only at pathologic analysis.

article i nfo Introduction: The placental anticoagulant protein Annexin A5 (ANXA5) is a multifunctional protein that is highly expressed on the apical surfaces of syncytiotrophoblasts, and plays an important role in haemostatic regulations, maintaining blood fluidity of the placenta. The aim of this study was to investigate the expression of ANXA5 in pregnancies complicated by preeclampsia (PE). Materials and Methods: Placental tissue samples were collected from 23 pregnancies with PE and 34 normal pregnancies. ANXA5 mRNA levels were measured by quantitative Real-Time PCR (qPCR), while ANXA5 protein expression was measured by Western Blot (WB) and immunohistochemistry. Results: ANXA5 mRNA expression in PE samples was lower than 1% of its expression in normal samples (mean ± SD: 0.002 ± 0.004 vs. 0.55 ± 0.38, p b 0.001), while ANXA5 protein levels in PE samples were approximately at 65% of the average normal expression (mean ± SD: 0.53 ± 0.30 vs. 0.81 ± 0.25, p = 0.001). Immunohistochemical analysis also verified the above results, since PE placentas tended to have low labelling indexes (LIs), in contrast to controls which demonstrated high LIs (p = 0.020). Statistical analysis of the WB data revealed that ANXA5 protein expression was increased in PE smokers vs. PE non-smokers (mean ± SD: 0.64 ± 0.23 vs. 0.41 ± 0.33, p = 0.027). Conclusions: These results suggest that ANXA5 downregulation could be part of the pathophysiology of PE and the possible impairment in coagulation processes, which are seen in pregnancies that demonstrate PE. Fur- ther studies may investigate whether ANXA5 could be used as a biomarker for the early detection of PE and for the prediction of its severity.

The objective of this study was to investigate the hypothesis that the altered epigenetic mechanisms that regulate IGF2 imprinting in placentas from fetal growth restricted (FGR) pregnancies affect IGF2 expression leading to impaired fetal growth. We investigated gene transcription, genotyping and the methylation patterns of IGF2 from 31 and 17 placentas from FGR-complicated and normal pregnancies, respectively. A statistically significant decrease in IGF2 mRNA levels was observed in the placentas from the FGR pregnancies. Loss of imprinting (LOI) was only detected in the abnormal placentas. The evaluation of the percentage of the methylated reference (PMR) of two different potentially differentially methylated regions (DMR) demonstrated significant PMR values in both sites for the normal and FGR pregnancies with no significant differences. Our results suggest the involvement of the IGF2 imprinted gene in placental function and fetal growth and the possible association of epigenetic alterations with the pathophysiology of fetal growth restriction.

Objective The human Placental Growth Hormone ( hPGH ) and the Insulin-like Growth Factor (IGF) system are implicated in fetal development. This study aimed to evaluate the expression of hPGH , IGF-I , IGFBP-1 and IGFBP-3 genes in placentas from pregnancies complicated by fetal growth restriction (FGR). Design The study group was comprised of term placentas from 47 FGR-complicated pregnancies of no recognizable cause. Thirty-seven placentas from normal pregnancies with appropriate for gestational age birth weight were used as controls. The expression status of the genes was evaluated by quantitative real-time PCR. Results hPGH , IGF-I and IGFBP-1 exhibited significantly lower expression compared to the controls ( p =0.003, p =0.049 and p =0.001, respectively). Numerically, lower IGFBP-3 expression was also demonstrated in the FGR-affected group, without however reaching statistical significance ( p =0.129). Significant co-expression patterns were detected among the study genes in both the FGR and normal pregnancies. Conclusion Decreased placental expression levels of hPGH , IGF-I and IGFBP-1 were demonstrated in pregnancies with FGR. Whether these alterations are a causative factor of FGR or accompany other pathogenetic mechanisms requires further investigation.

The expression of imprinted genes is regulated by epigenetic modifications, such as DNA methylation. Many imprinted genes are expressed in the placenta and affect nutrient transfer capacity of the placental exchange barrier. The H19 gene is abundantly expressed by the human placenta and is implicated in the pathogenesis of congenital growth disorders such as Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes. The aim of this study was to investigate the role of DNA methylation on H19 transcription and imprinting, in the pathophysiology of fetal growth restriction (FGR). Thirty one and 17 placentas from FGR-complicated and normal pregnancies were collected, respectively. We studied gene transcription, genotyping and methylation analysis of the AluI H19 on exon 5 polymorphism. Placental expression levels of H19 were significantly increased in the FGR group. The H19 mRNA levels were similar between normal placental samples that demonstrated loss and maintenance of imprinting. Placentas from growth-restricted pregnancies had lower methylation levels compared to normals, in the H19 promoter region. We have demonstrated an increased H19 transcription in the FGR group of placentas. The hypomethylation of the H19 promoters is compatible with the aberrant expression. The association of these two findings is reported for the first time in placental tissues, however, its significance remains unknown. Whether the results of this study represent an adaptation of the placenta to hypoperfusion, or they are part of FGR pathophysiology has to be further investigated.

The majority of second generation endometrial ablation techniques are contraindicated in abnormal shaped uteri. We present two cases of bicornuate uteri with menorrhagia that have been successfully treated with Hydrothermal Ablation (HTA). To our knowledge this is the first report that describes the application of HTA in bicornuate uteri. One treatment was adequate to treat one of the patients, but in the other patient each cavity had to be treated separately. Both women were amenorrheic six months after the operation. We consider HTA as a safe alternative to hysterectomy in women with menorrhagia and congenital uterine abnormalities since simultaneous hysteroscopic view of the endometrial cavity allows proper adjustment of the procedure according to the shape of the uterus.

Fetomaternal hemorrhage (FMH) or fetomaternal transfusion syndrome is the leakage of fetal red blood cells into the maternal circulation. Massive FMH can cause substantial fetal morbidity and mortality. Sonographic evidence of severe FMH syndrome includes fetal hydrops and other fetal anemia-related findings. The peak systolic velocity in the middle cerebral artery has extensively been used for the prediction of fetal anemia and for the timing of the first intrauterine intravascular transfusion (IIVT). We present a case of severe FMH syndrome that was diagnosed during the 24th week of pregnancy. A total of eight IIVT were performed. The actual increase in the fetal Hb after each transfusion was much lower than the expected. At 27 weeks of gestation, sonographic evaluation revealed areas of echogenicity around the posterior horns of the lateral ventricles suggesting ischemic damage. Due to these findings, no further IIVTs were offered and the fetus died a week later. The management of fetal anemia caused by severe FMH is difficult, and the anemic fetuses do not respond well to serial IIVTs as the transfer of blood to the maternal circulation continues.

We describe a rare case of a young woman with a large cystic adenomyotic lesion that was treated laparoscopically. The patient presented with severe dysmenorrhoea refractory to common analgaesics. She was initially diagnosed with right-sided ovarian endometrioma. MRI revealed a cystic lesion of 4 cm attached to the right uterine wall. Under laparoscopic vision, the uterine lesion was identified on the right portion of the uterine fundus close to the round ligament. Monopolar diathermy was used to dissect the lesion. When the incision reached the cystic cavity, dark-brown content flowed from the cyst. After resection was complete, the surgical wound was closed with two-layer interrupted sutures. The patient made a good recovery and was discharged the following day. Since patients with cystic adenomyosis are young, a minimally invasive procedure such as laparoscopic excision is considered optimal. The exact topography of the lesion is crucial in determining the site of the incision.

A young woman presented to the outpatient gynaecology clinic with a rapidly growing bulky tumour located at the external genitalia, which she first noticed 10 days prior to her visit. Examination revealed a 6×3 cm cauliflower-like mass located on the left genitofemoral fold. The initial biopsy had several features suggestive of a human papilloma virus (HPV) infection. A broad excision of the mass was subsequently performed. The biopsy confirmed the presence of a large condyloma acuminatum. Condyloma acuminatum is a slow-growing benign exophytic tumour that is associated with HPV infection. In cases where the tumour has aggressive features, as in our patient, the differential diagnosis has to include carcinoma or Buschke-Lowenstein tumour. The initial biopsy of the tumour in our patient, however, excluded malignancy.

We report a case of trisomy 21 mosaicism detected upon amniocentesis in a 36-year-old woman. Ultrasound examination at 23weeks’ gestation showed a fetus with hydrops, pulmonary hypoplasia, oligohydramnios, thickened placenta, and intrauterine growth retardation. Cytogenetic analysis revealed low-percentage (6%) mosaicism for trisomy 21. Hydrops fetalis and thickened placenta are uncommon findings in fetuses affected by trisomy 21 mosaicism. A short review of the literature is given regarding the sonographic findings associated with trisomy 21 mosaicism, and the genetic counseling in such cases.

Objective To present a case of successful term pregnancy in a patient with known Wegener's granulomatosis (WG). Design Case report. Setting University Hospital, Department of Obstetrics and Gynecology. Patient(s) A 22-year-old primigravida pregnant woman with a history of WG diagnosed 5 years before. Intervention(s) The patient was treated with corticosteroids and azathioprine throughout pregnancy, and cyclophosphamide was added postpartum. Main Outcome Measure(s) The disease was in partial remission at the onset of pregnancy, but two relapses occurred, at 33 weeks' gestation and 15 days after delivery. A 3150-g healthy boy was delivered at 37 weeks' gestation. Conclusion(s) Pregnancy in patients with WG requires preconceptional planning, careful clinical management, and vigorous treatment of active disease. There are 36 cases of WG in pregnancy reported in the literature. Owing to this rarity, the management is individualized and the pregnancy outcome is variable. Antenatal management and therapeutic options are discussed and a short review of the literature is presented.

Objective: To provide a review of the pathogenesis of polycystic ovary syndrome. Design: Literature survey. Result(s): Three major pathophysiologic hypotheses have been proposed to explain the clinical findings of polycystic ovary syndrome (PCOS) related to three major laboratory findings: the LH hypothesis, the insulin hypothesis and the ovarian hypothesis. Although the presence of many small follicles with a high androgen to estrogen ratio was first thought to represent a high rate of follicular atresia in polycystic ovaries, recent studies have demonstrated that the granulosa cells are viable and able to respond to FSH stimulation with normal increases in estradiol production. Thus, a new hypothesis has arisen that FSH activity is somehow blocked at the ovarian level. Conclusion(s): PCOS is a syndrome involving defects in primary cellular control mechanisms that result in the expression of chronic anovulation and hyperandrogenism. In this syndrome, the relation between the various parameters is of particular interest. These relations constitute the cornerstone of the pathogenesis of PCOS. The fact that the pathogenesis of PCOS has not yet been clarified, despite the plethora of relative information, may be the result of a general way of thinking in the interpretation of several scientific data, and especially those that refer to biochemical phenomena. The use of the various models of the theory of chaos, that permits a concrete approach for the interpretation of data, may constitute an optional procedure for the future understanding of the association of different parameters and their disturbances in the pathogenesis of the polycystic ovary syndrome.

A 42-year-old woman with Stage IA, grade 3 clear cell ovarian carcinoma arising within an endometrioma after multiple ovarian stimulation attempts was a unique case from a total of 900 patients who underwent laparoscopy for infertility and pelvic pain between 1996 and 2002 at Yale University. Her previous treatments included two laparoscopic cystectomies for left ovarian endometriomas and four cycles of IVF-ET that resulted in one miscarriage and two successful pregnancies. Although it has been suggested that controlled ovarian hyperstimulation may predispose to the development of ovarian cancer, more recent studies postulate a protective effect if fertility treatments ultimately result in successful pregnancy. Our unusual case serves as a reminder that clear cell adenocarcinoma may coexist with endometriosis, and that parity does not necessarily protect infertility patients against the development of ovarian cancer.