Genetic heterogeneity of platelet glycoproteins Ia and IIIa is associated with in vitro fertilisation implantation failure.

Thrombophilic genetic factors have been shown to play an important role in implantation outcome after in vitro fertilisation (IVF). In this pilot study we investigated the frequencies of glycoprotein Ia (GpIa)-C807T and GpIIIa-PlA1/PlA2 polymorphisms in 60 nulligravidae women with a history of unexplained IVF implantation failures and compared them with 60 healthy fertile women. We found statistically significant associations between the GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and IVF implantation failure (odds ratio [OR] = 3.45, 95% confidence interval [CI]: 1.63-7.30, p = 0.001; and OR = 2.86, 95% CI: 1.27-6.45, p = 0.010, respectively) with the risk being higher for combined carriers of GpIa-807T and GpIIIa-PlA2 alleles (OR = 10.13, 95% CI: 2.85-35.99, p < 0.001), suggesting a synergistic effect of the two polymorphisms. The above associations were strongest for the youngest age group. Our results indicate that GpIa-807T and GpIIIa-PlA2 may be susceptibility alleles for IVF implantation failure.

Ovarian cancer diagnosed during pregnancy: clinicopathological characteristics and management.

The aim of this study was to discuss the diagnostic and therapeutic dilemmas in cases of pregnant women with adnexal masses, reporting an interesting case with synchronous literature review. The patient, a gravida 2, para 1, 37 year-old woman was diagnosed with a large unilateral adnexal lesion during a scheduled third trimester ultrasound assessment. A large papillary papule with a network of blood vessels showing decreased resistance in blood flow was noticed as well. Surgical intervention revealed ascitic fluid and a large cystic mass arising from the right ovary. Cesarean section and right salpingooophorectomy, including the mass, were performed. Frozen section biopsy was positive for malignancy. Total hysterectomy and left salpingo-oophorectomy, total omentectomy, biopsies from the pelvic peritoneum, pelvic/para-aortic lymphadenectomy and appendicectomy followed. Histology showed mucinous ovarian adenocarcinoma Grade I Stage Ic according to FIGO classification. Surgical intervention, in cases of persisting adnexal lesions, is often necessary, even during pregnancy.

Preimplantation genetic diagnosis in marfan syndrome.

Marfan syndrome (MFS) is a systemic hereditable disorder of the connective tissue with mainly cardiovascular manifestations, such as aortic dilatation and dissection. We describe a case of a 32-year-old Caucasian woman, clinically asymptomatic with MFS who presented for genetic consultation to prevent the transmission of disease to her offspring. She underwent controlled ovarian stimulation (COH), in vitro fertilization (IVF) combined with preimplantation genetic diagnosis (PGD), and a singleton pregnancy with positive fetal heart rate was revealed. At 34 weeks' gestation she delivered vaginally a healthy premature male infant weighting 2440 gr. The patient remained asymptomatic during pregnancy, delivery, and 3 months postpartum. It is has to be mentioned that the availability of PGD is essential to prevent the transmission of disease to the next generation.

Prognostic significance and diagnostic value of PTEN and p53 expression in endometrial carcinoma. A retrospective clinicopathological and immunohistochemical study.

PURPOSE: To investigate the PTEN and p53 gene expression in endometrioid and serous papillary endometrial carcinomas and clarify their prognostic significance by studying the PTEN and p53 expression in relation to tumor stage and grade. METHODS: Archival pathological sections of 61 cases with endometrial cancer examined in a 5-year-period (January 2006-December 2010) were retrieved and re-examined. Immunohistochemical investigation was performed by the Ventana system. Anti-PTEN and anti-p53 monoclonal antibodies were used. Disease staging was made according to the FIGO staging system. RESULTS: Forty-nine (80.32%) cases were endometrioid adenocarcinomas. Patient age ranged from 39-75 years (mean 62.5). Grade 1 tumors:19/22 (86.3%) cases had stage Ib, 2/22 (9.09%) stage Ic and 1/22 (4.54%) stage IIIc. Eighteen of 22 (81.8%) cases were PTEN positive and 4/22 (18.2%) p53 positive. Grade 2 tumors: 17/ 23 (73.91%) cases had stage I b, 4/23 (17.39%) stage Ic and 2/23 (8.69%) stage IIIc. Seventeen of 23 (73.91%) cases were PTEN positive and 47sol;23 (17.3%) p53 positive. Grade 3 tumors: 2/4 (50%) cases had stage Ic and 2/4 (50%) stage IIIc. No case was PTEN positive and 2/4 (50%) were p53 positive. Twelve (19.35%) cases were serous papillary carcinomas. Patient age ranged from 63-79 years (mean 76). Five (41.66%) cases had stage Ic and 5 (41.66%) stage IIIc, with nodal metastases and peritoneal involvement. Two (16.66%) cases developed on endometrial polyps with minimal myometrial involvement (stage Ib) and in both cases elements of endometrioid adenocarcinoma were observed as well. Immunohistochemical study showed that 11 (91.66%) cases were p53 positive and 2 (16.66%) PTEN positive. CONCLUSION: PTEN and p53 immunoexpression helps both in accurate diagnosis and proper therapeutic approach of the various endometrial carcinomas. PTEN and p53 are also prognostic markers for these kind of tumors.

Autopsy findings in fetuses with cystic hygroma: a literature review and our center's experience.

PURPOSE OF INVESTIGATION: To report our experience of autopsied cases of fetal cystic hygroma (CH) and discuss the role of fetal autopsy in genetic counseling. METHODS: A review of autopsy reports at our institution revealed 18 cases of fetal CH over a 10-year period (from 2000 to 2010). The clinical data, results of cytogenetic analysis and prenatal ultrasound findings were also retrieved and compared to the autopsy findings. RESULTS: Fetal death was due to intrauterine death in eight cases, therapeutic abortion in eight cases and spontaneous abortion in two cases. Cytogenetic analysis was available in 12 cases, and the results showed an abnormal karyotype in seven cases (5 cases of Turner syndrome and 2 cases of trisomy 21). The mean size of CH was 5.4 cm. Other malformations or findings suggestive of the cause of fetal death were diagnosed in 10/18 cases (55.6%). The most common autopsy findings were hydrops and central nervous system anomalies. The autopsy findings were in agreement with the prenatal ultrasound findings in 13/18 cases (72.2%), while in five cases (27.8%) additional findings were detected during autopsy. The most common placental abnormalities were infarcts and calcifications. CONCLUSION: In addition to prenatal diagnostic studies, fetal autopsy and pathologic examination of fetal and placental tissues may help to establish the exact cause of death and disclose important information as to the presence of various fetal malformations or placental abnormalities.

Molecular mechanisms of preeclampsia.

Preeclampsia is one of the leading causes of maternal morbidity/mortality. The pathogenesis of preeclampsia is still under investigation. The aim of this paper is to present the molecular mechanisms implicating in the pathway leading to preeclampsia.

Obstetric hysterectomy: a review of cases over 16 years.

Emergency peripartum hysterectomy (EPH), is performed when life-threatening obstetric conditions occur. The authors attempt to assess the incidence of EPH as well as to investigate risk factors and patients' characteristics. A retrospective study of all cases of EPH performed at the 2nd Department of Obstetrics and Gynecology, Medical School of Athens University, from 1994 to 2009 has been conducted. Data were abstracted from individual medical charts and laboratory records. Among 16,182 deliveries, 15 EPH were performed (0.92 per 1,000 deliveries). Indication was uncontrollable haemorrhage due to placenta accreta (73.3%) or uterine atony (26.6%). Incidence of 1.54 EPHs per 1,000 caesarean sections and 0.51 per 1,000 vaginal deliveries, were noted. Morbidity rate was 46.6%. One (6.6%) mother died because of pulmonary embolism. In conclusion, peripartum hysterectomy is a severe but life-saving procedure. Caesarean section increases the risk of EPH. Obstetricians should always be prepared to confront this emergency situation.

Perinatal mortality in diabetic pregnancy.

Perinatal mortality rate (PMR) is one of the most important perinatal health indicators. PMR in diabetic pregnancies varies throughout the world and is higher than the background PMR. The prevalence of pregestational diabetes is increasing and is associated with an elevated risk of congenital malformations, macrosomia, preeclampsia, and preterm delivery. The incidence of PMR in preexisting diabetes mellitus ranges considerably, with congenital abnormalities and preterm labor the main factors contributing to the higher PMR. Women with gestational diabetes mellitus or impaired glucose tolerance are a mixed group that may have low to a high PMR, especially if they require insulin in their pregnancy. All the known diabetic women should plan their pregnancies and optimize glycemic control periconceptually and throughout pregnancy, as this reduces the frequency of congenital abnormalities, obstetric complications, and perinatal mortality.

Intrauterine inflammation and preterm delivery.

Spontaneous preterm delivery, prematurity, and low birth weight due to prematurity account for a great part of neonatal morbidity and mortality. Specifically, chronic amniotic fluid inflammation may cause preterm labor, with the involvement of different mediators that produce diverse aspects of the inflammatory response. Although bacteria are considered to be the main trigger for intrauterine infection/inflammation, viral infections also appear to be involved. Recently, molecular genetic techniques have helped us better understand the underlying pathophysiologic processes. This is especially important because epidemiological and experimental studies indicate that intrauterine infection and inflammation constitute a risk factor for adverse neurological outcome in preterm infants. Chronic subclinical chorioamnionitis associated with preterm birth can also modify lung development. Although no current clinical strategy is aimed at adapting the maternofetal inflammatory response, immunomodulators may serve as a future intervention in preterm embryos.

Polycystic ovarian syndrome and pregnancy outcome.

INTRODUCTION: Polycystic ovarian syndrome (PCOS) is a common disease of the endocrine system among the women of reproductive age with an incidence ranging from 5 to 10%. METHOD: This study is a mini-review of pregnancy and perinatal outcome in women with PCOS. RESULTS: The syndrome is associated with increased risk of pregnancy complications such as gestational diabetes, gestational hypertension, preeclampsia, and preterm labor, while no strong association was found with congenital anomalies or spontaneous miscarriages. Furthermore, women with PCOS seem to experience increased risk of cesarean delivery while their newborns face increased perinatal morbidity and mortality. Metformin use seems to reduce the risk of obstetrical complications; however, prospective studies are necessary on the field. CONCLUSION: Further studies should be organised in order to evaluate the role of PCOS in pregnancy.

Maternal serum levels of TNF-alpha and IL-6 long after delivery in preeclamptic and normotensive pregnant women.

AIM: To evaluate maternal TNF-alpha and IL-6 plasma levels in normotensive pregnant women, women with preeclampsia, and to examine the temporal changes in their levels from the antepartum to the postpartum period correlated with the regression of preeclampsia. METHOD: A prospective study was performed in the 2nd Department of Obstetrics and Gynecology, University of Athens. Blood samples were obtained: (1) antepartum at the time of clinical diagnosis of the syndrome, 2. 12-14 weeks postpartum. RESULTS: No statistically significant differences were found in IL-6 levels, whereas a difference was found in TNF-alpha levels between preeclamptic and controls in antepartum period (0.80 pg/ml versus 0.60 pg/ml, P : .04). Long after delivery, TNF-alpha levels were significantly higher in preeclamptic compared to normotensive controls (0.86 pg/ml versus 0.60 pg/ml, P : .004). No difference was observed in TNF-alpha before and after delivery in both groups. No difference was noticed in IL-6 levels in women of normotensive group long after delivery compared to that before delivery. Long after delivery IL-6 levels were statistically significant higher in preeclamptic women compared to normal controls (3.53 ± 0.52 pg/ml versus 1.69 ± 0.48 pg/ml, P : .02). CONCLUSION: Preeclamptic women remain under a status of increased inflammatory stress up to 12-14 weeks postpartum despite the fact that all the other signs of preeclampsia are resolved.

Intrauterine devices and extrauterine pregnancy. A literature review.

The incidence of ectopic pregnancy has been high over the last decades. Many risk factors are potential causes, among them IUDs use which might have a significant role. According to the current thinking, the use of IUD does not increase the risk of ectopic pregnancy. However, IUDs are more effective in protecting from intrauterine rather than ectopic pregnancy. Our review focuses on current and past IUD use, duration of its use, type of IUD and the associated risk of ectopic pregnancy. Fertility after IUD removal regarding the incidence of ectopic pregnancy is also discussed. Conflicting results regarding the association of ectopic pregnancy risk with the use of intrauterine devices exist.

Thermal balloon endometrial ablation: a systematic review.

OBJECTIVE: The aim of our study is to review the role of thermal balloon endometrial ablation (TBEA) as an alternative in treating abnormal uterine bleeding. METHODS: Articles relevant to our review and relevant references from the initially identified articles on the field that were archived by May 2007, were retrieved from Pubmed. RESULTS: Success rates ranged from 83 up to 94%, with patient's satisfaction ranging from 57 up to 94%. Persisted menorrhagia could reach 17% in some studies. CONCLUSION: TBEA is an effective alternative method used in the treatment of menorrhagea which results in a significant reduction in menstrual bleeding and high satisfaction rates. However, a longer follow-up is required to determine the role of such a treatment.

No effect of tocolytic therapy with atosiban on maternal serum interleukin-6 and tumor necrosis factor-alpha in threatened preterm labor.

OBJECTIVES: We aimed to evaluate the effect of intravenous administration of tocolytic therapy with an oxytocin antagonist drug (atosiban) on maternal serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in women with threatened preterm labor. METHODS: The study population consisted of 46 women with a singleton pregnancy admitted to our department with a diagnosis of threatened preterm labor at between 26 and 34 weeks of gestation. Atosiban was administered to all women. Nine women (group A) progressed to delivery within 48 hours of admission. The remaining 37 women were divided in two groups: group B consisted of 16 women who remained undelivered at 48 hours but experienced delivery within 7 days and group C consisted of 21 women who did not deliver within the next 7 days. Maternal serum IL-6 and TNF-alpha levels were assessed in duplicate by a high sensitivity ELISA kit on patient admission and again at the end of treatment with atosiban (36 hours post-admission). RESULTS: Serum IL-6 and TNF-alpha concentrations on admission were significantly higher in group A compared to those found in group B (p = 0.01) and group C (p = 0.04). Comparisons of serum IL-6 values on admission and at 36 hours after the initiation of atosiban treatment were comparable in group A (p = 0.95), group B (p = 0.39), and group C (p = 0.79). Similarly serum TNF-alpha levels on admission were not significantly different compared to those at the end of treatment in all groups (p = 0.85 for group A, p = 0.45 for group B, and p = 0.21 for group C). CONCLUSIONS: No effect of tocolytic therapy with atosiban was observed on serum IL-6 and TNF-alpha levels in women with threatened preterm labor.

Positive association of serum interleukin-1beta and CRH levels in women with pre-term labor.

OBJECTIVE: The aim of this study was to investigate the hypothesis that interleukin-1beta (IL-1beta) might be involved in the increase of the circulating levels of placental-derived CRH leading to the initiation of pre-term labor. SUBJECTS AND METHODS: Forty-eight primigravidae with a singleton viable pregnancy between 28 and 34 weeks of gestation were studied. The subjects were divided in two groups: group A consisted of 30 pregnant women (mean age+/-SD; 22+/-1.1 yr old) presented with pre-term labor (mean gestational age+/-SD; 30.6+/-2.3 weeks) and group B consisted of 18 pregnant women (24+/-2.6 yr old) with normal pregnancies (29.8+/-3.1 weeks). CRH and IL-1beta levels were measured in blood specimens collected from all the study subjects on admission. RESULTS: Women of group A presented significantly higher serum CRH levels (mean+/-SE; 1.18+/-1.83 ng/ml) compared to those of group B (0.48+/-0.67 ng/ml) (p<0.01). Similarly, serum IL-1beta levels were significantly higher in women of group A (0.45+/-0.12 pg/ml) compared to those of group B (0.31+/-0.08 pg/ml) (p<0.01). A positive correlation was found between serum IL-1beta and CRH (r=0.68, p=0.001) in women of group A (pre-term labor). CONCLUSIONS: Our findings suggest that the increased levels of IL-1beta and CRH found in pregnant women presented with pre-term labor might be involved in the pathophysiologic mechanism of the latter. Furthermore, a positive interaction might exist between IL-1beta and placental CRH which might lead to enhanced production of the second, facilitating, thus, the onset of labor.

Computerized analysis of fetal heart rate variability using the matching pursuit technique as an indicator of fetal hypoxia during labor.

OBJECTIVE: To determine whether the computerized analysis of fetal heart rate variability with the new matching pursuit technique can indicate fetal distress during labor. STUDY DESIGN: Eighty women were studied during the intrapartum period with external cardiotocography. In all cases, cord arterial pH and 5-min Apgar Scores were evaluated. Six cases that presented large segments of missing data were excluded from the study. The remaining 74 women were divided into two groups; 32 women with normal (Group A) and 42 women with non-reassuring FHR tracings (group B). Group B was divided in subgroup BI, including 24 women with pH > 7.20, and BII, including 18 women with pH < 7.20. In order to evaluate the FHR fluctuations, in different frequency ranges, we applied an adaptive time-frequency method, called Matching Pursuit. We estimated the power of the FHR signal in four frequency ranges. RESULTS: The 5-min Apgar Scores were significantly lower in both subgroup BI and subgroup BII (p = 0.003 and p = 0.003 respectively). The Low Low Frequency (LLF) parameter appears to recognize better the cases with lower pH (sensitivity 78.5%, specificity 52.3%) than the cases with non-reassuring FHR (66.6%, 56.2). The sensitivity and specificity of the Very Low Frequency (VLF) parameter were 72.2% and 59% respectively in recognizing the cases with lower pH and 64.2% and 53.1% in recognizing non-reassuring FHR. CONCLUSION: Fetal hypoxia during labor can be recognized using the MP technique for the analysis of FHR signal power in the VLF and LLF frequency ranges. Since the analysis is feasible in real-time, it can be a useful tool for the intrapartum evaluation of fetal well-being.

Myomectomy during cesarean section: a safe procedure?

A patient's frequent request is the simultaneous surgical removal of a previously diagnosed myoma during cesarean section. The aim of this study was to evaluate the safety and efficacy of myomectomy during cesarean section. From January 1995 until December 2004, 47 pregnant women with coexisting uterine myomas underwent cesarean section and simultaneous myomectomy. All cesarean sections were performed by residents while myomectomies were conducted by the senior staff. Intraoperative and postoperative complications such as blood loss were estimated and compared with 94 women with uterine myomas who underwent surgical delivery without removal of the fibroids. Furthermore, the length of hospitalization was compared between the two groups. Myomectomy added a mean time of 15 min to the operative time of cesarean section. No hysterectomy was performed at the time of the cesarean section. No complications were developed during the puerperium. The difference between the preoperative and postoperative hemoglobin mean value was statistically significant (P=0.001) but did not differ between isolated cesarean and myomectomy-combined cesarean groups. None of the patients received blood transfusion. The length of hospitalization was comparable between the two groups. Despite controversial literature data, we suggest that myomectomy during cesarean section could be generally recommended. Depending on size and location of myomas, the associated risks are similar to those of isolated cesarean section.