DNA methylation of HOXA10 in eutopic and ectopic endometrium.

STUDY QUESTION: Does the methylation status of the promoter region of the HOXA10 gene differ in eutopic and ectopic endometrium? SUMMARY ANSWER: The eutopic endometrium in women with endometriosis is significantly more methylated when compared with controls. WHAT IS KNOWN ALREADY: Expression of the HOXA10 gene, which is important for successful implantation, is reduced in women affected by endometriosis. STUDY DESIGN, SIZE AND DURATION: A pilot study was carried out including 18 women admitted for surgery for endometriosis-related pain (cases) and 12 women admitted for surgery because of non-endometriotic disease (control). Sample collection and analysis were performed between November 2010 and July 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissue (eutopic and ectopic) underwent sodium bisulfite DNA modification, PCR amplification of two regions of the HOXA10 promoter and pyrosequencing analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The eutopic endometrium of women with endometriosis was significantly more methylated compared with endometrium from the control group (sequence 1: 8.68% in cases and 6.25% in the control group: P = 0.037, sequence 2: 11.89% in cases and 9.25% in the control group: P = 0.032). The eutopic endometrium was significantly more methylated than the ectopic tissue in patients with endometriosis (mean difference -3.6 sequence 1: P = 0.001 and -6.0 sequence 2: P = 0.0001). LIMITATIONS, REASONS FOR CAUTION: The study had a limited sample size and the fertility status of the majority of patients in our study was unknown. WIDER IMPLICATIONS OF THE FINDINGS: Our data regarding methylation state of the ectopic tissues contribute to a better etiopathologic understanding of endometriosis. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no conflicts of interests to declare.

Expression of adhesion, attachment and invasion markers in eutopic and ectopic endometrium: a link to the aetiology of endometriosis.

BACKGROUND: Cell properties, such as attachment, adhesion and invasion, are important for the normal function of the endometrium. However, it is believed that the same properties may also be involved in the development of gynaecological diseases, such as endometriosis. Endometrial cells, shed by retrograde menstruation, may have an aberrant expression of molecules involved in these functions, leading to endometriosis. Therefore, the aim of this study was to investigate the expression of proteins involved in adhesion, attachment and invasion in eutopic and ectopic endometrium. METHODS: Endometrial biopsy specimens were collected from healthy volunteers (controls: proliferative phase, n = 10; secretory phase, n = 15) and from endometriosis patients (proliferative phase: n = 9, secretory phase: n = 10). Biopsy specimens from endometriomas were also collected (proliferative phase: n = 9, secretory phase: n = 10). Expression of apolipoprotein E (ApoE), integrin ß-2 (ITGB2), integrin ß-7 (ITGB7), Laminin γ-1 (LAMC1), CD24 molecule (CD24) and junctional adhesion molecule-1 (JAM-1) was evaluated with real-time reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: The endometrium from controls and women with endometriosis expressed ApoE, ITGB2, ITGB7, LAMC1, CD24 and JAM-1. Gene expression of ApoE and JAM-1 was decreased in both proliferative and secretory phase in the endometrium from women with endometriosis compared with control endometrium. Also, mRNA expression of LAMC1 was reduced in the endometrium from endometriosis patients compared with controls in the proliferative phase. An altered gene expression of CD24 was seen between the endometrium from endometriosis patients and endometriomas in the secretory phase. The ITGB2 protein expression was altered in epithelia cells between the endometrium from healthy volunteers and endometriosis patients in the secretory phase. CONCLUSIONS: We have shown differential expression of adhesion, attachment and invasion proteins in proliferative and secretory endometrium from controls and endometriosis patients and in endometriomas. This study suggests that molecules with these properties may have a role in the anchoring of endometrial cells at ectopic sites, thus initiating the development of endometriosis.

[Tamoxifen, endometrial cancer risk and liquid based cytology. A paradigmatic case]. / Tamoxifene, rischio oncologico endometriale e citologia in fase liquida. Un caso clinico paradigmatico.

Long-term users of tamoxifen (TMX) are at increased risk for developing endometrial cancer. Early diagnosis is mainly based on transvaginal scan (TVS) and hysteroscopy with endometrial biopsy. Nevertheless, TVS does not provide a definitive diagnosis in most cases, particularly due to its high false-positive rate. In addition TMX related changes, such as "pseudocistic" pattern, affect endoscopic evaluation of the endometrium and biopsy sampling (in particular blind procedures) frequently yields insufficient tissue for diagnosis. The cause of the high inadequacy rate of endometrial biopsies in women on TMX might be related to the increase in endometrial fibrous component. The present case emphasizes the main difficulties in surveillance and early diagnosis of endometrial pathologies in TMX users. Liquid-based endometrial cytology played a determinant role in the diagnostic pathway of this patient. We believe it could be used solely or in association with TVS leading to many advantages in the surveillance of women receiving TMX.

The LH/hCG Axis in Endometrial Cancer: A New Target in the Treatment of Recurrent or Metastatic Disease.

Endometrial cancer (EC) is a hormone-dependent cancer that currently represents the most frequent malignancy of the female reproductive tract. The involvement of steroid hormones in EC etiology and progression has been reported. More recently, gonadotropins, and, in particular LH/hCG, are emerging as novel regulators of tumor progression. In the present review, we discuss the role of the LH/hCG axis (i.e. LH/hCG and its receptors, LH/hCG-R) in both gonadal and nongonadal tissues, in physiological and neoplastic conditions. In cancer cells, LH/hCG mainly controls cell proliferation and apoptosis. In particular, in EC LH/hCG improves cell invasiveness, through a mechanism which involves the LH/hCG-R, which in turn activate protein kinase A and modulate integrin adhesion receptors. Indeed, the LH/hCG-R mRNA is expressed in primary ECs and this expression correlates with LH/hCG-induced cell invasiveness in vitro. These results lead to hypothesize that recurrent and metastatic ECs, which express LH/hCG-R, could benefit from therapies aimed at decreasing LH levels, through Gn-RH analogues. Hence, the LH/hCG axis could represent a prognostic factor and a new therapeutic target in EC.

Comparison of the number of uterine myomas detected by in-office transvaginal ultrasonography removed by laparotomic myomectomy: preoperative work-up concerns.

PURPOSE OF INVESTIGATION: To assess the ability of detecting the number of uterine myomas by transvaginal ultrasonography (TVS) performed supporting the clinical examination of general gynecologists' office practice. METHODS: A retrospective comparison of the number of myomas revealed by preoperative in-office TVS and documented after laparotomic myomectomy was conducted in 110 consecutive premenopausal patients referred for surgery. RESULTS: The sensitivity of TVS in revealing the exact number of myomas was 59.4% in the whole series. In the subgroup of 88 patients with a preoperative diagnosis of three or fewer myomas TVS missed at least one myoma in 31 (35.2%) cases, achieving a 64.8% sensitivity. Among the 72 women diagnosed with one myoma at preoperative TVS, 19 (26.4%) resulted to have two or more myomas at the end of surgery, reaching a 73.6% sensitivity of TVS in revealing the exact number of myomas. CONCLUSIONS: In-office TVS reinforces the clinical diagnosis of uterine myomas but it often fails in the detection of their number, resulting in a poor preoperative characterization of patients. The fact that one myoma may be overlooked in one-third of patients theoretically eligible for laparoscopic conservative surgery may motivate the implementation of US diagnosis when laparoscopic myomectomy is considered.

Clinical utility of liquid-based cytology for the characterization and management of endometrial polyps in postmenopausal age.

The proper management of endometrial polyps still represents a clinical ongoing challenge, especially when they are asymptomatic and occasionally discovered. The aim of this study was to evaluate liquid-based endometrial cytology to manage endometrial polyps in postmenopausal age by its ability to exclude hidden premalignant and malignant changes within polyps. Three hundred fifty-nine consecutive postmenopausal patients who underwent hysteroscopic diagnosis of endometrial polyp over a 3-year period and who were scheduled for surgical removal within the three subsequent months were retrospectively evaluated. Histologic results after resection during operative hysteroscopy or during hysterectomy were compared with liquid-based cytology and endometrial biopsy obtained at the time of diagnostic hysteroscopy. Eight of 359 patients (2.2%) had malignant or premalignant polyps interpreted as benign finding at hysteroscopy. Unsatisfactory samples were higher for endometrial biopsy compared to liquid-based cytology in the whole series and in the subgroup of low-risk asymptomatic patients (P < 0.001). Endometrial biopsy and liquid-based cytology revealed a sensitivity of 62% and 87.5%, respectively and a 100% specificity. Considering the subgroup of low-risk asymptomatic patients, liquid-based cytology disclosed all the five pathologic lesions with a 100% sensitivity and specificity. In conclusion, liquid-based cytology proved to be a useful tool to establish the nature of endometrial polyps in postmenopausal patients. Complete removal of the lesion should be offered to all symptomatic patients and those with established risk factors for endometrial cancer. Conversely, a wait and see attitude should be considered in case of asymptomatic low-risk polyps with typical appearance on hysteroscopy and negative liquid-based cytology.

Liquid-based endometrial cytology: cyto-histological correlation in a population of 917 women.

OBJECTIVE: Liquid-based cytology, because of its capacity to reduce the obscuring factors and to provide thin-layer specimens, represents an opportunity to reevaluate endometrial cytology. In order to assess the utility of the liquid-based method in endometrial diagnosis, we evaluated its accuracy in comparison with histology. METHODS: Nine hundred and seventeen women scheduled for hysteroscopy were enrolled in the study. After providing informed consent, all the women proceeded sequentially to hysteroscopy, endometrial cytology and then biopsy endometrial sampling. RESULTS: Cyto-histological correlations were possible in 519 cases (57%): in 361 (39%) cases the biopsy was inadequate, in 15 (2%) the cytology was inadequate, and in 22 (2%) both were inadequate. At biopsy 25 (3%) women had adenocarcinoma, 5 (1%) had adenomatous atypical hyperplasia and 21 (2%) had simple non atypical hyperplasia. At cytology two adenocarcinomas and one adenomatous atypical hyperplasia were underrated as atypical hyperplasias and as non-atypical hyperplasia; two simple non-atypical hyperplasias were reported as negative; and eight cases were false positive (non-atypical hyperplasia at cytology, negative at biopsy). In our population, the cytology provided sufficient material more often than biopsy (P < 0.04). Sensitivity was estimated at 96%, specificity at 98%, positive predictive value at 86% and negative predictive value at 99%. CONCLUSIONS: We concluded that endometrial cytology may be an efficient diagnostic method. It could be applied to selected patients solely or in association with ultrasonography. The combination of these two noninvasive procedures may improve their diagnostic accuracy and reduce unnecessary hysteroscopies, thereby producing benefits for women and society.

Feasibility and outcome of laser CO2 conization performed within the 18th week of gestation.

The purpose of this study is to evaluate the feasibility, safety, and potential therapeutic benefit of laser CO(2) conization of the cervix for in situ and minimally invasive carcinoma diagnosed during pregnancy. Twenty-six pregnant patients with biopsy-proven carcinoma in situ/cervical intraepithelial neoplasia III but colposcopically suspicious for invasion underwent laser CO(2) conization during the 18th week of gestation in an outpatient setting under local anesthesia. No major intraoperative or postoperative complications occurred, and cervical cerclage was not required in any case. Two cases (7.7%) of occult FIGO stage IA1 minimally invasive cervical cancers with free surgical margins were diagnosed. Both patients delivered vaginally at term and were free of disease at postpartum follow-up. Median length of gestation was 39.1 weeks with a median birth weight of 3450 g. All 1-min Apgar scores were 8 or greater. Twenty patients (76.9%) delivered vaginally, while six patients underwent cesarean section for indications not related to the prior conization. After a mean postpartum follow-up of 18 months (range 3-42), 92.3% of patients continued to have both cytologic and colposcopic evaluations negative for persistent or recurrent disease. Two cases of persistent intraepithelial disease were successfully managed by reconization. In summary, our data suggest that laser CO(2) conization performed within the 18th week of gestation is safe for both the patient and the fetus, provides reliable histologic diagnosis, and can be curative. Further studies are required to confirm the favorable risk-benefit ratio of laser CO(2) conization in the management of non-reassuring cervical lesions observed in the first half of pregnancy.

Liquid-based endometrial cytology: its possible value in postmenopausal asymptomatic women.

The incidence of endometrial adenocarcinoma in asymptomatic women is low. Nevertheless, some of these women might require endometrial surveillance. In this study, we evaluated the accuracy of liquid-based endometrial cytology compared to biopsy in asymptomatic postmenopausal women. Three hundred twenty women scheduled for hysteroscopy were enrolled for this study. After hysteroscopy, patients were submitted to endometrial cytology and to biopsy. Two hundred ninety-three (92%) women had sonographically thickened endometrium (>5 mm), 53 (17%) were on tamoxifen, and 16 (5%) were on hormonal substitutive treatment. The evaluation of the biopsies determined that six (2%) women had adenocarcinoma, one (<1%) had adenomatous atypical hyperplasia, and eight (3%) had simple nonatypical hyperplasia. Endometrial cytology evidenced 5 (2%) neoplastic cases, 2 (<1%) hyperplastic with atypia cases, and 25 (8%) hyperplastic without atypia cases. Two hundred twenty-two biopsies (69%) and 17 (5%) cytologies were inadequate. One adenocarcinoma and one simple nonatypical hyperplasia were underrated by cytology resulting, respectively, as atypical hyperplasia and as negative. Four cases were false positive (simple nonatypical hyperplasias on cytology, negative on biopsy). The sensitivity and specificity were estimated, respectively, at 94% and 95%; the positive and negative predictive value were estimated, respectively, at 80% and 99%. Endometrial cytology provided sufficient material more often than biopsy (P < 0.01). We suggest to introduce liquid-based endometrial cytology in the management of some subpopulations of asymptomatic postmenopausal women. Particularly, the combination of liquid-based endometrial cytology and transvaginal sonography may improve their diagnostic accuracy and reduce unnecessary more invasive and expensive procedures.

Ovarian cancer in the elderly: feasibility of surgery and chemotherapy in 89 geriatric patients.

Gynecological oncologists are faced with an increasing proportion of geriatric ovarian cancer patients. Comorbidities are frequently a matter of concern in this age group, and what is adequate treatment for such patients is still debated. The aims of this study were to analyze the feasibility of standard surgery and chemotherapy in a series of elderly ovarian cancer patients (>/=70 years) and to investigate the influence of age (70-75 vs >75 years) on survival. We retrospectively evaluated 89 elderly patients treated at our department between 1985 and 2005. Comorbidities, type of surgical procedure, complications, drugs and schedules of chemotherapy, number of cycles, toxicity, and clinical outcome were registered. Comorbidities were present in 71.9%. Only six patients were inoperable. Among the 83 patients who underwent surgery, 76.4% received adequate surgical treatment. Severe postoperative complications occurred in 16.8%, operative mortality was zero. A total of 801 cycles of chemotherapy were administered to 77 patients (median 10; range 1-38). Overall, G3-G4 toxicity was documented in 61.0%. The rates of dose reduction, treatment delay, and discontinuation were 13.0%, 20.7%, and 3.9%, respectively. Patients who received adequate surgery and those with residual disease <1 cm did significantly better than their counterparts (P= 0.04 and P < 0.001, respectively). No difference in survival according to age (70-75 vs >75 years) was found. Standard surgery and chemotherapy were feasible in elderly ovarian cancer patients. The type of surgery and the amount of residual disease, but not the age of the patients, significantly influenced the clinical outcome.

Expression and amplification of HER-2/neu oncogene in uterine carcinosarcomas: a marker for potential molecularly targeted treatment?

Surgery is the treatment of choice for uterine carcinosarcomas; nevertheless, the poor effect of chemotherapy and radiotherapy represents an insidious problem for patients with metastatic or unresectable disease, and indeed, new therapeutic approaches are clearly required to improve survival of uterine carcinosarcoma patients. The HER-2 oncogene, located on chromosome 17, encodes for a tyrosine kinase growth factor receptor. We analyzed HER-2/neu overexpression by immunohistochemistry in 28 uterine carcinosarcomas. HER-2/neu amplification with fluorescence in situ hybridization (FISH) was tested in positive cases. The expression of HER-2/neu was correlated with disease-free interval and survival (Kaplan-Meier estimates). We observed HER-2/neu overexpression in nine cases (32.1%) and HER-2/neu amplification in all the four HER-2/neu 3+ score positive cases tested by FISH. HER-2/neu expression was not correlated with clinical outcome. Patients with disease limited to the uterus (stages I-II) displayed a significantly better disease-free survival (P= 0.004) and actuarial survival (P= 0.01). Demonstration of HER-2/neu overexpression and amplification in uterine carcinosarcoma may represent the first rationale step for further investigations. Hence, the results of this analysis may support the challenge of a new therapeutic approach, which could test the role of anti-HER-2 (trastuzumab) in patients with advanced or metastatic uterine carcinosarcoma.

Clinical, ethical, and medical legal considerations on emergency contraception.

PURPOSE OF INVESTIGATION: To evaluate how many women required the so-called "emergency contraception" at our outpatient service and what the actual role is of this kind of pharmacological administration in interfering with ovulation and pregnancy, paying particular attention to the ethical and medico-legal aspects of this subject. METHODS: During the period from 1 December 1998 to 30 November 2003, emergency contraception was prescribed to a total of 1,160 women. With regard to the contraceptives used, in most cases (1,132, 97.6%) a combined oral estrogen-progestogen pill (ethinyloestradiol 0.05 mg plus levonorgestrel 0.25 mg) was prescribed; in some cases (20 patients, 1.8%) danazol (400 mg), in four women (0.3%) a progestin-only pill (levonorgestrel 0.75 mg), and in four other women (0.3%) an intrauterine device. RESULTS: It does not come out that there were any pregnancies in our study patients since none of them, who were told to come back for follow-up, were seen at our termination of pregnancy service or delivery room. CONCLUSION: The "Yuzpe regimen" of a combined oral estrogen-progestogen pill has been the most commonly used method for emergency contraception. A new method recently proposed, a progestin-only pill with levonorgestrel 0.75 mg, is having better results than the previous one, with a lower incidence of side-effects and higher efficacy. Moreover, the treatment with this method does not interfere in case of a pregnancy already being carried and cannot interrupt it.

Fetal and neonatal ovarian cysts: what's their real meaning?

PURPOSE OF INVESTIGATION: The management of fetal ovarian cysts is still controversial despite the improvement in prenatal diagnosis with ultrasonography. Some studies suggest an aggressive management, while others opt for a conservative one. The prognosis of the majority of congenital ovarian cysts is good since they have a benign origin. Sometimes, however, complications such as torsion or rupture can occur which often require surgical intervention after delivery. In this paper we report our experience and a brief review of the literature. METHODS: The authors report on 32 pregnant women in whom ultrasonography revealed the presence of an echo-rare or echo-free area in the fetal abdomen suggestive of an ovarian cyst. All women were followed-up during pregnancy with serial ultrasound examinations. Postnatal ultrasound controls confirmed the prenatal diagnosis in all cases. The diameters of the cysts ranged from 2.7 to 7.5 cm. RESULTS: In the 16 cases (50%) in which the cyst diameter was below 4 cm, periodic ultrasound examinations revealed a tendency towards spontaneous regression of the cysts. In the other 16 cases (50%) in which the cyst diameter exceeded 4 cm, cystectomy was necessary due to subsequent complications (torsion in 6 cases, 37.5%, and intracystic hemorrhage in the other 10, 62.5%). CONCLUSION: The most appropriate clinical approach in the management of benign feto-neonatal ovarian cysts is to adopt a wait-and-see policy, assessing the course of the condition by means of periodic ultrasound monitoring. Only when tumefactions measure more than 4 cm in diameter with attendant complications is surgical therapy indicated. Without complications, however, aspiration of the cystic contents is possible even in ovarian cysts exceeding 4 cm in diameter.

Diagnosis and treatment of endometriosis. A review.

The correct approach for endometriosis management is still unclear. This review explores recent data concerning diagnosis and treatment of endometriosis, trying to define guidelines for the most appropriate diagnostic approach and therapeutic regimen. At present, laparoscopy is still considered the gold standard in endometriosis diagnosis. The risks and the diagnostic limitations of laparoscopy and the inaccuracy of clinical examination justify the considerable efforts made to improve the diagnosis with imaging techniques. The therapeutic approach is still far from being defined as causal and focuses on management of clinical symptoms of the disease rather than on the disease itself. A first-line medical therapy should be tried in patients with pelvic pain not asking for a pregnancy. Surgical treatment is considered the best treatment for women with pain and or pelvic mass who wish to become pregnant in a short time. For infertile patients, medical therapy has a limited role. The 2 treatment options include surgery or in vitro fertilization (IVF). According to our results, it seems that correct management of infertile women with endometriosis is a combination of surgery and IVF in women who did not obtain post-surgery pregnancy spontaneously.

Cross-sectional and longitudinal evaluation of uterine artery Doppler velocimetry for the prediction of pre-eclampsia in normotensive women with specific risk factors.

OBJECTIVE: To evaluate the performance, in the prediction of pre-eclampsia, of (1) an abnormal mean uterine artery resistance index (RI; cross-sectional index) at 24 weeks of gestation, (2) the individual longitudinal flow pattern of results observed at 16, 20 and 24 weeks of gestation and (3) a multiple logistic regression model including the individual longitudinal flow pattern and the mean RI at 24 weeks. METHODS: A total of 144 normotensive pregnant women with risk factors for pre-eclampsia were evaluated with uterine artery color Doppler at 16, 20 and 24 weeks' gestation. The following indices were obtained: (1) cross-sectional index: the mean RI of both uterine arteries at 24 weeks' gestation was calculated for each patient and considered abnormal when >/= 0.58; (2) longitudinal indices: the individual longitudinal flow pattern of mean RI of both the main uterine arteries at 16, 20 and 24 weeks' gestation was derived for each subject and defined as (a) the typical physiological flow pattern, with a trend of decrease in values or (b) the non-physiological flow pattern. The probability of having a pregnancy complicated by pre-eclampsia was also calculated by means of a multivariate logit model. The log-odds was modeled as a function of variables related to maternal characteristics, the individual longitudinal flow pattern indicator, and of the mean RI at 24 weeks' gestation as a continuous variable. RESULTS: Pregnancies had a physiological course in 108 (75%) women, while 36 (25%) women developed pre-eclampsia during the third trimester. For the prediction of pre-eclampsia, the use of an abnormal uterine artery RI index (> or = 0.58) at 24 weeks showed a sensitivity of 77.8%, a specificity of 67.6%, a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 90.1%, with a likelihood ratio (LR) for an abnormal test of 2.4; with the longitudinal flow pattern indicator, sensitivity was 88.9%, specificity 82.4%, PPV 62.7% and NPV 95.7%, with a LR for an abnormal test of 4.9; the use of a logit model yielded a sensitivity of 72.2%, a specificity of 90.7%, a PPV of 72.2% and a NPV of 90.7%, with a LR for an abnormal test of 8.0. CONCLUSIONS: In this study the use of an individual longitudinal flow pattern indicator resulted in improving accuracy in the prediction of pre-eclampsia as compared with the traditional cross-sectional mean RI at 24 weeks. A further increase in specificity and PPV was obtained using a logit model that includes the longitudinal flow pattern indicator and the cross-sectional RI at 24 weeks. Since both the longitudinal flow pattern indicator and the logit model showed a high performance in predicting pre-eclampsia in women with risk factors for impaired placentation, they might be used to identify a high-risk population in which preventive measures and/or therapeutic options might be tested.

Fertilisation and implantation failure in an oral contraceptive user.

We report the case of a young woman taking a low-dose oral contraceptive (gestodene 0.075mg and ethinylestradiol 0.02mg) in whom we documented by both hormonal assays and sonographic evaluations the occurrence of ovulation, oocyte fertilization and embryo implantation. However, the implantation process did not complete and only a biochemical pregnancy was registered. On the basis of known actions of estroprogestin on endometrium that are not conducive to implantation, it is possible that the pregnancy loss was originated by oral contraceptive's hormonal influence at endometrial level.

Prediction of the development of pregnancy-induced hypertensive disorders in high-risk pregnant women by artificial neural networks.

Pregnancy-induced hypertensive disorders (PIHD) are common complications of pregnancy and are associated with increased maternal and fetal morbidity. In this study, artificial neural networks (aNN) and multivariate logistic regression (MLR) were applied to a set of clinical and laboratory data (urea, creatinine, uric acid, total proteins, hematocrit, iron and ferritin) collected at 16 and 20 weeks of gestation. The efficacy of the two approaches in predicting the development of PIHD in 303 consecutive normotensive pregnant women at high risk of pre-eclampsia and intrauterine fetal growth retardation was then compared. The aNN were trained with a randomly selected set of 187 patient records and evaluated on the remainder (n=116). MLR analysis was done with the same 116 patients. The performance of each model was assessed using receiver operator characteristic (ROC) curves. Pregnancies had a normal physiological course in 227 cases, whereas 76 (25.1%) women developed PIHD during the third trimester. The best aNN at 20 weeks yielded an area under the ROC curve of 0.952, the sensitivity of 86.2%, the specificity of 95.4%, the positive predictive value of 86.2% and the negative predictive value of 95.5% for PIHD. The corresponding values for the MLR at 20 weeks were 0.962, 79.3%, 97.7%, 92% and 93.4%, respectively. The computer-aided integrated use of these conventional tests seems to provide a useful means for and early prediction of PIHD development.

Time course of recovery and complications of HELLP syndrome with two different treatments: heparin or dexamethasone.

HELLP syndrome is a severe complication of pregnancy characterized by microangiopathic hemolytic anemia, hepatic dysfunction and thrombocytopenia. Though delivery is the ultimate therapeutic option, medical treatments, including the use of heparin or corticosteroids, have been employed in the attempt to improve maternal prognosis. The aim of this retrospective study was to compare the time course of recovery and the incidence of complications in women with HELLP syndrome receiving either heparin or dexamethasone. Between January 1990 and December 1998, 32 patients with HELLP syndrome were cared for at the Institute of Obstetrics and Gynecology of the University of Florence: 20 patients were treated with heparin, administered subcutaneously at a dose of 5000 IU every 12 h, whereas 12 women received dexamethasone, administered intravenously at a dose of 10 mg every 12 h. Categorical data were evaluated with chi-square and Fisher's exact test; continuous data were analyzed with Mann-Whitney U test; P < .05 was considered significant. In the subgroup treated with heparin the incidence of disseminated intravascular coagulation (DIC) (P < .02), the number of patients requiring blood transfusion (P < .05) and the length of stay at the Intensive Care Unit (ICU) (P < .04) were significantly increased as compared with the subgroup receiving dexamethasone; in this latter subgroup, significantly higher platelet count and hematocrit values, and significantly lower levels of lactate dehydrogenase (LDH) could be documented starting from day 2 after delivery. The results of our investigation suggest that the use of dexamethasone in patients with HELLP syndrome is associated with faster regression and lower incidence of complications in comparison to heparin.

Pressure lavage under ultrasound guidance: a new approach for outpatient treatment of intrauterine adhesions.

OBJECTIVE: To present pressure lavage under ultrasound guidance (PLUG) as a new therapeutic procedure for selected cases of intrauterine adhesions (IUA). DESIGN: An open clinical investigation with no control group. SETTING: Teaching hospital. PATIENT(S): Seven consecutive patients referred to our department for secondary amenorrhea due to IUA. INTERVENTION(S): A newly developed technique based on sonohysterography was used to monitor the effects of intrauterine injections of saline solution on the continuous accumulation of saline in the uterine cavity for the mechanical disruption of IUA. MAIN OUTCOME MEASURE(S): Lysis of intrauterine adhesions, restoration of menses, and increased pregnancy rate in infertile patients. RESULT(S): Five patients with mild IUA obtained satisfactory lysis of adhesions by the use of the PLUG technique. A second-look hysteroscopy after 1 month showed that filmy adhesions persisted in two patients with moderate IUA. These adhesions were removed successfully during hysteroscopy. Restoration of menses was obtained and has continued in all patients. Two of the three infertile patients became pregnant. CONCLUSION(S): This technique is safe and ideal as an in-office procedure. PLUG allows complete lysis in mild IUA cases, and the need for therapeutic, and possibly follow-up hysteroscopy, can be avoided. In moderate IUA cases, the procedure may represent a useful initial step in reducing the need for operative hysteroscopy.

What degree of maternal metabolic control in women with type 1 diabetes is associated with normal body size and proportions in full-term infants?

OBJECTIVE: To assess what degree of maternal metabolic control in women with type 1 diabetes is associated with normal fetal growth and results in normal neonatal body proportions in a group of full-term infants. RESEARCH DESIGN AND METHODS: We investigated the anthropometric characteristics of 98 full-term singleton infants born to 98 Caucasian women with type 1 diabetes enrolled within 12 weeks of gestation. The type 1 diabetic mother-infant pairs were divided into three groups on the basis of the daily glucose levels reached during the second and third trimesters of pregnancy (group 1: 37 mother-infant pairs with an average daily glucose level during the second and third trimesters of < or =95 mg/dl; group 2: 37 mother-infant pairs with an average daily glucose level during the second trimester of >95 mg/dl and during the third trimester of < or =95 mg/dl; group 3: 24 mother-infant pairs with an average daily glucose level during the second and third trimesters of >95 mg/dl; control group: 1,415 Caucasian mother-infant pairs with full-term singleton pregnancies and normal glucose challenge test screened for gestational diabetes. RESULTS: Infants of diabetic mothers in group 1 were similar to those of the control group in birth weight and in other anthropometric parameters. In contrast, offspring of diabetic mothers of groups 2 and 3 showed an increased incidence of large-for-gestational-age infants, significantly greater means of ponderal index and thoracic circumferences, and significantly smaller cranial/thoracic circumference ratios with respect to the control group. CONCLUSIONS: The results of our study suggest that, in diabetic pregnancies, only overall daily glucose values < or =95 mg/dl throughout the second and third trimesters can avoid alterations in fetal growth.