Phosphorylated insulin-like growth factor binding protein-1 in cervical secretions and sonographic cervical length in the prediction of spontaneous preterm delivery.

OBJECTIVES: The aim of this study was to evaluate the efficacy of the test for the decidual phosphorylated isoform of insulin-like growth factor binding protein-1 (phIGFBP-1) in endocervical secretions in predicting preterm delivery in women with uterine contractions. METHODS: The study included 210 women with a singleton pregnancy with documented uterine contractions and intact membranes at between 24 and 34 weeks' gestation who underwent the cervicovaginal phIGFBP-1 test and transvaginal sonographic measurement of cervical length. A receiver-operating characteristics (ROC) curve was used to determine the most useful cut-off point for cervical length. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for preterm delivery following univariate analysis. RESULTS: ROC curves indicated that 26 mm was the optimal cut-off value for cervical length in predicting preterm delivery. A cervical length of < 26 mm and the presence of phIGFBP-1 were statistically significant in univariate logistic regression analyses (P < 0.0001) with odds ratios of 16.18 and 9.29 for preterm delivery, respectively. Multivariate analysis of cervical length and phIGFBP-1 showed that they were independent and therefore useful in combination for predicting preterm delivery. CONCLUSIONS: Cervical length and the phIGFBP-1 test are independent variables that can be used together to predict preterm delivery in women with uterine contractions. A sonographically measured cervical length of > 26 mm with a negative phIGFBP-1 test in a patient with regular uterine contractions before 37 weeks' gestation seems to indicate a low risk of preterm delivery and may therefore allow avoidance of unnecessary therapies.

Human papilloma virus infection and cervical intraepithelial neoplasia in transplanted patients.

Progress in diagnosis and treatment has led to an increased number of transplantation patients who consequently have immunological depression and emergence of tumors. The incidence of cervical neoplasia, according to previous studies, is 11%; this tumor is the only one that can be investigated by screening before and after a graft. Our purpose was to evaluate whether transplanted patients showed an increased incidence of genital human papilloma virus (HPV) infection and whether this infection produced greater progression of disease in cases of low-risk HPV infections. Our study involved 151 transplant patients who underwent Papanicolaou (Pap) and HPV tests. Patients listed for grafts underwent Pap and HPV tests 6 months before and 6 months after transplantation. All patients had negative Pap tests before their grafts. After their grafts 16 patients (10.59%) had negative Pap tests, but positive viral typing. Eleven patients (7.28%) showed positive Pap tests, 6 of whom had low-grade squamous intraepithelial lesion (SIL) and 5 patients high-grade SIL. The final HPV infection incidence (15.23%) was consistent with the literature. The incidence of lower female genital tract intraepithelial lesions (7.28%) was higher than the healthy population or analogous studies (4.5%-8.5%). We showed a constant association between high-risk HPV infection and gynecologic intraepithelial neoplasia, whereas there was no association between low-risk broods HPV infection and neoplasia. In conclusion, screening should start at almost 6 months before grafting to avoid an irreversible situation that is difficult to treat.

Efficacy of an acidic vaginal gel on vaginal pH and interleukin-6 levels in low-risk pregnant women: a double-blind, randomized placebo-controlled trial.

BACKGROUND: Increased interleukin-6 (IL-6) levels and a vaginal pH of > 4.7 are associated with obstetric complications such as preterm delivery and low birth weight. Topical treatments, able to maintain a physiological vaginal pH, could help in the prevention of vaginal infections. STUDY AIM: In a randomized, double-blind, placebo-controlled trial, we evaluated the effects of an acidic buffering vaginal gel (Miphil) on vaginal pH and IL-6 levels in pregnant women. PATIENTS AND METHODS: Seventy low-risk women pregnant with a singleton (second trimester) were enrolled in the trial. Thirty-five were randomized to the acidic gel, 2.5 g every 3 days for 12 weeks, and 35 to the corresponding placebo. Vaginal pH and vaginal IL-6 level were measured at baseline and after 12 weeks. Women were then followed until delivery. The main outcome measures were vaginal pH, vaginal pH normalization (pH < 4.5) and vaginal IL-6 levels. RESULTS: Vaginal pH at baseline was 4.6 +/- 0.4 and 4.4 +/- 0.3 in the acidic gel and the placebo group, respectively. At baseline, a total of 40% (14/35) and 22% (8/35) of women in each group, respectively, had a vaginal pH of > or = 4.7. At week 12, the vaginal pH was 4.3 +/- 0.3 in the acidic gel group and 4.3 +/- 0.3 in the placebo group (NS). The acidic gel normalized the vaginal pH in ten out of 14 women (p = 0.04) in comparison with only one out of eight women in the placebo group (NS). The acidic gel induced a significant (p < 0.02) reduction of vaginal IL-6 from 12.0 +/- 7 to 8.9 +/- 5 pg/l (-36%). In the placebo group, IL-6 increased from 9.0 +/- 5 to 13.5 +/- 6.8 pg/l (+50%) (p = 0.05). Birth weight was 2978 +/- 700 g in the placebo group and 3241 +/- 477 g in the acidic gel group (p = 0.06). CONCLUSIONS: The use of the acidic gel in low-risk pregnant women is able to maintain a physiological vaginal ecosystem and prevents the increases of vaginal pH and vaginal IL-6. Prospective and controlled trials are warranted to evaluate whether this acidic gel can reduce obstetric complications linked to vaginal inflammation during pregnancy.

Biochemical markers for the prediction of spontaneous pre-term birth.

OBJECTIVES: The aim of this study was to identify predictive biochemical markers for preterm labor. METHODS: In this prospective study we included 225 asymptomatic Caucasian women consecutively enrolled at 24 weeks of gestation. The following data were collected only once at 24 weeks of gestation: vaginal pH, vaginal fFN, cervical and serum concentration of IL-6, IL-8 and TNFalpha, maternal blood serum, ferritin. Student's t-test, the chi(2)-test and multiple linear regression were used as statistical methods. RESULTS: There were no differences between the age of patients, parity and gestational age at sampling between women who delivered at term and those who delivered pre-term (<37 weeks' gestation). There was a significant increase of cervical IL-6 (pre-term 608+/-1595 pg/l vs. at term 58.9+/-112 pg/l) and serum ferritin (pre-term microg/l 74.4+/-1.1 vs. at term 26.3+/-56.5 microg/l) in pregnant women who delivered pre-term (P<0.05). No differences in cervical IL-8 and cervical TNFalpha between pre-term and term deliveries were found. Multiple linear regression confirmed that the vaginal pH value and cervical fFN test were the best predictive biochemical markers of pre-term birth (standardized coefficient Beta=0.33 and 0.22, respectively). CONCLUSIONS: In order to evaluate pregnancies for pre-term labor, the presence of pH>4.5 and a positive fFN test seems to be predictive of subsequent pre-term delivery.

Congenital or torsion-induced absence of Fallopian tubes. Two case reports.

Unilateral absence of a uterine tube is an extremely rare finding, for which there are two possible etiopathogenic causes: in some cases it is due to haemorrhage filling of the cavity and its reabsorption as a result of asymptomatic torsion of the uterine tube during adult life, in pediatric age or even during intrauterine life; alternatively, the absence may be congenital, associated with developmental alterations of the mesonephric and paramesonephric ducts. The article presents two cases of fallopian tube absence: a congenital monolateral absence and a tubal torsion during pregnancy. The symptomatology of the torsion of the fallopian tube in pregnancy can be milder than in the classic description with peritoneal reaction and severe clinical alteration. The main risk factors for tubal torsion are: adhesions and inflammatory processes, ovarian cysts, usually of dermoid type, menstrual period, pregnancy, abnormal long mesosalpinx and/or mesovarium, pelvic congestion induced by constipation and disturbed venous blood flow from the adnexa. A congenital defect of the mesonephric duct is followed by a homolateral defect of the paramesonephric duct. The resulting anomaly is characterized by the absence of the uterine tube, uterus-tube angle, kidney and ureter. Partial or total unilateral defects of a paramesonephric duct are more common than aplasia of both ducts. Some authors have suggested that an inadequate blood supply during the descent into the pelvis of the caudal part of the paramesonephric duct might feasibly lead to incomplete tube development.

Polycystic ovarian syndrome and pregnancy.

The paper describes a case of polycystic ovarian syndrome (PCOS) characterised by normal blood insulin levels and LH hypersecretion which explains the etiopathogenesis of the two voluminous ovarian masses originating from micro-cysts existing prior to pregnancy and undergoing abnormal growth during gestation owing to stimulation by beta-HCG (beta human chorionic gonadotropin). The ability of HCG ti stimulate ovarian steroidogenesis in pregnancy can result in enhanced testosterone and androstenedione levels. Our findings, like those of another recent report, emphasise the correlation between beta-HCG levels and testosterone values; the quantitative increase in beta-HCG probably plays an essential part in determining the abnormal development of the ovarian cysts, which remained morphologically unchanged up to delivery. Our patient's virilisation is explained by the increase in total testosterone in circulation. Fetal virilisation cannot be assessed in this patient because the mother gave birth to a male.

S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial.

OBJECTIVES: To evaluate the efficacy of S-adenosylmethionine (SAMe) and ursodeoxycholic acid (UDCA) in intrahepatic cholestasis of pregnancy (ICP). METHODS: Twenty patients in the last trimester of pregnancy were randomly assigned to receive either SAMe (1000 mg/day i.m.) or UDCA (450 mg/day) until delivery; the treatment lasted at least 15 days in all cases. RESULTS: After UDCA the women exhibited significantly lower levels of total bile acids (P < 0.02), but no significant differences were noted in AST, ALT, or alkaline phosphatase. All ten patients showed a complete resolution of pruritus. After SAMe no significant changes were noted in pruritus, total bile acids or liver function tests. No adverse reactions on mother or child were recorded during either UDCA or SAMe treatment and the outcome of pregnancy was favorable in both groups. CONCLUSIONS: These findings show that UDCA is more effective than SAMe in controlling pruritus and total bile acids, which are considered a prognostic parameter in ICP with respect to the fetus. Nevertheless, before UDCA is introduced as an effective and safe treatment for ICP, which also has a beneficial effect on fetal prognosis, we believe these results should be confirmed and extended in other clinical trials.

Transdermal estroprogestins versus transdermal estrogen plus oral dihydrogesterone replacement in menopause.

We studied 18 early (6 to 36 months) postmenopausal patients with a mean age of 51 years (47-53), who had never undergone hormone replacement therapy before and had no contraindications to hormone replacement. All cases of menopause were spontaneous. The treatment consisted in the continuous transdermal administration of 17-beta-estradiol (50 microg/daily) by skin patch to be replaced every 84 hours. The patients were further treated with a two-week progestogen administration every fortnight. This consisted of transdermal norethisterone acetate (0.25 mg/daily) combined with estradiol in the same patch in the first year, and oral dihydrogesterone (10 mg/daily) in the second year, without wash-out period. Before treatment (T0), and at the 12th (T1) and 24th (T2) month we measured the body mass index, the arterial blood pressure (AP), lipoproteins, coagulation parameters and bone metabolism parameters. The systolic pressure presented mean values (+/-SD) equal to 128.5+/-10.2 mmHg (T0), 131.1+/-7.4 mmHg (T1) and 130.4+/-7.5 mmHg (T2). Diastolic pressure values showed mean value ranging from 85.4+/-8.7 mmHg (T0) to 83.9+/-5.3 (T1) and 83.4+/-5.8 mmHg (T2). The detailed analysis of values of triglycerides, HDL cholesterol, apolipoprotein A1, apolipoprotein B and coagulation parameters at different times of therapy showed no statistically significant changes. With regard to bone metabolism, no statistically significant changes from baseline values were observed in parathormone, alkaline phosphatase, calcitonin, urinary calcium/creatinine ratio, and bone mineral content expressed by the bone density.

Hepatitis C virus infection in pregnancy.

OBJECTIVES: To evaluate the clinical aspects of hepatitis C virus (HCV) liver disease in anti-HCV+ve mothers, both during pregnancy and six months after delivery, and to assess the outcome of pregnancy. SETTING: Obstetric department for high risk pregnancies of the University of Padova, Italy. PARTICIPANTS: Seventeen hundred consecutive pregnant women were studied. METHODS: Each woman underwent the following: 1. serological screening for hepatitis surface antigen (HBsAg), antibodies to HCV (anti-HCV), antibodies to human immunodeficiency virus type 1 (HIV1) within the first trimester of pregnancy; and 2. clinico-biochemical assessment in order to ascertain previous or active liver disease and risk factors for viral infections. RESULTS: Twenty-nine (1.7%) of the 1700 women were found anti-HCV positive. Eight of them had an associated positivity for HIV infection. HCV-RNA was positive in 64.2% of anti-HCV positive women. Liver function tests (included transaminases) were within the normal range in 27 mothers (both during and six months after delivery). Only 2/29 women had a slight increase in AST/ALT; liver biopsy in these cases was compatible with mild chronic active chronic active hepatitis. In all women the outcome of pregnancy was favourable (12/29 anti-HCV positive mothers underwent caesarean delivery for causes independent from HCV infection). CONCLUSIONS: A substantial proportion of anti-HCV positive pregnant mothers, even if asymptomatic, have circulating HCV-RNA. The pregnancy does not induce a deterioration of liver disease, and vice versa, HCV infection does not increase the risk of obstetric complications.

[Maternal anemia and fetal outcome. Authors's experience]. / Anemia materna ed outcome fetale. Nostra esperienza.

A physiological pregnancy in which the only pathological datum proved to be a computerised NST at the 40th week of pregnancy is reported. The NST trace showed evidence of fetal distress: absence of acceleration, short term reduced variability and deceleration of the fetal beat. On the basis of further traces, constantly pathological, and of the echographic evaluation of the fetal "outcome", with a biophysical profile which revealed oligohydramnios and absence of active fetal movement, Cesarean Section was undertaken, resulting in the birth of a baby girl of 3180 g, 50 cms, with Apgar 8/10. The clinical interest in this case arises from the total lack of pathological anamnestic data in the pregnancy, except, at a more accurate evaluation, anemia due to martial shortcoming of modest entity in the 1st and in the 2nd trimesters, worsening in the course of the 3rd after an episode of cystopyelitis. The message of the clinical case described is that immediate and careful evaluation of NST must be integrated in every case with obstetric anamneses, echographic and hormonal parameters, without a careful interpretation of routine hematochemical parameters.

Iron balance in pregnancy in relation to anemia.

Blood levels of iron, transferrin and ferritin varied in the course of pregnancy (6th to 42nd week) in 136 women. Analysis of variance showed that the factor "weeks of pregnancy" (< or = 27 or > 27 weeks) was correlated differently with the variables "ferritin" and "iron" according to the presence or absence of anemia (Hb < or = or > or = 11 g/dl). In anemic women the correlation was significant (F-ratio = 5.90; P = 0.018) for iron (which decreased from initial low level until term) but not ferritin, whereas in non-anemic women the correlation was significant (F-ratio = 13.306; P = 0.0006) for ferritin (which decreased to less than 20 micrograms/ml around the 34th week) but not iron. In both anemic and non anemic subjects, transferrin levels increased with weeks of pregnancy. It is concluded that towards the end of pregnancy, some decrease in ferritin (> or = 15 micrograms/ml) is physiological, and in the absence of anemia (Hb > 11 g/dl) iron supplements are not necessary.

Hormonal profile following total abdominal hysterectomy and bilateral salpingo-oophorectomy in post-menopausal endometrial carcinoma.

The Authors report the results of study carried out on ten post-menopausal patients affected with endometrial carcinoma (FIGO stage I & II) who underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH & BSO). Estradiol, Testosterone and Prolactin plasma levels were assayed before surgery and in the 2nd, 10th and 30th post-operative day. The evaluation of the data supports the opinion that in postmenopause Estradiol origin is mainly extraglandular and the ovaries produce Testosterone; the evaluation of Prolactin levels before and after surgery, at last, cannot rule out the hypothesis of an hypothalamo-pituitary disfunction in post-menopausal patients affected with endometrial cancer.

Steroidogenesis in menopause and endometrial pathology.

After considering the postmenopausal variations in the hypothalamic-hypophyseal-ovarian feed-back system, the Authors review the medical literature about ovarian and adrenal contribution to postmenopausal steroidogenesis. Comparisons are made between postmenopausal sex-hormone levels in controls and in endometrial cancer affected patients; estradiol is given the main attention: its higher level in cancer patients seems closely related to their higher mean weight; indeed, no estradiol level difference is found between patients and controls correctly matched as to the body weight. The possible role of estradiol in the pathogenesis of endometrial cancer is then discussed basing on data obtained from women affected with diseases generally considered to be estrogen dependent.

Inadequate luteal phase and benign breast disease.

The Authors compare E2 and Progesterone plasma levels in the luteal phase of twelve normally menstruating women whose basal body temperature curves were biphasic and in which breast micronodularity and mastodynia were present, with those of ten breast disease-free controls. The significant difference (p less than 0.001) found in Progesterone levels gives strength to the opinion that Progesterone supply therapy can effectively improve both mastodynia and the clinical picture objectively documented.

Fibrinolysis in ovarian cancer.

Coagulation disorders, including thromboembolic phenomena and disseminated intravascular coagulation are recognised as a complication of neoplastic disease. In the present study the Fibrinogen Degradation Products (F.D.P.) were determined in 26 patients with Advanced Ovarian Cancer (stage III and IV FIGO) (mean = 38.1; S.D. = 37.6) and in ten healthy patients considered as controls (mean = 2.7; S.D. = 13). The significative difference (p less than 0.05) between the two groups points in evidence an increasing activation of Ffibrynolytic processes. The F.D.P. determination has revealed a good correlation (p less than 0.001) with the tumor extension as showed by the difference between third stage with large tumor masses (late) (mean = 44.5; S.D. = 24.5) and third stage with minimal residual disease after reductive surgery (early) (mean = 6.7; S.D. = 5.7).

Fibrinogen degradation products (F.D.P.) in ascitic fluid of patients affected by ovarian cancer.

Ascitic fluid samples from 10 patients with ovarian carcinoma and 10 with cirrhosis of the liver were examined for their content of components of the fibrinolytic system. Large amounts of fibrin/fibrinogen degradation products (F.D.P.) were found in the ascitic fluid in all patients with malignant tumors, but not in the other group. Determination of F.D.P. may therefore make it possible to differentiate between malignant and non-malignant ascitic fluid.

Acute reactive stage proteins in gynaecologic cancers.

The authors report the plasmatic variations of ARPS (acute reactive proteins stage) in fifty eight women, admitted to the Obstetric and Gynaecological Clinic of Padua's University in the years 1978-1979 aged between 35 and 80 years old; those patients were affected by different types of gynaecological neoplasms: twenty three had cervical cancer, eight endometrial cancer, twenty six ovarian cancer. An evident increase was seen in the ARPS in the patients studied. In particular there was an increase in he haptoglobin in the ovarian cancer patients as well as an increase in the alpha-1 antitrypsin in the cervical cancer patients. Regarding ARPS and the clinical stage of the tumour the variations were important between T0 and T1 that is between tumours localized in the affected organ and those outside the primitive site but always in the pelvis. No evident alterations were found between T1 or T2; there was no other increase in the ARPS in neoplasm outside the pelvis.