Nuchal translucency as a predictor of adverse pregnancy outcome.

BACKGROUND: Thickened nuchal translucency (NT) has been related to fetal genetic syndromes, structural abnormalities, and other diseases. The aim of this research was to evaluate the association of NT with adverse pregnancy outcomes. STUDY DESIGN: In the period 2002-2004 in 2104 pregnant women between 10+6 and 13+5 weeks' gestation, NT was evaluated as a parameter for aneuploidy screening: out of these, 734 singleton pregnant women that underwent 2nd trimester amniocentesis and whose pregnancy outcome were known were selected. NT was statistically correlated to pregnancy and neonatal outcome. RESULTS: Median gestational age (GA) at NT evaluation was 11+2 weeks' gestation. NT median was 1.1 mm (0.9-1.4 mm, 25th-75th centile, range 0.5-4.0 mm). After multiple logistic regressions, the variables significantly associated to NT values were: threatened preterm labor (p<0.008) and preterm labor (p<0.02). The best diagnostic accuracy point was NT>95th centile and >1.5 MoM for the prediction of threatened preterm labor. CONCLUSION: In this series, increased NT values were associated to threatened preterm labor and preterm labor in euploid fetuses: this finding may have clinical consequences in the management of such pregnancies.

Intravaginal gemeprost and second-trimester pregnancy termination in the scarred uterus.

OBJECTIVE: To investigate the effectiveness and complication rate of intravaginal gemeprost, a prostaglandin E(1) analogue, for second-trimester pregnancy termination in women with a scarred uterus. METHODS: Of 439 women undergoing induced abortion between the 13th and the 23rd week of pregnancy, 67 had a scarred uterus because of 1 or more cesarean sections or myomectomy. All women received a 1 mg dose of gemeprost intravaginally every 3 h, up to 5 times over 24 h. Those who did not respond received further cycles of gemeprost treatment. RESULTS: The rate of successful abortions among women with uterine scars was not different from that observed in the nulliparous controls, but previously vaginal delivery was associated with a shorter induction to abortion interval. The rate of severe complications did not differ between the groups, and was about 1%. CONCLUSION: The rate of complications following intravaginal administration of a PGE(1) analogue for second-trimester pregnancy termination was similar in women with a scarred or unscarred uterus.

Prostasome to sperm transfer of CD13/aminopeptidase N (EC 3.4.11.2).

Prostasomes are membranous vesicles (150-200 nm in diameter) that are present in human semen. They are secreted by the prostate gland and contain large amounts of cholesterol, sphingomyelin and Ca2+. In addition, some of their proteins are enzymes. Prostasomes enhance the motility of ejaculated spermatozoa and are involved in a number of additional biological functions. In previous papers, we demonstrated that lipid can be transferred from prostasomes to sperm by a fusion process occurring at slightly acidic pH. CD (cluster antigens) are ubiquitous proteins; in this paper, we demonstrate that CD13/aminopeptidase N is present is semen, where it is bound to prostasomes. Upon mixing prostasomes and sperm at slightly acidic pH (7 or less), aminopeptidase is transferred from prostasomes to sperm. This evidence comes from enzymatic activity determinations and from the use of the monoclonal antibody, anti-human CD13. The transfer was about 8% of total prostasomal activity at pH 5 and with a prostasome to sperm ratio of 2 (on a protein basis). The transfer did not occur at pH 8.0, but was measurable at pH 7. Therefore, this mechanism may represent a means of modifying the composition and the biological properties of ejaculated sperm.

Prognostic value of umbilical-middle cerebral artery pulsatility index ratio in fetuses with growth restriction.

OBJECTIVE: To study the utility of Doppler velocimetry and computerized cardiotocography in the management of intrauterine growth restriction and prediction of neonatal outcome. PATIENTS AND METHODS: Seventy-two pregnant women with fetuses showing growth restriction and delivered within 48 h of their last Doppler velocimetry evaluation. The last computerized cardiotocographic trace from these fetuses was used for statistical analysis, and the last trace from the healthy fetuses of 93 consecutive women undergoing cesarean section was used as control. Umbilical artery pulsatility index (UA PI), middle cerebral artery pulsatility index (MCA PI), UA PI/MCA PI ratio, and uterine artery resistance index (Ut RI) were assessed. RESULTS: Among women with growth-restricted fetuses, all parameters were significantly higher in those who had hypertension; and in those who had diabetes, only the UA PI/MCA ratio was significantly higher. Umbilical artery PI values and the UA PI/MCA ratio were higher in those who had a nonreassuring result to computerized nonstress test immediately before delivery. A multiple logistic analysis showed that the UA PI/MCA ratio was the only Doppler velocimetry parameter predicting cardiotocographic nonreactivity; furthermore, the predictivity of extended newborn hospitalization (longer than 15 days) was verified, with a sensitivity of 56% and a specificity of 92% when the ratio was higher than 1.26. CONCLUSION: The MCA PI of fetuses with growth restriction should be assessed. The UA PI/MCA ratio is predictive of a nonreactive computerized cardiotocography trace and of prolonged neonatal hospitalization.

Asymptomatic struma ovarii: a case report.

Struma ovarii is a rare ovarian neoplasm. This tumor is generally benign, although malignant transformation has been reported. The preoperative diagnosis is generally difficult. Thyroid hormones may be produced and in a few cases asymptomatic women may develop definitive clinical hypothyroidism after resection of struma ovarii. We report a case of a 39-year-old woman who underwent laparoscopic resection of an asymptomatic right ovarian mass. The pathologic diagnosis was struma ovarii. The postoperative period was uneventful and her thyroid function remained normal.

Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia.

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.

The in vitro inhibitory effect on thrombin by 2,3-diphosphoglycerate.

Thrombin incubated with 2,3-diphosphoglycerate (150 nmol 2,3-DPG/1 NIH thrombin unit) lost up to 70% of its clotting activity, whereas the esterase activity remained unchanged. No fibrinopeptide release by thrombin was observed in the presence of 2,3-DPG. The fibrin polymerization was normal. By chromatography on Amberlite IRC-50, alpha-thrombin was eluted at pH 8.0. In presence of 2,3-DPG, alpha-thrombin was not eluted. Likely, 2,3-DPG can interfere with thrombin.

The prognostic significance of acetowhitening of the vulva and HPV-DNA test. A multicentre study.

Acetowhitening of the vulva has been related to a subclinical human papillomavirus (HPV) infection. No consense has been reached about undertaking -or not- any therapy for these acetowhite changes. We have observed from our clinical experience and in a 10 years observational follow-up, that acetowhitening of the vulva regarding high risk (16-18) and low risk (6-11) HPV groups (as assessed by PCR analysis) significantly decreased; and acetowhitening areas negative to polymerase chain reaction (PCR), significantly increased from 53% (202/382) to 85% (276/325) (P<0.001). Our findings suggest that independently from HPV type and in the absence of cofactors, there is a statistically significant spontaneous remission of these areas.

Adrenomedullin production is increased in normal human pregnancy.

OBJECTIVE: Adrenomedullin, a recently discovered vasoactive peptide originally identified in pheochromocytoma, has been found to be increased in the plasma of pregnant women at term. This study was designed to elucidate whether adrenomedullin secretion is dependent on gestational age and the possible source and function of this peptide in human pregnancy. STUDY DESIGN: Adrenomedullin concentrations were determined by RIA in amniotic fluid and maternal plasma obtained from 110 pregnant women between 8 and 40 weeks of gestation. Subjects were stratified into five groups according to gestational age. In term patients (n = 15), adrenomedullin was also measured in the umbilical artery and vein separately. RESULTS: High concentrations of adrenomedullin were present in plasma and amniotic fluid samples from patients in the first, second and third trimester. There was no significant difference in mean maternal plasma concentration of adrenomedullin between the five patient groupings. Amniotic fluid adrenomedullin concentrations decreased from 81.2 +/- 11.7 pg/ml at 8-12 weeks of gestation to 63.7 +/- 6.0 pg/ml at 13-20 weeks of gestation and then increased at 21-28 weeks of gestation to 99.1 +/- 10.4 pg/ml. A further increase was found in samples collected after 37 weeks of gestation (132.6 +/- 10.1 pg/ml). In the umbilical vein, adrenomedullin concentration was higher (P < 0.05) than in the artery (65.7 +/- 6.1 pg/ml and 48.5 +/- 5.2 pg/ml respectively), suggesting that adrenomedullin in the fetal circulation derives from the placenta. CONCLUSIONS: Our results demonstrate the presence of adrenomedullin in maternal plasma and amniotic fluid throughout gestation, and show that its production starts very early in gestation, suggesting that this hormone may have an important role in human reproduction, from implantation to delivery.

Prenatal diagnosis of fetal cytomegalovirus infection after primary or recurrent maternal infection.

OBJECTIVE: To determine the reliability of prenatal diagnosis of cytomegalovirus infection in women with primary or recurrent infection. METHODS: Amniotic fluid (AF) samples from 117 pregnant women were evaluated for cytomegalovirus culture and cytomegalovirus-DNA detection. Neonatal and postnatal samples also were examined to confirm or exclude transmission of maternal-fetal cytomegalovirus infection. RESULTS: Of 25 women with primary cytomegalovirus infection, 13 (52%) had cytomegalovirus-positive AF samples by polymerase chain reaction (PCR), nine of which also were diagnosed by culture. All eight neonates born to mothers whose AF was cytomegalovirus-positive by PCR and culture were cytomegalovirus infected, and three were symptomatic. One aborted fetus had cytomegalovirus-DNAemia. Of four women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates and two aborted (one fetus had cytomegalovirus encephalopathy). Of 45 mothers with recurrent infection, two with AF cytomegalovirus-positive by PCR and culture, and another with cytomegalovirus-positive AF samples by PCR only, aborted cytomegalovirus-DNA-positive fetuses. Of the other seven women with cytomegalovirus-positive AF samples by PCR only, two delivered asymptomatic cytomegalovirus-infected neonates, two delivered neonates cytomegalovirus-positive by PCR only (one was symptomatic), and three delivered infants cytomegalovirus-negative by PCR and culture. All 47 mothers with nonactive cytomegalovirus infection and cytomegalovirus-negative AF samples had uninfected neonates. Polymerase chain reaction was superior to viral culture in sensitivity and negative predictive value (100% compared with 57% and 94%, respectively) but was lower in specificity and positive predictive value (97% and 83%, respectively, compared with 100%). CONCLUSION: Prenatal diagnosis of fetal cytomegalovirus infection should include PCR in addition to viral culture, particularly for congenital cytomegalovirus infections following maternal recurrence.

Amniotic fluid concentrations of adrenomedullin in preterm labor.

OBJECTIVE: To determine whether adrenomedullin levels in amniotic fluid were associated with preterm labor. METHODS: We measured immunoreactive adrenomedullin in amniotic fluid collected by amniocentesis from 36 women with clinical diagnosis of preterm labor or preterm premature rupture of membranes (PROM) and from 18 normal pregnant women. RESULTS: Amniotic fluid from cases of PROM and failure to respond to tocolysis were associated significantly with higher amniotic fluid adrenomedullin concentrations (177.0 +/- 22.5 pg/mL and 182.7 +/- 22.0 pg/mL, respectively, P < .01) than that from uncomplicated pregnancies (101.2 +/- 28.1 pg/mL) or preterm labor responsive to tocolysis (102.3 +/- 26.8 pg/mL). CONCLUSION: Amniotic fluid adrenomedullin is higher than normal in cases of PROM and preterm labor unresponsive to tocolysis, perhaps indicating enhanced synthesis from placenta or fetal membranes being stimulated by bacterial products.

The effect of glucocorticoid therapy on fetal lung maturity indices in hypertensive pregnancies.

OBJECTIVE: To assess fetal lung maturity tests in hypertensive pregnancies and to examine the effect of glucocorticoid therapy. METHODS: In a cohort study involving 68 pregnant women with hypertension, 34 received antenatal betamethasone before amniocentesis and 34 did not. Controls were 68 women with uncomplicated pregnancies, matched for gestational age at amniocentesis and fetal gender. Amniotic fluid (AF) samples were analyzed by lamellar body count, planimetric and stechiometric lecithin-sphingomyelin ratio (L/S), and presence of phosphatidylglycerol. RESULTS: Fetal lung maturity, as determined by lamellar body counts and by planimetric L/S, was lower in hypertensive pregnancies not treated with steroids than in controls (19,600 +/- 14,500 versus 39,800 +/- 22,700, P < .009, and 1.9 +/- 0.6 versus 3.9 +/- 1.8, P < .01, respectively). In the period of 24 to 33 weeks' gestation, the percentage of untreated pregnancies with mature lamellar body counts and mature L/S was significantly lower than that of controls (13% versus 33%, P < .001; 6% versus 40%, P < .002 and P < .003, respectively). In contrast, in patients treated with betamethasone, the percentage of cases with mature indices for both tests was not significantly different from that of controls, but was higher than that of untreated hypertensive patients (40% versus 13%, P < .001; 33% versus 6%, P < .001). Phosphatidylglycerol did not differ among groups. From 34 to 38 weeks, no difference was found in the percentage of mature cases for lamellar bodies in pregnant women with hypertension not treated with steroids in comparison with controls (68% versus 84%), nor between cases treated and controls (74% versus 84%). In the same period, no difference in L/S values was found among groups, and the percentage of cases positive for phosphatidylglycerol was lower in hypertensive pregnancies than in controls (47% versus 95%, P < .001) and was not affected by steroid treatment (37% versus 95%, P < .001). CONCLUSION: Fetal lung maturity, as reflected in AF tests, is delayed in hypertensive pregnant patients, and steroids increase all lung maturity indices except phosphatidylglycerol between 24 and 33 weeks' gestation.

CA 125 in peritoneal fluid: reliable values at high dilutions.

Forty-three samples of peritoneal fluid from women undergoing laparotomy or laparoscopy for various gynecologic diseases were examined to determine and characterize CA 125 antigen. The data were compared with the corresponding serum levels. CA 125 levels in undiluted peritoneal fluid ranged between 41-301 U/mL and were significantly higher than levels in serum, except in cases of ovarian carcinoma. However, when CA 125 of peritoneal fluid was measured at dilutions greater than 1:50, higher antigen levels were measured (1120-31,500 U/mL), with the highest CA 125 values in patients with ovarian carcinoma. Measurements at dilutions of less than 1:50 were also affected but did not show any decreased binding of the antigen. Immunoblotting analysis of serum and peritoneal fluid indicated the presence of two main bands in each. The monoclonal antibody OC 125 reacted strongly with peritoneal fluid CA 125, in agreement with the CA 125 values obtained by immunoradiometric assay using high dilutions. These data suggest that CA 125 measurements in peritoneal fluid are unreliable unless the samples are diluted 1:50 or more. Furthermore, the statistical difference found between patients with benign and malignant tumors and those with leiomyomata uteri and controls suggests that diluted peritoneal fluid could have a role in identifying abnormal antigen levels.

Changes in plasma adrenomedullin levels during the menstrual cycle.

We investigated whether the levels of adrenomedullin, a novel peptide produced by several tissues, including the pituitary gland, change during the ovarian cycle. We studied 13 healthy women with regular menstrual cycles. Plasma samples were collected at 7, 14, 21 and 28 days of the ovarian cycle and assayed for adrenomedullin 1-52 using a specific RIA. LH, FSH, 17beta-estradiol, and progesterone concentrations were also determined. The adrenomedullin profile during ovarian cycle was similar to that of LH; plasma adrenomedullin increased from 10.9 pg/ml at the 7th day to 15.1 pg/ml at the 14th, and decreased to 8.5 pg/ml in the subsequent menses. The changes in plasma adrenomedullin were related to changes in LH and 17beta-estradiol. The cause of the increase in adrenomedullin levels during the late follicular phase of the menstrual cycle is not clear. Since it has been demonstrated that adrenomedullin is involved in the regulation of hypothalamus-pituitary-adrenal gland and its secretion is regulated by sex hormones we speculate that adrenomedullin could also play a role in regulating the hypothalamus-pituitary-ovary feedback. Alternatively it may be involved in the regulation of fluid and electrolyte homeostasis during the menstrual cycle.

Multiple primer pairs polymerase chain reaction for the detection of human papillomavirus types.

A polymerase chain reaction (PCR) based on the use of multiple primers enabling the simultaneous detection of HPV-6b, -11, -16 and -18 in a single tube reaction was developed and validated on cervico-vaginal specimens, including tissues embedded in paraffin. This PCR setting proved to be specific and sensitive, allowing the detection of as few as 200 viral particles per specimen.

Serum and peritoneal fluid CA-125 levels in patients with endometriosis.

OBJECTIVE: To evaluate CA-125 in peritoneal fluid (PF) as an indicator of endometriosis. DESIGN: CA-125 levels in paired serum and PF were determined by the one-step immunoradiometric assay. For peritoneal samples, high dilution of the sample (1:100) was used to avoid false low results, caused by the "hook effect" phenomenon. PATIENTS: Forty-one women with and without endometriosis, undergoing laparoscopy or laparotomy during the follicular phase of the menstrual cycle, were selected. SETTING: 2nd Institute of Obstetrics and Gynecology, University of Rome "La Sapienza," Rome, Italy. MAIN OUTCOME MEASURE: Peritoneal fluid CA-125 levels obtained using diluted samples were significantly higher than those found using undiluted ones. RESULTS: CA-125 levels in PF were approximately 100 times higher than those found in paired serum, ranging from 970 to 10,636 U/mL. In patients with endometriosis, CA-125 levels in PF were significantly elevated when compared with the control group. In serum, CA-125 levels increased only in advanced stages of endometriosis. CONCLUSIONS: The sensitivity of the CA-125 test for endometriosis in PF is greater than in serum. Therefore, the measurement of CA-125 levels in PF could be useful in the detection of early stage endometriosis, which tends to be overlooked by the CA-125 serum test.

Intrauterine rupture of the intrauterine device "ML Cu 250": an uncommon complication: presentation of a case.

We have reported on fragmentation on removal of an ML Cu 250. The patient's management is discussed and the possible causes of fragmentation presented, with special reference to the IUD materials and/or design.

PIP: This paper presents a case of fragmentation on removal of an ML Cu 250 IUD. This device, which was introduced in 1974, has been widely and successfully used in multiparous and nulliparous women. The device is built as a small idented crown over a vertical copper-coiled stem. The patient in this case, a 36-year old woman with 3 previous vaginal deliveries, was seen for removal of the device 26 months after insertion. When vaginal extraction was attempted, the nylon string of the IUD broke. Ecotomography and x-rays revealed the IUD to be in a transversal position on the uterine fundus. A hysterectomy was deemed necessary for removal. At 1st effort, only the stem was removed. Further attempts yielded a fragment of the crown. Other fragments were not found after repeated trials. Although shedding of the IUD's copper coil is not uncommon in longterm IUD users, intrauterine fragmentation of the IUD frame is a rare complication. The literature includes 3 other reports of this complication in ML Cu 250 acceptors. This device is thought to be vulnerable to intrauterine fragmentation because of the combined effect of deep adhesions to the endometrium and low resistance points of the device frame. It is hypothesized that the adhesion is dependent on the crown teeth, which become embedded in the endometrial mucosa and determine both stiffness and high resistance to extraction. Comparative resistance trials are currently being conducted on several IUDs. Until the results of these trials become available, selective use and very cautious removal of the ML Cu 250 are advised.

beta-N-acetyl-D-glucosaminidase isoenzymes from human amnionic membranes.

Two beta-N-acetylglucosaminidase isoenzymes (A and B) have been identified and purified from amnionic fetal membrane. The final specific activity of A and B isoenzymes increased 225- and 185-fold respectively by a purification scheme, which included a lyophilized extract, chromatofocusing on PBE 94, pH range 5.5 to 4.0, and affinity chromatography on p-aminophenyl-2-acetamido-2-deoxy-1-thio-beta-D-glucopyranoside covalently linked to Sepharose-4B. Different electrophoretic mobility, thermostability and different thiol group modifications of the two isoenzymes were found. Acetate was a more effective competitive inhibitor than were iodoacetamide, N-acetylglucosamine and N-acetylgalactosamine more than glucosamine and galactosamine, confirming a specific 'acetamido receptor site' for both the isoenzymes.

Identification of an intermediate form of beta-N-acetylhexosaminidase in chorionic villi.

A minor form of beta-N-acetylhexosaminidase has been found in chorionic villi, in addition to the major forms A and B. This form does not hydrolyze the 4-methylumbelliferyl-2-acetamido-2-deoxy-beta-D-glucopyranoside-6-sulpha te substrate, is thermostable, has a higher mol mass (120,000) than A and B (100,000) and on analytical isoelectric focusing, it shows a microheterogeneity with values ranging between 6.3 and 7.0. For these characteristics, it resembles beta-N-Acetylhexosaminidase P from pregnancy serum, from which is chromatographically indistinguishable.

Distribution of SP1, immunoreactivity among different plasma proteins: real molecular heterogeneity or adsorption of SP1-beta to other plasma proteins?

Three SP1-containing factors from pooled term pregnancy sera were subjected to crossed immunoelectrophoresis. New patterns as far as electrophoretic mobilities and shapes of the immunoprecipitates were revealed. The appearance of an additional anodic radioimmunoassayable activity in agarose electrophoresis of mixed SP1-alpha and SP1-beta suggested a binding capacity of SP1-alpha for SP1-beta determinants. In the serum of a single patient at the third trimester of pregnancy we also found two SP1 variants, possessing little radioimmunological reactivity and with crossed immunoelectrophoretic characteristics quite different from those of the 'usual' alpha and beta SP1 forms. These results suggest that, in this particular case, the overall SP1 production cannot be evaluated by competitive binding assay and, that in general, SP1 is a complex antigen the heterogeneity of which can be determined following adsorption of some beta epitopes to another serum protein.