The use of intravenous methotrexate in the treatment of ectopic pregnancy.

Between January 1996 and December 2001, at the Department of Gynecology, Perinatology and Human Reproduction of the University of Florence, 49 ectopic pregnancies were submitted to medical treatment. The treatment schedule consisted of the administration of 100 mg of intravenous methotrexate (MTX). The patients included in this study fulfilled the following requisites: gestational period <8 weeks; diameter of the ectopic gestational sac <4 cm; serum level of human chorionic beta-gonadotropin (beta-hCG) <5000 IU/ml; absence of clinical and ultrasound signs of tube rupture with initial hemoperitoneum; hematochemical tests compatible with chemotherapic treatment. All patients were followed with a dosage of serum beta-hCG repeated every 2-3 days after chemotherapy and with an ultrasound every 3-4 days. In case of documented success of treatment the patient was hospitalized for no more than 3 days after administration of the drug. In 1 case therapy took place in a day-hospital regimen. Medical treatment was effective in 35 patients out of 49 (71.4%) and led to negative beta-hCG in a median time of 11 days, with a range between 2 and 48 days. In the 14 non-responsive cases (28.6%), after a mean time of 6 days we proceeded to a traditional surgical approach or laparoscopy. In none of the cases did we find significant pharmacological toxicity, while in 9 patients (18.3%), severe painful symptoms appeared immediately after treatment, but resolved within 24 hours. Our results are interesting and in agreement with other experiences found in the literature. In our opinion, the advisability of a second administration in case of slow response, the comparison with an analogous intramuscular treatment, a more precise definition of the eligibility criteria, long-term follow-up of the patients, especially in case of subsequent pregnancies should all be further considered.

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.

[Amniotic fluid analysis as a screening test in term and post-term pregnancy]. / La valutazione del liquido amniotico come test di screening nella gravidanza a termine ed oltre il termine.

BACKGROUND: To verify the hypothesis that isolated oligohydramnios in low-risk term or post-term pregnancy does not increase the risk of trauma to the fetus compared with a control group. METHODS: This prospective study compared a group of patients with low-risk pregnancy and oligohydramnios (AFI = or <50) and a control group which on ultrasonography performed 24 hours before delivery had an AFI volume >50 and = or <250 mm. The evaluation criteria included incidence of induction, modality of delivery and neonatal outcome. Statistical analysis was carried out using Student's "t"-test and the data set of categories was compared using the chi square test. RESULTS: From January 1997 to April 1999, 105 cases of oligohydramnios were compared with a control group (105 patients) matched for maternal age, gestation period and parity. The incidence of induction, fetal distress and variable deceleration was significantly higher in the group with AFI = or <50. The incidence of vacuum extractor, cesarean section, duration of labor and late deceleration did not differ between the two groups. No significant differences in neonatal outcome were found between the two groups. CONCLUSIONS: In patients with oligohydramnios without risk factors, the modality of delivery and neonatal outcome do not differ compared with those with normal amniotic fluid volume.

Antimicrobial prophylaxis in obstetric and gynecological surgery.

A major problem in obstetric and gynecological surgery, especially following cesarean section in labor, total vaginal or abdominal hysterectomy, or myomectomy, is postoperative wound infection. Consequently, the use of antimicrobial prophylaxis for cesarean section and for gynecological surgery has been advocated and shown to be effective in reducing postoperative morbidity, costs and duration of hospitalization. We reviewed 1021 patients who underwent cesarean section (597 elective, 424 emergency) and 814 gynecological patients undergoing abdominal (373) or vaginal (248) hysterectomy and myomectomy (193) between 1997-98 in the Obstetrics and Gynecology Clinic of the University of Florence. Before surgery 83.6% of obstetric and 75.1% of gynecological patients received 1 or 2 g of a first or second generation cephalosporin i.v. as a single-dose regimen at induction of anesthesia and sometimes a second postoperative dose. 1.5% of obstetric surgical patients had wound infection, as did 2.8% of gynecological surgery patients, with a mean postoperative hospital stay of 8 days. The short-term perioperative antimicrobial prophylaxis with cephalosporins is useful and provides the benefit of minimal toxicity and risk of chemoresistance.

First trimester screening for Down's syndrome using maternal serum PAPP-A and free beta-hCG in combination with fetal nuchal translucency thickness.

The aim of this study was to evaluate the potential effectiveness of maternal serum pregnancy-associated plasma protein A (PAPP-A) and free beta-hCG in combination with nuchal translucency thickness in first trimester screening for Down's syndrome. Maternal serum levels of PAPP-A and free beta-hCG were assayed in stored sera from 32 Down's syndrome and 200 unaffected pregnancies. Fetal nuchal translucency was measured by ultrasound at the time of blood sampling. Screening of Down's syndrome using a combination of maternal age, PAPP-A, free beta-hCG and nuchal translucency would achieve a detection rate of 75.8% for a false positive rate of 5%.

Comparison between two methods of standardization for gestational age differences in fetal nuchal translucency measurement in first-trimester screening for trisomy 21.

Our purpose was to compare two different methods of expressing nuchal translucency (NT) measurements in first-trimester screening for trisomy 21: the difference in millimeters from the median of nuchal translucency (delta value: delta NT) and the multiple of the expected median (MoM). Fetal nuchal translucency was measured in 32 fetuses with trisomy 21 and in 3180 normal fetuses at 9-13 weeks' gestation. For each fetus, the measured nuchal translucency was expressed both as a delta value and MoM. The effectiveness of the MoM-Gaussian vs. the delta value method in modifying the age-specific risk for trisomy 21 was compared by using both the maternal age distribution of our study population and the age distribution of a general obstetric population. The use of the MoM-Gaussian approach led to a reduction in the false-positive rate at a given detection rate, both in the study population (by 1.2-15.2%) and in the general population (by 0.4-2.4%). Our results suggest that the use of the MoM-Gaussian method might confer a potential advantage on the screening performance of nuchal translucency in combination with maternal age by decreasing the false-positive rate. Further studies in larger unselected populations will be needed to confirm the effectiveness of this approach.

[Maternal-fetal transmission of the acquired immunodeficiency virus. Authors' experience]. / Trasmissione materno-fetale del virus da immunodeficienza acquisita. Nostra esperienza.

UNLABELLED: The determination of human immunodeficiency virus (HIV) status of the newborn remains a major diagnostic problem as a routine test, which detects antibodies to HIV, is of limited value in evaluating newborns. However, the risk of infection for a baby whose mother is an HIV carrier is not yet clear. OBJECTIVE: A prospective study to evaluate maternal transmission of HIV in our population. In order to provide a better estimate of the effect of some of the risk factors associated with HIV transmission we present a stratification of the transmission rate by these factors. STUDY DESIGN: Between January 1990 and December 1994 were examined a total of 10.949 pregnancies. To evaluate maternal HIV transmission to the fetus we considered a positive routine diagnostic test, which detects antibodies to HIV, of definite significance only at the age of 18 months or over. RESULTS: Our prospective study shows an overall transmission rate in our population of 31.25%. Maternal disease stage, as reflected by CD4+ cell count, prematurity, mode of delivery (episiotomy) was correlated with HIV transmission. CONCLUSIONS: Although some risk factors have been recognized, our understanding of the various modes of transmission is still limited. We conclude from our experience and previous studies that the risk of maternal to newborn transmission of HIV must be determined according to the specific characteristics of each parturient population.

Chorion villosum does not express progesterone and estrogen receptors during the first trimester of pregnancy.

First-trimester chorion villosum plays the key role in the development of human placenta and secretes a large number of hormones and hormone-related substances. To test whether progesterone and estrogen could have regulatory effects on first-trimester chorion villosum functions, we investigated the presence of progesterone receptor (PR) and estrogen receptor (ER) in 47 chorion villosum samples from patients who underwent abortion during the first trimester of pregnancy. The study was carried out using immunohistochemical methods. No ER and PR positivity was evidenced in the 47 chorion villosum samples examined. The possibility that progesterone and estrogen play a role in the regulation of chorion villosum functions should therefore be excluded.

Maternal serum CA 125 levels in first trimester abortion.

OBJECTIVE: To assess the source of maternal serum CA 125 during the first trimester of pregnancy. STUDY DESIGN: CA 125 was measured in stored samples from nonviable pregnancies of 8-13 weeks gestation. The study group comprised 19 women with vaginal bleeding and 13 non-bleeders. Only patients in whom chromosome analysis of the products of conception demonstrated a normal caryotype were included. CA 125 levels were expressed in multiples of the median (MoM) for normal pregnancies of the same gestational age. RESULTS: Median MoM values of CA 125 were significantly higher in women with vaginal bleeding (1.81 MoM) as compared both to non-bleeders (0.82 MoM; p < 0.01-Mann-Whitney U-test) and to the normal pregnancies (1.01 MoM; p < 0.05). No significant difference was found between non-bleeding women and controls. CONCLUSIONS: The present study indicates that in non-viable pregnancies with euploid fetuses an increase in maternal serum CA 125 levels was found only in presence of decidual disruption associated to vaginal bleeding. These findings are compatible with a prevalent decidual source of this antigen.

[External version in the breech presentation: a review of the literature and our experience]. / Il rivolgimento per manovre esterne nella presentazione podalica: revisione della letteratura e nostra esperienza.

OBJECTIVE: To evaluate the possibility to decrease the rate of cesarean delivery for breech presentation through use of a protocol that calls for cephalic version. STUDY DESIGN: Between january 1991 and april 1994 we offered cephalic version under tocolysis to patients whose fetuses were in breech position beyond 36 weeks' gestation and who were not in active labor. The protocol included real time ultrasonic scanning and pre- and post-procedure electronic fetal monitoring. A variety of maternal and fetal factors considered likely to affect success were coded for each patient. RESULTS: The conditions for an attempt at external cephalic version were satisfied in 47 cases. External version was accomplished in 32 cases (68%). Among patients in whom version was successful 20% required cesarean delivery for routine obstetrical indications. No major complications were noted. Successful version was more likely in women with amniotic fluid index > 50 and in those with posterior placental situation. CONCLUSIONS: We conclude from our experience and previous studied that the external cephalic version is a reasonable alternative in the management of pathological presentations near term, provided that only low risk pregnancies are included.

Decidual progesterone and estrogen receptors in the first trimester of pregnancy.

Receptor content of human decidua in early pregnancy (weeks 6-12) was investigated. Fifty-three tissue samples were obtained from voluntary patients undergoing abortion and whose gestational age range from 6 to 12 weeks. Blood samples were drawn at the time of operation in order to measure circulating estradiol (E) and progesterone (P) concentrations. Tissue samples underwent first histological confirmation and then were analyzed for receptor content by immunohistochemistry (IH) and by the conventional ligand binding technique (LBA). Estrogen receptors (ER) appeared to be always undetectable by IH (53 samples). LBA measured a significant amount of ER (> 10 fmol/mg) in two samples, borderline values (3-10 fmol/mg) in 6 and no binding in the other three. No relation was apparent between PR levels and either gestational age or blood P concentration. ER were possibly downregulated by the high E levels, and their synthesis inhibited by the high P levels.

[Lunar phases and incidence of spontaneous deliveries. Our experience]. / Fasi lunari ed incidenza di parti spontanei. Nostra esperienza.

OBJECTIVE: To evaluate the relationship between lunar phases and birthrate. STUDY DESIGN: We examined 7842 spontaneous deliveries at Obstetric and Gynaecologic Clinic of University of Florence, between January 1988 and November 1992, covering 58 synodic lunar months. A lunar month was considered to be a period of 29.5 days and comprised four lunar phases: the full moon, the last quarter, the new moon and the first quarter. We compared the median number of births in each day of synodic month and in the periods of seven days centered on the first day of each moon phase. Statistical analysis was performed using the Kruskal-Wallis one-way analysis by ranks. RESULTS: Non significant differences were found in the incidence of spontaneous birth throughout the lunar cycle. CONCLUSIONS: These results do not support the hypothesis of a relationship between moon-phase changes and the incidence of spontaneous deliveries.

Humerus and femur length in fetuses with Down syndrome.

The aim of the study was to assess the value of sonographic measurement of fetal humerus and femur lengths in the second trimester as a screening tool for Down syndrome (DS). We reviewed retrospectively fetal sonographic biometry made at the time of amniocentesis between 15 and 19 weeks. The study group consisted of 27 DS fetuses. The control group comprised 500 normal fetuses chosen randomly. The expected humeral and femoral lengths for a given biparietal diameter were estimated by linear regression equations from the 500 normal fetuses. Receiver operating characteristic curve analysis was performed to evaluate both the detection rate and the false-positive rate of different cut-off values of measured to expected lengths ratios. The median femur and humeral lengths in DS fetuses were 0.91 times the expected values. No significant differences in the detection rate and false-positive rate were found between the humerus and femur lengths. When the humeral and femoral lengths were combined, we observed a remarkable reduction in the false-positive rate. A measured to expected length ratio of 0.91 detected 44.4 per cent of DS fetuses with 7.6 per cent false positives. These results suggest that the combination of femoral and humeral lengths may permit a more efficient use of ultrasound in screening for Down syndrome than the use of either alone.

[Echographic measuring of the length of the fetal femur in the screening for Down syndrome]. / Misurazione ecografica della lunghezza del femore fetale nello screening della sindrome di Down.

OBJECTIVE: Our purpose was to assess the value of sonographic measurement of fetal femur length in the second trimester, as a screening tool for Down's syndrome. STUDY DESIGN: We evaluated a consecutive series of fetuses scanned by a single sonologist at the time of amniocentesis between 15 and 19 weeks. The study group consisted of fetuses with Down's syndrome (N = 16); the control group comprised normal fetuses (N = 1163). A linear regression model of the normal femur length based on biparietal diameter (BPD), was established for our population; the ratios of measured to expected femur length for a viven BPD (FL M/E) were calculated in the two groups. To test statistical significance of observed differences between case and control population, unpaired t test was used. The ability of specific FL M/E cut-off values to discriminate between Down syndrome and normal fetuses was assessed by Fisher's exact test. RESULTS: The mean ratio of measured to expected femur length was significantly lower in the Down syndrome as compared with control population (0.9473, DS 0.0795) versus 1.0, DS 0.0745) (p < 0.0045). The ratio of 0.91 or less predicted Down's syndrome with a sensitivity of 43.7% and a false-positive rate of 8.6%. For women with risk of one in 250 and one in 1000 of having an affected fetus based on maternal age, a shortened femur yielded positive predictive values of one in 26 and one in 105, respectively. CONCLUSION: These results suggest that the sonographic measurement of fetal femur length for the screening of Down syndrome in the low-risk population is hindered by a high false positive rate (about 9%). It follows that the percentage of women requiring an amniocentesis would increase to un unacceptably high level. The utilization of this biometric marker may be helpful, in our opinion, for identifying fetuses at risk for Down syndrome in women between 35 and 38 years of age. These women in fact, are not offered amniocentesis for the prenatal diagnosis of Down's syndrome in the majority of italian institutions. The sonographic measurement of fetal femur length could detect about 45% of fetal Down's syndrome, offering an amniocentesis to 9% of women, with a consequent reduction of the cost required. Only a prospective study can evaluate the efficacy of this method to predict Down syndrome in such group of women.

Systemic absorption of 3H-fenticonazole after vaginal administration of 1 gram in patients.

Fourteen women, five with normal cervicovaginal mucosa (Group 1), five with cervical carcinoma (Group 2) and four with relapsing vulvovaginal candidiasis (Group 3) were enrolled and completed this open clinical trial. Each subject received a single dose of 1.82 +/- 0.3 g on average of vaginal paste (for ovules) containing about 1000 mg of 3H-fenticonazole nitrate (266 microCi). Twelve hours after vaginal administration, the paste was removed by vaginal washing. Blood, urine and stool samples were collected at specified time intervals for five days. Plasma, urine, stools and all used material in contact with the paste were assayed for radioactivity. No measurable levels of radioactivity were detected in plasma of subjects of Groups 1 and 3 while in 4 of the 5 subjects with cervical carcinoma (Group 2) fenticonazole was detected during the 24 h after administration with a peak level at about 8 hours. For a period of 5 days, 0.4-1.5% of the dose on average was recovered from urine, and 0.18-0.32% from feces. Based on the excretion data, the extent of vaginal absorption of fenticonazole nitrate in women with vulvovaginal candidiasis was 1.81 +/- 0.57% of the dose, while in women with normal cervicovaginal mucosa it accounted for 0.58 +/- 0.28% of the administered dose. In patients with cervical carcinoma, absorption was 1.12 +/- 0.53%. The maximum amount absorbed corresponds to an exposure of about 0.4 mg/kg of fenticonazole nitrate (for a subject weighing 50 kg). Consequently, the vaginal administration of one ovule containing 1000 mg of fenticonazole nitrate seems to be devoid of risk for patients.

Alpha-fetoprotein in obstetrics. Experience of a prenatal diagnosis center.

For several years the determination of maternal serum alpha-fetoprotein (MSAFP) levels has been utilized to screen the patients at increased risk for foetal neural tube defects. In this way, various problems have been more and more dealed, from the definition of "cut-off" levels which could be guarantee an acceptable rate of diagnoses, limiting however the number of normal pregnancies which undergo further ascertainments, to the search of indoneous protocols of diagnostic approach in cases of high MSAFP levels. The wide clinical use of MSAFP determination has lead to the availability of a large number of data in various classes of obstetrics population, and to search for new diagnostic chances offered by this metodology. Among these, a great interest has been pointed out to the use of MSAFP determination to screen for Down's syndrome foetuses and to utilize MSAFP as a predictive index of perinatal pathology. The Authors describe their own experience in these diagnostic fields.

Evaluation of maternal serum alpha-fetoprotein and ultrasound examination to screen fetal chromosomal abnormalities.

Maternal serum alpha-fetoprotein (MSAFP), anatomic anomalies and precocious defects of foetal growth were shown as possible "indicators" of foetal chromosomal pathology, in particular Down's syndrome, and thus suggested for prenatal screening of risk patients for this chromosomal abnormalities. The Authors carried out a retrospective study on 1472 patients who underwent amniocentesis for prenatal diagnosis. Between the 15th and the 20th week, a dosage of MSAFP was effected, in order to evaluate if the serum concentration of this substance could predict Down's syndrome. A contemporary study by echographic monitoring was effected on 500 patients from the 1st trimester of pregnancy, in order to detect possible foetal growth retardation precociously and to determine the karyotype in these cases. Results are very interesting and suggest both the dosage of MSAFP and the ecographic monitoring for prenatal screening of trisomy 21, especially in maternal age classes younger than 40 years, where the cost/benefit ratio of screening for maternal age is less favourable.

High maternal serum alpha-fetoprotein levels during the 2nd trimester of pregnancy: diagnostic approach.

The limit of the classic diagnostic protocols following the evidence of high maternal serum alpha-fetoprotein levels is represented by the high number of amniocenteses performed and that, in the most part of cases, give false negative results. Now days the introduction of high resolution ecographic equipments allows to us, in many cases, to clarify the diagnostic without further examinations. The Authors propose a diagnostic protocol that include the execution of high resolution ultrasound at the second withdrawal of serum alpha-fetoprotein, limiting the use of amniocentesis only when is necessary to determine the fetal karyotype. An high sensibility diagnostic system with a favourable cost/benefit ratio results from this approach.

Prophylaxis in gynaecological and obstetric surgery: a comparative randomised multicentre study of single-dose cefotetan versus two doses of cefazolin.

Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached. Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30-40% for vaginal hysterectomy, 10-35% for abdominal hysterectomy and 10-34% for caesarean section. To assess the role of two different cephalosporins as short term prophylaxis, we carried out a multicentre randomised study involving a single 2 g i.v. dose of cefotetan in comparison with two doses of cefazolin (2 g i.v. before surgery and after 8 hours). Criteria for exclusion were: exposure to antibiotics within 7 days, preoperative infection, hypersensitivity to beta-lactams. Four hundred and sixty patients entered the study, of which 229 received cefotetan and 231 cefazolin. No significant differences in mean age, obesity, preoperative weight loss, diabetes, type of disease, type of surgery (vaginal or abdominal hysterectomies and caesarean sections) and number of pregnancies and abortions existed between the two groups of patients. The total rate of infected patients undergoing hysterectomy was 8.6% (13/151) in the cefotetan group and 17.4% (29/167) in the cefazolin group (p less than 0.05). This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment, while wound infections were not significantly different (2.6% and 1.8% respectively). Among patients undergoing caesarean section, 9 of 78 (11.5%) and 7 of 64 (10.9%) were infected following cefotetan and cefazolin, respectively (not significant). Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin (25.5-44.8 vs. 7.4-9.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)