Absence of placental transfer of pentasaccharide (Fondaparinux, Arixtra) in the dually perfused human cotyledon in vitro.

The synthetic pentasaccharide, fondaparinux, is the first of a new antithrombotic class: selective factor Xa inhibitors. Comparative clinical trials of fondaparinux versus heparins in prevention and treatment of venous thromboembolism are ongoing. Little is known about fondaparinux during pregnancy, as women of child-bearing potential were excluded from clinical trials. No particular safety issue, for either mother or fetus, has been reported for heparins. The objective of this study was to compare in vitro the steady state placental transfer of fondaparinux and enoxaparin at the plasma concentrations reached during acute treatment of venous thromboembolism (1.75 microg/mL and 1 anti-Xa IU/mL respectively), using antipyrine (20 mg/L) as reference. No biological activity was detectable in the fetal venous effluent during perfusion of enoxaparin-antipyrine, fondaparinux-antipyrine or control media. Furthermore, fetal venous samples did not differ significantly from fetal arterial samples. This apparent absence of placental transfer supports further evaluation of fondaparinux in pregnant women.

Induction of labor in twin pregnancy after 36 weeks does not increase maternal-fetal morbidity.

OBJECTIVE: To compare maternal and perinatal outcomes in twin pregnancy patients without any fetal or maternal disease, managed by labor induction or expectant management after 36 weeks gestation. METHODS: We conducted a case-control study of 81 patients: labor induction (n=36) vs. expectant management (n=45). Labor was induced using oxytocin (n=18), vaginal prostaglandins (n=6) or intrauterine balloon catheter (n=12) according to the Bishop score. Maternal and perinatal outcome variables were compared among both groups. RESULTS: The characteristics of the labor induction group and the expectant management group were not statistically different, except for the rate of nulliparae (55.6% vs. 33.3%) and the rate of epidural analgesia (100% vs. 80%). There was no significant difference in labor time (6.5+/-2.8 h vs. 6.0+/-3.6 h), cesarean section rate (8.3% vs. 13.3%) or duration of maternal hospitalization (7.3+/-2.0 days vs. 7.5+/-2.3 days) in the labor induction group and in the expectant management group, respectively. The birth weight was higher in the labor induction group than in the expectant management group (2639+/-352 g vs. 2463+/-298 g, P<0.001). The rate of Apgar score <7 at 5 min was 0% and 3.3%, respectively. Neonatal intensive care unit admission occurred in 30.5% and 26.6% of the groups, respectively. No perinatal death was reported. CONCLUSION: Induction of labor may be proposed to patients with uneventful twin pregnancy after 36 weeks gestation without increasing maternal-fetal morbidity.

Placental transfer of SR49059 in the human dually perfused cotyledon in vitro.

SR49059 is an antagonist of vasopressin V(1a)receptors currently developed as a tocolytic drug. We investigated the transplacental transfer of SR49059 in vitro using the single pass dually perfused human cotyledon model. Thirteen placentae were collected from normal term pregnancies immediately after delivery. The placental transfer of SR49059 was tested at steady state at three different concentrations (100 ng/ml, 200 ng/ml and 500 ng/ml) along with that of antipyrine 20 mg/l as a reference substance. Concentrations were assayed by liquid chromatography with UV (antipyrine) or mass spectrometry (SR49059) detection. At steady state, the mean+/-s.d. fetal transfer rate of SR49059 was 10.80+/-4.33 per cent, 9.34+/-4.41 per cent, and 11.78+/-3.26 per cent at 100 ng/ml, 200 ng/ml and 500 ng/ml, respectively. The corresponding clearance indices were 0.29+/-0.14, 0.25+/-0.08, and 0.31+/-0.06, respectively. The absence of saturation kinetics is consistent with a passive mechanism of transfer. Moderate amounts of SR49059 are transferred from the maternal to the fetal circulation. The clearance index of SR49059 appeared to be very similar to that of ritodrine, which is currently used as a tocolytic.

[Medical and surgical treatment of functional ovarian cysts]. / Traitement médical et chirurgical des kystes de l'ovaire fonctionnels.

Most of symptomatic functional ovarian cysts (FOC) are treated by surgery. Oral contraceptives and ultrasound-guided puncture are not more efficient than expectant management for treating asymptomatic FOC in non menopausal women. The probability of a cyst being functional or benign in asymptomatic postmenopausal women is assessed by transvaginal ultrasonography, color Doppler flow imaging and CA 125 serum level measurement. Conservative management of simple cysts (anechoic, diameter < 5 cm with normal Doppler and CA 125 serum level) is more reasonable and safer than surgical treatment. The use of high-dose combination oral contraceptives has a protective effect against FOC, whereas low-dose pills have little or no effect. However, low-dose oral contraceptives or progestogen-only oral contraceptives do not increase the risk of FOC. In the case of recurrent or symptomatic FOC, the advantages of using higher dose formulations have not been proved. Expectant management is as effective as oral contraceptives for the resolution of FOC induced by ovarian stimulation. Tamoxifen treatment in premenopausal breast cancer patients is associated with ovarian overstimulation and FOC formation (> 35%). Co-treatment with Gn-RH agonist may be successful in this indication. Hormone replacement therapy may be associated with an increasing ovarian volume, but not with an increasing rate of FOC. The management of surgical-induced FOC (entrapped ovarian cyst, ovarian transposition) has never been assessed by controlled studies.

Placental transfer of pyrimethamine studied in an ex vivo placental perfusion model.

Pyrimethamine is used as and anti-infectious agent because of its antifolate properties. Its action is synergistic with that of dapsone and sulfamides on Toxoplasma gondii. The goal of the present study was to evaluate the placental transfer of pyrimethamine in an ex vivo model of perfused human placental cotyledon at term. Human placentas were perfused according to the slightly modified method of Schneider. The pyrimethamine fetal transfer rate was approximately 30%, while cotyledon clearance was about 1.8 ml/min. The placental transfer of pyrimethamine seems to be independent of the maternal concentrations of pyrimethamine, suggesting passive diffusion mechanisms or a nonsaturable active transport at the tested concentrations.

Trans fatty acids in adipose tissue of French women in relation to their dietary sources.

This study reports the fatty acid composition of subcutaneous adipose tissue in French women with special emphasis on the content of trans fatty acids originating from two main dietary sources, ruminant fats and partially hydrogenated vegetable oils (PHVO). Adipose tissue trans fatty acid levels from 71 women, recruited between 1997 and 1998, were determined using a combination of capillary gas chromatography and silver nitrate thin-layer chromatography. Results indicate that on average cis monounsaturates accounted for 47.9% of total fatty acids, saturates for 32.2%, and linoleic acid for 14.4%. Cis n-3 polyunsaturates represented only 0.7%. Total content of trans fatty acids was 2.32 +/- 0.50%, consisting of trans 18:1 (1.97 +/- 0.49%), trans 18:2 (0.28 +/- 0.08%), and trans 16:1 (0.06 +/- 0.03%). Trans 18:3 isomers were not detectable. The level of trans fatty acids found in adipose tissue of French women was lower than those reported for Canada, the United States, and Northern European countries but higher than that determined in Spain. Therefore, trans fatty acid consumption in France appears to be intermediate between that of the United States or North Europe and that of Spain. Based on the equation of Enig et al., we estimated the mean daily trans 18:1 acid intake of French women at 1.9 g per person. The major trans 18:1 isomer in adipose tissue was delta11 trans, as in ruminant fats. Estimates of relative contribution of trans fatty acid intake were 55% from ruminant fats and 45% from PHVO. This pattern contrasts sharply with those established for Canada and the United States where PHVO is reported to be the major dietary source of trans fatty acids.

[Endometrial thermocoagulation via balloon: technique, mechanism of action, and evaluation]. / Thermocoagulation endométriale par ballonnet: technique, mécanisme d'action et évaluation.

Thermal balloon endometrial ablation is indicated for women suffering from menorrhagia. This easy technique can be performed safely, without using operative hysteroscopy. The rate of minor complications is low (< 4%). Thermotherapy treats the endometrium and superficial myometrium tissues without risk of injury to the bladder and bowels. The success rate of this operation is 90% in selected patients of studies published between 1996 and 1998, with a follow-up period of 12-24 months. However, long-term randomized controlled studies are needed to compare thermotherapy and other endometrial ablation procedures.

[Maternal transport to the Bordeaux University Hospital: a retrospective study of 263 cases (1996-1998)]. / Le transfert des enfants in utero au Centre Hospitalier Universitaire de Bordeaux : analyse rétrospective de 263 cas (1996-1998).

OBJECTIVES: To describe a population of high risk pregnancies transported to a regional perinatal care centre (level III) and to analyze the advantages and limitations of the organization of this perinatal care network. METHODS: Retrospective study of 263 patients transported to the University Hospital of Bordeaux between September 1996 and September 1998. RESULTS: Maternal transport mainly came from the Gironde department (53%) and from level I care hospitals (66%). The rate of multiple pregnancies was 17%. Principal indications were preterm labor with or without rupture of fetal membranes (52%) and preeclampsia with or without intrauterine growth restriction (28%). The rate of returns to the referring care centre was 2%. The mean term at delivery was 32 WA. Forty-one percent of patients delivered within 24 hours of transport. The rate of caesarean sections was 55%. There were 303 live births. The mean duration of hospitalization of the neonates was 28 days. The rate of perinatal mortality was 6.2%. Among the 96 pregnancies beyond 32 WA, 17 (6.5%) could have been transported to some level IIb care hospitals, nearby the patient's residence, without changing maternal and neonatal prognosis. Neonatal mortality was not significantly different for maternel transport (18%) or neonatal transport (14%) in the group of premature infants born prior to 31 WA in our study. CONCLUSION: Our organization is currently trying to improve transport management (non-emergency situations, collaboration of level II care hospitals) and to increase the rate of returns to the referring care centres.

[Urinary incontinence in elderly women]. / L'incontinence urinaire de la femme âgée.

Urinary incontinence in elderly women, though due to several factors, is not inevitable; case-by-case management is often effective.

Passage of S-(+)- and R-(-)-ketoprofen across the human isolated perfused placenta.

Ketoprofen is a chiral non-steroidal anti-inflammatory drug (NSAID) available as a racemic (rac) mixture of S-(+)- and R-(-)-isomers. Its inhibitory effect on prostaglandin biosynthesis resides virtually in the S-form. Interestingly, R-ketoprofen does not undergo substantial metabolic inversion in humans. Though contraindicated during the last trimester of pregnancy, NSAIDs, including ketoprofen, are used as tocolytic agents in some cases. The S/R plasma concentration ratio was reported to average 2.3 in premature neonates whose mothers were given rac-ketoprofen and to be close to 1 in the maternal plasma. Thus, we investigated the placental transfer of rac-ketoprofen in vitro using Schneider's perfused human cotyledon model. Glucosed Earle solutions with and without human serum albumin (HSA) were used. Several maternal perfusates were tested with different rac-ketoprofen concentrations together with 20 mg L-1 of antipyrine as a reference substance. Ketoprofen enantiomers were assayed by a specific HPLC method with derivatization procedure. HSA concentrations in maternal perfusate influenced the placental transfer of ketoprofen enantiomers. In the absence of HSA in the maternal perfusate, the S-(+)/R-(-) concentration ratio was close to 1 in the fetal perfusate. By contrast, this ratio averaged 1.44 after addition of HSA 10 g L-1 on the maternal side. Similar results were found for dialysis experiments using an inert Spectrapor 2 membrane suggesting that the S-(+)-free concentration is superior to the R-(-)-free concentration in the presence of HSA. Direct measurements of the free concentrations by centrifugal ultrafiltration confirmed this hypothesis. Accordingly, the data observed in vivo may result, at least in part, from the stereoselective protein binding of ketoprofen.

[Can the type of GnRH used during long in vitro fertilization protocols influence the pregnancy rate?]. / Le type d'analogue de la GnRH utilisé au cours des protocoles longs en FIV peut-il influencer les taux de grossesse?

Luteal defect is common during IVF cycles using GnRH agonist. It could be interesting to make up for this problem by using short acting GnRH agonist (effective for 24 hours), more handy at the end of the stimulation. 160 patients included in a long IVF protocol at the Bordeaux CHRU FIV center have been randomized, from September 1993 to August 1994, for the analog's choice (long or short) at the beginning of the stimulation. The stimulation's parameters, the hormonal dosages and the pregnancy rate are independent of the galenic form used. In close, the use of long-acting GnRH analog (sympler to use) sems preferable.

[Thromboembolism and ovarian hyperstimulation]. / Accidents thrombo-emboliques et hyperstimulation ovarienne.

Three new cases of thromboembolic accidents involving the superior vena cave were associated with ovarian hyperstimulation and multiple pregnancy. On the basis of a review of the literature, three syndromes were individualized. First embolic arteries are infrequent and serious with an important morbidity; low doses of gonadotrophines is sufficient for causing this pathology. Second, thrombosis of the superior vena cava is late, during in vitro fertilization regimens with GnRH analogs complicated with serious hyperstimulation (degree III). Third, pregnancy is always present; pulmonary complications are very uncommon. Thrombosis of inferior vena cava is late, pregnancy is often present but women are frequently at risk of thromboembolic accident. Prevention of hyperstimulation is important. When present, HBPM is recommended for prevention of thromboembolism. Diagnostic of thrombosis is made with clinical examination and morphologic complementary exams such colour-vascular Doppler and magnetic resonance imaging. Curative treatment requires heparinization.

[Transplacental passage of epirubicin]. / Passage transplacentaire de l'épirubicine.

We studied the transplacental transfer of epirubicin, an anthracycline used for the treatment of different neoplastic disorders, in particular breast cancers, by in vitro perfusion of term human placenta. Placenta from women with uncomplicated pregnancy were collected immediately after vaginal delivery and put into 37 degrees C thermostated hood. Perfusion of foetal surface of the placenta by modified Earle's solution was started immediately after catheterisation at a flow rate of 6 ml/min and then so was the perfusion of the intervillous space at the rate of 12 ml/min. Samples were collected at different times after the initiation of the perfusion from arterial inflow and venous outflow respective of the maternal and foetal compartment. The transplacental transfer of epirubicin was investigated for two doses: 5 and 9 micrograms/ml. The mean transfer value of epirubicin is low (3.66 +/- 1.07%) for the two tested doses and is only slightly higher than doxorubicin transfer, which drug has provided rare accidents in the clinical reports. These results are in favour of a low placental toxicity of epirubicin. Clinical data have to be collected from pregnant women to confirm the low foetal toxicity of epirubicin.

[Placental penetration of cefpirome (HR 810): study of fetal concentrations after in vitro infusions of human placenta at term]. / Pénétration placentaire du cefpirome (HR 810): étude des concentrations foetales après perfusion in vitro de placenta humaine à terme.

Cefpirome (CPO) is a new parenteral cephalosporin with a wide antibacterial spectrum. In order to explore the possibility of using CPO in late pregnancy, we studied its placental transfer in vitro in a model of human placenta infusion. Mother-to-foetus in vitro transfer of CPO is high, similar to that of amoxicillin, with a placental clearance index of 0.20. A pharmacokinetic simulation based upon this result and data from literature suggests that CPO concentrations in foetal blood and amniotic fluid should be appropriate for the treatment of severe materno-foetal infections in late pregnancy. These preliminary results need to be confirmed by in vivo pharmacokinetic and clinical studies before recommending the use of CPO in late pregnancy.

[Evaluation of 3 diagnostic methods in premature rupture of membranes: diamine-oxidase assay, alpha-fetoprotein assay, colorimetric method evaluating the pH]. / Evaluation de trois méthodes diagnostiques dans la rupture prématurée des membranes: dosage de la diamine-oxydase, dosage de l'alpha-foeto-protéine, méthode colorimétrique évaluant le pH.

The authors set out to assess the three diagnostic methods available which can detect early breaking of the membranes: radio-enzymatic assay of diamine-oxidase (DAO), radioenzymatic assay of alpha-fetoprotein (AFP), colorimetric method for determining pH (Amnicator). Between June 1991 and March 1992, 114 samples of vaginal secretions were taken from 104 pregnant patients being followed up at Maternity Unit A, Bordeaux (France). The results of the assays were expressed in quantitative terms (microU/ml for DAO and ng/ml for AFP); ROC (Receiver Operating Characteristic) curves were used to determine the positivity threshold in terms of the sensitivity and specificity (20 microU/ml for DAO and 15 ng/ml for AFP). The sensitivity of the pH test was 97.5%, which was significantly better than that of DAO (90.2%) and even that of AFP (82.9%). However, there was no difference between the specificities of the pH, DAO and AFP tests (93.3%, 96.6% and 93.5% respectively). The data were compared with those in the literature. The problems in collecting the vaginal secretions probably accounts for the better results of the colorimetric test. This is a reliable, fast and easily reproducible test; these qualities make it the preferred test in EBM, and it can be completed using a radioenzymatic method (DAO) or immunoradiometric test (AFP).

Familial occurrence of hereditary renal adysplasia with müllerian anomalies.

We report on a family with unilateral or bilateral renal agenesis and Müllerian anomalies (vaginal atresia or minor anomalies). This family provides support for an autosomal dominant pattern of inheritance with incomplete penetrance and variable expressivity in hereditary renal adysplasia (HRA) associated with Müllerian defects.

[Induction in the scarred uterus]. / Déclenchement sur utérus cicatriciel.

Labor was induced in 41 women with uterine scarring and a fetus in the cephalic presentation and normal pelvis size. Due to various problems, these patients would have had to undergo cesarean section if this alternative had not been attempted. The use of prostaglandins E2 to increase maturation of the cervix, of Syntocinon and peridural analgesia made it possible to obtain delivery through the genital tract in 24 cases with the same level of fetal morbidity as for the babies delivered by cesarean.

Isolation of genital mycoplasmas from blood of febrile obstetrical-gynecologic patients and neonates.

In a prospective study, 1156 blood specimens collected from hospitalized febrile obstetrical-gynecologic patients and neonates with suspected sepsis, were inoculated into a conventional biphasic culture medium, Castaneda S and cultures incubated aerobically. 15-24 h later the broth cultures were subcultured to specific media for detection of mycoplasmas. Genital mycoplasmas were isolated in 15 samples (taken from 8 women) and in 2 from 1 neonate. Mycoplasmas and members of the family Enterobacteriaceae were the most frequent significant bacteria isolated from adult specimens. Mycoplasma isolations were associated with either postpartum or postabortum febrile infections in women. Four of the neonates, whose mothers were infected, showed respiratory distress at birth; 1 of them had mycoplasmas in the blood. All febrile states in obstetrical or gynecological patients, and in neonates, should routinely lead to blood cultures for detection of mycoplasmas and ureaplasmas.