[Cesarean section trends at the Toulouse University Hospital, from 1983 to 1993. Determinants and consequences]. / Evolution des taux de césarienne au CHU de Toulouse, de 1983 à 1993. Déterminants et conséquences.

OBJECTIVE: To examine the factors accounting for the increase in rate of cesarean section, between 1983 and 1993 (from 13.0% to 19.5%) in Toulouse University Hospital, a tertiary level center. DESIGN: Retrospective study of all single deliveries, excluding deaths in utero, between 1983 and 1993. RESULTS: Half the increase in overall rate was due to the numerical increase in women with a cesarean section history. The percentage of cesarean sections in these patients remained constant at 79% over this period. For the other patients, the increase in rate was due partly to an increase in risk factors, but mainly to a change in obstetric practice with a marked increase in elective cesarean section (70% of all cesarean sections in 1993). Major complications in the mothers were relatively rare, albeit significantly more frequent in the cesarean cases. Over the study period the percentage of infants requiring intensive care remained constant for the vaginal deliveries but declined for the cesarean sections. CONCLUSION: The increased rate of cesarean sections has not led to any increase in maternal complications, and appears to have had a small favorable influence on infant morbidity.

Paradoxical ovarian stimulations in the use of LHRH analogs.

In the case of in vitro fertilization, LHRH analogs are used to induce an hypophysary blockage, before the phase of stimulation, via administration of exogenous gonadotropin. During in vitro fertilization attempts using LHRH analogs, the blockage is controlled after 14 days of treatment through measurement of the plasmatic estradiol and pelvic ultra-sonography. In this retrospective study, which concerned 1075 in vitro fertilization cycles, a paradoxical ovarian stimulation with LHRH analogs was observed in 93 cases (8.7%), with high estradiol levels and follicular growth (detected by ultra-sonography), in spite of low FSH and LH levels. In 4 cases, a follicular puncture was performed, which allowed to collect oocytes from which embryos were obtained, thus confirming the observed follicular growth and maturation. The most probable hypothesis explaining this phenomenon seems to be a direct ovarian stimulation, effectuated in vivo by LHRH analogs. This stimulation is only observed in certain patients, and apparently more frequently, with certain LHRH analogs, probably through a variation in the expression of ovarian LHRH receptors.

Paradoxical ovarian stimulations in the use of LHRH analogs.

In the case of in vitro fertilization, LHRH analogs are used to induce a hypophysial blockage before the phase of stimulation, via administration of exogenous gonadotropin. During in vitro fertilization attempts using LHRH analogs, the blockage is controlled after 14 days of treatment by measuring plasmatic estradiol and by pelvic ultrasonography. In this retrospective study, which concerned 1075 in vitro fertilization cycles, a paradoxical ovarian stimulation with LHRH analogs was observed in 93 cases (8.7%) with high estradiol levels and follicular growth (detected by ultrasonography), in spite of low FSH and LH levels. In 4 cases, a follicular puncture was performed, which made it possible to collect oocytes from which embryos were obtained, thus confirming the observed follicular growth and maturation. The most probable hypothesis explaining this phenomenon seems to be direct ovarian stimulation effectuated in vivo by LHRH analogs. This stimulation is only observed in certain patients, and, more frequently it seems, with certain LHRH analogs, which is probably due to a variation in the expression of ovarian LHRH receptors.

Randomized trial of three luteinizing hormone-releasing hormone analogues used for ovarian stimulation in an in vitro fertilization program.

OBJECTIVE: To determine if biochemical differences in luteinizing hormone-releasing hormone analogues (LH-RH-a) have a clinical influence, we studied three of these molecules: buserelin acetate (group B), triptorelin (group T), and leuprorelin (group L). DESIGN: Clinical trial. SETTING: In Vitro Fertilization (IVF) Center. PATIENTS: Two hundred forty-six patients, undergoing their first IVF attempt, were randomly allocated to one group. The analogues were used in a long protocol for ovarian stimulation in an IVF program. RESULTS: After 15 days of LH-RH-a therapy, the follicle-stimulating hormone level was lower in group B (2.9 +/- 1, 4.3 +/- 1.7, 4.8 +/- 2.1 UI/L for B, T, and L groups, respectively; P less than 0.001), although no difference was found in LH and estradiol (E2) levels. After follicular growth stimulation by human menopausal gonadotropins (hMG), E2 level was significantly lower in B group (1,799 +/- 1,101, 2,440 +/- 1,298, 2,137 +/- 1,044 pg/mL for B, T, and L groups, respectively; P less than 0.01), as well as the E2 level per hMG ampule (67 +/- 51, 97 +/- 61, 82 +/- 49 for B, T, and L groups respectively; P less than 0.01). The pregnancy per stimulated cycle rate was not significantly different among the groups. CONCLUSIONS: These results suggest that LH-RH-a could act not only on the pituitary but also on the ovaries. Moreover, these data suggest that buserelin acetate could be preferentially used for high responders and triptorelin for poor responders.

Maternal and umbilical cord concentrations of fentanyl after epidural analgesia for cesarean section.

The maternal and umbilical concentrations of fentanyl were measured after epidural analgesia for cesarean section, using a highly sensitive radioimmunoassay method. Sixteen parturients were anesthetized with a single epidural injection of a mixture of 85 mg bupivacaine 0.5%, 60 mg etidocaine 1%, and 100 micrograms fentanyl with epinephrine 1:200,000. Apparent maternal individual maximum peak concentration (Cmax) of fentanyl was 0.38 +/- 0.16 ng/ml (mean +/- SD) (range 0.12-0.59 ng/ml) and the time to reach Cmax (Tmax) was 24 +/- 14 min (range 5-60 min). Infants were born 19 to 42 min after epidural administration of fentanyl (mean 27 min). Fentanyl concentrations in neonates was 0.13 +/- 0.04 ng/ml for the umbilical vein and 0.06 +/- 0.03 ng/ml for the artery. The fetus extraction ratio was 53 +/- 19% (range 20-83%). The large difference between arterial and venous concentrations of fentanyl may be due to a metabolization by the fetus and/or an uptake of the drug in the fetal tissues. Thus, even if fentanyl levels reaching the fetus after cesarean section under epidural anesthesia, using local anesthetics with 100 micrograms of fentanyl, are within safe range values, the likelihood of fentanyl uptake by fetal tissues calls for a cautious use of repeated fentanyl administration.

Influence of pregnancy on human immunodeficiency virus disease.

Over a period of 3 years (mean 16, extremes 3 and 36 months), we compared clinical and laboratory parameters of 128 female, human immunodeficiency virus (HIV)-infected patients, all in clinical stage II or III (CDC classification). 34 patients were pregnant and delivered a viable infant after at least 28 weeks of amenorrhea (group I), 29 patients were pregnant and had a spontaneous or induced abortion during the first or second trimester (group II), and 64 were non-pregnant female control patients (group III). The changes in the clinical stages over time were not statistically significant between the groups. The only laboratory parameters that were significantly higher in group I at the time of the delivery were: leucocyte count (p less than 0.001), lymphocyte count (p less than 0.05), and sedimentation rate (p less than 0.001). These changes are known to be related to pregnancy and not to HIV disease. All other laboratory parameters showed no significant differences within and between the groups. We conclude, that pregnancy--carried to term or interrupted--does not aggravate the natural evolution of HIV infection in clinical stage II and III patients.

Effect of clomiphene citrate on oestrogen secretion by human granulosa cells in culture.

The effect of clomiphene citrate (CC) and 17 beta-oestradiol (E2) on oestrogen secretion was studied in human preovulatory granulosa cells in culture. CC stimulated E2 secretion at 1 and 10 ng/ml (respectively, +36 +/- 14% and +33 +/- 5%) in basal conditions but had no effect on FSH-stimulated E2 secretion. On the other hand, E2 had no effect at any of the tested concentrations (0.1 ng/ml to 1000 ng/ml) on its own production. Since the plasma level of CC obtained in clinical use ranges from 1 to 10 ng/ml, this finding could explain the higher plasma oestrogen levels obtained with CC as compared to human menopausal gonadotrophin.

Oxytocin biosynthesis in serum-free cultures of human granulosa cells.

Human granulosa cells were collected from preovulatory follicles during follicular puncture for in-vitro fertilization. They were cultured in serum-free medium supplemented with ascorbic acid. Using a combination of high-performance liquid chromatography and radioimmunoassay, the oxytocin material present in the cell extracts and secreted into the medium was identified. When cells were deprived of ascorbate, intermediary forms resulting of the post-translational processing of pro-oxytocin/neurophysin were detected. These data demonstrate that oxytocin biosynthesis occurs in human granulosa cells.

Effects of pH on antipyrine transfer across the human placenta ex vivo.

The influence of pH variations on transplacental transfer of antipyrine was studied using a human placental cotyledon perfused ex vivo. The antipyrine transfer rate is positively correlated with the pH in the fetal circulation and negatively correlated with the pH in the maternal circulation. Thus, the transfer rate is negatively correlated with the difference between pH values in maternal and fetal circulations. The antipyrine transfer rate is also positively correlated with the flows in maternal and fetal circulations. The above parameters allowed to explain 50% of the variance on the transfer rates obtained in various experimental conditions. In a final series of experiments where these parameters for each placenta were fixed at identical values, a good reproducibility in the results was obtained, the variation coefficient being 17%. Thus, establishing the effect of variations in pH allowed a good standardization of the perfused cotyledon model. This effect cannot be explained by modifications in the ionized fraction of the antipyrine molecular and is probably due to physiological mechanisms.

Absence of correlation between the levels of ATP and other seminal compounds in semen and the results of human in-vitro fertilization.

As part of an in-vitro fertilization programme (IVF), semen levels of adenosine triphosphate, fructose, citrate, zinc, free L-carnitine and glycerophosphocholine were measured in 178 men. None of these substances appeared to have any predictive value with regard to the fertilizing potential of the semen during IVF.

Placental taurine and low birth weight infants.

In order to determine whether the decrease in taurine concentration in the placenta during pregnancy could affect fetal development, as has been observed in animals, we measured the concentration of taurine in placentas obtained after vaginal expulsion. 31 placentas from women with normal pregnancies of over 37 weeks who have given birth to infants of normal weight (3,200 +/- 310 g) were included in the study. In addition, 26 placentas of infants considered to be hypotrophic were also included (gestation over 37 weeks, birth weight: 2,260 +/- 230 g). The taurine was assayed using gaz-liquid chromatography. The concentration of taurine in the placenta was 2.80 +/- 0.56 mumol/g for the placentas of normal birth weight infants and 2.40 +/- 0.64 mumol/g for the placentas of hypotrophic infants (p less than 0.02). There is no significant correlation in normal and hypotrophic newborns between the gestation period, the weight and height at birth, the weight of the placenta, and the taurine concentration in the placenta. The taurine concentration in placentas of hypotrophic born infants is significantly reduced compared to the placentas from normal infants.

Effect of a luteinizing hormone-releasing hormone agonist (Buserelin) on steroidogenesis of cultured human preovulatory granulosa cells.

In order to ascertain whether there is a direct effect of luteinizing hormone-releasing hormone (LH-RH) agonists on ovarian steroidogenesis, human preovulatory granulosa cells were cultured in the presence of an LH-RH agonist (Buserelin, Hoechst Roussel Pharmaceuticals, Paris, France). Cultures were performed without serum but with precursors of estrogens and progestins. In basal conditions, Buserelin, at 1 ng/ml, increased estradiol and progesterone (P) secretion, while at concentrations of 10 and 100 ng/ml, no effect was observed. In the presence of follicle-stimulating hormone (FSH) or LH, Buserelin at 1 and 10 ng/ml did not modify the cell's steroidogenesis. However, at a concentration of 100 ng/ml, Buserelin decreased LH stimulation of P secretion. These results suggest that LH-RH agonists, at concentrations in the range of those obtained in clinical use, can modulate ovarian steroidogenesis by direct action.

Randomized trial of two media used for in vitro fertilization.

Culture media are important components of IVF. Their selection must meet the need for efficiency, and also economic and practical requirements. From these standpoints, we compared two widely used media: Ham's F10 supplemented with cord serum and Menezo B2 used without serum. The test followed a randomized protocol using two series of 159 and 162 oocytes. Since no difference was seen in efficiency assessed from cleavage rate, the discussion focuses on cost and ease of use.