[GnRH antagonists: yes or no?].
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Female↗
Biomedical subjects
R Frydman
Publications and source records attributed to R Frydman.
[Cervical cerclage with buried prosthetic band: technique, indications and results in a series of 28 pregnancies].
OBJECTIVES: We performed a retrospective study to evaluate the results of a new approach to cervical cerclage using a prosthetic band. MATERIALS AND METHODS: Twenty-four patients were recruited over an 8-year period between 1991 and 1999. All had a history of at least two late abortions and/or preterm delivery and a failed attempt with McDonald or Hervet cerclage. We used a cervical cerclage technique with prosthetic band inspired from the Shirodkar technique but which has been simplified and quite easy to reproduce. The technique consists in placing a prosthetic band around the internal os under the vaginal mucosa at the vesicovaginal reflection level. Outcome of pregnancy before and after inserting the prosthetic band was compared. RESULTS: Outcome of 28 pregnancies after cerclage were assessed (4 patients had two successive pregnancies with the same cerclage left in place). 82% of the children were liveborn after cerclage versus 21.7% before cerclage. 53.3% of the patients delivered at term after cerclage versus 2.8% before cerclage. We had 7.1% late miscarriages after cerclasge versus 65.2% before. There were no surgical complications. 22 of the 23 liveborn children were delivered by cesarean section. Conclusion. These results show that the cervical prosthesis is a solution of these patients with an obstetric history of cervical incompetence with failure of classical techniques.
Adult↗
[Value of amnioculture for choosing antibiotic treatment for premature rupture of membranes before 34 weeks gestation].
OBJECTIVE: This study attempts to answer the following question: is systematic amniocentesis an efficient tool for adjusting an antibiotic treatment in case of preterm premature rupture of membranes? METHODS: Retrospective study of 76 cases of preterm premature rupture of membranes that occurred between January 1994 and February 1997 in a French teaching hospital. RESULTS: Amniocentesis was impossible for 28 patients (Group I). In this group there was a 46% rate of neonatal sepsis (n=13). Amniocentesis was successful in 48 patients. 24 delivered within 48 hours after amniocentesis (Group IIa). In this group there was a 29% rate of neonatal sepsis (n=7), and amniotic fluid culture was positive in 33% of the cases. 24 delivered beyond 48 hours after amniocentesis (Group IIb). In this group there was a 21% rate of neonatal sepsis (n=5) and amniotic fluid culture was positive in 12.5% of the cases. Group I and IIa had a high risk of neonatal sepsis and could not benefit from amniocentesis culture results. CONCLUSION: Group IIa and IIb cannot be distinguished a priori, therefore systematic amniocentesis can only have a restricted impact on the management of antibiotic therapy. Even in the case of a negative amniotic fluid culture, antibiotic therapy is mandatory. If a systematic amniocentesis policy is used, one hundred amniocentesis have to be performed in order to adapt six antibiotic therapies. In the group with the highest risk of neonatal sepsis (severe oligohydramnios), amniocentesis cannot be performed. A policy of systematic amniocentesis restricted to the cases that are not delivered within the first 48 hours could be evaluated in a prospective randomized trial. Such a policy could help in deciding whether to stop, adapt, or continue the antibiotic therapy, or to induce the delivery in case of an asymptomatic chorioamniotitis.
Amniocentesis↗
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Journal Article↗
[Regionalization of perinatal care and in utero referrals].
Further improvement in perinatal morbidity and mortality figures implies in utero referral so high risk infants, particularly very early maturity infants, can be managed immediately in specialized centers. The success of such referrals depends directly on the coherence of the regional perinatal health care network. It has been demonstrated that the chances of survival and of sequelae-free survival are greater for very premature infants born in a center with a neonatal intensive care unit. The situation in France leaves room for improvement. Only 15% of the infants born before 33 months gestation and with birth weight under 1500 g are born in level III maternity wards equipped with a neonatal intensive care unit. The goal is 80%. We have tried to analyze the reasons behind this situation and propose ways to better organize perinatal health care.
Female↗
Pharmacological and biochemical study on the effects of selective phosphodiesterase inhibitors on human term myometrium.
This study was aimed at evaluating the in vitro effects of phosphodiesterase inhibitors and beta2-adrenoceptor agonists on spontaneous contractions of human term myometrium. Rolipram, RP 73401 (3-cyclopentyloxy-N-(3,5(-dichloro-4-pyridil)-4-methoxybenzamide) and Ro 20-1724 (1-4-(3-butoxy-4-methoxybenzyl)-2-imidozolidinone) (phosphodiesterase 4 inhibitors) inhibited spontaneous myometrial contractions (Emax approximately 100%; pD2 of 6.80+/-0.28, 6.84+/-0.32 and 6.31+/-0.03, respectively). Salbutamol and formoterol were less effective (Emax=40+/-6% and 35+/-12%, respectively) than phosphodiesterase 4 inhibitors to reduce myometrial contractility. Inhibitors of phosphodiesterase 3 (milrinone and siguazodan) and 5 (zaprinast) were marginally effective. Rolipram (10-30 nM) and siguazodan (0.1 microM) potentiated the response to salbutamol (Emax=75+/-12%, 88+/-8% and 73+/-12% and pD2=6.51+/-0.20, 6.93+/-0.29 and 6.48+/-0.16, respectively). Sodium nitroprusside (pD2=6.76+/-0.29) and theophylline (pD2=5.15+/-0.22) were effective inhibitors of myometrial contractions. Chromatographic separation of phosphodiesterase isoenzymes demonstrated that phosphodiesterase 4 is predominant but other phosphodiesterase isoenzymes were also identified. In conclusion, phosphodiesterase 4 inhibitors alone or combined with beta2-adrenoceptor agonists have potential interest as tocolytic agents.
Adrenergic beta-Agonists↗
Computerized assessment of endometrial echogenicity: clues to the endometrial effects of premature progesterone elevation.
OBJECTIVE: To determine whether premature progesterone elevation affects the timing of hyperechogenic transformation of the endometrium during the early luteal phase of controlled ovarian hyperstimulation (COH) cycles. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Fifty-nine women undergoing 59 IVF-ET cycles. INTERVENTION(S): Patients underwent COH with a GnRH agonist and hMG. Endometrial echogenicity was assessed on the days of hCG administration, oocyte retrieval, and ET. Results are expressed as the extent of submyometrial hyperechogenic area in relation to the total endometrial surface as determined by a computer-assisted analysis system. Patients were sorted according to whether their plasma progesterone level exceeded 0.9 ng/mL (n = 26) or not (n = 33) on the day of hCG administration. MAIN OUTCOME MEASURE(S): Endometrial echogenicity. RESULT(S): On the day of hCG administration, the degree of endometrial echogenicity was similar in both groups (41% vs. 40%), but after hCG administration, it increased significantly faster in the high progesterone group than in the low progesterone group (70% vs. 63% at oocyte retrieval and 90% vs. 79% at ET, respectively). CONCLUSION(S): End-follicular phase elevation in plasma progesterone (>0.9 ng/mL on the day of hCG administration) was associated with a faster increase in endometrial echogenicity during the early luteal phase of COH cycles. This observation is consistent with the hypothesis that premature progesterone elevation hastens the secretory transformation of the endometrium.
Adult↗
Herpes simplex virus encephalitis in pregnancy.
BACKGROUND: Although polymerase chain reaction (PCR) can detect herpes simplex virus (HSV) in the cerebrospinal fluid (CSF), HSV encephalitis remains a significant cause of neurologic impairment in pregnant women. Assessment of fetal contamination also remains a problem. CASES: We report two cases in which HSV encephalitis initially was not suspected and led to significant maternal neurologic impairment. In both cases, HSV PCR of CSF confirmed the diagnosis. In one case, fetal serum HSV PCR excluded fetal contamination. CONCLUSION: As soon as encephalitis in pregnancy is suspected, a combination of acyclovir and penicillin is recommended because the potential benefits far outweigh the risks. Using the HSV PCR, HSV infection in the fetus can be diagnosed.
Adult↗
Revival of the natural cycles in in-vitro fertilization with the use of a new gonadotrophin-releasing hormone antagonist (Cetrorelix): a pilot study with minimal stimulation.
Natural cycles were abandoned in in-vitro fertilization (IVF) embryo transfer, due to premature luteinizing hormone (LH) surges--and subsequent high cancellation rates. In this study, we investigated the administration of a new gonadotrophin-releasing hormone antagonist (Cetrorelix) in the late follicular phase of natural cycles in patients undergoing IVF and intracytoplasmic sperm injection (ICSI). A total of 44 cycles from 33 healthy women [mean age 34.1 +/- 1.4 (range 26-36) years] were monitored, starting on day 8 by daily ultrasound and measurement of serum concentrations of oestradiol, LH, follicle stimulating hormone (FSH) and progesterone. When plasma oestradiol concentrations reached 100-150 pg/ml, with a lead follicle between 12-14 mm diameter, a single injection (s.c.) of 0.5 mg (19 cycles) or 1 mg (25 cycles) Cetrorelix was administered. Human menopausal gonadotrophin (HMG; 150 IU) was administered daily at the time of the first injection of Cetrorelix, and repeated thereafter until human chorionic gonadotrophin (HCG) administration. Four out of 44 cycles were cancelled (9.0%). No decline in follicular growth or oestradiol secretion was observed after Cetrorelix administration. A total of 40 oocyte retrievals leading to 22 transfers (55%) was performed. In 10 cycles (25%), no oocyte was obtained. Fertilization failure despite ICSI occurred in six cycles (15%). In two patients the embryo was arrested at the 2 pronuclear (PN) stage. The stimulation was minimal (4.7 +/- 1.4 HMG ampoules). A total of seven clinical pregnancies was obtained (32.0% per transfer, 17.5% per retrieval), of which five are ongoing. Thus, a spontaneous cycle and the GnRH antagonist Cetrorelix in single dose administration could represent a first-choice IVF treatment with none of the complications and risks of current controlled ovarian hyperstimulation protocols, and an acceptable success rate.
Adult↗
Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome.
OBJECTIVES: To test the association between cytokine levels in the amniotic fluid and (i) the vascular invasion phase of intrauterine infection, (ii) the occurrence of periventricular leukomalacia; to assess the correlation between C-reactive protein levels, a recognised biological marker of inflammation in maternal serum and cytokine levels in the amniotic fluid. DESIGN: Prospective clinical study. SETTING: Fetal medicine unit and neonatal intensive care unit, Antoine Beclere Hospital, Clamart, France. SAMPLE: Thirty-one pregnancies complicated by chorioamnionitis leading to birth before 32 weeks of gestation. METHODS: Interleukin 1-beta, Interleukin 6 and TNF-alpha prospectively measured in the amniotic fluid. Histological examination of the placenta. Ultrasound examination and magnetic resonance imaging of the brains of the newborn infants performed within the first week of life. MAIN OUTCOME MEASURES: The occurrence of periventricular leukomalacia was assessed by transfontanellar ultrasound and magnetic resonance imaging. RESULTS: There was a significant positive correlation between the occurrence of histological chorioamnionitis, vascular extension of infection of the membranes, maternal inflammatory syndrome and neonatal sepsis. A strong association was found between maternal serum C-reactive protein concentrations and cytokine levels in the amniotic fluid. Interleukin-1beta was the best predictor of vascular extension of chorioamnionitis, and TNF-alpha was the best predictor of the development of severe early neonatal infection. There was no association between the amniotic fluid levels of cytokines and the development of periventricular leukomalacia. CONCLUSIONS: These data suggest that IL-1beta, IL-6 and TNF-alpha are produced in relation to intrauterine inflammation and infection, but cannot be directly implicated in the development of fetal cerebral white matter lesions.
Amniotic Fluid↗
Interleukin-6 levels in co-culture of human in vitro fertilization embryos with Vero cells are not predictive of future successful development.
PROBLEM: In an attempt to predict successful embryo transfer and implantation, we measured interleukin (IL)-6 levels in culture supernatants of co-cultured preimplantation human embryos. We tested whether all in vitro fertilized human embryos in co-cultures do secrete IL-6, and whether there was any difference in such production between embryos that successfully reached the blastocyst stage and blocked embryos. We also addressed the question of IL-6 secretion by co-culture support cells, namely Vero cells themselves. METHOD OF STUDY: Each fertilized oocyte was cultured individually and transferred in culture wells supplemented with a feeder layer of Vero cells at day 2. In vitro IL-6 production was measured by bioassay of the culture media. RESULTS: Because Vero cells themselves secrete IL-6, it became impossible, in co-culture, to quantify production of IL-6 by the sole embryos. On the other hand, the co-culture technique has shown us that embryos are likely to consume IL-6. There was no difference between blastocysts and blocked embryos. CONCLUSIONS: IL-6 levels in human embryo co-cultures do not correlate with future successful embryo transfer.
Adult↗
Pro-EPIL forms are present in amniotic fluid and maternal serum during normal pregnancy.
Recent observations based on immunohistochemistry and RT-PCR demonstrate that early placenta insulin-like peptide (EPIL), encoded by the INSL4 gene, is present in the placenta during gestation. In the present study, we report on the development of a specific immunoassay, entirely based on two monoclonal anti-peptide antibodies (mAbs), and its use for the detection of pro-EPIL forms in biological fluids during pregnancy. One mAb directed against the C-connecting peptide was used to capture pro-EPIL forms and their binding was revealed by a radiolabeled anti-A chain mAb as the indicator. A composite synthetic peptide, encompassing the C- and A-domains, was utilized as the standard. Under these experimental conditions, the assay displays a sensitivity limit of 2 ng/mL. Pro-EPIL molecular forms were detected in both amniotic fluid and maternal serum of pregnant women. At 12 to 16 weeks of pregnancy, the pro-EPIL level was higher in amniotic fluid (246 +/- 50.8 ng/mL) than in maternal serum (5 +/- 2.0 ng/mL). As gestation advanced, so the concentration of pro-EPIL forms decreased in amniotic fluid while its level increased in maternal serum. Interestingly, in amniotic fluid, the pattern of pro-EPIL concentration during pregnancy is very similar to that observed for human chorionic gonadotropin (hCG) and its free subunits. The pattern of serum pro-EPIL concentration is similar to that of the free alpha-subunit. Together with our previous immunohistochemical observations, these results indicate that pro-EPIL is preferentially secreted by cytotrophoblasts in amniotic fluid and that the biosynthesis of hCG subunits and EPIL may be regulated by common pathways. Overall, our observations strongly suggest that EPIL may play a critical physiological role during embryonic and foetal development.
Adult↗
Implication of apolipoprotein E and the L-arginine-nitric oxide system in preeclampsia.
OBJECTIVE: During pregnancy, Apolipoprotein (Apo) E is synthesized in the placenta to facilitate the uptake of maternal lipoproteins. Preeclampsia is associated with an abnormal lipid profile. Apo E levels may affect the production of nitric oxide. We investigated whether Apo E variations could be related to the high lipid levels and nitric oxide secretion in preeclamptic women. METHODS: Blood samples from 15 normotensive women and 12 mild and 23 severe cases of preeclampsia were assayed for standard lipid profile, Apo E, and nitrate. Urine samples were analyzed for nitrate and cyclic GMP. RESULTS: In women with mild preeclampsia, the triglyceride concentration was significantly higher (p < 0.05) than in normotensive women (3.30 +/- 1.38 versus 2.31 +/- 0.92 g/L) and associated with a higher (p < 0.01) triglyceride/Apo E ratio (0.71; range = 0.40-1.70). In women with severe preeclampsia, the triglyceride/Apo E ratio was similar to normotensive women [0.39 (range = 0.18-1.19) versus 0.41 (range = 0.18-0.79)] associated with a normal triglyceride level and a twofold higher serum nitrate level [36 (range = 1-63 mumol/L) versus 14 (range = 1-37 mumol/L)]. CONCLUSION: The triglyceride/Apo E ratio is significantly higher in mild preeclampsia. In the severe form, this ratio is similar to that of normotensive pregnant women, probably due to a better uptake of triglyceride. Moreover, in the severe form, it is associated with a twofold normal serum nitrate level. Thus, Apo E and the nitric oxide status may be implicated in preeclampsia.
Apolipoproteins E↗
Female and male human embryo growth rates are similar before the eight-cell stage.
OBJECTIVE: Our purpose was to assess the possible relationship between human embryo growth rates and sexual differentiation. STUDY DESIGN: We analyzed 142 conceptional in vitro fertilization and embryo transfer cycles undertaken in 137 women (151 embryos transferred) in which each embryo transferred led to a gestational sac. Embryos were sorted into three groups according to the number of blastomeres assessed just before embryo transfers < or = 3, 4, and > or = 5 blastomeres. RESULTS: Percentages of girls and boys remained roughly unaltered irrespective of the number of blastomeres observed just before embryo transfer: < or = 3 blastomeres, 45% and 55%; 4 blastomeres, 44% and 56%; and > or = 5 blastomeres, 45% and 55%, respectively (statistical power 90% at the 5% significance level). CONCLUSIONS: This indicates that embryo growth rates before the eight-cell stage are not related to the sex of the live-born infant, thereby dissuading the use of embryo growth rates in the appraisal of sex likelihood in regular in vitro fertilization-embryo transfer.
Blastomeres↗
Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome.
OBJECTIVE: To investigate whether the presence of cervical microorganisms, as detected on catheters used for ET, alters the outcome of IVF-ET. DESIGN: Prospective analysis. SETTING: The assisted reproduction unit of a hospital in Clamart, France. PATIENT(S): Two hundred seventy-nine controlled ovarian hyperstimulation (COH) cycles performed for IVF-ET. Inclusion criteria were a patient age of < or =38 years, a morphologically normal uterus, and > or =2 good-quality embryos transferred. INTERVENTION(S): The tips of catheters used for ruling out possible cervical obstruction before ET were subjected to quantitative (> or =10 colonies = positive culture group; <10 colonies = negative culture group) and qualitative microbial assessment. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): In 143 (51%) of 279 ETs, cultures were positive, predominantly for Escherichia coli (64%) and Streptococcus species (8%). Although data on patients, COH, and embryology were similar in both culture groups, clinical and ongoing pregnancy rates as well as implantation rates were significantly lower in the positive culture group than in the negative culture group (24% versus 37%; 17% versus 28%; and 9% versus 16%, respectively). CONCLUSION(S): The presence of microbial flora of the cervix on ET catheters is associated with poor IVF-ET outcome.
Adult↗
Management and outcome of triplet pregnancy.
The parameters involved in obstetrical follow-up of triplet pregnancies were evaluated in a retrospective study between 1975-1993 of the follow-up of 91 triplet pregnancies. During this long interval of time, many changes in management of triplets occurred. Considering these differences, two periods in the present study were compared: 1975-1986, which consists of a previously published retrospective analysis of 21 triplet pregnancies; and 1987-1993, during which the modalities of the 7-year follow-up described previously were applied to 70 triplet pregnancies. No improvement was observed between the two periods. Nineteen pregnancies were spontaneous. Thirty-seven allowed treatment with ovulation induction agents and 35 were due to in vitro Fertilization. Early diagnosis of multiple pregnancies allows installation measures for the prevention of prematurity. Management, initiated upon diagnosis, included home rest and a weekly follow-up at home by a midwife every week. Monthly consultations and ultrasounds were performed at the hospital. Hospitalization was not systematic but was done in cases of maternal complications. The mean term for the diagnosis of triplet pregnancy was 13.9 +/- 5.3 weeks. The mean gestational age was 33.4 weeks; 90% of the deliveries were by cesarean section. The mean weight of the neonates was 1716 g. The mean Apgar score at 1 and 5 m was 7.7 and 9.3, respectively. The perinatal mortality was 80 per 1000. The main neonatal complications resulted from prematurity. Authors compared rates of Hyaline Membrane Disease in infants of patients treated with corticosteroids and of patients who were not. Hyaline Membrane Disease occurred in 13% of the corticotherapy group and in 31% of the untreated group. The present study supports systematic corticotherapy between 28 and 34 weeks for triplet pregnancies.
Adult↗
Twin differences and similarities of birthweight and term in the French Romulus population.
This study was performed to examine the main characteristics of the French Romulus twin population: zygosity, chorionicity, sex, term and birthweight. A sample of 104 pairs of twins was distinguished by zygosity, chorionicity and sex, and divided into concordant and discordant birthweight groups. Fifty-three % (n = 55) of the fetus pairs studied were born at "ideal term" (35-38 weeks), and 25% (n = 26) were delivered at "preterm" (28-34 weeks). The very preterm (< 28 weeks), and "postterm" (> 38 weeks) represented altogether 22% (n = 23) of the sample. Of the 104 twin pairs, 68% (n = 71) differ by less than 15% in birthweight, and 32% (n = 33) have a birthweight difference higher than 15%. In dizygotic (DZ) pairs females had more tendency to be in the discordant group (p = 0.01) while in monochorionic-monozygotic (MC-MZ) pairs males were more discordant (p = 0.07). We found a significant interaction between sex and zygosity type (p = 0.02). Males had a birthweight difference significantly weaker than that of females in dichorionic-monozygotic (DC-MZ) and DZ twins whereas it was higher than that of females in MC-MZ twins. There were no MZ twin pairs with DC placentation over than 15% birthweight difference. Log linear analysis demonstrated a three-way interaction (p < 0.05) between term type, zygosity type and hypotrophy. Our data indicate that in the group of twins born between 35 and 38 weeks' gestation the crucial question still remains unsettled on how term and birthweight are related to zygotism and/or chorionicity.
Birth Weight↗
Randomized trial of conservative laparoscopic treatment and methotrexate administration in ectopic pregnancy and subsequent fertility.
Methotrexate treatment was compared to laparoscopic salpingotomy for conservative management of ectopic pregnancy in a prospective randomized study. One hundred patients were randomized into two groups using random numbers. Inclusion criteria were an ectopic pregnancy visualized by ultrasound with a pre-therapeutic score <13 as assessed by the following six criteria, graded from 1 to 3: gestational age, human chorionic gonadotrophin (HCG) concentration, progesterone concentration, abdominal pain, haemoperitoneal volume and diameter of the haematosalpinx. The treatments were either 1 mg/kg of methotrexate injected transvaginally into the ectopic pregnancy without anaesthesia or administered i.m. when the pregnancy could not safely or easily be punctured (group 1), or laparoscopic salpingotomy (group 2). Success was defined as the return to normal (<10 mIU/ml) of HCG concentrations. Treatment was successful for 45 of 51 patients in group 1 (88.2%) and 47 of 49 in group 2 (95.9%). Medical treatment was significantly (P < 0.05) associated with shorter postoperative stay (24 compared with 46 h), but HCG returned to normal more quickly after laparoscopic treatment (13 compared with 29 days). Spontaneous reproductive performance was similar in both groups, but overall intrauterine pregnancy was higher, and repeat ectopic pregnancy lower, after methotrexate treatment. In selected cases of ectopic pregnancy, with a pre-therapeutic score <13, methotrexate treatment appeared as safe and efficient as conservative treatment by laparoscopy and was associated with improved subsequent fertility.
Adolescent↗