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R Frydman

Publications and source records attributed to R Frydman.

At least 199 records · Page 11Linked to original sources

[In vitro modulation of the production of the cytokine HILDA/LIF, secreted by human endometrial explants: preliminary results].

Human endometrium from fertile women secrete HILDA/LIF in vitro. In endometrial explants from women suffering from an unexplained sterility or women whose fertilized eggs do not implant the in vitro secretion is significantly reduced. HILDA/LIF secretion is increased by IL-1 and decreased by IL-4. CSF-1 has little effects on secretion from fertile women but clearly inhibits secretion from some infertile women. Altogether, the results suggest that HILDA/LIF might be involved in human implantation.

Adult↗

Scheduled administration of a gonadotrophin-releasing hormone antagonist (Cetrorelix) on day 8 of in-vitro fertilization cycles: a pilot study.

To assess in a pilot study the ability of a single injection of a GnRH antagonist (Cetrorelix) to prevent premature luteinizing hormone (LH) surges in an in-vitro fertilization (IVF) embryo transfer programme when administered on a fixed day in the late follicular phase, ovarian stimulation was carried out in 11 women with two ampoules of human menopausal gonadotrophin per day beginning on day 2 of the menstrual cycle. A 3 mg dose of Cetrorelix was administered on day 8 of the stimulation cycle. A second injection was administered 72 h later if ovulation was not triggered in the meantime. We did not observe a premature LH surge in any of the cycles studied. The injection of 3 mg Cetrorelix was capable of preventing LH surge in all the patients studied, introducing a very simple treatment protocol. Among the patients who received two injections (n = 3), the day of the first administration was delayed in two subjects due to slow follicular maturation kinetics. Out of 11 patients, 10 had an embryo transfer. Four clinical pregnancies were obtained (40% per embryo transfer), of which 3 are ongoing (30% per embryo transfer). A simple administration protocol for a new GnRH antagonist (Cetrorelix) was able to prevent LH surges in the 11 patients studied.

Adult↗

[The discovery of a fertilizing substance in the air].

A fecondant substance has been recently isolated in the air. The discovery was made by observing that fertile couples loose their fertility when they are placed in a room where infertile couples had breathed. A major difference was observed in the respiration of infertile couples. They first inspire and then expire, contrary to the fertile couples who do the opposite. The ethical and pathophysiopolitical considerations are discussed. Emergency management in case of side effects observed with the use of the fecondant substance is described. This is the first description of a new aerial major compounds involved in human fertility.

Air↗

Ultrasound-guided injection of methotrexate versus laparoscopic salpingotomy in ectopic pregnancy.

OBJECTIVE: To compare local injection of methotrexate (MTX) under sonographic control to laparoscopic salpingotomy for conservative management of ectopic pregnancy (EP). DESIGN: Prospective randomized study. PATIENTS: Forty patients were randomized into two groups using a random number table. Inclusion criteria were an EP visualized by ultrasound with a pretherapeutic score < or = 13 as assessed by six criteria graded from 1 to 3: gestational age, hCG level, P level, abdominal pain, volume of the hemoperitoneum, and diameter of the hematosalpinx. INTERVENTIONS: Group 1 patients injected transvaginally with 1 mg/kg MTX into the EP without anesthesia versus group 2 patients undergoing laparoscopic salpingotomy. MAIN OUTCOME MEASURES: Postoperative hospital stay, decrease of hCG levels, success rate. RESULTS: The success rates, defined by hCG levels returned to normal (< 10 mIU/mL [conversion factor to SI units, 1.00]), were 19 of 20 in both groups. Medical treatment was associated significantly with shorter postoperative stay (24 versus 46 hours) and a higher initial hCG level. Human chorionic gonadotropin returned to normal more quickly after laparoscopic treatment (14 versus 28 days). CONCLUSIONS: In selected cases of EP with a pretherapeutic score < or = 13, MTX treatment appeared to be as safe and efficient as was conservative treatment by laparoscopy.

Adult↗

[The value of coculture in fertilization in vitro].

Coculture techniques on monolayers cells increase the rate of human blastocysts development. The selection of these heavier and more expensive methods should be reserved for cases which this work specifies. The rate of achieved pregnancies seems increased, embryo quality being, at this stage of later development, better estimated, from which a more objective selection. The window of endometrial receptivity to blastocysts implantation seems later than the one defined by the 2/8 cells stage. Last but not least, the cryopreservation of high quality blastocysts favours a high rate of recovery on defreezing.

Adult↗

[Prenatal diagnosis of fetal varicella in the second trimester of pregnancy].

The first case of prenatal diagnosis of congenital varicella by amniotic fluid viral culture and PCR is reported. Chickenpox is a benign disease in children, but it can lead to severe complications in the adult, especially in the pregnant woman. Five percent of women in childbearing age are not immunised, and the incidence of gestational chickenpox is between 1 and 7 per 10,000. The consequences of this primary infection during pregnancy can be severe for the mother, because of the risk of serious varicella pneumonia, and for the fetus. The fetal infection depends on the gestational age at which the maternal infection occurs. The 2% evaluated risk of fetopathy is maximal between the 7th and 20th week of amenorrhoea. The reported congenital abnormalities are essentially cutaneous, neurological, ophthalmological and musculo-squeletal lesions. A prenatal diagnosis can be suggested: the revelation of defects by ultrasound scan confirms the fetal affection, and can justify pregnancy termination; on the other hand, amniocentesis and cordocentesis are not totally safe, and cannot always assert the fetal contamination or its level of affection. From the therapeutical point of view, prevention with polyvalent gamma-globulin is prescribed to non-immunised pregnant women who have been in contact with the virus. On the opposite, in case of contracted chickenpox, the treatment of the mother with an association of polyvalent gamma-globulin and acyclovir is still controversial since, although probably effective, it may not be safe for the fetus. The solution may reside in the vaccination, soon available, of non-immunised women in childbearing age.

Acyclovir↗

[Results, evolution of assisted reproduction techniques].

During the last decade IVF and other assisted conception treatment (ACT) methods have become an internationally accepted form of treatment of infertile couple. The final definition of success following ACT is the couple who having received treatment have a live child. As IVF treatment gradually becomes more successful and as the number of babies born as a result of this treatment increases more attention is being focused on the outcome of ACT pregnancies. Recent and futur development of ACT are related.

Female↗

A single injection of a gonadotropin-releasing hormone (GnRH) antagonist (Cetrorelix) postpones the luteinizing hormone (LH) surge: further evidence for the role of GnRH during the LH surge.

OBJECTIVES: To assess the ability of a new third-generation GnRH antagonist, Cetrorelix (Asta Medica AG, Frankfurt am Main, Germany), to postpone the LH surge after a single injection during the late follicular phase. DESIGN: A single 5-mg (group 1, n = 7) or 3-mg (group 2, n = 3) dose SC of Cetrorelix was administered during the late follicular phase, on the day of the cycle when plasma E2 exceeded 150 pg/mL (550 pmol/L). Estradiol, LH, FSH, and P levels were measured daily from day 5 of the cycle until day 10 after antagonist administration. Transvaginal ultrasonographies were performed on the day of injection and after antagonist treatment. SUBJECTS: Ten normal women with regular ovulatory menstrual cycles. RESULTS: In group 1, Cetrorelix was administered on day 14.6 +/- 5 (mean +/- SD) of the cycle, when the mean plasma E2 level was 181 +/- 32 pg/mL (664 +/- 117 pmol/L) (mean +/- SD). Plasma LH and FSH decreased by 56% +/- 19% and 29.5% +/- 16% (mean +/- SD), respectively, reaching the nadir 24 hours after Cetrorelix administration. Estradiol decreased by 85% +/- 17%, reaching the nadir 48 hours after antagonist injection. In group 2, Cetrorelix was administered on day 14.3 +/- 1.2 of the cycle when the mean plasma E2 level was 169 +/- 21 pg/mL (618 +/- 77 pmol/L). Plasma LH and FSH decreased by 66% +/- 18% and 32% +/- 6%, respectively, reaching a nadir 24 hours after Cetrorelix administration. Estradiol decreased by 81% +/- 9%, reaching the nadir 24 to 48 hours after antagonist administration. The LH surge was interrupted in every case. In six of seven subjects from group 1, the LH surge was delayed, occurring 6 to 17 days after the antagonist injection. In the remaining woman, Cetrorelix was administered at the beginning of the LH surge (LH = 13 IU/L): the LH level fell immediately by 54%, and the surge was postponed by 3 days. In group 2, in three of three subjects, the LH surge was delayed, occurring 6 to 9 days after the antagonist injection. No adverse effects were observed, except for very slight and transient erythema and pruritus at the injection site. CONCLUSION: Cetrorelix is a very potent new GnRH antagonist. A single injection during the late follicular phase delays the LH surge, even if the latter has already begun. In addition, this new-generation GnRH antagonist is very well tolerated and simple to use. Our data reinforce the role of GnRH during the LH surge and point to a role for new GnRH antagonists in controlled ovarian hyperstimulation to avoid premature LH surges and subsequent luteinization.

Adult↗

The single or dual administration of the gonadotropin-releasing hormone antagonist Cetrorelix in an in vitro fertilization-embryo transfer program.

OBJECTIVE: To assess the ability of a GnRH antagonist (Cetrorelix, Asta Medica AG, Frankfurt, Germany) to prevent premature LH surges in an IVF-ET program using a simple protocol with one or two administrations. DESIGN: Controlled ovarian hyperstimulation was carried out in 17 women with three ampules a day of hMG, starting on day 2 of the menstrual cycle. A dose of 5 mg of Cetrorelix was administered when plasma E2 levels were between 150 and 200 pg/mL (conversion factor to Sl unit, 3.671) per follicle of > or = 14 mm. A second injection was performed 48 hours later if the triggering of ovulation was not decided in the meantime. RESULTS: Six patients received one injection and 11 patients received two administrations. Plasma LH levels showed a marked decrease and remained low after the administration of the GnRH antagonist. In six patients, the first administration of Cetrorelix was performed when a significant rise in LH plasma level was present. Even in these patients the GnRH antagonist was able to prevent an LH surge. The tolerance of the product was good. Six clinical pregnancies were obtained, of which four are ongoing (25% per ET). Two ongoing pregnancies were obtained after the transfer of a frozen-thawed embryo (35.3% per retrieval). CONCLUSIONS: The GnRH antagonist Cetrorelix in a simple, unique or dual administration, protocol was able to prevent premature LH surge in all of the 17 patients studied. If these results are confirmed by larger, randomized studies, the good tolerance and efficacy that we observed suggest a bright future for this product is assisted reproductive technologies.

Adult↗

Treatment of unruptured tubal pregnancy with methotrexate: pharmacokinetic analysis of local versus intramuscular administration.

OBJECTIVE: To determine the optimal dose and route of methotrexate (MTX) in the treatment of ectopic pregnancy (EP). DESIGN: Prospective randomized study. SETTING: Department of Obstetrics and Gynecology (A. Béclère Public Hospital, Clamart, France, Paris-Sud University). PATIENTS AND METHODS: Forty-eight patients with unruptured EP clearly visualized by ultrasound were randomly allocated into four groups of treatment (12 patients in each group): group 1, 1 mg/kg injected locally in the ectopic gestational sac and 1 mg/kg by IM administration 48 hours later; group 2, 1 mg/kg locally; group 3, 0.5 mg/kg locally; group 4, 1 mg/kg by IM administration. Inclusion criteria used a pretherapeutic score < or = 12. Blood samples were collected at time 0.25, 0.5, 1, 2, 6, 12, 24, 36, and 48 hours after MTX administration. Pharmacokinetics of MTX plasma levels were measured by fluorescence polarization immunoassay. Kinetic parameters were compared by Wilcoxon test and Mann-Whitney test. Plasma hCG concentrations were assessed on days 2, 5, and 10 and then weekly until they returned to undetectable levels. RESULTS: Success rate was 12 of 12, 11 of 12, 10 of 12, and 10 of 12 in groups 1, 2, 3, and 4, respectively. Six patients in group 3 required an additional MTX IM injection because of an inadequate decrease of hCG plasma levels. Five patients underwent surgery for abdominal pain or inadequate decrease of hCG. Area under the curve decreased more rapidly after injection in the gestational sac alone than after IM injection and was similar in groups 1 and 2 after local injection and lower in group 3. Terminal half-life and mean residence time remained similar in the four groups. Systemic side effects of MTX therapy occurred in three cases in groups 1 and 4. The regression curve of hCG plasma levels appeared similar in the four groups with a decrease to pretreatment values between days 6 and 8 after an initial rise after MTX was given. CONCLUSION: Area under the curve found after injection in the ectopic sac may be related to a decrease in bioavailability of MTX that links to trophoblastic cells. Patients in group 3 were clearly undertreated by 0.5 mg/kg MTX and required additional therapy. Residual values of MTX plasma levels were always below the limit of detection of our assay and confirmed that citrovarum factor rescue is unnecessary. Injection of 1 mg/kg of MTX in the ectopic sac appears as effective as systemic (IM) injection with less side effects for the patients.

Chorionic Gonadotropin↗

Four indications for embryo transfer at the blastocyst stage.

The transfer of blastocysts obtained by co-culture with 'Vero' (African green monkey kidney) cells was offered to infertile couples with the following indications: (i) repeated failure of implantation, (ii) patients in whom multiple pregnancies had to be avoided (malformed uterus or risk of descending uterus), (iii) patients where embryo development potential had to be assessed, and (iv) replacement of supernumerary embryos frozen at the blastocyst stage. In the 142 cycles analysed, the pregnancy rates per transfer were 37.2, 36.3, 13.0 and 13.6% respectively for the couples with indications i-iv. The respective implantation rates per blastocyst were 20.0, 16.7, 7.1 and 9.3%. In patients in whom multiple pregnancies had to be avoided, the transfer of a maximum of two blastocysts gave a pregnancy rate per cycle of 23.5%, without any multiple pregnancies. The freezing of supernumerary embryos at the blastocyst stage allowed us to replace them using simple protocols and to avoid cancellation of the transfer cycles. Embryo co-culture has been found to be an interesting technique for selected indications, making available a good number of blastocysts for transfer. The transfer of blastocysts allowed us to reduce the number of embryos transferred per patient and therefore also reduce the rate of multiple pregnancies (there were no triplet pregnancies in this study). These results need to be confirmed by larger, randomized studies with comparisons to control groups to evaluate the effectiveness of blastocyst transfers.

Adult↗

Psychological follow-up of children born after in-vitro fertilization.

We have studied from birth up to the 3rd year the psychological attitude of 33 in-vitro fertilization (IVF) children compared to two other groups: children born after ovarian stimulation without IVF (n = 33) and children conceived naturally (n = 33) during the same period. Fourteen children, born by oocyte donation, were also studied by the same methodology. In the IVF group, we found some feeding difficulties and sleep disorders in the infants at 9 months and some signs of depression in mothers. All these symptoms disappeared afterwards. The development of all the children is satisfactory and the relationship with their mother is excellent. In this preliminary study, we conclude that the method of assisted reproduction has no bad influence on the psychomotor development of these children.

Attitude↗

Exogenous follicle stimulating hormone ovarian reserve test (EFORT): a simple and reliable screening test for detecting 'poor responders' in in-vitro fertilization.

Predicting ovarian response to stimulation constitutes a pivotal task in the organization of a successful in-vitro fertilization (IVF) programme. The purpose of the current study was to determine whether a new ovarian reserve test, the exogenous follicle stimulating hormone ovarian reserve test (EFORT), could improve the predictive value of the classical follicle stimulating hormone (FSH) measurements on cycle day 3 of ovarian stimulation regarding results of IVF. In this prospective study, 52 IVF candidates aged 27-42 years underwent 52 consecutive IVF cycles. These women received 300 IU of purified FSH i.m. on cycle day 3. Blood samples were taken just before the injection to measure plasma FSH and oestradiol; 24 h later, plasma oestradiol concentration was determined. Two menstrual cycles later, ovarian stimulation was performed for IVF using a time-release gonadotrophin-releasing hormone agonist (GnRHa) and human menopausal gonadotrophin (HMG). For the interpretation of the EFORT results, we considered the post-FSH plasma oestradiol increment (delta E2) and the baseline plasma FSH values (bFSH). The results of these two parameters were compared with the subsequent quality of the ovarian response to stimulation for IVF and the pregnancy outcome. Our results indicated a statistically significant improvement of the predictive value of the bFSH on the ovarian stimulation outcome when the EFORT parameters (bFSH and delta E2) were analysed synergistically.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Mifepristone for labour induction after previous caesarean section.

OBJECTIVE: To evaluate the efficacy and tolerance of mifepristone in women undergoing induction of labour at term after previous caesarean section. DESIGN: A prospective double blind placebo controlled trial. SUBJECTS: Thirty-two women at term (after 37.5 weeks' amenorrhea) who had had a previous caesarean delivery with a low transverse uterine incision. All women had a clear clinical indication for induction of labour with unfavourable cervical conditions (Bishop's score < 4). They were randomised to receive either 200 mg of mifepristone or placebo on days one and two of a four-day observation period. RESULTS: Thirteen women entered spontaneous labour: 11 were treated with mifepristone and two were in the control group (P < 0.01). Thirteen women, still with an unfavourable cervix on day four needed cervical ripening with vaginal tablets of prostaglandins. Of these, four had received mifepristone and nine the placebo. Mean oxytocin requirements were lower in the mifepristone group (P < 0.01) and the mean time interval between day one and start of labour was also significantly shorter in this group. Mode of delivery and neonatal outcome were similar in both groups. CONCLUSIONS: Induction of labour is facilitated in term women with prior caesarean section by the use of mifepristone. This induction agent appears safe and useful with no adverse events on the fetus or mother.

Adult↗

Flecainide distribution, transplacental passage, and accumulation in the amniotic fluid during the third trimester of pregnancy.

OBJECTIVE: To study the disposition of flecainide acetate and its transplacental passage (both into the fetus and in the amniotic fluid) during the third trimester of pregnancy. DATA SOURCES: Reference articles and books are identified in the text. A literature review is presented. CASE SUMMARY: Flecainide distribution, transplacental passage, and accumulation into the amniotic fluid were studied in a patient at term presenting with a fetal supraventricular tachycardia diagnosed at 33 4/7 weeks of gestation. The fetal tachycardia was accompanied by cardiac failure with placental anasarca and hydramnios. Flecainide 100 mg po bid was prescribed initially; by the time of delivery, the dosage had been decreased to 50 mg bid. At delivery day (39 5/7 weeks), the pharmacokinetics of total flecainide were studied at plateau. DATA SYNTHESIS: The concentrations of flecainide at birth in fetal and maternal blood and in amniotic fluid were 235.4, 241.2, and 6426.5 micrograms/L, respectively. Calculation of a fetomaternal blood accumulation ratio of 0.97 showed that, at this gestational age, flecainide penetrates the placental membrane easily without accumulation in fetal blood. In contrast, the concentration of flecainide in amniotic fluid was approximately 27-fold that measured in maternal peripheral blood. Our results suggest the following: (1) close to term, the metabolic clearance (fetal hepatic clearance) of flecainide offers a high yield and its excretion by the fetal kidney is efficient; (2) given that amniotic fluid is constantly swallowed, it seems that, in contrast to what is seen in adults (relative oral bioavailability > or = 95 percent), the oral bioavailability of flecainide is possibly low in the fetus at term or close to term; under such circumstances, the drug would accumulate passively within the gestational sac; and (3) an alternative explanation is that the concentration in the fetus is, in part, the result of both transplacental crossing of the drug and reabsorption orally from the amniotic fluid. CONCLUSIONS: The regular therapeutic monitoring of flecainide is necessary and sufficient in the mother as the concentrations found appear to accurately reflect the degree of fetal accumulation. Because previous studies in infants and children have indicated few toxic adverse effects attributed to flecainide, it appears that the risk to a sucking infant of ingesting toxic amounts of flecainide in human breast milk is very low. Finally, the child of the patient described here has normal initial growth and development at the present time. The transplacental penetration of a drug can be considered, according to gestational age and the disorder being treated, as being of no consequence, dangerous, or desirable. Flecainide appears to fall into this last category.

Adult↗