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Biomedical subjects

R Frydman

Publications and source records attributed to R Frydman.

At least 37 records · Page 2Linked to original sources
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Full-term pregnancy with embryos from donated oocytes in a 36-year-old woman allografted for chronic myeloid leukemia.

We report the first case of full-term pregnancy arising from donated oocytes in a 36-year-old woman with chronic myeloid leukemia (CML), 6 years after allogeneic bone marrow transplantation (BMT) following total body irradiation (TBI) (12 Gy) and cyclophosphamide 120 mg/kg. The first attempt at implantation with her own cryopreserved ovocytes was unsuccessful. Thereafter, she became pregnant after donated oocyte implantation using estradiol and progesterone support replacing the defective ovarian function. The baby was normal. Unfortunately, 6 months later, she relapsed in chronic phase of CML.

Adult↗
PubMed1994

[Oncologic application of oocyte donation].

Antimitotic chemotherapy and/or radiation therapy can induce a premature ovarian failure in women. The improvement of the prognosis of cancer and the increasing in long-term survival mean that preservation of fertility should be considered before initiating therapy. An embryo cryopreservation can be proposed if the circumstances allow that possibility. Ten young women were included in our program and benefited from an oocyte retrieval before cancer therapy. Nine of them had an embryo cryopreservation, and one without partner an oocyte cryopreservation. Three patients had an embryo replacement without success, and in one case, a spontaneous full-term pregnancy was obtained after ovarian detransposition through coelioscopy. In the future, oocyte cryopreservation could appear a more suitable answer. Actually, oocyte donation with estrogen and progesterone replacement therapy gives good results (in our experience, 23.2 per cent of ongoing pregnancies per transfer). Nevertheless, after treatment against cancer, a study of the uterus with its arteries, and a particular adaptation of the treatment are necessary because of the risks of tissue damage impairing the embryo implantation. Indeed, in fifteen patients included in this group, eight women had fourteen transfers unfortunately without success. Consequently, the seven other women underwent complementary examinations. Two embryos were replaced in one patient with a more adjustable treatment allowing a full-term pregnancy.

Adult↗
PubMed1994

[Value of cryopreservation of human embryos during the blastocyst stage].

The recent development of co-culture technique has permitted to cryopreserve human embryos at the blastocyst stage. The aim of the present study was to compare pregnancy rates after transfers of embryos frozen at an early embryo stage (2-8 cell stage, group A; n = 175) with others frozen at blastocyst stage (group B; n = 98). Our results demonstrated that the frozen/thawed blastocyst survival is approximately 100%. In comparison the early embryos survival rate was 59% (P < 0.05). Moreover, pregnancy rates/embryo transfer in group A (16.4%) were significantly improved by comparison to those observed with early embryos (6.2%) (P < 0.05). In conclusion, our results demonstrate that embryo frozen/thawed at the blastocyst stage can be useful for improving pregnancy rates after cryopreservation.

Blastocyst↗
PubMed1994

[Conservative management of extra-uterine pregnancy].

Expectant management was studied in 35 patients representing 4.9% of all ectopic pregnancies during an 8 year period. Laparoscopy was performed in a first period to define the inclusion criteria: hematosalpinx < or = 2 cm and hemoperitoneum < or = 50 ml. In a second period, inclusion criteria used a predictive pretherapeutic score < or = 11 with a sonographic visualization of the ectopic pregnancy. This score involved six criteria graded on a scale from 1 to 3: gestational age, hCG and P level, existence of abdominal pain, size of hemoperitoneum and diameter of hematosalpinx assessed sonographically. The patients were on out-patients basis. Success rate was 85.7% (30/35 patients). When the pretherapeutic score was < or = 11 and the initial hCG level < 1,000 mUl/ml the success rate increased to 96%. Thirteen patients (87%) had patent tubes evaluated by hysterosalpingography on the side of the ectopic pregnancy. Twelve patients delivered one miscarriage occurred and none ectopic pregnancy was observed. Expectant management is a useful form of treatment for ectopic pregnancy in selected cases.

Abdominal Pain↗
PubMed1993

[Oocyte donors. Psychological aspects].

This study concerns 63 oocyte donors who were investigated after a semi-directed interview. In our procedure all "personalized anonymity" donation took place on two levels: symbolic donation for close recipient, real donation for unknown recipient. All donors agree with anonymity without which some would not have preceded. Narcissic weakness often linked with recent trauma (death...) is often seen in patients who do not achieve the gift. Oblativity and happy motherhood are the most important reasons for oocyte gift.

Adaptation, Psychological↗
PubMed1993

[Embryo expulsion induction in first trimester miscarriages. Use of mifepristone (RU 486) in a double blind prospective randomized study].

UNLABELLED: We investigated the use of oral mifepristone (RU486) for the induction of natural expulsion in women with spontaneously interrupted pregnancy in the first trimester in a double blind placebo controlled study against placebo. 46 women consulting for interrupted pregnancy diagnosed at ultrasound with no clinical sign of miscarriage were included in the trial. Main outcome measures were occurrence of natural expulsion, frequency of complete expulsion need for subsequent surgical evacuation, analgesia and need for transfusion. Natural expulsion occurred within 5 days in 82% patients receiving treatment versus 8% placebo treated patients (p < 0.001). All patients experienced bleeding after RU486 and 2 needed emergency aspiration for haemorrhagic expulsion. The treatment failed in 4 patients who underwent evacuation under local anesthesia. In the control group 19 patients underwent evacuation under local (n = 9) or general (n = 11) anesthesia. CONCLUSION: A standard oral pilot dose of 600 mg of Mifepristone induces natural expulsion in 82% women with non developing first trimester intra-uterine pregnancies.

Abortion, Incomplete↗
PubMed1993

[Must we still operate on ectopic pregnancies?].

Non surgical management of ectopic pregnancy has recently become an alternative to surgery. We have investigated a pretherapeutic score to define the indication for non-surgical and surgical treatment in 123 patients with ectopic pregnancy. The score was performed before the patients' inclusion in a non-surgical management scheme. The score used six criteria which were evaluated on a scale from 1 to 3: gestational age, human chorionic gonadotrophin (hCG) level, progesterone level, abdominal pain, haemoperitoneum volume and haematosalpinx diameter (estimated by laparoscopy or transvaginal ultrasound). Three scores, 10, 11 and 12 were studied in order to define a threshold beyond which surgical treatment should be performed. For each one, sensitivity, specificity and positive and negative predictive values were analysed. The success rate of non-surgical treatment was 82.1% (101/123). For patients undergoing medical treatment with a score < or = 12, the success rate was significantly higher compared with a success rate of 56% when the score was > 12. We conclude that a score < or = 12 permits non-surgical management with a success rate of 87%. A score > 12 indicates that laparoscopic surgery may be more suitable. The choice between different non-surgical approaches, did not influence the success rate. When ultrasound reveals embryo heart activity, medical treatment is always possible if the score is < or = 12.

Chorionic Gonadotropin↗
PubMed1993

[Value in gynecology of transvaginal pulsed and color Doppler. Study of ovarian vascularization].

Recently, pulsed Doppler has become available on high resolution vaginal ultrasound probes for studying ovarian blood flow. Doppler studies of ovarian blood flow are based on: semiquantitative analysis of Doppler flow waves recorded over the ovarian artery at its entry into the ovary; color Doppler mapping of intraovarian vessels. Semiquantitative analysis of the ovarian artery Doppler flow waves suffers from frequent difficulties at properly identifying the ovarian artery, particularly in multiparous women. Mapping of intraovarian vessels however, appears a most promising feature of vaginal Doppler for studying ovarian blood flow, provided that the proper ultrasound equipment is used. Specifically, transvaginal color Doppler mapping of intraovarian vessels allows for a positive visual detection of the onset of the ovulatory process prior to the actual follicular rupture. Thus, color Doppler mapping of ovarian vessels permits an improved and simplified approach for timing intercourses and inseminations in infertility patients. In controlled ovarian hyperstimulation (COH) used for in vitro fertilization (IVF), mapping of intraovarian vessels by color Doppler offers a fascinating new insight into normal and pathological responses of ovarian follicles to hCG. Finely, color Doppler appears a very promising asset to transvaginal ultrasounds for sorting suspicious ovarian cysts from their benign counter parts. In conclusion, we think that vaginal Doppler should be considered as a marvelous refinement of ultrasounds rather than as a truly new diagnostic tool. Yet vaginal color Doppler carries the potential for markedly improving the sensitivity and the specificity of vaginal ultrasound, particularly for diagnosing benign from potentially malignant ovarian conditions.

Arteries↗
PubMed1993

[Value of microfertilization for repeated in vitro fertilization failures: the role of female parameters].

UNLABELLED: Microfertilization technics as SUZI (sub-zonal insemination) can be indicated in cases of repeated in vitro fertilization (IVF) failure. Feminine parameters seem to play however an important role in optimalization of results. We studied 27 couples (32 IVF-SUZI cycles) who had previously presented 2 to 4 in vitro fertilization failures. These 32 cycles were divided in 2 groups according to women's age: group A < or = 35 and group B > 35 years. RESULTS: basal FSH levels were higher in group B (6.6 +/- 3.1 mIU/ml) in comparison to group A (3.7 +/- 1.5 mIU/ml). The amount of hMG necessary to accomplish ovarian stimulation was also higher in group B (39 +/- 21 ampules) than in group A (26 +/- 11 ampules). Maximal plasma estradiol levels were higher in group A (2,775 +/- 872 pg/ml) than in group B (1,824 +/- 559 pg/ml) such as the mean number of oocytes collected and micro-injected: 11.6 +/- 4.5 versus 4.7 +/- 2.2 in groups A and B, respectively. Eight pregnancies (44%), of which 7 were ongoing pregnancies, were obtained in group A. No pregnancy was obtained in group B. CONCLUSIONS: SUZI seems to be an available technic for treatment of repeated IVF failures; our results seem to indicate a decrease in SUZI results with age of the women (> 35 years old); they suggest the opportunity of a complete investigation of feminine parameters prior to each SUZI-IVF cycle.

Estradiol↗
PubMed1993

[Estradiol and progesterone physiological substitution effects on the hemodynamics of the humeral artery in women with inactive ovaries].

To determine the effects of female hormones on peripheral vasculature we studied the brachial artery circulation. Nine young women (27-37 yrs) having inactive ovaries received transdermal estradiol (E2) (0.1-0.4 mg/d) and vaginal progesterone (P) (300 mg/d) to duplicate the menstrual cycle levels of E2 and P. Brachial artery diameter, blood velocity and flow were measured by bidimensional pulsed Doppler in basal conditions, and during hand exclusion by a cuff inflated at suprasystolic pressure. Vascular resistance was calculated by the ratio of mean blood pressure over mean flow. Measurements were obtained before hormonotherapy (d0), on day 14 (d14, after E2), and on day 28 (d28, after E2 and P). The increase of brachial artery diameter began at d14 (3.73 +/- 0.12 mm, vs 3.66 +/- 0.11 mm; NS) to become significant at d28 (3.91 +/- 0.10 mm, p < 0.05). Blood velocity and flow increased at d28 (4.78 +/- 0.55 cm/s, vs 3.55 +/- 0.65 cm/s; P < 0.05 and 35.2 +/- 5.2 ml/mn vs 22.2 +/- 3.6 ml/mn, P < 0.05 respectively). No change was noted in mean blood pressure. The decrease of resistance began at d14, in order to be significant at d28 (158 +/- 17 mmHg/ml/s at d0 vs 263 +/- 31 mmHg/ml/s at d28; P < 0.05). Brachial vasoconstriction during hand exclusion, in response to low flow state disappeared at d14 with estradiol. In conclusion, in women deprived of ovarian function, physiological E2 and P replacement vasodilates small and large arteries, whereas E2 alone attenuates the large artery vasoconstriction in acute response to low flow state.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗