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Biomedical subjects

R Frydman

Publications and source records attributed to R Frydman.

At least 55 records · Page 3Linked to original sources
PubMed2001

Human chorionic gonadotropin: does it affect human endometrial morphology in vivo?

Human chorionic gonadotropin (hCG) is widely used as a surrogate to luteinizing hormone (LH) to trigger ovulation in controlled ovarian hyperstimulation (COH). Yet this molecule may exert direct effects on the endometrium. These effects, not mediated by ovarian hormones, are probably a consequence of stimulation of endometrial hCG/LH receptors. Because the half-life of hCG differs markedly from that of LH, possible pharmacological effects of hCG on the endometrium could alter endometrial receptivity in COH. Arguments supporting a clinical action of gonadotropins, and hCG in particular, on the endometrium abound. Notably, evidence has been reported of decidualization of stromal cells of the human endometrium in vitro as a result of exposure to gonadotropins, including hCG. The present article discusses, from a clinical standpoint, the main basis supporting the hypothesis that hCG administration as commonly used in infertility treatments may exert direct effects in vivo on endometrial histology and partake in endometrial transformations of the luteal phase. Preliminary results suggest that endometrial effects of hCG exist in vivo and should be taken into account when assessing the endometrial effects of hormones.

Cells, Cultured↗
PubMed2001

Assisting reproduction of infertile men carrying a Robertsonian translocation.

BACKGROUND: In order to provide better genetic counselling for Robertsonian translocation carriers, the meiotic segregation of chromosomes 13, 14 and 21 from six infertile (13;14) and (14;21) Robertsonian translocation carriers was examined. METHODS: Dual-colour fluorescence in-situ hybridization analysis using locus-specific probes was carried out on spermatozoa of translocation carriers. Spermatozoa from six proven fertile subjects were analysed using the same probes as controls. RESULTS: We observed that the frequencies of unbalanced spermatozoa were similar in the (13;14) translocation carriers (9.0, 10.0 and 12.9%) and in the (14;21) translocation carriers (8.7, 7.2 and 7.0%). These frequencies were significantly increased compared with the control population (P < 0.05). CONCLUSIONS: This high frequency might justify the use of preimplantation genetic diagnosis in these patients where the translocation is usually associated with infertility, requiring intracytoplasmic sperm injection, as it might improve the outcome of the assisted reproduction technique.

Adult↗
PubMed2001

Uterine contractility decreases at the time of blastocyst transfers.

High-frequency uterine contractions at the time of non-cavitating embryo transfer influence adversely IVF-embryo transfer outcome. This prompted us to quantify prospectively the possible decline in uterine contraction frequency occurring during later stages of the luteal phase of ovarian stimulation, up to the time of blastocyst transfers, in 43 IVF-embryo transfer candidates. Contractility was assessed on the day of human chorionic gonadotrophin (HCG) administration, 4 days after HCG (non-cavitating embryo transfer; HCG + 4), and 7 days after HCG (blastocyst transfers; HCG + 7). For this, 2 min sagittal uterine scans were obtained by ultrasound and digitized with a computerized system for the assessment of uterine contraction frequency. Our results indicated that a slight, yet significant, decrease in uterine contraction frequency, observed from the day of HCG (4.4 +/- 0.2 contractions/min) to HCG + 4 (3.5 + 0.2 contractions/min), was followed by a more pronounced, additional decrease between HCG + 4 and HCG + 7 (1.5 +/- 0.2 contractions/min; P < 0.001). In conclusion, during the luteal phase of ovarian stimulation, uterine contractility decreases progressively, and reaches a nearly quiescent status 7 days after HCG administration, at the time of blastocyst transfers. It is possible that such a uterine relaxation assists blastocyst implantation.

Adult↗
PubMed2001

Hysteroscopic resection of submucosal myomas in patients with infertility.

BACKGROUND: Submucosal myomas are associated with infertility, and may be treated by hysteroscopic resection. Improvement of the menstrual pattern after surgery has been examined and compared with pregnancy rate in a group of menorrhagic women with primary (n = 24) and secondary (n = 35) infertility. METHODS: The entire patient group (n = 59) was managed between January 1990 and September 1998. The submucosal myomas were intracavitary (n = 15), intramural class 1 (n = 34) and intramural class 2 (n = 10), and none was multiple submucosal myoma. The mean (+/- SD) age was 36.6 +/- 4.6 years; mean myoma size was 24.5 +/- 13.3 mm; mean duration of the procedure was 40 +/- 23 min; and mean follow-up was 26 +/- 18.8 months. Thirty-five patients had one or more associated infertility factors. RESULTS: An improvement in clinical symptoms was observed in 62% of patients. Sixteen patients (27%) conceived, and of these only six (10%) delivered at term. The pregnancy rate was significantly better when myoma was the exclusive aetiology of infertility (41.6%), and when the lesion was >/=50 mm in size (57.1%). CONCLUSIONS: Hysteroscopic myomectomy appears safe, and is effective in the control of menstrual disorders. However, the effect on infertility seems limited, particularly in terms of delivery rate. The advanced age of the patients may partly explain these results.

Abortion, Spontaneous↗
PubMed2001

Circulating procoagulant microparticles in women with unexplained pregnancy loss: a new insight.

One of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss.

Abortion, Habitual↗
PubMed2001

[Impact of systematically freezing embryos on ovum donation].

In France, all embryos obtained after ovum donation have to be frozen. We present a brief background on this policy and expose our results, then discuss the rationale of such a policy in order to upgrade knowledge on the mechanism of vertical HIV transmission.

Cryopreservation↗
PubMed2001

[GnRH antagonists in IVF].

New GnRH antagonists are available in clinical practice. The different studies have confirmed the efficacy of these antagonists in preventing the LH surge. Two protocols have been described: in the multiple dose regimens, small doses of antagonist (0.25 mg) are injected starting on stimulation day 5 or 6 until hCG. In the single dose protocol, one injection of a larger dose (3 mg) is proposed in the late follicular phase. Local and general tolerance of the two compounds is very good. The results obtained with both regimens as compared with GnRH agonists in long protocols are showing a reduction in the stimulation length, in the consumption of gonadotrophins and in the incidence of the OHSS. The pregnancy rates are comparable in the good prognosis patients selected in the published studies. When the final tuning of these new protocols will be done, the advantages of GnRH antagonists in reducing the complications and side effects of ovarian stimulation will give to GnRH antagonists an important place in IVF.

Chorionic Gonadotropin↗
PubMed2001

[Contribution of diagnostic ultrasonography in cases of repeated embryonic implantation failure in fertilization in vitro].

INTRODUCTION: To assess ultrasonic data in the context of repeated failure of implantation in assisted reproduction medicine. MATERIALS AND METHODS: We reviewed ultrasonic data (uterine score at follicular and luteal phase). The same ultrasound exploration was repeated for two consecutive cycles to assess the changes in abnormalities observed and compare findings in 16 patients with repeated failure of implantation and in 14 controls. The controls were women who became pregnant within the three months following the exploration. We then introduced acetylsalicylic acid and prednisolone as first line treatment and nitroglycerin as second line treatment to measure the effects induced in 14 pathological uterine scores. RESULTS: The score obtained under hormonal treatment was representative of other cycles (r = 0.812, p < 0.0014). The score was significantly lower and the luteal uterine artery pulsatility index was significantly higher in the repeated failure group than in the control group (p < 0.0001 and p = 0.008 respectively). For the 14 patients, treatment improved the uterine score in 8 with acetylsalicylic acid and prednisolone and in 4 with nitroglycerin. Two patients did not respond to treatment. Concerning the effect of therapy, of 14 patients, 8 had an improved uterine score with A + P, and with T; 2 patients did not respond to any treatment. CONCLUSION: The uterine score and luteal artery pulsatility index may be valuable tools for patients with implantation failure who all do not respond to the same therapy.

Arteries↗
PubMed2000

First specific preimplantation genetic diagnosis for ornithine transcarbamylase deficiency.

Ornithine transcarbamylase (OTC) deficiency is an X-linked dominant metabolic disorder with partial penetrance in heterozygous females. Affected boys usually die from hyperammonemia in the first few days of life, while clinical expression in carrier females ranges from no symptoms to neonatal death. A young couple whose boy had died of OTC deficiency in the neonatal period was referred to our genetic department for their subsequent pregnancy. The fetus was found to be affected, and after genetic counseling the pregnancy was terminated. Prenatal diagnosis of the third pregnancy identified a heterozygous female, who died after a normal birth at age 11 days from hyperammonemia. After this, the couple asked for preimplantation genetic diagnosis (PGD). We have developed a duplex nested PCR assay allowing the amplification of both the mutation and an informative restriction fragment length polymorphism (RFLP) located in the 3' end of the OTC gene. After nested amplification, allele identification was carried out for both loci by double restriction digestion and electrophoresis gel analysis. The co-amplification of both loci provided a means of detecting potential allele dropout or incomplete digestion. Two PGD cycles were carried out, a total of 14 embryos were analysed and a diagnosis could be obtained in 13/14 embryos. There were four unaffected male embryos, four heterozygous females and four unaffected females; the final embryo was an affected one of undetermined gender. In both cycles, three unaffected embryos could be transferred early on Day 4 post-insemination. The second cycle resulted in the birth of a baby boy devoid of the OTC mutation. This constitutes the first birth following PGD carried out by a French team.

Base Sequence↗
PubMed2000

New look at endometrial echogenicity: objective computer-assisted measurements predict endometrial receptivity in in vitro fertilization-embryo transfer.

OBJECTIVE: To determine whether endometrial echogenicity, assessed objectively by a computer-assisted system on the day of hCG administration, predicts endometrial receptivity in controlled ovarian hyperstimulation (COH) cycles for IVF-ET. DESIGN: Prospective analysis. SETTING: Assisted reproduction unit, Clamart, France. PATIENT(S): Two hundred twenty-one women (aged <38 years with a normal uterus and >/=2 grade A or B embryos transferred) undergoing 228 GnRH agonist and FSH/hCG cycles for IVF-ET. INTERVENTION(S): On the day of hCG administration, uterine ultrasound scans were digitized with an image analysis system. Endometrial echogenicity was assessed as the ratio of the extent of the hyperechogenic transformation over the whole endometrial thickness. According to this, cycles were sorted arbitrarily into six groups: <30% (n = 34), 31%-40% (n = 37), 41%-50% (n = 37), 51%-60% (n = 55), 61%-70% (n = 37), and >70% (n = 28). MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): The groups were similar in regard to population characteristics, ovarian response to COH, and embryology data. Pregnancy rates (59%, 57%, 35%, 20%, 16%, and 11%, respectively) and implantation rates (35%, 23%, 17%, 6%, 7%, and 3%, respectively) fell progressively and significantly from the low-echogenicity group to the high-echogenicity group. CONCLUSION(S): The present results confirm and extend previous observations that advanced hyperechogenic transformation of the endometrium is associated with poor IVF-ET outcome.

Adult↗
PubMed2000

Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a single dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin).

OBJECTIVE: To confirm the value of a single dose of 3 mg of cetrorelix in preventing the occurrence of premature LH surges. DESIGN: Multicenter randomized, prospective study. SETTING: Reproductive medicine units. PATIENT(S): Infertile patients undergoing ovarian stimulation for IVF-ET. INTERVENTION(S): A single dose of 3 mg of cetrorelix (Cetrotide; ASTA Medica, Frankfurt, Germany) (115 patients) was administered in the late follicular phase. A depot preparation of triptorelin (Decapeptyl; Ipsen-Biotech, Paris, France) was chosen as a control agent (39 patients). Ovarian stimulation was conducted with hMG (Menogon; Ferring, Kiel, Germany). MAIN OUTCOME MEASURE(S): Premature LH surges (LH level >10 IU/L), progesterone level greater than 1 ng/L, and IVF results. RESULT(S): No LH surge occurred after cetrorelix administration. The patients in the cetrorelix group had a lower number of oocytes and embryos. The percentage of mature oocytes and fertilization rates were similar in both groups, and the pregnancy rates were not statistically different. The length of stimulation, number of hMG ampules administered, and occurrence of the ovarian hyperstimulation syndrome were lower in the cetrorelix group. Tolerance of cetrorelix was excellent. CONCLUSION(S): A cetrorelix single-dose protocol prevented LH surges in all patients studied. It compares favorably to the "long protocol" and could be a protocol of choice in IVF-ET.

Adult↗
PubMed2000

Human chorionic gonadotropin administration does not increase plasma androgen levels in patients undergoing controlled ovarian hyperstimulation.

OBJECTIVE: To investigate the effects of hCG administered to patients undergoing controlled ovarian hyperstimulation on levels of ovarian hormones, including androgens. DESIGN: Prospective analysis. SETTING: Assisted Reproduction Unit, Hôpital Antoine Béclère, Clamart, France. PATIENT(S): Six infertile, normally ovulating volunteers. INTERVENTION(S): The women underwent controlled ovarian hyperstimulation with a GnRH agonist and hMG for IVF-ET. After the i.m. administration of hCG (10,000 IU), blood samples were drawn every 6 hours for 4 days. MAIN OUTCOME MEASURE(S): Plasma androstenedione, testosterone, progesterone, and E2 profiles. RESULT(S): Treatment with hMG increased plasma androstenedione and testosterone levels 1.4-fold and 2.6-fold, respectively. The administration of hCG did not increase plasma androstenedione and testosterone levels any further; mean daily levels remained at 2.3 ng/mL and 0.64 ng/mL, respectively. Circadian changes in androstenedione levels were evident after hCG administration. Plasma progesterone levels neared 10 ng/mL 19 hours after hCG administration, plateaued for 24 hours, and increased again thereafter. Plasma E2 levels declined during the first 2 days after hCG administration and then increased, concomitant with the second phase of progesterone elevation. CONCLUSION(S): In patients undergoing controlled ovarian hyperstimulation, androgen levels increased in response to hMG treatment, but no further elevation occurred after hCG administration. The rate of elevation of progesterone levels and the absolute levels achieved were 3-fold and 10-fold higher, respectively, than those observed during spontaneous menstrual cycles.

Adult↗
PubMed2000

Fetal biometric parameters, twin type and birth weight difference. A longitudinal study.

OBJECTIVE: To examine the relationship between twin type, divided by zygosity, chorionicity, and birth weight difference [more or less than 15% intertwin weight difference at delivery] on fetal biometric measurements, including biparietal diameter, transverse abdominal diameter, head and abdominal circumferences (AC) and head and abdominal areas, femur length (FL), transverse cerebellar diameter, cerebellar circumference and cerebellar area at 18, 23, 28 and 32 weeks of gestational age. STUDY DESIGN: A prospective and longitudinal study was done on 75 twin pairs that did not present the twin-twin transfusion syndrome (150 fetuses) divided into birth weight difference group I (<15%) and group II (>/=15%). The twin pairs were divided into three groups: dizygotic, monochorionic, and dichorionic-monozygotic. In each group the differences in various ultrasound indices were evaluated in reference to discordant growth or concordant growth. RESULTS: In our sample, there were no monozygotic twin pairs with dichorionic placentation with a birth weight difference of more than 15%. Significant associations of group and gestational age were found in dizygotic and monochorionic twins. Intrapair differences were significantly higher in group II (>/=15%) than in group I (<15%) for all fetal parameters studied except for AC, abdominal area and all cerebellar parameters. The value of these discrepancies increased according to gestational age except for FL. Significant interactions between group and zygosity type indicated that intrapair FL differences were more associated with group in monochorionic twins, whereas intrapair transverse cerebellar diameter differences were more associated with group in dizygotic twins. CONCLUSION: Our data show that most fetal biometric parameters are associated with birth weight discordancy. Abdominal area could be a relevant marker for twins with obstetric complications. Note that this is the first research that has studied a twin sample divided by both twin type and birth weight group.

Biometry↗
PubMed2000

Functional, biochemical and molecular biological evidence for a possible beta(3)-adrenoceptor in human near-term myometrium.

The possible existence of a beta(3)-adrenoceptor (beta(3)-AR) in human near-term myometrium was investigated by in vitro functional and biochemical studies and analysis of mRNA expression. SR 59119A and SR 59104A and CGP 12177 (two selective agonists and a partial agonist, respectively, of the beta(3)-AR), salbutamol and terbutaline (beta(2)-AR agonists) each produced a concentration-dependent relaxation of the myometrial spontaneous contractions. There were no differences in pD(2) values for the relaxing potencies of terbutaline, salbutamol, CGP 12177 and SR 59119A. The rank order for their relaxing efficacies was SR 59119A>SR 59104A>terbutaline approximately salbutamol approximately CGP 12177 (E(max)=52+/-7%, 42+/-12% and approximately 30% respectively). Propranolol, a beta(1)- and beta(2)-AR antagonist, and ICI 118551, a beta(2)-AR antagonist (both at 0.1 microM), did not affect the SR 59119A-induced relaxation whereas SR 59230A, a selective beta(3)-AR antagonist (1 microM), significantly reduced the maximal relaxing effect of SR 59119A. SR 59119A and salbutamol induced a significant increase in cyclic AMP levels that was antagonized by SR 59230A but not by propranolol for SR 59119A, and by propranolol but not by SR 59230A for salbutamol. The beta(3)-AR mRNA was positively expressed in myometrium preparations in a reverse transcription polymerase chain assay. The results presented provide the first evidence for the existence of the beta(3)-AR subtype in human near-term myometrium and suggest that the effects of SR 59119A might be mediated through an increase in cyclic AMP level.

Adrenergic beta-Agonists↗
PubMed2000

Diagnosis of small-for-gestational-age fetuses between 24 and 32 weeks, based on standard sonographic measurements.

OBJECTIVE: To create and validate a formula using sonographic biometry measurements for the optimal diagnosis of small-for-gestational-age (SGA) fetuses between 24 and 32 weeks of gestation. METHODS: A logistic model using gestational age, femur diaphysis length, abdominal and head circumferences to diagnose SGA was set up in a first group of 64 fetuses born between 24 and 32 weeks (group I). A Receiver Operating Characteristic (ROC) curve was drawn. Our model was compared with standard single ultrasound measurements or combined into an estimated fetal weight (EFW) formula. An external validation was carried out on a second group of 183 fetuses (group II) from another maternity unit (ROC curve and comparisons). RESULTS: The area under the ROC curve was 0.91 in group I and 0.93 in group II. Using a 0.5 cut off point for our model yielded a sensitivity of 76% and specificity of 91% for group I. This model is more specific than most other measurement methods with a similar sensitivity. Using the same cut off point (0.5) in Group II, our model was more specific (98%) but less sensitive (66%) when compared with single ultrasound measurements and EFW formulae. By varying the cut off point, we were able to demonstrate that, for a similar sensitivity, our model had a higher specificity than single ultrasound measurements and had similar specificity to EFW formulae. CONCLUSION: The logistic model we set up was able to calculate an SGA risk score between 24 and 32 weeks of gestation in a population at high risk for elective delivery. The cut off point with a view to diagnosis can vary and makes it possible to give greater importance to the sensitivity or specificity depending on the clinical context.

Abdomen↗