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Biomedical subjects

A Hazout

Publications and source records attributed to A Hazout.

At least 19 recordsLinked to original sources

[Intracytoplasmic injection of spermatozoa].

Management of male infertility has been totally changed with the development of intracytoplasmic sperm injection (ICSI). This technique, used for in vitro fertilization, consists in injecting a single spermatozoa into the ovum. Intracytoplasmic sperm injection can be proposed in case of severe male sterility (oligoasthenospermia) or after repeated failure of in vitro fertilization. Satisfactory rates of fecondation and pregnancy have been obtained. Results have also been obtained with sperm taken from the epididymis or testis. The risks involved concern the transmission of poorly understood genetic defects leading to the infertility. The rates of reported malformations and chromosome anomalies are quite low. Intracytoplasmic sperm injection can be useful in managing most cases of male infertility which to date have had to rely on donor sperm. Long-term results have not yet been obtained.

Female

A protocol using a low dose of gonadotrophin-releasing hormone agonist might be the best protocol for patients with high follicle-stimulating hormone concentrations on day 3.

We studied 98 in-vitro fertilization (IVF) patients with a high basal follicle stimulating hormone (FSH; >6.5 IU/l) concentration on day 3 who were treated with a low dose gonadotrophin-releasing hormone agonist (GnRHa) protocol and who had received in the previous 6 months a long protocol with GnRHa in a depot formula. The evaluation was made using the previous IVF cycle of the same patient as a control. The mean +/- SD age of the patients was 34.1+/-4.2 years. The use of a low dose agonist protocol ended with significantly less ampoules (37.5 versus 46.1), a shorter duration of stimulation (10.7 versus 12.3 days), a higher oestradiol concentration on day 8 (1068 versus 495 pg/ml), a higher number of mature oocytes (5.9 versus 4.4) and a higher number of good quality embryos (3.3 versus 2.3). The cancellation rate was lower (11 versus 24%). A GnRHa low dose protocol may be the protocol of choice for patients with high FSH concentrations on day 3. Larger randomized studies are needed to confirm these data.

Clinical Protocols

Perinatal outcome and follow-up of 82 children aged 1-9 years old conceived from cryopreserved embryos.

Embryo cryopreservation is routinely used in in-vitro fertilization (IVF)-embryo transfer programmes. Yet very few studies have reported the follow-up of children conceived with frozen/thawed embryos. This study was designed to follow up the total cohort of children conceived with cryopreserved embryos in A. Béclère Hospital in Clamart, France between 1986 and 1994. We were able to study 89 children, aged 1-9 years old, out of the 93 conceived during this period (lost to follow-up: 4.3%). The prematurity rate was 14.7% for the singleton and 85.7% for the twins. Half of these premature deliveries occurred during the 36th week of amenorrhea. In all, 8% of the singleton and 28.6% of the twins were small for gestational age. At the time of the study, only three children aged 1 and 2 years old were below the 10th percentile. The total malformation rate was 3.4% when two abortions performed during the study period were added to the one (short ureter) found in our study group. The medical and surgical illness as well as principal acquisitions for children <5 years old and scholastic performance for older children did not show pathological features.

Body Weight

[Ovarian stimulation using a protocol of low dose agonist in patients with an elevated basal FSH].

This study compare the ovarian response of patients with high day 3 FSH (> 6.5 UI/L), treated with two protocols; a protocol with a low dose of GnRH agonist and a so called "long protocol" with GnRH agonist in a depot formula. The ovarian response with the agonist low dose was better with less ampules (37.1 vs 46.6) and a shorter duration of stimulation (10.5 vs 12.4 days). The number of mature oocyte was higher (5.9 vs 4.5) as well as the number of good quality embryo (3.2 versus 2.3). The E2 levels on day 8 was higher (1065 vs 460 pg/ml). The cancellation rate was lower (14% vs 26%). The use of the low dose protocol gave a better ovarian response for patients with high 3 FSH. Large randomized studies are needed to confirm these data.

Adult

[Embryonal implantation. Fundamental and practical aspects].

The precise mechanisms of embryo implantation remain unclear: the uterus is a "hostile environment" which should become "neutral" at the time of implantation. Advances have been made both in terms of embryo quality and in implantation techniques, making better knowledge of the uterus-embryo dialogue essential. To meet this challenge, the Pharmaceutical firms Serono France and ARCEFAR have organized a symposium entitled "Embryo implantation: basic principles and practical aspects". The symposium, presided by André Hazout and Yves Menezo, will first focus on the fundamental role of the ovum then will explore the complex immunological processes involved in the uterus-embryo dialogue.

Cytokines

Cytogenetic analysis of uncleaved oocytes after intracytoplasmic sperm injection.

PURPOSE: This work analyzes the causes of cleavage failure after intracytoplasmic sperm injection (ICSI) and the effect of the procedure on the chromosomes of the oocytes. METHODS: Ninety-seven uncleaved oocytes from 39 patients with severe male infertility or repeated IVF failure were fixed; 79 were analyzable. We checked the decondensation stage of spermatozoa nucleus and the chromosomal abnormalities of the oocytes. RESULTS: Among the fixed oocytes, the spermatozoa nucleus was present in 97% of the cases, and it was undecondensed in 89% of the cases, showing no evolution at all. A low rate (2.6%) of premature chromosome condensation (PCC) of the spermatozoa and a low rate (2.5%) of female diploïdy were observed. Among the oocytes that could be karyotyped, we observed a high rate (45%) of chromosome breakage. CONCLUSION: ICSI fertilization failure was due mostly to the complete lack of evolution of the spermatozoa nucleus. Oocyte selection before ICSI seemed to lower the PCC rate. The high rate of oocyte chromosomal breakage rate has to be confirmed.

Chromosome Aberrations

Endometrium preparation with exogenous estradiol and progesterone for the transfer of cryopreserved blastocysts.

OBJECTIVE: To determine the implantation rates of cryopreserved blastocysts using controlled E2 and P replacement cycles in women with functioning ovaries. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. PATIENTS: Infertile women with cryopreserved blastocysts obtained from previous IVF attempts. INTERVENTIONS: Exogenous E2 was administered orally from cycle day 1 and P was started transvaginally from day 15. Blastocysts were transferred on the 5th day of endometrial exposure to P (day 19). MAIN OUTCOME MEASURES: Blastocyst implantation rate and pregnancy rate (PR). RESULTS: Ninety-eight percent of blastocysts survived thawing: 67 were transferred in 42 women. Eight pregnancies occurred giving a PR of 19% per ET and 11.9% per blastocyst. CONCLUSION: The high PR observed after transferring blastocysts on the 5th day of endometrial exposure to P in controlled E2 and P replacement cycles speaks for a forward slide of the window of transfer in case of blastocysts.

Adult

A new system for fallopian tube sperm perfusion leads to pregnancy rates twice as high as standard intrauterine insemination.

OBJECTIVE: To evaluate the relative efficacy of a new system for fallopian tube sperm perfusion in comparison with standard IUI in controlled ovarian hyperstimulation (COH) cycles. DESIGN: Prospective randomized trial. SETTING: Ovulation induction program of a tertiary outpatient care center, Hôpital Antoine Béclère, Clamart, France. PATIENTS: We studied 74 infertile women aged 20 to 38 years undergoing 100 cycles of COH from December 1993 to May 1994 only excluding cases of age > 38 years, obstructed or severely damaged fallopian tubes, E2 levels per mature follicle < 250 pg/mL (conversion factor to SI unit, 3.671) on the day of hCG administration, spontaneous LH surge, and cases of marked sperm abnormalities. INTERVENTIONS: Controlled ovarian hyperstimulation was achieved using three types of ovarian stimulation protocols: clomiphene citrate (CC) and hMG (n = 35). hMG alone (n = 35) or GnRH agonist and FSH and hMG (n = 30). Thirty-six hours after hCG administration, patients were assigned randomly to either IUI (group A, n = 50) or fallopian tube sperm perfusion (group B, n = 50). Intrauterine insemination was performed with 0.2 mL of sperm suspension according to a standard technique. Fallopian tube sperm perfusion was performed using a simple and reliable system that ensures a good cervical seal and allows to a pressurized injection of 4 mL of sperm suspension. MAIN OUTCOME MEASURES: Feasibility of the fallopian tube sperm perfusion method, clinical pregnancy (presence of gestational sac with heart beats at 6 weeks of amenorrhea), and ongoing pregnancy rates (PRs) (> 12 weeks of amenorrhea), incidence of complications (multiple pregnancies and ovarian hyperstimulation syndrome [OHSS]). RESULTS: Overall, the new fallopian tube sperm perfusion system was simple to handle and well tolerated by patients. In group A, we observed 10 clinical pregnancies (20% per cycle) of which 7 were ongoing (14%). In group B, 20 clinical pregnancies (40% per cycle) of which 17 ongoing pregnancies (34%) were obtained. These differences were statistically significant. The prevalence of twin and three or more sac pregnancies was similar in the two groups (3/10 and 0/10, respectively, in group A, and 5/20 and 2/20, respectively, in group B). No case of moderate or severe OHSS was observed in this series. CONCLUSIONS: Our results indicate that the new system for fallopian tube sperm perfusion is not only simple and reliable but also may lead to PRs twice as high as standard IUI in COH cycles.

Adult

[Tumor necrosis factor and underlying infection].

Tumor necrosis factor alpha (TNF alpha) is a cytokine with pleiotropic actions on several cell types. It is produced particularly by macrophages and by several cells not classically associated with the immune system. Many infections increase the production of TNF alpha; specially in the endometrium where too more TNF alpha can induce failure of implantation. A treatment using antibiotics and antiprostaglandins seem necessary to stop inflammatory process and to increase chance of pregnancy.

Anti-Bacterial Agents

Cocultured blastocyst cryopreservation: experience of more than 500 transfer cycles.

OBJECTIVE: To present our experience using cocultured cryopreserved and transferred blastocysts. DESIGN: Retrospective study of patients undergoing transfer of cryopreserved blastocysts. SETTING: Three different IVF centers. PATIENTS: Four hundred sixty-seven thawed cycles from January 1991 to June 1994. MAIN OUTCOME MEASURE: Pregnancy rate per cycle after transfer of pre-embryos developed from thawed blastocysts. RESULTS: One thousand two hundred thirty-nine blastocysts were thawed. Of these, 1,033 (83%) survived thawing and were transferred. Five hundred sixty-three thawed cycles resulted in 516 (92%) receiving intrauterine transfer. One hundred twelve clinical pregnancies were established, resulting in a 21.7% pregnancy per transfer with a 19% ongoing rate. The implantation rate of 13.4% results from 138 implanted pre-embryos. There was a higher PR in the programmed cycle (79/302; 26.2%) compared with the natural cycle (6/47;13%). CONCLUSIONS: Freezing at the blastocyst stage is a proven and reliable method in IVF technology. Although there may be fewer pre-embryos, their ability to implant appears to approach the potential of a fresh transfer.

Blastocyst

[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

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

[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

Comparison of short 7-day and prolonged treatment with gonadotropin-releasing hormone agonist desensitization for controlled ovarian hyperstimulation.

OBJECTIVE: To compare two treatment regimens associating a gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropin (hMG) for controlled ovarian hyperstimulation (COH). DESIGN: A prospective randomized trial. SETTING: The outpatient fertility clinic of a university tertiary care center, the Hôpital A. Béclère, Clamart, France. PARTICIPANTS: One hundred eighty-two in vitro fertilization (IVF) candidates undergoing new or repeat IVF cycles at Hôpital A. Béclère over a 4-month period. TREATMENT: Group 1 (7-day protocol): A short-acting preparation of GnRH-a (Tripteriline 0.1) was administered daily for 7 days, starting on cycle day 2. Ovarian stimulation with hMG was started on cycle day 4. Group 2 (long protocol): A timed release preparation of GnRH-a (Tripteriline 3.75 mg) was administered on cycle day 2. Ovarian stimulation with hMG was started after documented ovarian suppression. MAIN OUTCOME MEASURES: Response to COH, pregnancy rate (PR), tolerance. RESULTS: In the 7-day protocol, the amount of hMG required was markedly lower at 24 +/- 7 than in the long protocol group requiring 42.5 +/- 9.75 vials (75 IU) (mean +/- SD). No elevation of plasma LH occurred in either group. The number of oocytes retrieved was 7.3 +/- 1 and 10.7 +/- 1.2 (mean +/- SD) in the 7-day and long protocols, respectively. Yet, the number of embryos obtained and the PRs were similar in the two treatment groups. CONCLUSIONS: We observed that in COH, GnRH-a treatment could be interrupted safely several days before human chorionic gonadotropin administration without risking a premature increase of plasma luteinizing hormone. Moreover, the number of embryos available for fresh transfer and the ongoing PRs were similar in the new 7-day and in the classic long GnRH-a/hMG protocols, despite the smaller number of oocytes suggesting a greater efficiency of the 7-day protocol. The peak estradiol level and the hMG requirement were also lower in the 7-day GnRH-a/hMG protocol.

Adult

Premature elevation of plasma progesterone alters pregnancy rates of in vitro fertilization and embryo transfer.

OBJECTIVE: To determine if an increase in plasma P occurring before hCG administration might impair the outcome of IVF-ET. DESIGN: Five hundred eighty-five IVF-ET cycles were prospectively studied for the occurrence of plasma P elevation before hCG administration. SETTING: Tertiary institution, IVF-ET program, Hôpital A. Béclère. PATIENTS: Participating patients included IVF-ET candidates 23 to 42 years of age only, excluding the couples in whom a male factor was a primary or an accessory cause of infertility. MAIN OUTCOME MEASURES: To clarify the practical consequences on IVF-ET outcome of pre-hCG increases in plasma P, we studied 585 consecutive IVF-ET cycles. These were divided into two groups according to plasma P levels observed on the day of hCG administration; plasma P of 0.9 ng/mL (2.9 nmol/L) was taken as an arbitrary cutoff value. Group A included 485 IVF cycles in which plasma P was < or = 0.9 ng/mL (2.9 nmol/L); group B included the remaining 100 cycles in which plasma P was > 0.9 ng/mL (2.9 nmol/L). RESULTS: The number of mature oocytes retrieved, the oocyte cleavage rate, and the number of embryos obtained were similar in groups A and B. In contrast to this apparent similarity in oocyte quality, a decrease in pregnancy rate (PR) and a trend for a decrease in embryo implantation rate were observed in group B in comparison with group A. CONCLUSIONS: The similar fertilization and cleavage rates obtained in groups A and B suggest that pre-hCG elevation in plasma P does not lead to decreased oocyte quality. Yet the lower PR observed when plasma P rises prematurely suggests that the prolonged but discrete elevation in plasma P occurring in these cases might alter endometrium receptivity to embryo implantation.

Adult

[Cocultures: diagnostic and therapeutic value].

Results of french multiple collaborative studies are reported to evaluate the possible benefits of coculture in human IVF program. Prospective randomized study of IVF with transfer on day two versus IVF with transfer on day 6 shows that coculture does not improve overall results but leads to a reduction of triple or quadruple pregnancies. When applied to patients with more than 4 failures of embryo transfers on day 2, delayed transfer of blastocyst results in a high rate of clinical pregnancy (39%). Transfers of frozen-thawed blastocysts result in 17.8% ongoing pregnancies. Coculture is also a powerful tool for understanding early embryo development: when fertilization arises from sperm with poor characteristics or from frozen sperm of donor, embryo development appears to be altered: in these situations, rate of normally developing embryo is reduced and early embryo development becomes independent of fertilization rate.

Adult

[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