[Growth factors in the testicle].
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Biomedical subjects
Publications and source records attributed to A Hazout.
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50 cases of non obstructive azoospermia required testicular sperm extraction and ICSI. Results are promising but ability to find spermatozoa remains questionable. Further studies are necessary to improve success of the method. Genetic research also need to be developed for better understanding the process.
OBJECTIVE: To clarify whether embryo development to the blastocyst stage may be affected by premature P elevation during controlled ovarian hyperstimulation (COH) for IVF-ET with embryo coculture. DESIGN: Retrospective study. SETTING: Tertiary care infertility center. PATIENT(S): One hundred thirty-one women undergoing 153 IVF-ET cycles with embryo coculture. INTERVENTION(S): Patients underwent COH with GnRH agonist and hMG. Embryos were cocultured up to the blastocyst stage. According to plasma P levels on the day of hCG, two groups were defined: low P (P < or = 0.9 ng/mL; conversion factor to SI unit, 3.180) and high P (P > 0.9 ng/mL). MAIN OUTCOME MEASURE(S): Blastulation (number of blastocysts/number of noncavitating embryos x 100) and pregnancy rates (PRs). RESULT(S): Blastulation rates were similar in the low and high P groups (51% and 48%, respectively). Moreover, patients included in the high P groups achieved significantly lower clinical and ongoing PRs (12% versus 29% and 7% versus 25%, respectively). CONCLUSION(S): The lack of difference in blastulation rates between the groups further supports the hypothesis that premature P elevation does not alter oocyte and embryo quality. Hence, the observed decrease in PRs is likely to reflect impaired endometrial receptivity in the high P group.
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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.
The recently reported human pregnancies and births after fertilising oocytes with round spermatids recovered from the ejaculate of men with non-obstructive azoospermia have underscored the need for a more accurate evaluation of the nuclear and cytoplasmic maturation status of ejaculated germ cells. In this study we describe our first experience with a method combining the immunocytochemical visualisation of proacrosin with autosomal DNA fluorescence in situ hybridisation (FISH) to assess ejaculated germ cells from patients with a spermiogenesis defect. The proacrosin immunoreactivity, analysed with the use of the monoclonal antibody 4D4, has been detected in cells of round spermatid size presenting a haploid FISH figure as well as in larger cells whose ploidy corresponds to primary and secondary spermatocytes. These observations are in agreement with previously published results obtained, with the use of the same antibody, by immunocytochemical analysis of histological sections of testicular tissue. All the cells of round spermatid size possessing proacrosin immunoreactivity were found to be haploid by FISH. On the other hand, some of the haploid cells of round spermatid size did not possess proacrosin immunoreactivity. The structural pattern of proacrosin immunoreactivity was highly variable both in spermatids and in younger spermatogenic cells. These data show that cell size is the main criterion to be used for the identification of ejaculated round spermatids, whereas the presence of the developing acrosome represents only an auxiliary criterion. The scoring of acrosomal development in ejaculated spermatids may be useful as part of pre-treatment diagnosis before the inclusion of infertile couples in a spermatid conception programme.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.