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Biomedical subjects

J Mandelbaum

Publications and source records attributed to J Mandelbaum.

At least 19 recordsLinked to original sources

[Oocyte donation after the bioethics law. Medical, ethical and legal implications drawn form a series of 300 cases at the Tenon hospital].

This is the perfect example of the problems which are the consequences of the actual medicine. We carried out an ovocyte donation study at the Tenon Hospital, in Paris, between 1994 and 1999 involving 177 cryopreserved thawed embryo transfers among 300 recipients. This study enables us to stress the ethical difficulties posed by the so called bioethical laws of 1994. Simultaneously two consequences became clearly evident: a paucity of donors, and the necessity to only transfer frozen embryos due to decree of 1996 upon sanitary security that imposes the quarantine of embryos for six months. On the other hand, the use of this method has yielded important new information regarding embryo implantation and the importance of ovocyte quality that is closely correlated to donor age.

Bioethics↗

A gulf of difference: disputes over Gulf War-related illnesses.

The social discovery of Gulf War-related illnesses, like other occupational and environmental disease, is firmly rooted in ongoing disputes over causation. Pressure from veterans groups, as well as intra-governmental disputes, have driven innovative research directions and challenged the dominant epidemiological paradigm. This dominant epidemiological paradigm was originally a position that viewed stress as the primary causal factor. In the emerging dominant epidemiological paradigm, researchers view veterans' symptoms as similar to other multi-symptom diseases and conditions, but with a firmer respect for the reality of those symptoms. In addition, some researchers pursue interactions between stress and physical exposure. We examine the evolution of the DEP to demonstrate that in many disease disputes, an affected population challenges government and science decision-making, and even ways of knowing, in an attempt to negotiate a disease definition and etiology that results in better treatment and prevention. After considerable research effort, only limited evidence has been found for environmental causation, and even many researchers sympathetic to veterans are doubtful that much more will be found. We analyze the social discovery and ongoing contestation of these illnesses, and the consequent effects on health and public policy. For extension to other disease disputes, we provide an overall model of disease discovery and contestation, examining the key forces of government, science, and citizens.

Causality↗

ESHRE guidelines for good practice in IVF laboratories. Committee of the Special Interest Group on Embryology of the European Society of Human Reproduction and Embryology.

Education has always been a priority for the European Society of Human Reproduction and Embryology (ESHRE). Many efforts have been dedicated to promoting knowledge of techniques, procedures and strategies in order to ensure use of the highest quality practices in reproductive medicine. The need to develop a set of guidelines was a logical consequence that found its first expression in 1990, when Focus on Reproduction (vol. 1, pp. 10-38) published the first guidelines which were distributed among the membership. Five years later a new, more complete edition with several novel techniques and developments appeared in Human Reproduction (vol. 10, pp. 1246-1271). Both have proved to be invaluable references. Five more years have now passed. The necessity to produce current guidelines for good IVF laboratory practice has provided the strongest motivation. This originated from the increasing awareness that embryologists have a duty to prevent unintentional incidents that might result from poor practice in the laboratory. Therefore, the Embryology Special Interest Group (SIG) undertook to draw up guidelines aimed at giving support and guidance to the laboratory staff. All the aspects required to provide a safe working system were taken into consideration by members of the SIG and their effort produced this document. We hope that it will assist staff in achieving the best clinical outcome for their patients.

Cryopreservation↗

Oocytes.

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Cell Nucleus↗

[Therapeutic management of ovarian dystrophy and insufficiency in abortion disorders: recent data].

Many reports suggested that the high rate of miscarriage in women with polycystic ovaries may be due to increased urine and/or plasma LH concentration. In fact, with the exception of pulsatile GnRH, any treatment likely to increase the plasma LH level results in unchanged or rather low miscarriage rates. Conversely, a reduction in this rate by GnRH agonists is not conclusive. Excess weight may also increase the risk of miscarriage. In women with incipient ovarian failure, the miscarriage rate is mainly linked to age. No stimulation has been found to be effective in these patients. There is a need for more extensive evaluation in GnRH analog microdoses, recombinant FSH and GnRH antagonists. Oocyte donations from younger women are difficult to obtain because of the lack of donors in France.

Abortion, Spontaneous↗

Perivitelline space granularity: a sign of human menopausal gonadotrophin overdose in intracytoplasmic sperm injection.

The significance of the presence of coarse dark granules in the perivitelline space of oocytes has not been studied before. The study included 2288 intact oocytes [2063 in metaphase II (MII), 136 in metaphase I (MI), and 89 in germinal vesicle (GV)] retrieved in 206 intracytoplasmic sperm injection cycles stimulated by a long agonist protocol. The incidence of granules varied with oocyte maturity. It was detected in 34.3% and 4% of the MII and MI oocytes respectively, while none of the GV oocytes contained granules. The woman's age, hormonal values (oestradiol and progesterone), human chorionic gonadotrophin/oocyte retrieval interval, number of oocytes retrieved, and oocyte retrieval/injection interval were not related to the percentage of granular oocytes. Moreover, there was no correlation between the percentage of granular oocytes and the fertilization and cleavage rates, pregnancy outcome, as well as the implantation rate. Patients were divided into three groups according to the total human menopausal gonadotrophin (HMG) dose they received. There was a statistically significant difference between the three groups in the percentage of granular oocytes [17.4 +/- 5.2% versus 26.7 +/- 3.2% versus 45.4 +/- 4.2% in the low-dose (< 30 ampoules), intermediate dose (31-45 ampoules), and high-dose (> 45 ampoules) groups respectively]. We conclude that granularity in the perivitelline space is probably a physiological phenomenon related to the maturational events in oocytes and enhanced by exposure to high dosages of HMG.

Adult↗

Cryopreservation in human assisted reproduction is now routine for embryos but remains a research procedure for oocytes.

Human embryo cryopreservation represents an indispensable extension of in-vitro fertilization (IVF) programmes as long as they are based upon the recovery of a large number of oocytes. The most widely used procedures include the cryopreservation of human zygotes or embryos in early cleavage, using 1,2-propanediol and sucrose as cryoprotectants. Our results over a 10 year period (1986-1995) on 5032 thawed cycles involving 14 222 stored embryos make it possible to appraise the results and the contribution of embryo freezing to assisted reproduction. Embryos survived the freeze-thaw process in 73% of cases leading to 4590 transfers of 2.2 embryos (91% of thawed cycles). The clinical pregnancy rate per transfer was 16%, the live birth rate 12%, and the rate of babies born alive per transferred embryo was 6%. Embryo freezing monitored 10 years later produced an average of 8% of additional births. By then, 86% of stored embryos had been thawed for transfer to patients. Destruction or donation were required for only 8% of all frozen embryos and there was no news from the parental couple in relation to almost 6% of embryos. The fate of the vast majority of embryos was decided during the first 5 years of storage. Blastocyst cryopreservation is making new strides, thanks to co-culture systems and embryo selection. Micromanipulation procedures seem to have little impact on the outcome of embryo freezing. Human oocyte freezing is again clinically applied. Indeed, much of the concern about injuries to the oocyte structures through the freeze-thaw process do not seem to be justified, and the problems with frozen-thawed oocyte fertilization has been overcome using intracytoplasmic sperm injection (ICSI). As long as oocyte in-vitro maturation is not well controlled, better results will probably be obtained with mature oocyte cryopreservation. Emerging methods include the freezing of immature oocytes, follicles and ovarian tissue.

Cryopreservation↗

Incidence of sex chromosome abnormalities in spermatozoa from patients entering an IVF or ICSI protocol.

OBJECTIVE: The objective of this study was the determination of sex chromosome aneuploidy frequency in spermatozoa from patients included in an in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) protocol. METHODS: Spermatozoa from nineteen patients, including patients with normal seminal parameters according to World Health Organization (WHO) criteria and patients exhibiting abnormal seminal parameters, were analyzed by dual color fluorescence in situ hybridization (FISH) for aneuploidies of the X and Y chromosomes. Our technique, using only probes for sex chromosomes and not for autosomes, does not discriminate between hyperhaploid and diploid sperm nuclei. The results were analyzed in two different ways: in relation to the semen status, denoted normal or abnormal and with regard to the ability of the sperm to fertilize oocytes when IVF or ICSI was performed. RESULTS: Abnormal semen showed a significant increase in the overall rate of sperm nuclei with XY, XX and YY sex chromosome complements, 1.59% compared to normal semen, 0.78% (p<0.02). Semen shown to be able to fertilize oocytes only by ICSI showed a higher incidence of XY-bearing spermatozoa, 1.26%, compared to semen able to fertilize oocytes by conventional IVF, 0.37% (p<0.001). The incidence of XX-or YY-bearing sperm nuclei was also significantly elevated in the ICSI group (0.25% XX, 0.50% YY) (p<0.02) as compared to the IVF group (0.06% XX, 0.16% YY). CONCLUSIONS: We concluded that infertile men requiring ICSI treatment showed a higher incidence of sex chromosome aneuploidy, due to meiosis I and II nondisjunction, in their spermatozoa as compared to men requiring IVF for reasons of predominantly female infertility.

Aneuploidy↗

[Clinical use of recombinant gonadotropins (FSH, LH, hCG)].

The production of recombinant gonadotropins is independent of urine collection. They have a high specific activity and a better batch to batch consistency than urinary gonadotropins. In our IVF programme 62 normo-ovulatory patients less than 38 years old, with tubal or idiopathic infertility and normal sperm, were treated by r-FSH and randomized into four groups : with or without LHRH agonist, step-up or step-down stimulation. The overall results were higher in the agonist groups, but did not reveal any significant difference between step-up and step-down stimulation.

Adult↗

[Comparative randomized controlled study between human follicle- stimulating hormone (FSH-HP) and human menopausal gonadotropins (hMG) in in vitro fertilization].

We present the results of a prospective randomized trial comparing the issue of IVF-ET and of ICSI when either highly purified human folliculostimulin (FSH-HP) or human menopausal gonadotrophin (hMG) is used. There seems to be a trend to a better rate of ongoing pregnancies when FSH-HP is used although not statistically significant. The study has been stopped due to the lack of hMG.

Adult↗

Expression of leukaemia inhibitory factor receptor subunits LIFR beta and gp130 in human oocytes and preimplantation embryos.

The expression of both components of the high-affinity leukaemia inhibitory factor receptor, LIFR beta and glycoprotein 130 (gp130), was investigated in human oocytes and individual in-vitro cultured preimplantation embryos by reverse transcription-polymerase chain reaction (RT-PCR). Messenger RNA of both LIFR beta and gp130 was detected in as little as 1/30 and 1/12 sample equivalents of cDNA respectively, in oocytes (n = 4), 4-cell and expanded, blastacyst stage embryos. LIFR beta but not gp130 transcripts were detected at the 2-, 8- and 10-cell stages, and in cavitating and hatched blastocysts. In order to exclude a simian origin of these PCR products resulting from the Vero cell line that was used as a feeder during culture to the blastocyst stage, they were digested with restriction endonucleases Taql (LIFR beta) or Kpnl (gp130). Their human origin was confirmed. The results support an earlier finding of LIFR beta mRNA expression in human blastocysts, and extend these results to earlier stages and oocytes. This is the first report of LIFR beta and gp130 transcription in human oocytes. Taken together these results demonstrate that transcription of LIFR beta and gp130 takes place throughout human preimplantation development, and suggest that functional LIF receptors might be present at these stages. These results further confirm the feasibility of performing mRNA phenotyping of multiple genes with RNA derived from a single preimplantation stage embryo.

Antigens, CD↗

[Influence of infertility etiology and follicular stimulation protocols on pregnancy outcomes by in vitro fertilization].

During a retrospective study on 152 singles pregnancies obtained by in vitro fecondation at Tenon hospital, and followed in this department between January 1990 and December 1994, we have studied the influence of the IVF (tubal origin, masculine or idiopathic) and the type of stimulation (human menopausal gonadotrophin: hMG or follicle stimulating hormone: FSH) on the weight of the newborn and the pathologies that occurred during the pregnancy. No difference in the antecedents has been found in the different group of patients. This study shows a significative difference (p < 0.001) of the newborn's weight when the indication of IVF is tubal origin or masculine. Also, in all IVF indications, the weight is significantly (p < 0.01) higher after a follicular stimulation by FSH versus hMG. For the pregnancy pathologies, no significative difference has been noted, although arterial hypertension, fetal growth retardation and gestational diabetes appear to be more frequent in the group of women who had stimulation by hMG.

Adult↗

[Cryopreservation of human embryos after in vitro fertilization: immediate and long-term results].

Between 1990 and 1994, a clinical retrospective study has been carried out at Tenon Hospital on 1200 patients: during this periods. 4845 embryos have been cryopreserved and 31% of the patients had this procedure for their supranumerary embryos. The rate of implantation by embryo was 8% per transfer, comparable to those fresh embryos. Less than 1% of the embryos were abandoned. The contribution of cryopreservation to the IVF program is substantial, increasing pregnancy rate by 10%. Moreover, the rate of multiples pregnancies is significantly lower when implanting frozen thawed embryos (9.6%) vs fresh embryos (p < 0.001). There was no difference between frozen-thawed and fresh embryos, in the implantation rate by embryo, the mean gestational age, and birth weight of singleton, twin and triplet births. From a biological point de vue, a series of 3693 embryos, carried on the same period, in our center has showed that for the success of this procedure, the quality of the embryos was more important, than the duration of the storage. The incidence of major and minor congenital malformations was not different in the two groups of babies (less than 3%). But a retrospective analysis carried out on 84 children, showed 4 major abnormalities, after a follow up of 1 to 9 years. However these anomalies do not seem to have some evident correlation with the cryopreservation procedure; a larger series and a prospective study are needed to get significant results concerning the health of the children born after the procedure of cryopreserved embryos.

Birth Weight↗

[Oocyte fertilizability and embryo development in poor responders].

Oocyte quality (atresia, immaturity), fertilizability, the incidence of abnormal fertilization (parthenogenesis, triploidy) and embryo development (rate of division and morphology) are similar in poor and normal responders. Only, the small number of available embryos (0.9/patient vs 4.4) penalize these patients.

Adult↗