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Biomedical subjects

J Mandelbaum

Publications and source records attributed to J Mandelbaum.

At least 73 records · Page 4Linked to original sources
PubMed1988

Results of IVF in the treatment of polycystic ovary disease.

Sixteen patients with polycystic ovarian syndrome (PCO) were treated by in-vitro fertilization (IVF), 11 suffered from definitive tubal infertility and five had previously undergone multiple unsuccessful attempts at ovulation induction after conventional therapy. They were randomly allocated into two groups: A1 (six patients) treated with 'pure FSH' and A2 (10 patients) whose ovarian stimulation was performed by a combination of LHRH agonist and pure FSH. More oocytes were recovered in group A1 (7.5 +/- 2.2) and group A2 (10.3 +/- 5.8) than in a control group (B) but this difference was not significant. There was no difference between groups A and B in the number of immature oocytes, the oocyte fertilization rate (60%) and the number of embryos replaced per patient (2.8). Four pregnancies were achieved in the six patients in group A1, 5/9 in group A2 and 3/6 in group B. One severe hyperstimulation was recorded in group A1 but this patient developed a pregnancy which was normal at term. This small study suggests that IVF may be a solution to the treatment of PCO resistant to clomiphene citrate and HMG treatment and that the combination of pure FSH with an analogue of LHRH (in a short protocol of 15 days) does not seem to have an advantage over FSH stimulation alone and does not reduce the frequency of hyperstimulation.

Adult↗
PubMed1988

Comparison between long and short protocols of LHRH agonist in the treatment of polycystic ovary disease by in-vitro fertilization.

Two groups of patients with polycystic ovary disease were treated with analogues of LHRH to compare long and short protocols of pituitary desensitization. In group 1 (n = 15), decapeptyl was administered for 30 days associated with stimulation by pure FSH. In group 2 (n = 12) Buserelin was given for 15 days with the same ovarian stimulation. Patients were randomly assigned to the two groups. Six patients in each group had received treatment, for at least 4 months, to induce ovulation with clomiphene citrate or HMG and failed to conceive, despite the absence of a tubal factor. The best results were obtained using the long protocol. Androgen concentrations, particularly delta 4-androstenedione, were significantly lower on the day of oocyte retrieval in group 1 than in group 2 (2.52 +/- 0.73 ng/ml versus 4.44 +/- 2.62, respectively (P less than 0.02). Polycystic follicular formation was less pronounced in group 1 and no clinical hyperstimulations occurred in this group. The pregnancy rate was comparable in the two groups (six ongoing pregnancies in 21 cycles in the 15 patients in group 1 versus three pregnancies in 12 cycles in the 12 patients in group 2).

Adult↗
PubMed1988

Are clinical and biological IVF parameters correlated with chromosomal disorders in early life: a multicentric study.

A multicentric study was carried out to analyse in a large series: (i) the chromosomal status of unfertilized oocytes, (ii) errors at fertilization and (iii) the chromosomal complement of cleaved embryos. Parameters such as type of sterility, maternal age, stimulation treatment, doses of gonadotrophins administered and oocyte preincubation time before insemination were studied in relation to the incidence of chromosome abnormalities. Twenty-six per cent of the unfertilized oocytes and 29.2% of the embryos had chromosome anomalies. Maternal age significantly increased the rate of aneuploidy in oocytes: 38% in patients over 35 years (versus 24% in younger patients). Fertilization-related abnormalities were significant, i.e. 1.6% parthenogenesis and 6.4% polyploidy. Unexplained infertility was correlated with an increase in the rate of parthenogenesis (4.2%) when compared with tubal infertility (1.2%). Triploidy was found to be correlated with three parameters. A lower rate of triploidy was observed in the group of couples referred because of male sterility (1.9% versus 6.3% for tubal sterility), in HMG-treated patients (2.4% versus 7% with analogues of LHRH/HMG) and with a short 2-h preincubation time before insemination (3% versus 7.2% for greater than 2 h). A general model for natural selection against embryos carrying a chromosome imbalance was proposed.

Chromosome Aberrations↗
PubMed1988

[Timing of embryo transfer and success of pregnancy in the human].

The best moment for human embryo transfer has not yet been accurately determined. The human uterus is able to receive young embryos (2, 4 cell-stage and even pronucleated eggs), insure their growth and implantation at a rate that does not exceed, however, 15% for one transferred egg. At the present time in vitro culture to the blastocyst stage, which impairs human embryo viability, should be avoided. Contrary to classical IVF, it becomes possible to dissociate embryo and endometrial ages when transferring frozen-thawed eggs. Our study concerns 443 spontaneous, stimulated or artificial cycles, performed in patients with normal or without endogenous ovarian function (tabl. 1). There was trend towards enhanced pregnancy rates (17%) for synchronous as compared to one-day asynchronous transfers (9%) (tabl. 2). Similar data, widely stated in mammals, emphasize the necessity of a precise chronology of embryo transfer. Embryos only survive and get implanted when placed in a receptive uterus. The onset of the refractory period appears to be closely linked to the maternal steroid environment. Consequently, no pregnancies arose from transfer of donated embryos beyond 6 days of progestative supply in women deprived of endogenous ovarian function. In the same way, administration of progesterone 40 h before oocyte recovery seemed to advance the refractory phase. Indeed, a reduction in the pregnancy rate per transfer was observed in such circumstances without any obvious impairment of embryo viability (tabl. 4). The best pregnancy rate was obtained in synchronous transfers while a one-day disynchronization reduced this rate by half.

Animals↗
PubMed1988

[Failure of embryonic development].

Abnormal embryo development represents the major cause of implantation failures and accounts for the low rate of human fertility in vivo or in vitro. Chromosome abnormalities are widely involved in this process as 26% of oocytes, 8% of fertilizing spermatozoa and 29% of preimplantation embryos carry a chromosome aberration induced by meiotic (aneuploidy) or mitotic (mosaic) non disjunctions. Fertilization anomalies (possibly increased by in vitro procedures) were recorded: 1.6% of embryos resulted from parthenogenesis and 6.4% were polyploid (mainly polyspermic). A morphological, histological and ultrastructural study of embryos recovered after in vivo or in vitro fertilization showed some anomalies: multinucleated blastomeres, cytoplasmic fragments in the perivitelline space, vacuoles, associated or not with developmental impairement. Finally, a few embryos appeared to be free of abnormalities. The analysis of in vitro developmental capacities of normal or abnormal embryos showed great differences: parthenones exceptionally reached the blastocyst stage and therefore probably did not implant. The diploid embryos used in this study were (for ethical reasons) more or less fragmented and gave evidence of low developmental capacities, limited to the 3rd cleavage. Triploid embryos were able to further develop as some of them reached the early blastocyst stage; they represented the major cause of chromosomal 1st trimester abortions. It is interesting to note that 47% of tripronucleated ova divided directly into 3 and 6 cells (probably via a tripolar spindle) instead of 2 and 4 cells as classically described. Finally, tetraploid embryos expressed a precocious lethality as none developed beyond the 3rd cleavage. To conclude, many embryos carry genetic and/or cytological abnormalities which may be enhanced by superovulation treatments. The selection proceeds through all pre- and postimplantation steps, and as a matter of fact nor more than 0.6% newborns are abnormal.

Chromosome Aberrations↗
PubMed1988

[Chromosome analysis of ovocytes and human embryos collected after fertilization in vitro. A model of natural selection against aneuploidy].

Fertilization in-vitro offers the possibility of studying the karyotype of ovocytes obtained after superovulation, when they are not fertilized. Among 120 ovocytes, 30 p. cent presented a chromosomal anomaly. The same study was carried out on morphologically normal or abnormal embryos - and the percentage of chromosomal anomalies approximates here 27 p. cent. These studies offer a model of natural selection against chromosomal anomalies and confirm the limiting role of these anomalies in the success of FIV.

Aneuploidy↗
PubMed1987

Chromosome investigations in early life. II. Human preimplantation embryos.

Cytogenetic analysis of 68 human embryos at the 2- to 8-cell stage was performed according to Tarkowski's technique. Sixteen per cent of diploid embryos showed abnormalities, essentially diploid/haploid or triploid/haploid mosaicism. Considering the aspect of the embryos, 11% of healthy looking and 19% of fragmented embryos were chromosomally abnormal without, however, any statistical significance in this small series. Only 46.7% of the tripronucleate fertilized eggs showed a triploid chromosome complement. In 20% of the cases, however, diploid metaphases were found, and in the last 30% a triploid/diploid mosaicism. One per cent of the oocytes displayed a single pronucleus, and the resulting embryos contained haploid sets of chromosomes suggesting a parthogenetic activation. The overall rate of chromosome abnormalities, including 16% of abnormal diploid eggs, 6% of polyploid and 1% of haploid embryos, thus reaches 23% in this series.

Aneuploidy↗
PubMed1987

Ultrastructural and autoradiographic observations on multinucleated blastomeres of human cleaving embryos obtained by in-vitro fertilization.

Human embryos from the 2-cell to the morula stage developing in vitro after monospermic fertilization were incubated with [3H]thymidine or [3H]uridine and those possessing multinucleated blastomeres were examined by conventional transmission electron microscopy and by light- and electron-microscope autoradiography. Labelled DNA was present in all nuclei showing normal ultrastructural appearance, in pseudonuclei lacking nucleoli and their precursors and often demonstrating an unusual chromatin organization, free in the cytoplasm in structures resembling aggregates of dense chromatin and in small cytoplasmic vesicles in the close vicinity of these aggregates. The labelling with [3H]thymidine was not detected in about 50% of the cytoplasmic chromatin aggregates, suggesting that this extranuclear DNA was no longer replicated. Signs of extrusion of pseudonuclei to the extracellular space were occasionally observed. RNA synthesis could not be detected on free cytoplasmic chromatin, while [3H]uridine was incorporated into all nuclei and most pseudonuclei of multinucleated blastomeres of embryos at the 8-cell and morula stages. However, the major outburst of transcriptional activity and the ultrastructural cytoplasmic changes typical of the assumption of embryonic genome expression, occurring normally at the 8-cell stage, were observed only exceptionally.

Autoradiography↗
PubMed1987

Human embryo cryopreservation, extrinsic and intrinsic parameters of success.

Freezing and thawing (F - T) was applied to 490 early human embryos using propanediol as cryoprotectant. The survival rate of embryos frozen with propanediol alone did not exceed 31% (26/83). The combination of propanediol and sucrose, however, significantly increased the percentage of surviving (248/407 = 61%) and intact (188/407 = 46%) embryos and seemed to enhance embryo viability as suggested by the implantation rate (14.5 versus 8%) without, however, any statistical significance. Embryo survival, but not viability, was correlated with morphological features, whereas neither the age of embryos (1, 2 or 3 days post-insemination) nor the segmentation stage (regular or intermediate) were involved in F - T ability. Thirty-eight F - T embryos implanted when replaced in utero, representing 8% of all F - T embryos and 14% of the F - T replaced embryos. The pregnancy rate per transfer reached 19% (35/185) and was identical to the pregnancy rate per transfer of fresh embryos (253/1149 = 22%). In oocyte donation, too, embryo freezing did not impair the pregnancy rate (25%). In spontaneous cycles, synchronous transfer gave better results than asynchronous transfers (20 versus 10%), but spontaneous cycles had no significant advantage (16% pregnancy/transfer) as compared to stimulated (26%) and artificial (27%) cycles.

Blastomeres↗
PubMed1987

High-resolution autoradiographic localization of DNA-containing sites and RNA synthesis in developing nucleoli of human preimplantation embryos: a new concept of embryonic nucleologenesis.

Human embryos from the 2-cell to the morula stage, obtained by in vitro fertilization, were incubated with [3H]thymidine or [3H]uridine so as to achieve labelling of all replicating nuclear DNA and the newly synthesized RNA, respectively. The label was localized in different structural components of developing nucleoli using electron microscopic autoradiography. Careful study of the relationship between the structural pattern and nucleic acid distribution made it possible to define four stages of embryonic nucleologenesis. Homogeneous nuclear precursors (i) consist of nucleolar matrix elements appearing as filaments of 3 nm thickness, (ii) do not contain recently replicated DNA and (iii) lack RNA synthetic activity. Penetration of DNA into these bodies is a key event leading to their transformation into heterogeneous nucleolar precursors. In addition to the 3 nm matrix filaments, two types of 5 nm fibrillar components can be recognized in them. The denser type contains DNA and is the site of nucleolar RNA synthesis, while the more loosely arranged 5 nm fibrils are not labelled with [3H]thymidine and apparently represent the newly produced pre-rRNA detached from the transcribing rDNA filament. Compact fibrillogranular nucleoli are characterized by the first appearance of the granular component and reduction of the nontranscribing part of the fibrillar component, both indicating the activation of the machinery for rRNA processing. Finally, the granular component is most evident in reticulated nucleoli, occupying mostly the inner parts of their nucleolonema, while the transcription sites tend to be located at the nucleolar periphery. Our findings advocate a unique concept of embryonic nucleologenesis, different from any other nucleolar event during the cell cycle of differentiated cells. This developmental pattern is characterized by a gradual activation of rRNA synthesis and processing, mediated by progressive association of rDNA and, later on, the newly formed pre-rRNA with pre-existing nucleolar matrix elements that are originally topically separated from nucleolar organizer regions. This model may have a general validity in early animal embryos despite some interspecies variability in the timing of individual steps and resulting structural peculiarities.

Autoradiography↗
PubMed1987

From oocyte to embryo: a model, deduced from in vitro fertilization, for natural selection against chromosome abnormalities.

A cytogenetical analysis was performed on 151 unfertilized oocytes, 22 fertilized eggs at the pronuclear stage, and 108 cleaved embryos obtained in the course of in vitro fertilization (IVF). Thirty-two per cent of unfertilized oocytes were abnormal, carrying nullisomies or disomies, mainly of D and G chromosomes, and a structural anomaly (Gq-) in one case. Fertilized eggs showed frequent asynchronism in the development of pronuclei and only 2 out of 8 karyotyped pronuclei were normal. Cleaved embryos were classified according to the number of pronuclei observed 17 hours after insemination. One per cent displayed a single pronucleus, and haploid chromosome complements were found in the corresponding cleaved embryos which were considered to be parthenotes. The rate of chromosome abnormalities of diploid eggs depended on their morphological aspect. Healthy cleaved embryos carried 12.5% of anomalies while this rate reached 37% in fragmented embryos (p less than 0.05). Lastly, 6% of fertilized eggs displayed three pronuclei or more. Only 41% of the corresponding embryos were triploid. Diploidy or diploidtriploid mosaicism were often encountered. This leads to a 21% rate of abnormalities in the preimplantation embryos. Parental karyotyping and HLA typing were carried out in a series of eight couples with in vitro idiopathic infertility or recurrent embryo degeneration in vitro. No abnormality was noted. According to these results, a model of natural selection of normal conceptuses is proposed.

Aneuploidy↗
PubMed1986

Ultrastructure of the human preovulatory oocyte.

The ultrastructure of preovulatory human oocyte-cumulus complexes was described after inducing maturation by clomiphene, human menopausal gonadotropin (hMG), human chorionic gonadotropin (hCG) treatment. The majority of the oocytes was at metaphase II of meiosis, with a radially orientated spindle. The oocyte surface was covered by a multitude of microvilli. Cortical granules were nonuniformly distributed along the cortex. A cytoplasmic polarization was observed. The cytoplasmic organelles were in general uniformly dispersed, with the exception of a narrow segment within which cytoplasmic membranes and mitochondria formed clusters. The spindle was usually found at the borderline between the two regions of the cytoplasm. The functional significance of this polarization is not yet known.

Chorionic Gonadotropin↗