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Zsolt Peter Nagy

Publications and source records attributed to Zsolt Peter Nagy.

9 recordsLinked to original sources
PubMed2006

Artificial gametes.

In vitro fertilization (IVF) has been an efficient medical treatment for infertility in the past decades. However, conventional IVF approaches may be insufficient when gametes are lacking or non-viable thus precluding a significant number of patients from treatment. Ultimately, creation of artificial gametes may provide an universal solution for all indications. Somatic cell nuclear transfer (SCNT) has provided successful cloning in different animal species indicating that a derived technology may be applicable in infertility treatment procedures. Attempts to produce functional male or female gamete through nuclear transfer have been described through the process called haploidization. Initial successes have been observed, however, significant alterations at spindle construction and chromosomal segregation were also described. Stem cell technology may provide an alternative route to obtain fully functional gametes. Both sperm cells and oocytes were obtained using specific culture conditions for embryo originated stem cell. These two mainstream approaches are presented in the current review. Both of these techniques are involving sophisticated methods and consequently both of them demonstrate technical and ethical challenges. Related questions on (mitotic/meiotic) cell division, genetic/epigenetic alterations and cell renewal are needed to be addressed before clinical application.

Animals↗
PubMed2006

Interactions of the meiotic spindle with mitotic chromosomes in GV mouse oocytes.

During mitosis, a spindle checkpoint detects chromosome misalignment and halts the cell cycle progression. In meiosis of female germ cells, however, it is debatable whether such a checkpoint is present. This research employed a unique model in the mouse, mitotic chromosomes transferred to meiotic cytoplasts to investigate whether a meiotic oocyte's microtubule apparatus can effectively separate mitotic metaphase chromosomes, and whether a spindle checkpoint exists during its division. The intact germinal vesicle (GV) oocytes, enucleated GV cytoplasts, and enucleated GV cytoplasts at 15 h in-vitro maturation were transferred with a metaphase fibroblast cell. When mitotic chromosomes were transferred into enucleated or intact mouse GV oocytes, the first bipolar meiotic spindles were established and the reconstructed oocytes were able to extrude polar bodies. However, none of the reconstructed oocytes showed complete and accurate alignment of chromosomes, except the enucleated GV cytoplasts reconstructed after maturation. The spindle formation and polar body extrusion suggest that the first meiotic spindle was functional, and the chromosome misalignment did not prevent the onset of anaphase. The data indicate that a spindle checkpoint, providing surveillance of misaligned chromosomes, was overridden or compromised by the incompatibility between somatic chromosomes and meiotic spindles during the first meiotic division.

Anaphase↗
PubMed2005

Ganirelix acetate use in normal- and poor-prognosis patients and the impact of estradiol patterns.

OBJECTIVE: To evaluate cycle outcomes in patients with either poor or normal prognosis undergoing IVF treatment with a GnRH antagonist (ganirelix acetate) for LH suppression. DESIGN: Nonrandomized, noncontrolled, retrospective review. PATIENT(S): 204 patients, aged 23-41 years, undergoing IVF. INTERVENTION(S): Patients completed 225 consecutive cycles of IVF with a GnRH antagonist (Antagon; Organon, Roseland, NJ) for LH surge prevention. Sixty cycles were conducted in patients with a known poor prognosis, whereas 165 were conducted in patients with a normal IVF prognosis. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR), for the series as a whole and according to prognosis, and serum E2 patterns. RESULT(S): The PR per initiated cycle for the series as a whole was 33.3%. The pregnancy rate was 42.1% per ET for the entire series, with a cycle cancellation rate of 21%. When evaluated by prognosis, the poor-prognosis patients had PRs of 8.3% per attempt and 15% per transfer, whereas the normal-prognosis patients had PRs of 40% per attempt and 45% per transfer. Pregnancy rate did not vary by E2 pattern (drop, plateau, or rise). Oral contraceptive pretreatment was noted to be associated with high cancellation rates in the group of known poor responders, whereas for the group as a whole, cycle outcome was unaffected by the use of oral contraceptives. CONCLUSION(S): Use of GnRH antagonists in patients with an a priori poor IVF prognosis results in predictably poor outcomes. Patients without factors predicting poor outcome have acceptable PRs. The pattern of E2 rise immediately after initiation of GnRH antagonists does not predict cycle outcome. Oral contraceptives can be successfully used to schedule antagonist-based IVF cycles but might increase the risk of cycle cancellation in some patient populations.

Adult↗
PubMed2005

Current advances in artificial gametes.

The birth of Louise Brown, the first IVF baby, in 1978 marked a breakthrough in infertility treatment. In recent decades, several important new techniques have been introduced. One limiting factor has been the requirement to use reproductive cells (gametes) for fertilization and for embryonic development. Somatic cell nuclear transfer (cloning) has been successful in mammals, opening a potential new approach for the treatment of human infertility. In addition, nuclear transfer to achieve embryo development starting from somatic cells instead of gametes, and the creation of artificial oocytes/spermatozoa has been attempted. The present paper reviews the various alternative approaches to haploidization of somatic cells. It has been observed that chromosome segregation (of the donor somatic nucleus) may take place; however, this process is largely random, thus leading to major cytogenetic abnormalities. An alternative approach is related to stem cell technology, to be further explored in the future. Culture conditions may be adjusted so that the totipotent embryonic stem cells will differentiate to specific gametes, sperm cells or egg cells. Injecting spermatozoa produced in this manner into recipient oocytes has led to pronuclear formation and early cleavage stages in some embryos. Finally, the birth of parthenogenetic mice indicates that some of these epigenetic problems can be overcome, and that some of the embryos may survive to birth.

Animals↗
PubMed2003

Nuclear and microtubule dynamics of G2/M somatic nuclei during haploidization in germinal vesicle-stage mouse oocytes.

During the haploidization process, it is expected that diploid chromosomes of somatic cells will be reduced to haploid for the generation of artificial gametes. In the present study, we aimed to use enucleated mouse oocytes at the germinal vesicle-stage (G2/M) as recipients for somatic cells that are also synchronized to the G2/M stage for haploidization. The reconstructed oocytes were then induced to undergo meiosis in vitro and observed for their nuclear morphology and microtubule network formation at various expected stages of the meiotic division. Following in vitro maturation, more than half (62/119, 52.1%) of the reconstructed oocytes completed the first round of meiosis-like division, as evidenced by the extrusion of pseudopolar bodies (PBs). However, accelerated PB extrusion, approximately 3-4 h earlier than that by control oocytes occurred. Furthermore, abnormally large pseudo-PBs, as large as four times the normal PB sizes, were observed. During the process of in vitro maturation at both the expected stages of metaphase I (MI) and metaphase II (MII), condensed chromosomes were observed in 38.7% and 55.2% of oocytes, respectively. However, two other types of nuclear configurations were also observed: 1) uneven distribution of chromatin and 2) an interphase-like nucleus, indicating deficiencies in chromosome condensation. Following oocyte activation, more than half (21/33, 63.6%) of the reconstructed oocytes with pseudo-PBs formed separated pseudopronuclei (PN), suggesting formation of functional spindles. The formation of bipolar spindle-like microtubule network at both the expected MI and MII stages during in vitro maturation was confirmed by immunohistochemistry. In summary, this study demonstrated that a high proportion of G2/M somatic nuclei appear to undergo meiosis-like division, in two successive steps, forming a pseudo-PB and two separate pseudo-PN upon in vitro maturation and activation treatment. Moreover, the enucleated geminal vesicle cytoplast retained its capacity for meiotic division following the introduction of a somatic G2/M nucleus.

Animals↗
PubMed2003

Micromanipulation of the human oocyte.

Intracytoplasmic sperm injection (ICSI) provides an excellent outcome in a consistent manner, and is therefore used worldwide as a routine procedure. Since its introduction, few modifications have been made to its methodology. Recently, a combination of ICSI with micro-hole drilling by laser (LA-ICSI) of the zona pellucida appeared to decrease oocyte degeneration rates and to improve embryo quality and implantation. Cytoplasmic transfer is a more recently introduced procedure where the objective is to improve the quality of patients' oocytes by transferring cytoplasm from a good quality donor oocyte, in cases where it is assumed that cytoplasm is compromised. Nuclear transfer, involving exchange of nuclei between donor and receptor oocytes, is still an experimental procedure, the objective being similar to cytoplasmic transfer in improving oocyte/embryo quality. A nuclear transfer procedure involving somatic cells for reproductive purposes should not be used in humans, for ethical and technical considerations. On the other hand, nuclear transfer for therapeutic purposes to obtain stem cells may be considered in respect of its unique potential in medicine. Finally, the most recently emerged new concept under investigation is the haploidization of somatic cells for the purpose of creating artificial gametes.

Cell Cycle↗
PubMed2002

Laser-assisted removal of necrotic blastomeres from cryopreserved embryos that were partially damaged.

OBJECTIVE: To examine whether the developmental potential of embryos that were partially damaged after freezing and thawing can be improved by removal of necrotic blastomeres before embryo transfer. DESIGN: Prospective pilot study and observational clinical series. SETTING: Private hospital. PATIENT(S): Two hundred thirty-five infertile couples undergoing frozen embryo transfer. INTERVENTION(S): Removal of necrotic blastomeres from frozen-thawed human embryos. MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): Removal of necrotic blastomeres from partially damaged frozen-thawed embryos before transfer increased rates of pregnancy (45.7% vs. 17.1%), ongoing pregnancy (40.0% vs. 11.4%) and ongoing implantation (16.2% vs. 4.3%) compared with the control group, in which necrotic blastomeres were not removed. A similarly high implantation rate (16.7%) was seen a subsequent clinical series in which necrotic blastomeres were removed from all partially damaged embryos. CONCLUSION(S): The viability of partially damaged frozen-thawed embryos can be improved by removal of necrotic blastomeres before embryo transfer.

Adult↗
PubMedDate not supplied

Heterotopic triplet pregnancy: report and video of a case of a ruptured tubal implantation with living embryo concurrent with an intrauterine twin gestation.

This report presents a case of triplet heterotopic gestation after intracytoplasmic sperm injection (ICSI)-IVF treatment, with a left ruptured ectopic tubal implantation with a living embryo and successful outcome of the concurrent intrauterine twin gestation. A couple whose infertility was caused by oligoasthenozoospermia was referred for ICSI treatment. Three good quality embryos were transferred at the request of the patient. Early gestational control was performed by ultrasound at weeks 5 and 7 of gestation. The patient reported to the centre during week 7 with severe abdominal pain and with signs of peritoneal irritation. Transvaginal ultrasound revealed an extra-uterine ruptured implantantion. During the concomitantly performed laparoscopic procedure, a living embryo was observed after opening the extra-uterine embryonic sac. Heartbeat activity was present and lasted for 5 min after surgical resection of the tubal implantation. The patient was discharged from hospital without complications. The intrauterine twin gestation was not affected and two healthy infants were born at week 38 of gestation. Heterotopic pregnancy should be ruled out in patients submitted to IVF-embryo transfer, although no predisposing factors are present in some cases. Precise diagnosis may be delayed due to some important characteristics of the IVF-embryo transfer treatment. Nevertheless, this condition should be diagnosed by ultrasound before tubal rupture to avoid obvious complications. Laparoscopy remains the gold standard for diagnosis and treatment in these cases. The presentation of the heterotopic pregnancy was recorded on video and may be viewed on the internet at www.rbmonline.com/Article/710.

Adult↗