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Zev Rosenwaks

Publications and source records attributed to Zev Rosenwaks.

17 recordsLinked to original sources
PubMed2003

Estradiol increases pre- and post-synaptic proteins in the CA1 region of the hippocampus in female rhesus macaques (Macaca mulatta).

The role of estrogen (E) in promoting learning and memory in females has been well studied in both rodent and primate models. In female rats, E increases dendritic spine number, synaptogenesis, and synaptic proteins in the CA1 region of the hippocampus, an area of the brain that mediates learning and memory. In the present study, we used radioimmunocytochemistry to examine whether E and progesterone were capable of modulating the levels of pre- and postsynaptic proteins in the CA1 region of the female nonhuman primate hippocampus. It was found that E increased syntaxin, synaptophysin (presynaptic), and spinophilin (postsynaptic) levels in the stratum oriens and radiatum of the CA1 region, whereas combined E and progesterone treatment decreased these synaptic proteins to the levels found in untreated, spayed controls. Furthermore, progesterone treatment alone significantly increased synaptophysin levels in the stratum oriens and radiatum of the CA1 region. The levels of these synaptic proteins were unaltered by hormone treatment in the dentate gyrus, suggesting that this steroid-induced plasticity is hippocampal region specific. As these synaptic proteins are important components of the synaptic apparatus and reliable markers of synaptogenesis, it appears that E-induced increases in cognitive function of higher order mammals may be mediated in part by the effect of E on hippocampal synaptogenesis and synaptic plasticity.

Animals↗
PubMed2003

Neonatal outcome of triplet versus twin and singleton pregnancies: a matched case control study.

OBJECTIVE: To determine the neonatal outcome of triplet gestations versus that of singletons and twins matched for gestational age. STUDY DESIGN: All live born triplet gestations delivered between 1 April 1993 and 31 March 2000 were compared to an age matched control group consisting of live born twins and singletons. The neonatal outcome of 116 sets of triplets was compared to that of 116 sets of twins and 116 singletons. RESULTS: During a 7-year period 116 sets of triplet pregnancies were reviewed. Of 116 sets of live born triplets (348 newborns), 70.67% triplets were born between 33- and 36-week gestation, 28.44% between 28 and 32 weeks and 0.86% less than 28 weeks. Triplets were smaller in weight than singletons but not twins. Apgar score, use of prenatal steroid and sex ratio were similar in the three groups. Incidence of respiratory distress syndrome (RDS), use of surfactant, infants requiring intubation, pneumothorax, patent ductus arteriosus, sepsis, intraventricular hemorrhage, periventricular leucomalacia, retinopathy of prematurity, necrotizing enterocolitis, gastroesophageal reflux and jaundice requiring phototherapy were not statistically different among the three groups. Incidence of major and minor congenital anomalies, percent neonatal intensive care unit (NICU) admissions, and mean duration of NICU stay were also similar. There was no influence of birth order on neonatal outcome of triplet pregnancy and outcome did not significantly change over 7 years of the study period. CONCLUSIONS: Triplets have a similar outcome to twins and singletons when matched for gestational age. Since outcome is dependent on gestational age, the closer the gestational age is to term the better is the outcome.

Adult↗
PubMed2003

Cryopreservation of nuclear material as a potential method of fertility preservation.

OBJECTIVE: To establish a cryopreservation method for female nuclear materials with the aim of creating viable embryos or offspring by nuclear transfer. DESIGN: A randomized controlled study. SETTING: Clinical and academic research facility.B6D2F1 mice. INTERVENTION(S): Female pronuclei (FPNs) and second polar bodies (2PBs) isolated from superovulated mouse zygotes were cryopreserved, thawed, and transferred into donor zygotes. MAIN OUTCOME MEASURE(S): Survival rates after freeze-thaw and blastocyst formation rates were evaluated. RESULT(S): Female pronuclei and 2PBs preserved with three tested methods resulted in survival rates ranging from 11.5% to 85% for FPNs vs. 46.9% to 95.0% for 2PBs and blastocyst formation rates ranging from 0% to 35.5% for FPNs vs. 9.1% to 47.4% for 2PBs. Live birth offspring also resulted from both FPNs and 2PBs preserved with vitrification. CONCLUSION(S): We have established a new system to effectively revive frozen nuclei into viable embryos by a combination of nuclei preservation, zygote reconstruction, and coculturing of reconstructed zygotes with mouse embryonic fibroblast cells. Our data suggest that the preserved female genomic DNA material can be potentially used for future nuclear transfer to preserve female fertility.

Animals↗
PubMed2003

A technique for transplantation of ovarian cortical strips to the forearm.

OBJECTIVE: To describe a forearm heterotopic ovarian transplantation technique. DESIGN: Case study. SETTING: Academic medical center. PATIENT(S): One patient with stage IIIB squamous cell cervical carcinoma and one patient with recurrent benign ovarian cysts. INTERVENTION(S): Preparation of thin ovarian cortical slices and transplantation under the skin of the forearm. MAIN OUTCOME MEASURE(S): Follicular development and oocyte retrieval; cyclical estradiol (E(2)) and progesterone (P(4)) production; restoration of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels to reproductive age range. RESULT(S): Both patients were menopausal immediately after oophorectomy. The first patient developed a dominant follicle 10 weeks after transplantation, and her gonadotropin levels decreased to nonmenopausal levels. Percutaneous aspiration of ovarian follicles yielded a metaphase I (M-I) oocyte that was matured to metaphase II (M-II). The first patient's graft was functional for at least 21 months. In the second patient, ovarian follicle development was detected 6 months after transplantation, and periodic menstruation occurred thereafter. Spontaneous ovulation was confirmed by a midluteal increase in her P(4) levels. Menstruation and follicle development continued for more than 2 years after the transplant. CONCLUSION(S): Heterotopic transplantation of ovarian tissue to the forearm is a simple and promising technique to restore ovarian function in women who become menopausal due to chemotherapy, surgery, or radiation.

Adult↗
PubMed2003

Improvement in consistency of response to ovarian stimulation with recombinant human follicle stimulating hormone resulting from a new method for calibrating the therapeutic preparation.

Traditionally, therapeutic preparations of gonadotrophins are quantified with a rat in-vivo bioassay in biological international units (IU). This method was developed to cope with variability of production batch quality. The bioassay, however, presents some limitations, and differences in clinical responses when using different batches of urine-derived gonadotrophins have been reported. The production of human FSH by recombinant technology now allows the use of advanced physicochemical methods for quantifying FSH, which can be measured in microg of FSH proteins (in mass). The study reported here was designed and conducted to assess the clinical relevance of this new method for quantifying therapeutic preparation of FSH. Four bulk lots of recombinant human FSH (r-hFSH) were used to prepare batches filled by IU (FbIU) and four batches filled by mass (FbM). These eight batches were compared in a double-blind, randomized study in patients undergoing assisted reproductive technology. One hundred and thirty-one patients were enrolled in this study and met protocol criteria (66 in the FbM group and 65 in the FbIU group). The starting dose of recombinant human FSH (r-hFSH) was either 150 IU or 11 microg/day. Both preparations induced multiple follicular development and all patients underwent oocyte retrieval. The number of follicles >/= 11mm was 14.85 and 14.91, serum oestradiol concentration on day of human chorionic gonadotrophin (HCG) administration was 6524 and 6350 pmol/l, number of oocytes retrieved was 10.76 and 11.28, number of two-pronuclear (2 PN) oocytes was 5.2 and 5.00, number of viable embryos (replaced or cryopreserved) was 4.15 and 3.72, and clinical pregnancy rate was 30.3 and 26.2% respectively in the FbM and FbIU groups. Overall, the patients' response consistency was found to be superior with FbM (P = 0.039), and in particular for clinical pregnancy rates (P < 0.001). This new method for quantifying r-hFSH delivers an improved consistency in clinical outcome.

Animals↗
PubMed2003

The role of mitogen-activated protein kinase in insulin and insulin-like growth factor I (IGF-I) signaling cascades for progesterone and IGF-binding protein-1 production in human granulosa cells.

Insulin and IGF-I participate in the regulation of ovulation, steroidogenesis, and IGF-binding protein (IGFBP) production in the ovary. Insulin and IGF-I actions in the ovary are closely related. For example, insulin may amplify IGF-I action in the ovary by up-regulating type I IGF receptors and inhibiting IGFBP-1 production, thus increasing the bioavailability of IGF-I. It is hypothesized that ovarian effects of insulin in insulin-resistant states are mediated via an insulin action pathway(s) distinct from those involved in glucose transport. We previously reported that insulin-induced stimulation of progesterone and inhibition of IGFBP-1 production in the human ovary are mediated by signaling pathways that are independent of phosphatidylinositol 3-kinase, the enzyme whose activation is crucial for glucose transport. We now examined whether activation of MAPK is necessary to mediate insulin-induced or IGF-I-induced stimulation of progesterone or inhibition of IGFBP-1 production in human granulosa cells. Human granulosa cells were obtained during in vitro fertilization. Cells (0.5-1 x 10(5)) were incubated for 24 h in the presence of 0, 10, 10(2), or 10(3) ng/ml insulin or 0, 0.5, 1, 2.5, or 5 ng/ml IGF-I and in the presence or absence of 1 micro M PD98059, a specific inhibitor of ERK1/2 MAPK. The progesterone concentration in the tissue culture medium was measured by RIA (Pantex, Santa Monica, CA), and the IGFBP-1 concentration was measured by immunoradiometric assay (DSL-7800, Diagnostic Systems Laboratories, Inc., Webster, TX). MAPK activity was assessed using the MAPK IP-Kinase assay kit (Upstate Biotechnology, Inc., Lake Placid, NY). ANOVA was used to compare mean values of progesterone or IGFBP-1 concentrations. MAPK was stimulated by insulin up to 350% of the baseline value. Progesterone production in human granulosa cells was stimulated by insulin in a dose-related manner to 123% of the control value (P < 0.001), and IGFBP-1 production was inhibited to 25% of the baseline value (P < 0.001). Despite inhibiting MAPK activity by 99%, PD98059 (1 micro M) did not interfere with insulin-induced stimulation of progesterone or inhibition of IGFBP-1 production. MAPK was stimulated by IGF-I to 730% of the baseline value, with maximal stimulation achieved at 0.5 ng/ml IGF-I. Progesterone production in granulosa cells was stimulated by IGF-I to 130% of the control value (P < 0.001), whereas IGFBP-1 production was inhibited to 44% of the control value (P < 0.001). PD98059 (1 micro M) inhibited IGF-I-induced MAPK activity by 94%. In the presence of 1 micro M PD98059, IGF-I-induced stimulation of progesterone production was inhibited by 96% (P < 0.001). The inhibitory effect of IGF-I on IGFBP-1 production was reduced in the presence of 1 micro M PD98059 by 45% at 5 ng/ml IGF-I and was completely abolished in the presence of 1 micro M PD98059 at concentrations of IGF-I ranging from 0.5-2.5 ng/ml (P < 0.001). We conclude that, under conditions of our experiments, insulin-induced stimulation of progesterone or inhibition of IGFBP-1 production in human granulosa cells does not require MAPK activation, whereas similar effects of IGF-I are largely MAPK dependent.

Cells, Cultured↗
PubMed2002

In vitro culture and in vitro maturation of mouse preantral follicles with recombinant gonadotropins.

OBJECTIVE: To develop an effective method for in vitro maturation of preantral follicles isolated from mice ovarian tissue. DESIGN: Isolated preantral follicles were randomly allocated to designed experimental groups for study. SETTING: University-based research lab. PATIENT(S): Healthy, normal mice. INTERVENTION(S): Superovulation with pregnant mare serum gonadotropin and hCG. MAIN OUTCOME MEASURE(S): Morphological changes and E(2) production were assessed. RESULT(S): To obtain competent oocytes, preantral follicles must be cultured with medium containing insulin and recombinant gonadotropins (i.e., recombinant FSH and recombinant LH), with a change of medium daily. A high initial recombinant LH or recombinant FSH facilitates E(2) secretion, enhances granulosa cell outgrowth, and has earlier antral formation. However, prolonged culture in high-recombinant LH or recombinant FSH triggers early differentiation and luteinization of granulosa cells, which results in low metaphase II oocyte and blastocyst formation. CONCLUSION(S): We have developed a culture system that allows the successful maturation of preantral follicles in vitro. The matured follicles are a physiologically functional unit that not only secrete E(2) but also generate competent oocytes. In a special condition, 90% of the cultured follicles survived, 53.5% of them produced MII oocytes, and 50% of the derived MII oocytes were fertilized and reached the blastocyst stage after culture in vitro.

Animals↗
PubMed2002

Importance of the biopsy date in autologous endometrial cocultures for patients with multiple implantation failures.

OBJECTIVE: To analyze the effectiveness of autologous endometrial coculture by the cycle day of the endometrial biopsy. DESIGN: Retrospective study. SETTING: University-based IVF center. PATIENT(S): Two hundred eight patients with multiple IVF failures. INTERVENTION(S): Embryos were split and randomly allocated to growth on autologous endometrial coculture or conventional media. MAIN OUTCOME MEASURE(S): Embryo quality and pregnancy outcome. RESULT(S): The overall clinical pregnancy rate was 41.8%. Embryos grown on autologous endometrial coculture were of higher quality (more blastomeres and less fragmentation) than embryos grown with conventional media. Early luteal biopsies (<5 days after LH surge) for autologous endometrial coculture did not demonstrate an improvement in embryo quality as compared to the significant improvement demonstrated with later luteal endometrial biopsies (> or =5 days after LH surge). The date of the biopsy was predictive of pregnancy outcome when using autologous endometrial coculture (44.7% [> or =5 days after LH surge] vs. 18.8% [<5 days after LH surge], P=.012). CONCLUSION(S): We have demonstrated an improvement in embryo quality when using autologous endometrial coculture. The improvement in embryo quality and higher pregnancy rates were limited to biopsies > or =5 days after the LH surge. This suggests that mid/late luteal phase endometrium contains factors that enhanced embryo growth and subsequent implantation.

Adult↗
PubMed2002

Role of acupuncture in the treatment of female infertility.

OBJECTIVE: To review existing scientific rationale and clinical data in the utilization of acupuncture in the treatment of female infertility. DESIGN: A MEDLINE computer search was performed to identify relevant articles. RESULTS: Although the understanding of acupuncture is based on ancient medical theory, studies have suggested that certain effects of acupuncture are mediated through endogenous opioid peptides in the central nervous system, particularly beta-endorphin. Because these neuropeptides influence gonadotropin secretion through their action on GnRH, it is logical to hypothesize that acupuncture may impact on the menstrual cycle through these neuropeptides. Although studies of adequate design, sample size, and appropriate control on the use of acupuncture on ovulation induction are lacking, there is only one prospective randomized controlled study examining the efficacy of acupuncture in patients undergoing IVF. Besides its central effect, the sympathoinhibitory effects of acupuncture may impact on uterine blood flow. CONCLUSION: Although the definitive role of acupuncture in the treatment of female infertility is yet to be established, its potential impact centrally on the hypothalamic-pituitary-ovarian axis and peripherally on the uterus needs to be systemically examined. Prospective randomized controlled studies are needed to evaluate the efficacy of acupuncture in female fertility treatment.

Acupuncture↗
PubMed2002

Autologous endometrial coculture in patients with a previous history of poor quality embryos.

PURPOSE: To evaluate the effect of autologous endometrial coculture in patients (less than 36 years old) with a history of a single IVF failed cycle associated with poor quality embryos. METHODS DESIGN: Controlled clinical study. SETTING: University-based in vitro fertilization center. PATIENTS: Twenty-six patients with a history of a single prior failed IVF-ET with poor preembryo quality. INTERVENTION(S): Autologous endometrial coculture. MAIN OUTCOME MEASURES: Preembryo blastomere numbers and cytoplasmic fragmentation rates were compared between the treatment and previous cycle. Clinical pregnancy rates were analyzed. RESULTS: Twenty-six women with an average age of 32.8 +/- 2.9 years underwent treatment. On Day 3 the overall mean number of blastomeres per preembryo on coculture compared to conventional medium in a previous cycle was 6.1 +/- 1.8 vs. 5.1 +/- 1.3 (P = 0.01; Wilcoxon test). The average percentage of cytoplasmic fragments on coculture compared to the conventional medium in a previous cycle was 14% +/- 10 vs. 22% +/- 13 (P = 0.003; Wilcoxon test). At transfer the mean number of blastomeres per preembryo on coculture was 7.4 +/- 1.8 compared to 6.7 +/- 1.5 on conventional medium in a previous cycle (P = 0.02; Wilcoxon test). The clinical pregnancy rate (positive fetal cardiac activity) per patient was 88.5%. The delivery rate was 73.1% (19/26). CONCLUSIONS: There was an improvement in the preembryo quality for preembryos on autologous endometrial coculture compared to noncocultured preembryos from the same patient in a previous cycle. An excellent delivery rate was subsequently found.

Adult↗
PubMed2002

Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI.

BACKGROUND: Although ICSI provides a way of treating azoospermic men, concern has been raised about the potential risk for transmission of genetic abnormalities to the offspring. We quantified the incidence of chromosomal abnormalities in epididymal and testicular sperm retrieved from azoospermic patients undergoing ICSI. METHODS: Individual testicular sperm were collected from testicular biopsies with an ICSI pipette, and epididymal sperm were retrieved by microsurgical epididymal sperm aspiration. Samples were processed by fluorescent in-situ hybridization (FISH) for chromosomes 18, 21, X and Y and the results compared with those from normal ejaculated samples. RESULTS: The overall aneuploidy rate of 11.4% in men with non-obstructive azoospermia was significantly higher (P = 0.0001) than the 1.8% detected in epididymal sperm from men with obstructive azoospermia and also the 1.5% found in ejaculated sperm. No significant difference was found between the epididymal and ejaculated samples. When the chromosomal abnormalities were analysed, gonosomal disomy was the most recurrent abnormality in both obstructive and non-obstructive azoospermic patients, while autosomal disomy was the most frequent in ejaculated sperm. CONCLUSIONS: Sperm of non-obstructive azoospermic men had a higher incidence of chromosomal abnormalities, of which sex chromosome aneuploidy was the most predominant. Genetic counselling should be offered to all couples considering infertility treatment by ICSI with testicular sperm.

Adult↗
PubMed2002

Technical approaches to correction of oocyte aneuploidy.

BACKGROUND: This study describes the technical approaches used in treatment of age-related oocyte aneuploidy, the efficiency of each step of nuclear transplantation into mouse and human oocytes, and the ability of germinal vesicle (GV) transplantation to restore artificially induced ooplasmic damage. Finally, it examines the possibility of constructing viable female gametes by transferring diploid somatic cell nuclei into enucleated oocytes. METHODS: GV stage mouse oocytes were collected from unstimulated ovaries, and human GV oocytes were donated from consenting patients undergoing ICSI. Stromal (somatic) cells were isolated from uterine biopsies of consenting patients. Mouse cumulus cells were obtained after ovarian stimulation. GV ooplasts prepared by removing nuclei were transplanted either with GV nuclei or with somatic cells by micromanipulation. Grafted oocytes were electrofused and cultured to allow maturation, following which they were inseminated or analysed cytogenetically. Ooplasmic dysfunction was induced by photosensitization with a mitochondria-specific fluorescent dye. RESULTS: GV transplantation had an overall efficiency of 87 and 73% in the mouse and humans respectively. Maturation rates of 95 (mouse) and 64% (human) following reconstitution were comparable with those in control oocytes, as was the incidence of aneuploidy for five chromosome-specific probes after aneuploidy among the reconstituted oocytes. Photosensitization of oocytes significantly reduced the maturation rate to 4.2%, whereas 61.9% of oocytes matured after transfer of photosensitized GV karyoplasts into healthy ooplasts, with 52% of these mature oocytes being successfully fertilized by ICSI. Enucleated immature oocytes receiving mouse cumulus or human endometrial cell nuclei extruded a polar body in >40% of cases. Five out of seven successfully transferred aged human nuclei exhibited the expected number of signals with five chromosome-specific probes suggesting an appropriate chromosome separation in young ooplasm. CONCLUSIONS: Nuclear transplantation itself does not appear to interfere with chromosome segregation and can possibly rescue oocytes with damaged mitochondria. Finally, immature mouse ooplasm supported separation of somatic chromosomes to expected numbers, implying that haploidization may be occurring. The roles of genetic imprinting and fidelity of chromosome segregation are unknown.

Aneuploidy↗
PubMed2001

Preimplantation diagnosis for p53 tumour suppressor gene mutations.

Preimplantation genetic diagnosis (PGD) was introduced for high-risk couples to avoid establishing affected pregnancies potentially requiring termination following prenatal diagnosis. This opens the possibility for PGD for late onset disorders with genetic predisposition, including inherited cancer predisposition, because only embryos free from the predisposing gene may be transferred back to the patient, with no potential risk for pregnancy termination. PGD was performed for two couples, one with maternally and one with paternally derived p53 tumour-suppressor mutations, 902insC in exon 8 and G524A in exon 5, respectively. This involved a standard IVF protocol, allowing oocytes or embryos to be tested prior to their transfer back to uterus. Maternal mutation was tested by sequential PCR analysis of the first and second polar bodies, removed following maturation and fertilization of oocytes, while paternal mutation analysis required embryo biopsy at the cleavage stage. To avoid misdiagnosis due to allele drop out, multiplex nested PCR was applied, involving p53 mutation analysis simultaneously with the linked short tandem repeats in intron 1. Of 10 oocytes tested in two PGD cycles for 902insC mutation, four unaffected oocytes were pre-selected for transfer yielding no clinical pregnancy. Of 18 embryos analysed in two cycles for G524A mutation, seven mutation-free embryos were detected, two of which were transferred in each cycle, resulting in a singleton pregnancy and birth of a mutation-free child. This is the first PGD for inherited cancer predisposition determined by p53 tumour suppressor mutations, resulting in a clinical pregnancy and birth of a child free from inherited cancer predisposition.

Journal Article↗
PubMedDate not supplied

Ovarian hyperstimulation syndrome: strategies for prevention.

Ovarian hyperstimulation syndrome (OHSS) is a serious, iatrogenic complication of ovarian stimulation. The following report is a review of traditional and new strategies to prevent the development of OHSS. Techniques such as reducing the ovarian stimulus, coasting and cryopreservation are discussed. Other more investigative strategies are also summarized, including follicular aspiration, in-vitro maturation of immature oocytes, the use of gonadotrophin-releasing hormone (GnRH) agonists to trigger ovulation and the use of volume expanders such as hydroxyethyl starch. In addition, a review of the internal experience with OHSS at the authors' institution is described. All these preventative approaches are based on current understanding of the physiologic mechanisms involved in the pathogenesis of OHSS.

Albumins↗
PubMedDate not supplied

Oocyte-induced haploidization.

This paper describes the technical approach to treatment of age-related oocyte aneuploidy. Although one solution can be oocyte/embryo selection, another is represented by the nuclear transplantation procedure. The efficiency of nuclear transplantation into immature oocytes is described as a way of generating embryos, and the possibility that viable female gametes can be constructed by transfer of diploid somatic cell nuclei into enucleated oocytes. Germinal vesicle (GV)-stage mouse oocytes were collected from unstimulated ovaries and somatic nuclei were obtained from mouse cumulus cells obtained after ovarian stimulation. Spare human GV-stage oocytes were donated from consenting patients undergoing intracytoplasmic sperm injection (ICSI) treatment, and human somatic cells were stromal cells coming from uterine biopsies performed on consenting patients undergoing endometrial cell co-culture. GV ooplasts, prepared by enucleation, were transplanted with either GV or somatic nuclei by micromanipulation. Grafted oocytes were electrofused and cultured to allow maturation, following which they were selected at random for insemination or cytogenetic analysis. GV transplantation was accomplished with an overall efficiency of approximately 80 and 70% in the mouse and the human respectively. The maturation rate of 96% (mouse) and 62% (human) following reconstitution was comparable to that of control oocytes, as was the incidence of aneuploidy among the reconstituted oocytes. The reconstituted human oocytes were successfully fertilized by ICSI at a rate of 52%. After the transfer of mouse cumulus or human endometrial cell nuclei into enucleated immature oocytes, a polar body was extruded in >40%. In a limited number of observations where the nucleus of an aged oocyte was transferred into a younger ooplasm, the chromosomes segregated normally at the time of polar body extrusion. The technique of nuclear transplantation itself did not increase the incidence of chromosomal anomalies in the mouse or human, since their oocytes reconstituted with homologous donor GV resumed meiosis to metaphase II and maintained a normal ploidy. In addition, immature mouse ooplasts induced haploidization of transplanted somatic cell nuclei. Although further evaluation of their genetic status is needed, the procedure may offer a realistic way of producing normal oocytes in cases of aged-related infertility. While the procedure is technically similar to cloning, it would generate a unique individual as a result of the contribution of both parental genomes.

Aneuploidy↗