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ABSTRACT: Association of ESR1 gene PvuII, XbaI and (TA)n microsatellite polymorphisms and woman infertility was evaluated.
Infertile(n = 104) and fertile(n = 107) women were included in this study. We performed polymerase chain reaction-restriction fragment-length polymorphism analysis for detecting ESR1 polymorphisms.
PvuII and XbaI polymorphisms confered risk for infertility in a simple dominant manner in which a significant relationship was observed between infertile and control women. Infertile women had fewer(<18) short repeat alleles in promotor region. ESR1 genotypes were compared concerning maturation, fertilization, pregnancy rates and embryo quality. Although no difference was found in terms of pregnancy rates, maturation and fertilization rates were significantly smaller in pp and xx genotypes. Also, pp genotypes had significantly lower number of good quality embryos. Long TA repeat in promotor was found to be associated with low fertilization rate.
Polymorphisms at the ESR1 gene are associated with infertility in this Turkish infertile women population.
Journal of Assisted Reproduction and Genetics 10/2009; 26(9-10):503-10. · 1.84 Impact Factor
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Fertility and sterility 10/2009; 92(4):e43; author reply e44. · 3.97 Impact Factor
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ABSTRACT: To assess the effectiveness of intracytoplasmic sperm injection (ICSI) combined with piezoelectric stimulation in infertile couples with a history of total fertilization failure (TFF).
Prospective controlled trial.
Clinical IVF laboratory.
Seventy-one couples undergoing ICSI on sibling oocytes having at least one previous ICSI attempt with TFF.
ICSI or ICSI with piezoelectric activation.
Fertilization rate.
The patients were allocated to two groups: group I included 21 patients with only one previous TFF and group II included 50 patients with more than one previous TFF. Collectively, a total of 823 metaphase II (MII) oocytes were retrieved in 78 oocyte retrievals. In Group I, combined ICSI with piezoelectric stimulation was applied to 123/211 (58.2%) of MII oocytes (group IA), whereas standard ICSI procedure was applied to 88/211 (41.8%) of MII oocytes (group IB). The fertilization rate was 62% and 12% in group IA and group IB respectively. In group II, piezoelectric activation was applied in all 612 MII oocytes, of which 296 (48.3%) were fertilized. The rates for implantation and pregnancy/embryo transfer were obtained as 30.6% and 44.1%, respectively.
Piezoelectric activation seems to improve IVF outcome in patients with previous TFF history.
Fertility and sterility 06/2009; 94(3):900-4. · 3.97 Impact Factor
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ABSTRACT: To perform preimplantation genetic diagnosis (PGD) for a SURF1 gene mutation of the Leigh syndrome to transfer unaffected or carrier embryo/embryos.
Case report.
Clinical IVF laboratory.
A couple carrying an nt769 G/A mutation that is associated with Leigh syndrome.
Oocytes were fertilized by means of intracytoplasmic sperm injection. The resulting embryos were biopsied 3 days after fertilization. One blastomere was taken and whole-genome amplification was performed. Amplification of the mutation site was achieved by polymerase chain reaction (PCR) and restriction digestion was completed. Gel Imager was used to measure the digests of normal and mutant load.
Embryo testing by means of PGD-PCR and pregnancy. Successful preimplantation genetic diagnosis for a SURF1 gene mutation and transfer of healthy or carrier embryos.
Successful singleton pregnancy resulting in the delivery of healthy baby girl.
We report the first case of successful PGD for Leigh syndrome resulting in delivery of a healthy newborn.
Fertility and sterility 10/2008; 90(5):2017.e11-3. · 3.97 Impact Factor
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European Journal of Obstetrics & Gynecology and Reproductive Biology 10/2007; 134(1):126-7. · 1.97 Impact Factor
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ABSTRACT: To assess the karyotypic relationship between prefertilized/postfertilized oocytes and embryos using comparative genomic hybridization (CGH) on polar body-1 (PB-1), PB2, and blastomere biopsies and to evaluate IVF outcomes after transfer of blastocysts derived from euploid oocytes.
Prospective cohort.
Medical center.
Phase1: Fourteen oocyte donors (23-29 years). Phase 2: Forty-one healthy embryo recipients aged 29-43 years free of endometrial implantation dysfunction. In 30 cases own eggs were used. Eleven women used donated oocytes.
Phase 1: PB-1 biopsies followed intracytoplasmic sperm injection (ICSI), PB-2, and day 3 blastomere biopsies. Phase 2: PB-1 biopsy followed by ICSI using normal sperm and the subsequent embryo transfer of < or =2 blastocysts derived from euploid oocytes. Comparative genomic hybridization on all DNA derived from phase 1 and 2 biopsies.
Pregnancy and implantation rate.
Phase 1: 39% of oocytes and 88% of zygotes were euploid; >95% progressed to blastocysts. Mosaicism as evidenced by euploid oocytes developing into aneuploid zygotes or embryos occurred in 13% of concepti. Phase 2: Six of 30 women using own eggs, who failed to produce euploid oocytes, were cancelled. Thirty-five women underwent embryo transfers with < or =2 (mean, 1.3 +/- 0.7) blastocysts derived from euploid oocytes. The ongoing pregnancy/implantation rates per embryo transfer were 74% and 82%, respectively.
Transferring euploid embryos markedly improved IVF outcome. These findings, if corroborated, could initiate a paradigm shift in assisted reproductive technology (ART).
Fertility and sterility 05/2007; 87(5):1033-40. · 3.97 Impact Factor
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ABSTRACT: To explore the possible relationship between Y-chromosome microdeletions and a rare spermatogenic disorder, globozoospermia.
Twelve patients with 100% globozoospermia were evaluated. Each man was questioned about his medical and surgical history and underwent a thorough andrologic examination. Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin levels were measured. Routine sperm analysis and morphology with electron microscopy were done. A set of 17 Y-specific sequence-tagged sites spanning the 3 AZF regions and also RBM1, ZFY, SRY, sY78, CDY, BPY2 and PRY were tested to detect the existence of Y-chromosome microdeletions by polymerase chain reaction.
The mean age of the patients was 36 years (range, 27-42). No patient had abnormal blood concentrations of FSH, LH, testosterone or prolactin. Semen analysis revealed normal values for volume (2.2 mL) and concentration (32 x 10(6)/mL) but subnormal values for motility (37%) and progressive motility (24%). On light and electron microscopy, all the spermatozoa were round headed, with abnormal morphologic features. Patients had normal 46,XY karyotyping. No microdeletion of the Y chromosome was detected in any patient.
Although this study did not find any Y-chromosome microdeletions in patients with globozoospermia, the exact genetic locus resulting in this pathology requires further study.
The Journal of reproductive medicine 09/2006; 51(8):628-34. · 0.87 Impact Factor
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ABSTRACT: In non-obstructive azoospermic patients (NOA) besides the mechanical treatment, vital spermatozoa from the tissue obtained from testes by biopsy can be enzymatically prepared.
To increase the sperm recovery success of testicular sperm extraction (TESE), suitable for ICSI.
Prospective, clinical study. In 177 consecutive men who presented with clinical and laboratory data indicating NOA, tissue samples were obtained by microdissection TESE method. Initially, mature spermatozoa were searched for by mechanical extraction technique shredding the biopsy fractions. In cases with no spermatozoa was observed after maximum 30 min of initial searching under the inverted microscope, the procedure was then followed by enzymatic digestion using DNAse and collagenase type IV. In cases of at least a mature spermatozoon could be obtained properly, ICSI was performed.
Of 177 cases with NOA, conventional mincing method extended with enzymatic treatment yielded successful sperm recovery for ICSI in 102 (57%). Overall in vitro tissue-processing time for patients with sperm recovery failure after 30 min of mechanical searching, was between 80 and 105 min (mean 96+/-9). Cleavage, embryo transfer and clinical pregnancy rates in mechanical plus enzymatic TESE patients were not significantly different from those of only mechanically TESE performed patients (p>0.05).
Combination of conventional TESE and enzymatic digestion is an effective method to recover spermatozoa suitable for ICSI. The benefit of the mincing combined with enzyme to sperm retrieval for NOA is firstly to shorten the mechanical searching time, thus minimizing further cellular damage as well as exposure to external conditions, and secondly to reduce the number of cases with sperm recovery failures.
European Journal of Obstetrics & Gynecology and Reproductive Biology 05/2005; 120(1):80-6. · 1.97 Impact Factor
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ABSTRACT: Sister-chromatid exchange analysis (SCE) and alkaline comet assay measure and analyze DNA damage in mammalian cells. This study assesses whether ovulation induction agents increase DNA damage in the lymphocytes of infertile women undergoing superovulation.
Prospective case control study in a university based hospital. Baseline and hCG day peripheral blood samples were withdrawn from 20 women with undergoing superovulation for unexplained infertility and baseline and luteinizing hormone (LH) peak day samples were also withdrawn from another 20 infertile women with unexplained infertility.
There was increased SCE frequency and DNA damage determined by comet assay on the hCG day compared to the basal state. The SCE increase was correlated with the hCG day estradiol (E2) but not with ampoules of follicular stimulating hormone (FSH). The SCE frequency was also increased naturally ovulating women; however this was significantly less than that in FSH receiving women.
Increased DNA damage may indicate for increased potential for malignancies after superovulation.
European Journal of Obstetrics & Gynecology and Reproductive Biology 04/2004; 113(1):73-7. · 1.97 Impact Factor
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ABSTRACT: This report describes the dysmorphic features and frequency of 22q11.2 deletion (del22q11) in 30 Turkish patients with conotruncal heart defects (CTHDs). Fluorescence in situ hybridization (FISH) analysis revealed deletions in the 22q11.2 region in nine (30%) individuals. The CTHDs in this group were tetralogy of Fallot (four cases), double-outlet right ventricle (DORV) (two cases), transposition of great arteries (two cases), and ventricular septal defect (VSD) associated with other CTHDs (one case). The frequency of del22q11 in the study group was relatively high because many of the patients with dysmorphic findings also had cardiac anomalies involving the pulmonary artery, ductus arteriosus, or the aortic arch and its main branches. Twenty of the 30 patients exhibited several dysmorphic findings. Two of the nine patients with del22q11 exhibited no apparent dysmorphic features other than sacral dimple. Interestingly, one of the patients with del22q11 had a phenotypic appearance similar to that seen in oculo-auriculo-vertebral spectrum (OAVS). This individual had left microtia, atresia of the external meatus, mandibular asymmetry, and peripheral facial nerve paralysis. His mental development was normal and there were no abnormalities on ophthalmological examination. The CTHDs in this patient were situs inversus dextrocardia, DORV, pulmonary stenosis, and VSD. Radiographs of this patient showed platybasia, complete fusion of C2-C3, and posterior fusion of the T1-T2 vertebrae. This particular case indicates that the phenotypic features of del22q11 and OAVS may overlap.
American Journal of Medical Genetics Part A 02/2003; 116A(2):129-35. · 2.39 Impact Factor
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ABSTRACT: It has been hypothesized that non-human milk feeding may increase the risk for cancer or for a specific cancer or group of cancers as well as the risk for diseases such as type-1 diabetes mellitus and Crohn's disease. Regarding DNA damage leading to cancer development in the absence of human milk protection, a comparison between infants fed human milk and cow's milk has been performed. Each group consisted of 35 infants, whose ages ranged from 9 to 12 months. The level of DNA damage in the peripheral blood lymphocytes of infants has been studied by the comet assay. A significant increase has been found in the number of limited DNA-damaged (p < 0.001) and extensive DNA-damaged (p < 0.001) cells of infants fed cow's milk. To our knowledge, this is the first study using the comet assay on infants not breast-fed. Supporting our previous SCE study, these results suggest that there is some level of DNA damage in the lymphocytes of infants not breast-fed and this may lead to malignancy in childhood or later in life.
Biology of the Neonate 02/2003; 84(2):135-41. · 1.90 Impact Factor
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ABSTRACT: Despite the fact that primary nocturnal enuresis (PNE) is self-limited and pathologically benign, the emotional stress and inconvenience that it produces, warrants treatment. Imipramine is one of the widely used drugs in PNE treatment. Although some mutagenic effects were suggested in imipramine administration, this toxicity has never been investigated in enuretic patients. The aim of this study was to evaluate the association of exposure to imipramine with DNA damage.
Thirty-five children treated with imipramine for at least 4.5 months who were in otherwise good health were accepted into the investigation. Twenty healthy sisters or brothers of the patients who did not use any long-term drugs were studied simultaneously as the control group. Comet assay was used to evaluate DNA damage.
Damaged (limited and extensive migrated) cells of the enuretic children who were taking imipramine were statically higher than that of the control group (P < 0.05) indicating a detectable DNA damaging effect of imipramine in human lymphocytes.
Our finding suggests that the difference in comet scores between two groups was induced by the imipramine treatment. The other possibility to be considered is the psychological stress of the children who were concerned by the symptoms and their parent's anxiety. As our preliminary data were based on a limited number of children, further research is needed considering the importance of this possible toxic effects which may be associated with mutagenicity.
Pediatrics International 01/2003; 44(6):617-21. · 0.63 Impact Factor
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ABSTRACT: Pregnancy achieved with sperm from a patient with globozoospermia is rare, even after ICSI, since the activation of the oocyte may not occur in this disorder. Therefore, activation of the oocytes by piezoelectricity or calcium ionophores has been suggested, although spontaneous activation of the oocyte after ICSI has been reported in some cases. We report a successful pregnancy in a couple in which the male partner had globozoospermia with microdeletions in the Y chromosome with no further assisted activation after ICSI. During the diagnostic study of the husband, increased numerical chromosome abnormalities after fluorescent in-situ hybridization (FISH) and microdeletions in AZFa; sY86 and AZFb; sY 131 were detected. Out of the 13 oocytes injected, four fertilized and a twin pregnancy was obtained after replacement of four embryos. Healthy twin girls were delivered after a term pregnancy. Some patients with globozoospermia may also have Y chromosome microdeletions, which subsequently may be inherited by the male offspring in cases of achievement of pregnancy.
Human Reproduction 08/2002; 17(7):1833-6. · 4.47 Impact Factor
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ABSTRACT: There are many advantages of human milk for infants, including protection against cancer development and the advantages have been emphasized in several studies. In this study, infants fed by human milk has been compared with those fed by cow's milk concerning DNA damage.
The level of genetic damage in the peripheral blood lymphocytes of infants who were fed mainly by cow's milk and breast milk has been studied by sister chromatid exchange (SCE) analysis, which is a sensitive measurement of chromosomal damage. Each group consisted of 30 infants, whose ages ranged from 9 to 12 months.
A significant increase (P < 0.0001) was found in the frequencies of SCE of infants not breast-fed (n = 30, mean SCE/cell +/- SD: 8.66 +/- 1.15) compared to those who were breast-fed (n = 30, mean SCE/cell +/- SD: 4.93 +/- 0.82).
To our knowledge, there has been no published study investigating SCE ratio regarding DNA damage in infants not breast-fed. Molecular mechanism of DNA damage caused by the absence of human milk protection is a subject of future investigations.
Pediatrics International 04/2002; 44(2):127-30. · 0.63 Impact Factor
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ABSTRACT: Sister chromatid exchange (SCE) frequencies were studied in patients with different types of ovarian malignancies and in healthy volunteers. The level of DNA damage in patients with ovarian malignancy and control subjects has also been studied by alkaline single cell gel electrophoresis (SCGE), also known as the comet assay.
Peripheral blood was collected from 30 patients after histological confirmation of malignancy and 20 healthy female volunteers. The cells were evaluated according to their grade of damage.
We found that the sister chromatid exchange frequencies of cancer cases were significantly greater than that of controls (P < 0.001). The frequency of exchange in chromosomal groups A, B, and C, which include chromosomes 1-12, was higher than that of the other chromosomal groups in both groups. Comparison of the results of the alkaline comet assay in patient and control subjects showed a significant difference in the number of damaged cells. The frequency of limited migrated and extensive migrated cells in the women with ovarian malignancies was higher than that of control women (P < 0.001).
SCE and SCGE can be used successfully to monitor DNA damage in women with ovarian cancer.
Gynecologic Oncology 01/2002; 84(1):62-6. · 3.89 Impact Factor
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Annals of Saudi medicine 23(1-2):64-6. · 1.07 Impact Factor
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ABSTRACT: AIMS, BACKGROUND AND STUDY DESIGN: Few studies have investigated the karyotypes of colorectal carcinomas with emphasis on the correlation between cytogenetic findings and clinicopathologic features. The aim of our study involving 20 colorectal adenocarcinomas was to determine their genomic alterations at the chromosomal level by correlating the cytogenetic findings with the extent of DNA damage and clinicopathologic parameters and to compare the results with those of healthy controls. RESULTS: Cytogenetic evaluation of patients and controls revealed 10 abnormal karyotypes in patients with adenocarcinomas located in the rectum, sigmoid and rectosigmoid regions. Four had numerical and six had structural abnormalities. CONCLUSIONS: Statistical analysis revealed a significant difference compared with controls (P <0.01). The karyotypes and the extent of DNA damage assessed by the comet assay were also significantly correlated with tumor stage (P <0.01) using the Kruskal-Wallis non-parametric test, while no statistical significance was observed in relation to patient age and smoking.
Tumori 89(3):305-10. · 0.86 Impact Factor
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ABSTRACT: Within the pathology of human reproduction, genetic abnormalities play an important role in spontaneous abortions. This paper describes the morphologic, karyotypic features of a consecutive series of singleton spontaneous abortions collected as part of this study and also reports the application of the alkaline comet assay to assess levels of DNA damage in 31 couples comprised of 13 control couples and a patient group of 18 couples with a history of more than one fetal loss. For the cytogenetic analyses, the conventional lymphocyte culture method was applied to all subjects. In this analysis, two women with habitual abortion were determined to carry balanced chromosomal translocation. The alkaline comet assay (single cell gel electrophoresis technique) was applied also to lymphocytes. The comparison of the results of alkaline comet assay in patient and control individuals showed a significant difference in the number of damaged cells. The cells were evaluated according to their grades of damage as: normal (undamaged—no migration), limited migration, (at low damage level) and extensive migration (comet imaged cells—with increasing numbers of breaks, DNA pieces migrate freely into the tail forming a comet image). The frequency of limited migrated and extensive migrated cells in the women in the patient group were higher than in the women in the control group (p<0.001). However, all above parameters were equal for husbands in both the control and patient group (p>0.05).
Mutation Research/Genetic Toxicology and Environmental Mutagenesis.
