New Insights beyond Established Norms: A Scoping Review of Genetic Testing for Infertile Men.

Purpose : From a diagnostic standpoint, certain approaches to genetic screening in clinical practice remain ambiguous in the era of assisted reproduction. Even the most current guidelines do not provide definite guidance on testing protocols, leaving clinicians to carefully determine which tests best serve patients struggling with infertility. The lack of uniformity in the current practice of male fertility evaluation can prove to be quite costly, thus necessitating healthcare practitioners to carefully appraise the necessity and weigh the advantages against potential economic and psychological detriments. The objective of this review is to map the existing literature on the general topic of the clinical indications of routine karyotyping and/or AZF screening in infertile men, identify key concepts, determine where the gaps are, and lastly, provide an overview of the conclusions drawn from a body of knowledge that varies widely in terms of methodologies or disciplines. Materials and Methods : A thorough search was conducted for the published findings up until July 2023, utilizing PubMed (MEDLINE). This comprehensive search involved the use of specific search keywords, either individually or in combination. The search terms employed were as follows: "Karyotype", "Klinefelter" or "KS" or "47,XXY", "AZF" or "Azoospermi*" and/or "microdeletion*" in the title or abstract. Once the titles and abstracts of selected articles were obtained, the complete texts of linked papers were meticulously scrutinized. Results : A total of 191 records were identified from PubMed. During screening, 161 records (84.3%) were eliminated. Finally, 30 papers were included in this scoping review, which was conducted in 18 countries. The number of sequence tag sites (STSs) used in the studies varied from 5 to 59. The rate of AZF deletions among patients with NOA ranged from 1.3% to 53%. The mean frequency was estimated to be 5.6%. The rate of YCM among patients with XXY karyotype was nil in 19 out of 30 studies (63%), whilst, in the remaining studies, the rate varied from 0.8% to 67%. Conclusion : This review provides insights into managing male infertility. The presence of spermatozoa in ejaculation and successful surgical retrieval cannot be excluded for individuals with AZFb/AZFbc microdeletions. Screening for Y chromosome microdeletions is not needed for mosaic or classic KS. Only 1% of individuals with sperm concentration exceeding 1×106 sperm/mL and less than 5×106 sperm/mL exhibit AZF microdeletions; therefore, testing referral for such populations may need reassessment. Individuals with mosaic monosomy X karyotype and certain chromosomal anomalies should be referred for AZF deletion screening. These findings have implications for male infertility management and future research. .

A review of recent developments in the application of nanostructures for sperm cryopreservation.

In the 1970s, sperm cryopreservation was presented as a unique route to fertility preservation. The ability to cryopreserve sperm from all species is challenging. The sperm cryopreservation process encompasses various cellular stresses such as increased osmotic pressure, ice crystal formation, and thermal shock, therefore decreasing the quality of sperm. The nanostructures due to their inherent features such as reactivity, high uptake, active surface area, and antioxidant activity, have contributed to modifying freezing protocols. In this review, the current state of the art with regards to emerging applications of nanotechnology in sperm cryopreservation are reviewed, some of the most promising advances are summarized, and the limitations and advantages are comprehensively discussed.

Evaluation of Predicting Factors Affecting Sperm Retrieval in Patients with Klinefelter Syndrome: A Prospective Study.

BACKGROUND: This study aimed to evaluate the predicting factors affecting sperm retrieval. We prospectively assessed the relationship between sonographic and microdissection testicular sperm extraction (mTESE) findings in Klinefelter syndrome (KS). MATERIALS AND METHODS: In this prospective study, 44 azoospermic men with 47, XXY karyotypes participated in this study. In order to evaluate the amount of blood supply in different parts of testicular tissue, a doppler ultra-sonographic was performed. Also, for the detection of sperm in this group mTESE technique was performed. RESULTS: The age average of positive mTESE and negative mTESE groups was 29.4 and 33.6 years, respectively. By comparing the testicle volume (based on the data obtained from the clinical examinations conducted by the urologist) it was determined that there is no significant difference between mTESE positive and negative groups. Folliclestimulating hormone (FSH) levels in men with negative mTESE (P=0.03) and testosterone levels in men with positive mTESE significantly increased (P=0.017). The overall rate of testis vascularity was significantly higher in the positive mTESE group than in the negative mTESE group. The clinical pregnancy rate in positive mTESE men was 9% per cycle, 16.6% per embryos were transferred (ET), and 12.5% per cycle. CONCLUSION: Totally, our observation indicated that there is not a significant relationship between sonographic and mTESE results in KS patients. However, more investigations with bigger sample Size can be useful to validate our results.

Bridging the Gap between AZF Microdeletions and Karyotype: Twelve Years' Experience of an Infertility Center.

PURPOSE: Despite all past efforts, the current guidelines are not explicit enough regarding the indications for performing azoospermia factor (AZF) screening and karyotype, burdening clinicians with the decision to assess whether such tests are meaningful for the infertile male patient. These assessments can be costly and it is up to the healthcare practitioner to decide which are necessary and to weigh the benefits against economic/psychological harm. The aim of this study is to address such gaps and provide update on current management options for this group of patients. MATERIALS AND METHODS: To address such gaps in male infertility management and to elucidate whether AZF screening is indicated in individuals who concomitantly harbor chromosomal abnormalities we conducted a retrospective cohort analysis of 10,388 consecutive patients with non-obstructive azoospermia (NOA) and severe oligozoospermia. RESULTS: Previously, it has been suggested that all NOA cases with chromosomal defects, except males with 46,XY/45,X karyotype, have no indication for AZF screening. Our findings revealed that cases carrying the following chromosomal abnormalities inv(Y)(p11.2q12); idic(Y)(q11.2); 46,XY,r(Y); idic(Y)(p11.2) and der(Y;Autosome) (76/169; 44.9%; 95% CI, 37.7-52.5) should also be referred for AZF deletion screening. Here, we also report the correlation between sperm count and AZF deletions as a secondary outcome. In accordance with previously reported data from North America and Europe, our data revealed that only 1% of cases with >1×106 sperm/mL had Y chromosome microdeletions (YCMs). CONCLUSIONS: In the era of assisted reproduction, finding cost-minimization strategies in infertility clinics without affecting the quality of diagnosis is becoming one of the top prioritized topics for future research. From a diagnostic viewpoint, the results reflect a need to reconsider the different karyotype presentations and the sperm count thresholds in male infertility guidelines as indicators for YCM screening during an infertility evaluation.

Diagnostic Value of Pyruvate Kinase Isoenzyme Type M2 in Colon Cancer Proven with Colonoscopy.

BACKGROUND: Colonoscopy is the gold standard for colon cancer screening; it is also associated with a high cost and complication. Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed M2 pyruvate kinase (M2-PK). The aim of this study was to determine the diagnostic accuracy of fecal M2-PK for colon cancer. MATERIALS AND METHODS: Forty-nine patients with colon cancers and 49 healthy controls were selected consecutively among individuals undergoing screening colonoscopy for various indications. The diagnosis was confirmed by histology. M2-PK measurements were done by enzyme-linked immunosorbent assay of fecal occult blood test (FOBT) and immunological FOBT (IFOBT) according to the manufacturer's instructions. RESULTS: M2-PK > 9 (U/mL) was the best cutoff point in the detection of colon cancers. In this cutoff point, sensitivity and specificity were 87.8% and 91.8%, respectively, and accuracy was 89.8%. The sensitivity and specificity of IFOBT were 93.9% and 100%, respectively, and accuracy was 96.9%. The sensitivity and specificity of FOBT were 65.3% and 100%, respectively, and accuracy was 82.6%. CONCLUSION: IFOBT with high sensitivity and specificity and accuracy and low cost is the best fecal screening test. The current study suggests that fecal M2-PK can be used for high-risk colon cancer patients and negative IFOBT that refused colonoscopy as a precolonoscopy screening test.

The interleukin 28B gene polymorphism, rs8099917, in patients with chronic hepatitis C and response to the treatment with pegylated interferon and ribavirin.

BACKGROUND: The present study aimed to determine the frequency of the IL28B polymorphism rs8099917 in patients with genotype 1 hepatitis C virus (HCV) infection treated with pegylated-interferon-α2b (PEG-IFN-α2b) and ribavirin (RBV) and its treatment outcome. MATERIALS AND METHODS: The IL28B rs8099917 genotypes were determined among 100 HCV-infected patients and the viral load was also estimated. PEG-IFN-α2b and RBV combination were administrated to the patients for 48 weeks and the treatment outcome was defined. RESULTS: Sixty-seven (67%), 27 (27%), and 6 (6%) of 100 patients were determined as TT, GT, and GG genotype, respectively. The response rate to treatment was significantly higher in patients with TT genotype. CONCLUSION: According to the results of the present study, patients with IL28B rs8099917 TT genotype achieve higher sustained virological response than the GT and GG genotypes. Thus, when there are no alternatives, treatment with PEG-IFN-α2b and RBV combination can be suggested in patients with IL28B TT genotype.

Correlation between Vitamin D3 level and extrahepatic manifestation in chronic hepatitis type-C virus patients.

BACKGROUND: Chronic hepatitis type-C virus (HCV) infection is one of the most common worldwide viral disorders, which leads to various clinical complications as well as extrahepatic manifestations. Furthermore, Vitamin D3 has also been reported to have relationship with the mentioned complications. The aim is to evaluate the correlation between Vitamin D3 level and extrahepatic manifestation in chronic HCV patients. MATERIALS AND METHODS: This cross-sectional study has been carried out on 90 patients with chronic hepatitis C. The level of Vitamin D3 was assessed in plasma of 90 patients with chronic HCV. Genotyping was done and clinical and sign and symptoms of recruited patients were gathered. Extrahepatic manifestations were evaluated and the correlation of blood, hepatic, and immunological factors and the level of Vitamin D3 were assessed. RESULTS: Most of our patients were male (92% vs. 8%). Twenty-nine percent had the insufficient amount of Vitamin D3 (21-30 ng/ml), and the remains had the Vitamin D3 level between 13-20 ng/ml. Furthermore, our assessment demonstrated that deficiency of Vitamin D3 was associated with the extrahepatic manifestations such as purpura (odds radio [OR] [95% confidence interval (CI) 95%] = 8.80 [1.74-44.47], P = 0.004), vasculitis (OR [95% CI] = 11.70 [3.01-45.41], P < 0.001), arthralgia (OR [95% CI] = 20.26 [4.21-97.47], P < 0.001), myalgia (OR [95% CI] = 4.00 [1.01-17.27], P = 0.048), and glomerulonephritis (P = 0.021). CONCLUSION: According to our results, the extrahepatic manifestation in the patients with sufficient levels of Vitamin D3 would be less possible. In fact, it could be stated that deficiency in the Vitamin D3 can have a significant relationship with these manifestations.

Fecundity in an infertile man with r(15) - a challenge to the current paradigm.

Ring chromosome 15 [r(15)] is a rare condition with a mild-to-severe growth failure, mental disabilities, café-au-lait spots, specific facial features, fertility difficulties and other minor dysmorphic stigmata. Of almost 50 affected individuals reported in the literature, none were assessed for the precise breakpoint positioning, which creates uncertainty in defining a specific phenotype for the deleted segment. This study reports for the first time the vertical transmission of r(15) in three consecutive generations of a family, including a subfertile man, his mother and his newborn infant. Array comparative genomic hybridization results revealed a 563 kb deletion of 15q26.3, overlapping the OMIM genes SNRP1, PCSK6 and TM2D3. The hemizygosity was confirmed with real-time quantitative PCR. Regarding haploinsufficiency in 15q26.3, based on phenotypic characteristics of the carriers, the only rational conclusion is that SNRPA1, PCSK6 and TM2D3 are not gene-dosage sensitive and are probably inherited in an autosomal-recessive manner. Given growth deficiency in r(15) carriers, this shows that the growth retardation cannot be attributed entirely to IGF1R. The predominance of female patients with r(15) is the next as yet unanswered question; incomplete penetrance and/or variable expression of gene(s) in different genders may be involved, but further evidence is needed to support this idea.

Prevalence of occult hepatitis B virus infection in hemodialysis patients in Isfahan, Iran.

BACKGROUND: The absence of a detectable hepatitis B surface antigen (HBsAg) with or without hepatitis B core antibody (anti-HBc) or hepatitis B surface antibody (anti-HBs) in the presence of hepatitis B virus-DNA (HBV-DNA) is defined as occult HBV infection. This study was aimed to evaluate the prevalence of occult HBV infection in patients receiving hemodialysis (HD) in Isfahan, Iran. MATERIALS AND METHODS: This cross sectional study was done on 400 patients without acute or chronic HBV infection with end-stage renal disease undergoing regular HD. Blood samples were collected prior to the HD session, and serological markers of viral hepatitis B included HBsAg, anti-HBs and anti-HBc were measured using standard third generation commercially available enzyme immunoassays kit, then samples of positive anti-HBc and negative anti-HBs were tested for HBV DNA using quantitative real-time polymerase chain reaction techniques. Data were analyzed by SPSS using t-test and Chi-square test. RESULTS: The mean age of patients was 51.6 ± 11.2 years. Anti-HBc positive was observed in 32 (8%) of 400 studied patients with negative HBsAg. Of 32 patients with anti-HBc positive, 15 were males and 17 were females with mean age of 49.7 ± 12.6 years. Among 32 patients with anti-HBc positive, 10 patients were negative for anti-HBs. All of 10 patients were negative for HBV DNA. The prevalence of occult HBV infection was 0%. CONCLUSIONS: The prevalence of occult HBV infection in HBsAg negative patients undergoing HD was 0% and look to be among the lowest worldwide. So, occult HBV infection is not a significant health problem in HD patients in this region.

Association between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in middle age patient with non-alcoholic fatty liver disease.

BACKGROUND: Liver biopsy is required to diagnose non-alcoholic steatohepatitis in patients with suspected non-alcoholic fatty liver disease (NAFLD). This study aimed to examine the relationship between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in patient with NAFLD. MATERIALS AND METHODS: In this cross-sectional study, a total of 180 patients, with an age range of 18-60 year old, with NAFLD based on ultrasonograghic findings were evaluated. Age, sex, body mass index, diabetes mellitus, hypertension, family history of liver disease and laboratory parameters recorded for all patients. Hence, grade of steatosis and stage of fibrosis were evaluated by liver biopsy. RESULTS: A total of 220 patients were enrolled. Liver biopsy was performed in 180 patients. Mean age was 43 ± 10.6 years old and 66% were male. Ultrasonograghic findings showed mild, moderate and severe NAFLD was define in 100 (55.5%), 72 (40%) and 8 (4.5%) of patients, respectively. Liver biopsies showed that steatosis scores of <5%, 5-33% and 33-66% was define in 56 (31%), 116 (64%) and 9 (5%) of patients, respectively. Furthermore, fibrosis was defined as follow; none 92 (51%), mild 68 (38%), moderate 11 (6%), bridging 5 (3%) and cirrhosis 3 (2%) patients. There was no statistically significant relationship between ultrasonograghic findings and steatosis scores (P = 0.44), but statistically significant relationship was found between ultrasonograghic findings and fibrosis stage (P = 0.017). CONCLUSION: Findings revealed that, in patients with NAFLD, ultrasonographic finding were not in associate to steatosis, but were in relation with fibrosis stage.

Evaluation of 1100 couples with recurrent pregnancy loss using conventional cytogenetic, PGD, and PGS: hype or hope.

Recurrent pregnancy loss (RPL) is an important clinical problem, mostly resulting from chromosomal or genetic defects, while in 30-60% of cases, it is idiopathic. The aim of this study is to evaluate the frequency and types of chromosomal abnormalities, also pre-implantation genetic diagnosis (PGD) and pre-implantation genetic screening (PGS) outcomes among Iranian couples with RPL. This retrospective study was conducted on 1100 Iranian couples (2200 individuals) with RPL referred to Royan Institute between 2008 and 2014. Karyotyping had been performed using standard cytogenetic techniques. PGD results of RPL patients with abnormal karyotypes and PGS results of RPL patients with normal karyotypes were also analyzed. The frequency of chromosomal abnormalities in these patients was 4.95%. Women demonstrated more abnormalities (6.82%) in comparison to men (3.09%). The successful rate of pregnancy after PGD and PGS was 52 and 18.64%, respectively. The observation of 4.95% chromosomal abnormalities among the patients with RPL could support this hypothesis that there is a direct relationship between chromosomal abnormalities and RPL. More than half of the patients who underwent PGD had successful pregnancy; therefore, this approach can improve the success rate of pregnancy in them. The results of PGS cycles showed that this technique could increase the live birth rate in RPL patients.

Thrombophilic genes alterations as risk factor for recurrent pregnancy loss.

OBJECTIVE: The important polymorphisms leading to inherited thrombophilia are Factor V Leiden (FVL), Prothrombin G20210A and MTHFR C677T and A1298C. The frequencies also the correlation among these polymorphisms and RPL have been reported controversially in various populations. Our clinic is one of the referral centers in reproductive biomedicine in which patients in all over Iran refer to; thus the results of this study could be considered clinically beneficial. Besides, in the present study, not only the frequency of specific but also multiple thrombophilic gene alterations were compared in Iranian women with RPL and a control group. METHODS: The patients group comprised 330 women with three or more consecutive RPLs. The control population included 350 women with at least one child and no history of pregnancy loss. FVL, Prothrombin G20210A and MTHFR C677T polymorphisms were analyzed by Strip assay kit. MTHFR A1298C was genotyped by PCR-RFLP. RESULTS: The frequencies of FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C mutations in patients were 8.48, 4.24, 45.45 and 59.39%, and in controls were 2.86, 2.86, 34.28 and 6%, respectively. CONCLUSIONS: The present data showed that FVL, MTHFR polymorphisms also combined with thrombophilic gene mutations have a strong association with RPL.

Fecal calprotectin is a useful marker to diagnose ulcerative colitis from irritable bowel syndrome.

BACKGROUND: This study was aimed to evaluate the predictive value of fecal calprotectin in patients with ulcerative colitis from patients with irritable bowel syndrome (IBS). MATERIALS AND METHODS: Between May and October 2013, 88 adult patients, between the age 18 and 65 years with a history of chronic diarrhea of unknown origin were assessed. Standard colonoscopies were performed in all patients to assess ulcerative colitis. Before colonoscopies, they were asked to supply a stool specimen. Fecal calprotectin value was measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: The mean of age, gender combination, and body mass index were not significantly different between patients with ulcerative colitis or IBS. The duration of disease in ulcerative colitis patients was significantly higher than IBS patients (P < 0.0001). The level of calprotectin in ulcerative colitis patients was significantly higher than IBS patients (265.9 vs 115.8, respectively, P = 0.001). Also, cutoff value >164 µg/g with sensitivity and specify of 57 (CI: 41%-71.6%), and 75 (CI: 59.7%-56.8%), respectively, was the best for discrimination between patients with ulcerative colitis and those with IBS. CONCLUSION: Our results show that fecal calprotectin as a noninvasive method, which can be used to identify patients with ulcerative colitis from IBS patients has low sensitivity and specificity.

Efficacy of double dose recombinant hepatitis B vaccination in chronic hepatitis C patients, compared to standard dose vaccination.

BACKGROUND: Hepatitis B virus (HBV) vaccination is a well-known, safe and effective way for protection against HBV infection; however, non-responders remain susceptible to infection with HBV. This is so important in patients with any kind of chronic liver disease, especially chronic hepatitis C virus (HCV) patients in whom acute HBV infection may lead to decompensation of liver disease. Some of the studies have shown that immunogenicity of HBV vaccination is decreased in these patients. The aim of this study was to evaluate the efficacy and safety of double dose vaccination of HBV in these patients, compared with standard dose vaccination in similar patients and healthy adults. METHODS: A total of 64 patients with chronic HCV infection were randomized into 2 groups of 32. Group A received standard dose HBV vaccine, at 0, 1, 6 months, whereas group B received double dose HBV vaccine. Group C consisted of 32 healthy adults who also received standard dose vaccination. At 1 month after the end of vaccination, Hepatitis B surface antibody (HBsAb) titer was checked in all participants and the results were compared. RESULTS: There was no significant difference in age or sex among three groups. The response rate in groups B and C was 100% (all had HBsAb titer >10 mIU/mL), while in group A, 4 patients (12.5%) were non-responders (HBsAb titer < 10 mIU/mL). The difference in response rate was statistically significant between Group A and the other two groups (P < 0.05). CONCLUSIONS: The efficacy of standard dose HBV vaccination in patients with chronic HCV infection was suboptimal. Using double dose vaccination in these patients was an effective way to increase the antibody response.

Nutritional status in patients with ulcerative colitis in Isfahan, Iran.

BACKGROUND: Malnutrition is common among patients with inflammatory bowel disease. The present study aimed to investigate the nutritional status of ulcerative colitis (UC) patients in Isfahan, Iran. MATERIALS AND METHODS: In this descriptive analytical cross-sectional study, between Dec 2011 and Jun 2012, 99 patients with UC were randomly selected and evaluated. Age, sex, duration of disease, body mass index (BMI) and laboratory parameters recorded for all patients. Nutritional risk index (NRI) was calculated and its association with patients' variables was assessed with regard to UC disease severity. RESULTS: Twelve patients out of 99 patients had mild UC and 87 patients had moderate to severe UC. Based on the NRI, 90.9% were not malnourished and 9.1% were at moderate to severe risk for malnutrition. Among laboratory parameters only, serum potassium level in patients with moderate to severe UC was significantly higher than those with mild UC (P = 0.017). Other laboratory parameters were similar between patients stratified by US status. Patients age s significantly correlate with serum vitamin D, immunoglobulin a (IgA) and potassium level (P > 0.05), also duration of disease was significantly correlate with Phosphorus (P = 0.024) among laboratory parameters. CONCLUSION: In studied UC patients, malnutrition risk was based on degree of disease severity. Patients with moderate to severe UC were more at risk for malnutrition compared to the patients with mild UC. Furthermore, among laboratory parameters only serum potassium level was higher among patients with moderate to severe UC compared to others.

Prevalence and risk factors of hepatitis B and C viruses among hemodialysis patients in Isfahan, Iran.

BACKGROUND: The aim of this study was to assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) and their associated risk factors among hemodialysis patients in Isfahan, Iran in 2011. MATERIALS AND METHODS: In this cross-sectional study, a total of 499 chronic hemodialysis patients from eight governmental hemodialysis centers were tested. Demographic information, time duration on hemodialysis, history of blood transfusion, and the number of transfused blood units as risk factors to HBV and HCV infections were calculated. The status of HBsAg and anti-HCV was assessed by serological testing. RESULTS: The overall prevalence of HBV-positive and HCV-positive among study population was 1.2% and 5.2%, respectively. Age, sex, and time duration on hemodialysis were not statistically significant in HBV- and HCV-patients compared with other hemodialysis patients (P > 0.05). History of blood transfusion and the number of transfused blood units in HBV infected patients were similar to other patients (P > 0.05). The main risk factors in hemodialysis patients infected by HCV were history of blood transfusion and the number of transfused blood units (P < 0.0001). CONCLUSION: In conclusion, the prevalence of HBV and HCV infections in hemodialysis centers in Isfahan is lower than in some other cities of Iran. History of blood transfusion and the number of blood units transfused might be a risk factor for HCV gaining. However, further studies are needed to assess the role of other demographic and clinical risk factors in these patients.

A Rare De novo Complex Chromosomal Rearrangement (CCR) Involving Four Chromosomes in An Oligo-asthenosperm Infertile Man.

Complex chromosomal rearrangements (CCRs) are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization (FISH) procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor (AZF) region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms.

Delineating the association between isodicentric chromosome Y and infertility: a retrospective study.

OBJECTIVE: To report on 14 infertile patients who had a de novo form of the same isodicentric (idic)(Yq) karyotype with variable degrees of mosaicism. DESIGN: Retrospective study and review of the literature. SETTING: Medical genetics laboratory in a research institute for reproductive biomedicine. PATIENT(S): Fourteen infertile patients, including 13 male patients and 1 female patient who had infertility with the same idic(Y) karyotype. INTERVENTION(S): Conventional cytogenetic methods, fluorescence in situ hybridization (FISH) on seminal germ cells and blood, and polymerase chain reaction (PCR)-based molecular approaches. MAIN OUTCOME MEASURE(S): Karyotype, FISH, and PCR results. RESULT(S): Cytogenetic results revealed abnormal Y chromosome: 45,X/46,X,idic(Y)(q11.22). The FISH technique on blood lymphocytes confirmed a rearranged Y chromosome, with two centromeres and two SRY signals, and marker chromosome with various levels of mosaicism. Moreover, aneuploidy of sex chromosomes was also detected in haploid seminal germ cells. Multiplex PCR analysis of blood samples demonstrated microdeletion in AZFb and AZFc loci. CONCLUSION(S): Because of the resemblance between inversion of chromosome Y and idics(Y), use of confirmatory techniques (e.g., FISH or PCR-based methods) could help prevent medical errors in healthcare systems and precisely delineate chromosomal aberrations in infertile patients when clinical data fail to clarify the cause of infertility.

The response of mouse embryonic stem cells to low doses of γ-radiation: evidence for an adaptive response.

Low doses of ionizing radiation may induce an adaptive mechanism which protects embryonic stem cells against higher doses, a phenomenon which was reported previously for somatic cells. In this study, a possible adaptive response (AR) was evaluated by measuring cell survival (MTT assay) and chromosomal aberrations (micronucleus assay). Thymidine-synchronized mouse embryonic stem cells (mESCs) were exposed to 2.5, 3.7, or 5cGy (60)Co γ-rays and, after 5h challenged by a dose of 150cGy. mESCs pre-irradiated at 2.5cGy showed an adaptive response.