Semen Quality is Associated with Sperm Aneuploidy and DNA Fragmentation in the United Arab Emirates Population.

Background: Sperm chromosome aneuploidy and the extent of sperm DNA fragmentation (SDF) are contributing factors to male infertility. Their extent can be measured using platforms such as sperm chromatin dispersion (SCD) and sperm fluorescence in situ hybridization (sFISH). Additional studies, however, are needed to understand the clinical applicability of these in vitro tests based on statistically validated thresholds. Aim: The primary objective of this study was to report the incidence of SDF and chromosomal aneuploidy with respect to sperm quality in the United Arab Emirates (UAE) population. In addition, we wished to establish clinically useful SDF and aneuploidy cutoff values. Materials and Methods: A total of 302 subjects were enrolled in this study. The control group consisted of n = 100 (33.11%) reproductively-proven fertile men, and the case group consisted of n = 202 (66.89%) infertile men. The sperm quality of the cases was further subclassified as normospermia ("Normo," n = 88; 43.56%); teratozoospermia ("T," n = 40; 19.80%); oligoasthenoteratozoospermia ("OAT," n = 37; 18.32%); asthenoteratozoospermia ("AT," n = 19; 9.41%); or oligoteratozoospermia ("OT," n = 18; 8.91%). The assessments of SDF were done using SCD tests. Chromosomal aneuploidy (Chr 13, 18, 21, X, and Y) was investigated using sFISH. Furthermore, based on the fragmentation index, cases were divided into subfertile groups defined as low, medium, high, and severe. The Mann-Whitney test was used to set the upper threshold value for sFISH, and the odds ratio was used for SDF assessment. Results: Cases having sperm quality "AT," "OAT," and "OT" together with the moderate, high, and severe subfertile groups had the highest DNA fragmentation indices: 31.58%, 27.03%, and 22.22%, respectively. In the sFISH analyses, groups with sperm quality "OAT," "T," and "OT" exhibited high degrees of abnormalities: 86.49%, 52.50%, and 50%, respectively. The most common chromosomal abnormalities found were "sex chromosome hyperploidy (XY18)" and "diploid (Chr 13, 21)." The incidences of sperm quality with respect to SDF and sFISH are also reported in detail. Conclusions: This is the first study in the UAE which shows SDF and sFISH incidences together with sperm quality. This study also establishes SDF and sFISH cutoff values for the UAE population.

Low Gonadotropin Dosage Reduces Aneuploidy in Human Preimplantation Embryos: First Clinical Study in a UAE Population.

TYPE OF STUDY: Retrospective analysis of embryo aneuploidy in patients undergoing in vitro fertilization (IVF) cycles. AIM: To evaluate factors that might affect the incidence of embryo aneuploidy during IVF cycles. METHODS: Three hundred twelve IVF cases were included in the present study. Preimplantation genetic testing for aneuploidy (PGT-A) was performed for all the subjects involved. Subject stratification was done based on maternal age, gonadotropin drug dosage, and IVF outcomes data. Maternal age <35 years were placed in the "Young" age group and age ≥35 years were placed in the "Advanced Maternal Age" group. Similarly, IVF drug administered <200 International units (IU) was considered "low dosage," group and ≥200 IU were considered "high dosage" group. Patients were stratified into four groups-group 1: age <35 years and administered <200 IU; group 2: age <35 years and administered ≥200 IU; group 3: age ≥35 years and administered at <200 IU; and group 4: age ≥35 years and administered ≥200 IU. PGT-A results were attained using a next-generation sequencing-based protocol. Embryo transfer was guided by transabdominal ultrasound. Statistical significance was calculated with the use of chi-square test. RESULTS: One thousand fifty blastocyst trophectoderm biopsies from 312 IVF cases were retrieved. The IVF outcome of a total of 105 normal cases resulted in 65.71% pregnancies. Stratifying for maternal age and IVF drug stimulation with PGT-A analyses we found the euploid embryo percentages equal to 37.59% in Group 1; 16.18% in Group 2; 22.44% in Group 3; and 2.59% in Group 4. Similarly the aneuploid embryo (percentage)s were 62.40% for Group 1; 83.81% for Group 2; 77.55% for Group 3; and 87.40% for Group 4. CONCLUSION: This is the first clinical study reporting that gonadotropin dosage may act as a contributing factor in increasing aneuploidy incidences for the patients undergoing IVF cycles in the UAE population. This study shows that in all patient age groups, lower drug stimulation leads to an increasing trend in embryo euploidy.

Association of functional SNP-1562C>T in MMP9 promoter with proliferative diabetic retinopathy in north Indian type 2 diabetes mellitus patients.

OBJECTIVE: Retinal angiogenesis is a hallmark of diabetic retinopathy. Matrix Metalloproteinases (MMPs) are involved in degradation of extracellular matrix (ECM). Functional SNP-1562C>T in the promoter of the MMP-9 gene results increase in transcriptional activity. The present work was designed to evaluate the contribution of functional SNP-1562C>T of MMP-9 gene to the risk of proliferative diabetic retinopathy (PDR) in type 2 diabetes mellitus (T2DM) patients in north Indian Population. METHODS: This Case control study comprised of a total of 645 individuals in which 320 were T2DM patients out of which 73 had PDR, 98 had non- proliferative diabetic retinopathy (NPDR), 149 T2DM cases without any eye related disease (DM) and 325 non diabetic healthy individuals as controls (non DM controls). Genotyping for SNP-1562C>T of MMP-9 was done by polymerase chain reactions followed by restriction analyses with specific endonucleases (PCR-RFLP). DNA sequencing was used to ascertain PCR-RFLP results. RESULTS: T allele frequency in PDR patients was 32.1%, 20.4% in NPDR, 15.4% in DM and 13.7% in controls. Statistically significant difference was observed in both allele and genotype distribution between the PDR versus non-DM control group (p<0.0001 by T allele; p=0.002 by TT and p<0.0001 by CT genotype). CONCLUSIONS: The present study suggests that the functional SNP-1562C>T in the promoter of the MMP-9 gene could be regarded as a major risk factor for PDR as increased MMP-9 production from high expressing T allele may promote retinal angiogenesis.