Molecular Diagnosis of Human Papillomavirus: Comparison Between Cervical and Vaginal Sampling

Background: Human papillomavirus (HPV) is the most significant cause of cervical cancer. In view of the number of drawbacks associated with endocervical sampling, the gold standard for HPV detection, this study examined the utility and specificity of vaginal sampling as an alternative for endocervical sampling for the routine detection of HPV. Case study: The study comprised 51 women who tested positive and 54 women who tested negative for endocervical HPV by polymerase chain reaction (PCR), confirmed by histopathology. At the time of specimen collection, both (speculum-assisted) endocervical and vaginal (no speculum) scrapings were isolated from HPV positive and negativewomen, and HPV DNA was assessed by PCR using the MY09/MY11 primer system;HPV type was identified by hybridization of PCR products with type-specific biotinylated DNA probes. Each participant served as her own control. HPV was detected in vaginal and cervical scrapes from all HPV-positive but not HPV-negative women. In HPV-positive women the same HPV type was found in vaginal and endocervical scrapings (positive predictive value = 1.0). Conclusion: Correlation between vaginal and endocervical sampling methods was excellent in detecting the presence of HPV DNA and for identifying distinct HPV genotypes. Utilization of vaginal testing for routine HPV detection, and for the long-term follow-up of persistent HPV infection, is therefore recommended

AGE-DEPENDENT CHANGES IN ANTI-MÜLLERIAN HORMONE LEVELS IN LEBANESE FEMALES: CORRELATION WITH BASAL FSH AND LH LEVELS AND LH/FSH RATIO: A CROSS-SECTIONAL STUDY

Background To investigate the age-dependent changes in circulating anti-Müllerian hormone (AMH) levels in healthy Arabic-speaking Lebanese women, and to correlate changes in serum AMH levels with serum FSH and LH values, and LH/FSH ratio. Methods Cross-sectional study, involving 1190 healthy females, age 17–54 years, with regular menses and both ovaries. Serum AMH levels (ng/ml) were measured by ELISA. Results There was an inverse proportion of AMH and subject’s age, which declined from median 6.71 (2.91) ng/ml in young subjects, to 0.68 (0.45) ng/ml in subjects older than 50 years. Average yearly decrease in median AMH levels was 0.27 ng/ml/year through age 35, but then diminished to 0.12 ng/ml/year afterwards. Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of age as determinant of AMH levels. In contrast to AMH, FSH levels increased progressively from 5.89 (0.11–62.10) ng/ml in young subjects, to 38.43 (3.99–88.30) ng/ml in subjects older than 50 years. On the other hand, age-dependent changes in LH/FSH ratio paralleled those of AMH. Linear regression modeling testing the independent effect of AMH on FSH and LH, adjusted for age, showed that AMH was significant predictor of FSH and LH/FSH ratio, but not LH. This did not contribute significantly to baseline LH and FSH prediction. Conclusions Circulating AMH levels are inversely related to age as also shown elsewhere, and are predictors of LH/FSH ratio and FSH but not LH levels in eumenorrheic females

Common genetic variants in the sex hormone-binding globulin (SHBG) gene in idiopathic recurrent pregnancy loss: a case control study

Abstract Background A role for sex hormone-binding globulin (SHBG) in determining the pregnancy outcome was evidenced by the rise in SHBG levels during pregnancy linked with favorable pregnancy, while reduction in SHBG levels and hyperandrogenemia were linked with poor pregnancy outcome. Since SHBG production is genetically determined, this study investigated the association of SHBG polymorphisms with the susceptibility to recurrent pregnancy loss (RPL). Methods Retrospective case-control study, involving 308 women with RPL, and 310 control women RPL, defined as ≥3 consecutive miscarriages, and with the same partner, was the main outcome measure. SHBG genotyping was done by allelic exclusion method (real-time PCR). Results Of the seven tested SHBG SNP, lower MAF of rs6257 was seen in RPL cases than in control women, which was linked with lower risk of RPL, after controlling for key covariates. At the genotype level, significantly higher frequencies of heterozygous rs858521 and rs6259, and homozygous rs858521 genotype carriers, and reduced frequency of heterozygous rs6257 and homozygous rs6257 and rs6259 genotype carriers were seen in RPL cases vs. control women, respectively. Univariate regression analysis confirmed the positive association of rs858521 and rs6259 with RPL. Multivariate regression analysis confirmed the positive association of rs858521 heterozygote and homozygote genotypes with RPL; only heterozygous rs6259 remained associated with RPL. Haploview analysis demonstrated marked linkage disequilibrium among 6 of the 7 tested SHBG SNP. Of the possible 6-locus haplotypes, 12 were common, and were included in subsequent analysis. Within these haplotypes, only increased frequency of CCGTGA haplotypes was seen in RPL cases, thus conferring RPL susceptibility. Conclusions Specific SHBG variants, and SHBG haplotypes are associated with altered risk of RPL, suggesting role for SHBG as RPL candidate gene

Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case–control study

Abstract Background This study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity. Methods Retrospective case–control study performed in outpatient obstetrics/gynecology clinics. Study subjects comprised 308 women with RPL, defined as ≥ 3 consecutive miscarriages of unknown etiology, and 310 control women. ADIPOQ genotyping was done by allele exclusion method on real-time PCR. Results Of the 14 ADIPOQ variants tested, the minor allele frequency (MAF) of rs4632532, rs17300539, rs266729, rs182052, rs16861209, and rs7649121 were significantly higher, while rs2241767, and rs1063539 MAF were lower in RPL cases, hence assigning RPL-susceptibility and protection to these variants, respectively. Higher frequencies of heterozygous rs17300539 and rs16861209, and homozygous rs4632532, rs266729, and rs182052 genotypes, and reduced frequencies of heterozygous rs1063539 and rs2241767, homozygous rs2241766 genotypes were seen in RPL cases. ADIPOQ rs4632532, and rs2241766 were associated with RPL in obese, while rs1063539 and rs16861209 were associated with RPL in non-obese women; rs182052 and rs7649121 associated with RPL independently of BMI changes. Based on LD pattern, two haplotype blocks were identified. Within Block 1 containing rs4632532, rs16861194, rs17300539, rs266729, rs182052, rs16861209, rs822396, and rs7649121, increased frequency of CAGGACAT and TAACGAAA, and reduced frequency of TAGCGCAA haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection, respectively. Conclusion This is the first study to document contribution of ADIPOQ variants and haplotypes with RPL, and also to underscore the contribution of obesity to genetic association studies

Maternal and cord serum levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) among Lebanese pregnant women and predictors of exposure

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Maternal Serum, Cord and Human Milk Levels of Per- and Polyfluoroalkyl Substances (PFAS), Association with Predictors and Effect on Newborn Anthropometry

International audienceBackground: The understanding of per- and polyfluoroalkyl substances (PFAS) health effects is rapidly advancing among critical populations. Therefore, the objective of this study was to assess PFAS serum levels among Lebanese pregnant women, cord serum and human milk levels, their determinants, and effects on newborn anthropometry. Methods: We measured concentrations of six PFAS (PFHpA, PFOA, PFHxS, PFOS, PFNA and PFDA) using liquid chromatography MS/MS for 419 participants, of which 269 had sociodemographic, anthropometric, environmental and dietary information. Results: The percentage of detection for PFHpA, PFOA, PFHxS and PFOS was 36.3–37.7%. PFOA and PFOS levels (95th percentile) were higher than HBM-I and HBM-II values. While PFAS were not detected in cord serum, five compounds were detected in human milk. Multivariate regression showed that fish/shellfish consumption, vicinity to illegal incineration and higher educational level were associated with an almost twice higher risk of elevated PFHpA, PFOA, PFHxS and PFOS serum levels. Higher PFAS levels in human milk were observed with higher eggs and dairy products consumption, in addition to tap water (preliminary findings). Higher PFHpA was significantly associated with lower newborn weight-for-length Z-score at birth. Conclusions: Findings establish the need for further studies, and urgent action to reduce exposure among subgroups with higher PFAS levels