Conserved genes regulating human sex differentiation, gametogenesis and fertilization.

The study of the functional genome in mice and humans has been instrumental for describing the conserved molecular mechanisms regulating human reproductive biology, and for defining the etiologies of monogenic fertility disorders. Infertility is a reproductive disorder that includes various conditions affecting a couple's ability to achieve a healthy pregnancy. Recent advances in next-generation sequencing and CRISPR/Cas-mediated genome editing technologies have facilitated the identification and characterization of genes and mechanisms that, if affected, lead to infertility. We report established genes that regulate conserved functions in fundamental reproductive processes (e.g., sex determination, gametogenesis, and fertilization). We only cover genes the deletion of which yields comparable fertility phenotypes in both rodents and humans. In the case of newly-discovered genes, we report the studies demonstrating shared cellular and fertility phenotypes resulting from loss-of-function mutations in both species. Finally, we introduce new model systems for the study of human reproductive biology and highlight the importance of studying human consanguineous populations to discover novel monogenic causes of infertility. The rapid and continuous screening and identification of putative genetic defects coupled with an efficient functional characterization in animal models can reveal novel mechanisms of gene function in human reproductive tissues.

The reproductive potential of vitrified-warmed euploid embryos declines following repeated uterine transfers.

BACKGROUND: Recurrent implantation failure (RIF) represents a vague clinical condition with an unclear diagnostic challenge that lacks solid scientific underpinning. Although euploid embryos have demonstrated consistent implantation capabilities across various age groups, a unanimous agreement regarding the advantages of preimplantation genetic testing for aneuploidy (PGT-A) in managing RIF is absent. The ongoing discussion about whether chromosomal aneuploidy in embryos significantly contributes to recurrent implantation failure remains unsettled. Despite active discussions in recent times, a universally accepted characterization of recurrent implantation failure remains elusive. We aimed in this study to measure the reproductive performance of vitrified-warmed euploid embryos transferred to the uterus in successive cycles. METHODS: This observational cohort study included women (n = 387) with an anatomically normal uterus who underwent oocyte retrieval for PGT-A treatment with at least one biopsied blastocyst, between January 2017 and December 2021 at a university-affiliated public fertility center. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy and comprehensive 24-chromosome analysis of preimplantation embryos using Next Generation Sequencing (NGS). Women, who failed a vitrified-warmed euploid embryo transfer, had successive blastocyst transfer cycles (FET) for a total of three using remaining cryopreserved euploid blastocysts from the same oocyte retrieval cycle. The primary endpoints were sustained implantation rate (SIR) and live birth rate (LBR) per vitrified-warmed single euploid embryo. The secondary endpoints were mean euploidy rate (m-ER) per cohort of biopsied blastocysts from each patient, as well as pregnancy and miscarriage rates. RESULTS: The mean age of the patient population was 33.4 years (95% CI 32.8-33.9). A total of 1,641 embryos derived from the first oocyte retrieval cycle were biopsied and screened. We found no associations between the m-ER and the number of previous failed IVF cycles among different ranges of maternal age at oocyte retrieval (P = 0.45). Pairwise comparisons showed a significant decrease in the sustained implantation rate (44.7% vs. 30%; P = 0.01) and the livebirth rate per single euploid blastocyst (37.1% vs. 25%; P = 0.02) between the 1st and 3rd FET. The cumulative SIR and LBR after up to three successive single embryo transfers were 77.1% and 68.8%, respectively. We found that the live birth rate of the first vitrified-warmed euploid blastocyst transferred decreased significantly with the increasing number of previously failed IVF attempts by categories (45.3% vs. 35.8% vs. 27.6%; P = 0.04). A comparable decrease in sustained implantation rate was also observed but did not reach statistical significance (50% vs. 44.2 vs. 37.9%; P = NS). Using a logistic regression model, we confirmed the presence of a negative association between the number of previous IVF failed attempts and the live birth rate per embryo transfer cycle (OR = 0.76; 95% CI 0.62-0.94; P = 0.01). CONCLUSIONS: These findings are vital for enhancing patient counseling and refining management strategies for individuals facing recurrent implantation failure. By tailoring interventions based on age and ovarian reserve, healthcare professionals can offer more personalized guidance, potentially improving the overall success rates and patient experiences in fertility treatments. TRIAL REGISTRATION NUMBER: N/A.

The Effects of Long-Term Dienogest Therapy on In Vitro Fertilization Outcomes in Women with Endometriosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Assessing dienogest's efficacy in endometriosis patients undergoing in vitro fertilization (IVF). DATA SOURCES: Systematic search in databases (PubMed, MEDLINE, Embase, Web of Science, Cochrane CENTRAL, Google Scholar) until 1 October 2022. STUDY SELECTIONS: Randomized trials and observational studies comparing extended dienogest pre-treatment, no pre-treatment, or gonadotropin-releasing hormone (GnRH) agonist pre-treatment in endometriosis-linked IVF. OUTCOME MEASURES: live birth, clinical pregnancy rates, oocytes collected, miscarriage rate, gonadotropin consumption. DATA EXTRACTIONS AND SYNTHESES: Two authors independently assessed eligibility. Dichotomous variables were analyzed via a random-effect model and Mantel-Haenszel method to calculate weighted estimates and 95% confidence intervals (CI). I2 statistic gauged study heterogeneity; GRADE criteria evaluated evidence quality. CONCLUSIONS: Out of 191 publications, five studies with 723 participants were included. Uncertainty persists on whether prolonged dienogest affects live birth (RR 1.42, 95% CI 0.29 to 6.84; 3 studies, n = 289; I2 86%) and clinical pregnancy rates (RR 1.33, 95% CI 0.31 to 5.65; 3 studies, n = 289; I2 86%) compared to conventional IVF. Moreover, uncertainty remains regarding intervention impact on live birth (RR 1.46, 95% CI 0.63 to 3.37; 1 study, n = 34) and clinical pregnancy rates (RR 1.32, 95% CI 0.78 to 2.23; 3 studies, n = 288; I2 0%) versus long-term GnRH agonist therapy before IVF. Given limited data and very low evidence quality, doubts arise about the benefits of long-term dienogest pre-treatment before conventional IVF in endometriosis patients.

A homozygous missense variant in PTPN2 with early-onset Crohn's disease, growth failure and dysmorphic features in an infant: a case report.

Crohn's disease (CD) is a chronic idiopathic inflammatory bowel condition that can affect any part of the gastrointestinal tract. Several hundred candidate loci or genes including PTPN2 have been reportedly associated with CD. A whole-exome sequencing (WES) was conducted in a 9-year-old Lebanese girl with a CD onset at 13 months and in both her asymptomatic parents. The analysis detected an extremely rare homozygous variant in PTPN2: c.359C>T, p.(Ser120Leu) in the patient, while both her parents were heterozygous. This variant, located in the protein tyrosine phosphatase (PTP) domain within a highly conserved amino acid, is classified as VUS according to the American College of Medical Genetics (ACMG) criteria. To evaluate the hypothetical functional consequences of the identified variant, a quantitative expression analysis of PTPN2 was performed in blood tissues of the patient, her parents, and two healthy controls. PTPN2 expression was not noted in the patient compared to her parents and the normal controls, suggesting a functional PTPN2 impairment caused by c.359C>T. This variant c.359C>T, p.(Ser120Leu) in PTPN2 has never been previously described in the literature. Our report suggests an association of PTPN2: c.359C>T with early-onset CD.

Novel SCN9A variant associated with congenital insensitivity to pain.

BACKGROUND: Congenital insensitivity to pain (CIP) is a rare autosomal recessive syndrome characterized by lack of pain perception and a wide spectrum of clinical signs such as anosmia and hyposmia. Variants in SCN9A gene are associated with CIP. We here report on a Lebanese family with three CIP patients referred for genetic investigations. METHODS AND RESULTS: Whole exome sequencing analysis revealed the presence of a novel nonsense, homozygous SCN9A pathogenic variant: SCN9A (NM_001365536.1): c.4633G > T, p.(Glu1545*) in exon 26. CONCLUSION: Our three Lebanese patients had CIP, urinary incontinence and normal olfactory function while two of them also presented with osteoporosis and osteoarthritis; this association of features has not been previously reported in the literature. We hope that this report would contribute to a better delineation of the phenotypic spectrum associated with SCN9A pathogenic variants.

Analysis of ASS1 gene in ten unrelated middle eastern families with citrullinemia type 1 identifies rare and novel variants.

BACKGROUND: Citrullinemia type 1 (CTLN1) is a rare autosomal recessive disease caused by argininosuccinate synthetase (ASS) deficiency. Manifestations vary from the acute neonatal or "classic" form to a milder, late-onset, or "unconventional" form. To date, more than 93 variants in the ASS1 gene located on chromosome 9q43.11 (OMIM #215700) are reportedly responsible for CTLN1. Their incidence and distribution vary according to geographic origins and ethnicity, and a correlation, although not clearly delineated, has been established between the genotype and the phenotype of the disease. Though, in the Middle East, national descriptions of CTLN1 are still lacking. METHODS: A total of ten unrelated Middle Eastern families, five Lebanese, two Syrians, and three Iraqis with citrullinemia index cases, were included in this study. Upon informed consent, DNA was extracted from the whole blood of the index patients as well as their parents and siblings. Genetic analysis was carried out by Sanger sequencing of the ASS1 gene. RESULTS: Seven different variants were identified. Two novel variants, c.286C>A (p.(Pro96Thr), RNA not analyzed) in exon 5 and deletion c.685_688+6del(p.(Lys229Glyfs*4), RNA not analyzed) in exon 10, were found in one Lebanese and one Syrian family, respectively, and were correlated with early-onset and severe clinical presentation. Five other known variants: c.535T>C (p.(Trp179Arg), RNA not analyzed) in exon 8, c.787G>A (p.(Val263Met), RNA not analyzed) in exon 12, c.847G>A (p.(Glu283Lys), RNA not analyzed) in exon 13, c.910C>T (p.(Arg304Trp), RNA not analyzed) in exon 13, and c.1168G>A (p.(Gly390Arg), RNA not analyzed) in exon 15, were found in Lebanese, Syrian, and Iraqi families, and were associated with diverse clinical presentations. CONCLUSION: Two novel variants and five known variants were found in a total of ten unrelated Middle Eastern families.

Female infertility and diet, is there a role for a personalized nutritional approach in assisted reproductive technologies? A Narrative Review.

Female infertility is a major public health concern and a global challenge. It is a disorder of the reproductive system, defined as the inability to achieve a clinical pregnancy. Nutrition and other environmental factors are found to impact reproductive health in women as well as the outcome of assisted reproductive technologies (ART). Dietary factors, such as polyunsaturated fatty acids (PUFA), fiber as well as the intake of Mediterranean diet appear to exert beneficial effects on female reproductive outcomes. The exact mechanisms associating diet to female fertility are yet to be identified, although genomic, epigenomic, and microbial pathways may be implicated. This review aims to summarize the current knowledge on the impact of dietary components on female reproduction and ART outcomes, and to discuss the relevant interplay of diet with genome, epigenome and microbial composition.

Maternal vaccine hesitancy towards COVID-19 immunisation of children in Qatar: a population-based cross-sectional study.

OBJECTIVES: This study was conducted in Qatar to explore beliefs and attitudes among mothers towards coronavirus disease 2019 (COVID-19) vaccination for their children and to understand major factors influencing vaccine hesitancy among these mothers. METHODS: A population-based, online cross-sectional survey was conducted between 15 October and 15 November 2020. A composite questionnaire incorporating a validated vaccine hesitancy tool was developed and administered in both English and Arabic. Approval was obtained from the local ethics committee. Participation was voluntary and offered to all adult residents of Qatar through an online link available on social media platforms and local news portals. Only adult respondents who self-identified as mothers were included in the present study. No personal identifying data were collected. RESULTS: Of the mothers surveyed, 29.4% exhibited COVID-19 vaccine hesitancy regarding their children. This exceeded these mothers' rate of personal vaccine hesitancy (27.5%). Hesitancy rates varied significantly with ethnicity, with the highest among Qatari mothers (51.3%). Intention to vaccinate children did not differ significantly between mothers who accepted the vaccine for themselves and those who did not. Overall, the main reported concerns related to long-term vaccine safety. To a significant extent, mothers relied most on self-directed research on vaccine safety for decision-making. CONCLUSIONS: The rate of maternal COVID-19 vaccine hesitancy exceeded both those mothers' rate of personal vaccine hesitancy and the hesitancy rate in the general population. The intention to vaccinate children was independent of maternal vaccination history. Factors influencing maternal vaccine hesitancy differ from those influencing personal hesitancy and require an informed public health response.

CFTR mutational screening by next-generation sequencing reveals novel variants and a high carrier rate in a Middle Eastern population.

Cystic fibrosis is the most common life-limiting autosomal recessive disease in western countries with an incidence of 1:2500 in United States and 1:1000 in some European countries. Similar incidences were noted for the Middle East with variations from 1 in 2560 to 1 in 15,876 according to the degree of consanguinity. This is a preliminary systematic study that aims to assess the incidence and carrier rate of cystic fibrosis in the Middle Eastern Lebanese population; known for a high frequency of consanguinity. One hundred thirteen DNA samples were collected from neonatal blood cards obtained from newborns to healthy unrelated families with no previous history of Cystic fibrosis. Screening for Cystic Fibrosis-causing pathogenic variants was performed using next generation sequencing, and 17 different single nucleotide variants were detected, including six pathogenic and likely pathogenic. 5.5%-7% newborns were found to be carriers of a variant strongly suggestive of pathogenicity and comparable to published literature worldwide. This pilot analysis highlights the challenging interpretation of CFTR variants in a country underrepresented by large ethnic population analyses, and stresses the importance of premarital screening programs for Cystic fibrosis.

17p13.3 Microduplication Syndrome: Further Delineating the Clinical Spectrum.

17p13.3 microduplication syndrome has been associated with a clinical spectrum of phenotypes, and depending on the genes involved in the microduplication, it is categorized into two classes (Class I and Class II). We herein, describe two patients diagnosed with Class I 17p13.3 microduplication by BACs-on-Beads (BoBs) assay and further confirmed by fluorescence in situ hybridization (FISH). Our patients (Patient 1: 4-year-old male; Patient 2: 2-year-old male) presented with developmental delay, intellectual disability, and dysmorphic facial features. When compared with the literature, our patients manifested distinctive features (Patient 1: primary hypothyroidism; Patient 2: bilateral cryptorchidism) that were not previously described in the duplication 17p13.3 spectrum.

The Spectrum of ß-Thalassemia Mutations in the Population Migration in Lebanon: A 6-Year Retrospective Study.

ß-Thalassemia (ß-thal) is highly prevalent among the Mediterranean populations. In Lebanon, the carrier rate of the disease is estimated to be around 2.0-3.0%. In this retrospective study, we determined the spectrum of ß-thal mutations in a total of 170 individuals from a sample of 140 Lebanese, Iraqi and Syrian refugee families in Lebanon, over a period from 2012 to 2018. Twenty-eight different ß-globin gene mutations were identified. The most prevalent mutations were IVS-I-110 (G>A) (HBB: c.93-21G>A), IVS-II-1 (G>A) (HBB: c.315+1G>A), IVS-I-6 (T>C) (HBB: c.92+6T>C) and IVS-I-1 (G>A) (HBB: c.92+1G>A), accounting for the majority of mutations found in HBB mutations analysed in 250 alleles. Ten different ß-globin gene mutations that were not previously described in Lebanon were identified in our study. These mutations include the IVS-II-848 (C>A) (HBB: c.316-3C>A), codons 9/10 (+T) (HBB: c.30_31insT), codon 15 (-T) (HBB: c.46delT), -86 (C>G) (HBB: c.-136C>G), Cap +22 (G>A) (HBB: c.-29G>A), -28 (A>C) (HBB: c.-78A>C), codon 7 (GAG>TAG) (HBB: c.22G>T), codon 26 (GAG>TAG) (HBB: c.79G>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codons 82/83 (-G) (HBB: c.250delG). Of these, six mutations [codons 9/10, codon 15 (-T), -86, codon 7, codon 26, codons 82/83) were identified in Lebanese samples only; one mutation (IVS-II-848) was identified in both Lebanese and Iraqis; and three mutations (Cap +22, -28, codons 41/42) were identified in Iraqi samples only. Further studies will help better delineate the spectrum of ß-thal mutations among different ethnic groups, and provide crucial prevention strategies.

Paternal Exposure to Non-essential Heavy Metal Affects Embryo Cleavage and Implantation in Intracytoplasmic Sperm Injection (ICSI) Cycles: Evidence for a Paradoxical Effect.

Although the adverse effects of non-essential heavy metals on semen quality have been demonstrated in experimental animal models and occupational human exposure studies, little is known about the reproductive efficiency of exposed sperm during the process of intracytoplasmic sperm injection (ICSI). Our study aims to evaluate the effect of paternal exposure to non-essential heavy metals on embryo efficiency outcomes (embryo cleavage, fragmentation, implantation, and live birth) in ICSI cycle. Ninety-five heterosexual couples who underwent 95 ICSI cycles and 78 fresh embryo transfers between January 2003 and December 2009 were evaluated. Men whose female partner was undergoing ICSI were asked to provide semen and blood samples. Heavy metal levels (Pb, Cd, As, Hg, Ba, and U) were analyzed using an ion-coupled plasma-mass spectrometry (ICP-MS; Agilent 7500 ce, Agilent Technologies, Germany) equipped with a cell dynamic range (CDR). Paternal exposure to trace heavy metals was found to influence intermediate reproductive endpoints in ICSI cycles. After adjusting for paternal and maternal confounders, paternal blood concentrations of Cd [-0.30(-0.11,-0.02)], As [-0.26(-0.16,-0.11)], and U [-0.22(-0.24,-0.02)] were inversely associated with embryo cell cleavage on day 3. Counterintuitively, paternal blood and semen Pb levels [0.26(0.01,0.22); 0.25(0.03,0.14)] as well as semen U levels [0.27(0.01,0.19)] were positively associated with the proportion of implanted embryos. There were no significant associations observed for clinical pregnancy and live birth rates with any paternal heavy metal concentrations in semen and blood. These findings highlight the importance of paternal health for embryo efficiency outcomes in ICSI treatment cycles and the need for more male partner inclusive counseling in fertility practice. They also underline a paradoxical positive association between some heavy metal pollutants at low exposure levels and reproductive outcomes.

Cumulative Live-Birth Rates by Maternal Age after One or Multiple In Vitro Fertilization Cycles: An Institutional Experience.

BACKGROUND: The aim of this retrospective study is to investigate the cumulative live birth rate (CLBR) following one or more completed in vitro fertilization (IVF) cycles (up to 6 cycles) stratified by maternal age and type of infertility. MATERIALS AND METHODS: In this retrospective study, five hundred forty-seven women who received 736 fresh ovarian stimulation/embryo transfer cycles between January 2016 and December 2016 were included in the study at a tertiary care center located in Lebanon. RESULTS: In all women, the live birth rate for the first cycle was 33.0% [95% confidence interval (CI): 27.8-38.2]. The CLBR showed an increase with each successive fresh cycle to reach 56.9% (95% CI: 51.2-62.4) after 3 cycles and 67.9% (95% CI: of 62.5-73.0) after 6 cycles. The CLBR following 6 cycles reached 69.9% (95% CI: 63.8-75.6) in women younger than 35 years. In women older than 40 years, however, the live birth rate for the first cycle was significantly low at 3.1% (95% CI: 0.3-9.5) with a plateau in success rates after 4 cycles reaching 21.9% (95% CI: 9.2-40.0). Couples with different types of infertility had CLBRs ranging from 65% to 72%, with the exception of women with low ovarian reserve, where CLBRs reached 29.4% (95% CI: 10.3-56.0). CONCLUSION: The CLBR at a referral center in a Middle Eastern country reached 67.9 % after 6 cycles, with variations by age and type of infertility treatment. These findings are encouraging for patients insisting to extend their treatment beyond 4 to 5 cycles.

BACs-on-Beads™ assay, a rapid aneuploidy test, improves the diagnostic yield of conventional karyotyping.

BACs-on-Beads (BoBs™) assay is a rapid aneuploidy test (RAT) that detects numerical chromosomal aneuploidies and multiple microdeletion/microduplication syndromes. This study was conducted to appraise the usefulness of the BoB™ assay as a complementary diagnostic tool to conventional karyotyping for the rapid detection of chromosomal aneuploidies. A total of 485 prenatal (amniotic fluid and chorionic villi) and blood/products of conception samples were collected between July 2013 and August 2018, and analyzed by the BoBs™ assay and cytogenetic karyotyping and further validated by fluorescence in situ hybridization (FISH). Forty-three of 484 qualifying samples (8.9%) were identified as abnormal by the BoBs™ assay. The assay was comparable to karyotyping in the detection of common structural abnormalities (trisomy 21, trisomy 18, X, and Y), with a sensitivity of 96.0% and a specificity of 100%. BoBs™ assay detected 20 microdeletion and microduplication syndromes that were missed by karyotyping. BoBs™, however, missed 10 cases of polyploidies and chromosomal rearrangements which were identified by conventional karyotyping. Our findings suggest that BoBs™ is a reliable RAT which is suitable in combination with conventional karyotyping for the detection of common aneuploidies. The assay also improves the diagnostic yield by recognizing clinically relevant submicroscopic copy number gains and losses.

BRCA mutation screening and patterns among high-risk Lebanese subjects.

BACKGROUND: Previous studies have suggested that the prevalence of BRCA1 and 2 mutations in the Lebanese population is low despite the observation that the median age of breast cancer diagnosis is significantly lower than European and North American populations. We aimed at reviewing the rates and patterns of BRCA1/2 mutations found in individuals referred to the medical genetics unit at the American University of Beirut. We also evaluated the performance of clinical prediction tools. METHODS: We retrospectively reviewed the cases of all individuals undergoing BRCA mutation testing from April 2011 to May 2016. To put our findings in to context, we conducted a literature review of the most recently published data from the region. RESULTS: Two-hundred eighty one individuals were referred for testing. The prevalence of mutated BRCA1 or 2 genes were 6 and 1.4% respectively. Three mutations accounted for 54% of the pathogenic mutations found. The BRCA1 c.131G > T mutation was found among 5/17 (29%) unrelated subjects with BRCA1 mutation and is unique to the Lebanese and Palestinian populations. For patients tested between 2014 and 2016, all patients positive for mutations fit the NCCN guidelines for BRCA mutation screening. The Manchester Score failed to predict pathogenic mutations. CONCLUSION: The BRCA1 c.131G > T mutation can be considered a founder mutation in the Lebanese population detected among 5/17 (29%) of individuals diagnosed with a mutation in BRCA1 and among 7/269 families in this cohort. On review of recently published data regarding the landscape of BRCA mutations in the Middle East and North Africa, each region appears to have a unique spectrum of mutations.

The effect of bariatric surgery on inflammatory markers in women with polycystic ovarian syndrome.

AIM: The aims of this study is to address the improvement in CRP and adiponectin in obese PCOS and non PCOS after bariatric surgery, and to show that obese PCOS women have a slower rate of improvement when compared to obese non PCOS women. METHODS: This is a prospective case-control study evaluating the effect of weight loss by sleeve gastrectomy among obese PCOS patients. RESULTS: There was a 36.28% of weight loss among obese PCOS and 33.04% among the control group at 12 months. Both groups showed a significant increase in the adiponectin levels at 3, 6 and 12 months' post-surgery. The rate of increase was higher in the obese non PCOS women (4.93 ±â€¯1.79-9.79 ±â€¯3.9) compared to obese PCOS women (5.05 ±â€¯1.98-7.25 ±â€¯0.21). The CRP levels decreased with weight loss after the surgery to reach statistical significance at 3 months in obese PCOS group (4.18 ±â€¯3.94, p = 0.048). CONCLUSION: The degree of weight loss after surgery was effective in lowering CRP and increasing adiponectin levels in PCOS women. However, this improvement was slower compared to obese non PCOS patients. A genetic predisposition to insulin resistance might explain these findings.

The association between cardiovascular disease gene mutations and recurrent pregnancy loss in the Lebanese population.

Recurrent pregnancy loss (RPL) is a problem affecting up to 5% of women of childbearing age due to many factors. Studies have shown that RPL and cardiovascular disease (CVD) may have shared risk factors. We compared the prevalence of 12 cardiovascular disease related gene mutations in patients with a history of RPL to normal controls in a major tertiary care center in Lebanon. The CVD StripAssay (ViennaLab, Austria) was used to analyze the CVD genes on 70 women with RPL history as part of the initial routine workup for recurrent miscarriage at the American University of Beirut Medical Center. The obtained results were compared with data of controls from the Lebanese population using Fisher's exact test and Chi square analysis. Two genes of the CVD panel demonstrated a strong relationship with RPL, including, MTHFR (C677T homozygosity, A1298C homozygosity, and compound heterozygosity for C677T and A1298C) and Factor II (heterozygosity for G20210A). Moreover, a protective role of positive APO-E3 isoform was observed. This study is the first in the Lebanese population in associating RPL with a large panel of CVD related genes.

Associations of semen quality with non-essential heavy metals in blood and seminal fluid: data from the Environment and Male Infertility (EMI) study in Lebanon.

BACKGROUND: Human exposure to environmental pollutants is widespread. It was suggested that exposure to non-essential heavy metals may adversely affect semen development in men. PURPOSE: To evaluate associations between non-essential heavy metals in blood and seminal fluid and semen quality parameters in men. METHODS: Male partners of heterosexual couples were included. The following elements were measured in blood and seminal fluid: lead (Pb), cadmium (Cd), arsenic (As), barium (Ba), mercury (Hg), and uranium (U) using ion-coupled plasma-mass spectrometry. SETTING: The fertility clinic at the American University of Beirut Medical Center. MAIN OUTCOME MEASURES: Semen quality parameters (volume, concentration, total count, progressive motility, viability, and normal morphology). RESULTS: We found that participants with low-quality semen had significantly higher Cd and Ba concentrations in the seminal fluid than participants with normal-quality semen. We also observed significant associations between low sperm viability and higher blood Cd and Ba, as well as higher seminal Pb, Cd, Ba, and U. Furthermore, U concentrations in the seminal fluid were associated with increased odds ratios for below-reference progressive sperm motility and normal morphology. CONCLUSIONS: Environmental exposures to Pb, Cd, Ba, and U appear to adversely influence sperm development in men. In non-occupationally exposed men, measurements of heavy metals in the seminal fluid may be more predictive of below-reference sperm quality parameters than in blood.