Arab founder variants: Contributions to clinical genomics and precision medicine.

Background: Founder variants are ancestral variants shared by individuals who are not closely related. The large effect size of some of these variants in the context of Mendelian disorders offers numerous precision medicine opportunities.

Methods: Using one of the largest datasets on Mendelian disorders in the Middle East, we identified 2,908 medically relevant founder variants derived from 18,360 exomes and genomes and investigated their contribution to the clinical annotation of the human genome.

The mammalian sperm factor phospholipase C zeta is critical for early embryo division and pregnancy in humans and mice.

Study Question: Are sperm phospholipase C zeta (PLCζ) profiles linked to the quality of embryogenesis and pregnancy?

Summary Answer: Sperm PLCζ levels in both mouse and humans correlate with measures of ideal embryogenesis whereby minimal levels seem to be required to result in successful pregnancy.

What Is Known Already: While causative factors underlying male infertility are multivariable, cases are increasingly associated with the efficacy of oocyte activation, which in mammals occurs in response to specific profiles of calcium (Ca2+) oscillations driven by sperm-specific PLCζ. Although sperm PLCζ abrogation is extensively linked with human male infertility where oocyte activation is deficient, less is clear as to whether sperm PLCζ levels or localization underlies cases of defective embryogenesis and failed pregnancy following fertility treatment.

Antigen Unmasking Is Required to Clinically Assess Levels and Localisation Patterns of Phospholipase C Zeta in Human Sperm.

Mammalian oocyte activation is initiated by intracellular calcium (Ca) oscillations, driven by the testis-specific phospholipase C zeta (PLCζ). Sperm PLCζ analysis represents a diagnostic measure of sperm fertilisation capacity. The application of antigen unmasking/retrieval (AUM) generally enhanced the visualisation efficacy of PLCζ in mammalian sperm, but differentially affected the PLCζ profiles in sperm from different human males.

Recurrent spontaneous oocyte activation causes female infertility.

Purpose: Spontaneous oocyte activation (SOA) is a recently classified phenomenon characterized by the presence of a single pronucleus immediately following oocyte retrieval, without the apparent involvement of sperm. SOA currently remains poorly understood in humans, with no clear genetic or pathological factor(s). Herein, we report two separate cases of recurrent spontaneous oocyte activation, investigating potential avenues to identify causative etiology.

Oxidative stress and DNA damage status in couples undergoing fertilization treatment.

Unlabelled: This study examined the status of oxidative stress in 599 couples undertaking fertilization (IVF) treatment and its association with reproductive hormones, smoking, and outcomes. Oxidative stress biomarkers such as malondialdehyde, 8-hydroxy-2-deoxyguanosine, hydrogen peroxide (HO), catalase (CAT), and total antioxidant capacity (TAC) were determined in follicular fluid and seminal plasma. Tail moment (TM) was used to evaluate DNA damage in the sperm and granulosa cells.

Desalination and Detoxification of Textile Wastewater by Novel Photocatalytic Electrolysis Membrane Reactor for Ecosafe Hydroponic Farming.

In this study, a novel photoelectrocatalytic membrane (PECM) reactor was tested as an option for the desalination, disinfection, and detoxification of biologically treated textile wastewater (BTTWW), with the aim to reuse it in hydroponic farming. The anionic ion exchange (IEX) process was used before PECM treatment to remove toxic residual dyes. The toxicity evaluation for every effluent was carried out using the , Microtox test protocol.

ASTL is mutated in female infertility.

Female infertility is a relatively common phenotype with a growing number of single gene causes although these account for only a minority of cases. Here, we report a consanguineous family in which adult females who are homozygous for a truncating variant in ASTL display markedly reduced fertility in a pattern strikingly similar to Astl female mice. ASTL encodes ovastacin, which is known to trigger zona pellucida hardening (ZPH) as part of the cortical reaction upon fertilization.

A genomics approach to male infertility.

Purpose: Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility.

Methods: Patients with severe oligospermia and nonobstructive azoospermia were investigated using exome sequencing (ES) in parallel with the standard practice of chromosomal analysis.

Phospholipase C zeta profiles are indicative of optimal sperm parameters and fertilisation success in patients undergoing fertility treatment.

Background: Oocyte activation is driven by intracellular calcium (Ca ) oscillations induced by sperm-specific PLCζ, abrogation of which causes oocyte activation deficiency in humans. Clinical PLCζ investigations have been limited to severe male infertility conditions, while PLCζ levels and localisation patterns have yet to be associated with general sperm viability.

Materials And Methods: PLCζ profiles were examined within a general population of males attending a fertility clinic (65 patients; aged 29-53), examining PLCζ throughout various fractions of sperm viability.

A genomics approach to females with infertility and recurrent pregnancy loss.

Infertility affects 10% of reproductive-age women and is extremely heterogeneous in etiology. The genetic contribution to female infertility is incompletely understood, and involves chromosomal and single-gene defects. Our aim in this study is to decipher single-gene causes in infertile women in whom endocrinological, anatomical, and chromosomal causes have been excluded.

Cell-free DNA levels of twins and sibling pairs indicate individuality and possible use as a personalized biomarker.

Cell-free DNA (cfDNA) in the human blood circulation has been under investigation since its initial observation in 1948. Plasma cfDNA is known to be significantly elevated in diseased people. Due to possible variation in the population, evaluating cfDNA as a non-invasive biomarker at disease onset alone may not be sensitive enough to accurately diagnose diseases, particularly early stage cancers on a personal level.

The extent and predictors of phthalate exposure among couples undergoing in vitro fertilization treatment.

Phthalates are chemicals used as plasticizers and solvents in many consumer products but are suspected of disrupting the endocrine system and are known for their reproductive/developmental health risks. This study examined the extent and predictors of phthalate exposure among 599 couples undergoing in vitro fertilization. A questionnaire was administered to obtain sociodemographic, health, and lifestyle data, and two spot urine samples were collected from the couples to analyze eight phthalate metabolites, cotinine (COT) as a smoking index, and creatinine to adjust for urine dilution.

Couples exposure to phthalates and its influence on in vitro fertilization outcomes.

This prospective study examined the associations between the levels of eight urinary phthalate metabolites in 599 couples and in vitro fertilization (IVF) outcomes. We used log-binomial multivariate regression to estimate relative risks (RR) for the association between phthalate concentration and IVF binary outcomes (fertilization rate >50%, biochemical pregnancy, clinical pregnancy and live birth) for each woman after adjusting the model for the concentration in a male partner and each relevant confounders. RR was expressed per unit increase in log-transformed urinary metabolite concentration.

The relationships between urinary phthalate metabolites, reproductive hormones and semen parameters in men attending in vitro fertilization clinic.

Evidence from previous studies has shown that phthalates may play a role in male reproductive function; however, results are still inconclusive, and the mechanism remains unclear. In this study, we first assessed whether exposure to phthalates is associated with altered reproductive hormones and semen parameters in 599 men attending an in vitro fertilization clinic. Secondly, we evaluated whether reproductive hormones could play a mediating role in the association between phthalates and sperm parameters.

Exposure to phthalates in couples undergoing in vitro fertilization treatment and its association with oxidative stress and DNA damage.

This prospective study of 599 couples seeking fertility treatment and who were recruited between 2015 and 2017 was conducted to (a) explore the associations between phthalate exposure and in vitro fertilization (IVF) outcomes; and (b) examine the implication of oxidative stress as a mediator of these. We measured eight phthalate metabolites in two spot urine samples; oxidative stress biomarkers such as malondialdehyde, 8-hydroxy-2-deoxyguanosine, hydrogen peroxide, catalase (CAT), and total antioxidant capacity in follicular fluid and seminal plasma. We also examined DNA damage in sperm and granulosa cells.

Intramuscular progesterone (Gestone) versus vaginal progesterone suppository (Cyclogest) for luteal phase support in cycles of in vitro fertilization-embryo transfer: patient preference and drug efficacy.

Background: The requirement for luteal phase support (LPS) in stimulated IVF cycles is well established, however drug choice, and route of administration and duration of use are not. This report evaluates patients' preference and satisfaction by using either vaginal or intramuscular (IM) progesterone (P) supplementation for luteal phase support after in vitro fertilization and embryo transfer (IVF-ET).

Methods: It is a prospective cohort study done in a reproductive and infertility unit in a tertiary care hospital from March 2013 through February 2015 for four hundred and nine patients undergoing IVF-ET.

Female Infertility Caused by Mutations in the Oocyte-Specific Translational Repressor PATL2.

Infertility is a relatively common disorder of the reproductive system and remains unexplained in many cases. In vitro fertilization techniques have uncovered previously unrecognized infertility phenotypes, including oocyte maturation arrest, the molecular etiology of which remains largely unknown. We report two families affected by female-limited infertility caused by oocyte maturation failure.

Hepatitis B and C virus prevalence in couples attending an in vitro fertilization clinic in a tertiary care hospital in Saudi Arabia: comparison with ten years earlier.

Background: Viral hepatitis B (HBV) and C (HCV) are a major public health problem in Saudi Arabia. Recent data has indicated a major reduction in viral hepatitis prevalence in Saudi population. However, there is limited data for infertile Saudi couples.

Abstracts from the 3rd International Genomic Medicine Conference (3rd IGMC 2015) : Jeddah, Kingdom of Saudi Arabia. 30 November - 3 December 2015.

O1 Regulation of genes by telomere length over long distances Jerry W. Shay O2 The microtubule destabilizer KIF2A regulates the postnatal establishment of neuronal circuits in addition to prenatal cell survival, cell migration, and axon elongation, and its loss leading to malformation of cortical development and severe epilepsy Noriko Homma, Ruyun Zhou, Muhammad Imran Naseer, Adeel G. Chaudhary, Mohammed Al-Qahtani, Nobutaka Hirokawa O3 Integration of metagenomics and metabolomics in gut microbiome research Maryam Goudarzi, Albert J.

Association of blood groups with ovarian reserve and outcome of in vitro fertilization treatment.

Background: The association between ABO blood groups and ovarian reserve in infertile patients has been a point of controversy.

Objectives: The aim of this study was to assess the correlation of certain blood groups with ovarian reserve and response to treatment in patients undergoing infertility treatment.

Design: Retrospective medical record review.

TLE6 mutation causes the earliest known human embryonic lethality.

Background: Embryonic lethality is a recognized phenotypic expression of individual gene mutations in model organisms. However, identifying embryonic lethal genes in humans is challenging, especially when the phenotype is manifested at the preimplantation stage.

Results: In an ongoing effort to exploit the highly consanguineous nature of the Saudi population to catalog recessively acting embryonic lethal genes in humans, we have identified two families with a female-limited infertility phenotype.

Noninvasive Digital Detection of Fetal DNA in Plasma of 4-Week-Pregnant Women following In Vitro Fertilization and Embryo Transfer.

The discovery of cell-free fetal DNA (cfDNA) circulating in the maternal blood has provided new opportunities for noninvasive prenatal diagnosis (NIPD). However, the extremely low levels of cfDNA within a high background of the maternal DNA in maternal circulation necessitate highly sensitive molecular techniques for its reliable use in NIPD. In this proof of principle study, we evaluated the earliest possible detection of cfDNA in the maternal plasma by a bead-based emulsion PCR technology known as BEAMing (beads, emulsion, amplification, magnetics).

A retrospective analysis of the treatment results of 1557 patients with acute cholecystitis.

Objective: To analyse outcomes of variable management strategies for the treatment of Acute Cholecystitis in relation to morbidity, mortality and conversion to open surgery.

Methods: The retrospective study was conducted at Firat University Hospital, Turkey and comprised records of Acute Cholecystitis patients admitted between 2005 and 2011. Patients were divided into subgroups according to admission time as well as American Society of Anaesthesiologists score.