باروری و ناباروری
سال:1396 | دوره: | شماره: |تعداد مقالات:10

Personalized medicine or precision medicine was first defined for management of cancer patients with the idea that information of patient’s genes, proteins, metabolites and environment can be applied for its individualized management and it encompasses prevention, screening, diagnosis, prognosis, treatment, follow up, detection of recurrence and categorization of patient to defined subgroups for more effective treatment. Current evidence suggests the relative success of this approach in cancer patients. The development and implementation of personalized medicine required a set of objectives and valid biomarkers through genomics, transcriptomics, proteomics and metabolomics knowledge of huge samples cohorts regarding confounding factors, such as age, gender, habits, diet, and environment.

Currently, there are 20, 197 human protein-coding genes in the most expertly curated database (UniProtKB/Swiss-Pro). Big efforts have been made by the international consortium, the Chromosome-Centric Human Proteome Project (C-HPP) and independent researchers, to map human proteome. In brief, anno 2017 the human proteome was outlined. The male factor contributes to 50% of infertility in couples. However, there are limited human spermatozoa proteomic studies. Firstly, the development of the mapping of the human spermatozoa was analyzed. The human spermatozoa have been used as a model for missing proteins. It has been shown that human spermatozoa are excellent sources for finding missing proteins. Y chromosome proteome mapping is led by Iran. However, it seems that it is extremely challenging to map the human spermatozoa Y chromosome proteins based on current mass spectrometry-based proteomics technology. Post-translation modifications (PTMs) of human spermatozoa proteome are the most unexplored area and currently the exact role of PTMs in male infertility is unknown. Additionally, the clinical human spermatozoa proteomic analysis, anno 2017 was done in this study.

Background: Vascular Endothelial Growth Factor and NK cells have an interrelated role in angiogenesis that is critical for placentation and success ofin vitro fertilization. An attempt was made to assess a possible relationship between the two in this study.Methods: A case control study was performed comparing the serum levels of VEGF-A and its receptor VEGF-R1 with levels of NK cells, activated NK cells and NK cytotoxicity in 62 women with Repeated Implantation Failure (RIF). The healthy control group consisted of 72 women of similar age, without known issues in achieving pregnancy or evidence of autoimmunity. Levels of VEGF-A and VEGF-R1 were quantified by ELISA methods with standard curve interpolation. NK cell subsets were determined with flow cytometry using fluorescent-tagged anti-CD56, anti-CD16, anti-CD3 and anti-CD69. NK cytotoxicity was performed by incubating peripheral blood mononuclear cells and K562 cultured cells with propidium iodide, steroid, intralipid and intravenous immunoglobulin, using previously described methods. Statistical analysis involved Mann-Whitney-U and Spearman’s rank correlation testing with p-values defined as<0.05.Results: It was found that VEGF-A levels were significantly raised in women with RIF compared to healthy controls (362.9vs.171.6 pg/ml, p<0.0001), with no difference in VEGF-R1 levels between groups (1499vs.1202 pg/ml, p=0.4082). There was no correlation between VEGF-A or VEGF-R1 and the absolute levels of circulating NK cells, CD69 activated NK cells or NK cytotoxicity.Conclusion: The absence of correlation between VEGF-A or VEGF-R1 and NK cells suggests VEGF secretion and regulation is independent of NK cell activity in RIF.

Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested.Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44pg) plus progesterone (0.44 pg) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was considered significant.Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p<0.05); histological examination revealed an increase of cystic follicles (p<0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p>0.05vs. control group) and reduced cystic signs in the follicles (p<0.05 vs.dehyidroepiandrosterone treatment).Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment.

Background: The human Ubiquitously transcribed tetratricopeptide repeat gene, Ylinked (UTY) gene encodes histone demethylase involved in protein-protein interactions. UTY protein evidence at protein level predicted intracellular and secreted protein. UTY is also involved in spermatogenesis process.Methods: The high-risk non-synonymous single nucleotide polymorphism in the coding region of the UTY gene was screened by SNP database and identified missense variants were subjected to computational analysis to understand the effect on protein function, stability and structure bySIFT, PolyPhen 2, PANTHER, PROVEAN, I-Mutant 2, iPTREE-STAB, ConSurf, ModPred, SPARKS-X, QMEAN, PROCHECK, project HOPE and STRING.Results: A total of 151 nsSNPs variants were retrieved in UTY gene out of which one missense variant (E18D) was predicted to be damaging or deleterious using SIFT, PolyPhen 2, PANTHER and PROVEAN. Additionally, E18D variant showed less stability, high conservation and having role in post translation modification using i-Mutant 2 and iPTREE-STAB, ConSurf and ModPred, respectively. The predicted 3D model of UTY using SPARKS-X with z-score of 15.16 was generated and validated via QMEAN (Z-score of 0.472) and PROCHECK which plots Ramachandran plot (85.3% residues in most favored regions, 12.3% in additionally allowed regions, 2.0% in generously allowed regions and 4.0% were in disallowed regions) and it indicates a good quality model. STRING showed that UTY interacts with ten different proteins.Conclusion: This study revealed that SNP data available on database was deduced to find out the most damaging nsSNPsi.e. rs3212293 (E18D). Therefore, it provides useful information about functional SNPs for future prospects concerning infertility in men.

Background: The purpose of the study was to investigate the frequencies and types of Y chromosome microdeletions in infertile men and to analyze the relationship between the levels of reproductive hormones and Y microdeletions.Methods: A total of 1, 226 infertile men were screened for Y chromosome microdeletions using multiplex PCR assay. Karyotype analysis was performed on peripheral blood lymphocytes with standard G-banding. Serum reproductive hormone levels were measured.Results: Out of 1, 226 infertile patients, 134 (10.93%) had Y microdeletions. One hundred seven of 765 (13.99%) non-obstructive azoospermic patients and 27 of 133 (20.30%) severe oligozoospermic patients had Y microdeletions. Among the 134 infertile men with Y microdeletions, the most frequent microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZFabc (Yq), Yp (SRY)+Yq, and partial AZFc regions. Karyotype analysis was available for 130 of the 134 patients with Y microdeletions. Of them, 36 (27.69%) patients had sex chromosomal abnormalities. Levels of FSH and LH in patients with AZFc microdeletion were significantly lower, while those in patients with Yp (SRY)+Yq were significantly higher than in patients without Y microdeletions. Level of testosterone in patients with AZFabc (Yq) or Yp (SRY)+Yq was significantly lower than that in patients without Y microdeletions. However, there was no significant difference in the levels of reproductive hormones between all patients with and without Y microdeletions.Conclusion: These results highlight the need for Y chromosome microdeletion screening for correct diagnosis of male infertility. Obtaining reliable genetic information for assisted reproductive techniques can prevent unnecessary treatment and vertical transmission of genetic defects to offspring.

Background: The purpose of this study was to evaluate whether clinical pregnancy rate is affected by timing intrauterine insemination (IUI) according to serum LH surge, r-hCG trigger, or a combination of LH surge and r-hCG trigger in controlled ovarian hyperstimulation (COH) cycles for patients with a variety of infertility etiologies.Methods: The last 365 consecutive COH-IUI cycles performed at ONE Fertility Burlington in 2014 were reviewed and categorized according to method of IUI timing. Associations between categorical variables were analyzed using a combination of Chi-square and Fisher’s Exact tests, and between continuous variables using independent sample t-tests and logistic regression to a level of significance of p<0.05.Results: The overall clinical pregnancy rate in this sample was 18.1% (66.365).Administration of r-hCG prior to IUI resulted in a higher clinical pregnancy rate compared with spontaneous serum LH surge: 18.2%vs.5.8%, p=0.012. Patients in whom r-hCG was administered concomitantly with a serum LH surge had a higher clinical pregnancy than the r-hCG trigger group (30.8%vs.18.2%, p=0.004) and LH surge group (30.8%vs.5.8%, p<0.001). A sub-group analysis revealed that patients receiving r-FSH, rather than clomiphene or letrozole, had a significantly higher clinical pregnancy rate after r-hCG trigger as compared to the LH surge group (21.7% vs.2.1%, p=0.01).Conclusion: In subfertile couples undergoing COH-IUI, r-hCG administration was associated with an increased clinical pregnancy rate compared with spontaneous serum LH surge. When r-hCG was administered concomitantly with a serum LH surge, this benefit was amplified. The effect appears to be of particular importance in r-FSH-medicated cycles.

Background: Infertility is a common health problem requiring imaging to delineate the anatomical causes in women. Three dimensional multi-detector computed tomography hysterosalpingography (3D-MDCT-HSG) offers an easy workup for uterine, tubal and peritoneal factors.Methods: To present the spectrum of uterine, tubal and peritoneal factors on 3DMDCT-HSG and determine its diagnostic accuracy for female factor infertility, a prospective study was conducted on 25 infertile women with non-diagnostic HSG from November 2012 to March 2014. Sixty four slice MDCT acquired the scan during pre-ovulatory phase by contrast instillation into uterine cavity. A blinded reviewer interpreted the 3D-MDCT-HSG and results were compared with final diagnosis made on hystero-laproscopy in 22 patients. Diagnostic accuracy of 3D-MDCT-HSG for various factors was expressed as sensitivity, specificity, positive and negative predictive value.Results: MDCT-HSG demonstrated definite findings in 96% of patients having nondiagnostic HSG. In this study, tubal, uterine and peritoneal abnormalities were present in 68.75%, 56% and 32% of cases, respectively.48 tubes in 25 patients were evaluated of which 22 tubes were blocked constituting the commonest finding present in 15 (60%) patients. The sensitivity, specificity, positive predictive value and negative predictive value for uterine factors was 83.33%, 100%, 100% and 96.84%, respectively, for tubal factors 93.55%, 94.68%, 85.29% and 96.83%, respectively and for peritoneal factors 62.5%, 92%, 71.43% and 88.46%, respectively. Mean effective radiation dose was 1.76±0.18mSv in MDCT-HSG.Conclusion: 3D-MDCT-HSG can detect various factors responsible for female infertility especially tubal and uterine; in cases where HSG fails to clearly delineate the pathology.

Background: Pregnancy luteoma is a rare non neoplastic condition of the ovary. It is usually asymptomatic and found incidentally during imaging in pregnancy or during cesarean section. Pregnancy luteoma can also occur after ectopic pregnancy.Case Presentation: A 30 year old female presented to G.B. Pant Hospital, Andaman and Nicobar Islands institute of Medical Sciences, Port Blair in October 2015 with abdominal pain. After initial investigations, exploratory laporotomy was done for ruptured ectopic pregnancy. Enlarged ovary was removed along with the ruptured portion of fallopian tube. Histopathological examination revealed solid aggregates of large cells with abundant eosinophilic cytoplasm; diagnosis of pregnancy luteoma was given.Conclusion: It must be considered in the differential diagnosis of ovarian masses in pregnant females that early diagnosis of this entity may avoid unnecessary radical surgery.

Introduction: environmental health is broadly defined as the aspects of human health determined by physical, chemical, biological and social factors in the environment and encompasses the assessment and control of those factors. The exogenous and endogenous environmental health determinants include all that surround us, and environmental impact includes not only physical, chemical and biological factors, but also hormones, diet and lifestyle. As most humans develop in a predictable fashion, growing from a fertilized egg to fetus, newborn, toddler, child, adolescent, and adult, there is little doubt that environment is a powerful modifier of the human reproduction and development (1).