Analysis of 14-bp HLA-G polymorphism in middle-eastern women with recurrent implantation failure

Background: Implantation appears to be the major rate-limiting step in assisted reproductive techniques success. Recurrent implantation failure (RIF) is a common condition, being the failure to achieve a clinical pregnancy after transfer of four or more good-quality embryos in a minimum of two IVF cycles in a woman under the age of 40. Human leukocyte antigen G (HLA-G) is thought to play a key role in implantation by modulating cytokine secretion to enable the semi-allogeneic embryo to implant into the maternal endometrium. The aim of this study was to investigate the association between the 14-bp ins/del HLA-G polymorphism and rates of RIF. No similar studies were conducted nationally or regionally.Methods: The study was designed as a case-control study. A proportion of 30 patients with RIF were selected as the experimental group. The control group included 15 patients with at least one pregnancy following IVF procedure. Peripheral blood samples were collected from both groups. DNA was extracted and the polymorphism analysis was performed using (AMPLI - HLA-G polymorphism) kit, then PCR products were electrophoresed on 2% agarose gel. statistical analysis was performed using SPSS statistics software.Results: A total of 45 middle-eastern patients were recruited in this case-control study. High frequency of the polymorphism was found in both case (76.6%) and control (86.67%) groups, but with no significant difference between the two groups (p=0.429).Conclusions: There is no correlation between the 14-bp ins/del HLA-G polymorphism and RIF, thus it may be considered as a normal polymorphism and might not affect the level of HLA-G

Genetic analysis of the M2/ANXA5 haplotype in Syrian healthy population

Background: Annexin A5 (ANXA5) is an abundantly and ubiquitously expressed protein showing the highest levels of concentration in kidney, liver and placenta. ANXA5 plays a central role in the machinery of membrane repair by enabling of a protective 2D bandage at membrane damaged site, has properties anti-inflammatory, pro-fibrinolytic and anti-thrombotic. Four polymorphisms have been identified in the ANXA5 promoter, which were transmitted as a joint haplotype (M2). M2 haplotype decrease the ANXA5 gene promoter activity and mRNA expression which causes several troubles.Methods: The aim of this cross-sectional study is to determine the frequency of M2/ANXA5 haplotype in healthy Syrian individuals and compare the genotype and allele distribution with other populations. In this study 94 (female, 71 and male, 23) unrelated healthy Syrian nationals were involved. 94 DNA samples have been collected in order to determine the spread the genotype M2 haplotype using allele specific polymerase chain reaction (AS-PCR).Results: Our results indicate that the distribution of the alleles and genotypes of M2 haplotype vary considerably in different populations. In the Syrian population the distribution of M2 and wide type (WT) were M2/M2 9.6%, M2/WT 44.7%, WT/WT 45.7%. The M2 haplotype was found in 45 of women (allele frequency 31%) and in 15 of men (allele frequency 32%). The distribution of the ANXA5 genotypes in Syrian study group conformed to Hardy-Weinberg equilibrium (p=0.92).Conclusions: No significant differences were found at frequency distribution of different genotypes and M2 allele between women and men within this Syrian cohort. In comparison with the results of other studies, the results of this study demonstrate that the frequency and distribution of the M2 haplotype in Syrian population are different from most other populations worldwide

Management outcomes of ectopic pregnancy depending on different treatment modalities: a cohort study

Background: Ectopic pregnancy is the most common cause of maternal morbidity and mortality during the first trimester of pregnancy. The present study aimed to review and evaluate the management outcomes of ectopic pregnancy in Damascus University Maternity Hospital, Syria.Methods: A retrospective cohort study was performed on women referring to Damascus University Hospital of Obstetrics and Gynecology (OBGYN) for ectopic pregnancy. Patients were assigned into groups by method of treatment: expectant management (Group 1), single-dose methotrexate regimen (Group 2), two-dose methotrexate regimen (Group 3), and surgical intervention (Group 4). Parameters assessed were risk factors for ectopic pregnancies, transvaginal ultrasonography findings, serum human chorionic gonadotropin (hCG) levels on Days 0, 4, 7, and types of surgical intervention in women that underwent any surgical intervention. A treatment modality was considered successful when hCG levels declined to less than 5 mIU/L without further administration of methotrexate dose or need for surgery.Results: Seventy-seven women with ectopic pregnancy were admitted to the hospital during the study period. Groups 1, 2, 3, and 4 constituted 20.8%, 13.0%, 6.5% and 59.7% of the patients respectively. The most common encountered risk factors for ectopic pregnancy in the patients were history of previous intra-abdominal or pelvic surgery (57.1%) and history of miscarriage (41.6%). A statistically significant difference in the serum hCG concentrations measured on day 0, day 4, and day 7 were observed between the groups.Conclusions: The success rate in ectopic pregnancy treatment was 56.25% for the expectant management, 70% for the single-dose methotrexate regimen, and 40% for two-dose methotrexate regimen

The protein C deficiency and its effects on in-vitro fertilization outcome and recurrent pregnancy loss: a Syrian cohort study

Background: Protein C deficiency is a rare disease; it could be primary or secondary. Female patients with protein C deficiency may develop pregnancy-associated thrombosis. The clear association between the protein C deficiency and fertility or in-vitro fertilization (IVF) results has not been known yet. In our study, we aimed to determine the prevalence of protein C deficiency in Syrian infertile women and to assess the impact of protein C deficiency on abortion, recurrent IVF Failure, and IVF results.Methods: the electronic patients’ results were retrospectively screened. A total of 238 women, who had IVF cycles between January 2012 and December 2017 in a tertiary care hospital, met our including criteria.Results: the prevalence of protein C deficiency was 13.45%. There was a significant association between the protein C level and recurrent pregnancy loss (RPL). Furthermore, the protein C deficiency has an impact on the IVF results. Additionally, we did not find any association between protein C deficiency and age or number of previous IVF cycles.Conclusions: the protein C could be the hidden factor that affects IVF results. More research should be done to better understanding the role of protein C in infertility and IVF

An intronic polymorphism of the gene Plakophilin-3 is associated with IVF failure

Background: Implantation failure is determined when transferred embryos fail to implant following in vitro fertilization (IVF). In recent years, many studies suggest that implantation failure could be related to several genetic factors. In the current study, authors aimed to investigate the association of PKP3 rs10902158 (G>A) polymorphisms with the risk of implantation failure after ICSI treatment.Methods: 97 women, who underwent ICSI treatment owing to male factor infertility, were prospectively recruited in this cross-sectional study. Genomic DNA was prepared from peripheral blood samples in order to analyze the polymorphism (rs10902158) at the PKP3 gene by PCR-RFLP. The Results were presented as a genotype (GG, GA, and AA), and their relationship to IVF outcome was analyzed.Results: The patients were divided into two groups according to clinical pregnancy: the pregnant group included 51 patients (53%) and the non-pregnant group included 46 patients (47%). The clinical pregnancy outcome was significantly different between genotypes, which was 0%, 45.8% and 58.8% in the patients having the genotype AA, GA and GG respectively (p-value = 0.03).Conclusions: The presence of the allele A of the PKP3 SNP rs10902158 is associated with a reduced clinical pregnancy outcome in the patients undergoing ICSI treatment and may be helpful predictor for implantation failure

Evaluation of factor VIII value in normal women and whom encountered recurrent pregnancy loss: is there any significant difference?

Background: Recurrent pregnancy loss (RPL) is a serious problem on the women, it defined as two or more consecutive pregnancy losses before the fetus has reached birth. The aim of this study is to evaluate the association between the elevation in the factor VIII and RPL. Because women who have thrombophilia have increased risk of fetal loss in most studies.Methods: A total 72 women were recruited in this case control study. They divided into two groups: the RPL group included 41 women with a history of recurrent pregnancy loss and the control group included 31 healthy women, who had at least one successful pregnancy and none of them had a history of fetal loss or complicated pregnancy.Results: A majority of the patients of this study didn't have a high level of factor VIII, 9 of 41 (22%) patients of RPL group in comparison with 21 of 32 (65,6%) of control group, that suffer from the increase rate of FVIII, this means that factor VIII doesn't effect on RPL.Conclusions: The present study showed that the serum elevation in the factor VIII is not significantly associated with RPL

Predictive value of serum Inhibin-B levels as an indicator of the presence of testicular spermatozoa in non-obstructive azoospermia

Introduction: Inhibin-B is glycoproteins of the transforming growth factor-β superfamily, is produced almost exclusively by the Sertoli cells and has been proposed as direct markers of their function and indirect markers of spermatogenesis. Our objective was to evaluate the predictive value of serum Inhibin-B levels as an indicator of the presence of testicular spermatozoa in non-obstructive azoospermia (NOA), compared with other markers such as FSH and testicular volume. Material and methods: A total of 228 patients with idiopathic non-obstructive azoospermia (NOA) were recruited in this prospective study. Inhibin-B in serum has been evaluated before sperm retrieval by Enzyme-Linked Immuno-Sorbent Assay (Elisa), in addition to FSH and testosterone. Testicular volume was measured by sonography. Testicular Fine Needle Aspiration (FNA) and Testicular Sperm Extraction (TESE) were performed for sperm retrieval. The patients were classified according to the presence or absence of Testicular spermatozoa into two groups (I and II respectively). Results: Spermatozoa were retrieved in 87 patients (38.16%), classified as group I and were absent in 141 patients (61.84%) classified as group II. Mean serum Inhibin-B ± SD was significantly higher in group I than in group II, 71.77 versus 27.49 respectively (P < 0.001). The odds ratio of Inhibin-B for success of sperm retrieval was 1.0409 (95% CI: 1.0286–1.0533). Serum Inhibin-B demonstrated that the best inhibin-B value threshold for discriminating between successful and failed sperm retrieval was 35 pg/ml, with a sensitivity of 75.86 (95% Confidence interval [CI]: 65.5–84.4) and specificity of 80.85 (CI: 73.4–87.0) for the prediction of the presence of testicular spermatozoa as determined by the receiver operating characteristic (ROC) curve analysis and area under curve (AUC). Conclusions: Inhibin-B might be a predictive marker of persistent spermatogenesis in the men with non-obstructive azoospermia

Follicular fluid Vascular Endothelial Growth Factor (VEGF) could be a predictor for pregnancy outcome in normo-responders and polycystic ovary syndrome women undergoing IVF/ICSI treatment cycles

Objective: The aim of this study was to evaluate the serum and follicular fluid levels of Vascular Endothelial Growth Factor (VEGF) as possible predictive markers for IVF outcome in PCOS patients. Design: Prospective cross-sectional study. Materials and Methods: Forty patients with PCOS and 40 age and weight matched control women were included in this study. All of them were enrolled in the IVF program. Blood and follicular fluid (FF) samples were collected from all subjects on the day of oocyte retrieval. VEGF levels were measured in serum and follicular fluid (FF) using enzyme linked immunosorbent assay (ELISA). The correlation between VEGF levels and number of retrieved oocyte, number of mature oocyte, number of fertilized oocyte, number of embryos, percent of mature oocytes, fertilization rate and pregnancy was assessed. Results: PCOS patients showed higher serum VEGF levels than controls (297.46 ± 159.45 pg/ml vs. 134.08 ± 113.06 pg/ml, p value = 0.0001) and higher FF VEGF levels compared to controls (1358.92 ± 820.86 pg/ml vs. 987.58 ± 236.62 pg/ml, p value = 0.007). Serum VEGF levels were not significantly correlated with the number of retrieved oocyte in both PCOS (r = 0.37, p value = 0.19) and control women (r = −0.03, p value = 0.83), and FF VEGF levels were not significantly correlated with the number of retrieved oocyte in both PCOS (r = −0.06, p value = 0.7) and control women (r = −0.13, p value = 0.43). Both serum and FF VEGF levels were not significantly correlated with the number of mature oocyte, number of fertilized oocyte, number of embryos, percent of mature oocytes or fertilization rate. Serum VEGF levels were not significantly different between pregnant and non-pregnant women in both PCOS (256.69 ± 139.11 pg/ml vs. 300.20 ± 114.60 pg/ml, p value = 0.416) and control women (107.98 ± 115.51 pg/ml vs. 154.39 ± 111.09 pg/ml, p value = 0.271), whereas FF VEGF levels were significantly lower in FFs from the group of pregnancy than those from the group of no-pregnancy in both PCOS (812.04 ± 308.16 pg/ml vs. 1936.78 ± 771.79 pg/ml, p value = 0.0001) and control women (822.45 ± 199.45 pg/ml vs. 1171.98 ± 139.60 pg/ml, p value = 0.0001). FF VEGF levels had a significant predictive value of pregnancy in both PCOS (p value = 0.0001) and control women (p value = 0.0001). Conclusion: FF VEGF levels may serve as a reliable predictive marker for pregnancy in both normal women and women with polycystic ovary syndrome undergoing IVF

Follicular fluid antimullerian hormone (AMH) does not predict IVF outcomes in polycystic ovary syndrome patients

Introduction: AMH, is a member of the transforming growth factor (TGF-β) produced by granulosa cells with the highest expression being in small antral follicles. Our objective is to evaluate the predictive value of follicular AMH levels as an indicator of IVF outcomes in PCOS patients. Material and methods: A total of 63 patients undergoing the IVF trail were recruited for this prospective case-control study. The patients were classified into three groups: Group I: 43 patients with Polycystic ovary syndrome (PCOS). Group II: 20 normo-ovulatory patients were recruited for the IVF trail because of the male infertility factor (control group). Group III: consists of 33 patients from group I recruited to determine the effect of controlled ovarian hyperstimulation (COH) on serum AMH levels. Serum AMH levels were performed on day 3 of the menstrual cycle whereas the follicular fluid AMH level has been evaluated at the time of oocyte retrieval by enzyme linked immune-sorbent assay (AMH Gen II ELISA kit, Beckman Coulter, Inc. USA). AMH concentrations were adjusted to its protein content, to avoid possible bias due to FF volume variability. The relationship between follicular fluid AMH (FF AMH) levels and the number of oocytes retrieved, number of mature oocytes, number of embryos, fertilization and clinical pregnancy rate were assessed. The demographic data were similar between two groups as regards age and BMI. Results: Both serum AMH levels and FF AMH levels were significantly higher in PCOS patients than in the controls, the values for serum levels were (5.07 ± 3.39 ng/ml, 3.07 ± 2.09 ng/ml) respectively and for follicular fluid levels were (67 ± 50.7 ng/g∗, 38.5 ± 44.4 ng/g) respectively. Serum AMH levels showed a positive correlation with oocytes retrieved and mature oocyte number, but there was no significant correlation with good quality embryo number, fertilization rate or clinical pregnancy rate in PCOS patients. On the other hand FF AMH levels do not show correlation with any of the IVF outcomes mentioned above in PCOS patients. Interestingly, the interval change in serum AMH levels between baseline AMH levels and levels after COH had a significant predictive value of pregnancy. Conclusions: Serum AMH levels can predict the number of the retrieved oocytes and mature oocytes, whereas FF AMH may not be a valuable predictor for IVF outcomes in PCOS patients

Allergic rhinitis, asthma and laryngopharyngeal reflux disease: a cross-sectional study on their reciprocal relations

Abstract Allergic rhinitis (AR) is a common medical condition worldwide. It is an inflammation in the nasal mucosa due to allergen exposure throughout the year. Laryngopharyngeal reflux (LPR) is another medical condition that can overlap with AR. LPR can be considered an extra oesophageal manifestation of gastro-oesophageal reflux disease (GORD) or a different entity. Its diagnosis imposes a real challenge as it has a wide range of unspecific symptoms. Although AR and LPR are not life-threatening, they can severely affect the quality of life for years and cause substantial distress. Moreover, having AR is associated with having asthma which is also in turn associated with GORD. This is a cross-sectional study which used surveys distributed online on Social Media and targeted people across Syria. All participants who responded to the key questions were included. Reflux symptom index (RSI) was used for LPR, and score for allergic rhinitis (SFAR) was used for AR. Demographic questions and whether the participant had asthma were also included in the survey. We found that there was an association between the symptoms of LPR and AR p < 0.0001 (OR, 2.592; 95% CI 1.846–3.639), and their scores were significantly correlated (r = 0.334). Having asthma was associated with LPR symptoms p = 0.0002 (OR 3.096; 95% CI 1.665–5.759) and AR p < 0.0001 (OR 6.772; 95% CI 2.823–16.248). We concluded that there was a significant association between having LPR, AR, and asthma. We need more studies to distinguish between their common symptoms and aetiologies