Interleukin 12B rs3212227 and rs6887695 single nucleotide polymorphisms are associated with the susceptibility to preeclampsia: Genetic, haplotype and bioinformatics analysis.

It is well-known that functional single nucleotide polymorphisms (SNPs) in IL-12B gene might intensely change the protein expression level, or modify its functions, which might result in immune disorders. The association between common IL-12B SNPs with preeclampsia (PE) risk has remained unclear yet. In a case-control study, 253 PE patients and 250 healthy subjects were genotyped for SNPs in IL-12B rs3212227 by PCR-RFLP and in IL-12B rs6887695 by AS-PCR. Novel in-silico analysis were performed to predict the potential functions of these polymorphisms, as well. The rs3212227 variation in IL12B gene showed an association with susceptibility to PE. The AC and CC genotypes and also C allele of this SNP were more frequent in patients. Likewise, they were frequent in early onset and late onset PE. The G allele and GC and CC genotype of rs6887695 SNP correlated negatively with PE development and it shown protective effect on PE risk. In addition, the AG and CC haplotypes of IL-12B were more prevalent in PE patients. Then, IL12B AC haplotype was less frequent in PE compare to healthy pregnant women. In-silico analysis of IL-12B rs3212227 gene polymorphism might not have significant impact on the mRNA structure and transcription of IL-12B. The results of our study revealed a significant relationship between rs3212227A/C and rs6887695G/C polymorphisms in IL-12B gene and the risk of PE in the Iranian population.

IL-27 variants might be genetic risk factors for preeclampsia: based on genetic polymorphisms, haplotypes and in silico approach.

Pre-eclampsia (PE) is a disorder that occurs only during pregnancy. PE is associated with neonate mortality and morbidity. Overexpression of IL-27 and its receptor have been reported frequently in the trophoblast cells of patients with PE. In this study, we aimed to evaluate the relationship between genetic polymorphisms of IL-27 rs153109, and rs17855750 in an Iranian cohort of 170 PE patients and 170 normal pregnant women using the PCR-RFLP method. In the total PE, the frequency of heterozygous and mutant homozygous genotypes of rs153109 was significantly higher, severe, and mild PE groups. The genotypes and alleles frequencies of rs17855750 gene polymorphism were associated with PE susceptibility in total, severe and early-onset sub-group patients. Haplotype analysis of IL-27 rs153109 and rs17855750 polymorphisms revealed that the mutant GG haplotype frequencies significantly increased the risk of preeclampsia in total PE and different sub-group patients, while the wild AT haplotypes were associated with decreased risk of pre-eclampsia in total and sub-group patients. The in-silico analysis showed the transition of allele A to allele G in rs153109 SNP, would lead to create a new binding site and consequently may lead to changes in IL-27 gene expression. We found that rs17855750 A>G polymorphism might be influence the function of IL-27 protein. The data attained in our study propose the incidence of IL-27rs153109 and rs17855750 SNPs might be capable to be utilized as indicators for the genetic susceptibility to PE.

Interleukin-23 receptor (IL-23R) gene polymorphisms and haplotypes associated with the risk of preeclampsia: evidence from cross-sectional and in silico studies.

PURPOSE: Pre-eclampsia is a relatively common pregnancy disorder. Serum concentrations of certain pro-inflammatory molecules and cytokines like interleukin-23 may affect the pathogenesis of pre-eclampsia. The interleukin-23 receptor (IL-23R) gene plays an important role in the progression of inflammatory and autoimmune diseases and IL-23 polymorphisms might influence the susceptibility of pre-eclampsia. The aim of the recent study was to establish the association between IL-23R gene polymorphisms and the susceptibility for developing of pre-eclampsia. METHODS: One hundred and fifty-eight pregnant patients with pre-eclampsia and 153 controls were genotyped using RFLP-PCR and AS-PCR. Also, an in silico analysis was performed to predict possible effects of these variations on IL-23R mRNA and protein structures. RESULTS: The frequency of the AG genotype of rs11209026 is related to a higher risk of pre-eclampsia. The mutant C and A allele in rs10889677 and rs11209026 SNPs, respectively, are correlated with the risk of pre-eclampsia and they are more frequent in severe late onset PE. We found higher frequency of the haplotype CG in patients with pre-eclampsia in comparison to healthy controls, as well as, the CG haplotype frequency significantly increased the risk of PE in severe, early onset, and late onset sub-groups. The results of computational analysis predicted rs11209026 and rs10889677 SNPs as functional variations, which can influence IL-23R mRNA and protein. CONCLUSIONS: The results of present study show positive association between polymorphisms in the IL-23R gene and pre-eclampsia. Therefore, the presence of IL-23R rs11209026, rs10889677 polymorphism might be markers for the genetic susceptibility to pre-eclampsia.

Association between maternal circulating IL-27 levels and preeclampsia.

In this study, we investigated the relationship between serum level of IL-27 with preeclampsia and its severity. Fifty-six preeclamptic, 21 health pregnant and 20 health nonpregnant women formed the study group. The levels of IL-27 in maternal circulation were determined by ELISA. IL-27 serum levels were found to be elevated in healthy pregnant and preeclamptic groups as compared to non-pregnant women, this increase was significant in preeclamptic cases (p=0.0004). Moreover, a significant difference of IL-27 serum level was observed between groups and the healthy pregnant controls, (p=0.0095). Notably, the level of IL-27 was considerably elevated in women with severe preeclampsia, but not with mild preeclampsia as compared with healthy pregnant women (p=0.0056, p=0.0964, respectively). Furthermore, IL-27 serum levels were significantly differences in early onset and late onset sever preeclampsia than in gestation matched healthy pregnancies (p=0.0376, p=0.0085, respectively). In conclusion, our results suggest IL-27 might be a useful biomarker for disease severity in preeclampsia.

Normal and indeterminate pattern of fetal cardiotocography in admission test and pregnancy outcome.

AIM: The aim of this study was to evaluate the prognostic value of normal and indeterminate patterns of cardiotocography in admission test (AT) and pregnancy outcome. MATERIAL AND METHODS: A prospective study enrolled 818 intrapartum singleton pregnancies with gestational age of >34 weeks, in the latent phase and with intact membrane. Cases were divided into the high- and low-risk groups. Non-Stress Test was interpreted according to the 2008 National Institute of Child Health and Human Development workshop. Adverse pregnancy outcomes were compared between groups based on AT interpretation. RESULTS: Out of 818 patients, 492 (60%) were categorized as low-risk and 326 (40%) as high-risk pregnancies. In low-risk patients, 410 (83.3%) had normal and 82 (16.7%) had indeterminate AT. These figures were 249 (76.4%) and 77 (23.6%) in high-risk patients, respectively, and two cases (0.6%) had abnormal AT. In both groups, thick meconium staining, non-reassuring fetal heart rate pattern, cesarean section and cesarean section due to non-reassuring fetal heart rate pattern were significantly more frequent in indeterminate AT than normal ones (P < 0.001). In high-risk pregnancies with indeterminate AT, the risk of low birthweight and neonatal intensive care unit (NICU) admission increased. The positive predictive value was less than 30% in predicting thick meconium staining, non-reassuring fetal heart rate pattern, PH ≤ 7.2 and NICU admission in both groups. Overall, negative predictive value of AT for neonatal death and NICU admission was 100% and 96%, respectively. CONCLUSIONS: Indeterminate patterns of cardiotocography can predict adverse pregnancy outcomes and when facing this condition, obstetricians should act cautiously.

Comparison of serum levels of interleukin 33 in combination with serum levels of C-reactive protein, Immunoglobulin G, Immunoglobulin A, and Immunoglobulin M in recurrent pregnancy loss: A case-control study.

Background: One of the critical cases of recurrent pregnancy loss is immunological factors, whereas obtaining effective prevention or treatment is necessary for cognition of reasons. Objective: In this study, we tried to evaluate some immunological factors related to recurrent pregnancy loss. Materials and Methods: This case-control study was conducted on 66 women at the age of 18-35 yr who were referred to the Clinic of Gynecology and Obstetrics, Ali Ibn Abi Taleb hospital, Zahedan, Iran, from August-December 2019. Interleukin 33 (IL-33) serum levels were measured using enzyme-linked immunosorbent assay. Immunoglobulin G, Immunoglobulin A, Immunoglobulin M (IgM), and C-reactive protein levels were measured by serology and hematology methods. Results: The mean age of total participants was 30.8 ± 3.80 yr. The mean serum IL-33 in the case group was 318.5 ± 254.1 pg/ml and was lower than the control group (354.2 ± 259.9 pg/ml), which was not statistically significant (p = 0.52). The level of C-reactive protein in the case and control was not significantly different (p = 0.27), and Immunoglobulin A and Immunoglobulin G in the case and control were also not significantly different (p = 0.46, and p = 0.16, respectively), but there were significant differences (p = 0.003) between the level of the IgM in the case and control groups. Conclusion: No statistically significant difference was observed in the IL-33 serum level, for at least 4-6 months after the last abortion in the case group and the final live birth in the control group. In contrast, serum levels of IgM were statistically significant. Finally, the need for more studies is felt according to the different results of the previous studies in this field.

The presence, severity, and onset of preeclampsia is associated with maternal interleukin-23 level: A case-control study.

Background: Scientific evidence support that imbalance between inflammatory and anti-inflammatory cytokines play a critical role in preeclampsia (PE). Objective: To investigate the relationship between the maternal serum level of interleukin (IL)-23, a pro-inflammatory cytokine, PE and its severity risk was investigated. Materials and Methods: The case-control study included a total of 145 women counting 75 PE cases, 35 healthy pregnant and 35 healthy non-pregnant controls from Zahedan, southeast of Iran. The maternal levels of IL-23 in circulation were determined via enzyme-linked immunosorbent assay. Results: The maternal serum levels of IL-23 were increased in PE and its 2 subgroups severe PE and mild PE, so that these increases were significant in PE and severe PE, but not in mild PE compared with the controls (p < 0.001 and p < 0.001, p = 0.08, respectively). Besides, the maternal IL-23 serum level was statically significant in the early onset PE, but not in the late onset-PE group compared to healthy pregnant controls (p < 0.001, p = 0.46 respectively). Conclusion: The results of our study showed a positive association between IL-23 level and PE, especially in severe type and early onset PE, which suggests that IL-23 may be involved in the pathogenesis of this systemic syndrome.

Evaluation of The Relationship between Cell-Free DNA Fetal Fraction of The Circulatory System and Fetal and Maternal Pregnancy Prognosis: A Prospective Study.

BACKGROUND: Non-invasive prenatal testing (NIPT), sometimes called noninvasive prenatal screening (NIPS), is a non-invasive prenatal genetic test using cell-free DNA in maternal blood. This method is used to diagnose fetal aneuploidy disorders such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13), which causes disability disorders or significant postpartum defects. The aim of this study was to investigate the relationship between high and low fetal fraction (FF) and prognosis of maternal pregnancy. MATERIALS AND METHODS: In this prospective study, after obtaining informed consent, 10 ml of blood was collected from 450 mothers with singleton pregnancies with gestational age above 11 weeks (11-16) at the request of NIPT for cell-free DNA BCT test. After obtaining the test results, maternal and embryonic results were evaluated based on the amount of non-cellular DNA FF. Data analysis was performed by using SPSS software version 21 and independent t test, chi-square statistical tests. RESULTS: Based on test results, 20.5% of women were nulli par. The mean FF index in the studied women was 8.3% with a standard deviation of 4.6. The minimum and maximum values were 0 and 27, respectively. The frequency of normal, low and high FFs was 73.2, 17.3 and 9.5%, respectively. CONCLUSION: High FF has fewer risks to the mother and fetus than low FF. The use of FF level (high or low) can help us determining the prognosis of pregnancy and using it to better manage the pregnancy.

Pregnancy in Non-Communicating Rudimentary Horn of A Unicornuate Uterus.

Diagnosis and management of pre-rupture stage of the pregnant horn are difficult and usually missed on a routine ultrasound scan. Also most cases are detected after rupture of pregnant horn. We presented a 28-year-oldG2 L1 woman with diagnosis of rudimentary horn pregnancy (RHP) at 14 weeks of gestation. We diagnosed her with a normal intrauterine pregnancy, whereas a pregnancy in a right-sided non-communicating rudimentary horn with massive hemoperitoneum was later discovered on laparotomy. RHP has a high risk of death for mother, so there must be a strong clinical suspicion for the diagnosis of RHP. Although there is a major advancement in field of diagnostic ultrasound and other imaging modalities, prenatal diagnosis has remained elusive and a laparotomy surgery is considered as a definitive diagnosis.

Assessment of Serum Progesterone Level on the Day of hCG Injection in Infertile Polycystic Ovarian Syndrome Patients Referred to Women's Hospital, Tehran, 2009.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common causes of endocrine disorders and main reasons for infertility due to unovulation and recurrent abortions. There is no consensus on effect of serum progesterone level on the day of human chorionic gonadotropin (hCG) injection. This study aims to evaluate the effect of plasma levels of progesterone on the day of hCG injection on the rate of pregnancy in in vitro fertilization (IVF) cycles of PCOS cases. MATERIALS AND METHODS: A stratified cohort study was conducted over a period of one year (2009) on 38 infertile women with PCOS who were suitable candidates for the IVF program. Patients were evaluated for other causes of infertility with hysterosalpingography (HSG), laparoscopy and normal sperm analysis. Patients were placed on the long protocol, followed by oocyte pick up, and finally IVF-embryo transfer (ET). Study patients were grouped according to progesterone levels of greater or less than 1.2 ng/ml on the day of hCG injection. Pregnancy rates were defined in each group. Levels on day of hCG day clinical pregnancy outcome were assessed. Experimental data were then compared against Fisher's exact test in SPSS version 18. RESULTS: The overall pregnancy rate in this study was 26.3%. In the group with progesterone levels more than 1.2 ng/ml on the day of hCG injection, the clinical pregnancy rate was 4 (21.1%) and chemical pregnancy rate was 3(15.8%). In the group with progesterone levels less than 1.2 ng/ml, the clinical pregnancy rate was 1(5.3%) and chemical pregnancy rate was 2(10. 5%). CONCLUSION: This study showed that PCOS patients with progesterone levels more than 1.2 ng/ml on the day of hCG injection resulted in higher chemical and clinical pregnancy rates. However, no significant statistical differences were found between the two groups. For further verification, we recommend additional studies with larger numbers of subjects.

Effect of predictive value of progesterone level on the day of HCG injection for IVF success in women with infertility due to tubal factor or polycystic ovarian syndrome referred to the women hospital, Tehran, 2009.

BACKGROUND: Polycystic ovarian syndrome is one of the most common causes of endocrine disorders and main reason of infertility due to anovulation and recurrent abortions. Progesterone has been shown to have an important role in fertilization of oocyte and fetal implantation. OBJECTIVE: The purpose of this study was to compare the predictive value of progesterone level on IVF success in women with infertility due to tubal factor or PCOS. MATERIALS AND METHODS: In a stratified cohort study, we assigned 76 infertile women of 20-38 years old who referred to women hospital into two equal groups with fallopian tube factor infertility and PCOS. We measured the plasma levels of progesterone and estradiol on the day of HCG administration. The patients were divided into two groups based on progesterone level cut off point of 1.2ng/ml. Thereafter the incidence of pregnancy (chemical by ß-HCG measurement and clinical by ultrasonography up to the 6 weeks after fetal transfer) was compared in these groups. RESULTS: Total pregnancy rates were 15.8% in patients with tubal factor infertility and 26.3% in women with PCOS. In women with PCOS, the pregnancy rate was less in patients with progesterone level <1.2 ng/ml. However this difference was not statistically significant. Likewise, we did not observe any significant differences in pregnancy rate in patients with fallopian tube factor infertility. CONCLUSION: Serum progesterone level on the day of HCG administration is not well predictive of the IVF success in infertile women due to fallopian tube factor or PCOS. To obtain more uniform results, we recommend use of larger samples while the bias variable is taken into account and the ROC curve is used for determination of the unique serum progesterone level.