What is the effect of the early follicular phase FSH/LH ratio on the number of mature oocytes and embryo development?

Background/aim: Basal level of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and antral follicle count are used as predictors of ovarian reserve before starting ovulation induction. We aimed to investigate the predictor potential of early follicular phase FSH/LH ratio on controlled ovarian hyperstimulation-intracytoplasmic sperm injection (COH-ICSI) cycle outcomes. Materials and methods: This retrospective cohort study was conducted with 648 COH-ICSI cycles performed between 2012 and 2014. Cycles were classified according to their basal FSH/LH ratio, group 1(G1) = FSH/LH ratio < 2, N = 473 and group 2(G2) = FSH/LH ratio ≥ 2, N = 175. Demographic characteristics and stimulation parameters were evaluated. Retrieved total oocyte count (TOC), mature oocyte count (MOC), transferred embryo number, and pregnancy results were obtained and transferred to computer by SPSS 21.0 programme. Results: TOC and MOC of G1 were significantly higher than those of G2. The total gonadotrophin doses of G2 were significantly higher than G1. There was no significant difference between groups for transferred embryo number. Pregnancy and live birth rates were similar in both groups. Conclusion: In our population, increased FSH/LH ratio did not affect the rates of pregnancy and live birth negatively.

Timing the Juvenile-Adult Neurohormonal Transition: Functions and Evolution.

Puberty and metamorphosis are two major developmental transitions linked to the reproductive maturation. In mammals and vertebrates, the central brain acts as a gatekeeper, timing the developmental transition through the activation of a neuroendocrine circuitry. In addition to reproduction, these neuroendocrine axes and the sustaining genetic network play additional roles in metabolism, sleep and behavior. Although neurohormonal axes regulating juvenile-adult transition have been classically considered the result of convergent evolution (i.e., analogous) between mammals and insects, recent findings challenge this idea, suggesting that at least some neuroendocrine circuits might be present in the common bilaterian ancestor Urbilateria. The initial signaling pathways that trigger the transition in different species appear to be of a single evolutionary origin and, consequently, many of the resulting functions are conserved with a few other molecular players being co-opted during evolution.

AstA Signaling Functions as an Evolutionary Conserved Mechanism Timing Juvenile to Adult Transition.

The onset of sexual maturation is the result of a hormonal cascade peaking with the production of steroid hormones. In animals undergoing a program of determinate growth, sexual maturation also coincides with the attainment of adult size. The exact signals that time the onset of maturation and the mechanisms coupling growth and maturation remain elusive. Here, we show that the Drosophila neuropeptide AstA and its receptor AstAR1 act as a brain trigger for maturation and juvenile growth. We first identified AstAR1 in an RNAi-based genetic screen as a key regulator of sexual maturation. Its specific knockdown in prothoracicotropic hormone (PTTH)-producing neurons delays the onset of maturation by impairing PTTH secretion. In addition to its role in PTTH neurons, AstAR1 is required in the brain insulin-producing cells (IPCs) to promote insulin secretion and systemic growth. AstAR1 function is mediated by the AstA neuropeptide that is expressed in two bilateral neurons contacting the PTTH neurons and the IPCs. Silencing brain AstA expression delays the onset of maturation, therefore extending the growth period. However, no pupal overgrowth is observed, indicating that, in these conditions, the growth-promoting function of AstAR1 is also impaired. These data suggest that AstA/AstAR1 acts to coordinate juvenile growth with maturation. Interesting, AstA/AstAR1 is homologous to KISS/GPR54, a ligand-receptor signal required for human puberty, suggesting that an evolutionary conserved neural circuitry controls the onset of maturation.

The impact of plasma SOCS3 levels and endometrial leukocytes on unexplained infertility

Background/aim: To investigate the possible differences in endometrial leukocyte subtype distribution between women with unexplained infertility and normal fertile women and to determine whether there is a correlation between endometrial leukocyte counts and plasma cytokine levels in unexplained infertility. Materials and methods: This case-control study involved 79 infertile and 40 fertile women. Peripheral venous blood samples and endometrial samples were obtained on day 21 of the menstrual cycle. Plasma interleukin-4 (IL4), IL6, IL10, IL17, IL35, interferongamma (IFN-g), tumor necrosis factor-alpha (TNF-a), transforming growth factor-beta (TGF-b), and suppressor of cytokine signaling-3 (SOCS3) levels were determined by enzyme-linked immunosorbent assay. Endometrial CD8, CD56, and CD163 counts were detected by immunohistochemistry. Results: CD8 and CD56 counts were significantly higher, while CD163 count was significantly lower in infertile women than in fertile women. Plasma SOCS3, IL35, and IL4 levels of the infertile group were significantly lower than those of the fertile group (P < 0.01); the remaining cytokine levels were significantly higher in the infertile group than in the fertile group (P < 0.01). Conclusion: We observed aberrant cytotoxic immune activity in infertile women. The interaction between plasma SOCS3 levels and staining degree of endometrial leukocytes may be either the reason for or result of infertility leading to unavailability of the environment for implantation.

Evaluation of vitamin C and vitamin E for prevention of postoperative adhesion: a rat uterine horn model study.

AIM: To investigate the effectiveness of intraperitoneal vitamin C (VC) and vitamin E (VE) in the prevention of postoperative adhesion formation in a rat uterine horn model. METHODS: Twenty-eight Wistar albino rats were divided into four groups in which: control group, the abdomen was opened and closed without any intervention; adhesion group, a 2-cm linear incision was performed on the uterine horn and closed; VC group, VC was administrated i.p., and 15 min later a 2-cm incision was performed on the uterine horn and closed; and VE group, VE was administrated i.p., and 15 min later a 2-cm incision was performed on the uterine horn and closed. Re-laparotomy was performed 15 days later. Right uterine horn adhesions were evaluated according to macromorphological characteristics and tissue sections were further examined for fibrosis, angiogenesis and vascular endothelial growth factor (VEGF), type I collagen and malondialdehyde (MDA) scoring. Kruskal-Wallis anova and Mann-Whitney U-test were utilized for statistical analysis. RESULTS: Adhesion area and also strength were significantly lower in the VC group and the VE group compared with the adhesion group. Fibrosis and angiogenesis scores were observed to be significantly higher in the adhesion group compared with the VC group and the VE group. MDA and VEGF immunoreactivity were also found to be significantly lower in the VC group and the VE group compared with the adhesion group. However, there was no significant difference between the VC group and the VE group with respect to all the above parameters. CONCLUSION: Administration of VC or VE i.p. was observed to be effective in the prevention of postoperative adhesion formation in an experimental model.

What is the impact of SOCS3, IL-35 and IL17 in immune pathogenesis of recurrent pregnancy loss?

OBJECTIVE: To investigate the plasma levels of interleukin-4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), IL-17, IL-35 and suppressor of cytokine signaling 3 (SOCS3) in the women with history of idiopathic recurrent pregnancy loss (RPL) and in the fertile controls. METHODS: This study was conducted with 60 idiopathic RPL cases and 40 age-matched fertile controls. Mid-follicular plasma levels of IL-17, IFN-gamma, TNF-alpha, TGF-beta, IL-6, IL-4, IL-10, SOCS3 and IL-35 were assayed by an enzyme linked immunosorbent assay. RESULTS: The mean age of RPL and control cases were 31.6 ± 0.6 and 32.1 ± 0.7 years, respectively. While plasma IL-35 and SOCS3 levels of RPL group were significantly lower than that of the control group; IFN-gamma, TNF-alpha, IL-4, IL-6, IL-10, IL-17 and TGF-beta levels of RPL group were significantly higher than that of the control group. The comparison of cytokine ratios between RPL and control groups indicated significantly high TNF-alpha/IL-10, TNF-alpha/IL-4, IFN-gamma/IL-10, IFN-gamma/IL-6 and IFN-gamma/IL-4 ratios in the RPL group. IL-35/IL-17 ratio was significantly low in the RPL group compared to that in the control group. Overstimulation of TNF-alpha presented moderate influence on recurrent miscarriage risk. CONCLUSION: Decreased SOCS3 and IL-35 plasma levels and increased Th1/Th2 cytokine ratios in RPL cases pointed out the supression of anti-inflammatory process and this supression might play an important role in the pathogenesis of idiopathic RPL.

What is the impact of Th1/Th2 ratio, SOCS3, IL17, and IL35 levels in unexplained infertility?

Implantation necessitates complex interactions among the developing embryo, decidualizing endometrium, and developing maternal immune tolerance and/or alterations in cellular and humoral immune responses. Overstimulation of T helper 1 (Th1) or Th2 cytokines in systemic and local environments, alterations of the prevalence of IL17 and regulatory T cell (Treg) cytokines have also been suggested to contribute to the pathogenesis of implantation failure. We aimed to investigate the plasma levels of IL4, IL6, IL10, TNFα, IFNγ, TGFß, IL17, IL35, and SOCS3 in infertile and fertile women. This case-control study was conducted with 80 women suffering from unexplained infertility and 40 fertile women. Peripheral venous blood samples were drawn on day 21 of the menstrual cycle. The extracted plasma samples were assayed by an enzyme linked immunosorbent assay. Statistical analysis was performed using SPSS version 16.0. Our main findings were as follows: despite the significantly high IL17 and IL35 plasma levels of infertile women, IL35/IL17 ratio was significantly lower in the infertile group compared with that in the fertile group; SOCS3 plasma levels showed an inverse relation with plasma levels of all cytokines except IL35; increased plasma IL17 levels (>3.42 pg/mL) have a negative impact on fertility; TNFα/IL10, IFNγ/IL10, IFNγ/IL6, and IFNγ/IL4 ratios were significantly higher in infertile group compared with those in the fertile group. It is not possible to show the major immunological factor(s) of unexplained infertility, but our findings point out that the decreased suppressor activity of the immune system may play a role in implantation failure.

Plasma IL-17, IL-35, interferon-γ, SOCS3 and TGF-ß levels in pregnant women with preeclampsia, and their relation with severity of disease.

UNLABELLED: Abstract Objective: To research the hypothesis of preeclampsia (PE) is associated with increased systemic inflammatory responses of Th1-type as well as decreased Th2-type responses; we evaluated the maternal plasma levels of IFN-gamma, TNF-alpha, TGF-beta, IL-4, IL-6, IL-10, IL-17, IL-35 and SOCS3 in preeclamptic and healthy pregnants. METHODS: This study was conducted with 40 preeclamptic (study group) and 40 normotensive pregnant (control) women in third trimester when they were admitted to the labor and delivery unit. The extracted maternal plasma samples were assayed by an enzyme-linked immunosorbent assay. Statistical analysis was performed by SPSS 16.0 version. RESULTS: While IFN-gamma and TGF-beta levels of preeclamptic women were significantly higher (p < 0.01), IL-35 and IL-17 levels of preeclamptic women were significantly lower (p < 0.01) than those of controls. The ratios of IFN-gamma/IL-10, IFN-gamma/IL-6, IFN-gamma/IL-4 were significantly high and ratio of IL-35/IL-17 was significantly low in the PE group compared to those in the control group. Maternal plasma SOCS3 levels showed negative correlation with blood pressure and proteinuria severity, but none of the cytokines showed influence on blood pressure and proteinuria after adjusting for maternal and gestational age. CONCLUSIONS: Increased IFN-gamma/TGF-beta production and reduced IL-35/IL-17/SOCS3 production in preeclamptic women may lead to less cytokine inhibitory activity in PE, which may account for the increased proteinuria and blood pressure in PE.

Is there any relation between IL-6 gene -174 G>C polymorphism and postmenopausal osteoporosis?

OBJECTIVE: IL-6 gene single nucleotide polymorphisms (SNPs) have been reported to have a protective effect against bone resorption. We aimed to investigate the association between bone mineral density and IL-6 promoter region -174 G>C SNP. STUDY DESIGN: This study included 356 postmenopausal Turkish women, of whom 201 were osteoporotic (lumbar spine T score<-2.5 SD) and 155 non-osteoporotic (lumbar spine T score>-1.5 SD). Bone mineral density (BMD) measures were obtained using dual-energy X-ray absorptiometry. SNP of the IL-6 gene (-174 G>C) was examined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The frequencies of the variant C allele (24% vs. 30%, p=0.074) and mutant CC genotype (12% vs. 20%, p=0.094) were higher in non-osteoporotic women. Lumbar spine and total hip BMD values were lowest among women with the G/G genotype, intermediate in the heterozygotes, and highest in women with the C/C genotype. The GG (p=0.022) and GC (p=0.037) genotypes were covariates which approached statistical significance in the regression model fitting of BMD. CONCLUSION: IL-6 promoter region SNP showed an association with BMD in this postmenopausal Turkish population and these data suggest that the wild GG genotype influences the phenotype.

Our clinical experience about prenatal diagnosis and neonatal outcomes of fetal central nervous system anomalies.

OBJECTIVE: To present a retrospective analysis of the prenatal diagnosis and the outcome of fetuses diagnosed with central nervous system (CNS) anomalies. MATERIALS AND METHODS: We reviewed the medical records and ultrasound data of 69 cases diagnosed with CNS anomalies from 2007 to 2008. We described the prenatal diagnosis, associated findings, and outcome of these patients. RESULTS: Sixty-nine patients were diagnosed with CNS anomalies. Of these, 31 had ventriculomegaly + hydrocephaly, 14 had spina bifida + meningomyelosel, 5 had choroid plexus cyst, 5 had Dandy Walker malformation, 3 had sacrocoxigeal teratoma, 2 had encephalosel, 1 had microcephaly, and 1 had Arnold Chiari malformation. Eight amniocentesis, three cord blood sampling, and two fetal reduction procedure were performed. Nine pregnancy termination and 36 delivery were performed. Neurosurgical correction was performed for neonates with spina bifida, hydrocephaly and sacrocoxigeal teratoma. Twenty-one neonates were discharged with cure, 4 neonates with follow-up, 7 neonates with paraplegia, and 13 neonates died. CONCLUSION: The outcome of fetuses with CNS anomalies was shown to depend mainly on the degree of neural tube defect and the associated anomalies were the most important factors in surviving.