A comparative study on the results of agonist and antagonist protocols based on serum AMH levels in patients undergoing intracytoplasmic sperm injection

Background: Serum concentrations of antimullerian hormone (AMH) correlate with ovarian response during assisted reproduction treatment (ART) cycles. Objective: This retrospective study attempted to evaluate the selection of ovarian stimulation protocols based on serum AMH levels in patients and its impact on the results of ART. Materials and Methods: Based on AMH levels, the patients with tubal factor infertility were divided in three groups of normal, low and high AMH levels. Oocyte, good embryo number and pregnancy rate in each group were analyzed. Results: Using agonist and antagonist protocols, an increase in serum AMH led to higher number of oocytes and better quality embryos. At all low, normal and high AMH levels, the agonist protocol led to a more significant increase in the number of oocytes than the antagonist protocol (p<0.05). The number of high quality embryos significantly increased by the agonist protocol than antagonist protocol in women with normal AMH levels of 1.3-2.6 ng/ml (p=0.00). Moreover, the results for the number of high quality embryos at AMH �2.6 ng/ml was in favor of the antagonist protocol (p=0.00). The results showed the lowest pregnancy rate at AMH �1.3 ng/ml. At AMH �2.6 ng/ml, there was a significant increase in pregnancy rate through the antagonist protocol (p=0.04). Conclusion: Findings of this study suggested that the ART results are predictable, taking into account the AMH levels. The protocol specific to each patient can be used given the AMH level in each individual. This is because the results of each protocol depend on individual conditions. © 2016, Research and Clinical Center for Infertitlity. All rights reserved

The Effect of Estradiol and Progesterone on Toll Like Receptor Gene Expression in A Human Fallopian Tube Epithelial Cell Line

OBJECTIVE: Toll like receptors (TLRs) are one of the main components of the innate im- mune system. It has been reported that expression of these receptors are altered in the female reproductive tract (FRT) during menstrual cycle. Here we used a fallopian tube epithelial cell line (OE-E6/E7) to evaluate the effect of two sex hormones in modulating TLR expression. MATERIALS AND METHODS: In this experimental study, initially TLR gene expression in OE- E6/E7 cells was evaluated and compared with that of fallopian tube tissue using quanti- tative real time-polymerase chain reaction (qRT-PCR) and immunostaining. Thereafter, OE-E6/E7 cells were cultured with different concentrations of estradiol and progesterone, and combination of both. qRT-PCR was performed to reveal any changes in expression of TLR genes as a result of hormonal treatment. RESULTS: TLR1-10 genes were expressed in human fallopian tube tissue. TLR1-6 genes and their respective proteins were expressed in the OE-E6/E7 cell line. Although estradiol and progesterone separately had no significant effect on TLR expression, their combined treatment altered the expression of TLRs in this cell line. Also, the pattern of TLR expres- sion in preovulation (P), mensturation (M) and window of implantation (W) were the same for all TLRs with no significant differences between P, M and W groups. CONCLUSION: These data show the significant involvement of the combination of es- tradiol and progesterone in modulation of TLR gene expression in this human fal- lopian tube cell line. Further experiments may reveal the regulatory mechanism and signalling pathway behind the effect of sex hormones in modulating TLRs in the hu- man FRT

Variable localization of Toll-like receptors in human fallopian tube epithelial cells

Objective: To determine the localization, expression, and function of Toll-like receptors (TLRs) in fallopian tube epithelial cells. Methods: The localization of TLRs in fallopian tube epithelial cells was investigated by immunostaining. Surprisingly, the intensity of staining was not equal in the secretory and ciliated cells. After primary cell culture of fallopian tube epithelial cells, ring cloning was used to isolate colonies of ciliated epithelial cells, distinct from non-ciliated epithelial cells. The expression of TLRs 1-10 was examined by quantitative real-time polymerase chain reaction, and protein localization was confirmed by immunostaining. The function of the TLRs was determined by interleukin (IL)-6 and IL-8 production in response to TLR2, TLR3, TLR5, TLR7, and TLR9 ligands. Results: Fallopian tube epithelial cells expressed TLRs 1-10 in a cell-type-specific manner. Exposing fallopian tube epithelial cells to TLR2, TLR3, TLR5, TLR7, and TLR9 agonists induced the secretion of proinflammatory cytokines such as IL-6 and IL-8. Conclusion: Our findings suggest that TLR expression in the fallopian tubes is cell-type-specific. According to our results, ciliated cells may play more effective role than non-ciliated cells in the innate immune defense of the fallopian tubes, and in interactions with gametes and embryos

Ovarian cysts formation during depot formulation of GnRH-a therapy and the effect of pretreatment with oral contraceptive pills on subsequent implantation and pregnancy rate in ART cycles

Long protocol of Gonadotropin-Releasing Hormone-analougue (GnRH-a) can result in the formation of ovarian cyst by the transient initial stimulatory effect which increases the levels of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These cysts require surgical drainage or result in poor ovarian response. Ovarian cyst formation can be prevented by taking oral contraceptives (OCs) which suppress LH and FSH after initiation of GnRH-a therapy. This study was designed to investigate ovarian cyst formation during therapy with depot formulation of GnRH-a and also the effect of taking (OCs) before starting the treatment with depot formulation of GnRH-a, on the formation of ovarian cyst, implantation and pregnancy rate in assisted reproductive tecnique (ART) cycles. Fifty four infertile women who were candidate for ART, underwent two treatment protocols in a prospective randomized trial: (a) OC+HMG+diphereline and (b) HMG+diphereline. In group (a) patients were pretreated with OC for 14 days starting from the first day of mensturation and on the day 14 received 3.75 mg IM depot diphereline. Patients in group (b) received 3.75 mg diphereline by intramuscular injection on the second day of menstruation. Sonography was performed on the first day of menstruation and also 7 and 14 days after diphereline injection. Ovarian cyst incidence, gonadotropin consumption, follicular growth, implantation rate and pregnancy in the two groups were studied. No ovarian cyst with diameter over 26 mm was developed with depot formulation of GnRH-a in any of the two groups (a and b). There was no significant difference between the two groups in the follicular growth (9.2±2.1 and 9.4±2.9), number of oocyte (5.0±2.8 and 5.4±5.7), implantation rate (0.02±0.08 and 0.03±0.10) and pregnancy rate (0.09 and 0.11). We divided the patients into two groups based on their ages: (20-34) and (�35). It showed no significant difference in the gonadotropin consumption, mean number of follicles and mean number of embryos in groups (a and b) based on their ages. No ovarian cyst developed with depot formulation of GnRH-a. So, in women with a history of ovarian cyst formation in previous cycles depot form of GnRH-a may be considered. Pretreatment with OCs during therapy with depot formulation of GnRH-a and gonadotropin didn't increase the number of oocyte, implantation rate and pregnancy. Copyright © 2008 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services

BMJ open effect of FTY720 (fingolimod) on graft survival in renal transplant recipients: A systematic review protocol

Introduction: Studies have shown that FTY720 has inconsistent effects in kidney transplant recipients. Several review articles on FTY720 have been published, but most have focused on the mechanism of action of FTY720. Therefore, this review aims to evaluate and determine the beneficial and harmful effects of FTY720 therapy in kidney transplant recipients. Methods and analysis: We electronically searched the following databases: PubMed, Scopus, the Web of Sciences, EMBASE, Cochrane databases and the Cochrane Central Registry of Controlled Trials. Any clinical, randomised controlled trials relating to FTY720 for treating kidney transplant recipients were included without publication status or language restriction. Study selection, data extraction and assessment of study quality were performed independently by two researchers. Data were synthesised by either the fixed effects or the random effects model according to a heterogeneity test. If the extracted data were suitable for meta-analysis, STATA software was used to combine the relative risks for dichotomous outcomes, and the mean differences for continuous outcomes with 95 CIs were measured. Death, loss of function and incidence of acute kidney rejection were assessed as the primary outcomes. Renal graft function, malignancy, delayed graft function and infection were evaluated as secondary outcomes. Ethics/dissemination: This review does not require formal ethics approval because the data are not individualised. The resulting review article will be submitted for publication in a peer-reviewed journal

Sex hormones alter the response of Toll-like receptor 3 to its specific ligand in fallopian tube epithelial cells.

Objective: The fallopian tubes play a critical role in the early events of fertilization. The rapid innate immune defense is an important part of the fallopian tubes. Toll-like receptor 3 (TLR3), as a part of the innate immune system, plays an important role in detecting viral infections. In this basic and experimental study, the effect of sex hormones on the function of TLR3 in the OE-E6/E7 cell line was investigated. Methods: The functionality of TLR3 in this cell line was evaluated by cytokine measurements (interleukin [IL]-6 and IL-1b) and the effects of sex hormones on TLR3 were tested by an enzyme-linked immunosorbent assay kit. Additionally, TLR3 small interfering RNA (siRNA) and a TLR3 function-blocking antibody were used to confirm our findings. Results: The production of IL-6 significantly increased in the presence of polyinosinic-polycytidylic acid (poly(I:C)) as the TLR3 ligand. Using a TLR3-siRNA-ransfected OE-E6/E7 cell line and function-blocking antibody confirmed that cytokine production was due to TLR3. In addition, 17-β estradiol and progesterone suppressed the production of IL-6 in the presence and absence of poly(I:C). Conclusion: These results imply that sex hormones exerted a suppressive effect on the function of TLR3 in the fallopian tube cell line when different concentrations of sex hormones were present. The current results also suggest that estrogen receptor beta and nuclear progesterone receptor B are likely to mediate the hormonal regulation of TLR3, as these two receptors are the main estrogen and progesterone receptors in OE-E6/E7 cell line

Localization and variable expression of Gαi2 in human endometrium and Fallopian tubes

Background: Heterotrimeric G proteins take part in membrane-mediated cell signalling and have a role in hormonal regulation. This study clarifies the expression and localization of the G protein subunit Gαi2 in the human endometrium and Fallopian tube and changes in Gαi2 expression in human endometrium during the menstrual cycle. Methods: The expression of Gαi2 was identified by Polymerase chain reaction (PCR), and localization confirmed by immunostaining. Cyclic changes in Gαi2 expression during the menstrual cycle were evaluated by quantitative real-time PCR. Results: We found Gαi2 to be expressed in human endometrium, Fallopian tube tissue and in primary cultures of Fallopian tube epithelial cells. Our studies revealed enriched localization of Gαi2 in Fallopian tube cilia and in endometrial glands. We showed that Gαi2 expression in human endometrium changes significantly during the menstrual cycle, with a higher level in the secretory versus proliferative and menstrual phases (P < 0.05). Conclusions: Gαi2 is specifically localized in human Fallopian tube epithelial cells, particularly in the cilia, and is likely to have a cilia-specific role in reproduction. Significantly variable expression of Gαi2 during the menstrual cycle suggests Gαi2 might be under hormonal regulation in the female reproductive tract in vivo. © 2007 Oxford University Press.postprin

Design and evaluation of a novel nanodrug delivery system for reducing the side effects of clomiphene citrate on endometrium

Background: Stimulation of ovulation with clomiphene citrate can cause side effects on endometrial receptivity. Formulation with nano-size may be an alternative therapy for women with ovulatory disorders. In this study, we investigated sustained-release clomiphene citrate by using Phosal-based formulation (PBF) and evaluate its decreased side effect on the endometrial receptivity. Methods: In the in-vitro study, CC loaded PBF was analyzed using Zetasizer, Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM). In the in-vivo study, 24 female mice were randomly divided into three groups: CC (5 mg/kg), CC/PBF (5 mg/kg) and SS (1 ml) daily administered and injected with 5 IU HCG and mated after two days. At day 4.5, pregnant mice were euthanized and endometrial tissue was extracted for quantitative polymerase chain reaction (Q-PCR) analysis. Results: The optimized PBF contained Phosal 50PG/glycerol in a 2:8 ratios (w/w) and the particle size of optimum formulation was 67 ± 0.30551 nm and the release of CC from CC-containing PBF was slightly faster in the first 24 h; wherein, 29 of CC was released, and 76 of CC was released up to 120 h. The mRNA levels of leukemia inhibitory factor (LIF), leukemia inhibitory factor receptor alpha (LIFR), HOXA10, Heparin-binding epidermal growth factor (HB-EGF), and epidermal growth factor (EGF) were significantly upregulated and MUC1 and PGR mRNA levels were significantly downregulated in the CC-containing PBF-treated animals compared with only CC group (P < 0.05). Conclusion: Sustained release formulation of clomiphene citrate increased its targeting efficiency and improved the impact of the CC on implantation. Figure not available: see fulltext. © 2019, Springer Nature Switzerland AG

The Effect of Synbiotic Supplementation on Growth Parameters in Mild to Moderate FTT Children Aged 2–5 Years

Synbiotic (probiotic bacteria and prebiotic) has beneficial effects on the gastrointestinal tract. This study was designed to investigate the effect of synbiotic supplementation on the growth of mild to moderate failure to thrive (FTT) children. A randomized, triple-blind, placebo-controlled trial was conducted involving 80 children aged 2–5 years with mild to moderate FTT, who were assigned at random to receive synbiotic supplementation (109 colony-forming units) or placebo for 30 days. The weights, height, and BMI were recorded in a structured diary, and the questionnaires were completed to monitor the numbers of infection episodes, gastrointestinal problems, admission to hospital, and appetite improvement during the study. Sixty-nine children completed the study. There were no differences in the demographic characteristic between the two groups. The mean weight was similar at baseline. After 30 days of intervention, the mean weight of the participants in the synbiotic group increased significantly than those in the placebo group (600 ± 37 vs. 74 ± 32 g/month P 0.000). BMI changes in synbiotic and placebo group were 0.44 and 0.07 kg/m2, and that the differences among the two groups were significant.(P 0.045) Furthermore, the height increment in synbiotic and placebo group was 0.41 and 0.37 cm respectively with no significant difference (P 0.761). Administration of 30-day synbiotic supplementation may significantly improve weight and BMI in Iranian children with mild to moderate FTT, but there is no effect on the height in this study. Further studies should be designed to found out the effect of synbiotic on growth parameters in undernourished and well-nourished children. © 2019, Springer Science+Business Media, LLC, part of Springer Nature