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Introduction: Infections of the female reproductive tract may contribute to infertility to a various extent depending on the site of inflammation, especially in fallopian tube. Histologically, fallopian tube is formed by a ciliated and non-ciliated epithelium. The immune system related to epithelial cells of the FRT provides the first reaction to sexually transmitted pathogens. Recognition of these pathogens is attributed to the family of Toll like receptors (TLR) as a major part of the innate immune system. This study clarifies the different expression and localization of the TLRs in fallopian tube epithelial cells. Materials and Methods: We firstly investigated TLRs localization in fallopian tube epithelial cells by immunostaining, surprisingly we found the intensity of staining was not equal in epithelial cells, then after primary cell culture of fallopian tube epithelial cells was performed. Ring cloning was used to isolate colonies of ciliated from non- ciliated epithelial cells and then the expression of TLR1-10 was examined by Quantitative real time PCR. Results: We found TLR1-10 to be expressed in Fallopian tube epithelial cells, our studies revealed enriched localization of TLRs in Fallopian tube ciliated epithelial cells. We showed that TLRs expression in fallopian cells, with a higher level in the cilia cells versus non-ciliated cells (p<0.05). Conclusion: TLRs is localized in human Fallopian tube epithelial cells, particularly in the ciliated cells, and is likely to have a cilia-specific role in protection of reproductive tract. [ABSTRACT FROM AUTHOR]

Introduction: Toll Like Receptors are the main family of pattern recognition receptors. They recognize pathogen-associated molecular patterns and constitute a major part of the innate immune system. Previously it was reported that expression of these receptors are altered in the female reproductive tract during different stages of menstrual cycle. Here we used a fallopian tube epithelial cell line (OE-E6/E7) for investigating the role of sex hormones in modulating TLRs expression in fallopian tube. Materials and Methods: Initially TLRs expression in OE-E6/E7 cells was compared to that of fallopian tube tissue to validate the use of these cells as a model for investigation of TLR expression in the fallopian tube. To investigate the effect of sex hormones on the expression of TLRs 1-6 in fallopian tube epithelial cell line (OE-E6/E7), initially TLRs 1-6 expression in OE-E6/E7 cells was compared to that of fallopian tube tissue with RT-PCR and immunostaining. Thereafter OE-E6/E7 cells were cultured with different concentrations of estrogen (0.1, 1, 10, 100 nM) and progesterone (1, 10, 100, 1000 nM) and combination of them, control (C) (without any additional treatment of sex hormone), menstruation (M) (1nM progesterone and 0.1 nM estradiol), pre-ovulation (P) (6.5 nM progesterone and1.5 nM estradiol) and window of implantation (W) (35 nM progesterone and 1 nM estradiol), in 5% CO2 atmosphere in 75 ml flasks 24 hours in the absence of phenol red and serum. Quantitative polymerase chain reaction was performed to reveal any changes in TLRs gene expression as a result of hormonal treatment. Results: TLR1-6 genes were expressed in human fallopian tube tissue and TLR 1-6 genes and proteins were expressed in OE-E6/E7 cell line. Although estrogen and progesterone had no significant effect on TLRs expression alone, combination of them altered the expression of TLRs in OE-E6/E7 cell line. Conclusion: In conclusion, the present investigation firmly points to involvement of combination of estrogen and progesterone in modulation of TLRs gene expression in human fallopian tube cells. Further experiments should reveal the regulatory mechanism and signaling pathway behind this effect of sex hormones in modulating innate immunity in the human female reproductive tract. [ABSTRACT FROM AUTHOR]

Introduction: Toll-like receptors (TLR) are one of the major compartments of innate immune system. It was revealed that the TLR have relevance in ovulation, sperm capacitation and fertilization. So, in this study, the expression of TLR, their adaptor molecules and cytokines in human fallopian tube cell line under the effect of human normal spermatozoa was evaluated. Materials and Methods: TLR mRNA and protein were evaluated in OE-E6/E7 cell line. Semen samples from 10 donors were collected and co-incubated with OEE6/ E7 cell line and used as sperm group, and cell line without spermatozoa was used as control group. Afterwards, the level of TLR, their adaptor molecule and cytokine mRNA expression was compared using qPCR in sperm and control groups, and supernatant was used for ELISA assay of IL-6, IL-8, TNF-α and IFN-a. To determine whether elevated cytokine reaction to spermatozoa in OE-E6/E7 cell line is mediated via TLR, TLR3 function-blocking antibody was used. Results: OE-E6/E7 cell line expressed TLR 1-6 genes and proteins. TLR expressions, especially TLR3 and TLR5, in OE-E6/E7 cell line under the effect of spermatozoa were significantly higher. Also, levels of adaptor molecules and cytokine production were increased in sperm group than in control group (p<0.05). Using TLR3 function-blocking antibody confirm that cytokines production were due to TLR3 stimulation by sperm. Conclusion: It may be hypothesised that TLR are essential for spermatozoa and fallopian tube immunological interaction. IL-6, IL-8 and IFN-p have many physiological roles in fallopian tube, in addition to protecting it against invading pathogen, which is really important in reproductive system especially in fallopian tube that is susceptible to infections. [ABSTRACT FROM AUTHOR]

Introduction: Toll Like Receptors are the major compartment of innate immune system. It was revealed that the TLRs have physiological relevance in ovulation, sperm capacitation, fertilization and pregnancy. So, in this study the expression of TLRs in human fallopian tube cell line under effect of the sperm was evaluated.The effect of sperm physical contact with fallopian tube epithelial layer or just presence of sperm without physical contact on TLR expression also was evaluated. Materials and Methods: Sperms from 8 healthy donors were added in 4 groups for 24 hours: 1- sperm group: coculture of normal sperm with OE-E6/E7 cell line, 2-sperm + membrane group: coculture of normal sperm with OE-E6/E7 by using membrane supports, to prevent contact between the epithelial cells and spermatozoa, 3-Control group and 4- control + membrane group. Afterward, Toll like receptors expressions were compared in these groups by Q- PCR. In the next part, the level of TLR, their adaptor molecule and cytokines were compared with Q- PCR in sperm and control group and supernatant were used for ELISA assay. Results: OE-E6/E7 expressed TLR 1-6 genes and proteins. The mean relative expression of TLR 2, 4, 5 and 6 in sperm+ membrane group were higher significantly in compare with 3 other groups. TLRs expressions in OE-E6/E7 under effect of sperm were significantly increased in TLR3 and TLR5. Also, their signaling pathways as well as cytokine production were higher in sperm group than control (p<0.05). Conclusion: TLRs are a new insight in physiology of maternal interaction with sperm. [ABSTRACT FROM AUTHOR]

Objective: Sperm parameters and DNA integrity are crucial factors in ART outcomes. This study compared four sperm preparation methods (microfluidics, MACS, zeta potential, and swim-Up) for sorting spermatozoa with normal parameters and chromatin integrity., Methods: This study evaluated semen samples from 25 couples with male factor infertility. The semen samples were divided into four portions: one prepared by MACS, one by zeta potential, the other by microfluidics, and the last by swim-up. After preparation, sperm viability, motility, and morphology were assessed based on the WHO guidelines. DNA intergrity was assessed by SDF assay, and the CMA3 staining test was used to evaluate sperm chromatin packaging., Results: Compared to other preparation techniques, microfluidic preparation significantly improved sperm parameters, including motility, viability, morphology, and DNA integrity as well as chromatin packaging (p-value <0.05). The results also demonstrated that sperm motility, viability, and sperm DNA integrity as well as chromatin packaging, were not significantly different after preparation with MACS and Zeta potential methods. However, the MACS and Zeta methods produced improved sperm parameters and better DNA integrity than the swim-up method., Conclusions: Our results indicate that microfluidics can improve sperm quality compared to other methods of sperm preparation. When the microfluidic chip is not available, considering the similar results of sperm preparation by MACS and Zeta potential methods, it is preferred to use the Zeta method for the ART cycle due to its simplicity and cost-effectiveness.

Background: Success of assisted reproductive techniques depends on multiple factors including maternal endocrine status, hormonal balance, and paternal sperm quality. A comprehensive pre-treatment evaluation allows better prediction of outcomes and avoidance of unnecessary procedures and expenses., Methods: To examine the impact of female hormonal profiles and sperm DNA damage on the success of assisted reproduction, medical data were extracted from the clinical records of infertile couples including couples' age and levels of maternal anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL), as well as the DNA fragmentation index (DFI) in men. Any correlation between these parameters and clinical outcomes was investigated., Results: DFI and FSH independently influenced the rate of high-quality embryos. A decrease in maternal age and PRL levels increased the rate of these embryos. On the other hand, an increase in maternal body mass index (BMI) or AMH levels was associated with a reduced chance of achieving high quality embryos. In addition, any reduction in PRL levels could be associated with a higher fertilization rate. FSH levels above the normal range contribute to a reduced rate of high-quality embryos. Overall, our findings demonstrate the complex interplay between different factors and their influence on fertilization success and emphasize the importance of optimizing these variables to achieve the best possible outcome., Conclusion: Several factors can influence the outcome of infertility treatment. These factors include paternal DFI, maternal age, BMI, AMH, FSH, and PRL levels., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2024 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.)

Objective: Successful assisted reproductive technology (ART) requires a receptive endometrium with appropriate thickness and the presence of specific cytokines, chemokines, and growth factors. Despite advancements in ART, the success rates remain suboptimal, particularly in individuals with thin endometrium resistant to treatment. In this study, we evaluated the potential effects of LifeCell, a product of BioNano Technology, on the growth, development, and acceptance of endometrial cells., Study Design: We cultured endometrial cells in a defined medium with different concentrations of LifeCell and examined cell growth, development, and the expression of genes involved in endometrial receptivity., Results: Co-culture of primary human endometrial cells with 5 % Life cell solution significantly stimulated the endometrial cell growth, development and receptivity genes expression. The expression levels of FGF2 and CSF in the 72 h co-cultured were significantly increased compared with other groups (P < 0.01). HOXA10 and LIF significantly increased in the 72 h co-cultured compared with 24 h co-cultured and control groups but had no significant level compared with 48 h cocultured. HOXA10 significantly increased in the 48 h cocultured compared with control group. IL-6 and Hb-EGF increased in the 48 h co-cultured compared to other groups but had no significant level. VEGF increased in the treated groups compared to control but had no significant level. The expression of OPN, unlike the other genes, decreased in the treated group compared to the control, which was not significant., Conclusions: These findings suggest that LifeCell may be a potential option for patients with treatment-resistant thin endometrium in cases of infertility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Male fertility preservation is still challenged by cell damage induced during sperm cryopreservation and impaired sperm structure and function. Sperm ultra-rapid freezing, despite a higher protective effect compared to conventional freezing method, is still associated with suboptimal sperm cryosurvival and needs to be modified to increase its efficiency in sperm protection. Sperm freezing media supplemented with antioxidants can improve sperm parameters following freezing-warming process. In this study, we aimed to investigate the effect of employing ultra-rapid freezing and myo-inositol on sperm cryosurvival. Thirty semen samples with normal sperm parameters were collected and each one was divided into four portions to cryopreserve by conventional freezing, ultra-rapid freezing, conventional freezing + myo-inositol 2 mg/ml, and ultra-rapid freezing + myo-inositol 2 mg/ml. Sperm samples warmed after at least 24 h of freezing and sperm cryosurvival were analyzed by evaluation of sperm motility, viability, morphology and DNA fragmentation index (DFI). Freezing method had a significant influence on post-thaw sperm DFI and morphology (p < 0.05) and the interaction between freezing method and antioxidant supplementation significantly affected sperm morphology (p < 0.05). The highest percentage of sperm normal morphology and minimal DFI was achieved using ultra-rapid freezing supplemented by myo-inositol antioxidant compared to other groups (P < 0.05). The highest sperm DNA damage after freezing-warming was observed following the conventional freezing method. In conclusion, sperm freezing method was identified as factor strongly influencing sperm DFI and morphology after thawing/warming. Sperm samples can be rapidly frozen using the modified freezing media supplemented by myo-inositol without impacting sperm DNA and morphology., Competing Interests: Declaration of compenting interest The authors declare no conflict of interest., (Copyright © 2024 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

Pre-incubation of the cumulus-oocyte complex (COCs) may lead to better function of cumulus cells (CCs) and higher oocyte quality by changing the transcriptomic profile of CCs. 140 cumulus cell samples were isolated from 12 participants and divided into two groups based on pre-incubation time. In the T0 group, the COCs were immediately dissected to separate the CCs from around the oocytes. In the T2 group, CCs were prepared after 2 h of incubation. Then, the transcriptomic profile of the CCs of the non pre-incubation group was compared to the 2-h pre-incubation group. Confirmation of RNA sequencing results was done via qRT‑PCR. The CCs transcriptome analysis showed 17 genes were downregulated and 22 genes upregulated in the T2 group compared to the T0 group. Also, the pathways related to ATP production (oxidative phosphorylation, electron transport chain, and Mitochondrial complex I assembly model OXPHOS system), TNF-alpha signaling pathway, and glucocorticoid receptor pathway increased in the T2 group compared to the T0 group. Also, the TGF-β pathway was decreased in the T2 group compared to the T0 group. This study showed that 2 h pre-incubation leads to changes in important pathways in CCs, which positively affects oocyte quality., (© 2024. The Author(s).)

Background: A significant association between endometrial vascularity and pregnancy has been shown in previous research, while poor vascularization was attributed to repeated implantation failure (RIF). One possible approach to enhance angiogenesis for successful implantation is endometrial scratching (ES)., Objective: The purpose was to investigate endometrial responses to scratching by profiling angiogenesis-related gene expression in unexplained RIF participants., Materials and Methods: In this randomized controlled trial study, 20 infertile women with unexplained RIF were assigned to 2 groups by the balanced block randomization method (n = 10/each group): the intervention group (group A) (who received ES in the follicular phase) and the control group (group B). Endometrial biopsy was performed in the secretory phase. Gene expression profiling was performed using a polymerase chain reaction-array kit for human-angiogenic growth factors. The implantation and clinical pregnancy rates were also assessed., Results: Among the angiogenesis-promoting genes, FGF1 , FGF13 , FGF2 , TGFA , ANG , ANGPT1 , and VEGFA were significantly upregulated (p < 0.05). IL12A (an angiogenesis-inhibiting cytokine) was significantly upregulated (p < 0.01). In contrast, 15 genes with angiogenesis-related functions, including CXCL11 , CXCL13 , CXCL3 , CXCL5 , CXCL6 , EREG , FIGF , FST , IL10 , LEP , PPBP , PROK1 , RHOB , TNF , and TYMP, were downregulated after ES. No significant differences were observed between the intervention (group A) and control (group B) groups in terms of implantation (43.75% vs. 28.57%) or clinical pregnancy rates (75% vs. 57.1%)., Conclusion: ES induced significant alterations in the expression of angiogenesis-related genes, with notable up/downregulation of key angiogenic/antiangiogenic factors. These findings enhance our understanding of the molecular responses triggered by ES, underscoring the potential influence of ES on the complex processes of angiogenesis crucial for implantation., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2024 Aghajanpour et al.)

Background: The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies., Methods and Results: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002)., Conclusions: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Among the primary objectives of contemporary assisted reproductive technology research are achieving the births of healthy singletons and improving overall fertility outcomes. Substantial advances have been made in refining the selection of single embryos for transfer, with the aim of maximizing the likelihood of successful implantation. The principal criterion for this selection is embryo morphology. Morphological evaluation systems are based on traditional parameters, including cell count and fragmentation, pronuclear morphology, cleavage rate, blastocyst formation, and various sequential embryonic assessments. To reduce the incidence of multiple pregnancies and to identify the single embryo with the highest potential for growth, invasive techniques such as preimplantation genetic screening are employed in in vitro fertilization clinics. However, new approaches have been suggested for clinical application that do not harm the embryo and that provide consistent, accurate results. Noninvasive technologies, such as time-lapse imaging and omics, leverage morphokinetic parameters and the byproducts of embryo metabolism, respectively, to identify noninvasive prognostic markers for competent single embryo selection. While these technologies have garnered considerable interest in the research community, they are not incorporated into routine clinical practice and still have substantial room for improvement. Currently, the most promising strategies involve integrating multiple methodologies, which together are anticipated to increase the likelihood of successful pregnancy.

Sperm must pass a complex route in the female reproductive tract (FRT) to reach the fertilization site and join the oocyte. Thus, it should employ several mechanisms to survive against the female immune system, fertilize the oocyte, and successfully transmit paternal genes to the next generation. In addition to self-protection, sperm may be involved in the immune tolerance to the developing embryo and regulating the FRT for embryo implantation and subsequent pregnancy. Hence, this review intends to summarize the mechanisms that protect sperm in the FRT: including immunomodulatory factors that are carried by seminal plasma, cell-to-cell and molecular interaction of sperm with epithelial and immune cells of the FRT, high regulated secretions of inflammatory factors such as cytokines, chemokines, and growth factors, inducing immune tolerance to paternal antigens, and specialized expression of cell receptors and binding proteins. In most of these events sperm induces the FRT to protect itself by modulating immune responses for its own benefit. However, not all sperm in the semen are able to trigger the survival mechanisms and only high-quality sperm will overcome this challenge. A clear understanding of the molecular mechanisms that maintain sperm viability and function in the FRT can lead to new knowledge about infertility etiology and a new approach in assisted reproductive technologies for the preparation and selection of the best sperm based on the criteria that physiologically happen in-vivo., Competing Interests: Declaration of Competing Interest No competing or financial interest was declared., (Copyright © 2024. Published by Elsevier B.V.)

Study Question: Is a microfluidic sperm sorter (MSS) able to select higher quality sperm compared to conventional methods?, Summary Answer: The MSS selects sperm with improved parameters, lower DNA fragmentation, and higher fertilizing potential., What Is Known Already: To date, the few studies that have compared microfluidics sperm selection with conventional methods have used heterogeneous study population and have lacked molecular investigations., Study Design, Size, Duration: The efficiency of a newly designed MSS in isolating high-quality sperm was compared to the density-gradient centrifugation (DGC) and swim-up (SU) methods, using 100 semen samples in two groups, during 2023-2024., Participants/materials, Setting, Methods: Semen specimens from 50 normozoospermic and 50 non-normozoospermic men were sorted using MSS, DGC, and SU methods to compare parameters related to the quality and fertilizing potential of sperm. The fertilizing potential of sperm was determined by measurement of phospholipase C zeta (PLCζ) and post-acrosomal sheath WW domain-binding protein (PAWP) expression using flow cytometry, and the chromatin dispersion test was used to assess sperm DNA damage., Main Results and the Role of Chance: In both normozoospermic and non-normozoospermic groups, the MSS-selected sperm with the highest progressive motility, PLCζ positive expression and PLCζ and PAWP fluorescence intensity the lowest non-progressive motility, and minimal DNA fragmentation, compared to sperm selected by DGC and SU methods (P < 0.05)., Limitation, Reasons for Caution: The major limitations of our study were the low yield of sperm in the MSS chips and intentional exclusion of severe male factor infertility to yield a sufficient sperm count for molecular experiments; thus testing with severe oligozoospermic semen and samples with low count and motility is still required. In addition, due to ethical considerations, at present, it was impossible to use the sperm achieved from MSS in the clinic to assess the fertilization rate and further outcomes., Wider Implications of the Findings: Our research presents new evidence that microfluidic sperm sorting may result in the selection of high-quality sperm from raw semen. This novel technology might be a key to improving clinical outcomes of assisted reproduction in infertile patients., Study Funding/competing Interest(s): The study is funded by the Iran University of Medical Sciences and no competing interest exists., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In today's world, it is unavoidable for older adults to use technology, which causes some challenges for them. In this qualitative study, we used grounded theory to evaluate information and communication technology (ICT) adoption strategies among Iranian older adults. The participants included 18 older adults, five experts, and five family members of older adults. The data collection method included conducting semi-structured interviews, taking field notes, and observation. The data were analyzed using the Corbin and Strauss approach. Three main themes were extracted as follows: support from others, effort for learning, and smart choice. The subthemes of support from others included creativity in educating older adults; having access to an educational supporter; and receiving informational, emotional, and financial support. The subthemes of effort for learning included utilizing aids, adaptive measures, shortcut techniques, and self-learning. The subthemes of smart choice included physical characteristics, technical features, price sensitivity, and availability of an active sales representative. Accordingly, it is essential to teach older adults to increase their ICT adoption rate and continued use of technology. In this respect, developing a standard ICT manual for older adults can be beneficial., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between BMP15 and GDF9 variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of BMP15 and GDF9 were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of BMP15 and GDF9 genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32-4.11, p = 0.004).The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Frailty syndrome is a state of increased vulnerability to stressors, marked by lowered physical strength and increased dependence on others. The well-established changes in gut microbiota associated with old age suggest a probable relationship between gut microbiota and frailty., Methods and Results: This study was aimed at finding the relationship between gut microbiota and frailty syndrome, by comparing the sociodemographic data and the gut microbiota profiles of 23 non-frail and 14 frail elderly individuals. We used the quantitative polymerase chain reaction method (qPCR) to determine the bacterial loads of Bifidobacteria, Lactobacillus, Bacteroidetes, Prevotella, and Escherichia coli in stool samples from test subjects. We discovered a significant increase in the bacterial load of Prevotella in frail elderly individuals aged 70 or above. Other bacterial loads and ratios were not significantly different between the two groups., Conclusions: More comprehensive studies with larger sample sizes and encompassing a wider range of inflammation-related bacteria need to be performed to discover the existence and exact nature of these relations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The cryopreservation-thawing process of spermatozoa cells has negative impacts on their structure, function, and fertility parameters, which are known as cryoinjury. Asthenozoospermia patients are more susceptible to cryoinjury. Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases sperm glucose uptake via the induction of glucose transporters, resulting in increased sperm motility. This study aimed to investigate the efficiency of GM-CSF supplementation of the cryopreservation media for semen samples of asthenoteratozoospermia patients. The study was carried out on 20 semen samples from infertile men referred to diagnosing semen analysis. To avoid subjective bias, two main sperm motility parameters, including velocity along the curvilinear path and velocity along the straight-line path were considered by the computer-assisted sperm analysis system. Afterward, each semen sample was divided into three equal aliquots and randomly assigned to one of the following groups: group I (control, freezing media only), group II (+GM-CSF, freezing medium supplemented with 2 μL/mL GM-CSF), or group III (GM-CSF added after thawing and washing). Following semen thawing, standard parameters, mitochondrial membrane potential (MMP), and the DNA Fragmentation Index were analyzed. Total sperm motility (progressive and non-progressive) improved significantly in group III samples after a 30-minute incubation with GM-CSF compared with the control group (26.5% ± 3.1% vs. 17.51% ± 2.59%). However, no differences in progressive motility or sperm morphology were found among the three thawed samples. The percentage of vitality was significantly higher in group III compared with the other two groups (28.38% ± 3.4% vs. 22.4% ± 3.08% and 22.14% ± 2.77%, respectively) ( p  < 0.05). JC-1 levels (a marker of MMP) were not significantly different between the examined groups (44.95% ± 8.26% vs. 36.61% ± 6.95% vs. 46.67% ± 7.7%, for control, group II, and group III, respectively) ( p  > 0.05). GM-CSF may be advantageous as an additive after freezing, improving total motility and viability after 30 minutes of post-thaw incubation; however, when supplied to the freezing media before cryopreservation, it is unable to protect against cryoinjury.

Conventional sperm selection based on motility and morphology fails to provide detailed information on sperm functional and molecular status. Magnetic-activated cell sorting (MACS) protocol aims to optimize this process by selecting apoptotic sperm cells. Phospholipase C zeta-1 (PLCz1) is a physiological stimulus for oocyte activation and early embryonic development. The purpose of this study was to examine seminal parameters, DNA fragmentation index (DFI), and PLCz1 expression levels in MACS-DGC sorted specimens (DFI > 30%) and assess early development in resulting embryos. Semen specimens from 60 patients diagnosed with male factor infertility were collected and processed by either density gradient centrifugation (DGC) or MACS-DGC protocols. Pre and post-preparation analysis was performed. PLCz1 expression was assessed using the RT-PCR method. Retrieved eggs from their partners were divided into two groups in which they were injected with different sorted sperm. The fertilization rate and embryonic development were evaluated. While sperm's progressive motility and morphology significantly improved, there was a substantial decline in DFI following MACS-DGC. Fertilization rates were almost the same between the groups, and the latter resulted in remarkably more top-quality embryos and more blastocysts. PLCz1 expression was considerably higher in the MACS-DGC group. By eliminating apoptotic cells, the MACS-DGC technique could sort highly PLCz1-expressed sperm, optimize sperm selection in individuals with elevated DFI, development of resulting embryos.

Assisted reproductive techniques can help many infertile couples conceive. Therefore, there is a need for an effective method to overcome the widespread problems of infertile men and women. Oocyte and sperm quality can increase the chances of successful in vitro fertilisation. The maturation environment in which gametes are present can affect their competency for fertilisation. It is well established that myo-inositol (MI) plays a pivotal role in reproductive physiology. It participates in cell membrane formation, lipid synthesis, cell proliferation, cardiac regulation, metabolic alterations, and fertility. This molecule also acts as a direct messenger of insulin and improves glucose uptake in various reproductive tissues. Evidence suggests that MI regulates events such as gamete maturation, fertilisation, and embryo growth through intracellular Ca 2 + release and various signalling pathways. In addition to the in-vivo production of MI from glucose in the reproductive organs, its synthesis by in vitro-cultured sperm and follicles has also been reported. Therefore, MI is suggested as a therapeutic approach to maintain sperm and oocyte health in men and women with reproductive disorders and individuals of reproductive age.

Objective: Although intracytoplasmic sperm injection (ICSI) is a way to deal with in vitro fertilization failure, 3% of couples still experience repeated fertilization failure after attempted ICSI, despite having sperm within normal parameters. These patients are a challenging group whose sperm cannot fertilize the egg during ICSI. Unfortunately, no test can predict the risk of fertilization failure. Phospholipase C zeta (PLCζ) and transition nuclear proteins (TNPs) are essential factors for chromatin packaging during sperm maturation. This study aimed to assess PLCζ1 and TNP1 expression in the sperm of patients with fertilization failure and the correlations among the DNA fragmentation index, PLCζ1 and TNP1 gene and protein expression, and the risk of fertilization failure., Methods: In this study, 12 infertile couples with low fertilization rates (<25%) and complete failure of fertilization in their prior ICSI cycles despite normal sperm parameters were chosen as the case group. Fifteen individuals who underwent ICSI for the first time served as the control group. After sperm analysis and DNA fragmentation assays, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were performed to compare the gene and protein expression of PLCζ and TNP1 in both groups., Results: DNA fragmentation was significantly higher in the fertilization failure group. The qRT-PCR and Western blot results demonstrated significantly lower PLCζ and TNP1 gene and protein expression in these patients than in controls., Conclusion: The present study showed that fertilization failure in normozoospermic men was probably due to deficient DNA packaging and expression of TNP1.

Purpose: We aimed to assess the cost-effectiveness of the vitamin D supplementation program in Iranian adolescents reducing adolescent depressive Symptoms., Methods: In the current cost-effectiveness analysis, the viewpoint of Iran's Ministry of Health was selected. The target population was 1,519,762 Iranian high school students (733,657 girls and 786,105 boys). The total costs of the vitamin D supplementations program were based on the reports of the Nutrition Improvement Office of Iran's Ministry of Health and were adjusted to 2018. The variable of Quality-Adjusted Life Years (QALYs) was considered a suitable variable for estimating the effectiveness of vitamin D supplementation. We chose one year as the time horizon. A decision tree model was constructed in TreeAge Pro. The results of the cost-effectiveness analysis were reported in term of the Incremental Cost-Effectiveness Ratio (ICER)., Results: The results of our study showed that the estimated cost per QALY gained of the vitamin D supplementation program is equal to 1528.6676 $, which indicates that vitamin D supplementation in adolescents(11-18Y) is a cost-effective and a dominant strategy in preventing depression through the cost-saving and QALYs increment compared to the no intervention. Sensitivity analysis showed that the possible variations in vitamin D supplement costs could not alter the results, and vitamin D supplementation may be a predominant and cost-effective strategy to prevent adulthood depression with a 100% probability., Conclusion: The national program of vitamin D supplementation among Iranian adolescents was a cost-efficient strategy reducing adolescent depressive Symptoms through the cost-saving and QALYs increment compared to the no intervention., (© 2023. The Author(s).)

Background: Seminal plasma exosomes are now recognized to play a complex role in the regulation of the female reproductive system infertility. The objective of this study was to assess the effect of exosomes derived from the sperm of men with oligoasthenoteratozoospermia on endometrial implantation-related genes., Methods: To isolate the exosomes, we employed an ultracentrifugation method on samples derived from 10 fertile men with normal sperm parameters and 10 men with oligoasthenoteratozoospermia. The size distribution and ultrastructure of the exosomes were then characterized using transmission electron microscopy and dynamic light scattering. We detected an exosome marker using western blot analysis and confirmed the cytoplasmic localization of the exosomes by incubating them with DiI dye and visualizing them using fluorescence microscopy. After 6 hours of in vitro treatment of endometrial epithelial cells with 100 µg/ml seminal exosome, the endometrial receptivity genes were examined using qRT-PCR. To perform data analysis and quantification, we utilized Image J and Prism software. P< 0.05 were considered statistically significant., Results: After 6 hours of treatment, the mRNA levels of MUC1, LIF, G-CSF, CX3CL1, and VEGF were significantly downregulated in the endometrial epithelial cells treated with oligoasthenoteratozoospermia exosomes compared to the normal group. Although changes were observed in the mean mRNA levels of IL8 and TGF-β genes in the oligoasthenoteratozoospermia group compared to the normal group, these differences did not reach statistical significance (p > 0.05)., Conclusions: Oligoasthenoteratozoospermia exosomes have a distinct effect on endometrial receptivity compared to normal exosomes, leading to reduced expression of implantation-related genes., Competing Interests: The authors declare no conflicts of interest.

Although the role of myo-inositol (MYO) in promoting the oocyte quality of PCOS patients has been documented in human studies; the cellular effects of this supplement on oocytes have not been directly examined due to ethical limitations. In the first phase of this study, MYO dosimetry was carried out simultaneously with the PCOS model development. An effective dose was obtained following the assessment of fasting insulin and testosterone levels using ELISA and ovarian morphology appraisal by histopathology. In the second phase, following the continuous administration of the effective dose of MYO and dehydroepiandrosterone (DHEA), cellular evaluation was performed. The quality of oocytes from superovulation was analyzed by examining maturity and normal morphology percentage using a stereomicroscope, intracellular reactive oxygen species (ROS) and glutathione (GSH) levels using fluorometry, and ATP count evaluation using ELISA. The results revealed that, among the four different MYO concentrations, the 0.36 mg/g dose compared with the DHEA group reduced testosterone levels and large atretic antral follicles (LAtAnF) diameter. This dose also increased the corpus luteum count and the granulosa:theca (G/T)layer thickness ratio in antral follicles. Furthermore, this dose increased mature oocytes and normal morphology percentage, ATP count, and GSH levels; however, it decreased ROS levels in mature oocytes. Our findings provide the grounds for further cellular and molecular studies on the PCOS mouse model, suggesting that the improvement in mitochondrial function and its antioxidant properties is probably one of the mechanisms by which MYO increases oocyte quality.

Objective: The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro., Methods: Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array., Results: The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway., Conclusion: The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.

Background: Micro RNAs (miRNAs) are small non-coding RNAs known as essential regulators of cell-cell communication. Recent studies have revealed that miRNAs are secreted by a blastocyst in culture media. We hypothesized that endometrial epithelial cells take up embryo-derived miRNAs as well as other soluble factors and regulate their receptivity-related gene expression., Methods and Results: Blastocyst culture media (BCM) were collected from the individually cultured embryos, while human endometrial epithelial cells (HEECs) were collected from healthy fertile volunteers. To evaluate the effect of BCM on the endometrial receptivity gene expression, HEECs were co-cultured with implanted BCM, non-implanted BCM, and a control culture medium. After determining altered gene expression in the HEECs, the miRNAs-related genes through bioinformatics databases were identified and evaluated in the BCM. Co-culture of primary HEECs with BCM significantly stimulated the expression levels of VEGFA, HBEGF, HOXA10, and LIF in the implanted group compared with non-implanted and control groups. The fold changes of miR-195 significantly diminished in the implanted BCM group compared with the non-implanted BCM group. Reduced fold changes of miR-29b, 145 and increased miR-223 were also observed in the implanted BCM group compared with the non-implanted ones., Conclusion: miRNAs could function as potential gene expression regulators during implantation. These molecules are secreted by human blastocyst, taken up by endometrial epithelial cells, and cause a change in the endometrial function. We found that BCMs can be effective in implantation process by stimulating related receptivity gene expression., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Medical education is socially responsible for a global educational movement that transforms the development and presentation of medical schools in higher education. Therefore, in the present systematic review, we aimed to evaluate the impact of socially accountable health professional education. Published research articles were reviewed by searching the relevant terms invalid databases. In the initial search, 2340 records were obtained. At this stage, 1482 records were deleted due to duplication, and 773 records were removed due to indirect connection with the subject. Then, 85 articles were retrieved for full-text review. Finally, the complete review led to the selection of nine studies that met all inclusion criteria. Based on the results of the present systematic review, among the nine reviewed articles, four studies (44.44%) evaluated the effectiveness of social accountability on increasing the sense of empowerment, self-confidence, competencies such as teamwork, communication skills, and readiness for work. Three studies (33.333%) assessed the effectiveness of social accountability on providing further and better medical services and reducing infant mortality. Also, in two articles (22.22%), students' lack of knowledge about social accountability was studied. Social accountability can help cultivate a healthy and skilled medical workforce and be effective in improving health services provided to the people. On the other hand, there are different perceptions and views on what social responsibility really is and how its effectiveness can be measured. Also, it is highly important to provide awareness in this regard for students., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Family Medicine and Primary Care.)

This study investigates the relationship between sperm DNA damage in recurrent implantation failure (RIF) patients treated with comparative genomic hybridisation array-intracytoplasmic sperm injection (CGH array-ICSI) cycles and embryo aneuploidy screening. Forty-two RIF couples were selected. Sperm DFI was measured using TUNEL by flow cytometry. Two groups were defined as follows: (i) sperm with high DFI (> 20%); and (ii) low DFI (< 20%). Semen parameters, total antioxidant capacity (TAC), and malondialdehyde formation (MDA) were also measured in both groups. Following oocyte retrieval and ICSI procedure, blastomere biopsy was performed at the 4th day of development and evaluated with CGH-array. The high DFI group had a significant ( p  = 0.04) increase in the number of aneuploid embryos compared to the low one. According to Poisson regression results, the risk of aneuploidy embryos in the high DFI group was 55% higher than the low DFI group (RR = 1.55; 95% CI = 1.358-1.772). Moreover, chromosomal analysis showed an elevation of aneuploidy in chromosomes number 16 and 20 in the high DFI group compared to the low DFI group ( p  < 0.05). The high DFI in RIF patients may significantly affect the risk of aneuploidy embryos. Therefore, embryo selection by CGH-array should be considered for couples with high levels of sperm DNA fragmentation.

Purpose: Sperm quality plays a vital role in successful fertilization and pregnancy. Patients with fertilization failure (total failure or low-fertilization rate) despite having normal semen parameters are a challenging group whose sperm cannot fertilize the oocyte via the intracytoplasmic sperm injection (ICSI) technique. Microfluidics is offered as a new method for proper sperm sorting., Methods: This study aimed to evaluate sperm parameters, DNA fragmentation index (DFI), expression of phospholipase C zeta 1 (PLCZ1), and transition nuclear proteins 1 (TNP1) mRNAs in sperm selected by microfluidic sperm sorting (MSS) chip compared with conventional density gradient centrifugation technique in patients with fertilization failure following ICSI. Subsequence fertilization rate and embryo quality were assayed., Results: Normal morphology and total motility were significantly higher, and DFI was significantly lower in sperm selected by the MSS chip in fertilization failure and control groups. The RT-PCR results demonstrated a significant increase in the expression of PLCZ1 and TNP1 genes in sperm of both groups selected by MSS chips compared to the DGC method. In addition, with the selected sperm by MSS chip, an increase in fertilization rate and improvement of embryo quality was obtained., Conclusion: The present study findings show that sperm sorting by the microfluidic method improves fertilization rate in patients with poor fertilization outcomes following ICSI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Poor sperm quality in oligoasthenoteratospermia patients negatively affects assisted reproductive technology outcomes. Therefore, the development of sperm media is necessary to improve sperm parameters. This study investigated the effect of GM-CSF via PI3K/AKT pathway on sperm quality in OAT patients. Semen samples were collected from 20 OAT patients, and each sample was divided into two groups: Experiment and Control. In the experimental group, the samples were incubated with medium containing GM-CSF, and control samples were incubated without GM-CSF. Sperm parameters, mitochondrial membrane potential, acrosome reaction and DFI were studied; in addition, gene expression of PI3KR1, PI3KCA, GLUT1, GLUT3 and AKT1 was analysed, evaluation of PAKT/TAKT, and expression of GLUT 1, 3 was examined; subsequent fertilization rate and embryo quality were assessed. Our data showed that GM-CSF supplementation could significantly increase motility, mitochondrial activity, gene expression of PI3KCA, AKT1, the protein level of PAKT/TAKT and expression of GLUT 1, 3 while it decreases DNA fragmentation. The fertilization rate and embryo quality significantly improved in the treatment group. LY294002 had adverse effects on sperm motility and the PAKT/TAKT ratio. GM-CSF can improve in vitro sperm quality and could be a suitable supplement to sperm media for OAT patients., (© 2022 Wiley-VCH GmbH.)

Background: In the general geriatric population, Geriatric syndromes (GSs) predict greater likelihood of hospitalization, increased health care use and cost. The present study aimed to compare GSs among young and elderly patients with rheumatoid arthritis (RA)., Methods: In a cross-sectional study a total of 98 participants, including 65 elderly (≥60 years) and 33 young adult patients (<60 years) with RA who referred to the geriatric and rheumatologic clinic were enrolled. Patients were categorized into three groups (healthy elderly, n=27; elderly with RA, n=38; and young people with RA, n=33). GSs were assessed using mini-mental state exam (MMSE), five-item geriatric depression scale-15 (GDS-15), mini nutritional assessment (MNA), and asking patients about history of falls in the past year. The RA activity in patients was assessed using disease activity for rheumatoid arthritis score-28 (DAS-28) scale, serum ESR (mm/h) level., Results: There was a statistically significant differences in terms of DAS-28 (2.23±1.01 vs. 0.64±0.97, P=0.025) and ESR (28.10±6.64 vs. 23.09±7.65 mm/h, P=0.042) between healthy elderly and RA elderly patients. Elderly patients with RA were significantly more prone to have cognitive impairment (P=0.002), fall (P=0.005), malnutrition (P<0.001), urinary incontinence (P<0.001), and functional disability (P=0.021) compared to healthy elderlies and young RA patients. The results of binary logistic regression revealed that in elderly RA patients, higher DAS-28 score [odds ratio (OR) = 1.96; 95% CI 1.03, 3.84; P=0.041] was an independent risk factors for the GSs., Conclusion: The prevalence of some features of GSs were higher in the elderly RA patients than healthy elderly and young RA patients., (© 2022 Niksolat F., et al.)

The present study investigated the effects of DNA fragmentation of spermatozoa on the growth factors expression by a human oviduct epithelial cell line (OE-E6/E7). Two separate groups were examined in this study. The cell line was cultured in the presence of spermatozoa with normal DNA fragmentation index (DFI) or abnormal DFI. Total RNA from the cell line in each group was isolated, and relative expression of objective genes was analysed using PCR array. Also, the concentration of VEGF, BMP-2, BMP-7 and MSTN in the supernatant of cell culture was analysed by the ELISA method. The PCR array analysis revealed that most of the growth factors had been upregulated in the abnormal group. However, the differences between groups were statistically significant (p < 0.05) for five genes, including VEGF-A, BMP-2, BMP-6, BMP-7 and OSM. Furthermore, MSTN was the only gene that down-regulated significantly under the influence of the spermatozoa with abnormal DFI. Moreover, the results of ELISA analysis were in agreement with the data of the PCR array. It has been concluded that DNA fragmentation in human spermatozoa can probably change regular events throughout the oviducts. Consequently, the genes of interest may change sperm function and probably its fate in the female reproductive tract., (© 2022 Wiley-VCH GmbH.)

Objective: Despite the treatment of anovulation, infertility is still one of the main complications in PCOS women during reproductive age, which appears to be mainly due to impaired uterine receptivity. This study investigated the transcriptome profiles of endometrium in PCOS patients and healthy fertile individuals as the control group., Methods: Total mRNA was extracted from endometrial tissues of PCOS patients (n = 12) and healthy fertile individuals (n = 10) during the luteal phase. After cDNA synthesis, PCR array was performed using Human Female Infertility RT 2 Profiler PCR Array kit (Qiagen, Cat.No: PAHS-164Z) for evaluating expression of 84 genes contributing to the female infertility., Results: PCR Array data analysis identified significantly greater expression of CSF, IL11, IL15, IL1r1, IL1b, TNF, LIF, TNFRSF10B, TGFβ, C3, ITGA4 (Cd49d), SPP1, and Calca in PCOS women than in controls (P < 0.05). However, the expression of LIFR, C2, CD55, CFD, CALCA, LAM1, LAMC2, MMP2, MMP7, MMP9, ESR, SELL, ITGB3, and VCAM1 was significantly lower in PCOS group than in controls (P < 0.05). The results revealed dysregulation of immune-inflammatory molecules, complement activation and downregulation of IGF-I as well as adhesion molecules in PCOS group., Conclusion: The findings of this study indicated some potential causes of reduced receptivity of endometrium thus compromising the fertility in PCOS patients.

Research Question: The mechanism of Myo-Inositol, as an adjuvant, on key signaling pathways related to oocyte maturation, fertilization rate, and embryo quality as well as ovarian steroidogenesis in cumulus cells of PCOS patients, is still unclear., Design: Infertile patients who were candidates for ART cycles were divided into three groups (n = 30 in each group), including group 1: PCOS patients only receiving folic acid, group 2: PCOS patients receiving daily Myo-Inositol combined with folic acid, and a control group (group 3): normal ovulatory women without PCOS receiving only folic acid from 1 month prior to IVF cycle until the day of ovum pick up. During the ART procedure, oocytes maturation, fertilization rate, and embryo quality were assessed. The gene expressions of FSHR, LHR, CYP11A1, CYP19A1, 3β-HSD2, and StAR were also analyzed using qRT-PCR. Western blot analysis was performed for the evaluation of AKT, ERK, CREB, and AMPK phosphorylation., Result: Despite equal number of retrieved oocytes, the percentages of MII oocytes, fertilization rate, and embryo quality were found to be significantly higher in group 2 due to the administration of inofolic. The expressions of all the studied genes were significantly higher in the cumulus cells of group 1 compared to the group 2. Higher phosphorylation of ERK1/2 was found in the groups 2 and 3 compared to the group 1. On the other hand, p-Akt has significantly decreased in the group 2 compared to the group 1., Conclusion: Our study provides new insight into the molecular mechanism underlying the positive effect of Myo-Inositol on intrinsic ovarian defects in PCOS, steroidogenesis, oocyte maturation, fertilization rate, and embryo quality., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Intrauterine insemination (IUI) is a widely utilized method for treating the infertile couples. The aim of the present study was to determine the pregnancy and abortion rates after IUI and to examine the relationship of sperm parameters with these rates., Methods: This retrospective study was performed on 911 infertile couples undergoing IUI treatment in Shahid Akbarabadi IVF Centre from May 2017 to May 2019. To evaluate the correlation of sperm parameters with the clinical pregnancy and abortion rates, odds ratio (OR) with 95% confidence intervals (CI) was calculated., Results: In this study, the pregnancy rate following IUI was 15.7% (143/911), and among women who achieved pregnancy, the abortion rate was 42.0% (60/143). According to the multiple logistic regression analysis, none of the sperm parameters was associated with the pregnancy rate. Couples with either male or female factor infertility etiologies were more likely to get pregnant than those with unexplained infertility. Regarding the abortion rate, multiple logistic regression analysis revealed that normal sperm count was related to a lower abortion rate (adjusted OR=0.25, 95% CI=0.07-0.91)., Conclusion: The present study did not reveal a significant relationship between none of the sperm parameters and pregnancy rate after IUI treatment. However, among women who got pregnant, continuation of the pregnancy was associated with the normal sperm count. Furthermore, analysis of all semen parameters together in comparison to one parameter alone might be more accurate to predict pregnancy or abortion. Further prospective cohort studies with a large number of couples are required., (Copyright © 2020, Babol University of Medical Sciences.)

Background: Endometrial scratching (ES) has been proposed as a potential treatment for implantation improvement in unexplained repeated implantation failure (uRIF) patients, however, little is known about its exact molecular mechanisms., Objective: This randomized controlled trial (RCT) was conducted on twenty uRIF patients to investigate the expression of innate and adaptive immune signaling genes after ES., Methods: Ten uRIF patients in the intervention (twice endometrial sampling in follicular and luteal phases) and 10 uRIF patients in the control group (only luteal phase sampling) were randomly enrolled. Gene expression analysis with innate and adaptive immune response PCR-array kit between intervention and control groups were performed., Results: Among innate immune-associated genes, a significant decrease was observed in the expression of APCS, CPR, CCL2, NLRP3, HLA-A, TLR3 and TLR4 in the intervention group. In adaptive immune-related genes, the expression level of CD80, CD86, CXCR3, IFNγ, IFNα1, IFNβ, MBL2, CCR6, CCR8 and IL17A were decreased and CSF2, GATA3, and IL4 increased significantly in the intervention group (P < 0.05). Of 14 uRIF patients, five live birth (35.71 %) was achieved., Conclusion: ES in uRIF patients may exert positive effects on the endometrial preparation which increases its receptivity for embryo implantation by modulating the expression of an array of immune signaling pathway genes., (Copyright © 2021 Elsevier B.V. All rights reserved.)