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The aim of the study was to determine the semen parameters of a proven fertile population and to compare these parameters with that of a subfertile group in the same region. Sixty-nine fertile male patients were studied and compared with 93 patients recruited at an infertility clinic. A sub-sample of patients was matched according to age. Sixty-one were studied in the fertile group and 62 in the infertile group. Receiver operator characteristics analysis was done on the sub-sample. The threshold value of the progressive motility was 42% and it was the best parameter with sperm morphology to distinguish between the two groups. At 69% sensitivity and 67% specificity the sperm morphology threshold was 12% normal forms. If the positive and negative predictive value was used to screen the general population to identify the subfertile group, a 5% normal morphology threshold was indicated with 14% progressive motility, 30% motility and a concentration of 9x10(6)/ml or lower. The negative predictive values of the parameters were good and achieved 90% in most cases. The sensitivity of the semen parameters at the reported thresholds was poor and indicated a large overlap in the distributions of these variables in the fertile and infertile groups. To distinguish between the fertile and subfertile population, the most significant finding of this study was the progressive motility with a threshold level of 14%. The cut-off value of the sperm morphology (5%) in vivo was consistent with the previous publications in assisted reproduction programmes for sperm morphology. [ABSTRACT FROM AUTHOR]

Background: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells. Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an imbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known., Methods: Primary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypes in vitro . The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients., Results: TRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cells in vitro . Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content., Conclusions: TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gunalp, Helvaci, Oner, Bursalı, Conforte, Güner, Karakülah, Szegezdi and Sag.)

Various aspects of the in vitro culture conditions can impact the functional response of immune cells. For example, it was shown that a Ca2+ concentration of at least 1.5 mM during in vitro stimulation is needed for optimal cytokine production by conventional αβ T cells. Here we extend these findings by showing that also unconventional T cells (invariant Natural Killer T cells, mucosal-associated invariant T cells, γδ T cells), as well as B cells, show an increased cytokine response following in vitro stimulation in the presence of elevated Ca2+ concentrations. This effect appeared more pronounced with mouse than with human lymphoid cells and did not influence their survival. A similarly increased cytokine response due to elevated Ca2+ levels was observed with primary human monocytes. In contrast, primary human monocyte-derived macrophages, either unpolarized (M0) or polarized into M1 or M2 macrophages, displayed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ concentrations promoted phenotypic M1 differentiation by increasing M1 markers on M1 and M2 macrophages and decreasing M2 markers on M2 macrophages. However, the cytokine production of macrophages, again in contrast to the lymphoid cells, was unaltered by the Ca2+ concentration. In summary, our data demonstrate that the Ca2+ concentration during in vitro cultures is an important variable to be considered for functional experiments and that elevated Ca2+ levels can boost cytokine production by both mouse and human lymphoid cells., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Eskiocak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Macrophages are highly plastic cells that can polarize into functionally distinct subsets in vivo and in vitro in response to environmental signals. The development of protocols to model macrophage polarization in vitro greatly contributes to our understanding of macrophage biology. Macrophages are divided into two main groups: Pro-inflammatory M1 macrophages (classically activated) and anti-inflammatory M2 macrophages (alternatively activated), based on several key surface markers and the production of inflammatory mediators. However, the expression of these common macrophage polarization markers is greatly affected by the stimulation time used. Unfortunately, there is no consensus yet regarding the optimal stimulation times for particular macrophage polarization markers in in vitro experiments. This situation is problematic, (i) as analysing a particular marker at a suboptimal time point can lead to false-negative results, and (ii) as it clearly impedes the comparison of different studies. Using human monocyte-derived macrophages (MDMs) in vitro, we analysed how the expression of the main polarization markers for M1 (CD64, CD86, CXCL9, CXCL10, HLA-DR, IDO1, IL1β, IL12, TNF), M2a (CD200R, CD206, CCL17, CCL22, IL-10, TGM2), and M2c (CD163, IL-10, TGFβ) macrophages changes over time at mRNA and protein levels. Our data establish the most appropriate stimulation time for the analysis of the expression of human macrophage polarization markers in vitro. Providing such a reference guide will likely facilitate the investigation of macrophage polarization and its reproducibility., Competing Interests: The authors have declared that no competing interests exist.

Expression of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by immune cells can lead to the induction of apoptosis in tumor cells. However, it becomes increasingly clear that the interaction of TRAIL and its death receptors (DRs) can also directly impact immune cells and influence immune responses. Here, we review what is known about the role of TRAIL/DRs in immune cells and immune responses in general and in the tumor microenvironment in particular.

Autoimmune estrogen dermatitis is a cyclical cutaneous eruption that occurs premenstrually and goes to the rapid resolution within a few days of menstrual cycles. The disorder has variable clinical manifestations consisting of macules, papules, vesicles, urticarial lesions, bullae, eczematous plaques, and erythema multiforme-like lesions. Herein, we present a case of a 30-year-old woman with attacks of edema and erosions involving the oral and genital mucosal sites on every first day of her menstruation period. She had also multiple endocrinological problems such as hypotroidism and infertility. To determine the sex hormon sensitivity, intradermal skin tests were performed. Based on her personal history and skin test findings, a diagnosis of autoimmune estrogen dermatitis was made. After the oophorectomy, she was free from the skin and mucosal symptoms. We propose that it is important to suspect the diagnosis of autoimmune estrogen dermatitis in patients who present with recurrent cylic eruptions and it must be kept in mind that these patients might have a concomitant infertility.

The parameters measured in the standard semen analysis may be insufficient for exact differentiation between fertile and infertile men. Therefore, we assume that the high rate of apoptotic sperm in ejaculate may play a role on the aetiology of unexplained infertility. Couples with unexplained infertility treated by ovulation induction and intrauterine insemination were consecutively enrolled (n = 94). To determine the proapoptotic sperm rate, the ejaculate from patients was stained with annexin V. Thirteen of the 94 couples (13.8%) conceived after intrauterine insemination. The annexin V-positive sperm rate was found to be 20.0% in the whole group. In women failing to conceive, the annexin V-positive sperm rate was 20.8% compared to 15.7% in patients who achieved pregnancy. Although there is a trend towards higher preapoptotic sperm rate in couples failing to get pregnant with insemination, the difference did not reach statistical significance.

Objective: To investigate whether the histological changes observed in testicular tissue might be correlated with pregnancy outcome in intracytoplasmic sperm injection-testicular sperm extraction (TESE) cycles in nonobstructive azoospermic patients. Embryo quality was also tested in various types of histology., Study Design: We retrospectively analyzed the pathology results of 209 testicular biopsies from nonobstructive azoospermic patients in our assisted reproductive technologies clinic. According to the final pathology reports, the study group was divided into the following categories: Group A (Sertoli-cell-only), Group B (maturation arrest), Group C (hypospermatogenesis), Group D (normal spermatogenesis), and Group E (mixed pattern)., Results: Spermatozoa were identified in 114 of 209 cases (54.5%). Sperm retrieval and presence of motile spermatozoa after TESE was highest in normal spermatogenesis and lowest in Sertoli-cell-only groups. Fertilization rate was highest in the normal spermatogenesis and hypospermatogenesis groups. Embryo grades on day 3 were comparable between groups. Clinical pregnancy per embryo transfer was also similar. Both fertilization and clinical pregnancy rates were statistically higher in favor of motile spermatozoa group., Conclusion: Testicular histopathology not only gives information regarding the probability of retrieving sperm at TESE, but also is a good predictor of fertilization. Once a motile spermatozoon is identified, the chance of clinical pregnancy might improve probably due to relatively good optimal microenvironment within the testis.

Backgrounds: What is not clear as yet is not only the etiology, but also the management of osseous metaplasia. We describe an infertile patient with osseous metaplasia and subsequent pregnancy after treatment and review the literature from infertility perspective., Method: We presented a 30-year-old woman with 8 years of secondary infertility who conceived spontaneously after removal of osseous tissue by operative hysteroscopy (HS) following one failed in vitro fertilization cycle. The current literature regarding the osseous metaplasia and fertility potential after removal of osseous tissue was also systematically reviewed in which 21 reports (n = 64 women) were eligible., Results: The available data suggest that restoration of endometrial cavity with HS or curettage provides a spontaneous pregnancy rate of 54.2% within 12 months., Conclusion: According to the available data, irrespective from the duration of subfertility, spontaneous pregnancy should be expected for at least 1 year following the 'complete' restoration of endometrial cavity. In that context, further infertility treatments such as assisted reproduction cycles should be postponed, unless there is another reason for infertility., (© 2015 S. Karger AG, Basel.)

Objective: To determine and compare the immunolocalization of functionally important antigens in human spermatozoa in an unexplained infertility (UI) group., Materials and Methods: In this study, the sperm samples of 20 patients undergoing evaluation belonging to normozoospermic group, whose primary reason of infertility was under investigation for this purpose, were screened. CD46, CD55 and CD52, CD69, CD98, fMLP, HI307, and 80280 were stained on the spermatozoa through indirect immunofluorescence technique., Results: In addition to CD46, CD55, and CD52 antigens, which are known to be localized on human spermatozoa, significant immunolocalization of several novel antigens including: CD52, CD69, CD98, fMLP, HI307, and 80280 were determined on the spermatozoa of the unexplained infertility group, possibly reflecting important roles in the pathophysiology of such unresolved clinical situations., Conclusion: Identification and characterization of antigens present on sperm cells is crucial for understanding of the diagnosis and treatment of unexplained infertility. Further studies were conducted to evaluate a possible correlation between the expression of these antigens and clinical outcomes in different well-defined infertility groups.

Steroid cell tumors (SCTs) of the ovary are a rare subgroup of sex cord tumors, account for less than 0.1% of all ovarian tumors, and also will present at any age. These tumors can produce steroids, especially testosterone, and may give symptoms like hirsutism, hair loss, amenorrhea, or oligomenorrhea. For the evaluation of androgen excess, testosterone and dehydroepiandrosterone sulfate (DHEA-S) are the first laboratory tests to be measured. A pelvic ultrasound and a magnetic resonance imaging are useful radiologic imaging techniques. Although steroid cell tumors are generally benign, there is a risk of malignant transformation and clinical malignant formation. Surgery is the most important and hallmark treatment.

Purpose: To investigate the relationship between hyaluronan binding (HB) assay and pregnancy rates in intrauterine insemination (IUI) cycles., Methods: This prospective cohort study was done in Hacettepe University, a tertiary care center for reproductive medicine. Seventy-one consecutive couples who suffered from unexplained infertility and underwent controlled ovarian hyperstimulation (COH) and IUI were enrolled into the study., Results: From the 71 IUI patients, the clinical pregnancy rate was 14.1% (10 of 71). HB ratio from the overall patient number was 48.6±25.9. The mean HB ratio in pregnant and non-pregnant groups was comparable (50.2±25.2 vs. 48.3±26.2, respectively, p>0.05)., Conclusions: Hyaluronan binding assay does not predict pregnancy rates in IUI cycles in couples with unexplained infertility.

Aim: The aim of this study was to evaluate the sole effect of sperm concentration on fertilization, embryo quality and pregnancy rates in patients undergoing ICSI cycles., Materials and Methods: 560 ICSI cycles performed for male factor infertility were divided into four groups according to sperm concentration retrospectively. Group 1 consisted of 86 couples whose sperm concentration was less than 1x10(6), group 2 consisted of 169 couples whose sperm concentration ranged between 1x10(6) and 5x10(6), group 3 consisted of 95 couples whose sperm concentration ranged between 5x10(6) and 10x10(6) and group 4 consisted of 210 couples whose sperm concentration ranged between 10x10(6) and 20x10(6)., Results: Fertilization rate was significantly lower in the first three groups compared to the last group (p<0.05). The first three groups were comparable with each other. There were no differences according to ovarian response to stimulation, embryo quality and clinical pregnancy rates between the four groups., Conclusion: Lower sperm concentration has detrimental effects on the outcomes of ICSI cycles. This situation is more evident in men with severe and extremely severe oligozoospermia.

Objective: We aimed to evaluate the agreement of 2-dimensional (2D) and 3-dimensional (3D) ultrasonography (USG) with true ovarian volume (OV), as calculated precisely after oophorectomy., Study Design: A total of 46 ovaries from 30 patients were prospectively enrolled. Preoperatively, all ovaries were assessed by 2D and 3D USG for volume estimation and results were compared with true OV that was calculated with Archimedes' principles following oophorectomy., Results: The correlation coefficients of 2D and 3D USG with true OV were similar (0.65 vs 0.67, respectively). The mean bias (upper and lower limits of agreement) between 2D and true OV was 1.41 (-3.84 to 6.66) mL. The respective figure for 3D and true OV were 0.33 (-4.71 to 5.37) mL. While estimation by 2D USG brought 18% larger, 3D USG revealed 11% smaller values than the true OV., Conclusion: Three-dimensional OV estimation might present improvement in means of lower mean bias than 2D USG., (Copyright © 2012 Mosby, Inc. All rights reserved.)