Live birth rate with double ovarian stimulation is superior to follicular phase ovarian stimulation per started cycle in poor ovarian responders.

AIM: To compare the outcome of double ovarian stimulation (DOS) with follicular phase ovarian stimulation (FPS) per started cycle in poor ovarian responders (PORs). METHODS: A total of 204 PORs who underwent ovulation induction for in vitro fertilization, cryopreservation of all embryos available, and frozen embryo transfer cycle were retrospectively analyzed. Of those, 146 received single FPS, and 58 received DOS. All viable embryos were cryopreserved and subsequently transferred within 1-6 months. RESULTS: The number of oocytes collected and the number of mature oocytes per started cycle were higher in the DOS group compared to the FPS group (6.0 ± 1.9 vs. 2.8 ± 1.3 and 4.3 ± 1.3 vs. 2.2 ± 1.2, respectively, p = 0.001). Clinical pregnancy rate and live birth rate per started cycle were also significantly higher in the DOS group than the FPS group (41.4% vs. 16.4% and 36.2% vs. 15.1%, respectively, p < 0.001). The cancellation rate of embryo transfer due to no viable embryo was significantly lower in the DOS group (10.3%) than the FPS group (40.4%) (p = 0.001). In the DOS group, numbers of oocytes (3.2 ± 1.2 vs. 2.7 ± 1.1, p = 0.006), MII oocytes (2.6 ± 1.0 vs. 2.1 ± 0.8, p = 0.001), and cryopreserved blastocysts (1.5 ± 0.8 vs. 1.1 ± 0.7, p = 0.002) were significantly higher in the luteal ovarian stimulation compared to follicular ovarian stimulation. CONCLUSIONS: Live birth per started cycle with DOS is superior to FPS in PORs. Luteal phase stimulation contributes to improving pregnancy rates in these patients.

Differential expression of Oct-4, CD44, and E-cadherin in eutopic and ectopic endometrium in ovarian endometriomas and their correlations with clinicopathological variables.

BACKGROUND: Endometriosis is an estrogen-dependent inflammatory disease that often causes infertility and chronic pelvic pain. Although endometriosis is known as a benign disease, it has demonstrated characteristics of malignant neoplasms, including neoangiogenesis, tissue invasion, and cell implantation to distant organs. Octamer-binding protein 4 (Oct-4) is a molecular marker for stem cells that plays an essential role in maintaining pluripotency and self-renewal processes in various types of benign and malignant tissues. CD44 is a multifunctional cell surface adhesion molecule that acts as an integral cell membrane protein and plays a role in cell-cell and cell-matrix interactions. E-cadherin is an epithelial cell-cell adhesion molecule that plays important role in the modulation of cell polarization, cell migration, and cancer metastasis. The aim of this study was to investigate the expression patterns of Oct-4, CD44, and E-cadherin in eutopic and ectopic endometrial tissues from women with endometrioma compared to control endometrial tissues from women without endometrioma. METHODS: In the present study, Oct-4, CD44, and E-cadherin expressions were evaluated in eutopic and ectopic endometrial tissue samples from women with endometrioma (n = 32) and compared with those of control endometrial tissue samples from women without endometrioma (n = 30). RESULTS: Immunohistochemical expression of Oct-4 was significantly higher in the ectopic endometrial tissue samples of women with endometrioma than in the control endometrial tissue samples (p = 0.0002). Conversely, CD44 and E-cadherin expressions were significantly lower in the ectopic endometrial tissue samples of women with endometrioma than in the control endometrial tissue samples (p = 0.0137 and p = 0.0060, respectively). Correlation analysis demonstrated significant correlations between Oct-4 expression and endometrioma cyst diameter (p = 0.0162), rASRM stage (p = 0.0343), and total rASRM score (p = 0.0223). Moreover, CD44 expression was negatively correlated with the presence of peritoneal endometriotic lesions (p = 0.0304) while E-cadherin expression was negatively correlated with the presence of deep infiltrating endometriosis (p = 0.0445). CONCLUSIONS: Increased expression of Oct-4 and decreased expression of adhesion molecules in endometriotic tissues may contribute to the development and progression of endometriosis.

Serum vitamin D levels in healthy urban population at reproductive age: effects of age, gender and season.

OBJECTIVE: The aim of the study was to determine the effects of age, gender and season on vitamin D status in healthy urban population at reproductive age. Also, we investigated the distribution of population into different groups regarding 25(OH)D levels. METHODS: Serum 25(OH)D levels of 21,317 participants: 5,364 men (25.1%) and 15,953 women (74.8%), aged between 18-45 years, applying to two medical centres for check-up located in the same city were retrospectively analyzed. Group I consisted of 14,720 participants (11,257 women and 3,463 men) in the first centre and Group II consisted of 6,597 participants (4,696 women and 1,901 men) in the second centre. RESULTS: The mean 25(OH)D levels did not differ between women and men in both groups: 23.4 (SD = 14.4) and 23.1 (SD = 12.6) in Group I, and 22.6 (SD = 15.9) and 23.1 (SD = 14.3) in Group II, respectively, (p > 0.05). Similar trends exhibiting lower mean 25(OH)D levels at younger ages and higher levels at later ages were observed in both groups; a seasonal variation of 25(OH)D levels was observed in both genders with the highest levels in August and September and the lowest levels from February through April; percentages of women with 25(OH)D level of < 5 ng/ml were significantly higher than of men in Group I (1.4% vs. 0.2%, respectively, p < 0.001) and in Group II (4.1% vs. 1.1%, respectively, p < 0.001). CONCLUSION: There is a slight increase in serum 25(OH)D levels from 18 through 45 years of age in healthy population. The seasonal variation of 25(OH)D levels is prominent in both genders with men having slightly lower levels in some months of winter and higher levels in summer as compared to women. The prevalence of women having 25(OH)D levels less than 5 ng/ml is higher than that of men.

Differential Expressions of Ki-67, Bcl-2, and Apoptosis Index in Endometrial Cells of Women With and Without Type II Diabetes Mellitus and Their Correlation with Clinicopathological Variables.

The objective of this study was to investigate proliferation, apoptosis, and antiapoptotic molecule expression in endometrial cells of reproductive-aged women with and without type II diabetes mellitus (T2D). In this case-control study, a total of 80 endometrial tissue specimens from reproductive-aged women (35 in the proliferative phase and 45 in the secretory phase) were examined. The age and body mass index (BMI) were matched between the groups. Formalin-fixed and paraffin-embedded endometrial tissue samples were used for immunohistochemistry analysis. The presence of proliferation was evaluated with Ki-67 expression, antiapoptotic function of cells was evaluated with Bcl-2 expression, and apoptosis was evaluated with terminal deoxynucleotidyl transferase (TUNEL) immunoreactivity in both the glandular epithelium and stroma of endometrial tissue samples from women with and without T2D. Ki-67 expression in the glandular epithelium and Bcl-2 expression in both the glandular epithelium and stroma were significantly higher in endometrial tissue samples of women in the T2D group than the control group (p = 0.0008, p = 0.0022, and p = 0.0261, respectively). TUNEL immunoreactivity was significantly lower in the glandular epithelium of women in the T2D group than the control group (p = 0.0001). Glandular Ki-67 expression correlated positively with BMI, use of insulin, and hemoglobin A1c level (p = 0.0034, p = 0.0154, and p = 0.0011, respectively). Glandular Bcl-2 expression correlated positively with BMI and duration of T2D (p = 0.0090 and p = 0.0109, respectively). Stromal Bcl-2 expression correlated positively with duration of T2D (p = 0.0069). TUNEL immunoreactivity in the glandular epithelium correlated negatively with duration of T2D (p = 0.0340) and positively with the use of oral antidiabetic agents (p = 0.0226). Compared to age and BMI-matched controls, women with T2D experienced increased cell proliferation and decreased apoptosis in the glandular epithelium and increased antiapoptotic function in both the glandular epithelium and stromal cells. High BMI values in women with diabetes seemed to contribute to increased cell proliferation and increased antiapoptotic function in the glandular epithelium but not the stromal cells.

Overexpression of programmed cell death ligand 1 in patients with CIN and its correlation with human papillomavirus infection and CIN persistence.

BACKROUND: HPV causes specific cell-mediated immunity in the cervix. Mononuclear cells such as helper T cells (CD4+), cytotoxic T cells (CD8+), and dendritic cells play a critical role in the initiation of the HPV-specific immune response and destruction of virus-infected cervical epithelial cells. The programmed cell death ligand 1 (PD-L1) gene encodes an immune inhibitory receptor ligand and overexpression of PD-L1 inhibits T-cell activation and cytokine production. The aim of this study was to investigate the expression of PD-L1 in cervical tissue and its correlation with clinicopathological findings. METHODS: In this cross-sectional study, a total of 94 women who were referred for colposcopy due to abnormal Papanicolaou (PAP) test results and/or HPV positivity were evaluated. The presence of HR-HPV-DNA was analyzed using type- and gene-specific primers along with commercial real-time polymerase chain reaction. The cervical examination was done with a colposcope. Cervical biopsies were obtained from the areas that were evaluated as abnormal during the colposcopy. Histopathological result of cervical biopsies were defined as no intraepithelial neoplasia (CIN 0), mild CIN (CIN I), and moderate-to-high CIN (CIN II-III). All women were classified into four groups based on their HR-HPV positivity and cervical biopsy results: Group I (controls; n = 29), HR-HPV (-) CIN 0; Group II (n = 21), HR-HPV (+) CIN 0; Group III (n = 20), HR-HPV (+) CIN I; and Group IV (n = 24), HR-HPV (+) CIN II-III. A semi-quantitative scoring system was used to evaluate the degree of Ki-67, p16, and PD-L1 immunoreactivity in the cervical tissue samples. RESULTS: We found that PD-L1 expression in both mononuclear cells and in cervical epithelial cells gradually increases from the HR-HPV (-), CIN 0 group to the HR-HPV (+), CIN II-III group (p = 0.0003 and p = 0.0394, respectively) and mononuclear PD-L1 expression was correlated with HPV type, initial Pap test results, HPV persistence, and CIN persistence or recurrence (p = 0.0180, p = 0.0109, p = 0.0042, and p = 0.0189, respectively). Moreover, mononuclear PD-L1 expression was also correlated with Ki-67 and p16 immunoreactivity (p = 0.0432 and p = 0.0166, respectively). Epithelial PD-L1 expression was only correlated with HPV type and the presence of HPV persistence (p = 0.0122 and p = 0.0292, respectively). CONCLUSION: During the initial evaluation of the cervical histology results, the assessment of PD-L1 expression-especially in mononuclear cells in cervical tissue samples-may provide more information on the progression of HR-HPV infection and its persistence.

Placental fractalkine immunoreactivity in preeclampsia and its correlation with histopathological changes in the placenta and adverse pregnancy outcomes.

Introduction: Preeclampsia is a systemic inflammatory disorder and a major cause of maternal and fetal mortality. Fractalkine (CX3CL1) is a member of the chemokine family with multiple functions in the organization of the immune system. It is up-regulated in inflammatory disorders. During inflammation, fractalkine enhances tissue destruction and inflammatory cell invasion. We aimed to investigate the alteration of fractalkine in the placental tissues of pregnant women with preeclampsia and the correlation of this alteration with clinicopathological variables.Materials and methods: Alteration of fractalkine in placental tissue specimens was determined immunohistochemically in 84 pregnant women: 33 women with mild preeclampsia, 19 women with severe preeclampsia, and 30 women with normal pregnancy. Preeclampsia was diagnosed using current guidelines of the American College of Obstetricians and Gynecologists.Results: Pregnant women with mild and severe preeclampsia revealed significantly higher fractalkine expression in syncytiotrophoblast cells than in the normotensive group (p = .0051 and .0001, respectively). The expression of fractalkine in preeclampsia was positively correlated with clinical parameters including the presence of intrauterine growth restriction, systolic and diastolic blood pressure, and 24-h urine protein, whereas it was negatively correlated with plasma albumin levels and placental weight. Additionally, the pathological changes in the placenta-including the presence of syncytiotrophoblast basement membrane thickening, increased number of syncytial knots, and vascularization of terminal villi were significantly correlated with fractalkine expression in pregnant women with preeclampsia.Conclusions: Overexpression of fractalkine in pregnant women with preeclampsia, as well as the correlation between fractalkine expression and poor pregnancy outcomes and placental histopathological changes may be associated with the underlying mechanisms of preeclampsia.