Are ICSI results affected by months and seasons? A retrospective cohort study of fresh and frozen cycles.

In present study, we aimed to investigate the effect of seasonal variation on ICSI results both in fresh and frozen embryo transfer cycles. Between January 2007 and December 2019, a total of 4039 ICSI cycles (3227 fresh and 812 frozen ET) which resulted in embryo transfer were included in the study. We found no significant difference in the pregnancy outcome among different seasons and months. The best results were obtained for spring (41.0%) and the least for winter (37.1%) in fresh cycles and the best for spring (42.5%) and the least for winter (29.7%) in FET cycles. In monthly distribution, the best results were obtained for September (57.0%) and the least for November (24.1%) in fresh cycles and the best for October (49.3%) and the least for December (20.2%) in FET cycles. Our study did not show any significant influence of the months or seasons on clinical pregnancy rates in either fresh and frozen embryo transfers. However, the difference among months in frozen cycles was notable although it did not reach statistical significance. It can be suggested that the strict control of reproductive hormones especially in fresh cycles as well as the standardized laboratory temperature minimize the influence of seasonal effect on ICSI outcome.

A Histopathological Evaluation of Ovarian Hyperstimulation Syndrome on Reproductive and Vital Organs and the Role of the VEGF-PKA Pathway in a Mouse Model.

Ovarian hyperstimulation syndrome (OHSS) is one of the most common and iatrogenic complications of in vitro fertilization therapy, which is an exaggerated response to excess hormones resulting in the development of a large number of maturing follicles. Although the complications of and reasons for the condition are well known, the overall histopathological effects on systemic organs and the extent of the damage have not been fully elucidated. Besides, the mechanism that underlies the situation is not very well known. The aim of the present work was to analyse the histopathological effects of OHSS on reproductive (uterus and ovary) and vital organs (liver and kidney) and the possible role of the VEGF-PKA pathway in triggering the condition. Balb/c mice were used to establish an OHSS model. The OHSS group were injected with overdose PMSG while the normal responder group were injected with an optimal dose. Histopathological evaluation was utilised in the liver, kidney, ovary, and uterus stained with hematoxylin and eosin, Masson's trichrome, and periodic acid-Schiff stain. The expression profiles of VEGF (vascular endothelial growth factor), PKA (protein kinase A), and p-PKA (an activated form of PKA) were detected with immunohistochemistry and Western blotting. OHSS was demonstrated to have a negative histopathological effect on all of the organs analysed. These effects were associated with an overall increase in the expression levels of VEGF, PKA, and p-PKA. OHSS has a serious histopathological negative effect on the systemic and reproductive organs and is proven to affect overall health, and thus should be considered a dangerous complication during ART techniques. The activation of the VEGF-PKA pathway, which is indicated by the expression levels of VEGF, PKA, and p-PKA, is demonstrated to accompany this complication, which should be further elucidated to understand the mechanisms underlying the condition.

Seminal oxidation-reduction potential as a possible indicator of impaired sperm parameters in Turkish population.

Oxidative stress (OS) has been shown to have a key role in male infertility. Recently, a new measurement method has been developed to measure the overall oxidation-reduction potential (ORP) in a semen sample known as the MiOXSYS system. The aim of this study was to investigate the correlation of sperm parameters with oxidative stress levels determined by ORP and to evaluate whether the current limit is able to distinguish abnormal sperm parameters from normal ones in Turkish population. Semen samples of 121 patients who applied for infertility investigation were divided into two groups as (OS +; n:39) and (OS -; n:82). Semen parameters were compared between groups. Sperm concentration, total motility and progressive motility were found to be significantly lower in OS (+) patients compared to those OS (-), while immotile sperm count was significantly higher in OS (+) patients. Oxidative stress determined by MiOXSYS system was found to be related to reduced sperm parameters in Turkish population, which may be used as an indicator of poor sperm parameters and a support to routine semen analysis. In addition, recommended reference value was found to be reliable in distinguishing normal from impaired semen parameters.

Factors related to follicular oxidative stress in intracytoplasmic sperm injection cycles and its effects on granulosa cells.

The aim of the present study was to investigate several common conditions that may potentially be correlated with follicular oxidative status during an intracytoplasmic sperm injection (ICSI) cycle and that include the serum oestrogen level on the day of oocyte pick-up, maternal age and pregnancy outcome. Patients that were enrolled in the study were classified randomly into three groups using their numerical order. The first group were classified based on maternal age (<35 and ≥35 years) (n = 398), the second group on the serum oestradiol (E2) level on the day of human chorionic gonadotropin (hCG) administration (levels >90th percentile and ≤ 90th percentile) (n = 491) and the third group on pregnancy outcome (positive/negative) (n = 376). The groups were matched for the other variables (stimulation protocol, dose of gonadotropin, duration of stimulation, antral follicle count, body mass index, basal follicle stimulating hormone (FSH), and E2 levels and day of hCG trigger) to prevent the possible contribution of those parameters to the results. Each group was matched for other variables (stimulation protocol, dose of gonadotrophin, duration of stimulation, antral follicle count, body mass index, basal FSH and E2 levels and day of hCG trigger) that may have affected the outcome, except for the parameter under investigation. Maternal age (P = 0.044,168 r = 0.418), oestrogen level on day of hCG administration (P = 0.001, r = 0.436) and pregnancy outcome (AUC = 0.65, P = 0.071) were found to be correlated with follicular oxidative status. The results obtained will help us to shield patients from possible situations that may cause oxidative stress and therefore adverse outcomes of an ICSI cycle.

Effects o follicular fluid oxidative status on human mural granulosa cells, oocyte competency and ICSI parameters.

PURPOSE: The aim of the present study was to understand the molecular and genetic alterations involved in follicular fluid oxidative process by investigating human mural granulosa cells and to find possible biomarkers for oocyte competency and ICSI outcome measures. METHODS: A total of 166 patients were included in the study. Total antioxidant and oxidant levels of follicular fluids were measured on the day of oocyte pick-up and oxidative status were calculated. Expression profiles of three potential target proteins in cases of oxidative stress (Hsp70, Tgf-ß, Notch1), DNA status and chromatin integrity of mural granulosa cells were analyzed. RESULTS: TAS levels were positively correlated with the Hsp70 and Tgf-ß expression patterns of mural granulosa cells. Mature oocyte rate and fertilization rates were affected negatively by the presence of oxidative stress and a significant positive correlation was found with the oxidative status and the fertilization rate, whereas no correlation with the remaining ICSI parameters in the overall group. CONCLUSIONS: Oxidative stress detected in follicular fluid adversely affects fertilization rates post-ICSI however no effect on the remaining parameters including embryo quality, pregnancy, and implantation rates. DNA damage, chromatin integrity were increased, whereas Hsp70 and Tgf-ß were decreased in mural granulosa cells in cases of oxidative stress which may indirectly reflect the oocyte competency and may be used as biomarkers for ICSI outcome measures.

Adjuvant effects of chemotherapeutics and Metformin on MFE-319 endometrial carcinoma cell line.

We aimed to investigate the cytotoxicity of Metformin, Cisplatin, and Paclitaxel on MFE-319 endometrial carcinoma cell line using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and immunocytochemistry assays. Half maximal inhibitory concentration (IC50) doses of three drugs alone and in the dual combinations were applied to the cells. Immunocytochemical method was performed for the cell survival and for phosphatidylinositol 3-kinase (PI3K), phosphorylated extracellular regulated kinases (pErk)-1∕2, Akt-1, phosphorylated Akt (pAkt)-1∕2∕3 cell growth markers and angiogenic vascular endothelial growth factor (VEGF). Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was found that these drugs caused a decrease in the immunoreactivities of these markers. Particularly, dual combination of Paclitaxel and Cisplatin decreased the immunoreactivities of PI3K, pErk-1∕2, Akt-1, and pAkt-1∕2∕3. Cisplatin and Paclitaxel were more effective than Metformin; on the other hand, Metformin has been shown to enhance the efficacy of these two drugs. In vitro or in vivo further studies are needed to investigate the efficacy of these three drugs via PI3K∕Akt signal pathway.

Intracytoplasmic morphologically selected sperm injection, but for whom?

Intracytoplasmic sperm injection (ICSI) is performed in cases of infertility by injecting a motile and morphologically normal sperm cell under a routine ×400 magnification at which is hard to distinguish morphologically healthy sperm. Recently, the use of high-powered differential interference contrast optics gave the opportunity to select a sperm under ultra-high magnification of ×10,160. The aim of the present study was to evaluate the efficacy of the intracytoplasmic morphologically selected sperm injection (IMSI) technique in different infertility populations undergoing ICSI. Main outcome measures of routine ICSI were compared with IMSI in three different groups of patients (1, non-selected; 2, male infertility; and 3, repeated implantation failure group). Results were analysed to evaluate the effects of the IMSI procedure and to find the most suitable group of patients who may benefit from the procedure. IMSI caused a significant increase in the fertilization and top quality embryo rates in the male infertility group and a significant increase in fertilization and pregnancy rates in the repeated implantation failure group, whereas no effect was observed in the non-selected group with patients of various indications. A positive effect of IMSI on the outcome of male factor infertility and repeated implantation failure patients was observed. Data observed confirmed that the application of IMSI was beneficial for a selected group of patients with male factor infertility and repeated implantation failure.