Clinical effectiveness of spindle-view intracytoplasmic sperm injection compared to conventional intracytoplasmic sperm injection in patients with poor ovarian response and previous implantation failure.

OBJECTIVE: This study aimed to determine the clinical advantage of spindle-view intracytoplasmic sperm injection (SVICSI; a novel technology) over conventional intracytoplasmic sperm injection (cICSI) in patients with poor ovarian response (POR) and previous implantation failure. METHODS: The study included 37 patients who underwent SVICSI followed by fresh embryo transfer (FET) at a single fertility clinic from January to December 2022, 58 patients who underwent cICSI followed by FET at the same fertility clinic from January to December 2021 as a control group. All study participants met the Bologna criteria for POR and had at least three or more previous failed embryo transfers. RESULTS: The number of blastocyst transfers was significantly higher in the SVICSI group than in the cICSI group. A good-quality cleavage embryo rate, blastocyst rate, and good-quality blastocyst rate were also significantly higher in the SVICSI group than in the cICSI group. There were no significant differences in the rates of fertilization, implantation, clinical pregnancy, or clinical abortion between the two groups. CONCLUSION: In patients with POR, those who underwent SVICSI appeared to have better embryos than those who underwent cICSI. However, whether SVICSI improved clinical outcomes such as implantation and pregnancy rates cannot be proven.

Relationship between hematologic parameters related to systemic inflammation and insulin resistance-associated metabolic parameters in women with polycystic ovary syndrome.

OBJECTIVE: The aim of the present study was to evaluate the associations between hematologic parameters related to systemic inflammation and insulin resistance-associated metabolic parameters in women with polycystic ovary syndrome (PCOS). METHODS: Eighty-two women between the ages of 18 and 35 years who were diagnosed with PCOS were included in this study. A 2-hour 75-g oral glucose tolerance test (OGTT) was administered to all study participants; fasting and postprandial glucose and insulin levels were measured simultaneously during the 2-hour OGTT. Hematologic parameters were derived from a standard complete blood count and a differential count of fasting-state blood samples. The correlations between hematologic parameters and insulin resistance-associated clinical and metabolic parameters were evaluated using the Spearman rank correlation and partial correlation coefficients. Hematologic parameters related to systemic inflammation were compared between the two groups, categorized by the presence or absence of insulin resistance. RESULTS: Significant differences in the absolute neutrophil count, absolute monocyte count, platelet count, and neutrophil-lymphocyte ratio were found between the insulin-resistant group and insulin-nonresistant group. Correlation analysis found that all hematological parameters, except for the platelet-lymphocyte ratio, were associated with at least one insulin resistance-associated metabolic parameter. However, these significant correlations between hematological and metabolic parameters were attenuated after controlling for the effects of other covariates using partial correlation analysis. CONCLUSION: The association between hematologic parameters indicative of systemic inflammation and insulin resistance-associated metabolic parameters seems to be strongly influenced by other anthropometric covariates in women with PCOS.

Triglyceride and glucose index for identifying abnormal insulin sensitivity in women with polycystic ovary syndrome.

OBJECTIVE: We aimed to evaluate whether triglyceride and glucose (TyG) indices are useful in identifying insulin sensitivity/resistance in women with polycystic ovary syndrome (PCOS). METHODS: One hundred and seventy-two Korean women aged 18-35 years who were diagnosed with PCOS were included in this study. Fasting-state insulin sensitivity assessment indices (ISAIs) derived from a combination of fasting insulin and glucose levels were calculated for all study participants, and abnormal insulin sensitivity was defined as any of the evaluated ISAIs being out of the established normal range. Correlation analysis was conducted to assess the relationship between the TyG index and other clinical and biochemical parameters. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value of the TyG index for identifying abnormal insulin sensitivity, and unpaired t-tests were used to compare biochemical parameters between individuals with a TyG index below the cutoff and individuals with a TyG index above the cutoff value. RESULTS: All clinical parameters, except age and other insulin resistance-related biochemical parameters, were significantly related to the TyG index. The ROC curve analysis revealed an optimal TyG cutoff value of 8.126 (sensitivity, 0.807; specificity, 0.683) for identifying abnormal insulin sensitivity. In the comparative analysis, all ISAIs and parameters derived from the lipid profiles differed significantly between the TyG groups. CONCLUSION: The TyG index is a feasible surrogate marker for predicting insulin sensitivity/resistance in women with PCOS.

Association between polycystic ovarian morphology and insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: The aim of the present study was to determine whether polycystic ovarian morphology (PCOM) is related to insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: A total of 147 Korean women aged 18 to 35 years and diagnosed with PCOS were included in this study. Fasting blood tests and standard 2-hour 75-g oral glucose tolerance tests were performed for all participants. PCOM-related parameters including total antral follicle count (TFC) and total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasonography. Correlation analysis was conducted to assess the relationships of TFC and TOV with insulin resistance-related clinical and biochemical parameters using Spearman rank correlation coefficients and linear regression analysis, with partial correlations used to control for the effects of confounding covariates. RESULTS: Fasting insulin levels, low-density lipoprotein levels, and insulin sensitivity assessment indices (ISAIs) were significantly correlated with TFC, but neither postprandial blood glucose levels nor insulin levels were significantly associated with TFC. No insulin resistance-related parameter was significantly correlated with TOV. These results did not change after adjustments for other anthropometric covariates. Fasting insulin and some ISAIs differed significantly between groups categorized by the median TFC value (TFC ≤54 and TFC >54). CONCLUSION: TFC, but not TOV, was found to be related to fasting insulin resistance-related parameters in women with PCOS.

Initial Preoperative Hemoglobin Level Affects the Rate of Decline in Anti-Müllerian Hormone Levels after Laparoscopic Ovarian Cystectomy in Women with Ovarian Endometriosis.

OBJECTIVES: To determine the factors affecting the decline in ovarian reserve following laparoscopic ovarian cystectomy (LOC) in women with ovarian endometriosis. METHODS: This retrospective study included 22 women, aged 25-45 years, with regular menstrual cycles who underwent unilateral LOC and were diagnosed with ovarian endometriosis at a university hospital. Blood samples were collected preoperatively and on the third postoperative day to determine the serum anti-Müllerian hormone (AMH) levels for assessment of the decline in ovarian reserve during the early postoperative period. RESULTS: The preoperative hemoglobin level, white blood cell count, and AMH level were associated with changes in the AMH level after unilateral LOC. Among these parameters, only the preoperative hemoglobin level was correlated with the rate of decline in postoperative AMH levels. The preoperative serum AMH level was correlated with the amount of postoperative AMH change but not with its rate of decline. CONCLUSIONS: Preoperative hemoglobin levels may be associated with the rate of decline in AMH levels in the early postoperative period after unilateral LOC.

Association between the serum estrone-to-estradiol ratio and parameters related to glucose metabolism and insulin resistance in women with polycystic ovary syndrome.

OBJECTIVE: We aimed to evaluate associations between the ratio of serum estrone (E1) to estradiol (E2) and parameters related to serum glucose metabolism and insulin resistance in women with polycystic ovary syndrome (PCOS). METHODS: In total, 133 women between the ages of 18 and 35 diagnosed with PCOS were enrolled in this study. All participants with PCOS underwent blood tests to determine hormonal and biochemical metabolic parameters and a standard 2-hour 75-g oral glucose tolerance test. They were divided into two groups according to the serum E1-to-E2 ratio: group 1 (E1/E2 ratio <2.0) and group 2 (E1/E2 ratio ≥2.0). RESULTS: In the comparative analysis, the waist-to-hip ratio (WHR) was the only clinical variable that was significantly different between the two groups. Patients with a higher E1/E2 ratio showed higher fasting insulin levels, homeostasis model for insulin resistance, and postprandial glucose level at 2 hours (PPG2). In a correlation analysis, only PPG2 was significantly related to the serum E1/E2 ratio. However, after controlling for the confounding effects of body mass index (BMI) and WHR, fasting glucose was also significantly correlated with the serum E1/E2 ratio. CONCLUSION: Women with PCOS with a higher serum E1/E2 ratio were found to be more likely to show higher fasting insulin and postprandial glucose levels. Significant correlations were found between the serum E1/E2 ratio and both fasting and postprandial serum glucose levels after adjusting for BMI and WHR in women with PCOS.

Effects of thymosin ß4-derived peptides on migration and invasion of ovarian cancer cells.

BACKGROUND: Thymosin ß4 (Tß4) is a highly conserved actin binding protein associated with the metastatic potential of tumor cells by stimulating cell migration. The role of Tß4 and its derived fragment peptides in migration of ovarian cancer cells has not been studied. OBJECTIVE: To analyze the effects of Tß4 and its derived fragment peptides on ovarian cancer cell migration and invasion, we applied Tß4 and three Tß4-derived synthetic peptides to SKOV3 ovarian cancer cells. METHOD: The migration and invasion of SKOV3 cells treated with Tß4(1-43), Tß4(1-15), Tß4(12-26), Tß4(23-), and untreated control were analyzed by in vitro migration and invasion assay with transwell plate. Cell proliferation assay was conducted to identify the effect of Tß4 and its derived peptide on SKOV3 cell proliferation. The expression of Tß4 related proteins related with cell proliferation was analyzed by Western blot after treatment with Tß4 and its derived peptides. RESULTS: Cell migration and invasion were significantly increased in Tß4 peptide-treated SKOV3 cells compared with untreated control. All three Tß4-derived fragment peptides including those without an actin binding site significantly stimulated migration and invasion of SKOV3 cells. Tß4 and its derived peptide significantly stimulated SKOV3 cell proliferation and up-regulated the expression of RACK-1 protein. CONCLUSIONS: The Tß4 peptide and all of its derived fragment peptides including those without an actin binding motif stimulate migration and invasion of SKOV3 ovarian cancer cells. All peptides significantly increased RACK-1 expression and cell proliferation of SKOV3 cells. These results suggest that Tß4 stimulates migration and invasion of SKOV3 cells by stimulation of cell proliferation through up-regulation of RACK-1 protein.

Predictive capability of fasting-state glucose and insulin measurements for abnormal glucose tolerance in women with polycystic ovary syndrome.

OBJECTIVE: The aim of the present study was to evaluate the predictive capability of fasting-state measurements of glucose and insulin levels alone for abnormal glucose tolerance in women with polycystic ovary syndrome (PCOS). METHODS: In total, 153 Korean women with PCOS were included in this study. The correlations between the 2-hour postload glucose (2-hr PG) level during the 75-g oral glucose tolerance test (OGTT) and other parameters were evaluated using Pearson correlation coefficients and linear regression analysis. The predictive accuracy of fasting glucose and insulin levels and other fasting-state indices for assessing insulin sensitivity derived from glucose and insulin levels for abnormal glucose tolerance was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Significant correlations were observed between the 2-hr PG level and most fasting-state parameters in women with PCOS. However, the area under the ROC curve values for each fasting-state parameter for predicting abnormal glucose tolerance were all between 0.5 and 0.7 in the study participants, which falls into the "less accurate" category for prediction. CONCLUSION: Fasting-state measurements of glucose and insulin alone are not enough to predict abnormal glucose tolerance in women with PCOS. A standard OGTT is needed to screen for impaired glucose tolerance and type 2 diabetes mellitus in women with PCOS.

Two Cases of Primary Ovarian Insufficiency Accompanied by High Serum Anti-Müllerian Hormone Levels and Preservation of Ovarian Follicles.

Primary ovarian insufficiency (POI) is defined as the presence of amenorrhea for ≥ 4 months accompanied by evidence of two serum follicle-stimulating hormone levels in the menopausal range in women aged < 40 years. Anti-Müllerian hormone (AMH) has been recognized as the most reliable marker of ovarian reserve status, and its serum level is very low or undetectable in women with POI. Here we report two cases of patients who were diagnosed with POI despite high serum AMH levels and preservation of ovarian follicles, as revealed by ultrasound. In addition, we have presented a review of the current literature regarding this condition.

Influence of combined oral contraceptives on polycystic ovarian morphology-related parameters in Korean women with polycystic ovary syndrome.

OBJECTIVE: This study aimed to assess the effect of combined oral contraceptives (COCs) on polycystic ovarian morphology (PCOM) and serum anti-Müllerian hormone (AMH) levels in Korean women with polycystic ovary syndrome (PCOS). METHODS: This university hospital study enrolled 36 Korean women who were newly diagnosed with PCOS based on the Rotterdam criteria and were treated with COCs for at least 1 year. We retrospectively evaluated the ovarian volume and number of antral follicles using ultrasonography and assessed serum AMH levels at baseline and after 1 year of COC treatment. RESULTS: Significant decreases in ovarian volume and antral follicle count were observed after 1 year of COC treatment. Compared to baseline, serum AMH levels were significantly decreased after 1 year. CONCLUSION: COC treatment significantly affects ultrasound-assessed PCOM and serum AMH levels of patients with PCOS.

Effect of Hysterectomy on Ovarian Reserve in the Early Postoperative Period Based on the Type of Surgery.

OBJECTIVES: This study aimed to evaluate the influence of simple hysterectomy on the ovarian reserve based on the type of surgery. METHODS: Eighty-six premenopausal women between 31 and 48 years who underwent hysterectomy for benign gynecologic disease without additional adnexal surgery at a university hospital participated in this study. Seventy-one patients underwent laparoscopy-assisted vaginal hysterectomy (LAVH), and 15 patients underwent abdominal hysterectomy (AH). Blood samples were obtained from all study participants on preoperative day and 3 days after the operation to determine the anti-Müllerian hormone (AMH) levels. RESULTS: The postoperative reduction of the mean serum AMH level in the LAVH group (0.42 ± 0.76 ng/mL) was greater than that in the AH group, although the difference was not statistically significant (0.01 ± 0.60 ng/mL) (P = 0.053). The mean baseline AMH level (2.59 ± 2.33 ng/mL) was significantly reduced to 2.24 ± 2.08 ng/mL at 3 days after hysterectomy, and the mean rate of decline of AMH levels after surgery was 13.61% ± 30.81%. In subgroup analysis based on the type of surgery, the mean serum AMH level decreased significantly after surgery in the LAVH group, but no significant changes were found in serum AMH levels before and after the surgery in the AH group. CONCLUSIONS: These preliminary results suggest that simple hysterectomy affects the early postoperative decline of ovarian reserve, and these results might vary depending on the type of surgery.

Relationship between early follicular serum estrone level and other hormonal or ultrasonographic parameters in women with polycystic ovary syndrome.

The aim of this study was to investigate the relationship between serum estrone (E1) level and other cardinal features in women with polycystic ovary syndrome (PCOS). 133 Korean women aged 18-35 years who were newly diagnosed with PCOS at a university hospital were included in the present study. Blood samples were collected from all participants during the early follicular phase to determine the serum E1 level and other biochemical hormonal parameters. The total antral follicle count (TFC) and the total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasound. A significant correlation was found between serum E1 and luteinizing hormone (LH) levels in women with PCOS. In addition, statistically significant correlations were observed between serum E1 level and other hormonal parameters, including testosterone, free testosterone, dehydroepiandrosterone sulfate, and 17α-hydroxyprogesterone. With respect to the ultrasound features, serum E1 levels were significantly correlated with TFC and TOV. All results did not change after adjusting for body mass index (BMI). In conclusion, serum E1 level is significantly correlated with serum LH and androgen levels, and it may be a useful marker for representing the status of the ovarian volume in women with PCOS.

Inter-ovarian differences in ultrasound markers of ovarian size in women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to establish whether differences in ovarian size exist between the right and the left ovary of the same individual in women with polycystic ovary syndrome. METHODS: In total, 206 Korean women with polycystic ovary syndrome were included in this study. In all participants, a transvaginal or transrectal ultrasound examination was conducted in the early follicular phase of the menstrual cycle. RESULTS: A significant linear correlation was found between the two ovaries with regard to antral follicle count and ovarian volume. The mean antral follicle count in the right ovary (26.75±11.72) was significantly higher than that in the left ovary (23.98±10.85), and the mean volume of the right ovary (11.06±5.17 cm3) was significantly different from that of the left ovary (9.12±4.89 cm3). CONCLUSION: Ovarian size is different between the right and the left ovary in women with polycystic ovary syndrome.

Monocytosis as a prognostic factor for survival in stage IB and IIA cervical cancer.

Objective: To measure hematologic parameters derived from the white blood cell (WBC) count and differential count (DC) as prognostic factors for survival in patients with stage IB and IIA cervical cancer. Methods: We retrospectively examined demographic, clinicopathologic, and laboratory parameters in a cohort of 233 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer who underwent surgical resection. We further assessed the effects of the WBC count and DC-derived hematologic parameters on progression-free survival (PFS) and overall survival (OS) after controlling for other parameters. Results: Patients were followed up for a median of 46.6 months (range, 9-142 months). The Kaplan-Meier estimates of PFS and OS at 5 years were 88.5% and 92.3%, respectively. In a multivariate analysis, we identified the absolute monocyte count (AMC) (hazard ratio [HR], 11.78; P <0.001) and tumor size (HR, 5.41; P = 0.003) as the strongest prognostic factors affecting PFS. We also identified AMC (HR, 23.29; P <0.001), tumor size, (HR, 5.27; P = 0.033), and lymph node involvement (HR, 3.90; P = 0.027) as the strongest prognostic factors affecting OS. AMC remained prognostic with respect to PFS or OS in a Cox model that controlled for the neutrophil-lymphocyte ratio or lymphocyte-monocyte ratio, although neither ratio was a significant prognostic factor for survival. Conclusions: Monocytosis and an increased tumor size were found to be independent prognostic factors affecting both PFS and OS in patients with stage IB and IIA cervical cancer.

The Neutrophil-Lymphocyte Ratio Predicts Recurrence of Cervical Intraepithelial Neoplasia.

OBJECTIVE: The purpose of the present study was to determine the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in recurrence of cervical intraepithelial neoplasia (CIN). METHODS: We evaluated the NLR as a prognostic marker in the entire cohort of 230 patients who had undergone surgical resection and were diagnosed with CIN. Subjects were categorized into two different groups based on the NLR (NLR-high and NLR-low) using cutoff values determined by receiver operating characteristic (ROC) analysis. The primary research objective for this study was to validate the impact of the NLR on recurrence-free survival (RFS) in patients with CIN. The secondary objective was to evaluate the impact of other hematologic parameters on RFS in CIN patients. RESULTS: Using the entire cohort, the most appropriate NLR cut-off value for CIN recurrence selected on the ROC curve was 2.1. The NLR-low and NLR-high groups included 167 (72.6%) and 63 patients (27.4%), respectively. According to Kaplan-Meier analysis, RFS rates during the entire follow-up period were considerably lower in the NLR-high group than in the NLR-low group (P = 0.0125). In multivariate survival analysis using Cox proportional hazard model, we identified the NLR, absolute eosinophil count (AEC), hemoglobin concentration, and mean corpuscular volume (MCV) as valuable prognostic factors that impact RFS. CONCLUSIONS: The NLR is an independent prognosticator for RFS following surgical resection in CIN patients. We also found that the AEC, hemoglobin level, and MCV were strongly associated with RFS, as determined by multivariate analysis using a Cox model. These hematological parameters might provide additional prognostic value beyond that offered by standard clinicopathologic parameters.

Association between serum gonadotropin level and insulin resistance-related parameters in Korean women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the relationship between serum gonadotropin level and parameters related to insulin resistance in Korean women with polycystic ovary syndrome (PCOS). METHODS: This retrospective study included 138 women aged 18 to 35 years who were newly diagnosed with PCOS according to the Rotterdam consensus. Participants were divided into three groups based on the serum luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio in the early follicular phase: group 1 (LH/FSH <1), group 2 (1.0≤ LH/FSH >2.0), and group 3 (LH/FSH ≥2.0). The correlations between the LH/FSH ratio and various metabolic parameters were evaluated using Pearson correlation coefficients. RESULTS: Patients with higher LH/FSH ratios showed higher total antral follicle counts and higher total ovarian volume. In the comparison of anthropometric and biochemical parameters among the three groups, the waist to hip ratio was the only parameter that differed significantly among the groups (P=0.003). Correlation analysis revealed no significant correlations between serum LH/FSH ratios and biochemical parameters related to insulin resistance. However, after adjustments for age and body mass index, a significant correlation between total cholesterol level and serum LH/FSH ratio was observed (r=0.221, P=0.018). CONCLUSION: Most parameters related to insulin resistance, with the exception of total cholesterol level, are unrelated to the inappropriate pattern of serum gonadotropin secretion in Korean women with PCOS.

Comparison of early postoperative decline of serum antiMüllerian hormone levels after unilateral laparoscopic ovarian cystectomy between patients categorized according to histologic diagnosis.

OBJECTIVE: To evaluate the change of ovarian reserve after unilateral laparoscopic ovarian cystectomy (LOC) in the early postoperative period between patients divided according to histologic diagnosis of cyst type. MATERIALS AND METHODS: Sixty-five patients who were undergoing unilateral LOC for benign ovarian disease were included in this study. All participants were divided into three groups according to histologic diagnosis: endometrioma (n=26), mature teratoma (n=24), and other benign cyst (n=15). Serum samples were collected preoperatively and 3-days postoperatively and assayed for antiMüllerian hormone (AMH) levels, and the changes between the two samples were analyzed. RESULTS: Preoperative AMH levels were not significantly different between the three groups. On postoperative Day 3 AMH levels of all three groups were significantly reduced compared with preoperative AMH levels. The rates of decline of AMH levels after LOC in patients with endometrioma (26.37±20.70%) and in those with teratoma (28.25±22.16%) were both significantly higher than those with other benign cyst (12.03±18.56%). No statistically significant differences were found in the rate of decline of AMH levels between patients with endometrioma and teratoma. Decline of AMH after LOC was not significantly correlated with age, body mass index, the size of cyst, or preoperative AMH levels. CONCLUSION: Our results suggest that ovarian reserve is reduced after unilateral LOC in the early postoperative period, and that the postoperative decline of AMH levels after LOC is similar between patients with endometrioma and those with mature teratoma.

Efficacy of hyaluronan-rich transfer medium on implantation and pregnancy rates in fresh and frozen-thawed blastocyst transfers in Korean women with previous implantation failure.

OBJECTIVE: To evaluate the effect of hyaluronan-rich transfer medium on pregnancy and implantation rates in fresh and frozen-thawed embryo transfers in Korean women with previous implantation failure. METHODS: This retrospective study included 283 blastocyst transfers in patients with previous embryo transfer failure at a private fertility clinic. In the study group (n=88), blastocyst transfers were performed using an hyaluronan-rich transfer medium prior to transfer, whereas blastocyst transfers without any treatment served as controls (n=195). According to the type of transfer (fresh elective or frozen-thawed), all the blastocyst transfers were divided into two study and two control groups. RESULTS: The patient's mean age, serum anti-Müllerian hormone level, causes of infertility, embryo quality, and the number of transferred embryos were comparable between the study and control groups. There were no significant differences in clinical pregnancy rate (45.5% vs. 43.1%), implantation rate (28.9% vs. 28.8%), and clinical abortion rate (10.0% vs. 8.3%) between the two groups, and these findings were not changed after subgroup analysis according to the type of transfer. CONCLUSION: The use of hyaluronan-rich transfer medium in the blastocyst transfer does not appear to have any significant effect on the implantation and pregnancy rates in patients with previous implantation failure.