Influence of GnRH antagonist in reproductive women on in vitro fertilization and embryo transfer in fresh cycles.

The aim of the present study was to evaluate the influence of a gonadotropin-releasing hormone (GnRH) antagonist compared with a GnRH agonist on in vitro fertilization (IVF) cycle outcome in reproductive women. The characteristics of treatment and outcomes of pregnancy were retrospectively compared between the antagonist (GnRH-A, antagonist group) and agonist (GnRH-a, agonist group) regimens. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was also used to evaluate whether the endometrial thickness (cm), progesterone (P) level (ng/ml) and estradiol (E2) level (pg/ml) on the day of human chorionic gonadotropin (hCG) administration (hCG day) had the ideal sensitivity and specificity for predicting clinical pregnancy. There were no significant differences in the baseline profiles of luteinizing hormone, E2 and P between the GnRH-A and GnRH-a groups (P=0.646, 0.224 and 0.119, respectively). However age, body mass index and follicle stimulating hormone (FSH) level significantly differed between the two groups (P<0.001, =0.025 and <0.001, respectively). Regarding treatment, there were significant differences in the stimulation duration (recombinant FSH days of usage), dose of gonadotrophins, E2, and P levels on hCG day, endometrial thickness on hCG day, mean number of total oocytes retrieved, mean number of two pronuclei oocytes, mean number of embryos available and mean number of embryos transferred (all P<0.001). The rate of clinical pregnancy was lower with the GnRH antagonist than with the GnRH agonist (P<0.001). Additionally, the live birth rate in the GnRH-A group was significantly lower than that in the GnRH-a group (P<0.001). The rate of ectopic pregnancy did not differ significantly between the treatment groups (P=0.840). However, the rate of ovarian hyperstimulation syndrome (OHSS) in group GnRH-A was significantly lower than that in group GnRH-a (P=0.039). Therefore, in the present series of patients who underwent IVF embryo transfer cycles, a GnRH antagonist protocol was associated with significantly lower rates of clinical pregnancy and live birth compared with a GnRH agonist protocol; however, the rate of OHSS was significantly lower with GnRH antagonist compared with GnRH agonist. Furthermore, the results of the influence of endometrial thickness on clinical pregnancy, based on the ROC curve (AUC), demonstrated that the AUC was 0.553 [95% confidence interval (CI): 0.521-0.585], and with a cutoff of 9.25 cm, the Youden index [sensitivity-(1-specificity)] was 0.085. The results of the influence of E2 level on hCG day on the clinical pregnancy rate revealed an AUC of 0.613 (95% CI: 0.581-0.644), and with a cutoff of 1,520 pg/ml, the Youden index was 0.184. The results of the influence of P level on hCG day (ng/ml) on the clinical pregnancy rate revealed an AUC of 0.526 (95% CI: 0.494-0.558), and with a cutoff of 0.415 ng/ml, the Youden index was 0.061. These results of the ROC curve analyses demonstrated that neither the endometrial thickness nor the E2 and P levels on hCG day had the ideal sensitivity or specificity for predicting clinical pregnancy.

Mutation analysis of the TUBB8 gene in primary infertile women with arrest in oocyte maturation.

Tubulin beta eight class VIII (TUBB8) is a subtype of ß-tubulin that only exists in primates. Mutations in the TUBB8 gene have been proven to cause oocyte maturation arrest. The aim of this study was to identify the new types of mutations in TUBB8. Six women (families) with oocyte maturation arrest and 100 healthy controls were recruited. The sequence of the TUBB8 gene was amplified and analyzed by Sanger sequencing, which revealed a de novo heterozygous variant c.292G > A (p.G98R) of TUBB8 in one affected individual. This TUBB8 variant was absent in the 100 fertile females and was predicted to be highly damaging to the function of the TUBB8 protein by SIFT and PolyPhen-2. This novel variant extends the spectrum of TUBB8 mutations and the presence of a TUBB8 mutation is being considered to be indicative of a poor prognosis for the success of assisted reproductive treatment.

GnRH antagonist for patients with polycystic ovary syndrome undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer in fresh cycles.

The aim of the present study was to evaluate the influence of a gonadotropin-releasing hormone (GnRH) antagonist compared with a GnRH agonist on the in vitro fertilization cycle outcome in patients with polycystic ovary syndrome. The outcomes of pregnancy were evaluated. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was also used to evaluate whether the endometrial thickness (cm) and estradiol (E2) level (pg/ml) on the day of human chorionic gonadotropin (hCG) administration (the hCG day) had the best sensitivity and specificity for predicting a clinical pregnancy. The results demonstrated that there were significant differences in the E2 and progesterone levels between the two treatment groups on the hCG day. Furthermore, the mean number of total oocytes retrieved, mean number of 2 pronuclei oocytes, mean number of oocytes cleaved (P<0.05), mean number of embryos available (P=0.022) and mean number of embryos transferred (P=0.014) were significantly different. Additionally, the rates of ectopic pregnancy (P=0.984) and ovarian hyperstimulation syndrome (P=0.976) did not differ significantly between the treatment groups. Although the biochemical pregnancy (P=0.592), clinical pregnancy (P=0.617) and live birth (P=0.365) rates were lower with the GnRH antagonist than with the GnRH agonist, there were no significant differences in the outcomes between the two groups. Analysis of the influence of endometrial thickness with respect to the clinical pregnancy using the ROC (AUC) method revealed that when the best cutoff of 9.75 cm was used, the sensitivity was 62.5%, the specificity was 43.1% and the AUC was 0.53. Additionally, the Youden index was 0.056. Analysis of the influence of the E2 level on the hCG day on clinical pregnancy, using the ROC (AUC) method showed that the best cutoff was 2,984.5 pg/ml, which had a sensitivity of 68.8% and specificity of 52.9%, while the AUC was 0.573 (with a Youden index of 0.217). Furthermore, the results demonstrated that neither the endometrial thickness nor the E2 level on the hCG day had the best sensitivity and specificity for predicting a clinical pregnancy.

Impact of XRCC1, GSTP1, and GSTM1 Polymorphisms on the Survival of Ovarian Carcinoma Patients Treated with Chemotherapy.

BACKGROUND: Single nucleotide polymorphic variants of DNA repair genes may improve drug efficacy through altering expression levels of the encoded proteins. This study evaluated the influence of genetic polymorphism GSTP1 Ile105Val, GSTM1 (null/non-null) and 2 XRCC1 polymorphisms (Arg194Trp and Arg399Gln) on the survival of ovarian carcinoma patients treated with chemotherapy. METHODS: 106 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms were genotyped by pyrosequencing. RESULTS: The genotypes XRCC1 194Arg/Trp and XRCC1 194Trp/Trp conferred no significant risk of death when compared to 194Arg/Arg (hazard ratio (HR) 1.01, 95% confidence interval (CI) 0.33-3.09, and HR 0.89, 95% CI 0.31-2.57, respectively). Similarly, those carrying the XRCC1 399Arg/Gln genotype had no increased risk of death compared to the XRCC1 399Arg/Arg (HR 0.85, 95% CI 0.39-1.86); no homozygous carriers of the glutamine allele (XRCC1 399 Gln/Gln) were detected. The GSTP1 105Ile/Val had no increased risk of death compared to the GSTP1 105Ile/Ile (HR = 1.20, 95% CI = 0.55-2.63) and no homozygous carriers of the valine allele (GSTP1 105Val/Val) were detected in the study. Compared to the non-null genotype of GSTM1, the mortality rate was nonsignificantly reduced in patients with the null genotype (HR 1.07, 95% CI 0.48-2.42). However, overall survival of the patients treated with the carboplatin-based regimen was significantly longer than for those treated with alternative chemotherapy (plog-rank = 0.006). CONCLUSIONS: The present findings suggest that there are no correlations between genotypes and survival.

Single nucleotide polymorphisms in glutathione S-transferase P1 and M1 genes and overall survival of patients with ovarian serous cystadenocarcinoma treated with chemotherapy.

The effects of platinum-based drugs are controlled by genes that are involved in DNA detoxification, including glutathione S-transferase (GST)P1 and GSTM1, which have been associated with increased benefits in the chemotherapeutic treatment of patients with ovarian cancer. The present study assessed the effect of single nucleotide polymorphisms in GST genes on the overall survival (OS) of patients with ovarian serous cystadenocarcinoma that were treated with chemotherapy. A total of 95 patients received treatment with a carboplatin-based or alternative chemotherapy. Polymorphisms in the patients were genotyped using the following methods: Pyrosequencing, to identify GSTP1 Ile105Val; a relative quantification method, to identify the copy number variation in GSTM1; and polymerase chain reaction followed by gel electrophoresis, to identify the null vs. non-null genotypes of GSTM1. The association between genotypes and OS of patients was assessed using Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The OS of patients treated with paclitaxel + carboplatin-based chemotherapy was significantly increased, compared with patients treated with alternative forms of chemotherapy (P=0.035). The OS of patients did not differ significantly between different GSTP1 genotypes (log-rank test, P=0.17). Cox proportional hazards regression analysis revealed that, since the start of the treatment, there was not a significant association between the GSTP1 isoleucine allele and the OS for heterozygous carriers of the isoleucine allele [hazards ratio (HR), 1.78; 95% confidence interval (CI), 0.77-4.12; P=0.18] and no homozygous carriers of the valine allele had been detected (HR, 0.00). There was no significant difference between GSTM1 genotypes, according to Kaplan-Meier survival analysis (log-rank test, P=0.83). Patients that possessed ≤1 copy of GSTM1 exhibited no decrease in OS (HR, 0.96; 95% CI, 0.37-2.51; P=0.94), compared with patients that possessed two copies of GSTM1 (HR, 0.71; 95% CI, 0.22-2.28; P=0.56). Overall, the present results suggest that there are no associations between polymorphisms in the GSTP1 and GSTM1 genes and the OS of patients with ovarian cancer following administration of adjuvant chemotherapy.