Reproductive and transcriptome characteristics of endometrium at the window of im-plantation in patients after fertility-sparing treatment of endometrial intraepithelial neoplasm or cancer.

Background: Progestin therapy is an option for patients with endometrial carcinoma (EC) or endometrial intraepithelial neoplasm (EIN) who fit specific criteria of fertility-sparing treatment. However, the implantation rate remains low among females receiving in vitro fertilization (IVF) even after the complete reversal of endometrial lesions. Methods: Here, ten patients with EC/EIN achieved complete regression (CR) in histology. Their relevant metabolic and IVF parameters were collected. An endometrial sampling at the window of implantation (WOI) and transcriptome analysis were conducted among them, and four healthy controls were analyzed to analyze endometrial receptivity. Results: On average, it took ten patients five months to achieve CR after four curettage procedures. The interquartile range of endometrium thickness on trigger day was between 8.8 and 10.0 mm, while the range was 15.2-18.5 mm for controls. Five patients got pregnant after a frozen-embryo transfer. According to ERA analysis, the endometrial sampling at WOI showed pre-receptive status in four cases. In total, 1458 differential expression genes were identified, and 70 belonged to the ERA genes. ImmuneScore indicated decreased NK cells in the endometrium, affecting endometrial receptivity. Conclusions: Even after EC/EIN reversal in histology, endometrial receptivity has already been compromised regarding altered WOI and immune microenvironment, leading to a low pregnancy rate.

Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis.

OBJECTIVE: Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS. METHODS: PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro. RESULTS: NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis. CONCLUSION: Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.

Single-dose administration of a short-acting gonadotropin-releasing hormone agonist does not affect cycle outcome in frozen-thawed embryo transfer cycles.

OBJECTIVE: This prospective study aimed to assess the effect of short-acting gonadotropin-releasing hormone agonist (GnRHa) administration on pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles. METHODS: Patients who planned to have FET in Peking Union Medical College Hospital (China) were recruited for this study and randomly assigned into two groups. Patients in the experimental group (n = 460) received triptorelin acetate on the day of embryo transfer along with routine luteal support. Patients in the control group (n = 433) only received luteal support. One dose (0.1 mg) of a short-acting GnRHa was administered on the day of blastocyte transfer. The rates for clinical pregnancy, biochemical pregnancy, implantation, miscarriage, and ectopic pregnancy were compared between the groups. RESULTS: There were no significant differences in the number and quality of blastocytes transferred between the two groups. In the experimental and control groups, the clinical pregnancy rate was 56.3% and 50.58%, the biochemical pregnancy rate was 15.78% and 18.94%, and the median implantation rate was 39.98% and 38.01%, respectively, with no significant difference between the groups. Biochemical pregnancy and abortion and the ectopic pregnancy rate were not significantly different between the two groups. CONCLUSION: In FET cycles, a GnRHa does not affect the pregnancy outcome.

The effect of a transient premature luteinizing hormone surge without elevated serum progesterone on in vitro fertilization outcomes in a gonadotropin-releasing hormone antagonist flexible protocol.

During controlled ovarian stimulation, the LH rising before triggering can lead to follicular luteinizations. However, LH can be suppressed immediately and no progesterone elevation with GnRH antagonist. This study retrospectively compared fresh IVF/ICSI cycle outcomes in antagonist protocols between the group with and the group without a premature LH surge. Logistic regression models were fitted to reduce the relevant confounders. Compared between premature LH surge group and control group, the implantation rates were 12.9% (30/233) vs 25.0% (141/536), p = .000; clinical pregnancy rates were 21.0% (25/119) vs 41.6% (119/286), p = .000; live birth rates were17.6% (21/119) vs 29.7% (85/286), p = .012. After adjusting for age, BMI, bFSH, and infertility factors, the adverse effects were still as pronounced for the clinical pregnancy rate (OR = 0.39, 95% CI = 0.24-0.66) and live birth rates (OR = 0.54, 95% CI = 0.32-0.93. In a GnRH antagonist flexible protocol, a transient premature LH surge which can be suppressed immediately after the initiation of antagonist without elevated serum progesterone, will cause a detrimental effect on the development of the embryo and IVF/ICSI pregnancy outcomes in fresh embryo transfer cycles.

Factors Associated with Effectiveness of Treatment and Reproductive Outcomes in Patients with Thin Endometrium Undergoing Estrogen Treatment.

BACKGROUND: Thin endometrium is associated with poor reproductive outcomes; estrogen treatment can increase endometrial thickness (EMT). The aim of this retrospective cohort study was to investigate the factors influencing the effectiveness of estrogen treatment and reproductive outcomes after the treatment in patients with thin endometrium. METHODS: Relevant clinical data of 101 patients with thin endometrium who had undergone estrogen treatment were collected. Possible factors influencing the effectiveness of treatment were analyzed retrospectively by logistic regression analysis. Eighty-seven infertile women without thin endometrium who had undergone assisted reproduction served as controls. The cases and controls were matched for age, assisted reproduction method, and number of embryos transferred. Reproductive outcomes of study and control groups were compared using Student's t-test and the Chi-square test. RESULTS: At the end of estrogen treatment, EMT was ≥8 mm in 93/101 patients (92.1%). Effectiveness of treatment was significantly associated with maximal pretreatment EMT (P = 0.017) and treatment duration (P = 0.004). The outcomes of assisted reproduction were similar in patients whose treatment was successful in increasing EMT to ≥8 mm and the control group. The rate of clinical pregnancy in patients was associated with the number of good-quality embryos transferred in both fresh (P = 0.005) and frozen-thawed (P = 0.000) embryo transfer cycles. CONCLUSIONS: Thinner EMT before estrogen treatment requires longer treatment duration and predicts poorer treatment outcomes. The effectiveness of treatment depends on the duration of estrogen administration. Assisted reproductive outcomes of patients whose treatment is successful (i.e., achieves an EMT ≥8 mm) are similar to those of controls. The quality of embryos transferred is an important predictor of assisted reproductive outcomes in patients treated successfully with exogenous estrogen.

Brain-derived neurotrophic factor from follicular fluid is positively associated with rate of mature ooocytes collected and cleavage rate in intracytoplasmic sperm injection patients.

PURPOSE: The aim of the study was to evaluate the correlation between BDNF and oocyte maturation and to verify whether BDNF could predict in vitro fertilization (IVF) outcome. METHODS: The follicle fluid (FF) for BDNF, E(2) and P assay were obtained from 59 patients undergoing intracytoplasmic sperm injection (ICSI). The women were divided into two groups by pregnancy outcome and their clinical and lab data were compared. And the correlation of BDNF with E(2), P, age, and IVF data were analyzed. RESULTS: Positive correlation was observed between BDNF and E(2) concentration in FF. BDNF was positively correlated with the rate of mature oocytes collected and cleavage rate. CONCLUSIONS: The BDNF in FF could not predict IVF outcome, but BDNF in FF might play an important role in the maturation of oocyte and development of oocyte into preimplantation embryo.

[Relationship between endometriosis fertility index and pregnancies after laparoscopic surgery in endometriosis-associated infertility].

OBJECTIVE: To evaluate the relationship between endometriosis fertility index (EFI) and pregnancies after laparoscopic surgery in endometriosis-associated infertility. METHODS: From Jan. 2005 to Jan. 2010, medical documents of 350 infertile patients due to endometriosis undergoing laparoscopic surgery were studied retrospectively. Pregnancy outcomes were followed up by telephone. EFI was calculated by history factors, least function score and some aspects of the revised American Fertility Society (r-AFS) endometriosis stage. The cumulative pregnancy rate was calculated and compared by Kaplan-Meier survival analysis. RESULTS: Within 3 years after surgery, the cumulative pregnancy rates among patients with EFI score 8, 9, 10 were 62.5%, 69.8% and 81.1%, respectively. There was no significant difference in pregnancy rates among those three groups of patients (P = 0.24). The cumulative pregnancy rates among patients with EFI score 5, 6, 7 were 49.8%, 43.9% and 41.6%, respectively, which did not reach statistical difference (P = 0.83). The cumulative pregnancy rates of EFI score 8 - 10 was significantly higher than that of EFI score 5 - 7 (71.8% vs. 44.4%, P = 0.000). The patients with EFI score 0 - 4 was quite small with only 33 cases, among which 15 cases were pregnant. CONCLUSIONS: There is relationship between EFI and pregnancy in patients with endometriosis-associated infertility. EFI is meaningful to guide post-surgical treatment.

[Cost-effectiveness analysis of two therapeutic methods for prolactinoma].

OBJECTIVE: To evaluate the therapeutic responses to transsphenoidal surgery and medical therapy in terms of normalization of prolactin (PRL), mortality, morbidity and the cost-effectiveness of PRL normalization in order to establish an individualized therapeutic protocol for the patients with prolactinoma. METHODS: A retrospective study was undertaken of a consecutive series of patients with prolactinoma who were followed for at least 1 year after transsphenoidal surgery or medical treatment. The clinical characteristics and the long-term outcomes (normalization of PRL, morbidity or mortality) were assessed. Utilizing the principle of medical economics and data from the two types of treatment, we worked out a Markov chain and calculated the lowest cost of two kinds of therapeutic protocols. RESULTS: (1) The success rate of normalizing serum PRL through surgical treatment in microadenoma was 85% (22/26), and that of medical treatment was 95% (19/20). There was no statistical difference between the two therapies (P > 0.05). The success rate of normalizing serum PRL through surgical treatment in macroadenoma was 45% (19/42), and that of medical treatment was 5/5. There was a statistical difference between the two therapies (P < 0.05). (2) According to the Markov model, it would cost a microprolactinoma patient 25,129.25 yuan to normalize serum PRL by surgical treatment. This is comparable to the cost of medical treatment which would be 24,943.99 yuan. Whereas for a macroprolactinoma patient surgery would cost 35,208.20 yuan and medical treatment would cost 25,344.38 yuan. CONCLUSIONS: Medical therapy is superior to surgical treatment in regard to complication rate and cost-effectiveness for macro- and extra big prolactinomas. Transsphenoidal surgery remains an option for patients with microadenomas. Markov model is an effective way to predict the treatment cost for patients with hyperprolactinoma at different ages and with different causes.