Establishment of a prediction model for the impact of endometrial thickness on the day of embryo transfer on ectopic pregnancy in frozen-thawed embryo transfer cycle.

Objective: This study aims to investigate the factors affecting the ectopic pregnancy (EP) rate in the frozen-thawed embryo transfer (FET) cycle. Methods: This study retrospectively analyzed 5606 FET cycles, including 5496 cycles resulting in intrauterine pregnancy and 110 cycles resulting in EP. Smooth curve fitting and piece-wise linear regression were utilized to evaluate a non-linear association between endometrial thickness (EMT) and EP. Multiple logistic regression analysis was used to study the effect of EMT on the embryo transfer (ET) day and other indexes on EP rate after adjusting for confounding factors. A nomographic prediction model was employed to predict EP occurrence. The predictive efficacy of the model was assessed using the area under the receiver operating characteristic (ROC) curve (AUC), utilizing the bootstrap sampling method for internal validation. Results: After accounting for the confounding factors, the segmented linear regression analysis indicated that the EMT inflection point was 9 mm; the EP rate significantly decreased by 28% with each additional millimeter of EMT up to 9 mm (odds ratio (OR) = 0.72; 95% confidence interval (CI), 0.53-0.99; P = 0.0412) while insignificantly decreased when the EMT was greater than 9 mm (OR = 0.91; 95% CI, 0.76-1.08; P = 0.2487). Multivariate logistic regression analysis revealed that after adjusting for confounders, EP risk significantly increased in the number of previous EPs ≥ 1 (OR = 2.29; 95% CI, 1.26-4.16; P = 0.0064) and tubal factor infertility (OR = 3.86; 95% CI, 2.06-7.24; P < 0.0001). Conversely, EP risk was significantly reduced by the increased EMT (OR = 0.84; 95% CI, 0.74-0.96; P = 0.0078) and the blastocyst transfer (OR = 0.45; 95% CI, 0.27-0.76; P = 0.0027). These variables were used as independent variables in a nomogram prediction model, resulting in an AUC of 0.685. The nomination models were internally verified using self-sampling (bootstrap sampling resampling times = 500). This validation yielded an AUC of 0.689, with a sensitivity of 0.6915 and a specificity of 0.5790. The internal validation indicated minimal fluctuations in the AUC, signifying a relatively stable model. Conclusion: Undergoing EMT on the day of ET poses a separate EP risk in the FET cycle; to mitigate the EP incidence, the EMT should exceed 9 mm before ET. Furthermore, previous EPs and tubal factor infertility were additional factors independently increasing EP risk. Furthermore, implementing blastocyst transfer demonstrated that EP incidence was significantly reduced. Utilizing a nomogram predicting system enables EP risk evaluation before ET for individual patients, establishing a basis for devising clinical strategies for ET.

Determination of tryptophan and its indole metabolites in follicular fluid of women with diminished ovarian reserve.

Tryptophan (TRP) and its indole metabolites exhibit numerous biological effects, especially their antioxidant properties. This study used untargeted metabolomics in conjunction with targeted metabolomics to investigate the differential expression of tryptophan and its indole metabolites in follicular fluid (FF) of diminished ovarian reserve (DOR) and normal ovarian reserve (NOR) populations. This study included patients with DOR (n = 50) and females with NOR (n = 35) who received in vitro fertilization and embryo transfer. Untargeted metabolomics suggests that diminished ovarian reserve affects the metabolic profile of FF, TRP and indole metabolites were significantly down-regulated in the DOR group. Targeted metabolomics quantification revealed that the levels of TRP, IPA and IAA in the FF of the DOR group were significantly lower than those of the NOR group (P < 0.01). The concentration of TRP in FF is positively correlated with the available embryo rate in NOR females. These results provide data support to explore the pathogenesis of DOR and to look for new biomarkers and ovarian protectors. Additionally, alterations in TRP and its indole metabolites in FF may indirectly reflect the interaction between intestinal flora and the follicular microenvironment.

Reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with a septate uterus: a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to analyze the reproductive outcomes of natural pregnancy after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility. DATA SOURCES: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform, VIP Database, and Chinese Biomedical Literature Database (CBM) databases were electronically searched. The search time frame was from inception up to July 2021. The English search terms were (arcuate* and uter*), (sept* and uter*), (subseptate* and uter*), metroplast*, septoplast*, and resect*. STUDY ELIGIBILITY CRITERIA: Selection criteria included randomized controlled trials, cohort studies, and case series that explored reproductive outcomes after hysteroscopic septum resection in patients with recurrent miscarriage, primary infertility, or secondary infertility with or without a control group. METHODS: The primary outcomes were the live birth rate and eventual postoperative live birth rate after hysteroscopic septum resection. The secondary outcomes were the clinical pregnancy rate, preterm birth rate, and miscarriage rate. Study-level proportions of outcomes were transformed using the Freeman-Tukey double-arcsine transformation to calculate pooled values for the postoperative rates; the counted data were analyzed using relative risk as the effect analysis statistic, and each effect size was provided with its 95% confidence interval. Heterogeneity between the results of the included studies was analyzed using the I2 test. RESULTS: Overall, 5 cohort studies and 22 case series involving 1506 patients were included. In patients with a septate uterus and recurrent miscarriage, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 1.77; 95% confidence interval, 1.26-2.49; P=.001; I2=0%), resulting in a postoperative live birth rate of 66% (95% confidence interval, 59-72), and septum resection was associated with a reduced preterm birth rate (relative risk, 0.15; 95% confidence interval, 0.04-0.53; P=.003; I2=0%) and miscarriage rate (relative risk, 0.36; 95% confidence interval, 0.20-0.66; P=.0009; I2=0%). In patients with a septate uterus and primary infertility, hysteroscopic septum resection was associated with an increased live birth rate (relative risk, 4.12; 95% confidence interval, 1.19-14.29; P=.03; I2=0%) and clinical pregnancy rate (relative risk, 2.28; 95% confidence interval, 1.04-4.98; P=.04; I2=0%). The postoperative live birth rate was 37% (95% confidence interval, 30-44), and the miscarriage rate of patients with primary infertility was reduced (relative risk, 0.19; 95% confidence interval, 0.06-0.56; P=.003). The efficacy of hysteroscopic septum resection in patients with secondary infertility was unclear. However, their postoperative live birth rate was found to be 41% (95% confidence interval, 2-88). CONCLUSION: Hysteroscopic septum resection is associated with an increased live birth rate and a reduced miscarriage rate in patients with recurrent miscarriage or primary infertility, indicating that septum resection may improve the reproductive outcomes of these patients. The effectiveness of septum resection was unclear for patients with secondary infertility. These findings are limited by the quality of the included studies, warranting further randomized controlled trials, including only patients with recurrent miscarriage or primary infertility.

Progestin-primed ovarian stimulation protocol with or without clomiphene citrate for poor ovarian responders: a retrospective cohort study.

OBJECTIVE: To explore the efficacy of progestin-primed ovarian stimulation (PPOS) combined with clomiphene citrate (CC) versus PPOS protocol used alone on cycle characteristics and pregnancy outcomes for women with the poor ovarian response (POR). METHODS: We performed a retrospective cohort study and a total of 578 POR patients who underwent IVF/ICSI cycles were collected and divided into Group A (HMG 300 IU/d + MPA 10 mg/d) and Group B (HMG 300 IU/d + MPA 10 mg/d + CC 50 mg/d). The primary outcome measure was the number of oocytes retrieved, other outcome measures were cycle characteristics and clinical pregnancy rate. RESULTS: The baseline information between the two groups were not statistically significant (P > 0.05). Compared with Group A, Group B had a lower total dose of human menopausal gonadotrophin (HMG) (2998.63 ± 1051.09 vs. 3399.18 ± 820.75, P < 0.001) and the duration of stimulation (10.21 ± 3.56 vs. 11.27 ± 2.56, P < 0.001). Serum luteinizing hormone level was higher in Group B on human chorionic gonadotrophin injection day (P < 0.001). The number of oocyte for retrieval, maturation, and fertilization were significantly lower in Group B than that in Group A (P < 0.001). However, the oocyte retrieval rate, maturation rate, fertilization rate, and viable embryo rate showed no statistical difference in the two groups (P > 0.05). After adjusting for confounders, the clinical pregnancy rate (OR 1.286; 95% CI 0.671-2.470) and live birth rate (OR 1.390; 95% CI 0.478-3.990) were comparable between the two groups. CONCLUSIONS: PPOS protocol combined with CC reduces the total dose of HMG and the duration of stimulation, and can also achieve similar oocyte yields and clinical pregnancy rate compared with the PPOS protocol used alone in poor ovarian responders.

The follicular fluid metabolome in infertile individuals between polycystic ovary syndrome and diminished ovarian reserve.

Follicular fluid is the microenvironment of oocytes that plays a crucial role in oocyte development. This study intended to explore the follicular fluid metabolomics in diminished ovarian reserve (DOR), polycystic ovarian syndrome (PCOS), and normal ovary response (NOR) groups. For metabolomic analysis, we collected the follicular fluid samples from 28 patients with DOR, 28 patients with NOR, and 28 patients with PCOS. The identified metabolites were annotated using KEGG to determine the metabolic pathway disturbances in PCOS and DOR. Based on the regression model, we conducted ROC analysis to identify PCOS and DOR biomarkers in the follicular fluid. The present results identified that the DOR and NOR groups' differential metabolites were primarily enriched in the choline pathway. The concentrations of pregnanediol-3-glucuronide and 2-hydroxyestrone sulfate in the DOR and NOR groups were substantially different. The metabolites in the purine metabolism pathway were mainly enriched in the PCOS and NOR groups. N-Acetyl-S-(N-methylcarbamoyl) cysteine and 3,4-dehydrothiomorpholine in the PCOS and NOR groups were substantially different. We also identified metabolic alterations in PCOS and DOR follicular fluid, which provides novel ways for PCOS and DOR diagnosis and therapy.

Endometrial compaction after human chorionic gonadotrophin administration reduces ectopic pregnancy rate following fresh embryo transfer in vitro fertilization/intracytoplasmic sperm injection cycles in patients with non-thin endometrium: a retrospective cohort study.

BACKGROUND: This study aims to study whether the change of endometrial thickness between the day of human chorionic gonadotrophin (HCG) administration and the day of embryo transfer (ET) has any effect on ectopic pregnancy (EP) rate following fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. METHODS: This study retrospectively analyzed 3134 patients who underwent fresh IVF/ICSI ET, including 3022 intrauterine, 112 ectopic cycles. Multiple logistic regression analysis and stratified analysis were used to study the effect of endometrial compaction after HCG administration on EP in patients with non-thin endometrium after adjusting for confounding factors. RESULTS: After adjusting for confounders, multiple logistic regression analysis found that the risk of EP in the compaction group was significantly lower than that in the non-compaction group (OR = 0.49; 95% CI: 0.31-0.78; P = 0.0023). The results of the stratified analysis demonstrated the EP rate in patients with an endometrial thickness ≥ 8 mm on the day of ET; the compaction group significantly reduced the incidence of EP (OR = 0.49; 95% CI: 0.31-0.79; P = 0.0036). In patients with an endometrial thickness ≥ 8 mm on the day of ET, the incidence of EP had no statistical significance in two group (OR = 1.02; 95% CI: 0.18-5.88; P = 9790). CONCLUSION(S): In patients with non-thin endometrium, endometrial thickness compaction from the day of HCG to the ET day reduced the risk of EP significantly.

Dulaglutide, a long-acting GLP-1 receptor agonist, can improve hyperandrogenemia and ovarian function in DHEA-induced PCOS rats.

OBJECTIVE: The purpose of this study was to explore the effect of dulaglutide on DHEA induced PCOS rats and its mechanism, to provide new drugs and research directions for clinical treatment of PCOS. METHODS: In this study, the PCOS model was established by giving female SD rats subcutaneous injection of DHEA for 21 consecutive days. After modeling, the treatment group was injected subcutaneously with three doses of dulaglutide for 3 weeks. The model group was injected with sterile ultrapure water, and the normal group did not get any intervention. The body weight changes of rats in each group were recorded from the first day when rats received the administration of dulaglutide. Three weeks later, the rats were fasted the night after the last treatment, determined fasting insulin and fasting glucose the next day. After the rats were anesthetized by chloral hydrate, more blood was collected from the heart of the rat. The serum insulin, testosterone and sex hormone binding globulin (SHBG) levels were detected by the enzyme-linked immunoassay method. After removing the adipose tissue, the obtained rat ovary tissue was used for subsequent experimental detection, using HE staining for morphology and follicular development analysis; qRT-PCR for the detection of 3ßHSD, CYP17α1, CYP19α1, and StAR gene expression in ovarian tissue; and western blotting analysis of CYP17α1, CYP19α1, StAR protein expression and insulin level to verify whether dulaglutide has a therapeutic effect on PCOS in rats. RESULTS: After treated with different concentrations of dulaglutide, we found that the body weight of rats in the treatment groups were reduced. Compared with the rats in PCOS group, the serum androgen level of rats in the treatment groups was significantly decreased, and the serum sex hormone binding protein content was significantly increased, and there was statistically significant difference between these groups and PCOS group. In terms of protein expression and gene regulation, the expression of 3ßHSD, CYP19α1 and StAR in the ovarian tissue of rats in treatment groups were decreased significantly after received the treatment of dulaglutide, and there was statistically significant difference between these groups and PCOS group. In addition, dulaglutide reduced the insulin content in the ovarian tissue of PCOS rats. CONCLUSION: Dulaglutide may reduce the hyperandrogenemia of PCOS rats by regulating the content of serum SHBG and the expression of 3ßHSD, CYP19α1, and StAR related genes and proteins, thereby inhibiting the excessive development of small follicles and the formation of cystic follicles in the ovaries of PCOS rats, thereby improving polycystic ovary in PCOS rats. In addition, dulaglutide may reduce the weight of PCOS rats, further reducing the level of high androgen in PCOS rats, and improving the morphology of their polycystic ovaries.