Nenghui Liu

To evaluate the risk factors associated with WOI (window of implantation) displacement based on ERT (endometrial receptivity test), and to confirm the association of ectopic pregnancy with WOI displacement. This is a retrospective study at the Reproductive Medicine Center of Xiangya Hospital from January 2020 to April 2024, consisting of 934 patients who performed ERT. The patients underwent 3771 assisted reproductive technology (ART) cycles and 2629 embryo transfer (ET) cycles, with each patient experiencing at least one implantation failure. The study utilized generalized estimation equation (GEE) models to examine factors associated with WOI displacement, adjusting for confounding factors like age, body mass index (BMI), and infertility type. Non-linear relationships between age or BMI with WOI displacement were explored using generalized additive models (GAM) with thresholds detected by segmented regression. Among the patients, 60.17% were in the receptive phase, 39.40% in the pre-receptive phase, and 0.43% in the post-receptive phase. Ectopic pregnancy history increased the risk of WOI displacement by 62% (aOR 1.62, 95%CI 1.03–2.53, P = 0.035), patients over 35 years old had a 50% higher risk of WOI displacement compared to patients under 34 (aOR 1.50, 95% CI 1.12-2.00, P = 0.007). Secondary infertility showed a 26% lower risk of WOI displacement than primary infertility without statistical significance (aOR 0.74 95% CI 0.54–1.02, P = 0.062). BMI ≥ 22 kg/m2 was associated with a 25% increased risk of WOI displacement without statistical significance (aOR 1.25, 95% CI 0.94–1.67, P = 0.12). Ectopic pregnancy and advanced age (≥ 35) are significantly associated with increased risk of WOI displacement. Primary infertility and higher BMI (≥ 22 kg/m2) tend to increase the risk of WOI displacement though without statistical significance. Not applicable.

Whether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET). This is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes. There is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction0.05). MTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.

Purpose Whether the dominant status of vaginal Lactobacillus is associated with IVF/ICSI outcomes. Methods This is a propensity score-matched retrospective cohort study consists of 2285 women undergoing their first fresh autologous IVF cycles. We divided the patients into the Lactobacillus-dominant group and non-Lactobacillus-dominant group based on the abundance of Lactobacillus in Gram-stained vaginal smear examined by microscopy. We compared IVF outcomes between the two groups. We matched Lactobacillus-dominant women with non-Lactobacillus-dominant women by propensity score (PS) to reduce the impact of confounding factors. We evaluated the effect of vaginal Lactobacillus on live birth using univariate and multivariate analysis models. We also conducted interaction and stratified analyses. Results Compare to the Lactobacillus-dominant group, the biochemical pregnancy rate (50.12% vs. 57.61%, P = 0.03), clinical pregnancy rate (40.98% vs. 50.82%, P < 0.01), and live birth rate (31.83% vs. 41.22%, P < 0.01) were significantly lower in the non-Lactobacillus-dominant group, the preclinical pregnancy loss rate (18.22% vs. 11.79%, P = 0.05) and preterm birth rate (33.09% vs. 21.59%, P = 0.02) were significantly higher in the non-Lactobacillus-dominant group. However, the miscarriage rate (18.86% vs. 15.67%, P = 0.40) and ectopic pregnancy rate (1.41% vs.1.64%, P = 0.78) were similar between the two groups. Loss dominance of Lactobacillus in the vagina was an independent risk factor for live birth (OR 0.66, 95% CI 0.50–0.88). Conclusions Loss dominance of Lactobacillus in the vagina negatively affects IVF outcomes by decreasing the chances of pregnancy and live birth, increasing risks of preclinical pregnancy loss and preterm birth.

Although previous studies have shown a relationship between uterine leiomyoma and pregnancy outcomes, this relationship is not yet completely understood. Many review articles have addressed this effect, but to date, none has classified this relationship according to the characteristics of the leiomyoma (i.e., type, size, number, and location). This review was conducted to evaluate and classify the relationship between leiomyoma characteristics and the effects of a leiomyoma on pregnancy and prenatal outcomes to facilitate decision-making in preconception and prenatal counselling. We examined articles published in English regarding any leiomyoma characteristics with obstetric outcomes during pregnancy using a collection of subject headings and key terms: ‘leiomyomata,‘ ‘myoma,‘ ‘leiomyoma,‘ ‘fibroid,‘ and ‘pregnancy.‘ Many studies regarding the influence of leiomyoma characteristics on outcomes of pregnancy were identified, and the common conclusion was that the outcomes were dependent on leiomyoma characteristics. Most studies focussed on leiomyoma size, followed by type, location, and number of lesions. Different leiomyoma characteristics are related to diverse pregnancy outcomes. Therefore, it may be possible to predict the extent of the effects of these tumours on pregnancy outcomes by identifying all leiomyoma characteristics.

Objective To investigate whether polymorphism of MTHFR C677T or MTHFR A1298C is associated with recurrent implantation failure (RIF). Study Design This is a systematic review and meta-analysis. Pubmed, EMBASE, and CNKI (China national Knowledge Infrastructure) were searched for case–control studies that evaluated the associations between MTHFR polymorphisms (MTHFR C677T and MTHFR A1298C) and RIF. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were reported to evaluate the strength of association. Data were synthesized using the random-effect model. Results Nine case–control studies consisted of 1812 women were included in the quantitative meta-analyses (754 were RIF patients, 1058 were control participants). The synthesized results showed that polymorphism of MTHFR C677T (allele model: OR 1.23, 95% CI 0.99–1.53; dominant model: OR 1.24, 95% CI 0.99–1.54; recessive model: OR 1.31, 95% CI 0.78–2.12; homozygotic model: OR 1.39, 95% CI 0.84–2.28; heterozygotic model: OR 1.14, 95% CI 0.90–1.45) or MTHFR A1298C (allele model: OR 1.11, 95% CI 0.78–1.59; dominant model: OR 0.91, 95% CI 0.65–1.26; recessive model: OR 2.04, 95% CI 0.90–4.64; homozygotic model: OR 1.86, 95% CI 0.79–4.38; heterozygotic model: OR 0.77, 95% CI 0.59–0.99) was not significantly associated with RIF. Conclusions Significant association of MTHFR polymorphisms (including MTHFR C677T and MTHFR A1298C) and RIF could not be confirmed.

Recently, perinatal outcomes and cumulative live birth rate (CLBR) have widely been utilized to assess the fertility outcomes and safety of assisted reproductive technology (ART), but more robust research is needed to address the success rates of live-healthy births resulting from this procedure, particularly for patients with low prognosis. This study aims to assess and comparative perinatal outcomes and CLBR per cycle of in vitro fertilization/Intracytoplasmic sperm injection (IVF/ICSI) between four groups of low prognosis characterized by POSEIDON criteria. A retrospective assessment was done among infertile women with a low prognosis undergoing IVF/ICSI at a reproductive center in China. Data were collected between January 2011 and December 2015 with a follow-up of at least two years, and censoring was defined by three-cycle completion, discontinuation, or having a live birth. Participants were grouped into 4 groups according to the POSEIDON classification (POSEIDON1, POSEIDON2, POSEIDON3, and POSEIDON4). The main outcomes were perinatal and obstetric outcomes with CLBR per cycle after IVF/ICSI procedure. And IVF/ICSI-technique outcomes as a secondary outcome. Statistical analyses were performed by SPSS, and a p value of < 0.05 was considered significant. A total of 461 eligible participants underwent a total of 825 IVF/ICSI cycles. POSEIDON1 had the best perinatal outcomes in terms of live births (≥ 28w) (54.8%). POSEIDON4 had a higher risk for perinatal and obstetric complications with abortion rate (9.8%); LBW (11.7%), PTD (23.5%), PROM (11.7%), and gestational diabetes (17.6%). POSEIDON2 had a high rate for malpresentation (14.2%), and cesarean delivery(57.2%), while POSEIDON3 was much associated with the occurrences of placenta previa (9.3%) compared to other groups (p value = 0.001). After adjusting odds ratio by age and BMI, POSEIDON4 had the least odds for biochemical pregnancy (p value = 0.019); and the least odds for clinical pregnancy (p value = 0.001) of the four groups. CLBR per cycle was better in POSEIDON1 and increased with an increasing number of cycles in all groups during the three cycles. Conservative CLBR after three complete cycles were 77.27%, 42.52%, 51.4% and 22.34%, while optimistic CLBR were 79.01%, 51.19%, 58.59% and 34.46% in POSEIDON1 to POSEIDON4, respectively. Younger women with low prognosis and normal ovarian reserve have a higher probability for live births and better perinatal outcomes compared with older women with poor or normal ovarian reserve. Besides, young women with low prognosis, despite ovarian reserve status, can increase their probability of conception and get relatively higher CLBR by undergoing multiple cycles of IVF/ICSI. Age is therefore considered as a critical parameter in predicting the perinatal outcome and CLBR.

Purpose To investigate the role and underlying mechanism of H19 in regulating angiogenic capacity of extravillous trophoblasts. Methods Gain and loss of function experiments were performed using a human first-trimester extravillous trophoblast (EVT) cell line, HTR-8/SVneo cells. H19 was overexpressed or knocked down in HTR-8 cells by transfecting plasmid harboring whole-length H19 sequence (pH19) or siRNA specially targeting H19, respectively (siH19). Cell migration and tube-formation assay were assessed in the indicated groups. Gene expression was detected by RT-qPCR, Western blot, and ELISA assay. Results Overexpression of H19 in EVT cells increased cell migration and tube formation, while downregulation of H19 in EVT cells decreased cell migration and tube formation. Furthermore, we found that H19 played its role by VEGFA. In addition, we demonstrated the H19/miR-106a-5p/VEGFA regulatory axis in EVT. Experiments of the clinical specimen showed that H19 was very abundantly expressed in human first-trimester trophoblasts, and we found that the expression of H19 and VEGFA were significantly downregulated in the villous tissues from idiopathic recurrent miscarriage (RM) patients; moreover, the expression of H19 and VEGFA was positively correlated. Conclusion H19/miR-106a-5p/VEGFA axis plays a role in regulating the angiogenic capacity of EVT, which might contribute to idiopathic RM.

Integrin β3 (ITGB3), which is the target gene of the miRNA let-7 that can be antagonized by long noncoding RNA (lncRNA) H19, is well known to have a critical role in endometrium receptivity. However, the regulation of ITGB3 in cell–cell or cell–extracellular matrix adhesion and invasion for the maintenance of early pregnancy remains unknown. This study aimed to explore the role of the H19/let-7/ITGB3 axis in regulating trophoblastic spheroid adhesion and in vitro invasion ability using the HTR-8/SVneo cell line and to investigate the expression levels of lncRNA H19 and ITGB3 in human products of conception. The in vitro knockdown of H19 resulted in decreased expression of ITGB3 at the mRNA and protein levels and reduced the adhesion and invasion ability. In the embryonic chorion tissue of spontaneous abortion (SA), the expressions of H19 and ITGB3 at both the mRNA and protein levels decreased. The results of quantitative RT-PCR, Western blot analysis, dual-luciferase report gene and functional miRNA let-7 rescue experiments, adhesion assay and in vitro transwell invasion assay confirmed that H19 regulated trophoblastic spheroid adhesion with endometrial stromal cells through the H19/let-7/ITGB3 axis, thereby providing an improved understanding of the molecular mechanism of SA.

Purpose To detect the expression level of imprinted gene H19 in the endometrium of patients with repeated implantation failure (RIF) who were undergoing in vitro fertilization and embryo transfer (IVF-ET) or frozen embryo transfer (FET). Methods Patients who underwent IVF/FET in Reproductive Medicine Center of Xiangya Hospital during April 1, 2015 to October 31, 2015 were chosen. The endometrium was collected from patients with repeated implantation failure during mid-luteal phase. Real-time quantitative reverse transcription PCR (qRT-PCR) and western blot were used to determine the expression of H19 lncRNA and integrin β3 protein. Data analysis was performed using SPSS 19.0. Results When compared with the control group, decreased expression of H19 was detected in the RIF group (P = 0.04). The expression of integrin β3 protein was also decreased in the RIF group compared to that in the control group (P = 0.04). The expression of H19 lncRNA was positively correlated with the expression of integrin β3 protein (R = 0.477, P = 0.018). Conclusions The expression of H19 lncRNA and integrin β3 protein were down-regulated in the RIF patients.