Background and Aims: The association of dyslipidemia with reproductive outcomes is largely unknown, especially in recurrent implantation failure (RIF) patients. This study aimed to explore the impact ...of abnormal blood lipid levels on embryo genetic status and pregnancy outcomes in unexplained RIF (uRIF) patients after preimplantation genetic testing for aneuploidy (PGT-A). Method: In this retrospective study, they were divided into 4 groups according to the levels of cholesterol and triglyceride: non-hyperlipidemia group (NonH group), simple hypercholesterolemia group (SHC group), simple hypertriglyceridemia group (SHC group) and mixed hyperlipidemia group (MixH group). Additionally, patients were divided into 2 groups according to their HDL-C level. Embryos’ genetic status and pregnancy outcomes after transfer of euploid embryos were analyzed. Binary logistic regression and/or generalized estimating equation model were conducted to investigate the association of different types of dyslipidemia with aneuploid embryo rate and cumulative live-birth rate. Results: A total of 474 women were divided into four groups: NonH group (N=349), SHC group (N=55), SHT group (N=52) and MixH group (N=18). Compared with the NonH group, SHC group had a significantly increased aneuploid embryo rate 48.3% vs. 36.7%, P=0.006; adjusted OR (95% CI) = 1.52(1.04-2.22), as well as a reduced number of good-quality blastocysts 3.00±2.29 vs. 3.74±2.77, P=0.033. The SHC group showed a lower cumulative live-birth rate (47.0% vs. 40.0%), good birth outcome (37.2% vs. 34.5%) and a higher risk of clinical pregnancy loss (11.1% vs. 17.9%) but did not reach statistical significance. The incidences of obstetric or neonatal complications and other adverse events were similar in the four groups. Conclusion: We found that uRIF women with hypercholesterolemia had an increased proportion of aneuploid embryos and a reduced number of high-quality embryos, while different types of hyperlipidemias had no correlation with cumulative live birth rate as well as pregnancy and neonatal outcomes.
Background and Aims: The epigenetic mechanisms involved in the etiology of unexplained recurrent pregnancy loss (uRPL) is largely unknown. This study aims to investigate the molecular mechanisms of ...circRNAs modulating decidua function by regulating methylation modification of histones and whereby participating in uRPL. Method: RNA sequencings on decidua of uRPL couples and endometrial stromal cells (ESCs) after overexpressed with circSTK40 were performed to confirm the regulatory relationship between circSTK40 and SETD1B. Functional experiments including TUNEL, autophagy double-label system, the tests of glucose intake, lactic acid production were performed to determine the effects of circSTK40 and SETD1B on ESCs. Mechanism studies were conducted using RNA pulldown, RNA binding protein immunoprecipitation, chromatin immunoprecipitation et al. Results: The expression levels of circSTK40 and SETD1B were significantly downregulated in the decidua of uRPL patients, and a positive regulatory relationship was observed between them. Both circSTK40 and SETD1B promoted cell survival and participated in the maintenance of pregnancy by regulating apoptosis, autophagy and glycolysis of decidualized ESCs. After the knockdown of SETD1B, the protective effect of circSTK40 could be eliminated, resulting in elevated apoptosis, reduced autophagy level and increased cellular glycolysis, leading to pregnancy loss. Regarding mechanism studies, circSTK40 is directly bound to SETD1B and histone H3 to promote their interaction and increase the methylation level of H3K4. H3K4me2 and H3K4me3 reversely bound to the promoter region of SETD1B and enhanced its transcription, resulting in upregulation of SETD1B, and consequently formed a SETD1B/H3K4me2/3 regulatory loop. Conclusion: CircSTK40 influences cell survival by modulating the SETD1B/H3K4me2/me3 regulatory loop. Downregulation of circSTK40 and SETD1B in decidua may contribute to uRPL via promoting cell apoptosis. Our findings indicate a novel epigenetic mechanism for uRPL pathogenesis involving circSTK40 activity and histone methylation modification.
Thin endometrial thickness (EMT) has been suggested to be associated with reduced incidence of pregnancy rate after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment, but ...the effect of thin endometrium on obstetric outcome is less investigated. This study aims to determine whether EMT affects the incidence of obstetric complications in fresh IVF/ICSI-embryo transfer (ET) cycles.
We conducted a retrospective cohort study collecting a total of 9266 women who had singleton livebirths after fresh IVF/ICSI-ET treatment cycles at the Center for Reproductive Medicine Affiliated to Shandong University between January 2014 and December 2018. The women were divided into three groups according to the EMT: 544 women with an EMT ≤8 mm, 6234 with an EMT > 8-12 mm, and 2488 with an EMT > 12 mm. The primary outcomes were the incidence of obstetric complications including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), placental abruption, placenta previa, postpartum hemorrhage (PPH) and cesarean section. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for associations between the EMT measured on the day of human chorionic gonadotropin (HCG) trigger and the risk of the outcomes of interest.
The HDP incidence rate of pregnant women was highest in EMT ≤ 8 mm group and significantly higher than those in EMT from > 8-12 mm and EMT > 12 mm group, respectively (6.8% versus 3.6 and 3.5%, respectively; P = 0.001). After adjustment for confounding variables by multivariate logistic regression analysis, a thin EMT was still statistically significant associated with an increased risk of HDP. Compared with women with an EMT > 8-12 mm, women with an EMT ≤8 mm had an increased risk of HDP (aOR = 1.853, 95% CI 1.281-2.679, P = 0.001).
A thin endometrium (≤8 mm) was found to be associated with an increased risk of HDP after adjustment for confounding variables, indicating that the thin endometrium itself is a risk factor for HDP. Obstetricians should remain aware of the possibility of HDP when women with a thin EMT achieve pregnancy through fresh IVF/ICSI-ET treatment cycles.
Pregnancy-induced hypertension (PIH) is one of the most common pregnancy complications that seriously affects the mother and fetus. The incidence of PIH is higher in pregnancies conceived after ...assisted reproductive technology (ART) than in spontaneous pregnancies; thus, exploring potential serum biomarkers before PIH onset is of great significance for effective early prediction and prevention of PIH in the ART population. Cytokines are involved in the inflammatory response and immune regulation, which play an essential role in the pathogenesis of PIH. A description of the cytokine profile in the first trimester of pregnancy could help identify new diagnostic tools and develop targeted therapies for PIH in the ART population. The concentrations of classical predictive markers for PIH and another 48 cytokines were measured in the first-trimester pregnancy serum samples from 33 PIH patients and 33 matched normotensive controls (NC), both of whom conceived after ART treatment. The measured values were compared and analyzed between NC and PIH, followed by comprehensive bioinformatic analysis and logistic regression analysis. There was no significant difference in classical predictive markers, including Activin A, PlGF, sFLT1 (VEGFR), and sFLT1/PlGF, between the PIH and NC groups (
P
> 0.05), while 29 cytokines were significantly lower in the PIH group than in the NC group (
P
< 0.05). Logistic regression analysis revealed that 17 cytokines (IL-2Rα, M-CSF, IL-6, IL-2, β-NGF, IL-7, IL-12 (p70), SCF, IL-10, IL-9, MIG, GM-CSF, LIF, IL-1α, MCP-3, IL-4, and HGF) in the first-trimester pregnancy serum were significantly negatively correlated with the subsequent onset of PIH. With the top 3 cytokines (IL-7, MIG, and SCF) of receiver operating characteristic (ROC) analysis, we constructed an efficient multifactor combined detection and prediction model for PIH in ART pregnancy. Classical early predictors for hypertensive disorder complicating pregnancy cannot distinguish PIH from their normal peers in ART pregnancy. In comparison, the description of the cytokine profile in the first trimester of pregnancy enables us to distinguish high-risk ART pregnancy for PIH, permitting enough time for PIH prevention therapy. The cytokine profile we described also provides immunological insight into the further mechanistic exploration of PIH.
Abstract
Background
Chromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate ...whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion.
Methods
A total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed.
Results
There were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%,
P
= 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%,
P
= 0.256).
Conclusions
Due to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.
The aim of the retrospective cohort study was to investigate the prognostic effect of subchorionic hematomas (SCH) in the first trimester on pregnancy outcomes after euploid embryo transfer.
We ...retrospectively analyzed women achieving singleton pregnancy by PGT-A or PGT-SR from January 2017 to January 2022. Patients were enrolled in the study if they had a viable intrauterine pregnancy at ultrasound between 6 0/7 and 8 0/7 weeks of gestation. Pregnancy outcomes as well as the incidence of maternal complications were compared between patients with and without SCH. Logistic regression was used for adjusting for potential confounding factors.
A total of 1539 women were included, of which 298 with SCH and 1241 with non-SCH. The early miscarriage rate in SCH group was significantly higher than that in the non-SCH group (10.1% vs. 5.6%, adjusted odds ratio aOR 1.99, 95% confidence interval CI 1.25-3.16, P = 0.003). The live birth rate in SCH group was significantly lower than that in the non-SCH group. (85.6% vs. 91.2%, aOR 0.57, 95% CI 0.39-0.84, P = 0.005). In addition, SCH group had an increased risk of hypertensive disorder of pregnancy (HDP) (8.9% vs. 5.2%, P = 0.022), especially in hematoma with bleeding (19.3% vs. 6.0%, P = 0.002). The incidence of gestational diabetes mellitus (GDM), major congenital abnormalities rate, normal birth weight rate and low birth weight rate were similar between the two groups.
The presence of SCH in the first trimester was associated with worse pregnancy outcomes after euploid embryo transfer, including an increased risk of early miscarriage and hypertensive disorder of pregnancy, along with a reduced live birth rate.
The mechanism of brain injury following subarachnoid hemorrhage (SAH) has not yet been clarified. The glymphatic system (GS), a glia-dependent waste clearance pathway, drains away soluble waste ...proteins and metabolic products, even some toxic factors from the brain. Aquaporin-4 (Aqp4) is highly expressed on the astrocyte foot processes and facilitates the interstitial fluid (ISF) transportation in the GS system. In this study, the role of Aqp4 in the GS injury after SAH was explored using Aqp4 gene knockout (Aqp4
) Sprague Dawley rats. The results of MRI, fluorescent imaging, and transmission electron microscopy (TEM) indicated that, after SAH, the inflow of cerebrospinal fluid (CSF) into the brain and the clearance of ISF from the brain were both significantly decreased. Meanwhile, the expression level of Aqp4 around the artery was markedly higher than that around the vein following SAH. Aqp4 knockout exacerbated the GS damage after SAH. In summary, after SAH, there was an apparent GS impairment, and Aqp4 played key roles in modulating the function of GS in the brain.
Abstract
Background
Recurrent implantation failure (RIF) brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a ...promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF. But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome.
Methods/design
This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial (1:1 ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) or pre-implantation genetic testing for aneuploidy (PGT-A) will be enrolled and randomly assigned to two parallel groups. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant. The primary outcome is live birth rate.
Discussion
The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF.
Trial registration
Chinese Clinical Trial Registry,
ChiCTR1800018783
. Registered on 9 October 2018.
Serum cytokine profile and T helper (Th)1/Th2 cell balance are related to the success of embryo implantation, although not yet firmly linked to recurrent implantation failure (RIF), a repeated ...failure to achieve clinical pregnancy following multiple high-quality embryo transfer. In this prospective study, comprehensive bioinfomatic analysis and logistic regression analysis were used to compare the serum cytokine profiles of 41 RIF patients with those of 29 subjects with first-cycle successful pregnancy in the mid-luteal phase and to assess the alterations of cytokine profiles in patients with clinical pregnancy at five weeks post-transplantation. We found several elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, and increased Th1/Th2 cytokine ratios in RIF patients compared to control subjects. Specifically, the receiver operating characteristic (ROC) curve generated using multiple indicators provides a high predictive value for diagnosing RIF (area under the curve AUC = 0.94, 95% confidence interval CI 0.87-1.00,
P
< 0.0001), with a sensitivity of 96.55% and a specificity of 87.50%. Meanwhile, at five weeks post-transplantation, patients in both groups diagnosed with clinical pregnancy exhibited increased levels of several cytokines compared with pre-pregnancy levels, and a gradual shift in Th1/Th2 balance toward Th2. These findings suggest that inflammatory serum cytokines and the predominance of Th1 cells likely contribute to RIF and possibly reflect the immune environment at the maternal-fetal interface, suggesting their value as outcome indicators in assisted reproductive therapy.
BACKGROUND
Although uterine fibroids have been associated with spontaneous miscarriage, to our knowledge there have been no studies in the literature assessing their role in the recurrent miscarriage ...(RM) population. The aims of this study are to examine the impact of different types of fibroids on the pregnancy outcome of women with RM and to investigate to what extent resection of fibroids distorting the uterine cavity affects the outcome of a future pregnancy.
METHODS
The study analysed retrospective and prospective data from a large tertiary referral RM clinic. Couples were investigated as per an established protocol. Fibroids were diagnosed using combined transvaginal ultrasound and hysterosalpingography. Fibroids distorting the uterine cavity were resected via hysteroscopy. Two study groups were subsequently examined: women with cavity-distorting fibroids who underwent surgery (n =25) and women with fibroids not distorting the cavity who did not undergo any intervention (n =54). The latter was compared with a control group of women with unexplained RM (n =285).
RESULTS
The prevalence of fibroids was found to be 8.2% (79/966). In total, 264 pregnancies of women with fibroids and 936 pregnancies of women with unexplained RM were analysed. Women with intracavitary distortion and undergoing myomectomy significantly reduced their mid-trimester miscarriage rates in subsequent pregnancies from 21.7 to 0% (P< 0.01). This translated to an increase in the live birth rate from 23.3 to 52.0% (P< 0.05). Women with fibroids not distorting the cavity behaved similarly to women with unexplained RM achieving a 70.4% live birth rate in their subsequent pregnancies without any intervention.
CONCLUSIONS
Fibroids are associated with increased mid-trimester losses amongst women with RM. Resection of fibroids distorting the uterine cavity can eliminate the mid-trimester losses and double the live birth rate in subsequent pregnancies. Women with fibroids not distorting the uterine cavity can achieve high live birth rates without intervention.
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