Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

Outcomes of fetal reduction versus expectant management in dichorionic triamniotic triplets.

OBJECTIVE: To compare the outcomes of dichorionic triamniotic (DCTA) triplets who underwent fetal reduction (FR) to singletons or twins with those managed expectantly. METHODS: We conducted a retrospective study of DCTA triplets with three living fetuses at 11-14 weeks over a 7-year period. Pregnancy outcomes were compared following different management strategies. RESULTS: Of 108 included patients, 22 underwent expectant management (EM), 28 were reduced to dichorionic diamniotic twins, and 58 to singletons. The median gestational age at birth for EM, FR to twins, and singletons was 33.1 weeks, 37.0 weeks, and 38.6 weeks, respectively (P < 0.001). Prematurity before 37 and 34 weeks was less common following FR to singletons and twins than in ongoing triplets (18.9%, 46.2% and 90.5%, P < 0.001; 13.2%, 26.9% and 57.1%, P < 0.001). Neonatal birth weight was higher in triplets reduced to singletons and twins compared with EM cases (3140g, 2315g, and 1860g, P < 0.001). However, rates of miscarriage, pregnancies with ≥1 survivor, maternal complications, and adverse neonatal outcomes were comparable among the three groups. CONCLUSIONS: In our experience, FR in DCTA triplets could reduce prematurity risk compared to EM, but it confers no survival advantage. Fetal reduction to singletons may result in more favorable outcomes than those reduced to dichorionic twins.

Outcome of monochorionic triamniotic triplet pregnancies: Expectant management versus fetal reduction.

OBJECTIVE: To compare the outcomes of monochorionic triamniotic (MCTA) triplets managed expectantly with those reduced to twins. METHOD: This was a retrospective cohort study comparing expectant management (EM) with fetal reduction (FR) to twins in 43 consecutive MCTA triplets with 3 live fetuses at 11-14 weeks between 2012 and 2021. RESULTS: Nineteen patients managed expectantly and 24 triplets reduced to twins were included. The rate of pregnancy with at least one survivor was 84.2% in the EM group and 66.7% in the FR group (P = 0.190). Compared to the EM cases, triplets reduced to twins had a higher median gestational age at delivery (36.0 vs. 33.3 weeks; P < 0.001), a higher mean birth weight (2244.3 ± 488.6 g vs. 1751.1 ± 383.2 g; P < 0.001) and a lower risk of preterm birth before 34 weeks (11.8% vs. 64.7%; P = 0.001). There were no significant differences in the risk of miscarriage, pregnancy complications and composite adverse neonatal outcomes. CONCLUSION: In MCTA triplets, FR to twins could reduce the risk of preterm birth, whereas EM seems to be a reasonable choice when the priority is at least one survivor. However, due to the small sample size of this study, these findings must be interpreted with great caution.

Transgelin 2 is required for embryo implantation by promoting actin polymerization.

Infertility has been a great challenge in reproductive medicine. At least 40% of human pregnancy losses are clinically unrecognized and occur because of embryo implantation failure. Identification of the proteins and biochemical factors involved in embryo implantation and that are essential for crosstalk between the embryo and uterus can further increase female fertility rates. The actin cytoskeleton and actin-binding proteins (ABPs) are of great importance for cell morphology and rearrangement, which is crucial for trophoblast adhesion and invasion. However, the research on ABPs in embryo implantation is insufficient. In this report, we found that transgelin (TAGLN)2 is highly expressed in mouse blastocyst trophoblasts. Notably, inhibition of mouse blastocyst trophoblast TAGLN2 by lentivirus-mediated RNA interference significantly impaired embryo adhesion and implantation ability. Further in vitro experiments demonstrated that TAGLN2 knockdown with small interfering RNA observably decreased the invasion and migration abilities of human trophoblast cells. Immunofluorescence colocalization and microscale thermophoresis analysis showed that TAGLN2 directly binds to actin. In addition, knockdown of TAGLN2 in trophoblast cells resulted in a remarkable reduction in F-actin rather than G-actin. Our findings reveal an unidentified role of TAGLN2 in regulation of trophoblast invasion and adhesion by promoting actin polymerization.-Liang, X., Jin, Y., Wang, H., Meng, X., Tan, Z., Huang, T., Fan, S. Transgelin 2 is required for embryo implantation by promoting actin polymerization.

Forty-five consecutive cases of complicated monochorionic multiple pregnancy treated with microwave ablation: A single-center experience.

OBJECTIVE: To describe our preliminary experience in the application of microwave ablation for selective fetal reduction in complicated monochorionic multiple pregnancies. METHODS: In this prospective study, 45 consecutive complicated monochorionic multiple pregnancies that underwent microwave ablation for selective fetal reduction from July 2015 to February 2017 were analyzed from the first case onward. All patients were managed at the Peking University Third Hospital in Beijing, China. RESULTS: There were 45 cases (twins in 40 and triplets in five) treated by microwave ablation. The median gestational age at surgery was 21.3 weeks (range, 15.9-25.7 wk), with a mean total ablation time of 8.5 ± 4.2 (7.2-9.7) minutes. There were 12 (26.7%) cases of postprocedural fetal loss. Thirty-three women delivered alive at a median gestational age of 37.6 weeks (range, 28.6-40.4 wk). There were no neonatal deaths in our cohort, and the overall survival rate was 73.3% (33/45). Preterm premature rupture of membranes occurred in 9 (20.0%) cases with a median of 7.0 weeks (range, 0.9-16.3 wk) after the surgery. None of the surviving cotwins had evidence of thermal injury or neurological abnormalities. CONCLUSION: Microwave ablation appears to be a safe and effective method for selective feticide in complicated monochorionic pregnancies.

The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction.

In perinatal medicine, intrauterine growth restriction (IUGR) is one of the greatest challenges. The etiology of IUGR is multifactorial, but most cases are thought to arise from placental insufficiency. However, identifying the placental cause of IUGR can be difficult due to numerous confounding factors. Selective IUGR (sIUGR) would be a good model to investigate how impaired placentation affects fetal development, as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors. Herein, we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins. Specifically, we identified a total of 5481 proteins, of which 233 were differentially expressed (57 up-regulated and 176 down-regulated) in IUGR twins. Bioinformatics analysis indicates that these differentially expressed proteins (DEPs) are mainly associated with cardiovascular system development and function, organismal survival, and organismal development. Notably, 34 DEPs are significantly enriched in angiogenesis, and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed. Moreover, we found decreased expression of metadherin (MTDH) in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro. Collectively, our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins, and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.

Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2.

Originally discovered in the circulation of pregnant women as a protein secreted by placental trophoblasts, the metalloprotease pregnancy-associated plasma protein A (PAPP-A) is also widely expressed by many other tissues. It cleaves insulin-like growth factor-binding proteins (IGFBPs) to increase the bioavailability of IGFs and plays essential roles in multiple growth-promoting processes. While the vast majority of the circulatory PAPP-A in pregnancy is proteolytically inactive due to covalent inhibition by proform of eosinophil major basic protein (proMBP), the activity of PAPP-A can also be covalently inhibited by another less characterized modulator, stanniocalcin-2 (STC2). However, the structural basis of PAPP-A proteolysis and the mechanistic differences between these two modulators are poorly understood. Here we present two cryo-EM structures of endogenous purified PAPP-A in complex with either proMBP or STC2. Both modulators form 2:2 heterotetramer with PAPP-A and establish extensive interactions with multiple domains of PAPP-A that are distal to the catalytic cleft. This exosite-binding property results in a steric hindrance to prevent the binding and cleavage of IGFBPs, while the IGFBP linker region-derived peptides harboring the cleavage sites are no longer sensitive to the modulator treatment. Functional investigation into proMBP-mediated PAPP-A regulation in selective intrauterine growth restriction (sIUGR) pregnancy elucidates that PAPP-A and proMBP collaboratively regulate extravillous trophoblast invasion and the consequent fetal growth. Collectively, our work reveals a novel covalent exosite-competitive inhibition mechanism of PAPP-A and its regulatory effect on placental function.