Clinical evaluation of the effect for prophylactic balloon occlusion in pregnancies complicated with placenta accreta spectrum disorder: A systematic review and meta-analysis.

BACKGROUND: Placenta accreta spectrum (PAS) disorder is a critical and severe obstetric condition associated with high risk of intraoperative massive hemorrhage and cesarean hysterectomy. Severe obstetric hemorrhage is currently one of the leading causes of maternal death worldwide. Prophylactic balloon occlusions, including prophylactic balloon occlusion of the abdominal aorta (PBOAA) and prophylactic balloon occlusion of the internal iliac arteries (PBOIIA), are the most common means of controlling hemorrhage in patients with PAS disorder, but their effectiveness is still debated. OBJECTIVE: A systematic review and meta-analysis were conducted to evaluate the clinical effectiveness of prophylactic balloon occlusion during cesarean section (CS) in improving maternal outcomes for PAS patients. SEARCH STRATEGY: MEDLINE, EMBASE, OVID, PubMed and the Cochrane Library were systematically searched from the inception dates to June 2022, using the keywords "placenta accreta spectrum disorder/morbidly adherent placenta (placenta previa, placenta accreta, placenta increta, placenta percreta), balloon occlusion, internal iliac arteries, abdominal aorta, hemorrhage, hysterectomy, estimated blood loss (EBL), packed red blood cells (PRBCs)" to identify the systematic reviews or meta-analyses. SELECTION CRITERIA: All articles regarding PAS disorders and including the application of balloon occlusion were included in the screening. DATA COLLECTION AND ANALYSIS: Two independent researchers performed the data extraction and assessed study quality. EBL volume and PRBC transfusion volume was regarded as the primary endpoints. Random and fixed effects models were used for the meta-analysis (RRs and 95% CIs), and the Newcastle-Ottawa Scale was used for quality assessments. MAIN RESULTS: Of 429 studies identified, a total of 35 trials involving the application of balloon occlusion for patients with PAS disorder during CS were included. A total of 19 studies involving 935 patients who underwent PBOIIA were included in the PBOIIA group, and 851 patients were included in control 1 group. Ten studies including 428 patients with PAS who underwent PBOAA were allocated to the PBOAA group, and 324 patients without PBOAA were included in control 2 group. Simultaneously, we compared the effect on PBOAA and PBOIIA including seven studies, which referred to 267 cases in the PBOAA group and 313 cases in the PBOIIA group. The results showed that the PBOIIA group had a reduced EBL volume (MD: 342.06 mL, 95% CI: -509.90 to -174.23 mL, I2 = 77%, P < 0.0001) and PRBC volume (MD: -1.57 U, 95% CI: -2.49 to -0.66 U, I2 = 91%, P = 0.0008) than that in control 1 group. With regard to the EBL volume (MD: -926.42 mL, 95% CI: -1437.07 to -415.77 mL, I2 = 96%, P = 0.0004) and PRBC transfusion volume (MD: -2.42 U, 95% CI: -4.25 to -0.59 U, I2 = 99%, P = 0.009) we found significant differences between the PBOAA group and control 2 group. Prophylactic balloon occlusion (PBOAA and PBOIIA) had a significant effect on reducing intraoperative blood loss and blood transfusion volume in patients with PAS. Moreover, PBOAA was more effective than PBOIIA in reducing intraoperative blood loss (MD: -406.63 mL, 95% CI: -754.12 to -59.13 mL, I2 = 92%, P = 0.020), but no significant difference in controlling PRBCs (MD: -3.48 U, 95% CI: -8.90 to 1.95 U, I2 = 99%, P = 0.210) between the PBOIIA group and the PBOAA group. Hierarchical analysis was conducted by differentiating gestational weeks and maternal age to reduce the high heterogeneity of meta-analysis. Hierarchical analysis results demonstrated the heterogeneities of the study were reduced to some extent, and gestational weeks and maternal age might be the cause of increased heterogeneity. CONCLUSION: Prophylactic balloon occlusion is a safe and effective method to control hemorrhage and reduce PRBC transfusion volume for patients with PAS, and PBOAA could reduce more intraoperative blood loss than PBOIIA. However, we found no statistical difference in lessening packed red blood cell transfusion volume for PAS patients. Hence, preoperative prophylactic balloon occlusion is the recommended application for PAS patients in obstetric CSs. Furthermore, PBOAA is preferred for controlling intraoperative bleeding in patients with corresponding medical conditions.

Risk-stratified management strategies for intrahepatic cholestasis of pregnancy: A tertiary center population review over nearly 5 years.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes, resulting in a higher risk of perinatal morbidity and mortality. METHODS: The authors conducted a retrospective study of 2385 singletons with ICP who underwent risk-stratified management strategies. To explore the risks of perinatal outcomes of ICP, subgroup analyses were performed using different total bile acid (TBA) levels. RESULTS: In this study, there was only one stillbirth and one neonatal death. Among the study cohort, 2299 patients had ICP with a TBA level ≥10 µmol/L and 86 had ICP with a TBA level <10 µmol/L. The 2299 patients with ICP (TBA level ≥ 10 µmol/L) were divided into three groups: mild ICP (n = 1803), severe ICP (n = 400), and extremely severe ICP (n = 96). Increased TBA concentration was associated with an increased incidence of preterm birth, newborn asphyxia, neonatal intensive care unit hospitalization, meconium-stained amniotic fluid, and low birth weight in the three groups (P < 0.05). Furthermore, severe and extremely severe ICP with hypotonic absonant uterine contraction had a significant effect on neonatal asphyxia (odds ratio, 5.06 [95% confidence interval, 1.09-23.37]; P < 0.05) and meconium-stained amniotic fluid (odds ratio, 2.37 [95% confidence interval, 1.43-3.93]; P < 0.05). CONCLUSIONS: Hypotonic absonant uterine contractions could be high-risk stressors for severe and extremely severe ICP; hence, proper prenatal care is recommended. Risk-stratified management strategies for ICP are critical to obtaining better maternal-fetal outcomes.

Stress regulation of WFS1 and PERK-p-eIF2α-ATF4 signaling pathway in placental tissue cells of intrahepatic cholestasis of pregnancy.

INTRODUCTION: The placental tissue stress of intrahepatic cholestasis of pregnancy (ICP) is activated by ERS under hypoxia condition. PERK signaling pathway is the key pathway for UPR regulation, and is first to activated during ERS. WFS1, as an important regulatory gene of UPR pathway, participates in ERS regulation. The purpose of our study is to explore the expression level and mutual regulation mechanisms of WFS1 and PERK-mediated UPR pathway in ICP placental tissue cell under stress. METHODS: Blood and placenta samples were obtained from the ICP patients and ethinylestradiol (EE)-induced intrahepatic cholestasis pregnant rats. IHC and WB were used to detect the expression of WFS1, key factors of PERK pathway (GRP78, PERK, eIF2a, P-eIF2α, ATF4) and placental stress peptides (CRH, UCN). Furthermore, qPCR was carried out to detect mRNA expression of above indicators. RESULTS: The expression levels of WFS1 and key factors of PERK pathway were significantly increased in severe ICP placental tissues. Moreover, qPCR and WB showed that relative mRNA and protein expression levels of WFS1 and key factors of PERK pathways in placenta tissues of severe ICP and EE-induced intrahepatic cholestasis pregnant rats were higher than those in control group to varying degrees, while CRH and UCN were descended. Meanwhile, after WFS1-siRNA targeted silencing of the WFS1 gene, the protein expression levels of PERK, P-eIF2α, ATF4 were significantly increased, while CRH and UCN protein were significantly decreased. DISCUSSION: Our study revealed that the activation of WFS1 and PERK-p-eIF2α-ATF4 signaling pathway may contribute to stress regulation in placental tissue cells of intrahepatic cholestasis of pregnancy, thereby avoiding adverse pregnancy outcomes.

The spatial expression of mTORC2-AKT-IP3R signal pathway in mitochondrial combination of endoplasmic reticulum of maternal fetal interface trophoblast in intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) is complicated by adverse fetal outcomes and even fetal death, the mechanism remains unclear. This study aims at evaluating the differential expression of mTORC2-AKT-IP3R signaling pathway, which accurately regulate Ca2+ transfer across mitochondria-associated membranes (MAMs) and determine the stress intensity experienced by endoplasmic reticulum (ER) and mitochondria, in patients diagnosed with ICP. METHODS: We combined western blot analysis and placental immunofluorescence co-localization detection to assess the expression and co-localization of the mTORC2-AKT-IP3R signaling pathway in severe (maternal total bile acid (TBA) levels ≥40 µmol/L) and mild (maternal TBA 10-40 µmol/L) ICP. RESULTS: Compared with the control and mild ICP groups, phosphorylated protein kinase B (p-AKT) levels were significantly upregulated in the severe ICP group. Placental Rictor levels were lower in the mild ICP group than in the control group and were further downregulated in the severe ICP group. IP3R3 and p-IP3R3 levels were lower in placentas in the severe ICP group than in those in the mild ICP and control groups. Moreover, the co-localization of IP3R3 and p-AKT in patients in the mild and severe ICP groups was significantly elevated compared with that in patients in the control group. CONCLUSIONS: In patients with severe ICP, limited expression of Rictor and elevated p-AKT levels would suppress IP3R3/p-IP3R3 levels in MAMs. This inhibition might influence the transportation of Ca2+ from the ER to the mitochondria, thus weaken the stress adaptation associated with MAMs. Our results reveal the possible pathophysiological mechanism of adverse fetal outcomes in ICP.

Unique microRNA expression profiles in plasmic exosomes from intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is strongly associated with an increased risk of adverse perinatal outcomes. Total bile acid (TBA) levels in the late second or third trimester are a major factor in the diagnosis. Here, we sought to establish the miRNA expression profile of plasm exosomes of ICP and identify possible biomarkers for the diagnosis of ICP. METHODS: This case-control study involved 14 ICP patients as the experimental group and 14 healthy pregnant women as the control group. Electron microscopy was used to observe the presence of exosomes in plasma. Nanosight and Western blotting of CD63 was used to assess exosome quality. Among them, three ICP patients and three controls were used for isolation plasmic exosome and preliminary miRNA array analysis. The Agilent miRNA array was utilized to dynamically monitor the miRNA expression in plasmic exosomes of included patients in the first trimester(T1), second trimester (T2), third trimester (T3), and delivery (T4). Then, Quantitative real-time Polymerase chain reaction was used to identify and validate differentially expressed miRNAs in plasma-derived exosomes. RESULTS: The expression levels of hsa-miR-940, hsa-miR-636, and hsa-miR-767-3p in plasma-derived exosomes of ICP patients were significantly higher than those of healthy pregnant women. Besides, these three miRNAs were also significantly up-regulated at the plasma, placental, and cellular levels (P < 0.05). The diagnostic accuracy of hsa-miR-940, hsa-miR-636, and hsa-miR-767-3p was further evaluated by the ROC curve, the area under the curve (AUC) values for each were 0.7591, 0.7727, and 0.8955, respectively. CONCLUSIONS: We identified three differentially expressed miRNAs in the plasma exosomes of ICP patients. Hence, hsa-miR-940, hsa-miR-636, and hsa-miR-767-3p may be potential biomarkers for enhancing the diagnosis and prognosis of ICP.

Antiphospholipid Antibodies Increase the Risk of Fetal Growth Restriction: A Systematic Meta-Analysis.

Objective: Antiphospholipid syndrome (APS) is a chronic autoimmune disease with a high prevalence in females. Published data have identified pregnant women with APS may suffer from recurrent miscarriage, fetal death. However, the association between antiphospholipid antibody (aPL) and fetal growth restriction (FGR) remains controversial. This study aims to systematically review the literature on population-based studies investigating an association between aPL and FGR. Methods: The literature was searched on 1 November, 2021, using Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), following the MOOSE checklist. Study inclusion criteria focused on peer-reviewed published articles that reported an association between aPL and FGR. Quality assessment was performed based on the Newcastle-Ottawa scale. The between-study heterogeneity was assessed by the Q test. Publication bias was assessed by funnel plots. Results: Twenty-two studies (with 11745 pregnant women) were included in the final analysis. Pooled odds ratio for association of aPL, anticardiolipin antibodies (ACA), anti-beta2 glycoprotein 1 antibodies (ß2GP1), and FGR was 1.26 (95%CI 1.12, 1.40), 2.25 (95%CI 1.55, 2.94), and 1.31 (95% CI 1.12, 1.49), respectively. Lupus anticoagulant (LA) did not increase the chance of FGR (OR 0.82, 95%CI 0.54, 1.10). Conclusions: Our meta-analysis showed that aPL increased the risk of FGR. The risk of FGR varies with the aPL types. ACA and ß2GP1 are strongly associated with FGR. There are currently insufficient data to support a significant relationship between LA and FGR.

Identification of a heterozygous variant of ZP2 as a novel cause of empty follicle syndrome in humans and mice.

STUDY QUESTION: Is a recurrent heterozygous mutation in ZP2, c.1925G>A (p.R642Q), associated with the Empty follicle syndrome (EFS)? SUMMARY ANSWER: ZP2, c.1925G>A (p.R642Q), led to female infertility related to EFS in humans and mice and resulted in ZP2 accumulation in the cytoplasm of oocytes. WHAT IS KNOWN ALREADY: EFS is a complex disease defined as a complete failure of oocyte retrieval after ovarian stimulation and after repeated aspirations and flushing of mature ovarian follicles. Furin-mediated cleavage is a post-translational modification (PTM) involved in various physiological processes, but the clear role of PTM mediated by furin cleavage of ZP2 protein on female fertility needs to be further explored. PTM is required for proteins to function in physiological conditions, and its perturbation has been linked to a growing number of human pathologies. Zona pellucida (ZP) proteins, which are important for oocyte development, are regulated post-translationally by well-characterized glycosylation events, as well as by furin-mediated cleavage. However, knowledge of the relevance of the consensus furin cleavage site of ZP proteins in female reproduction remains lacking. STUDY DESIGN, SIZE, DURATION: This was a basic medical research project to assess the pathogenicity of a heterozygous mutation in the ZP2 gene in EFS. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 3 families with EFS and a control group 2213 women with proven fertility. Whole-exome sequencing detected a heterozygous mutation in the ZP2 gene in all EFS patients. The mouse strain Zp2Arg635Gln/+ (ZP2R642Q) was generated by CRISPR-Cas9-mediated genome editing. RNA-sequencing was applied to investigate transcriptional changes in the ovaries of heterozygous ZP2R642Q knock-in (KI) mice compared to WT mice. MAIN RESULTS AND THE ROLE OF CHANCE: We found a heterozygous mutation of ZP2, c.1925G>A (p.R642Q), in unrelated females with EFS, which was inherited in an autosomal-dominant manner. We used CRISPR-Cas9 to generate a mouse model encoding the orthologous variant of ZP2R642Q detected in humans, and the female ZP2R642Q KI mice recapitulated the human EFS phenotype. We further found the decreased expression of key genes involved in oocyte maturation in ZP2R642Q KI mice compared to WT mice by RNA-sequencing analysis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Only three families affected by EFS with the mutation were available because of its rare incidence. Although we have found different expressions of the several indispensable genes related to oocyte development between WT mice and ZP2R642Q KI mice through RNA-sequencing analysis, the specific regulatory mechanisms of the oocyte apoptosis in ZP2R642Q KI mice need to be studied further. WIDER IMPLICATIONS OF THE FINDINGS: These results are expected to open new avenues for researchers in the exploration of potential therapeutic strategies in treating EFS. STUDY FUNDING/COMPETING INTEREST(S): This project is funded by the National Key Research and Development Program of China (2018YFC1002804, 2017YFC1001500 and 2016YFC1000200). All authors declared no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Whole-exome sequencing of a cohort of infertile men reveals novel causative genes in teratozoospermia that are chiefly related to sperm head defects.

STUDY QUESTION: Can whole-exome sequencing (WES) and in vitro validation studies identify new causative genes associated with teratozoospermia, particularly for sperm head defect? SUMMARY ANSWER: We investigated a core group of infertile patients, including 82 cases with unexplained abnormal sperm head and 67 individuals with multiple morphological abnormalities of the sperm flagella (MMAF), and revealed rare and novel deleterious gene variants correlated with morphological abnormalities of the sperm head or tail defects. WHAT IS KNOWN ALREADY: Teratozoospermia is one of the most common factors causing male infertility. Owing to high phenotypic variability, currently known genetic causes of teratozoospermia can only explain a rather minor component for patients with anomalous sperm-head shapes, and the agents responsible for atypical sperm head shapes remain largely unknown. STUDY DESIGN, SIZE, DURATION: We executed WES analysis of a Chinese cohort of patients (N = 149) with teratozoospermia to identify novel genetic causes particularly for defective sperm head. We also sought to reveal the influence of different abnormalities of sperm morphology on ICSI outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS: In this study, a cohort of 149 infertile men (82 with abnormal sperm head and 67 with MMAF) were recruited. We implemented WES on infertile patients and analyzed the negative effects of the mutations of candidate genes on their protein conformations and/or expression. We also investigated the candidate genes' spatiotemporal expression/localization during spermatogenesis in both humans and mice, and explored their interactions with proteins that are known to be involved in sperm development. We also compared the ICSI outcomes of the affected individuals with various aberrations in sperm morphology. MAIN RESULTS AND THE ROLE OF CHANCE: We identified rare and deleterious variants of piwi like RNA-mediated gene silencing 4 (PIWIL4: 1/82 patients, 1.21%), coiled-coil and C2 domain containing 1B (CC2D1B: 1/82 patients, 1.21%), cyclin B3 (CCNB3: 1/82 patients, 1.21%), KIAA1210 (KIAA1210: 2/82 patients, 2.43%) and choline phosphotransferase 1 (CHPT1: 1/82 patients, 1.21%), which are novel correlates of morphological abnormalities of the sperm head; functional evidence supports roles for all of these genes in sperm head formation. The mutations of septin 12 (SEPTIN12: 2/82 patients, 2.43%) are suggested to be associated with acrosome defects. We additionally observed novel causative mutations of dynein axonemal heavy chain 2 (DNAH2: 1/67 patients, 1.49%), dynein axonemal heavy chain 10 (DNAH10: 1/67 patients, 1.49%) and dynein axonemal heavy chain 12 (DNAH12: 1/67 patients, 1.49%) in patients with MMAF, and revealed a significantly lower fertilization rate of the abnormal sperm-head group compared to the MMAF group following ICSI. Consequently, our study also suggests that the mutations of PIWIL4 and CC2D1B might be circumvented by ICSI to a degree, and that CHPT1 and KIAA1210 loss-of-function variants might be associated with failed ICSI treatment. LIMITATIONS, REASONS FOR CAUTION: In this study, we discovered the relationship between the genotype and phenotype of the novel causative genes of sperm head deformities in humans. However, the molecular mechanism of the relevant genes involved in sperm head development needs to be further illuminated in future research. Furthermore, evidence should be provided using knockout/knock-in mouse models for additional confirmation of the roles of these novel genes in spermatogenesis. WIDER IMPLICATIONS OF THE FINDINGS: This cohort study of 149 Chinese infertile men documents novel genetic factors involved in teratozoospermia, particularly in anomalous sperm head formation. For the first time, we suggest that SEPTIN12 is related to human acrosomal hypoplasia, and that CCNB3 is a novel causative gene for globozoospermia in humans. We also uncovered variants in two genes-KIAA1210 and CHPT1associated with acrosomal biogenesis in patients with small or absent acrosomes. Additionally, it is postulated that loss-of-function mutations of PIWIL4 and CC2D1B have a contribution to the abnormal sperm-head formation. Furthermore, we are first to demonstrate the influence of different sperm morphologies on ICSI outcomes and indicates that the abnormal sperm head may play a significant role in fertilization failure. Our findings therefore provide valuable information for the diagnosis of teratozoospermia, particularly with respect to abnormalities of the sperm head. This will allow clinicians to adopt the optimal treatment strategy and to develop personalized medicine directly targeting these effects. STUDY FUNDING/COMPETING INTEREST(S): This work was financed by the West China Second University Hospital of Sichuan University (KS369 and KL042). The authors declare that they do not have any conflicts of interests. TRIAL REGISTRATION NUMBER: N/A.

A novel CCDC39 mutation causes multiple morphological abnormalities of the flagella in a primary ciliary dyskinesia patient.

RESEARCH QUESTION: Male infertility is a widespread symptom in patients with primary ciliary dyskinesia (PCD). PCD-related male infertility is often caused by asthenozoospermia, with barely normal sperm morphology. Multiple morphological abnormalities of the sperm flagella (MMAF) are a major cause of asthenozoospermia, characterized by various malformed morphologies of sperm flagella. To date, a limited number of genes have been suggested to be involved in the pathogenesis of both PCD and MMAF. What other genes associated with both PCD and MMAF are waiting to be discovered? DESIGN: Whole-exome sequencing (WES) was performed to identify the pathogenic mutation associated with MMAF in a PCD patient. Peripheral venous blood and semen samples were collected from the PCD patient. Transmission electron microscopy (TEM), immunofluorescence staining and western blotting were conducted to confirm the pathogenicity of the identified mutation. RESULTS: A novel homozygous mutation in CCDC39, c.983 T>C (p. Leu328Pro), was identified in two PCD-affected siblings of a consanguineous family showing a typical PCD phenotype, while the proband was infertile, which is associated with characterized MMAF. Furthermore, TEM revealed the abnormal ultrastructure of the patient's sperm flagella. Moreover, immunofluorescence staining revealed that CCDC39 was almost undetectable in the spermatozoa, which was further confirmed by western blotting. The outcome of intracytoplasmic sperm injection (ICSI) in the patient with the CCDC39 mutation was also favourable. CONCLUSION: This study demonstrates that a novel loss-of-function mutation of CCDC39 is involved in the pathogenesis of PCD and MMAF and initially reported that ICSI treatment has a good outcome. Therefore, the novel variant of CCDC39 contributes to the genetic diagnosis, counselling and treatment of male infertility in PCD patients with MMAF phenotype.

Effect of prophylactic balloon occlusion of internal iliac artery in pregnancies complicated by placenta previa and accreta.

BACKGROUND: Placenta previa and accreta are serious obstetric conditions that are associated with a high risk of intraoperative massive hemorrhage, the prophylactic intravascular balloon occlusion technique is increasingly used in managing uncontrolled hemorrhage in cesarean section (CS). We aim to examine the clinical effectiveness of prophylactic balloon occlusion of the internal iliac artery (PBOIIA) during CS in improving maternal outcomes for patients with placenta previa and accreta. METHODS: A total of 420 women with placenta previa and accreta who underwent CS from January 2014 to December 2018 were included retrospectively. Patients were divided into balloon group in which patients had PBOIIA (n = 248) and the control group in which patients did not have PBOIIA (n = 172). Meanwhile, we performed a subgroup analysis in whether taking parallel transverse uterine incision (PTUI) surgery. Information on conditions of patients and newborns, perioperative blood indicators, surgical outcomes were collected. RESULTS: Median estimated blood loss (mEBL) was 2200 mL in the balloon group and 2150 mL in the control group respectively, there was no significant difference between two-groups comparison (P > 0.05), and the rate of patients with hysterectomy was also has no difference between the two groups (36.3% verus 35.5%, P > 0.05), while there is a significant difference between two groups in the amount of PRBCs transfused [3 (0-31.5) verus 3 (0-39), P <0.05], moreover, the proportion of PRBCS> 8 units in the balloon group is significantly lower than that in control group (11.29% verus 23.26%, P <0.05).. However, the total hospitalization costs (45,624.4 ± 11,061.9 verus 37,523.1 ± 14,662.2, CYN) and surgery costs (19,910.6 ± 2622.6 verus 11,850.5 ± 3146.1, CYN) in balloon group were significantly higher than those in control group (P < 0.05). Subgroup analysis showed PTUI surgery had no significant differences in EBL (P >0.05), but it could significantly decrease hysterectomy rates (P <0.05). CONCLUSIONS: PBOIIA has no significant effect on reducing intraoperative EBL and hysterectomy rate in patients with placenta previa and accreta. and although it could reduce the intraoperative PRBCs in patients with massive hemorrhage, it significantly increases the financial cost for patients. Therefore, PBOIIA should not be routinely recommended to patients with placenta previa and accreta.

A novel mutation in DNAH17 is present in a patient with multiple morphological abnormalities of the flagella.

RESEARCH QUESTION: Asthenoteratospermia is characterized by malformed spermatozoa with motility defects, which results in male infertility. Multiple morphological abnormalities of the sperm flagella (MMAF) is a hallmark of asthenoteratospermia. The genetic causes of MMAF, however, are unknown in about one-third of cases. Which other MMAF-associated genes are waiting to be discovered? DESIGN: Whole-exome sequencing was conducted to identify causative genes in a man with MMAF. Immunofluorescence staining and western blot were applied to assess the pathogenicity of the identified variant. Intracytoplasmic sperm injection (ICSI) was used to assist fertilization for the patient with MMAF. RESULT: Sanger sequencing of the family demonstrated that the infertile man carried a homozygous DNAH17 variant (c. 4810C>T [p.R1604C]). The obviously decreased DNAH17 expression was observed in HEK293T cells transfected with MUT-DNAH17 plasmid compared with cells with WT-DNAH17 plasmid. Immunofluorescence analysis showed that this mutation induced significant decrease in DNAH17 expression, which negatively affected the DNAH8 expression in the patient's spermatozoa. Moreover, the outcome of ICSI in the patient was unsuccessful. CONCLUSION: Our study revealed a novel homozygous missense mutation in DNAH17 involved in MMAF phenotype. The finding of the novel mutation in DNAH17 enriches the gene variant spectrum of MMAF, further contributing to diagnosis, genetic counselling and prognosis for male infertility.

The additional use of hydroxychloroquine can improve the live birth rate in pregnant women with persistent positive antiphospholipid antibodies: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of additional treatment with hydroxychloroquine (HCQ) for pregnant women with persistent positive antiphospholipid antibodies or antiphospholipid antibody syndrome (APS). METHOD: We conducted a systematic search of the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases from inception to 31th December 2019. Two authors performed study selection, data collection, and data analysis independently. RESULT: Five retrospective studies involving 477 pregnancies were selected. The live birth rate was significantly improved in the experimental group (OR, 3.29; 95 % CI, 1.45-7.49; P = 0.004). Additionally, pregnancy loss was associated with the additional use of HCQ (OR, 0.30;95 % CI, 0.13-0.69; P = 0.004). However, HCQ had no significant association with preterm delivery (OR, 0.43; 95 % CI, 0.13-1.37; P = 0.16) and fetal growth restriction showed an OR of 0.22 (95 % CI, 0.13-1.88; P = 0.55). CONCLUSION: These data suggest that receiving HCQ as an additional treatment can improve the live birth rate in pregnant women with persistent antiphospholipid antibodies.

Risk scoring system with MRI for intraoperative massive hemorrhage in placenta previa and accreta.

BACKGROUND: Placenta previa and accreta are serious obstetric conditions that are associated with a high risk of intraoperative massive hemorrhage. PURPOSE: To develop a scoring system for intraoperative massive hemorrhage combining MRI and clinical characteristics to predict the risk of massive hemorrhage in placenta previa and accreta STUDY TYPE: Retrospective cohort study. SUBJECTS: In all, 374 patients consisting of 259 patients with placenta previa and accreta after previous cesarean section (CS) for the derivation cohort and 115 patients for the validation cohort. FIELD STRENGTH/SEQUENCE: 1.5T single-shot fast spin-echo sequence. [Correction added on October 23, 2019, after first online publication: The field strength in the preceding sentence was corrected.] ASSESSMENT: Using the derivation cohort, clinical and MRI data were collected and multivariable logistic regressions analysis was conducted to develop a scoring system for prediction of intraoperative massive bleeding (blood loss volume > 2000 mL). Finally, the scoring system was validated on 115 patients. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, X 2 statistics, multivariable analysis, and receiver operating characteristic (ROC) analysis. RESULTS: Ten indicators, including clinically maternal age (1 point), preoperative hemoglobin level (1 point), gravidity number (1 point), number of CS (1 point), and MRI T2 dark intraplacental bands (4 points), cervical canal length (3 points), placenta thickness on the uterine scar area (4 points), empty vascular shadow of the uterus (1 point), low signal discontinuity in the muscular layer of the posterior wall of the bladder (6 points) and attachment position of the placenta (1 point) were imputed. From the ROC analysis, a total score of 7 points was identified as the optimal cutoff value, allowing good differentiation of intraoperative massive bleeding in the derivation cohort (AUC, 0.863; 95% confidence interval [CI]: 0.811-0.916) and in the validation cohort (AUC, 0.933; 95% CI: 0.885-0.980). DATA CONCLUSION: The scoring system for intraoperative massive hemorrhage consists of MRI and clinical indicators, and using a cutoff value of 7 points for a high risk of massive bleeding, the developed scoring system could accurately assess the risk of intraoperative massive hemorrhage in patients with placenta previa and accreta. This scoring system can potentially reduce the incidence of intraoperative massive bleeding by identifying patients at high risk. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 5 J. Magn. Reson. Imaging 2020;51:947-958.

Parallel transverse uterine incisions, a novel approach for managing heavy hemorrhage and preserving the uterus: A retrospective cohort study for patients with anterior placenta previa and accreta.

Placenta previa and accreta with prior cesarean section is an extremely serious condition that is associated with maternal morbidity and mortality from obstetric hemorrhage. The aim of our study was to evaluate the efficacy and advantages of a novel surgical technique, parallel transverse uterine incisions (PTUI), during conservative cesarean delivery in patients with placenta previa and accreta.This was a retrospective cohort study including 124 pregnant women, who had at least 1 prior cesarean section and were diagnosed with anterior placenta previa and accreta between January 2014 and October 2017. Using the hospital's information system, patients were retrospectively classified into undergoing either the PTUI surgery (Group A) or the ordinary cesarean section (Group B). Surgical outcomes and maternal complications during hospitalization were collected. The results from 2 groups were compared and analyzed statistically. Multivariable regression analyses were further used to assess the effect of PTUI on severe maternal outcomes.Patients who underwent PTUI were not statistically different from patients who underwent the ordinary cesarean section in terms of maternal and infants' characteristics. However, PTUI was associated with remarkably reduced intraoperative blood loss (P = .005), related vaginal blood loss after surgery (P = .026), and transfusion requirement of packed red cells (P = .000), compared to the ordinary cesarean section. Moreover, cesarean hysterectomy (3.3% vs 21.9%; P = .002) and intensive care unit admission (1.7% vs 29.7%; P = .000) were significantly fewer among patients who underwent PTUI. Multivariable regression analyses further showed that the risk of intraoperative hemorrhage (ß = -2343.299, P = .000) and cesarean hysterectomy (odds ratio = 0.027, P = .018) were both significantly decreased by PTUI.PTUI is a novel approach that may significantly reduce maternal complications, while preserving the uterus for patients with anterior placenta previa and accreta.

The association between antiphospholipid antibodies and late fetal loss: A systematic review and meta-analysis.

INTRODUCTION: Antiphospholipid syndrome is a chronic autoimmune disease with a high prevalence in females. Published data have identified that antiphospholipid antibodies (APLA) of antiphospholipid syndrome are risk factors for poor pregnancy outcomes, such as recurrent spontaneous abortion, intrauterine growth restriction and preeclampsia. However, the association between APLA and late fetal loss is not fully understood and remains controversial. The aim of this study is to identify and analyze the recent publications to better understand the association between APLA and late fetal loss. MATERIAL AND METHODS: The literature was searched on 31 January 2019 using Ovid, Medline, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) to evaluate the association between APLA and late fetal loss, with articles published before January 2019, according to the PRISMA statement. Without imposing regional restrictions, referenced articles were selected. Quality assessment was conducted independently by two reviewers, based on the Newcastle-Ottawa scale. For the meta-analysis, we used odds ratios (random effects model). The between-study heterogeneity was assessed by Q test. Publication bias was assessed by funnel plots. RESULTS: Nineteen studies (with 10 265 cases) were included in the final analysis. The odds ratio (OR) for the late fetal loss with lupus anticoagulant was 5.02 (95% confidence interval [CI] 2.14-7.89). Seven included studies reported that lupus anticoagulant had a statistically significant association with late fetal loss. The results did not show a statistically significant association between anticardiolipin antibodies and late fetal loss. The pooled odds ratio for the association of anticardiolipin antibodies with late fetal loss was 3.47 (95% CI 0.68-6.26). However, we did find the relation between anticardiolipin antibodies and late fetal loss among cohort studies (OR 2.27, 95% CI 1.20-3.44). Anti-beta2 glycoprotein 1 antibodies (ß2GP1) showed a significant association with late fetal loss (OR 3.13, 95% CI 0.75-5.50). CONCLUSIONS: Lupus anticoagulant is strongly associated with late fetal loss in antiphospholipid syndrome patients. However, the association between anticardiolipin antibodies and late fetal loss is inconsistent. There are currently insufficient data to support a significant relation between ß2GP1 and late fetal loss.

Effect of epilepsy in pregnancy on fetal growth restriction: a systematic review and meta-analysis.

PURPOSE: Epilepsy is one of the most common neurological diseases during pregnancy. However, the influence of epilepsy on fetal growth is not understood. Thus, this study conducted a meta-analysis to determine the influence of epilepsy during pregnancy on fetal growth restriction (FGR). METHODS: BIOSIS, Medline, Embase, and PubMed databases were searched between January 2000 and January 2016. Without imposing language or regional restrictions, referenced articles were selected. RESULTS: Final analysis included 684 citations from 11 studies. Estimated risk of FGR was 1.28-fold higher in epileptic pregnant women than in non-epileptic women [95% confidence interval (95% CI) 1.09-1.50, p < 0.05]. Given the course of previous studies, hierarchical analysis of pregnant women who use antiepileptic drugs (AEDs) was conducted. Results show that FGR rate is significantly increased even if AEDs were taken [odds ratio 1.26, 95% CI 1.13-1.41, p < 0.05]. CONCLUSIONS: Although modest bias cannot be avoided, our meta-analysis indicated that epilepsy participates in fetal development as an unfavorable factor, and AEDs seemed to be useless in decreasing the occurrence rate of FGR.