Performance of preimplantation genetic testing for aneuploidy for patients with unexplained recurrent pregnancy loss and repeated implantation failure.

Objective: The primary objective was to investigate whether the utilization of next-generation sequencing (NGS) for preimplantation genetic testing for aneuploidy (PGT-A) could enhance the reproductive outcomes in patients with unexplained recurrent pregnancy loss (uRPL) or unexplained repeated implantation failure (uRIF) undergoing intracytoplasmic sperm injection (ICSI) cycles. Materials and methods: We studied the reproductive outcomes of uRPL or uRIF sufferers in Chengdu women and children's central hospital from July 2020 to Jan 2024 retrospectively. These patients were categorized into two groups based on whether they underwent PGT-A or not. As the patients in the PGT-A group all had ICSI and frozen-thawed embryo transfer (FET), only patients who underwent ICSI and FET were included in the non-PGT-A group for comparison. Demographic characteristics and reproductive outcomes were compared in uRPL or uRIF sufferers. Results: For uRPL group, a significant increased ongoing pregnancy rate (63.6 % vs 26.1 %, p = 0.002) and reduced pregnancy loss rate (18.4 % vs 73.3 %, p < 0.001) were found in the PGT-A group in comparison with those in the non-PGT-A group. For uRIF group, no significant difference was noted in the HCG-positive rate, ongoing pregnancy rate, or pregnancy loss rate between the two groups. It is noteworthy that the maternal age in the PGT-A group was significantly higher than that in the non-PGT-A group (p = 0.048). Conclusions: NGS-based PGT-A effectively optimized the reproductive outcomes in uRPL sufferers. Although its benefits in uRIF appeared to be limited, there is a potential advantage for those with advanced maternal age. Considering the small sample size, further randomized controlled trials are warranted to validate these findings.

Lessons to Learn About the Misdiagnosis of a Rare Case in China: Bart Syndrome or Carmi Syndrome?

Objective: We report a case of Carmi Syndrome in a neonate. Aim: To share our lessons in diagnosis of the case of Carmi Syndrome. Case Report: Carmi Syndrome is an extremely rare autosomal recessive genetic disorder characterized the coexistence of pyloric atresia and junctional epidermolysis bullosa, and with aplasia cutis congenita in approximately 28% patients. In this case, a full-term male neonate was born to a G4P2+1L1 multipara through cesarean section delivery in hospital in a non-consanguineous marriage with 4000mL of II°meconium-stained amniotic fluid. He was found extensive skin loss over lower legs and other parts, with scattered blisters and bilateral microtia. Plain abdominal X-ray revealed a large gastric air bubble with no gas distally. The mother had an intrauterine fetal loss previously for reasons unknown. The dermatologist diagnosed the newborn with Bart Syndrome, while the pediatric surgeon diagnosed congenital pyloric atresia(CPA). The parents refused further treatment and the neonate passed away about 30 hours after birth. Outcome: The neonate passed away about 30 hours after birth. Conclusion: Lessons from this case:①.Rule out Carmi Syndrome in patients with PA, and differentiate Bart syndrome and Carmi Syndrome in patients with abnormal skin manifestations. ②. For rare and/or severe diseases, multidisciplinary teams(MDTs) should be establish. ③. Genetic counseling and prenatal diagnosis are necessary prior to subsequent childbearings. ④.Termination of pregnancy might be contemplated if certain indicators are revealed.

Gasless transvaginal natural orifice transluminal endoscopic surgery for hysterectomy and salpingectomy on a robot platform with flexible devices in a porcine model.

In this report, we described a new technique of gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices in a porcine model. As a result, the gynecological procedures were successfully completed. The total operative time was 110 min, while the docking time was 10 min. The estimated blood loss was estimated to be 10 mL with no intraoperative complications. It revealed that gasless V-NOTES for hysterectomy and salpingectomy on a robotic platform with flexible devices appeared to be feasible and safe in the porcine model and has the potential for clinical use in human beings.

Preimplantation genetic testing for aneuploidy optimizes reproductive outcomes in recurrent reproductive failure: a systematic review.

Introduction: Recurrent reproductive failure (RRF) is a common pregnancy complication, imposing great physical, emotional and financial burden for the suffered couples. The leading cause of RRF is believed to be aneuploid embryo, which could be solved by preimplantation genetic testing for aneuploidy (PGT-A) in theory. With molecular genetic development, PGT-A based on comprehensive chromosomal screening (CCS) procedures and blastocyst biopsy is widely applied in clinical practice. However, its effects in RRF were not defined yet. Methods: A systematic bibliographical search was conducted without temporal limits up to June, 2023. Studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. Results: Twenty studies about the effects of PGT-A based on CCS procedures and blastocyst biopsy in RRF were included. It revealed that PGT-A could optimise the reproductive outcomes of RRF sufferers, especially in those with advanced age. However, in patients with multiple occurrences of pregnancy losses, the benefits of PGT-A were limited. Discussion: More randomized controlled trials with large sample size are required to evaluate the benefits of PGT-A in RRF sufferers and identify which population would benefit the most.

Transvaginal natural Orifical transluminal Endoscopy for sacrocolpopexy: A case series report.

Background: To describe the surgical technique and operative outcomes of transvaginal natural orifice transluminal endoscopic surgery (V-NOTES) for sacrocolpopexy with or without robotic surgical system in patients with pelvic organ prolapse (POP). Methods: Patients with POP undergoing traditional transvaginal natural orifice transluminal endoscopic surgery (TV-NOTES) or robotic transvaginal natural orifice transluminal endoscopic surgery (RV-NOTES) for sacrocolpopexy performed by one surgeon from Sep 2020 to Jan 2023 in our hospital were included in this study. The baseline demographics and operative outcomes were collected and analyzed. In addition, some surgical skills were presented. The operative outcomes of V-NOTES for sacrocolpopexy performed by three beginners were also presented. Results: Eight patients who underwent TV-NOTES, and two patients who underwent RV-NOTES were included in this study. The mean operative time was 180 ± 49 min, and the estimated blood loss was 107 ± 82 ml for these ten cases. Particularly, the operative time of the two patients who underwent RV-NOTES was 275 and 132 min, while the estimated blood loss (EBL) was 100 and 50 ml respectively. During the follow-up period, no mesh exposure and recurrence were observed. In addition, five cases of TV-NOTES for sacrocolpopexy by beginners were all successfully completed. Conclusion: Both TV-NOTES and RV-NOTES appeared to be feasible and safe for sacrocolpopexy.

Prevalence and genotype distribution of HPV6/11/16/18 infections among 180,276 outpatient females from a Women's and Children's Central Hospital, 2015-2021, Chengdu, China.

The aims of this study on human papilloma virus (HPV) 6/11/16/18 infection among females in Chengdu were to provide more targeted strategies for the prevention and treatment of cervical cancer and genital warts. In this study, the infection status of 20 genotypes was analysed by gene chip technology. The prevalence rates of HPV-6, -11, -16, and -18 infection among 180,276 cases were 0.94%, 0.57%, 3.22%, and 1.28%, respectively. The prevalence of HPV 6/11/16/18 showed a bimodal U-shaped curve with age; the first and second peak occurred among females < 20 and ≥ 60 years old, respectively. As the multiplicity of infections involving HPV6/11/16/18 increases, the infection rate decreases. The ratios of HPV16 single infection showed a yearly increase. The top five genotypes with HPV-16, -18, -6, and -11 in coinfection were HPV52/58/53/51/33, HPV 52/16/53/58/51, HPV52/16/58/51/53 and HPV16/52/58/59/18, respectively, HPV16/18/6/11 were mainly coinfected with HR-HPV. In sum, among the five vaccines available, nonavalent vaccine is more suitable for Chengdu females. For young females prioritizing vaccination is essential in the current context, while HPV screening remains an effective approach for older females. Additionally, in patients with genital warts, it is necessary to assess the presence of high-risk HPV infection and manage it appropriately in patients with genital warts.

Does endometrial receptivity array improve reproductive outcomes in euploid embryo transfer cycles? a systematic review.

Besides chromosomal normality, endometrial receptivity is an important factor in determining successful pregnancies. Endometrial receptivity array (ERA), a promising endometrial receptivity test, was speculated to improve the reproductive outcomes. However, its effectiveness is controversial in clinical practice. Therefore, we conducted this review to investigate its role in in vitro fertilization (IVF) treatment. To eliminate the interference of embryo quality, we only analyzed studies that originally reported the reproductive outcomes of patients who underwent ERA-guided euploid embryo transfer (EET). Unexpectedly, it revealed that ERA could not optimize the reproductive outcomes in EET cycles, no matter in general infertile population or in patients with a history of previous failed embryo transfers.

The risk factors and impact of subchorionic hematoma in the first trimester in IVF twin pregnancies: a prospective cohort study.

Objective: This study aimed to identify the risk factors for subchorionic hematoma (SCH) in the first trimester of in vitro fertilization (IVF) twin pregnancies and investigate the impact of SCH on pregnancy outcomes. Study design: A prospective cohort study was conducted at Chengdu Women and Children's Central Hospital. The study recruited patients who were identified with twin pregnancies in the first trimester, undergoing IVF treatment from January 2020 to May 2021. The demographic characteristics and pregnancy outcomes were compared between the SCH and the non-SCH groups. A logistic regression analysis was used to determine the risk factors for SCH and adverse pregnancy outcomes. Results: In the first trimester, 38% of patients developed SCH. The independent risk factors for SCH included male factor, hydrosalpinx, polycystic ovary syndrome (PCOS), previous miscarriage, and adenomyosis. With respect to the pregnancy outcomes, only the rate of twin pregnancy loss before 20 gestational weeks was significantly higher in the SCH group than in the non-SCH group. After adjusting for the confounding factors, the presence of SCH diminished the ovarian reserve, and previous miscarriage was independently related to twin pregnancy loss before 20 gestational weeks. Conclusion: This may be the first study to evaluate the risk factors of SCH in twin pregnancies who underwent IVF-ET/FET treatment, which may provide some theoretical basis for clinical practice in the future. Furthermore, it was found that the occurrence of SCH was associated with the loss of both pregnancies before 20 gestational weeks. Therefore, these patients should be offered increased surveillance and timely treatment.

The comparison of gasless and traditional robot-assisted transvaginal natural orifice transluminal endoscopic surgery in hysterectomy.

Study objective: To describe the surgical technique and compare the operative outcomes of gasless and traditional robot-assisted transvaginal natural orifice transluminal endoscopic surgery (GR-vNOTES vs. TR-vNOTES) in hysterectomy. Methods: The patients undergoing hysterectomy via GR-vNOTES or TR-vNOTES between February 2020 and January 2022 in our hospital were included. Clinical data regarding patient demographics, operative time, blood loss, complications, and postoperative hospital stays were collected and analyzed. Results: Five cases underwent hysterectomy via GR-vNOTES, and nine cases via TR-vNOTES. The baseline demographics and operative outcomes were not significantly different in GR-vNOTES and TR-vNOTES groups. There was no conversion to multiport robotic laparoscopy, conventional laparoscopy or laparotomy. No complications were seen in both groups, except two cases had fever postoperatively in the TR-vNOTES group. For those with early stage cervical/endometrial cancer, no recurrence or metastasis was observed in the follow-up of six months. Conclusion: Both GR-vNOTES and TR-vNOTES were feasible and safe for hysterectomy. GR-vNOTES was a promising alternative to TR-vNOTES in hysterectomy.

The landscape of circular RNA in preterm birth.

Background: Preterm birth (PTB) is a multifactorial syndrome that seriously threatens the health of pregnant women and babies worldwide. Recently, circular RNAs (circRNAs) have been understood as important regulators of various physiological and pathological processes. However, the expression pattern and potential roles of circRNAs in PTB are largely unclear. Methods: In this study, we extracted and analyzed the circRNA expression profiles in maternal and fetal samples of preterm and term pregnancies, including maternal plasma, maternal monocytes, myometrium, chorion, placenta, and cord blood. We identified the circRNAs which is associated with PTB in different tissues and explored their relationships from the perspective of the overall maternal-fetal system. Furthermore, co-expression analysis of circRNAs and mRNAs, target microRNAs (miRNAs), and RNA-binding proteins (RBPs), provided new clues about possible mechanisms of circRNA function in PTB. In the end, we investigated the potential special biofunctions of circRNAs in different tissues and their common features and communication in PTB. Results: Significant differences in circRNA types and expression levels between preterm and term groups have been proved, as well as between tissues. Nevertheless, there were still some PTB-related differentially expressed circRNAs (DECs) shared by these tissues. The functional enrichment analysis showed that the DECs putatively have important tissue-specific biofunctions through their target miRNA and co-expressed mRNAs, which contribute to the signature pathologic changes of each tissue within the maternal-fetal system in PTB (e.g., the contraction of the myometrium). Moreover, DECs in different tissues might have some common biological activities, which are mainly the activation of immune-inflammatory processes (e.g., interleukin1/6/8/17, chemokine, TLRs, and complement). Conclusions: In summary, our data provide a preliminary blueprint for the expression and possible roles of circRNAs in PTB, which lays the foundation for future research on the mechanisms of circRNAs in PTB.

Development and validation of a transcriptomic signature-based model as the predictive, preventive, and personalized medical strategy for preterm birth within 7 days in threatened preterm labor women.

Preterm birth (PTB) is the leading cause of neonatal death. The essential strategy to prevent PTB is the accurate identification of threatened preterm labor (TPTL) women who will have PTB in a short time (< 7 days). Here, we aim to propose a clinical model to contribute to the effective prediction, precise prevention, and personalized medical treatment for PTB < 7 days in TPTL women through bioinformatics analysis and prospective cohort studies. In this study, the 1090 key genes involved in PTB < 7 days in the peripheral blood of TPTL women were ascertained using WGCNA. Based on this, the biological basis of immune-inflammatory activation (e.g., IFNγ and TNFα signaling) as well as immune cell disorders (e.g., monocytes and Th17 cells) in PTB < 7 days were revealed. Then, four core genes (JOSD1, IDNK, ZMYM3, and IL1B) that best represent their transcriptomic characteristics were screened by SVM and LASSO algorithm. Therefore, a prediction model with an AUC of 0.907 was constructed, which was validated in a larger population (AUC = 0.783). Moreover, the predictive value (AUC = 0.957) and clinical feasibility of this model were verified through the clinical prospective cohort we established. In conclusion, in the context of Predictive, Preventive, and Personalized Medicine (3PM), we have developed and validated a model to predict PTB < 7 days in TPTL women. This is promising to greatly improve the accuracy of clinical prediction, which would facilitate the personalized management of TPTL women to precisely prevent PTB < 7 days and improve maternal-fetal outcomes.

IL-27 Mediates Th1 Cells Infiltration in Fetal Membranes in Preterm Labor.

The objective of this study is to investigate the effect of IL-27 on Th1 cells infiltration in human fetal membranes (FMs) in preterm labor (PL). The expression of Th1 cells specific transcription factor (T-bet), Th1 cells infiltration related molecules (CXCL9, CXCL10, CXCL11, and ICAM-1), and IL-27 receptor α subunit (IL-27Rα) was compared in human FMs from pregnant women in PL group and term labor (TL) group. In vitro, rhIL-27 was added to the culture medium of amniotic epithelial cells (WISH cells) to detect the expression of CXCL9, CXCL10, CXCL11, and ICAM-1. Furthermore, the underlying signaling pathway was detected by single-sample gene set enrichment analysis and western blot analysis. The expression of T-bet and CXCL9, CXCL10, CXCL11, and ICAM-1 as well as IL-27Rα was higher in human FMs from PL group than TL group. In vitro, rhIL-27 could upregulate the expression of CXCL9, CXCL10, CXCL11, and ICAM-1 in WISH cells. Using gene-set enrichment analysis of FMs, JAK/STAT signaling pathway was found to be activated by IL-27 signaling in PL. Using western blot analysis, JAK2/STAT1/STAT3 signaling pathway was confirmed to be enhanced in rhIL-27 treated WISH cells. In addition, AG490 (JAK2 inhibitor) could inhibit the secretion of CXCL9, CXCL10, and CXCL11 in WISH cells stimulated by rhIL-27. Our results suggested that IL-27 may promote Th1 cells infiltration in human FMs in PL, by promoting the expression of CXCL9, CXCL10, and CXCL11 at least partly through JAK2/STAT1/STAT3 signaling pathway.

The Role of IL-27 in the Systemic Inflammatory Response That Accompanies Preterm Labour.

This study aimed to investigate whether interleukin-27 (IL-27) activates maternal peripheral blood mononuclear cells (PBMCs) and induces inflammatory responses in amniotic epithelial cells in preterm labour (PL). The expression of IL-27p28, EBI3 and IL-27Rα was compared in maternal PBMCs of the PL, term labour (TL) and term not in labour (TNL) groups. The relationship between IL-27 and molecules associated with PBMC activation was investigated using bioinformatic and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analyses. We investigated the inflammatory effects of IL-27 in PBMCs and its underlying mechanisms in vitro. In addition, we treated amniotic epithelial cells (WISH cells) with a PBMC-conditioned medium to identify the inflammatory effects of IL-27-treated PBMCs in amniotic epithelial cells. The expression of IL-27p28 and IL-27Rα in PBMCs of the PL group was higher than that in the TL/TNL groups. Bioinformatic analysis revealed that IL-27 was positively correlated with IFNG, IL6, IL1ß, CXCL10 and ICAM1 in the whole blood samples of pregnant women in the PL group, which was confirmed using qRT-PCR. Furthermore, rhIL-27 promoted the expression of Th1 cell-related molecules (T-bet, IFN-γ and ICAM-1) and proinflammatory cytokines (IL-6 and IL-1ß) in PBMCs in vitro, which was partially mediated by the JAK2/STAT1 pathway. In addition, it enhanced the expression of IL-27p28, EBI3 and IL-27Rα in PBMCs. Moreover, the expression of IL-6, IL-1ß and TNF-α in WISH cells was significantly increased by the conditional medium derived from IL-27-treated PBMCs. IL-27 upregulated the expression of Th1 cell-related molecules and proinflammatory cytokines in PBMCs partially mediated by the JAK2/STAT1 pathway. Inflammatory responses were induced in WISH cells by a conditional medium derived from IL-27-treated PBMCs. Therefore, IL-27 may contribute to PL by promoting inflammation in maternal PBMCs and amniotic epithelial cells.

Comparison of emergency cesarean hysterectomy with and without prophylactic placement of intravascular balloon catheters in patients with placenta accreta spectrum.

OBJECTIVE: The objective of the study was to compare outcomes of women with placenta accreta spectrum(PAS) who underwent emergency cesarean hysterectomy with and without prophylactic intravascular balloon catheters.Methods Sixty-three cases who had emergency hysterectomy related to PAS disorders were retrospectively analyzed. Subjects with prophylactic intravascular balloon catheter placement plus hysterectomy were compared with those who had hysterectomy alone. The cases were divided into three groups: infrarenal aortic artery balloon occlusion (IAABC) group (who had IAABC plus hysterectomy, n = 31), internal iliac artery balloon occlusion (IIABOC) group (who had IIABOC plus hysterectomy, n = 17), and hysterectomy alone group (control group n = 15). RESULTS: Outcome measures were not significantly different between the IIABOC group and the control group. IAABC plus hysterectomy resulted in a better outcome than hysterectomy alone, with less amount of estimated blood loss (EBL) during cesarean section (2000 vs 3000 ml, p = .011) and 24 h after cesarean section (2010 vs 4520 ml, p = .004), less operation time(90 vs 106 min, p = .01), and a lower rate of major blood loss(42 vs 93%, p = .029). IAABC plus hysterectomy resulted in better outcomes than IIABOC plus hysterectomy, with less amount of EBL during cesarean section (2000 vs 3000 ml, p = .005) and 24 h after cesarean section (2010 vs 3000 ml, p = .035), a lower rate of major blood loss(42 vs 100%, p < .001), less operation time (90 vs 100 min, p = .038), and less fetus radiation dose（1.9 mGy vs 22.4 mGy, p < .001). CONCLUSIONS: IAABC was more effective in emergency cesarean hysterectomy related to PAS disorders.

The dual role of IL-27 in CD4+T cells.

Interleukin-27 (IL-27), a member of the IL-6/IL-12 family, has diverse regulatory functions in various immune responses, and is recognised as a potent agonist and antagonist of CD4+T cells in different contexts. However, this dual role and underlying mechanisms have not been completely defined. In the present review, we summarise the dual role of IL-27 in CD4+T cells. In particular, we aimed to decipher its mechanism to better understand the context-dependent function of IL-27 in CD4+T cells. Furthermore, we propose a possible mechanism for the dual role of IL-27. This may be helpful for the development of appropriate IL-27 treatments in various clinical settings.

Identification of the correlations between interleukin-27 (IL-27) and immune-inflammatory imbalance in preterm birth.

Preterm birth (PTB) is an immune-inflammatory disease that needs to be resolved. This study aimed to identify the role of interleukin-27 (IL-27), an immunomodulatory factor, in PTB and its associated mechanisms. Here, we analyzed the high-throughput of samples data from the maternal-fetal interface to the peripheral circulation obtained from public databases and reported that the elevated IL-27 was involved with the onset of PTB. Further bioinformatics analyses (e.g. GeneMANIA and GSEA) revealed that IL-27 overexpression in the peripheral circulation as well as maternal-fetal interface is related to the activation of the immune-inflammatory process represented by IFN-γ signaling, etc. In addition, IL-27 and immune infiltration correlation analysis demonstrated that IL-27 mediates this immune-inflammatory imbalance, plausibly mainly through monocyte-macrophage and neutrophils. This finding was further validated by analyzing additional datasets. Overall, this is the first study to elaborate on the role of IL-27-mediated immuno-inflammation in PTB from the perspective of bioinformatics, which may provide a novel strategy for the prevention and treatment of PTB.

A new technique of laparoscopic para-aortic lymphadenectomy optimizes perioperative outcome.

OBJECTIVE: The aim of the present study was to introduce a new technique for laparoscopic para-aortic lymphadenectomy (PAL): an invented retroperitoneum suspension needle combined with modified trocar placement. METHODS: This prospective pilot study randomly categorized women with cervical cancer of stage I-II into 2 groups. The patients in the study group would have laparoscopic PAL with our new technique, while those in the control group with control method. Patients' characteristics and perioperative outcomes were compared between the 2 groups. RESULTS: A total of 37 patients were included in our study, of which 20 cases in the study group and 17 cases in the control group. As a result, the mean number of para-aortic lymph nodes (PALNs) resected in the study group was significantly more than that in the control group (p<0.001). The time for resecting PALNs (p<0.001) and total operative time (p<0.001) in the study group decreased significantly than those in the control group. CONCLUSIONS: For laparoscopic PAL, this new technique was effective and practical.

Perinatal outcomes and offspring growth profiles in twin pregnancies complicated by gestational diabetes mellitus: A longitudinal cohort study.

AIMS: To evaluate the influence of gestational diabetes mellitus (GDM) on the perinatal outcomes of twin pregnancies and its impact on fetal growth profiles of twin offspring from 6 weeks to 12 months of corrected age. METHODS: A longitudinal cohort study was conducted among pregnant women with twins and their twin offspring. All information on perinatal outcomes and child growth trajectories from 6 weeks to 12 months of corrected age were obtained and analyzed using a general linear model and logistic regression models. RESULTS: GDM was not correlated with adverse perinatal outcomes of twin pregnancies; however, in monochorionic diamniotic (MCDA), but not dichorionic diamniotic (DCDA) twin pregnancies, GDM was correlated with gestational hypertension disorder and a fetus being small for gestational age (OR, 2.68; 95% CI 1.16-6.04 and OR, 0.35; 95% CI 0.16-0.76, respectively). In both MCDA and DCDA groups, GDM was positively associated with a higher risk of childhood overweight at 6 months of corrected age (2.32 [1.05, 5.09] and 2.00 [1.13, 3.53]). CONCLUSIONS: GDM had a greater impact on MCDA twin pregnancies in terms of maternal gestational hypertension disease and small for gestational age of newborns. Additionally, twin offspring exposed to GDM had a higher risk of being overweight at 6 months of corrected age irrespective of chorionicity. CLINICAL TRIAL REGISTRATION: ChiCTR-OOC-16008203.