Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

Diagnostic value of non-coding RNAs in ovarian cancer.

The type of primary tumour of the ovary ranks first among all organs in the body. Although the incidence of malignant ovarian tumour ranks third among gynaecological malignancies, it is the most fatal type. A lack of effective diagnostic methods for early ovarian cancer remains, and the efficacy of advanced ovarian cancer is often unsatisfactory; the five-year survival rate of stage III-IV is less than 30%. Non-coding RNA is RNA that does not have protein-coding potential and was once considered as 'junk DNA'. However, increasing number of studies have shown that the disorder of non-coding RNA is related to a variety of diseases, including the occurrence and development of tumours. We summarised the dysregulated non-coding RNAs (miRNAs, circRNAs, and lncRNAs) reported currently in ovarian cancer and their functional mechanisms, and the clinical value of different types of ncRNAs as diagnostic or predictive markers for ovarian cancer, providing further evidence for non-coding RNAs to be considered as biomarkers of ovarian cancer.

Roles of noncoding RNAs in preeclampsia.

Preeclampsia (PE) is an idiopathic disease that occurs during pregnancy. It comprises multiple organ and system damage, and can seriously threaten the safety of the mother and infant throughout the perinatal period. As the pathogenesis of PE is unclear, there are few specific remedies. Currently, the only way to eliminate the clinical symptoms is to terminate the pregnancy. Although noncoding RNA (ncRNA) was once thought to be the "junk" of gene transcription, it is now known to be widely involved in pathological and physiological processes, including pregnancy-related disorders. Moreover, there is growing evidence that the unbalanced expression of specific ncRNA is involved in the pathogenesis of PE. In the present review, we summarize the expression patterns of ncRNAs, i.e., microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), and the functional mechanisms by which they affect the development of PE, and examine the clinical significance of ncRNAs as biomarkers for the diagnosis of PE. We also discuss the contributions made by genetic polymorphisms and epigenetic ncRNA regulation to PE. In the present review, we wish to explore and reinforce the clinical value of ncRNAs as noninvasive biomarkers of PE.

The psychosocial impact of premature ovarian insufficiency on male partners and their perceptions of the disease.

Premature ovarian insufficiency (POI) is affecting about 1% women of reproductive age. However, current studies have primarily focused on women with the views of male partners greatly absent from the literature. We conduct this research to investigate the psychosocial effect of POI on male partners and their perceptions of the disease.52 male partners of POI patient (experiment group) and 52 controls (control group) were available for analysis. Anxiety, depression, and marital relationship were assessed for male partners in both groups. A questionnaire about perceptions of POI was completed by the experiment group. Male partners of POI patient experienced greater levels of anxiety (10.96 versus 4.88; P < 0.01) and depression (12.23 versus 5.19; P < 0.01) compared with controls. In addition, they experienced worse marital relationship in several aspects than their counterparts. The findings also demonstrate that most POI patient male partners had inadequate and inaccurate knowledge about their partners' disease, which may be the results of insufficient professional counseling from health-care practitioners. Moreover, their understanding level of the disease was correlated to anxiety (r = -0.64; P < 0.01), depression (r = -0.38; P < 0.01), and communication (r = 0.28; P < 0.05).The study highlights the need for health-care services, as well as support and professional information resources aimed at POI patients' male partners.

[Research progress of kisspeptin in female reproductive endocrine and assisted reproductive techniques].

In recent years, it has been found that kisspeptin plays some key roles in the physiological processes of the brain, such as gender differentiation, positive and negative feedback of sex hormones, onset of puberty, and transduction of energy signals in the body, which suggests that kisspeptin may be a key molecule for the maturation and regulation of female reproductive function. In addition to the systemic roles of the kisspeptin, its local roles in reproductive organs are constantly being discovered. With the discovery that kisspeptin is involved in the pathological process of reproductive endocrine diseases such as isolated hypogonadotropic hypogonadism (IHH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF) and pathological hyperprolactinemia, exogenous application of kisspeptin to solve reproductive problems has become a new hot topic. The review focuses on the research progress of kisspeptin in the female reproductive system, especially on its application in assisted reproduction.

Aberrant expression of imprinted lncRNA MEG8 causes trophoblast dysfunction and abortion.

Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs whose nucleotides are longer than 200 bp. Previous studies have shown that they play an important regulatory role in many developmental processes and biological pathways. However, the contributions of lncRNAs to placental development are largely unknown. Here, our study aimed to investigate the lncRNA expression signatures in placental development by performing a microarray lncRNA screen. Placental samples were obtained from pregnant C57BL/6 female mice at three key developmental time points (embryonic day E7.5, E13.5, and E19.5). Microarrays were used to analyze the differential expression of lncRNAs during placental development. In addition to the genomic imprinting region and the dynamic DNA methylation status during placental development, we screened imprinted lncRNAs whose expression was controlled by DNA methylation during placental development. We found that the imprinted lncRNA Rian may play an important role during placental development. Its homologous sequence lncRNA MEG8 (RIAN) was abnormally highly expressed in human spontaneous abortion villi. Upregulation of MEG8 expression in trophoblast cell lines decreased cell proliferation and invasion, whereas downregulation of MEG8 expression had the opposite effect. Furthermore, DNA methylation results showed that the methylation of the MEG8 promoter region was increased in spontaneous abortion villi. There was dynamic spatiotemporal expression of imprinted lncRNAs during placental development. The imprinted lncRNA MEG8 is involved in the regulation of early trophoblast cell function. Promoter methylation abnormalities can cause trophoblastic cell defects, which may be one of the factors that occurs in early unexplained spontaneous abortion.

Caveolin-1 promotes trophoblast cell invasion through the focal adhesion kinase (FAK) signalling pathway during early human placental development.

Normal implantation and placental development depend on the appropriate differentiation and invasion of trophoblast cells. Inadequate trophoblast cell invasion results in pregnancy-related disorders, which endanger both mother and fetus; however, the mechanism of early placental development has not been fully explained. In this study we conducted gene expression profile analysis using mouse placental tissues at different developmental stages (embryonic day (E)7.5, E14.5 and E19.5) using series tests of cluster (STC) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses. Focal adhesion kinase (FAK) signalling pathway-related gene expression levels were verified using quantitative reverse transcription polymerase chain reaction and western blot. The results showed that caveolin-1 (Cav1) was downregulated in the placenta of unexplained spontaneous abortion subjects compared with that of induced abortion. Furthermore, by modulating CAV1 expression levels, CAV1 was shown to promote human trophoblast cell proliferation, migration and invasion by activating the FAK signalling pathway. These results indicate that CAV1 and the FAK signalling pathway are crucial for early placental development, which sheds new light on our understanding of the mechanisms of human trophoblast cell invasion and early development of the placenta.

Outcomes of poor responders following growth hormone co-treatment with IVF/ICSI mild stimulation protocol: a retrospective cohort study.

PURPOSE: No research has studied the effect of GH co-treatment in mild stimulation protocol for poor responders. We therefore conducted this retrospective analysis to assess the outcome of IVF/ICSI cycles after the adjunct GH use to the mild stimulation protocol in poor responders. METHODS: 132 poor responders who received mild stimulation protocol at Reproductive Medicine Center of Changzheng Hospital from January 2014 to December 2016 were included in this study. Good-quality embryo rate, clinical pregnancy rate, and live birth rate were compared between the GH group (n = 61) and control group (n = 71). RESULTS: IVF good-quality embryo rate (68.1 versus 51.5%; P = 0.008*) and ICSI good-quality embryo rate (53.9 versus 36.7%; P = 0.045*) was significantly higher in the GH group. Though the clinical outcomes did not reach a statistically significant difference between the two groups due to the limited sample size, there was a trend of higher rate in GH group in the aspect of clinical pregnancy rate (52.4 versus 47.1%; P = 0.609) and live birth rate (35.7 versus 27.5%; P = 0.392). CONCLUSION: The results suggested that the adjuvant GH treatment in mild stimulation protocol for poor responders could significantly improve good-quality embryo rate, and might therefore improve the clinical outcomes.

The mutation-free embryo for in vitro fertilization selected by MALBAC-PGD resulted in a healthy live birth from a family carrying PKD 1 mutation.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD, autosomal dominant PKD or adult-onset PKD) is the most prevalent and potentially lethal kidney disease that is hereditary and lacks effective treatment. Preimplantation genetic diagnosis (PGD) of embryos in assistant reproductive technology (ART) helps to select mutation-free embryos for blocking ADPKD inheritance from the parents to their offspring. However, there are multiple pseudogenes in the PKD1 coding region, which make blocking ADPKD inheritance by PGD complicated and difficult. Therefore, this technique has not been recommended and used routinely to ADPKD family plan. METHODS AND RESULTS: Here, we report a new strategy of performing PGD in screening (target-) mutation-free embryos. We firstly used a long-range PCR amplification and next generation sequencing to identify the potential PKD1 mutant(s). After pathogenic variants were detected, multiple annealing and looping-based amplification cycles (MALBAC), a recently developed whole genome amplification method, was used to screen embryo cells. We successfully distinguished the mutated allele among pseudogenes and obtained mutation-free embryos for implantation. The first embryo transfer attempt resulted in a healthy live birth free of ADPKD condition and chromosomal anomalies which was confirmed by aminocentesis at week 18 of gestation, and by performing live birth genetic screening. CONCLUSIONS: The first MALBAC-PGD attempt in ADPKD patient resulted in a healthy live birth free of ADPKD and chromosomal anomalies. MALBAC-PGD also enables selecting embryos without aneuploidy together and target gene mutation, thereby increasing implantation and live birth rates.

Molecular regulation of ovarian cancer cell invasion.

The molecular mechanism underlying ovarian cancer invasiveness and metastasis remains unclear. Since significant downregulation in microRNA 200 (miRNA200) family (miR200a, miR200b, and miR200c) has been reported in the invasive ovarian cancer cells, here, we used two human ovarian cancer cell lines, OVCAR3 and SKOV3, to study the molecular basis of miR200, matrix metalloproteinase 3 (MMP3) activation, and cancer invasiveness. We found that overexpression of either miR200 family member in OVCAR3 or SKOV3 cells significantly inhibited production and secretion of MMP3 and cancer invasiveness. Moreover, forced MMP3 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that miR200 family inhibited ovarian cell invasiveness via downregulating MMP3. Furthermore, ZEB1, a major target of miR200, was inhibited by miR200 overexpression. Forced ZEB1 expression abolished miR200-induced inhibition of ovarian cancer cell invasiveness, suggesting that ZEB1 is a direct target of miR200 for inhibiting ovarian cell invasiveness. Finally, phosphorylated SMAD3 (pSMAD3), a major partner of ZEB1, was efficiently inhibited by miR200, which could be restored by forced expression of ZEB1, but not by forced expression of MMP3, suggesting that ZEB1/pSMAD3 is signaling cascade upstream of MMP3 in this model. Taken together, our data suggest that miR200 family inhibited ovarian cancer cell invasiveness and metastasis by downregulating MMP3, possibly through ZEB1/pSMAD3.

Hysteroscopic Management of Symptomatic Cesarean Scar Diverticulum in Patients Undergoing Frozen-Thawed Embryo Transfer: Impact on Clinical Pregnancy Rates and Pregnancy Complications.

This retrospective cohort study aimed to compare the clinical outcomes of patients with cesarean scar defect (CSD) undergoing frozen embryo transfer (FET) with or without hysteroscopic repair surgery. The study included 82 patients, with 48 patients in surgical group A (undergoing CSD repair) and 34 patients in surgical group B (undergoing hysteroscopic treatment for other uterine lesions). The results showed that patients in group A had a larger CSD volume and a different shape compared to group B. However, there was no significant difference in clinical pregnancy rates between the two groups. Additionally, there were no differences in miscarriage, live birth, or preterm birth rates, and no complications such as scar pregnancy or placental abnormalities were observed in either group. These findings suggest that hysteroscopic treatment of CSD in symptomatic patients undergoing FET does not increase the risk of pregnancy complications and can lead to comparable clinical pregnancy rates with asymptomatic patients. Further studies with larger sample sizes are needed to confirm these results and evaluate long-term reproductive outcomes following CSD repair.

Spatiotemporal patterns of the pregnancy microbiome and links to reproductive disorders.

The microbiome of females undergoes extensive remodeling during pregnancy, which is likely to have an impact on the health of both mothers and offspring. Nevertheless, large-scale integrated investigations characterizing microbiome dynamics across key body habitats are lacking. Here, we performed an extensive meta-analysis that compiles and analyzes microbiome profiles from  >10,000 samples across the gut, vagina, and oral cavity of pregnant women from diverse geographical regions. We have unveiled unexpected variations in the taxonomic, functional, and ecological characteristics of microbial communities throughout the course of pregnancy. The gut microbiota showed distinct trajectories between Western and non-Western populations. The vagina microbiota exhibited fluctuating transitions at the genus level across gestation, while the oral microbiota remained relatively stable. We also identified distinctive microbial signatures associated with prevalent pregnancy-related disorders, including opposite variations in the oral and gut microbiota of patients with gestational diabetes and disrupted microbial networks in preterm birth. This study establishes a comprehensive atlas of the pregnancy microbiome by integrating multidimensional datasets and offers foundational insights into the intricate interplay between microbes and host factors that underlie reproductive health.

Single-cell transcriptomic profiling unveils insights into ovarian fibrosis in obese mice.

BACKGROUND: Adiposity profoundly impacts reproductive health in both humans and animals. However, the precise subpopulations contributing to infertility under obese conditions remain elusive. RESULTS: In this study, we established an obese mouse model through an eighteen-week high-fat diet regimen in adult female mice. Employing single-cell RNA sequencing (scRNA-seq), we constructed a comprehensive single-cell atlas of ovarian tissues from these mice to scrutinize the impact of obesity on the ovarian microenvironment. ScRNA-seq revealed notable alterations in the microenvironment of ovarian tissues in obese mice. Granulosa cells, stromal cells, T cells, and macrophages exhibited functional imbalances compared to the control group. We observed heightened interaction strength in the SPP1-CD44 pairing within lgfbp7+ granulosa cell subtypes and Il1bhigh monocyte subtypes in the ovarian tissues of obese mice. Moreover, the interaction strength between Il1bhigh monocyte subtypes and Pdgfrb+ stromal cell subtypes in the form of TNF - TNFrsf1α interaction was also enhanced subsequently to obesity, potentially contributing to ovarian fibrosis pathogenesis. CONCLUSIONS: We propose a model wherein granulosa cells secrete SPP1 to activate monocytes, subsequently triggering TNF-α secretion by monocytes, thereby activating stromal cells and ultimately leading to the development of ovarian fibrosis. Intervening in this process may represent a promising avenue for improving clinical outcomes in fertility treatments for obese women.

miR-340-3p-modified bone marrow mesenchymal stem cell-derived exosomes inhibit ferroptosis through METTL3-mediated m6A modification of HMOX1 to promote recovery of injured rat uterus.

BACKGROUND: Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia-reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive. METHODS: The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs. RESULTS: We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3'-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury. CONCLUSIONS: Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.

Association between FAS A670G polymorphism and susceptibility to cervical cancer: evidence from a meta-analysis.

Previous studies published to evaluate the association between FAS A670G polymorphism and susceptibility to cervical cancer provided conflicting findings. A meta-analysis of published case-control studies was performed to get a comprehensive evidence for the possible association. We searched in PubMed and Wanfang databases for eligible studies published before February 10, 2013. The odds ratio (OR) with 95% confidence interval (95% CI) was used to evaluate the association. Ten studies with a total of 4,904 participants were finally included into the meta-analysis. Overall, there was no obvious association between FAS A670G polymorphism and susceptibility to cervical cancer under all four genetic models (G versus A: OR = 0.97, 95% CI 0.84-1.11, P = 0.64; GG versus AA: OR = 0.92, 95% CI 0.69-1.24, P = 0.60; GG/AG versus AA: OR = 0.99, 95% CI 0.77-1.26, P = 0.92; GG versus AA/AG: OR = 0.92; 95% CI 0.68-1.25, P = 0.59). Subgroup analyses by ethnicity further showed that there was no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians. There was no risk of publication bias. In summary, the meta-analysis suggests that there is no association between FAS A670G polymorphism and susceptibility to cervical cancer in both Caucasians and Asians.

LncRNA DANCR counteracts premature ovarian insufficiency by regulating the senescence process of granulosa cells through stabilizing the interaction between p53 and hNRNPC.

BACKGROUND: Premature ovarian insufficiency (POI) is one of the common women reproductive endocrine diseases which adversely impacts female fertility, but the etiology and pathogenesis still remain elusive. Recently increasing researches focus on the roles of lncRNA in POI. LncRNA DANCR was involved in cell differentiation and multiple cancers. It's highly expressed in ovary while the role of DANCR in POI is still unknown. RESULTS: Here, we identify a new POI related lncRNA DANCR, which negatively contributes to ovarian granulosa cells aging and follicular atresia. DANCR is proved to be decreasingly expressed in POI patients' granulosa cells. Additionally, Dancr knockout (Dancr-/-) mice were constructed and characterized with POI phenotypes and fertility decline, compared with Dancr+/+ mice. Further, in vitro experiments indicated that DANCR knockdown in granulosa cells led to cell aging and series of aging-related changes including proliferation inhibition, cell cycle G1 arrest and DNA damage. Mechanism research revealed DANCR binds with hNRNPC and p53, while DANCR knockdown attenuates the binding of hNRNPC and p53, thus enhancing protein level of p53 and promoting granulosa cells aging significantly. CONCLUSION: The newly identified lncRNA DANCR inhibits p53-dependent granulosa cells aging by regulating hNRNPC-p53 interaction, and eventually counteracting POI. This provides new insights into the pathogenesis of POI and provides a potential target for future diagnosis and treatment.

Research on a New Intelligent and Rapid Screening Method for Depression Risk in Young People Based on Eye Tracking Technology.

Depression is a prevalent mental disorder, with young people being particularly vulnerable to it. Therefore, we propose a new intelligent and rapid screening method for depression risk in young people based on eye tracking technology. We hypothesized that the "emotional perception of eye movement" could characterize defects in emotional perception, recognition, processing, and regulation in young people at high risk for depression. Based on this hypothesis, we designed the "eye movement emotional perception evaluation paradigm" and extracted digital biomarkers that could objectively and accurately evaluate "facial feature perception" and "facial emotional perception" characteristics of young people at high risk of depression. Using stepwise regression analysis, we identified seven digital biomarkers that could characterize emotional perception, recognition, processing, and regulation deficiencies in young people at high risk for depression. The combined effectiveness of an early warning can reach 0.974. Our proposed technique for rapid screening has significant advantages, including high speed, high early warning efficiency, low cost, and high intelligence. This new method provides a new approach to help effectively screen high-risk individuals for depression.

A case of extramedullary solitary plasmacytoma arising at the uterine cervix.

Extramedullary plasmacytomas are localized plasma cell neoplasms that arise in tissues other than bone and bone marrow. Primary plasmacytomas of the female genital tract are extremely rare and present a substantial diagnostic challenge. We report a case of a 38-year-old woman who presented with an endocervical polypoid. Surgical removal of the polyp was carried out. The final pathological report revealed primary plasmacytoma of the uterine cervix. The diagnosis was further facilitated by the use of immunohistochemistry and clonal immunoglobulin heavy-chain gene rearrangement. We performed a simple hysterectomy by laparoscopy on the patient and kept a close follow-up. She has remained well for more than eight years. The clinical characteristics and histopathologic findings of plasmacytoma of the uterine cervix are discussed.

Effect of new biological patch in repairing intrauterine adhesion and improving clinical pregnancy outcome in infertile women: study protocol for a randomized controlled trial.

BACKGROUND: Endometrial fibrosis caused by intrauterine adhesion (IUA) can lead to hypomenorrhea, amenorrhea, and even infertility and abortion. The postoperative recurrence rate of severe IUA remains high, giving rise to low pregnancy rates. An extracellular matrix (ECM) scaffold, a new biological material that can promote cell proliferation and differentiation at lesions, has been widely used in general surgery and neurosurgery. The present study applied ECM scaffolds in obstetrics and gynecology for the first time to improve endometrial fibrosis, repair severe IUA, and improve pregnancy outcomes for infertile patients. METHODS: This paper presents a prospective randomized single-blind controlled superiority study of infertile women aged ≤40 years with IUA. According to the scoring criteria for IUA established by the American Fertility Society, patients with moderate or severe IUA were randomized into two groups at a ratio of 1:1; patients in the experimental group were treated with an ECM scaffold (small intestinal submucosa [SIS]) + intrauterine balloon, while patients in the control group were treated with an intrauterine balloon only. A hysteroscopic examination of adhesion repair was performed again after 2 months of postoperative hormone replacement therapy. Endometrial tissue was sampled during the two operations, and immunohistochemistry was used to observe endometrial and microvascular proliferation. After thawing and resuscitation, a postoperative frozen embryo transfer was performed on the participants in both groups, and their endometrial thickness, intrauterine volume, endometrial vascularization flow index, endometrial flow index, and uterine artery blood flow resistance were evaluated by 3D ultrasonography. The rates of embryo implantation, clinical pregnancy, and early spontaneous abortion were observed. DISCUSSION: The ECM scaffold (SIS) + intrauterine balloon method was able to repair endometrial fibrosis and improve IUA. This new technique represents a novel treatment method for improving the pregnancy outcome of infertile patients with moderate/severe IUA. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR2100052027 . Registered on October 14, 2021.