Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception.

The number of children born after assisted reproductive technology (ART) is accumulating rapidly, and the health problems of the children are extensively concerned. This study aims to evaluate whether ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET), and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST), and sucrose preference test (SPT) was carried out. Aged (18 months old), but not young (3 months old), male offspring in the IVF-ET and IVF-FET groups, compared with those in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in the future.

Using 17ß-estradiol heparin-poloxamer thermosensitive hydrogel to enhance the endometrial regeneration and functional recovery of intrauterine adhesions in a rat model.

Mechanical damage or infection to the endometrium can lead to the formation of adhesions in the uterine cavity, which may result in reduced reproductive outcome and/or pregnancy complications. The prognosis of this disease is poor due to few effective treatments and the complex environment of endometrium. Heparin-Poloxamer Hydrogel (HP hydrogel) is a nontoxic and biodegradable biomaterial, which has been commonly used as a sustained-release delivery system. In this study, we applied a mini-endometrial curette to scrape the endometrium of rats to mimic the process of curettage in patients. After the establishment of IUA model in rats, we injected the thermo-sensitive hydrogel(E2-HP hydrogel) into the injured uterine cavity and evaluated the therapeutic effect of E2-HP hydrogel on the recovery of IUA. Our results showed that E2-HP hydrogel can significantly facilitate the regeneration of injured endometrium along with inhibiting the cell apoptosis in IUA model. Furthermore, we revealed that E2-HP hydrogel on the recovery of IUA was closely associated with the upregulation of kisspeptin through activating the ERK1/2 and MAPKs p38 pathways. In conclusion, E2-HP hydrogel can effectively transfer E2 into the injured endometrium and it can be considered as a promising therapeutic method for the women with intrauterine adhesions.

Impact of pelvic dimensions on anastomotic leak after anterior resection for patients with rectal cancer.

AIM: The impact of pelvis on the development of anastomotic leak (AL) in rectal cancer (RC) patients who underwent anterior resection (AR) remains unclear. The aim of this study was to evaluate the impact of pelvic dimensions on the risk of AL. METHODS: A total of 1058 RC patients undergoing AR from January 2013 to January 2016 were enrolled. Pelvimetric parameters were obtained using abdominopelvic computed tomography scans. RESULTS: Univariate analyses showed that pelvic inlet, pelvic outlet, interspinous distance, and intertuberous distance were significantly associated with the risk for AL (P < 0.05). Multivariate analysis confirmed that pelvic inlet and intertuberous distance were independent risk factors for AL (P < 0.05). Significant factors from multivariate analysis were assembled into the nomogram A (without pelvic dimensions) and nomogram B (with pelvic dimensions). The area under curve (AUC) of nomogram B was 0.72 (95% CI 0.67-0.77), which was better than the AUC of nomogram A (0.69, [95% CI 0.65-0.74]), but didn't reach a statistical significance (P = 0.199). Decision curve supported that nomogram B was better than nomogram A. CONCLUSION: Pelvic dimensions, specifically pelvic inlet and intertuberous distance, seemed to be independent predictors for postoperative AL in RC patients. Pelvic inlet and intertuberous distance incorporated with preoperative radiotherapy, preoperative albumin, conversion, and tumor diameter in the nomogram might provide a clinical tool for predicting AL.

The casein kinase 2α promotes the occurrence polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease characterized by hyperandrogenism, polycystic ovaries, and anovulation. Previous studies have revealed that androgen receptors (ARs) are strongly associated with hyperandrogenism and abnormalities in folliculogenesis in patients with PCOS. However, the kinases responsible for androgen receptor activity, especially in granulosa cells, and the role of casein kinase 2α (CK2α) specifically in the pathogenesis of PCOS, remain unknown. Here, we show that both CK2α protein and mRNA levels were higher in luteinized granulosa cells of patients with PCOS compared with non-PCOS, as well as in the ovarian tissues of mice with a dehydroepiandrosterone-induced PCOS-like phenotype, compared with controls. In addition, CK2α not only interacted with AR in vivo and in vitro, but it also phosphorylated and stabilized AR, triggering AR and ovulation related genes excessive expression. CK2α also promoted cell proliferation in the KGN cell line and inhibited apoptosis. Collectively, the finding highlighted that the CK2α-AR axis probably caused the etiology of the PCOS. Thus, CK2α might be a promising clinical therapeutic target for PCOS treatment.

Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis.

BACKGROUND: As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. LncRNA MIR100HG promotes cell proliferation in TNBC. However, few studies have investigated the molecular mechanism of MIR100HG in TNBC. Thus, additional in-depth investigations are needed to unravel its associated regulatory mechanism. METHODS: MIR100HG and miR-5590-3p expression in TNBC tissue samples and cell lines was detected by RT-qPCR. Flow cytometry, transwell, wound-healing, CCK8 and colony formation assays were performed to analyse cell apoptosis, cell cycle, invasion, migration and proliferation. The protein expression of orthodenticle homeobox 1 (OTX1) and proteins in the ERK/MAPK signalling pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the interaction between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the interaction between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues. RESULTS: MIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth. CONCLUSIONS: MIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC.

Baseline and early 3D-CUBE volume reconstruction of locally advanced rectal cancer to predict tumor response after neoadjuvant chemotherapy.

PURPOSE: To explore whether volumetric measurements of 3D-CUBE sequences based on baseline and early treatment time can predict neoadjuvent chemotherapy (NCT) efficacy of locally advanced rectal cancer (LARC). MATERIAL AND METHOD: 73 patients with LARC were enrolled from February 2014 to January 2018. All patients underwent MRIs during the baseline period before NCT (BL-NCT) and the first month of NCT (FM-NCT), and tumor volume (TV) was measured using 3D-CUBE, and tumor volume reduction (TVR) and tumor volume reduction rate (TVRR) were calculated. In addition, tumor invasion depth, tumor maximal length, range of tumor involvement in the circumference of intestinal lumen and distance from inferior part of tumor to the anal verge were measured using baseline high-spatial-resolution T2-weighted MRIs. All patients were categorized into sensitive and insensitive groups based on post-surgical pathology after completion of the full courses of NCT. The receiver operating characteristic (ROC) curve was used to analyze the value of different MRI parameters in predicting efficacy of NCT. RESULTS: Statistically significant differences in TV of BL-NCT, TVR and TVRR from BL-NCT to FM-NCT were detected between sensitive and insensitive groups (P < 0.05, respectively). The areas under the curves (AUC) of ROC of TVR and TVRR in predicting efficacy of NCT (0.890 [95% CI, 0.795∼0.951], 0.839 [95% CI, 0.735∼0.915]) were significantly better than that of TV (0.660 [95% CI, 0.540∼0.767]) (P < 0.05, respectively). CONCLUSION: Reconstruction of 3D-CUBE volume in the first month of NCT is necessary, and both TVR and TVRR can be used as early predictors of NCT efficacy.

Generation of functional hepatocyte-like cells from human bone marrow mesenchymal stem cells by overexpression of transcription factor HNF4α and FOXA2.

BACKGROUND: Our previous study showed that overexpression of hepatocyte nuclear factor 4α (HNF4α) could directly promote mesenchymal stem cells (MSCs) to differentiate into hepatocyte-like cells. However, the efficiency of hepatic differentiation remains low. The purpose of our study was to establish an MSC cell line that overexpressed HNF4α and FOXA2 genes to obtain an increased hepatic differentiation efficiency and hepatocyte-like cells with more mature hepatocyte functions. METHODS: Successful establishment of high-level HNF4α and FOXA2 co-overexpression in human induced hepatocyte-like cells (hiHep cells) was verified by flow cytometry, immunofluorescence and RT-PCR. Measurements of albumin (ALB), urea, glucose, indocyanine green (ICG) uptake and release, cytochrome P450 (CYP) activity and gene expression were used to analyze mature hepatic functions of hiHep cells. RESULTS: hiHep cells efficiently express HNF4α and FOXA2 genes and proteins, exhibit typical epithelial morphology and acquire mature hepatocyte-like cell functions, including ALB secretion, urea production, ICG uptake and release, and glycogen storage. hiHep cells can be activated by CYP inducers. The percentage of both ALB and α-1-antitrypsin (AAT)-positive cells was approximately 72.6%. The expression levels of hepatocyte-specific genes (ALB, AAT, and CYP1A1) and liver drug transport-related genes (ABCB1, ABCG2, and SLC22A18) in hiHep cells were significantly higher than those in MSCs-Vector cells. The hiHep cells did not form tumors after subcutaneous xenograft in BALB/c nude mice after 2 months. CONCLUSION: This study provides an accessible, feasible and efficient strategy to generate hiHep cells from MSCs.

Clinical Significance of 2 Deep Posterior Perianal Spaces to Complex Cryptoglandular Fistulas.

BACKGROUND: Confusion exists regarding the clinical significance of the deep posterior intersphincteric space and deep postanal space to complex perianal fistulas. OBJECTIVE: The purpose of this study was to assess the clinical significance of the 2 deep posterior perianal spaces and to describe in detail the courses of posterior complex cryptoglandular fistula extensions. DESIGN: This was a retrospective study. MRI-based characteristics of selected perianal fistulas were independently evaluated by examiners who focused on lesions in these 2 spaces and were blinded to each other's findings. SETTINGS: This study was conducted in the colorectal surgery and radiology departments of a large university teaching hospital in China. PATIENTS: Included in the study were patients who underwent pelvic MRI for posterior perianal fistula between October 2012 and December 2014. MAIN OUTCOME MEASURES: The occurrence rates of these 2 deep perianal space lesions in posterior cryptoglandular fistulas were determined. RESULTS: A total of 513 primary posterior cryptoglandular fistulas were identified in 508 patients, including 167 deep posterior intersphincteric space lesions (32.6%) and 23 deep postanal space lesions (4.5%). Of those, 173 fistulas (33.7%) were evaluated as complex. The former and latter spaces were involved in 79.2% (137/173) and 13.3% (23/173) of posterior complex fistulas. Compared with deep postanal space lesions, deep posterior intersphincteric space lesions were more common in cases with high transsphincteric or suprasphincteric fistulas (80.1% vs 15.8%), synchronous multiple transsphincteric fistulas (82.4% vs 20.6%), horseshoe-like fistulas (85.5% vs 14.5%), and supralevator fistulas (93.5% vs 16.1%). Similar incidences were also seen in cases with ischioanal-involved horseshoe-like fistulas (75.0% vs 25.0%). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The deep posterior intersphincteric space is more likely than the deep postanal space to be involved in complex cryptoglandular fistulas and is likely to play a more important role in the management of complex cryptoglandular fistulas.

Restaging of locally advanced rectal cancer with magnetic resonance imaging and endoluminal ultrasound after preoperative chemoradiotherapy: a systemic review and meta-analysis.

BACKGROUND: Magnetic resonance imaging and endoluminal ultrasound play an important role in the restaging of locally advanced rectal cancer after preoperative chemoradiotherapy, yet their diagnostic accuracy is still controversial. OBJECTIVE: Meta-analysis was performed to estimate the diagnostic performance of MRI and endoluminal ultrasound. DATA SOURCES: Electronic databases from 1996 to March 2012 were searched. STUDY SELECTION AND INTERVENTIONS: Either MRI or endoluminal ultrasound was used to restage rectal cancer after chemoradiotherapy or radiation. MAIN OUTCOME MEASURES: T category, lymph node, and circumferential resection involvement were measured. RESULTS: The sensitivity estimate for rectal cancer diagnosis (T0) by endoluminal ultrasound (37.0%; 95% CI, 24.0%-52.1%) was higher (p = 0.04) than the sensitivity estimate for MRI (15.3%; 95% CI, 6.5%-32.0%). For T3-4 category, sensitivity estimates of MRI and endoluminal ultrasound were comparable, 82.1% and 87.6%, whereas specificity estimates were poor (53.5% and 66.4%). For lymph node involvement, there was no significant difference between the sensitivity estimates for MRI (61.8%) and endoluminal ultrasound (49.8%). Specificity estimates for MRI and endoluminal ultrasound were 72.0% and 78.7%. For circumferential resection margin involvement, MRI sensitivity and specificity were 85.4% and 80.0%. LIMITATIONS: To identify the heterogeneity, metaregression was performed on covariates. However, few of the covariates were identified to be statistically significant because of the lack of adequate original data. CONCLUSION: Accurate restaging of locally advanced rectal cancer by MRI and endoluminal ultrasound is still a challenge. Identifying T0 rectal cancer by imaging is not reliable. Before performing surgery, restaging is important, but some of the T0-2 patients are likely overestimated as T3-4. Both modalities for lymph node involvement are not very good. Magnetic resonance imaging may be a good method to reassess circumferential resection margin.

Enhancing biohydrogen production from xylose at low temperature (20 °C) using natural FeS2 Ore: Thermodynamic analysis and mechanistic insights.

This study investigates the efficacy of pyrite in enhancing biohydrogen production from xylose at low temperature (20 °C). Higher hydrogen yield rates (Rm) and reduced lag time (λ) were achieved across initial xylose concentrations ranging from 2-10 g/L. At an optimal xylose concentration of 5 g/L, pyrite reduced λ by 2.5 h and increased Rm from 1.3 to 2.7 mL h-1. These improvements are attributed to pyrite's ability to enhance the secretion of extracellular polymeric substance and flavins, facilitate NADH and NAD+ generation and transition, and favor biohydrogen production. Thermodynamic analyses and Gibbs free energy calculations further elucidated pyrite's role in the full reaction process and rate-limiting steps at low temperature. This study offers valuable insights into improving the efficiency of biohydrogen production at low temperature, with significant implications for energy conservation.

Sperm morphological abnormalities in autosomal dominant polycystic kidney disease are associated with the Hippo signaling pathway via PC1.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder mostly caused by mutations in PKD1 or PKD2 genes. Here, we report thirteen ADPKD males with infertility and investigated the sperm morphological defects associated with PC1 disruption. Methods: Targeted next-generation sequencing was performed to detect PKD1 variants in patients. Sperm morphology was observed by immunostaining and transmission electron microscopy, and the sperm motility was assessed using the computer-assisted sperm analysis system. The Hippo signaling pathway was analyzed with by quantitative reverse transcription polymerase chain reaction (qPCR) and western blotting in vitro. Results: The ADPKD patients were infertile and their sperm tails showed morphological abnormalities, including coiled flagella, absent central microtubules, and irregular peripheral doublets. In addition, the length of sperm flagella was shorter in patients than in controls of in in. In vitro, ciliogenesis was impaired in Pkd1-depleted mouse kidney tubule cells. The absence of PC1 resulted in a reduction of MST1 and LATS1, leading to nuclear accumulation of YAP/TAZ and consequently increased transcription of Aurka. which might promote HDAC6-mediated ciliary disassembly. Conclusion: Our results suggest the dysregulated Hippo signaling significantly contributes to ciliary abnormalities in and may be associated with flagellar defects in spermatozoa from ADPKD patients.

Associations Between Asthma and Polycystic Ovary Syndrome: Current Perspectives.

A potential correlation between polycystic ovary syndrome (PCOS) and asthma, used to be identified as diseases originating from two independent systems, has been supported by increasing evidence. From an epidemiological perspective, mounting studies have confirmed that women suffering from PCOS exhibit increased susceptibility to asthma. Meanwhile, PCOS and asthma seem to share several mutual pathological conditions, such as metabolic disorders, hormonal fluctuation, proinflammatory state, etc. Here, we further elucidate the correlation between asthma and PCOS by focusing on the internal common pathophysiology and adverse influences on women's health. Understanding the internal connection between PCOS and asthma may shed light on developing new prevention and control strategies to fight against these conditions.

Associations of Sperm mtDNA Copy Number, DNA Fragmentation Index, and Reactive Oxygen Species With Clinical Outcomes in ART Treatments.

Recent studies have suggested that sperm mitochondrial DNA copy number (mtDNA-CN), DNA fragmentation index (DFI), and reactive oxygen species (ROS) content are crucial to sperm function. However, the associations between these measurements and embryo development and pregnancy outcomes in assisted reproductive technology (ART) remain unclear. Semen samples were collected from 401 participants, and seminal quality, parameters of sperm concentration, motility, and morphology were analyzed by a computer-assisted sperm analysis system. DFI, mtDNA-CN, and ROS levels were measured using sperm chromatin structure assay, real-time quantitative polymerase chain reaction, and ROS assay, respectively. Among the participants, 126 couples underwent ART treatments, including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), and 79 of the couples had embryos transferred. In 401 semen samples, elevated mtDNA-CN and DFI were associated with poor seminal quality. In 126 ART couples, only mtDNA-CN was negatively correlated with the fertilization rate, but this correlation was not significant after adjusting for male age, female age, seminal quality, ART strategy, number of retrieved oocytes, controlled stimulation protocols, and cycle rank. Regarding pregnancy outcomes, sperm mtDNA-CN, ROS, and DFI were not associated with the clinical pregnancy rate or live birth rate in 79 transferred cases. In conclusion, increased mtDNA-CN and DFI in sperm jointly contributed to poor seminal quality, but sperm mtDNA-CN, ROS, and DFI were not associated with clinical outcomes in ART.

lncRNA MIR503HG inhibits cell proliferation and promotes apoptosis in TNBC cells via the miR-224-5p/HOXA9 axis.

Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer. This study investigated the molecular mechanism and influences of MIR503HG, miR-224-5p, and homeobox A9 (HOXA9) on TNBC cell growth and migration. Dual-luciferase reporter gene and RNA immunoprecipitation were performed to examine the regulation of MIR503HG, miR-224-5p, and HOXA9. Cell proliferation, apoptosis, migration, and invasion were evaluated by colony formation, flow cytometry, and Transwell assays. Finally, nude mice were employed to investigate the influence of MIR503HG on TNBC tumor growth. HOXA9 protein levels were detected by immunohistochemical staining. MIR503HG and HOXA9 expression were reduced in TNBC, while miR-224-5p was increased. Overexpression of MIR503HG or HOXA9 reduced the cell migration ability and proliferation and promoted apoptosis, and knockdown of MIR503HG or overexpression of miR-224-5p exhibited the opposite effects. Furthermore, MIR503HG promoted HOXA9 expression by inhibiting miR-224-5p. Overexpression of miR-224-5p reversed the effects of MIR503HG overexpression on TNBC cells, while overexpression of HOXA9 reversed the effect of MIR503HG knockdown. Additionally, an in vivo study proved that MIR503HG inhibited TNBC tumor growth via the miR-224-5p/HOXA9 axis. MIR503HG inhibited cell proliferation and promoted the apoptosis of TNBC cells via the miR-224-5p/HOXA9 axis, which may function as a novel target for the treatment of TNBC.

Different Strategies of Preimplantation Genetic Testing for Aneuploidies in Women of Advanced Maternal Age: A Systematic Review and Meta-Analysis.

BACKGROUND: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. METHOD: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). RESULTS: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03-1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04-1.79). CONCLUSION: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy.

Association between gestational anemia in different trimesters and neonatal outcomes: a retrospective longitudinal cohort study.

BACKGROUND: Previous studies investigated the association between gestational anemia and neonatal outcomes. However, few studies explored whether the effects of gestational anemia could be eliminated by subsequent correction of anemia in the later stages of pregnancy. This study aimed to investigate the relationship between anemia in different trimesters and neonatal outcomes. METHODS: The study was conducted in Shanghai, China, with a sample of 46,578 pregnant women who delivered between January 1, 2016 and July 1, 2019. A multivariable logistic regression model was adopted to analyse the associations between maternal anemia and neonatal outcomes. RESULTS: The incidence of gestational anemia was 30.2%, including 4.4% in the first trimester, 9.6% in the second trimester, and 16.2% in the third trimester. Only 24.5% (507/2066) of anemia that occurred in the first trimester and 29.6% (1320/4457) that occurred in the second trimester could be corrected in the later stages of pregnancy. Anemia occurring in the first trimester was associated with small for gestational age [odds ratio (OR) 1.46; 95% confidence interval (CI) 1.20-1.78] and with fetal distress (OR 1.23; 95% CI 1.08-1.40). Anemia corrected in the first trimester also was associated with a higher risk of small for gestational age. CONCLUSIONS: Gestational anemia is a public health problem in China impacting neonatal health. Anemia in pregnancy could be corrected in only about a quarter of the women. Anemia in the first trimester, whether corrected or not, still led to lower birth weight; therefore, the prevention of anemia prior to pregnancy is important.

Case Report: Preimplantation Genetic Testing and Pregnancy Outcomes in Women With Alport Syndrome.

BACKGROUND: Alport syndrome, a monogenic kidney disease, is characterized by progressive hemorrhagic nephritis, sensorineural hearing loss, and ocular abnormalities. Mutations in COL4A5 at Xq22 accounts for 80-85% of X-linked Alport syndrome patients. Three couples were referred to our reproductive genetics clinic for prenatal or preconception counseling. METHODS: Prenatal diagnoses were performed by amplifying targeted regions of COL4A5. Targeted next-generation sequencing (NGS)-based haplotype analysis or karyomapping was performed in two patients. Pregnancy outcomes in the three patients were collected and analyzed. Published Alport syndrome cases were searched in Pubmed and Embase. RESULTS: Prenatal diagnoses in two cases showed one fetus harbored the same pathogenic mutation as the proband and the other was healthy. The couple with an affected fetus and the patient with a family history of Alport syndrome chose to take the preimplantation genetic testing (PGT) procedure. One unaffected embryo was transferred to the uterus, and a singleton pregnancy was achieved, respectively. Two patients presented non-nephrotic range proteinuria (<3 g/24 h) during pregnancy and the three cases all delivered at full-term. However, published Alport cases with chronic kidney disease or proteinuria during pregnancy were came with a high rate (75%) of adverse maternal and fetal outcomes. CONCLUSION: The PGT procedure performed in this study was proven to be practicable and might be expanded to be applied in other monogenic diseases. Moderate or severe renal impairments in Alport syndrome were strongly associated with adverse maternal and fetal outcomes, and baseline proteinuria was a potential predictor for pregnancy outcomes of Alport syndrome as other kidney diseases.