Emerging evidence links dysbiosis in gut microbiota with metabolic irregularities in gestational diabetes mellitus (GDM). However, alterations in blood microbiome of GDM individuals remain unexplored. Blood has traditionally been regarded as a sterile compartment, yet emerging evidence of a circulating microbiome raises the possibility that it also contributes to metabolic disease. This study aims to characterize, for the first time, the blood microbiome of women with gestational diabetes mellitus (GDM) relative to healthy pregnant women using 16 S rRNA sequencing, and to determine whether microbial diversity, taxonomic composition, and predicted functional pathways differ between the two groups, thereby clarifying the potential relevance of the blood microbiome to GDM pathogenesis and biomarker development. In this case-control study, bacterial DNA was extracted from blood samples of 40 GDM patients and 40 healthy pregnant women controls. The V2, V3, V5, V6, and V8 hypervariable regions of the 16 S rRNA gene were amplified using a multiplex (5R) sequencing strategy and sequenced on an Illumina MiSeq platform. α and β diversity indices were used to compare microbial diversity between groups, linear discriminant analysis effect size (LEfSe) was used to identify differentially abundant taxa, and PICRUSt-based Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway predictions were performed to explore potential functional differences. The α diversity, as indicated by the Shannon index, exhibited a noteworthy reduction within the GDM group. We observed notable differences in β-diversity between the cohorts. The GDM group’s blood microbiome was characterized by a significant enrichment of the Nocardioidaceae and Planococcaceae families. Conversely, the microbiome of healthy pregnant controls was significantly enriched with bacteria belonging to the order Enterobacterales, notably the genus Escherichia. Furthermore, functional analysis brought to light substantial differences in 30 pathways between the two groups. Specifically, pathways linked to GDM, such as fatty acid metabolism, propionate metabolism, butyrate metabolism, and several amino acid metabolism pathways (including histidine metabolism, lysine degradation, and tryptophan metabolism), compared to their healthy counterparts were upregulated in the GDM group. In contrast, pathways associated with electron transfer carriers, transcription factors, RNA transport, the phosphotransferase system (PTS), transcriptional regulation proteins, as well as carbohydrate digestion and absorption, compared to their healthy counterparts were markedly downregulated in individuals with GDM. GDM is associated with a distinct blood microbial signature, characterized by reduced α diversity, altered β diversity, and specific taxonomic and predicted functional differences relative to healthy pregnancy. These findings suggest that circulating bacterial DNA signatures may hold promise as candidate biomarkers for GDM and warrant validation in larger, longitudinal studies incorporating direct microbiological and metabolic measurements. This study has been registered in the National Medical Research Registration and Filing Information System, with the registration number MR3324015166 (20231126).
Non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) can detect embryo chromosomal aneuploidy by analyzing the cell-free DNA in embryo culture media. However, evidence for its clinical efficacy is insufficient. In this investigator-initiated, multicenter, double-blind, randomised controlled trial, women aged 35-42 who agreed to single frozen-thawed blastocyst transfer with at least two blastocysts were enrolled from 13 fertility centers in China. Eligible participants were randomly assigned (1:1) to the niPGT-A(n = 594) or morphology group(n = 595) using a computer-generated block randomization list, stratified by participating center. In the niPGT-A group, embryos were selected for the first transfer cycle based on niPGT-A results, whereas in the morphology group, embryos were selected according to standard morphological criteria. The primary outcome was the ongoing pregnancy rate (OPR) (pregnancy beyond 12 weeks). Secondary outcomes included clinical pregnancy, miscarriage (pregnancy loss before the 28th week, with those before the 12th week as early miscarriages), and live birth rates. The trial has been completed. The modified intention-to-treat population(mITT) contained 581 couples in the morphology group and 571 in the niPGT-A group. Among 1152 randomised patients, OPR was 38.7% (221/571) in the niPGT-A group and 36.8% (214/581) in the morphology group (adjusted p = 0.49). There were no statistically significant between group differences in the rates of clinical pregnancy (47.6% vs 49.9%, adjusted p = 0.49), miscarriage (21.0% vs 27.6%, adjusted p = 0.06) and live birth (37.0% vs 35.5%, adjusted p = 0.59). Early miscarriage was significantly lower in the niPGT-A group compared with that of the morphology group (18.0% vs 25.2%, adjusted p = 0.03). Maternal and neonatal outcomes did not differ significantly between groups. No serious adverse events were reported in either group. The results indicated that there was insufficient evidence to establish a statistically significant difference in OPR between the two treatment arms. The results of this trial do not provide a basis for recommending routine use of niPGT-A in this good-prognosis population (NCT04339166). Non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) can detect embryo chromosomal aneuploidy by analyzing the cell-free DNA in embryo culture media, but evidence for clinical efficacy is insufficient. Here the authors report a randomised controlled trial involving 1,152 women aged 35–42 years that shows no difference in the primary outcome of ongoing pregnancy rate between the intervention group with niPGT-A and the control group with morphological selection.
Testicular torsion-detorsion induces testicular ischemia–reperfusion injury (TIRI), which is associated with excessive reactive oxygen species (ROS) generation. Proanthocyanidin (PC), a potent organic antioxidant, can inhibit oxidative stress. However, its inherent limitations, including poor targeting, short circulation time, and low membrane permeability, hinder its therapeutic efficacy. To overcome these limitations, a macrophage membrane-coated chitosan/hyaluronic acid (MM-CH) is developed as a biocompatible nanocarrier for encapsulating PC. Retaining critical macrophage membrane proteins, this biomimetic nanotherapeutic (MM-PC-CH) prolongs circulation and enhances active targeting to the injured testis. MM-PC-CH was effectively internalized by Sertoli cells. The activities of SOD, CAT and MDA, as well as the levels of IL-6, TNF-α and IL-10, apoptosis by flow cytometry and TUNEL assay were evaluated. The results demonstrated significant antioxidant, anti-inflammatory and anti-apoptotic effects, as well as inhibition of lactate levels. In vivo evaluations confirm that injected MM-PC-CH specifically accumulates in the injured testis, providing robust testicular protection and effectively alleviating TIRI. This study presents a promising biomimetic nanotherapy for alleviating testicular torsion by enhancing the targeted delivery of proanthocyanidin, providing an innovative strategy for precise treatment of various reproductive diseases with clinical translational value.
OBJECTIVE:The aim of this study was to compare the aneuploidy rates of blastocysts obtained via conventional in vitro fertilization (IVF) using sperm prepared by the swim-up (SU) and density gradient centrifugation (DGC) methods, as detected by non-invasive chromosomal screening (NICS). This comparison would provide more evidence for selecting the appropriate semen processing technique for patients undergoing conventional IVF with NICS. METHODS:A retrospective analysis was conducted on patients who underwent conventional IVF and NICS at our hospital from January 2022 to May 2024.Patients were grouped by semen - processing method (SU and DGC groups). Semen parameters before and after processing on oocyte - retrieval day, oocyte numbers (retrieved, MII), and 2PN embryos were compared. Fertilization, cleavage, D3 high - quality embryo, embryo ploidy, and aneuploidy rates between the two groups were analyzed. RESULTS:There were no statistically significant differences in multiple indicators such as the number of retrieved oocytes between the two groups (P > 0.05); the rate of high-quality embryos on Day 3 in the DGC group was significantly higher than that in the SU group (53.9 % vs. 48.20 %, P = 0.011).The proportion of embryos with Grade A in the DGC group was 31.8 % (262/824), while that in the SU group was 39.4 % (119/302), showing a statistical difference (P = 0.017). The euploidy rate in the DGC group was 21.7 % (179/824) and the aneuploidy rate was 71.2 % (587/824), while the euploidy rate in the SU group was 25.8 % (78/302) and the aneuploidy rate was 68.9 % (208/302). There was no significant difference between the two groups (P > 0.05). CONCLUSION:The SU method yielded a higher proportion of Grade A embryos but did not reduce aneuploidy rates, suggesting its potential as a simpler, cost-effective alternative to DGC for NICS in conventional IVF.
Does non-invasive preimplantation genetic testing (niPGT) increase the ongoing pregnancy rate among women without good-grade blastocysts? In women lacking good-grade blastocysts, embryo transfer based on niPGT could significantly reduce early miscarriage rate and increase ongoing pregnancy rate compared with morphology-based selection. The pregnancy success rate of assisted reproductive technology is influenced by the quantity of blastocysts retrieved. Blastocyst quality tends to decrease as the maternal age increases, particularly for women over the age of 35. Our previous studies have found that embryo selection based on niPGT decreased early miscarriage and improved the live birth rate for some specified patients, such as those with recurrent pregnancy loss. The clinical efficacy of niPGT in women of advanced maternal age(AMA), especially those without good-quality blastocysts, needs further investigation. We conducted a cohort study involving 1,312 patients between April 2020 and August 2024. The data were derived from a multicenter randomized controlled trial (registration number: NCT04339166). Blastocysts were grouped into three quality categories: good- (AA, AB, or BA), moderate- (BB), and low-grade (C for either inner cell mass or trophectoderm). Patients were then divided into three groups: those with only low-grade blastocysts, those only with moderate- or low-grade embryos, and those with good-grade blastocysts. 1,132 women aged 35-42 undergoing single frozen-thawed blastocyst transfer were enrolled for blastocyst quality distribution analysis. Blastocysts were cultured individually. Spent culture mediums (SCM) from Day 4 to Day 5/6/7 were collected for niPGT. Embryos were graded A, B, or C based on their euploidy probability. Clinical outcomes of the first embryo transfer cycles were compared between patients who transferred grade A or B embryos in the niPGT group and those in the morphology group. Among the 1,312 patients, 19.7% (259) had only low-grade blastocysts, 41.7% (547) only had moderate- or low-grade blastocysts, and 38.6% (506) had high-quality embryos. Among the patients who had only low-grade blastocysts, the early miscarriage rate in the niPGT group was significantly lower than that in the morphology group (13.0%, 3/23 vs 42.9%, 12/28; p = 0.020). The ongoing pregnancy and live birth rates were higher in the inPGT group, although the differences were not significant (30.8%, 20/65 vs. 21.3%,16/75; p = 0.203). Among the patients who had only moderate- or low-grade embryos, the miscarriage rate was significantly lower in the niPGT group (19.3%,27/140 vs 44/148,29.7%, p = 0.040), the ongoing pregnancy rate was 38.2% (112 of 293) in the niPGT group and 30.8% (102 of 331) in the morphology group(p = 0.055). The live birth rate was higher in the niPGT group (36.2%,106/293 vs 30.2%, 100/331, p = 0.114). Among the patients with good-grade blastocysts, there were no significant differences between the niPGT and morphology groups in early pregnancy loss (14.0%,17/121 vs 20.6%,29/141, p = 0.167), ongoing pregnancy (49.3%,104/211 vs 45.5%,111/244, p = 0.418), or live birth rate (47.4%,100/211 vs 43.4%,106/244, p = 0.399). Due to a post-hoc subgroup analysis of randomized clinical trials, residual confounding could not be excluded. In addition, the inter- and intra-operator variations in blastocyst grading were difficult to control. AMA women have a higher probability of lacking good-quality blastocysts. Women in this situation may benefit from niPGT. Our findings suggest that niPGT can effectively reduce early miscarriage rates. Therefore, AMA patients should consider preserving SCMs for niPGT to improve clinical outcomes when high-quality blastocysts are unavailable for transfer. No
Introduction:Nitric oxide (NO) plays a pivotal role in female reproductive processes, yet its clinical translation is limited by its short half-life and rapid systemic clearance. This study aimed to develop a stabilized NO delivery system to enhance oocyte maturation and quality for potential applications in assisted reproductive technologies (ART). Methods:Lipid-based microbubbles (NO-MBs) were constructed via lyophilization to encapsulate and stabilize therapeutic NO gas. The effects of NO-MBs on in vitro oocyte maturation were evaluated using immature mouse oocytes, with conventional NO donors (e.g., SNP) as controls. Oocyte quality was assessed through Ca2+ levels, mitochondrial membrane potential (MMP), and intracellular reactive oxygen species (ROS). In vivo studies further examined oocyte retrieval, fertilization rates, and blastocyst cell apoptosis. Mechanistic investigations focused on the ERK signaling pathway. Results:The key parameters of the optimized lipid-based microbubbles for NO gas delivery were as follows: particle concentration (2.23 × 10⁷ MBs/mL) and diameter (0.919 ± 0.807 μm). NO-MBs demonstrated superior biosafety and efficacy compared to conventional NO donors. In vitro, NO-MBs significantly increased the maturation rate of immature mouse oocytes (72.00% vs. 57.77% in controls) while improving oocyte quality, as evidenced by elevated Ca2+ levels, enhanced MMP, and reduced ROS. In vivo, NO-MBs enhanced oocyte retrieval and fertilization rates and reduced blastocyst cell apoptosis. Mechanistically, NO-MBs uniquely activated phosphorylated ERK, suggesting ERK pathway involvement in oocyte maturation. Discussion:These findings highlight NO-MBs as a novel, clinically relevant strategy for targeted NO delivery in reproductive medicine. By optimizing NO release and bioavailability, NO-MBs offer a promising approach to improve oocyte quality and developmental outcomes in ART. Further studies are warranted to explore their broader applications in reproductive health.
BACKGROUND:During the process of sperm cryopreservation, the overproduction of reactive oxygen species (ROS) triggers oxidative stress thereby leading to a reduction in sperm motility and quality. Therefore, it is a feasible strategy to mitigate oxidative damage during cryopreservation by adding antioxidants to freezing media. RESEARCH DESIGN AND METHODS:In this study, we explored the potential of melatonin to protect sperm from oxidative stress-induced damage by evaluating sperm-related parameters after thawing through self-assembly with a hyaluronic acid-bilirubin conjugate into nanoparticles (M@HBn). RESULTS:The optimized M@HBn exhibited uniform spherical morphology with average particle size of 112.57 ± 9.8 nm, PDI of 0.22 ± 0.02, a surface potential of - 0.43 ± 1.02 mV and entrapment efficiency of 85.1 ± 4.6%. The addition of 5 μM M@HBn demonstrated a notable enhancement in frozen-thawed human spermatozoa viability, motility, and DNA integrity by scavenging ROS. Additionally, the use of M@HBn supplementation in freezing medium resulted in the most mitochondrial stability and total viability as compared to the other groups. CONCLUSIONS:These findings suggest that M@HBn have the potential to serve as a novel drug delivery platform for protecting spermatozoa against from cryodamage while enhancing the quality of cryopreserved sperm and the bioavailability of melatonin.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder with significant impacts on women’s reproductive health. Interleukin (IL)-2 receptor subunit gamma (IL2RG), a common receptor for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, has been shown to interrupt estrous cycle, yet its role in PCOS remains unclear. The evaluated expression levels of IL2RG in human granulosa cells (GCs) and IL2RG-dependent cytokines (IL-2, IL-4, IL-15) in follicular fluid were demonstrated in 18 PCOS patients and 22 control subjects. The positive correlation between IL2RG and PCOS was analysed through GEO databases. In vivo, we found that in the PCOS model (6 mg/100 g body-weight of dehydroepiandrosterone subcutaneous injection for 21 days), the ovarian index, testosterone, glucose, and LH/FSH levels were elevated, and the estrous cycle was disrupted. Knocking down IL2RG (KO) restored the above levels. However, in the dehydroepiandrosterone-treated group, these levels did not recover even after IL2RG was knocked-down. The decreased expression of Gasdermin E (GSDME) but increased caspase-3 level in IL2RG KO rats compared with WT were found. In vitro, knockdown of IL2RG by siRNA inhibited caspase-3-mediated GSDME cleavage in testosterone-induced KGN cells. Furthermore, the caspase-3 inhibitor Z-DEVD-FMK and the caspase-1 inhibitor Belnacasan alleviated pyroptosis in testosterone-induced KGN cells by lactate dehydrogenase test, fluorescence assay, and flow cytometry. IL2RG is expressed higher in PCOS patients, exerting an inhibitory effect on caspase-3-mediated GSDME cleavage upon knockdown. However, the knockout of IL2RG led to the conversion of GSDME-mediated pyroptosis into apoptosis. This study explores the function of IL2RG and provides insights for therapeutic targets in PCOS.
Assisted reproductive technology (ART) is the most effective method to treat infertility and the pathogenesis of implantation failure after in vitro fertilization-embryo transfer (IVF-ET) is a challenging filed in infertility. Microbes in the female reproductive tract are considered to be associated with gynecological and obstetric diseases. However, its effects on embryo implantation failure are unsured. This study aimed to investigate reproductive tract dysbiosis, identify different bacteria in reproductive tract as potential biomarkers of embryo implantation failure and demonstrate the pathogenesis through metabolites analysis. We compared the data from 16S rRNA gene and metagenome in reproductive tracts through QIIME2 and HUMAnN2 by the times of embryo implantation failure on 239 infertile patients and 17 healthy women. Our study revealed a strong positive correlation between Lactobacillus abundance and embryo implantation success (IS) after IVF-ET. The microbial community composition and structure in reproductive tract showed substantially difference between the embryo implantation failure (IF) and healthy control. Moreover, we established a diagnostic model through receiver operating characteristic (ROC) with 0.913 area under curve (AUC) in IS and multiple implantation failures (MIF), verified its effectiveness with an AUC = 0.784 demonstrating microbial community alterations could efficiently discriminate MIF patients. Metagenome functional analyses of vaginal samples from another independent infertile patients after IVF-ET revealed the L-lysine synthesis pathway enriched in IF patients, along with ascended vaginal pH and decreased Lactobacillus abundance. This study clarifies several independent relationships of bacteria in vagina and endometrial fluid on embryo implantation failure and undoubtedly broadens the understanding about female reproductive health.
This study was designed to evaluate pregnancy outcomes between morulae transferred on day 4 (D4) and blastocysts transferred on day 5 (D5). From September 2017 to September 2020, 1963 fresh transfer cycles underwent early follicular phase extra-long protocol for assisted conception in our fertility center were divided into D4 (324 cases) and D5 (1639 cases) groups, and the general situation and other differences of patients in both groups were compared. To compare the differences in pregnancy outcomes, the D4 and D5 groups were further divided into groups A and B based on single and double embryo transfers. Furthermore, the cohort was divided into two groups: those with live births (1116 cases) and those without (847 cases), enabling a deeper evaluation of the effects of D4 or D5 transplantation on assisted reproductive outcomes. In single embryo transfer, there was no significant difference between groups D4A and D5A (P > 0.05). In double embryo transfer, group D4B had a lower newborn birthweight and a larger proportion of low birthweight infants (P < 0.05). The preterm delivery rate, twin delivery rate, cesarean delivery rate, and percentage of low birthweight infants were lower in the D5A group than in the D5B group (P < 0.05). Analysis of factors influencing live birth outcomes further confirmed the absence of a significant difference between D4 and D5 transplantation in achieving live birth (P > 0.05). When factors such as working life and hospital holidays are being considered, D4 morula transfer may be a good alternative to D5 blastocyst transfer. Given the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) success rate and risk of twin pregnancy, D4 morula transfer requires an adapted decision between single and double embryo transfer, although a single blastocyst transfer is recommended for the D5 transfer in order to decrease the twin pregnancy rate. In addition, age, endometrial thickness and other factors need to be taken into account to personalize the IVF program and optimize pregnancy outcomes.
PURPOSE:To investigate the relationship between blood lead levels (BLLs) and IVF clinical outcomes in infertile females and to further explore the possible involvement of granulosa cell (GC) endoplasmic reticulum (ER) stress in the process.METHODS:One hundred twenty-three infertile women undergoing IVF cycles were included in the current study. All participants were divided into three (low, medium, and high) groups determined by BLL tertiles. Gonadotropin releasing hormone (GnRH) agonist regimen for ovarian stimulation was used for all patients, with follicular fluids being collected on the day of oocyte retrieval. Lactate dehydrogenase (LDH) levels in follicular fluid and the endoplasmic reticulum stress-signaling pathway of granulosa cells (GCs) were examined.RESULTS:The oocyte maturation rate and high-quality embryo rate on cleaved stage decreased significantly as BLL increased. For lead levels from low to high, live birth rate (68.29%, 56.10%, 39.02%; P=0.028) showed negative correlations with BLLs. Also, follicular fluid Pb level and LDH level was significantly higher in the high lead group versus the low group. Binomial regression analysis revealed significant negative correlation between BLLs and live birth rate (adjusted OR, 0.38; 95% CI, 0.15-0.95, P=0.038). Further analysis of the endoplasmic reticulum stress (ER stress) signaling pathway of GCs found that expressions of GRP78, total JNK, phosphorylated JNK, and CHOP increased and BCL-2 decreased with increasing BLLs.CONCLUSIONS:BLLs are negatively associated with final clinical outcomes in IVF patients that may be related to increased ER stress response and GC apoptosis. Thus, reducing Pb exposure before IVF procedures may improve final success rates.
In assisted reproduction techniques, oocytes encounter elevated levels of reactive oxygen species (ROS) during in vitro maturation (IVM). Oxidative stress adversely affects oocyte quality, hampering their maturation, growth, and subsequent development. Thus, mitigating excessive ROS to safeguard less viable oocytes during IVM stands as a viable strategy. Numerous antioxidants have been explored for oocyte IVM, yielding considerable effects; however, several aspects, including solubility, stability, and safety, demand attention and resolution. In this study, we developed nanoparticles by self-assembling endogenous bilirubin and melatonin hormone coated with bilirubin-conjugated glycol chitosan (MB@GBn) to alleviate oxidative stress and enhance oocyte maturation. The optimized MB@GBn exhibited a uniform spherical shape, measuring 128 nm in particle size, with a PDI value of 0.1807 and a surface potential of +11.35 mV. The positively charged potential facilitated nanoparticle adherence to the oocyte surface through electrostatic interaction, allowing for functional action. In vitro studies demonstrated that MB@GB significantly enhanced the maturation of compromised oocytes. Further investigation revealed MB@GB's effectiveness in scavenging ROS, reducing intracellular calcium levels, and suppressing mitochondrial polarization. This study not only offers a novel perspective on nano drug delivery systems for biomedical applications but also presents an innovative strategy for enhancing oocyte IVM.
PurposePropofol, a widely utilized anesthetic, is employed to alleviate pain and anxiety in outpatient oocyte retrieval procedures. However, its potential impact and safety profile in the context of in vitro fertilization and embryo transfer (IVF-ET) remain unclear.MethodsThis retrospective study enrolled 1187 patients undergoing IVF-ET, and divided into two groups depending on whether they received propofol (propofol group, n=140) or not (control group, n=1047) for anesthesia during oocyte retrieval.ResultsThe baseline characteristics were comparable between the groups. Compared with control group, the number of oocytes retrieved in propofol group was more (p=0.012), while both the estradiol (E2) level on the trigger day and the pre-ovulatory follicle count were higher in propofol group ((p<0.01). Additionally, the rate of preterm delivery was significantly higher in the propofol group (p<0.001). To further analyze the effect of propofol on the oocyte retrieval rate, patients were divided into three subgroups depending on the pre-ovulatory follicle count (≤10, 11–20, and >20) to eliminate the influence of inconsistency in the estimation of the pre-ovulatory follicle count between the two groups. Analysis revealed that the use of propofol during oocyte retrieval was particularly advantageous in the subgroup with a pre-ovulatory follicle count of 11–20, yielding a higher oocyte retrieval rate (p<0.001).ConclusionThe use of propofol in oocyte retrieval did not adversely affect fertilization, embryo quality, or clinical outcomes. Moreover, it was found to increase the oocyte retrieval rate among patients with an estimated pre-ovulatory follicle count of 11–20. These findings offer valuable evidence supporting the clinical application of propofol in oocyte retrieval procedures.
The scheme of NO microbubble hydrogel for testicular transplantation. Nitric oxide microbubble hydrogel promoted angiogenesis and functional recovery of grafts.
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of the graft will reinstate the deficit. The data presented represents the current status of the study.
OBJECTIVE Infertile people undergoing assisted reproductive technology (ART) treatment in China may experience severe infertility-related stress and illness anxiety (IA). However, little relevant research has been conducted until now. DESIGN This study investigated the IA of 340 infertile people undergoing ART treatment, including 43 males, 292 females and 5 who preferred not to answer, in 2 tertiary general public hospitals in Wen Zhou, China. MAIN OUTCOME MEASURES Blood samples for thyroid-stimulating hormone (TSH) levels were obtained from 107 women to explore the relationship between IA and TSH. The questionnaire contained the Mandarin version of the Fertility Problem Inventory, the Resilient Trait Scale for Chinese Adults and the Whiteley Index, measuring infertility stress, resilience and IA, respectively. RESULTS An incidence rate of 44.1% of IA among infertile people undergoing ART treatment in China was determined, and 30.2% of men and 46.6% of women had severe IA (χ2 = 4.05, p < 0.05). The risk of severe IA in women was around twice that in men (OR = 2.01, 95% CI: 1.01-4.01). Women's IA level was significantly associated with their TSH level (β = 0.27, p < 0.01). Resilience played a moderating role in the relationship between parenthood importance and illness anxiety. CONCLUSION This study highlighted the importance and urgency of providing holistic care for illness anxiety of infertile people undergoing ART treatment in China, especially women. The findings of this study indicated that mind-body therapies and resilience empowerment workshops could be conducive to infertile people's holistic health.