Objective:To evaluate the impact of oral melatonin on clinical pregnancy outcomes in elderly infer-tile patients with diminished ovarian reserve(DOR)after in vitro fertilization and embryo transfer(IVF-ET).Methods:Sixty-two elderly infertile patients with DOR who underwent IVF at the Reproductive Medicine Center of Qinghai Province People's Hospital from January 1,2022 to June 30,2023 were selected.They were divided into intervention group(24 cases)and control group(38 cases)according to whether they received oral melatonin pretreatment before ovulation induction.Follicular fluid without diluent or blood contamination was collected from the first large follicle on the day of oocyte retrieval,and melatonin levels and 8-hydroxy-2'-deoxyglycoside(8-OHdG)levels in the follicular gluid were measured.Ovulation promotion indicators and pregnancy outcomes were compared and analyzed between the two groups.Results:The concentration of melatonin in follicular fluid in the intervention group was significantly higher than that in the control group(31.75 ng/L vs.10.40 ng/L,P＜0.001),the concentration of 8-OHdG was lower than that of the control group(133.61 ng/L vs.145.30 ng/L,P=0.004);the implantation rate in the intervention group was significantly higher than that in the control group(56.10％vs.26.87％,P=0.002),and the biochemical pregnancy rate in the intervention group was significantly higher than that in the control group(12.50％vs.0,P=0.050).There were no significant differences in normal fertilization rate,high-quality embryo rate,clinical pregnancy rate and cumulative live birth rate between the two groups(P＞0.05).Conclusions:Oral melatonin can increase its level in follicular fluid,which is beneficial in improving endom-etrial receptivity,and has a certain positive effect on improving IVF-ET outcomes.

Successful embryo implantation requires high-quality embryos and endometrium with high receptivity. However, there is no universally recognized authoritative technique for evaluating endometrial receptivity (ER) at present. In recent years, the application of artificial intelligence (AI) technology in the assessment of ER has achieved remarkable progress. In ultrasound image analysis, AI has improved the accuracy of endometrial segmentation and measurement through deep learning technology, and can combine clinical data for pregnancy outcome prediction. In histological analysis, AI algorithms can quickly and accurately identify histological features of the endometrium and analyze the ratio of epithelial and stromal cells. In genomic diagnosis, AI analyzes endometrial gene expression through machine learning methods to provide scientific basis for personalized embryo transfer. Although AI shows great potential in the assessment of ER, its application still faces challenges such as data standardization and algorithm generalization ability. In the future, through multi-center data sharing and algorithm optimization, AI is expected to play a greater role in assisted reproductive technology. This article reviews the application of AI in ER assessment, summarizes the latest research progress, and provides references for further research.

Objective:To investigate the prevalence of infertility and the factors affecting it in women of reproductive age in Qinghai Province.Methods:From July to December 2024, a multi-stage stratified cluster random sampling approach was used to recruit women aged 20-49 years in 10 districts across 8 cities in Qinghai Province for a questionnaire survey assessing the prevalence of infertility. Univariate and multivariate binary logistic regression analyses were then performed to identify factors associated with infertility in Qinghai Province.Results:A total of 3 925 questionnaires were distributed, with 3 837 valid responses ultimately collected. Preliminary screening identified 581 infertility cases, yielding an infertility rate of approximately 15.1%. Among these, 170 cases were primary infertility and 411 were secondary infertility, accounting for 29.26% and 70.74% of infertility cases, respectively. The highest infertility rate was observed in Yushu City, Yushu Prefecture, at 26.1% (71/272), followed by Chengxi District, Xining City at 25.3% (174/688). The lowest infertility rate was recorded in Delingha City, Haixi Prefecture, at only 2.9% (9/311). Univariate analysis revealed that household registration status ( P<0.001), age ( P=0.016), age at marriage ( P=0.001), highest educational attainment ( P<0.001), per capita annual income ( P=0.001), body mass index (BMI, P=0.005), altitude ( P<0.001), age at menarche ( P=0.011), menstrual regularity ( P<0.001), menstrual cycle ( P=0.001), menstrual duration ( P<0.001), presence of blood clots ( P<0.001),whether the women smoking ( P=0.008), whether the women staying up late ( P=0.022), and whether the husband staying up late ( P<0.001) were independent factors for infertility. Multivariate binary logistic regression analysis revealed that non-agricultural household registration ( OR=1.637, 95% CI: 1.304-2.054, P<0.001), BMI≥24.0 kg/m2 ( OR=1.326, 95% CI: 1.077-1.632, P=0.008), age at menarche >14 years ( OR=1.405, 95% CI: 1.158-1.705, P=0.001), irregular menstrual cycles ( OR=1.512, 95% CI: 1.127-2.029, P=0.006), menstrual cycle <21 d ( OR=1.572, 95% CI: 1.237-1.998, P<0.001), menstrual duration <7 d ( OR=2.080, 95% CI: 1.529-2.831, P<0.001), and smoking ( OR=2.359, 95% CI: 1.056-5.271, P=0.036) were independent risk factors for infertility. Age and altitude were not independent risk factors for infertility in Qinghai Province. Conclusion:The prevalence of infertility in Qinghai Province is approximately 15.1%. Non-agricultural household registration, BMI≥24.0 kg/m2, age at menarche >14 years, irregular menstrual cycles, menstrual cycle <21 d, menstrual duration <7 d, and smoking are factors influencing infertility, while high altitude does not increase the risk of infertility among women in Qinghai Province.

Successful embryo implantation requires high-quality embryos and endometrium with high receptivity. However, there is no universally recognized authoritative technique for evaluating endometrial receptivity (ER) at present. In recent years, the application of artificial intelligence (AI) technology in the assessment of ER has achieved remarkable progress. In ultrasound image analysis, AI has improved the accuracy of endometrial segmentation and measurement through deep learning technology, and can combine clinical data for pregnancy outcome prediction. In histological analysis, AI algorithms can quickly and accurately identify histological features of the endometrium and analyze the ratio of epithelial and stromal cells. In genomic diagnosis, AI analyzes endometrial gene expression through machine learning methods to provide scientific basis for personalized embryo transfer. Although AI shows great potential in the assessment of ER, its application still faces challenges such as data standardization and algorithm generalization ability. In the future, through multi-center data sharing and algorithm optimization, AI is expected to play a greater role in assisted reproductive technology. This article reviews the application of AI in ER assessment, summarizes the latest research progress, and provides references for further research.

Objective:To investigate the prevalence of infertility and the factors affecting it in women of reproductive age in Qinghai Province.Methods:From July to December 2024, a multi-stage stratified cluster random sampling approach was used to recruit women aged 20-49 years in 10 districts across 8 cities in Qinghai Province for a questionnaire survey assessing the prevalence of infertility. Univariate and multivariate binary logistic regression analyses were then performed to identify factors associated with infertility in Qinghai Province.Results:A total of 3 925 questionnaires were distributed, with 3 837 valid responses ultimately collected. Preliminary screening identified 581 infertility cases, yielding an infertility rate of approximately 15.1%. Among these, 170 cases were primary infertility and 411 were secondary infertility, accounting for 29.26% and 70.74% of infertility cases, respectively. The highest infertility rate was observed in Yushu City, Yushu Prefecture, at 26.1% (71/272), followed by Chengxi District, Xining City at 25.3% (174/688). The lowest infertility rate was recorded in Delingha City, Haixi Prefecture, at only 2.9% (9/311). Univariate analysis revealed that household registration status ( P<0.001), age ( P=0.016), age at marriage ( P=0.001), highest educational attainment ( P<0.001), per capita annual income ( P=0.001), body mass index (BMI, P=0.005), altitude ( P<0.001), age at menarche ( P=0.011), menstrual regularity ( P<0.001), menstrual cycle ( P=0.001), menstrual duration ( P<0.001), presence of blood clots ( P<0.001),whether the women smoking ( P=0.008), whether the women staying up late ( P=0.022), and whether the husband staying up late ( P<0.001) were independent factors for infertility. Multivariate binary logistic regression analysis revealed that non-agricultural household registration ( OR=1.637, 95% CI: 1.304-2.054, P<0.001), BMI≥24.0 kg/m2 ( OR=1.326, 95% CI: 1.077-1.632, P=0.008), age at menarche >14 years ( OR=1.405, 95% CI: 1.158-1.705, P=0.001), irregular menstrual cycles ( OR=1.512, 95% CI: 1.127-2.029, P=0.006), menstrual cycle <21 d ( OR=1.572, 95% CI: 1.237-1.998, P<0.001), menstrual duration <7 d ( OR=2.080, 95% CI: 1.529-2.831, P<0.001), and smoking ( OR=2.359, 95% CI: 1.056-5.271, P=0.036) were independent risk factors for infertility. Age and altitude were not independent risk factors for infertility in Qinghai Province. Conclusion:The prevalence of infertility in Qinghai Province is approximately 15.1%. Non-agricultural household registration, BMI≥24.0 kg/m2, age at menarche >14 years, irregular menstrual cycles, menstrual cycle <21 d, menstrual duration <7 d, and smoking are factors influencing infertility, while high altitude does not increase the risk of infertility among women in Qinghai Province.

Objective:To evaluate the impact of oral melatonin on clinical pregnancy outcomes in elderly infer-tile patients with diminished ovarian reserve(DOR)after in vitro fertilization and embryo transfer(IVF-ET).Methods:Sixty-two elderly infertile patients with DOR who underwent IVF at the Reproductive Medicine Center of Qinghai Province People's Hospital from January 1,2022 to June 30,2023 were selected.They were divided into intervention group(24 cases)and control group(38 cases)according to whether they received oral melatonin pretreatment before ovulation induction.Follicular fluid without diluent or blood contamination was collected from the first large follicle on the day of oocyte retrieval,and melatonin levels and 8-hydroxy-2'-deoxyglycoside(8-OHdG)levels in the follicular gluid were measured.Ovulation promotion indicators and pregnancy outcomes were compared and analyzed between the two groups.Results:The concentration of melatonin in follicular fluid in the intervention group was significantly higher than that in the control group(31.75 ng/L vs.10.40 ng/L,P＜0.001),the concentration of 8-OHdG was lower than that of the control group(133.61 ng/L vs.145.30 ng/L,P=0.004);the implantation rate in the intervention group was significantly higher than that in the control group(56.10％vs.26.87％,P=0.002),and the biochemical pregnancy rate in the intervention group was significantly higher than that in the control group(12.50％vs.0,P=0.050).There were no significant differences in normal fertilization rate,high-quality embryo rate,clinical pregnancy rate and cumulative live birth rate between the two groups(P＞0.05).Conclusions:Oral melatonin can increase its level in follicular fluid,which is beneficial in improving endom-etrial receptivity,and has a certain positive effect on improving IVF-ET outcomes.

Objective To investigate the role of PPARγ/GluT4 axis in insulin resistance(IR),cell proliferation and apoptosis of granulosa cells.Methods A total of 45 married women with PCOS who received routine IVF-ET assisted pregnancy treatment in Center of Reproductive Medicine,Qinghai Provincial People's Hospital were enrolled in this study from August 2018 to August 2020.All the patients were divided into IR group(PCOS-IR group,HOMA-IR≥2.57,n=23)and non-IR group(PCOS-NIR group,HOMA-IR<2.57,n=22)according to HOMA-IR.Meanwhile,21 married patients with infertility due to male or fallopian tube factors were enrolled as control group(Con).miR-27a mimics,miR-27a inhibitors(miR-27a inhibitor)and corresponding controls(mimics NC and inhibitor NC)transfected PCOS-IR granulosa cells,which were then divided into miR-27a mimics group,miR-27a inhibitor group,mimics-NC group and inhibitor-NC group.Double luciferase report test confirmed that miR-27a binded to PPARγ.Cell proliferation and apoptosis were detected by CCK-8 method and Annexinv-FITC/PI method.The expression of miR-27a,GluT4,PPARγ,Bax related to B lymphomas-2,Cleaved caspase-3 and B lymphomas-2(Bcl-2)were detected by RT-qPCR and Western blot respectively.Results Compared with Con group,the expression of miR-27a increased(P<0.01),while the expression of PPARγ mRNA and protein decreased in PCOS-NIR and PCOS-IR groups(P<0.01).Compared with PCOS-NIR group,the expression of miR-27a increased(P<0.05),while the expression of PPARγ mRNA and protein decreased in PCOS-IR group(P<0.01).The double luciferase report showed that there was a targeted binding site between PPARγ and miR-27a.Compared with inhibitor-NC group,the cell activity increased at 24 h,48 h,72 h and 96 h in miR-27a inhibitor group(P<0.05 or P<0.01),while the apoptosis rate decreased inmiR-27a inhibitor and mimics-NC group(P<0.05 or P<0.01).Compared with miR-27a inhibitor group,the apoptosis rate increased,and the cell activity decreased at 24,48,72 and 96 h in mimics-NC and miR-27a mimics groups(P<0.05 or P<0.01).Compared with the inhibitor-NC group,the expression of miR-27a,Bax and Cleaved caspase-3 increased(P<0.05 or P<0.01),while the expression of GluT4,PPARγ and Bcl-2 decreased in miR-27a mimics group(P<0.01).In miR-27a inhibitor group,the protein expressions of GluT4,PPARγ and Bcl-2 increased(P<0.05 or P<0.01),while miR-27a,Bax and Cleaved caspase-3 decreased(P<0.01).Compared with miR-27a inhibitor group,the expressions of miR-27a,Bax and Cleaved caspase-3 increased(P<0.01),while the expressions of GluT4,PPARγ and Bcl-2 decreased in mimics-NC and miR-27a mimics groups(P<0.05 or P<0.01).Conclusion The expression level of miRNA-27a is related to IR,cell proliferation,and apoptosis of granulosa cells,which may be related to PPARγ signal path.

Assisted reproductive technology (ART) is considered to be an important means to help infertile women get pregnant. With the development of technology, the safety of ART has been paid more and more attention. However, the neonatal pregnancy outcome of ART is worse than that of natural conception. The operation of ART may affect the development and health of offspring through epigenetic mechanisms. DNA methylation is the most studied epigenetic regulatory mechanism. This article briefly reviewed the research progress of DNA methylation in ART embryo and fetal development, aiming to provide a new idea for clinical treatment.

Assisted reproductive technology (ART) is considered to be an important means to help infertile women get pregnant. With the development of technology, the safety of ART has been paid more and more attention. However, the neonatal pregnancy outcome of ART is worse than that of natural conception. The operation of ART may affect the development and health of offspring through epigenetic mechanisms. DNA methylation is the most studied epigenetic regulatory mechanism. This article briefly reviewed the research progress of DNA methylation in ART embryo and fetal development, aiming to provide a new idea for clinical treatment.

Objective To study the effect of cyclophosphamide(CP) and its metabolites acrolein(ACR) on PTEN gene deleted on chromosome 10 after acting on ovarian cancer cellsSKOV3.Methods Different concentrations of CP and ACR were selected to act on recombinant PTEN protein.The phosphorylation activity of PTEN was detected by PNPP.The expression of PTEN protein was detected by Western blot.The binding mode of drug with protein was detected by the biotin combined with protein;meanwhile the expression change of P53/TP53 in PTEN gene pathway was analyzed.The target protein was obtained by immunoprecipitation(IP) after different drug concentrations acting on the cells.The phosphorylation activity of the target protein was detected by high performance liquid chromatography(HPLC).Results After the drug metabolites acting on recombinant PTEN protein,the phosphorylation activity was decreased with the increase of drug concentration,while the expression of ACR antibody action was increased with the drug concentration elevation.The expression of protein and biotin in different experimental groups was increased with the increase of drug concentration.The PTEN phosphorylation activity was decreased with the drug concentration increased in cells,and so did the expression of TP53 protein.Conclusion CP metabolite ACR induces the cytotoxicity by inhibiting PTEN protein phosphorylation activity.