Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.

Objective:To investigate the effect of atosiban on hemodynamic parameters of uterine arteries and clinical effect evaluation in patients with previous implantation failure undergoing frozen-thawed embryo transfer.Methods:A retrospective cohort study was conducted to analyze 298 cycles of FET in the Department of Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University from January 2021 to June 2023. Patients were categorized into atosiban group ( n=149) and control group ( n=149) according to whether administered atosiban or not. The related indicators and clinical outcomes were compared between the two groups. Hemodynamic parameters of the uterine arteries, including bilateral uterine artery peak systolic velocity/diastolic velocity (S/D), pulsatility index (PI), resistance index (RI), and serum levels of prostaglandin F2α (PGF2α) and oxytocin were compared before and after atosiban treatment. Univariate and multivariate logistic regression analysis were applied to assess the effect of atosiban on pregnancy outcomes. The effect of atosiban on live birth rate was analyzed by age stratification. Results:The implantation rate [51.92% (135/260)], the clinical pregnancy rate [67.11% (100/149)] and the live birth rate [59.06% (88/149)] in atosiban group were significantly higher than those in control group [41.13% (102/248), P=0.015; 51.01% (76/149), P=0.005; 40.27% (60/149), P=0.001]; and the early miscarriage rate [9.00% (9/100)] was lower than that of control group [19.74% (15/76), P=0.040]. Multivariate logistic regression analysis showed that atosiban was an independent influencing factor of live birth rate ( OR=2.236, 95% CI: 1.371-3.646, P=0.001). The post-treatment right uterine artery blood flow S/D [4.61 (4.00, 5.36)], PI [1.81 (1.58, 2.05)], RI [0.79 (0.75, 0.82)], and left uterine artery blood flow S/D [4.62 (3.83, 5.61)], PI (1.84±0.38), RI [0.79 (0.74, 0.82)] were all lower than those before treatment [right S/D 4.93 (4.06, 6.04), P<0.001; PI 1.93 (1.60, 2.17), P=0.001; RI 0.80 (0.76, 0.83), P<0.001; left S/D 5.05 (4.20, 6.32), P<0.001; PI 1.95±0.43, P<0.001; RI 0.81 (0.76, 0.84), P<0.001]. Besides, the levels of PGF2α [97.01 (85.15, 109.93) ng/L] and oxytocin [41.18 (37.16, 46.78) ng/L] after treatment in atosiban group were significantly lower than those before treatment [119.71 (108.85, 129.99) ng/L, P<0.001; 51.87 (46.44, 55.54) ng/L, P<0.001). Moreover, the endometrial peristalsis waves in atosiban group were significantly less after treatment [1.00 (0.00, 2.00) times/min] than before treatment [2.00 (1.00, 3.00) times/min], and the difference was statistically significant ( P<0.001). Conclusion:Atosiban can improve uterine artery blood flow and reduce endometrial peristalsis waves in women with previous implantation failure, which increases endometrial blood perfusion. Additionally, it can also reduce the levels of PGF2α and oxytocin, and optimize the pregnancy outcome of the frozen-thawed embryo transfer.

Objective:To investigate the potential effects of melatonin on improving mitochondrial function and reducing oxidative stress in granulosa cells in aged women with ovarian insufficiency in vitro, as well as explore the underlying mechanisms. Methods:Granulosa cells were extracted from waste follicular fluid obtained from patients undergoing assisted reproductive technology at the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from March to June 2022. According to the age of the patients, they were divided into two groups: the aged group (age ≥38 years old, 6 cases) and the young control group (age <35 years old, 6 cases). The mitochondrial ultrastructure of the granulosa cells was examined using transmission electron microscopy. Intracellular ATP levels were measured using an ATP detection kit, while mitochondrial DNA (mtDNA) copy number was assessed using real-time fluorescence quantitative PCR. Mitochondrial membrane potential was evaluated using the JC-1 fluorescent probe, reactive oxygen species (ROS) content was measured using the MitoSOX? Red mitochondrial oxide indicator, and protein expressions of SIRT3 and SOD2 were determined using Western blotting. According to the random number table method, samples from the aged group were randomly allocated to either the melatonin treatment group or blank control group (5 cases in each group) to assess the impact of in vitro melatonin treatment on the aforementioned mitochondrial parameters. SIRT3 in granular cells was down-regulated by transfection of siRNA, and the above indexes were detected before and after melatonin addition and compared with the negative control group. Results:In comparison to the young group, the aged group exhibited distinct differences in the ultrastructure of granulosa cell mitochondria. Specifically, the mitochondrial structure appeared unclear, with sparse and irregularly arranged ridges. Furthermore, significant reductions were observed in ATP levels ( P=0.012), mtDNA copy number ( P=0.005), and mitochondrial membrane potential ( P=0.009) in the aged group, while ROS content was increased ( P=0.003). Additionally, the levels of SIRT3 and SOD2 were significantly decreased ( P<0.001 and P=0.002, respectively). These differences were statistically significant. Following in vitro melatonin culture, improvements were observed in the mitochondrial ultrastructure, as well as increases in ATP levels ( P<0.001), mtDNA copy number ( P=0.038), and mitochondrial membrane potential ( P=0.002). Correspondingly, SIRT3 and SOD2 levels increased ( P=0.011 and P=0.031, respectively), while ROS content decreased ( P<0.001). These changes were statistically significant. After siRNA transfection, the expression of SIRT3 in the granulosa cells was significantly down-regulated ( P<0.001). After melatonin treatment, the ATP levels ( P<0.001), the mtDNA copy number ( P=0.001), and the mitochondrial membrane potential ( P<0.001) were all lower than those in the negative control group without SIRT3 downregulation, and the ROS content was higher than that in the negative control group ( P<0.001), with statistical differences. Similarly, the effects of melatonin on reducing ROS were also significantly diminished. Conclusion:In vitro melatonin culture has the potential to enhance mitochondrial function and alleviate oxidative stress in granulosa cells from aged women with ovarian insufficiency. Furthermore, in addition to its direct antioxidative properties, melatonin may regulate the levels of SIRT3 and SOD2 to reduce ROS.

Objective:To investigate the potential effects of melatonin on improving mitochondrial function and reducing oxidative stress in granulosa cells in aged women with ovarian insufficiency in vitro, as well as explore the underlying mechanisms. Methods:Granulosa cells were extracted from waste follicular fluid obtained from patients undergoing assisted reproductive technology at the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from March to June 2022. According to the age of the patients, they were divided into two groups: the aged group (age ≥38 years old, 6 cases) and the young control group (age <35 years old, 6 cases). The mitochondrial ultrastructure of the granulosa cells was examined using transmission electron microscopy. Intracellular ATP levels were measured using an ATP detection kit, while mitochondrial DNA (mtDNA) copy number was assessed using real-time fluorescence quantitative PCR. Mitochondrial membrane potential was evaluated using the JC-1 fluorescent probe, reactive oxygen species (ROS) content was measured using the MitoSOX? Red mitochondrial oxide indicator, and protein expressions of SIRT3 and SOD2 were determined using Western blotting. According to the random number table method, samples from the aged group were randomly allocated to either the melatonin treatment group or blank control group (5 cases in each group) to assess the impact of in vitro melatonin treatment on the aforementioned mitochondrial parameters. SIRT3 in granular cells was down-regulated by transfection of siRNA, and the above indexes were detected before and after melatonin addition and compared with the negative control group. Results:In comparison to the young group, the aged group exhibited distinct differences in the ultrastructure of granulosa cell mitochondria. Specifically, the mitochondrial structure appeared unclear, with sparse and irregularly arranged ridges. Furthermore, significant reductions were observed in ATP levels ( P=0.012), mtDNA copy number ( P=0.005), and mitochondrial membrane potential ( P=0.009) in the aged group, while ROS content was increased ( P=0.003). Additionally, the levels of SIRT3 and SOD2 were significantly decreased ( P<0.001 and P=0.002, respectively). These differences were statistically significant. Following in vitro melatonin culture, improvements were observed in the mitochondrial ultrastructure, as well as increases in ATP levels ( P<0.001), mtDNA copy number ( P=0.038), and mitochondrial membrane potential ( P=0.002). Correspondingly, SIRT3 and SOD2 levels increased ( P=0.011 and P=0.031, respectively), while ROS content decreased ( P<0.001). These changes were statistically significant. After siRNA transfection, the expression of SIRT3 in the granulosa cells was significantly down-regulated ( P<0.001). After melatonin treatment, the ATP levels ( P<0.001), the mtDNA copy number ( P=0.001), and the mitochondrial membrane potential ( P<0.001) were all lower than those in the negative control group without SIRT3 downregulation, and the ROS content was higher than that in the negative control group ( P<0.001), with statistical differences. Similarly, the effects of melatonin on reducing ROS were also significantly diminished. Conclusion:In vitro melatonin culture has the potential to enhance mitochondrial function and alleviate oxidative stress in granulosa cells from aged women with ovarian insufficiency. Furthermore, in addition to its direct antioxidative properties, melatonin may regulate the levels of SIRT3 and SOD2 to reduce ROS.

Objective:To explore the mechanism of peripheral blood mononuclear cells (PBMCs)-derived exosomes on improving endometrial receptivity by miR-1306.Methods:The models of mice with implantation disorders were prepared by subcutaneous injection of mifepristone. And they were divided into implantation disorder group and PBMCs intervention group, 12 mice in each group. The normal group was set up. PBMCs intervention group was given intrauterine injection of PBMCs-derived exosomes, while normal group and implantation disorder group were given the same volume of buffer solution. The pregnancy rates and number of embryos implantation in different groups were compared. The expression of miR-1306 in endometrial tissues was detected by RT-PCR. The levels of reactive oxygen species (ROS), interleukin-6 (IL-6), monocyte chemcattractant protein-1 (MCP-1) and superoxide dismutase (SOD) in endometrial tissues were detected by enzyme-linked immunosorbent assay. The expressions of pregnancy-related proteins in endometrial tissues were detected by Western blotting. The endometrial epithelial cells were divided into control group, experimental group, negative control group and miR-1306 inhibitor group. Except control group, cells were co-cultured with PBMCs-derived exosomes by Transwell in the other groups. The activity, proliferation and apoptosis of cells were detected by MTT, Edu and Annexin-V/PI flow, respectively. The level of ROS in cells was detected by kits. And expressions of the related proteins were detected by Western blotting.Results:The pregnancy rate [8.33% (1/12), number of embryos implantation [0(0, 0)], expression of miR-1306 in endometrial tissue (0.24±0.05) and SOD level [(5.66±0.72) U/mL] in implantation disorder group were significantly lower than those in normal group [100% (12/12), 16.50 (14.00, 19.00), 1.03±0.05, (8.69±1.21) U/mL, P<0.05], while levels of ROS [(4.87±0.39) U/mL], IL-6 [(116.51±5.78) ng/L] and MCP-1 in endometrial tissues [(36.84±3.56) μg/L], and expressions of KIR2DL4 (0.87±0.06), nuclear factor erythroid-2-related factor 2 (Nrf2, 0.76±0.06), Kelch-like ECH-associated protein1 (Keap1, 0.79±0.05), receptor interacting protein 1 (RIP1, 0.94±0.04) and RIP3 (0.86±0.05) were significantly higher than those in normal group [(2.41±0.19) U/mL, (83.79±6.68) ng/L, (12.32±2.09) ng/mL, 0.27±0.03, 0.31±0.05, 0.23±0.04, 0.34±0.03, 0.31±0.05, all P<0.05]. The pregnancy rate [75.00% (9/12)], number of embryos implantation [13.00 (13.00, 14.75)], expression of miR-1306 in endometrial tissues (0.82±0.05) and SOD level [(7.24±0.84) U/mL] in PBMCs intervention group were significantly higher than those in implantation disorder group (all P<0.05), while levels of ROS [(3.43±0.30) U/mL], IL-6 [(94.69±3.99) ng/L] and MCP-1 in endometrial tissues [(27.03±3.48) μg/L], and expressions of KIR2DL4 (0.54±0.08), Nrf2 (0.48±0.05), Keap1 (0.43±0.05), RIP1 (0.56±0.05) and RIP3 (0.49±0.03) were significantly lower than those in implantation disorder group (all P<0.05). The cells activity [(126.63±1.25)%], proliferation rate [(53.54±2.82)%] and ROS level [(3.12±0.31) U/mL] in experimental group were significantly higher than those in control group [100%, (23.18±3.07)%, (2.51±0.28) U/mL, all P<0.05], while apoptosis rate [(5.69±0.47)%], expressions of KIR2DL4 (0.36±0.06), Nrf2 (0.30±0.06), Keap1 (0.26±0.04), RIP1 (0.27±0.05) and RIP3 (0.26±0.06) were lower than those in control group [(27.13±2.97)%, 0.84±0.06, 0.75±0.05, 0.68±0.05, 0.80±0.06, 0.80±0.07, all P<0.05]. The cells activity [(83.48±5.34)%] and proliferation rate [(38.42±4.28)%] in miR-1306 inhibitor group were significantly lower than those in negative control group [(127.12±4.08)%, (53.57±2.09)%, all P<0.05], while apoptosis rate [(13.63±1.77)%], ROS level [(6.49±0.62) U/mL], expressions of KIR2DL4 (0.67±0.07), Nrf2 (0.57±0.05), Keap1 (0.50±0.05), RIP1 (0.64±0.06) and RIP3 (0.61±0.08) were significantly higher than those in negative control group [(5.71±0.78)%, (3.23±0.31) U/mL, 0.36±0.07, 0.30±0.07, 0.27±0.06, 0.28±0.07, 0.28±0.06, all P<0.05]. Conclusion:PBMCs-derived exosomes can improve pregnancy rate in mice with implantation disorders, which may improve inflammatory response by promoting miR-1306 expression and inhibiting KIR2DL4 expression, and is also related to relieving excessive oxidative stress and apoptosis of endometrium.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

Objective:To explore the mechanism of peripheral blood mononuclear cells (PBMCs)-derived exosomes on improving endometrial receptivity by miR-1306.Methods:The models of mice with implantation disorders were prepared by subcutaneous injection of mifepristone. And they were divided into implantation disorder group and PBMCs intervention group, 12 mice in each group. The normal group was set up. PBMCs intervention group was given intrauterine injection of PBMCs-derived exosomes, while normal group and implantation disorder group were given the same volume of buffer solution. The pregnancy rates and number of embryos implantation in different groups were compared. The expression of miR-1306 in endometrial tissues was detected by RT-PCR. The levels of reactive oxygen species (ROS), interleukin-6 (IL-6), monocyte chemcattractant protein-1 (MCP-1) and superoxide dismutase (SOD) in endometrial tissues were detected by enzyme-linked immunosorbent assay. The expressions of pregnancy-related proteins in endometrial tissues were detected by Western blotting. The endometrial epithelial cells were divided into control group, experimental group, negative control group and miR-1306 inhibitor group. Except control group, cells were co-cultured with PBMCs-derived exosomes by Transwell in the other groups. The activity, proliferation and apoptosis of cells were detected by MTT, Edu and Annexin-V/PI flow, respectively. The level of ROS in cells was detected by kits. And expressions of the related proteins were detected by Western blotting.Results:The pregnancy rate [8.33% (1/12), number of embryos implantation [0(0, 0)], expression of miR-1306 in endometrial tissue (0.24±0.05) and SOD level [(5.66±0.72) U/mL] in implantation disorder group were significantly lower than those in normal group [100% (12/12), 16.50 (14.00, 19.00), 1.03±0.05, (8.69±1.21) U/mL, P<0.05], while levels of ROS [(4.87±0.39) U/mL], IL-6 [(116.51±5.78) ng/L] and MCP-1 in endometrial tissues [(36.84±3.56) μg/L], and expressions of KIR2DL4 (0.87±0.06), nuclear factor erythroid-2-related factor 2 (Nrf2, 0.76±0.06), Kelch-like ECH-associated protein1 (Keap1, 0.79±0.05), receptor interacting protein 1 (RIP1, 0.94±0.04) and RIP3 (0.86±0.05) were significantly higher than those in normal group [(2.41±0.19) U/mL, (83.79±6.68) ng/L, (12.32±2.09) ng/mL, 0.27±0.03, 0.31±0.05, 0.23±0.04, 0.34±0.03, 0.31±0.05, all P<0.05]. The pregnancy rate [75.00% (9/12)], number of embryos implantation [13.00 (13.00, 14.75)], expression of miR-1306 in endometrial tissues (0.82±0.05) and SOD level [(7.24±0.84) U/mL] in PBMCs intervention group were significantly higher than those in implantation disorder group (all P<0.05), while levels of ROS [(3.43±0.30) U/mL], IL-6 [(94.69±3.99) ng/L] and MCP-1 in endometrial tissues [(27.03±3.48) μg/L], and expressions of KIR2DL4 (0.54±0.08), Nrf2 (0.48±0.05), Keap1 (0.43±0.05), RIP1 (0.56±0.05) and RIP3 (0.49±0.03) were significantly lower than those in implantation disorder group (all P<0.05). The cells activity [(126.63±1.25)%], proliferation rate [(53.54±2.82)%] and ROS level [(3.12±0.31) U/mL] in experimental group were significantly higher than those in control group [100%, (23.18±3.07)%, (2.51±0.28) U/mL, all P<0.05], while apoptosis rate [(5.69±0.47)%], expressions of KIR2DL4 (0.36±0.06), Nrf2 (0.30±0.06), Keap1 (0.26±0.04), RIP1 (0.27±0.05) and RIP3 (0.26±0.06) were lower than those in control group [(27.13±2.97)%, 0.84±0.06, 0.75±0.05, 0.68±0.05, 0.80±0.06, 0.80±0.07, all P<0.05]. The cells activity [(83.48±5.34)%] and proliferation rate [(38.42±4.28)%] in miR-1306 inhibitor group were significantly lower than those in negative control group [(127.12±4.08)%, (53.57±2.09)%, all P<0.05], while apoptosis rate [(13.63±1.77)%], ROS level [(6.49±0.62) U/mL], expressions of KIR2DL4 (0.67±0.07), Nrf2 (0.57±0.05), Keap1 (0.50±0.05), RIP1 (0.64±0.06) and RIP3 (0.61±0.08) were significantly higher than those in negative control group [(5.71±0.78)%, (3.23±0.31) U/mL, 0.36±0.07, 0.30±0.07, 0.27±0.06, 0.28±0.07, 0.28±0.06, all P<0.05]. Conclusion:PBMCs-derived exosomes can improve pregnancy rate in mice with implantation disorders, which may improve inflammatory response by promoting miR-1306 expression and inhibiting KIR2DL4 expression, and is also related to relieving excessive oxidative stress and apoptosis of endometrium.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

Objective:To identify the differentially expressed genes, construct circular RNA-microRNA-messenger RNA (cirRNA-miRNA-mRNA) regulatory network, and detect the differentially expressed genes with the clinical samples from patients with polycystic ovary syndrome (PCOS) for further investigating of the mechanisms of pathogenesis and providing novel biomarkers for PCOS, to further explore the pathogenesis of PCOS and provide therapeutic targets.Methods:The software 'R' was used to analyze the data from gene expression omnibus (GEO). The differentially expressed genes (mRNA, miRNA and circRNA) were identified, and the mRNA-miRNA-cirRNA regulatory network was predicted by CircInteractome and Starbase database. The retrospective study was performed based on the PCOS patients in the Department of Reproductive Medicine, the Second Affiliated Hospital of Zhengzhou University during January to December in 2018. The cumulus cells were collected from the PCOS (named PCOS group, n=40) and healthy women (named control group, n=20). Reverse transcription real time quantitative PCR (RT-qPCR) was performed to further detect and verify the differentially expressed genes and the network. Results:Analysis from GEO database identified the differentially expressed genes including 278 mRNAs, 23 miRNAs and 2402 circRNAs in PCOS group compared with non-PCOS group ( P<0.05 and |log 2FC|>0.8); 256 mRNA-miRNA-circRNA regulatory networks were established with the differentially expressed genes including 13 mRNAs, 2 miRNAs and 40 circRNAs from the database analysis. The verification with the clinical samples finally revealed the regulatory networks of mRNA pregnancy-associated plasma protein A (PAPPA)-miRNA (hsa-miR-127-3p)-circRNA (hsa_circ_0086809/hsa_circ_0063556) were associated with PCOS ( P=0.004, P=0.002, P=0.014, P=0.003). Conclusion:The expressions of mRNA (PAPPA), miRNA (hsa-miR-127-3p) and circRNA (hsa_circ_0086809/hsa_circ_0063556) in the cumulus cells and their regulatory networks were associated with PCOS.

Objective:To identify the differentially expressed genes, construct circular RNA-microRNA-messenger RNA (cirRNA-miRNA-mRNA) regulatory network, and detect the differentially expressed genes with the clinical samples from patients with polycystic ovary syndrome (PCOS) for further investigating of the mechanisms of pathogenesis and providing novel biomarkers for PCOS, to further explore the pathogenesis of PCOS and provide therapeutic targets.Methods:The software 'R' was used to analyze the data from gene expression omnibus (GEO). The differentially expressed genes (mRNA, miRNA and circRNA) were identified, and the mRNA-miRNA-cirRNA regulatory network was predicted by CircInteractome and Starbase database. The retrospective study was performed based on the PCOS patients in the Department of Reproductive Medicine, the Second Affiliated Hospital of Zhengzhou University during January to December in 2018. The cumulus cells were collected from the PCOS (named PCOS group, n=40) and healthy women (named control group, n=20). Reverse transcription real time quantitative PCR (RT-qPCR) was performed to further detect and verify the differentially expressed genes and the network. Results:Analysis from GEO database identified the differentially expressed genes including 278 mRNAs, 23 miRNAs and 2402 circRNAs in PCOS group compared with non-PCOS group ( P<0.05 and |log 2FC|>0.8); 256 mRNA-miRNA-circRNA regulatory networks were established with the differentially expressed genes including 13 mRNAs, 2 miRNAs and 40 circRNAs from the database analysis. The verification with the clinical samples finally revealed the regulatory networks of mRNA pregnancy-associated plasma protein A (PAPPA)-miRNA (hsa-miR-127-3p)-circRNA (hsa_circ_0086809/hsa_circ_0063556) were associated with PCOS ( P=0.004, P=0.002, P=0.014, P=0.003). Conclusion:The expressions of mRNA (PAPPA), miRNA (hsa-miR-127-3p) and circRNA (hsa_circ_0086809/hsa_circ_0063556) in the cumulus cells and their regulatory networks were associated with PCOS.