Objective To analyze the coordination strategies of residual solvent control in various pharmacopoeias with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guidelines for residual solvents(ICH Q3C),aiming to provide ideas and solutions for coordinating residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Methods Through literature research and review,compare the coordination process between residual solvent control in various pharmacopoeias and ICH Q3C,analyze the implementation strategies of mainstream pharmacopoeia residual solvent control and ICH Q3C coordination in foreign countries,and clarify the differences in residual solvent control between the Chinese Pharmacopoeia and foreign pharmacopoeias.Results It is necessary to coordinate the control of residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Conclusion It is recommended to steadily promote the overall coordination of residual solvent control in Chinese pharmacopoeia and ICH by drawing on the experience of coordination between foreign pharmacopoeias and ICH Q3C,based on the national conditions of China.

Objective To analyze the coordination strategies of residual solvent control in various pharmacopoeias with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guidelines for residual solvents(ICH Q3C),aiming to provide ideas and solutions for coordinating residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Methods Through literature research and review,compare the coordination process between residual solvent control in various pharmacopoeias and ICH Q3C,analyze the implementation strategies of mainstream pharmacopoeia residual solvent control and ICH Q3C coordination in foreign countries,and clarify the differences in residual solvent control between the Chinese Pharmacopoeia and foreign pharmacopoeias.Results It is necessary to coordinate the control of residual solvents in the Chinese Pharmacopoeia with ICH Q3C.Conclusion It is recommended to steadily promote the overall coordination of residual solvent control in Chinese pharmacopoeia and ICH by drawing on the experience of coordination between foreign pharmacopoeias and ICH Q3C,based on the national conditions of China.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.

Objective:To explore the expression levels of adrenomedullin (ADM) in follicular fluid of patients with polycystic ovary syndrome (PCOS) and its correlation with ovarian function and inflammation.Methods:To conduct a cohort study, the data on infertile couples who received an antagonistic regimen of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) to promote ovulation from March to December 2023 at the Reproductive Medicine Center of Shanxi Children's Hospital (Shanxi Maternal and Child Health Hospital) were collected. PCOS patients were selected as the PCOS group, and patients who underwent IVF/ICSI assisted pregnancy solely due to tubal and/or male factors during the same period were selected as control group. The general clinical data of two groups of patients were analyzed, and the expression of ADM, interleukin 1β (IL-1β), IL-18, transforming growth factor β (TGF-β) in the follicular fluid were compared between the two groups of patients. And taking the concentration of ADM in follicular fluid as the main research indicator, correlation and multiple linear regression analysis were conducted with other indicators. Simultaneously the ADM mRNA expression, cell cycle and cell apoptosis of granulosa cells were compared between the two groups. Results:This study included 20 cases in the PCOS group and 20 cases in control group. Compared with control group, the expression of ADM in follicular fluid and granulosa cells of patients with PCOS were significantly lower (both P<0.001), while its testosterone, the ratio of luteinizing hormone and follicle-stimulating hormone, antral follicle count (AFC), number of retrieved eggs, ovarian sensitivity index, as well as IL-1β, IL-18 and TGF-β in follicular fluid were higher and negatively correlated with ADM ( r=-0.37, P=0.019; r=-0.32, P=0.047; r=-0.50, P<0.001; r=-0.38, P=0.017; r=-0.38, P=0.016; r=-0.44, P=0.005; r=-0.37, P=0.018; r=-0.54, P<0.001). Multiple linear regression showed that AFC, gonadotropin initiation dose, IL-1β and TGF-β were the independent related factors that affect local ADM levels ( r=-0.37, P=0.008; r=-0.27, P=0.035; r=-0.28, P=0.028; r=-0.45, P<0.001). There was no statistically significant difference in the cell cycle of granulocytes between the two groups ( P>0.05), but the apoptosis rate (AR) of granulocytes was higher in the PCOS group than in control group (median AR in the PCOS group was 46.07%, median AR in control group was 28.57%, n=10, P=0.036). Conclusion:The decreased expression of ADM in follicles of PCOS patients is related to ovarian endocrine disorders, multiple vesicles, high ovarian responsiveness and local inflammatory status.

Objective:To analyse the influence of endometrial polyps (EPs) treatment on the frozen-thawed embryo transfer (FET) pregnancy outcome.Methods:Using a retrospective case-control study, the data of patients were collected who received in vitro fertilization (IVF) and hysteroscopy in the Reproductive Medicine Center of Children's Hospital of Shanxi and Women Health Center of Shanxi from June 2021 to December 2022. Patients undergoing hysteroscopy were studied. According to the diagnosis results of hysteroscopy and pathology, they were selected as the EPs group or the non-endometrial polyps (NEPs) group. Then analysis of EPs risk factors was made, and the pregnancy outcome of FET after the EPs treatment was compared. Results:A total of 3 413 patients underwent hysteroscopy in this study. The EPs group included 444 patients and the NEPs group included 1 501 patients respectively. The prevalence of EPs was 13.01% (444/3 413). There were significant differences between EPs group and NEPs group in gravidity, parity, spontaneous abortion times, induced abortions times, basal follicle-stimulating hormone (bFSH), basal luteinizing hormone (bLH), infertility duration, infertility types, the prevalence of chronic endometritis, the history of polyps removal and endometriosis (all P<0.05). Multivariate logistic regression analysis of risk factors associated with EPs showed that infertility duration ( OR=1.068, 95% CI: 1.029-1.109, P<0.001), chronic endometritis ( OR=1.925, 95% CI: 1.481-2.502, P<0.001), primary infertility ( OR=1.803, 95% CI: 1.408-2.308, P<0.001), history of polyps removal ( OR=9.424, 95% CI: 5.586-15.897, P<0.001), endometriosis ( OR=2.432, 95% CI: 1.344-4.401, P=0.003) were independent risk factors for EPs, and bLH ( OR=0.954, 95% CI: 0.916-0.993, P=0.022) was an independent protective factor for EPs. Compared with NEPs transplantation group, there were no significant differences in clinical pregnancy rate, on-going pregnancy rate and none implantation rate in the EPs treatment transplantation group (all P>0.05). Conclusion:Infertility duration, chronic endometritis, primary infertility, history of polyps removal, endometriosis were independent risk factors, and bLH was an independent protective factor. Patients in EPs treatment transplantation group could achieve the similar pregnancy outcome as NEPs transplantation group.

Objective:To analyse the influence of endometrial polyps (EPs) treatment on the frozen-thawed embryo transfer (FET) pregnancy outcome.Methods:Using a retrospective case-control study, the data of patients were collected who received in vitro fertilization (IVF) and hysteroscopy in the Reproductive Medicine Center of Children's Hospital of Shanxi and Women Health Center of Shanxi from June 2021 to December 2022. Patients undergoing hysteroscopy were studied. According to the diagnosis results of hysteroscopy and pathology, they were selected as the EPs group or the non-endometrial polyps (NEPs) group. Then analysis of EPs risk factors was made, and the pregnancy outcome of FET after the EPs treatment was compared. Results:A total of 3 413 patients underwent hysteroscopy in this study. The EPs group included 444 patients and the NEPs group included 1 501 patients respectively. The prevalence of EPs was 13.01% (444/3 413). There were significant differences between EPs group and NEPs group in gravidity, parity, spontaneous abortion times, induced abortions times, basal follicle-stimulating hormone (bFSH), basal luteinizing hormone (bLH), infertility duration, infertility types, the prevalence of chronic endometritis, the history of polyps removal and endometriosis (all P<0.05). Multivariate logistic regression analysis of risk factors associated with EPs showed that infertility duration ( OR=1.068, 95% CI: 1.029-1.109, P<0.001), chronic endometritis ( OR=1.925, 95% CI: 1.481-2.502, P<0.001), primary infertility ( OR=1.803, 95% CI: 1.408-2.308, P<0.001), history of polyps removal ( OR=9.424, 95% CI: 5.586-15.897, P<0.001), endometriosis ( OR=2.432, 95% CI: 1.344-4.401, P=0.003) were independent risk factors for EPs, and bLH ( OR=0.954, 95% CI: 0.916-0.993, P=0.022) was an independent protective factor for EPs. Compared with NEPs transplantation group, there were no significant differences in clinical pregnancy rate, on-going pregnancy rate and none implantation rate in the EPs treatment transplantation group (all P>0.05). Conclusion:Infertility duration, chronic endometritis, primary infertility, history of polyps removal, endometriosis were independent risk factors, and bLH was an independent protective factor. Patients in EPs treatment transplantation group could achieve the similar pregnancy outcome as NEPs transplantation group.

Objective:To explore the clinical outcome of blastocysts with different developmental time and grades of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles, and to compare and analyze their transcriptome characteristics.Methods:The clinical data of patients with euploid blastocyst transplantation selected by PGT-A in Center for Reproductive Medicine of Women Health Center of Shanxi from January 2017 to December 2021 were retrospectively analyzed. A total of 295 transplantation cycles were divided into groups according to the day of embryo blastulation [day 5 (D5) group and day 6 (D6) group] and blastocyst grade (good-quality group and fair-quality group) and their clinical outcomes were compared. By comparing the single-cell RNA sequencing (scRNA-seq) data of blastocysts of different developmental time and grades from GEO and ENA data platforms, the transcriptome level differences among different groups were analyzed.Results:1) There were no significant differences in age of male and female, type of infertility, infertility duration, body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and number of oocytes retrieved between D5 and D6 groups (all P>0.05). The M Ⅱ oocyte rate [86.35% (2051/2375) vs. 82.71% (1770/2140), P=0.001], blastocyst formation rate [68.08% (725/1065) vs. 62.14% (540/869), P=0.006], implantation rate [72.78% (115/158) vs. 52.55% (72/137), P<0.001], clinical pregnancy rate [56.33% (89/158) vs. 43.80% (60/137), P=0.032] and live birth rate [53.80% (85/158) vs. 40.87% (56/137), P=0.027] in D5 group were significantly higher than those in D6 group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 2) There were no significant differences in age of male and female, type of infertility, infertility duration, BMI, FSH, LH, estradiol and number of oocytes retrieved between good-quality and fair-quality groups (all P>0.05). The M Ⅱ oocyte rate [87.06% (1251/1437) vs. 83.50% (2570/3078), P=0.002], blastocyst formation rate [73.38% (499/680) vs. 61.08% (766/1254), P<0.001], implantation rate [77.90% (74/95) vs. 56.50% (113/200), P<0.001], clinical pregnancy rate [61.05% (58/95) vs. 45.50% (91/200), P=0.013] and live birth rate [56.84% (54/95) vs. 43.50% (87/200), P=0.032] in good-quality group were significantly higher than those in fair-quality group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 3) Based on the scRNA-seq data from GEO and ENA data platforms, we mined differentially expressed genes (DEGs) in the inner cell mass (ICM) and trophectoderm (TE) of D5 and D6 blastocysts, good-quality blastocysts and fair-quality blastocysts. Compared with D6 group, KEGG enrichment analysis showed that DEGs up-regulated of ICM/TE in D5 group were significantly enriched in 285/288 signaling pathways. DEGs up-regulated of ICM/TE were significantly enriched in 207/3 signaling pathways in the good-quality group compared with the fair-quality group. Conclusion:In terms of implantation and clinical pregnancy ability, D5 blastocysts were better than D6 blastocysts, and good-quality blastocysts were better than fair-quality blastocysts. Transcriptome level analysis of blastocysts with different developmental time and grades showed significant differences in transcriptome characteristics. The analysis of blastocyst transcriptome level has predictive value for blastocyst implantation and clinical pregnancy ability.

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women, which is characterized by polycystic ovary changes, hyperandrogenism and anovulation. A large number of studies have confirmed that miRNAs play an important role in the pathophysiology of PCOS. The miRNA-17-92 gene cluster is a family of miRNAs containing multiple cistron clusters. It was initially considered to be an oncogene, but it can trigger a variety of physiological and pathological processes in many diseases. In recent years, more and more evidence has showed that miRNA-17-92 gene cluster plays an important role in the development of PCOS. In this study, we reviewed the roles of miRNA-17-92 gene cluster in the development of PCOS.

Recurrent spontaneous abortion (RSA) is a common adverse pregnancy outcome in women of childbearing age and its etiology is complex and still not clear. The maternal-fetal interface microenvironment plays a key role in maintaining pregnancy. There are trophoblast cells, decidual stromal cells and immune cells in the maternal-fetal interface microenvironment. The abnormal number or function of these cells may induce changes in the microenvironment of maternal-fetal interface, such as spiral artery remodeling disorder and abnormal decidualization, which may lead to RSA. This review discusses the role and mechanism of these three main cells in RSA.

Objective:To explore the clinical outcome of blastocysts with different developmental time and grades of preimplantation genetic testing for aneuploidies (PGT-A) embryo transfer cycles, and to compare and analyze their transcriptome characteristics.Methods:The clinical data of patients with euploid blastocyst transplantation selected by PGT-A in Center for Reproductive Medicine of Women Health Center of Shanxi from January 2017 to December 2021 were retrospectively analyzed. A total of 295 transplantation cycles were divided into groups according to the day of embryo blastulation [day 5 (D5) group and day 6 (D6) group] and blastocyst grade (good-quality group and fair-quality group) and their clinical outcomes were compared. By comparing the single-cell RNA sequencing (scRNA-seq) data of blastocysts of different developmental time and grades from GEO and ENA data platforms, the transcriptome level differences among different groups were analyzed.Results:1) There were no significant differences in age of male and female, type of infertility, infertility duration, body mass index (BMI), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and number of oocytes retrieved between D5 and D6 groups (all P>0.05). The M Ⅱ oocyte rate [86.35% (2051/2375) vs. 82.71% (1770/2140), P=0.001], blastocyst formation rate [68.08% (725/1065) vs. 62.14% (540/869), P=0.006], implantation rate [72.78% (115/158) vs. 52.55% (72/137), P<0.001], clinical pregnancy rate [56.33% (89/158) vs. 43.80% (60/137), P=0.032] and live birth rate [53.80% (85/158) vs. 40.87% (56/137), P=0.027] in D5 group were significantly higher than those in D6 group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 2) There were no significant differences in age of male and female, type of infertility, infertility duration, BMI, FSH, LH, estradiol and number of oocytes retrieved between good-quality and fair-quality groups (all P>0.05). The M Ⅱ oocyte rate [87.06% (1251/1437) vs. 83.50% (2570/3078), P=0.002], blastocyst formation rate [73.38% (499/680) vs. 61.08% (766/1254), P<0.001], implantation rate [77.90% (74/95) vs. 56.50% (113/200), P<0.001], clinical pregnancy rate [61.05% (58/95) vs. 45.50% (91/200), P=0.013] and live birth rate [56.84% (54/95) vs. 43.50% (87/200), P=0.032] in good-quality group were significantly higher than those in fair-quality group, and the results of miscarriage rate, preterm birth rate, proportion of male and birth weight between the two groups were not statistically significant. 3) Based on the scRNA-seq data from GEO and ENA data platforms, we mined differentially expressed genes (DEGs) in the inner cell mass (ICM) and trophectoderm (TE) of D5 and D6 blastocysts, good-quality blastocysts and fair-quality blastocysts. Compared with D6 group, KEGG enrichment analysis showed that DEGs up-regulated of ICM/TE in D5 group were significantly enriched in 285/288 signaling pathways. DEGs up-regulated of ICM/TE were significantly enriched in 207/3 signaling pathways in the good-quality group compared with the fair-quality group. Conclusion:In terms of implantation and clinical pregnancy ability, D5 blastocysts were better than D6 blastocysts, and good-quality blastocysts were better than fair-quality blastocysts. Transcriptome level analysis of blastocysts with different developmental time and grades showed significant differences in transcriptome characteristics. The analysis of blastocyst transcriptome level has predictive value for blastocyst implantation and clinical pregnancy ability.