Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective To screen the mutations of ABCC8 gene in probands of maturity-onset diabetes of the young pedigrees,and investigate it sgenetic and clinical characteristics.Methods Whole exome sequencing were performed to screen ABCC8 mutations in 56 MODY probands who were admitted to Department of Endocrinology and Metabolism,Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2021 to December 2023.The mutations were verified by Sanger sequencing,and all participants were genotyped.Clinical phenotypes of the mutation carriers were compared with non-DM controls within the families.The identified mutations were evaluated by bioinformatic softwires.Then the pharmacogenomic characteristics of the mutation carriers were analyzed.Results Two heterozygous mutations D655V and R825Q were identified in two MODY probands and their families respectively,and the D655V was a novel mutation.Bioinformatics studies showed that both mutations were deleterious and pathogenic.In comparison with non-DM controls in the two families,mutation carriers with diabetes exhibited significantly lower fasting insulin/fasting plasma glucose,two-hour postprandial insulin/two-hour postprandial insulin plasma glucose,homeostatic model assessment-β(P<0.05).Treatment with oral hypoglycemic agents such as metformin or insulin in these mutation carriers resulted in a moderate reduction in plasma glucose levels.However,switching to targeted Sulfonylurea's(SUs)proved to be more effective.Conclusions In this study,the prevalence of MODY12 is 3.6%in these MODY pedigrees.The remarkable hypoglycemic efficacy of SUs suggests that both D655V and R825Q were activating mutations of ABCC8,and maybe the cause of MODY12 characterized by impaired insulin secretion.

Objective To compare the positive rate ofthyroid autoantibodies in infertile women with different ovarian reserve function,and investigate the immune factors of diminished ovarian reserve.Methods A cross-sectional study was conducted on infertile women admitted to Department of Reproductive Medicine of Beijing Gynaecology and Obstetrics Hospital from June to December,2020.The levels of anti-Müllerian hormone (AMH ),thyroid stimulating hormone (TSH ),thyroglobulin antibody (TGAb ) and thyroid peroxidase antibody (TPOAb)were detected in the 526 enrolled infertile patients.According to their AMH level,they were divided into normal ovarian reserve group and diminished ovarian reserve group.After they were stratified according to their age,the differences of TSH,TGAb and TPOAb levels were compared in the different age groups to analyze the related factors for diminished ovarian reserve.Results Univariate analysis showed that the diminished ovarian reserve group had significantly higher positive rates of TPOAb (18.8％ vs 11.1％,P=0.024)and TGAb (18.8％ vs 8.0％,P=0.001 )than the normal ovarian reserve group.Multivariate logistic regression analysis indicated that age and TGAb positivity were related to diminished ovarian reserve[OR=1.083(95％ CI:1.021～1.150),P=0.008;OR=1.159(95％ CI:1.034～1.301 ),P=0.011].Subgroup analysis suggested that the positive TGAb and TPOAb were significantly correlated with AMH level in the 36-～40-year-old group (P<0.05).Conclusion The infertile women with diminished ovarian reserve have higher TGAb and TPOAb levels,and the diminishment in those aged 36～40 years might be related to the positive TGAb and TPOAb.

Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.

To analyze whether the serum concentration of estradiol on the day of progesterone conversion could predict the pregnancy outcome of frozen-thawed embryo transfer in hormone replacement cycle. In this paper, a case-control study was conducted to retrospectively analyze the 230 cycles of hormone replacement therapy-frozen thawed embryo transfer(HRT-FET)conducted by the Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to December 2020. The concentration of serum estradiol was between 139.5-3 941.0 pg/ml. According to the percentile of serum estradiol concentration on the day of endometrial transformation, patients were divided into three groups: control group (<25th percentile, n=58), high estradiol group (25th-75th percentile, n=112) and ultra-high estradiol group (>75th percentile, n=60). Comparing the basic characteristics and pregnancy outcome of the three groups, the main observation index was the live birth rate, and the secondary observation index was the clinical pregnancy rate. F test and Kruskal-Wallis ( H) test were used to compare the measurement data, and χ 2 test was used to compare the counting data. The results showed that there was no significant difference in age, anti-Müllerian hormone(AMH), antral follicle count(AFC), body mass index(BMI), years of infertility and the proportion of primary infertility among the three groups( F=2.375, H=5.479, H=5.374, F=1.391, H=4.779, χ2=1.969, P>0.05). FET cycle treatment: There was no significant difference in the concentration of progesterone (P) before transformation, the thickness of endometrium on the day of transformation, the proportion of single embryo transfer and blastocyst transfer among the three groups ( H=5.359, H=5.957, χ2=0.626, χ2=4.532, P>0.05). The days of estrogen administration before endometrial transformation in the three groups during the FET cycle were 13.0 (12.0, 14.0) days in the high estradiol group and 13.0 (12.0, 15.0) days in the ultra-high estradiol group, which were significantly longer than those in the control group 13.0(12.0, 13.3)days. The E2 concentration before intimal transformation in high estradiol group was 1 560.4 (1 170.2, 1 848.2) pg/ml, while that in ultra-high estradiol group was 2 420.9 (2 131.0, 2 849.2) pg/ml, which was significantly higher than that in control group 238.8 (206.9, 287.0) pg/ml. The pregnancy outcome of the three groups: the clinical pregnancy rate of the three groups was 37.9% in the control group, 51.8% in the high estradiol group and 40.0% in the ultra-high estradiol group, of which the high estradiol group had the highest clinical pregnancy rate, followed by the ultra-high estradiol group. But there was no significant difference among the three groups (χ2=3.853, P>0.05). The embryo implantation rate of the three groups was 19.3%, 25.0%, 32.8%, respectively, and the embryo implantation rate of the ultra-high estradiol group was the highest, but there was no significant difference among the three groups (χ2=5.544, P>0.05).The live birth rate of the three groups was 37.9%, 39.3%, 40.0%, respectively, and the difference was not statistically significant (χ2=0.05, P>0.05). A total of 14(13.5%) abortions occurred in 104 clinical pregnancies, all of which occurred in the high estradiol level group. Of the 104 clinical pregnancies, 24 (23.1%) had twin pregnancies, which occurred in the high estradiol level group (10 cases) and the ultra-high estradiol level group (14 cases). There were no twin pregnancies in the control group. Ectopic pregnancy occurred in 4 of 230 FET cycles (1.7%), 2 in control group and 2 in high estradiol group, and no ectopic pregnancy in ultra-high estradiol group.

To analyze whether the serum concentration of estradiol on the day of progesterone conversion could predict the pregnancy outcome of frozen-thawed embryo transfer in hormone replacement cycle. In this paper, a case-control study was conducted to retrospectively analyze the 230 cycles of hormone replacement therapy-frozen thawed embryo transfer(HRT-FET)conducted by the Department of Reproductive Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to December 2020. The concentration of serum estradiol was between 139.5-3 941.0 pg/ml. According to the percentile of serum estradiol concentration on the day of endometrial transformation, patients were divided into three groups: control group (<25th percentile, n=58), high estradiol group (25th-75th percentile, n=112) and ultra-high estradiol group (>75th percentile, n=60). Comparing the basic characteristics and pregnancy outcome of the three groups, the main observation index was the live birth rate, and the secondary observation index was the clinical pregnancy rate. F test and Kruskal-Wallis ( H) test were used to compare the measurement data, and χ 2 test was used to compare the counting data. The results showed that there was no significant difference in age, anti-Müllerian hormone(AMH), antral follicle count(AFC), body mass index(BMI), years of infertility and the proportion of primary infertility among the three groups( F=2.375, H=5.479, H=5.374, F=1.391, H=4.779, χ2=1.969, P>0.05). FET cycle treatment: There was no significant difference in the concentration of progesterone (P) before transformation, the thickness of endometrium on the day of transformation, the proportion of single embryo transfer and blastocyst transfer among the three groups ( H=5.359, H=5.957, χ2=0.626, χ2=4.532, P>0.05). The days of estrogen administration before endometrial transformation in the three groups during the FET cycle were 13.0 (12.0, 14.0) days in the high estradiol group and 13.0 (12.0, 15.0) days in the ultra-high estradiol group, which were significantly longer than those in the control group 13.0(12.0, 13.3)days. The E2 concentration before intimal transformation in high estradiol group was 1 560.4 (1 170.2, 1 848.2) pg/ml, while that in ultra-high estradiol group was 2 420.9 (2 131.0, 2 849.2) pg/ml, which was significantly higher than that in control group 238.8 (206.9, 287.0) pg/ml. The pregnancy outcome of the three groups: the clinical pregnancy rate of the three groups was 37.9% in the control group, 51.8% in the high estradiol group and 40.0% in the ultra-high estradiol group, of which the high estradiol group had the highest clinical pregnancy rate, followed by the ultra-high estradiol group. But there was no significant difference among the three groups (χ2=3.853, P>0.05). The embryo implantation rate of the three groups was 19.3%, 25.0%, 32.8%, respectively, and the embryo implantation rate of the ultra-high estradiol group was the highest, but there was no significant difference among the three groups (χ2=5.544, P>0.05).The live birth rate of the three groups was 37.9%, 39.3%, 40.0%, respectively, and the difference was not statistically significant (χ2=0.05, P>0.05). A total of 14(13.5%) abortions occurred in 104 clinical pregnancies, all of which occurred in the high estradiol level group. Of the 104 clinical pregnancies, 24 (23.1%) had twin pregnancies, which occurred in the high estradiol level group (10 cases) and the ultra-high estradiol level group (14 cases). There were no twin pregnancies in the control group. Ectopic pregnancy occurred in 4 of 230 FET cycles (1.7%), 2 in control group and 2 in high estradiol group, and no ectopic pregnancy in ultra-high estradiol group.

Polycystic ovary syndrome (PCOS), a common clinical endocrine disorder, is the main cause of anovulatory infertility in women of childbearing age. The clinical practice guideline for ovulation induction in PCOS patients has been supported by the Society of Obstetricians and Gynaecologists of Canada (SOGC) in 2018. First line management of infertility once a diagnosis of PCOS is made should include weight loss and lifestyle modifications. Subsequently, first line medical therapy for ovulation induction should include selective estrogen receptor modulator—clomiphene citrate (CC) and aromatase inhibitor—letrozole (LE). The gonadotropins (Gn) should be considered as the second-line medical therapy, and in vitro fertilization treatment should be the third-line medical therapy. Insulin resistant patients can take the insulin sensitizer—metformin. When there are other indications for laparoscopy, laparoscopic ovarian drilling (LOD) may be considered in cases of CC or LE resistant PCOS. The clinical preventive action, that individual and progressive principles should be followed to normalize ovulation induction in PCOS patients.

Polycystic ovary syndrome (PCOS), a common clinical endocrine disorder, is the main cause of anovulatory infertility in women of childbearing age. The clinical practice guideline for ovulation induction in PCOS patients has been supported by the Society of Obstetricians and Gynaecologists of Canada (SOGC) in 2018. First line management of infertility once a diagnosis of PCOS is made should include weight loss and lifestyle modifications. Subsequently, first line medical therapy for ovulation induction should include selective estrogen receptor modulator—clomiphene citrate (CC) and aromatase inhibitor—letrozole (LE). The gonadotropins (Gn) should be considered as the second-line medical therapy, and in vitro fertilization treatment should be the third-line medical therapy. Insulin resistant patients can take the insulin sensitizer—metformin. When there are other indications for laparoscopy, laparoscopic ovarian drilling (LOD) may be considered in cases of CC or LE resistant PCOS. The clinical preventive action, that individual and progressive principles should be followed to normalize ovulation induction in PCOS patients.

Inhibin B(INHB) and anti-Müllerian hormone(AMH) detection have important clinical significance in assisted reproductive technology.INHB for evaluation of male testis function is very meaningful,playing a guiding role in the treatment of oligospermatism.INHB has very high clinical diagnosis value for evaluation of ovarian reserve function,being an important indicator to predict the effect of controlled ovarian hyperstimulation.AMH for evaluation of women ovarian function is significant,and is a diagnosis index of reproductive domain related diseases such as polycystic ovary syndrome and one of the important indices for evaluation of assisted reproductive outcomes.

Objective To investigate the prediction value of ultrasound endometrial pattern at the day of hCG administration on clinical outcome in patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods 679 cycles of IVF-ET conducted between January 2011 and December 2012 in Beijing Obstetrics and Gynecology Hospital were reviewed retrospectively.All cycles were divided into three groups based on the endometrial pattern measured on the hCG day:group A (n =411) with triple line endometrium,group B (n =228) with no obvious triple line endometrium,group C (n =40) with homogeneous hyperechoic endometrium.Clinical outcomes such as implantation rate,pregnancy rate and miscarriage rate were analyzed.Results Among three groups,the implantation rates were 27.05％,20.33％,19.57％,respectively (x2 =9.04,P =0.01); the pregnancy rates were 34.31％,25.00％,12.50％,respectively (x2 =12.20,P =0.00).The implantation rate and pregnancy rate in group A were higher than the other two groups (P ＜0.05).The miscarriage rates were 16.31％,19.30％,40.00％,respectively(P ＞ 0.05),there were no significant difference among them.Conclusions The ultrasound endometrium pattern on the day of hCG administration has predictive value on clinical outcome in patients undergoing in vitro fertilization-embryo transfer.