A FKBP5 mutation is associated with Paget's disease of bone and enhances osteoclastogenesis

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.

Effects of cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome of in vitro fertilization-embryo transfer cycle / 中华妇产科杂志

Objective To investigate the impact of previous cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. Methods Totally 622 infertility patients were retrospectively investigated who underwent first IVF/ICSI-ET cycle in Reproductive Hospital Affiliated to Shandong University from January 2013 to June 2014. There were 153 cases who had been removed ovarian cyst by cystectomy surgeries recruited as study group, in which 44 cases of ovarian endometriosis cyst, 35 cases of benign ovarian teratomas, 67 cases of simple ovarian cyst and 7 cases of ovarian mucinous cystadenoma. In contrast, 469 infertility patients with tubal-factor infertility or male factor were included as control group. The age-matched women in the control group had no ovarian surgery previously. The indicators of ovarian reserve and pregnancy outcome were analyzed between two groups. The influence of different types of ovarian cysts on ovarian reserve and pregnancy outcome in IVF/ICSI-ET cycles were also studied, ovarian endometriosis cyst was studied as Group A, and Group B consisted of benign ovarian teratomas, simple ovarian cyst and mucinous cystadenoma. Results (1) The significantly lower serum antimullerian hormone (AMH) level (median: 1.92 versus 2.90 mg/L), antral follicle count (AFC; median: 12.0 versus 13.0), retrieved oocytes (12 ± 5 versus 13 ± 6) and the number of embryo cryopreserved (median:1.0 versus 3.0) were found in study group compared with control group (all P0.05). A better clinical pregnancy rate was achieved in control group (61.6%, 241/391) than that in study group (61.4%, 81/132), but no significant difference was existed (P=0.96). (2) Compared to Group B, Group A had fewer AFC, lower serum AMH level, retrieved oocytes and the number of embryo cryopreserved (11±4 versus 13±5;1.65 versus 2.15 mg/L;9±4 versus 13±5;0 versus 2.0;all P0.05). Conclusions Ovarian reserve declines after the cystectomy for ovarian benign cysts and the cystectomy has a negative impact on IVF/ICSI-ET cycle, resulting in a decrease of the number of retrieved oocytes and the number of embryo cryopreserved, but do not influence clinical pregnancy outcome. Ovarian reserve is impaired more seriously by cystectomy for ovarian endometriosis cyst than other ovarian benign cyst.

Association between single nucleotide polymorphism of rs2252673 of INSR gene and polycystic ovarian syndrome / 中华妇产科杂志

Objective This study is designed to determine whether an association exists between single nucleotide polymorphism (SNP) variant rs2252673 of insulin receptor(INSR) gene and polycystic ovarian syndrome (PCOS) in Han Chinese in order to identify INSR as a genetic susceptibility factor for PCOS.Methods A total of 224 women with PCOS,192 controls and 672 participants consisting of 224 trios (mother,father and offspring with PCOS) were recruited from the Hospital for Reproductive Medicine Affiliated to Shandong University,from July 2007 to April 2013.Genomic DNA was extracted according to the manufacturer' s protocol.SNP rs2252673 of INSR gene was amplified by PCR and then sequenced on an automated sequencer.Moreover,clinical and metabolic features of the patients with PCOS were compared according to the genotypes.The subjects were divided into twot groups according to body mass index (BMI),and then the results were compared between two groups.And the transmitted disequilibrium test (TDT) was applied for data analysis.Results (1) There were three kinds of genotype of CC,CG and GG.Genotype frequencies of rs2252673 were 8.0％,38.8％,53.1％ and 14.6％,42.2％,43.2％ in the PCOS group and the control group,respectively.The allele frequencies of C and G were 27.5％,72.5％ and 35.7％,64.3％ in the PCOS group and the control group,respectively.There were statistical differences in genotype frequencies and allele frequencies between two groups (all P＜0.05).(2)No significant differences were observed in the different genotype according to clinical and metabolic characteristics of women with PCOS (P＞0.05).But when merging the genotype CG and GG,carriers of the CG and GG genotypes in women with PCOS were slightly associated with total cholesterol (TC) levels (t=2.072,P=0.048) and lower high-density lipoprotein (HDL) levels (t=2.274,P=0.026).Although statistical significance was not achieved,there was an increased tendency in fasting blood glucose (FBG) and fasting insulin (FINS) levels in CG and GG genotypes in PCOS cases.(3)Between the obesity and the non-obesity with PCOS,there was no statistical significance in the genotype and allele frequencies (x2=0.054,P=0.974; x2=0.022,P=0.883).(4)The results of families based analysis shown that genotype distribution of the SNP rs2252673 was in Hardy-Weinberg equilibrium (P＞0.05).After the TDT,the G allele in SNP rs2252673 was over transmitted in families (transmitted∶ non-transmitted=120∶ 88; x2=4.923,P=0.027).There was a transmitted disequilibrium in rs2252673,which implies the association of INSR and PCOS were independent of population stratification.Conclusions There were a association between the SNP variant rs2252673 of INSR gene and the susceptibility to PCOS in Han Chinese women,which was independently of body mass index.The carrier of G allele frequency of rs2252673 may have higher risk of PCOS.

Correlation analysis between polycystic ovary syndrome susceptibility genes and metabolic phenotypes / 中华妇产科杂志

Objective To investigate the relationship between polycystic ovary syndrome (PCOS) susceptibility single nucleotide polymorphisms (SNP) and metabolic phenotypes in glucose and lipid metabolism and explore the pathophysiological mechanism of the susceptibility genes.Methods Three of PCOS susceptibility locus 2p16.3 (rs13405728 of LHCGR gene),2p21 (rs13429458,rs12478601 of THADA gene) and 9q33.3 (rs2479106,rs10818854 of DENNDIA gene) were selected and the metabolic phenotypes were compared between different genotypes of SNP in PCOS patients (using dominant model).Results Low-density lipoprotein cholesterol was significantly increased in CC genotype group than in TC + TT groups at rs12478601 of THADA gene [(2.5 ± 0.8),(2.4 ± 0.8) mmol/L; P =0.01].Serum insulin level of 2 hours after 75 g glucose intake was significantly higher in GG + AG groups than that of AA group at rs2479106 of DENND1A gene[(71 ±65),(64 ±50) mU/L;P =0.05],and the prevalence of type Ⅱ diabetes in first-degree relatives of patients were also increased [9.9％ (66/666),6.9％ (52/751) ; P ＜ 0.05].No association was found between metabolic phenotypes and genotypes of rs13429458,rs10818854,and rs13405728.Conclusions Genetic factors probably have effect on the metabolic characteristics of PCOS.THADA gene is related to lipid metabolism,while DENND1A gene may be involved in insulin metabolism in patients with PCOS.

clinical characteristics and etiological study of nonalcoholic fatty liver disease in Chinese women with PCOS

Polycystic ovary syndrome [PCOS] is highly associated with non-alcoholic fatty liver disease [NAFLD]. There are extensive ethnic differences in the clinical manifestations, pathological changes, and ovarian changes in women with PCOS. To investigate the prevalence and clinical characteristics of NAFLD in Chinese women with PCOS. Non-pregnant women with PCOS [N= 602] and matched controls without PCOS [N=588] were recruited. Basal endocrine, oral glucose tolerance test, insulin release level, lipid level, blood pressure, and body mass index [BMI] were measured. Liver biochemical and B-hepatitis and C-hepatitis indices were determined. NAFLD was significantly more prevalent in women with PCOS than controls [32.9% vs.18.5%] and included 113 [57.1%] mild, 75 [37.8%] moderate and 10 [5.1%] severe cases. Luteinizing hormone was significantly lower in PCOS women with NAFLD than without NAFLD. In the PCOS group, NAFLD prevalence and severity increased with BMI. The liver index was significantly higher [p<0.001], and the quantitative insulin sensitivity check index and high density lipoprotein cholesterol were significantly lower [p<0.001] in the PCOS group than controls. Insulin resistance, abdominal obesity, diabetes mellitus, abnormal glucose tolerance, liver dysfunction, dyslipidemia, hypertension, and metabolic syndrome were significantly more prevalent in the NAFLD group than controls. Chinese women with PCOS have a high prevalence of mostly mild and moderate NAFLD, not significantly associated with hyperandrogenism that increased significantly with BMI. Insulin resistance and metabolic abnormalities are important factors associated with NAFLD. Chinese women with BMI >/= 24 kg/m[2] P2P should be screened for NAFLD

CFTR gene mutation in patients with congenital bilateral absence of vas deferens / 中华泌尿外科杂志

Objective To study the frequency of cystic fibrosis transmembrane conductance regulator(CFTR)mutations in patients with congenital bilateral absence of vas deferens(CBAVD).Methods Eighty-five CBAVD patients were collected from May 2007 to May 2009.The diagnosis of CBAVD included azoospermia,normal of 4 sex hormone items,absence of seminal vesicle,normal volume of testicular and epididymis dilated siltation.And 85 normal fertile men served as controls.Genomic DNA was isolated from peripheral blood.The mutations of CFTR exons 10,11 were detected by PCR-single strand conformation polymorphism,and direct sequencing was performed on 85 cases of CBAVD and the control males.Results Of the 85 CBAVD,10 cases(11.8％)exhibited an abnormal CFTR gene mutation,with 4 cases I556V,2 cases M469V,and 1 case of E527N,A F508,L558S,S485C.No mutations were detected in 85 controls.There was a significant difference between the 2 groups(x2 =8.606,P =0.003).Conclusions CBAVD might be caused by the CFTR mutations.The frequencies and the spectrum of CFTR mutations might be different from those Caucasian population in the west country.

Pregnancy outcomes of patients with polycystic ovary syndrome undergoing in vitro fertilization and embryo transfer / 中华妇产科杂志

Objectives To study pregnant outcomes of patients with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET),and analyze the differences of pregnant outcomes in patients with various phenotypes of PCOS.Methods From Jan.2005 to Feb.2010,631 PCOS patients (PCOS group)and 1423 patients with tubal infertility (control group) who underwent IVF-ET with matched age and body mass index were selected in Center for Reproductive Medicine of the Provincial Hospital Affiliated to Shandong University.Retrospective study was carried out,and pregnancy outcomes were compared between two groups.Results The rates of abortion and preterm birth in PCOS group were significantly higher than those in control group [22.7％ ( 143/631 ) vs.18.69％ (266/1423) and 11.2％ (38/339) vs.6.4％ (51/794) respectively,all P ＜0.05 ].The rates of gestational diabetes mellitus were 1.5％ (5/339) in PCOS and 0.6％ (5/794) in control group,respectively; the rates of pregnancy induced hypertension syndrome were 4.7％ (16/339) in PCOS and 3.0％ (24/794) in control group; gestational days were(272 ± 13) days in PCOS and(273 ± l0)days in control group; the rates of neonatal deformity were 0.6％ (2/339) in PCOS and O.8％ (6/794) in control group; weight of newborn infants in the two groups was(3.5 ±0.5 ) kg; and there was no significant difference between two groups in the above index ( all P ＞ O.05 ).Ovulatory PCOS patients had similar abortion rate [ 18.6％ (19/102) ] and preterm birth rate [ 8.2％ (4/49) ] when compared with those of control group (P ＞ 0.05 ).Conversely,oligo-ovulatory PCOS patients showed higher abortion rate [ 23.4％ ( 124/529 ) ] and preterm birth rate [ 11.7％ (34/290) ] than those of control group ( P ＜ 0.05 ).Conclusions PCOS patients after IVF-ET have an increased abortion rate and preterm birth rate.However,ovulatory PCOS did not present various pregnancy complications.Non-polycystic ovary PCOS patients have worse pregnancy outcome.Ovarian dysfunction might be related to obstetric complications.

Characteristics of glucose metabolism in non-obese and obese women with polycystic ovarian syndrome / 中华妇产科杂志

Objective To investigate characteristics of glucose metabolism of non-obese and obese women with polycystic ovary syndrome (PCOS). Methods From May 2006 to April 2009, 1928 PCOS patients treated in Reproductive Medicine Center of Shandong Provincial Hospital Affiliated to Shandong University were enrolled in this study, which were divided into 901 cases [body mass index (BMI) ≥25 kg/m2] in obese group and 1027 cases in non-obese (BMI < 25 kg/m2) group. The prevalence of type 2 diabetes mellitus (T2DM), oral glucose tolerance test, impaired fasting glucose (IFG), impaired glucose tolerance(IGT) were compared between the two groups. Results (1) Blood glucose levels: at the time of fasting, 30, 60, 120 and 180 minutes, the levels of glucose were (5. 3±1.1), (9. 0±2. 4), (9. 3±4. 4),(7.5±2.8) ,(5.3±1.8)mmol/L in obese group and (5.0±0. 8) ,(8.4±3.5),(8.0±4.2),(6.5±3.2) ,(4. 9±1.6) mmol/L in non-obese group, which all showed statistical difference at every time point (P < 0. 01). (2)The level of insulin: at the time of fasting, 30, 60, 120 min, the level of insulin were (13±7), (81±51), (102±65), (83±63) mU/L in obese group and (8±5) ,(57±35) ,(62±44),(46±39) mU/L in non-obese group, which all showed statistical differenceatevery time point (P <0. 01). However, at time point of 180 minutes, the level of insulin did not exhibit significantly difference between obese and non-obese group (P > 0. 05). (3) The prevalence of abnormal glucose metabolism: the rate of IFG was 4. 98% (96/1928). The rate of abnormal glucose tolerance was 23. 08% (445/1928). The rate of IGT were 13.05% (134/1027) in non-obese group and 24. 20% (218/901) in obese group,which also showed remarkable difference (P < 0. 01). The rate of T2DM were 2. 53% (26/1027) in nonobese group and 7.44% (67/901) in obese group, which reached significant difference (P < 0. 01).Conclusion Abnormal glucose metabolism was observed more frequently in overweight or obese PCOS women.

Effects of cryopreservation time and thawing method of human oocyte vitrification on the outcome of assisted reproduction / 中华妇产科杂志

Objective To evaluate the effects on pregnancy outcome of freezing time from oocyte retrieval and thawing method for metaphase Ⅱ human oocytes vitrification. Methods From Mar 2007 to Mar 2009, the clinical outcome of 30 infertile women undergoing vitrified-thawing oocytes of in vitro fertilizationembryo transfer(IVF-ET) in the Reproductive Medical Center of the First Affiliated Hospital of Zhengzhou University was studied retrospectively, including 21 women with double fallopian tube obstruction and 9 women's husband azoospermia. All infertile women were divided into three groups, including 5 cases in group A (freezing between 4 and 5 hours from oocyte retrieval and conventional thawing method), 9 cases in group B (freezing within 2 hours from retrieval and conventional thawing method) and 16 cases in group C (freezing within 2 hours from retrieval and improved thawing method). The vitrified oocytes were preserved for 2 months to I year and thawed for Intracytoplasmic sperm injection (ICSI) and embryo transfer. The outcome of IVF and pregnancy were recorded. Results (1) The rates of oocyte survival was (65±33) % in group B and (72±23)% in group C and the rate of transfer cycle was 9/9 in group B and 16/16 in group C, which were all significantly higher than (16±17) % of oocyte survival and 1/5 of transfer cycle in group A (P = 0. 001,0. 021). However, the rate of oocyte survival and transfer cycle between group B and group C did not reach statistical difference (P > 0. 05). The rate of implantation and clinical pregnancy of (33±38) % and 9/16 in group C were significantly higher (4±11)% and 1/9 in group B (P =0. 033,0. 040).(2)The mean age of women in group C were (28.6±2.1) in oneself oocyte, (28.0±4.6) in donor oocyte and (28.1±3.4) in donor sperm. The rate of oocyte survival was (73±25) %, (88±10) % and (66±25) %. The rate of fertilization rate was (84. 6±0. 9) %, (79. 3±2. 0) % and (82. 8±15.0) %. The rate of implantation was (20. 0±44. 7) %, (33. 0±0. 1) % , (41.6±41.7) %. The rate of clinical pregnancy was 1/5 in oneself cycles,3/3 in donor oocyte cycles, 5/8 banked donor sperm cycles in group C. All above clinical parameters were not statistically different (P >0. 05). (3) In group A, one women underwent IVFET and no clinical pregnancy was observed. One women pregnancy was terminated at two months in group B.The clinical pregnancies rate of group C was 9/16, late abortion occurred in 1 woman, the other 8 women underwent term pregnancy, including 5 male infants and 4 female infants. All of infants showed normal Karyotype. Live-birth rates per warmed oocyte was 5.9% (8/135). The mean gestational weeks and birth weight of the infants were (39. 4±0. 9) weeks and (3574±569) g, respectively. Conclusions Embryo quality and clinical outcome of thawing cycles could be significantly improved when oocyte vitrification was performed within 2 hours from oocyte retrieval and improved thawing method.

Association of genetic variants in urotensin Ⅱ gene with polycystic ovary syndrome / 中华内分泌代谢杂志

Objective To investigate the correlation of single nucleotide polymorphisms( SNP) of rs228648 and rs2890565 in urotensin Ⅱ (UTS2)gene with polycystic ovary syndrome(PCOS). Methods The genotypes of two SNPs in UTS2 gene were determined through polymerase chain reaction Tin-shift genotyping method. 101 Chinese Han families trios in Shandong Province consisting of fathers,mothers,and affected daughters with PCOS and 105 healthy women were recruited. The physiological and biochemical parameters including serum follicular stimulating hormone(FSH),luteinizing hormone( LH),testosterone,fasting plasma glucose,and insulin were also measured. Results The distributions of three genotypes and two alleles of SNP rs228648 in UTS2 gene were similar between PCOS group and control group. The distributions of genotypes of SNP rs2890565 in UTS2 gene differed significantly between PCOS group and control group (P<0. 05). The frequency of A allele of SNP rs2890565 in UTS2 gene was significantly higher in PCOS group than that in control group( P<0.05). Transmission disequilibrium test(TDT) did not show significantly biased transmission of two different alleles from parents to affected daughters at rs228648 locus (P>0. 05) ,but showed an excess transmission of A allele from heterozygous parents to affected offspring at rs2890565 locus (P<0. 05). The carriers with GG genotype of SNP rs228648 had significantly higher HOMA-IR compared to those with AA and AG genotypes. The carriers with AA or AG genotype of SNP rs2890565 had significantly higher fasting plasma glucose and fasting insulin compared to those with GG genotypes. HOMA-IR in cases with AA genotype was significantly higher than that with GG genotype. Conclusions There is no association of SNP rs228648 with PCOS, but exists association with insulin resistance. The genetic polymorphism of UTS2 gene rs2890565 may be associated with PCOS,and the higher frequency of A allele is likely to contribute to PCOS.

Use of recombinant human luteinizing hormone for ovulation stimulation in in vitro fertilization-embryo transfer / 中华妇产科杂志

Objective To evaluate application of recombinant human luteinizing hormone (r-hLH)used in ovarian stimulation of assisted reproductive technique and impact on outcome of pregnancy. Methods From Apr. To Jul. 2009, 123 patients with low LH level ( < 1 U/L) at day 3 of menstruation and downregulation of pituitary function undergoing in vitro fertilization-embryo transfer (IVF-ET) in Reproductive Medical Center, Provincial Hospital Affiliated to Shandong University were enrolled in this study, whom were classified into 66 cases treated by r-hLH in r-hLH group and 57 cases without r-hLH treatment in non-r-hLH group. In the mean time, 145 patients with normal level of serum LH ( 1-2 U/L) not given by r-hLH treatment and undergoing IVF-ET were matched as control group. Total amount of gonadotropin, estradiol levels and LH levels on the administration of human chorionic gonadotropin ( hCG), number of oocytes retrieved, number of 2PN zygotes, rate of high quality embryos, the rates of implantation and clinical pregnancy were compared among these three groups. Results The level of serum LH on the day of hCG administration were ( 1.59 ± 0.77 ) U/L in r-hLH group, (0.54 ± 0.25 ) U/L in non-r-hLH group and (2.39 ± 1.01 ) U/L in control group, which reached tatistical difference between every two groups (P < 0.05). The rates of high quality embryo were 59.36％ in r-hLH group, 57.79％ in non-r-hLH group,which were significantly lower than 65.94％ in control group, respectively (P < 0. 05 ). The rates of 2PN were 67.62％ in r-hLH group and 68. 32％ in control group, which were significantly higher than 62. 84％ in non-r-hLH group, respectively ( P < 0.05 ). The rates of implantation of 29.77％ in r-hLH group were significantly higher than 18.26％ in non-r-hLH group ( P < 0.05 ). The total amount of gonadotropin,estradiol level on the day of hCG administration, the number of oocytes retrieved, and clinical pregnancy rate were not significantly different among those three groups ( P > 0.05 ). Conclusion The administration of recombinant human uteinizing hormone in patients who are profoundly suppressed after down-regulation with long protocol can get more quality embryos, the higher rates of 2PN and implantation.

Prevention of Fat Liquefaction Following Cesarean Section Using Povidone lodine in Obese Pregnant Women:A Clinical Observation of 300 Cases / 中华医院感染学杂志

OBJECTIVE To explore clinical results of fat liquefaction of incision wound following cesarean section for obese pregnant women.METHODS Totally 300 obese pregnant women with cesarean section were randomly divided into three groups: group A,iodine(PVP-Ⅰ) group(using PVP-Ⅰ(0.5%) after suturing the abdominal rectus sheath);group B(normal saline group);group C(control group without any liquid).All patients were preoperatively used antibiotics to control the infection.The rate of puerperal morbidity,white cell count and wound infection were observed.RESULTS All parameters of group A were lower than group B or C.There were significant differences among three groups(P

Correlation of free fetal DNA with β-human chorionin gonadotropin in circulation in pregnant women with high-risk of Down's syndrome / 中华妇产科杂志

Objective To investigate significance and correlation of free fetal DNA (fDNA) and β-human chorionic gonadotropin(β-hCG) in circulation in pregnant women with high-risk of Down's syndrome (DS). Methods Pregnant women with a male fetus at second trimester screening for Down's syndrome were chosen, including 5 women with a trisomy 21 fetus (DS group), 21 women with DS high-risk pregnant women (DS high-risk group) matched with 22 normal pregnant women as control group. Free fDNA in maternal plasma were extracted. Male DYS14 gene was labled as fDNA, real-time PCR was used to detect fDNA expression. The concentration of β-hCG in maternal serum was detected by chemiluminescence immune assay. The relationship between level of free fDNA and β-hCG concentration was analyzed by Pearson correlation analysis. Results (1) The mean level of free fDNA was (127±58 ) GE/ml in DS group, which was significantly higher than (78±28) GE/ml in DS high-risk group and (48±21 ) GE/ml in control group,respectively (P<0.01). When compared the level of free fDNA between DS high-risk group and control group, it reached statistical difference (P<0.01). (2) The mean concentration of β-hCG was (97±43) kU/L in DS group, which was significantly higher than (58±25) kU/L in DS high-risk group and (38±19) kU/L in control group, respectively (P<0.01). The level of β-hCG in DS high-risk group was also significantly higher than control group (P<0.01). (3) The positive relationship between the level of free fDNA in maternal plasma and β-hCG concentration in maternal serum was observed amongthree groups (r=0.83,P<0.05;r=0.76,P<0.01;r=0.86,P<0.01). Conclusions Free fDNA in maternal plasma might be a candidate marker used for prenatal DS screening. However, its clinical value need to be evaluated because of positive correlation between free fDNA and β-HCG in maternal circulation.

Association of the polymorphism of codon 121 in the ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene with polycystic ovary syndrome in Chinese women

To determine the association of polymorphism of codon 121 in the ecto-nucleotide pyrophophastase/phosphodiesterase 1 [E-NPP1/PC-1] gene in Chinese women with polycystic ovary syndrome [PCOS]. A total of 51 PCOS patients and 61 healthy women from the Chinese Han population from the Center Reproductive Medicine of Provincial Hospital affiliated to Shandong University from June 2005 to July 2006 were recruited for the determination of the polymorphism of the E-NPP1/PC-1 gene. Genomic DNA was extracted from peripheral blood monocytes of patients and controls, and genotyping of the gene was performed by using polymerase chain reaction, which was followed by sequencing. The frequency of the 121Q allele was 13 and 18%, respectively, in PCOS patients and healthy women, while the frequency of the 121K allele was 87 and 82% in the 2 groups. There is no significant difference in the E-NPP1/PC-1 polymorphism between PCOS patients and healthy controls among Chinese Han women. Ecto-nucleotide pyrophophastase/phosphodiesterase 1 polymorphism has no association with PCOS. Further studies are still needed to elucidate whether or not the E-NPP1/PC-1 gene has a functional role in PCOS

Relationship between single nucleotide polymorphism-56 of calpain-10 gene and glucose and lipid metabolism in polycystic ovary syndrome patients / 中华妇产科杂志

Objective To study the effect of desogestrel and ethinyl estradiol(DEE)pre-treatment combined with gonadotropin releasing hormone agonist(GnRH-a)stimulation in in vitro fertilization-embryo transplantation(IVF-ET).MethodsA retrospective analysis was performed in 101 infertile women who received a short protocol of GnRH-a for IVF-ET treatment from June 2004 to June 2007 in the Reproductive Medicine Center of First Affiliated Hospital of Wenzhou Medical College.Patients had been pre-treated with oral contraceptive pill(OCP)for two months before GnRH-a combined with recombinant follicle stimulation hormone(r-FSH)treatment(study group,n=42)or had not been pretreated with OCP(control group,n=59).A statistical analysis of two groups was carried out for the assessment of ovulation stimulating effect of OCP and its influence on the IVF.Results Serum FSH was significantly decreased after OCP in the study group.Twelve pregnancies were obtained including 1 case of spontaneous abortion at 7 weeks in the study group,and 11 pregnancies were obtained including 2 cases of spontaneous abortion during 7-9 weeks in control group.The clinical pregnancy rates in the study group(23％,12/53)was higher than that in the control group(17％,11/63),but the differences were not significant(P＞0.05).The miscarriage rate in the study group(8％,1/12)was lower than that in the control group(18％,2/11),however no significant differences were found between them(P＞0.05).The cycle cancellation rate in patients of the study group(5％,3/56)was significantly lower than that in patients of the control group(17％,13/76,P＜0.05).The differences between patients of the two groups with respect to age,basal level of FSH and luteinizing hormone (LH),antral follicle counts,the mean number of oocyte retrieval,the days of stimulation,total dose of rFSH used,fertilization rate and embryo cleavage rate,however were insignificant.ConclusionOCP pretreatment combined with short protocol of GnRH-a stimulation in IVF could significantly decrease the cycle cancellation rate,with a declining miscarriage rate and increasing pregnancy rate.

Analysis of therapeutic outcomes of polycystic ovary syndrome patients with hyperprolactinemia / 中华妇产科杂志

Objective To study effect of drug treatment in polycystic ovary syndrome patients withhyperprolactinemia.Methods We retrospectively studied 63 women with polycystic ovary syndrome and hyperprolactinemia from the Reproductive Medicine Center,Provincial Hospital between January 2005 andMarch 2007.According to the beginning time of bromocriptine,all women were divided into two groups.Group Ⅰ was composed of 48 cases who received bromocriptine administration before induction of ovulation cycles,and the dose of bromocriptine was modulated depending on the level of serum prolactin.When serum prolactin was controlled at normal levels,we decreased the dosage of bromocriptine step by step(1.25 mgonce),and then continued the treatment at maintenance dosage for no less than 3 weeks.After a baselineultrasonographic examination on day 3,patients were treated with clomiphene citrate at a dosage of 100 mg (2 tablets/day)for 5 days of a normal cycle or progesterone-induced bleeding.On day 9,we monitored the growth conditions of follicles routinely with trans-vaginal uhrasound.If there was no dominant follicle,we added human menopausal hormone(hMG,75 U/d)to the protocol.Human chorionic gonadotropin(hCG,6000-10000 IU)was given intramuscularly when the mean diameter of a follicle reached at least 18 mm.At the same time we instructed the patients to have sexual intercourses or carried out artificial inseminationsbefore and after ovulation.Group Ⅱ were 15 cases in which induction of ovulations were commenced almostsimultaneously with beginning of bromocriptine.The same protocol was given to patients in group Ⅱ.The procedures of ovulation induction and the outcomes of treatment were analyzed and compared.Results Compared with groupⅡ.the days of using hMG in Group Ⅰ was shorter by instructing the time of sexualintercourse.The difference was significant(P=0.004).And there were similar results in the artificial insemination cycles(P=0.009).The rate of pregnancy in group Ⅰ(40%,19/48)was higher than that in groupⅡ(27%,4/15),but the difference was not obvious(P=0.525).Conclusion Bromocriptine administration before the stimulated ovulation therapy can decrease the total dosage and treatment course of ovulating drugs.Induction of ovulations simultaneously with start of bromocriptine therapy can shorten the treatment time of infertility.

Clinical analysis of assistant treatment proposals for infertile women with polycystic ovary syndrome / 中华妇产科杂志

Objective To study the clinical outcomes of assistant treatment proposals for infertile women with polycystic ovary syndrome (PCOS). Methods PCOS patients were divided into four groups according to the assistant treatment proposals between Jan 2003 and Dec 2007 in Reproductive Medicine Center of the Provincial Hospital Affiliated to Shandong University. The four proposals were letrozole(LE) or clomiphene(CC) citrate ovulation induction group, in vitro fertilization and embryo transplantation group, ultrasound-guided immature follicle puncture group, and in vitro maturation and fertilization of oocytes from unstimulated cycles group. The treatment results were analyzed. Results (1) The ovulation rate was 66% (38/58) vs 47% (21/45). The mean endometrial thickness [ (0. 89±0. 13) vs (0. 78±0. 08) cm] and cervical mucus score (11.9±1.8 vs 9. 9±1.8 ) on the day of human chorionic gonadotropin ( hCG ) administration in LE group were both higher than that in CC group, while mature follicle ( 1.08±0. 28 vs 1.73±0. 59) and serum estradiol level [ (983±138) vs (1676±372) pmol/L] in LE group were lower than that in CC group(P <0. 05). (2) One southend five hundred and eighty-four patients accepted in vitro fertilization-embryo transplantation therapy because of PCOS (PCOS group) and 1615 patients because of tube factors (control group). The patients′ ages and infertility years were matched between the two groups. Total doses of Gn [ (980±1192) vs ( 1194±1389) IU] of PCOS group were lower than those of control group. The mean days of using gonadotropin [ (9.6±1.8) vs (9. 5±1. 8) d], serum estradiol (E2) levels on the hCG day [ ( 15 752±6206) vs (9675±4818) pmol/L], mean obtained oocytes (21±6 vs 9±3), mean fertilized oocytes ( 15±6 vs 7±3) and mean cleavaged oocytes ( 12. 9±5.7 vs 5.7±2. 8 ) of PCOS group were higher than those of the control group( P < 0. 05 ). Moderate and severe ovarian hyperstimulation syndrome (OHSS) rates (4. 86% vs 1.67% ) of PCOS group were higher than that of the control group. The pregnant rate (44. 7% vs 45.0% ) of PCOS group was similar to the control group ( P > 0. 05 ). (3) One hundred and nine PCOS patients were given ultrasound-guided immature follicle puncture therapy. After treatment, the testosterone level, luteinizing hormone (LH) level and LH/follicle stimulating hormone (FSH) ratio of the patients became normal. The basic follicle number decreased. (4) A total of 304 in vitro maturation cycles were performed. After embryo transfer, 76 pregnancies were reported. Conclusions There are many choices for the infertile patients with PCOS, such as LE or CC citrate ovulation induction, in vitro fertilization and embryo transplantation, ultrasound-guided immature follicle puncture, and in vitro maturation and fertilization of oocytes from unstimulated cycles. We can provide individualized treatment according to the medical treatment conditions, doctors′ professional capability and the patients′ situation.

Clinical characteristics of women with polycystic ovary syndrome without detection of polycystic ovary / 中华内分泌代谢杂志

876 women with polycystic ovary syndrome (PCOS) were collected from Sep 2004 to Oct 2006. Among them 800 patients with polycystic ovary ultrasound image belonged to group A; the other 76 women without polyeystic ovary ultrasound image belonged to group B. As compared with group A, group B showed significantly higher hirsutism scores, serum testosterone, cholesterol, and lower density lipoprotein. Significantly higher prevalences of diabetes mellitus and hypertension appeared in the first degree relatives in group B than in group A.

Replacement of androgen receptor gene causes complete androgen insensitivity in a large family / 中华妇产科杂志

Objective To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic testing in a large family. Methods PCR was performed to amplify the coding region of androgen gene, followed by direct sequencing in the patients with CAIS and relatives in this family. Results A missense mutation Arg773His was identified in the patients (homozygous) and carriers(heterozygous). Conclusions Mutation Arg773His in the AR gene leads to CAIS in this family. Molecular genetic testing of CAIS facilitates not only prenatal genetic diagnosis but also preimplantation genetic diagnosis and offers genetic counseling for future pregnancies to abandon the transmission of the mutated X chromosome to the coming generation.

Influence of epidermal growth factor and gonadotrophin on the in vitro maturation of human oocytes / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the effect of epidermal growth factor(EGF) and different concentrations of gonadotrophin (Gn) on the in vitro maturation of human oocytes.</p><p><b>METHODS</b>EGF was added to the vitro culture medium in order to observe the effect of Gn combined with or without EGF on the result of in vitro maturation. The concentrations of hCG and FSH were changed respectively to observe the difference between the results.</p><p><b>RESULTS</b>Adding EGF to the culture medium improved the maturation rate of oocyte significantly (P < 0.05). There was no difference between the results with different concentrations of hCG and FSH in the culture medium.</p><p><b>CONCLUSION</b>EGF can improve the results of the in vitro maturation of human oocytes by increasing the maturation rate significantly. Increasing the concentration of Gn does not influence the results of in vitro maturation.</p>