The Study For The Obstetric Outcome Of Pregnant Women With Polycystic Ovary Syndrome And The Association Study With Preeclampsia

PART ONE:THE STUDY FOR THE OBSTETRIC OUTCOME AND THE CORRELATED FACTORS IN GRAVIDAS WITH POLYCYSTIC OVARY SYNDROMEBackground:Polycystic ovary syndrome(PCOS) is a complex reproductive metabolic disorder affecting approximately 6-8% of the reproductively mature women. Various studies have suggested that maternal PCOS is associated with an increased rate of adverse obstetric outcomes, while the conclusions were inconsistent. Many of the studies focused only on the result and no study reported the prediction of risk factors for every adverse outcome caused by PCOS.Aim:To determine whether maternal PCOS is associated with adverse obstetric and neonatal outcomes and explore the related factors or the main predictors for adverse outcomes.Methods: ① Between July 2007 and May 2014,492 single pregnancy women who were suffering from PCOS diagnosed in the reproductive centre in Jinan Maternity and Child care hospital were studied as PCOS group,at the same time 512 healthy gravidas were screened and enrolled as control group in the study. The pregnancy complication and neonatal outcome were compared between the two groups.② 205 gravidas of PCOS without any pregnancy complication selected randomly were control group, and the gravidas with pregnancy complication were observe group respectivly.The general index (including agen weight、BMI、 waistline、waist-to-hip ratio、gestation weightgain、family history)、the basal hormone index(including FSH、LH、E2、PRL、T)、sex hormone-binding globulin(SHBG)、fasting glucose and insulin before pregnancy were compared between the two groups, and find out the independent risk factors of the complication using binary Logistic regression analysis.Results:① Compared with control group, patients with PCOS bore significantly higher incidence of apontaneous abortion (SAB) (19.1% vs 8.8%, P<0.001)、gestational diabetes mellitus (GDM) (12.1% vs 6.9%, P:0.010) and pregnancy induced hypertension (PIH) (12.3% vs7.3%, P：0.014). The incidence of other pregnancy complications including ectopic pregnancy。placenta praevia、 placental abruption、postpartum haemorrhage、premature rupture of membrane had no difference between the two groups. For newborn, the incidence of premature infant(7.6% vs 4.0%, P:0.024) and admission at neonatal intensive care unit(NICU) (11.3% vs 7.1%, P:0.035) in PCOS-group was higher significantly than in control group.The incidence of macrosomia and fetal growth restriction(FGR) was higher in PCOS-group than in control group,but no statistical difference existed. And in other facts of neonate such as the birthweight、length、Apagar score of 5 minutes、 malformation、sex ratio, no statistical difference existed between the two groups.②Among PCOS gravidas, the values of the prepregnancy age、weight、BMI、 waist line、waist-to-hip ratio(WHR)、T、INS、HOMA-IR and SHBG were higher in SAB group than in control group, while only age (OR:1.095; 95%CI:1.000-1.199)、 WHR(OR:2.259; 95%CI:1.340-3.807) and T (OR:1.021; 95%CI:1.007-1.035) were the independent risk factors of SAB. In GDM group,10 factors including prepregnancy BMI、waistline、WHR、gestation weightgain before 24 weeks、serum T、SHBG、glucose、insulin、HOMA-IR and family history of DM were highter than in control group. While WHR(OR:2.849; 95%CI:1.451-5.595)、gestation weightgain before 24 weeks (OR:1.384; 95%CI:1.141-1.676)、HOMA-IR (OR:2.242; 95%CI:1.207-4.162) and SHBG (OR:0.968; 95%CI:0.948-0.990) were the independed risk factors. In PIH group, the values of the factors including prepregnancy age、weight、BMI、waistline、WHR、gestation weightgain before 24 weeks、INS and HOMA-IR were higher than in control group. And only prepregnancy WHR (OR:2.121; 95%CI:1.159-3.882) and gestation weightgain before 24 weeks (OR:1.417; 95%CI:1.186-1.694) were the independed risk factors of PIH. The related risk factors of premature delivery were the complications of GDM and PIH. The women conceived naturally or by ovulation induction had no statistical difference.Conclusion:The increased risk for adverse obstetric outcomes was observed in patients with PCOS. They experienced a higher incidence of SAB、GDM and PIH. Their offspring were at an increased risk of neonatal complications, including preterm birth and admission at NICU. The factors such as prepregnant WHR、gestation weightgain、serum T、serum SHBG、HOMA-IR contribute to the observed adverse outcomes. The ovulation stimulants (clomiphene、letrozole、HMG) have no influence on the outcomes. In order to improve the health status of maternities and offsprings of PCOS, the methods were needed including correcting the prepregnancy abnormal endocrine and metabolic status, and controlling of prepregnancy WHR and gestation weightgain is of crucial significance for that.PART TWO:ASSOCIATION STUDY BETWEEN POLYCYSTIC OVARY SYNDROME ASSOCIATED GENES DENND1A,LHCGR,THADA AND PREECLAMPSIABackground:Women with polycystic ovary syndrome(PCOS) has a higher risk of developing preeclampsia after pregnancy. And preeclampsia is positively associated with insulin resistance, hyperandrogenism and obesity, which are the typical features of PCOS. It seems there are some associations between preeclampsia and PCOS in genetic background. In the previous Genome-wide association study (GWAS) three susceptibility loci of PCOS were identified, which included rs13405728 (LHCGR gene), rs13429458 (THADA gene), and rs2479106 (DENND1A gene). At present, there have been no study reports about the association between the three genetic variants and preeclampsia.Aim:This study evaluated the effect of PCOS genetic variants (rs13405728 in LHCGR gene; rs13429458 in THADA gene and rs2479106 in DENND1A gene) on preeclampsia risk in Han Chinese populations.Material and methods:A total of 784 northern Han Chinese women were genotyped for the three genetic variants by polymerase chain reaction and direct sequencing.Results:No significant difference was found in the allele frequencies of the three genetic variants between cases and controls before and after pregestational BMI and maternal age adjustment (P>0.05). Genotype frequency of the SNPrs2479106 was significantly different between cases and controls when analyzed under recesive models (P=0.02). There was also a significant difference in the genotype frequencies of the SNP rs13429458 between cases and controls under additive models (P=0.01). There was no significant difference in genotype frequencies of rs13405728 variant between preeclampsia women and controls.Conclusion:Genetic variants locating at THADA and DENNDIA were associated with preeclampsia in Han Chinese women, which provided new information on the genetic relationship between preeclampsia and PCOS.