Study On The Relationship Of FMR1 Gene In Diminished Ovarian Reserve And The Predictive Value Of Blood Biochemical Indexes On Follicular Development

Chapter 1 Study on the relationship of FMR1 gene in diminished ovarian reserveObjective:To clarify the role of FMR1 CGG repeat number in the assessment of ovarian reserve is helpful to understand the cause of diminished ovarian reserve(DOR).Methods:Select female patients and divide them into two groups according to AMH or basal follicle stimulating hormone(bFSH)level:DOR group(AMH<1.1 ng/ml or 10 IU/1<bFSH<25 IU/1)and control Group(AMH>1.1 ng/ml and bFSH<10 IU/1).Inclusion criteria:age<40 years old,no serious systemic disease,no pregnancy or breastfeeding in the past 6 months,no hormone medications in the first 3 months of enrollment,no history of gynecological endocrine diseases,no history of ovarian cyst surgery.Using three-primer PCR combined with capillary electrophoresis technology to detect the FMR1 CGG repeats.Name the smaller number of CGG repeats as Allele 1,and the larger number as Allele 2.Results:The difference between the AMH levels(respectively:0.7±0.3 ng/ml,3.6±2.5 ng/ml),basic FSH levels(respectively:8.0±4.0 IU/1,5.2±1.3 IU/1),age,and testosterone levels in the DOR group(n=121)and the control group(n=430)were statistically significant(P<0.001).The overall distribution of FMR1 CGG repeats in the DOR group and the control group was almost the same.The most common number of CGG repeats in both groups were 29 and 30.In Allele 2 of both groups,in addition to the main peak with the number of CGG repeats of 29-31,the second peak(minor peak)was also found at 36-37 CGG repeats.According to the number of CGG repeats,it is divided into 7 consecutive groups(respectively:<25,25-29,30-34,35-39,40-44,45-54,55-200)and 4 consecutive groups(respectively as:<25,25-34,35-44 and>44),there is no difference between the Allele 1 distribution,Allele 2 distribution in the DOR group and the control group of different CGG repeat number groups(P>0.05).According to the age level,they are divided into four groups(respectively:18-24,25-29,30-34,35-39 years old).The age of the DOR group is mainly distributed in the 35-39 years old age group(78 Cases,64.5%);while the control group is mainly distributed in the age group 30-34 years old(193 cases,44.9%).In this study,women of childbearing age with menstrual disorders or decreased fertility but no family history of fragile X syndrome carry a premutation rate of 1/275,combined with previous studys of pregnancy without a family history of fragile X syndrome in Hong Kong,China and Taiwan,China,the female FMR1 premutation carrier rate is 1/1325 and 1/1955,respectively.The premutation carrier rate of pregnant women without a history of miscarriage in northern China is 1/1679,while the premutation carrier rate of pregnant women with history of spontaneous abortion or induced labor due to delayed embryonic development in northern China is 1/320,suggesting that the FMR1 premutation carrier rate in women with a history of spontaneous abortion,induced labor due to embryonic development delay,or decreased fertility is much higher than that of normal pregnant women.Conclusion:1.The FMR1 premutation has a low incidence in DOR patients and normal women.The dynamic mutation of FMR1 CGG repeats is not an important pathogenic mutation of DOR patients.2.The existence of secondary peaks may be related to different results between different races.3.Testosterone may have a positive role in protecting ovarian function.4.FMR1 screening for women who have a history of spontaneous abortion,induced labor due to embryonic developmental delay,or infertility may be helpful to clinicians’ diagnosis and treatment.Chapter 2 Study on the predictive value of blood biochemical indicators for follicular developmentObjective:To clarify the relationship between serum AMH level and serum basic sex hormones,vitamin D and lipid concentrations,as well as predictors of ovarian hypofunction(DOR)and polycystic ovary syndrome(PCOS),is helpful to understand the regulatory factors of follicular development And mechanism.Methods:According to the AMH level and whether there is polycystic ovary status,they are divided into three groups:DOR group(AMH<1.1 ng/ml and no polycystic ovary condition),control group(AMH>1.1 ng/ml and no polycystic ovary)and PCOS group(preserved in polycystic ovary state).Exclusion criteria include:ovarian cyst;hyperprolactinemia;ovarian surgery;ovarian hematoma;malignant disease.Results:The differences of age(respectively:35.2±4.0 years,32.1±4.2 years,27.9±5.8 years),basic FSH(They are:11.3±15.8 IU/1,5.3±1.7 IU/1,4.5±1.2 IU/1),AMH(respectively:0.6±0.3 ng/ml,3.6±2.3 ng/ml,7.8±4.2 ng/ml),testosterone levels(respectively:24.2±8.5 ng/dl,28.4±10.2 ng/dl,43.4±19.8 ng/dl)between DOR group(n=133),control group(n=588)and PCOS group(n=108)were statistically significant(P<0.05).Age(r=-0.393,P<0.001),FSH(r=-0.197,P<0.001)and the neutrophil percentage(r=-0.09,P=0.028)were negatively correlated with AMH.LH(r=0.287,P<0.001),testosterone(r=0.569,P<0.001),homocysteine(r=0.114,P<0.01),estradiol(r=0.095,P<0.01)and prolactin(r=0.084,P<0.05)was positively correlated with AMH.Linear regression analysis indicated that age(95%CI:-0.266～-0.184),FSH(95%CI:-0.448～-0.358)and estradiol(95%CI:-0.165～-0.149)make AMH decrease(P<0.001),while LH(95%CI:0.337～0.475)and testosterone(95%CI:0.308～0.344)increased AMH(P<0.001).The binary Logistics analysis of the DOR group,after adjusted for age,basal FSH,and neutrophil percentage in this Logistics model indicated that,testosterone level increasing by 1 ng/dL was associated with a 0.97-fold decrease in DOR risk(95%CI:0.94-1.00,P=0.051).The binary logistic analysis of the PCOS group suggested that,in the logistic regression model adjusted for AMH,basal FSH,prolactin and homocysteine,every 1 ng/dL increase in testosterone level was associated with the occurrence of polycystic ovary syndrome There was a 1.07-fold increase in risk(95%CI:1.03-1.11,P<0.001).Conclusion:1.Age is an important factor in predicting AMH levels,ovarian dysfunction,and the occurrence of polycystic ovary syndrome.2.Basal FSH is negatively correlated with AMH,and elevated FSH levels are related to increased risk of ovarian dysfunction.3.LH is positively correlated with AMH,and elevated LH levels are associated with an increased risk of polycystic ovary syndrome.4.Testosterone is positively correlated with AMH,and elevated testosterone levels are associated with an increased risk of polycystic ovary syndrome and a decreased risk of ovarian dysfunction.The normal growth of follicles requires proper androgen levels.