| Recent studies have shown that obesity has a negative impact on female reproductive systems,is one of the common causes of infertility[1,2],and is a risk factor that affects the outcome of assisted reproductive technology(ART)treatment[3,4].One of the key steps in ART is controlled ovarian hyperstimulation(COH).In the COH process,individualized treatment regimens based on the patient's ovarian function require the proper assessment of ovarian responsiveness to exogenous gonadotropin(Gn).Basal follicle stimulating hormone(FSH)/luteinizing hormone(LH),antral follicle count(AFC)and anti-mullerian hormone(AMH)are presently widely used in the clinical evaluation of ovarian response,and are generalized as "traditional indicators" of ovarian response.Since 2011,some scholars have proposed new independent indicators for assessing ovarian response,including the follicular output rate(FORT)[5],ovarian sensitivity index(OSI)[6]and follicular sensitivity index(FSI)[7],which have not been applied in clinical practice,and these were summarized as "new indicators" of ovarian response.The calculation formulas were as follows:FORT=peovulatory follicle count(PFC)/AFC,OSI=Number of retrieved oocytes/Total dose of FSH×1000,FSI=PFC/AFC×Total dose of FSH×100,000.In the formula,PFC refers to the number of follicles with a diameter of 16 to 22 mm on the day of human chronic gonadotropin(HCG)injection.Body mass index(BMI)is the most commonly used indicator for clinical assessment of obesity,there have been reports that BMI is negatively related to ovarian response[8,9].However,there are few studies on new indicators of ovarian response,such as FORT,OSI and FSI.ObjectivesTo explore the association of follicular output rate(FORT),ovarian sensitivity index(OSI),follicular sensitivity index(FSI)and body mass index(BMI)with ovarian response and in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)treatment outcome.To evaluate the value of FORT,OSI and FSI as a measure of ovarian response in IVF/ICSI treatment.Materials and Methods1.Study population:This study was a retrospective cohort study that retrieved IVF/ICSI fertility cycles from March 2016 to September 2018 in the electronic database of the Reproductive Center of Third Affiliated Hospital of Zhengzhou University.2.Inclusion criteria:?age?40 years old;?the COH protocol is the early follicular long protocol ovarian stimulation;?fresh embryo transfer cycles.Exclusion criteria:?patients with recurrent spontaneous abortion;?patients with chromosomal abnormalities on either side of the couple;?combined with endometriosis,abnormal uterine cavity,hydrosalpinx,ovarian cyst,ovarian deficiency and other organic diseases;?patients with expected low ovarian response(age?40 years,AMH<1.1 ng/mL,AFC<5,basal FSH>12 IU/L)[10,11];?Patients with chronic metabolic diseases;?Patients with donated oocytes.3.Grouping:The study cohort was divided into three groups based on the Chinese adult BMI classification[12]:normal group,18.5 kg/m2?BMI<24 kg/m2;overweight group,24 kg/m2?BMI<28 kg/m2;obese group,BMI>28 kg/m2.4.Definition of ovarian high response:the number of oocytes retrieved was>15[13,14].5.Statistical analysis:All statistical analyses were performed using SPSS 21.0 and MedCalc 19.0.6.Continuous variables are expressed as mean ± standard deviation or median(quartile).Categorical variables were expressed as the number of cases(n)with the percentage of occurrence(%).One-way ANOVA and nonparametric test were respectively used to compare the mean or median of continuous variables,and the Bonferroni test was used to compare two groups.Chi-square test was used to compare the categorical variables.Binary logistic regression analysis was used to test the association of independent influencing factors with live birth and clinical pregnancy,while controlling for confounders of interest.The adjusted odds ratios(OR)with 95%confidence interval(CI)and P-values were recorded.Pearson's correlation analysis was used to compare the relationship between relevant parameters and ovarian response.Receiver operator characteristic(ROC)curves were used to compare the diagnostic value of BMI and ovarian response indicators for ovarian hyperresponsiveness and the predictive value of clinical pregnancy outcomes.The statistical significance was set at P<0.05.ResultsAfter screening by the above inclusion and exclusion criteria,a total of 3486 cycles were included in this study,including 1982 in the normal group and 1144 in the overweight group;360 in the obese group..1.The association of FORT,OSI,FSI and BMI with ovarian response and IVF/ICSI treatment outcome(1)Analysis and comparison of IVF/ICSI treatment data in different BMI groups:With the increase in BMI,the years of infertility(3.21±2.29 VS 3.67±2.76 VS 4.13±2.72,P=0.000),AFC(17.50±5.69 VS 18.68±6.14 VS 20.33±5.88,P=0.000),COH days(13.49±2.21 VS 14.15±2.96 VS 14.69±3.29,P=0.000)and total Gn dose[2175.0(1650.0,2925.0)VS 2662.5(1990.6,3412.5)VS 2993.8(2328.1,3625.0),P=0.000]gradually increased,while FORT(0.56±0.23 VS 0.52±0.24 VS 0.48±0.21,P=0.000),OSI(6.61±3.88 VS 5.28±3.16 VS 4.67±2.72,P=0.000)and FSI(26.39±13.72 VS 20.77±11.64 VS 17.33±9.43,P=0.000)gradually decreased,and the differences between the three groups were statistically significant.Compared with the overweight group and obese group,the number of oocytes retrieved(13.23±5.01 VS 12.72±5.00 VS 12.70±5.12,P=0.012),fertilized oocytes(8.43±4.16 VS 8.08±4.14 VS 7.92±4.28,P=0.019)and available embryos(6.701±3.85 VS 3.89±3.19 VS 3.79±3.37,P=0.006)in the normal group increased,the differences between the three groups were statistically significant,and there were no significant difference between the overweight group and obese group(P>0.05).(2)Impact of BMI on IVF/ICSI pregnancy outcomes:Compared with the normal group and the overweight group,the embryo implantation rate(49.60%VS 47.50%VS 41.06%,P=0.000),clinical pregnancy rate(61.80%VS 59.30%VS 53.10%,P=0.007),and live birth rate(49.60%VS 46.50%VS 40.30%,P=0.003)in the obese group were reduced,the differences between the three groups were statistically significant,and there were no significant difference between the overweight group and obese group(P>0.05).The binary logistic regression analysis revealed that BMI was risk factors for clinical pregnancy[OR(95%CI)=0.964(0.940,0.988),P=0.003]and live birth[OR(95%CI)=0.973(0.950,0.997),P=0.027].(3)Impact of BMI on pregnancy outcome in patients with singleton pregnancy:In the three cohorts,time to live birth increased with increasing BMI and the differences between the three groups were significant(316.6±10.00 VS 324.6±10.26 VS 333.3±11.42,P=0.000);Compared with the overweight group and obese group,the neonatal weight(3365±474.9 VS 3522±482.2 VS 3571±514.7,P=0.000)and large for gestational age(LGA)delivery rate(20.20%VS 37.10%VS 37.30%,P=0.000)in the normal group decreased,the differences between the three groups were statistically significant.There were no significant differences in gestational age,miscarriage rate and premature birth rate among singleton pregnancy groups(P>0.05).(4)Correlation between BMI and FORT,OSI,FSI:Pearson correlation analysis showed that FORT(r=-0.140,P=0.000)?OSI(r=-0.219,P=0.000)?FSI(r=-0.299,P=0.000)were negatively correlated with BMI.2.The value of FORT,OSI and FSI as a measure of ovarian response in IVF/ICSI treatment.(1)Pearson correlation analysis with the number of oocytes retrieved:AFC(r=0.250,P=0.000)?AMH(r=0.263,P=0.000)?FORT(r=0.279,P=0.000)?OSI(r=0.783,P=0.000)?FSI(r=0.383,P=0.000)were positively correlated with the number of oocytes retrieved.Age(r=-0.089,P=0.000),BMI(r=-0.057,P=0.001)and basal FSH/LH(r=-0.128,P=0.000)were negatively correlated with the number of oocytes retrieved.And the correlation between the new index of ovarian response and the number of oocytes retrieved(r value)is higher than the traditional index.(2)Comparison of predictive ability of various ovarian response indicators to ovarian hyperresponsiveness and clinical pregnancy outcomes:The ROC curve analysis revealed that the diagnostic value of OSI(AUC=0.884,95%CI:0.873?0.895,P=0.000)and FSI(AUC=0.678,95%CI:0.662?0.694,P=0.010)for high ovarian response were superior to traditional indicators,but there were no advantage in predicting clinical pregnancy outcome.Conclusions1.Obesity is an independent risk factor for clinical pregnancy and live birth,but it does not affect the premature and miscarriage rates of women with single pregnancy.Obese and overweight female offspring has a significantly higher risk of LGA..2.FORT,OSI and FSI are negatively correlated with BMI,which can be used as new tools for assessing ovarian response.However,there appears to be no advantage in predicting the outcome of IVF/ICSI treatment outcomes. |
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