Rational Application Of GnRH Antagonist Protocols In Women With Poor Ovarian Response

Objectives:To compare the therapeutic effect of fixed GnRH antagonist protocol and flexible GnRH antagonist protocol in IVF-ET outco me of poor ovarian response(POR)patients based on POSEIDON criteria and further explore the relationship between the timing of GnRH antagonist application and IVF outcome unexpected POR patients.Methods:Infertility patients accepted in vitro fertilization-embryo transfer(IVF-ET)or intracytoplasmic sperm injection(ICSI)were collected from January 1,2015 to July 1,2020 in the reproductive medicine department of the second Hospital of Jilin University.Based on the Poseidon criteria,the en rolled patients were divided into unexpected POR group and expected POR group.Unexpected POR group: patients with normal ovarian reserve markers(AFC ≥ 5 or AMH ≥ 1.2 ng/ml);(2)meet the criteria of POSEIDON 1 and 2 groups.The unexpected POR group was f urther divided into GnRH-ant fixed protocol group and GnRH-ant flexible protocol group.Unexpected POR group:(1)abnormal ovarian reserve markers(AFC < 5 or AMH< 1.2ng/ml);(2)meet the criteria of Poseidon 3 and 4 groups.The unexpected POR group was fu rther divided into GnRH-ant fixed protocol group and GnRH-ant flexible protocol group.The patients’ general data,ovulation induction data,laboratory indicators and cycle outcome of patients in each group were collected.Results:There was no significant difference in baseline characteristics(age,BMI,duration of infertility,type of infertility,basic hormone level,antral follicle count,anti-Mullerian hormone)between group A1 and group A2.The number of Gn days,the total dose of Gn and the diameter of dominant follicles in group A1 were lower than those in group A2.Over 70%of patients in group A1 and group A2 chose fresh cycles.The clinical pregnancy rate and live birth rate of fresh embryo transfer in group A2 were higher than those in group A1.The cumulative live birth rate per cycle in group A1 was 32.4%.The cumulative live birth rate per cycle in group A2 was 33.8%.In group B,30.6% of the patients used fixed GnRH-ant protocol,and 69.4% of the patients used flexible GnRH-ant protocol.Ther e was no significant difference in baseline characteristics before the beginning of COH cycle between group B1 and group B2.The number of Gn days,the total dose of Gn,the level of E2 on GnRH-ant application day in group B1 were significantly lower than those in group B2(P < 0.05).The clinical pregnancy rate and live birth rate of ET in group B2 were higher than those in group B1,while the opposite trend was observed in both groups who accepted frozen embryo transfer(FET).In addition,there was no si gnificant difference in cumulative live birth rate per cycle in both groups(P ≥ 0.05).Effects of hormone level and dominant follicle diameter in GnRH-ant application day in POR patients using flexible GnRH-ant protocol:(1)The ROC curve was used to analy ze the E2 and P levels on the GnRH-ant adding day in group A2,and the area under the curve(AUC)of the diameter of dominant follicles is over 0.5,which was of diagnostic value.The AUC of E2 is greater than P and the diameter of dominant follicle is gre ater than 0.7,which has high diagnostic value.When the level of E2 > 497.44 pg/ml,P > 1.05 mm,the diameter of dominant follicle > 14.65 mm,the clinical pregnancy rate decreased significantly.(2)ROC curve was used to analyze the diagnostic value of dail y hormone level of antagonist and dominant follicle diameter to abortion in A2 group.The level of E2,LH,P and the diameter of dominant follicle AUC > 0.5 on the day of adding antagonists have diagnostic value.When E2 level > 825.82 pg/ml,the dominant follicle diameter was > 13.45 mm,and the abortion rate decreased significantly.(3)ROC curve was used to analyze the diagnostic value of daily hormone level of antagonist and dominant follicle diameter in group A2 for live birth.The AUC of E2 and P on th e day of adding GnRH-ant and the diameter of dominant follicle is between 0.5and 0.7,which had lower diagnostic ability.When E2 level is higher than 497.44 pg/ml,P level is over 0.45 mm,the diameter of dominant follicle is over 14.65 mm,the live birt h rate decreased.(4)ROC curve was used to analyze the diagnostic value of daily hormone level of antagonist and dominant follicle diameter in group B2 for clinical pregnancy.The AUC of E2,LH,P level and the diameter of dominant follicles on the day af ter adding GnRH-ant were all greater than 0.5,which was of diagnostic value.Among them,the AUC of LH level and dominant follicle diameter are more than 0.7,which has strong diagnostic ability.The clinical pregnancy rate decreased significantly when th e level of E2 is over 392.27 pg/ml,LH is over 2.96 m IU/ml or the diameter of dominant follicle is over 15.25 mm.(5)ROC curve was used to analyze the diagnostic value of daily hormone level of antagonist and dominant follicle diameter in group B2 for abor tion.The AUC of E2,LH,P level and the diameter of dominant follicles on the day of adding GnRH-ant were less than0.7,and the diagnostic value was lower.When the level of E2 is over 565.14 pg / ml,the diameter of dominant follicle is over15.15 mm,the abortion rate decreased.(6)ROC curve was used to analyze the diagnostic value of daily hormone level of antagonist and dominant follicle diameter in group B2 for live birth.The AUC of E2 and LH on the day of adding GnRH-ant and the diameter of domina nt follicles are greater than0.5,which have diagnostic value.Among them,the AUC of LH level and dominant follicle diameter are more than 0.7,which have strong diagnostic value.When the level of E2 was higher than 274.1pg / ml,the diameter of domina nt follicle was over 15.25 mm,the live birth rate decreased significantly.Conclusion:For unexpected POR patients,the number of Gn days and the total dose of Gn in the fixed protocol were lower than those in the flexible regimen.Considering the complia nce and economic factors of patients,unexpected POR patients are more suitable for GnRH-ant fixed protocol.For expected POR patients,there was no difference in cumulative live birth rate per cycle between GnRH-ant fixed regimen and GnRH-ant flexible reg imen,but the clinical pregnancy rate of flexible regimen was higher.Clinicians can flexibly adjust the patient’s GnRH-ant regimen to achieve the best cycle outcome.When patients with unexpected POR were treated with GnRH-ant flexible regimen,GnRH-ant could be added to the serum when the E2 level is over 497.44ng/ml or dominant follicle diameter was 13.45-14.65 mm.It is expected that when POR patients are treated with GnRH-ant flexible regimen,GnRH-ant can be added when the serum E2 level is 274.1-565.14ng/ml or the dominant follicle diameter is 15.15-15.25 mm.