| BACKGROUND AND OBJECTIVEIn 2016,the POSEIDON team proposed a new standard for patients with poor ovarian response(POR)— the POSEIDON criteria.The purpose is to classify patients with different prognoses and different reproductive potential to provide guidance for individualized management.Young infertile patients with good ovarian reserve are more likely to obtain larger and better quality oocytes,but some patients with normal ovarian reserve still have ovarian "suboptimal response" or "poor response" after controlled ovarian hyper-stimulation.So when facing these patients with normal response,whether the appropriate ovulation induction strategy can be selected according to different prognoses so as to improve their assisted pregnancy outcomes and reduce the incidence of poor response.On the other hand,there is no clear guideline and consensus on the most appropriate dose of follicle stimulating hormone and the maximum Gn initiation dose,and multiple dosing regimens are advocated.In this study,patients with normal ovarian reserve(AMH 1.2-2.6 ng/ml)were analyzed from the perspective of the incidence of low response and the incidence of suboptimal response,the therapeutic effects of long protocol Gn RH agonist and Gn RH antagonist were compared,and the better ovarian stimulation protocol was further stratified according to age and AMH to compare the therapeutic effects of different starting doses,providing a basis for more effective management of this part of the infertile population.MATERIALS AND STUDY METHODSA retrospective analysis of patients who visited the Reproductive Center of the Third Affiliated Hospital of Guangzhou Medical University on January 1,2010 and November 30,2020 for the first time for IVF/ICSI assisted pregnancy treatment was performed.Inclusion criteria Patients who met the IVF/ICSI-ET indications were enrolled in this study.The range of AMH results was 1.2 ng/ml to 2.6 ng/ml within 1 year.controlled ovarian hyper-stimulation protocol was long protocol Gn RH agonist and Gn RH antagonist protocol.Patients had regular menstrual cycles.Exclusion criteria :Cancellation of ovulation induction or oocyte retrieval due to personal factors during treatment;ovarian syndrome;suffering from other endocrine diseases(hyperthyroidism,hypothyroidism,hyperprolactinemia,pituitary microadenoma,adrenal hyperplasia,diabetes,etc.);history of recurrent miscarriage(spontaneous abortion ≥ 2 times);immune system diseases;genetic diseases,chromosomal abnormalities;uterine malformations or the presence of endometrial organic disease;PGT/PGD,egg/sperm donation cases.Grouping criteria: 1.According to different COH regimens,they were divided into two groups: long protocol Gn RH agonist and Gn RH antagonist regimen.2.According to the results of the number of oocytes retrieved from fresh cycles after ovarian stimulation with long Gn RH agonist protocol,the patients were divided into poor response group(≤ 3),suboptimal response group(4 ～ 9)and expected response group(≥ 10).3.The cases of long Gn RH agonist regimen were further stratified according to age and AMH.The age stratification conditions were age < 35 years,35～ 37 years and ≥ 38 years.The AMH stratification conditions were 1.2 ng/ml ≤ AMH< 2.0 ng/ml and 2.0 ng/ml ≤ AMH ≤ 2.6 ng/ml.The criteria for gonadotropin initiation dose grouping were ≤ 200 IU(group A),201 ～ 250 IU(group B),and > 250 U(group C).RESULTSComparison of the effect of long Gn RH agonist regimen and antagonist regimen in AMH 1.2 ～ 2.6 ng/ml population:1 Compared with the antagonist regimen,the long Gn RH agonist regimen group had a reduced risk of low response(OR = 0.668,95% CI: 0.486 – 0.922),a reduced risk of suboptimal response(OR = 0.777,95% CI: 0.643 – 0.939),and a reduced risk of cycle cancellation due to no oocyte retrieval(OR = 0.239,95% CI: 0.087 – 0.655),and the risk of canceling cycles due to high P was reduced(OR = 0.372,95% CI:0.253 – 0.545)(all P < 0.05).2 multivariate logistic regression analysis showed that: relative to the expected response group,(1)the risk of oocytes abnormalities was increased in the poor response group(OR = 31.828,95% CI: 3.335 – 303.764),the risk of fertilization abnormalities was increased(OR = 8.483,95% CI: 3.026 – 23.777),and the risk of cancellation of transfer due to poor embryo quality was increased(OR = 5.106,95%CI: 3.052 – 8.542),all P < 0.05;(2)the risk of cancellation of transfer due to poor embryo quality was increased in the suboptimal response group(OR = 2.001,95% CI:1.340 – 2.988)(P < 0.05),and there was no significant difference in the risk of oocytes abnormalities and fertilization abnormalities(P > 0.05);3 long Gn RH agonist regimen and antagonist regimen had no significant effect on pregnancy outcome after fresh transfer(P > 0.05),and the independent predictors affecting pregnancy outcome were mainly age,AFC,b FSH,endometrial thickness,and number of embryos transferred. the effect of using different starting doses when applying long Gn RH agonist regimens in the population with AMH 1.2 ～ 2.6 ng/ml was compared.1 The need to increase the amount of Gn during induction was an independent predictor of low/suboptimal response,and the chance of low and suboptimal response was reduced in the non-incremental group relative to the incremental group,with ORs(95% CI)of 0.455(0.325-0.639)and 0.653(0.556-0.768),respectively(all P < 0.05);2 b FSH,AMH,AFC,BMI,and Gn initiation dosage were independent predictors of the need to increase Gn dosage during induction,of which b FSH and BMI were associated with an increased risk of the need to increase Gn dosage,and AMH,AFC,and Gn initiation dosage were associated with a decreased risk of the need to increase Gn dosage(all P < 0.05);3 < 35 years old,AMH 1.2 ～ 2.6 ng/ml and 35 ～ 37 years old,AMH2 ～ 2.6 ng/ml:the application effect of priming dose > 250 IU group 201 ～ 250 IU group is similar;≤ 200 IU group needs to increase the proportion of cycles of Gn dosage.4 35 ～ 37 years old,AMH 1.2 ～ 2 ng/ml,starting dose ≤ 200 IU group,the median average daily Gn dosage was 200 IU.The proportion of cycles requiring increased Gn dosage was lower in the > 250 IU group,but it could not improve egg quality and pregnancy outcomes;5 ≥ 38 years old,AMH 1.2 ～ 2.6 ng/ml,≤ 200 IU 201 ～ 250 IU group had similar total Gn dosage and average daily Gn dosage.(1)When AMH 1.2 ～ 2.0 ng/ml,due to less age,b FSH and AFC in > 250 IU group,the number of oocytes retrieved,fertilization rate,excellent embryo clinical,clinical pregnancy rate and continued pregnancy rate were significantly reduced(P < 0.05).(2)When AMH2 ～ 2.6 ng/ml,although the age,b FSH and AFC of > 250 IU group were less,the number of oocytes retrieved,fertilization rate,excellent embryo clinical,clinical pregnancy rate and continued pregnancy rate were similar to those of the other two groups.Conclusion1 For the population with AMH 1.2 ～ 2.6 ng/ml,the long Gn RH agonist regimen benefits more than the antagonist regimen in terms of the incidence of low response/suboptimal response and the impact on fresh cycle transplantation.There was no significant difference in the risk of OHSS between the two regimens,but the long-acting long regimen required the use of a Gn dose.2 For the overall population with AMH 1.2 ～ 2.6 ng/ml,the daily Gn dosage of 150 IU may be insufficient.(1)For the population < 35 years old,AMH 1.2 ～ 2.6 ng/ml and 35 ～ 37 years old,AMH 2-2.6 ng/ml,the starting dose is not recommended to exceed 250 IU;(2)For the population ≥ 35 years old,AMH 1.2-2.6 ng/ml,it is recommended to increase the starting dose of Gn to at least 200 IU;(3)For the population ≥ 38 years old,AMH2 ～ 2.6 ng/ml,> 250 IU starting dose has some benefit;for the elderly(especially > 40 years old),AMH < 2 ng/ml,the ovarian reserve is low and the embryo quality is poor,even the starting dose > 250 IU cannot compensate for the age-related decrease in pregnancy outcomes. |
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