Comparison Of Blastocyst Rates Of Poor Ovarian Response Patients With Luteal Phase Stimulation Based On POSEIDON Criteria.

Background:Patients with poor ovarian response(POR)is a conundrum for patients and clinicians during assisted reproductive technology(ART)treatment.With the increase of the birth demand from advanced age women,the proportion of POR patients is growing annually.There was no unified diagnostic standard for POR until 2011.In 2011,the European Society for Human Reproduction and Embryology developed a consensus for POR diagnosis(Bologna Criteria),but there are some limitations in its clinical application,such as incomplete diagnostic criteria and lacking of evaluation indicators for oocytes' quality.And in 2016,the group of patient-oriented strategies encompassing individualized oocyte number(POSEIDON)proposed an improved classification and criteria.Low prognosis groups are stratified into four sub-groups according to ovarian reserve markers and age.At present,the common protocols used for controlled ovarian hyperstimulation(COH)in patients with POR include mini-stimulation protocol,GnRH antagonist protocol and natural cycle etc.However,the number of oocytes obtained and the outcome of pregnancy are not satisfactory.In 2009,Kuang et al.first used luteal phase stimulation(LPS)in an advanced aged woman with low ovarian reserve,and achieved the outcome of twin live birth,which provided a new strategy for POR patients.In recent years,LPS protocol has been widely used in clinic,especially in the advanced age women with decreased ovarian reserve,but it is still controversial whether LPS protocol is optimal for all POR patients.Objective To investigate the blastocyst rate of four groups of POR patients under the POSEIDON classification.Methods 220 women with POR who received IVF/ICSI-ET treatment in the Affiliated Reproductive Hospital of Shandong University from January 2017 to September 2019 with luteal phase hyperstimulation protocol were collected.The patients were divided into four groups according to POSEIDON classification,PG1:patients with young age and normal ovarian reserve(<35 years,AMH?1.2ng/mL);PG2:advanced age women with normal ovarian reserve(?35years,AMH?1.2ng/mL);PG3:young age patients with low ovarian reserve(<35 years,AMH<1.2ng/mL);PG4:patients with advanced age and low ovarian reserve(?35years,AMH<1.2ng/mL).All patients received luteal phase stimulation after natural cycle ovulation or hCG triggered ovulation.The differences of gonadotropin dosage,length of stimulation,average number of retrieved oocytes,fertilized oocytes(2PN)rate and high-grade blastocyst rate(D5 or D6)were compared among four groups.The numbers of oocytes retrieved and good blastocyst rate(D5 or D6)was analysed as the primary outcome parameters.The fertilized oocytes,gonadotropin dosage,and length of stimulation were secondary outcome parameters.Results1.Baseline characteristics of poor ovarian respondersThere are 13,37,44,126 patients in PG1,PG2,PG3,PG4 respectively.There were significant differences in age,AMH,bFSH and husband age among groups(P<0.05).We did not find any significant difference for BMI and cycle attempts(P>0.05).2.Comparison of cycle characteristicsThe average number of oocyte collected from PG1 to PG4 was 4.77(62/13),3.59(133/37),2.05(90/44),2.33(293/126)with significant difference(P<0.001,F=10.51).Blastocyst rate was 50.00%,34.12%,51.72%and 27.86%,respectively.There were significant differences in high-quality blastocyst rate(P<0.01).Fertilized oocytes rates were 51.61%,63.91%,64.44%and 68.60%respectively,with no significant difference(P=0.08).Multiple comparison:(1)PG1 vs.PG2 According to serum bFSH and AMH level,both groups had normal ovarian reserve.For PG2 patients with advanced age,the average number of oocytes and high-quality blastocyst rate had no significant difference compared with PG1(P=0.12?P=0.12).However,compared with PG2,an increasing trend in average number of oocytes and blastocysts rate was observed in PG1.(2)PG3 vs.PG4 The ovarian reserve of the two groups decreased significantly based on the level of bFSH and AMH.There were no significant differences in the average number of oocytes(P=0.39).While,as younger patients in PG3(<35 years),the rate of high-grade blastocyst was significantly higher than PG4(?35 years),with statistical difference(P<0.001).(3)PG1 vs.PG3 Both of them were young patients,whereas ovarian reserves in PG1 were better than PG3.More oocytes were retrieved in PG1 compared with PG3,with significant difference(P<0.001).However,no difference was observed in blastocyst rate between the two groups(P=0.88).(4)PG2 vs.PG4 Ovarian reserves of PG2 were better than PG4,and the average number of oocytes was higher in PG2 than PG4(P=0.005).However,there was no significant difference in blastocyst rate existed between the two groups(P=0.29).Conclusion1.Age is the key factor affecting ovarian reserve and quality of embryo.In young age patients with POR,the rate of high-quality blastocysts is much higher than that in elderly patients.Increasing the number of oocytes will increase the number of blastocysts,but for advanced age POR patients,more oocytes obtained could not significantly improve the blastocyst rate.2.For patients with POR,individual protocols of controlled ovarian hyperstimulation are suggested.Luteal phase stimulation is more effective in POR patients with young age and diminished ovarian reserve.