| In the past 40 years,although assisted reproductive technology has been widely used,there are still some clinical problems that need to be resolved:5.6%～35.1%of in vitro fertilization(IVF)patients undergoing ovarian stimulation have poor ovarian response(POR).In 2011,in order to reach a consensus,the European Society of Human Reproduction and Embryology(ESHRE)first proposed the Bologna group for POR.The Bologna criterion uniformly defines and distinguishes the ovarian response state,but such a definition of POR has certain limitations and heterogeneity.In 2016,the Poseidon working group proposed the POSEIDON group,which combined qualitative and quantitative parameters for more detailed stratification,creating more homogeneous subgroups.So far,there are few domestic and foreign data evaluating the pregnancy outcome of the low prognosis population defined by the Poseidon group.ObjectivesIn this study,we first compared the clinical outcomes of clomiphene letrozole mild stimulation protocol and progestin primed ovulation stimulation(PPOS)protocol in POSEIDON group.Combine the CC+LE+Gn and PPOS protocol into non down-regulation ovulation stimulation protocols,and then include two conventional ovulation stimulation protocols:GnRH-a long protocol,GnRH antagonist protocol,compare the above three protocols in different categories of POSEIDON group,so as to provide basis for the selection of suitable ovulation stimulation protocols for low prognosis population.Materials and Methods1.Study population:A retrospective analysis of 4270 cycles of clinical data of patients with POSEIDON criterion underwent in vitro fertilization/intracytoplasmic sperm injection-embryo transfer(IVF/ICSI-ET)at the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from November 2015 to September 2019.1.1 Inclusion criteria:①Patients who meet any group of the POSEIDON group;②Patients who use one of the GnRH-a long protocol,GnRH-ant protocol,and clomiphene letrozole(CC+LE)mild stimulation protocol and PPOS protocol to assist with IVF/ICSI.1.2 Exclusion criteria:①Incomplete data cycle;②People with chromosomal abnormalities or PGT assisted pregnancy in both or one of the spouses;③Related diseases that affect the outcome of IVF pregnancy,such as untreated hydrosalpinx,grade III or IV endometriosis,uterus adenomyosis,untreated endometrial disease,abnormal or abnormal development of the uterus.2.Grouping2.1 According to the POSEIDON criterion,they are divided into four groups:POSEIDON group 1[PG1,age<35 years,anti-Müllerian hormone(AMH)≥1.2μg/L,number of antral follicles(AFC)≥5,number of eggs obtained after previous standard ovulation induction ≤9];POSEIDON group 2(PG2,age≥ 35 years,AFC≥ 5,AMH≥1.2μg/L,number of eggs obtained after previous standard ovulation induction≤9);POSEIDON group 3(PG3,age<35 years,AFC<5,AMH<1.2μg/L);POSEIDON group 4(PG4,age>35 years,AFC<5,AMH<1.2μg/L).PG1 has 531 cycles,PG2 has 309 cycles,PG3 has 2043 cycles,and PG4 has 1256 cycles.Each group was further divided into three groups,namely the GnRH-a long protocol(group A),the GnRH antagonist protocol(group B),and non down-regulation ovulation stimulation protocols(group C,including CC+LE+Gn protocol and PPOS protocol).2.2 The first part:Include patients who meet the POSEIDON criterion,and compare the differences in clinical outcomes between the CC+LE+Gn mild stimulation protocol and the PPOS protocolInclude 599 cycles of IVF/ICSI-ET cycles in compliance with POSEIDON criterion application CC+LE+Gn protocol,and 420 cycles of PPOS protocol.The two groups of patients underwent IVF/ICSI freezing of whole embryos,and the differences in the implantation rate,clinical pregnancy rate,early miscarriage rate,ectopic pregnancy rate and live birth rate during the first frozen embryo transfer cycle were observed.2.3 The second part:To compare the differences in the clinical outcomes of the three ovarian stimulation protocol in the four groups of patients under the POSEIDON criterionThe patients who met the POSEIDON criterion were enrolled using the GnRH-a long protocol(group A)for a total of 2738 cycles[A1(n=277),A2(n=153),A3(n=1727),A4(n=581)],using GnRH antagonist(group B)for a total of 513 cycles[B1(n=92),B2(n=142),B3(n=128),B4(n=151)],and using non down-regulation ovulation stimulation protocols(group C)for a total of 1019 cycles[C1(n=162),C2(n=145),C3(n=188),C4(n=524)].Observe the differences in implantation rate,clinical pregnancy rate,early abortion rate,ectopic pregnancy rate and live birth rate after the first transplantation.3.Statistical analysis:Use SPSS25.0 software.Measurement data were expressed as mean ± standard deviation,and comparison between measurement data was performed by t test;count data was expressed by rate(%),and comparison between groups was analyzed by χ2 test.When comparing the three groups in pairs,the analysis of variance of the data between the groups uses the SNK-q method,and the non-parametric rank sum test is used for the comparison of the uneven variances between the groups;the use of Logistic single-factor/multi-factor model analysis may affect the factors of pregnancy are expressed by relative risk(OR)and its 95%CI.The statistical significance was set at P<0.05.Results1.Comparison of clinical and embryo laboratory indicators and clinicaloutcomes between CC+LE+Gn mild stimulation group and PPOS groupIn the CC+LE+Gn mild stimulation group,the amount of Gn[(2538.07±767.97)IU vs.(2748.28±858.93)IU]and the number of Gn days[(9.22±2.11)d vs.(9.62±2.49)d]were significantly less in the PPOS group,the difference was statistically significant(P<0.001,P=0.007);there was no statistical difference in the number of retrieved oocytes,the number of 2PN,the number of usable embryos,the number of high quality embryos,the endometrial preparation plan,the endometrial thickness on the transfer day,the number of transferred embryos,and the transfer rate of blastocysts between the two groups(P>0.05).After correcting for confounding factors,the clinical pregnancy rate(33.65%)of the PPOS protocol was significantly higher than that of CC+LE+Gn mild stimulation(27.42%),and the difference was statistically significant(P=0.041);there was no significant difference in implantation rate,early abortion rate,ectopic pregnancy rate,and live birth rate between the two groups(P>0.05).2.Comparison of clinical,embryonic laboratory indicators and clinical outcomes of three ovarian stimulation protocol in four groups of patients underPOSEIDON criterion classificationIn the four groups of POSEIDON criterion classification(PG1,PG2,PG3,PG4),the amount of Gn and the number of days of Gn increased significantly compared with groups B and C in group A(PG1,PG2,PG3,and PG4);the endometrial thickness on the transfer day showed a decreasing trend from groups A,B,and C,and the difference between the three groups was statistically significant(P<0.05);the number of 2PN and the number of available embryos in group A were significantly higher than those in groups B and C(P<0.05);There was no significant difference in the incidence of ovarian hyperstimulation syndrome among the three protocol(P>0.05).In PG1,the implantation rate,clinical pregnancy rate,and live birth rate were not statistically different among the three groups Al,B1,and C1(P>0.05);in PG2,the implantation rate of group A2 was higher than that of group C2(32.35%vs.20.40%),The clinical pregnancy rate(44.29%vs.20.69)and the live birth rate(31.42%vs.15.17%)were significantly higher(P<0.05);In the PG3 population,the implantation rate of group A3 was significantly higher than the other two groups(45.48%vs.36.00%,45.48%vs.31.37%),and the clinical pregnancy rate was significantly higher than the other two groups(59.11%vs.45.24%,59.11%vs.42.55%),the difference was statistically significant(P<0.05),and the live birth rate between the three groups was significantly different(44.57%vs.31.75%vs.21.28%,P<0.05),showing a gradual downward trend.Group A3 is the highest,followed by Group B3,and Group C3 is the lowest;In PG4,the implantation rate(35.89%vs.19.37%vs.12.73%),pregnancy rate(49.27%vs.28.38%vs.21.00%),and live birth rate(31.64%vs.16.89%vs.9.82%)among the three groups in PG4,the difference was significant(P<0.05),and the three groups A4,B4,and C4 showed a gradual downward trend;There were no significant differences the rates of early abortion and ectopic pregnancy among the four groups of patients with different ovarian stimulation protocol according to the POSEIDON criterion classification(P>0.05).Multivariate logistic regression showed that age,ovulation stimulation protocol,total number of Gn days,and the number of retrieved oocytes were independent influencing factors of live birth;for the unexpected low response group(PG1,2),the live birth rates of groups A,B,and C were On a downward trend,the live birth rate of group A was significantly higher than that of group C(OR=3.027,95%CI:1.329-6.895;P=0.008;OR=2.927,95%CI:1.293-6.629;P=0.010);Among the PG3 population,group A had the highest live birth,followed by group B,and group C had the lowest(OR=2.251,95%CI:1.298-3.902,P=0.004;OR=1.881,95%IC:1.048-3.376;P=0.034;OR=0.724,95%IC:0.473-0.908,P=0.037);In PG4,the live birth rate of groups A,B,and C showed a downward trend.Compared with group C,the live birth rate of group A was significantly higher(OR=2.192,95%IC:1.061-4.527;P=0.034).Conclusions1.After classifying POSEIDON group patients with low prognosis,the GnRH-a long protocol has the highest number of live births in each group,and can be used as the first stimulation protocol.2.In PG1,PG2 and PG4 groups,the live birth rate of GnRH-a long-term protocol,GnRH antagonist protocol and non down-regulation ovulation stimulation protocols showed a decreasing trend,but there was no statistical difference;In the three protocols of PG3 group,the live birth rate of patients decreased in turn,and there was significant statistical difference,so GnRH antagonist protocol can be used as the second choice in poor ovarian response patients. |
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