Abstract
Study question
Study aim is to compare implantation,clinical pregnancy and livebirth rates between giving1500IU of hCG4hours after GnRHagonist,on trigger day or GnRHagonist as alone trigger with luteal support withHCG1500IU.35h later on OPUday.
Summary answer
Adjuvant doze of1500IUhCG4h after bolus of GnRHagonist on trigger day significantly improve quality of blastocyst,implantation,clinical pregnancy and live birth rates without increasing the risk ofOHSS.
What is known already
The use of GnRHagonist for final oocyte maturation in antagonist cycle significantly decrease the incidence of OHSS,but there have been studies showing lower pregnancy rates in patients triggered with GnRHagonist compared with hCG in autologous cycles,attributed to a defective luteal phase, especially in high–risk patients despite intensive luteal phase support.To improve the results of IVF,an alternative approach is adding a small bolus dose of hCG(1500IU)35h later,on the OPU day after GnRHagonist trigger which provides more sustained support for the corpus luteum.The question is does low doses of hCGgiven on the same day with GnRHagonist trigger is making better quality oocytes.
Study design, size, duration
Single center prospective longitudinal cohort study fromJanuary2017 to Decembar2019.The initial inclusion criteria were:women age≥18and≤39years,AMH≥3,3ng/ml and ≥12 antral follicles on basal ultrasound.Patients with history of OHSS and PCO are also included in the study.Patients with applied “freeze-all” technique with peak estradiol≥4000pg/ml on trigger day>18oocytes on the OPU day,and recognized significant risk for developing OHSS were also included.The cumulative implantation,clinical pregnancy and live birth rates were analyzed,only in embryos from the same COS protocol in every patient.
Participants/materials, setting, methods
A total of 231 patients were entered for final analysis,who underwent a flexible antagonist protocol,ICSI and fresh or thawed ET on 3th(38.53%) or 5th( 61.47%)day in women’s autologous cycles.Patients were randomized in one of two groups: GroupA-Dual trigger group 1500IUof hCG 4h after GnRH agonist application on trigger day and GroupB –1500IU of HCG 35h later,on the OPU day.We used nonparametric and parametric statistical tests.Significant differences were considered all values of p < 0.05
Main results and the role of chance
Both groups are homogenous regarding several variables:age,BMI,type of sterility,smoking status,AMH,PCO, spermogram.There is no significant difference between the two(AvsB)groups according to average number of retrieved oocytes(13.6 vs 14.6 p > 0,05),M II oocytes(11.03 vs 11.99 p > 0.05).The dual trigger group(A)had a higher fertility rate(69.99% vs 64.11% p < 0,05)compared with GnRHagonist trigger group(B).There are no significant difference between groups(AvsB)according to cumulative average number of:transferred embryos(2.4vs2.5 p > 0.05)TQE transfered on 3th day(1.5.vs 1.3.p>0.05);transferred blastocyst(2.6 vs2.7 >0.05);cryo embryos(2.5vs1.9 p > 0.05),but there are significant difference according to cumulative implantation rate of transferred blastocyst in favor of group A(48.18% vs 33.89%p<0.05).Analyzes of morphological characteristics of transferred blastocyst depicted in the order of degree of blastocyst expansion,inner cellular mass(ICM)and trofoectoderm(TE) and ranking overall blastocysts quality from“excellent”,“good”,“average” and “pore” ,shows that there are significantly more percentage of patient with embryo transfer of “excellent” or even one “excellent” blastocyst in group A (30.56%,31.94% vs 21.54%,23.08% p < 0.05) in opposite of percentage of patients with embryo transfer with “poore “” blastocyst in group B (37.5% vs 46.15.%p<0.05). Clinical pregnanacy rate (71.68% vs 50.84% p < 0.05) , and live birth rate (60,18% vs 42,58% ), were significantly higher in group A. There were no cases of moderate or severe OHSS in both groups.
Limitations, reasons for caution
Dual trigger in GnRH antagonist protocols should be advocated as a safe approach but undetected high risk patients are reasons for caution for developing clinically significant OHSS.
Wider implications of the findings: Adjuvant low dose of hCG on GnRHagonist trigger day improve clinical pregnancy and live birth rates without increasing the risk of clinically significant OHSS.Protocol of dual trigger and freezing all oocytes or embryos in patients with high risk of developing OHSS is promising technique in everyday practice.
Trial registration number
8698
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