P-283 RCT Comparing day 3 - fresh embryo transfer cycles with freeze all cycles in IVF-ICSI cycles
Authors: Singh R , Singh M 
Published: June 2022

Abstract

Study question
Is the Cumulative live birth rate in freeze-all cycles comparable to Day- 3 Fresh Embryo Transfer Cycles ?

Summary answer
Yes the Cumulative live birth rate in freeze-all cycles is comparable to Day- 3 Fresh Embryo Transfer Cycles.

What is known already
Freezing of all embryos in IVF-ICSI cycles is beneficial in PCOS- High Responders but not in Normal and Poor-Responders.
Freeze-All protocols offers no additional benefit in pregnancy rates in normal responder patients.
Increasing pregnancy rates after frozen-thawed embryo transfer have encouraged wider implementation of a freeze-all (elective freezing of all embryos) strategy in assisted reproductive technology treatment A freeze-all strategy that uses gonadotropin releasing hormone agonist triggering can minimise the risk of ovarian hyperstimulation syndrome Existing studies are lacking that compare a freeze-all strategy using gonadotropin releasing hormone agonist triggering with a fresh transfer strategy using human chorionic gonadotropin triggering.

Study design, size, duration
112-Non-PCOS-Infertile patients undergoing IVF-ICSI cycles between 2018-2021, were included in this study. Patients were eligible if at day 3 at least two good quality embryos were present. After informed consent, all patients were randomised by computer to either Fresh Day-3 Embryo -Transfer protocol or a Freeze-All protocol. In the freeze-all group, all good embryos were cryopreserved and then thawed on the day of ET in the following cycle.

Participants/materials, setting, methods
112-Non-PCOS-Infertile patients were eligible if at day 3 at least two good quality embryos were present. After informed consent, all patients were randomised to either Fresh Day-3 Embryo -Transfer protocol or a Freeze-All protocol. In the freeze-all group, all good embryos were cryopreserved and then thawed on the day of ET in the following cycle. The primary outcome was clinical pregnancy rate.
Baseline characteristics of all Infertile patients were comparable in both study groups

Main results and the role of chance
Clinical Pregnancy Rate was 36% in Fresh Embryo Transfer cycles and 38% in Freeze All cycles, the difference being not statistically significant.
Multiple gestation and abortion rates were also comparable in both the groups
Ongoing pregnancy rate did not differ significantly between the freeze-all and fresh transfer groups. In women with regular menstrual cycles, a freeze-all strategy with gonadotropin releasing hormone agonist triggering for final oocyte maturation did not result in higher ongoing pregnancy rates than a fresh transfer strategy. By using gonadotropin releasing hormone agonist triggering in the freeze-all group and a predefined cutoff level for ovarian hyperstimulation syndrome risk in the fresh transfer group, ovarian hyperstimulation syndrome was practically eliminated in both groups. Time to pregnancy was longer in the freeze-all group, therefore fresh embryo transfer should be used as the gold standard if no apparent treatment advantage or immediate risk of ovarian hyperstimulation syndrome is present because it is vital for patients not to postpone pregnancy.

Limitations, reasons for caution
In both treatment groups, the individualised starting dose of gonadotropin was based on female age/weight, AFC, AMH & previous response to stimulation. Randomisation was performed at baseline, and patients and doctors were blinded to the randomisation group until the day of ovulation triggering to avoid influence on ovarian stimulation dosing.

Wider implications of the findings
Therefore, caution should be exercised while choosing between Fresh ET and Freeze-All protocol in non-PCOS patients.
In normal responder patients, a Freeze-All protocol in IVF-ICSI cycles, had comparable pregnancy rates with Day-3 Fresh-ET.
Freeze-All protocols offers no additional benefit in normal responder and this technique should be reserved for High Responders.

Trial registration number
not applicable