O-022 Shall we go “natural” for endometrial preparation in egg donation programs? Live birth rates and obstetrical outcome from 797 frozen single-blastocyst transfers cycles
Authors: Moffa F , Garcia-Faura A , Novo S , Perez-Alzueta A , Acin L , Moreno A , Peinado L , Ruiz P , Lolicato F , Rovira S , Antic M 
Published: June 2023

Abstract

Study question
Frozen single blastocyst transfer in modified natural cycle (mNC) increases success rates reducing obstetric risks in egg recipients, compared to Hormone Replacement Therapy (HRT) protocols?

Summary answer
In egg recipients, single-blastocyst transfer in mNC showed higher pregnancy rates, lower miscarriage rates, higher new-born rates compared to HRT, being preterm birth rate comparable.

What is known already
When choosing endometrial preparation protocols for egg recipients, we must consider medication safety and costs, cycle’s cancellation rate, clinical outcomes as maternal and fetal risks. The superiority of mNC over HRT for frozen embryo transfers (FET) has been reported in terms of delivery and miscarriage rates as well as obstetrical complications, but few data are available on egg recipients, being HRT protocols the routine treatment in most cases.
In donor programs, when a blastocyst freeze-all strategy or egg banking is applied, there is no longer need for donor-recipient synchronization and many FET could be performed in mNC cycles.

Study design, size, duration
Retrospective single-centre comparative clinical study, including 797 frozen single-blastocyst transfer (FSBT) initiated cycles between January 2020 and December 2021: 590 (74%) in HRT protocol and 207 (26%) in mNC protocol.
The two groups were homogeneous for donor’s age (25,4 yo HRT Vs 25,8 yo mNC), recipient’s age (42,1 yo HRT Vs 42,4 yo mNC), severe male factor (6% HRT Vs 4% mNC), and the need for a sperm donor (28% HRT Vs 22% mNC).

Participants/materials, setting, methods
Among 797 started cycles, we compared cancellation rates between HRT and mNC groups due to either medical reasons (inadequate endometrium, bleeding, ovulatory leak) or other issues (no embryo survival, flight cancellations, COVID-19 restrictions).
We studied the clinical outcomes of the 683 FSBT performed, comparing HRT and mNC cycles for pregnancy rate, clinical pregnancy rate, miscarriage rate, live birth rate, and preterm birth rate &lt;35 weeks. We used Chi-square test to compare groups (p &lt; 0,05).

Main results and the role of chance
CANCELLATION RATES: Out of the 797 endometrial preparation cycles started, the overall cancellation rate was 14% from which 72,8% due to medical reasons (inadequate endometrium, bleeding, ovulatory leak) and 27,2% due to other issues (no embryo survival, SARS-Cov-2 related issues, flight cancellations, etc.); when evaluating cancellation for medical reasons, we didn’t find significant differences between HRT protocol cycles (9%) and mNC protocol cycles (7%), p = 0,33.
CLINICAL OUTCOMES: Out of the 683 frozen single blastocyst transfers performed, no twin pregnancies occurred as expected.
There were no statistically significant differences between HRT Vs mNC endometrial preparation protocol when comparing pregnancy rates (59% Vs 63%, p = 0,35), clinical pregnancy rates (49% Vs 57%, p = 0,10) and miscarriage rates (19% Vs 16%, p = 0,48). Live birth rate was significantly higher in the mNC (47%) compared to HRT (38%), p = 0,046.
Overall preterm birth rate &lt;35 weeks was 3,9%, including &lt;32 weeks 1,1% and &lt;28 weeks 0,3%. There were no significant differences between HRT and mNC endometrial preparation protocol for preterm birth rate &lt;35 weeks (3,6% Vs 4,6%, p = 0,75).

Limitations, reasons for caution
Single-centre retrospective comparative trial. Homogeneity studies included several confounding variables, but other bias could have been studied such as uterine factor, PGT-A rate or previous fertility treatments.

Wider implications of the findings
In donor programs, the use of modified natural cycle should be encouraged as first option irrespectively from recipient’s age for FET in normo-ovulatory patients, considering the increased live birth rates when compared to HRT-FET cycles. Moreover, mNC cycles are more patient’s friendly and cost-effective.

Trial registration number
not applicable