O-145 From mathematical modeling to real-life clinical data: live birth rates up until the tenth blastocyst transfer without PGT-A
Authors: Mackens S , Loreti S , Goyens E , De Vos M , Tournaye H , Somigliana E , De Munck N , Blockeel C 
Published: June 2023

Abstract

Study question
What is the cumulative live birth rate (CLBR) from the first until the tenth consecutive blastocyst transfer, across all age-groups, if no PGT-A is applied?

Summary answer
Our clinical data confirm existing mathematical models: without PGT-A, a CLBR of 70.0% after three, 88.9% after seven and 95.9% after ten transfers was observed.

What is known already
The rate of ‘true’ repeated implantation failure (RIF) from endometrial origin is an important topic of debate in our scientific community. Its existence was challenged with the reporting of CLBRs &gt;90% after three consecutive euploid blastocyst transfers. These findings are not directly applicable when PGT-A is not routinely performed. Mathematical models have been developed to tackle this issue by taking into account (1) the anticipated euploidy rate based on the oocyte’s age and (2) the probability of an euploid embryo to implant. So far, no actual patient data have confirmed the validity of this model.

Study design, size, duration
This is a single-center, retrospective, observational cohort study including 4320 unique women who underwent up to ten consecutive blastocyst transfers between 2010 and 2020. All age categories were included, as well as fresh/frozen and single/double embryo transfers. Patients using donor oocytes, PGT or cleavage stage embryo transfers were excluded or led to drop-out in the study.

Participants/materials, setting, methods
Patient characteristics were retrieved and cumulative outcomes were analyzed. A Kaplan-Meier curve was plotted for CLBR. For each transfer cycle the live birth rate (LBR), double embryo transfer rate (DET) and multiple pregnancy rate were calculated.

Main results and the role of chance
The mean age of the patients included in the study was 31.8 (±4.5) years at the time of the first ovarian stimulation. The mean body mass index was 23.7 (± 4.3) kg/m2 and mean basal FSH 6.8 (±2.3) IU/L. The mean number of stimulations per patient was 1.21 (±0.5) and a total mean number of 4.6 (±3.2) blastocysts were obtained per patient. The mean time to the pregnancy leading to live birth was less than one year (0.3±0.7).
We observed the highest LBR (46.3%, 2002/4320) after the first blastocyst transfer followed by 35.4% (593/1672), 32.3% (275/851), 32.2% (147/456), 32.8% (78/238), 21.3% (26/122), 23.9% (17/71), 25.6% (10/39), 31.8% (7/22), 18.2% (2/11) for the second until the 10th transfer, respectively.
The Kaplan-Meier curve showed CLBRs to mount from 70.0% after the third, up to 88.9% after the seventh and 95.9% after the tenth blastocyst transfer.
We noticed a steady increase in DET rate from only 6.4% in the first up to &gt; 27% as of the fourth and &gt;44% as of the seventh transfer with acccompanied multiple pregnancy rates of 1.3% over 10.9% and 11.8%, respectively.

Limitations, reasons for caution
The main limitation is the study’s retrospective nature. As our center performs cleavage stage and blastocyst transfer, the included population is a good prognosis one as embryology allowed to perform extended culture. Nevertheless, to investigate RIF due to endometrial causes, this could also be seen as an asset.

Wider implications of the findings
These patient data confirm mathematical models and further question the prevalence of insurmountable, endometrial origin RIF. Preserved LBRs (even in higher cycle ranks) and a CLBR &gt;95% provide hope and reassurance to couples with failed embryo transfers and encourage them to continue treatment if blastocysts are available.

Trial registration number
NA