P-206 An evaluation of the incidence of total failed fertilization (TFF) following conventional IVF (cIVF) and the outcome of subsequent intracytoplasmic sperm injection (ICSI) cycles
Authors: Nanassy L , Schöpper B , Schultze-Mosgau A , Depenbusch M , Eggersmann T K , Hiller R A F , Griesinger G 
Published: June 2023

Abstract

Study question
What is the incidence of TFF following conventional IVF (cIVF) and the chance of live birth in subsequent ICSI treatment cycles after TFF?

Summary answer
The incidence of TFF might be higher than previously reported and establishment of in-house benchmarks are recommended. Treatment continuation results in acceptable live birth rates.

What is known already
TFF following a cIVF is a devastating outcome for patients and physicians. The fear of this unfortunate event is assumable one of the main drivers for overutilizing ICSI. The incidence of TFF after cIVF should be less than 5 % of stimulated cycles based on ESHREs recommended performance indicators. Data on TFF of an unselected population is indeed however only available from an era when ICSI was not in use and showed a higher rate. We investigated the incidence of TFF and evaluated the chance of live birth following of such event at the first cycle.

Study design, size, duration
A single center, retrospective chart review for the time period of 2010-2021 was done to identify all cycles where cIVF did not result in at least one oocyte with ≥ 2 pronuclei. Also, patients who had more than 2 oocytes retrieved in their first cycle and continued their treatment using ICSI as a fertilization method in their upcoming cycles were selected.

Participants/materials, setting, methods
A total of 5772 initiated IVF cycles were identified in the electronic database for the examined time period. Criterion for cIVF was normozoospermia and applied as fertilization method in 1001 (17.3%) cycles. All the cases where TFF was noted following cIVF were retrieved and the number of oocytes, the rank of the cycle, female age and the result of upcoming cycles if any were recorded. Data was analyzed using Chi-Square test, p &lt; 0.05 was considered significant.

Main results and the role of chance
A total of 125 TFF cycles were identified out of the 1001 cIVF cycles (12.49% failed fertilization rate per cIVF). A significantly higher frequency of TFF was seen in cycles where less than 3 oocytes were retrieved compared to those with more than two oocytes (38/99 [38.38%] vs. 87/902 [9.65%], p &lt; 0.001). No statistical difference was detected between the risk of TFF occurring at the first, second or the third rank cIVF cycle (87/664 [13.10%], 30/224 [13.39%], 5/75 [6.67%] respectively; p &gt; 0.05). The differences remained non-significant when only cycles with more than 2 oocytes were analyzed (67/608 [11.02%], 16/199 [8.04%], 4/68 [5.88%] respectively; p &gt; 0.05). Also, different age groups showed similar incidence of TFF (16/157 [10.19%], 41/362 [11.33%], 54/381 [14.17%] and 14/101 [13.86%] in &lt; 30, 31-35, 36-40 and &gt;40 years of age respectively; p &gt; 0.05). A total number of 56 patients were identified who continued their treatment using ICSI as fertilization method in their upcoming cycles. These patients completed 101 cycles resulting in 3 TFF cases (3%) and a fertilization rate of 75.1% (524/698) which was significantly higher to our baseline ICSI fertilization rate (70.9% [25231/35568]; p &lt; 0.05). Nineteen of these 56 patients (33.9%) ended up giving at least one live birth following treatment continuation.

Limitations, reasons for caution
Selection criteria, e.g. patient characteristics and treatment type such as PGT-A, for choice of fertilization method are probably a source of variation in TFF incidence between centers. It is recommended that laboratories establish their own benchmark values based on their own data for the incidence of TFF.

Wider implications of the findings
Previous studies identified serum luteinizing hormone and progesterone levels at trigger and the number of oocytes as critical predictors for TFF. The similar chance of TFF after previous successful fertilization suggests more involvement of female factors in TFF. Acceptable live birth rates can be achieved following treatment continuation.

Trial registration number
not applicable