Is Rescue ICSI a useful tool in the routine IVF lab for patients undergoing total IVF fertilization failure?*

Even though IVF in clinical practice has a long history going back to 1978 with
considerable scientific breakthroughs since then, the incidence of unexpected
total fertilization failure (TFF) after conventional IVF remains one of the
most frustrating events for both patients and embryologists. In most cases, the
etiology behind such an event is unexplained and unexpected.TFF is defined as
the complete lack of fertilization at the standard checking time of 18-± 1 h
post- insemination. This means that the obvious fertilization signs, female and
male pronuclei, are not visible in any of the inseminated mature oocytes in the
metaphase of meiosis II (MII) of the patient. The idea of rescue ICSI (R-ICSI)
is not a new one; it consists in performing intracytoplasmatic sperm injection
(ICSI) 18-24hours later on oocytes that following IVF insemination have shown
no signs of fertilisation on the day after oocyte retrieval.
From the perspective of fertilization rate, pregnancies and live birth, the use
of R-ICSI is supported in the literature. Arpit et al (2017), in their
systematic review have concluded that although pregnancy rates are not as
promising as fertilization rates, R-ICSI should be offered as an option to
couples going through a total fertilization failure as it can result in the
birth of healthy babies. A retrospective cohort study (Zhu et al., 2023)
assessed the clinical outcomes of TFF cases, in a 10-year period, reported that
all 215 new-borns out of the 1291 embryo transfers were reported healthy.
Successful live births after use of R- ICSI have been worldwide reported. An
economic analysis, comparing the group that did receive R-ICSI versus the group
that abandoned the fresh cycle and started a new one, showed a 25% reduction in
the costs involved per live birth when R-ICSI was applied. Cost-effectiveness
of the R-ICSI procedure in terms of TFF was considered worthwhile (Shalom-paz
et al., 2011).

The main objective of this study is to evaluate whether the application of
rescue ICSI (R-ICSI), to patients having a failed fertilization with a standard
insemination procedure (IVF) can increase the chance of ongoing pregnancies
either with the use of fresh or cryopreserved embryos that are the result of
the intervention. The secondary objective is to assess the cost efficiency of
the salvaged treatment compared to an abandoned IVF cycle.

The study is a pilot pre-post intervention clinical trial.

We will compare the ongoing pregnancies between the pre intervention group (no
R-ICSI) versus the post intervention group (R-ICSI).

The potential benefit for the patients is a possible chance for a fresh embryo
transfer and therefore a chance of pregnancy compared to no chance at all. In
the case there are supernumerary embryos in the same attempt, patients would
profit from freezing any extra embryos of good quality for future use.
The associated burden for the patients participating in the study will probably
involve an extra visit to the fertility centre with the purpose of providing a
second sperm sample. If possible, and depending on the semen quality the day
after oocyte recovery (OR), this step may be avoided. Following the second
attempt to fertilize the oocytes, all treatment steps are given a 24-hour
delay. The patients participating in the study will be asked to provide
information to their IVF doctor regarding the outcome of their treatment (i.e.
pregnancy, and live birth outcome). This procedure is standard in our centre
for all IVF patients. No extra questionnaires need to be filled by the
patients. There are no extra costs or compensation for the couples that decide
to participate in this study.