Should rescue ICSI be re-evaluated considering the deferred transfer of cryopreserved embryos in in-vitro fertilization cycles? A systematic review and meta-analysis

Abstract

Background: Total fertilization failure represents a particularly frustrating condition for couples undergoing in vitro fertilization. With the aim of reducing the occurrence of total fertilization failure, intracytoplasmic sperm injection (ICSI) has become the first choice over conventional in vitro fertilization (IVF) procedures although evidence of improved results is still debated and its use in couples without male factor infertility is not recommended. Among the strategies potentially useful to promote the use of conventional IVF, we herein call attention to the late rescue ICSI, which consists in performing ICSI after 18-24 h from conventional insemination on oocytes that show no signs of fertilization. This treatment has however been reported to be associated with a low success rate until recent observations that embryos derived from late rescue ICSI may be transferred after cryopreservation in a frozen-thawed cycle with improved results. The aim of the present study was to assess whether frozen embryos deriving from rescue ICSI performed about 24 h after conventional IVF may represent a valuable option for couples experiencing fertilization failure.

Methods: A systematic review on the efficacy of late rescue ICSI was performed consulting PUBMED and EMBASE.

Results: Including twenty-two original studies, we showed that clinical pregnancy rate per embryo transfer and implantation rate obtainable with fresh embryo transfers after rescue ICSI are not satisfactory being equal to 10 and 5%, respectively. The transfer of cryopreserved rescue ICSI embryos seems to offer a substantial improvement of success rates, with pregnancy rate per embryo transfer and implantation rate equal to 36 and 18%, respectively. Coupling rescue ICSI with frozen embryo transfer may ameliorate the clinical pregnancy rate for embryo transfer with an Odds Ratio = 4.7 (95% CI:2.6-8.6).

Conclusion: Results of the present review support the idea that r-ICSI coupled with frozen embryo transfer may overcome most of the technical and biological issues associated with fresh transfer after late r-ICSI, thus possibly representing an efficient procedure for couples experiencing fertilization failure following conventional IVF cycles.

Trial registration: Prospero registration ID: CRD42021239026 .

Keywords: Delayed ICSI; IVF; Intracytoplasmic sperm injection; Rescue ICSI; Total fertilization failure.

Fig. 1

Prisma 2020 flow-diagram of study selection process

Fig. 2

Quantitative synthesis of the studies reporting clinical pregnancy (upper panel) and implantation rate (lower panel) per embryo transfer in fresh cycles following rescue-ICSI performed 15–24 h after conventional IVF resulting in total or partial fertilization failure

Fig. 3

Quantitative synthesis of the studies reporting clinical pregnancy (upper panel) and implantation rate (lower panel) per embryo transfer in frozen cycles following rescue-ICSI performed 15–24 h after conventional IVF resulting in total or partial fertilization failure. Cases with preimplantation genetic testing were excluded

Fig. 4

Meta-analysis of studies comparing frozen and fresh rescue-ICSI cycles. Odds Ratios (OR) for clinical pregnancy rate per embryo transfer (upper panel) and implantation rate (lower panel) are shown