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.

OXIDATIVE STRESS AND REPRODUCTIVE FUNCTION: Oxidative stress and in vitro ageing of the post-ovulatory oocyte: an update on recent advances in the field

“…Despite its increasing utility, rescue ICSI continues to generate unsatisfactory clinical pregnancy (10%) and implantation rates (5%) (Paffoni et al 2021). These data reflect the findings of a recent meta-analysis of 22 original studies encompassing 1686 rescue-ICSI cycles with 12,945 inseminated oocytes (Paffoni et al 2021) and correlate well with observations that embryos originating from post-ovulatory aged oocytes are generally of poorer quality and exhibit delayed or impaired development during embryogenesis ) (Fig. 1).…”

“…Further supporting this premise, clinical studies assessing the effects of in vivo post-ovulatory oocyte ageing have reported significant correlations with delayed fertilisation and early pregnancy loss (Wilcox et al 1998). The mechanisms underlying these low implantation and ensuing pregnancy rates have been attributed to time-and ROS-dependent deterioration in oocyte quality but may also be influenced by the loss of synchronisation between endometrial growth and embryo development (Paffoni et al 2021). The latter of these may allude to the evolutionary advantage of post-ovulatory ageing, whereby limiting the fertilisation of low-quality oocytes arising from desynchronisation of ovulation and insemination assists in avoiding complicated or ill-fated pregnancies and a possible wasted investment of resources.…”

“…Despite the significant challenges faced by post-ovulatory aged oocytes in undergoing fertilisation, there are circumstances when this process can occur unimpeded, such as during the use of rescue ICSI. Rescue ICSI refers to the practice of performing ICSI on oocytes that did not show signs of fertilisation 18-24 h after conventional insemination (Paffoni et al 2021). Rescue ICSI has evolved as a plausible method to reduce the occurrence of total fertilisation failure, a devastatingly frustrating condition that affects 5-20% of couples undergoing ART (Combelles et al 2010).…”

Fertilization and neonatal outcomes after early rescue intracytoplasmic sperm injection: a retrospective analysis of 16,769 patients

“…Poor results were reported because of oocyte aging [ 3 ] and asynchronization between endometrial growth and embryo development [ 4 ]. Frozen embryo transfer seemed to improve with pregnancy rates (31–41%) and implantation rate (11–27%) [ 5 ], but it made no difference with fertilization. Subsequently, R-ICSI was performed earlier in an attempt to improve pregnancy rates since the 1990s [ 6 – 8 ].…”

Opportunities and Limits of Conventional IVF versus ICSI: It Is Time to Come off the Fence

“…A breakthrough in the field of r-ICSI cycles has recently come from the observation that good results can be achieved when r-ICSI embryos are transferred after cryopreservation in a subsequent frozen-thawed cycle [ 158 , 159 ]. A recent review by our group [ 160 ] including 22 original studies on late r-ICSI confirmed unsatisfactory results in fresh cycles with clinical pregnancy rate per embryo transfer and implantation rate equal to 10% and 5%, respectively. On the contrary, transfer of cryopreserved r-ICSI embryos was shown to ameliorate success rates, with pregnancy rate per embryo transfer equal to 37% with an odds ratio (OR) = 4.7 (95% CI: 2.6–8.5).…”