Randomized allocation of oocytes to IVF or ICSI for IVF-naïve cases with unexplained infertility in an IVF-ICSI Split protocol favors ICSI to optimize live birth outcomes

Abstract

In assisted reproduction treatments (ART), applying the ICSI method for fertilization of oocytes rather than traditional IVF method, is regarded as controversial for two reasons, namely utility and safety. Our study examines an IVF-ICSI Split model for couples with unexplained infertility, where male factor is meticulously excluded and ART is conducted by a strict algorithm, a commitment to blastocyst culture, along with single embryo transfers and a high commitment to cryopreservation. From 242 treatment cycles, 3346 oocytes recovered (13.8 per OPU) were randomly allocated to IVF or ICSI and the fertilization rates standardized to the number of 2PNS arising from each group applying the metaphase II oocyte number identified for the ICSI group, as the denominator for both groups. The fertilization rates were significantly higher overall for ICSI (83.2% vs 65.4%; p<0.0001), being most pronounced for women under 40 years. The resultant embryos had equivalent implantation rates in both fresh ET and frozen (FET) cycles with no significant differences in pregnancy rates, miscarriage rates or live birth outcomes indicating equivalent embryo quality. However, there were significantly higher numbers of ICSI-generated embryos cryopreserved and subsequent FET procedures showed higher live birth rates (21 births vs 6 births; p<0.005) and potential livebirths (214 births vs 104 births; p<0.0001). No congenital fetal abnormalities were detected in any of the 199 babies delivered during the study period to December 2020, neither IVF-generated nor ICSI-generated. Whilst the data strongly favors ICSI, there were 2 women (from 26 with fertilization in one arm only) who demonstrated fertilization only in the IVF arm of the study. We conclude that the IVF-ICSI Split model should be undertaken on all IVF-naïve women with unexplained infertility to determine the appropriate fertilization mode, albeit ICSI will be safely preferred for >90% of cases.

The Sperm DNA Fragmentation Assay with SDF Level Less Than 15% Provides a Useful Prediction for Clinical Pregnancy and Live Birth for Women Aged under 40 Years

“…The cumulative live birth rate (CLBR) represents the live births arising from ET and FET procedures, from a single oocyte pick-up (OPU). Following our SDF studies with the Halosperm test reported firstly in 2016 [27] and a second study in 2021 [31], we have encouraged all new cases presenting to PIVET, especially those who have never had ART procedures elsewhere, i.e., IVF-naïve cases, to undergo an IVF-ICSI Split modality ensuring that all non-male factor cases have the best opportunity to achieve fertilisation and generate some embryos (avoiding the 5% chance of complete failed fertilisation and 15% chance of reduced fertilisation). A study which analysed four controlled and prospective trials, also found that those authors were unanimous in their conclusion that total fertilization failure of an IVF cycle can be prevented and fertilization can be improved if half of sibling oocytes are subjected to ICSI [32].…”

“…Certain female factors are also encouraged to undertake ICSI, particularly where few oocytes are recovered (<4), or those with poorly explained infertility where intra-uterine insemination (IUI) treatments have failed and where either of the gametes (oocytes or spermatozoa) have been cryopreserved. Finally, those cases who have previously under-taken an IVF-ICSI Split modality for unexplained infertility will need little persuasion to undertake ICSI treatments, as over 25% of patients with unexplained infertility may have disordered zona pellucida-induced acrosomal reaction (DZPIAR) [36] and subsequently the ICSI fertilization rates were better than IVF-Only [31].…”