O-297 Contribution of Frozen Embryo Transfer Cycles to ICSI Clinical Outcomes in Male Factor Infertility
Authors: Johal J , Xie P , Cheung S , Rosenwaks Z , Palermo G 
Published: June 2023

Abstract

Study question
What is the benefit of adding frozen embryo transfer (FET) cycles to ICSI clinical outcomes in male factor infertility?

Summary answer
FET carried out on spare embryos that reached blastocyst stage remarkably contributed to additional clinical pregnancies in ICSI cycles for male factor infertility.

What is known already
Current trends in reproductive medicine lean toward full-preimplantation development and eventually to PGT-A to select a single euploid embryo for transfer. The utilization of this approach, while beneficial in most couples, is not ideal for male factor infertility due to the tendency of being characterized by impaired embryo development. So, we wonder if the utilization in FET cycles of leftover embryos that reached to blastocyst stage or those that eventually reached day 5 for aneuploidy testing contributed to the clinical outcomes.

Study design, size, duration
In the past 7 years, we included 22,289 couples who underwent ICSI while the large majority (84.8%) received a fresh embryo transfer, of which 70.9% were transferred at day 3. Leftover embryos, together with those euploid after PGT-A at blastocyst stage, were replaced in subsequent FET cycles. The clinical outcomes including clinical pregnancy rate (CPR) and deliveries were compared between the fresh embryo transfer and those after FET in total and after PGT-A.

Participants/materials, setting, methods
Couples with male factor underwent ICSI in standard fashion using exclusively ejaculated sample. For fresh embryo transfer cycles, embryos were transferred either at day 3 or at day 5. For FET cycles, embryos were cultured up to exclusively blastocyst stage and cryopreserved by vitrification. For aneuploidy, NGS was carried out for PGT-A. FET was carried out in natural or programmed cycles.

Main results and the role of chance
In the cohort underwent fresh embryo transfer, 18,896 couples underwent 37,751 ICSI cycles, where 322,916 oocytes were injected and 243,768 (75.5%) fertilized. Additionally, 3,393 patients received 4,712 FET in total with a fertilization of 69.8% (46,163/66,171) that did not differ from the fresh transfer group. The number of average embryos transferred in fresh cycles was 2.4±2 while FET was carried out exclusively on single embryo. Fresh transfer yielded 37.3% (14,087/37,751) CPR, while overall FET cycles achieved a higher CPR at 52.2% (2,462/4,712, P&lt;0.0001). Similarly, the delivery rate in fresh cycles was 31.8% (12004/37751) and became 45.5% (2145/4712) in the FET (P&lt;0.0001).
To identify the advantage of selecting a single euploidy embryo, we compared FET on leftover unscreened blastocyst to those that were planned for PGT-A. Spare embryo transfers involved 1774 patients in 2282 cycles with a fertilization rate of 67.7% (18,905/27,937). For the PGT-A cycles, 1619 couples in 2430 cycles achieved a comparable fertilization rate of 71.3% (27,258/38,234), In this comparison, the FET on spare unscreened embryos achieved a CPR at 47.0% (1,072/2,282) while in the PGT-A group reached CPR at 57.2% (1390/2430, P&lt;0.0001). Similarly, the delivery rate was 37.6% (857/2,282) in the FET and PGT-A was 53.0% (1,288/2,430) (P&lt;0.0001).

Limitations, reasons for caution
The comparison is retrospective and is carried out on male factor infertility where day 3 embryo transfer were performed almost exclusively on fresh cycle to overcome poor embryo development. Nonetheless, those spare embryos that reached blastocyst stage and those that electively underwent aneuploidy testing significantly contributed to enhance clinical outcomes.

Wider implications of the findings
ICSI can overcome most of male infertility; however, the risk of impaired embryo development proposes a transfer at cleavage stage. The advanced embryo culture condition together with time-lapse allowed us to monitor embryos up to the blastocyst stage that once transferred, improving clinical outcomes, especially for embryos with confirmed euploidy.

Trial registration number
N/A