Associations of conventional insemination compared to intracytoplasmic sperm injection on fertilization and pregnancy outcomes among individuals utilizing cryopreserved donor sperm

BACKGROUND: Intracytoplasmic sperm injection (ICSI) has not been shown to be superior to conventional insemination for non-male factor infertility indications in cycles using fresh sperm, however fertilization and reproductive outcomes have not been explored in the setting of cryopreserved sperm. METHODS: This retrospective cohort study included 4413 patient couples between 2010 and 2021 that underwent autologous retrieval cycles utilizing cryopreserved donor sperm with linked subsequent fresh and frozen single blastocyst transfers at a large network of private practice fertility clinics in the United States. The primary exposure was insemination method; conventional insemination or ICSI. The primary outcome of interest was fertilization percentage. Secondary outcomes included percentages of blastulation, total fertilization failure, clinical pregnancy, and live birth. Adjusted associations were evaluated accounting for relevant confounders. RESULTS: At first retrieval, patients in the conventional insemination group had a higher mean number of oocytes retrieved (14.29 [7.70] vs. 13.58 [8.84]) and number of fertilized oocytes (8.70 [5.27] vs. 7.89 [5.88]) compared to the ICSI group. Mean fertilization and blastulation percentages were also higher in those who utilized conventional insemination (61% and 45%) compared to those who utilized ICSI (56% and 34%). After multiple retrievals, adjusted associations examining fertilization method and outcomes showed conventional insemination was associated with a 12% (95% CI [0.05, 0.19]) higher mean blastulation percentage, increased likelihood of clinical pregnancy (RR 1.64; 95% CI [1.27, 2.12]), and higher live birth (RR=1.45; 95% CI [1.06, 2.00]) compared to ICSI. CONCLUSIONS: Use of conventional insemination in cycles involving cryopreserved donor sperm was associated with improved blastulation and increased likelihood of clinical pregnancy and live birth compared to ICSI. These findings suggest that routine ICSI use in this population may warrant reconsideration and that conventional insemination could remain an appropriate option in selected cases utilizing cryopreserved donor sperm.