Comparison of Clinical Outcomes between the Fourth Day and the Fifth Day Embryo Transfer in IVF/ICSI Cycles: A Retrospective Cohort Study before and after PSM

Abstract

Background: The question of whether extending embryo culture can provide more benefits for clinical outcomes has been raised. It is important to explore whether the fourth day morulae could be a widely used alternative transplantation option to replace the fifth day blastocysts. Methods: This study involved 1167 patients undergoing their first in in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. They were divided into two groups: those undergoing embryo transfer on the fourth day (D4 ET, n = 974 patients) and those undergoing embryo transfer on the fifth day (D5 ET, n = 193 patients). The time of the study was between January 2018 and June 2021. We used logistic regression to calculate propensity scores based on several variables such as female age, female body mass index (BMI), infertility duration, basal follicle-stimulating hormone (FSH), basal luteinizing hormone (LH), antral follicle count (AFC), follicular output rate (FORT), number of embryos transferred, number of transferable embryos, and number of high-quality embryos on day 3. The nearest neighbor random match algorithm was employed to determine the matches for each individual in the study population. The propensity score matching (PSM) was performed with a ratio of 1:1, ensuring equal representation of treated and control groups in the analysis. After PSM, 198 patients were included in the two groups. Results: Before matching, patients in the D4 ET group had lower AFC (16 [13, 20] vs. 17 [14, 22], p = 0.027). Estradiol on the human chorionic gonadotropin (hCG) day, FORT, number of oocytes retrieved, number of normal fertilization, number of transferable embryos, and number of high-quality embryos on day 3 were lower in the D4 ET group. After PSM, these characteristics were similar in the two groups, except for the number of high-quality embryos on day 3, which was lower in the D4 ET group (3 [2, 3.5] vs. 4 [2, 4], p = 0.035). The D4 ET group showed a higher live birth rate (54.21% vs. 44.88%, p = 0.015), with a lower rate of 1 embryo transferred (21.36% vs. 43.01%, p < 0 .001) before PSM. D4 ET increased live birth rate in fresh cycles relative to D5 ET before PSM (odds ratio (OR) = 1.552, 95% confidence interval (95% CI): 1.036~2.323, p = 0.033). No significant differences were observed in blastocyst formation rate (33.57 vs. 34.05, p = 0.618; 35.10 vs. 33.80, p = 0.468) and cumulative live birth rate (70.02 vs. 73.58, p = 0.322; 69.70 vs. 72.73, p = 0.638) between the two groups before and after PSM in the fresh cycles. There was no significant difference in endometrial thickness (8.8 [8, 10] vs. 8.9 [8, 9.6], p = 0.689; 8.6 [8, 10] vs. 8.9 [8, 9.7], p = 0.993), one embryo transferred rate (28.35 vs. 25.84, p = 0.639; 22.86 vs. 24.44, p = 0.724), clinical pregnancy rate (54.88 vs. 61.80, p = 0.243; 57.14 vs. 73.33, p = 0.129), live birth rate (43.90 vs. 50.56, p = 0.263; 45.71 vs. 55.56, p = 0.382) between the two groups before and after PSM in the first frozen ET cycle after fresh ET. Conclusions: D4 ET did not have a significant adverse impact on clinical outcome in fresh cycles and first frozen ET cycles relative to D5 ET.