Abstract
Study question
Does rapid or delayed insemination after egg retrieval affect fertilization, blastocyst development and live birth rates in CI and ICSI cycles?
Summary answer
When performing CI or ICSI <1.5h and >6.5h after retrieval, detrimental effects are moderate on fertilization but do not impact blastocyst usage and birth rates.
What is known already
Several studies have shown that CIor ICSI performed between 3 to 5 h after oocyte retrieval has improved laboratory outcomes. However, some studies indicate that insemination of oocytes, by either CI or ICSI, within 2 hours or more than 8 hours after oocyte retrieval has a detrimental effect on the reproductive outcome. With some ART centres experiencing an increase in workload, respecting these exact time intervals is frequently challenging.
Study design, size, duration
A single-center retrospective cohort analysis was performed on 6559 patients (9575 retrievals and insemination cycles) between January 1st2017 to July 31st2019. The main outcome measures were live-birth rates. Secondary outcomes included analysis of fertilization per all oocytes retrieved, blastocyst utilization, clinical pregnancy, and miscarriage rates. All analyses used time of insemination categorized in both CI and ICSI cycles. Fertilization rates across categories was analyzed by ANOVA and pregnancy outcomes compared using Chi-square tests.
Participants/materials, setting, methods
As part of laboratory protocol, oocyte retrieval was performed 36 h post-trigger. Cycles involving injection with testicular/epidydimal sperm, donor or frozen oocytes were excluded. The time interval between oocyte retrieval and insemination was analyzed in eight categories: 0 (0- <0.5h), 1 (0.5-<1.5h), 2 (1.5-<2.5h), 3 (2.5-<3.5h), 4 (3.5-<4.5), 5 (4.5-<5.5), 6 (5.5-<6.5) and 7 (6.5-<8h). The number of retrievals in each group (0–7) was 586, 1594, 1644, 1796, 1836, 1351, 641 and 127 respectively.
Main results and the role of chance
This study had a mean patient age of 36.0 years and mean of 12.2 oocytes per retrieval in each category. There were 4,955 CI and 4,620 ICSI retrievals. The smallest groups were time category 7 and 0 for CI and ICSI respectively. The results showed that the mean fertilization rate per egg retrieved for CI ranged from 54.1 to 64.9% with a significant difference between time category 0 and 5 (p < 0.001) and category 1 and 5 (p < 0.0.001). Mean fertilization rate for ICSI per egg retrieved ranged from 52.8 to 67.3% with no significant difference between time categories compared to category 5. Blastocyst utilization rate for CI and ICSI were not significantly different for all time categories. In the CI and ICSI groups there were 6,540 and 6,178 total fresh and frozen transfers. The miscarriage and clinical pregnancy rate in CI and ICSI were not significantly different across time categories. The overall mean live birth rate for CI was 32.4% (range: 23.1 to 35.5%). Live-birth rates differed significantly (p = 0.04) in CI with time categories 0 and 7 the lowest. In the ICSI group, the overall mean live birth rate was 30.8% (range: 29.1 to 35.7%),with no significant differences between time categories.
Limitations, reasons for caution
As this is a retrospective study, the influence of uncontrolled variables cannot be excluded. The group spread was uneven with the early and late time categories having the lowest number of representative retrievals and this could have affected the results obtained.
Wider implications of the findings: Our results indicate that both CI and ICSI are optimal when performed between 1.5–6.5 hours after oocyte retrieval. Further prospective studies on reproductive outcomes related to time of insemination are warranted. This data indicates a minimal detrimental effect when it is untenable to follow strict insemination time intervals.
Trial registration number
2015P000122
ICSI Does Not Improve Live Birth Rates but Yields Higher Cancellation Rates Than Conventional IVF in Unexplained Infertility
