Understanding the implications of follicular output rate (fort) and follicle to oocyte index (foi) on embryo morphokinetics

The follicular output rate (FORT) and follicle to oocyte index (FOI), qualitative markers of ovarian response, may reflect the follicular development dynamic in response to gonadotropins. Whether FOI and FORT may predict, not only the response to COS, but also embryo developmental potential is unknown. Morphological changes with the exact time-point of occurrence may be assessed by time-lapse imaging (TLI) and may be a valuable approach to evaluate the correlation between FORT and FOI and the competences of developing embryos. The objective of this study was t0 investigate if there are any effects of FORT and FOI on embryos morphokinetics. This historical cohort study was performed in a private university-affiliated IVF centre between February/2019 and December/2021. Kinetic data were analysed in 8,376 embryos derived from 2,470 patients undergoing ICSI cycles, individually cultured in a TLI incubator (EmbryoScope®Plus). The timing of specific events from the point of insemination was determined using TLI. The FORT and FOI were determined, and the effects of the levels of these parameters on morphokinetic events and ICSI clinical outcomes were investigated. Embryos were split into groups according to FOI value: FOI<50 (Low-FOI, n=894) and FOI≥50 (high-FOI, n=7,482), and according to the FORT value: FORT values below the 33rd percentile, FORT<27.3 (low-FORT, n=2,556), between the 33rd and the 67th percentile, FORT: 27.3–47.6 (medium-FORT, n=2,970), and above the 67th percentile, FORT>47.6 (high-FORT, n=2,850). Morphokinetics and clinical outcomes were compared between the FOI and FORT groups using generalized linear models. Slower timing to pronuclei appearance (tPNa), to two (t2), four (t4), six (t6), seven (t7), and eight cells (t8), timing to morulation (tM), timing to blastulation (tB), to complete the second cell cycle (cc2, t3-t2) and to complete synchronous divisions (s1), (s2), and (s3) were observed for embryos derived from cycles with a low-FORT were compared with those with a high-FORT. A higher KID-score D5 was observed among embryos derived from cycles with a high-FOI when compared with those with a low-FOI. Increased blastocyst formation and implantation rates were noted among cycles with higher FOIs. An increased time to complete morphokinetic events was observed among embryos derived from cycles with low-FORT, followed by those with medium-FORT. Embryos derived from cycles with high-FORT presented a higher Kid-Score, followed by those from cycles with medium-FORT. Significantly higher rates of blastocyst formation and implantation were observed in embryos derived from cycles with high-FORT, followed by those with medium-FORT. There is a significant positive effect of FORT and FOI on embryo morphokinetic development.