Abstract

Follicle growth can be obtained with different preparations or combinations of gonadotrophins. Approaches combining FSH with LH-like-action gonadotrophins have been associated with improved IVF outcomes. Whether a controlled ovarian stimulation (COS) regimen based on r-FSH and r-LH leads to better outcomes compared with a protocol using human menopausal gonadotropin (hMG) is still under debate. The goal for the present study was to compare the effect of two FSH plus LH-like protocols on morphokinetic events in a time-lapse imaging (TLI) system. This retrospective cohort study was performed in a private university-affiliated IVF center from March 2019 to December 2020 and included 1268 embryos, cultured in a TLI incubator, from 198 ICSI cycles. Cycles were split into two groups depending on the protocol applied for COS: 142 patients (904 embryos) were stimulated with rFSH + rLH, whereas 56 patients (364 embryos) were treated with hMG. The effects of the COS protocol on morphokinetic events and ICSI outcomes were compared among the groups taking into account clustering of data (multiple embryos per cycle), using generalized mixed models. Evaluated kinetic markers were: pronuclei appearance (tPNa), timing to pronuclei fading (tPNf), timing to two (t2), three (t3), four (t4), five (t5), six (t6), seven (t7), and eight cells (t8), and timing to start of blastulation (tSB) and to blastulation (tB). Durations of the second (t3-t2) and third (t5-t3) cell cycles (cc2 and cc3, respectively) and timing to complete synchronous divisions s1 (t2-tPNf), s2 (t4-t3), and s3 (t8-t5) were also evaluated. The post hoc achieved power was > 99.0%. When compared with the protocol with hMG, COS using rFSH + rLH leaded to faster tPNa (7.4h ± 0.30 vs 6.5h ± 0.18, p<0.007), tPNf (25.6h ± 0.40 vs 24.4h ± 0.25, p<0.009), t5 (50.0h ± 0.60 vs 48.5h ± 0.37, p<0.035), and t6 (52.9h ± 0.58 vs 51.5h ± 0.37, p<0.043). The s3 were also decreased in rFSH + rLH protocols (10.4h ± 0.36 vs 8.9h ± 0.58, p<0.033). As for the clinical outcomes, no significant differences were noted among the groups for pregnancy (40.0% ± 11.0 vs 33.0% ± 10.9, p=0.398) and implantation rates (28.0% ± 6.2 vs 22.2% ± 8.4, p=0.76), for rFSH + rLH and hMG groups respectively. Stimulation protocols using associations of rFSH and rLH lead to faster initial embryo development when compared with protocols using hMG.

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