Abstract

Abstract Study question Can intra-cycle FSH levels measured at baseline, mid-cycle, and on trigger day predict blastocyst euploid rate? Summary answer Repeat measurements of FSH were not useful for predicting the euploid rate of blastocysts after accounting for the effects of female age. What is known already During the follicular phase of ovarian stimulation cycles, blood FSH levels are kept at supraphysiologic levels for a longer period compared to naturally occurring ovulation cycles during which FSH levels recede in response to rising estradiol. Some studies suggested maintaining higher than necessary blood FSH concentrations may have a detrimental effect on embryo quality and ploidy and recommended intra-cycle FSH monitoring. Whether intra-cycle measurements of FSH can be used to predict euploid rate is yet to be determined. Study design, size, duration Retrospective study was performed at tertiary IVF refereral center, including 373 cycles between April 2017 and February 2022. All GnRH (Gonadotropin-Releasing-Hormone) antagonist stimulation cycles using only recombinant FSH were included. Included patients were between 19 and 44 years old and all embryos underwent aneuploidy testing with Next Generation Sequencing using trophectoderm biopsy. Patients with PCOS, surgical sperm extraction, or warmed oocytes were excluded. Participants/materials, setting, methods Patients with primary or secondary infertility and an indication for ovarian stimulation for IVF/ICSI with PGT-A were included. Ovarian stimulation cycles were monitored according to the clinical routine by ultrasound and repeated measurement of FSH, E2, and progesterone at baseline, mid-cycle, and on trigger day. FSH changes were evaluated as delta differences between basal to mid-cycle levels and from mid-cycle to trigger levels. Main results and the role of chance 1,119 intra-cycle measurements of FSH were obtained from 373 cycles of 344 women. The median age of included women was 31 years (IQR:27-34), with AMH levels of 3.28ng/ml (IQR: 2.13-4.24). The euploid rate per fertilized oocyte was analyzed in categories of low (≤33.3%), normal (33.3 to 66.6%), and high (>66.6%). Delta change in serum FSH values from baseline to mid-cycle was not significantly different between groups (median change: 7.6 IU, 7.4 IU, and 6.2 IU; low, normal, and high euploid rate groups, respectively, P = 0.481). Again, delta change in mid-cycle to trigger day FSH was not significantly different between groups either (median change: -0.2 IU, 0.0 IU, 0.6 IU; low, normal, and high euploid rate groups, respectively, P = 0.151). After adjusting for the effect of age, basal FSH values (OR: 1.11, 95% CI:0.91-1.34, P = 0.248), delta FSH change to mid-cycle (OR: 0.99, 95% CI:0.91-1.07, P = 0.951) or delta change to trigger day (OR: 1.14, 95% CI:0.99-1.31, P = 0.067) was not significantly associated with high euploid rates. Performance of age alone compared to age and delta of FSH measurements combined for predicting high euploid rates, as measured with area under the curve (AUC) values, were AUC: 0.63 (95% CI: 0.54-0.71) and AUC: 0.66 (0.58-0.73), respectively (P = 0.369). Limitations, reasons for caution This was a retrospective study including only recombinant FSH cycles and findings represented here may not be generalizable to larger populations. Sample power may not be adequate to detect some effect sizes. Wider implications of the findings We could not demonstrate a direct relationship between euploid rate and delta change in intra-cycle FSH measurements. More studies using more diverse populations and larger sample sizes may be needed to further investigate this association. Trial registration number Not applicable

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