Association of LH rising before luteal support and reproductive outcomes in artificial frozen embryo transfer cycles

In natural cycles, rising estradiol (E2) suppresses pituitary luteinizing hormone (LH) secretion until a threshold is reached, triggering the LH surge and ovulation. During artificial-cycle frozen embryo transfer (AC-FET), prolonged E2 exposure may induce endogenous LH elevation before progesterone administration. Limited studies have examined the impact of LH dynamics on reproductive outcomes in AC-FET cycles. This study investigated the association between LH rising before luteal support and reproductive outcomes and further explored the relative contributions of basal LH, and pre-P LH.

This retrospective cohort study included patients aged 25-44 years undergoing D3 or D5 AC-FET without GnRH agonist suppression. A total of 582 cycles were categorized according to the LH rising ratio, defined as pre-progesterone LH divided by basal LH. Cycles were classified as LH rising ratio <3 (group 1) or ≥3 (group 2). Outcomes included implantation (IR), clinical pregnancy (CPR), ongoing pregnancy (OPR), and abortion rates (AR).

In D3 embryo transfer cycles, an LH rising ratio ≥3 was associated with lower IR (21.1% vs. 13.2%; OR 0.57, 95% CI 0.38-0.82) and CPR (43.3% vs. 28.4%; OR 0.52, 95% CI 0.31-0.87). AR was higher and OPR lower, although not statistically significant. Similar trends were observed in D5 cycles without statistical significance. After adjustment using multivariable generalized estimating equation models, the associations in D3 cycles remained significant. However, decoupling analyses suggested that the LH rising ratio primarily functioned as a surrogate marker of lower basal LH rather than an independent effect of elevated pre-P LH, as basal LH remained associated with implantation outcomes whereas pre-P LH did not. Quartile analyses did not demonstrate a threshold effect for either basal LH or pre-P LH.

A higher LH rising ratio before progesterone supplementation was associated with reduced implantation and clinical pregnancy rates in D3 AC-FET cycles. Additional analyses suggest that the LH rising ratio may primarily serve as a surrogate marker of lower basal LH rather than an independent effect of elevated pre-P LH. The relationship between LH dynamics and reproductive outcomes remains complex and may not be fully explained by basal or pre-P LH alone.