Live-birth rates after four consecutive failed IVF cycles within one year: A retrospective cohort study of patients aged 35 years and older.

Research question Does experiencing four consecutive failed in vitro fertilization (IVF) cycles within one year identify patients aged ≥ 35 years using autologous oocytes who have an extremely low probability of achieving a live birth in subsequent cycles? Design This retrospective observational cohort study used routinely collected electronic health records from Clalit Health Services (CHS), Israel's largest integrated healthcare system (≈4.7 million members), between December 2012 and October 2023. Patients aged ≥ 35 years undergoing IVF with autologous oocytes were included, limited to cycles involving oocyte retrieval and fresh embryo transfer. Per-cycle and cumulative live-birth rates were estimated according to age and prior treatment history. A prognostic marker ("Marker 4″) was defined as four failed IVF cycles occurring within 12 months. Exact binomial (Clopper-Pearson) methods were used for the per-cycle confidence intervals, and a discrete-time life-table estimator with complementary log-log bands for the cumulative rates.

RESULTS

The cohort comprised 16,299 patients undergoing 46,148 IVF cycles. Among patients aged ≥ 35 years undergoing IVF, after a minimum of 4 failed cycles, the overall per-cycle live-birth rate was 15.61 % (95 % CI 14.46-16.82 %) without Marker 4, compared with 2.51 % (95 % CI 2.13-2.94 %) with Marker 4 - a 6.2-fold difference (84 % relative reduction). The cumulative live-birth rate reached 64.02 % without Marker 4 versus 16.14 % with Marker 4, a 4-fold difference.

CONCLUSIONS

Four consecutive IVF failures within one year identify a subgroup of patients aged ≥ 35 years with extremely low per-cycle and cumulative probabilities of live birth using autologous oocytes. This simple, time-based clinical marker may support counseling regarding treatment futility and inform decisions about continuing IVF or transitioning to alternative reproductive options.