Exploring Co-Occurring Clinical and Treatment Characteristics Associated with In Vitro Fertilization Failure in Polycystic Ovary Syndrome: An Association Rule Mining Approach
Xuehong Zhu, Lina Ge, Guanghui Dong, Yanlin Tang, Zhong Lin, Feng HanBackground: Polycystic ovary syndrome (PCOS) is a leading cause of anovulatory infertility and a frequent indication for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). Multivariable regression estimates adjusted associations, whereas association rule mining (ARM) can describe frequently co-occurring attributes; however, ARM outputs are unadjusted and may be sensitive to analytic specification. Objectives: We used ARM alongside multivariable logistic regression and internal robustness analyses to describe combinations of clinical and treatment-related variables that co-occurred with clinical pregnancy failure among women with PCOS undergoing IVF/ICSI. Methods: We retrospectively analyzed 733 deidentified patients with PCOS from the Reproductive Hospital of Guangxi. The original one-hot-encoded analytic file was linked to a supplemental clinical record file containing continuous age, BMI, infertility duration, anti-Müllerian hormone, total gonadotropin dose, fertilization method, embryo-transfer day, number of embryos transferred, and embryo score. Embryo quality was derived from D3 cleavage-stage and blastocyst morphology records. Multivariable logistic regression was used to estimate adjusted associations. ARM results were assessed using Fisher’s exact test, Benjamini–Hochberg false discovery rate (FDR) correction, 1000 bootstrap resamples, fivefold cross-validation, and threshold/cutoff sensitivity analyses. Results: In the multivariable model (n = 730), age remained associated with clinical pregnancy failure (adjusted odds ratio [aOR] = 1.04 per year, 95% CI 1.00–1.08, p = 0.031), whereas BMI was not independently associated with failure (aOR = 1.00 per kg/m2, 95% CI 0.96–1.05, p = 0.860). Transfer of two embryos (aOR = 0.55, 95% CI 0.35–0.85, p = 0.008), D5 blastocyst transfer (aOR = 0.49, 95% CI 0.32–0.75, p = 0.001), and transfer of at least one high-quality embryo (aOR = 0.63, 95% CI 0.43–0.93, p = 0.020) were associated with lower odds of failure. Under the primary host-factor specification, age > 35 years + BMI ≥ 24 kg/m2 + pelvic adhesion defined 48 patients, 30 of whom had clinical pregnancy failure (support = 0.07; confidence = 0.63; lift = 1.38; FDR q = 0.098). In the secondary treatment-inclusive analysis, infertility duration > 5 years + no high-quality embryo transferred defined 43 patients with 30 failures (support = 0.06; confidence = 0.70; lift = 1.54; FDR q = 0.026). Lift represents the subgroup failure proportion divided by the overall failure proportion and is not an adjusted risk ratio. The rule composition and the number of FDR-supported rules changed under alternative cutoffs and confidence thresholds. Conclusions: ARM described transparent but specification-sensitive co-occurrence profiles that complement, rather than compete with, regression. Treatment-inclusive profiles combine baseline and downstream cycle characteristics and are therefore especially exploratory. These findings require prospective multicenter validation before any clinical decision-support use.