The Alignment Paradox of Medical Large Language Models in Infertility Care: Decoupling Algorithmic Improvement from Clinical Decision-making Quality

Abstract

Large language models (LLMs) are increasingly adopted in clinical decision support, yet aligning them with the multifaceted reasoning pathways of real-world medicine remains a major challenge. Using more than 8,000 infertility treatment records, we systematically evaluate four alignment strategies: Supervised Fine-Tuning (SFT), Direct Preference Optimization (DPO), Group Relative Policy Optimization (GRPO), and In-Context Learning (ICL) through a dual-layer framework combining automatic benchmarks with blinded doctor-in-the-loop assessments. GRPO achieves the highest algorithmic accuracy across multiple decision layers, confirming the value of reinforcement-based optimization for structured prediction tasks. However, clinicians consistently prefer the SFT model, citing clearer reasoning processes (p = 0.035) and higher therapeutic feasibility (p = 0.019). In blinded pairwise comparisons, SFT attains the highest winning rate (51.2%), outperforming both GRPO (26.2%) and even physicians' original decisions (22.7%). These results reveal an alignment paradox: algorithmic improvements do not necessarily translate into higher clinical trust, and may diverge from human-centered preferences. Our findings highlight the need for alignment strategies that prioritize clinically interpretable and practically feasible reasoning, rather than solely optimizing decision-level accuracy.