Background/Aims: This study aimed to determine the immunohistochemical characteristics of intramural leiomyomata that enlarged during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Methods: For this retrospective case-control clinical study and immunohistochemical analysis, 5 patients with enlarged intramural leiomyomata during COH for IVF, who had undergone myomectomy immediately after a failed IVF cycle, were recruited retrospectively. Fifteen consecutive patients who had had myomectomy for intramural leiomyomata < 5 cm, but had never undergone any infertility treatment, served as the control group. Histological examinations and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), transforming growth factor-beta (TGF-beta) and fibronectin were performed on all specimens taken from the study and control groups. The main outcome measures were defined as histological and immunohistochemical scores. Results: Hematoxylin and eosin as well as PCNA staining showed increased mitotic index, cellularity and proliferation index in these growing leiomyomata ( study group). There were neither increased mitoses nor cellularity in the leiomyomata of the control group, while PCNA, TGF-beta and fibronectin scores in the study group were significantly higher than those in the control group (p < 0.001). Conclusion(s): This study is the first to report increased TGF-beta, PCNA, cellularity and mitosis in leiomyomata enlarging during COH for IVF. Further studies with larger sample size are needed to determine the role of TGF-beta, PCNA and fibronectin in the growth of leiomyomata during COH. Copyright (c) 2008 S. Karger AG, Basel.