Abstract
For patients with estrogen-sensitive tumors, there is a concern that the high estrogen state induced by controlled ovarian stimulation (COS) for oocyte retrieval may stimulate the growth of cancer cells. Protocols using aromatase inhibitors (AIs) have been developed to suppress the elevated estrogen levels during ovarian stimulation. However, studies have shown that COS with AI may induce apoptosis in cumulus and granulosa cells due to an increase in the androgen/estrogen ratio, which is associated with decreased oocyte quality. In the present study, we examined the hormonal dynamics in follicular fluid collected from patients with breast cancers who underwent COS with AI for fertility preservation (n = 11). In addition, we examined the relative gene expressions of several oocyte quality predictor genes in the cumulus and granulosa cells. The control samples were collected from patients with general infertility who underwent COS without AI (n = 17).
Methods: The study population included patients with breast cancer who underwent COS with AI for oocyte retrieval for fertility preservation (n = 11, AI group) and patients with general infertility who underwent COS without AI for oocyte retrieval for in vitro fertilization (IVF) (n = 17, control group). The follicular fluid was collected at the time of oocyte retrieval. Estradiol (E2), progesterone, testosterone, and anti- Müllerian hormone (AMH) levels in the follicular fluid were measured by enzyme-linked immunosorbent assay (ELISA), and relative gene expressions of bone morphogenetic protein 3 (BMP3), prostaglandin-endoperoxide synthase 2 (PTGS2) and hyaluronan synthase 2 (HAS2) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR).
Results: Compared to the control group, the levels of E2 were significantly suppressed while the testosterone and AMH levels increased in the AI group. No significant differences were observed in the progesterone levels. The relative gene expressions of BMP3, PTGS2 and HAS2 in cumulus and granulosa cells showed no significant differences between the two groups.
Conclusion: We confirmed that COS with AI suppressed the E2 levels in the follicular fluid of patients with breast cancer. The elevated testosterone level in follicular fluid did not alter the BMP3, PTGS2 and HAS2 gene expressions in cumulus and granulosa cells nor affect the number of oocytes retrieved.
