Follicular homocysteine as a marker of oocyte quality in PCOS and the role of micronutrients

PURPOSE: Does follicular homocysteine predict the reproductive potential of oocytes following FSH stimulation in PCOS women? Can it be modulated by dietary interventions? METHODS: This was a prospective, randomized, interventional clinical study. Forty-eight PCOS women undergoing in vitro fertilization at a private fertility clinic were randomized for a dietary supplementation providing micronutrients involved in homocysteine clearance or no treatment. The supplement was assumed 2 months before stimulation until pick-up day. Monofollicular fluids were collected and frozen. After embryo transfer, the fluids from the follicles generating the transferred embryos were thawed and analyzed. RESULTS: Follicular homocysteine showed a negative correlation with clinical pregnancy both in the whole population (r = − 0.298; p = 0.041) and in controls (r = − 0.447, p = 0.053). The support achieved a non-significantly lower concentration of follicular homocysteine (median [IQR]–7.6 [13.2] vs 24.3 [22.9]). Supplemented patients required far less FSH for stimulation (1650 [325] vs 2250 [337], p = 0.00002) with no differences in the number of oocytes collected, MII rate, and fertilization rate. Supplemented patients enjoyed higher blastocyst rate (55% [20.5] vs 32% [16.5]; p = 0.0009) and a trend for improved implantation rate (64% vs 32%; p = 0.0606). Clinical pregnancy rates were 58% vs 33% in controls (p = ns). CONCLUSION: Follicular homocysteine is a suitable reporter that might be investigated as a tool for oocyte-embryo selection. A diet enriched with methyl donors may be useful in PCOS and supplements may also help. These findings may be also true for non-PCOS women, which warrants investigation. The study was approved by the Acibadem University Research Ethics Committee (2017–3-42). Clinical trial retrospective registration number ISRCTN55983518.