Ovarian stimulation drugs alter the metabolite content of the growing follicle: in vivo spectroscopic evaluation of follicle fluid

J Turk Ger Gynecol Assoc. 2021 May 28;22(2):132-138. doi: 10.4274/jtgga.galenos.2020.2020.0104. Epub 2021 Jan 4.


Objective: To determine and compare metabolite content using magnetic resonance spectroscopy (MRS) of growing follicles in patients with polycystic ovary syndrome (PCOS) receiving recombinant follicle stimulating hormone (rFSH), clomiphene citrate (CC) or aromatase inhibitor (AI) for ovarian stimulation.

Material and methods: Thirty patients diagnosed with PCOS and infertility and scheduled for ovarian stimulation were divided by therapy, rFSH/CC/AI, into three equal groups. Five fertile cases were designated as the control group. When the follicle diameters reached 16-18 mm in each group, patients underwent MRS and the metabolite content of a dominant follicle was analyzed. N-acetylaspartate, lactate (Lac), creatine (Cr), and choline (Cho) metabolite levels in parts per million were measured in the spectra.

Results: A ~three-fold decrease in dominant follicle Cho content was found in patients receiving CC compared to control subjects. Similarly, the dominant follicle Cho intensities of patients given rFSH and AI were noted to be significantly higher than those who received CC. Only dominant follicle Lac levels of the patients who received CC were found to be significantly higher than the other groups. Cr peak intensities of patients receiving CC were found to be approximately three times less than control subjects. Cr signal intensity was significantly higher in patients receiving rFSH or AI than in patients receiving CC. While two patients became pregnant in the CC group, three patients in the AI group and five patients in the rFSH group became pregnant. The main metabolites detected in patients who conceived in each group were Cho and Cr. In cases who could not conceive, while Lac and lipid signals increased, Cho and Cr signals decreased.

Conclusion: Unlike CC, ovarian stimulation with rFSH or AI does not alter dominant follicle metabolite content. The developmental capacity of a growing egg may be determined non-invasively with MRS.

Keywords: MR spectroscopy; rFSH; aromatase inhibitor; clomiphene citrate; dominant follicle.