P-223 Follicular fluid from women stimulated with hMG protocol displays altered energy metabolism and this impacts embryo morphokinetics
Authors: Fortini S , Del Collado Barrondo M , Giovanna Basso C , Ejzenberg D , Frantz N , Sousa R  G B , Nichi M , Milazzotto M  P 
Published: July 2024

Abstract

Study question
Does different type of ovarian stimulation affect follicle metabolism?

Summary answer
Patients stimulated hMG-only show increased levels of glucose and MDA in follicular fluid and longer Cc3 embryo time compared to patients stimulated rFSH and hMG.

What is known already
Oocyte growth and maturation strongly rely on energy metabolism. However, there is a notable lack of studies examining the influence of ovarian stimulation protocols on individual follicular fluid. While certain studies indicate changes in genes associated with glucose metabolism in patients subjected to different protocols, there remains a need for prospective studies in this field.

Study design, size, duration
This is a single-center prospective analysis from March 2022 to August 2022 including 20 patients. From the total, 14 were stimulated with rFSH + hMG and 6 with hMG only. A total of 81 embryos were submitted to morphokinetics analysis. Patients with Polycystic Ovary Syndrome (PCOS), Ovarian insufficiency, Endometriosis in stages III and IV, and patients who have already undergone other attempts at the clinic were excluded.

Participants/materials, setting, methods
Patients were firstly assessed by age, body mass index (BMI), and dosage of stimulation hormones. Puncture of follicles was performed individually after system wash and only follicular fluid (FF) with no visible blood contamination were submitted for analysis. FFs were analyzed for glucose, lactate, insulin (specific fluorometric assays), and MDA (important oxidative stress marker). Morphokinetics analyses were performed for all available embryos from day 0 until day 6.

Main results and the role of chance
Body Mass Index (BMI) and ages were similar among the categories (p = 0.388 and p = 0.373, respectively). FSH dosage used in both groups was not different (p = 0.85) but LH used was higher in patients treated with human menopausal gonadotropin (hMG) (p = 0.002). Women whose treatment was hMG presented more glucose in FF (p = 0.02) and MDA (p = 0.02) while no differences were observed for insulin and lactate content (p = 0.57 and p = 0.72 respectively). There was a significant increase of 3º Cell Cicle (Cc3) time of embryos from women treated with hMG only. Taken together, these data suggest that hMG is modifying the glucose metabolism by interrupting glycolysis in the oocyte, resulting in a higher amount in FF, which increases Malondialdehyde (MDA) levels. Considering that oocytes from women treated with hMG only had an altered metabolic profile, this could impact the further embryo development, with consequences specifically at the time of the embryonic metabolic shift.

Limitations, reasons for caution
The limited number of patients is a limitation of the study and the lack of standardization in the use of trigger, despite of not having significant difference.

Wider implications of the findings
Understanding the implication of hormones in follicular microambient might help individualization of hormones usage and improve the outcomes of IVF treatment.

Trial registration number
44895621.1.0000.5594