P-649 Impact of systemic FSH levels on the embryo ploidy status in ovarian stimulation for IVF/ICSI
Authors: Del Gallego Bonilla R , Lawrenz B , Patel R , Melado L , Elkhatib I , Bayram A , Abdala A , El-Damen A , Fatemi H.M 
Published: June 2022

Abstract

Study question
Does systemic serum FSH-level per mature oocyte (FSH/MII) on the day of final oocyte maturation affect the ploidy status of the embryo cohort?

Summary answer
Higher serum FSH/MII levels negatively affect the euploid rate of the embryo cohort.

What is known already
In ovarian stimulation cycles, follicular phase systemic FSH-levels have to be kept above a certain threshold to achieve and maintain multifollicular growth. This contrasts the natural pattern, where FSH-levels decline steadily in the later follicular phase as a result of the increasing estrogen level. Until now, it is unclear, whether this unphysiological pattern of the systemic FSH course has an influence on the ploidy status of the biopsied blastocysts.

Study design, size, duration
Retrospective study performed at a tertiary ART referral center, including 582 cycles between March 2017 and December 2020. All GnRH (Gonadotropin-Releasing-Hormone) antagonist stimulation cycles used only recombinant FSH as gonadotropin. Patients aged between 19 and 48. All embryos underwent Preimplantation Genetic Testing for Aneuploidies (PGT-A) by Next Generation Sequencing with trophectoderm biopsy. Patients with surgical sperm extraction or warmed oocytes were excluded.

Participants/materials, setting, methods
Patients with primary or secondary infertility and an indication for ovarian stimulation for IVF/ICSI with PGT-A were included. Ovarian stimulation cycles were monitored according to clinical routine by ultrasound and repeated measurement of FSH, estradiol (E2), progesterone (P4) and LH throughout the cycle. The FSH/MII ratio was calculated as the ratio of the systemic FSH-level on the day of trigger (DoT) to the total number of mature oocytes (MII) after denudation.

Main results and the role of chance
FSH-levels at DoT revealed a wide range of systemic levels, from 2.12 to 47 IU/L. Patients had a mean age (±SD) of 30.49±4.99 years, Body Mass Index (BMI) of 27.58±5.14 kg/m2, Anti-Müllerian Hormone (AMH) of 4.20±3.05 ng/ml and 17.54±8.63 oocytes were collected with the oocyte pick up procedure.
In the univariate analysis, a significant negative correlation was found between euploid rate and the FSH/MII ratio (β=-3.194, p &lt; 0.001). Other parameters found to be negatively correlated were age (β=-1.055, p &lt; 0.001), systemic FSH-level at DoT (β=-0.652, p &lt; 0.01), total stimulation dose (β=-0.477, p &lt; 0.01) and basal FSH-level (β=-1.605, p &lt; 0.05). Alternatively, basal antral follicle count (AFC; β = 0.416, p &lt; 0.05) and total follicle count at DoT (β = 0.507, p &lt; 0.01) were observed to have a positive significant correlation with the euploid rate.
After adjusting for potential confounders in a multivariate analysis, three parameters were still observed to be significantly correlated: FSH/MII ratio remained a negative factor for euploid rate (β=-2.753, p &lt; 0.01) besides the parameters age (β=-0.837, p &lt; 0.01) and E2 at DoT (β=-0.439, p &lt; 0.05).

Limitations, reasons for caution
The retrospective character of this study can be seen as a limitation as well as the fact that the results cannot be translated to patients using either only HMG, or a combination of recombinant FSH and HMG for ovarian stimulation.

Wider implications of the findings
Due to the fact that higher FSH/MII ratios are associated with a decreased euploid rate, FSH-level measurements should be introduced into ovarian stimulation monitoring, as the gonadotropin dosage might be adjusted according to the systemic FSH-levels. This represents a further step on the treatment individualization towards a more personalized medicine.

Trial registration number
not applicable