P-604 Inhibin B in Low Ovarian Reserve Patients: Correlation With Ovarian Reserve Markers and Oocyte Yield
Authors: Sibal J , Lawrenz B , Kumar A , Kalra B , Ata B , Patel R , Kalafat E , Elkhatib I , Fatemi H , Melado L 
Published: June 2023

Abstract

Study question
Is there a correlation between Inhibin B (InhB) serum levels and oocyte yield after ovarian stimulation (OS) in women with low ovarian reserve?

Summary answer
InhB presents a positive relationship with oocyte yield during OS in women with AMH&lt;1.1ng/mL.

What is known already
InhB is produced by granulosa cells in the ovary with the goal of suppressing FSH production. Assay and intercycle variability have been the main limitations affecting specificity and reproducibility of InhB as a marker of ovarian reserve or oocyte yield after OS. This fact is attributed to low specific antibodies for the molecule in previous assays, exhibiting cross-reactivity with other glycoproteins in the transforming growth factor beta family. High specific ELISA assay,measuring bioavailable InhB (bio-InhB), may provide more accurate results, specially important in poor responders, as results may involve clinical decisions on whether or not to proceed with OS.

Study design, size, duration
Prospective observational study measuring bio-InhB in 72 women with low ovarian reserve, performing OS for IVF/ICSI, at a tertiary referral fertility center, from February 2019 to December 2021. Low ovarian reserve was defined as AMH serum levels &lt;1.1ng/ml (Elecsys, Roche), following Bologna criteria. All patients performed OS for IVF/ICSI in a GnRH-antagonist protocol.

Participants/materials, setting, methods
On day 2/3 of cycle, before starting OS, AFC, FSH, LH, estradiol, progesterone and AMH (Elecsys, Roche) were measured. Extra serum samples were frozen at -20C for subsequent bio-InhB analysis (AnshLabs, Texas). Ethical approval was obtained (Research Ethics Committee-REFA033c) and informed consent was signed for all participants.

Main results and the role of chance
Patient characteristics were [Median(IQR)]: age: 39(36-42)years, BMI: 28.51(26.1-30.1) Kg/m2, AFC: 5.5(4-7), FSH:8.23(6.4-12.5) mIU/mL, LH: 6.54(4.51-8.91) mIU/mL, Estradiol: 41.18(28.47-56.44) pg/mL, AMH: 0.64(0.29-0.81)ng/mL, InhB: 62.69(33.78-97.92) pg/mL. Stimulation outcomes were: follicle number on day of trigger (Fdot): 5(3-7), cumulus-oocyte-complexes (COC’s): 3(2-4.5) andmetaphase II oocytes (MII): 3(1-4). Inh-B showed significant positive correlation (Spearman correlation) with AMH (rs = 0.35, p = 0.003), although was better with AFC (rs = 0.43, p &lt; 0.001). Moreover, Inh-B serum levels presented positive association with oocyte yield: Fdot (rs = 0.41, p &lt; 0.001), COC’s (rs = 0.36, p = 0.002) and MII (rs = 0.37, p = 0.002).
AUROC analysis was performed to investigate which model predicted better a bad outcome (defined as &lt; =3COC’s after OS) in low ovarian reserve women. No significant benefit was observed when Inh-B was added to AMH+AFC model (AUROC AMH+AFC: 0.757; AUROC AMH+AFC+Inh-B: 0.759, p = 0.843).

Limitations, reasons for caution
Although clinical assessment was performed in the same centre following the same methodology, inter-observer variability for AFC is a limitation. Besides, fresh AMH serum samples were analysed using Elecsys assay, yet frozen serum samples were shipped to Ansh Lab (Texas) for batched Inh-B analysis.

Wider implications of the findings
Bio-InhB is correlated to oocyte yield during OS. Although no additional benefit for prediction in women with AMH&lt;1.1ng/mL was observed when added to other currently used markers, future research should explore the utility of bio-inhB on other outcomes associated to ovarian reserve, as embryo quality and ploidy.

Trial registration number
Not applicable