P-658 Clinical outcomes from ART in predicted hyperresponders: in-vitro maturation of oocytes versus conventional ovarian stimulation
Authors: Mostinckx L , Goyens E , Mackens S , Roelens C , Boudry L , Uvin V , Segers I , Schoemans C , Drakopoulos P , De Vos M 
Published: June 2023

Abstract

Study question
Do ongoing pregnancy rates (OPR) differ in predicted hyperresponders undergoing ART after in-vitro maturation of oocytes (IVM) compared with conventional ovarian stimulation (COS)?

Summary answer
One cycle of IVM is non-inferior to one cycle of COS in women with serum AMH levels &gt;10ng/mL.

What is known already
Women with high antral follicle count (AFC) and elevated serum AMH levels, indicating an increased functional ovarian reserve, are prone to hyperresponse during ART treatment. To avoid iatrogenic complications of COS, IVM has been proposed as a mild-approach alternative treatment in predicted hyperresponders, including women with polycystic ovary syndrome (PCOS) who are eligible for ART. To date, inferior pregnancy rates from IVM compared to COS have hampered the uptake of IVM by ART clinics. However, it is unclear whether the efficiency gap between IVM and COS may differ depending on the extent of AMH elevation.

Study design, size, duration
This study is a retrospective cohort analysis of clinical and laboratory data from the first completed highly purified human menopausal gonadotropin (HP-hMG) primed, non-hCG triggered IVM or COS (FSH or HP-hMG stimulation in a GnRH antagonist protocol) cycle with ICSI in predicted hyperresponders ≤36 years of age at a tertiary referral university hospital. A total of 1707 cycles were included between January 2016 and June 2022.

Participants/materials, setting, methods
Predicted hyperresponse was defined as a serum AMH level &gt;3.25ng/mL (Elecsys® AMH, Roche Diagnostics). The primary outcome was cumulative ongoing pregnancy rate (OPR) assessed 10-11 weeks after embryo transfer. The predefined non-inferiority limit was -10.0%. The analysis was adjusted for AMH strata. Time-to-pregnancy (TTP), defined by the time interval between egg retrieval and date of successful embryo transfer, was a secondary outcome. Statistical analysis was performed using a multivariable regression model controlling for potential confounders.

Main results and the role of chance
Data from 463 IVM cycles were compared with those from 1244 COS cycles. Women in the IVM group more often had a diagnosis of Rotterdam PCOS (434/463, 93.7%) compared to those undergoing COS (522/1193, 43.8%), were significantly younger (29.5 years vs 30.5 years, p ≤ 0.001), had a higher BMI (25.7kg/m² vs 25.1kg/m², p ≤ 0.01) and higher AMH (11.6ng/mL vs 5.3ng/mL, p ≤ 0.001). Although IVM cycles yielded more cumulus oocyte complexes (COCs) (25.8 COC vs 15.0 COC, p ≤ 0.001), both groups had similar numbers of mature oocytes (MII) (11.9 MII vs 10.6 MII, p = 0.9).
In the entire cohort, non-adjusted cumulative OPR from IVM was significantly lower (198/463, 42.8%) compared to COS (794/1244, 63.8%), p ≤ 0.001. When analysing OPR across different serum AMH strata, cumulative OPR in both groups converged with increasing serum AMH, and OPR from IVM was non-inferior compared to COS from serum AMH levels &gt;10ng/mL onwards (113/221, 51.1% [IVM]; 29/48, 60.4% [COS]). Time-To-Pregnancy was shorter in the IVM group compared to COS (11.3 weeks vs 21.0 weeks, p ≤ 0.001). Multivariable regression analysis adjusting for ART type, age, BMI, oocyte number and PCOS phenotype showed that the number of COCs was the only parameter associated with OPR in predicted hyperresponders with a serum AMH &gt;10ng/mL.

Limitations, reasons for caution
These data should be interpreted with caution as the retrospective nature of the study holds the possibility of unmeasured confounding factors. Patients enrolled in a clinical IVM program received one-to-one care, in contrast with COS patients who received standard care, which may have influenced TTP.

Wider implications of the findings
Among subfertile women who are eligible for ART, IVM and COS resulted in comparable reproductive outcomes in a subset of women with a serum AMH &gt;10ng/mL. These findings should be corroborated by an RCT comparing both treatments in selected patients with elevated AMH.

Trial registration number
Not applicable