P-258 In-vitro oocyte maturation (IVM) in the ART clinic – What can we learn from our failed cycles?
Authors: Agius M P , Segers I , Mostinckx L , De Munck N , De Vos M 
Published: June 2023

Abstract

Study question
Why do some IVM cycles remain unsuccessful? Which factors contribute to failure in producing a usable embryo in IVM cycles?

Summary answer
Failure to obtain usable embryos after IVM was associated with oocyte dysfunction, inappropriate patient selection and unanticipated low oocyte yield.

What is known already
In-vitro maturation of oocytes retrieved from antral follicles has been offered as a mild-ART-approach to subfertile women with increased functional ovarian reserve, ovarian resistance to gonadotropins and in the context of fertility preservation.
When using monophasic IVM culture systems, oocyte maturation, embryological development and pregnancy outcomes are generally lower compared to conventional ART (cART). Women who yield high numbers of cumulus oocyte complexes from a single egg retrieval procedure, such as those with polycystic ovary syndrome (PCOS), have been considered the best candidates for IVM, to compensate for the lower maturation rate and lower embryo yield from IVM cycles.

Study design, size, duration
This was a single-tertiary center, retrospective cohort study between May 2018 and February 2022 including 277 patients: 53 patients with failed IVM and 224 patients with a successful IVM cycle (inter-patient analysis). All ART cycles from patients with one failed IVM were investigated (intra-patient analysis). Failed IVM cycles were grouped: (i) ≤20% oocyte maturation; (ii) fertilization failure; (iii) embryo development failure. Patients with FSH resistance, fertility preservation or egg donation were excluded.

Participants/materials, setting, methods
Only patients with AMH &gt;2.27 ng/ml were included. Oocytes retrieved in minimally stimulated non-hCG triggered IVM cycles were matured in a monophasic IVM system. Embryos were vitrified at cleavage stage and transferred in a hormonally substituted (HRT) cycle. Baseline patient characteristics, endocrinology and embryological data were analyzed. Intra-patient analysis was done using all ART cycles (failed IVM, IVM and cART) performed in one patient.

Main results and the role of chance
Inter-patient analysis revealed similar age, BMI and free testosterone, whereas AMH was lower in patients with a failed cycle (8.8 ± 3.5 vs 10.9 ± 6.4 ng/mL, p = 0.03). As expected, maturation, fertilization and useable embryos differed significantly in failed vs successful cycles: respectively 31% vs 48%; 40% vs 65%; 0% vs 50%; p &lt; 0.0001.
Out of 53 patients with a failed IVM cycle, 6 had oocyte maturation problems, 11 had failed fertilization and 36 had impaired embryological development.
Intra-patient analysis revealed that in the failed oocyte maturation group, 2/6 patients had maturation problems that persisted in cART cycles, indicating oocyte dysfunction. Similarly, recurrent fertilization failure was noted in 3/11 patients, due to insufficient sperm quality (n = 2). In 8/36 patients, insufficient embryo quality was observed both after IVM and cART. Hence 13/53 (24.5%) failed IVM cycles were attributed to intrinsic patient characteristics. A subgroup of patients with a failed IVM cycle had normal maturation (3/6), fertilization (7/11) or good embryos (18/36) in other IVM or cART cycles. Factors associated with cycle failure included technical issues during egg retrieval resulting in unanticipated low oocyte yield (n = 14/40), and suboptimal inclusion criteria (no PCOS, n = 3/40).

Limitations, reasons for caution
This was a retrospective study and holds the possibility of unmeasured confounding factors.

Wider implications of the findings
Risk factors for IVM failure should be identified (e.g. non-PCOS, poor operator experience) and any underlying intrinsic patient conditions should be managed within a multi-disciplinary team. Optimal patient selection is key. Analysis of failed cycles helps clinicians to estimate the prognosis of future ART cycles in women with elevated AMH.

Trial registration number
not applicable