Apply Biphasic IVM for POSEIDON Group 1

In assisted reproductive technology (ART), patients with poor or suboptimal ovarian response to controlled ovarian hyperstimulation pose significant clinical challenges, leading to the development of the POSEIDON classification in 2016. In particular, POSEIDON group 1a includes young patients (under 35 years of age) with normal ovarian reserve parameters (AFC ≥5 and/or AMH ≥1.2 ng/mL) who nevertheless have a low number of retrieved oocytes (<4 oocytes) following standard ovarian stimulation. The cause of this is often attributed to genetic factors, such as FSH receptor (FSHR) or LH receptor (LHR) polymorphisms, leading to ovarian resistance or reduced sensitivity to exogenous gonadotropins". Current traditional IVF treatment strategies for this group typically focus on increasing gonadotropin dosages, adding recombinant LH, or applying double stimulation protocols (DuoStim) to maximize the number of oocytes retrieved and obtain at least one euploid blastocyst. However, these approaches not only substantially increase treatment costs and the psychological burden on patients, but may also elevate the risk of ovarian hyperstimulation syndrome (OHSS) due to the presence of a high number of antral follicles. Moreover, their true effectiveness remains controversial, as the pathophysiology is related to reduced receptor sensitivity rather than a simple hormonal deficiency.

The application of biphasic IVM in POSEIDON group 1 patients represents a biologically and clinically rational strategy. This technique leverages the advantage of preserved ovarian reserve (a high number of small follicles) to retrieve immature oocytes without relying on high-dose gonadotropin stimulation, thereby bypassing receptor resistance mechanisms. In addition, it nearly eliminates the risk of OHSS and reduces treatment costs. Previous studies investigating IVM in patients with poor ovarian response mainly focused on rescuing immature oocytes retrieved during conventional stimulation cycles (rescue-IVM) to increase embryo availability. However, pregnancy outcomes derived from rescue-IVM have generally been low.

Biphasic IVM offers a promising alternative approach. This protocol includes a prematuration phase using C-type Natriuretic Peptide (CNP) to temporarily arrest meiotic progression for 24 hours, thereby restoring synchronization between nuclear and cytoplasmic maturation, followed by a 30-hour maturation phase. This strategy significantly improves oocyte developmental competence and blastocyst formation rates. The aim of this study is to evaluate the efficacy and safety of biphasic IVM in patients classified as POSEIDON Group 1a.

Inclusion criteria

• Women aged 18 - < 35 years
• At least one IVF cycle have been failed and classified as having a poor response to POSEIDON group Ia.
• POSEIDON group Ia ( < 35 age; AMH >= 1.2 ng/ml and/or AFC >=5 antral follicles; have < 4 oocytes was retrieved at previous IVF cycle)
• Agree to apply biphasic-IVM treatment.
• Agree to freeze all embryos and to transfer the frozen embryos afterward.
• Agree to participate in the study.

Exclusion criteria

• Egg-donation cycle
• Uterine abnormalities: adenomyosis, large uterine fibroids (≥5 cm), bicornuate uterus, uterine adhesions.
• Sperm surgical (PESA, TESE, mTESE)
• PGT