Apply Biphasic IVM for POSEIDON Group 1

Official title

Efficacy and Safety of Biphasic IVM in Low Prognosis Patients Classified as Poseidon Group 1A

Overview

The goal of this clinical trial is to learn if biphasic In Vitro Maturation (IVM) works to help young women who produce very few oocytes after controlled ovarian stimulation. The study focuses on women under age 35 who have a good number of follicles in their ovaries but do not respond well to standard ovarian stimulation by Gonadotropin (known as POSEIDON Group 1a). The main questions it aims to answer are: How many mature oocytes can be obtain after biphasic -VM? Researchers will use biphasic-IVM system to see if it can bypass the problems these patients face with standard treatments, such as high costs and the risk of medical complications like Ovarian Hyperstimulation Syndrome (OHSS). Participants will: Have their immature eggs collected from the ovaries without the need for high-dose hormone injections. Have their eggs matured in a specialized laboratory using a two-step process (biphasic IVM) to improve egg quality. Follow up with researchers to check the number of embryos created and the safety of the procedure.

Detailed description

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.

Interventions

• Procedure Biphasic-IVM
  After consenting to undergo biphasic IVM, patients will be scheduled for immature oocyte retrieval between cycle days 1 and 6. No FSH, hMG, hCG, or GnRH agonist will be administered for oocyte maturation. Oocyte retrieval will be performed transvaginally under ultrasound guidance. A 20G aspiration needle (Kitazato®, Japan or Vitrolife®, Sweden) will be connected to a suction device with a negative pressure of -120 mmHg. Follicular fluid will be transferred to the laboratory for oocyte identific

Primary outcome measures

• Number of matured oocytes after biphasic-IVM [Time frame: From enrollment to the last of treatment at 12 months]

Secondary outcome measures (12)

• Number of patients have no oocyte retrieved [Time frame: From enrollment to the last of treatment at 12 months]
• Number of patients have no matured oocytes after biphasic IVM [Time frame: From enrollment to the last of treatment at 12 months]
• Number of patients have no embryos [Time frame: From enrollment to the end of treatment at 12 months]
• Recovery rate [Time frame: From enrollment to the end of treatment at 12 months]
• Maturation rate [Time frame: From enrollment to the end of treatment at 12 month]
• Number of fertilized oocytes [Time frame: From enrollment to the last of treatment at 12 months]
• Number of embryos day-3 oocytes [Time frame: From enrollment to the last of treatment at 12 months]
• Day-3 embryos rate [Time frame: From enrollment to the last of treatment at 12 months]
• Number of good embryos day-3 [Time frame: From enrollment to the last of treatment at 12 months]
• Number of frozen embryos day-3 [Time frame: From enrollment to the last of treatment at 12 months]
• Number of blastocyst embryos [Time frame: From enrollment to the last of treatment at 12 months]
• Blastocyst rate [Time frame: From enrollment to the last of treatment at 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Vietnam · 1 center

• IVFMD, My Duc Hospital — Ho Chi Minh City

Publications

• Yalcinkaya E, Caliskan E, Budak O. In vitro maturation may prevent the cancellation of in vitro fertilization cycles in poor responder patients: A case report. J Turk Ger Gynecol Assoc. 2013 Jul 10;14(4):235-7. doi: 10.5152/jtgga.2013.68335. eCollection 2013. PMID 24592113
• Alviggi C, Conforti A, Esteves SC, Vallone R, Venturella R, Staiano S, Castaldo E, Andersen CY, De Placido G. Understanding Ovarian Hypo-Response to Exogenous Gonadotropin in Ovarian Stimulation and Its New Proposed Marker-The Follicle-To-Oocyte (FOI) Index. Front Endocrinol (Lausanne). 2018 Oct 17;9:589. doi: 10.3389/fendo.2018.00589. eCollection 2018. PMID 30386293
• Conforti A, Esteves SC, Di Rella F, Strina I, De Rosa P, Fiorenza A, Zullo F, De Placido G, Alviggi C. The role of recombinant LH in women with hypo-response to controlled ovarian stimulation: a systematic review and meta-analysis. Reprod Biol Endocrinol. 2019 Feb 6;17(1):18. doi: 10.1186/s12958-019-0460-4. PMID 30728019
• Haahr T, Esteves SC, Humaidan P. Individualized controlled ovarian stimulation in expected poor-responders: an update. Reprod Biol Endocrinol. 2018 Mar 9;16(1):20. doi: 10.1186/s12958-018-0342-1. PMID 29523204
• Grynberg, M. and Fanchin, R. (2021) 'IVM in non-PCOS indications', in In Vitro Maturation of Human Oocytes. CRC Press.
• Herrero, L., Pareja, S., Losada, C. and Cobo, A. (2018) 'In vitro maturation (IVM) for patients with poor ovarian response: a pilot study', Journal of Clinical Medicine, 7(12), p. 524.
• Humaidan, P., Alviggi, C., Fischer, R. and Esteves, S.C. (2016) 'The 'POSEIDON' stratification of 'Low Prognosis Patients in Assisted Reproductive Technology': we can stop looking for the ideal patient', Human Reproduction, 31(10), pp. 2201-2211.
• Kushnir, V.A., Gleicher, N., Barad, D.H. and Albertini, D.F. (2018) 'A single-center study of in vitro maturation in patients with low ovarian reserve', Journal of Ovarian Research, 11(1), pp. 1-6.

Identifiers

NCT: NCT07632300 · 07/26/DD-BVMD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗