Apply Biphasic IVM for POSEIDON Group 1 (POSEIDON-Ia)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Adult Females; Healthy Adult Male
• Intervention / Treatment: Procedure: Biphasic-IVM

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 (Humaidan et al., 2016). 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." (Alviggi et al., 2018). 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 (Haahr et al., 2018; Conforti et al., 2019).

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 (Grynberg et al., 2021). 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 (Elias et al., 2014; Herrero et al., 2018; Kushnir et al., 2018).

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 (Sanchez et al., 2019; Vuong et al., 2020). The aim of this study is to evaluate the efficacy and safety of biphasic IVM in patients classified as POSEIDON Group 1a.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tuong M Ho, MD; Phone Number: +84903633377‬; Email: tuongho.ivfmd@gmail.com
• Study Contact Backup: Name: Ho L. Le, MD; Phone Number: +84356177147; Email: bsho.ll@myduchospital.vn

Study Locations

• Vietnam
  • Hồ Chí Minh
    • Ho Chi Minh City, Hồ Chí Minh, Vietnam, 70000
      • IVFMD, My Duc Hospital
      • Contact: Ho L. Le, MD; Phone Number: 84356177147; Email: bsho.ll@myduchospital.vn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Biphasic-IVM; Participants in this arm will undergo a biphasic In Vitro Maturation (IVM) protocol

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 identification under a stereomicroscope and filtered using a mesh system to avoid oocyte loss. Cumulus-oocyte complexes (COCs) will be washed and placed into four-well culture dishes containing CAPA medium. After 24 hours of prematuration culture in CAPA medium, the oocytes will be transferred to IVM medium for an additional 30 hours. Subsequently, oocytes will be denuded and assessed for nuclear maturation status. Mature oocytes obtained after IVM culture will undergo intracytoplasmic sperm injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of matured oocytes after biphasic-IVM	Count the number of oocytes with the first polar body extruded after biphasic IVM culture	From enrollment to the last of treatment at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients have no oocyte retrieved	Count the number of patients with no oocytes retrieved	From enrollment to the last of treatment at 12 months
Number of patients have no matured oocytes after biphasic IVM	Count the number of patients with no matured oocytes after biphasic IVM	From enrollment to the last of treatment at 12 months
Number of patients have no embryos	Count the number of patients with no embryos	From enrollment to the end of treatment at 12 months
Recovery rate	Number of GV oocytes/number of follicles	From enrollment to the end of treatment at 12 months
Maturation rate	Number of matured oocytes after biphasic-IVM/number of GV oocytes	From enrollment to the end of treatment at 12 month
Number of fertilized oocytes	Number of 2PN oocytes after ICSI 16 - 18 hours	From enrollment to the last of treatment at 12 months
Number of embryos day-3 oocytes	Number of cleavage embryos after ICSI 64 hours	From enrollment to the last of treatment at 12 months
Day-3 embryos rate	Number of day-3 embryos/number of 2PN	From enrollment to the last of treatment at 12 months
Number of good embryos day-3	Mean number of usable embryos day-3	From enrollment to the last of treatment at 12 months
Number of frozen embryos day-3	Mean number of Day-3 cryopreserved embryos	From enrollment to the last of treatment at 12 months
Number of blastocyst embryos	Mean number of Day-5 embryos	From enrollment to the last of treatment at 12 months
Blastocyst rate	Number of blastocyst/ number of 2 PN	From enrollment to the last of treatment at 12 months
Number of good blastocyst embryos	Mean number of usable blastocyts embryos	From enrollment to the last of treatment at 12 months
Number of frozen blastocyst embryos	Mean number of Day-5 cryopreserved embryos	From enrollment to the last of treatment at 12 months
Pregnancy rate	Serum beta-hCG level > 25 mIU/ml after transfer 11 - 13 days	From enrollment to the last of treatment at 12 months
Implantion rate	Number of visible gestational sac (included ectopic pregnancy)/ number of embryos transferred	From enrollment to the last of treatment at 12 months
Clinical pregnancy rate	At least one gestational sac was observed on ultrasound at 7 gestational weeks	From enrollment to the end of treatment at 12 months
Ongoing pregnancy rate	At least one fetus with heart beat was observed on ultrasound at 12 gestational weeks	From enrollment to the end of treatment at 12 moths
Live birth rate	The complete expulsion or extraction of a product of human conception from its mother irrespective of pregnancy duration which, after separation, breathes or shows any sign of life, such as a beating heart, umbilical cord pulsation, or voluntary muscle movement	From enrollment to the end of treatment at 12 moths
Ectopic pregnancy rate	Percentage of patients with ectopic pregnancy	From enrollment to the end of treatment at 12 months
Miscarriage rate < 12 gestational weeks	Percentage of patients with miscarriage pregnancy < 12 weeks	From enrollment to the end of treatment at 12 months
Multiple pregnancy rate	Percentage of patients with multiple pregnancy (> 1 gestational sac)	From enrollment to the end of treatment at 12 months
OHSS rate	Percentage of patients with OHSS requiring hospitalization	From enrollment to the end of treatment at 12 months
Internal bleeding after OPU	Percentage of patients with internal bleeding after OPU requiring hospitalization	From enrollment to the end of treatment at 12 months
Fertilization rate	Number of 2PN/ Number of MII	From enrollment to the end of treatment at 12 months

Collaborators and Investigators

• Sponsor: Mỹ Đức Hospital
• Investigators: Principal Investigator: Ho L. Le, MD

Publications and helpful links

General 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.
• 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.
• 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.
• 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.
• 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.
• Sanchez, F., Leuzinger, L., Romero, S., De Vos, M., Heindryckx, B. and Smitz, J. (2019) 'In vitro maturation with a prematuration step (CAPA-IVM) improves the meiotic and developmental capacity of human oocytes', Human Reproduction, 34, pp. 1-15.
• Vuong, L.N., Le, A.H., Ho, V.N.A., Pham, T.D., Sanchez, F., Leuzinger, L., Heindryckx, B., Smitz, J. and Mol, B.W. (2020) 'Effectiveness of biphasic in vitro maturation in women with polycystic ovary syndrome: a randomized controlled trial', Human Reproduction, 35(12), pp. 2737-2747.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): March 30, 2027

Study Registration Dates

• First Submitted: June 2, 2026
• First Submitted That Met QC Criteria: June 2, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 07/26/DD-BVMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No