Healthy Adult Females, Healthy Adult Male
Conditions
Brief summary
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
PROCEDUREBiphasic-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.
Sponsors
Mỹ Đức Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of matured oocytes after biphasic-IVM | From enrollment to the last of treatment at 12 months | Count the number of oocytes with the first polar body extruded after biphasic IVM culture |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients have no oocyte retrieved | From enrollment to the last of treatment at 12 months | Count the number of patients with no oocytes retrieved |
| Number of patients have no matured oocytes after biphasic IVM | From enrollment to the last of treatment at 12 months | Count the number of patients with no matured oocytes after biphasic IVM |
| Number of patients have no embryos | From enrollment to the end of treatment at 12 months | Count the number of patients with no embryos |
| Recovery rate | From enrollment to the end of treatment at 12 months | Number of GV oocytes/number of follicles |
| Maturation rate | From enrollment to the end of treatment at 12 month | Number of matured oocytes after biphasic-IVM/number of GV oocytes |
| Number of fertilized oocytes | From enrollment to the last of treatment at 12 months | Number of 2PN oocytes after ICSI 16 - 18 hours |
| Number of embryos day-3 oocytes | From enrollment to the last of treatment at 12 months | Number of cleavage embryos after ICSI 64 hours |
| Day-3 embryos rate | From enrollment to the last of treatment at 12 months | Number of day-3 embryos/number of 2PN |
| Number of good embryos day-3 | From enrollment to the last of treatment at 12 months | Mean number of usable embryos day-3 |
| Number of frozen embryos day-3 | From enrollment to the last of treatment at 12 months | Mean number of Day-3 cryopreserved embryos |
| Number of blastocyst embryos | From enrollment to the last of treatment at 12 months | Mean number of Day-5 embryos |
| Blastocyst rate | From enrollment to the last of treatment at 12 months | Number of blastocyst/ number of 2 PN |
| Number of good blastocyst embryos | From enrollment to the last of treatment at 12 months | Mean number of usable blastocyts embryos |
| Number of frozen blastocyst embryos | From enrollment to the last of treatment at 12 months | Mean number of Day-5 cryopreserved embryos |
| Pregnancy rate | From enrollment to the last of treatment at 12 months | Serum beta-hCG level \> 25 mIU/ml after transfer 11 - 13 days |
| Implantion rate | From enrollment to the last of treatment at 12 months | Number of visible gestational sac (included ectopic pregnancy)/ number of embryos transferred |
| Clinical pregnancy rate | From enrollment to the end of treatment at 12 months | At least one gestational sac was observed on ultrasound at 7 gestational weeks |
| Ongoing pregnancy rate | From enrollment to the end of treatment at 12 moths | At least one fetus with heart beat was observed on ultrasound at 12 gestational weeks |
| Live birth rate | From enrollment to the end of treatment at 12 moths | 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 |
| Ectopic pregnancy rate | From enrollment to the end of treatment at 12 months | Percentage of patients with ectopic pregnancy |
| Miscarriage rate < 12 gestational weeks | From enrollment to the end of treatment at 12 months | Percentage of patients with miscarriage pregnancy \< 12 weeks |
| Multiple pregnancy rate | From enrollment to the end of treatment at 12 months | Percentage of patients with multiple pregnancy (\> 1 gestational sac) |
| OHSS rate | From enrollment to the end of treatment at 12 months | Percentage of patients with OHSS requiring hospitalization |
| Internal bleeding after OPU | From enrollment to the end of treatment at 12 months | Percentage of patients with internal bleeding after OPU requiring hospitalization |
| Fertilization rate | From enrollment to the end of treatment at 12 months | Number of 2PN/ Number of MII |
Countries
Vietnam
Contacts
CONTACTHo L. Le, MD
CONTACTTuong M Ho, MD
PRINCIPAL_INVESTIGATORHo L. Le, MD
Outcome results
None listed