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.
研究概览
详细说明
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.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Tuong M Ho, MD
- 电话号码：+84903633377
- 邮箱：tuongho.ivfmd@gmail.com
研究联系人备份
- 姓名：Ho L. Le, MD
- 电话号码：+84356177147
- 邮箱：bsho.ll@myduchospital.vn
学习地点
-
-
Hồ Chí Minh
-
Ho Chi Minh City、Hồ Chí Minh、越南、70000
- 招聘中
- IVFMD, My Duc Hospital
-
接触：
- Ho L. Le, MD
- 电话号码：84356177147
- 邮箱：bsho.ll@myduchospital.vn
-
-
参与标准
资格标准
适合学习的年龄
- 成人
接受健康志愿者
描述
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
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Biphasic-IVM
Participants in this arm will undergo a biphasic In Vitro Maturation (IVM) protocol
|
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. |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of matured oocytes after biphasic-IVM
大体时间：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
|
From enrollment to the last of treatment at 12 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of patients have no oocyte retrieved
大体时间：From enrollment to the last of treatment at 12 months
|
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
大体时间：From enrollment to the last of treatment at 12 months
|
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
大体时间：From enrollment to the end of treatment at 12 months
|
Count the number of patients with no embryos
|
From enrollment to the end of treatment at 12 months
|
|
Recovery rate
大体时间：From enrollment to the end of treatment at 12 months
|
Number of GV oocytes/number of follicles
|
From enrollment to the end of treatment at 12 months
|
|
Maturation rate
大体时间：From enrollment to the end of treatment at 12 month
|
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
大体时间：From enrollment to the last of treatment at 12 months
|
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
大体时间：From enrollment to the last of treatment at 12 months
|
Number of cleavage embryos after ICSI 64 hours
|
From enrollment to the last of treatment at 12 months
|
|
Day-3 embryos rate
大体时间：From enrollment to the last of treatment at 12 months
|
Number of day-3 embryos/number of 2PN
|
From enrollment to the last of treatment at 12 months
|
|
Number of good embryos day-3
大体时间：From enrollment to the last of treatment at 12 months
|
Mean number of usable embryos day-3
|
From enrollment to the last of treatment at 12 months
|
|
Number of frozen embryos day-3
大体时间：From enrollment to the last of treatment at 12 months
|
Mean number of Day-3 cryopreserved embryos
|
From enrollment to the last of treatment at 12 months
|
|
Number of blastocyst embryos
大体时间：From enrollment to the last of treatment at 12 months
|
Mean number of Day-5 embryos
|
From enrollment to the last of treatment at 12 months
|
|
Blastocyst rate
大体时间：From enrollment to the last of treatment at 12 months
|
Number of blastocyst/ number of 2 PN
|
From enrollment to the last of treatment at 12 months
|
|
Number of good blastocyst embryos
大体时间：From enrollment to the last of treatment at 12 months
|
Mean number of usable blastocyts embryos
|
From enrollment to the last of treatment at 12 months
|
|
Number of frozen blastocyst embryos
大体时间：From enrollment to the last of treatment at 12 months
|
Mean number of Day-5 cryopreserved embryos
|
From enrollment to the last of treatment at 12 months
|
|
Pregnancy rate
大体时间：From enrollment to the last of treatment at 12 months
|
Serum beta-hCG level > 25 mIU/ml after transfer 11 - 13 days
|
From enrollment to the last of treatment at 12 months
|
|
Implantion rate
大体时间：From enrollment to the last of treatment at 12 months
|
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
大体时间：From enrollment to the end of treatment at 12 months
|
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
大体时间：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
|
From enrollment to the end of treatment at 12 moths
|
|
Live birth rate
大体时间：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
|
From enrollment to the end of treatment at 12 moths
|
|
Ectopic pregnancy rate
大体时间：From enrollment to the end of treatment at 12 months
|
Percentage of patients with ectopic pregnancy
|
From enrollment to the end of treatment at 12 months
|
|
Miscarriage rate < 12 gestational weeks
大体时间：From enrollment to the end of treatment at 12 months
|
Percentage of patients with miscarriage pregnancy < 12 weeks
|
From enrollment to the end of treatment at 12 months
|
|
Multiple pregnancy rate
大体时间：From enrollment to the end of treatment at 12 months
|
Percentage of patients with multiple pregnancy (> 1 gestational sac)
|
From enrollment to the end of treatment at 12 months
|
|
OHSS rate
大体时间：From enrollment to the end of treatment at 12 months
|
Percentage of patients with OHSS requiring hospitalization
|
From enrollment to the end of treatment at 12 months
|
|
Internal bleeding after OPU
大体时间：From enrollment to the end of treatment at 12 months
|
Percentage of patients with internal bleeding after OPU requiring hospitalization
|
From enrollment to the end of treatment at 12 months
|
|
Fertilization rate
大体时间：From enrollment to the end of treatment at 12 months
|
Number of 2PN/ Number of MII
|
From enrollment to the end of treatment at 12 months
|
合作者和调查者
调查人员
- 首席研究员：Ho L. Le, MD
出版物和有用的链接
一般刊物
- 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.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他研究编号
- 07/26/DD-BVMD
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.