New Application of Sequential in Vitro Muturation System for Infertility Patients With Polycystic Ovary Syndrome
New Application of Oocyte Sequential Culture and in Vitro Muturation System for Infertility Patients With Polycystic Ovary Syndrome: a Multi-center Prospective Randomized Clinical Trial
1 other identifier
interventional
300
1 country
5
Brief Summary
Oocyte in vitro maturation (IVM) is an artificial reproductive technologies (ART) in which cumulus-oocyte complex (COC) are collected at the immature germinal vesicle (GV) stage from unstimulated or FSH-primed ovaries and matured in vitro before fertilization. IVM has been proposed as a more patient-friendly ART alternative to conventional IVF. Contrary to IVF, IVM is the only ART method with no cases of OHSS reported. Hence, patients with PCOS represent the major target population for IVM treatment. In clinical practice of standard IVM, COCs are aspirated from unstimulated or mildly stimulated ovaries and rapidly removed from the meiotic-inhibiting influence of the follicle and the follicular fluid. Regardless of in vitro gonadotrophin treatment, oocytes mature spontaneously in vitro, hence undergoing meiotic resumption in the absence of the usual elaborate cascade of endocrine and paracrine molecular signals that induce maturation in vivo. As such, the maturation of oocytes by standard IVM techniques is an artefact that compromises subsequent oocyte developmental competence. Numbers of studies have been proposed to improve the efficiency of IVM system. Synchronization of meiotic and cytoplasmic maturation in antral oocytes arrested at the immature GV-stage remains a major challenge and is of fundamental importance for successful fertilization. High intra-oocyte levels of cyclic adenosine monophosphate (cAMP), is crucial to maintain the nearly fully-grown oocytes under meiotic arrest and to induce oocyte maturation. Research in animal models has indicated that a non-physiological drop of cAMP levels in the oocyte results in asynchronous nuclear and cytoplasmic maturation. Investigators have reported the development of a novel in vitro simulated sequential oocyte maturation system. Critical to success of the approach is a pre-IVM phase that generates a rapid increase in COC cAMP levels. Secondly, the system utilizes an extended IVM phase containing sufficient FSH to drive meiotic induction in the presence of a type-3 PDE inhibitor. The high levels of cAMP in the oocyte and the induced nature of oocyte maturation mimics some of the key, newly characterized molecular signals that occur during oocyte maturation in vivo. Technical and conceptual elements were first developed using mouse, bovine and human COCs. Investigators propose a randomized clinical trial to compare a novel sequential culture system with the traditional standard oocyte IVM system for PCOS patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 2018
Shorter than P25 for phase_3
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2018
CompletedFirst Submitted
Initial submission to the registry
December 8, 2018
CompletedFirst Posted
Study publicly available on registry
December 12, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2020
CompletedDecember 12, 2018
December 1, 2018
7 months
December 8, 2018
December 10, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Clinical pregnancy rate
The fetal heart beat in an intrauterine gestational sac under ultrasound will be defined as clinical pregnancy.
7 weeks gestation
Secondary Outcomes (15)
Oocyte maturation rate
30 and 46 hours after oocyte retrieval
Fertilization rate
30 and 46 hours after oocyte retrieval
Cleavage rate
24 hours after ICSI
Day 3 embryo rate
72 hours after ICSI
Good quality embryo rate at cleavage-stage
72 hours after ICSI
- +10 more secondary outcomes
Study Arms (2)
sequential oocyte IVM group
EXPERIMENTALFrom day 7\~9 of the menstrual cycle, 225 IU HMG (Menotrophins for Injection) per day will be administrated for 3 days. COCs were removed from aspirated follicular fluid and transferred into HEPES-buffered collection medium. The immature oocytes will be cultured in sequential IVM medium 1 for 6 hours (37℃, 5% CO2), and removed into sequential IVM medium 2 for further cultivation. After 24 and 40 hours cultivation, the mature oocytes will be fertilized by intracytoplasmic sperm injection (ICSI). Two of the D3 embryos (if available) which graded as top-quality embryo will be vitrified and the rest of embryos will be cultivated extendedly. Thawed embryo transfer (TET) will give preference to D3 embryos and carried out with a hormone replacement cycle.
traditional oocyte IVM group
ACTIVE COMPARATORFrom day 7\~9 of the menstrual cycle, 225 IU HMG (Menotrophins for Injection) per day will be administrated for 3 days. On the day of ovulation, COCs were aspirated and the immature oocytes will be cultured in traditional standard oocyte IVM system (Sage). 30 and 44 hours after cultivation, the maturity of oocytes will be assessed and the mature oocytes will be fertilized by intracytoplasmic sperm injection (ICSI). Two of the D3 embryos (if available) which graded as top-quality embryo will be vitrified and the rest of embryos will be cultivated extendedly. Thawed embryo transfer (TET) will give preference to D3 embryos and carried out with a hormone replacement cycle. If biochemical pregnancy is not achieved, thawed blastocysts transfer will be performed.
Interventions
The immature oocytes will be cultured in sequential oocyte IVM medium 1 for 6 hours (37℃, 5% CO2). After flushed 3 times, COCs were removed into sequential oocyte IVM medium 2 for further cultivation.
intracytoplasmic sperm injection (ICSI)
Patients administrates oestrogen (Progynova) 3mg twice a day for 10 to 12 days. From the day when endometrium reach a thickness of 8 mm and above, luteal phase support will be given with 10 mg progesterone (Dydrogesterone Tablets,) triple per day and utrogestan (Laboratories Besins International, Paris, France) 0.2g triple per day, until 14 days after embryo transfer.
COCs were aspirated and the immature oocytes will be cultured in traditional standard oocyte IVM system (Sage). 30 and 44 hours after cultivation, the maturity of oocytes will be assessed.
Eligibility Criteria
You may qualify if:
- Women age ≤35 years;
- AMH level ≥5.6ng/ml;
- Women diagnosed as PCOS according to Chinese PCOS diagnosis criteria;
- Written informed consent.
You may not qualify if:
- Women who diagnosed as uterus abnormality, adenomyosis, submucous myoma, intrauterine adhesion;
- Women who diagnosed as untreated hydrosalpinx;
- Women who had underwent unilateral ovariectomy;
- Women with medical condition that represent contraindication to assisted reproductive technology or pregnancy;
- Women or their partner with abnormal chromosome karyotype;
- Male partner with oligoasthenozoospermia or obstructive azoospermia;
- Male partner whose sperm is collected by surgery;
- Patients request withdrawal and exit the trial because adverse events occur during the trial.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
The Sixth Affiliated Hospital, Sun Yat-Sen University
Guangzhou, Guangdong, 510610, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
Reproductive medical hospital affiliated to Shandong University
Jinan, Shandong, 250001, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000, China
Tenth People's Hospital of Tongji University
Shanghai, 200072, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Xiao-yan Liang, M.D. & Ph.D
The Sixth Affiliated Hospital, Sun Yat-sen University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- doctor
Study Record Dates
First Submitted
December 8, 2018
First Posted
December 12, 2018
Study Start
December 1, 2018
Primary Completion
July 1, 2019
Study Completion
March 1, 2020
Last Updated
December 12, 2018
Record last verified: 2018-12