New Application of Sequential in Vitro Muturation System for Infertility Patients With Polycystic Ovary Syndrome

NCT ID: NCT03773263

Last Updated: 2018-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-31

Study Completion Date

2020-03-31

Brief Summary

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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.

Detailed Description

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A multi-center, prospective, randomized clinical trial will be conducted, of comparing sequential oocyte IVM system with traditional oocyte IVM system for high OHSS risk PCOS patients (AMH\>5.6ng/ml). The inclusion criteria will be infertile patients diagnosed by the Chinese PCOS criteria, aged below 35 years, and without other known factors interfere reproductive or metabolic functions. 300 PCOS patients will be included and randomized into either of two groups: group A will administrate sequential oocyte IVM system and group B will administrate traditional standard oocyte IVM system. The comparison will be made between groups, and both groups are conducted with the HMG administration and embryo vitrification freezing. The primary outcome of the study is live birth rate. The embryo development and pregnancy outcomes will be followed up and compared between groups.

Conditions

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Polycystic Ovary Syndrome Infertility

Keywords

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sequential IVM system PCOS infertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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sequential oocyte IVM group

From 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.

Group Type EXPERIMENTAL

sequential IVM system

Intervention Type DRUG

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)

Intervention Type PROCEDURE

intracytoplasmic sperm injection (ICSI)

Thawed embryo transfer (TET)

Intervention Type PROCEDURE

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.

traditional oocyte IVM group

From 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.

Group Type ACTIVE_COMPARATOR

intracytoplasmic sperm injection (ICSI)

Intervention Type PROCEDURE

intracytoplasmic sperm injection (ICSI)

Thawed embryo transfer (TET)

Intervention Type PROCEDURE

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.

traditional IVM system

Intervention Type DRUG

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.

Interventions

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sequential IVM system

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.

Intervention Type DRUG

intracytoplasmic sperm injection (ICSI)

intracytoplasmic sperm injection (ICSI)

Intervention Type PROCEDURE

Thawed embryo transfer (TET)

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.

Intervention Type PROCEDURE

traditional IVM system

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.

Intervention Type DRUG

Other Intervention Names

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sage

Eligibility Criteria

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Inclusion Criteria

1. Women age ≤35 years;
2. AMH level ≥5.6ng/ml;
3. Women diagnosed as PCOS according to Chinese PCOS diagnosis criteria;
4. Written informed consent.

* Patients request withdrawal and exit the trial because adverse events occur during the trial.

Exclusion Criteria

* 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;
Maximum Eligible Age

35 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Hospital for Reproductive Medicine Affiliated to Shandong University

UNKNOWN

Sponsor Role collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role collaborator

First Affiliated Hospital of Wenzhou Medical University

OTHER

Sponsor Role collaborator

Shanghai 10th People's Hospital

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Yanhong Deng

doctor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Xiao-yan Liang, M.D. & Ph.D

Role: STUDY_DIRECTOR

The Sixth Affiliated Hospital, Sun Yat-sen University

Locations

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The Sixth Affiliated Hospital, Sun Yat-Sen University

Guangzhou, Guangdong, China

Site Status

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status

Reproductive medical hospital affiliated to Shandong University

Jinan, Shandong, China

Site Status

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Site Status

Tenth People's Hospital of Tongji University

Shanghai, , China

Site Status

Countries

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China

Central Contacts

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Xiao-yan Liang, M.D. & Ph.D

Role: CONTACT

Phone: 020-38048013

Email: [email protected]

Facility Contacts

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Xiao-yan Liang, M.D. & Ph.D.

Role: primary

Other Identifiers

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newivf20181206

Identifier Type: -

Identifier Source: org_study_id