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

• Status: Unknown status
• Trial end date: 2020-03-01
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sun Yat-sen University
• Collaborators: First Affiliated Hospital of Wenzhou Medical University; Hospital for Reproductive Medicine Affiliated to Shandong University; Shanghai 10th People's Hospital; The First Affiliated Hospital with Nanjing Medical University

Criteria

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.

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;

• Subjects are found breach the inclusion criteria, or in accordance with exclusion criteria during the test, excluded;

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