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:
Participant gender:
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
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