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