Clinical trial NCT04562883: Single vs. Group CAPA-IVM Culture of Cumulus-oocyte Complexes
Official title: Effect of Single vs. Group CAPA-IVM Culture of Human Cumulus-oocyte Complexes From Small Antral Follicles in a SIBLING Oocyte Study Design
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: IVF
PCOS
IVM
Keywords: CAPA-IVM
Single culture
Group culture
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2020-09-24
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Oocyte in vitro maturation (IVM) is a minimal-stimulation ART with reduced hormone-related side effects and risks for the patients. However, the approach is not widely used because of an efficiency gap compared to conventional ART. In order to further optimize and adapt the CAPA-IVM system in the IVM clinic, this pilot study aims to check the feasibility of applying a single COC CAPA-IVM strategy versus the group COC culture CAPA-IVM

Detailed description: Oocyte in vitro maturation (IVM) is a minimal-stimulation ART with reduced hormone-related side effects and risks for the patients. However, the approach is not widely used because of an efficiency gap compared to conventional ART.

Oocytes retrieved for IVM procedures derive from a heterogeneous pool with variable cellular and molecular characteristics that indicate its immature status. Thus, in vitro systems that permit and enhance acquisition and synchronization of meiotic competence (ability to resume meiosis in response to an ovulatory stimulus) and developmental competence (ability to be fertilized and support early embryo development) before the meiotic trigger are crucial for the optimization of human IVM systems.

A novel two-step IVM culture system (named CAPA-IVM) involving a pre-maturation culture with C-type natriuretic peptide (CNP) and a maturation step in presence of Amphiregulin (AREG), both more physiological compounds improving oocyte competence, have been introduced in previous clinical studies. So far these pilot studies proved to increase the rates of oocyte maturation, good quality embryos on day 3, good quality blastocyst, and as a result a higher embryo yield. CAPA-IVM blastocysts have shown similar rates of methylation and gene expression at gDMRs compared to COS embryos; and the expression of ma-jor epigenetic regulators was similar between both groups. Furthermore, an improvement in pregnancy rates strengthens the clinical relevance of the use of CAPA-IVM strategy.

In order to further optimize and adapt the CAPA-IVM system in the IVM clinic, this pilot study aims to check the feasibility of applying a single COC CAPA-IVM strategy versus the group COC culture CAPA-IVM. A single COC culture would permit to perform a non-invasive molecular analysis per matured oocyte, in order to identify quality genes ex-pressed in cumulus cells post-IVM (cumulus biomarkers), which could be subsequently used to identify the embryo(s) with highest potential of implantation.

Eligibility criteria: Inclusion Criteria:

* Having polycystic ovarian morphology: at least 25 follicles (2-9 mm) throughout the whole ovary and/or increased ovarian volume (\>10ml) (it is sufficient that 1 ovary fits these criteria)
* No major uterine or ovarian abnormalities
* Having at least 15 follicles on the OPU day
* Patients consent to participate in the study

Exclusion Criteria:

* High (\>grade 2) grade endometriosis
* Cases with extremely poor sperm (serve OAT: density \<1 million, mobility \<10% and sperm from testicular surgery)

Primary outcomes:
measure: Number of good quality embryos
timeFrame: At least 3 days after intra-cytoplasmic sperm injection
Secondary outcomes:
measure: Maturation rate
timeFrame: Two days after oocytes pick-up
measure: Fertilization rate
timeFrame: 16-18 hours after intra-cytoplasmic sperm injection
measure: Cleavage rate
timeFrame: At least 3 days after intra-cytoplasmic sperm injection
measure: Expansion rate
timeFrame: After at least 30 hours of maturation culture
measure: The relative expression ratio ( R ) of human cumulus cell genes
timeFrame: cumulus cells will be collected after at least 30 hours of maturation culture, storaged at -80oC until RNA purification
measure: Positive pregnancy test
timeFrame: at 2 weeks after the embryo placement after the completion of the first transfer
measure: Clinical pregnancy
timeFrame: 5 weeks after embryo placement after the completion of the first transfer
measure: Ongoing pregnancy
timeFrame: At 12 weeks' gestation
measure: Implantation rate
timeFrame: 3 weeks after embryo transferred after the completion of the first transfer
measure: Multiple pregnancy
timeFrame: 5 weeks after embryo placement after the completion of the first transfer
measure: Multiple delivery
timeFrame: At 24 weeks' gestation
measure: Miscarriage
timeFrame: at 24 weeks of gestation after the completion of the first transfer
measure: Live birth
timeFrame: At 24 weeks of gestation
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: My Duc Hospital
Study officials:
affiliation: Hope Research Center
name: Tuong M Ho, MD, MCE
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanchez F, Le AH, Ho VNA, Romero S, Van Ranst H, De Vos M, Gilchrist RB, Ho TM, Vuong LN, Smitz J. Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles. J Assist Reprod Genet. 2019 Oct;36(10):2135-2144. doi: 10.1007/s10815-019-01551-5. Epub 2019 Aug 9.
citation: Vuong LN, Le AH, Ho VNA, Pham TD, Sanchez F, Romero S, De Vos M, Ho TM, Gilchrist RB, Smitz J. Live births after oocyte in vitro maturation with a prematuration step in women with polycystic ovary syndrome. J Assist Reprod Genet. 2020 Feb;37(2):347-357. doi: 10.1007/s10815-019-01677-6. Epub 2020 Jan 4.
citation: Sanchez F, Romero S, De Vos M, Verheyen G, Smitz J. Human cumulus-enclosed germinal vesicle oocytes from early antral follicles reveal heterogeneous cellular and molecular features associated with in vitro maturation capacity. Hum Reprod. 2015 Jun;30(6):1396-409. doi: 10.1093/humrep/dev083. Epub 2015 Apr 22.
citation: Saenz-de-Juano MD, Ivanova E, Billooye K, Herta AC, Smitz J, Kelsey G, Anckaert E. Genome-wide assessment of DNA methylation in mouse oocytes reveals effects associated with in vitro growth, superovulation, and sexual maturity. Clin Epigenetics. 2019 Dec 19;11(1):197. doi: 10.1186/s13148-019-0794-y.
citation: Sanchez F, Lolicato F, Romero S, De Vos M, Van Ranst H, Verheyen G, Anckaert E, Smitz JEJ. An improved IVM method for cumulus-oocyte complexes from small follicles in polycystic ovary syndrome patients enhances oocyte competence and embryo yield. Hum Reprod. 2017 Oct 1;32(10):2056-2068. doi: 10.1093/humrep/dex262.