Clinical trial NCT06087354: Low vs. Air Oxygen Concentration CAPA-IVM Culture of Cumulus-oocyte Complexes
Official title: Effect of Low Versus Air Oxygen Concentration in In-vitro Maturation With Biphasic Capacitation-IVM (CAPA-IVM) Culture of Human Cumulus-oocyte Complexes in PCOS Patients: a Sibling Oocyte Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: IVM
PCOS (Polycystic Ovary Syndrome)
Keywords: Low oxygen
CAPA-IVM
Cumulus-oocyte complexes
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
First posted: 2023-10-17
Enrollment: 20
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has demonstrated enhanced maturation of human oocytes in vitro and successful live births. However, CAPA-IVM has shown lower rates of embryo formation when compared to conventional in vitro fertilization/ intra cytoplasmic sperm injection (IVF/ICSI) cycles. To optimize the CAPA-IVM culture system, this pilot study aims to evaluate the impact of low oxygen versus air oxygen concentrations on embryological outcomes in PCOS patients.

Detailed description: Oocyte in vitro maturation (IVM) is an alternative approach to assisted reproductive technology (ART) that has the advantage of minimal stimulation, resulting in reduced hormone-related side effects and risks, especially in women with polycystic ovary syndrome (PCOS). Oocytes retrieved for IVM procedures are derived from a diverse pool of follicles with an average diameter of between 2 and 10mm and are characterized by variable cellular and molecular attributes that indicate their immature status. Therefore, the development of an IVM culture system that could enable and enhance the acquisition and synchronization of meiotic and developmental competence prior to the meiotic resumption is essential for optimizing human IVM protocols.

IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM), has been shown to improve the competence of human oocytes matured in vitro and result in live births. The pre-maturation culture of CAPA-IVM utilizes C-type natriuretic peptide (CNP), and maturation takes place in the presence of amphiregulin (AREG), both of which are physiological compounds that have been shown to prevent spontaneous meiotic resumption of oocytes (CNP) and enhance oocyte competence (AREG) during IVM.

To date, the results of pilot studies have shown that CAPA-IVM increases the rates of oocyte maturation, good-quality embryos on day 3 and good-quality blastocysts, resulting in a result, a higher embryo yield was obtained compared with standard IVM. Additionally, the reported cumulative live birth rate after use of CAPA-IVM, and its non-inferiority to the cumulative live birth rate with standard in vitro fertilization highlight the clinical utility and potential of this approach. Improvements in the culture system could make CAPA-IVM more effective, but these need to be investigated.

The oxygen concentration during the IVM process plays a crucial role in oocyte maturation. The use of oxygen concentrations higher than physiological levels can lead to cell damage and affect embryo development. Recent studies in mice have suggested using lower oxygen concentrations to improve IVM outcomes. However, the effectiveness of using lower oxygen concentrations in human IVM remains unproven. Therefore, this pilot study aims to compare the effectiveness of lower oxygen concentration conditions versus air oxygen in CAPA-IVM on embryology outcomes in PCOS women.

Eligibility criteria: Inclusion Criteria:

* ≤38 years
* Having polycystic ovarian morphology: at least 25 follicles (2-9 mm) throughout the whole ovary and/or increased ovarian volume (\>10ml)
* Having at least 20 follicles on the Oocyte Pick-up day
* Patients consent to culture embryos to the blastocyst

Exclusion Criteria:

* Cases with severe male factor (concentration \<5 million/ml, cryptozoospermia, azoospermia)
* Oocyte donation
* Pre-implantation genetic testing

Primary outcomes:
measure: Number of blastocyst
timeFrame: At least 5 days after intra-cytoplasmic sperm injection
Secondary outcomes:
measure: Number of matured oocytes
timeFrame: Two days after oocytes pick-up
measure: Number of normal fertilized oocytes
timeFrame: 16-18 hours after intra-cytoplasmic sperm injection
measure: Number of day-3 embryos
timeFrame: At least 3 days after intra-cytoplasmic sperm injection
measure: Number of good-quality day-3 embryos
timeFrame: At least 3 days after intra-cytoplasmic sperm injection
measure: Number of good-quality blastocyst
timeFrame: At least 5 days after intra-cytoplasmic sperm injection
measure: Number of vitrified blastocyst
timeFrame: At least 5 days after intra-cytoplasmic sperm injection
measure: Positive pregnancy test
timeFrame: At 2 weeks after the completion of the first frozen embryo 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: Miscarriage
timeFrame: at 12 weeks of gestation after the completion of the first transfer
Other outcomes:
Locations:
city: Ho Chi Minh City
country: Vietnam
facility: My Duc Hospital
Study officials:
affiliation: Mỹ Đức Hospital
name: Tuong M Ho
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, Ho VNA, Ho TM, Dang VQ, Phung TH, Giang NH, Le AH, Pham TD, Wang R, Smitz J, Gilchrist RB, Norman RJ, Mol BW. In-vitro maturation of oocytes versus conventional IVF in women with infertility and a high antral follicle count: a randomized non-inferiority controlled trial. Hum Reprod. 2020 Nov 1;35(11):2537-2547. doi: 10.1093/humrep/deaa240.
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: Preis KA, Seidel GE Jr, Gardner DK. Reduced oxygen concentration improves the developmental competence of mouse oocytes following in vitro maturation. Mol Reprod Dev. 2007 Jul;74(7):893-903. doi: 10.1002/mrd.20655.
citation: Akin N, Ates G, von Mengden L, Herta AC, Meriggioli C, Billooye K, Stocker WA, Ghesquiere B, Harrison CA, Cools W, Klamt F, Massie A, Smitz J, Anckaert E. Effects of lactate, super-GDF9, and low oxygen tension during bi-phasic in vitro maturation on the bioenergetic profiles of mouse cumulus-oocyte complexdagger. Biol Reprod. 2023 Oct 13;109(4):432-449. doi: 10.1093/biolre/ioad085.