Effect of GM-CSF on CAPA-IVM System Success Rates in PCOS

NCT04774432 | Unknown DMC

• 1 other identifier: 01/21/DD-BVMD
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

In-vitro maturation (IVM) of human oocytes obtained from minimally stimulated or unstimulated ovaries offers a more "patient friendly" treatment option than the conventional Assisted Reproductive Technology (ART) treatment with controlled ovarian hyperstimulation (COH). However, maturation rate and the total blastocyst yield in oocytes undergoing in vitro maturation are still limited. This pilot study aims to evaluate the addition of an important growth factor known as Granulocyte macrophage colony stimulating factor (GM-CSF). The investigators hypothesize that the addition of GM-CSF to human IVM culture media will increase pregnancy rates to comparable levels to that of IVF, making it a viable clinical option for couples undergoing assisted reproductive treatment.

Conditions

IVF; PCOS; IVM

Keywords

GM-CSF; CAPA-IVM

Outcome Measures

Primary Outcomes (1)

• Blastulation rate

  Percentage of blastocyst by 2 types of IVM culture with or without GM-CSF

  At least seven days after oocyte pick up

Secondary Outcomes (6)

• Embryology data (maturation rate, fertilization rate, grade 1 and grade 2 blastocyst rate)

  Maturation rate: 2 days after OPU, Fertilization rate: 3 days after OPU, grade 1 and 2 blastocyst: at least 7 days after OPU

• Ongoing Pregnancy Rate after the first transfer of the started treatment cycle.

  At 12 weeks' gestation

• Cumulative ongoing pregnancy rate at 6 months after randomization

  At 12 weeks' gestation at 6 months after randomization. After 6 months, most patients doing IVM have finished all their frozen embryos; therefore, we consider this time point for analyzing the cumulative ongoing pregnancy rate.

• Adverse events (OHSS rate, miscarriage rate, ectopic rate)

  OHSS rate: at 03 days after oocytes pick-up and 14 days after embryo transfer, Miscarriage rate: Before 22 weeks of gestational age, ectopic rate: At 5-7 weeks of gestation

• The relative expression ratio ( R ) of human cumulus cell genes

  cumulus cells will be collected after at least 30 hours of maturation culture, storaged at -80oC until RNA purification

Study Arms (2)

GM-CSF group

ACTIVE COMPARATOR

Patients will be randomly allocated to intervention group with GM-CSF added to CAPA and maturation medium. Following the 24h CAPA period, the evaluation of maturation (MII, GVBD, GV) will be done after 30 hrs IVM step. Mature eggs are fertilized using Intracytoplasmic sperm injection (ICSI). Fertilized oocytes will be placed in a time-lapse incubator (ASTEC) and their development until the Day 5/6 (blastocyst formation) will be followed.

Other: GM-CSF group

Control group

ACTIVE COMPARATOR

Patients will be randomly allocated to control group without the addition of GM-CSF to CAPA and maturation medium. Following the 24h CAPA period, the evaluation of maturation (MII, GVBD, GV) will be done after 30 hrs IVM step. Mature eggs are fertilized using Intracytoplasmic sperm injection (ICSI). Fertilized oocytes will be placed in a time-lapse incubator (ASTEC) and their development until the Day 5/6 (blastocyst formation) will be followed.

Other: Control group

Interventions

GM-CSF group OTHER

GM-CSF added to CAPA and maturation medium

GM-CSF group

Control group OTHER

GM-CSF will not be added to CAPA and maturation medium

Control group

Eligibility Criteria

• Age: 18 Years - 36 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed as PCOS using Rotterdam criteria (AFC=25 or the ovarian volume \>10ml)
• Agree to participate in the study

You may not qualify if:

• No major uterine or ovarian abnormalities
• Endometriosis grade 2 or upper
• Severe OAT (concentration \<1 million/ml, motility \<10%), surgical sperm

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (1)

My Duc Hospital

Ho Chi Minh City, Vietnam

RECRUITING

Related Publications (6)

• Guzman L, Ortega-Hrepich C, Albuz FK, Verheyen G, Devroey P, Smitz J, De Vos M. Developmental capacity of in vitro-matured human oocytes retrieved from polycystic ovary syndrome ovaries containing no follicles larger than 6 mm. Fertil Steril. 2012 Aug;98(2):503-7.e1-2. doi: 10.1016/j.fertnstert.2012.01.114. Epub 2012 Feb 23.

  PMID: 22365339 BACKGROUND

• Guzman L, Adriaenssens T, Ortega-Hrepich C, Albuz FK, Mateizel I, Devroey P, De Vos M, Smitz J. Human antral follicles <6 mm: a comparison between in vivo maturation and in vitro maturation in non-hCG primed cycles using cumulus cell gene expression. Mol Hum Reprod. 2013 Jan;19(1):7-16. doi: 10.1093/molehr/gas038. Epub 2012 Sep 6.

  PMID: 22956770 BACKGROUND

• Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006 Jan-Feb;12(1):13-21. doi: 10.1093/humupd/dmi036. Epub 2005 Aug 25.

  PMID: 16123051 BACKGROUND

• 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.

  PMID: 28938744 BACKGROUND

• Ho VNA, Braam SC, Pham TD, Mol BW, Vuong LN. The effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilization in women with a high antral follicle count. Hum Reprod. 2019 Jun 4;34(6):1055-1064. doi: 10.1093/humrep/dez060.

  PMID: 31111879 BACKGROUND

• Ziebe S, Loft A, Povlsen BB, Erb K, Agerholm I, Aasted M, Gabrielsen A, Hnida C, Zobel DP, Munding B, Bendz SH, Robertson SA. A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization. Fertil Steril. 2013 May;99(6):1600-9. doi: 10.1016/j.fertnstert.2012.12.043. Epub 2013 Feb 4.

  PMID: 23380186 BACKGROUND

MeSH Terms

Interventions

Control Groups

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Tuong M Ho, MD

  Hope Research Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lan N Vuong, PhD

CONTACT

+84903008889; drlan@yahoo.com.vn

Dang Q Vinh, MD

CONTACT

+84908225481; BSVINH.DQ@MYDUCHOSPITAL.VN

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 1, 2021
• Study Start: March 10, 2021
• Primary Completion: March 2, 2022
• Study Completion: December 31, 2022
• Last Updated: July 16, 2021

Record last verified: 2021-07

Locations

VN (1)