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. 2022 Feb 7;2022(2):hoac003. doi: 10.1093/hropen/hoac003

Table II.

An overview of study design and outcomes of AOA protocols utilizing A23187, CultActive and protocols supplemented with GM-CSF.

Endpoint type Study type Fertilized oocytes (Total) Experimental group (Population) Control group Primary findings References
Efficacy

  • Prospective

  • (A23187)

  • In vitro matured

  • (333)

  • No fertility history

  • (26 women)

 Standard ICSI

  • Improved fertilization rate.

  • Cleavage score and embryo quality remained unchanged.

 Nazarian et al. (2019)
Efficacy

  • Prospective

  • (A23187)

  • In vitro matured

  • (40)

  • History of globozoospermia

  • (5 women)

 None Treatment successfully produced live births for males with globozoospermia. Shang et al. (2018)
Safety

  • Retrospective

  • (A23187)

  • In vivo matured

  • (Undisclosed)

  • History of ICSI failure or low fertilization rate without oocyte abnormality

  • (678 pregnancies)

 Standard ICSI

  • No increase in:

  •  - Foetal defects including structural or chromosomal malformations)

  •  - Unhealthy newborns

  •  - First and second trimester abortions

  •  - Intrauterine foetal death

  •  - Ectopic/chemical pregnancies

  •  - Gestational age

  •  - Birth weight

  •  - Newborn gender

 Miller et al. (2016)
Safety

  • Prospective

  • (A23187)

  • In vitro matured, vitrified

  • (49)

  • Endometriosis, male factor, tubal, or idiopathic aetiologies of infertility

  • (12 women)

 IVF

  • No increase in number of chromosome segregation errors in meiosis II.

  • Evidence suggested affected second polar body extrusion.

 Capalbo et al. (2016)
Safety and Efficacy

  • Retrospective, Case-control

  • (A23187)

  • In vivo matured

  • (>180)

  • History of ICSI failure or low fertilization rate

  • (45 women)

 Standard ICSI from previous cycles

  • Improved fertilization rates

  • No change in:

  •  - Cleavage rates

  •  - Number of live births.

  •  - Abortion rates

  •  - Congenital anomalies

 Sdrigotti et al. (2015)
Safety

  • Retrospective

  • (A23187)

  • In vivo matured or unfertilized, aged oocytes post-ICSI

  • (79)

  • History of total or near total ICSI failure

  • (3 women)

 None

  • All AOA-born children presented normal:

  •  - Physical and mental development

  •  - Normal chromosome ploidy

  • No increase in genetic variations or chromosomal alterations

 Lu et al. (2014)
Safety and Efficacy

  • Unblinded Clinical Trial

  • (A23187)

  • In vivo matured

  • (313)

  • Teratozoospermia

  • (31 women)

 Standard ICSI

  • No change in rates of:

  •  - Implantation

  •  - Fertilization

  •  - Pregnancy rates

  •  - Multiple pregnancies

  •  - Spontaneous abortion

 Eftekhar et al. (2013)
Safety and Efficacy

  • Retrospective

  • (A23187)

  • In vivo matured

  • (2360)

  • History of ICSI failure or low fertilization rate

  • (185 women)

 Standard ICSI from previous cycles

  • Improved fertilization and implantation rates

  • No congenital birth defects observed.

 Yoon et al. (2013)
Safety and Efficacy

  • Retrospective

  • (A23187)

  • In vivo matured

  • (1476)

  • History of ICSI failure or low fertilization rate.

  • (89 women)

 Standard ICSI from previous cycles

  • Improved rates of:

  •  - Fertilization,

  •  - Implantation and pregnancy

  • No change in:

  •  - Abortion rates

  •  - Birth weight

  •  - Malformation rates

 Montag et al. (2012)
Safety and Efficacy

  • Prospective

  • (A23187 with GM-CSF)

  • Aged, unfertilized oocytes post-ICSI

  • (18 assessing safety,

  • 140 assessing efficacy)

  • No fertility history

  • (66 couples)

 Standard ICSI

  • Standard AOA resulted in chromosomal abnormalities in all embryos

  • Supplementation with GM-CSF improved rates of:

  •  - Activation

  •  - Cleavage

  •  - High quality embryos

  •  - Embryo development

  •  - Blastulation

  • 62.5% GM-CSF supplemented embryos were chromosomally normal.

 Economou et al. (2017)
Safety and Efficacy

  • Prospective, Retrospective, Multi-Center

  • (CultActive)

  • In vitro matured

  • (138)

  • Low oocyte count, OAT, or frozen sperm

  • (1837 women)

 Standard ICSI Improved fertilization and pregnancy rates, and comparable embryogenesis. Karabulut et al. (2018)
Safety and Efficacy

  • Prospective, Single Blind

  • (CultActive)

  • In vivo matured, then fertilized by IMSI

  • (49)

  • History of low fertilization and teratozoospermia

  • (12 women)

 Standard ICSI and split by sibling oocytes No improvement in fertilization rates and impeded embryogenesis quality. Aydinuraz et al. (2016)
Efficacy

  • Prospective

  • (CultActive)

  • In vivo matured

  • (77)

  • History of ICSI failure. Fresh or frozen sperm obtained via testicular sperm extraction

  • (4 women)

 Standard ICSI from previous cycles

  • Successful:

  •  - Pronuclei production and fusion

  •  - Cleaved blastomeric stage transition

  •  - Progressive embryogenesis

 Darwish and Magdi (2015)
Safety and Efficacy

  • Prospective, Multi-Center

  • (CultActive)

  • In vivo matured

  • (2071)

  • History of ICSI failure

  • (101 women)

 Standard ICSI from previous cycles

  • Improved rates of:

  •  - Fertilization

  •  - Implantation

  •  - Pregnancy

  • No change in:

  •  - Embryo quality

  •  - Rates of malformation.

 Ebner et al. (2015)
Safety and Efficacy

  • Prospective, Multi-Center

  • (CultActive)

  • In vivo matured

  • (1370)

  • History of ICSI failure or low fertilization rate

  • (66 women)

 Standard ICSI from previous cycles

  • Improved rates of:

  •  - Fertilization

  •  - Implantation

  •  - Pregnancy

  • No change in:

  •  - Embryo quality

  •  - Rates of malformation.

 Ebner et al. (2012)

AOA, artificial oocyte activation; GM-CSF, granulocyte-macrophage colony stimulating factor; IMSI, intra-cytoplasmic morphologically selected sperm injections; OAT, oligoasthenoteratozoospermia.