1. Definition and principle
2. Indications
3. Prerequisites and work-up
4. Procedure steps
5. Outcomes and complications
6. Counselling, ethics, and legal issues
7. ICSI versus conventional IVF

1. Definition and principle
2. Indications
3. Prerequisites and work-up
4. Procedure steps
5. Outcomes and complications
6. Counselling, ethics, and legal issues
7. ICSI versus conventional IVF

Intracytoplasmic Sperm Injection (ICSI)

Definition

Principle

Indications

A. Male-factor indications

1. Severe oligozoospermia
2. Severe asthenozoospermia
3. Severe teratozoospermia, particularly with associated poor count or motility
4. Azoospermia with surgically retrieved sperm:
   • Epididymal sperm aspiration
   • Testicular sperm aspiration/extraction
5. Obstructive azoospermia, including congenital bilateral absence of vas deferens
6. Ejaculatory dysfunction or failure to obtain ejaculated sperm
7. Presence of antisperm antibodies in selected cases
8. Use of cryopreserved sperm when count or quality is very poor

B. Non-male-factor indications

1. Previous total or near-total fertilization failure with conventional IVF
2. Few oocytes available, where failed fertilization would be particularly consequential
3. Oocytes being fertilized before preimplantation genetic testing
4. Selected fertility-preservation cycles

Procedure

1. Controlled ovarian stimulation with gonadotropins.
2. Monitoring by ultrasound and hormonal assessment.
3. Trigger for final oocyte maturation followed by transvaginal ultrasound-guided oocyte retrieval.
4. Semen collection or surgical sperm retrieval and laboratory preparation.
5. Denudation of oocytes by removal of cumulus and corona cells to assess maturity.
6. Selection of a mature metaphase-II oocyte, recognized by a first polar body.
7. Immobilization and aspiration of one morphologically suitable sperm into an injection micropipette.
8. Holding pipette stabilizes the oocyte. The injection pipette is passed through zona pellucida and oolemma, and sperm is deposited in the ooplasm.
9. Fertilization check after about 16-18 hours, looking for two pronuclei.
10. Embryo culture followed by fresh or frozen embryo transfer; surplus suitable embryos may be cryopreserved.

Advantages

• Effective treatment for severe male-factor infertility.
• Permits fertilization with epididymal or testicular sperm.
• Reduces dependence on sperm number and motility.
• Enables use of sperm in obstructive azoospermia and some non-obstructive azoospermia cases.
• Facilitates IVF with preimplantation genetic testing where sperm contamination must be minimized.

Limitations

• Does not correct the underlying infertility.
• Fertilization may still fail despite injection.
• Pregnancy and live-birth outcomes are strongly influenced by female age and oocyte quality, not merely by the injection procedure.
• More expensive and technically demanding than conventional IVF.
• Unnecessary use in non-male-factor infertility may add cost without improving outcomes.

Complications and risks

1. Oocyte damage or degeneration during denudation or injection. Reported degeneration rates are about 5%-19%.
2. Usual IVF-related risks:
   • Ovarian hyperstimulation syndrome
   • Complications of oocyte retrieval, such as bleeding, infection, or injury
   • Multiple pregnancy if more than one embryo is transferred
   • Ectopic pregnancy
3. Genetic risks:
   • ICSI may transmit the underlying paternal cause of infertility.
   • Y-chromosome microdeletions may be inherited by male offspring.
   • Men with severe oligozoospermia or azoospermia have increased prevalence of chromosomal abnormalities.
   • Slightly higher frequency of sex-chromosome abnormalities or translocations has been reported, although this may arise from paternal gamete defects rather than ICSI itself.
4. Possible association with imprinting disorders has been reported, but absolute risk is low and causality is difficult to establish.

Pre-ICSI counselling and evaluation

• Complete infertility evaluation of both partners.
• Semen analysis, preferably repeated when abnormal.
• Counsel that ICSI success is closely linked to maternal age and ovarian reserve.
• In severe oligozoospermia or azoospermia, consider:
  • Karyotyping
  • Y-chromosome microdeletion testing
  • CFTR mutation assessment in congenital bilateral absence of vas deferens
• Genetic counselling is particularly important in Y-chromosome microdeletions, chromosomal rearrangements, CFTR-related disease, and congenital absence of vas deferens.
  Emery's Elements of Medical Genetics and Genomics, p. 719.

ICSI versus conventional IVF

Conclusion