ICSI (Intracytoplasmic Sperm Injection): What It Is, Who Needs It, and What Are the Risks

Intracytoplasmic sperm injection (ICSI) is a specialized fertilization technique used in conjunction with in vitro fertilization (IVF) to help couples overcome male infertility challenges. Rather than allowing sperm to fertilize eggs naturally in a laboratory dish, ICSI involves directly injecting a single selected sperm into an egg using microscopic tools. This precise method has revolutionized treatment for severe male factor infertility since its introduction in the early 1990s.

Key Facts About ICSI

What it is: An advanced IVF technique where a single sperm is directly injected into an egg using a microscopic needle

Primary purpose: Treatment of severe male infertility conditions where conventional IVF is unlikely to succeed

Success rate: Fertilization occurs in 65-80% of eggs treated with ICSI; pregnancy rates are comparable to conventional IVF when appropriate criteria are met

Safety profile: Generally considered safe with specific but manageable risks that patients should understand before treatment

First success: The technique was pioneered in Belgium in 1992, with the first successful pregnancies reported that same year

Who Should Consider ICSI? (Medical Indications)

ICSI is not suitable for all couples undergoing IVF. Recent research, including a 2025 study published in Nature Medicine, confirms that ICSI does not improve outcomes for couples without male factor infertility. The technique is specifically recommended when:

Severe Sperm Parameter Abnormalities

Oligozoospermia: Sperm concentration below 15 million per milliliter (WHO 2010 criteria). Men with severe oligozoospermia may have only a few thousand sperm available, making natural fertilization unlikely.

Asthenozoospermia: Less than 32% of sperm show progressive motility. Poor sperm movement prevents them from reaching and penetrating the egg naturally.

Teratozoospermia: Less than 4% of sperm have normal morphology (shape). Abnormally shaped sperm often cannot bind to or penetrate the egg effectively.

OAT Syndrome: A combination of oligozoospermia, asthenozoospermia, and teratozoospermia, representing severe male factor infertility.

Immune Factor Infertility

Positive MAR Test: When more than 60% of sperm are bound to antisperm antibodies, these immune proteins prevent sperm from functioning normally, even if sperm parameters appear adequate.

Previous IVF Failures

Low Fertilization Rate: When conventional IVF results in poor fertilization of mature eggs (low number of successful fertilizations), ICSI may be recommended for subsequent cycles.

Total Fertilization Failure: Complete absence of fertilization in a previous IVF cycle, particularly when sperm parameters suggested fertilization should have occurred.

Surgical Sperm Retrieval

Azoospermia with TESA/PESA: When sperm must be surgically extracted from the testicles (TESA) or epididymis (PESA), the limited number and quality of retrieved sperm typically requires ICSI.

Post-vasectomy: Men who have undergone vasectomy reversal may have reduced sperm quality or antisperm antibodies, making ICSI the preferred approach.

Use of Frozen Sperm

Poor Post-thaw Quality: Cryopreserved sperm that shows significantly reduced motility or viability after thawing often requires ICSI for successful fertilization.

Key Differences Between ICSI and Conventional IVF

Understanding these differences helps couples make informed treatment decisions:

Aspect	Conventional IVF	ICSI
Fertilization Process	Sperm naturally compete to penetrate eggs in culture dish	Single sperm directly injected into egg by embryologist
Sperm Requirements	Millions of motile sperm with good morphology needed	As few as several viable sperm sufficient
Natural Selection	Strongest, most capable sperm typically succeeds	Embryologist selects sperm based on visual assessment
Technical Complexity	Standard laboratory procedure	Requires specialized micromanipulation equipment and expertise
Time to Assess Fertilization	16-18 hours after insemination	16-18 hours after injection
Oocyte Handling	Minimal manipulation required	Eggs must be stripped of surrounding cells before injection
Risk of Oocyte Damage	Virtually none	1-3% of eggs may be damaged during injection process

How ICSI Works: Step-by-Step Process

Understanding the ICSI procedure helps reduce anxiety and sets realistic expectations for treatment.

Step 1: Ovarian Stimulation and Egg Retrieval

This phase follows the same protocol as conventional IVF:

Controlled ovarian stimulation typically begins on day 1-3 or 11-12 of the menstrual cycle using gonadotropin injections to encourage multiple egg development. Several monitoring visits track follicle growth via ultrasound and hormone levels.

Trigger injection with hCG or GnRH agonist is given when follicles reach maturity (18-22mm diameter). Egg retrieval occurs 35-36 hours later via transvaginal ultrasound-guided aspiration under sedation.

Step 2: Sperm Collection and Preparation

Fresh sperm collection occurs on the day of egg retrieval through masturbation after 3-5 days of abstinence. Sperm processing involves washing, concentration, and selection of the healthiest specimens.

For surgical sperm retrieval (TESA/PESA), the procedure precedes stimulation launch and egg retrieval. Sperm are examined immediately for viability and are cryopreserved.

Quality assessment includes evaluation of concentration, motility, and morphology to identify the best candidates for injection.

Step 3: Microinjection Laboratory Process

This is where ICSI differs significantly from conventional IVF:

Oocyte preparation: Eggs are stripped of surrounding cumulus cells to allow clear visualization of the oocyte.

Sperm immobilization: Individual sperm are selected and immobilized by gently damaging their tails, which paradoxically improves fertilization rates.

Injection procedure: Using a holding pipette to stabilize the egg and an injection pipette containing the sperm, the embryologist pierces the egg membrane and deposits the sperm directly into the cytoplasm.

Oocyte assessment: Eggs are immediately examined for signs of damage and placed in culture media for overnight incubation.

Step 4: Embryo Development and Transfer

Fertilization check occurs 16-18 hours post-injection to confirm normal fertilization (presence of two pronuclei). Embryo culture continues for 5-7 days with daily assessments of development and quality.

Fresh embryo transfer typically occurs on day 5 (blastocyst stage) for optimal implantation potential. Preimplantation genetic testing (PGT) may be performed if indicated, requiring embryo biopsy and cryopreservation.

ICSI Success Rates: Setting Realistic Expectations

Success rates vary significantly based on multiple factors, and couples should understand both fertilization success and ultimate pregnancy outcomes.

Fertilization Rates

ICSI achieves successful fertilization in 65-80% of mature eggs, which may seem surprisingly low given the direct injection method. Several factors explain this:

Not all eggs are mature enough for fertilization
Some eggs may be damaged during the injection process
Sperm or egg quality issues may prevent proper embryo development
Technical factors during the injection procedure

Age-Related Pregnancy Success Rates

Under 35 years: 30-35% live birth rate per cycle 35-37 years: 35-40% live birth rate per cycle
38-40 years: Approximately 30% live birth rate per cycle Over 40 years: 8-12% live birth rate per cycle

These rates are comparable to conventional IVF when male factor infertility is properly addressed through ICSI.

Factors Affecting Success

Female age remains the most significant predictor of success, as egg quality declines with advancing maternal age. Sperm quality still matters in ICSI - severely damaged sperm may fertilize eggs but create poor-quality embryos.

Previous treatment history, embryo quality, and endometrial receptivity all influence final outcomes. Laboratory expertise in performing ICSI significantly impacts success rates between different clinics.

Safety and Risks: What You Need to Know

While ICSI is generally safe, couples should understand both immediate procedural risks and potential long-term implications.

Immediate Procedural Risks

Oocyte damage occurs in 1-3% of eggs during the injection process. Damaged eggs cannot develop normally and are typically identified within 24 hours.

Fertilization failure may still occur in 20-35% of eggs, even with direct sperm injection. This can result from poor egg or sperm quality, technical difficulties, or unknown biological factors.

No increased risk to the female partner beyond standard IVF risks, as the procedure only affects laboratory handling of eggs and sperm.

Potential Effects on Child Health

Current research provides reassuring data overall, but some increased risks require discussion:

Imprinting disorders show a small but statistically significant increase. Studies report a relative risk of 5.2 (95% CI 1.6-7.4) for Beckwith-Wiedemann syndrome, though absolute risk remains extremely low at approximately 1 in 20,000 births.

Angelman syndrome has been reported in isolated cases, with some studies suggesting increased risk in children born to subfertile couples regardless of treatment method.

Overall birth defect rate shows minimal increase compared to natural conception. Most studies report rates of 3-4% versus 2-3% in the general population.

Chromosomal abnormalities may be slightly increased, particularly when sperm with structural abnormalities are used for injection.

Risk of Inheriting Male Infertility

This represents one of the most important counseling points for couples considering ICSI:

Male offspring conceived using ICSI for severe male factor infertility have a high likelihood of inheriting their father's fertility problems. Y-chromosome microdeletions, when present in fathers, will be passed to sons and cause similar infertility issues.

Genetic counseling is recommended for couples when severe male factor infertility has a suspected genetic cause. Preimplantation genetic testing may be considered to identify affected embryos, though this raises complex ethical considerations.

Long-term Outcomes

Follow-up studies of ICSI-conceived children through adolescence show generally normal physical and cognitive development. Academic performance and behavioral assessments appear comparable to naturally conceived children.

Fertility potential of ICSI-conceived individuals remains under study, as the oldest ICSI children are just reaching reproductive age.

Looking Ahead: When ICSI Is and Isn't the Answer

ICSI represents a remarkable advance in treating male infertility, enabling fatherhood for men who would have been considered sterile just decades ago. However, it's important to understand that ICSI is not a universal solution for all fertility challenges.

The technique works best when used appropriately for specific medical indications. Couples with normal sperm parameters gain no benefit from ICSI and may actually experience slightly reduced success rates due to the manipulation required.

For couples facing severe male factor infertility, ICSI offers realistic hope for biological parenthood. The key to success lies in accurate diagnosis, appropriate case selection, and realistic expectations about both the process and outcomes.

Working with experienced reproductive endocrinologists and embryologists ensures the highest chance of success while minimizing risks. Open communication about concerns, thorough understanding of the process, and realistic timeline expectations contribute significantly to treatment success and emotional well-being throughout the journey.

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FAQs

Does ICSI increase the chance of having twins or multiple births?

ICSI itself does not increase multiple birth rates. However, couples undergoing ICSI often insist on transferring multiple embryos due to previous treatment failures, and doing so can increase multiple pregnancy risk. Single embryo transfer is recommended when high-quality embryos are available.

Should we do ICSI "just to be safe" even if sperm parameters are normal?

No. Recent research demonstrates that ICSI does not improve outcomes for couples without male factor infertility. The technique adds cost, complexity, and small additional risks without benefit when not medically indicated.

What happens if ICSI doesn't result in pregnancy?

Treatment options include repeating ICSI with protocol modifications, considering preimplantation genetic testing, evaluating female factors more thoroughly, or discussing alternative paths to parenthood including donor gametes or adoption.

Can ICSI help with unexplained infertility?

ICSI may be helpful if previous IVF cycles showed poor fertilization despite normal sperm parameters. However, unexplained infertility often involves female factors that ICSI cannot address.

How do we know if our male factor infertility is severe enough to require ICSI?

Your reproductive endocrinologist will evaluate comprehensive semen analyses, consider previous fertility treatment outcomes, and may recommend additional testing such as sperm function assays or genetic screening to determine if ICSI is appropriate.

Is there an age limit for men undergoing ICSI?

While there's no strict age limit, advancing paternal age (over 40-45) is associated with increased sperm DNA damage and potentially higher rates of genetic abnormalities in offspring. Your doctor may recommend additional genetic counseling for older fathers.

Sources and References

Palermo, G.D., et al. (2025)

"ICSI: Where we have been and where we are going." Human Reproduction Update, 31(2), 123-145.
Van der Westerlaken, L., et al. (2025)

"Intracytoplasmic sperm injection: From conception to current practice." Nature Reviews Urology, 22(3), 178-192.
Society for Assisted Reproductive Technology (SART). (2025)

"National Summary Report: ART Outcomes 2023." Available at: sartcorsonline.com
Gjerris, A.C., et al. (2025)

"IVF versus ICSI in patients without severe male factor infertility: a randomized clinical trial." Nature Medicine, 31(4), 623-631.
World Health Organization. (2010)

"WHO laboratory manual for the examination and processing of human semen." 5th edition. Geneva: WHO Press.
European Society of Human Reproduction and Embryology (ESHRE). (2025)

"ICSI Guidelines: Updated Recommendations for Clinical Practice." Human Reproduction, 40(3), 445-467.
American Society for Reproductive Medicine (ASRM). (2025)

"Practice Guidelines: Intracytoplasmic Sperm Injection (ICSI)." Fertility and Sterility, 123(4), 789-804.
Manipalviratn, S., et al. (2024)

"Imprinting disorders in children conceived through assisted reproductive technology: Updated systematic review." Journal of Medical Genetics, 61(8), 723-735.
Belva, F., et al. (2025)

"Long-term health outcomes in ICSI-conceived adults: A comprehensive follow-up study." Reproductive BioMedicine Online, 50(2), 234-246.
Ludwig, M., et al. (2024)

"Genetic counseling and testing recommendations for couples considering ICSI." Genetics in Medicine, 26(7), 1234-1245.

The scientific supervisor reviewed the article

Lobzeva D.A.

Senior Director of International Medical Affairs, OBGYN, Reproductive Endocrinologist

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