IMSI, PICSI & MACS in IVF: Sperm Selection Evidence Review

Key Takeaways

Large trials and Cochrane reviews show that IMSI, PICSI, and MACS do not raise live-birth rates over standard ICSI. A 2026 Cochrane update finds that PICSI probably lowers miscarriage a little. ESHRE and the UK HFEA advise against routine use. AUA/ASRM also advises against routine sperm DNA testing at a first visit.

Key evidence: ESHRE Good Practice Recommendations on Add-ons in ART (2023) · The HABSelect RCT: PICSI vs Conventional ICSI (Lancet 2019) · HFEA Treatment Add-ons: PICSI Traffic-Light Review

Sperm Selection Techniques Explained by Dr. Senai Aksoy

This video was recorded in French. English and Arabic subtitles are available in the YouTube player settings.

When you plan IVF, clinic price lists often list extra lab steps such as IMSI, PICSI, and MACS. Each step aims to help the lab pick a better sperm before ICSI (intracytoplasmic sperm injection).

What matters most to couples is whether a step leads to a baby at home. In research, a clinical pregnancy means a pregnancy seen on an ultrasound scan, while a live birth means having a living baby. Under ESHRE’s 2023 add-on guidance, none of these three methods has reliably raised live-birth rates over standard ICSI.

How IMSI, PICSI, and MACS differ from standard ICSI

In standard ICSI, a lab specialist checks moving sperm under an inverted microscope at 200× to 400× zoom. One moving sperm with a normal shape is drawn into a fine glass needle and placed into the egg.

IMSI, PICSI, and MACS add a sorting step in the dish before injection, each using a different filter.

• IMSI (intracytoplasmic morphologically selected sperm injection). Uses digital lenses at 6,000× to 10,000× to inspect the sperm head in real time. The aim is to skip sperm with tiny fluid spaces (vacuoles) linked to DNA packing faults.
• PICSI (physiological intracytoplasmic sperm injection). Places sperm on a dish coated with hyaluronic acid, a natural gel found around the egg. Mature sperm tend to stick to this layer and have shown less DNA damage in some lab tests.
• MACS (magnetic-activated cell sorting). Passes the sample past tiny magnetic beads coated with Annexin V protein. The beads hold back sperm showing early signs of cell death (apoptosis), leaving the rest for ICSI.

Sorting sperm in a dish makes sense on paper. Even so, a cleaner lab sample does not mean more babies born.

The clinical evidence: what the trials show

To test if an add-on helps couples, researchers use randomised trials (where couples enter each group by chance). They also use systematic reviews and meta-analyses, which pool results from several trials.

1. IMSI: high magnification, unchanged birth rates

Checking sperm at 10,000× zoom sounds appealing. Yet a 2020 Cochrane review on IMSI across 13 randomised trials (2,775 couples) found no clear rise in live births over standard ICSI, with very low-certainty proof overall.

ESHRE’s 2023 add-ons group notes that hunting for vacuole-free sperm takes extra time at the bench. That extra time has not been shown to harm embryos, nor has it raised birth rates.

2. PICSI: no live-birth gain, probably slightly fewer miscarriages

The largest test of PICSI is the UK HABSelect trial (Miller et al., The Lancet 2019), which enrolled 2,772 couples at 16 UK clinics. Full-term live birth was 27.4% with PICSI and 25.2% with standard ICSI. That small gap was not statistically significant (meaning chance alone could explain it).

As a secondary result, miscarriage per assigned couple was lower with PICSI (4.3% vs 7.0%). The June 2026 Cochrane update on sperm selection (Garg et al.) pooled two trials. It concluded that PICSI probably lowers miscarriage slightly (moderate certainty), while live births showed no clear gain (low certainty). Because HABSelect was built to test live birth rather than miscarriage, the lower miscarriage rate is a secondary finding, and live births did not rise.

3. MACS: thin trial data and large clinic records

Randomised trial data for MACS are thin. The results summary of the 2026 Cochrane update (five trials, 3,752 women) reports no MACS-versus-ICSI comparison. The update also removed four earlier studies over concerns about data trustworthiness.

A team at IVIRMA Spain also ran a retrospective cohort study—meaning it looked back at past clinic records—covering 48,586 own-egg ICSI cycles (Gil Juliá et al., 2021). Pregnancy and live-birth rates per transfer did not differ between MACS and standard prep. A small statistical rise appeared only in cumulative live-birth models per egg or embryo used, which the authors judged to have limited clinical impact.

Guidelines, regulation, and safety

Because extra lab steps add bench work and raise IVF treatment costs without proven birth gains, major medical bodies urge caution.

• ESHRE (2023). Its good practice guidance on add-ons advises against routine use of IMSI, PICSI, or MACS.
• UK HFEA ratings. The British regulator rates PICSI as “black” for the chance of having a baby with ICSI in male-factor infertility (moderate or high quality evidence shows no effect), and “grey” for lowering miscarriage in women over 35. It rates IMSI as “grey” (not enough data to rate effectiveness).
• AUA/ASRM (2024). The male infertility guideline advises against routine sperm DNA testing at a couple’s first check-up. When couples face recurrent pregnancy loss, however, it recommends male chromosome (karyotype) testing and sperm DNA analysis.

Safety and birth-defect data

All three methods sort sperm in the dish before injection rather than changing the egg or embryo. Published studies show no clear rise in birth defects (congenital anomalies), though long-term follow-up stays limited.

In 2023, ESHRE noted a lack of dedicated safety studies for IMSI and MACS. The UK HFEA reports no extra known risks for IMSI beyond the baseline risks of standard ICSI.

Situations where a doctor may discuss these options

Certain test results or past cycle setbacks sometimes bring these lab steps up in clinic. In each case, treating root causes comes before changing dishes.

Persistently high sperm DNA fragmentation

Sperm DNA tests use varied lab methods and cut-offs, so one high number needs context. Doctors first check for fixable causes like varicocele, smoking, heat, recent fever or infection, and medicines. Our guides on improving sperm quality and varicocele repair vs IVF/ICSI cover these steps. If DNA damage stays high on repeat tests after treatable causes are fixed, a doctor may discuss PICSI or MACS. Neither option, however, has shown proven gains in embryo quality or live births for this group.

Unexplained recurrent pregnancy loss

After repeated losses, doctors check womb, hormone, clotting, and parent chromosome factors alongside sperm DNA (AUA/ASRM 2024). Some teams discuss PICSI because HABSelect and the 2026 Cochrane update saw fewer miscarriages. They note it is not an established treatment for recurrent loss.

Severe sperm-head defects after failed ICSI fertilisation

A 0% normal shape score on a semen test is very different from having zero sperm—a condition covered in our guide to azoospermia and micro-TESE. When severe head defects follow unexplained fertilisation failure in a past ICSI cycle despite mature eggs, some teams discuss IMSI.

Dr. Aksoy’s clinical perspective

Dr. Aksoy’s Approach: Evidence-Based Selection vs Add-on Hype

“I never prescribe IMSI, PICSI, or MACS as routine treatment packages. An elevated DNA fragmentation result, recurrent pregnancy loss, or severe teratozoospermia is not an automatic green light for laboratory add-ons.

My first priority is always to determine whether sperm DNA damage is truly persistently elevated and to treat the underlying root causes: clinical varicoceles, smoking, scrotal heat exposure, medications, subclinical infections, and lifestyle factors. In recurrent miscarriage, we must equally investigate maternal, uterine, and chromosomal factors before focusing solely on the sperm dish.

In carefully selected couples, I may discuss PICSI as an option, while explaining that its effect on miscarriage remains uncertain and its live-birth benefit is unproven. MACS is reserved for very narrow research or registry protocols. IMSI is considered only when severe teratozoospermia is accompanied by prior unexplained fertilization failure in standard ICSI—never solely because morphology is 0%.

To patients asking to try every possible add-on, my advice is clear: a failed cycle does not mean we missed a secret laboratory trick. Stacking multiple weak-evidence add-ons multiplies costs and clouds our clinical judgment. We discuss each tool’s evidence, costs, and the valid option of performing standard, high-quality ICSI without add-ons—and we only make a change when it is medically justified.”

— Dr. Senai Aksoy

Frequently Asked Questions for Dr. Aksoy

PICSI or standard ICSI? Does PICSI really make a difference with sperm DNA damage or previous failed attempts?

In standard ICSI, the embryologist selects a suitable sperm under the microscope and injects it into the egg. In PICSI, we use the sperm’s ability to bind to hyaluronic acid. This property may help us select sperm that are more mature and carry less DNA damage, but it does not guarantee that the sperm’s DNA is healthy.

Large studies have not shown PICSI to meaningfully increase the chance of a live birth compared with standard ICSI. There are, however, data suggesting it may reduce the risk of miscarriage to some extent.

I may consider PICSI in particular when sperm DNA fragmentation is high or when a couple has experienced recurrent pregnancy loss. Even then, I first examine the possible causes of the DNA damage and the results of previous treatments. I do not consider it necessary to switch to PICSI simply because one IVF attempt has failed. It can be considered in selected patients, though even in these groups a definite live-birth advantage has not been proven.

When sperm morphology is 0%, does IMSI give better results than standard ICSI?

A 0% normal morphology result on a semen analysis worries patients a great deal. However, this result does not mean there are no usable sperm, or that pregnancy will necessarily be impossible. Sperm shape assessment is based on specific criteria, and results can vary between laboratories.

With IMSI, we examine sperm at much higher magnification than in standard ICSI, allowing us to see subtle differences, particularly in head structure. Seeing in greater detail, however, does not necessarily mean we are selecting healthier sperm or that we will achieve more healthy babies.

Studies in men with severe morphology abnormalities have not reliably shown that IMSI increases live-birth rates compared with standard ICSI.

In a patient with this result, I first evaluate the sperm count, motility, and the specific type of morphology abnormality. In particular, if the same structural defect appears across all sperm, that requires separate investigation. I do not regard IMSI as superior to standard ICSI simply because morphology is 0%.

Is it worth paying an extra laboratory fee for IMSI, PICSI, or MACS?

When my patients ask whether one of these methods will give them a higher chance of pregnancy, I first want to understand what we are trying to correct. IMSI examines sperm at high magnification, PICSI selects sperm able to bind to hyaluronic acid, and MACS tries to separate out sperm carrying certain cell-death markers. In other words, the three do not do the same job.

However, these methods have not been shown to increase the chance of a live birth for every patient compared with standard ICSI. While there is some evidence that PICSI may reduce miscarriage risk, the results for IMSI and MACS are more uncertain.

My decision is shaped by the details of the semen analysis, DNA fragmentation results if available, how fertilisation and embryo development went in any previous cycles, and the laboratory’s experience.

I do not consider it necessary to pay high fees for add-on procedures that do not target a specific problem and are recommended solely because they are more advanced technology. We can discuss these methods in selected situations, but we cannot tell in advance with certainty how much a patient will benefit from them.

Sources

• Teixeira DM, Hadyme Miyague A, Barbosa MA, Navarro PA, Raine-Fenning N, Nastri CO, Martins WP. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Cochrane Database Syst Rev 2020;2(2):CD010167. doi:10.1002/14651858.CD010167.pub3.
• Miller D, Pavitt S, Sharma V, et al. Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect): a parallel, two-group, randomised trial. The Lancet 2019;393(10170):416–422. PMID: 30712901.
• Garg A, Nakhla O, Steeper M, Afroz A, Lepine S, McDowell SJ, Kroon B, Glujovsky D, Yazdani A, Lensen S. Advanced sperm selection techniques for assisted reproduction (2026 update). Cochrane Database Syst Rev 2026;6(6):CD010461. doi:10.1002/14651858.CD010461.pub4.
• Lepine S, McDowell S, Searle LM, Kroon B, Glujovsky D, Yazdani A. Advanced sperm selection techniques for assisted reproduction (2019 version). Cochrane Database Syst Rev 2019;7(7):CD010461. doi:10.1002/14651858.CD010461.pub3.
• Gil Juliá M, Hervás I, Navarro-Gómez Lechón A, Quintana F, Amorós D, Pacheco A, et al. Sperm selection by magnetic-activated cell sorting before microinjection of autologous oocytes increases cumulative live birth rates with limited clinical impact: a retrospective study in unselected males. Biology (Basel) 2021;10(5):430. PMID: 34066115; doi:10.3390/biology10050430.
• ESHRE Add-ons Working Group; Lundin K, Bentzen JG, Bozdag G, et al. Good practice recommendations on add-ons in reproductive medicine. Hum Reprod 2023;38(11):2062–2104. PMID: 37747409; doi:10.1093/humrep/dead184.
• Human Fertilisation and Embryology Authority (HFEA). Physiological intracytoplasmic sperm injection (PICSI) treatment add-on rating. Accessed 2 November 2026.
• Human Fertilisation and Embryology Authority (HFEA). Intracytoplasmic morphologically selected sperm injection (IMSI) treatment add-on rating. Accessed 2 November 2026.
• Brannigan RE, Hermanson L, Kaczmarek J, Kim SK, Kirkby E, Tanrikut C. Updates to male infertility: AUA/ASRM guideline (2024). J Urol 2024;212(6):789–799. doi:10.1097/JU.0000000000004180.

Dr. Senai Aksoy

Dr. Senai Aksoy studied and trained in France before returning to Turkey, where he was a member of the ICSI team at Sevgi Hospital, Ankara — the country's first ICSI centre (1994-95) — and a co-author on the first Turkish ICSI publications produced in collaboration with the Brussels Van Steirteghem group (Human Reproduction, 1996; PMID 8671323). He helped build the IVF programme at the American Hospital Istanbul and has been running his own fertility practice since 1998.

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The content has been created by Dr. Senai Aksoy and medically approved.