IVF Reads / IVF Add-Ons: What the Randomized Trials Actually Found

IVF Add-Ons: What the Randomized Trials Actually Found

Geeta
Written by GeetaPublished Updated
AI summary

The UK Human Fertilisation and Embryology Authority (HFEA), whose add-on ratings were last reviewed in September 2026, rates no common IVF add-on green for improving the chance of having a baby. It rates PGT-A, endometrial receptivity testing, steroids and IVIG red, and time-lapse imaging and PICSI black (no effect). Hyaluronan transfer medium (embryo glue) is the exception with moderate-quality evidence of benefit: the 2020 Cochrane review found it probably increases live birth (RR 1.21, 95% CI 1.10 to 1.31) but also multiple pregnancy (RR 1.45).

  • HFEA (2026): PGT-A rated red for the chance of a baby for most patients, green for reducing miscarriage, grey for older women.
  • PGT-A trial (NEJM 2021, 1,212 women aged 20-37 with three or more good blastocysts): cumulative live birth 77.2% with PGT-A versus 81.8% without.
  • Endometrial receptivity testing (JAMA 2022, 767 patients): live birth 58.5% versus 61.9% per transfer with standard timing; HFEA rates it red.
  • Embryo glue (Cochrane 2020, 10 trials, 4,066 participants): live birth RR 1.21; multiple pregnancy RR 1.45; ESHRE 2023 recommends it, HFEA rates it amber.
  • Time-lapse imaging (TILT, Lancet 2024, 1,575 patients): live birth 33.7% versus 33.0% with standard care; HFEA rates it black.
  • ESHRE 2023 does not recommend NK-cell or blood immune testing, or immune treatments such as intralipid and IVIG, for IVF patients without an immune disease.

Are IVF add-ons worth paying for?

For most people, mostly not. The UK fertility regulator, the HFEA, rates none of the common add-ons green for improving the chance of having a baby, and it rates several — PGT-A, endometrial receptivity testing, steroids and IVIG — red, meaning they may lower your chances or carry safety concerns.

The one add-on with moderate-quality evidence of a real, if small, benefit is hyaluronan transfer medium, often sold as embryo glue — and it raises the chance of twins when more than one embryo is transferred. The HFEA's own advice to people paying for treatment is to consider whether the money would do more as another cycle of proven treatment than as extras on one cycle.

After a failed cycle, "anything that might help" is a hard offer to turn down. That is exactly why it is worth knowing what each extra has actually been shown to do before you pay for it.

Add-ons rated green by the HFEA for the chance of a baby0Across the ten add-ons on this page. Red (may reduce effectiveness or safety concerns): PGT-A, endometrial receptivity testing, steroids, IVIG. Black (no effect): time-lapse imaging, PICSI. Amber (conflicting evidence): endometrial scratching, embryo glue. Grey (too little good evidence): assisted hatching, IMSI, intralipids, treatments after sperm DNA fragmentation testing.HFEA, Treatment add-ons with limited evidence, last reviewed 28 September 2026, and each add-on's own page

How do the traffic-light ratings work?

The HFEA's Scientific and Clinical Advances Advisory Committee rates each add-on on the published evidence, and reviews a rating when new evidence appears or at least every five years. Five colours are used:

  • Green — high-quality evidence that it works.
  • Amber — conflicting moderate or high-quality evidence; some trials positive, some not.
  • Grey — not enough moderate or high-quality evidence to rate it.
  • Black — moderate or high-quality evidence that it makes no difference.
  • Red — safety concerns, or evidence that it may reduce the chance of success.

A UK rating is useful in India because the trials behind it are international and the biology is the same. We have not found an Indian body that grades add-ons this way. What Indian law does do is require every clinic to tell you the advantages, disadvantages, cost, side effects and risks of each procedure, including the risk of multiple pregnancy (ART Act 2021, section 21(c)) — so you are entitled to ask for this in writing.

Which add-ons may lower your chances?

PGT-A (embryo chromosome screening). Rated red for the chance of a baby for most patients, because it often leaves fewer embryos to transfer and can lengthen the time to a birth. In the largest trial, 1,212 women aged 20 to 37 with at least three good blastocysts had a cumulative live birth rate of 77.2% with PGT-A against 81.8% without it. ASRM's 2024 committee opinion says its value as a routine screening test "has not been demonstrated". More on this in our PGT-A article and on the PGT-A treatment page.

Two caveats keep this honest. The HFEA rates PGT-A green for reducing miscarriage — in that trial pregnancy loss was 8.7% against 12.6% — but notes that fewer miscarriages need not mean more babies; ASRM calls the miscarriage benefit unclear. And for older women the HFEA rating is grey: there is not enough good evidence either way. In India, section 25 of the ART Act also says pre-implantation genetic testing "shall be used to screen the human embryo for known, pre-existing, heritable or genetic diseases only" — ask any clinic offering PGT-A how it applies that in your case.

Endometrial receptivity testing (ERA). Rated red. A double-blind trial of 767 patients transferring a single tested embryo found live birth in 58.5% of transfers timed by the test against 61.9% with standard timing. It also needs a womb-lining biopsy and a freeze-all cycle. ESHRE's 2023 recommendations: the available tests are not recommended.

Steroids and IVIG for the immune system. Both rated red because of safety concerns, and ESHRE does not recommend them. The HFEA notes that blood NK-cell tests measure cells in the blood, not the womb, and "offer no useful information" about pregnancy. This does not apply to anyone with a diagnosed immune disease, whose treatment should continue under their own specialist.

Which have been tested and made no difference?

Time-lapse imaging. Rated black. The TILT trial randomised 1,575 patients: live birth was 33.7% with time-lapse imaging and 33.0% with standard care. It appears to be safe; it is simply not shown to add babies. Details in our review of TILT.

PICSI (hyaluronan-selected sperm). Rated black for couples having ICSI for male-factor infertility. In a trial of 2,752 couples, term live birth was 27.4% with PICSI and 25.2% with ICSI (odds ratio 1.12, 95% CI 0.95 to 1.34). A 2026 Cochrane review found it probably reduces miscarriage; the HFEA rates that benefit grey — too little evidence — for women over 35.

Where is the evidence genuinely mixed?

Embryo glue (hyaluronan-enriched transfer medium). The add-on most often dismissed alongside the others, and the one that does not belong with them. The 2020 Cochrane review pooled 10 trials of 4,066 participants and found it probably increases live birth (RR 1.21, 95% CI 1.10 to 1.31; moderate-quality evidence): if 33 in 100 would have a baby without it, between 37 and 44 would with it. ESHRE 2023 recommends it, while noting the effect was seen after fresh transfers and not frozen ones. The HFEA rates it amber.

The catch is twins. The same review found multiple pregnancy rose too (RR 1.45, 1.24 to 1.70), probably because many trials transferred more than one embryo. ESHRE's advice is to pair it with single-embryo transfer.

Endometrial scratching. Rated amber for IVF and ICSI, and grey for recurrent implantation failure. The largest trial, 1,364 women, found live birth of 26.1% in both groups. ESHRE does not recommend it routinely; it can be painful and carries a small infection risk. See our review of that trial.

Where is there too little good evidence to say?

Grey does not mean harmless or useless. It means nobody can yet say, which is different from the confidence with which these are usually offered.

  • Assisted hatching, including laser hatching. Cochrane 2021: live birth OR 1.09 (0.92 to 1.29) across 14 trials, low-quality evidence, with a possible rise in multiple pregnancy. ESHRE does not recommend it. See the laser-assisted hatching page.
  • IMSI (high-magnification sperm selection). Cochrane 2020: live birth RR 1.11 (0.89 to 1.39) across 929 couples, very low-quality evidence. ESHRE: not for routine use.
  • Intralipids. Two trials of 244 patients gave an uncertain result; ESHRE does not recommend them and lists serious reported side effects.
  • Sperm DNA fragmentation testing. ESHRE does not recommend routine testing. The HFEA notes there is no agreed method or cut-off, and rates the treatments that usually follow a high result — antioxidants, sperm sorting — grey, and switching to testicular sperm red. More in our DNA fragmentation article.
For most patients, having routine cycles of proven fertility treatment are effective without using any treatment add-ons.— HFEA, Treatment add-ons with limited evidence (2026)

What should you do if you are offered one?

Ask, in writing, before you agree. The ART Act already obliges the clinic to explain advantages, disadvantages, cost and risks, so these are not awkward questions:

  1. Why is this recommended for me specifically, and what is the HFEA rating for it?
  2. What did the largest randomised trial find for live birth — not pregnancy tests or implantation?
  3. What does it cost, and is it itemised separately on my quote?
  4. What would change if I declined it?

Then weigh the money. An ICMR study of 148 couples at five tertiary hospitals found an average out-of-pocket spend of ₹2,30,668 per IVF cycle in private hospitals and ₹1,10,104 in public ones, with drugs the largest share. Add-ons sit on top of that. The HFEA and other UK bodies agreed in October 2023 that unproven treatments should be offered only within research, without an extra charge.

Sometimes the honest answer is that nothing extra is needed — or that the question is about testing, timing or a simpler treatment rather than more technology. Our guides to IVF costs in India and choosing a clinic cover the rest of the quote.

A disclosure: IVF Pulse runs fertility clinics in Bangalore and publishes treatment pages for PGT-A and assisted hatching. The ratings and trial results above apply to those as much as to anyone else's.

Been handed a list of add-ons?

Bring the quote. We will set out the HFEA rating and the trial result for each item, so you can decide what to keep.

Keep reading

15 References

  1. Human Fertilisation and Embryology Authority. Treatment add-ons with limited evidence (published 16 October 2023, last reviewed 28 September 2026), with the individual add-on pages for PGT-A, endometrial receptivity testing, endometrial scratching, hyaluronate-enriched transfer medium, immunological tests and treatments, IMSI, PICSI, assisted hatching, time-lapse imaging and sperm DNA fragmentation. Source of every traffic-light rating, the safety notes and the 'multiple cycles' advice. HFEA
  2. HFEA. Pre-implantation genetic testing for aneuploidy (PGT-A): red for chance of a baby, green for reducing miscarriage, grey for older women; mosaic results; safety. HFEA
  3. ESHRE Add-ons working group. Good practice recommendations on add-ons in reproductive medicine. Hum Reprod 2023;38(11):2062-2104. PMID 37747409. Source of the recommend / not recommended verdicts, including 'Hyaluronic acid addition to transfer media is recommended', the intralipid figures and the acupuncture verdict. Human Reproduction (ESHRE)
  4. Heymann D, Vidal L, Or Y, Shoham Z. Hyaluronic acid in embryo transfer media for assisted reproductive technologies. Cochrane Database Syst Rev 2020;9:CD007421. PMID 32876946. Supersedes the 2014 version. Live birth RR 1.21 (1.10-1.31), multiple pregnancy RR 1.45 (1.24-1.70). Cochrane Database of Systematic Reviews
  5. Practice Committees of ASRM and SART. The use of preimplantation genetic testing for aneuploidy: a committee opinion. Fertil Steril 2024;122(3):421-434. PMID 38762806. American Society for Reproductive Medicine
  6. Yan J, et al. Live birth with or without preimplantation genetic testing for aneuploidy. N Engl J Med 2021;385:2047-2058. PMID 34818479. 1,212 women aged 20-37; cumulative live birth 77.2% vs 81.8%; pregnancy loss 8.7% vs 12.6%. New England Journal of Medicine
  7. Doyle N, et al. Effect of timing by endometrial receptivity testing vs standard timing of frozen embryo transfer on live birth. JAMA 2022;328(21):2117-2125. PMID 36472596. 767 patients; live birth 58.5% vs 61.9% per transfer. JAMA
  8. Lensen S, et al. A randomized trial of endometrial scratching before in vitro fertilization. N Engl J Med 2019;380:325-334. PMID 30673547. 1,364 women; live birth 26.1% in both groups. New England Journal of Medicine
  9. Bhide P, et al. Time-lapse imaging systems for embryo incubation and selection in IVF (TILT). Lancet 2024;404:256-265. PMID 39033010. 1,575 patients; live birth 33.7% vs 33.0%. The Lancet
  10. Miller D, et al. Physiological, hyaluronan-selected intracytoplasmic sperm injection for infertility treatment (HABSelect). Lancet 2019;393:416-422. PMID 30712901. 2,752 couples; term live birth 27.4% vs 25.2%, OR 1.12 (0.95-1.34). The Lancet
  11. Advanced sperm selection techniques for assisted reproduction. Cochrane Database Syst Rev 2026;6:CD010461. PMID 42227305. HA-ICSI probably slightly decreases miscarriage (RR 0.59, moderate certainty). Cochrane Database of Systematic Reviews
  12. Lacey L, et al. Assisted hatching on assisted conception (IVF and ICSI). Cochrane Database Syst Rev 2021;3:CD001894. PMID 33730422. Live birth OR 1.09 (0.92-1.29), 14 RCTs, low quality. Cochrane Database of Systematic Reviews
  13. Teixeira DM, et al. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Cochrane Database Syst Rev 2020;2:CD010167. PMID 32083321. Live birth RR 1.11 (0.89-1.39), 929 couples, very low quality. Cochrane Database of Systematic Reviews
  14. The Assisted Reproductive Technology (Regulation) Act, 2021 (No. 42 of 2021), Gazette of India. Section 21(c) duty to counsel on chances of success, advantages, disadvantages, cost and risks including multiple pregnancy; section 25 limits on pre-implantation genetic testing. Government of India
  15. Patil P, et al. Out-of-pocket expenditure experienced by couples seeking IVF services at tertiary care facilities in India. PLoS One 2026;21(7):e0351080. PMID 42455781 (ICMR-NIRRCH). 148 couples; mean ₹2,30,668 private, ₹1,10,104 public per cycle; drugs 55% of spend. PLoS One (ICMR-NIRRCH)

Frequently asked questions

Five questions the sections above do not answer.

What does a 'mosaic' PGT-A result mean?

It means the biopsy found a mix of cells with the normal and an abnormal number of chromosomes. The HFEA says mosaic embryos may have a lower chance of pregnancy, but healthy live births after transferring them have been reported, and clinics differ in how they report and whether they transfer them. Ask what your clinic's policy is before testing, because it decides whether some embryos are discarded.

Is laser assisted hatching different from assisted hatching?

Only in the tool. The HFEA's rating covers hatching done with acid, a laser or other instruments, and it is grey for all of them. ESHRE's 2023 recommendations do not recommend assisted hatching by any method, and the 2021 Cochrane review found it may slightly raise the twin rate.

Do add-ons help after repeated failed transfers?

The evidence is thinner here, not stronger. The HFEA rates endometrial scratching grey specifically for recurrent implantation failure, PGT-A grey for older women, and ESHRE does not recommend immune testing or immune treatments for these patients. A review of why transfers failed usually tells you more than an extra procedure.

If an add-on does not work, is it at least harmless?

Not always. The HFEA lists real costs beyond money: PGT-A can lead to viable embryos being discarded, receptivity testing needs a biopsy and a freeze-all cycle, steroids and IVIG carry serious side-effect risks, and embryo glue and assisted hatching may raise the twin rate. Time-lapse imaging has no known extra risk.

Can a clinic charge for an add-on that is still being researched?

The UK consensus statement of 19 October 2023, agreed between the HFEA and professional and patient bodies, says treatments without strong evidence of safety or effectiveness should only be offered in a research setting, and patients should not be charged extra to take part. That statement binds UK clinics, not Indian ones, but it is a fair standard to hold any clinic to.