SIFES-MR issues guidance on 28 IVF add-ons

The Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) has issued new guidelines on 28 IVF add-ons, outlining which may help in certain situations, which lack evidence, and which should be limited to research.

IVF add-ons are extra tests, procedures or treatments offered alongside standard IVF, often for an additional cost. Many add-ons are widely used but lack strong evidence.

The Italian Society of Fertility and Sterility and Reproductive Medicine (SIFES-MR) has now published guidance on 28 IVF add-ons (Cimadomo et al. 2025). To develop these recommendations, they brought together a panel of doctors, embryologists and researchers from across Italy, working in both public and private clinics. Over two years, the panel met six times, reviewed the latest studies up to 2024, including randomized trials and meta-analyses, and compared existing recommendations from other major groups, including:

The European Society of Human Reproduction and Embryology (ESHRE)
The Human Fertilisation and Embryology Authority (HFEA)
The Indian Society for Assisted Reproduction (ISAR)
and the American Society for Reproductive Medicine (ASRM)

The panel used a formal consensus process to agree on 28 statements, which were reviewed and approved by the society’s executive committee and members. Each add-on was assessed for its effectiveness, safety and cost.

I’ve grouped their positions on these add-ons into three categories below: Supported or considered for use, Not supported for use, or Insufficient evidence/Research only.

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🔗 Original studies are referenced in this post or within the linked Remembryo posts.

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Table of Contents

IVF add-ons supported or considered for select patient groups

Based on the available evidence and guidance from other professional organizations, SIFES-MR either supports or considers the following add-ons appropriate for certain patients or situations.

Karyotype analysis

A blood test that looks at the number and structure of chromosomes to detect large genetic abnormalities that may cause infertility, miscarriage, or failed IVF.
SIFES-MR consensus: Support for men with severe oligozoospermia (very low sperm count) or non-obstructive azoospermia, and consider for RPL or cases with multiple failed cycles; not recommended for all IVF patients.
ESHRE/HFEA/ISAR/ASRM consensus: No specific recommendation for universal use.

Expanded carrier screening

A genetic test before pregnancy that checks both partners for hundreds of inherited conditions to identify couples at risk of having a child with a disorder.
SIFES-MR consensus: Support offering to IVF couples after appropriate counseling; additional cost may be justified.
ESHRE/HFEA/ISAR/ASRM consensus: No unified recommendation; generally not detailed in current guidelines.

Hysteroscopy

A procedure using a thin camera through the cervix to look for and sometimes treat uterine abnormalities like fibroids, polyps, or scar tissue. It’s routine use for all IVF patients is debated, as it is a surgical method with additional risks and costs.
SIFES-MR consensus: Support when transvaginal ultrasound suggests abnormalities; optional after multiple failed transfers; not recommended for all patients before IVF.
ESHRE/ISAR consensus: More data is needed; HFEA: No stance; ASRM: Support.

Embryo glue (hyaluronic acid) in embryo transfer medium

Special embryo transfer fluid containing hyaluronic acid, a substance that can help embryos stick to the uterine lining.
SIFES-MR consensus: Support for patients with multiple implantation failure; stronger data needed for routine use; monitor for multiple pregnancy risk.
ESHRE consensus: Support; HFEA: Unclear due to conflicting evidence; ISAR: May be useful in multiple failures; ASRM: No stance.

Corticosteroids

Medications that reduce immune activity and inflammation, sometimes used before embryo transfer to improve outcomes.
SIFES-MR consensus: Support only for patients with autoimmune disorders or other clear medical needs; not recommended as a general IVF add-on.
ESHRE/HFEA/ASRM consensus: Not recommended for routine IVF; ISAR: No clear stance.

Rescue in vitro maturation (rescue IVM)

Maturing immature eggs in the lab after retrieval, potentially useful when urgent treatment (like cancer therapy) prevents full stimulation.
SIFES-MR consensus: Support for emergency fertility preservation in cancer patients; not recommended for routine use. More research needed, especially in poor prognosis patients without many mature eggs.
ESHRE consensus: Acknowledge limited evidence and safety data. HFEA/ISAR/ASRM: No clear stance.

PGT-A

Tests embryos for abnormal chromosome structure or numbers to avoid transferring those that are unlikely to result in a healthy birth.
SIFES-MR consensus: Support for advanced maternal age (≥35) or RPL; mosaic results should not be treated as aneuploid.
ESHRE/HFEA consensus: Do not recommend routine use; HFEA: Acknowledge reduced miscarriage risk; ISAR: No stance; ASRM: Case-by-case; support in AMA with good ovarian reserve.

ICSI for non-severe male factor infertility

A laboratory technique where a single sperm is injected directly into an egg for insemination, mainly used for poor sperm quality or certain lab procedures, but often used routinely in cases of non-male factor infertility.
SIFES-MR consensus: Support when required for PGT, IVM, frozen eggs, or after previous low fertilization; not supported for routine use without severe male factor infertility.
ESHRE/HFEA consensus: Not supported for routine use in couples without severe male factor infertility; ISAR: No clear stance; ASRM: Selective use only.

Chronic endometritis testing/treatment

Chronic endometritis is an inflammation of the uterine lining, usually caused by bacteria, that is more common in women with unexplained infertility or repeated implantation failures, and may improve live birth rates if treated.
SIFES-MR consensus: May be investigated in patients with multiple failed transfers; not supported routinely.
ESHRE consensus: Can be considered for patients with multiple failed transfers. HFEA/ISAR/ASRM: No stance.

IVF add-ons not supported for use

SIFES-MR doesn’t support the following add-ons based on available evidence.

Intracytoplasmic morphologically selected sperm injection (IMSI)

Technique involving the selection of sperm at very high magnification before ICSI.
SIFES-MR consensus: Not supported; contradictory results.
ESHRE/HFEA/ISAR/ASRM consensus: Evidence inconclusive; not recommended.

Endometrial scratch

Intentionally injuring the uterine lining before transfer to try to improve implantation, possibly mediated by promoting inflammation.
SIFES-MR consensus: Not supported.
ESHRE consensus: Not supported; HFEA: Doubtful; ISAR/ASRM: No stance.

Endometrial receptivity (ERA) testing

A test done before transfer where an endometrial biopsy is used to predict the window for optimal embryo transfer timing, based on gene expression.
SIFES-MR consensus: Not supported; no proven benefit.
ESHRE/HFEA consensus: Not supported; ISAR/ASRM: No stance.

Time-lapse technology

The use of time-lapse imaging (ie. embryo scope) to track embryo development and select embryos based on developmental timing patterns.
SIFES-MR consensus: While beneficial for IVF lab operations, it’s not supported for improving patient outcomes.
ESHRE consensus: Advise against to improve outcomes; HFEA: No clinical benefit; ISAR: More evidence needed; ASRM: No stance.

Mitochondrial DNA measurement (mitoscore)

Measuring mtDNA in embryos to choose the “healthiest” ones for transfer, based on the idea that embryos with higher metabolism (and higher number of mitochondria) may have lower potential.
SIFES-MR consensus: Not supported; no proven benefit.
ESHRE consensus: Not supported; HFEA/ISAR/ASRM: No stance.

Assisted hatching

A procedure where a hole or thinning is applies to the outer shell (zona) of the embryo before transfer, thought to improve the embryo’s ability to hatch.
SIFES-MR consensus: Not supported unless part of PGT-A workflow.
ESHRE/ASRM consensus: Not supported; HFEA/ISAR: More data needed.

IVF add-ons with insufficient evidence and for research use only

SIFES-MR believes these add-ons do not have enough evidence to support or reject their use and that more research is needed.

Physiological ICSI (PICSI)

Choosing sperm that bind to hyaluronic acid, thought to indicate good quality, before ICSI.
SIFES-MR consensus: Not supported; evidence too limited.
ESHRE consensus: Not supported; HFEA/ISAR: No clear stance; ASRM: Insufficient evidence.

Growth hormone, DHEA or testosterone for ovarian stimulation

Hormonal supplements that can be added before ovarian stimulation that aim to improve egg yield or quality.
SIFES-MR consensus: More studies needed before GH and DHEA can be supported. Testosterone may be considered in patients with diminished ovarian reserve (Poseidon 3–4).
ESHRE/HFEA/ISAR consensus: Not recommended routinely; ASRM: No stance.

Platelet-rich plasma (PRP) or stem cells for ovarian stimulation

Techniques involving the injection of PRP or stem cells into ovaries to “rejuvenate” function and improve egg quality and quantity.
SIFES-MR consensus: While some research is promising, more studies are needed and should be done in research settings. Several RCTs are ongoing and results should be published soon.
ESHRE consensus: Not supported (lack of RCTs). HFEA/ISAR/ASRM: No stance.

Magnetic activated cell sorting (MACS) / microfluidics sperm selection (ie. zymot)

Lab methods to select higher quality sperm, especially those with lower sperm DNA fragmentation damage.
SIFES-MR consensus: Possible role in cases of RPL or high DNA fragmentation, but limited data means these techniques should be reserved for research only.
ESHRE/HFEA/ISAR/ASRM consensus: No stance.

Artificial oocyte activation (AOA)

A technique that uses a chemical (calcium ionophore) to trigger egg activation after sperm injection. Thought to improve fertilization in patients with low/no fertilization.
SIFES-MR consensus: Some research is promising for patients with total fertilization failure, but there are safety concerns and not enough data to be recommended.
ESHRE/ASRM consensus: Insufficient evidence; HFEA/ISAR: No clear stance.

Rescue ICSI

Rescue ICSI is where ICSI is performed a day after conventional IVF when no eggs have fertilized.
SIFES-MR consensus: More research needed for patients with fertilization failure.
ASRM consensus: May result in births but with low success, but more data is needed. ESHRE/HFEA/ISAR: No stance.

Supplementing culture media with GM-CSF

Embryo culture media is supplemented with GM-CSF, a growth factor, to potentially improve embryo development.
SIFES-MR consensus: More research needed.
ESHRE consensus: Not supported; ISAR: Insufficient evidence; ASRM/HFEA: No stance.

Undisturbed culture in time-lapse incubators

Culturing embryos in a time-lapse incubator without removing them for checks can help minimize changes in temperature, pH, etc., which may be beneficial for the embryo.
SIFES-MR consensus: More research needed.
ESHRE/ASRM consensus: No stance; ISAR: Not supported.

Non-invasive PGT-A (niPGT)

Embryos can release DNA into their culture media, and this spent culture media can be evaluated by PGT, instead of using a biopsy.
SIFES-MR consensus: More research is needed as results don’t show high concordance with biopsy-based PGT-A; shouldn’t be used to discard embryos if aneuploid.
ESHRE consensus: Advise against clinical use; HFEA/ISAR/ASRM: No stance.

Microbiome analysis and treatment

Involves testing for bacteria in the vagina or uterus, treating harmful species with antibiotics, and then supplementing with Lactobacillus probiotics to potentially improve IVF outcomes.
SIFES-MR consensus: Research only; no standard protocols or proven benefit (study results aren’t consistent).
ESHRE consensus: Not supported; HFEA/ISAR/ASRM: No stance.

Immunological tests and therapies

Immunological testing in reproductive medicine examines factors like natural killer (NK) cells, KIR/HLA genetics, and cytokine profiles, but these measures are highly variable, difficult to interpret, and lack proven links to effective treatments.
SIFES-MR consensus: Current evidence does not support routine immune blood tests, uterine NK cell assessments, or KIR/HLA typing in IVF, though a fetal HLA-C2 and maternal KIR AA mismatch in women with repeated implantation failure may warrant further study.
ESHRE consensus: Not recommended; HFEA/ASRM: Insufficient evidence; ISAR: No stance.

Intrauterine platelet-rich plasma (PRP)

Involves injecting PRP into the uterus to improve lining or implantation before embryo transfer.
SIFES-MR consensus: May help in repeated implantation failure or thin endometrium, but stronger evidence is needed with safety data.
ESHRE consensus: Not recommended. HFEA/ISAR/ASRM: No stance.

Intrauterine hCG

involves injecting hCG into the uterus before embryo transfer.
SIFES-MR consensus: Efficacy and safety data are lacking.
ESHRE consensus: Not recommended. HFEA/ISAR/ASRM: No stance.

Granulocyte colony-stimulating factor (G-CSF)

A growth factor given by intrauterine or subcutaneous injection before embryo transfer to improve outcomes.
SIFES-MR consensus: Efficacy and safety data are lacking
ESHRE/ASRM consensus: Not recommended; HFEA/ISAR: No stance.

Conclusion

The SIFES-MR panel reviewed the evidence for 28 IVF add-ons and reached a strong consensus on each one. Some may help in certain situations or for specific patients, but many do not have enough reliable evidence to support routine use. The panel is especially concerned about add-ons that may carry safety risks or are promoted without clear proof of benefit.

The authors write that better research, cost studies and collaboration between clinics, researchers and technology providers are needed. Recommendations should be updated as new evidence becomes available so that only safe and proven add-ons become part of standard IVF care.

If you’d like to read ESHRE’s recent guidance on IVF add-ons, check out the following post:

Evidence-based recommendations from ESHRE for 27 IVF add-ons

Researchers in a 2023 study review the use of 27 IVF add-ons and provide recommendations by ESHRE, with only several that are recommended or could be considered for the general infertility population. Read more.

Related studies

These additional publications were referenced by the authors of the paper and haven’t been covered on Remembryo. They may be helpful if you’re exploring this topic further. This section is available for paid subscribers.

Reference

Cimadomo D, Cozzolino M, Busnelli A, Carosso A, Conforti A, Massarotti C, Spadoni V, Vaiarelli A, Venturella R, Vitagliano A, Zacà C, Borini A. IVF add-ons: effectiveness, efficiency, safety, and additional costs – A position statement by the SIFES-MR. Eur J Obstet Gynecol Reprod Biol. 2025 Jul 29;313:114609. doi: 10.1016/j.ejogrb.2025.114609. Epub ahead of print. PMID: 40749411.

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About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.