ERA, PRP and Immunological Protocols in IVF: What Works, What Is Unproven, and How to Tell the Difference

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Clinics offer dozens of additional procedures alongside standard IVF. Some of them are a genuine advance. Others are expensive experiments. Here is how to tell one from the other.

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In 2023, the British Fertility Society published guidance on add-on procedures in IVF. The document contained an uncomfortable finding: the majority of widely offered add-ons do not have sufficient evidence for routine use. Some are very well studied. Others are barely studied at all. A third group has been studied — and the results came back negative. This does not mean all add-on procedures are useless. It means that in reproductive medicine, market demand for 'something extra' is currently outpacing the science. For patients paying out of pocket for every IVF cycle, this is critically important to understand.

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ERA: endometrial receptivity analysis

ERA (Endometrial Receptivity Analysis) is one of the most discussed and most studied add-ons. The logic is straightforward: embryo transfer should occur at the moment of maximum endometrial receptivity — the so-called 'implantation window'. Standard protocols assume this window is the same for all women. ERA tests whether this is actually true for a specific patient. How it works: in a test cycle (no embryo transfer), an endometrial biopsy is taken at the time corresponding to the presumed implantation window. The sample undergoes gene expression analysis — the activity of 248 genes characteristic of receptive endometrium is measured. The result determines whether the patient's real implantation window coincides with the standard one, or is shifted. In the next cycle, transfer is scheduled at the personalised moment.

The data are more contradictory than the concept. Early studies showed improved outcomes in women with a history of failed embryo transfers. But the large randomised controlled STAR trial (2021), involving nearly nine hundred patients, found no statistically significant improvement in IVF outcomes with ERA compared with standard protocol. Disappointing — but this is exactly how evidence-based medicine works. Current consensus: ERA is not recommended as a routine procedure for all patients. It may be considered in recurrent implantation failure — although evidence even in this group is mixed. Cost: 500–1,500 euros per test.

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PRP therapy of ovaries and endometrium: hope or fashion

PRP (Platelet-Rich Plasma) arrived in reproductive medicine from orthopaedics and sports medicine, where it is used to accelerate tissue healing. The plasma — centrifuged from the patient's own blood — contains a high concentration of platelets and growth factors. In reproductive medicine, PRP is used in two fundamentally different contexts.

Endometrial PRP: in 'thin endometrium' (under seven millimetres) — a condition in which implantation is impaired — PRP is introduced into the uterine cavity or endometrium. Several small studies showed encouraging results. However, large randomised trials are lacking. Regulatory bodies (NICE in the UK, ASRM in the USA) do not recommend endometrial PRP as a proven method for standard use. Ovarian PRP: in low ovarian reserve and POI — injection of PRP directly into ovarian tissue. Isolated cases of menstrual restoration and even pregnancies in women with POI following PRP have been described. But these are isolated cases, not systematic data. At present, ovarian PRP is an experimental procedure without proven efficacy.

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Immunological protocols: when immunity attacks the embryo

The immunological approach to IVF failure is one of the most actively developing and simultaneously most controversial areas. The idea:

Interventions offered:

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Other add-ons: a brief overview

IMSI (intracytoplasmic morphologically selected sperm injection): a modification of ICSI in which sperm is selected under much greater magnification — 6,000× instead of the standard 400×. Meta-analyses have not shown significant superiority of IMSI over standard ICSI for live birth rates. Assisted hatching: micro-surgical or laser creation of an opening in the embryo's shell before transfer. A 2021 Cochrane review found no improvement in live birth rates on average. Time-lapse monitoring: continuous video recording of embryo development in the incubator. Informative from a data perspective, but minimal or zero impact on live birth rates compared with standard monitoring. PGT-A (preimplantation genetic testing for aneuploidy): one of the best-justified add-ons, particularly for women over 35 and patients with recurrent miscarriage. Reduces miscarriage rates and increases success per transfer for appropriate patient groups.

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How to make decisions about add-ons

Questions worth asking before agreeing to any additional procedure: Are there randomised controlled trials of this method? What did they show? Is this method recommended by leading professional organisations — ESHRE, ASRM, NICE? What is the cost relative to the likely benefit for me specifically? A good clinic will never take offence at such questions. A good doctor will never push additional procedures without clear indications. A warning sign: a clinic that offers the whole add-on package 'for safety' as a standard option.

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The bottom line

Add-on procedures in IVF are not a homogeneous group. PGT-A with specific indications — justified. ERA with recurrent failures — possibly reasonable, data mixed. Immunological protocols for antiphospholipid syndrome — yes; for 'elevated NK cells' without clear criteria — questionable. PRP — a promising idea without sufficient evidence. Critical thinking and questions to your doctor are the best filter in a world where market demand outpaces the science.

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Glossary

ERA (Endometrial Receptivity Analysis) — endometrial receptivity test. Gene expression analysis of an endometrial biopsy to identify a personalised implantation window.
PRP (Platelet-Rich Plasma) — platelet-rich plasma. Used in reproductive medicine to treat the endometrium or ovaries. Evidence base is limited.
NK cells (natural killer cells) — immune system cells. Their role in implantation failure is under study; correlation between blood NK levels and implantation remains unproven.
PGT-A (preimplantation genetic testing for aneuploidy) — embryo screening for chromosomal abnormalities before transfer. The best-evidenced add-on for specific patient groups.
Antiphospholipid syndrome — an autoimmune condition in which antibodies to phospholipids are produced. A proven immunological cause of pregnancy loss; heparin and aspirin treatment has an evidence base.
Time-lapse monitoring — continuous video recording of embryo development in the incubator. Informative but without proven impact on live birth rates.
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