Recurrent Implantation Failure — when embryos don't stick.

What is RIF?

Recurrent implantation failure is the situation where, despite multiple transfers of morphologically good-quality embryos in a properly prepared uterus, no pregnancy results. Definitions vary — some require 2 failed transfers, others 3, and some specify a total number of transferred embryos.

RIF isn't a single disease. It's a phenotype with multiple possible causes, some of which can be identified and addressed, and some of which we don't yet have good tests or treatments for.

The workup — what to investigate

Uterine

• Hysteroscopy — the most direct evaluation. Polyps, submucous fibroids, septum, adhesions, and chronic endometritis can all be identified and treated.
• Saline ultrasound (HSG / saline-infusion sonography) — complementary imaging.
• Tubal status check — hydrosalpinx if not previously addressed.

Embryo

• PGT-A — many morphologically good embryos are chromosomally abnormal. Selecting normal embryos substantially improves per-transfer outcomes.
• Embryo morphokinetics at the IVF lab — time-lapse imaging if available.
• Sperm DNA fragmentation — high fragmentation reduces implantation rates.

Timing — the window of implantation

• ERA test — identifies displaced implantation window. Selectively used in RIF after other causes are ruled out.

Endocrine and metabolic

• Thyroid function (with anti-TPO antibodies).
• Prolactin.
• Vitamin D and metabolic optimisation.

Immune and thrombophilia

• Antiphospholipid antibodies — well-established and treatable.
• Inherited thrombophilias — selectively, based on personal/family history.
• NK cells and reproductive immunology — weak evidence, not routinely pursued.

Uterine causes — the most actionable

Hysteroscopy in RIF often reveals:

• Endometrial polyps — common, easy to remove, meaningful improvement in subsequent transfer rates.
• Submucous fibroids — clearly reduce implantation; hysteroscopic resection helps.
• Uterine septum — congenital, often missed on ultrasound, addressable in a single procedure.
• Asherman syndrome — intrauterine adhesions, treatable hysteroscopically.
• Chronic endometritis — subtle, increasingly recognised. Treated with antibiotics if diagnosed on biopsy.
• Hydrosalpinx — if present, treated by salpingectomy or tubal clipping before another transfer.

Embryo-side issues

A morphologically beautiful blastocyst can still be chromosomally abnormal. PGT-A directly tests this. In RIF, particularly when maternal age is 35+, PGT-A is one of the highest-yield interventions.

Sperm DNA fragmentation is another underrated factor. Sperm with high fragmentation can fertilise eggs and produce visually normal embryos that then fail to implant or implant briefly and miscarry.

Timing — the implantation window

ERA identifies women whose endometrial receptivity is shifted earlier or later than the standard timing. Personalised transfer timing can rescue otherwise good cycles. Evidence has become more nuanced in recent trials, but ERA remains a reasonable selective add-on after 2–3 unexplained failed transfers.

The immune question

Reproductive immunology has been controversial for years. Most large studies have not shown clear benefit from immune-targeted interventions (intralipids, IVIG, steroids, anti-TNF agents) in RIF without a specific autoimmune diagnosis. Antiphospholipid syndrome is the well-evidenced exception — that we test for and treat with aspirin and heparin.

We don't pursue speculative immunology testing or treatments that lack good evidence.

Treatment strategies

• Treat what we find. Polyp removal, septum resection, antibiotics for endometritis, hydrosalpinx management, PGT-A for embryo selection.
• Personalised timing via ERA if other causes are ruled out.
• Sperm DNA fragmentation — address with lifestyle, antioxidants, varicocele repair, or use of testicular sperm.
• Empirical adjuncts (aspirin, progesterone support, immunomodulation) — only with clear evidence-based indications.
• Consider second-opinion review of lab quality, embryo grading, and protocol design.

How I work with RIF

RIF is one of the most demoralising situations in fertility care. By the time someone arrives with multiple failed transfers, they've usually been told different things by different clinicians. My approach:

1. One structured workup, completed in 2–3 visits. No drip-feeding tests across months.
2. Hysteroscopy with a low threshold. Most uterine factors are subtle and don't show on ultrasound; hysteroscopy is the most reliable evaluation.
3. Honest framing of what's evidence-based and what isn't. No speculative interventions.
4. A clear plan. Whether the next transfer happens here, at another centre, or only after a specific treatment — you leave the consultation with a defined next step, not vague optimism.