Clinical definition of RIF: Failure to achieve a clinical pregnancy after 3 or more high-quality embryo transfers, or 3+ natural cycles with confirmed ovulation and adequate luteal phase. This is not a diagnosis of infertility — it is a specific failure pattern that warrants investigation.
| Investigation Area |
Category |
Specific Test(s) |
What It Detects |
What Changes If Positive |
| Endometrial Receptivity |
Uterine |
ERA biopsy (Endometrial Receptivity Array) |
Whether your personal "window of implantation" is displaced by 12–24 hours from the standard protocol day |
Personalised transfer timing adjusted to your ERA result. Studies show improved implantation rates in ERA-displaced patients. |
| Chronic Endometritis |
Uterine |
Endometrial biopsy + CD138 staining (standard biopsy often misses this) |
Subclinical bacterial infection of the uterine lining — no pain, no discharge, no symptoms. Found in 14–67% of RIF patients depending on the study. |
2-week antibiotic course (doxycycline or ciprofloxacin). Resolution confirmed by repeat biopsy. Implantation rates normalise after treatment in most cases. |
| Embryo Quality / Chromosomes |
Embryo |
PGT-A (Preimplantation Genetic Testing for Aneuploidy) |
Chromosomal abnormalities in embryos that appear morphologically normal. Up to 50–60% of embryos in women over 37 are chromosomally abnormal. |
Only euploid (chromosomally normal) embryos transferred. Reduces miscarriage rate significantly and increases per-transfer success rate. |
| Sperm DNA Fragmentation |
Embryo |
SCSA or TUNEL sperm DNA fragmentation index (DFI) |
DNA damage within sperm that does not affect fertilisation but impairs embryo development at the blastocyst stage and beyond. Standard semen analysis misses this entirely. |
Antioxidant protocols, lifestyle modification, testicular sperm extraction (TESE), or ICSI from surgical sperm if DFI is very high. |
| Uterine NK Cell Activity |
Immune |
Uterine NK cell biopsy (uNK) or peripheral blood NK assay |
Elevated natural killer cell activity in the uterine lining that may attack trophoblastic (embryo) cells. Controversial area — not all REs investigate this routinely. |
Intralipid infusions, prednisolone, or tacrolimus protocols depending on RE preference and severity of findings. |
| Thrombophilia / Clotting Disorders |
Systemic |
Factor V Leiden, MTHFR, antiphospholipid antibody panel, protein S/C |
Clotting tendencies that impair blood flow to the developing implantation site, causing early loss before clinical pregnancy is confirmed. |
Low-dose aspirin, low molecular weight heparin (Clexane/Lovenox), or folate supplementation depending on specific mutation found. |
| Thyroid Antibodies |
Systemic |
TSH, free T4, anti-TPO antibodies, anti-thyroglobulin antibodies |
Subclinical hypothyroidism (TSH 2.5–4.5) and thyroid autoimmunity — even without overt thyroid disease — are associated with implantation failure and early miscarriage. |
TSH optimisation to below 2.5 mIU/L before next transfer. Low-dose levothyroxine if indicated. Selenium supplementation for antibody reduction. |
The ERA Test: Why It Matters More Than Most Clinics Discuss
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Approximately 20–30% of patients with recurrent implantation failure have a "displaced window of implantation" — meaning their endometrium reaches peak receptivity 12–24 hours earlier or later than the standard protocol assumes. The ERA biopsy identifies this displacement. For these patients, simply adjusting the transfer time — not changing medications, embryos, or protocol — is sufficient to achieve success.
Questions to Ask Your Reproductive Endocrinologist If You've Had Repeated Failures With Correct Timing
- Has my endometrium been tested for chronic endometritis using CD138 immunohistochemistry — not just standard H&E staining?
- Have my embryos been tested with PGT-A, and if so, what was the euploid rate for my age group?
- Has my partner's sperm DNA fragmentation index been assessed, separate from a standard semen analysis?
- Would I be a candidate for an ERA biopsy to identify if my window of implantation is displaced from the standard protocol?
- Has a full antiphospholipid antibody panel been run, including anticardiolipin IgG/IgM and beta-2 glycoprotein antibodies?
- What is my TSH level, and has it been optimised to below 2.5 mIU/L ahead of my next transfer attempt?
Important: This section is intended for educational awareness only. Recurrent implantation failure investigation requires a board-certified reproductive endocrinologist and individualised diagnostic workup. The tests and interventions listed above represent a clinical framework — which specific investigations are appropriate for your situation can only be determined by your medical team based on your full history.