Recurrent implantation failure

What counts as recurrent implantation failure

There is no single agreed definition. In practice, recurrent implantation failure (RIF) is considered when good-quality embryos — usually three or more, or two or more euploid blastocysts — have been transferred without a pregnancy. The number matters less than the pattern: embryos that should have worked, did not.

That distinction is important, because the commonest reason a transfer fails is simply embryo aneuploidy, which is a numbers problem rather than a uterine one. Before investigating the uterus exhaustively, it is worth establishing whether the embryos themselves were ever likely to implant.

Why implantation fails

Implantation needs three things to align: a competent embryo, a receptive endometrium, and an immune and hormonal environment that permits the pregnancy to establish. Failure is usually traced to one of the following.

• Embryo factors — aneuploidy, poor blastocyst development, laboratory or culture conditions.
• The uterine cavity — septa, adhesions, polyps, submucous fibroids, or a previously undetected anomaly.
• Chronic endometritis — low-grade inflammation of the lining, often silent, diagnosed on CD138 immunohistochemistry.
• Endometrial thickness and receptivity — a lining that will not grow, or a displaced window of implantation.
• Adenomyosis — frequently missed and a recognised cause of implantation failure.
• Male factor — high sperm DNA fragmentation can produce embryos that look normal but fail after transfer.
• Endocrine and metabolic factors — thyroid dysfunction, prolactin, insulin resistance, vitamin D deficiency.
• Immune and clotting factors — evaluated selectively, not as a routine panel for everyone.

How it is investigated

The aim of the workup is a reason, not a longer list of tests. A hysteroscopy examines the cavity directly and allows an endometrial sample for CD138 testing where chronic endometritis is suspected. Endometrial thickness and pattern are reviewed across the cycle, and receptivity testing is considered where the history suggests a displaced window.

The male side is re-examined properly rather than accepted from an old semen analysis — DNA fragmentation testing is often more informative than count and motility once ICSI is already being used.

Dr Gupta has published on GnRH agonist pre-treatment and its effect on endometrial CD138 plasma cell density and implantation outcomes in recurrent implantation failure with adenomyosis, work presented at international congress.

What changes in the next cycle

Only once there is an explanation does the protocol change, and the change follows the finding: treating chronic endometritis before transfer, correcting a cavity abnormality hysteroscopically, suppressing adenomyosis before a frozen transfer, adjusting the transfer timing where receptivity is displaced, or addressing sperm DNA fragmentation on the male side.

Where no cause is found, that is said plainly. Repeating an identical cycle and expecting a different result is not a plan, and neither is adding every available adjunct at once — ESHRE has been clear that IVF add-ons should be offered with an honest discussion of what the evidence does and does not show.