Recurrent miscarriage and reproductive immunology

When to investigate

Recurrent pregnancy loss is usually defined as two or more consecutive miscarriages. Waiting for a third before investigating is no longer standard practice, particularly where the woman is older, where losses occurred after a heartbeat was seen, or where there has been difficulty conceiving as well.

The standard workup

• Genetic — parental karyotype, and cytogenetic analysis of products of conception where available. Aneuploidy remains the single commonest cause of sporadic loss.
• Anatomic — uterine septum, adhesions, submucous fibroids and adenomyosis, assessed by ultrasound and hysteroscopy.
• Endocrine — thyroid function and antibodies, prolactin, glycaemic control, PCOS and insulin resistance.
• Thrombophilia — antiphospholipid antibodies, which are treatable and must not be missed.
• Immune — evaluated selectively where the above are normal and the losses remain unexplained.
• Male factor — sperm DNA fragmentation, increasingly recognised in recurrent loss.

Lymphocyte immunisation therapy: what it is

LIT involves immunising the woman with lymphocytes from her partner, with the aim of shifting the maternal immune response so that the pregnancy is tolerated rather than rejected. It works through blocking antibodies and regulatory T cells.

Dr Gupta has published live birth outcomes after low-dose LIT with partner lymphocytes in women with recurrent miscarriage in Fertility & Reproduction, and presented the work at the ESHRE annual meeting.

Where the evidence actually stands

This needs saying plainly, because LIT is sometimes offered with more confidence than the literature supports. In unexplained recurrent miscarriage, the majority of studies report improved pregnancy outcomes. In recurrent implantation failure the evidence is considerably weaker and the case for it is not settled.

LIT is considered in selected couples after other causes have been excluded. It is not a routine treatment, and it is not offered as a first step.

It is a blood-derived therapy and carries the requirements and precautions that implies, including partner screening. The distinction between what is well supported and what remains uncertain is explained before anyone consents to it.

What good care looks like here

Most couples with recurrent loss do eventually carry a pregnancy, and a meaningful proportion do so without any specific treatment beyond correcting what is found and being properly supported through the next pregnancy. Early scanning, thyroid and glycaemic control, progesterone where indicated, and continuity of care matter more than an aggressive protocol.