Presentation: Patient experiencing recurrent miscarriage

A couple attend clinic having had three consecutive first-trimester miscarriages. The woman has had one previous spontaneous vaginal delivery with a previous partner and has no live children with her current partner.

• Genomic testing is typically indicated after a couple have had three consecutive pregnancy losses.
• Testing may be offered for all subsequent pregnancy losses after three consecutive pregnancy losses, unless a genomic cause is identified.

• Consult the National Genomic Test Directory. From this directory you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Refer to local guidance on recurrent early pregnancy loss. Referral to a recurrent pregnancy loss clinic is advised.
• Referral to clinical genetics is not routinely indicated for recurrent early pregnancy loss but may be advisable where testing identifies a genomic cause or there is a known family history of a genetic disorder.
• R318 Recurrent miscarriage with products of conception available for testing: This indication is for the third and each subsequent miscarriage where products of conception are available:
  • R318.1 Common aneuploidy testing, which may include trisomy 21, trisomy 18, trisomy 13 and certain sex chromosomal anomalies; and
  • R318.2 Microarray testing to look for any duplicated or deleted chromosomal segments.
• R297.1 Possible structural chromosomal rearrangement – karyotype: Parental blood karyotyping should be offered to both parents where products-of-conception testing has shown an unbalanced chromosomal anomaly.
• Where there are less than three early pregnancy losses but other features suggestive of a chromosomal anomaly or genetic cause, alternative testing pathways can be considered.
  • R22 Fetus with a likely chromosomal abnormality: For cases of isolated miscarriage with additional features suggestive of chromosome abnormality.
  • R412 Fetal anomalies with a likely genetic cause – non urgent. Testing can be used in cases of fetal anomaly with likely genetic cause.
• For many of the tests (particularly whole genome and exome sequencing), parental samples are also needed or are helpful.
• For tests that are undertaken using whole genome sequencing (WGS), you will need to:
  • complete an NHS GMS test order form with details of the proband and parents. Include details of the phenotype (refer to human phenotype ontology (HPO) terms or the clinical summary) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support).
  • complete an NHS GMS record of discussion form for each person being tested. Note that, if you are undertaking trio testing of an affected child and their parents, you will need three of these forms. (see How to complete a record of discussion form for support).
  • parental samples should be submitted alongside the child’s sample. This is called trio testing. If this is not possible, such as when testing a child in care or a parent is unavailable for testing, the child may be tested as a singleton.
• For tests that do not include WGS, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub (GLH).
  • include details of the phenotype in the test order form (refer to HPO terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
  • parental samples may be needed for interpretation of the proband’s result. Parental samples can be taken alongside that of the proband, and their DNA stored, or can be requested at a later date if needed.
• All of the above tests are DNA based and an EDTA sample (purple-topped tube) is required.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• NHS England: National Genomic Test Directory

References:

• Regan L, Rai R, Saravelos S and others. ‘Recurrent Miscarriage Green-top Guideline No. 17‘. British Journal of Obstetrics and Gynaecology 2023: volume 130, issue 12, pages e9–e39. DOI: 10.1111/1471-0528.17515

For patients

• Royal College of Obstetricians and Gynaecologists: Recurrent and late miscarriage patient information leaflet