Presentation: Pregnant woman experiencing recurrent miscarriage

A couple attend clinic having had three 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 of the products of conception is typically indicated after a couple have had three pregnancy losses.
• After three pregnancy losses, genomic testing may be offered for all subsequent pregnancy losses, unless a genomic cause is identified.
• If genomic testing of the pregnancy loss has not been possible, after five untested pregnancy losses a couple may, in some instances, be offered genomic testing themselves.

• Consult the National Genomic Test Directory. From here 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 Genomic testing in the devolved nations.
• For information about the genes that 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 condition.
• Genomic testing options may include the following.
• • 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. It involves:
• • • R318.1 Common aneuploidy testing, which can include trisomy 21, trisomy 18, trisomy 13 and certain sex chromosomal anomalies; and/or
• • • R318.2 Microarray testing to look for any duplicated or deleted chromosomal segments.
• • R297.1 Possible structural chromosomal rearrangement – karyotype or targeted chromosomal analysis. Targeted chromosomal analysis should be offered to both parents where products-of-conception testing has shown an unbalanced chromosomal anomaly. If parents have experienced five pregnancy losses together and none of the losses have undergone genomic testing, the parents may be offered blood karyotype testing.
• Where there are less than three early pregnancy losses but other features suggestive of a chromosomal anomaly or genetic cause are present, alternative testing pathways can be considered.
• • R22 Fetus with a likely chromosomal abnormality: This is for cases of isolated miscarriage with additional features suggestive of chromosome anomaly.
• • R412 Fetal anomalies with a likely genetic cause – non urgent: This can be used in cases of fetal anomaly with a likely genetic cause.
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• 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.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• 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 & Gynaecologists: Recurrent miscarriage