Carrier Screening and Conceiving with a Known Genetic Condition

The honest picture, with numbers

Most people who carry a gene for a recessive condition have no idea. Carriers usually have no symptoms, or only mild ones, and there is often no family history to alert anyone — which is precisely why screening exists.

The arithmetic of recessive inheritance is fixed and worth memorising. If both partners carry a recessive gene for the same condition, ACOG sets out the chances for each pregnancy: a 25% (1 in 4) chance the child inherits both copies and has the condition, a 50% (1 in 2) chance the child is a carrier like the parents, and a 25% chance the child inherits neither. If only one partner is a carrier, there is a 50% chance the child is a carrier and no chance of the child being affected by that recessive condition.

ACOG's position is that all women thinking about pregnancy or already pregnant are offered carrier screening for cystic fibrosis, haemoglobinopathies (which include sickle cell disease and the thalassaemias) and spinal muscular atrophy, with additional screening available. Screening uses blood, saliva or a cheek swab. Usually the partner more likely to be a carrier is tested first; if that result is negative, no further testing is needed, and if it is positive the other partner is tested.

Chromosomal rearrangements are a separate issue from recessive carrier status. The RCOG notes that in about 6 in 100 couples who have had three miscarriages, one parent carries their own chromosomes in an unusual but balanced arrangement — harmless to them, but capable of producing an unbalanced arrangement in an embryo.

Targeted or expanded screening

ACOG describes two approaches. Targeted (or ethnicity-based) screening tests for conditions based on your ancestry or family history. Expanded carrier screening tests for many conditions from a single sample, without regard to race or ethnicity; some commercial panels cover more than 100 disorders, usually focusing on severe conditions that affect quality of life from an early age.

Neither is automatically better, and ACOG's advice is to discuss the benefits and limitations of each with an obstetrician-gynaecologist or a genetic counsellor before testing. Two caveats travel with expanded panels in particular: companies build their own condition lists, so "expanded" means different things at different labs; and ACOG notes that in a small number of cases results are wrong in either direction — false negatives and false positives both occur.

The timing point ACOG makes is the practical one: getting tested before pregnancy gives you a greater range of options and more time to make decisions.

What your options are if you are both carriers

ACOG lists them without editorialising, and so will we. Before pregnancy, you can conceive and have prenatal diagnostic testing; you can use IVF with embryo testing, or with donor eggs or sperm; you can choose not to become pregnant; you can adopt. After conception, the options narrow. Carrier screening is voluntary — ACOG's own framing is that there is no right or wrong choice.

Embryo testing in the UK

Where a specific inherited condition is known, pre-implantation genetic testing for monogenic disorders (PGT-M) tests embryos created through IVF for that condition; PGT-SR does the equivalent for chromosomal structural rearrangements. Both require IVF even if you have no fertility problem.

The UK route is regulated. The HFEA decides which conditions may be tested for, and more than 2,000 genetic conditions have been approved for PGT-M. If your condition is not on the approved list, a licensed clinic must apply to the HFEA to add it, against strict criteria including the seriousness of the condition and the likelihood of inheritance — and that process can take time. The HFEA is also explicit that PGT-M and PGT-SR are not 100% accurate, and that sometimes there are no suitable embryos to transfer.

Genetic testing in male factor infertility

Genetic testing also enters fertility care from a different direction, and NICE NG257 sets out exactly when. For men, and trans women and non-binary people with male reproductive organs:

• Y chromosome microdeletion testing where there is idiopathic azoospermia, or a sperm concentration below 1 million per ml.
• Cystic fibrosis (CFTR) mutation testing where there is idiopathic suspected obstructive azoospermia or a vasal abnormality on examination.
• Karyotype testing for idiopathic azoospermia, and consideration of it where sperm concentration is persistently below 5 million per ml.
• Genetic counselling offered where a specific genetic defect associated with male factor infertility is found.

These results change management, not just information. NICE recommends against surgical sperm retrieval where there is a Y chromosome AZFa or AZFb microdeletion, because it will not succeed. A CFTR result has implications for a partner's carrier status and for any future child. This is a good example of a test that is worth doing because it changes what happens next.

What to do next

1. Ask for a referral to genetic counselling before testing, not after. A genetic counsellor will help you decide which panel is appropriate and what you would do with each possible result. That conversation is much harder to have retrospectively.
2. Test the partner more likely to be a carrier first, unless you are testing both in parallel for time reasons. A negative result there ends the question for that condition.
3. Ask exactly which conditions a panel covers and what its detection rate is for your ancestry. A negative expanded screen reduces risk; it does not eliminate it.
4. If a condition runs in your family, check the HFEA's approved PGT-M list before assuming embryo testing is or is not available, and ask a licensed clinic whether an application would be needed.
5. Think about who else in your family this affects. ACOG notes that a carrier result may be relevant to relatives, that there is no legal obligation to tell them, and that a genetic counsellor can advise on how.

Practical and legal points people miss

In the United States, the Genetic Information Nondiscrimination Act of 2008 makes it illegal for most health insurers to require or use genetic test results in decisions about coverage, rates or pre-existing conditions, and illegal for employers to discriminate on genetic information. ACOG is clear about the gap: GINA does not apply to life insurance, long-term care insurance or disability insurance. If those matter to you, the sequencing of tests and applications is worth thinking about before you test.

When to seek help

Ask for genetic counselling before conceiving if: you or your partner have a known genetic condition or carrier status; there is a family history of a serious inherited condition, unexplained childhood deaths or intellectual disability; you and your partner are related; you belong to a population with a higher carrier frequency for a specific condition; or you have had recurrent miscarriage, where the RCOG recommends genetic counselling for any couple in whom a chromosomal rearrangement is found.

NICE NG257 also recommends referral at first presentation for fertility assessment where either partner has a known or suspected clinical cause of infertility — a diagnosed genetic condition affecting reproduction is exactly that, so you do not need to wait a year.