Preconception (counseling, screening, PGT, ART)

Preconception genetic counseling is offered to any reproductive-age couple, ideally before conception. Core elements:

• Family history (3-generation pedigree): look for autosomal recessive, autosomal dominant, X-linked, and chromosomal patterns.
• Ancestry assessment: drives ancestry-specific carrier screening (Ashkenazi Jewish, French Canadian, Mediterranean, Southeast Asian).
• Personal medical history: including prior pregnancy losses, infertility, prior affected children, and known carrier status.
• Discussion of reproductive options if a risk is identified (see below).

Carrier screening identifies asymptomatic heterozygotes for recessive and X-linked conditions.

• Targeted (ethnicity-based) panels test a small set of disorders most prevalent in a specific ancestry group.
• Expanded carrier screening panels test 100-500+ conditions independent of ancestry; ACMG and ACOG recommend offering this to all reproductive-age patients as one option.
• Sequential vs. concurrent testing: a partner can be tested only if the other is a carrier (sequential, lower cost) or both partners tested at once (concurrent, faster).
• A positive result in one partner triggers reflex testing of the other to determine reproductive risk (1 in 4 if both heterozygous for an AR condition).

PGT is performed on embryos generated by IVF, before transfer.

• PGT-A (aneuploidy): screens for whole-chromosome gains/losses. Used to improve IVF outcomes; not for a specific disease indication.
• PGT-M (monogenic): tests for a known familial single-gene disorder. Requires a probe or assay built from the proband's specific variant.
• PGT-SR (structural rearrangements): detects unbalanced segregants in a parent who carries a balanced translocation or inversion.

PGT does not eliminate the need for prenatal diagnostic testing in pregnancy because of mosaicism and technical false negatives.

When natural conception is not desired or not possible:

• IVF (in vitro fertilization) is the platform for PGT and is also used for infertility, advanced maternal age, and same-sex couples.
• Donor gametes (sperm or egg) are an option when one partner has a high-risk genetic condition or carries a chromosome rearrangement with a high recurrence risk.
• Gestational surrogacy is used when carrying a pregnancy is medically contraindicated.

When both partners are carriers for the same autosomal recessive condition (1-in-4 affected pregnancy risk):

• Natural conception with prenatal diagnostic testing (CVS or amniocentesis) and option for termination of an affected pregnancy.
• IVF with PGT-M to transfer only unaffected embryos.
• Donor gametes (sperm or egg) from a non-carrier.
• Adoption.
• Remain childfree.

Non-directive counseling: present all options without bias toward a specific choice.