Table 3.

Comparison of OI reproductive options

Pre-pregnancy testing
	Genetic Testing			PCS
Target user	People affected with OI			People with risk of OI (OI family history, consanguinity, founder population origin)
Advantages	Fast and informative			Fast and informative
Limitations	VUS; negative results of genetic test			Parental mosaicism; de novo OI; VUS
Fertilisation methods
	Natural pregnancy		IVF with PGT-M	IVF with donor germ cells	IVF with donor embryo
Genetically related child	Yes		Yes	No	No
Child without OI	Unknown		Yes	Yes	Yes
OI mother’s health challenges	Pregnancy, delivery		Superovulation, pregnancy, delivery	Superovulation, pregnancy, delivery	Pregnancy, delivery
Limitations	PGT-M unavailable, high chance of OI affected pregnancy, de novo variants, variable phenotypic expressivity of OI		De novo variants	De novo variants, PCS need to be done for sex cell donors	De novo variants
Prenatal testing
	NIPT	Ultrasound	CVS	Amniocentesis	Cordocentesis
Non-invasive	Yes	Yes	No	No	No
Week of gestation	7th–10th	20th	10th–12th	15th–20th	22nd-24th
Tests foetal abnormalities, OI	Yes	Yes	Yes	Yes	Yes
Differs OI 2–3	No	No	No	No	No
Risk of misdiagnosis	Yes (placental mosaicism)	Yes (differential diagnosis)	Yes (placental mosaicism)	No	No
Limitations	Unavailable before 7th week of gestation, high mother’s BMI	Unavailable at early gestation weeks	Unavailable at early gestation weeks, risk of miscarriage ~ 1%	Unavailable at early gestation weeks, risk of miscarriage ~ 0.5–1%	Unavailable at early gestation weeks, risk of miscarriage ~ 1–2%

BMI Body mass index, CVS Chorionic villus sampling, IVF PGT-M In vitro fertilisation with preimplantation genetic testing for monogenic disease, NIPT Non-invasive prenatal testing, PCS Preconception carrier screening, VUS Variant of unknown significance