. Author manuscript; available in PMC: 2023 Jul 4.

Published in final edited form as: Lancet Haematol. 2023 Jan 25;10(3):e225–e234. doi: 10.1016/S2352-3026(22)00353-2

Table 1. Putative infertility risks associated with sickle cell disease and its treatments and cures.

Few infertility risks are universal features of SCD, underscoring the need for individualized care that considers age, sex, genotype, disease complications and measures of treatment dose, duration and adherence. Uncertainties related to infertility risks can be incorporated into information sharing about disease complications and treatment benefits.

	People with ovaries	People with testicles

Untreated sickle cell disease	Ovarian reserve decline is accelerated in adulthood^4,5,6; some adolescents and young adults have diminished ovarian reserve^6,9,10	Hypogonadism^7,8
		Sperm abnormalities^7,8
	Pregnancy is high-risk for maternal and fetal morbidity & mortality²	Priapism, & erectile dysfunction^7,8

Disease modifying therapies	Hydroxyurea: associated with diminished ovarian reserve^6,9,10; concern for early embryonal developmental changes, teratogenesis²	Hydroxyurea: toxic to sperm (reversibility suggested), outstanding questions about long-term effects to spermatogonial pool¹¹
	Red cell transfusions: ovarian follicle iron deposition possible¹², pituitary iron overload uncommon, chelators are teratogenic	Transfusions: testicular and pituitary iron deposition possible¹³
	L-glutamine, crizanlizumab, voxelotor: no data	L-glutamine, crizanlizumab, voxelotor: no data

Curative/HSCT preparative regimens	Alkylating Agents: gonadal toxicity and infertility¹⁴	Alkylating Agents: gonadal toxicity and infertility¹⁴
Curative/HSCT preparative regimens	Total Body Irradiation: Reduced ovarian reserve, infertility, uterine damage reducing future blastocyst implantation¹⁴	Total Body Irradiation: shielding spares the testicles¹⁴