Sickle cell disease and infertility risks: implications for counseling and care of affected girls and women

ABSTRACT

Introduction

Sickle cell disease (SCD), its treatments and cures present infertility risks. Fertility counseling is broadly indicated for affected girls and women and fertility preservation may appeal to some. Several streams of evidence suggest that the reproductive lifespan of women with SCD is reduced. Pregnancy is associated with high miscarriage rates. There are enduring questions about the effects of highly effective hydroxyurea treatment on female fertility. Current conditioning regimens for gene therapy or hematopoietic stem cell transplant are gonadotoxic. Fertility preservation methods exist as non-experimental standards of care for girls and women. Clinicians are challenged to overcome multifactorial barriers to incorporate fertility counseling and fertility preservation care into routine SCD care.

Areas covered

Here we provide a narrative review of existing evidence regarding fertility and infertility risks in girls and women with SCD and consider counseling implications of existing evidence.

Expert opinion

Addressing fertility for girls and women with SCD requires engaging concerns that emerge across the lifespan, acknowledging uncertainty and identifying barriers to care, some of which may be insurmountable without public policy changes. The contemporary SCD care paradigm can offer transformative SCD treatments alongside comprehensive counselling that addresses fertility risks and fertility preservation opportunities.

KEYWORDS:

• Sickle cell disease
• fertility
• infertility
• pregnancy
• curative therapies
• patient counseling

Article highlights

• Survival into adulthood is a near-universal outcome for children with sickle cell disease in high income settings.

• Infertility risks are a consequence of sickle cell disease, and its chronic and curative therapies.

• A treatment paradigm that acknowledges the risks of untreated sickle cell disease, the benefits of treating sickle cell disease, and the potential for compromised fertility in the future is warranted.

• Non-experimental fertility preservation interventions exist for pre-pubescent girls and pubescent girls and women with sickle cell disease. These interventions have disease-specific risks.

• Access to assisted reproductive technologies including fertility preservation, in vitro fertilization and preimplantation genetic testing are inaccessible to many due to inadequate insurance, lack of experts and high cost.

• We suggest a counseling regarding infertility risks that (1) invites discussion with patients and families, (2) involves a care team with fertility preservation experts, (3) claims solid ground where evidence exists to inform care, and (3) embrace uncertainty as there is much that remains unknown.

Abbreviations

SCD	=	Sickle cell disease
HSCT	=	Hematopoietic stem cell transplantation
AMH	=	Anti-Mullerian hormone
AFC	=	Antral follicle count
POI	=	Premature ovarian insufficiency
DOR	=	Diminished ovarian reserve
ART	=	Assisted reproductive technologies
OTC	=	Ovarian tissue cryopreservation
IVM	=	Matured in vitro
OHSS	=	Ovarian hyperstimulation syndrome

Declaration of interest

LH Pecker is funded through NIH/NHLBI K23HL146841 and NIH/NHLBI U01 HL156620–01, the American Society of Hematology, Doris Duke Charitable Foundation Grant #2020147, the Mellon Foundation, and Alexion, and has served as a consultant for Global Blood Therapeutics and Novo Nordisk. LH Pecker is a co-founder of the Sickle Cell Reproductive Health Education Directive and serves on the Medical Advisory Committee of the Foundation for Women and Girls with Blood Disorders. K Cameron is funded through NIH/NICHD K12 HD103036. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors wish to thank Jayla Scott for their support with submitting this manuscript.

Additional information

Funding

This paper was funded by the Doris Duke Charitable Foundation [#2020147], and the U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute [K23HL146841 and U01 HL156620-01.]