Fertility After Curative Therapy for Sickle Cell Disease: A Comprehensive Review to Guide Care

Overview

Journal J Clin Med

Specialty General Medicine

Date 2022 May 14

PMID 35566443

Authors

Robert Sheppard Nickel

Jacqueline Y Maher

Michael H Hsieh

Meghan F Davis

Matthew M Hsieh

Lydia H Pecker

Affiliations

Soon will be listed here.

Abstract

Curative therapy for sickle cell disease (SCD) currently requires gonadotoxic conditioning that can impair future fertility. Fertility outcomes after curative therapy are likely affected by pre-transplant ovarian reserve or semen analysis parameters that may already be abnormal from SCD-related damage or hydroxyurea treatment. Outcomes are also likely affected by the conditioning regimen. Conditioning with myeloablative busulfan and cyclophosphamide causes serious gonadotoxicity particularly among post-pubertal females. Reduced-intensity and non-myeloablative conditioning may be acutely less gonadotoxic, but more short and long-term fertility outcome data after these approaches is needed. Fertility preservation including oocyte/embryo, ovarian tissue, sperm, and experimental testicular tissue cryopreservation should be offered to patients with SCD pursing curative therapy. Regardless of HSCT outcome, longitudinal post-HSCT fertility care is required.

Citing Articles

Beyond the traditional oncology patient: the role of palliative care in patients with sickle cell disease receiving stem cell transplantation or gene therapy.

Collins G, Levine D, Leonard A, Sharma A, Johnson L Front Oncol. 2025; 15:1535851.

PMID: 40018407 PMC: 11865843. DOI: 10.3389/fonc.2025.1535851.

Late effects of hemopoietic stem cell transplant for sickle cell disease: monitoring and management.

Goldenberg M, Lanzkron S, Pecker L Expert Rev Hematol. 2024; 17(12):891-905.

PMID: 39499235 PMC: 11669372. DOI: 10.1080/17474086.2024.2423368.

How I treat sickle cell disease with gene therapy.

Sharma A Blood. 2024; 144(26):2693-2705.

PMID: 39356871 PMC: 11830977. DOI: 10.1182/blood.2024024519.

Ovarian Tissue Cryopreservation for Fertility Preservation in Patients with Hemoglobin Disorders: A Comprehensive Review.

Haering C, Coyne K, Daunov K, Anim S, Christianson M, Flyckt R J Clin Med. 2024; 13(13).

PMID: 38999197 PMC: 11242023. DOI: 10.3390/jcm13133631.

Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation.

George S, Veludhandi A, Xiang Y, Liu K, Stenger E, Arnold S Transplant Cell Ther. 2024; 30(9):912.e1-912.e13.

PMID: 38972510 PMC: 11344653. DOI: 10.1016/j.jtct.2024.06.029.

References

Matthews M, Pollack R . Acute pain crisis in a patient with sickle cell disease undergoing ovarian simulation for fertility preservation prior to curative stem cell transplantation: case report and literature review. J Assist Reprod Genet. 2017; 34(11):1445-1448. PMC: 5699988. DOI: 10.1007/s10815-017-1008-1. View

Goossens E, Jahnukainen K, Mitchell R, van Pelt A, Pennings G, Rives N . Fertility preservation in boys: recent developments and new insights . Hum Reprod Open. 2020; 2020(3):hoaa016. PMC: 7275639. DOI: 10.1093/hropen/hoaa016. View

Guzick D, Overstreet J, Factor-Litvak P, Brazil C, Nakajima S, Coutifaris C . Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2002; 345(19):1388-93. DOI: 10.1056/NEJMoa003005. View

Peigne M, Decanter C . Serum AMH level as a marker of acute and long-term effects of chemotherapy on the ovarian follicular content: a systematic review. Reprod Biol Endocrinol. 2014; 12:26. PMC: 3987687. DOI: 10.1186/1477-7827-12-26. View

Zhao J, Beebe K, Magee K, Salzberg D, Stahlecker J, Miller H . Adolescent male fertility following reduced-intensity conditioning regimen for hematopoietic stem cell transplantation in non-malignant disorders. Pediatr Transplant. 2019; 23(6):e13496. DOI: 10.1111/petr.13496. View

Grigg A . Effect of hydroxyurea on sperm count, motility and morphology in adult men with sickle cell or myeloproliferative disease. Intern Med J. 2007; 37(3):190-2. DOI: 10.1111/j.1445-5994.2006.01290.x. View

Boga C, Asma S, Ozer C, Kilicdag E, Kozanoglu I, Yeral M . Gonadal Status and Sexual Function at Long-Term Follow-up after Allogeneic Stem Cell Transplantation in Adult Patients with Sickle Cell Disease. Exp Clin Transplant. 2022; . DOI: 10.6002/ect.2021.0392. View

Friedman G, Freeman R, Bookchin R, Boyar R, Murthy G, Hellman L . Testicular function in sickle cell disease. Fertil Steril. 1974; 25(12):1018-21. DOI: 10.1016/s0015-0282(16)40809-5. View

Fronczak C, Kim E, Barqawi A . The insults of illicit drug use on male fertility. J Androl. 2011; 33(4):515-28. DOI: 10.2164/jandrol.110.011874. View

10.

Braye A, Tournaye H, Goossens E . Setting Up a Cryopreservation Programme for Immature Testicular Tissue: Lessons Learned After More Than 15 Years of Experience. Clin Med Insights Reprod Health. 2019; 13:1179558119886342. PMC: 6868573. DOI: 10.1177/1179558119886342. View

11.

Green D, Kawashima T, Stovall M, Leisenring W, Sklar C, Mertens A . Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study. J Clin Oncol. 2009; 27(16):2677-85. PMC: 2690392. DOI: 10.1200/JCO.2008.20.1541. View

12.

. Mature oocyte cryopreservation: a guideline. Fertil Steril. 2012; 99(1):37-43. DOI: 10.1016/j.fertnstert.2012.09.028. View

13.

Uijldert M, Meissner A, de Melker A, van Pelt A, van de Wetering M, van Rijn R . Development of the testis in pre-pubertal boys with cancer after biopsy for fertility preservation. Hum Reprod. 2017; 32(12):2366-2372. DOI: 10.1093/humrep/dex306. View

14.

Osegbe D, Akinyanju O . Testicular dysfunction in men with sickle cell disease. Postgrad Med J. 1987; 63(736):95-8. PMC: 2428240. DOI: 10.1136/pgmj.63.736.95. View

15.

Gille A, Pondarre C, Dalle J, Bernaudin F, Chalas C, Fahd M . Hydroxyurea does not affect the spermatogonial pool in prepubertal patients with sickle cell disease. Blood. 2020; 137(6):856-859. DOI: 10.1182/blood.2020008146. View

16.

Loren A, Senapati S . Fertility preservation in patients with hematologic malignancies and recipients of hematopoietic cell transplants. Blood. 2019; 134(9):746-760. DOI: 10.1182/blood.2018846790. View

17.

Fung E, Harmatz P, Lee P, Milet M, Bellevue R, Jeng M . Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol. 2006; 135(4):574-82. DOI: 10.1111/j.1365-2141.2006.06332.x. View

18.

Bresters D, Emons J, Nuri N, Ball L, Kollen W, Hannema S . Ovarian insufficiency and pubertal development after hematopoietic stem cell transplantation in childhood. Pediatr Blood Cancer. 2014; 61(11):2048-53. DOI: 10.1002/pbc.25162. View

19.

de Kat A, van der Schouw Y, Eijkemans M, Herber-Gast G, Visser J, Verschuren W . Back to the basics of ovarian aging: a population-based study on longitudinal anti-Müllerian hormone decline. BMC Med. 2016; 14(1):151. PMC: 5046975. DOI: 10.1186/s12916-016-0699-y. View

20.

Elchuri S, Williamson R, Brown R, Haight A, Spencer J, Buchanan I . The effects of hydroxyurea and bone marrow transplant on Anti-Müllerian hormone (AMH) levels in females with sickle cell anemia. Blood Cells Mol Dis. 2015; 55(1):56-61. DOI: 10.1016/j.bcmd.2015.03.012. View