Successful Fertility Restoration after Allogenic Hematopoietic Stem Cell Transplantation

Abstract

Objective Myeloablative conditioning regimens given prior to hematopoietic stem cell transplantation (HSCT) frequently cause permanent sterility in men. In patients with sickle cell disease (SCD) we use a nonmyeloablative regimen with sirolimus, alemtuzumab, and low-dose total-body irradiation (300 centigrays) with gonadal shielding preceding allogeneic HSCT. We report here the restoration of azoospermia in a patient with SCD after allogeneic HSCT. We discuss the impact of our patient’s underlying chronic medical conditions and the therapies he had received (frequent blood transfusions, iron chelating drugs, ribavirin, hydroxyurea, opioids), as well as the impact of the nonmyeloablative conditioning regimen on male gonadal function, and we review the literature on this topic. Methods We determined the patient’s reproductive hormonal values and his semen parameters before, during, and after HSCT and infertility treatment. In addition, we routinely measured his serum laboratory parameters pertinent to SCD and infertility, such as iron and ferritin levels. A karyotype analysis was performed to assess the potential presence of Klinefelter syndrome. Finally, imaging studies of the patient’s brain and testes were done to rule out further underlying pathology. Results A 42-year-old man with SCD, transfusional iron overload, and hepatitis C underwent a nonmyeloablative allogeneic HSCT. One year later he desired to father a child but was found to be azoospermic in the context of hypogonadotropic hypogonadism. Restoration of fertility was attempted with human chorionic gonadotropin (2,000 IU) plus human menopausal gonadotropin (75 IU follicle-stimulating hormone) injected subcutaneously 3 times weekly. Within 6 months of treatment, the patient’s serum calculated free testosterone value normalized, and his sperm count and sperm motility improved. After 10 months, he successfully initiated a pregnancy through intercourse. The pregnancy was uncomplicated, and a healthy daughter was delivered naturally at term. Conclusion Despite exposure to several gonadotoxins, transfusional iron overload and nonmyeloablative conditioning with radiation causing severe testicular atrophy suggesting extensive damage to seminiferous tubules and possibly Leydig cells, gonadotropins were efficacious in restoring our patient’s reproductive capability.

Reproductive issues in sickle cell disease

“…59 Many speculate that these types of conditioning regimens may limit toxicity and preserve fertility. 51,59 However, due the unpredictable risk of infertility, patients may opt for procedures to preserve fertility before HSCT regardless of conditioning regimens.…”

“…[55][56][57][58] Even when gonadal failure develops after these less toxic conditioning regimens, fertility may be improved after hormonal therapy. 59 Many speculate that these types of conditioning regimens may limit toxicity and preserve fertility. 51,59 However, due the unpredictable risk of infertility, patients may opt for procedures to preserve fertility before HSCT regardless of conditioning regimens.…”

“…59 Many speculate that these types of conditioning regimens may limit toxicity and preserve fertility. 51,59 However, due the unpredictable risk of infertility, patients may opt for procedures to preserve fertility before HSCT regardless of conditioning regimens.There is growing consensus that individuals at risk for gonadal failure after exposure to gonadotoxic drugs should be offered fertility preservation. Although experience is limited, patients with SCD have success with procedures and therapies that preserve fertility.…”

Blood and marrow transplantation for sickle cell disease: Is less more?

“…In this regard it appears that non-myeloablative regimens may have a benefit over myeloablative conditioning regimens. Other patients have been able to have children post BMT after ovarian autografting, allografting, and hormonal manipulation (33–35). Therefore, while fertility preservation seems an achievable goal in patients receiving non-myeloablative transplants this issue requires detailed discussions with the patient (and parents if still underage) to be sure that the potential outcomes are reviewed and there is an understanding about the possible loss of fertility of the patient.…”

Adolescent male fertility following reduced‐intensity conditioning regimen for hematopoietic stem cell transplantation in non‐malignant disorders

“…Despite the increased use of RIC preparative regimens for HSCT, there is little published data examining the effects of RIC on fertility in male patients . Panasiuk et al evaluated gonadal hormonal function in survivors of HSCT in childhood by comparing patients who received myeloablative regimens containing busulfan and Cy (N = 51, 28 boys) and RIC regimens containing Flu and Mel (N = 40, 19 boys).…”