Treatment of gonadal damage in recipients of allogeneic or autologous transplantation for haematological malignancies

Abstract

Summary:Management of iatrogenic gonadal reproductive failure and sexual morbidity assumes a priority, especially in young recipients of high-dose chemotherapy and stem cell transplantation (SCT). Hormone replacement treatment (HRT) is beneficial for correction of sexual symptoms and osteoporosis in both sexes, especially in females. Sperm banking is the standard technique for preservation of fertility in adult and sexually mature adolescent males. Testicular tissue cryopreservation has a place in well-selected azoospermic adults and in mentally and sexually competent adolescents. In vitro fertilisation using superovulation with embryo-cryopreservation (for future embryo transfer) is the most tried method in female SCT recipients with good results. In mentally and sexually competent adolescents and adults without a partner, ovarian cortical tissue cryopreservation has a place for subsequent re-implantation to orthotopic or heterotopic sites. Gonadotrophin releasing hormone (GnRH) co-treatment during chemotherapy, is a promising method for the future. The adult gonad has two important functions: gametogenesis (spermatogenesis in males and oogenesis in females, respectively) and sex steroidogensis (production of testosterone in males and oestrogen and progesterone in females, respectively). Gonadal damage induced by high-dose chemotherapy or chemo-radiotherapy and stem cell transplantation, affects both components of gonadal function, resulting in infertility, and sexual dysfunction, which may compromise quality of life of the survivors. This article

Effects of various antireabsorptive treatments on bone mineral density in hypogonadal young women after allogeneic stem cell transplantation

“…There is evidence that HRT does not increase the risk of cGVHD exacerbation and prevents some adverse effects of long-lasting ovarian failure in young women. 26,27 Oral bisphosphonates proved to be effective for treating postmenopausal and glucocorticoid-induced osteoporosis. 14,15,17 In a previous study from our group, a 12-month treatment with a daily dose of 5 mg of risedronate increased BMD by 5.9% at the LS and prevented bone loss at the femoral neck in a mixed population of allo-transplanted patients.…”

“…4,7 Damaging effects on bone mass were attributed to hypogonadism, immunosuppressive and myeloablative treatments, immobilization, increased cytokine release, reduced dietary intake and metabolic alterations of calcium and vitamin D. 5,6 One of the most important risk factors for bone loss is precocious ovarian failure (POF), which is a common allo-SCT sequela. [8][9][10] Calcium and vitamin D supplementation and hypogonadism replacement are commonly used in clinical practice after SCT, while bisphosphonates are added only in patients with osteoporosis. Little information is available so far on the effects of preventive or therapeutic intervention on post-transplant bone loss; 1,[11][12][13] no systematic evaluation has been performed to compare the activity of different agents to prevent or treat osteoporosis following allo-SCT.…”

Ovarian recovery after stem cell transplantation

“…The potential therapeutic interventions currently utilized for protecting and restoring infertility include: GnRHa, in vitro fertilization (IVF) using superovulation and embryo cryopreservation (the most commonly used method), ovarian tissue cryopreservation, or oocyte freezing. 25 Therefore, all sexually active recipients of SCT should receive counseling regarding pregnancy prior to the initiation of high-dose chemotherapy. Likewise, patients must be counseled on the use of effective birth control measures to prevent unwanted pregnancies, especially when subsequent treatment involves possibly teratogenic drugs.…”

Quality of life, reproduction and sexuality after stem cell transplantation with partially T-cell-depleted grafts and after conditioning with a regimen including total body irradiation

“…Methods to counter gonadotoxic effects are studied. Chatterjee et al 3 have stated the necessity of prospective data and randomized controlled studies to determine the clinical potential of GnRH agonist co-treatment in the prevention of chemoradiotherapeutic damage. Sometimes, spontaneous restoration of fertility occurs.…”

“…2 Management of iatrogenic gonadal reproductive failure and sexual morbidity are important in young recipients of SCT. 3 The Nijmegen allogeneic transplantation programme was started in May 1981. This study provides an overview of the problems our patients experienced after SCT with respect to QOL, reproduction and sexuality.…”