[Management of endocrine dysfunctions after allogeneic hematopoietic stem cell transplantation: a report of the SFGM-TC on gonadal failure and fertility]. / Suivi et prise en charge des troubles endocriniens en post-greffe de cellules souches hématopoïétiques: insuffisance gonadique et fertilité

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of short and long-term endocrine dysfunction following allogeneic stem cell transplantation. The key aim of this workshop was to give an overview gonadal failure, fertility preservation and post-transplant.

Male Obesity Associated Gonadal Dysfunction and the Role of Bariatric Surgery.

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction.

High prevalence of recurrent thrombosis in subsets of cancer patients with isolated gonadal vein thrombosis: a single center retrospective study.

PURPOSE: Cancer patients are a high-risk population for venous thromboembolism (VTE); the natural history of gonadal vein thrombosis (GVT) occurring in cancer patients is not well described in the medical literature. METHODS: Utilizing a software program the computerized tomographic scan reports of patients at a single cancer center from January 1, 2004 to June 30, 2011 were searched for the term GVT. Patients included in this analysis had a diagnosis of cancer, an isolated GVT (i.e. no evidence of thrombosis at another site), no symptoms referable to the GVT, and at least six months of follow-up information. All subsequent recurrent VTE events were confirmed by imaging studies. RESULTS: 196 cancer patients with GVT were identified. The majority of patients in this analysis had metastatic disease (118, 61.2%) as well as active cancer (167, 85.2%). Twenty patients (10.8%) developed recurrent VTE (median follow-up 14.5 months); median time to recurrent VTEs was 5.5 months (range 0-19 months). When considering only patients with without a recent history of gynecologic surgery, VTE recurrence rates were 14.3%. Active cancer was the only risk factor significantly associated with recurrent VTE (P=0.047). CONCLUSIONS: Based upon the patient's risk factors for VTE, treatment of an incidentally detected GVT in cancer patients with anticoagulation, as per guidelines for other VTE sites, may be indicated in certain high risk subgroups, especially those patients with active cancer who have not had prior pelvic surgery.

[Thyroid gland dysfunction, disorders of somatic and sexual development, disturbances of fertility after hematopoietic stem cell transplantation]. / Zaburzenia funkcji i morfologii tarczycy, zaburzenia wzrastania i dojrzewania plciowego oraz plodnosci po przeszczepieniu komórek krwiotwórczych.

Since the 1980s, hematopoietic stem cell transplantation (HSCT) has been performed for malignant and non-malignant disorders leading to increasing numbers of long-term survivors. Some of them develop long-term posttransplantation complications, among them endocrine complications that arise many years after HSCT and demand to be treated till the end of patients´ life. In the paper "classical", observed several years after HSCT had been used as a treatment procedure, endocrine complications are discussed and the review of literature regarding this problem is presented. Thyroid dysfunction, disorders of somatic and sexual development are presented in details. Gonad dysfunction with the problem of fertility disturbances is reported. The paper presents the etiopathogenesis, methods of prevention, as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

Cyclophosphamide and lupus nephritis: when, how, for how long?

Ever since the introduction of cyclophosphamide (CY), the management of lupus nephritis has dramatically changed, and its prognosis has greatly improved. Based on randomized controlled trials and long-term observational studies, pulse therapy with CY in combination with methyl-prednisolone (MP) is the "gold standard" of therapy for severe lupus. The realization of the significant gonadal toxicity intensified the efforts for the development of alternative immunosuppressive agents. In a large, randomized controlled trial, newer agents such as mycophenolate mofetil (MMF) have demonstrated comparable efficacy and less toxicity for moderately severe disease. To date, combinations of monthly pulses of CY with MP remain the gold standard for the induction of remission in severe lupus. For maintenance, less toxic agents such as azathioprine or MMF are equally effective and are routinely used in the current therapy of lupus.

Optimizing potential for fertility: fertility preservation considerations for the pediatric endocrinologist.

Whether for the prepubertal or pubertal child, the goal of fertility preservation is to obtain cells or tissues to be used to produce future children. For the prepubertal child, preservation efforts involve germ cells, earlier forms of sperm, and immature follicles, rather than mature spermatozoa or follicles. Options for prepubertal children include for boys freezing testicular tissue and extracting testicular sperm or for girls obtaining ovarian cortical or follicular tissue for storage. These procedures involve extraction and storage of immature gametes for subsequent in vitro maturation, although attempts for sperm currently involve only animal studies. For adolescent subjects who have sufficient gonadal development and reserve, sperm, oocytes, and ovarian cortex can be retrieved as among adults.

Late complications after hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to patients with leukemia, lymphoma and severe non-malignant diseases. More than 40,000 HSCTs are performed annually worldwide. Therefore, the number of long-term survivors, free of the disease for which they were transplanted is continuously increasing. Despite the improved prognosis of HSCT, long-term outcome may be impaired by transplant-associated morbidity and mortality. Long-term survivors can present a variety of malignant and non-malignant complications, impairing physical and psychological performance, normal integration in family and social life, and quality of life. Conditioning regimens, particularly when including total-body irradiation as well as graft-versus-host disease, play a key role in the development of late effects. However, with increasing time since transplantation new types of late effects may emerge. Awareness on long-term effects after HSCT is crucial to provide adapted pretransplant counseling, and recommendations for post-transplant screening, prevention and early treatment.

[Gonadal dysfunction in males following treatment of childhood malignancy. Current concepts]. / Zaburzenia funkcji gonad u mezczyzn po leczeniu przeciwnowotworowym w dziecinstwie. Aktualny stan wiedzy.

Cytotoxic chemotherapy and radiotherapy have improved the survival rates in many malignant conditions, particularly in paediatric patients with haematologic malignancies. Treatment is associated with significant morbidity in many patients, and alterations in gonadal function are among the most common long-term side effects of therapy. Chemotherapy and radiotherapy may damage germ-cell spermatogonia, resulting in impaired spermatogenesis or sterility in the male. This review describes gonadal dysfunction in males at risk of chemotherapy and radiotherapy and the type of malignancy in childhood induced infertility. The detection and diagnostic methods of gonadal damage in males after treatment for a childhood malignancy are also described and therapeutic strategies for preventing these problems are outlined.