Article

Assessment of male fertility in patients with Hodgkin's lymphoma treated in the German Hodgkin Study Group (GHSG) clinical trials

June 2008
Annals of Oncology 19(10):1795-801

June 2008
19(10):1795-801

DOI:10.1093/annonc/mdn376

Source
PubMed

Authors:

Thorsten Reineke

Duale Hochschule Baden-Württemberg Karlsruhe

Andreas Josting

OnkoBer

Show all 9 authorsHide

Infertility is one of the most significant side-effects in long-term survivors of successfully treated Hodgkin's lymphoma (HL). The fertility status was assessed in male HL patients enrolled into trials of the German Hodgkin Study Group from 1988 to 2003. In pre-treatment analysis (n = 202), 20% of patients had normozoospermia, 11% azoospermia and 69% had other dyspermia. In post-treatment analysis (n = 112), 64% of patients had azoospermia, 30% other dyspermia and 6% normozoospermia (P < 0.001). Azoospermia was observed in 90% of patients treated with chemotherapy alone, 67% of those treated with combined modality and 11% of those treated with radiotherapy alone (P < 0.001). Azoospermia was more frequent after 4x cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, dacarbazine (COPP/ABVD) (91%), 8x bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone (BEACOPP) baseline (93%) and 8x BEACOPP escalated (87%) compared with 2x COPP/ABVD (56%; P = 0.003). There was a statistically significant difference in post-treatment follicle-stimulating hormone (FSH) levels between patients with azoospermia and those with preserved spermatogenesis (P = 0.001). Depending on the treatment received, male HL patients are at high risk of infertility after treatment. FSH might be used as surrogate parameter for male fertility in future studies.

Hematological Malignancies and Fertility

Chapter

Mar 2020
ADV EXP MED BIOL

In the last decades, survival rate of hematological malignancies has been significantly improved and sparing reproductive potential after treatment has become one of the goals in both male and female patients. A comprehensive consultation with reproductive specialists before the onset of any kind of cancer treatment procedure is an essential issue which would increase the likelihood of parenting in survivors. In this context, cryopreservation of oocyte, embryo or ovarian tissue in reproductive aged women and sperm or testicular tissue cryopreservation in adult male are feasible approaches that must be considered before gonadotoxic therapy. Notably, all options should be regarded as experimental during pre-pubertal period. Herein, we aim to review the available literature with regard to safety, efficacy of fertility preservation methods and the pregnancy outcomes in patients with hematological malignancies.

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: A prospective study by the French CECOS network

Article

Full-text available

Oct 2016

Objective: To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. Design: Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months. Setting: University hospitals. Patient(s): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. Intervention(s): Semen analyses and aneuploidy study by FISH were performed at each time point. Main outcome measure(s): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. Result(s): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment. Conclusion(s): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.

Childhood cancer and hematological disorders negatively affect spermatogonial quantity at diagnosis: a retrospective study of a male fertility preservation cohort

Article

Full-text available

Jan 2023

STUDY QUESTION What is the impact of cancer or hematological disorders on germ cells in pediatric male patients? SUMMARY ANSWER Spermatogonial quantity is reduced in testes of prepubertal boys diagnosed with cancer or severe hematological disorder compared to healthy controls and this reduction is disease and age dependent: patients with central nervous system cancer (CNS tumors) and hematological disorders, as well as boys <7 years are the most affected. WHAT IS KNOWN ALREADY Fertility preservation in pediatric male patients is considered based on the gonadotoxicity of selected treatments. Although treatment effects on germ cells have been extensively investigated, limited data are available on the effect of the disease on the prepubertal male gonad. Of the few studies investigating the effects of cancer or hematologic disorders on testicular function and germ cell quantity in prepuberty, the results are inconsistent. However, recent studies suggested impairments before the initiation of known gonadotoxic therapy. Understanding which diseases and at what age affect the germ cell pool in pediatric patients before treatment is critical to optimize strategies and counseling for fertility preservation. STUDY DESIGN, SIZE, DURATION This multicenter retrospective cohort study included 101 boys aged <14 years with extra-cerebral cancer (solid tumors), CNS tumors, leukemia/lymphoma (blood cancer), or non-malignant hematological disorders, who were admitted for a fertility preservation programme between 2002 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS In addition to clinical data, we analyzed measurements of testicular volume and performed histological staining on testicular biopsies obtained before treatment, at cryopreservation, to evaluate number of spermatogonia per tubular cross-section, tubular fertility index, and the most advanced germ cell type prior to chemo-/radiotherapy. The controls were data simulations with summary statistics from original studies reporting healthy prepubertal boys’ testes characteristics. MAIN RESULTS AND THE ROLE OF CHANCE Prepubertal patients with childhood cancer or hematological disorders were more likely to have significantly reduced spermatogonial quantity compared to healthy controls (48.5% versus 31.0% prevalence, respectively). The prevalence of patients with reduced spermatogonial quantity was highest in the CNS tumor (56.7%) and the hematological disorder (55.6%) groups, including patients with hydroxyurea pre-treated sickle cell disease (58.3%) and patients not exposed to hydroxyurea (50%). Disease also adversely impacted spermatogonial distribution and differentiation. Irrespective of disease, we observed the highest spermatogonial quantity reduction in patients <7 years of age. LIMITATIONS, REASONS FOR CAUTION For ethical reasons, we could not collect spermatogonial quantity data in healthy prepubertal boys as controls and thus deployed statistical simulation on data from literature. Also, our results should be interpreted considering low patient numbers per (sub)group. WIDER IMPLICATIONS OF THE FINDINGS Cancers, especially CNS tumors, and severe hematological disorders can affect spermatogonial quantity in prepubertal boys before treatment. Consequently, these patients may have a higher risk of depleted spermatogonia following therapies, resulting in persistent infertility. Therefore, patient counseling prior to disease treatment and timing of fertility preservation should not only be based on treatment regimes, but also on diagnoses and age. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Marie Curie Initial Training Network (ITN) (EU-FP7-PEOPLE-2013-ITN) funded by European Commision grant no. 603568; ZonMW Translational Adult stem cell research (TAS) grant no. 116003002. No competing interests. TRIAL REGISTRATION NUMBER N/A.

Preservation of fertility in patients with hematological malignancies

Article

May 2020
JPN J CLIN ONCOL

Oncofertility is the medical field that bridges oncology and reproduction that seeks to give healthcare providers and patients the opportunity to optimize residual fertility. The treatment for hematological malignancies carries gonadal toxicity, so that the preservation of fertility should be considered in all patients in childhood, adolescence and young adulthood. Most patients who receive only chemotherapy remain fertile, whereas those who receive regimens consisting of high-dose alkylating agents or total body irradiation can develop permanent infertility. In postpubertal patients, there are established methods for preserving fertility, such as the cryopreservation of sperm, oocytes and embryos. Although ideally performed before the initiation of gonadotoxic treatment, these procedures for fertility preservation can be performed any time prior to the loss of gonadal function. In contrast, a standard option is not available in prepubertal patients, and the preservation of fertility must be sought through experimental methods. Future advances in reproductive medicine may overcome this limitation. Gonadal tissue cryopreservation might be performed in the hope that sperm or mature oocytes could later be extracted from cryopreserved tissue. Healthcare providers, including hematologists, reproductive endocrinologists, nurses, clinical psychotherapists and embryologists, need to optimize the patient's fertility through shared decision-making while always remaining aware of the rapidly progressing developments in reproductive medicine.

Recovery from hypogonadism and male health in adult allogeneic stem cell transplantation

Article

Mar 2018

Objective: There is a substantial lack of data about men's health in adult allogeneic stem cell transplantation. Methods: We conducted prospective unicentric non-interventional clinical study on men's health with a follow-up time of one year. Results: Between 11/2013 and 12/2015, we were able to include 27 patients. AML was the most frequent underlying disease (25.9%), we mainly used intermediate intense conditioning protocols (77.8%). Erectile dysfunction, loss of libido and loss of efficiency were the most frequent symptoms of hypogonadism. At inclusion of the study hypogonadism was already frequent. Primary hypogonadism was found in eight cases (29.6%) and secondary hypogonadism in one case (3.7%). We did not observe hypogonadism 6 months after inpatient treatment anymore, but there might still be the impairment of fertility because of still rising FSH levels at the end of the observation period. There were no significant associations of hypogonadism with myeloablative conditioning or kind of donor. Interestingly, there is a significant association with nicotine abuse (p=0.049). Conclusions: On the whole, male hypogonadism was found in one-third of the patients who underwent allogeneic stem cell transplantation. This article is protected by copyright. All rights reserved.

5-Flourouracil-induced toxicity in both male and female reproductive systems: A narrative review

Article

Full-text available

Dec 2023
HUM EXP TOXICOL

The chemotherapeutic drug 5-flourouracil (5FU) is frequently used to treat a wide range of solid malignant tumors, such as colorectal, pancreatic, gastric, breast, and head and neck cancers. Its antitumoral effects are achieved by interfering with the synthesis of RNA and DNA and by inhibiting thymidylate synthase in both malignant and non-malignant cells. Therefore, it can be responsible for severe toxicities in crucial body organs, including heart, liver, kidney, and reproductive system. Given the fact that 5FU-induced reproductive toxicity may limit the clinical application of this drug, in this study, we aimed to discuss the main locations and mechanisms of the 5FU-induced reproductive toxicity. Initially, we discussed the impact of 5FU on the male reproductive system, which leads to damage of the seminiferous epithelial cells and the development of vacuoles in Sertoli cells. Although no noticeable changes occur at the histopathological level, there is a decrease in the weight of the prostate. Additionally, 5FU causes significant abnormalities in spermatogenesis, including germ cell shedding, spermatid halo formation, polynucleated giant cells, and decreased sperm count. Finally, in females, 5FU-induced reproductive toxicity is characterized by the presence of atretic secondary and antral follicles with reduced numbers of growing follicles, ovarian weight, and maturity impairment.

Fertility preservation and monitoring in adult patients diagnosed with lymphoma: consensus-based practical recommendations by the Fondazione Italiana Linfomi & Società Italiana della Riproduzione Umana

Article

Full-text available

Sep 2023

Introduction Fertility preservation (FP) and monitoring has considerable relevance in the multidisciplinary approach to cancer patients. In these consensus-based practical recommendations, the scientific societies Fondazione Italiana Linfomi (FIL) and Società Italiana della Riproduzione Umana (SIRU) reviewed the main aspects and identified the optimal paths which aim to preserve and monitor fertility in patients diagnosed with lymphoma at the different phases of the disease and during long-term survivorship. Methods For the Panel, eleven experts were selected for their expertise in research and clinical practice on onco-fertility and lymphoma. The Panel’s activity was supervised by a chairman. A series of rank-ordering key questions were proposed according to their clinical relevance and discussed among the Panel, focusing on patients diagnosed with non-Hodgkin’s lymphomas and Hodgkin lymphoma. Agreement among all the Panelists on the content and terminology of the statements was evaluated by a web-based questionnaire according to the Delphi methodology. Results From the literature review a total of 78 questions or sentences, divided into the 6 areas of interest, were identified. By applying the Gwet's AC, k was: Section 1: 0,934 (Very good); Section 2: 0,958 (Very good); Section 3: 0,863 (Very good); Section 4: 0,649 (Good); Section 5: 0,936 (Very good); Section 6 raw agreement 100%. Two rounds of Delphi allowed to provide the maximum agreement. All statements were newly discussed in a round robin way and confirmed for the drafting of the final recommendations. Discussion These recommendations would be useful for onco-hematologists, gynecologists, urologists, and general practice physicians who take care of young lymphoma patients to guarantee an evidence-based oncofertility assessment and treatment during the oncologic pathway.

Fertility preservation during oncological treatment

Article

Full-text available

Aug 2023

Zinc Oxide Nanoparticles and Cancer Chemotherapy: Helpful Tools for Enhancing Chemo-sensitivity and Reducing Side Effects?

Article

Full-text available

Aug 2023
BIOL TRACE ELEM RES

Cancer chemotherapy is still a serious challenge. Chemo-resistance and destructive side effects of chemotherapy drugs are the most critical limitations of chemotherapy. Chemo-resistance is the leading cause of chemotherapy failure. Chemo-resistance, which refers to the resistance of cancer cells to the anticancer effects of chemotherapy drugs, is caused by various reasons. Among the most important of these reasons is the increase in the efflux of chemotherapy drugs due to the rise in the expression and activity of ABC transporters, the weakening of apoptosis, and the strengthening of stemness. In the last decade, a significant number of studies focused on the application of nanotechnology in cancer treatment. Considering the anti-cancer properties of zinc, zinc oxide nanoparticles have received much attention in recent years. Some studies have indicated that zinc oxide nanoparticles can target the critical mechanisms of cancer chemo-resistance and enhance the effectiveness of chemotherapy drugs. These studies have shown that zinc oxide nanoparticles can reduce the activity of ABC transporters, increase DNA damage and apoptosis, and attenuate stemness in cancer cells, leading to enhanced chemo-sensitivity. Some other studies have also shown that zinc oxide nanoparticles in low doses can be helpful in minimizing the harmful side effects of chemotherapy drugs. In this article, after a brief overview of the mechanisms of chemo-resistance and anticancer effects of zinc, we will review all these studies in detail.

Effect of Malignancy on Semen Parameters

Article

Full-text available

Jun 2022

Purpose: We aimed to examine how various types of cancer, classified histologically, affect semen quality. Methods: The study group included 313 patients who were diagnosed with cancer and reached for a sperm cryopreservation before a gonadotoxic treatment (PG-Tx group). Their semen parameters were compared to those of two control groups: (a) individuals who attended a fertility investigation and were found to be above the limit of the lower reference value of the WHO 2010 manual (ARL group), and (b) fertile men, whose semen parameters were obtained from the dataset of the WHO 2020 manual. Results: Semen quality was significantly poorer in the PG-Tx group than in the ARL group. Differences included a 65.6% decrease in concentration, a 12.1% decrease in volume, a 72.7% decrease in total count, and a 33.0%, 22.2%, and 24.7% decrease in total motility, rapid motility, and progressive motility, respectively. Linear regression models comparing the PG-Tx and ARL groups revealed that the maximum reduction in total motility and concentration was in men with germ-cell tumors, whereas the minimum reduction was in hematological tumors. Similarly, all sperm quality parameters were significantly lower in the PG-Tx group than in the fertile-men group (p < 0.0001). Conclusions: While the effect of malignancy on semen parameters is debatable, we found that all examined types of cancer significantly impaired sperm quality parameters. Although the median of most semen parameters of patients with cancer were still in the normal WHO range, their fifth percentile, represents men with a delayed time to pregnancy.

Reproductive Issues in Long-Term Surviving Patients following Therapy for Hodgkin’s Disease in the Republic of North Macedonia: Risks of Infertility According to First-Line Treatment Regimens

Article

Full-text available

Mar 2022

Infertility as a consequence of therapy presents a high psychosocial burden for HL patients. In the cohort of our analyzed patients, within the post-ABVD surviving patients, alterations of the spermogram were documented in a total of 6.1% of the male patients and 5.4% of the female patients developed amenorrhea. On the other hand, within the subgroup of surviving patients following BEACOPP chemotherapy, 60% of the male patients manifested defects in their spermogram, and as high as 28.6% of the female survivors reported loss of their monthly cycle. It has been reported on several occasions that even prior to treatment, the sperm of HL patients manifests poorer quality characteristics when analyzed against control specimens from healthy male donors. The analyzed results in ABVD-treated male HL patients confirm ABVD to be a safe regimen for males of all age categories, as well as for female patients under the age of thirty. In women above the age of 30, the infertility risk rate is relatively low (14%), which leaves the decision of preserving fertility to themselves. For all BEACOPP-treated female, as well as male patients, a consult with a reproductive medicine specialist is warranted prior to therapy, due to the high infertility risk, and the final decision should be made on an individual basis.

Response-adapted omission of radiotherapy and comparison of consolidation chemotherapy in children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma (EuroNet-PHL-C1): a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial

Article

Full-text available

Dec 2021
LANCET ONCOL

Background Children and adolescents with intermediate-stage and advanced-stage classical Hodgkin lymphoma achieve an event-free survival at 5 years of about 90% after treatment with vincristine, etoposide, prednisone, and doxorubicin (OEPA) followed by cyclophosphamide, vincristine, prednisone, and procarbazine (COPP) and radiotherapy, but long-term treatment effects affect survival and quality of life. We aimed to investigate whether radiotherapy can be omitted in patients with morphological and metabolic adequate response to OEPA and whether modified consolidation chemotherapy reduces gonadotoxicity. Methods Our study was designed as a titration study with an open-label, embedded, multinational, non-inferiority, randomised controlled trial, and was carried out at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed intermediate-stage (treatment group 2) and advanced-stage (treatment group 3) classical Hodgkin lymphoma who were younger than 18 years and stratified according to risk using Ann Arbor disease stages IIAE, IIB, IIBE, IIIA, IIIAE, IIIB, IIIBE, and all stages IV (A, B, AE, and BE) were included in the study. Patients with early disease (treatment group 1) were excluded from this analysis. All patients were treated with two cycles of OEPA (1·5 mg/m² vincristine taken intravenously capped at 2 mg, on days 1, 8, and 15; 125 mg/m² etoposide taken intravenously on days 1–5; 60 mg/m² prednisone taken orally on days 1–15; and 40 mg/m² doxorubicin taken intravenously on days 1 and 15). Patients were randomly assigned to two (treatment group 2) or four (treatment group 3) cycles of COPP (500 mg/m² cyclophosphamide taken intravenously on days 1 and 8; 1·5 mg/m² vincristine taken intravenously capped at 2 mg, on days 1 and 8; 40 mg/m² prednisone taken orally on days 1 to 15; and 100 mg/m² procarbazine taken orally on days 1 to 15) or COPDAC, which was identical to COPP except that 250 mg/m² dacarbazine administered intravenously on days 1 to 3 replaced procarbazine. The method of randomisation (1:1) was minimisation with stochastic component and was centrally stratified by treatment group, country, trial sites, and sex. The primary endpoint was event-free survival, defined as time from treatment start until the first of the following events: death from any cause, progression or relapse of classical Hodgkin lymphoma, or occurrence of secondary malignancy. The primary objectives were maintaining 90% event-free survival at 5 years in patients with adequate response to OEPA treated without radiotherapy and to exclude a decrease of 8% in event-free survival at 5 years in the embedded COPDAC versus COPP randomisation to show non-inferiority of COPDAC. Efficacy analyses are reported per protocol and safety in the intention-to-treat population. The trial is registered with ClinicalTrials.gov (trial number NCT00433459) and EUDRACT (trial number 2006-000995-33), and is closed to recruitment. Findings Between Jan 31, 2007, and Jan 30, 2013, 2102 patients were recruited. 737 (35%) of the 2102 recruited patients were in treatment group 1 (early-stage disease) and were not included in our analysis. 1365 (65%) of the 2102 patients were in treatment group 2 (intermediate-stage disease; n=455) and treatment group 3 (advanced-stage disease; n=910). Of these 1365, 1287 (94%) patients (435 [34%] of 1287 in treatment group 2 and 852 [66%] of 1287 in treatment group 3) were included in the titration trial per-protocol analysis. 937 (69%) of 1365 patients were randomly assigned to COPP (n=471) or COPDAC (n=466) in the embedded trial. Median follow-up was 66·5 months (IQR 62·7–71·7). Of 1287 patients in the per-protocol group, 514 (40%) had an adequate response to treatment and were not treated with radiotherapy (215 [49%] of 435 in treatment group 2 and 299 [35%] of 852 in treatment group 3). 773 (60%) of 1287 patients with inadequate response were scheduled for radiotherapy (220 [51%] of 435 in the treatment group 2 and 553 [65%] of 852 in treatment group 3. In patients who responded adequately, event-free survival rates at 5 years were 90·1% (95% CI 87·5–92·7). event-free survival rates at 5 years in 892 patients who were randomly assigned to treatment and analysed per protocol were 89·9% (95% CI 87·1–92·8) for COPP (n=444) versus 86·1% (82·9–89·4) for COPDAC (n=448). The COPDAC minus COPP difference in event-free survival at 5 years was −3·7% (−8·0 to 0·6). The most common grade 3–4 adverse events (intention-to-treat population) were decreased haemoglobin (205 [15%] of 1365 patients during OEPA vs 37 [7%] of 528 treated with COPP vs 20 [2%] of 819 treated with COPDAC), decreased white blood cells (815 [60%] vs 231 [44%] vs 84 [10%]), and decreased neutrophils (1160 [85%] vs 223 [42%] vs 174 [21%]). One patient in treatment group 2 died of sepsis after the first cycle of OEPA; no other treatment-related deaths occurred. Interpretation Our results show that radiotherapy can be omitted in patients who adequately respond to treatment, when consolidated with COPP or COPDAC. COPDAC might be less effective, but is substantially less gonadotoxic than COPP. A high proportion of patients could therefore be spared radiotherapy, eventually reducing the late effects of treatment. With more refined criteria for response assessment, the number of patients who receive radiotherapy will be further decreased. Funding Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder Gießen, Kinderkrebsstiftung Mainz, Tour der Hoffnung, Menschen für Kinder, Programme Hospitalier de Recherche Clinique, and Cancer Research UK.

Fertility preservation in boys facing gonadotoxic cancer therapy

Article

Oct 2021

Patient survival following childhood cancer has increased with contemporary radiation and chemotherapy techniques. However, gonadotoxicity associated with treatments means that infertility is a common consequence in survivors. Novel fertility preservation options are emerging, but knowledge about these options amongst urologists and other medical professionals is lacking. Pre-pubertal boys generally do not produce haploid germ cells. Thus, strategies for fertility preservation require cryopreservation of tissue containing spermatogonial stem cells (SSCs). Few centres worldwide routinely offer this option and fertility restoration (including testicular tissue engraftment, autotransplantation of SSCs and in vitro maturation of SSCs to spermatozoa) post-thaw is experimental. In pubertal boys, the main option for fertility preservation is masturbation and cryopreservation of the ejaculate. Assisted ejaculation using penile vibratory stimulation or electroejaculation and surgical sperm retrieval can be used in a sequential manner after failed masturbation. Physicians should inform boys and parents about the gonadotoxic effects of cancer treatment and offer fertility preservation. Preclinical experience has identified challenges in pre-pubertal fertility preservation, but available options are expected to be successful when today’s pre-pubertal boys with cancer become adults. By contrast, fertility preservation in pubertal boys is clinically proven and should be offered to all patients undergoing cancer treatment.

Parenthood Rates and Use of Assisted Reproductive Techniques in Younger Hodgkin Lymphoma Survivors: A Danish Population-Based Study

Article

Jun 2021

PURPOSE The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care. MATERIALS AND METHODS All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use. RESULTS A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 v 57.1; P = .871 for males and 63.8 v 61.2; P = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 v 60.8; P = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% v 6.3%; P < .001; females 13.6% v 5.5%; P = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators. CONCLUSION The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.

Male and Female Fertility: Prevention and Monitoring Hodgkin’ Lymphoma and Diffuse Large B-Cell Lymphoma Adult Survivors. A Systematic Review by the Fondazione Italiana Linfomi

Article

Full-text available

Jun 2021

Background: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between the end of treatment and conception. Methods: MEDLINE, the Cochrane Library, and EMBASE were systematically searched up to September 2020 for published cohort, case-control, and cross-sectional studies on fertility issues. Results: Forty-five eligible studies were identified. Gonadotoxicity was related to sex, type and dosage of treatment, and, in females, to age. After receiving alkylating-agent-containing regimens, less than 30% of males recovered spermatogenesis, and 45% of females ≥30 years in age retained regular menstrual cycles. Sperm cryopreservation was offered to the majority of patients; sperm utilization resulted in a 33-61% pregnancy rate. After ovarian tissue transplantation, the spontaneous pregnancy and live birth rates were 38% and 23%; after IVF, the live birth rate was 38.4%. No data could be extracted on the utilization rate of cryopreserved mature oocytes. The results of studies on GnRH analogs are controversial; therefore, their use should not be considered an alternative to established cryopreservation techniques. Sperm count, FSH, and inhibin-B levels were appropriate measures to investigate male fertility; serum AMH levels and antral follicle count were the most appropriate markers for ovarian reserve. No data could be found regarding the optimal interval between the end of treatment and conception. Conclusions: The risk of infertility should be discussed with adult lymphoma patients at the time of diagnosis, and fertility preservation options should be proposed before first-line treatment with alkylating-agent-containing regimens.

Semen quality in non-Hodgkin lymphoma survivors: a monocentric retrospective study

Article

Full-text available

Nov 2020

STUDY QUESTION How is semen quality affected by treatment in survivors of non-Hodgkin lymphoma (NHL)? SUMMARY ANSWER Before cancer treatment, most NHL subjects were normozoospermic and, while standard first-line treatments seemed compatible with post-treatment recovery after 18 months, salvage therapy followed by haematopoietic stem cell transplant caused permanent damage to spermatogenesis in many cases, with 66% azoospermic subjects in the long term. WHAT IS KNOWN ALREADY Testicular function has been widely investigated in relation to the most common malignancies in men of reproductive age, such as testicular cancer and Hodgkin lymphoma, but NHL has been somewhat under-investigated. The available reports generally show a post-treatment worsening of semen parameters in NHL survivors, but they involved small caseloads or a subgroup of broader caseloads, and their results are not comparable. STUDY DESIGN, SIZE, DURATION We conducted a retrospective analysis of 222 subjects who attended our University Hospital Sperm Bank between 2002 and 2017 for sperm cryopreservation after a diagnosis of NHL. PARTICIPANTS/MATERIALS, SETTING, METHODS The study included 222 patients with NHL who underwent sperm cryopreservation before any antineoplastic treatment. Subjects with any comorbidity and/or other conditions interfering with sperm parameters were excluded. All patients underwent a careful medical history and physical examination at the time of sperm cryopreservation (T0) and had at least one follow-up visit at 6 (T6), 12 (T12), 18 (T18) and/or 24 months (T24) or more than 24 months (T > 24), with a median follow-up of 47.5 months (range 28–140 months). Fertility information was collected through the administration of a questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE Pre-treatment, more than 80% of NHL patients were normozoospermic and in 15.9% of cases had already fathered a child. Aggressive lymphomas were associated with worse baseline semen volume and total sperm number compared to indolent subtypes (P < 0.05). Post-treatment analyses showed that standard first-line treatments alone had a more favourable outcome than intensified regimens for semen parameters, with total sperm number returning to near-baseline values at 18 months (T0: 195.0 ± 189.8 versus T18: 113.4 ± 103.1, P = 0.278), and a 7.7% prevalence of azoospermia at 2 years. In this subgroup receiving standard first-line treatments, radiotherapy of the pelvis versus other ‘high’ sites (mediastinum, latero-cervical and axillary lymph nodes, etc.) was associated with an increased risk of developing post-treatment azoospermia (odds ratio 4.29, 95% CI 1.81–10.14; P = 0.001). Two-thirds of subjects who had relapsed or had disease progression after first-line treatment and then underwent salvage treatment ± haematopoietic stem cell transplant became azoospermic. Fertility data were available for 176 patients: 15.9% already had at least one child prior to the NHL diagnosis and 12.5% (22 patients) desired children after treatment. Fourteen patients achieved fatherhood: 12 through natural conception and two following ART. LIMITATIONS, REASONS FOR CAUTION The main limitations of the study are the lack of data on blood hormones for evaluation of testicular function as a whole and the non-compliance of several patients in attending follow-up visits at all time points, resulting in a reduced sample size for the treatment subgroup analyses. Furthermore, despite a good fertility questionnaire response rate (>80%), the low number of NHL survivors actively seeking fatherhood limits the generalization of results. WIDER IMPLICATIONS OF THE FINDINGS The increased survival of NHL patients of reproductive age makes it essential to focus on the testicular toxicity of the treatment. Sperm cryopreservation must be suggested before any treatment. Two years after first-line treatments, sperm number showed signs of recovery: this finding is of the utmost importance for oncofertility counselling, as it indicates that only a standard first-line chemotherapy in many patients may be compatible with at least a partial spermatogenesis recovery in the long term. Nonetheless, it is expected that up to 30% of subjects will require treatment intensification, which could result in permanent testicular damage; in such cases the use of banked semen might represent the patient’s best chance for future fertility. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a grant from the Italian Ministry of Education and Research (MIUR-PRIN 2015-2015XSNA83-002) and the ‘Sapienza’ University of Rome, Faculty of Medicine. The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Ethical Considerations in Therapeutic Clinical Trials Involving Novel Human Germline-Editing Technology

Article

Full-text available

Feb 2020

Much of the international community opposes editing the human germline. Yet, given enough experience to become better acquainted with strengths and limitations, prominent international figures are cautiously optimistic about using CRISPR-like novel technologies for clinical applications. Not only might such applications be morally (ethically) permissible, but clinical trials for therapeutic aims could be necessary. Here, we assess critical dimensions of early-phase trials deploying germline-editing technologies for "bench-to-bedside" translation. While assuming no overarching position favoring or opposing such research, our discussion primarily focuses on normative considerations. First, we evaluate the imperative of conducting trials to produce reliable, reproducible knowledge and advancement, if possible, for human diseases that are incurable and/or whose treatments are deficient. Second, we address complexities in assessing risk and potential-benefit profiles. Third, we review the moral foundations of trial participation through well-established and accepted bioethical principles: autonomy, nonmaleficence, beneficence, and distributive justice. Finally, we raise critical questions about the scope of regulatory authority and investigator and funder accountability for these applications that could have everlasting impacts.

Treatment of advanced stage classical Hodgkin lymphoma: a pathway through the maze

Article

Jan 2018

Fertility of adult in survivors of childhood Hodgkin lymphoma

Article

Jan 2018

Fertility preservation in Hodgkin’s lymphoma patients that undergo targeted molecular therapies: an important step forward from the chemotherapy era

Article

Full-text available

Jun 2018

In total, 80%-90% of Hodgkin's lymphoma (HL) patients are curable with combination chemoradiotherapy. Due to improvements in therapeutic strategies, 50% of all relapsed/refractory patients may undergo complete clinical responses and have long-term survival. Treatment options for HL are effective, but may have a negative impact on post-chemotherapy fertility. Thus, cryopreservation of semen prior to treatment is recommended for male patients. For female patients, assisted reproductive techniques (ART) consult and fertility preservation should be offered as a therapeutical option. In the last years, new targeted molecules have been available for HL treatment. These new drugs showed a high rate of overall responses in the setting of heavily pretreated patients, most of them in relapse after autologous stem cell transplantation, a group previously considered very poor risk. Up to 50% of patients have a complete response and an improved overall survival. Future studies will address the usefulness of novel molecules as a frontline therapy. Considering the high response and survival rates with monoclonal antibody-based therapeutics, fertility has become a concerning issue for long-term HL survivors. As progress has been made regarding ART, with the rigorous steps planned for HL patients, more survivors will become parents.

Adolescent and Young Adult Oncology, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

Article

Full-text available

Jan 2018

This selection from the NCCN Guidelines for Adolescent and Young Adult (AYA) Oncology focuses on treatment and management considerations for AYA patients with cancer. Compared with older adults with cancer, AYA patients have unique needs regarding treatment, fertility counseling, psychosocial and behavioral issues, and supportive care services. The complete version of the NCCN Guidelines for AYA Oncology addresses additional aspects of caring for AYA patients, including risk factors, screening, diagnosis, and survivorship.

High cytokine expression and reduced ovarian reserve in patients with Hodgkin lymphoma or non-Hodgkin lymphoma

Article

Jul 2016

Objective: To investigate the ovarian reserve in female lymphoma patients and the potential relationships with the cytokine network. Design: Age-matched control study. Setting: Women's university hospital. Patient(s): Seventy-three lymphoma patients (57 with classic Hodgkin lymphoma [HL] and 16 with non-Hodgkin lymphoma [NHL]), approaching our center for ovarian tissue cryopreservation (study group) were compared with 25 age-matched healthy volunteers (control group). Intervention(s): Measurements of antimüllerian hormone (AMH), soluble interleukin-2 receptor (SIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α) levels. Main outcome measure(s): The AMH and cytokine levels of the lymphoma patients and the healthy volunteers were compared. Correlations between AMH with SIL-2R, IL-6, and IL-8 levels were performed. Result(s): The AMH showed significant lower concentrations in lymphoma patients than in the control group. Higher significant concentrations in lymphoma patients than in control group were found for SIL-2R and IL-6. No differences were observed comparing HL and NHL groups and within the stages of HL group for AMH and all the cytokines analyzed. Finally, significant inverse correlations were observed in lymphoma patients between AMH and SIL-2R, IL-6, and IL-8 levels, but not with TNF-α levels. Positive correlations between SIL-2R with IL-6, and IL-6 with IL-8 were also shown. Conclusion(s): In patients with HL or NHL at baseline the cytokine network is particularly active and the ovarian reserve is reduced. A strong negative correlation between AMH and SIL-2R, IL-6, and IL-8 has been also evidenced.

Fertility preservation in patients undergoing gonadotoxic treatments: a Canadian Fertility and Andrology Society clinical practice guideline

Article

Dec 2023
REPROD BIOMED ONLINE

Application of interim PET-CT in first-line treatment decision-making for lymphoma中期PET-CT在淋巴瘤一线治疗决策中的应用

Article

Oct 2023

Recent advances in lymphoma treatment have significantly improved the survival of patients; however, the current approaches also have varying side effects. To overcome these, it is critical to implement individualized treatment according to the patient’s condition. Therefore, the early identification of high-risk groups and targeted treatment are important strategies for prolonging the survival time and improving the quality of life of patients. Interim positron emission tomography-computed tomography (PET-CT) has a high prognostic value, which can reflect chemosensitivity and identify patients for whom treatment may fail under this regimen. To date, many prospective clinical studies on interim PET (iPET)-adapted therapy have been conducted. In this review, we focus on the treatment strategies entailed in these studies, as well as the means and timing of iPET assessment, with the aim of exploring the efficacy and existing issues regarding iPET-adapted treatment. It is expected that the improved use of PET-CT examination can facilitate treatment decision-making to identify precise treatment options.

Gonadal Complications

Chapter

Feb 2017

Overview Improvements in cancer therapy over the past 50 years have allowed survivors of pediatric sarcomas and leukemias, and young adults with high‐grade lymphomas, Hodgkin disease, and testicular tumors to reach adulthood but suffer the long‐term consequences of those therapies. Alterations in gonadal function are frequent and distressing side effects of modern cancer therapy. Women face symptoms of premature ovarian failure, including menopause, sterility, and presumably accelerated osteoporosis and possible early heart disease. Men experience oligo‐azoospermia and subclinical Leydig cell dysfunction, leading to infertility and long‐term effects of “andropause” including decreased bone density, lean muscle mass, decreased libido, and increased risk of coronary artery disease. With recognition has come better documentation of the frequency and severity of these complications, more effective patient counseling, and innovative approaches to attenuate gonadal toxicity. Options include hormonal manipulation, selection of alternative treatments, and pretreatment cryopreservation of embryos or germ cells, but these choices must be offered pretherapy, and patients remain uninformed of potential loss of fertility or options to preserve it. As cancer therapies improve and the number of cancer survivors increases, the practicing oncologist must address these issues in a timely and sensitive manner.

Research Progress on the Correlation between Tumors and Male Reproductive Function

Article

Full-text available

Jan 2023

琨张

Gonadal Complications

Chapter

Oct 2022

Overview Anticancer therapies often cause alterations in gonadal function for both men and women, which can cause infertility. This chapter reviews the assessment of gonadal function in men and women, effects of specific anticancer therapies on gonadal function (including cytotoxic chemotherapy, targeted agents, and radiation), and pregnancy implications of select anticancer therapies. Protective measures for fertility preservation are discussed in detail, including standard of care modalities (sperm cryopreservation in men and embryo or oocyte cryopreservation in women) and experimental techniques.

Erkrankungs- und therapiebedingte Spätfolgen beim Hodgkin-LymphomDisease- and treatment-related late sequelae in Hodgkin lymphoma

Article

May 2022

Background Given the impressive long-term remission rates in recent years, current clinical research focuses on late sequelae beyond diagnosis and treatment of Hodgkin lymphoma (HL).Objectives Following treatment of HL, early recognition and treatment of late sequelae is important. Comprehensive care should also be offered to recovering patients in the follow-up phase.ResultsIn the long term, the general overall quality of life of HL patients and survivors is lower than in controls of the same age. The development of cancer-related fatigue (CRF), which can persist long after primary treatment, prevents long-term survivors from continuing their previous lives and returning to work. Other complications include the development of second malignant neoplasms (SMN), which represent a significant mortality risk for former patients. Organ toxicities include cardiac, pulmonary, and gonadal damage. The latter are particularly relevant for young survivors who have not yet completed family planning. Before initiating therapy, the patients should be informed about the possibility of fertility-preserving measures.Conclusion In view of persistent impairment of quality of life and the negative impact of CRF on the employment of former HL patients, models for targeted care during therapy and in the aftercare phase should urgently be further developed. Recent clinical trials in HL aim at balancing efficacy against acute and chronic sequelae.

ART in Male Cancer Patients Including Sperm Donation

Chapter

Jan 2022

Infertile male cancer survivors may benefit from the use of sperm cryopreserved before starting antineoplastic treatments or by attempting testicular sperm retrieval, if they did not bank sperm, or by using donor sperm.

Stellenwert der Radiotherapie bei Morbus Hodgkin in intermediären Stadien

Article

Dec 2021

Stellenwert der Radiotherapie bei Morbus Hodgkin in intermediären StadienRadiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): Ergebnisse der HD17-Studie (GHSG)A multicentre phase III trial

Article

Full-text available

Aug 2021

A Descriptive Study Exploring Semen Quality Among Indian Cancer Patients

Article

Apr 2021

Purpose: To descriptively explore semen quality among Indian men with various types of malignancies. We evaluated semen parameters of male patients referred to our hospital before commencing their cancer treatment. Methods: Four hundred sixty-one male patients who were within the age range of 15-50 years were recruited with diagnosed malignancies. Pre-treatment semen analyses were performed on these patients to collect data on the volume, sperm concentration, motility, and normal forms (morphology). These semen parameters were compared between cancer groups (testicular cancer, hematological cancer, and other cancers). Further comparisons were also drawn to World Health Organization (WHO) semen parameter levels (2010, fifth edition) for normal outcomes. Results: There were no notable variations observed in semen volume (mL) and progressive motility (%) between cancer groups. These parameters were within the WHO normal semen criteria. Differences in normal forms (%) between cancer groups were not observed either; however, they were marginally lower compared with the WHO criteria. Sperm concentration was evidently lower in testicular cancer 34 × 106/mL (IQR: 10.1-60 × 106/mL) compared with hematological cancers 66 × 106/mL (IQR: 23-84.21 × 106/mL) and other cancers (IQR: 27-86.3 × 106/mL). Testicular cancer patients also presented with the largest semen disorder diagnosis (Asthenozoospermia, Oligoasthenozoospermia, Oligozoospermia, and Azoospermia) compared with two other groups. Conclusion: Males with testicular cancer have shown to have lower semen quality between cancer groups and compared with WHO criteria, increasing their likelihood of them being infertile. This study further allows us to understand these outcomes, particularly in the Indian subpopulation, propagating changes in guidelines in oncofertility and medical counseling. Clinical Trials Registry-India number: CTRI/2020/09/027720.

PET-gestützte Behandlung des Morbus Hodgkin im frühen günstigen Stadium

Article

Oct 2020

Parameters associated with sperm quality prior to chemotherapy in lymphoma patients

Article

Aug 2020

Sperm quality in lymphoma patients may be reduced even prior to initiation of chemotherapy. The objective of this study was to examine the relationship between lymphoma prognostic factors and sperm quality prior to chemotherapy. A retrospective cohort study was conducted in a Hadassah Medical Center sperm bank and the Hematology department. The cohort included 101 Hodgkin's and 90 non‐Hodgkin's lymphoma patients that underwent sperm cryopreservation before chemotherapy between 1998 and 2015. Known lymphoma prognostic factors were compared between patients with normal and impaired sperm parameters. The Prognostic Score Ratio (PSR), an index representing the number of negative lymphoma prognostic measures that found in a lymphoma patient, was additionally calculated and compared between the groups. Among the prognostic factors of lymphoma, the following factors were found to be associated with impaired sperm parameters—low albumin (p < 0.001) and haemoglobin (p < 0.001) levels, B symptoms (p = 0.021) and PSR (p < 0.001). Logistic regression showed significant association of albumin and haemoglobin with reduced sperm quality (OR = 2.7 and OR = 13.5, p < 0.05; respectively). To conclude, low albumin and haemoglobin levels are related to reduced sperm quality. The linkage between these prognostic factors and sperm quality may be related to a general inflammatory status.

Novel aspects on gonadotoxicity and fertility preservation in lymphoproliferative neoplasms

Article

May 2020
CRIT REV ONCOL HEMAT

The topic of fertility preservation in patients with a lymphoproliferative disease offers new aspects of debate, due to the introduction of novel chemotherapeutic regimens and small molecules in the clinical landscape. Cancer related infertility is mostly dependent on gonadotoxic treatments and fertile female patients are today addressed to the oocyte cryopreservation or to ovarian cortex fragment cryopreservation. These methods present advantages and disadvantages, which will be discussed in the present review, together with the options for male patients. The recent discovery of functional ovarian stem cells (OCSs) in woman ovarian cortex, opens new avenues offering a innovative procedure for fertility preservation through as model of regenerative medicine. Here, we review the gonadotoxic potential of “classical” chemotherapeutic treatments as well as of “novel” targeted therapies actually employed for lymphoproliferative neoplasms in young patients and revisit both the today available and future chances to preserve and restore fertility after the cancer healing.

Gonadal Dysfunction and Fertility Preservation in Hodgkin Lymphoma Patients

Chapter

Mar 2020

Patients with Hodgkin lymphoma (HL) are generally young, and high cure rates can be achieved. Thus, HL diagnosis and therapy frequently occur at a time of life when family planning plays an important role. It is therefore of major importance for the patients to discuss this subject and to consider fertility preservation techniques as early as possible after diagnosis.

Use of antioxidant could ameliorate the negative impact of etoposide on human sperm DNA during chemotherapy

Article

Feb 2020
REPROD BIOMED ONLINE

Research question Infertility is a common adverse event in young patients with testicular tumors under cisplatin-based therapies. Tight, scheduled combined-therapies often make it impossible for patient semen cryopreservation. Current studies on the toxicity of these drugs are scarce with respect to etoposide. Additionally, to prevent gonadotoxicity, antioxidants such as N-acetylcysteine (NAC) have been employed as adjuvants. We have shown that when used after in vitro exposure to etoposide, NAC has the ability to decrease DNA damage in human sperm, with no benefit when used prior to exposure. However, in a clinical setting, the damage induced during chemotherapy may be so extensive that when the treatment ends, NAC may not be able to mitigate such damage, and therefore, we test here for concomitant use of NAC with etoposide in protecting human sperm in vitro. Design Twenty semen samples were submitted to four experimental conditions: control, NAC-only incubation, etoposide-only incubation, and concomitant etoposide and NAC incubation. After in vitro incubation, semen parameters, sperm chromatin condensation, sperm DNA fragmentation, sperm oxidative stress and sperm metabolism were used to evaluate the protective role of NAC in human sperm from the etoposide effect. Results Etoposide did not affect semen parameters, nor did it cause sperm oxidative damage or alterations in glycolytic profile. However, it induced chromatin decondensation and DNA fragmentation, which were fully prevented by NAC. Conclusions NAC was able to protect sperm DNA integrity during etoposide treatment in vitro, suggesting that NAC may be useful as an adjuvant agent in preserving male fertility during chemotherapy treatments.

Multicenter cooperative prospectiveretrospective observational program for diagnostics and treatment of Hodgkin disease in the North-Western District of Russian Federation (RNWOHG-HD1 Protocol, the full-text version in Russian)

Article

Dec 2017

Multicenter prospective escalation-deescalation PET-guided clinical study in classical type Hodgkin disease in the North-West of Russian Federation (RNWOHG-HD1): rationale and design

Article

Dec 2017

Currently there is no established standard of care for Hodgkin’s disease (HD) in Russian Federation (RF). The mortality from HD in RF is 28,3%, thus improvement of care is required. Here we describe the design and the rational for the first cooperative prospective study in the Nort-West region of RF, RNWOHG-HD1. The key points of the protocol are discussed, including escalation from ABVD to BEACOPPesc in case of PET-positive disease after first two cycles in the favorable prognosis group, and de-escalation to randomized ABVD/AVD in case of PET(-) status after first two BEACOPPesc courses in the unfavorable prognosis group. The protocol also is planned to facilitate access to second and third line treatments, including brentuximab, as well as autologous and allogeneic stem cell transplantation. © 2017, Universitatsklinikum Hamburg - Eppendorf. All rights reserved.

Clinical Features of Hodgkin Lymphoma

Chapter

Jan 2018

Stephen M. Ansell

Hodgkin lymphoma patients typically present with lymphadenopathy that involves lymph node sites in a contiguous fashion, while extranodal sites of disease are less common. Systemic symptoms including fevers, drenching night sweats, weight loss, and pruritus may be present at diagnosis. A comprehensive clinical evaluation is important prior to therapy to confirm the stage of disease, identify adverse prognostic factors and anticipate complications due to comorbid conditions. Information gleaned from the careful assessment of the patient, and from radiological and laboratory testing, will allow for an appropriate selection of therapy. Imaging studies, particularly the use of PET scans, are an important part of this initial clinical evaluation but are also critical during and after therapy to evaluate response for prognostic purposes. Because the outcome of Hodgkin lymphoma patients is usually good and many patients may be cured, long-term follow-up of patients is necessary to detect and manage potential complications of therapy.

FDA-approved drugs that are spermatotoxic in animals and the utility of animal testing for human risk prediction

Article

Full-text available

Feb 2018
J ASSIST REPROD GEN

Purpose: This study reviews FDA-approved drugs that negatively impact spermatozoa in animals, as well as how these findings reflect on observations in human male gametes. Methods: The FDA drug warning labels included in the DailyMed database and the peer-reviewed literature in the PubMed database were searched for information to identify single-ingredient, FDA-approved prescription drugs with spermatotoxic effects. Results: A total of 235 unique, single-ingredient, FDA-approved drugs reported to be spermatotoxic in animals were identified in the drug labels. Forty-nine of these had documented negative effects on humans in either the drug label or literature, while 31 had no effect or a positive impact on human sperm. For the other 155 drugs that were spermatotoxic in animals, no human data was available. Conclusion: The current animal models are not very effective for predicting human spermatotoxicity, and there is limited information available about the impact of many drugs on human spermatozoa. New approaches should be designed that more accurately reflect the findings in men, including more studies on human sperm in vitro and studies using other systems (ex vivo tissue culture, xenograft models, in silico studies, etc.). In addition, the present data is often incomplete or reported in a manner that prevents interpretation of their clinical relevance. Changes should be made to the requirements for pre-clinical testing, drug surveillance, and the warning labels of drugs to ensure that the potential risks to human fertility are clearly indicated.

Influence radio and chemotherapy cancer patients to development of male infertility (Literature review)

Article

Dec 2016

I.T. Gavrysh

The questions that reflect the pathogenesis of disorders under the influence of radiation and chemotherapy on spermatogenesis considered dose effects resulting from the course of treatment, a group of drugs used for chemotherapy protection principles reflected spermatogenesis in cancer patients and methods of recovery. Actuality further research. © 2016 National Research Center for Radiation Medicine. All rights reserved.

Comparison of first-line chemotherapy including escalated BEACOPP versus chemotherapy including ABVD for people with early unfavourable or advanced stage Hodgkin lymphoma

Article

May 2017

Background: There are two different international standards for the treatment of early unfavourable and advanced stage Hodgkin lymphoma (HL): chemotherapy with escalated BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone) regimen and chemotherapy with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) regimen. Objectives: To determine the advantages and disadvantages of chemotherapy including escalated BEACOPP compared to chemotherapy including ABVD in the treatment of early unfavourable or advanced stage HL as first-line treatment. Search methods: We searched for randomised controlled trials in MEDLINE, CENTRAL and conference proceedings (January 1985 to July 2013 and for the update to March 2017) and Embase (1985 to November 2008). Moreover we searched trial registries (March 2017; www.controlled-trials.com, www.clinicaltrialsregister.eu/ctr-search/search, clinicaltrials.gov, www.eortc.be, www.ghsg.org, www.ctc.usyd.edu.au, www.trialscentral.org/index.html) SELECTION CRITERIA: We included randomised controlled trials examining chemotherapy including at least two cycles of escalated BEACOPP regimens compared with chemotherapy including at least four cycles of ABVD regimens as first-line treatment for patients with early unfavourable stage or advanced stage HL. Data collection and analysis: The effect measures we used were hazard ratios (HRs) for overall survival (OS), progression-free survival (PFS) and freedom from first progression.We used risk ratios (RRs) relative risks to analyse harms: treatment-related mortality, secondary malignancies (including myeloid dysplastic syndrome (MDS) or acute myeloid leukaemia (AML)), infertility and adverse events.Quality of life was not reported in any trial, therefore not analysed. Two review authors independently extracted data and assessed quality of trials. Main results: We screened 1796 records and identified five eligible trials in total i.e. one trial could be added on the previous review. These trials included only adults (16 to 65 years of age). We included all five trials with 3427 people in the meta-analyses: the HD9 and HD14 trials were co-ordinated in Germany, the HD2000 and GSM-HD trials were performed in Italy and the EORTC 20012 was conducted in Belgium. The overall risk of performance and detection bias was low for overall survival (OS), but was high for other outcomes, as therapy blinding was not feasible. The remaining 'Risk of bias' domains were low and unclear.All trials reported results for OS and progression-free survival (PFS). In contrast to the our first published review (2011) the addition of results from the EORTC 20012 BEACOPP escalated increases OS (3142 participants; HR 0.74 (95% confidence interval (CI) 0.57 to 0.97; high-quality evidence). This means that only 90 (70 to 117) patients will die after five years in the BEACOPP escalated arm compared to 120 in the ABVD arm. This survival advantage is also reflected in an increased PFS with BEACOPP escalated (3142 participants; HR 0.54 (95% CI 0.45 to 0.64); moderate-quality evidence), meaning that after five years only 144 (121 to 168) patients will experience a progress, relapse or death in the BEACOPP escalated arm compared to 250 in the ABVD arm.There is no evidence for a difference for treatment-related mortality (2700 participants, RR 2.15 (95% CI = 0.93 to 4.95), low-quality evidence).Although the occurrence of MDS or AML may increase with BEACOPP escalated (3332 participants, RR 3.90 (95% CI 1.36 to 11.21); low-quality evidence)), there is no evidence for a difference between both regimens for overall secondary malignancies (3332 participants, RR 1.00 (95% CI 0.68 to 1.48), low-quality evidence). However, the observation time of the studies included in the review is too short to be expected to demonstrate differences with respect to second solid tumours which would not be expected to show significance until around 15 years after treatment.We are very uncertain how many female patients will be infertile due to chemotherapy and which arm might be favoured (106 participants, RR 1.37 (95% CI 0.83 to 2.26), very low-quality evidence). This is a very small sample, and the age of the patients was not detailed. No analysis of male fertility was provided.Five trials reported adverse events and the analysis shows that the escalated BEACOPP regimens probably causes more haematological toxicities WHO grade III or IV ((anaemia: 2425 participants, RR 10.67 (95% CI 7.14 to 15.93); neutropenia: 519 participants, RR 1.80 (95% CI 1.52 to 2.13); thrombocytopenia: 2425 participants, RR 18.12 (95% CI 11.77 to 27.92); infections: 2425 participants, RR 3.73 (95% CI 2.58 to 5.38), all low-quality evidence).Only one trial (EORTC 20012) planned to assess quality of life, however, no results were reported. Authors' conclusions: This meta-analysis provides moderate- to high-quality evidence that adult patients between 16 and 60 years of age with early unfavourable and advanced stage HL benefit regarding OS and PFS from first-line chemotherapy including escalated BEACOPP. The proven benefit in OS for patients with advanced HL is a new finding of this updated review due to the inclusion of the results from the EORTC 20012 trial. Furthermore, there is only low-quality evidence of a difference in the total number of secondary malignancies, as the follow-up period might be too short to detect meaningful differences. Low-quality evidence also suggests that people treated with escalated BEACOPP may have a higher risk to develop secondary AML or MDS. Due to the availability of only very low-quality evidence available, we are unable to come to a conclusion in terms of infertility. This review does for the first time suggest a survival benefit. However, it is clear from this review that BEACOPP escalated may be more toxic that ABVD, and very important long-term side effects of second malignancies and infertility have not been sufficiently analysed yet.

Hodgkin lymphoma

Chapter

Apr 2017

Robert Chen

A 52-year-old male patient presented to a primary care office with shortness of breath and a nonproductive cough of 3 months’ duration. In addition, he had also noticed fever, chills, and night sweats for the past 2 months.

Male Hypogonadism Due to Cancer and Cancer Treatments

Chapter

Apr 2017

Survival rates after cancer treatment have increased dramatically in recent decades, resulting in an increasing focus on the harmful effects of cancer treatment for these patients. One of the major long-term effects of cancer and its treatment is compromised reproductive function in both males and females. These effects may occur as a result of direct effects on the gonad or indirect effects via damage to the hypothalamus or pituitary. In males, there may be impairment of testicular function prior to the commencement of treatment while the direct effects of exposure to cytotoxic therapies may also damage the seminiferous epithelium leading to oligo- or azoospermia. In addition to effects on the germ cells, Leydig cell dysfunction may occur, resulting in impaired testosterone production. This chapter describes the effects of cancer and its treatment on male reproductive function in terms of damage to the seminiferous epithelium and testosterone production. We also discuss the options, both established and experimental, for fertility preservation in these patients.

Response to ovarian stimulation is not impacted by a breast cancer diagnosis

Article

Jan 2017
HUM REPROD

Study question: Does a breast cancer diagnosis impact ovarian function in the setting of fertility preservation? Summary answer: Ovarian reserve and ovarian stimulation outcomes are similar in patients with a new diagnosis of breast cancer and patients undergoing elective fertility preservation. What is known already: Prior studies, with small study populations, lack of controlling for individual differences in ovarian reserve and infertile controls, have reported conflicting outcomes for cancer patients undergoing ovarian stimulation for fertility preservation. Study design, size, duration: This retrospective cohort analysis included 589 patients undergoing ovarian stimulation for fertility preservation between 2009 and 2015. Participants/materials, setting, methods: Women with a recent breast cancer diagnosis (n = 191) and women desiring elective fertility preservation (n = 398) underwent ovarian stimulation with an antagonist protocol at an academic medical center. The aromatase inhibitor letrozole was administered to breast cancer patients with estrogen-sensitive disease. Main results and the role of chance: Baseline antral follicle count (AFC) was not different between the breast cancer patients and controls (15.4 ± 10.4 [mean ± SD] vs 15.4 ± 10.0, P = NS), even after categorization by age. Total (19.4 ± 0.9 [mean ± SEM] vs 17.0 ± 0.5, P = NS) and mature (MII) oocytes retrieved (13.7 ± 0.7 vs 13.2 ± 0.4, P = NS), adjusted for age, BMI and total gonadotropin dose, were also similar between the two groups. Letrozole use was associated with a decreased maturity rate (MII/total oocytes retrieved) compared to elective cryopreservation (0.71 ± 0.01 vs 0.77 ± 0.01, P < 0.001), although the mature oocyte yield [MII/AFC] was comparable (1.01 ± 0.06 vs 0.93 ± 0.03, P = NS). Limitations, reasons for caution: The single center design may impact generalizability. Additionally, the lack of subsequent embryo and pregnancy data is an inherent weakness. Wider implications of the findings: In females, a breast cancer diagnosis does not impact gonadal function as measured by AFC or ovarian stimulation outcomes. Breast cancer patients should be counseled that their response to ovarian stimulation for fertility preservation is similar to that of patients undergoing elective oocyte cryopreservation. Study funding/competing interests: None. Trial registration number: N/A.

New therapy outlooks in Hodgkin lymphoma

Article

Jan 2017
B CANCER

Classical Hodgkin lymphoma (HL) is a curable disease in 80% of advanced and 90% of localized stages. An improvement of the HL curability is still possible with the emergence of first-line therapy with a better balance between efficacy and toxicity and early identification patients with high risk of failure requiring specific treatment. 18FDG PET-CT gained a major role in the baseline staging and response assessment to HL treatment. The prognostic value of early PET-CT allowed to develop PET-CT guided therapies able to optimize the balance between efficacy and toxicity including the modulation of the chemotherapy intensity or the omission of radiotherapy for some localized diseases. New drugs emerged in the treatment of relapse or refractory HL (brentuximab vedotine [BV], immunological checkpoint inhibitor anti-PD1). Although their place in the strategies of salvage therapy is still debated several trials have reported relevant efficacy in some unmet medical need: refractory patients or relapses after auto/allograft. This review addresses the questions of PET-CT-based therapeutic strategies in first-line and the impact of new drugs targeting the micro-environment (anti-PD1) or the Hodgkin Reed Sternberg cells (BV). Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Increased healthcare use up to 10 years among relapse-free Hodgkin lymphoma survivors in the era of intensified chemotherapy and limited radiotherapy

Article

Dec 2016
AM J HEMATOL

With today's excellent cure rates for Hodgkin lymphoma (HL), the number of long-term survivors is increasing. This study aims to provide a global assessment of late adverse effects for working-age HL survivors treated with contemporary protocols (combination chemotherapy and limited radiotherapy). From Swedish nationwide registers we identified 1017 HL survivors diagnosed in 2000-2009, aged 18-60 years (median 32) and surviving at least one year post-diagnosis, and 4031 age-, sex- and calendar-year-matched population comparators. Incidence rate ratios (IRR) and 95% confidence intervals (95%CI) for outpatient visits and inpatient bed-days after the first year up to 14 years post-diagnosis (through 2013) were estimated across treatment subgroups, considering relapse-free time and using negative binomial regression. Scheduled outpatient visits for HL were excluded. The rate of outpatient visits was nearly double (IRR=1.8, 95%CI:1.6-2.0) that among comparators and higher rates persisted up to 10 years post-diagnosis. The rate of inpatient bed-days among relapse-free survivors was more than three-fold (IRR=3.6, 95%CI:2.7-4.7) that of comparators and the increase persisted up to four years post-diagnosis. Patients requiring 6-8 chemotherapy courses had higher rates of outpatient visits (IRR=1.4, 95%CI:1.1-1.7) and bed-days (IRR=4.7, 95%CI:2.9-7.8) than patients treated with 2-4 courses+radiotherapy. Previously seldom reported reasons for the excess healthcare use included chest pain, keratitis, asthma, diabetes mellitus and depression. Contemporary treatment, chemotherapy in particular, was associated with excess healthcare use among HL survivors during the first decade post-diagnosis. The reasons for healthcare visits reflected a wide range of disorders, indicating the need of broad individualized care in addition to specific screening programs. This article is protected by copyright. All rights reserved.

Late endocrine effects of cancer and cancer therapies in survivors of childhood malignancies

Article

Mar 2016

The development of several cancer treatment modalities including surgery, radiotherapy and chemotherapy has improved the survival rates of childhood cancers over recent decades, leading to an increase in the population of childhood cancer survivors. Detailed epidemiological studies have demonstrated that childhood cancer survivors frequently develop medical complications months or years after cancer treatment. Endocrine complications are common in survivors, particularly those exposed to radiotherapy, total body irradiation and alkylating agents, and may involve dysfunction of the hypothalamic-pituitary axes, gonads, thyroid gland, bone and body composition as well as metabolic abnormalities. Early identification and proper management of these disorders can significantly improve the quality of life and reduce the morbidity and potentially mortality in this population. Multidisciplinary teams, expert physicians and the development of healthcare structures are key elements for improving the screening, surveillance, cost effectiveness and overall management of endocrine late effects of cancer therapies in childhood cancer survivors. The aim of the present review was to discuss the most important and common late endocrine effects of childhood cancer treatment.

Minimal Treatment of Low-Risk, Pediatric Lymphocyte-Predominant Hodgkin Lymphoma: A Report From the Children's Oncology Group

Article

Full-text available

May 2016

Purpose: Children's Oncology Group study AHOD03P1 was designed to determine whether excellent outcomes can be maintained for patients with low-risk, pediatric lymphocyte-predominant Hodgkin lymphoma (LPHL) with a strategy of resection alone or minimal chemotherapy. Patients and methods: Patients with stage IA LPHL in a single node that was completely resected were observed without further therapy; recurrences were treated with three cycles of doxorubicin/vincristine/prednisone/cyclophosphamide (AV-PC). Patients with unresected stage IA or stage IIA LPHL were treated with three cycles of AV-PC. Patients with less than a complete response (CR) to AV-PC received 21-Gy involved-field radiation therapy (IFRT). Results: A total of 183 eligible patients were enrolled; 178 were evaluable. Of these, 52 patients underwent complete resection of a single node. There were 13 relapses at a median of 11.5 months; 5-year event-free survival (EFS) was 77% (range, 62% to 87%). A total of 135 patients received AV-PC; 126 were treated at diagnosis and nine at relapse after surgery alone. Eleven patients receiving AV-PC had less than CR and received IFRT. Fourteen first events occurred among 135 patients (12 relapses and two second malignancies). Two relapses occurred in patients who had received IFRT. Five-year EFS was 88.8% (95% CI, 81.8% to 93.2%). Five-year EFS for the entire cohort was 85.5% (95% CI, 79.2% to 90.1%); overall survival was 100%. Conclusion: Some 75% of highly selected pediatric patients with LPHL may be spared chemotherapy after surgical resection alone. Pediatric LPHL has excellent EFS with chemotherapy that is less intensive than standard regimens; > 90% of patients can avoid radiation therapy. The salvage rate for the few relapses is high, with 100% survival overall.

Semen cryopreservation and artificial insemination for Hodgkin's disease

Article

Full-text available

Mar 1987

Seventy-nine men with Hodgkin's disease were treated with chemotherapy protocols at Memorial Sloan-Kettering Cancer Center and had pretreatment semen analysis performed at the area semen bank. The patients were evaluated to determine: the quality of pretreatment semen, the effect of treatment on spermatogenesis, and the success rate of artificial insemination after semen cryopreservation. Pretreatment sperm concentration, fresh motility, fresh progression, postthaw motility and postthaw progression were all significantly decreased in men with Hodgkin's disease compared with normal controls. Posttreatment semen analysis in 44 men showed azoospermia in 80%, sperm concentration, less than or equal to 10 X 10(6)/mL in 11%, and sperm concentration greater than 10 X 10(6)/mL in 9%. Eleven couples attempted artificial insemination using cryopreserved semen, thus far resulting in three pregnancies. Semen cryopreservation and artificial insemination offer a partial solution to posttreatment azoospermia in this population, but further methods are needed to minimize gonadal toxicity without compromising therapy for Hodgkin's disease.

The management of Hodgkin's disease: Half a century of change: The Kaplan Memorial Lecture

Article

Full-text available

Sep 1996

S A Rosenberg

The results of treating more than 2600 patients with Hodgkin's disease at Stanford over a 35-year period are summarized. It is now a reality that Hodgkin's disease can be cured with initial treatment programs in virtually all patients, except the elderly. Histologic factors, staging methods, and prognostic groups are becoming less and less relevant. The current protocols used at Stanford and elsewhere will be reviewed to emphasize that combined modality is really the key to improving the cure rate and minimizing late complications.

Seminal cytokine concentrations (IL-1??, IL-2, IL-6, sR IL-2, sR IL-6), semen parameters and blood hormonal status in male infertility

Article

Full-text available

Aug 1997

Several lines of evidence indicate that cyokines are involved in male fertility. They are secreted by different parts of the male genital tract and may exert effects on steroidogenesis, spermatogenesis and sperm functions. We measured the concentrations of interleukins (IL-beta, IL-2, IL-6) and those of interleukin soluble receptors (sR IL-2, SR IL-6) in semen of fertile subjects (n = 21) and of patients with a range of andrological diseases (n = 119). The seminal concentrations of cytokines were analysed according to semen parameters as well as to the blood hormonal profiles of follicle stimulating hormone, luteinizing hormone and testosterone. An increase of IL-1beta was observed in the group of patients with infertility. No difference was found between the different subgroups defined on the basis of progressive motility, percentage of abnormal forms and diagnosis of infection. The seminal cytokine concentrations were independent of the blood hormonal status. Our data suggest that the determination of interleukins (-1beta, -2 and -6) or interleukin soluble receptors (sR IL-2, sR IL-6) in human spermatozoa does not provide convenient information in male routine infertility work-up.

Male gonadal dysfunction in patients with Hodgkin's disease prior to treatment

Article

Full-text available

Sep 2001

Infertility after treatment of patients with Hodgkin's disease (HD) is considered as a side effect of alkylating agent containing chemotherapy regimens. To investigate whether gonadal failure is related primarily to the toxic effect of chemotherapy or rather to the disease itself, we investigated the fertility status before the onset of treatment. Semen quality and hormonal status were evaluated in 158 patients with first diagnosis of HD enrolled into trials of the German Hodgkin Lymphoma Study Group (GHSG). The median age of the patients was 28 years (range 16-52). Twenty patients (13%) were classified as early stage HD, 63 patients (40%) as intermediate stage, and 75 patients (47%)) as advanced stage according GHSG grading. Sixty-seven patients (42%) showed systemic symptoms. Semen analysis was performed according to WHO guidelines. Follicle-stimulating hormone (FSH) and luteinising hormone (LH) plasma levels were measured by specific double-antibody radio-immune-assay (RIA) methods. Prior to treatment, severe damage of fertility, i.e.. azoospermia and oligoasthenoteratospermia (OAT-syndrome) was found in 13 (8%) and 20 patients (13%), respectively. Thirty-eight patients (24%) had single, i.e., oligo-(O), astheno-(A) or teratospermia-(T), and 40 patients (26%) showed combined damages, i.e., OA, OT or AT. In 47 patients (30%) a normal sperm count was found. Thus, III patients (70%) showed semen abnormalities before the onset of treatment. In a multivariate analysis elevated ESR (P < 0.003) and advanced stage of disease (P < 0.01) could be distinguished as prognostic factors for severe damage of fertility. No correlation was found between pre-therapeutic gonadotropine levels and fertility status. Patients with HD have an increased risk for inadequate semen quality even prior to treatment. Infertility is more frequent in patients with elevated ESR and advanced stage of disease. This association demonstrates the predominant influence of the disease on fertility. Assuming HD is the major initial cause for infertility efforts should be made to identify new non-gonadal toxic chemotherapies to be able to regain fertility after effective therapy. Further investigations have to be performed to clarify mechanisms inducing fertility defects in patients with HD.

ABVD Plus Subtotal Nodal Versus Involved-Field Radiotherapy in Early-Stage Hodgkin's Disease: Long-Term Results

Article

Full-text available

Aug 2004

Radiation therapy (RT) alone can cure more than 80% of all patients with pathologic stage IA, IB, and IIA Hodgkin's disease, but some prognostic factors unfavorably affect treatment outcome. Combined-modality approaches improved results compared with RT, but the optimal extent of RT fields when combined with chemotherapy warranted additional evaluation. In February 1990, we activated a prospective trial in patients with early, clinically staged Hodgkin's disease to assess efficacy and tolerability of four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by either subtotal nodal plus spleen irradiation (STNI) or involved-field radiotherapy (IFRT). Main patient characteristics were fairly well balanced between the two arms. Complete remission was achieved in 100% and in 97% of patients, respectively. The 12-year freedom from progression rates were 93% (95% CI, 83% to 100%) after ABVD and STNI, and 94% (95% CI, 88% to 100%) after ABVD and IFRT, whereas the figures for overall survival were 96% (95% CI, 91% to 100%) and 94% (95% CI, 89% to 100%), respectively. Apart from three patients who developed second malignancies in the STNI arm, treatment-related morbidities were mild. Present long-term findings suggest that, after four cycles of ABVD, IFRT can achieve a worthwhile outcome. The limited size of our patient sample, however, had no adequate statistical power to test for noninferiority of IFRT versus STNI. Despite this, ABVD followed by IFRT can be considered an effective and safe modality in early Hodgkin's disease with both favorable and unfavorable presentation.

Decline in Semen Quality Among Fertile Men in Paris During the Past 20 Years

Article

Oct 1995

Gonadal function following chemotherapy for Hodgkin's disease: a comparative study of MVPP and a seven-drug hybrid regimen.

Article

Jan 1995

PURPOSE AND METHODS Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy.RESULTSSemen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular ...

Empehlungen zur Nomenkdatur in der Andrologie

Article

Male Gonadal Dysfunction in Hodgkin's Disease

Article

Apr 1981

Ramona M. Chapman

Forty-seven men (median age, 31.5 years) were studied prospectively to assess the effect of Hodgkin's disease and subsequent chemotherapy on gonadal function. Before therapy, 16 (43%) of 37 men were functionally subfertile, as assessed by impotence (four of 37) and "inadequate" sperm counts (12 of 37). Histological abnormalities were noted in eight of nine pretreatment testicular biopsy specimens. Additionally, changes were noted in blood hormone levels and libido. After completion of only two cycles of chemotherapy, 14 of 14 men became persistently azoospermic, with blood follicle-stimulating hormone levels four to five times normal. Posttreatment testicular biopsy specimens confirmed germ cell aplasia. During therapy 17 (81%) of 21 men had mild or no libido; irritability in 16 (84%) of 19 and violence in four (18%) of 22 caused additional family distress. While it is clear that cytotoxic therapy induces infertility, these data further indicate that a proportion of men have gonadal dysfunction prior to treatment. (JAMA 1981;245:1323-1328)

Long-term gonadal dysfunction and its impact on bone mineralization in patients following COPP/ABVD chemotherapy for Hodgkin's disease

Article

Oct 1992

Only limited data is currently available on long-term gonadal toxicity and its impact on bone mineralization in men and women treated for Hodgkin's disease. The present study was therefore conducted to evaluate gonadal toxicity and bone loss in 49 patients with Hodgkin's disease 2-10 (median 5.37) years after chemotherapy. Most patients were treated with the COPP/ABVD regimen +/- irradiation according to the protocols of the German Hodgkin Study Group. Blood samples were tested for gonadotropins (FSH, LH), gonadal steroids, parathyroid hormone, osteocalcin, and calcitonin. Bone mineral density was measured using single- and dual-energy quantitative computed tomography as well as single-photon absorptiometry. FSH serum levels were significantly increased in 21/27 (80%) men demonstrating germ-cell aplasia. 13/15 (86%) men showed azoospermia after the COPP/ABVD regimen. In contrast, testosterone levels were within normal limits in all men tested, suggesting normal Leydig-cell function. 17/22 (77%) women exhibited increased FSH and LH levels, indicating premature ovarian failure. Women with therapy-induced ovarian failure had a significantly lower trabecular (98 +/- 34) and cortical (292 +/- 48 mg/cm3) spinal bone density than those with normal ovarian function. Men showed no evidence of bone loss after therapy. These data suggest severe gonadal toxicity in both men and women treated with the COPP/ABVD regimen. In female patients, drug-induced ovarian failure has a significant impact on bone mineralization.

Testicular dysfunction in Hodgkin’s disease before and after treatment

Article

Feb 1991
EUR J CANCER

Over a 7-year period, semen analysis was performed in 92 male patients with Hodgkin's disease prior to therapy. In 67% of patients semen revealed a decreased chance for fertility (i.e. oligozoospermia, asthenozoospermia and/or teratozoospermia). The mean basal levels of follicle-stimulating hormone (FSH), luteinising hormone, testosterone and prolactin were in the normal range. In 77 patients in complete remission after alternating MOPP/ABVD (mechlorethamine, vincristine, procarbazine, prednisone; doxorubicin, bleomycin, vinblastine, dacarbazine), testicular function was assessed. 87% of patients were azoospermic, 9% had semen abnormalities and only 4% were normospermic. Recovery of spermatogenesis was documented in only 17 of 42 (40%) reassessed patients after a median time of 27 months and was generally not affected by pretreatment sperm quality. After chemotherapy, the mean value of FSH [20.45 (S.E. 1.7) mUI/ml] was significantly superior compared with that of the mean pretreatment values. No difference was documented in the mean testosterone and prolactin values tested before and after treatment. Our findings indicate that, of patients with Hodgkin's disease, about half are affected by hypogonadism before starting chemotherapy. By utilising alternating MOPP/ABVD, persistent testicular dysfunction was documented in half of the patients.

The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence

Article

Apr 1990

Testicular function was evaluated in 75 boys after treatment for Hodgkin's disease with involved-field or extended-field irradiation and stage-dependent chemotherapy (vincristine, prednisone, procarbazine, Adriamycin [doxorubicin], and cyclophosphamide [OPPA/COPP]). Although pubertal development and testosterone levels were normal in all patients, 18 of 75 (24.0%) had elevated basal and 65/74 (87.8%) elevated stimulated luteinizing hormone (LH) levels, demonstrating chemotherapy-induced Leydig cell damage. In addition, there was a 40.5% and 53.4% incidence of elevated basal and stimulated FSH values, respectively, indicating severe impairment of spermatogenesis as confirmed by azoospermia in four patients. Testicular dysfunction was observed in patients treated before as well as during puberty. The incidence of elevated basal follicle stimulating hormone (FSH) and LH values was significantly higher in patients who had received higher cumulative doses of chemotherapy, i.e., 28.9% and 13.2% with two OPPA, 45.5% and 36.4% with two OPPA/two COPP, and 62.5% and 43.8% with two OPPA/four to six COPP, respectively. Chemotherapy for Hodgkin's disease causes a high and apparently dose-related incidence of testicular dysfunction in prepubertal as well as in pubertal boys affecting Leydig cell function as well as spermatogenesis. Circumstantial evidence indicates that procarbazine is the major gonadotoxic agent involved.

Gonadal toxicity after combination chemotherapy for Hodgkin's disease. Comparative results of MOPP vs ABVD

Article

Jun 1985
Eur J Canc Clin Oncol

The comparative gonadal toxicity following two equally effective and non-cross-resistant regimens (MOPP and ABVD) was prospectively evaluated in 53 males with Hodgkin's disease. The median age was 29 yr (range 16-45). MOPP produced azoospermia in 28/29 patients (97%) while ABVD induced oligoazoospermia in 13/24 patients (54%). Follicle-stimulating hormone levels were consistently and significantly increased after MOPP while their median value remained within normal range after ABVD. Sperm count was repeated in 34 patients. Recovery of spermatogenesis occurred in 3/21 cases treated with MOPP and in all 13 cases given ABVD. Present findings confirm that the two alkylating agents, mechlorethamine and procarbazine, included in the MOPP regimen cause sterility in most patients while the drugs included in ABVD are not associated with permanent gonadal dysfunction.

Reproductive and endocrine gonadal capacity in patients with COPP chemotherapy for Hodgkin's Disease

Article

Feb 1987

Testicular and ovarian functions were assessed in 33 patients with Hodgkin's disease 1 to 17 years after cessation of COPP chemotherapy with cyclophosphamide, vincristine, procarbazine, prednisone. Diagnostic procedures consisted of hormone measurements, interviews, and semen analyses. In women serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17 beta-estradiol, progesterone, prolactin, and in men FSH, LH, 17 beta-estradiol, testosterone, and prolactin were determined. Semen analyses were performed in all men. Information concerning pregnancies, pregnancy outcome, future fertility wishes, sexual functions, menstrual pattern, and incidence of premature menopausal symptoms was ascertained by interview and questionnaire. Nineteen of 19 (100%) men showed elevated serum FSH levels between 715 and 1910 (median 1095) ng/ml and azoospermia, 1 to 11 years after therapy. Serum levels of testosterone were within normal limits in 18/19 (95%) of the men, and LH values were normal in all men. Permanent ovarian failure occurred in 8/14 (57%) women, causing infertility and premature menopausal symptoms. The incidence of ovarian failure in women over 24 years was 86% (6/7) versus 28% (2/7) in those under 24 years at the time of treatment. In women receiving estrogen replacement, incidence and severity of these symptoms were significantly reduced. Of 14 women 3 (21%) became pregnant and delivered 5 healthy children after treatment. Our results suggest irreversible sterility and normal Leydig cell function after COPP chemotherapy in all men. Drug-induced ovarian failure was age-related and caused premature menopausal symptoms, detracting from the quality of the patient's life. To reduce premature menopausal symptoms and to prevent adverse cardiovascular and metabolic late sequelae, hormonal replacement is indicated. Pregnancies ending in normal live births can be achieved after COPP chemotherapy in young women. In both men and women, serum FSH and LH levels proved to be feasible markers to determine degree and duration of endocrine and reproductive gonadal injury after chemotherapy.

Evaluation of semen and pituitary gonadotropin function in men with untreated Hodgkin's disease

Article

Jul 1985
FERTIL STERIL

The reproductive capacities of 35 patients with Hodgkin's disease were assessed before treatment by semen evaluation and determination of basal hypothalamic-hypophyseal function and after stimulation with gonadotropin-releasing hormone (GnRH). Sixty-five percent of the patients had asthenozoospermia, 46% had teratozoospermia, and 28% had oligozoospermia. Normal semen was more frequently seen in asymptomatic patients (7 of 18) than in symptomatic patients (2 of 15). All the patients had normal basal follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and significantly low testosterone (T) levels (P less than 0.01). The FSH response to 100 micrograms of GnRH was normal, but the LH responses were all significantly low, both as delta % (28.4% +/- 18.7% versus 52.4% +/- 25.3%, P less than 0.005) and as peak values (36.7 +/- 20.7 mIU/ml versus 59.4 +/- 26.4 mIU/ml, P less than 0.01). It is believed that abnormal semen is a specific symptom of Hodgkin's disease, secondary to functional insufficiency of the hypothalamic-hypophyseal axis, with a relative decrease in T production.

Hodgkin disease in Connecticut from 1935 to 1962. The bimodal incidence curve in the general population and survival in untreated patients

Article

Jan 1975
ARCH INTERN MED

Recovery of spermatogenesis after treatment for Hodgkin's disease: Limiting dose of MOPP chemotherapy

Article

Jul 1984

The sperm production of 25 patients with Hodgkin's disease treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy was studied retrospectively. All but two patients also received radiotherapy treatment to pelvic and/or non-pelvic fields. Sperm counts were obtained from patients treated either with three or fewer (MOPP-2 group) or with five or more (MOPP-6 group) chemotherapy cycles. Recovery of spermatogenesis following treatment-induced azoospermia was significantly higher among the MOPP-2 patients (Mann-Whitney rank sum test, p = 0.001). Patients in this group who did not receive pelvic irradiation appeared to have greater recovery rates (p = 0.06). The results suggest that three cycles of MOPP chemotherapy represent a maximum exposure compatible with the recovery of spermatogenesis.

Gonadal Function In Hodgkin's Disease: Long-Term Follow-Up Of Chemotherapy

Article

Jan 1983

A long-term study of gonadal function was conducted in 46 men and 28 women in prolonged remission of advanced Hodgkin's disease after cyclical combination chemotherapy with nitrogen mustard, vinblastine, prednisolone, and procarbazine. The mean follow-up was 6.9 years. Azoospermia or profound oligospermia occurred in 36 of the men, but late recovery was occasionally observed. Testosterone secretion was preserved. Amenorrhoea and gonadal hormone deficiency developed in 22 of the women and never recovered. Partial or complete chemical sterilisation and gonadal hormone deficiency is currently a consequence of cure of advanced Hodgkin's disease in most patients.

Male gonadal dysfunction in Hodgkin's disease. A prospective study

Article

May 1981

Clark ST, Radford JA, Crowther D, Swindell R, Shalet SMGonadal function following chemotherapy for Hodgkin's disease: A comparative study of MVPP and a seven-drug hybrid regimen. J Clin Oncol 13: 134-139

Article

Jan 1995

Gonadal function was assessed in 89 patients after chemotherapy for Hodgkin's disease (HD). Thirty-seven patients had received mechlorethamine, vinblastine, prednisolone, and procarbazine (MVPP) and 52 patients, a hybrid combination of chlorambucil, vinblastine, prednisolone, procarbazine, doxorubicin, vincristine, and etoposide (ChIVPP/EVA). Fifty men (MVPP, n = 21; ChIVPP/EVA, n = 29) with a median age of 26 years (range, 16 to 54) and 39 women (MVPP, n = 16; ChIVPP/EVA, n = 23) with a median age of 30 years (range, 15 to 47) were studied at a median of 30 months (range, 4 to 83) following chemotherapy. Semen analysis showed azoospermia in 35 of 37 men, and increased serum follicle-stimulating hormone (FSH) levels in this group confirmed severe germinal epithelial damage. Analysis of pretreatment semen in 28 men showed azoospermia in one, oligospermia in four (sperm count < 20 x 10(6)/mL), and a normal sperm count in the remaining 23. In the women, 26 of 34 (76%) with a regular menstrual cycle before commencing chemotherapy became amenorrheic following treatment. Menses returned in 10 women, who had a median age of 25 years (range, 21 to 34), and there were two pregnancies in this group. In the other 16, with a median age of 36 years (range, 27 to 47), amenorrhea persisted and premature ovarian failure was confirmed by increased serum gonadotrophins and reduced estradiol (E2) concentrations. Of the original eight women in whom menses were maintained following treatment, two subsequently developed amenorrhea and the clinical and biochemical features of an early menopause. In total, 18 of 34 women (53%) required hormone replacement therapy for chemotherapy-induced ovarian failure. There was no statistically significant difference in the frequency or severity of gonadal dysfunction between MVPP- and ChIVPP/EVA-treated patients. We conclude that both of these chemotherapy schedules cause substantial damage to gonadal function in both sexes.

Decline in Semen Quality among Fertile Men in Paris during the Past 20 Years

Article

Mar 1995

Several studies have suggested a population-wide decline in the quality of semen over the past 50 years, but clear evidence for decreasing semen quality in recent decades is lacking. From 1973 through 1992 we measured the volume of seminal fluid, the sperm concentration, and the percentages of motile and morphologically normal spermatozoa in 1351 healthy fertile men. The data on the semen samples were collected at one sperm bank in Paris. The data in each calendar year were analyzed as a function of the year of donation, the age of each patient, the year of birth, and the duration of sexual abstinence before semen collection. There was no change in semen volume during the study period. The mean concentration of sperm decreased by 2.1 percent per year, from 89 x 10(6) per milliliter in 1973 to 60 x 10(6) per milliliter in 1992 (P < 0.001). During the same period the percentages of motile and normal spermatozoa decreased by 0.6 percent and 0.5 percent per year, respectively (both P < 0.001). After adjustment in multiple regression analyses for age and the duration of sexual abstinence, each successive calendar year of birth accounted for 2.6 percent of the yearly decline in the sperm concentration and for 0.3 percent and 0.7 percent, respectively, of the yearly declines in the percentages of motile and normal spermatozoa (all P < 0.001). During the past 20 years, there has been a decline in the concentration and motility of sperm and in the percentage of morphologically normal spermatozoa in fertile men that is independent of the age of the men.

Systemic interleukin-1 ?? and interleukin-2 secretion in response to acute stress and to corticotropin-releasing hormone in humans

Article

Nov 1994

Acute stress results in activation of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH and cortisol secretion is stimulated by corticotropin-releasing hormone (CRH). It has also been shown that activation of the HPA axis during stress is accompanied by changes in the immune response. However, little is known about the influence of acute stress on the release of cytokines such as interleukin-1 (IL-1) or interleukin-2 (IL-2). In this study, we determined serum IL-1 alpha and IL-2 levels in 19 patients undergoing the acute stress of angioplasty for coronary artery disease. A second protocol was devised to determine serum IL-1 alpha and IL-2 concentrations as well as lymphocyte subpopulations in 10 normal volunteers receiving 1 microgram kg-1 human CRH intravenously. Finally, IL-1 alpha concentrations were measured in CRH-incubated mononuclear cell (MNC) and monocyte cultures. In response to the stress of angioplasty, ACTH and cortisol as well as IL-1 alpha and IL-2 concentrations were clearly above baseline levels (IL-1 alpha, mean +/- SEM, baseline: 1.39 +/- 0.34 ng ml-1, after angioplasty: 2.64 +/- 0.73 ng ml-1, P < 0.05; IL-2, baseline: 1.2 +/- 0.13 ng ml-1, after angioplasty: 2.8 +/- 1.14 ng ml, P < 0.05). A similar pattern was obtained in normal subjects in response to CRH (Il-1 alpha, baseline: 0.8 +/- 0.2 ng ml-1, after angioplasty: 3.7 +/- 1.4 ng ml-1, P < 0.05; IL-2, baseline: 1.9 +/- 0.4 ng ml-1, after angioplasty: 5.4 +/- 2.2 ng ml-1, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

High and unchanged sperm counts of Finnish men

Article

Mar 1996

Several recent reports have suggested that the sperm counts of normal men are declining in most countries. In this study the sperm counts of Finnish men, and their possible changes during the past 28 years, were investigated. The material consisted of semen samples from 238 normal healthy men of unknown fertility and 5481 men from infertile couples. The means (medians) of semen volume, sperm density and total sperm count in normal men were 3.3 (3.0) ml, 133.9 (94.0) x 10(6)/ml and 396.6 (309.0) x 10(6), respectively. These parameters and the relative frequency distribution of the sperm density were similar to those reported elsewhere in the 1940s. Multiple linear regression analysis revealed a significant decrease in semen volume, whereas sperm density and total sperm count of infertile men had not changed significantly during the past 28 years. In addition, no change in sperm counts was associated with the year of men's birth.

Distinct expression levels of cytokines and soluble receptors in seminal plasma of fertile and infertile men

Article

Aug 1996
FERTIL STERIL

To compare the levels of interleukin (IL) 1 beta, IL-6, tumor necrosis factor (TNF) alpha, and soluble TNF (sTNF) receptors types I and II, and IL-1 receptor antagonist in seminal plasma of fertile and infertile men. Prospective and comparative study. Andrology clinic of a university hospital. Four groups of normogonadotropic men: group 1, donors with proven fertility (controls, n = 15); group 2, azoospermic men (n = 12); group 3, infertile men with oligoteratoasthenospermia (n = 20); and 11 men with oligoteratoasthenospermia and genital infection (n = 11). None. Measurement of cytokines and cytokine-soluble receptors in the semen by specific commercial kits. The levels of IL-1 beta, TNF-alpha, and IL-6 were similar in seminal plasma of controls and infertile men. The mean level of sTNF-I receptor in the seminal plasma of group 4 was 2.4 +/- 0.2 ng/mL, which was significantly lower than observed in seminal plasma of group 1 (3.88 +/- 0.5 ng/mL), the group 3 (4.1 +/- 0.4 ng/mL), or group 2 (3.03 +/- 0.35 ng/mL). The soluble receptor of TNF-II could not be detected in any group. Interleukin 1ra was 120 +/- 10 pg/mL in seminal plasma of group 1, but increased levels were detected in group 2 (420 +/- 180 pg/mL), group 3 (480 +/- 90 pg/mL), and even higher (760 +/- 120 ng/mL) in group 4 patients. During genital infection cytokines and various soluble receptors of immunoregulatory cytokines are expressed distinctly in seminal plasma. These factors also may be involved in the regulation of sperm cell functions and thus may affect male fertility. Our results may indicate local production of these factors in the secondary sex glands, independently of spermatogenesis.

Gonadal Function Following ABVD Therapy for Hodgkin's Disease

Article

Aug 1997
AM J CLIN ONCOL-CANC

To assess the effect of combination chemotherapy with doxorubicin, bleomycin, viablastine, and decarbazine (ABVD) on gonadal function in patients treated for Hodgkin's disease, we assessed 38 male patients with Hodgkin's disease who were > 15 years of age and in complete remission for the development of secondary sexual characteristics, sexual habits, and fatherhood after treatment. Semen analysis and serum hormone level estimation of follicle-stimulating hormone (FSH), leutinising hormone (LH), and testosterone (T) were done in all cases. Twenty-six patients received ABVD therapy and 12 received a combination of ABVD with COPP or MOPP (cyclophosphamide or nitrogen mustard, vincristine, procarbazine, and prednisone). Radiation of the pelvic region was done in one case. Median time between completion of therapy and assessment of gonadal function was 34 months (range, 12-68 months). Secondary sexual characteristics developed normally in all patients. Azoospermia was seen in one patient from the ABVD group and 10 patients from the COPP/ABVD group (p < 0.001). Serum FSH levels were significantly higher in the COPP/ABVD group than in the ABVD group (23.5 versus 4.7 mlu/ml; p < 0.001) The levels were in the normal range in 23 patients from the ABVD group, as compared to four in the COPP/ABVD group (88.5% versus 33.3%; p < 0.001). Three patients treated with ABVD fathered children post-therapy. We conclude that ABVD is associated with relatively better preservation of gonadal function.

Testicular sperm extraction combined with intracytoplasmic sperm injection in the treatment of men with persistent azoospermia postchemotherapy

Article

Oct 2001

Men who remain azoospermic long after undergoing chemotherapy have generally been considered sterile. The authors report their experience with testicular sperm extraction (TESE) combined with intracytoplasmic sperm injection (ICSI) applied to azoospermic men who previously received chemotherapy for a variety of indications. Among 231 cycles in 198 patients who underwent TESE-ICSI for nonobstructive azoospermia from 1995 to 2000, 20 TESE procedures in 17 patients who previously received chemotherapy were identified. All TESE procedures were performed with microsurgical control under local anesthesia with sedation or general anesthesia. The pretreatment hormonal profile, histology of testicular biopsies, and outcomes of TESE-ICSI in this subgroup of patients were analyzed. The mean patient age was 37.4 years (range, 28-54 years), and the mean follicle-stimulating hormone level was 21.8 mIU/mL (range, 7.1-43.1 mIU/mL). The mean age for female partners was 33.5 years (range, 22-43 years). Six patients had received chemotherapy for Hodgkin lymphoma (34%), four patients had received chemotherapy for testicular neoplasm (24%), two patients had received chemotherapy for non-Hodgkin lymphoma (12%), two patients had received chemotherapy for leukemia (12%), one patient had received chemotherapy for Wilms tumor (6%), one patient had received chemotherapy for mediastinal germ cell tumor (6%), and one patient had received chemotherapy for nephrotic syndrome (6%). Three patients (18%) received additional radiation therapy. The mean interval from chemotherapy to TESE was 16.3 years (range, 6-34 years). All patients had at least two semen analyses to confirm azoospermia. A total of 20 attempts of TESE-ICSI were performed (mean, 1.2 attempts per patient). Testicular histology revealed Sertoli cell-only pattern in 76% of patients. The remaining 24% of patients had hypospermatogenesis as their most advanced spermatogenic pattern. Among the men with Sertoli cell-only pattern, 23% had sperm retrieved by TESE. Sperm retrieval was accomplished in 9 of 20 attempts (45%), with biochemical pregnancy after sperm retrieval in 4 of 9 couples (45%) and clinical pregnancy in 3 of 9 couples (33%). Live deliveries were achieved in 2 of 9 couples (22%). Two healthy boys and one girl were delivered. No correlation was noted between the outcome of TESE-ICSI and the underlying conditions that were treated with chemotherapy nor with the chemotherapeutic agents used. Using TESE-ICSI, sperm retrieval leading to pregnancy and the delivery of healthy children is possible for men with long-standing azoospermia after chemotherapy. The prognosis for sperm retrieval was not influenced clearly by the chemotherapy regimen or the disease treated. Diagnostic biopsy also was of limited value in predicting the outcome of sperm retrieval. Despite prolonged nonobstructive azoospermia after undergoing chemotherapy, men no longer should be considered sterile in the era of advanced assisted reproductive techniques.

Knowledge and Experience Regarding Cancer, Infertility, and Sperm Banking in Younger Male Survivors

Article

May 2002

The goal of this study was to survey male patients aged 14 to 40 years at diagnosis and recently treated in two cancer centers to determine their knowledge, attitudes, and experiences regarding cancer-related infertility and sperm banking. A postal survey about cancer-related infertility and sperm banking was offered to 904 men diagnosed with cancer within the previous 2 years. Eight percent opted out of the study. The others were sent the survey, with a cover letter stating elements of informed consent. Although the return rate was only 27%, yielding a sample of 201 men, responders did not differ significantly from nonresponders by institution, age, ethnicity, or cancer site. Overall, 51% of men wanted children in the future, including 77% of men who were childless at cancer diagnosis. Despite some anxieties about their own survival and risks to their children's health, men felt that the experience of cancer increased the value they placed on family closeness and would make them better parents. Only 60% of men recalled being informed about infertility as a side effect of cancer treatment, and just 51% had been offered sperm banking. Those who discussed infertility with their physicians had higher knowledge about cancer-related infertility and were significantly more likely to bank sperm. Only 24% of men banked sperm, including 37% of childless men. Lack of information was the most common reason for failing to bank sperm (25%). All men who are about to receive cancer treatment that could impair fertility should be counseled about such side effects and given adequate information to make an informed decision about banking sperm.

Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease

Article

Jun 2003
NEW ENGL J MED

Faced with unsatisfactory results of treatment for advanced Hodgkin's disease, we investigated three combinations of chemotherapy. From 1993 to 1998, 1201 eligible patients 15 to 65 years of age who had newly diagnosed Hodgkin's disease in unfavorable stage IIB or IIIA or stage IIIB or IV were randomly assigned to receive eight cycles of cyclophosphamide, vincristine, procarbazine, and prednisone alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD); bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP); or increased-dose BEACOPP, each followed by local radiotherapy when indicated. Enrollment in the COPP-ABVD group was stopped in 1996 owing to inferior results. For the final analysis, 1195 of 1201 patients could be evaluated: 260 in the COPP-ABVD group, 469 in the BEACOPP group, and 466 in the increased-dose BEACOPP group; the median follow-up was 72, 54, and 51 months, respectively. The rate of freedom from treatment failure at five years was 69 percent in the COPP-ABVD group, 76 percent in the BEACOPP group, and 87 percent in the increased-dose BEACOPP group (P=0.04 for the comparison of the COPP-ABVD group with the BEACOPP group and P<0.001 for the comparison of the increased-dose BEACOPP group with the COPP-ABVD group and with the BEACOPP group), and the five-year rates of overall survival were 83 percent, 88 percent, and 91 percent, respectively (P=0.16 for the comparison of the COPP-ABVD group with the BEACOPP group, P=0.06 for the comparison of the BEACOPP group with the increased-dose BEACOPP group, and P=0.002 for the comparison of the COPP-ABVD group with the increased-dose BEACOPP group). Rates of early progression were significantly lower with increased-dose BEACOPP than with COPP-ABVD or standard BEACOPP. Increased-dose BEACOPP resulted in better tumor control and overall survival than did COPP-ABVD.

Successful paternity with microassisted fertilization after total body irradiation-based conditioning for autologous bone marrow transplantation

Article

Feb 2003
Hematol J

We present the case of a 20-year-old man with acute lymphoblastic leukemia who received chemotherapy with vincristine, adriamycin, cyclophosphamide, methotrexate, teniposide (VM-26), and bleomicin, followed by an autologous bone marrow transplantation after total body irradiation (TBI)-cyclophosphamide-based conditioning regimen. At 14 years, despite the severe oligoasthenospermia, he fathered a healthy child by assisted reproductive technique (ART) consisting in controlled ovarian hyperstimulation of the patient's wife, transvaginal ovum pick up and microinjection of the ovum with a previously isolated sperm cell from the patient (intracytoplasmatic sperm injection, ICSI). As far as we know, that is the first documented case of successful paternity using microassisted fertilization with ICSI technique in a patient submitted to TBI-based bone marrow transplantation.

Secondary Amenorrhea After Hodgkin’s Lymphoma Is Influenced by Age at Treatment, Stage of Disease, Chemotherapy Regimen, and the Use of Oral Contraceptives During Therapy: A Report From the German Hodgkin’s Lymphoma Study Group

Article

Oct 2005

Long-term survivors of successfully treated Hodgkin's lymphoma (HL) are at risk for late complications. Among these, infertility for female patients is of major importance. The subject of this analysis is to evaluate the menstrual status after HL therapy. From 1994 to 1998, the German Hodgkin's Lymphoma Study Group conducted clinical trials for early-, intermediate-, and advanced-stage HL (trials HD7 to HD9) involving a total of 3,186 patients. A survey was carried out to evaluate the menstrual status after therapy. The following factors were assessed concerning their influence on amenorrhea: age, treatment, stage, and the use of oral contraceptives during chemotherapy. A total of 405 women aged younger than 40 years answered the study questions. After a median follow-up of 3.2 years, 51.4% of the women receiving eight cycles of dose-escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) had continuous amenorrhea. Amenorrhea was significantly more frequent after dose-escalated BEACOPP compared with doxorubicin, bleomycin, vinblastine, and dacarbazine; cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine; or standard BEACOPP (P = .0066). Amenorrhea after therapy was most pronounced in women with advanced-stage HL (P < .0001), in women older than 30 years at treatment (P = .0065), and in women who did not take oral contraceptives during chemotherapy (P = .0002). Most women who are treated for advanced-stage HL experience amenorrhea after therapy. Amenorrhea is significantly more frequent in women with advanced-stage HL receiving eight cycles of dose-escalated BEACOPP and in women older than 30 years at first treatment. Furthermore, the data show a statistical association between the use of oral contraceptives and return of menstrual cycle, which is subject to further investigation.

The Kaplan Memorial Lecture

Jan 1996
ANN ONCOL
555-560

The Kaplan Memorial Lecture. Ann Oncol. 1996; 7: 555-560.

Distinct expression levels of cytokines and soluble cytokine receptors in seminal plasma of fertile and infertile men

Jan 1996
135

Huleihel

The effects of different cumulative doses of chemotherapy on testicular function. Results in 75 patients treated for Hodgkin's disease during childhood or adolescence

Jan 1990
1298

Bramswig

Assessment of male fertility in patients with Hodgkin's lymphoma treated in the German Hodgkin Study Group (GHSG) clinical trials

Abstract

No full-text available

Recommended publications

Treatment of advanced Hodgkin's lymphoma: Standard and experimental approaches

FDG-PET for Early Response Assessment in Lymphomas: Part 1-Hodgkin Lymphoma

Barrett Esophagus in Long-term Survivors of Childhood Solid Tumors

Hodgkin Lymphoma in Older Patients: An Uncommon Disease in Need of Study