Oocyte collection and outcome following oncologic treatment: a retrospective multicentre study.

PURPOSE: This study assesses fertility treatment outcomes in female patients who had undergone successful oocyte retrieval following cancer therapy. METHODS: Between January 2020 and December 2022, we collected fertility treatment data from six participating centres in Spain and Germany. All patients associated with this data had undergone successful oocyte retrieval following cancer treatment. RESULTS: Women had most frequently been diagnosed with a haematological (41.9%), breast (22.6%) or gynaecological malignancy (12.9%); two thirds (67.7%) had previously received a chemotherapy, half a radiotherapy (53.3%) and 45.2% had undergone surgery. On average, 7 years (range 0-28) had passed between cancer treatment and first ovarian stimulation cycle. Forty-nine ovarian stimulation cycles had been conducted on these 31 women between 2004 and 2021 (mean age at first oocyte collection following treatment: 34.8 ± 5.7 years). On average, 7 oocytes were collected per cycle (range 0-26) and 11 were collected per patient (range 0-51). Out of the 190 oocytes collected for immediate use of artificial reproductive technique, 139 were fertilised at a rate of 73%. Live birth rate per fresh transfer was 45% (9/20); no births were reported following cryotransfer (0/10). Mean values of anti-Mullerian hormone (AMH) before stimulation declined with time since treatment; however, oocytes were successfully collected from four women with an AMH of <0.5 ng/ml, although no pregnancies were reported. Ten pregnancies were documented; 3 ended in miscarriage. Two twin and 5 single pregnancies resulted in nine live births. On average, children were carried to term. CONCLUSION: In this small cohort, oocytes were successfully collected after chemotherapy and radiotherapy, despite-in individual cases-low AMH values. Further studies are needed to enrich the database and ultimately provide appropriate counselling to female cancer patients regarding expectations and ART outcome following cancer therapy.

The role of transcriptional regulators in the control of gene expression in prokaryotes based on Pseudomonas aeruginosa model bacterium / Rola regulatorów transkrypcji w kontroli ekspresji genów prokariotycznych na przykladzie modelowej bakterii Pseudomonas aeruginosa.

Bacteria from Pseudomonas aeruginosa species are often found in environments such as water or soil, but are also known to be opportunistic pathogens of humans and animals. Characteristic feature of these bacteria is their high ability to survive in very different ecological niches. Such capability of adaptation to changing conditions is derived from the extended regulatory networks and the use of a rich repertoire of genome-encoded proteins, pathways and adaptive mechanisms. Transcriptional regulators are key components of gene expression regulation responding to environmental signals by turning on or off specific pathways. Studies on transcription factos using transcriptomic and genomic methods provide knowledge about the mechanisms of their action, regulated genes and processes enabling understanding complex regulatory networks controlling cell life. The aim of this work is to present the results of research on the regulation of bacterial transcription visualized on the basis of P. aeruginosa pathogen and the characteristics of the mechanism of regulation of genes involved in the virulence of this bacterium.

S1 Guideline: Impairment of gonadal function After Cancer in Childhood and Adolescence.

A possible negative consequence of cancer treatment is the fertility impairment of young cancer survivors. However, most former patients express the wish to have biological children. Fertility-preserving measures are available and are - under certain circumstances - financed by health insurance. Separate information at the time of diagnosis and during follow-up care should be adapted to the individual risk and enable those affected to make a self-determined decision about cryopreservation of germ cells or germ cell tissue. Hyopgonadotropic hypogonadism can be treated by the pulsatile administration of gonadotropins. Affected individuals can be reassured. A health restriction of the offspring due to the cancer treatment is not to be expected, even after artificial insemination.

Implementation of a clinical long-term follow-up database for adult childhood cancer survivors in Germany: a feasibility study at two specialised late effects clinics.

PURPOSE: Childhood cancer survivors (CCS) are at risk for increased morbidity and reduced quality of life associated with treatment-related late effects. In Germany, however, only a few of the more than 40,000 CCS registered in the German Childhood Cancer Registry (GCCR) currently benefit from adequate clinical long-term follow-up (LTFU) structures. To establish a comprehensive knowledge base on CCS' long-term health in Germany, a database was developed in cooperation with the GCCR. Following a first evaluation phase at two German university centres, this database will be implemented more widely within Germany allowing longitudinal documentation of clinical LTFU data. METHODS: The feasibility study cohort comprised 208 CCS aged 18 or older whose medical, mental and psychosocial health data were collected during routine LTFU or first clinic visits in adult care. CCS were enrolled from 04/2021 to 12/2022, and data entry was completed by 03/2023. Descriptive data analysis was conducted. All CCS were stratified into three risk groups (RG) based on their individual risk for developing late effects resulting from their respective diagnoses and treatments. RESULTS: Chronic health conditions of various organ systems associated with late and long-term effects of cancer therapy affected CCS in all RG supporting the clinical relevance of risk-adapted LTFU. Enrolment into the database was feasible and broadly accepted amongst CCS. CONCLUSION: Implementation of a clinical follow-up care infrastructure and database in Germany will pave the way to collect clinically evaluated and regularly updated health data of potentially over 40,000 German CCS and facilitate future national and international cooperation.

Desire for biological parenthood and patient counseling on the risk of infertility among adolescents and adults with hemoglobinopathies.

BACKGROUND: Both diagnosis and treatment of hemoglobinopathies have been associated with an increased risk of fertility impairment. German guidelines recommend annual monitoring of fertility parameters to enable early detection of fertility impairment and/or to offer fertility preservation (FP) when indicated. We explored the general desire for parenthood, the frequency of recalling fertility counseling and testing, and the utilization of FP in adolescents and adults with hemoglobinopathies. PROCEDURE: In a cross-sectional study, patients aged 12-50 years, treated in Germany, Austria, or Switzerland, were surveyed on fertility-related aspects. Medical data, including fertility testing results, were collected from patient records. RESULTS: Overall, 116/121 eligible patients, diagnosed with sickle cell disease (70.7%), thalassemia (27.6%), or other hemoglobinopathy (1.7%), participated in our study (57.8% female, median age 17.0 years, range 12-50 years). All participants required treatment of the underlying hemoglobinopathy: 68.1% received hydroxyurea, 25.9% required regular blood transfusions, and 6.0% underwent hematopoietic stem cell transplantation (HSCT). Most patients (82/108, 75.9%) stated a considerable to strong desire for (future) parenthood, independent of sex, education, diagnosis, or subjective health status. Fertility counseling was only recalled by 32/111 patients (28.8%) and least frequently by younger patients (12-16 years) or those treated with regular blood transfusions or hydroxyurea. While fertility testing was documented for 59.5% (69/116) in medical records, only 11.6% (13/112) recalled previous assessments. FP was only used by 5.4% (6/111) of patients. CONCLUSION: Most patients with hemoglobinopathies wish to have biological children, yet only few recalled fertility counseling and testing. Adequate patient counseling should be offered to all patients at risk for infertility.

Sperm and testicular tissue cryopreservation and assisted reproductive technology outcomes in male cancer patients: a 15-year experience.

OBJECTIVE: To explore the characteristics of cancer patients who cryopreserved sperm/testicular tissue samples in the Cryobank of Charité-Universitätsmedizin Berlin between 2004 and 2019, and the ART utilization rate with associated outcomes. METHODS: Retrospective data were available for 506 cancer patients, of which 46 (9.1%) had used their samples for artificial reproductive technologies (ART). Corresponding cycle information was collected from external fertility centers. RESULTS: Our cohort included 53/506 (10.5%) patients aged < 18 years at diagnosis. While adolescents and adults mainly banked sperm, adolescents showed higher rates of testicular tissue cryopreservation before (11.8%, 6/51 vs. 6.4%, 26/406) and after treatment (16.7%, 4/24 vs. 7.8%, 13/167). At study conduction, storage had been ended for 44.8% (269/601) of samples. The majority of samples used for ART were requested within the first 3 years after cryopreservation (71.5%, 28/39, range = 0-12 years). Pregnancy rate was 51.4% (19/37 cycles), resulting in 11 singleton births, 3 twin pairs, and 4 miscarriages. CONCLUSION: With the new advantage of public health insurance coverage of fertility preservation (FP) in Germany, an increased utilization has already been noticed in our center, emphasizing the necessity of further knowledge for individual counseling. Adolescent cancer patients need to be addressed specifically, as these patients show especially low cryopreservation rates.

Parenthood for childhood cancer survivors: unfounded fear of cancer development in offspring and related health behaviors.

Current literature reveals no increased risk for adverse non-hereditary health outcomes in the offspring of childhood cancer survivors (CCS), yet survivors reported concerns regarding their offspring's health. To investigate how the fear of cancer development in offspring influences parental behavior related to health and prevention, survey reports from 256 European adult CCS and 256 age- and sex-matched siblings who participated in a multicenter study on offspring health were analyzed in the present study. Analyses of covariance and chi-square tests were conducted to test for differences between CCS and siblings in outcome variables (all related to healthy parenting behavior). CCS reported higher fear levels (p = 0.044, Partial η2 = 0.01) and less alcohol consumption (p = 0.011, Phi = 0.12) and smoking (p = 0.022, Phi = 0.11) during pregnancy than siblings. In survivor families, children were breastfed less often (p < 0.001, Phi = 0.18). Partial correlation analyses showed that CCS' fear levels decreased with increasing age (r = -0.16, p = 0.014), time since oncological therapy (r = -0.19, p = 0.003), and number of children (r = -0.21, p = 0.001). Overall, due to their own experiences with cancer, many CCS harbor misperceptions regarding the health outcomes of their offspring. Although the fear decreases with increasing distance from the active disease, any fear should be taken seriously, even if unfounded, and combated through targeted educational measures.

Functional Characterization of TetR-like Transcriptional Regulator PA3973 from Pseudomonas aeruginosa.

Pseudomonas aeruginosa, a human opportunistic pathogen, is a common cause of nosocomial infections. Its ability to survive under different conditions relies on a complex regulatory network engaging transcriptional regulators controlling metabolic pathways and capabilities to efficiently use the available resources. P. aeruginosa PA3973 encodes an uncharacterized TetR family transcriptional regulator. In this study, we applied a transcriptome profiling (RNA-seq), genome-wide identification of binding sites using ChIP-seq, as well as the phenotype analyses to unravel the biological role of PA3973. Transcriptional profiling of P. aeruginosa PAO1161 overexpressing PA3973 showed changes in the mRNA level of 648 genes. Concomitantly, ChIP-seq analysis identified more than 300 PA3973 binding sites in the P. aeruginosa genome. A 13 bp sequence motif was indicated as the binding site of PA3973. The PA3973 regulon encompasses the PA3972-PA3971 genes encoding a probable acyl-CoA dehydrogenase and a thioesterase. In vitro analysis showed PA3973 binding to PA3973p. Accordingly, the lack of PA3973 triggered increased expression of PA3972 and PA3971. The ∆PA3972-71 PAO1161 strain demonstrated impaired growth in the presence of stress-inducing agents hydroxylamine or hydroxyurea, thus suggesting the role of PA3972-71 in pathogen survival upon stress. Overall our results showed that TetR-type transcriptional regulator PA3973 has multiple binding sites in the P. aeruginosa genome and influences the expression of diverse genes, including PA3972-PA3971, encoding proteins with a proposed role in stress response.

The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors.

CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615−5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401−4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account.

Health of children born to childhood cancer survivors: Participant characteristics and methods of the Multicenter Offspring Study.

INTRODUCTION: Research on childhood cancer survivor offspring has been limited to genetic disease occurrence, malformations or non-hereditary cancers. However, previous surveys indicated that survivors harbor fears about their (prospective) children's overall health. Our Multicenter Offspring Study examined extensive health aspects in children born to survivors and their siblings providing comprehensive information to be used in patient counseling to elucidate and alleviate existing concerns. METHODS: Using a specifically designed questionnaire, childhood cancer survivors and their siblings were surveyed on their offspring's health (Supplementary material). Recruitment strategies depended on local infrastructures and standards of participating centers, including registry-based and direct approaches. Group differences were tested non-parametrically and effect sizes were calculated. RESULTS: In total, 1126 survivors reported on 1780 offspring and 271 siblings reported on 441 offspring. Response rates ranged from 32.1% (Czech Republic) to 85.0% (Austria). Respondents were more likely to be female (p = .007), older at time of survey (p < .001), diagnosed 1980-1999 (p < .001) and treated with chemotherapy (p < .001). Compared to siblings, survivors were younger at time of survey (35 years vs. 39 years, p < .001) and at first birth (29 years vs. 30 years, p < .001). Survivor and sibling offspring only differed in terms of age at survey (6.3 years vs. 8.9 years, p < .001). CONCLUSION: The Multicenter Offspring Study investigates a wide variety of health aspects in offspring born to survivors and their siblings in five European countries. Our study cohorts form a solid basis for future analyses; yet, certain limitations, due to differences in approach among participating centers, must be considered when interpreting findings.

Health-related quality of life of children born to childhood cancer survivors in Germany.

OBJECTIVE: Rising childhood cancer survival rates have increased the importance of health-related quality of life (HRQL) assessment. While survivors show comparable HRQL to peers, concerns that cancer treatment could impact the health of prospective children were reported. No previous publications address HRQL of childhood cancer survivor offspring. METHODS: We assessed survivor offspring HRQL using the parental KINDL questionnaire. Matched-pair analysis was conducted with data from the general population (KiGGS study) using age, gender and education (1:1, n = 1206 cases). Multivariate analyses were conducted to detect the influence of parental diagnose and treatment on offspring HRQL. RESULTS: Overall, within KINDL dimensions, survivors reported comparable to higher HRQL for their children than the general population. Survivor parents reported significantly (p < 0.001) higher psychological (86.7% vs. 83.0%, Cohen's d = 0.3) and self-esteem (79.1% vs. 73.3%, Cohen's d = 0.5) well-being scores for younger children (3-6-year-olds). As time since diagnosis increased, parents reported higher well-being scores. Accordingly, recently diagnosed survivors reported significantly lower psychological well-being scores (p = 0.28; OR = 0.457; 95% CI = 0.228-0.918) for their children. With increasing age, average HRQL scores decreased in both cohorts; yet, this drop was less pronounced for survivor offspring. The biggest difference between age groups (7-10- vs. 14-17-year-olds) was found for school-specific well-being (6.2-point drop in survivor offspring vs. 18.2-point drop in KiGGS offspring). CONCLUSION: Comparable to higher parentally assessed HRQL was reported for survivor offspring compared to peers. These findings are reassuring and consistent with self-reported HRQL in childhood cancer survivors. Type of parental cancer diagnosis and treatment showed no negative impact on offspring HRQL.

Health outcomes in offspring born to survivors of childhood cancers following assisted reproductive technologies.

PURPOSE: An increasing number of childhood cancer survivors are using assisted reproductive technologies (ART) to overcome treatment-related fertility impairment. We report perinatal and health outcomes of offspring born to survivors following ART. METHODS: The FeCt Multicenter Offspring Study surveyed the health of offspring of childhood cancer survivors. Health outcomes in offspring born to survivors following ART (n = 57, 4.6%) or after spontaneous conception (n = 1182) were assessed in the German cohort (n = 1239) using bivariate analysis. Findings were put into the context of the general German population by health outcome assessment in 1:1 matched-pair analysis (n = 2478). RESULTS: Nearly twice the survivors used ART compared with numbers reported for the German general population (4.6% vs. 2.6%). Successful pregnancies were achieved after a median of two cycles, mainly using non-cryopreserved oocytes/sperm. Multiple sibling births (p < 0.001, 28.1% vs. 3.0%) and low birth weight (p = 0.008; OR = 2.659, 95% CI = 1.258-5.621) occurred significantly more often in offspring born to survivors who utilized ART than spontaneously conceived children, whereas similar percentages were born preterm or too small for their gestational age. ART did not increase the prevalence of childhood cancer or congenital malformations in offspring born to survivors. CONCLUSION: ART use by childhood cancer survivors was successful with both fresh and cryopreserved oocytes/sperm, and did not influence perinatal health or health outcomes when known confounders were taken into account. IMPLICATIONS FOR CANCER SURVIVORS: Oncofertility is an important component of patient care. Our study implicates that the utilization of ART by adult survivors of childhood cancer does not put offspring at additional risk for adverse perinatal or health outcomes.

Fertility education for adolescent cancer patients: Gaps in current clinical practice in Europe.

OBJECTIVE: As adolescent cancer patients may suffer from infertility following treatment, fertility counselling is essential. Our aim was to explore the current situation in four European countries in terms of (I) education about the risk for infertility, (II) counselling on fertility preservation, (III) patients' knowledge on fertility, (IV) sufficiency of information and (V) uptake of cryopreservation. METHODS: In total, 113 patients (13-20 years) at 11 study centres completed a self-report questionnaire three and six months after cancer diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: As many as 80.2% of participants reported having received education about the risk for infertility prior to treatment, 73.2% recalled counselling on fertility preservation. Only 52.3% stated they felt sufficiently informed to make a decision. Inability to recall counselling on fertility preservation (OR = 0.03, CI: 0.00-0.47) and female gender (OR = 0.11, CI: 0.03-0.48) was associated with lower use of cryopreservation, whereas older age was associated with higher use. CONCLUSION: Fertility counselling was available to a relatively high proportion of patients, and it did influence the utilisation of cryopreservation. However, many patients did not feel sufficiently informed. Further improvement is needed to enable adolescent cancer patients to make an informed decision on fertility preservation.

Determinants of utilization of cryopreservation of germ cells in adolescent cancer patients in four European countries.

Infertility is a relevant late-effect following cancer treatment; yet, a large proportion of survivors cannot recall having been informed of this risk. In an intervention study, we examined if and how supportive patient information material on fertility/fertility-preserving measures influences utilization of cryopreservation in adolescent cancer patients. The control group, recruited 03/2014-01/2016, received the usual patient education at initial diagnosis. The intervention group, recruited 04/2016-10/2017, received patient education supported by a fertility flyer and brochure. Patients and parents were each asked questions on utilization of cryopreservation in a questionnaire 3 and 6 months after initial diagnosis. Patient core and therapy data were obtained from medical records. Overall, cryopreservation rates showed no significant difference between the control (32.7%, n = 37/113) and intervention group (36.6%, n = 37/101). In the control group, cryopreservation was associated with gender (OR 0.100, CI 0.023-0.427), age (OR 1.559, CI 1.077-2.258) and recalling information on fertility protection (OR 33.663, CI 2.100-539.574); in the intervention group, cryopreservation was related to gender (OR 0.093, CI 0.026-0.330) and the estimated infertility risk (OR 43.665, CI 2.157-883.974).Conclusion: Cryopreservation rates did not overall increase following the intervention; however, the individual risk seemed to be brought into attention more: Those at risk, including younger patients, cryopreserved at higher rates.What is Known:•Infertility is a relevant late-effect following adolescent cancer.•Guidelines recommend to offer fertility protection before cancer treatment.•A relevant proportion of adolescents with cancer are not aware of this risk.•Fertility protection seems under-used in cancer patients at risk for infertility.What is New:•Information material on fertility and protection in adolescents did not increase overall rates of cryopreservation.•Cryopreservation rates were improved according to individual risk for infertility.•Our flyers and brochures on fertility in cancer patients are available in various languages.

Fertility-Related Wishes and Concerns of Adolescent Cancer Patients and Their Parents.

Purpose: Within a multicenter European study, we explored fertility-related wishes, concerns, and decision-making of adolescent cancer patients and their parents. Patients and Methods: Patients and parents were each asked to complete a fertility-related questionnaire 3 months after initial diagnosis. In total, 113 of 142 (79.6%) eligible patients participated; 53.1% were male and the median age was 16 years (range 13-20 years). The questionnaire was completed by 111 parents. Univariate analyses were conducted using nonparametric methods with alpha = 5%. For multivariate analyses, binary logistic regression was conducted. Results: Both patients (86.1%) and parents (96.3%) indicated a strong desire for biological parenthood for themselves/their children. Female patients (odds ratio [OR] = 3.70; confidence interval [CI]: 1.43-9.50) and parents (OR = 2.70; CI: 1.21-6.00) were more likely to report a high fear of cancer recurrence. Patients who estimated their risk for fertility impairment being high were more likely to be concerned about their fertility (OR = 5.69; CI: 1.41-22.98). Parents who received fertility preservation information were more likely to recommend its use to their children (OR = 5.50; CI: 1.07-28.40), whereas parents of female patients were less likely to do so (OR = 0.13; CI: 0.03-0.61). Conclusions: The prospect of fertility following cancer treatment is important for adolescent cancer patients and their parents, yet it is associated with many concerns. Counseling regarding fertility preservation can be more effective when the individual needs of patients and their parents are taken into consideration.

Fertility knowledge and associated empowerment following an educational intervention for adolescent cancer patients.

INTRODUCTION/OBJECTIVES: Fertility preservation is a major concern for adolescent cancer patients; yet, educational gaps remain. Our intervention study examined whether specially designed educational materials regarding fertility preservation increase knowledge and empowerment of patients and parents. METHODS: Eleven paediatric-oncological centres in four European countries agreed to enrol all eligible patients and parents in a questionnaire survey at 3 and 6 months after diagnosis. Treating physicians were surveyed on their medical consultation regarding fertility. RESULTS: Educational intervention increased knowledge in both patients (n = 113 and n = 101 in the control and intervention groups, respectively) and parents (n = 111 and n = 99 in the control and intervention groups, respectively), but the difference did not achieve statistical significance (knowledge difference patients: 5.6% (t0)/13.1% (t1); parents: 6.4% (t0)/3.8% (t1)). Parents of older patients (OR = 1.3, 95%CI = 1.1-1.7) and higher educational groups (OR = 6.2, 95%CI = 2.1-18.3) in the intervention group (OR = 1.9, 95%CI = 1.03-3.7) achieved higher knowledge levels. Empowerment was significantly improved in both patients (p = 0.046, d = 0.27) and parents (p = 0.046, d = 0.48) in the intervention group. DISCUSSION/CONCLUSIONS: In our study, the use of specifically prepared flyers and brochures successfully raised the level of fertility preservation knowledge in parents of older patients as well as parents with higher educational levels. Overall, the intervention improved patient and parent empowerment. Subsequent projects will include simpler information and digital material to particularly reach out to younger and less educated individuals.

Fertility Preservation for Patients with Malignant Disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) - Recommendations and Statements for Girls and Women.

AIM: The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline. METHODS: This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40). RECOMMENDATIONS: The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patient's personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.

Impact of chemotherapy and radiotherapy in childhood on fertility in adulthood: the FeCt-survey of childhood cancer survivors in Germany.

PURPOSE: Improved treatment for childhood cancer has led to better survival rates of 83 % today. However, long-term side effects including infertility of pediatric patients receiving oncologic treatment remain unclear. We examined the association of chemotherapy and radiotherapy with infertility in survivors of pediatric cancer. METHODS: A questionnaire on fertility was sent to adult survivors listed in the German Childhood Cancer Registry. Fertility status was defined based on information on attempts to conceive, pregnancies, births, menstrual cycle and previous fertility test results. RESULTS: Therapeutic data were obtained from treatment optimization trials. We included 618 childhood cancer survivors (384 women) who reported information allowing us to classify their current fertility status as 'fertile/probably fertile' or 'probably infertile'. Thirty-one percent of 83 female and 29 % of 117 male survivors reported infertility based on previous fertility tests. 'Probably infertile' adult survivors were more likely to have received pelvic radiotherapy (women: adjusted OR 20.24, 95 % CI 4.69-87.29; men: 12.22; 1.18-126.70) than those who were 'fertile/probably fertile'. Etoposide, particularly ≥5,000 mg/m(2) in women, and carboplatin and/or cisplatin in both sexes seemed to have independent risk potential for infertility. Similarly, cancer treatment during or post-puberty compared to treatment before puberty showed a trend toward increased infertility, particularly in male survivors. CONCLUSIONS: Patients and families need to be informed about fertility-preserving measures prior to and also after chemotherapy and radiotherapy.

Suspected infertility after treatment for leukemia and solid tumors in childhood and adolescence.

BACKGROUND: With improved cure rates of cancer in children and adolescents, the long-term effects of oncological treatment, including impaired fertility, have become an important clinical issue. METHODS: In 2008, we conducted a nationwide survey in Germany in which we asked 4689 female and male patients who had been treated for cancer in childhood or adolescence for information on menstruation, previous fertility testing (if any), attempts to conceive, and pregnancies. In a complementary study carried out in 2009, 748 former cancer patients in Berlin were offered hormone testing and sperm analysis. The defined criteria for suspected infertility were, in women, anti-muellerian hormone levels below 0.1 ng/mL; in men, FSH levels above 10 IU/L and inhibin B levels below 80 pg/mL, or azoospermia. RESULTS: The respondents to the nationwide survey included 1476 leukemia survivors and 1278 persons who had had a solid tumor. 104 former leukemia patients and 96 former solid tumor patients had already undergone fertility testing, leading to the suspicion of infertility in 26% and 34% of the persons in these respective groups (95% confidence intervals [CI], 18%-34% and 25%-43%). The patients who were tested in the Berlin study included 59 leukemia survivors and 104 persons who had had a solid tumor. The frequency of suspected infertility in these two groups was 25% and 27%, respectively (95% CI, 14%-36% and 18%-36%). CONCLUSION: Up to one-third of adults who undergo fertility testing after having been treated for cancer in childhood or adolescence have suspected infertility. Patients and their parents should be counseled about the possibility of infertility and about fertility-preserving measures.