Magdalena Balcerek

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.

Impact of cranial irradiation and brain tumor location on fertility: a survey.

As survival rates of patients with childhood brain tumors have increased to 75%, treatment related side effects are of particular importance. The present study evaluated questionnaire-based fertility characteristics in cancer survivors treated with irradiation to the hypo-thalamic-pituitary-axis.A nationwide survey was conducted in collaboration with the German Childhood Cancer Registry. Questionnaire and treatment data could be retrieved for 1110 former childhood cancer patients with cranial irradiation and/or chemotherapy.Survivors receiving ≥30 gray vs. 18-29 gray and 0-17 gray to the pituitary gland reported less pregnancies or less with their partners (7.4% vs. 32.8% vs. 12.4%; p<0.001), were more often infertile (40% vs. 9.4% vs. 12.5%; p<0.001) and the female participants, had a higher frequency of permanent amenorrhea (16.7% vs. 1.7% vs. 0%; p<0.001).Irradiation of the pituitary gland ≥ 30 gray seemed to be associated with less pregnancies and increased permanent amenorrhea in women. Future studies need to be conducted to confirm these results. Increased knowledge of treatment related side effects might help brain tumor patients to improve their family planning if necessary by gonadotropine replacement.

Age at Menarche in Childhood Cancer Survivors: Results of a Nationwide Survey in Germany

Background/Aims: With rising cure rates of childhood cancer, side effects of treatment are attracting increasing interest. The present analysis evaluates the influence of tumor localization, radiotherapy and chemotherapy on the age of menarche. Methods: 4,689 former pediatric oncology patients, diagnosed 1980–2004, were contacted in collaboration with the German Childhood Cancer Registry. Results: 1,036 out of 1,461 female participants reported their age at menarche and had an oncological diagnosis before menarche. The median age at menarche was 13 years, compared to 12.8 years in the German general population. A significant delay of menarche was seen in patients with pituitary radiation doses of ≧30 Gy (mean 13.6 years, SD 2.2) compared to <30 Gy (mean 12.5 years, SD 1.4, p = 0.05). Patients with additional spinal radiation were even older at menarche (mean 14.4 years, SD 2.5). Pelvic and pelvic-near radiation significantly delayed onset of menarche (mean 14.0 years, SD 1.9 and mean 14.3, SD 2.6, respectively, p < 0.001). Only some chemotherapeutic agents (carboplatin/cisplatin, etoposide) were associated with a menarcheal delay of <1 year. Conclusion: Overall, female childhood cancer survivors showed a normal menarcheal age. Pituitary radiation dosage of ≧30 Gy, spinal and pelvic radiotherapy were associated with a moderate delay in the occurrence of menarche.

Nationwide Survey on the Health of Offspring from Former Childhood Cancer Patients in Germany

BACKGROUND Increased risk for infertility from cancer treatment and fear of health impairment in their offspring may prevent survivors of childhood cancer from having own children. Even though most studies report no increased risk for malformations, in our German fertility study 2008 a higher occurrence of cleft lip and palate was found in offspring of former patients. METHODS Since 2010 we assess offsprings health in a survey-based multicenter study, comparing diseases, well-being, healthcare utilization and health-related behavior between offspring from survivors, siblings or the general population. Within a first nationwide survey wave survivors who were known to have at least one child by previous fertility studies, received a questionnaire supported by the German Childhood Cancer Registry. Questionnaires were based on the KiGGS study on childrens health in the German general population conducted by the Robert-Koch Institute (n=17,641). RESULTS Questionnaires on 418 children were answered by 65% (254/393) of survivors contacted to participate in the first nationwide offspring study wave. Participants were more likely to be female (p<0.01), to have achieved higher educational levels (p<0.05) and to be a survivor of a soft tissue tumor (p<0.05). Former patients expressed moderate to high anxiety for the occurrence of cancer in 74% and feared other diseases in their children in 20%. CONCLUSION Offspring health is a topic of major relevance to former patients. Our offspring study is currently being extended to ~1500 offspring of childhood cancer survivors in Europe.

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 patientʼs personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.