Anja Borgmann-Staudt

Patient Counselling on the Risk of Infertility and Its Impact on Childhood Cancer Survivors: Results from a National Survey

Fertility can be impaired by radiation and chemotherapy among childhood cancer survivors. Therefore, timely and adequate patient counselling about the risk of infertility and preservation methods is needed. The primary study objective was to assess remembered counselling among childhood cancer survivors. As a second objective, the impact of lacking patient counselling on offspring-related attitudes and behaviour was examined. Counselling regarding the late effects of gonadotoxicity that could be recalled by patients was assessed using a questionnaire sent by the German Childhood Cancer Registry. The questionnaire was answered by 2754 adult childhood cancer survivors (53.1% female, mean = 25.7 years). The proportion of patients who could not remember patient counselling about the late effects of chemo-/radiotherapy on fertility decreased significantly over time. In 1980 to 1984 67%, in 2000 to 2004 50% of the patients reported no memories of counselling (p < .001). Counselled patients feared significantly less that their children may have an increased cancer risk (4.4% vs. 6.7%, p = .03). They were also more likely to undergo fertility testing than patients who could not recall counselling (odds ratio = 2.91, 95% confidence interval [2.12, 3.99]). Patients reported an increased memory of patient counselling over the past 25 years. Still, a 50% rate of recalled counselling shows an ongoing need for adequate and especially sustainable counselling of paediatric cancer patients about infertility and other long-term adverse treatment effects. Those who reported a lack of counselling had offspring-related fears more frequently, which stopped them from having children.

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.

Association between self‐reported questionnaire data on fertility and results of hormone analyses in women after childhood cancer: A cross‐sectional study

Aim:  The aim of this study was to compare self‐reported questionnaire‐based information on fertility impairment with results from hormone analyses in women who underwent chemoradiotherapy during childhood and adolescence.

Childhood leukemia and its impact on graduation and having children: results from a national survey

Abstract To assess the level of graduation, the wish to have children and the course of pregnancy among former patients with childhood leukemia in comparison to the general German population and depending on gender, a nationwide survey was conducted in 2008. In total 63.6% (1476/2319) of the contacted survivors of childhood leukemia participated (mean age 25.7 years, range 19–43 years). Survivors graduated at higher levels of school compared to the general population, with 48.6% (female) versus 38.0% and 52.6% (male) versus 35.8% (p 0.001). Also, 93.3% of female and 89.3% of male survivors indicated a similar general wish to have children compared to the general population. Survivors reported parenthood less frequently compared to the general population (p 0.001). The course of pregnancy in survivors was characterized by fewer abortions (p 0.001). Having leukemia in childhood and adolescence impairs the likelihood of becoming a parent but reduces neither the wish to have children nor the level of graduation.

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 Among Female Survivors of Childhood, Adolescent, and Young Adult Cancer: Protocol for Two Pan-European Studies (PanCareLIFE)

Background Despite a significant number of studies on female fertility following childhood, adolescent, and young adult (CAYA) cancer, studies establishing precise (dose-related) estimates of treatment-related risks are still scarce. Previous studies have been underpowered, did not include detailed treatment information, or were based on self-report only without any hormonal assessments. More precise assessments of who is at risk for sub- or infertility are needed. Objective The objective of our study is to describe the design and methods of 2 studies on female fertility (a cohort study and a nested case-control study) among female survivors of CAYA cancer performed within the European PanCareLIFE project. Methods For the cohort study, which aims to evaluate the overall risk of fertility impairment, as well as the risk for specific subgroups of female CAYA cancer survivors, 13 institutions from 9 countries provide data on fertility impairment. Survivors are defined as being fertility impaired if they meet at least one of 8 different criteria based on self-reported and hormonal data. For the nested case-control study, which aims to identify specific treatment-related risk factors associated with fertility impairment in addition to possible dose-response relationships, cases (fertility impaired survivors) are selected from the cohort study and matched to controls (survivors without fertility impairment) on a 1:2 basis. Results Of the 10,964 survivors invited for the cohort study, data are available from 6619 survivors, either questionnaire-based only (n=4979), hormonal-based only (n=72), or both (n=1568). For the nested case-control study, a total of 450 cases and 882 controls are identified. Conclusions Results of both PanCareLIFE fertility studies will provide detailed insight into the risk of fertility impairment following CAYA cancer and diagnostic- or treatment-related factors associated with an increased risk. This will help clinicians to adequately counsel both girls and young women, who are about to start anticancer treatment, as well as adult female CAYA cancer survivors, concerning future parenthood and to timely refer them for fertility preservation. Ultimately, we aim to empower patients and survivors and improve their quality of life. Registered Report Identifier RR1-10.2196/10824

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.

Unexpected pregnancy after allogeneic stem cell transplantation.

Premature ovarian failure is a considerable problem following treatment of childhood cancer that depends on clinical risk factors and treatment. This year, we reported in your journal that an imminent infertility can be early identified by repeated, considerably reduced anti-Müllerian hormone values. This information can improve the patients’ chances of having children of their own through either suitably timed family planning or the use of reproductive medical methods. To emphasize the need and adequate use of reliable prognostic fertility markers after cancer therapy, we want to report a recent and unexpected pregnancy after allogeneic hematopoietic stem cell transplantation (HSCT). The future mother received an allogeneic HSCT with a conditioning regimen of busulfan with 4 ¥ 4 mg/kg bodyweight (BW) and cyclophosphamide with 2 ¥ 60 mg/kg BW at the age of 11 years due to the diagnosis of paroxysmal nocturnal hemoglobinuria. The patient developed an arterial hypertension 3 years after transplantation. The menarche occurred at the age of 13 years. Since then, she has had no further menstrual period in the following years. Four years after HSCT, the patient was diagnosed with a hypergonadotropic hypogonadism due to lower estradiol, higher luteinizing hormone and follicle-stimulating hormone values. Furthermore, a stagnation of the pubertal development occurred, which was treated subsequently with an estradiol-replacement-therapy. At the age of 18 years, she had a complete pubertal development with Tanner stages B5 and P5. Based on this development, the patient was told that she was infertile. Recently, this woman gave birth to an extremely low BW preterm infant at 25 weeks of gestation. She learned about her pregnancy at 22 weeks of gestation, most likely related to her notion of permanent infertility and her obesity concealing the gain in weight and abdominal girth. After 24 weeks 5/7 of gestation, progressive hypertension (175/105 mmHg), low platelet counts (91/nL) and tripled liver enzymes to the standard value prompted a cesarean section. A baby girl was born with a BW of 720 g and Apgar values of 7, 8 and 9 after 1, 5 and 10 min who eventually required prolonged mechanical ventilation and abdominal surgery for ileal volvulus. In conclusion, the need and adequate use of reliable prognostic fertility markers after cancer therapy needs to be emphasized. With the resulting information, the patient should be counseled regarding the possibility of timed family planning or the use of reproductive medical methods. Still, this counseling has to include the small chance of an unexpected pregnancy.