Do Surgical Interventions Influence Psychosexual and Cosmetic Outcomes in Women with Disorders of Sex Development?

Clinical practice developed to promote psychosexual well-being in DSD is under scrutiny. Although techniques for genital surgery have much improved lately, long-term studies on psychosexual functioning and cosmetic outcome on which to base treatment and counseling are scarce. We studied 91 women with a DSD. Feminizing surgery was performed in 64% of the women; in 60% of them, resurgery in puberty was needed after a single-stage procedure. Both patients and gynecologists were satisfied with the cosmetic appearance of the genitalia. However, forty percent of these females experienced sexuality-related distress and 66% was at risk for developing a sexual dysfunction, whether they had surgery or not. Recognizing the difficulty of accurate assessment, our data indicate that feminizing surgery does not seem to improve nor hamper psychosexual outcome, especially in patients with severe virilization

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer

Purpose: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18–39 years) cancer. Methods: This study included n = 1457 male and n = 2112 female long-term survivors (M age = 43–45 years; 5–22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.Results: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2–3.6]), not having children (OR = 5.0; 95%CI [3.2–7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to “others”), and more intense treatments (OR = 1.5; 95%CI [1.1–2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. Conclusions: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors’ well-being. Implications for Cancer Survivors: The extent to which cryopreservation positively affects survivors’ well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.</p

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer

Purpose: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18–39 years) cancer. Methods: This study included n = 1457 male and n = 2112 female long-term survivors (M age = 43–45 years; 5–22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.Results: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2–3.6]), not having children (OR = 5.0; 95%CI [3.2–7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to “others”), and more intense treatments (OR = 1.5; 95%CI [1.1–2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. Conclusions: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors’ well-being. Implications for Cancer Survivors: The extent to which cryopreservation positively affects survivors’ well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.</p

Female reproductive function after treatment of childhood acute lymphoblastic leukemia

Background The aim was to evaluate self-reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data. Procedure Self-reported reproductive characteristics were assessed by questionnaire among 357 adult 5-year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy [CT]-only group, CT and radiotherapy [RT] group) were analyzed. Results Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P < .01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio [OR] [95% CI]: 0.3 [CI 0.1-0.6], 0.5 [0.3-0.9], and 0.4 [0.2-0.9], respectively). Survivors in the CT-only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function. Conclusion Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative

Pregnancy, time to pregnancy and obstetric outcomes among female childhood cancer survivors: results of the DCOG LATER-VEVO study

Purpose: To evaluate pregnancy rates, time to pregnancy (TTP) and obstetric outcomes in female childhood cancer survivors (CCSs) and to identify specific diagnosis- and treatment-related factors associated with these outcomes. Methods: The study is part of the DCOG LATER-VEVO study, a nationwide multicenter cohort study evaluating fertility among long-term Dutch female CCSs. Data were collected by questionnaire. The current study included 1095 CCSs and 812 controls, consisting of sisters of CCSs and a random sample of women from the general population. Results: Among the subgroup of women who ever had the desire to become pregnant, the chance of becoming pregnant was significantly lower for CCSs than controls (OR 0.5, 95%CI 0.4–0.8). Moreover, TTP was 1.1 times longer for CCSs compared to controls (p = 0.09) and was significantly longer in survivors of CNS and renal tumours. Overall, no differences were found between CCSs and controls regarding the probability of ever having had a miscarriage, still birth, or induced abortion. However, CCSs had a significantly increased risk of delivering preterm (OR 2.2, 95%CI 1.3–3.7) and delivering via caesarean section (OR 1.8, 95%CI 1.2–2.6). Treatment with lower abdominal/pelvic radiotherapy was strongly associated with several adverse obstetric outcomes. Conclusion: CCSs are less likely to have ever been pregnant. Among those who do become pregnant, certain subgroups of CCSs are at increased risk of longer TTP. Moreover, as pregnant CCSs, especially those treated with lower abdominal/pelvic radiotherapy, are more likely to develop various adverse obstetric outcomes, appropriate obstetric care is highly advocated

Reproductive outcomes and reproductive health care utilization among male survivors of childhood cancer: A DCCSS-LATER study

Background: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. Methods: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. Results: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p <.001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p =.86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p <.001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p =.001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p =.001). Conclusions: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists

Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function

STUDY QUESTION: Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)? SUMMARY ANSWER: Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy. WHAT IS KNOWN ALREADY: Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability. STUDY DESIGN, SIZE, DURATION: CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n =465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS: To evaluate ovarian function, anti-Miillerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Meta-analysis across the three independent cohorts showed a significant interaction effect (P= 3.0 x 10(-4)) between rs11668344 of BRSK 1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score >= 8000 mg/m(2)), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION: While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS: Further research, validating our findings and identifying additional risk contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer

A survey of fertility preservation options available to cancer patients around the globe

Purpose: Oncofertility focuses on providing fertility and endocrine-sparing options to patients who undergo life-preserving but gonadotoxic cancer treatment. The resources needed to meet patient demand often are fragmented along disciplinary lines. We quantify assets and gaps in oncofertility care on a global scale. Methods: Survey-based questionnaires were provided to 191 members of the Oncofertility Consortium Global Partners Network, a National Institutes of Health–funded organization. Responses were analyzed to measure trends and regional subtleties about patient oncofertility experiences and to analyze barriers to care at sites that provide oncofertility services. Results: Sixty-three responses were received (response rate, 25%), and 40 were analyzed from oncofertility centers in 28 countries. Thirty of 40 survey results (75%) showed that formal referral processes and psychological care are provided to patients at the majority of sites. Fourteen of 23 respondents (61%) stated that some fertility preservation services are not offered because of cultural and legal barriers. The growth of oncofertility and its capacity to improve the lives of cancer survivors around the globe relies on concentrated efforts to increase awareness, promote collaboration, share best practices, and advocate for research funding. Conclusion: This survey reveals global and regional successes and challenges and provides insight into what is needed to advance the field and make the discussion of fertility preservation and endocrine health a standard component of the cancer treatment plan. As the field of oncofertility continues to develop around the globe, regular assessment of both international and regional barriers to quality care must continue to guide process improvements

Survey of Third-Party Parenting Options Associated With Fertility Preservation Available to Patients With Cancer Around the Globe

Purpose: In the accompanying article, “Analysis of Fertility Preservation Options Available to Patients With Cancer Around the Globe,” we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. Methods: We provide data on the legalities of third-party assisted reproductive technologies and other family-building options in the 28 oncofertility-practicing countries surveyed. Results: We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. Conclusion: Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients

Survey of third-party parenting options associated with fertility preservation available to patients with cancer around the globe

bstract PURPOSE In the accompanying article, “Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe,” we showed that specific fertility preservation services may not be offered at various sites around the world because of cultural and legal barriers. We assessed global and regional experiences as well as the legal status of third-party reproduction and adoption to serve as a comprehensive international data set and resource for groups that wish to begin oncofertility interventions. METHODS We provide data on the legalities of third-party assisted reproductive technologies and other familybuilding options in the 28 oncofertility-practicing countries surveyed. RESULTS We found regional and country differences that will be important in the development of tailored resources for physicians and for patient brochures that are sensitive to these local restrictions and cultural norms. CONCLUSION Because many patients first consult Web-based materials, the formal assessment of the availability of these options provides members of the global oncofertility community with data to which they might otherwise not have ready access to better serve their patients