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

Present and future options for the preservation of fertility in female adolescents with cancer.

Fertility and sexuality are important aspects in the quality of life of long-term survivors of cancer. Adolescents in particular are in a very vulnerable period of their lives with respect to future fertility and sexuality. Special attention should be paid to preserve their fertility whenever possible. The gonadotoxic effect of chemotherapy is largely drug- and dosedependent and is related to age. The effect of radiotherapy is also dependent on dose and age and on the radiation therapy field. The prepubertal ovary is the least susceptible to gonadotoxicity. Ablative regimens for stem cell transplantation have an extremely high risk of ovarian failure. Alternative chemotherapy protocols can reduce long-term gonadotoxicity. Alkylating agents impose the highest risk in causing ovarian failure and should be avoided whenever possible. Up to now, the results of gonadoprotective hormonal therapy have been disappointing and contradictory. Transposition of the ovaries should be considered in each case of planned pelvic or whole body irradiation, where ovarian involvement is unlikely and chemotherapy not necessary. Cryopreservation of preimplantation embryos will seldom be possible in female adolescents due to the lack of a stable relationship with a male partner. Cryopreservation of mature and immature oocytes (necessitating in vitro maturation) is still assumed not to be safe for the offspring. Cryopreservation and transplantation of ovarian tissue seems to be the most promising way of future fertility preservation in female adolescents. At present, it is in its early experimental stage. Its safety and possibilities for fertility preservation in humans are not proven as yet. Additionally, technical and ethical issues need to be addressed. The counseling of female adolescents who are facing the threat of cancer needs careful consideration with regards to the psychosocial impact of the treatment and its consequences. Special attention should be paid to aspects of future quality of life, in particular: fertility and sexuality

Complete protection against cryodamage of cryopreserved whole bovine and human ovaries using DMSO as a cryoprotectant

Contains fulltext : 182452.pdf (publisher's version ) (Open Access)PURPOSE: This study aims to determine the optimal cryopreservation protocol for whole ovaries intended for preservation of fertility in women. METHODS: We investigated the optimal cryopreservation procedure for whole ovaries in a bovine model. The following parameters were investigated to determine their effect on ovarian tissue viability: type of cryoprotectant, administration route of the cryoprotectant (perfusion and/or submersion), and the maximum tolerable interval between death of the animal and start of the cryopreservation process. The resulting optimal cryopreservation procedure for bovine ovaries was subsequently tested on human ovaries. In vitro glucose uptake, histology, and immunohistochemistry were used to assess the integrity of the ovarian tissue. RESULTS: Starting the cryopreservation procedure (including perfusion with and submersion in DMSO) within 10-15 min after death of the animal proved critical, resulting in a 90-100% protection level against cryodamage. When cryopreserving human ovaries using the same protocol, over 95% protection against cryodamage was observed on all tissue levels. In addition, no apparent morphological damage to either the follicles or the vascular endothelium was observed. CONCLUSION: Our findings suggest that using the optimized protocol presented in this paper allows good cryopreservation of whole human ovaries and represents an important step in considering whole ovary autotransplantation for clinically applied fertility preservation

[National guideline 'Cryopreservation of ovarian tissue']

Contains fulltext : 69276.pdf (publisher's version ) (Closed access)The treatment of children and young adults with cancer increasingly results in cure, but for a number of female patients this is at the expense of infertility. For women and girls with cancer and the wish to have children in the future, cryopreservation of ovarian tissue may be a solution in the absence of alternatives for the conservation of fertility. Because of the uncertain effectiveness and safety of cryopreservation of ovarian tissue, the Dutch national guideline 'Cryopreservation of ovarian tissue' advises removing and freezing ovarian tissue only if this is done within the framework of scientific research. Reimbursement of this procedure and financing of the relevant and necessary research have not yet been arranged

Ovarian reserve and oocyte maturity in cancer patients

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The influence of dietary sodium restriction on renal and ovarian renin and prorenin production during ovarian stimulation

Contains fulltext : 23156___.PDF (publisher's version ) (Open Access

[Herlyn-Werner-Wunderlich syndrome]

Item does not contain fulltextBACKGROUND: Many patients are admitted to accident and emergency departments with acute abdominal pain. Herlyn-Werner-Wunderlich syndrome (HWWS) is one of the less well-known causes of this. It is characterised by uterine didelphys with an obstructed hemivagina and ipsilateral renal agenesis or dysplasia. CASE DESCRIPTION: A 16-year-old girl presented to the emergency department with progressive abdominal pain and a previous history of renal and anal abnormalities. Acute appendicitis was suspected because of both tenderness on pressure and rebound tenderness, and a raised C-reactive protein level. Abdominal ultrasonography revealed a cystic structure, probably of ovarian or tubal origin. An emergency laparoscopy was performed as ovarian torsion was suspected. This revealed uterine didelphys with an abnormal right horn. Additional abdominal MRI scan diagnostic revealed abnormalities consistent with HWWS. CONCLUSION: Congenital urogenital abnormalities should be included in the differential diagnosis of patients with a previous history of renal or anal abnormalities who present with progressive abdominal pain or dysmenorrhoea

Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing's sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE