Cryopreservation of ovarian tissue for fertility preservation in breast cancer patients: time to stop?

Fertility preservation is currently offered to young women with breast cancer to increase their chances of motherhood after a potentially gonadotoxic treatment. Ovarian stimulation with oocyte vitrification and cryopreservation of ovarian tissue remain the most commonly used methods of choice. Whichever method is preferred is very much dependent on the practice and experience of the clinics, although for breast cancer in particular one method might be superior to the other. Cryopreservation of ovarian tissue is inevitably associated with the iatrogenic reduction of the ovarian reserve of a patient and should only be offered to women with a high risk of premature ovarian insufficiency following treatment. However, for younger breast cancer survivors, pregnancy and delivery rates are reassuringly high, even after chemotherapy. Despite its widespread use, few women come back to make use of their cryopreserved tissue. It is argued here that cryopreservation of ovarian tissue is not an appropriate option for breast cancer patients and discuss the reasons for this opinion.

New expert advice on cancer in pregnancy.

Cancer in pregnancy is rare, and most physicians lack knowledge in handling pregnant cancer patients. This review summarises the present knowledge on this condition. In the Netherlands, an Advisory Board on Cancer in Pregnancy was established in 2012. The board supports Dutch physicians' decisions in the management of pregnant patients with cancer. In 2021 the International Advisory Board on Cancer in Pregnancy was established, and in continuation, the Danish Advisory Board on Cancer in Pregnancy (DABCIP) has now been founded. DABCIP consists of 22 members from 13 different medical disciplines.

Fertility preservation in women with benign gynaecological conditions.

Although a wealth of data has been published regarding fertility preservation (FP) in women with malignant diseases who receive gonadotoxic treatment, the role of FP in non-malignant conditions has been studied to a much lesser extent. These include benign haematological, autoimmune, and genetic disorders, as well as a multitude of benign gynaecological conditions (BGCs) that may compromise ovarian reserve and/or reproductive potential due to pathogenic mechanisms or as a result of medical or surgical treatments. Alongside accumulating data that document the reproductive potential of cryopreserved oocytes and ovarian tissue, there is potential interest in FP for women with BGCs at risk of infertility; however, there are currently insufficient data about FP in women with BGCs to develop guidelines for clinical practice. The purpose of this article is to appraise the available evidence regarding FP for BGC and discuss potential strategies for FP based on estimated ovarian impairment and on short-term and long-term reproductive goals of patients. Cost-effectiveness considerations and patients' perspectives will also be discussed.

Cryopreservation of ovarian tissue as fertility preservation in young women with multiple sclerosis before stem cell transplantation.

BACKGROUND: Women of fertile age who receive autologous hematopoietic stem cell transplantation (AHSCT) due to multiple sclerosis (MS) are at risk of loss of ovarian function and infertility because of the conditioning regimen with alkylating agents. OBJECTIVE: To present our data on fertility preservation by ovarian tissue cryopreservation (OTC) in young women with MS before AHSCT. METHODS: Retrospective, observational cohort study RESULTS: Eight women had OTC. After AHSCT four had premature ovarian insufficiency (POI), and two of these had autotransplantation of their cryopreserved ovarian tissue. Both women regained ovarian function, and a spontaneous pregnancy was achieved resulting in the delivery of a healthy baby. CONCLUSION: OTC preserves fertility in young women with MS at risk of POI.

Intrafollicular Concentrations of the Oocyte-secreted Factors GDF9 and BMP15 Vary Inversely in Polycystic Ovaries.

CONTEXT: The oocyte-secreted factors growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play essential roles in follicle development and oocyte maturation, and aberrant regulation might contribute to the pathogenesis of polycystic ovary syndrome. OBJECTIVE: Are there measurable differences in concentrations of GDF9, BMP15, and the GDF9/BMP15 heterodimer in small antral follicle fluids from women with and without polycystic ovaries (PCO)? DESIGN AND SETTING: Follicle fluids (n = 356) were collected from 4- to 11-mm follicles in unstimulated ovaries of 87 women undergoing ovarian tissue cryopreservation for fertility preservation. PATIENTS: Twenty-seven women with PCO were identified and 60 women without PCO-like characteristics (non-PCO women) were matched according to age and follicle size. MAIN OUTCOME MEASURES: Intrafollicular concentrations of GDF9, BMP15, GDF9/BMP15 heterodimer, anti-Mullerian hormone (AMH), inhibin-A and -B, total inhibin, activin-B and -AB, and follistatin were measured using enzyme-linked immunosorbent assays. RESULTS: The detectability of GDF9, BMP15, and the GDF9/BMP15 heterodimer were 100%, 94.4%, and 91.5%, respectively, and concentrations were significantly negatively correlated with increasing follicle size (P < 0.0001). GDF9 was significantly higher in women with PCO (PCO: 4230 ±â€…189 pg/mL [mean ±â€…SEM], n = 188; non-PCO: 3498 ±â€…199 pg/mL, n = 168; P < 0.03), whereas BMP15 was lower in women with PCO (PCO: 431 ±â€…40 pg/mL, n = 125; non-PCO: 573 ±â€…55 pg/mL, n = 109; P = 0.10), leading to a significantly higher GDF9:BMP15 ratio in women with PCO (P < 0.01). Significant positive associations between BMP15 and AMH, activins, and inhibins in non-PCO women switched to negative associations in women with PCO. CONCLUSIONS: Intrafollicular concentrations of GDF9 and BMP15 varied inversely in women with PCO reflecting an aberrant endocrine environment. An increased GDF9:BMP15 ratio may be a new biomarker for PCO.

Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis.

BACKGROUND: Ovarian tissue cryopreservation involves freezing and storing of surgically retrieved ovarian tissue in liquid or vapour nitrogen below -190°C. The tissue can be thawed and transplanted back with the aim of restoring fertility or ovarian endocrine function. The techniques for human ovarian tissue freezing and transplantation have evolved over the last 20 years, particularly in the context of fertility preservation in pre-pubertal cancer patients. Fresh ovarian tissue transplantation, using an autograft or donor tissue, is a more recent development; it has the potential to preserve fertility and hormonal function in women who have their ovaries removed for benign gynaecological conditions. The techniques of ovarian tissue cryopreservation and transplantation have progressed rapidly since inception; however, the evidence on the success of this intervention is largely based on case reports and case series. OBJECTIVE AND RATIONALE: The aim of this study was to systematically review the current evidence by incorporating study-level and individual patient-level meta-analyses of women who received ovarian transplants, including frozen-thawed transplant, fresh or donor graft. SEARCH METHODS: The review protocol was registered with PROSPERO (CRD42018115233). A comprehensive literature search was performed using MEDLINE, EMBASE, CINAHL and Cochrane Central Register of Controlled Trials from database inception to October 2020. Authors were also contacted for individual patient data if relevant outcomes were not reported in the published manuscripts. Meta-analysis was performed using inverse-variance weighting to calculate summary estimates using a fixed-effects model. OUTCOMES: The review included 87 studies (735 women). Twenty studies reported on ≥5 cases of ovarian transplants and were included in the meta-analysis (568 women). Fertility outcomes included pregnancy, live birth and miscarriage rates, and endocrine outcomes included oestrogen, FSH and LH levels. The pooled rates were 37% (95% CI: 32-43%) for pregnancy, 28% (95% CI: 24-34%) for live birth and 37% (95% CI: 30-46%) for miscarriage following frozen ovarian tissue transplantation. Pooled mean for pre-transplant oestrogen was 101.6 pmol/l (95% CI: 47.9-155.3), which increased post-transplant to 522.4 pmol/l (95% CI: 315.4-729; mean difference: 228.24; 95% CI: 180.5-276). Pooled mean of pre-transplant FSH was 66.4 IU/l (95% CI: 52.8-84), which decreased post-transplant to 14.1 IU/l (95% CI: 10.9-17.3; mean difference 61.8; 95% CI: 57-66.6). The median time to return of FSH to a value <25 IU/l was 19 weeks (interquartile range: 15-26 weeks; range: 0.4-208 weeks). The median duration of graft function was 2.5 years (interquartile range: 1.4-3.4 years; range: 0.7-5 years). The analysis demonstrated that ovarian tissue cryopreservation and transplantation could restore reproductive and hormonal functions in women. Further studies with larger samples of well-characterized populations are required to define the optimal retrieval, cryopreservation and transplantation processes. WIDER IMPLICATIONS: Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function. Although this technology was developed as a fertility preservation option, it may have the scope to be considered for endocrine function preservation.

Family Formation and Socio-Economic Status among 35-Year-Old Men Who Have Survived Cancer in Childhood and Early Adulthood: A Register-Based Cohort Study.

INTRODUCTION: The number of children and young adults who survive cancer has steadily increased over the past decades. Consequently, life circumstances after cancer have gained increasing importance. The aim of this study was to explore family formation and socio-economic status among 35-year-old men having survived cancer in childhood or early adulthood compared to an age-matched comparison group. METHODS: This study is a national, register-based cohort study among 35-year-old men. Men diagnosed with cancer in childhood and early adulthood were registered between 1978 and 2016. At the time of diagnosis, each patient was randomly matched with 150 men without cancer from the background population within the same birth year. Those still alive at the age of 35 years were included in the study population. RESULTS: The study population consisted of 4,222 men diagnosed with cancer in childhood or early adulthood and 794,589 men in the age-matched comparison group. Men who have survived cancer during childhood or early adulthood have a reduced probability of having children, and lower probability of getting married or of cohabitation than those from an age-matched comparison group. Men who have survived CNS cancer also have a lower probability of having a higher education than high school and a higher probability of being outside the workforce than those from an age-matched comparison group. DISCUSSION/CONCLUSION: Many men who have survived cancer during childhood or early adulthood are influenced by their cancer later in life, which was apparent in family formation, educational achievements, and labour market attachment. Continued focus on rehabilitation and needs for support among the male survivors of childhood and youth cancer is warranted.

[Fertility preservation].

Fertility preservation should be considered in girls and young women faced with a potentially gonadotoxic treatment such as chemotherapy. IVF can be performed with the aim to collect and freeze the oocytes, or ovarian tissue can be cryopreserved and transplanted back to the patient at a later stage. Whichever method is chosen depends upon the age of the patient, the gonadotoxicity of her treatment and the time frame. It is important to refer young cancer patients to fertility preservation counselling before treatment starts, as argued in this review.

Futures and fears in the freezer: Danish women's experiences with ovarian tissue cryopreservation and transplantation.

RESEARCH QUESTION: Ovarian tissue cryopreservation (OTC) and subsequent re-transplantation is gaining ground as a valid technique to preserve fertility in patients facing imminent cancer treatment. This study explores patients' experiences with OTC and transplantation, including their reflections on long-term storage of tissue and the use of surplus tissue. DESIGN: Semi-structured qualitative interviews with 42 Danish women undergoing OTC between 2003 and 2018, 32 of whom had ovarian tissue transplanted. RESULTS: Overall, OTC was associated with positive experiences linked to the production of future-oriented hope and reproductive possibilities. It also generated a range of worries, particularly regarding hormone-sensitive cancers and the risk of re-transplanting malignant cells, and the women's arduous journeys to conceive after cancer resonated through the accounts. Moreover, the women's understanding of, and access to, information about the OTC procedure and its prospects affected the ways in which they approached storage and transplantation of their frozen tissue. Finally, the interviews showed how the stored ovarian tissue was also infused with potentiality beyond the scope of reproduction, both as a remedy to restore hormonal cycles and in the imagination of the-yet-to-be-discovered potential informing the women's reflections on donation and destruction. CONCLUSION: Although OTC is a 'hope technology' compared with freezing of oocytes and embryos, ovarian tissue is interlinked with risk and disease and positioned as an asset beyond the scope of reproduction. Importantly, this study underscores the need for provision of specialized information, follow-up, and fertility counselling after OTC and cancer treatment.

[Fertility counselling of younger women after cancer treatment].

Girls and younger women of fertile age are at risk of infertility and premature ovarian insufficiency, if they have received chemotherapy or radiotherapy. While many are offered fertility preservation before treatment, many are left with a need for follow-up after treatment, which is pointed out in this review. At the fertility clinic at Rigshospitalet, Denmark, a follow-up clinic has been introduced for previous cancer patients with focus on reproductive health, including assessment of ovarian function, planning of future pregnancies and initiation of hormone replacement therapy if needed.

Ovarian cortical follicle density in infertile women with low anti-Müllerian hormone.

PURPOSE: To evaluate the association between anti-Müllerian hormone (AMH) and follicle density in infertile women with diminished ovarian reserve (DOR) versus women with normal ovarian reserve? METHODS: Case-control study comparing follicle densities in ovarian cortex from 20 infertile women with DOR (AMH ≤ 5 pmol/L) and 100 controls with presumed normal ovarian reserve. RESULTS: For all women > 25 years, the follicle densities correlated positively with AMH levels. For each single picomole per liter increase in AMH the follicle density increased by 6% (95% CI 3.3-8.5%) when adjusted for age. This was similar for women with DOR and controls. The follicle density was 1.8 follicles/mm3 cortical tissue in women with DOR versus 7.0 in age-paired controls (p = 0.04). The women with DOR had a median AMH of 1.8 pmol/L versus 14.4 pmol/L in the age-paired control group (p < 0.001). The ratio of AMH/follicle density was 1:1 (1.8/1.8) in women with DOR and 2:1 (14.4/7.0) in the age-paired controls. Analyses for gonadotropin receptor polymorphisms could not explain the characteristics of women with DOR. The proportion of secondary follicles was higher in women with DOR compared with controls (4.6% versus 1.4%, p = 0.0003). Pooling all patients, the follicle density decreased significantly by 7.7% for every year added (p < 0.0001). The women with DOR had lower follicle densities than the controls, but the slopes were equal in the two cohorts. CONCLUSIONS: Follicle density and AMH concentrations correlate also when AMH is low. However, AMH is only a reliable marker for the true ovarian reserve when age is included in the estimation and women with DOR may have more follicles than their AMH levels imply.

Biopsying, fragmentation and autotransplantation of fresh ovarian cortical tissue in infertile women with diminished ovarian reserve.

STUDY QUESTION: Can ovarian biopsying per se and/or autotransplantation of fragmented ovarian cortical tissue activate dormant follicles and increase the number of recruitable follicles for IVF/ICSI in women with diminished ovarian reserve (DOR)? SUMMARY ANSWER: Ovarian biopsying followed by immediate autotransplantation of fragmented cortical tissue failed to increase the number of recruitable follicles for IVF/ICSI 10 weeks after the procedure either at the graft site or in the biopsied ovary, but 12 of the 20 women subsequently had a clinical pregnancy during the 1-year follow-up. WHAT IS KNOWN ALREADY: Infertile women with DOR constitute a group of patients with poor reproductive outcome mainly due to the low number of mature oocytes available for IVF/ICSI. Recent studies have shown that in vitro activation of residual dormant follicles by both chemical treatment and tissue fragmentation has resulted in return of menstrual cycles and pregnancies in a fraction of amenorrhoeic women with premature ovarian insufficiency. STUDY DESIGN, SIZE, DURATION: This is a prospective clinical cohort study including 20 women with DOR treated at the fertility clinic, Rigshospitalet, Denmark, during April 2016-December 2017. Non-pregnant patients were on average followed for 280 days (range 118-408), while women who conceived were followed until delivery. Study follow-up of non-pregnant patients ended in September 2018. PARTICIPANTS, MATERIALS, SETTING, METHODS: The study included infertile women aged 30-39 years with preserved menstrual cycles, indication for IVF/ICSI and repeated serum measurements of anti-Müllerian hormone (AMH) ≤ 5 pmol/L. Patients were randomized to have four biopsies taken from either the left or the right ovary by laparoscopy followed by fragmentation of the cortical tissue to an approximate size of 1 mm3 and autotransplanted to a peritoneal pocket. The other ovary served as a control. Patients were followed weekly for 10 weeks with recording of hormone profile, antral follicle count (AFC), ovarian volume and assessment for ectopic follicle growth. After 10 weeks, an IVF/ICSI-cycle with maximal ovarian stimulation was initiated. MAIN RESULTS AND THE ROLE OF CHANCE: No difference in the number of mature follicles after ovarian stimulation 10 weeks after the procedure in the biopsied versus the control ovaries was observed (1.0 vs. 0.7 follicles, P = 0.35). In only three patients, growth of four follicles was detected at the graft site 24-268 days after the procedure. From one of these follicles, a metaphase II (MII) oocyte was retrieved and fertilized, but embryonic development failed. Overall AMH levels did not change significantly after the procedure (P = 0.2). The AFC increased by 0.14 (95% CI: 0.06;0.21) per week (P < 0.005), and the biopsied ovary had on average 0.6 (95% CI: 0.3;-0.88) follicles fewer than the control ovary (P = 0.01). Serum levels of androstenedione and testosterone increased significantly by 0.63 nmol/L (95% CI: 0.21;1.04) and 0.11 nmol/L (95% CI: 0.01;0.21) 1 week after the procedure, respectively, and testosterone increased consecutively over the 10 weeks by 0.0095 nmol/L (95% CI: 0.0002;0.0188) per week (P = 0.045). In 7 of the 20 patients, there was a serum AMH elevation 5 to 8 weeks after the procedure. In this group, mean AMH increased from 2.08 pmol/L (range 1.74-2.34) to 3.94 pmol/L (range 3.66-4.29) from Weeks 1-4 to Weeks 5-8. A clinical pregnancy was obtained in 12 of the 20 (60%) patients with and without medically assisted reproduction (MAR) treatments. We report a cumulated live birth rate per started IVF/ICSI cycle of 18.4%. LIMITATIONS, REASON FOR CAUTION: Limitations of the study were the number of patients included and the lack of a non-operated control group. Moreover, 9 of the 20 women had no male partner at inclusion and were treated with donor sperm, but each of these women had an average of 6.8 (range 4-9) unsuccessful MAR treatments with donor sperm prior to inclusion. WIDER IMPLICATIONS OF THE FINDINGS: Although 12 out of 20 patients became pregnant during the follow-up period, the current study does not indicate that biopsying, fragmenting and autotransplanting of ovarian cortical tissue increase the number of recruitable follicles for IVF/ICSI after 10 weeks. However, a proportion of the patients may have a follicular response in Weeks 5-8 after the procedure. It could therefore be relevant to perform a future study on the possible effects of biopsying per se that includes stimulation for IVF/ICSI earlier than week 10. STUDY FUNDING/COMPETING INTEREST(S): This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. The funders had no role in the study design, data collection and interpretation, or decision to submit the work for publication. None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER: NCT02792569.

EUropean REcommendations for female FERtility preservation (EU-REFER): A joint collaboration between oncologists and fertility specialists.

In recent years, following the improved prognosis of patients with cancer, interest and attention has grown around fertility issues in these patients. International guidelines on fertility preservation in patients with cancer recommend that physicians discuss with all patients of reproductive age (or their parents/guardians, if children) the risk of infertility arising from their cancer or its treatment. Oncofertility counselling is recommended at the earliest opportunity and prior to cancer treatment, to help patients make informed decisions on pursuing fertility preservation. Currently, however, such discussions are not being routinely held. In June 2017, an esteemed group of European oncofertility experts met to discuss current unfulfilled needs in oncofertility for female cancer patients. This expert group has produced here a number of key recommendations in order to guide oncologists, haematologists, and other involved professionals with oncofertility discussions and appropriate referrals for further fertility preservation counselling and follow-up.

Prevalence of deaths in a cohort of girls and women with cryopreserved ovarian tissue.

INTRODUCTION: Ovarian tissue cryopreservation (OTC) is increasingly offered to women in need of fertility preservation. However, little is known about the risk of these women dying before they use the preserved material. MATERIAL AND METHODS: From 1999 to 2016, 927 girls and women underwent OTC in our center, before receiving gonadotoxic treatment. All patients were without disseminated disease and with an estimated chance of survival after 5 years of >50%. For each patient the specific indication for OTC was noted, and through a national registry linked to a personal identification number, we were able to identify those who had died and the date and cause of death. RESULTS: By December 2017, 124/927 patients had died from their disease (13%). The highest relative prevalence of death was seen in patients with liver cancer (2/2; 100%), gall bladder cancer (2/2; 100%), stomach cancer (1/1; 100%), hemophagocytic lymphohistiocytosis (2/3; 66%), scleroderma (1/2; 50%), and sarcoma (24/78; 31%). The lowest risk of dying was seen in the group of individuals with non-Hodgkin lymphoma (3/30; 10%) and breast cancer (31/313; 10%). The shortest time from OTC to death was seen in those with hemophagocytic lymphohistiocytosis (mean interval 0.25 years), gall bladder cancer, non-Hodgkin disease and acute myeloid leukemia (mean interval 0.7 years) and the longest time from OTC to death was in women with breast cancer (mean interval 3.4 years). Of those who died, 34 had received chemotherapy at some point before OTC, indicating a relapse or non-responsiveness to the initial treatment. CONCLUSIONS: Patients with upper gastrointestinal cancers and sarcoma had the highest risk of dying from their disease. Breast cancer patients had the lowest risk. This knowledge may guide clinicians in their decisions on whether to offer OTC to girls and younger women with a life-threatening disease.

Autotransplantation of fragmented ovarian cortical tissue: a laparoscopic demonstration.

OBJECTIVE: To describe and demonstrate a simple and secure procedure for laparoscopic autotransplantation of fragmented ovarian cortical tissue in women with diminished ovarian reserve as part of in vitro activation (IVA) of ovarian follicles. DESIGN: Step-by-step video explanation of the surgical procedure with still pictures and surgical video clips to demonstrate the detailed technique. SETTING: Fertility clinic and obstetrics and gynecology department at a university hospital. PATIENT(S): Women with idiopathic diminished ovarian reserve and indication for in vitro fertilization (IVF), aged 25 to 39 years with an antral follicle count bilaterally of ≤5, antimüllerian hormone level of ≤5 pmol/L, and two ovaries. INTERVENTION(S): The laparoscopic autotransplantation consists of six steps: [1] obtaining ovarian cortical biopsy samples, [2] preparing the peritoneal pocket, [3] fragmenting the ovarian cortical tissue into pieces of approximately 1 mm3, [4] installing the tissue fragments into a catheter, [5] transplanting the tissue fragments into the peritoneal pocket, and [6] closing the peritoneal pocket with a surgical clip. After the procedure, the patients are evaluated with blood samples and ultrasound scans followed by controlled ovarian stimulation. Ethics committee approval was obtained. MAIN OUTCOME MEASURE(S): Feasibility of a six-step laparoscopic autotransplantation procedure using fragmented ovarian cortical tissue. RESULT(S): A simple, fast laparoscopic procedure for taking biopsy samples and autotransplanting cortical tissue fragments in an all-in-one procedure ensures the rapid handling and correct placement of the small tissue fragments. The procedure is performed in an outpatient setting with an operation time of 1 hour. We have performed this procedure on 20 patients with no complications. CONCLUSION(S): In vitro activation is a new, developing option for women in fertility treatment who have diminished ovarian reserve. Fragmentation of murine ovarian tissue has shown to suppress the Hippo pathway, thereby initiating proliferation and growth. This surgical procedure resembles that used when transplanting pieces of frozen-thawed ovarian tissue for fertility restoration, but the fragmented ovarian tissue is only 1 mm3, which makes it difficult to transplant. Until now no surgical procedures for transplanting small IVA fragments of cortical tissue has been published. With this video we report in detail a simple way of autotransplanting small fragments of IVA cortical tissue using what is already accessible in the operating theater. Among the many advantages of this procedure are its short duration (1 hour) and outpatient setting, which enable fast recovery and minimal postoperative pain. The procedure also allows fast handling and minimal manipulation of the tissue (limited to the fragmentation). The effect of autotransplantation of fragmented tissue in women with diminished ovarian reserve is currently being studied in ongoing trials. If the technique is combined with chemical IVA, a better outcome may be seen.

Cryobanking of human ovarian tissue: Do women still want their tissue stored beyond 5 years?

Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond an initial 5-year period. Between 1999 and 2006, a total of 201 girls and young women had one ovary cryopreserved for fertility preservation in Denmark. One hundred of these met our inclusion criteria, which included a follow-up period of at least 5 years, and were mailed a questionnaire. The response rate was 95%. Sixteen of the patients (17%) stated that they wanted disposal of their tissue; the main reason was completion of family (63%). The mean age of those requesting disposal was 36.6 years, whereas those still wanting their tissue stored were significantly younger, with a mean age of 33.0 years (P < 0.008). In conclusion, most women with ovarian tissue cryobanked requested continued cryostorage after an initial period of at least 5 years. The main reason for requesting disposal was successful completion of a family.