Undergoing Fertility Preservation Research Articles

Viable Options for Fertility Preservation in Breast Cancer Patients: A Focus on Latin America.

Thanks to the improved survival outcomes observed in recent years, a growing attention has been given to the quality of life issues faced by young women with breast cancer such as fertility preservation and concerns related to future pregnancies. However, several challenges remain for young women with breast cancer considering undergoing fertility preservation strategies. Further specific issues on this regard should be taken into account in Latin America, where patients and physicians face particular barriers that hinder the routine adoption of this practice. Hence, further efforts are needed to overcome these deficiencies and improve the correct referral of breast cancer patients to fertility preservation strategies. The aim of the present review is to focus on the risk of anticancer treatment-related premature ovarian failure and infertility in young breast cancer patients, to summarize the current knowledge on the available options for fertility preservation, and to discuss the safety issues of pregnancy in breast cancer survivors. Furthermore, this review aims to highlight the specific clinical challenges in this field encountered by healthcare providers and young breast cancer patients from Latin American countries.

Effect of First Line Cancer Treatment on the Ovarian Reserve and Follicular Density in Girls Under the Age of 18 Years

Objective To study the impact of first-line antineoplastic treatment on ovarian reserve in young girls returning for ovarian tissue cryopreservation (OTC) in connection with a relapse. Design Retrospective case-control study. Setting University hospitals. Patient(s) Sixty-three girls under the age of 18 years who underwent OTC before (group 1: 31 patients) and after (group 2: 32 patients) their initial cancer treatment. Intervention(s) None. Main Outcome Measure(s) Follicular densities (follicles/mm 3 ) measured from an ovarian cortical biopsy before OTC. The ovarian volume (mL) of entire ovaries excised for OTC was also monitored. Result(s) There was no statistically significant difference in the mean age or follicular density between groups 1 and 2 (334 ± 476/mm 3 vs. 327 ± 756/mm 3 ). In contrast, the ovarian volume and total number of ovarian cortex chips cryopreserved were statistically significantly lower in patients who received gonadotoxic treatment before OTC (mean ± standard deviation [SD]: ovarian volume, 5.3 ± 3.1 mL vs. 2.9 ± 2.1 mL, respectively; number of cortex chips: 21.3 ± 8.1 vs. 15.2 ± 7.1, respectively). The reduction in the estimated ovarian reserve ranged from 10% to 20% in children to around 30% in adolescent girls (>10 years). Conclusion(s) Girls under the age of 10 tolerate a gonadotoxic insult better than adolescents, who may experience up to a 30% reduction in the ovarian reserve via first-line gonadotoxic treatment, which at present is considered to have little effect on the follicle pool. This information will improve counseling of young female cancer patients in deciding whether to undergo fertility preservation treatment.

The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review.

Can controlled ovarian hyperstimulation (COH) for fertility preservation be effectively conducted in women with breast cancer without worsening their prognosis? COH with co-administration of letrozole suppresses oestradiol levels without significantly impacting oocyte yield or decreasing disease-free survival rates. Oestradiol has the capacity to stimulate the proliferation of breast cancer cells. COH can cause oestradiol levels to rise by an order of magnitude above physiological levels. Concern exists regarding the effect of supra-physiological oestradiol levels in women with a recent diagnosis of breast cancer. A systematic review of the literature was performed using MEDLINE (PubMed database), EMBASE and the Cochrane Library. The search was restricted to articles written in English. No restrictions regarding the date of publication were applied. Safety was assessed in terms of relapse rates and cancer-related mortality rates. Peak oestradiol concentrations were recorded for different stimulation protocols. Efficacy was measured in terms of the total number of oocytes collected and proportion of mature oocytes. The primary outcome was mortality/recurrence in premenopausal women with Stage I-IIIB breast cancer who underwent COH in the immediate post-operative period, prior to chemotherapy. This is a systematic review of randomized control trials (RCTs), case control and cohort studies reporting on the primary outcome of mortality/recurrence after COH in women with early breast cancer, or secondary outcomes of oocyte yield and peak oestrogen concentration. Owing to the small number of RCTs available, other study types were included. The last electronic search was run in April 2016. Two prospective non-randomized studies reported relapse and breast cancer-related mortality rates in 397 women with breast cancer, of whom 149 underwent COH. Twelve studies reported the peak oestradiol concentrations of 882 women undergoing COH with letrozole co-administration. Four studies compared the oocyte yield of 248 women who underwent COH plus letrozole with 254 women who underwent standard COH. Two studies compared peak oestradiol concentrations and oocyte yield in 61 women who underwent COH with tamoxifen co-administration and 49 women who underwent COH without tamoxifen. One study compared letrozole and tamoxifen co-administration, and another study compared the co-administration of letrozole and anastrozole. The search identified 1002 records of which 15 were included in the final analysis. There was no evidence of a decline in relapse-free survival rates in the two studies of women with breast cancer who received COH with letrozole co-administration compared with women who did not undergo fertility preservation procedures. The largest of these studies reported recurrences in 6/120 (5.0%) women who received COH plus letrozole compared with 12/217 (5.5%) women who did not undergo COH (mean follow-up 5.0 versus 6.9 years; hazard ratio for recurrence 0.77, 95%CI 0.28-2.13). Conclusions regarding women with breast cancer who received tamoxifen during COH could not be made due to insufficient data. Peak oestradiol concentrations (338-829 pg/ml) were suppressed by letrozole when commenced on Days 2-3, with no decrease in oocyte yield. Tamoxifen does not suppress oestradiol concentrations, but may convey protection via its inhibitory action on the oestrogen receptor. Any statements regarding the safety of COH in women with breast cancer are based on a limited number of observational studies. High quality evidence is unlikely to become available for ethical and practical reasons. Whilst available data do not indicate a decline in disease-free survival, a small effect cannot be excluded. Breast cancers are heterogeneous in their genetic profile and receptor status, making the results of studies difficult to generalize to individual cases. The implication of alterations in other hormone levels such as androgens, progestins or vascular endothelial growth factor secondary to COH in women with breast cancer has not been quantified. The co-administration of 5 mg of letrozole daily commencing on Day 2 and continuing throughout COH is recommended as it reduces peak oestradiol concentrations without significantly decreasing oocyte yield. The use of a GnRH agonist trigger is beneficial as oestradiol concentrations rapidly decrease post-administration and rates of ovarian hyperstimulation are lower than with an hCG trigger, without a corresponding reduction in clinical pregnancy or live birth rates in cryopreservation cycles. The protective effect of tamoxifen has not been evaluated although theoretically may be of benefit due to its action on the oestrogen receptor. None. None.

Fertility preservation and decisional regret in young breast cancer survivors: A longitudinal analysis.

106 Background: Fertility is important to many young breast cancer survivors (YBCS), who face difficult decisions on whether to undergo fertility preservation prior to treatment. Because few longitudinal data assessing decisional regret are available, the objectives of this study were to assess longitudinal changes in decisional regret on fertility preservation following breast cancer diagnosis; determine if fertility preservation treatment decisions are related to decreased decisional regret. Methods: From 3 academic breast cancer programs, 169 YBCS younger than age 45 were recruited at diagnosis between 2009 and 2012 and followed prospectively for ovarian function. Participants completed questionnaires on fertility preservation choices and the Decisional Regret Scale (DRS) during study visits every 6 months for up to 5 years. DRS is scored 0 (no regret) to 100 (highest regret). DRS was dichotomized as none versus any decisional regret. Generalized linear models estimated the change in DRS over time and the association between patient characteristics and DRS. Results: Mean age at diagnosis was 38.7 (SD 4.8). Median total follow-up was 176 days (IQR 84 to 1415 days). Enrollment DRS was available for 89 women; 48% reported decisional regret about fertility preservation (median DRS=20). Participants worried about future fertility were more likely to report decisional regret (p=0.009). 31% underwent fertility preservation, but this was not associated with decisional regret (p=0.65). In repeated measures analysis for the entire cohort, no significant change in DRS occurred over this time period (OR 0.8, 95% CI 0.4-1.7). Worry about future fertility remained significantly associated with DRS over time (OR 55.1, 95% CI 7.7-395.1). Conclusions: In a cohort of YBCS, experiencing decisional regret about fertility preservation persists for years after diagnosis. Those worried about future fertility are more likely to experience decisional regret regarding fertility preservation.

Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients.

Can a counseling tool be developed for women desiring elective oocyte cryopreservation to predict the likelihood of live birth based on age and number of oocytes frozen? Using data from ICSI cycles of a population of women with uncompromised ovarian reserve, an evidence-based counseling tool was created to guide women and their physicians regarding the number of oocytes needed to freeze for future family-building goals. Elective oocyte cryopreservation is increasing in popularity as more women delay family building. By undertaking elective oocyte freezing at a younger age, women hope to optimize their likelihood of successful live birth(s) using their thawed oocytes at a future date. Questions often arise in clinical practice regarding the number of cryopreserved oocytes sufficient to achieve live birth(s) and whether or not additional stimulation cycles are likely to result in a meaningful increase in the likelihood of live birth. As relatively few women who have electively cryopreserved oocytes have returned to use them, available data for counseling patients wishing to undergo fertility preservation are limited. A model was developed to determine the proportion of mature oocytes that fertilize and then form blastocysts as a function of age, using women with presumably normal ovarian reserve based on standard testing who underwent ICSI cycles in our program from January, 2011 through March, 2015 (n = 520). These included couples diagnosed exclusively with male-factor and/or tubal-factor infertility, as well as cycles utilizing egg donation. Age-specific probabilities of euploidy were estimated from 14 500 PGS embryo results from an external testing laboratory. Assuming survival of thawed oocytes at 95% for women <36 y and for egg donors, and 85% for women ≥36 y, and 60% live birth rate per transferred euploid blastocyst, probabilities of having at least one, two or three live birth(s) were calculated. First fresh male-factor and/or tubal-factor only autologous ICSI cycles (n = 466) were analyzed using Poisson regression to calculate the probability that a mature oocyte will become a blastocyst based on age. Egg donation cycles (n = 54) were analyzed and incorporated into the model separately. The proportion of blastocysts expected to be euploid was determined using PGS results of embryos analyzed via array comparative genomic hybridization. A counseling tool was developed to predict the likelihood of live birth, based on individual patient age and number of mature oocytes. This study provides an evidence-based model to predict the probability of a woman having at least one, two or three live birth(s) based on her age at egg retrieval and the number of mature oocytes frozen. The model is derived from a surrogate population of ICSI patients with uncompromised ovarian reserve. A user-friendly counseling tool was designed using the model to help guide physicians and patients. The data used to develop the prediction model are, of necessity, retrospective and not based on patients who have returned to use their cryopreserved oocytes. The assumptions used to create the model, albeit reasonable and data-driven, vary by study and will likely vary by center. Centers are therefore encouraged to consider their own blastocyst formation and thaw survival rates when counseling patients. Our model will provide a counseling resource that may help inform women desiring elective fertility preservation regarding their likelihood of live birth(s), how many cycles to undergo, and when additional cycles would bring diminishing returns. None. Not applicable.

Extracellular-like matrices and leukaemia inhibitory factor for in vitro culture of human primordial follicles.

The possibility of maturing human primordial follicles in vitro would assist fertility restoration without the danger of reseeding malignancies. Leukaemia inhibitory factor (LIF) and certain culture matrices may promote human follicular growth. The present study compared human primordial follicular growth on novel culture matrices, namely human recombinant vitronectin (hrVit), small intestine submucosa (SIS), alginate scaffolds and human recombinant virgin collagen bioengineered in tobacco plant lines (CollPlant). The frozen-thawed ovarian samples that were used had been obtained from girls or young women undergoing fertility preservation. In the first part of the study, 20 samples were cultured for 6 days on hrVit or SIS with basic culture medium alone or supplemented with one of two concentrations of LIF (10ngmL-1 and 100ngmL-1), with and without LIF-neutralising antibody. In the second part of the study, 15 samples were cultured for 6 days on alginate scaffolds or CollPlant matrices with basic culture medium. Follicular development was assessed by follicular counts and classification, Ki67 immunohistochemistry and 17β-oestradiol and anti-Müllerian hormone measurements in spent media samples. Primordial follicular growth was not enhanced by LIF. Despite some significant differences among the four matrices, none appeared to have a clear advantage, apart from significantly more Ki67-stained follicles on alginate and CollPlant matrices. Further studies of other culture matrices and medium supplements are needed to obtain an optimal system.

Fertility Preservation in Pediatric and Adolescent Patients Undergoing HSCT: a Cross-Sectional Survey of the EBMT Pediatric WP

Introduction: Fertility preservation is crucial in the setting of hematopoietic stem cell transplantation (HSCT) due to the severe impact of infertility on quality of life in long term survivors. Many chemotherapy agents as well as CNS or pelvic irradiation can affect gonads leading to impairment of pubertal development and/or infertility. In the last years different fertility preservation guidelines especially for cancer patients have been published. Despite these recommendations options for fertility preservation are not well established in children, it's discussed only in about 42% (Terenziani et al. PBC 2014) of all eligible patients. We present here a survey conducted by the Pediatric WP of the EBMT.Aim: to analyze and compare the different fertility preservation practices for children and adolescents across the EBMT centers and to identify hence the unmet needs in the field.Material and Methods: The survey was conducted between September 2014 and December 2015. 177 pediatric centers reporting to the EBMT were asked to fill-out a form with 24 questions related to fertility preservation strategies. Questions focused on institutional availability of a fertility preservation program and its options, number of patients included in the program, payers and suggestions for improvement.Results: 38 (21%) centers from 16 countries replied. In 2013 the number of HSCT per center ranges from 2 to 60. Totally, 834 children were transplanted in the 38 centers, 22% of the reported HSCT in children (3789) in 2013 from the EBMT centers. Of the 834 patients 612 (73%) were prepubertal and 203 (25%) postpubertal. 322/834 (39%) patients received a fertility preservation counselling and 243 (29%) of them had a fertility preservation procedure. Half of the 38 centers reported to have a fertility preservation program with standard operating procedure (SOP) for counselling. Centers with SOP counselled patients significantly more often than those without (Figure 1A). Regarding the number of applied procedures, no significant difference was found between centers with and without a SOP (Figure 1B). Centers with SOP counselled earlier (at the beginning of treatment/diagnosis; 61% versus 29%), and an interdisciplinary counselling team was largely used (60%). This team involved hematologists, gynecologists and /or reproductive medicine specialists. The most frequently cited reasons for missing counselling were lack of time (59%), refusal by parents (35%) and expected poor prognosis (29%). Reasons explaining parents/patients refusal were psychological distress (52%) and overwhelming feeling (50%) in this life-threatening moment. All responding centers considered the topic of fertility preservation as very relevant. Better education, more resources and financial funding emerged as pivotal factors to support and implement such programs.Conclusion: This EBMT survey showed the great interest for fertility preservation in participating centers. The collected data indicated that less than half of pediatric and adolescent patients undergoing HSCT in 2013 received a counselling on fertility preservation and/ or underwent fertility preservation procedures. This emphasizes the need for enhanced education of the transplant team and active multidisciplinary collaboration in the field. Fertility preservation becomes a standard of care; this data represents the basis to further efforts toward fertility preservation standardization in the EBMT community. [Display omitted] DisclosuresBader:Servier: Consultancy, Honoraria; Neovii Biotech: Research Funding; Riemser: Research Funding; Medac: Consultancy, Research Funding; Novartis: Consultancy, Honoraria.

Do Patient Characteristics Decide if Young Adult Cancer Patients Undergo Fertility Preservation?

The Fertility Attitudes and Cancer Treatment Study (FACTS) is a two-phase research initiative aimed to understand factors involved with decision making for future fertility. The FACTS will improve services and utilization of fertility preservation (FP) before cancer treatment. Phase-I examined patient characteristics as associated with FP decision. A retrospective cohort study of 108 reproductive-aged (18-45 years) males and females who received a fertility consultation before cancer treatment from January 1, 2012 to April 30, 2014 was conducted. Chi-square, student's t-test, and logistic regression were conducted to examine associations with FP decision. The utilization rate of FP following fertility consultation was 49%. Gender was the most significant factor contributing to FP decision; 74% of those who choose FP were male (odds ratio = 12.5; 95% confidence interval 5.1-31.4). Those who opted for FP were more likely to be Caucasian (p = 0.042), have a solid tumor (p = 0.03), and have a shorter time from diagnosis to fertility consultation (29.5 vs. 58.8 days; p = 0.017). Age, relationship, tumor location, treatment plan, and parity were not significant predictors of FP. Current perceptions about patient demographics do not predict FP utilization by young adult cancer patients. Providing patients an informed fertility consultation has demonstrated an increase in FP utilization to nearly one-half of patients. Despite gender being a significant factor in choosing FP, the study did not provide reasons as to why. The phase-II study will explore patients' reasons for FP decision in a qualitative design to understand these differences.

Random start stimulation allows for minimal treatment delays with neoadjuvant breast cancer treatment

Time delay to cancer treatment places increased anxiety upon the patient and oncology team. These potential delays have prevented women from undergoing fertility preservation treatment. Most recently, the movement toward neoadjuvant therapy for breast cancer has increased the potential for delay. Alternative ovarian stimulation strategies have been implemented to minimize delays to cancer treatment. In the study, we sought to determine whether random start stimulation allows for minimal delays to neoadjuvant chemotherapy start in breast cancer patients.

Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients

Study question Can a counseling tool be developed for women desiring elective oocyte cryopreservation to predict the likelihood of live birth based on age and number of oocytes frozen? Summary answer Using data from ICSI cycles of a population of women with uncompromised ovarian reserve, an evidence-based counseling tool was created to guide women and their physicians regarding the number of oocytes needed to freeze for future family-building goals. What is known already Elective oocyte cryopreservation is increasing in popularity as more women delay family building. By undertaking elective oocyte freezing at a younger age, women hope to optimize their likelihood of successful live birth(s) using their thawed oocytes at a future date. Questions often arise in clinical practice regarding the number of cryopreserved oocytes sufficient to achieve live birth(s) and whether or not additional stimulation cycles are likely to result in a meaningful increase in the likelihood of live birth. As relatively few women who have electively cryopreserved oocytes have returned to use them, available data for counseling patients wishing to undergo fertility preservation are limited. Study design, size, duration A model was developed to determine the proportion of mature oocytes that fertilize and then form blastocysts as a function of age, using women with presumably normal ovarian reserve based on standard testing who underwent ICSI cycles in our program from January, 2011 through March, 2015 (n = 520). These included couples diagnosed exclusively with male-factor and/or tubal-factor infertility, as well as cycles utilizing egg donation. Age-specific probabilities of euploidy were estimated from 14 500 PGS embryo results from an external testing laboratory. Assuming survival of thawed oocytes at 95% for women <36 y and for egg donors, and 85% for women ≥36 y, and 60% live birth rate per transferred euploid blastocyst, probabilities of having at least one, two or three live birth(s) were calculated. Participants/materials, setting, method First fresh male-factor and/or tubal-factor only autologous ICSI cycles (n = 466) were analyzed using Poisson regression to calculate the probability that a mature oocyte will become a blastocyst based on age. Egg donation cycles (n = 54) were analyzed and incorporated into the model separately. The proportion of blastocysts expected to be euploid was determined using PGS results of embryos analyzed via array comparative genomic hybridization. A counseling tool was developed to predict the likelihood of live birth, based on individual patient age and number of mature oocytes. Main results and the role of chance This study provides an evidence-based model to predict the probability of a woman having at least one, two or three live birth(s) based on her age at egg retrieval and the number of mature oocytes frozen. The model is derived from a surrogate population of ICSI patients with uncompromised ovarian reserve. A user-friendly counseling tool was designed using the model to help guide physicians and patients. LIMITATIONS, REASONS FOR CAUTION The data used to develop the prediction model are, of necessity, retrospective and not based on patients who have returned to use their cryopreserved oocytes. The assumptions used to create the model, albeit reasonable and data-driven, vary by study and will likely vary by center. Centers are therefore encouraged to consider their own blastocyst formation and thaw survival rates when counseling patients. Limitations, reasons for caution Our model will provide a counseling resource that may help inform women desiring elective fertility preservation regarding their likelihood of live birth(s), how many cycles to undergo, and when additional cycles would bring diminishing returns. Study funding/competing interests None. Trial registration number Not applicable.

Ovarian tissue cryopreservation and transplantation among alternatives for fertility preservation in the Nordic countries - compilation of 20 years of multicenter experience.

IntroductionThe aim of this study is to report the current status of ovarian tissue cryopreservation among alternatives for fertility preservation in the Nordic countries.Material and methodsA questionnaire was sent to 14 Nordic academic reproductive centers with established fertility preservation programs. It covered fertility preservation cases performed up to December 2014, standard procedures for ovarian tissue cryopreservation and oocyte cryopreservation and reproductive outcomes following ovarian tissue transplantation.ResultsAmong the Nordic countries, Denmark and Norway practice ovarian tissue cryopreservation as a clinical treatment (822 and 164 cases, respectively) and their programs are centralized. In Sweden (457 cases), ovarian tissue cryopreservation is practiced at five of six centers and in Finland at all five centers (145 cases). Nearly all considered ovarian tissue cryopreservation to be experimental. In Iceland, embryo cryopreservation is the only option for fertility preservation. Most centers use slow‐freezing methods for ovarian tissue cryopreservation. Most patients selected for ovarian tissue cryopreservation were newly diagnosed with cancer and the tissue was predominantly retrieved laparoscopically by unilateral oophorectomy. Only minor complications were reported. In total, 46 women have undergone ovarian tissue transplantation aiming at recovering fertility, 17 healthy children have been born and several additional pregnancies are currently ongoing. Whenever patients’ clinical condition is permissive, oocyte cryopreservation after hormonal stimulation is preferred for fertility preservation. Between 2012 and 2014, a smaller proportion of females have undergone fertility preservation in the Nordic centers, in comparison to males (1:3).ConclusionsOverall, ovarian tissue cryopreservation was reported to be safe. Slow freezing methods are still preferred. Promising results of recovery of fertility have been reported in Nordic countries that have initiated ovarian tissue transplantation procedures.

Formal evaluation of PYNK: Breast Cancer Program for Young Women-the patient perspective.

The aim of the present study was to assess patient satisfaction with pynk: Breast Cancer Program for Young Women so as to determine how the program might be improved and to provide feedback to donors. All pynk patients who had consented to have their information entered in our database and who supplied us with their e-mail address were invited to complete a 58-item online questionnaire consisting of multiple choice and open-ended questions. Domains included demographics, provision of written and spoken information, support, infertility risk, research awareness, attitudes toward discharge, and general feedback. Of 120 pynk patients approached, 61 (51%) participated. More than 90% were satisfied or very satisfied with the timing, usefulness, and clarity of spoken and written information given, and 69% found the service and support provided by the nurse navigator to be the most helpful component of the program. Of those who had received systemic therapy, 93% recalled a health care provider initiating a discussion of the risk of treatment-related infertility, and 67% were referred to a fertility clinic. On the negative side, 11%-27% were unaware of various services provided by pynk, and 11% were unaware of pynk's ongoing research. One third of patients were unhappy or ambivalent about the prospect of discharge from the program. Patient satisfaction with this novel program for young women with breast cancer is high. This study highlights the critical role that the nurse navigator plays in patient support and dissemination of information. In contrast to other reported surveys of young cancer patients, pynk patients are routinely given the opportunity to undergo fertility preservation.

Abstract P4-11-05: Safety of fertility preservation indicated by a diagnosis of breast cancer: A Swedish registry-matched cohort study

Abstract Purpose The number of women that perform fertility preservation (FP) before initiating chemotherapy for treatment of breast cancer is increasing. Our purpose was to investigate the safety of performance of fertility preservation with and without hormonal stimulation in the incidence rate of breast cancer relapse. Patients and methods The study was designed as a matched cohort study. Women who had undergone FP at the Reproductive Medicine clinic of Karolinska University Hospital (N=187), irrespective of whether hormonal stimulation was required or not, were considered exposed. For all exposed women, two age-matched women who had not undergone fertility preservation were identified in the Regional Breast Cancer Registry Stockholm-Gotland and the Swedish National Quality Registry for Breast Cancer (N=319). The proportional hazards assumption was evaluated by applying the Grambsch-Therneau test on the Schoenfeld residuals obtained from each model, respectively. When interpreting the test results, a significance level of 5% was used to determine statistical significance. Results In the exposed cohort, a higher proportion of women underwent FP with hormonal stimulation aiming at freezing eggs or embryos (81%, N=142), whereas only 19% underwent freezing of ovarian tissue or attempted egg retrieval without hormonal stimulation (N=35). The mean follow up time was 6.3 years (range: 1.5-17.8 years), and median follow-up: 5.7 years. There was no evidence of non-proportional hazards with respect to the effects of fertility preservation on the risk of relapse in the whole FP cohort, irrespective if the women underwent hormonal stimulation or not for FP, or of receptor status or tumour size at diagnosis. A stratified Cox regression model that allowed separate baseline hazard functions for each level for the investigation of the effect of number of involved lymph nodes was performed. In this model, the effect of fertility preservation on the risk of relapse was virtually unchanged (IRR: 1.02, 95% CI:0.56-1.84). Conclusion Fertility preservation either using hormone stimulation or not is unlikely to cause substantially increase recurrence risk of breast cancer, and irrespective of the receptor status, tumorur size of lymph node compromise. The incidence of breast cancer relapse after hormonal or non-hormonal fertility preservation was not different from that of matched controls from the Regional Breast Cancer Registry in this large cohort study. Citation Format: Rodriguez-Wallberg KA, Eloranta S, Krawiec K, Lissmats A, Liljegren A. Safety of fertility preservation indicated by a diagnosis of breast cancer: A Swedish registry-matched cohort study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-05.

Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy.

Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy? Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy. Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy. A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre. The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy. Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ∼30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre- versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post-oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post-chemotherapy group). There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step. Although more oocytes were collected and matured from chemotherapy-naïve paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy. The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests. N/A.

Practices and attitudes regarding women undergoing fertility preservation: a survey of the national physicians cooperative (NPC)

Practices and attitudes regarding women undergoing fertility preservation: a survey of the national physicians cooperative (NPC)

To bank or not? A decision model to assess future fertility for young women with cancer

Women of childbearing age with a diagnosis of cancer must decide whether to undergo fertility preservation (FP) prior to therapy. Depending on gonadotoxicity of treatment and personal preference, patients may be willing to accept the risk of infertility or choose FP such as oocyte cryopreservation (OC). Using decision tree analysis, we aim to determine the live birth rate (LBR) 5yrs after cancer diagnosis for patients treated with high (HRT), moderate (MRT), or low (LRT) gonadotoxic therapy. LBRs are calculated based on decision to pursue OC or attempt natural conception after treatment (no action). Decision tree analysis was used to analyze women between 25yrs and 40yrs to determine LBR 5yrs after cancer diagnosis depending on if pursued OC or no action. A 5-year wait between cancer diagnosis and attempt of pregnancy was assumed. If no treatment-induced menopause, natural conception was attempted for 6 months. Risk of menopause was calculated for LRT, MRT and HRT using data from the American Society of Clinical Oncology (ASCO) Guidelines. Chance of unassisted conception was obtained from the prospective “Time to Conceive” study, and modified for each of the LRT, MRT and HRT to account for lower LBR after chemotherapy(2). Unassisted conception was attempted again if miscarriage occurred. If no LB, those who chose OC underwent up to two cycles with frozen oocytes. If patient did not freeze eggs, she underwent IVF with up to one frozen embryo transfer (FET). Probabilities of enough eggs for a 2nd cycle and embryos for FET were calculated from IntegraMed Database and LBRs from CDC(3). For women who did not bank eggs, the best possible LBR for those who underwent HRT, MRT and LRT was age 25 at cancer diagnosis (10%, 27%, and 50% respectively (Figure 1 and 2). By age 35, the LBR dropped significantly for women who did not bank eggs. For those that did bank eggs, LBR for all therapies remained > 60% if diagnosed before 33yrs of age. LBR dropped to <50% with banked eggs if women banked at age > 34yrs, 36yrs, and 38yrs with HR, MR, and LR therapy respectively (Figure 1 and 2). At any age, all cancer treatments decrease fertility by almost half. Egg banking prior to treatment is most beneficial in HRT. HRT and MRT decrease reproductive window by up to 5yrs. Chances of LB with banked eggs is best if frozen before age 33.

Oocyte cryopreservation for cancer patients is inconsistently and suboptimally covered among national health insurance companies

Patients undergoing fertility preservation (FP) in anticipation of gonadotoxic therapy have improved quality of life as cancer survivors. For many patients the financial burden for FP presents an insurmountable barrier to care. Advocacy efforts have increasingly focused on improving health insurance coverage for cancer patients to include FP. The American Society for Reproductive Medicine and the American Society of Clinical Oncology describe embryo cryopreservation, oocyte cryopreservation and sperm cryopreservation as clinically accepted and non-experimental options for patients wishing to undergo FP.

Our act on fertility preservation for young breast cancer patients in our single institute.

109 Background: Along with increasing number of newly diagnosed Japanese breast cancer patients, the number of breast cancer survivors in reproductive age is also increasing. Among newly diagnosed Japanese breast cancer patients, 3182(6.6%) are under age 40 in 2011, which was 1610 in 2006. In our institute, we have been cooperating with gynecologists and providing fertility preservation program since 2010. Our aim is to access our team management, clinical impact and outcome of fertility preservation among young breast cancer patients in our institute. Methods: A patient, 1)without distant metastasis, 2)systemic chemotherapy and/or hormonal therapy planned, 3)within reproductive age and 4)willing to preserve fertility, will be referred to oncofertility clinic. Chart review was done retrospectively. Results: Ninety-five patients had consultation to the oncofertility clinic between April 2010 and April 2015. The average age at consultation was 34.1(range 22-44). Almost all patient had invasive cancer; cStage0:4%, cStageI:31%, cStageII:53%, cStageIII:11%. Fifty-five percent had estrogen receptor (ER) positive/HER2 negative, 31% had ER positive/HER2positive, 2% had ER negative/HER2 positive and 12% had ER negative/HER2 negative breast cancer. Forty-five had counseling without any procedure, 22 underwent ovarian tissue cryopreservation, 17 underwent embryo cryopreservation and 8 underwent oocyte cryopreservation. Because observation period is still short, we haven’t had any case that got pregnant or delivered, yet. Conclusions: The number of patient who choose to underwent fertility preservation is increasing. We have actually started facing proposition, when we shall lay aside adjuvant therapy and let them plan to be conceived. Taking risk into account, we are now evaluating the safety of cancer treatment and outcome of each procedure which undergone multidisciplinary deliberate decision-making process.

Reasons Why Young Women Accept or Decline Fertility Preservation After Cancer Diagnosis

ObjectiveTo understand young women’s reasons for accepting or declining fertility preservation after cancer diagnosis to aid in the development of theory regarding decision making in this context. DesignQualitative descriptive. SettingParticipants’ homes or other private location. ParticipantsTwenty-seven young women (mean age, 29 years) diagnosed with cancer and eligible for fertility preservation. MethodsRecruitment was conducted via the Internet and in fertility centers. Participants completed demographic questionnaires and in-depth semi-structured interviews. Tenets of grounded theory guided an inductive and deductive analysis. ResultsYoung women’s reasons for deciding whether to undergo fertility preservation were linked to four theoretical dimensions: Cognitive Appraisals, Emotional Responses, Moral Judgments, and Decision Partners. Women who declined fertility preservation described more reasons in the Cognitive Appraisals dimension, including financial cost and human risks, than women who accepted. In the Emotional Responses dimension, most women who accepted fertility preservation reported a strong desire for biological motherhood, whereas women who declined tended to report a strong desire for surviving cancer. Three participants who declined reported reasons linked to the Moral Judgments dimension, and most participants were influenced by Decision Partners, including husbands, boyfriends, parents, and clinicians. ConclusionThe primary reason on which many but not all participants based decisions related to fertility preservation was whether the immediate emphasis of care should be placed on surviving cancer or securing options for future biological motherhood. Nurses and other clinicians should base education and counseling on the four theoretical dimensions to effectively support young women with cancer.

Fertility Preservation for Women with Sickle Cell Disease (SCD)

Objective: Peripheral blood stem cell transplant (PBSCT) can now cure SCD in adults, but may result in a loss of future fertility. Little is documented regarding fertility preservation in women with SCD. The aim of this study was to perform fertility preservation for women with SCD scheduled for PBSCT.Design: Prospective cohort of women with SCD undergoing fertility preservation prior to PBSCT at a large research hospital.Materials and Methods: Patients underwent standard controlled ovarian hyperstimulation (COH) using an antagonist protocol cycle with leuprolide trigger under close multidisciplinary (including reproductive endocrinologists and hematologists) monitoring. All patients were continued on therapeutic or started on prophylactic anticoagulation prior to beginning COH, and maintained on hydroxyurea.Results: Nine reproductive aged women were screened; 1 declined participation, 1 was diagnosed with unrecognized premature ovarian insufficiency, 1 had her fertility preservation cycle canceled due to poor response to fertility medications and 2 patients are scheduled for upcoming cycles. The remaining four women (ages 20, 34, 24, 27) successfully underwent COH, transvaginal oocyte retrieval and cryopreservation of mature eggs (n= 8, 13, 15, 21 oocytes, respectively). The third patient underwent two cycles due to low mature oocyte yield from her initial cycle. Headaches were reported by patients 1 and 2 following gonadotropin injections, with a negative neurologic workup including MRI in patient 2. Patient 3 underwent an exchange transfusion on day 10 of stimulation, which did not adversely impact serum reproductive hormone levels. Patients 3 and 4 reported an acute exacerbation of their chronic pain during COH, which responded well to intravenous fluids, IV and oral pain medications. Therefore, despite severe SCD and co-morbid conditions, the side effects were manageable. There were no venous thrombotic events.Conclusion: These results provide support that fertility preservation can be safely performed in women with SCD under the care of a multidisciplinary team. The safest stimulation protocol (i.e. antagonist cycle with leuprolide trigger for final oocyte maturation) was successful in all patients despite multiple risk factors for failed leuprolide trigger. Fertility preservation is important not only before PBSCT to cure their underlying disease, but also because of high rates of premature ovarian insufficiency in the SCD population post-transplant.Support: Intramural NICHD and NHLBI, NIH. DisclosuresNo relevant conflicts of interest to declare.