A Prospective Study on Fertility Preservation in Prepubertal and Adolescent Girls Undergoing Hematological Stem Cell Transplantation.

BACKGROUND: Hematological stem cell transplantation (HSCT) is an established method which has markedly increased the survival rate of hematologic malignancies since its introduction in the 1980's. The conditioning for HSCT has known gonadotoxic effects and often leads to premature loss of fertility. In this study we have prospectively followed a cohort of girls undergoing HSCT and studied the outcomes of fertility preservation treatments performed before or after HSCT, as well as the long-term reproductive outcome. METHODS: In this one-center prospective study, 39 girls counselled for fertility preservation prior to or after conditioning for HSCT for malignant or benign diseases at childhood or adolescence between 1990 and 2017 were included. The patients were presented with the option to undergo cryopreservation of ovarian tissue or oocytes depending on their age and the time available. Follicle counts of the ovarian tissue and number of oocytes collected before or after HSCT were compared between patients treated for benign and malignant diseases. Hormone measurements post HSCT treatment, including FSH and AMH, reproductive outcomes and overall survival until January 2021 were investigated. RESULTS: In total, 34 girls and adolescents underwent fertility preservation before or after HSCT. Before HSCT, ovarian tissue was cryopreserved in 15 patients and two patients had oocytes preserved. Thirteen patients cryopreserved ovarian tissue after HSCT and seven patients returned to cryopreserve oocytes. Follicles were present in all tissue samples collected prior to HSCT, and in more than half of the samples collected post-HSCT. Half of the patients had spontaneous menarche or resumed menstruation post HSCT. Overall, 35 patients had survived at end of follow up and 7 patients had achieved parenthood. CONCLUSIONS: Since fertility loss is common following HSCT, fertility preservation should be offered to all patients. Fertility preservation treatments can be performed both before and after HSCT. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT04602962, identifier NTC04602962.

Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study.

STUDY QUESTION: How efficacious and safe are the current approaches to controlled ovarian stimulation (COS) aimed at fertility preservation (FP) in women with breast cancer (BC)? SUMMARY ANSWER: In women with BC undergoing COS aiming at egg/embryo cryopreservation, letrozole-based protocols and those randomly started were equally effective compared with conventional COS, and the overall survival was similar between the women that proceeded to FP and those who did not. WHAT IS KNOWN ALREADY: Cryopreservation of oocytes and embryos is an established method for FP in women with BC. Recent improvements to COS protocols include concomitant use of letrozole, random-cycle start day of stimulation and the use of GnRHa for the egg maturation trigger. To date, limited sample size of the available studies has not allowed investigation of differences in the efficacy of the different approaches to COS for FP in this patient population. STUDY DESIGN, SIZE, DURATION: A prospective multicenter study with national coverage including 610 women with BC counseled between 1 January 1995 and 30 June 2017 at six Swedish FP regional programs. PARTICIPANTS/MATERIALS, SETTING, METHODS: After counseling, 401 women elected to undergo COS. Treatments differed in the use or not of concomitant letrozole, a conventional or random-cycle day COS initiation and the use of hCG versus GnRHa trigger for oocyte maturation. Numbers of cryopreserved oocytes and embryos were defined as primary outcome. Pregnancy attempts, reproductive outcomes and long-term survival, investigated by the linking of individuals of the cohort to the total population register of the Swedish Tax Agency (up to 25 November 2018), were evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Using letrozole or not resulted in similar numbers of oocytes and embryos cryopreserved (meanoocytes = 9.7 versus 10 and meanembryos 4.0 versus 5.3, respectively), similar to COS with random versus conventional start (meanoocytes 9.0 versus 10.6 and meanembryos 4.8 versus 4.8). In COS with letrozole, a GnRHa trigger was associated with a higher number of oocytes retrieved (P < 0.05) and embryos cryopreserved (P < 0.005), compared with conventional hCG trigger. Of 99 women who returned to fertility clinics after cancer treatment, 32 proceeded to thawing of oocytes or embryos and 10 of them had live births. The all-cause survival between the women that underwent COS and those who did not was similar and did not differ between the two groups. LIMITATIONS, REASONS FOR CAUTION: Data on tumor characteristics and estrogen receptor (ER) status were not known for all women at the time of FP counseling and planning of COS, thus protocols with letrozole have been used for both estrogen-sensitive and non-estrogen-sensitive BC. For the same reason, subsequent adjustment for ERs in the BC or tumor characteristics as potential confounders were not performed as these parameters were not available and did not influence the provision of FP through COS. WIDER IMPLICATIONS OF THE FINDINGS: The results of our study support the premise that recently introduced potential improvements to COS protocols for FP in women with BC are efficacious and safe. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by research grants from the Swedish Cancer Society, the Stockholm County Council, the Percy Falk Stiftelsen, Radiumhemmets Forskningsfonder, The Swedish Breast Cancer Association and Karolinska Institutet to K.A.R.W. J.B. reports grants from Amgen, AstraZeneca, Pfizer, Roche, Sanofi-Aventis and Merck, outside the submitted work, and payment from UpToDate to Asklepios Medicine HB for a chapter on BC prediction and prognostication. All the other authors have no competing interests to report.

A prospective study of women and girls undergoing fertility preservation due to oncologic and non-oncologic indications in Sweden-Trends in patients' choices and benefit of the chosen methods after long-term follow up.

INTRODUCTION: In Scandinavian countries, programs for fertility preservation are offered free of charge at tertiary-care university hospitals to all patients facing treatments with risk of subsequent sterility. In this prospective study we aimed to investigate trends in female patients' choices after counseling and fertility preservation outcomes during follow up in relation to benign vs malignant indications. MATERIAL AND METHODS: Data on 1254 females including 1076 adults and 178 girls who received fertility preservation counseling for either oncologic (n = 852) or benign indications (n = 402) at Karolinska University Hospital, Stockholm, between 1 October 1998 and 1 December 2018 were analyzed. As appropriate, t tests and chi-square tests were used to compare groups. Logistic regression was used to compare outcomes among groups depending on indications. RESULTS: Adult women generally elected to undergo oocyte retrieval after controlled ovarian stimulation for cryopreservation of embryos or oocytes (n = 538, 73%), whereas a minor proportion opted for cryopreservation of ovarian tissue retrieved through laparoscopy (n = 221, 27%). More than half of the women with a partner chose either not to fertilize their oocytes aiming at cryopreservation of oocytes or to share obtained oocytes attempting both cryopreservation of oocytes and cryopreservation of embryos. All pre-pubertal (n = 48) and 73% of post-pubertal girls (n = 66) elected cryopreservation of ovarian tissue. In recent years, an increasing number of teenagers have opted for controlled ovarian stimulation aiming at cryopreservation of oocytes, either before (n = 24, 17%) or after completion of cancer treatment (n = 15, 10%). During follow up, 27% of the women returned for a new reproductive counseling, additional fertility preservation or to attempt pregnancy. Utilization rates among individuals who were alive and of childbearing age by December 2018 indicated 29%, 8% and 5% for embryos, oocytes and ovarian tissue with live birth rates of 54%, 46% and 7%, respectively. Women with benign indications were significantly younger than women with previous malignant indications at the time of attempting pregnancy. Although the pregnancy rates were similar among both groups, the live birth rate was significantly higher in women with benign vs previous malignant indications (47% vs 21%, P = .002). CONCLUSIONS: Trends in fertility preservation choices have changed over time. Women with previous malignancy had lower live birth rates than women with benign fertility preservation indications.