Ovarian Tissue Oocyte-In Vitro Maturation for Fertility Preservation.

Mature oocyte vitrification is the standard of care to preserve fertility in women at risk of infertility. However, ovarian tissue cryopreservation (OTC) is still the only option to preserve fertility in women who need to start gonadotoxic treatment urgently or in prepubertal children. During ovarian cortex preparation for cryopreservation, medullar tissue is removed. Growing antral follicles reside at the border of the cortex-medullar interface of the ovary and are broken during this process, releasing their cumulus-oocyte complex (COC). By thoroughly inspecting the medium and fragmented medullar tissue, these immature cumulus-oocyte complexes can be identified without interfering with the OTC procedure. The ovarian tissue-derived immature oocytes can be successfully matured in vitro, creating an additional source of gametes for fertility preservation. If OTC is performed within or near a medical assisted reproduction laboratory, all necessary in vitro maturation (IVM) and oocyte vitrification tools can be at hand. Furthermore, upon remission and child wish, the patient has multiple options for fertility restoration: ovarian tissue transplantation or embryo transfer after the insemination of vitrified/warmed oocytes. Hence, ovarian tissue oocyte-in vitro maturation (OTO-IVM) can be a valuable adjunct fertility preservation technique.

Live births following fertility preservation using in-vitro maturation of ovarian tissue oocytes.

STUDY QUESTION: Can oocytes extracted from excised ovarian tissue and matured in vitro be a useful adjunct for urgent fertility preservation (FP)? SUMMARY ANSWER: Ovarian tissue oocyte in-vitro maturation (OTO-IVM) in combination with ovarian tissue cryopreservation (OTC) is a valuable adjunct technique for FP. WHAT IS KNOWN ALREADY: Despite the impressive progress in the field, options for FP for cancer patients are still limited and, depending on the technique, clinical outcome data are still scarce. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study conducted at a university hospital-affiliated fertility clinic between January 2012 and May 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study included 77 patients who underwent unilateral oophorectomy for OTC. Cumulus-oocyte complexes (COCs) obtained during ovarian tissue processing were matured in vitro for 28-42 h. Oocytes reaching metaphase II stage were vitrified or inseminated for embryo vitrification. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 1220 COCs were collected. The mean oocyte maturation rate was 39% ± 23% (SD). There were 64 patients who had vitrification of oocytes (6.7 ± 6.3 oocytes per patient). There were 13 patients who had ICSI of mature oocytes after IVM, with 2.0 ± 2.0 embryos vitrified per patient. Twelve patients have returned to the clinic with a desire for pregnancy. For seven of these, OTO-IVM material was thawed. Two patients had OTO-IVM oocytes warmed, with survival rates of 86% and 60%. After ICSI, six oocytes were fertilised in total, generating three good quality embryos for transfer, leading to a healthy live birth for one patient. In five patients, for whom a mean of 2.0 ± 0.8 (SD) embryos had been vitrified, seven embryos were warmed in total: one embryo did not survive the warming process; two tested genetically unsuitable for transfer; and four were transferred in separate cycles to three different patients, resulting in two healthy babies. In this small series, the live birth rate per patient after OTO-IVM, ICSI and embryo transfer was 43%. LIMITATIONS, REASONS FOR CAUTION: The retrospective study design and the limited sample size should be considered when interpreting results. WIDER IMPLICATIONS OF THE FINDINGS: The results of the study illustrate the added value of OTO-IVM in combination with OTC. We report the first live birth following the use of this appended technique combined with oocyte vitrification. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. M.D.V. reports honoraria for lectures in the last 2 years from MSD and Ferring, outside the submitted work, as well as grant support from MSD. The other authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Fertility preservation does not delay the initiation of chemotherapy in breast cancer patients treated with adjuvant or neo-adjuvant chemotherapy.

PURPOSE: To investigate whether fertility preservation (FP) in adult women diagnosed with breast cancer (BC) may impact the time interval between diagnosis and start of chemotherapy in an adjuvant or neo-adjuvant setting. METHODS: Retrospective cohort study of breast cancer patients diagnosed between January 2012 and December 2017 undergoing FP at a tertiary-care academic fertility centre before neo-adjuvant (NAC) or adjuvant chemotherapy (AC), and matched control breast cancer patients who had no FP. FP interventions included oocyte vitrification following ovarian stimulation or after in-vitro maturation (IVM) of immature oocytes, and/or ovarian tissue cryopreservation. Controls from the patient database of the affiliated Breast Cancer Clinic were matched for tumour characteristics and type of treatment. Time intervals between cancer diagnosis and the start of chemotherapy were analysed. RESULTS: Fifty-nine BC patients underwent FP: 29 received NAC and 30 received AC. The average interval between diagnosis and chemotherapy in BC patients with NAC was 28.5 days (27.3 (range: 14.0-44.0) days in cases and 29.6 (range: 14.0-62.0) days in controls (NS)); this interval was 58.9 days in BC patients with AC (57.2 (range: 36.0-106.0) days in cases and 60.7 (range: 31.0-105.0) days in controls (NS)). CONCLUSION: Fertility preservation does not delay the start of chemotherapy in breast cancer patients.

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

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

Survey of Fertility Preservation Options Available to Patients With Cancer Around the Globe.

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

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

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.

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

In vitro maturation (IVM) of oocytes recovered from ovariectomy specimens in the laboratory: a promising "ex vivo" method of oocyte cryopreservation resulting in the first report of an ongoing pregnancy in Europe.

PURPOSE: We present our center's experience with 34 consecutive cases who underwent in vitro maturation (IVM) of oocytes obtained from ovariectomy specimens and compare our data with updated literature data. METHODS: Feasibility and efficiency of oocyte collection during ovarian tissue processing was assessed by the recovery rate, maturation rate, and embryological development after IVM. RESULTS: On average, 14 immature oocytes were retrieved per patient during ovarian tissue processing in 33/34 patients. The overall maturation rate after IVM was 36%. The maturation rate correlated with the age of the patient and the duration of IVM. Predominately, oocyte vitrification was performed. Eight couples preferred embryo cryopreservation. Here, a 65% fertilization rate was obtained and at least one good-quality day 3 embryo was cryopreserved in 7/8 couples. The retrieval of oocytes ex vivo resulted in mature oocytes or embryos available for vitrification in 79% of patients. One patient with ovarian insufficiency following therapeutic embolization of the left uterine and the right ovarian artery because of an arteriovenous malformation had an embryo transfer of one good-quality warmed embryo generated after IVM ex vivo, which resulted in an ongoing clinical pregnancy. CONCLUSIONS: IVM of oocytes obtained ex vivo during the processing of ovarian cortex prior to cryopreservation is a procedure with emerging promise for patients at risk for fertility loss, as illustrated by the reported pregnancy. However, more data are needed in order to estimate the overall success rate and safety of this novel approach.