Ovarian tissue cryopreservation and transplantation is a form of fertility preservation offered to young women at high risk of losing ovarian function after cancer treatment. While there have been successful births resulting from orthotopic site grafts, we report the first case of an ongoing pregnancy from a heterotopic graft in a patient who had previously undergone bilateral oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two oocytes. These were fertilized with ICSI and two embryos were transferred. Serial ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus, this first demonstration of a pregnancy from a heterotopic graft site provides unequivocal evidence that cryopreservation preserves complete follicle development and that normal ovarian function can occur at a non-ovarian site. This provides optimism for further efforts to assist women who have had oophorectomy and pelvic surgery or radiotherapy, without an appropriate orthotopic site for grafting.

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STUDY QUESTION What is the evidence to guide the management of women who wish to conceive following abdominopelvic radiotherapy (AP RT) or total body irradiation (TBI)? SUMMARY ANSWER Pregnancy is possible, even following higher doses of post-pubertal uterine radiation exposure; however, it is associated with adverse reproductive sequelae and pregnancies must be managed in a high-risk obstetric unit. WHAT IS KNOWN ALREADY In addition to primary ovarian insufficiency, female survivors who are treated with AP RT and TBI are at risk of damage to the uterus. This may impact on its function and manifest as adverse reproductive sequelae. STUDY DESIGN, SIZE, DURATION A review of the literature was carried out and a multidisciplinary working group provided expert opinion regarding assessment of the uterus and obstetric management. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive outcomes for postpubertal women with uterine radiation exposure in the form of AP RT or TBI were reviewed. This included Pubmed listed peer-reviewed publications from 1990 to 2019, and limited to English language.. MAIN RESULTS AND THE ROLE OF CHANCE The prepubertal uterus is much more vulnerable to the effects of radiation than after puberty. Almost all available information about the impact of radiation on the uterus comes from studies of radiation exposure during childhood or adolescence. An uncomplicated pregnancy is possible, even with doses as high as 54 Gy. Therefore, tumour treatment doses alone cannot at present be used to accurately predict uterine damage. LIMITATIONS, REASONS FOR CAUTION Much of the data cannot be readily extrapolated to adult women who have had uterine radiation and the publications concerning adult women treated with AP RT are largely limited to case reports. WIDER IMPLICATIONS OF THE FINDINGS This analysis offers clinical guidance and assists with patient counselling. It is important to include patients who have undergone AP RT or TBI in prospective studies to provide further evidence regarding uterine function, pregnancy outcomes and correlation of imaging with clinical outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study received no funding and there are no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Numerous chronic diseases have a substantial hereditary component. Recent advances in human genetics have allowed the extent of this to be quantified via genome-wide association studies, producing polygenic risk scores (PRS), which can then be applied to individuals to estimate their risk of developing a disease in question. This technology has recently been applied to embryo selection in the setting of IVF and preimplantation genetic testing, with limited data to support its utility. Furthermore, there are concerns that the inherent limitations of PRS makes it ill-suited for use as a screening test in this setting. There are also serious ethical and moral questions associated with this technology that are yet to be addressed. We conclude that further research and ethical reflection are required before embryo selection based on PRS is offered to patients outside of the research setting.

Recurrent implantation failure (RIF) is an imprecisely defined disorder lacking a robust scientific basis. The incomplete understanding of RIF provides significant diagnostic and therapeutic challenges, and a better understanding of the underlying issues is necessary to improve outcomes. We propose a novel concept termed ‘Theoretical Cumulative Implantation Rate’, the calculation of which is based on objective data, to define whether a patient should be diagnosed with RIF. An updated definition to assist with patient counselling and planning research studies, which is more precise and standardised, is well overdue.