Abstract

Abstract Study question Does fertility treatment (FT) increase the risk of recurrence of Borderline Ovarian Tumours (BOTs)? Summary answer There is a significant association between recurrence of BOTs and exposure to FT (p = 0.025). What is known already The association between pregnancy or controlled ovarian stimulation (COS) and risk of recurrence of BOTs is a controversial topic of interest amongst clinicians and women undergoing treatment. Some studies report a risk of non- invasive relapse following ovarian stimulation between 19.4-23%, whereas earlier case-control studies have shown no significant association.It is important to consider that most studies are limited by their retrospective analysis, with an emphasis on the incidence of primary BOTs following exposure to FT. Whereby, data regarding the risk of disease recurrence following spontaneous pregnancy (SP) or COS specifically, remains sparse. Study design, size, duration A retrospective cohort of women who underwent fertility sparing surgery (FSS) for the management of BOTs between the 1st January 2004 and 31st December 2020 at Imperial College Healthcare NHS Trust, with prospective follow up of reproductive outcomes and recurrence of disease following surgery. Participants/materials, setting, methods Subgroup analysis included a control group of all women not exposed to FT or SP and a non-control group of those who achieved either SP or underwent FT following FSS for the management of BOTs. The recurrence rate of BOTs was determined within each subgroup. Main results and the role of chance 90 women underwent FSS for BOTs. Subgroup analysis confirmed 38.9% (35/90) were in the control group, 50% (45/90) in the non-control and 11.1% (10/90) lost to follow up. In the non-control group, 35.6% (16/45) achieved SP only and 64.4% (29/45) underwent FT. FT included COS for oocyte cryopreservation only (24.4%; 11/45), intracytoplasmic sperm insemination (ICSI) ± fresh or frozen embryo transfer (24.4%; 11/45) and those who underwent COS but also achieved SP without returning to their cryopreserved gametes (15.5%; 7/45). Within the non-control group, 75.6% (34/45) of women conceived, with a livebirth rate per pregnancy of 58.7% (27/46). The recurrence rate in the control and non-control groups were 20% (7/35) and 22.2% (10/45) respectively (p = 0.025) and 24.1% (7/29) following FT. Recurrence rates were 18.8% (3/16) after SP only, 0% (0/11) following oocyte cryopreservation only, 18.2% (2/11) ICSI ± embryo transfer and 71.4% (5/7) in those who underwent COS and achieved a SP. All recurrence of disease presented as serous BOTs. Within the FT group, logistic regression analysis demonstrated no significant predictors of disease recurrence. A combination of SP and FT is significantly associated with recurrence when compared to the following groups: control (p = 0.000), SP only (p = 0.001) and COS only (p = 0.015). Limitations, reasons for caution Due to the partial retrospective nature of the study, certain clinical information was not adequately documented and the subgroups compared were of unequal sample size, whilst overall sample size is also considered low. There was also a lack of control for confounders which may affect disease recurrence. Wider implications of the findings Despite the risk of recurrence of BOTs associated with FT, cases are often non invasive and successfully managed with further FSS with excellent prognosis. This evidence should be used to counsel women of reproductive age to ensure they can fulfil their reproductive aspirations, despite a diagnosis of BOT. Trial registration number NA

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