P-365 Fertility preservation in patients with borderline ovarian tumors: safety and reproductive outcomes
Authors: Shai D , Rossella M , Cioffi R , Ohayon A , Helpman L , Papaleo E , Vanni V  S , Bergamini A , Candiani M , Korach J , Mangili G , Meirow D 
Published: July 2024

Abstract

Study question
Do borderline ovarian tumors (BOT) patients, undergoing controlled ovarian stimulation (COS) face higher recurrence risks, and what are the associated reproductive outcomes?

Summary answer
Even in advanced-stage or bilateral BOT, COS does not significantly impact recurrence rates. Additionally, COS for fertility preservation(FP)provides a viable option for future reproductive potential.

What is known already
The primary approach for treating BOTs involves surgical intervention, emphasizing complete tumor removal. Conservative surgery is an option for young women seeking to preserve reproductive potential. However, the recurrence risk following conservative surgery is significant, reaching up to 25%, necessitating repeat surgeries that impact ovarian reserve. Existing evidence on the safety of COS in terms of BOT recurrence remains inconclusive. Concerns about a potential association between COS and tumor progression persist, particularly in advanced-stage and bilateral disease cases. This study address these gaps in knowledge and provide more clarity on the safety of COS in BOT patients.

Study design, size, duration
A retrospective cohort study was conducted across two tertiary, university-affiliated medical centres: IRCCS San Raffaele Hospital, Milan, Italy, and SHEBA Medical Hospital, Tel-Aviv University, Israel. The study included 165 patients diagnosed with borderline ovarian tumors who underwent conservative surgery between 2012 and 2023.

Participants/materials, setting, methods
Participants aged 18-42 years with BOT (stages I-III) and undergoing conservative treatment were stratified into two groups: those opting COS for FP(41 patients)and a control group without such intervention (124 patients). COS involved GnRH antagonist random-start protocols utilizing menotropins and/or recombinant FSH. GnRH-agonist or hCG were used for triggering. Oocyte vitrification or fertilization and embryo freezing was performed. Statistical analyses, including Pearson’s chi-square, Fisher’s exact test, T test, and logistic regression, were employed for evaluation.

Main results and the role of chance
In the course of COS cycles and oocyte retrieval, no complications were observed. Among 165 participants, 33% experienced BOT recurrence over a median of 28.5 months (range: 12.7 to 42.7). Patients with recurrence were younger (29 vs. 32 years, P = 0.04), had advanced-stage (26 vs. 18, p &lt; 0.0001), and bilateral disease (38% vs. 19%, p = 0.01). Of the 41 undergoing COS, 19 experienced recurrence, comparable to the control group (36 patients, p = 0.055). Notably, all COS-related recurrences were BOT histotype, not invasive carcinoma, managed through a second surgery.
No significant differences in ovarian stimulation cycles (2.4 vs 1.7, p = 0.7) or retrieved oocytes (11.8 vs 10.6, p = 0.6) were detected between women with and without recurrence. In multivariate analysis, advanced disease significantly increased recurrence odds (aOR=3.7, 95% CI: 1.7-7.9, P &lt; 0.001), while COS did not (aOR=1.7, 95% CI: 0.7-3.9, P = 0.16). This suggests that while age and disease stage play roles, COS alone may not significantly influence recurrence rates.
Importantly, among women undergoing COS for FP, 17 achieved at least one pregnancy, totaling 24 pregnancies, with 18 live births. Six were spontaneous, and three used frozen embryos from FP cycles. This underscores the reproductive success of FP through COS, providing hope for fulfilling childbearing desires post-BOT diagnosis.

Limitations, reasons for caution
Limitations include the retrospective nature, a selection bias in the COS group, and the rarity of the disease leading to a small sample size. Despite these, the recurrence rate in the COS group was comparable to a systematic review, and caution is advised in interpreting these results.

Wider implications of the findings
Our study suggests that COS does not significantly contribute to recurrence risk in BOT patients, even in advanced stages. FP through COS enhances the likelihood of live births in these patients. While cautious interpretation is warranted, these findings offer hope and call for larger prospective studies to confirm these results.

Trial registration number
not applicable