Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology.

BACKGROUND: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown. METHODS: This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018. Ovarian tumor risk in ART-treated women was compared with risks in the general population and the subfertile non-ART group. Statistical tests were 2-sided. RESULTS: After a median follow-up of 24 years, 158 invasive and 100 borderline ovarian tumors were observed. Ovarian cancer risk in the ART group was increased compared with the general population (standardized incidence ratio [SIR] = 1.43, 95% confidence interval [CI] = 1.18 to 1.71) but not when compared with the non-ART group (age- and parity-adjusted hazard ratio [HR] = 1.02, 95% CI = 0.70 to 1.50). Risk decreased with higher parity and with a larger number of successful ART cycles (resulting in childbirth, Ptrend = .001) but was not associated with the number of unsuccessful ART cycles. Borderline ovarian tumor risk was increased in ART-treated women compared with the general population (SIR = 2.20, 95% CI = 1.66 to 2.86) and with non-ART women (HR = 1.84, 95% CI = 1.08 to 3.14). Risk did not increase with more ART cycles or longer follow-up time. CONCLUSIONS: Increased ovarian cancer risk in ART-treated women compared with the general population is likely explained by nulliparity rather than ART treatment. The increased risk of borderline ovarian tumors after ART must be interpreted with caution because no dose-response relationship was observed.

Outcome of surveillance and prophylactic salpingo-oophorectomy in asymptomatic women at high risk for ovarian cancer.

OBJECTIVE: Women at high risk of ovarian cancer are currently offered two options: either surveillance or prophylactic bilateral salpingo-oophorectomy. The efficacy and outcome of surveillance remain unclear. METHODS: We performed a retrospective study. Between 1994 and 2000, we screened 383 high-risk women, of which 152 were BRCA1/2 mutation carriers. Surveillance consisted of annual gynecological examination, transvaginal ultrasound, and serum CA125 measurement. Exploratory or prophylactic surgery was performed in selected cases. RESULTS: There were no screen-detected primary ovarian cancers. Abnormal results at surveillance were observed in 74 (19.3%) of women; in 47 (63.5%), the abnormalities disappeared spontaneously. Exploratory surgery was performed in 20 (27.0%) women in whom one malignancy was found (metastatic breast cancer in the ovary). A rising CA125 value prompted further (non-surgical) evaluation in three women with a history of breast cancer: recurrent breast cancer was diagnosed in two women; in the third, a chondrosarcoma was found. 133 women opted for prophylactic bilateral salpingo-oophorectomy, whereby two unexpected malignancies were found (fallopian tube cancer and metastatic breast cancer). One interval primary ovarian cancer occurred, presenting as papillary serous carcinoma of the peritoneum 14 months after prophylactic bilateral salpingo-oophorectomy. Complications of prophylactic surgery were encountered in 15 (11.5%) women. CONCLUSIONS: Ovarian cancer surveillance has limited sensitivity, and a high number of false positive findings. This can lead to unnecessary surgical interventions, possibly resulting in surgery-related complications. It is important to inform high-risk women of these limitations. For now, prophylactic bilateral salpingo-oophorectomy remains the optimal risk-reducing strategy for women at high risk.