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

Mandy Spaan; Alexandra W van den Belt-Dusebout; Cornelis B Lambalk; Hester H van Boven; Roel Schats; Marian Kortman; Frank J M Broekmans; Joop S E Laven; Evert J P van Santbrink; Didi D M Braat; Lucette A J van der Westerlaken; Ben J Cohlen; Astrid E P Cantineau; Jesper M J Smeenk; Minouche M van Rumste; Mariëtte Goddijn; Ron J T van Golde; Paul A M Meeuwissen; Carl J C M Hamilton; Gabriële M Ouwens; Miranda A Gerritsma; Michael Schaapveld; Curt W Burger; Flora E van Leeuwen

doi:10.1093/jnci/djaa163

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

Mandy Spaan, Alexandra W van den Belt-Dusebout, Cornelis B Lambalk, Hester H van Boven, Roel Schats, Marian Kortman, Frank J M Broekmans, Joop S E Laven, Evert J P van Santbrink, Didi D M Braat, Lucette A J van der Westerlaken, Ben J Cohlen, Astrid E P Cantineau, Jesper M J Smeenk, Minouche M van Rumste, Mariëtte Goddijn, Ron J T van Golde, Paul A M Meeuwissen, Carl J C M Hamilton, Gabriële M OuwensMiranda A Gerritsma, Michael Schaapveld, Curt W Burger, Flora E van Leeuwen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	163
Pages (from-to)	699-709
Number of pages	11
Journal	Journal of the National Cancer Institute
Volume	113
Issue number	6
Early online date	17 Nov 2020
DOIs	https://doi.org/10.1093/jnci/djaa163
Publication status	Published - Jun 2021

Keywords

IN-VITRO FERTILIZATION
STIMULATION
REGISTRY
COHORT
BREAST

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Spaan, M., van den Belt-Dusebout, A. W., Lambalk, C. B., van Boven, H. H., Schats, R., Kortman, M., Broekmans, F. J. M., Laven, J. S. E., van Santbrink, E. J. P., Braat, D. D. M., van der Westerlaken, L. A. J., Cohlen, B. J., Cantineau, A. E. P., Smeenk, J. M. J., van Rumste, M. M., Goddijn, M., van Golde, R. J. T., Meeuwissen, P. A. M., Hamilton, C. J. C. M., ... van Leeuwen, F. E. (2021). Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology. Journal of the National Cancer Institute, 113(6), 699-709. Article 163. https://doi.org/10.1093/jnci/djaa163

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title = "Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology",

abstract = "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.",

keywords = "IN-VITRO FERTILIZATION, STIMULATION, REGISTRY, COHORT, BREAST",

author = "Mandy Spaan and {van den Belt-Dusebout}, {Alexandra W} and Lambalk, {Cornelis B} and {van Boven}, {Hester H} and Roel Schats and Marian Kortman and Broekmans, {Frank J M} and Laven, {Joop S E} and {van Santbrink}, {Evert J P} and Braat, {Didi D M} and {van der Westerlaken}, {Lucette A J} and Cohlen, {Ben J} and Cantineau, {Astrid E P} and Smeenk, {Jesper M J} and {van Rumste}, {Minouche M} and Mari{\"e}tte Goddijn and {van Golde}, {Ron J T} and Meeuwissen, {Paul A M} and Hamilton, {Carl J C M} and Ouwens, {Gabri{\"e}le M} and Gerritsma, {Miranda A} and Michael Schaapveld and Burger, {Curt W} and {van Leeuwen}, {Flora E}",

year = "2021",

month = jun,

doi = "10.1093/jnci/djaa163",

language = "English",

volume = "113",

pages = "699--709",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "6",

}

Spaan, M, van den Belt-Dusebout, AW, Lambalk, CB, van Boven, HH, Schats, R, Kortman, M, Broekmans, FJM, Laven, JSE, van Santbrink, EJP, Braat, DDM, van der Westerlaken, LAJ, Cohlen, BJ, Cantineau, AEP, Smeenk, JMJ, van Rumste, MM, Goddijn, M, van Golde, RJT, Meeuwissen, PAM, Hamilton, CJCM, Ouwens, GM, Gerritsma, MA, Schaapveld, M, Burger, CW & van Leeuwen, FE 2021, 'Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology', Journal of the National Cancer Institute, vol. 113, no. 6, 163, pp. 699-709. https://doi.org/10.1093/jnci/djaa163

TY - JOUR

T1 - Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology

AU - Spaan, Mandy

AU - van den Belt-Dusebout, Alexandra W

AU - Lambalk, Cornelis B

AU - van Boven, Hester H

AU - Schats, Roel

AU - Kortman, Marian

AU - Broekmans, Frank J M

AU - Laven, Joop S E

AU - van Santbrink, Evert J P

AU - Braat, Didi D M

AU - van der Westerlaken, Lucette A J

AU - Cohlen, Ben J

AU - Cantineau, Astrid E P

AU - Smeenk, Jesper M J

AU - van Rumste, Minouche M

AU - Goddijn, Mariëtte

AU - van Golde, Ron J T

AU - Meeuwissen, Paul A M

AU - Hamilton, Carl J C M

AU - Ouwens, Gabriële M

AU - Gerritsma, Miranda A

AU - Schaapveld, Michael

AU - Burger, Curt W

AU - van Leeuwen, Flora E

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

KW - IN-VITRO FERTILIZATION

KW - STIMULATION

KW - REGISTRY

KW - COHORT

KW - BREAST

U2 - 10.1093/jnci/djaa163

DO - 10.1093/jnci/djaa163

M3 - Article

C2 - 33769500

SN - 0027-8874

VL - 113

SP - 699

EP - 709

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 6

M1 - 163

ER -