Likelihood of childbirth in women with one versus two ovaries: a Swedish population-based study of women treated with unilateral oophorectomy for benign indications.

STUDY QUESTION: What is the likelihood of future childbirth in women undergoing unilateral oophorectomy (UO) for benign indications, when compared to age-matched women with intact ovaries?

SUMMARY ANSWER: A significantly reduced likelihood of future childbirth was observed in women with a history of UO, when compared to women with intact ovaries.

WHAT IS KNOWN ALREADY: At the time of this study, the prevailing view is that a single ovary is sufficient to maintain fertility. This is the first large-scale observational study reporting an association between UO for benign indications and a decreased chance of future childbirth in a population-based cohort that was followed until the end of reproductive age.

STUDY DESIGN SIZE DURATION: This population-based register study included all Swedish women born 1955-1966, followed until the end of female reproductive age. We identified 17 856 women who underwent UO (exposed) and 171 731 age-matched controls. After exclusions, the exposed cohort consisted of 10 469 women of fertile age with a benign indication for UO and 101 753 age-matched controls.

PARTICIPANTS/MATERIALS SETTING METHODS: All cases of UO were identified by surgery codes and diagnosis of benign diseases, and up to 10 controls per case, matched by age and county, were used in the analysis. Childbirth data were collected from the Swedish Medical Birth Register, and childbirth rates were compared between exposed cases and age-matched controls.

MAIN RESULTS AND THE ROLE OF CHANCE: The childbirth rate post-surgery was lower in women with UO compared to age-matched controls having intact ovaries: 25.5% versus 28.7%, respectively (risk ratio (RR) 0.89; confidence interval (95% CI) 0.86-0.91). Subgroup analysis of women who were nulliparous at the time of UO (N = 4083) versus their age-matched controls (N = 18 770) also indicated a lower childbirth rate: 41.3% vs 66%, respectively (RR 0.63; 95% CI 0.61-0.65). Additionally, an interaction analysis among the nulliparous women indicated that the reduced likelihood of having children was associated with older age at the time of UO.

LIMITATIONS REASONS FOR CAUTION: In this register-based study, the desire for pregnancy could not be captured, and it was unknown if it was similar among cases and controls. Although malignant indications of UO could be excluded in the study, the histopathology of the removed ovaries was not available; thus, it was not possible to adjust for specific diseases potentially affecting fertility, and therefore, residual confounding is a limitation. Additional limitations included the lack of adjustment for lifestyle factors, as such data was only available from the medical birth register, and thus only accessible for the women who had given birth.

WIDER IMPLICATIONS OF THE FINDINGS: This large population-based study demonstrates a significant association between unilateral oophorectomy for benign indications and a reduced likelihood of subsequent childbirth; however, causality cannot be inferred from these observational data.

STUDY FUNDING/COMPETING INTERESTS: This work was funded by the Swedish Cancer Society (20 0170 F), the Swedish Research Council (Dnr 2021-06116 and Dnr 2023-01872), the Radiumhemmets Research Funds Grant for clinical researchers 2020-2026, the Childhood Cancer Fund (Dnr PR2022-0081), the Stockholm County Council (FoUI-953912) and the Karolinska Institutet Research grants Dnr 2020-01963 to K.A.R.W.The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The authors had full access to all study data and the final responsibility for the decision to submit for publication.K.A.R.W. has received: research grants from NovoNordisk, Merck, Gideon Richter and Ferring Pharmaceuticals; royalty for Student Literature (medical text book), Sweden; consulting fees from the Swedish Ministry of Health and Welfare as expert in assisted reproduction and fertility preservation for transgender people; consulting fees from SpringWorks; honoraria from Roche and Pfizer for chairmanship and lectures for education of oncologists; honoraria from Organon for lectures for ob/gyn and reproductive medicine specialists; and honoraria from IBSA for Advisory Board for educational events. K.AR.W. has also received support from Organon for participation in Journées Fertilité 2023, Paris, France, and support from Region Stockholm for participation as chair of the Swedish Interest Group in Reproductive Medicine Fert-ARG, for the Swedish Society of Obstetrics and Gynecology SFOG; participates at advisory board for Merck, Nordic countries, and on an advisory board for Ferring, National coordinator of study; and has received Time-lapse equipment for pre-clinical research from Merck pharmaceuticals and a grant for experimental in vitro research from Ferring Pharmaceuticals. The remaining authors have no conflicts of interest to declare.

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