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Assisted reproductive technology and risk of ovarian cancer and borderline tumors in parous women: a population-based cohort study.

ABSTRACT: The study aimed to investigate if assisted reproductive technology (ART) treatment or a diagnosis of infertility were associated with the risk of ovarian cancer or borderline ovarian tumors (BOT) in parous women. In a population-based register study of 1,340,097 women with a first live birth in Sweden 1982-2012, the relationship between ART treatments, infertility and incidence of ovarian cancer or BOT were investigated using Cox regression analysis. In the cohort, 38,025 women gave birth following ART, 49,208 following an infertility diagnosis but no ART and 1,252,864 without infertility diagnosis or ART. During follow-up, 991 women were diagnosed with ovarian cancer and 747 with BOT. Women who gave birth following ART had higher incidence of both ovarian cancer (adjusted hazard ratio [aHR] 2.43, 95% confidence interval [CI] 1.73-3.42) and BOT (aHR 1.91, 95% CI 1.27-2.86), compared to women without infertility. Compared to women with infertility diagnoses and non-ART births, women with ART births also had a higher incidence of ovarian cancer (aHR 1.79, 95% CI 1.18-2.71) and BOT (aHR 1.48, 95% CI 0.90-2.44). Our results suggest that women who have gone through ART have a higher risk of ovarian cancer and BOT. At least part of that risk seems to be due to the underlying infertility and not the treatment per se, since the increased risk was smaller when comparing to other infertile women. As ART treatments are becoming more common and ovarian cancer usually occur in women of advanced age, larger studies with longer follow-up are needed in order to confirm or refute our findings.

SUBMITTER: Lundberg FE

PROVIDER: S-EPMC6861355 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Assisted reproductive technology and risk of ovarian cancer and borderline tumors in parous women: a population-based cohort study.

Lundberg Frida E FE Johansson Anna L V ALV Rodriguez-Wallberg Kenny K Gemzell-Danielsson Kristina K Iliadou Anastasia N AN

European journal of epidemiology 20190803 11

The study aimed to investigate if assisted reproductive technology (ART) treatment or a diagnosis of infertility were associated with the risk of ovarian cancer or borderline ovarian tumors (BOT) in parous women. In a population-based register study of 1,340,097 women with a first live birth in Sweden 1982-2012, the relationship between ART treatments, infertility and incidence of ovarian cancer or BOT were investigated using Cox regression analysis. In the cohort, 38,025 women gave birth follow ...[more]

PMID: 31377935

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Project description:Study questionDo women who give birth after assisted reproductive technology (ART) have an increased risk of cancer compared with women who give birth without ART?Summary answerWithout correction, the results indicate an increase in overall cancer risk, as well as a 50% increase in risk of CNS cancer for women giving birth after ART, however the results were not significant after correcting for multiple analyses.What is known alreadyStudies regarding the effects of hormonal treatments involved with ART on subsequent cancer risk have provided inconsistent results, and it has also been suggested that infertility itself could be a contributory factor.Study design, size, durationA population-based cohort consisting of all women registered in the Medical Birth Registry of Norway as having given birth between 1 January 1984 and 31 December 2010 was assembled (n = 812 986). Cancers were identified by linkage to the Cancer Registry of Norway. Study subjects were followed from start of first pregnancy during the observational period until the first cancer, death, emigration, or 31 December 2010.Participants/materials, setting, methodsOf the total study population (n = 806 248), 16 525 gave birth to a child following ART. Cox regression analysis computed hazard ratios (HR) and 95% confidence intervals (CI) comparing cancer risk between ART women and non-ART women; for overall cancer, and for cervical, ovarian, uterine, central nervous system (CNS), colorectal and thyroid cancers, and for malignant melanoma.Main results and the role of chanceA total of 22 282 cohort members were diagnosed with cancer, of which 338 were ART women and 21 944 non-ART women. The results showed an elevated risk in one out of seven sites for ART women. The HR for cancer of the CNS was 1.50 (95% CI 1.03- 2.18), and among those specifically subjected to IVF (without ICSI) the HR was 1.83 (95% CI 1.22-2.73). Analysis of risk of overall cancer gave an HR of 1.16 (95% CI 1.04-1.29). Among those who had delivered only one child by the end of follow-up, the HR for ovarian cancer was 2.00 (95% CI 1.08-3.65), and for those nulliparous at entry the HR was 1.80 (95% CI 1.04-3.11). However, all findings became non-significant after correcting for multiple analyses.Limitations, reasons for cautionThe results of elevated risk of overall cancer and CNS cancer lost significance when adjusting for multiple analyses, implying an important limitation of the study. The follow-up time was relatively short, especially for ART women. In addition, as the cohort was relatively young, there were few incident cancers, especially for some rarer cancer forms, such as uterine cancer. Risk assessments according to different causes of infertility could not be done.Wider implications of the findingsIn light of the findings in the present study, further studies should be made on risk of CNS and ovarian cancer, and continued monitoring of all those treated with ART is encouraged. Our findings may only be generalizable to women who give birth after ART, and the risk for women who remain nulliparous after ART remains to be assessed.Study funding/competing interestThe study was funded by the Norwegian National Advisory Unit on Women's Health. All authors claim no competing interests.

Project description:ObjectivesTo compare the differences in the prevalence of birth defects among offspring conceived by assisted reproductive technology (ART) and conceived spontaneously (non-ART), and assess the contribution of ART to birth defects.DesignA population-based retrospective cohort study.SettingBeijing.ParticipantsPregnant women whose expected date of childbirth was verified as occurring between October 2014 and September 2015, and were registered on the Beijing Maternal and Child Health Information Network System, were the recorded pregnancy outcomes. 2699 ART offspring and 191 368 non-ART offspring (live births, stillbirths and medical terminations) were included in our study.InterventionsNone.Outcome measuresRisk ratios (RR) for birth defects were calculated among ART conceptions and non-ART conceptions with confounding factors by using logistic regression models.Results194 067 offspring were included in the present study, and 2699 (1.4%) were conceived using ART. Among all the births, the prevalence of any birth defect in the ART offspring (5.5%) was significantly higher than in the non-ART offspring (3.8%) (crude RR, 1.49, 95% CI 1.26 to 1.76). After adjusting for confounding factors, ART use was still associated with an increased risk of any birth defect (5.4% vs 3.5% in ART and non-ART group, adjusted RR (aRR), 1.43, 95% CI 1.08 to 1.90), especially for chromosomal abnormalities (0.5% vs 0.2% in ART and non-ART group, aRR, 3.11, 95% CI 1.28 to 7.58), in singleton births to mothers <35 years. Circulatory system malformations and musculoskeletal system malformations were observed to have a non-significant increase in offspring conceived by ART. However, the associations between ART and birth defects were not detected in multiple births or mothers ≥35 years.ConclusionsThis study confirmed a small but significant association between ART and birth defects. However, the risk tends to be non-significant under the conditions of advanced maternal age or multiple pregnancies.

Project description:Background: Thyroid dysfunction is prevalent in reproductive-age women and has been identified as a risk factor for female infertility. However, it remains largely unclear whether subtle thyroid dysfunction, as estimated by moderately high thyrotropin (TSH) levels within the normal range, is associated with ovarian reserve in infertile women before assisted reproductive technology (ART) treatment. Methods: This cross-sectional study involved 3501 euthyroid infertile women, including 2189 women with TSH levels ≤2.5 μIU/mL and 1312 women with high-normal TSH levels (2.51-4.20 μIU/mL). Ovarian reserve markers were compared between women with low- and high-normal TSH levels. Correlation analysis and regression models were used to estimate the association of TSH levels with ovarian reserve. In addition, the association of subtle thyroid dysfunction with ovarian reserve was further evaluated after stratification for different infertility diagnoses and statuses of thyroid autoimmunity (TAI). Results: In the total population, women with high-normal TSH levels had significantly decreased anti-Müllerian hormone (AMH) concentrations (p < 0.001), a lower bilateral antral follicle count (AFC) (p < 0.001), and a higher prevalence of diminished ovarian reserve (DOR) (p = 0.018) than women with low-normal TSH levels. The TSH levels showed a negative association with both AMH levels (r = -0.050, p = 0.003) and bilateral AFC (r = -0.071, p < 0.001). Furthermore, the association of high-normal TSH levels with decreased AMH and AFC was more prominent in infertile women with ovulation dysfunction (p = 0.002, p = 0.002), unexplained infertility (p = 0.020, p = 0.028), or negative TAI (both p < 0.001). Conclusions: These data suggested that subtle thyroid dysfunction was associated with DOR in infertile women before ART treatment, which will add evidence that strengthens the systematic screening of TSH levels/TAI in infertile women and will contribute to the discussion of specific TSH cutoff values in predicting ovarian reserve.

Dataset Information

Assisted reproductive technology and risk of ovarian cancer and borderline tumors in parous women: a population-based cohort study.

Publications

Assisted reproductive technology and risk of ovarian cancer and borderline tumors in parous women: a population-based cohort study.

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