Gynaecology and Gynaecologic Oncology

Are hormonal and reproductive factors associated with the risk of ovarian- and other hormone-related cancers in later life of the women? Are preconceptional and prenatal hormonal exposures associated with adverse reproductive performance and health in offspring?

Currently, more than 1.5 % of all births are the result of a successful IVF treatment. Since hormonal and reproductive factors are known to be involved in the etiology of cancers of the female reproductive system, a stimulating effect of fertility drugs on the risk of these cancers is possible. In addition, evidence is increasing that prenatal exposures affect health and disease risk in later life. Low statistical power, lack of control for important confounders, and short follow up time (mostly average of five years) of women and offspring have limited previous studies of fertility treatment.

The Dutch study OMEGA is a large-scale nation-wide historical study consisting of OMEGA cohort I (from 1980-1995) and OMEGA cohort II (from 1980-2001) including 25.353 and 17.771 women, respectively: in total 43.124 women. All participants were identified in all twelve IVF hospitals that have legal permission to provide IVF-treatment in the Netherlands. The total exposed group consists of 32.265 women who were treated with at least one IVF cycle, and 10.859 women who were subfertile but not treated with IVF.

This study examines whether women who received one or more IVF treatment cycle(s) with ovarian stimulation are at increased risk of ovarian cancer and other hormone-related cancers. Data on reproductive variables and other risk factors for hormone-related cancers were obtained from the participating women, whereas detailed information on subfertility treatment was abstracted from the medical files. Unique is that data from the offspring of a subgroup of these women has been collected as well; 68% of all women completed a questionnaire.

Research activities: Students who are participating in our research themes will participate in all phases of the studies; the designing of the study, the recruitment and clinical data sampling, the performing of measurements and the data analysis. The final aim is the writing of a full paper. Because of the complexity of the data base statistical knowledge and experience with complex data warehouse is mandatory.

In the OMEGA study the following research themes can be investigated:

Theme 1: Hormonal stimulation treatment and women‚ and health in later life

Dr. H.J. van Beekhuizen

  • Ovarian cancer and other hormone-related cancers. In 2011 this group has published for the first time a significant relation between IVF treatment and Borderline Tumor of the Ovary (BTO). Furthermore, a significant relation with the occurrence of ovarian cancer was noted after 15 years of IVF. We now can perform the second analyses including OMEGA II study expanding the number of women consequently increasing statistical power. At this moment analyses are ongoing.
  • Age of starting tobacco smoking and the risk of breast cancer. The nationwide OMEGA cohort study comprises 40.000 women who were treated for subfertility in one of the 12 Dutch IVF-clinics between 1980-2000. All women were asked to fill in a questionnaire, including questions on start and period of smoking, amount of cigarettes per day, menarche, menopause, parity and family history of cancer. Approximately 25.000 women returned a completed questionnaire. Breast cancer incidence in the period 1989-2013 was ascertained through linkage with the population-based Netherlands Cancer Registry (NCR).
  • Because in The Netherlands many girls start smoking at an early age, this large cohort is suitable to investigate the association between smoking at an early age and the risk of breast cancer. It is important to adjust for (possible) confounding, such as age at menarche and menopause, number of children and family history of cancer. Person-years analyses and Cox regression analyses will be performed using Stata statistical software.
  • Menopause. Five papers were published between the relation of early menopause and poor IVF outcome. Due to lack of further funding this item was expired.