Human Reproduction, Vol. 18, No. 9, 1951-1958,
September 2003
© 2003 European Society of Human Reproduction and Embryology
Risk of benign gynaecological diseases and hormonal disorders according to responsiveness to ovarian stimulation in IVF: a follow-up study of 8714 women
1 Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, 2 Research Bureau, Isala klinieken, Zwolle, 3 Department of Obstetrics and Gynaecology, Academic Hospital Free University, Amsterdam and 4 Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, The Netherlands
5 To whom correspondence should be addressed at: Research Bureau, Isala klinieken, PO Box 10500, 8000 GM Zwolle, The Netherlands. e-mail: h.klip{at}isala.nl
BACKGROUND: Over the past decade, attention has been focused increasingly on the long-term health effects of IVF in women. Assuming that hormonal changes due to stimulation regimens for IVF are strongest among ‘high’ responders, we evaluated whether responsiveness to ovarian stimulation in IVF is predictive of the risk of benign gynaecological disorders >12 months after the last IVF cycle. METHODS: A nationwide historical cohort study of women who underwent IVF treatment was conducted. After a median time of 4.6 years following the last IVF treatment cycle, 8714 cohort members completed a health survey questionnaire that inquired about reproductive variables and the occurrence and age at onset of specific medical conditions including uterine leiomyoma, surgically removed ovarian cysts and thyroid disorders. Detailed data on cause of subfertility and IVF treatment were collected from the medical records. Women were included in the ‘high responders’ group when on average 
14 oocytes were retrieved per IVF cycle (n = 1562), in the ‘normal responders’ group when they had a mean number of 4–13 retrieved oocytes (n = 6033), and in the ‘low responders’ group when they had a mean number of 0–3 retrieved oocytes per cycle (n = 1119). RESULTS: Among women with a high response to ovarian stimulation, we found a borderline significantly decreased risk of uterine leiomyoma [relative risk (RR) = 0.6; 95% confidence interval (CI) 0.4–1.0] and surgically removed ovarian cysts (RR = 0.6; 95% CI 0.3–1.0) in comparison with ‘normal responders’. After OHSS, the age-adjusted RRs were 1.8 (95% CI 0.9–3.8) for having surgically removed ovarian cysts and 1.0 (95% CI 0.4–2.2) for uterine leiomyoma (both not significant). CONCLUSIONS: Despite the small number of events observed, highly elevated risks of gynaecological disorders and hormonal diseases in women undergoing IVF treatment can be excluded based on the present data and this follow-up period. Women with a low response to ovarian stimulation tended to have higher risks of benign gynaecological diseases than high responders.
Key words: IVF/long-term follow-up/OHSS/ovarian cysts/uterine leiomyoma
* The OMEGA project group included the following persons: M.Kortman, MD and E.R.te Velde MD PhD (University Medical Center, Utrecht), N.Macklon MD PhD (Erasmus University, Medical Center, Rotterdam), C.A.M.Jansen MD PhD (Diaconessenhuis, Voorburg), R.A.Leerentveld MD PhD (Isala klinieken, Zwolle), W.N.P.Willemsen MD PhD (Academic Hospital Nijmegen, St Radboud), R.Schats MD PhD (Academic Hospital, Free University, Amsterdam), N.Naaktgeboren PhD and F.M.Helmerhorst MD PhD (Leiden University Medical Center), R.S.G.M.Bots MD PhD (St Elisabeth Hospital, Tilburg), A.H.M.Simons MD (Academic Hospital, Groningen), H.V.Hogerzeil MD PhD (Academic Medical Center, Amsterdam), J.L.H.Evers MD PhD (Academic Hospital, Maastricht) and P.A.van Dop MD PhD (Catharina Hospital, Eindhoven).
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