Melanoma risk after ovarian stimulation for in vitro fertilization.
OBJECTIVE
Do women treated with ovarian stimulation for IVF have an increased risk of melanoma?


CONCLUSIONS
Ovarian stimulation for IVF does not increase risk of melanoma, even after a prolonged follow-up.


BACKGROUND
Although exposure to ultraviolet radiation is the major risk factor for melanoma, associations between female sex steroids and melanoma risk have also been suggested. The results of available studies on fertility drugs and melanoma risk are inconclusive since most studies had several methodological limitations such as short follow-up, a small number of cases and no subfertile comparison group.


METHODS
In 1996, a nationwide historic cohort study (the OMEGA-cohort) was established to examine the risk of cancer after ovarian stimulation for IVF. After a median follow-up of 17 years, cancer incidence was ascertained through linkage with the Netherlands Cancer Registry. Melanoma risk in the cohort was compared with that in the general population and between the IVF group and non-IVF group using multivariable Cox regression analyses.


METHODS
The cohort comprises 19 158 women who received IVF between 1983 and 1995 and a comparison group of 5950 women who underwent subfertility treatments other than IVF. Detailed IVF-treatment data were obtained from the medical records and complete information on parity and age at first birth was obtained through linkage with the Dutch Municipal Personal Records Database.


RESULTS
In total, 93 melanoma cases were observed. The risk of melanoma was not elevated among IVF-treated women, neither when compared with the general population (standardized incidence ratio = 0.89; 95% confidence interval (CI): 0.69-1.12), nor when compared with the non-IVF group (adjusted hazard ratio (HR) = 1.27; 95% CI: 0.75-2.15). A higher number of IVF cycles was associated with apparent but statistically non-significant risk increases (5-6 cycles HR = 1.92; ≥7 cycles HR = 1.79). However, no significant trend emerged. In women with more follicle stimulating hormone/human menopausal gonadotrophin ampoules comparable non-significant risk increases were found. A longer follow-up did not increase melanoma risk. Nulliparous women did not have a significantly higher melanoma risk than parous women (HR = 1.22; 95% CI: 0.81-1.84). However, women who were 30 years of age or older at first birth had a significantly higher melanoma risk than women who were younger than 30 years at first birth (age: 30-34 years HR = 4.57; 95% CI: 2.07-10.08, >34 years HR = 2.98; 95% CI: 1.23-7.21).


CONCLUSIONS
Despite our large cohort, the number of melanoma cases was rather small, especially in our comparison group, which hampered subgroup analyses.


CONCLUSIONS
Our results are reassuring for women who underwent IVF or are contemplating to start IVF. Since our cohort study is one of the largest published so far, with long-term follow-up, a subfertile comparison group, and detailed IVF-treatment data, our results add important information to the available evidence.


BACKGROUND
This study was supported by grants from the Dutch Cancer Society (NKI 2006-3631), the Health Research and Development Counsel (28-2540) and the Dutch Ministry of Health.
Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, CX 1066, The Netherlands.
M
M
Spaan
Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, CX 1066, The Netherlands.
A W
AW
van den Belt-Dusebout
Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, CX 1066, The Netherlands.
M
M
Schaapveld
Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, CX 1066, The Netherlands.
T M
TM
Mooij
Department of Obstetrics and Gynaecology, Erasmus Medical Center, Postbus 2040, Rotterdam, CA 3000, The Netherlands.
C W
CW
Burger
Department of Epidemiology, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, CX 1066, The Netherlands f.v.leeuwen@nki.nl.
F E
FE
van Leeuwen
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005307:Fertilization in Vitro / Q000009:adverse effects*; D006801:Humans; D008545:Melanoma / Q000175:diagnosis* / Q000209:etiology*; D008875:Middle Aged; D009426:Netherlands; D010062:Ovulation Induction / Q000009:adverse effects*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000209:etiology*
in vitro fertilization; infertility; melanoma; ovarian stimulation; parity