The use of assisted reproductive
technologies is increasing. With advancement in the understanding of
reproductive physiology and advancements in the techniques of reproductive
medicine, its use is now extended to link this specialty with cancer treatment as
well in the form of preserving fertility.
On the other hand, the possible link
between fertility drugs and cancer of reproductive organs remains controversial
and there is still an ongoing debate on the long-term effects of assisted
reproductive technology techniques such as ovulation induction, in-vitro
fertilization on the risk of ovarian, endometrial, cervical and breast cancer
and also on risk of melanoma.
Here we discuss few studies which have been
conducted worldwide to look into his ongoing controversial issue-
Ovulation-inducing drugs and ovarian
cancer risk: results from an extended follow-up of a large US infertility
cohort
Britton
Trabert et al, Fertil Steril.
2013 December; 100(6)
A retrospective cohort of 9,825 women were evaluated
for infertility at five clinical sites in the United States between 1965 and 1988
with follow-up through 2010.
Among women evaluated for infertility,
there was no association of ovarian cancer risk with ever use of clomiphene
citrate (adjusted RR 1.34, 95% CI 0.86–2.07) or gonadotropins (RR 1.00, 95% CI
0.48–2.08) and no evidence that any of several more detailed subgroups of usage
were related to an increased risk. Though it was found in the analysis that
women who used Clomiphene citrate and remained nulligravid did demonstrate much
higher risks than those who successfully conceived compared with nonusers
(respectively, RR 3.63, 95% CI 1.36–9.72 vs. RR 0.88, 95% CI 0.47– 1.63).
IVF
and breast cancer: a systematic review and meta-analysis
Theodoros N. et al Human Reproduction
Update, Vol.20, No.1 pp. 106–123, 2014
Eight cohort studies were analyzed with a
total cohort size of
1 554 332 women among whom 14 961 incident
breast cancer cases occurred, encompassing 576 incident breast cancer cases
among women exposed to IVF. No significant association between IVF and breast
cancer was observed either in the group of studies treating the general
population (RR 1⁄4 0.91, 95% confidence interval (CI): 0.74 – 1.11) or
infertile women (RR 1⁄4 1.02, 95% CI: 0.88 – 1.18), as a reference group.
Though it was noticed that pregnant and/or parous women after IVF (pooled
effect estimate 1⁄4 0.86, 95% CI: 0.73–1.01) were marginally protected but it
was not protective with those who were 30 years at first IVF treatment (pooled
effect estimate 1⁄4 1.64, 95% CI: 0.96–2.80).
the conclusion from this analysis was that
in the current scenario COH for IVF does not seem to impart increased breast
cancer risk, but still what is needed is longer follow-up periods, comparisons
versus infertile women, subgroup analyses aiming to trace vulnerable subgroups,
adjustment for various confounders and larger informative data sets before
conclusive statements for the safety of the procedure are reached.
Controlled ovarian hyperstimulation for IVF: impact
on ovarian, endometrial and cervical cancer—a systematic review and
meta-analysis
Charalampos
Siristatidis et al , Human Reproduction Update, Vol.19, No.2 pp. 105–123, 2013
Nine cohort studies were synthesized,
corresponding to a total size of 109 969 women exposed to IVF, among whom 76 incident
cases of ovarian, 18 of endometrial and 207 cases of cervical cancer were
studied. The synthesis of studies with general population as the reference
group pointed to a statistically significant positive association between IVF
and increased risk for ovarian (RR 1⁄4 1.50, 95%
The conclusion from this analysis was that IVF
does not seem to be associated with elevated cervical cancer risk, nor with
ovarian or endometrial cancer when the confounding effect of infertility was
neutralized . Of importance is only one study provided follow-up longer than 10
years for the group exposed to IVF. Hence what is needed is future cohort
studies preferably using infertile women as the reference group, rely on
IVF-registered valid exposure data, adjust for a variety of meaningful
confounders and adopt relatively longer follow-up periods before sound
conclusions are drawn.
Melanoma risk after ovarian stimulation
for in vitro fertilization.
Spaan M et al. Hum Reprod. 2015
May;30(5):1216-28.
This study was part of OMEGA project group
looking into association of ovarian stimulation on development of cancer. The
cohort comprised of 19158 women who received IVF between 1983-1995 and a
comparison group of 5950 womenwho underwent subfertility treatment other than
IVF. . 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 were 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).
Conclusion – the above reviews have tried to address an important aspect and
so far infer that treatment of infertility in the form of ovulation induction,
in-vitro fertilization does not confer high risk for cancer in reproductive
system. Interestingly studies have also highlighted that patients who remain
infertile despite these treatments have shown some increased risk in cancer
development though numbers studies in these sub-groups were small and properly
designed studies to answer these questions further. Extrapolation of these
global studies to Indian context has also to be considered when counseling our
patients.

