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Ovulation stimulation and ovarian cancer

The prevalence of infertility in the world ranges from 3 to 33%. Such a variation is associated with different diagnostic approaches and the availability of medical care. Nevertheless, one in 7 heterosexual couples is expected to face this problem, whose solution can involve the use of agents for ovulation stimulation in ovulation induction, insemination or IVF programmes. 

The agents for ovulation stimulation include:
  • Antiestrogens (citrate clomiphene);
  • (SERM) Selective Estrogen Receptor Modulators (Tamoxifen);
  • Human Menopausal Gonadotropin (HMG);
  • Human Chorionic Gonadotropin (HCG); 
  • Gonadotropin-releasing hormone agonists (GnRH-Ag);
  • Gonadotropin releasing hormone antagonists (GnRH-A);
  • Recombinant follicle-stimulating and luteinizing hormones (FSH, LH);
  • Growth hormone. 

These agents can be administered either separately or in combination with each other. 
The causes for the development of ovarian cancer and borderline ovarian tumours are not explicitly determined but the protective role of pregnancy, lactation and early menopause as well as of the administration of hormonal contraceptives has been discussed over many years. The absence of ovulation was thus postulated as a protection against cancer, whereas its presence was thought to be a biological promoter of ovarian cancer. 

In the period from 1990 to 2010, a large number of studies were carried out aiming to determine or refute the connection between ovulation stimulation and cancer, infertility and cancer, the history of delivery and cancer. But researchers failed to reach common ground. 

In this article, we would like to cover and discuss the results of the Cochrane review of 2013 that included: 
  1. Thirteen cohort studies, among which:
  • seven studies compared the risk of ovarian cancer in infertile women who had undergone treatment with agents for ovulation induction and in women who had not;
  • five studies compared the risk of cancer in women who had undergone therapy with these agents with the prevalence of cancer in the general population;
  • one study compared patients who had conceived with the help of ART methods and successfully delivered a child with those with a natural pregnancy. 
One study was conducted in the USA, six – in Israel, two – in Great Britain, one – in Australia, two – in Sweden, one – in the Netherlands and one – in Finland. 
The information was gathered over the period from 1960 to 2009. By the time the analysis was carried out, all patients had reached the premenopausal age or had had a premature menopause, and were not diagnosed with cancer at the time of their inclusion into study. The patient observation period comprised 10 to 30 years.

2 Eleven case-control studies over the period from 1994 to 2008. These studies were carried out in the USA, Denmark, Italy and Israel. 

So what are the results of these studies?

First of all, it turned out that there was no significant difference in the incidence rate of ovarian cancer between patients who received various combinations of stimulating agents and the general population.