Preface

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According to the United Nation's section on Human Rights: “All men and women, without racial, national or religious discrimination, preserve the right to create family and the right for reproduction”. Long term infertility, however, and ‘unwanted childnessness’, especially related with cancer, are responsible for one of the worst of crises humans have to endure.

During the last three decades or so, a dazzling array of medical breakthroughs has made ‘curing Infertility’ more than just a dream. In the process though, ‘preserving fertility’ in cancer cases and not only, appears to be a compelling necessity.

Cancer is better known as a disease of the older age. It is interesting to notice however that, its frequency in younger ages has increased recently and/or is now diagnosed more often. In the last 25 years, due to the steady improvement of the 5 year survival rates, the number of cancer survivors has increased considerably, up to 60-70%. For the year 2010, in the developed countries at least, it was estimated that, there would be one cancer survivor per 250 adults.

Preservation of fertility in cured young cancer patients is ‘a determining factor for their future quality of life.’ Unfortunately, aggressive chemo or radiotherapy and radical surgical interventions very often lead to loss of fertility. This is partially due to the fact that fertility preservation methods like gamete, embryo, testicular and ovarian tissue cryopreservation, are new and often unknown, especially to other specialists primarily involved in the management of young patients suffering from malignant diseases.

Women diagnosed with gynaecological cancer who wish to have children after treatment, should speak to a fertility specialist in addition to their oncologist before making treatment decisions. Fertility preservation is becoming routine practice and ‘oncofertility’ an emerging subspeciality in its own night in some countries.

‘Superspecialization’ unaccompanied by the appropriate “team approach” with the expanse of medical knowledge within the related speciality and beyond, is already being critizised by certain health scholars. A more ‘holistic approach’ of health problems, especially in th field of cancer and reproduction, is deemed more necessary.

Following the “red alert” in the early ‘90s invoked by Whittemore's announcement that “ nulliparous women treated with fertility drugs have a high risk of ovarian cancer”, a lot of research has been carried out worldwide and anxiety spread to the public, as expected: “ Is there a relation between reproduction and cancer, mostly ovarian and breast cancer? and if so, are the various infertility treatments responsible for it or the subfertility itself? ”

A review of the literature of the last 20 years on subfertility and fertility drugs and risk of gynaecological cancer shows that most studies refer to a low number of cases with a short follow-up, often with no control group of subfertile women unexposed to fertility drugs. Also, with lack of information about confounders like: dose, duration and the kind of drug and subfertility, oral contraceptive use, life style, education, parity, family history etc.

While the data to date generally are reassuring in not showing large increases in cancer risk associated with the usage of fertility drugs, exposures should continue to be monitored since the vast majority of women who were previously exposed are just now beginning to enter typical cancer age ranges. Additional studies are needed to evaluate the risks associated with some of the newer treatment modalities, including exposures associated with in vitro fertilization.

For instance, are there any specific factors involved like number of IVF cycles and retrieved oocytes, ovarian hyperstimulation and years after IVF? Furthermore, what about malignant conditions in children born after assisted reproductive technology?

It is a fact that an estimated 1.5-3% of all live births result from IVF. Some cancers may be initiated during the early stages of fetal development. “Are children born after IVF at increased risk for cancer compared to children conceived naturally?”

According to the initiation-promotion-progression model derived from experimental chemical carcinogenesis, cancers can originate in early fetal life. Is there an association between ART and Epigenetics? Could genetic imprinting defects through abnormal DNA methylation before fertilization, lead to cancers in both adults and children?

It has been observed that in mature spermatozoa (Ejaculated and elongated spermatozoa) imprints are stable, while immature spermatozoa retrieved after testicular aspiration used for ICSI, might have defective gene inprinting. As a result an association between abnormal genomic imprinting and hypospermatogenesis has been suggested and freezing of mature sperm with the use of cryopreservants may also disturb stable male imprints.

However, precise risks of imprinting and childhood cancers in children conceived with ART still remain unclear. Observational evidence exists but, isn't it still too early? Most studies are case reports, small, with a short follow up, without controls and cannot prove causal relationship.

ART so far, does not seem to be associated with an increased risk of cancer in children. Cancer during childhood is rare and findings are based on small numbers. Most of them are still too young and longer follow-up is necessary. However, with many more women resorting to ART, careful counselling should be offered to all couples especially those requiring ICSI for abnormal sperm parameters, but the question is: to which extent? Further clinical research and long-term studies are urgently required in this area.

In this issue, many of the above considerations are analysed and discussed by a panel of distinct international authors who present their research and innovative approaches to one of the most sensitive as well as controversial subjects of “Reproduction and Cancer”.