Fertility preservation for women with malignant diseases: ethical aspects and risks

As cancer treatment becomes more and more effective, there is greater life expectancy for cancer patients. Because of this, depending upon the modality used in the treatment of cancer, the matter of infertility emerges before us as an issue of increasing significance. Sperm cryopreservation and embryo cryopreservation are well-established methods of fertility preservation (FP). Besides these validated FP options, some FP techniques such as oocyte cryopreservation and ovarian tissue cryopreservation are as yet in the experimental stage. FP medicine has experienced some rapid developments in recent years. The advances in this branch of medicine, however, have also brought about new ethical, medical and legal issues. Some of these include problems with obtaining the informed consent of minors, issues that arise because of the experimental nature of some methods, financial problems and the accessibility of FP methods, and the question of what happens to gametes when a patient dies. This review seeks to discuss, in the light of current literature, some ethical and technical issues and risks related to the implementation of FP methods in women with cancer.     

Strategies for fertility preservation after anti-cancer therapy

A tremendous advance in the field of cancer therapy resulted in a substantial improvement of long-term survival of oncological patients. The most frequent side effect of either chemotherapy or radiotherapy is a partial or complete lost of fertility potential. This paper reviews current knowledge on the fertility preservation strategies for patients facing oncological problems and the risks of iatrogenic infertility. The cryopreservation of spermatozoa or testicular tissue combined with assisted reproductive technology is the optimal solution for male patients. In the case of female patients, the use of ovarian transposition, ovarian suppression and ovarian tissue cryopreservation seem to be the valuable options for fertility prevention. The cryopreservation of embryos is another possible solution, although this procedure is only limited to the couples. On the other hand, there are still controversies regarding the ethical issues concerning gametes and embryos banking.     

Fertility Preservation for Prepubertal Girls: Update and Current Challenges

With increasing rates of diagnosis of childhood cancers and the evolution of more effective treatment options resulting in prolonged life spans, fertility preservation counseling is an integral component of the discussion at the time of diagnosis of childhood cancers. The primary fertility preservation option that exists for prepubertal girls is ovarian tissue cryopreservation. Although ovarian tissue cryopreservation is still considered to be experimental in nature, live births have resulted from orthotopic tissue transplantation. Fertility preservation should be offered to all prepubertal girls at high-risk for premature ovarian failure as a result of gonadotoxic treatment. Ethical and legal questions surrounding these issues must be considered as more and more pediatric patients pursue fertility preservation.     

Fertilitätserhalt bei Krebs

Survival rates of female cancer patients are improving steadily. Clinicians are increasingly confronted with the long-term effects of chemotherapy and radiotherapy on the fertility of young women. Premature ovarian failure in women who wish to become pregnant is devastating both for the patient and her partner. In the case of predictable loss of gonadal function due to a planned cancer treatment fertility preservation options should be offered to the patient. Current methods of fertility preservation include conventional reproductive techniques as well as GnRH analogue treatment, cryopreservation of oocytes and cryopreservation of ovarian tissue. Most of these techniques are still experimental and should only be decided after individual and patient-specific informed consent as well as interdisciplinary counselling.     

Cancer and fertility: strategies to preserve fertility

Fertility preservation is a key component of cancer management in young people. The Fourth Evian Annual Reproduction Workshop Meeting was held in April 2009 to discuss cancer and fertility in young adults. Specialists in oncology, assisted reproduction, embryology and clinical genetics presented published data and ongoing research on cancer and fertility, with particular focus on strategies to preserve fertility. This report is based on the expert presentations and group discussions, supplemented with publications from literature searches and the authors' knowledge. Fertility preservation should be considered for all young people undergoing potentially gonadotoxic cancer treatment. A variety of options are required to facilitate safe and effective fertility preservation for individual patients. Sperm banking is a simple and low-cost intervention. Embryo cryopreservation is the only established method of female fertility preservation. Oocyte cryopreservation offers a useful option for women without a male partner. Emergency ovarian stimulation and cryopreservation of ovarian tissue (followed by tissue transplantation or in-vitro maturation of oocytes) are experimental techniques for women who require urgent cancer treatment. Further prospective studies are required to validate cryopreservation of oocytes and ovarian tissue, in-vitro maturation of oocytes and new vitrification techniques and to identify any long-term sequelae of slow freezing of embryos.     

Fertility preservation in women with breast cancer

Fertility preservation is an important issue for young women diagnosed with breast cancer. The most well-established options for fertility preservation in cancer patients, embryo and oocyte cryopreservation, have not been traditionally offered to breast cancer patients as estradiol rise during standard stimulation protocols may not be safe for those patients. Potentially safer stimulation protocols using tamoxifen and aromatase inhibitors induce lower levels of estradiol whereas similar results in terms of number of oocyte and embryo obtained to standard protocols. Cryopreservation of immature oocytes and ovarian cortical tissue, both still experimental methods, are also fertility preservation options for breast cancer patients.     

Medical, ethical, and legal considerations in fertility preservation

The past 2 decades have seen a significant rise in cancer survival rates, and an increasing proportion of survivors at reproductive age are interested in childbearing. Although assisted reproduction provides physicians with an array of potential possibilities to help patients whose fertility is compromised by cancer treatment, there is still a dearth of regulation regarding the application of this technology. The present paper reviews the current options for fertility preservation, with a particular focus on the legal and ethical challenges that confront providers of this type of care.     

Ovarian tissue cryopreservation and gynecologic oncology: a review.

Sperm cryopreservation permits young men, undergoing cancer treatments, to preserve their fertility. Ovarian tissue cryopreservation have the same goal for young women and could also be an option for children. However, only primordial follicles survive after freezing and a follicular maturation is needed after thawing. This maturation has not yet been realized in humans, pregnancies have only been obtained in animal models. As cryopreservation is yet effective in humans, many teams have already cryopreserved the ovarian tissue of patients who have nothing to lose as their follicular reserve would have been destroyed or severely depleted by cancer treatment.The preservation of fertility is rarely an issue in gynecologic oncology because it usually concerns post-menopausal women. However, they are early-onset forms of gynecologic cancers and in these cases fertility is often threatened. Ovarian tissue cryopreservation may be performed when curative or prophylactic ovariectomy must be undergone, when chemotherapy with high-dose alkylating agents is planned or when pelvic radiation is needed (particularly in cases requiring chemotherapy combined with radiotherapy). In some of these situations it would be dangerous to graft back the tissue to the patient as cancer cells could remain within the grafts, the best solution in this case would be the in vitro follicular maturation.     

Fertility preservation for medical reasons in girls and women: British fertility society policy and practice guideline

Fertility preservation in the female poses several challenges due to the invasive nature of the techniques available to achieve it. The guideline aims to bring together the evidence available for the measures for fertility preservation and their outcome. The guideline addresses fertility preservation for medical reasons and includes both oncological and non-oncological causes. The techniques that the guideline considers are: (i) embryo and oocyte cryopreservation; (ii) ovarian tissue cryopreservation; (iii) GnRH agonist suppression and (iv) ovarian transposition. Although ovarian tissue cryopreservation is still considered experimental, the availability of this technique is gaining momentum as more live births from auto-transplanted tissue are reported. The guideline also highlights use of current treatment modalities for benign and malignant conditions that have a better fertility sparing profile. The guideline recommends a multidisciplinary approach in counselling women and girls about the risk to their fertility and available techniques. The role of psychological support in assisting women and girls with decision-making is highlighted. The guideline also highlights the risks associated with these techniques. Women need to be medically fit to undergo invasive procedures. Fertility preservation techniques are appropriate when treatment has curative intent. Fertility preservation is a subject of on-going research on outcomes of different techniques and at the time of publication, studies are still likely to emerge adding to the available literature.     

Gonadentoxizität

Current strategies of cancer treatment, including chemotherapy and radiotherapy, achieve high rates of remission and survival but are often associated with sterility. Therefore, the question arises of how to preserve the fertility of these patients or how to reverse sterility. For men, fertility preservation can be easily done by cryopreservation of sperm. For women, things are more difficult, but different options exist. Before radiotherapy, ovariopexy can be performed. Other possibilities are cotreatment with GnRH analogs to protect the ovaries, and cryopreservation of embryos and oocytes after stimulation with gonadotropins. Although this kind of treatment is possible, it is time-consuming and therefore not an ideal option because the start of cancer treatment must be postponed. However, cryopreservation of ovarian tissue can be done directly after ovarian biopsy by laparoscopy. Later, the ovarian tissue can be retransplanted. Three births have been documented worldwide after cryopreservation and retransplantation of ovarian tissue. In Germany, the first retransplantation of ovarian tissue was recently performed. Fertility-preserving procedures should be offered to patients who are facing fertility loss.     

Oocyte cryopreservation as a fertility preservation measure for cancer patients

Advances in cancer treatment have allowed women to live longer, fuller lives. However, gonadotoxic therapies used to effect cancer ‘cures’ often significantly impair a woman’s reproductive potential. Thus, in accordance with improved survival rates, there is an increase in demand for fertility preservation. Initially, fertility preservation was limited to embryo cryopreservation; therefore, the number of patients enrolling was relatively low. Recently, substantial improvements have increased available options, specifically oocyte cryopreservation, thereby expanding and altering the make-up of the patient population undergoing treatment for fertility preservation. Patient diversity requires the treating physician(s) to be cognizant of issues specific to cancer type and stage. Furthermore, patients often have comorbidities which must be attended to and addressed. Although not all patients will be candidates for, or will elect to pursue, fertility preservation, all should receive counselling regarding their options. This practice will ensure that the reproductive rights of those patients facing impending sterility are maintained. Here, fertility preservation protocols, practices and special considerations, categorized by most frequently encountered cancer types, are reviewed to guide reproductive endocrinologists in the management of fertility preservation in such patients. The formation of a multidisciplinary patient-structured team will ensure a successful, yet safe, fertility-preservation outcome.Advances in cancer treatment have allowed women to live longer, fuller lives. However, therapies used to treat cancer often significantly impair a woman’s future ability to have children by damaging her eggs or removing key reproductive organs. Given that women are now often living well beyond their cancer diagnosis and treatment, there is an increased interest in preserving reproductive potential. Thus, the field of fertility preservation has been developed and continues to grow. Initially, fertility preservation was limited to freezing embryos formed by combining an egg with spermatozoa. One drawback of this approach is that it requires both female and male contributions. Recently, substantial improvements have expanded the available options, including freezing unfertilized eggs, affording female patients fertility preservation without a requisite male partner or donor. Cancer patients vary widely, requiring the treating physician(s) to be cognizant of issues specific to individual cancer types and extent of disease. Furthermore, cancer patients often have co-existing medical conditions which must be attended to and addressed. Although not all patients will be candidates for, or elect to pursue, fertility preservation, all should receive counselling regarding their options. This will ensure that the reproductive rights of cancer patients facing impending sterility are maintained. Here, we review fertility preservation protocols, practices and special considerations, categorized by the most commonly encountered cancer types, to guide physicians in the management of fertility preservation in such patients. We advocate the formation of a multidisciplinary patient-structured team to ensure a successful and safe fertility-preservation outcome.     

Vitrification of embryos and oocytes for fertility preservation in cancer patients

As survival rates and the life expectancy of those with malignancy have increased, more women in their reproductive years are referred for fertility preservation. Chemotherapy and radiotherapy can severely affect ovarian function, and the effect is irreversible. Therefore, it is optimal to attempt fertility preservation before chemotherapy and radiotherapy are initiated. Oocyte and embryo cryopreservation is the most common option for fertility preservation in women. Several reports have proven that embryo and oocyte cryopreservation can achieve a successful pregnancy. This review discusses the impact of chemotherapy and radiotherapy on ovarian function, and the importance of oocyte and embryo cryopreservation for fertility preservation. In addition, the current status of pregnancy outcomes and potential for cryopreserved oocytes to result in live births in cancer patients was reviewed. This may provide useful information for decision‐making in cancer patients regarding oocyte and embryo cryopreservation and fertility preservation.     

Frozen Hope: Fertility Preservation for Women With Cancer

Young women diagnosed with cancer have the option of preserving their fertility by using assisted reproductive technology (ART) techniques prior to undergoing cancer treatment. This article presents a composite case of a young woman with cancer who had many unanswered emotional and ethical questions about her future as a parent. Fertility preservation techniques, including preimplantation genetic diagnosis (PGD), and related patient education are described. Current literature regarding reproductive counseling for cancer survivors is reviewed. Resources for providing psychosocial support for decisions about fertility preservation are lagging behind the rapid pace of scientific advancements in cancer treatment and ART. As more young women are surviving cancer and taking steps to preserve fertility, there is great need for the provision of psychologic support services and the establishment of ethical guidelines to aid them on this path. Women's health care providers can provide support to cancer survivors facing fertility and parenting issues by becoming knowledgeable about the long‐term aspects of decision making and developing educational materials and guidelines for these patients.     

Y a-t-il une place pour la cryopréservation ovocytaire après le traitement du cancer ?

The number of young cancer women theoretically eligible for fertility preservation before chemotherapy is steadily increasing. Nevertheless, the number of patients who can really benefit from complex ART techniques such as ovarian tissue or oocyte/embryo cryopreservation remains very low mainly because of a too short time-interval between the cancer diagnosis and its treatment. Lack of adequate information regarding post treatment infertility risk and logistical difficulties to access to a highly specialized cryopreservation centre are also reasons of importance. It is now well-established that these patients are at high risk of infertility even if they return to a normal ovarian function. Therefore, for patients who could not benefit from fertility preservation before cancer treatment, and who have recovered spontaneous menstrual cycle, one might raise the question of oocyte freezing once the cancer cured.     

Reproduction beyond cancer: a message of hope for young women

OBJECTIVE: Aggressive chemotherapy and radiotherapy or radical oncological surgery in young women with cancer has greatly enhanced these patients' life expectancy, but these treatments often cause infertility or premature ovarian failure due to a massive destruction of the ovarian reserve. The objective of this review is to discuss the effect of the various cancer treatments on fertility and present the various fertility sparing operations and fertility preservation strategies. METHOD: An extensive survey of the most up-to-date literature was performed. RESULTS: This review discusses the impact of current cancer treatment on fertility potential and the various surgical and assisted-reproduction innovations available today for the most common cancers in young women. Although the ability to retain reproductive potential is becoming a major quality-of-life factor in an increasing number of young female cancer survivors, they are still being poorly counseled with regard to the negative impact of the treatment on their fertility and on their options for fertility preservation. CONCLUSION: As the emerging discipline of fertility preservation is steadily attracting increasing interest, developments in the near future promise to be very exciting. However, in everyday routine work, better interdisciplinary cooperation between gynecological and pediatric oncologists, surgeons, immunologists, and endocrinologists is necessary so that individualized options for fertility preservation can be offered in advance of surgical procedures or cancer treatments.     

Stratégies de préservation de la fertilité chez la femme jeune atteinte de cancer du sein ou d’hémopathie maligne

The incidence of cancer in young patients as well as survival rates is steadily increasing. The question of fertility capacity is therefore of great importance regarding the quality of life after cancer. According to the ASCO recommendations, every patient should be advised about the chemotherapy-induced ovarian damage and fertility preservation possibilities. Several options can be discussed: embryo and/or oocytes freezing and ovarian tissue cryopreservation. Fertility preservation techniques are progressing rapidly but it still remains difficult to establish precise flow-charts according to age, marital status, type, dose and timing of chemotherapy.     

Recommendations for fertility preservation in patients with lymphoma, leukemia, and breast cancer

Fertility issues should be addressed to all patients in reproductive age before cancer treatment. In men, cryopreservation of sperm should be offered to all cancer patients in reproductive age regardless of the risk of gonadal failure. In women, the recommendation of fertility preservation should be individualized based on multiple factors such as the urgency of treatment, the age of the patient, the marital status, the regimen and dosage of cancer treatment.     

Female fertility preservation in the pediatric and adolescent cancer patient population

The 5-year survival rate for childhood cancer is over 80%, thereby increasing the number of young women facing infertility in the future because of the gonadotoxic effects of chemotherapy and radiation. The gonadotoxic effects of childhood cancer treatment vary by the radiation regimen and the chemotherapeutic drugs utilized. Although the American Society of Clinical Oncology guidelines recommend fertility preservation for all patients, there are several barriers and ethical considerations to fertility preservation in the pediatric and adolescent female population. Additionally, the fertility preservation methods for pre- and postpubertal females differ, with only experimental methods available for prepubertal females. We will review the risk of chemotherapy and radiation on female fertility, the approach to fertility preservation in the pediatric and adolescent female population, methods of fertility preservation for both pre- and postpubertal females, barriers to fertility preservation, cost, and psychological and ethical considerations.     

Fertility preservation options for women with malignancies

Cancer is not rare in younger women. There has been a remarkable improvement in the survival rates due to progress in cancer treatment. The necessary treatment for most of the common cancer types occurring in younger women implies either removal of the reproductive organs or cytotoxic treatment that could partially or definitively affect reproductive function. Early loss of ovarian function not only puts the patients at risk for menopause-related complications at a very young age, but is also associated with loss of fertility. Further, women in the western hemisphere have been delaying initiation of childbearing to later in life. The results of these changes have led to an increase in patients facing the risk of premature ovarian failure, and therefore seeking help in preserving their fertility. This increase in demand has resulted in a proliferation of techniques to preserve fertility. Indeed, the number of options is increasing; some are more established procedures, such as embryo cryopreservation, and some are still experimental, such as ovarian cryopreservation. Because of the variations in type and dose of chemotherapy, the type of cancer, the time available before onset of treatment, the patient's age and the partner status, each case is unique and requires a different strategy of fertility preservation. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to recall the potential early loss of ovarian function secondary to radiotherapy and/or chemotherapy for cancer at a young age; explain the increasing demands for fertility preservation; and summarize the limited number of proven, safe, and efficacious methods.