Fertility preservation is a rapidly expanding new field. It has been our estimate that approximately 1% of women at reproductive age and even a larger percentage of men will face a fertility-threatening medical treatment. Galvanized by the first descriptions of success with transplantation of cryopreserved ovarian tissue and accelerated by the rapid advent of assisted reproduction technologies, fertility preservation brought tremendous opportunities and excitement to the field of women’s health and cancer survivorship ( Figure ). The recent recognition of oocyte cryopreservation by the American Society of Reproductive Medicine as an established fertility preservation method is the result of rapid advances in cryopreservation technologies. Women with estrogen-sensitive malignancies such as breast cancer are also not left out. The development of ovarian stimulation protocols with aromatase inhibitors enabled safer oocyte and embryo cryopreservation before chemotherapy in this most common type of cancer in reproductive-age women. For postpubertal male patients, an established method of semen cryopreservation has long been available. For prepubertal boys, research is advancing in the area of testicular cryopreservation.

A simplified scheme for fertility preservation options for females

In prepubertal girls, ovarian tissue cryopreservation may be the only practical option. In postpubertal female children and single women, a wider range of options is available. Embryo cryopreservation is the most established method for adult patients with a male partner or who wish to use donor sperm. Oocyte cryopreservation, now considered an established method of fertility preservation by the American Society of Reproductive Medicine and American Society of Clinical Oncology, is an option for older postpubertal female children and single women. In cases in which there is insufficient time for ovarian stimulation, ovarian tissue cryopreservation and immature oocyte retrieval for in vitro maturation (followed by oocyte or embryo cryopreservation) may be considered also. In vitro growth of isolated immature follicles is a theoretic option that may offer advantages in the future for female patients who have undergone ovarian freezing when there is a risk of ovarian involvement with cancer. The simplest approach to fertility preservation could have been a pharmacologic intervention; however, there is no proven hormonal treatment to preserve fertility. In the future, with the discovery of the mechanisms that are responsible for the chemotherapy-induced damage to the primordial follicles, targeted pharmacologic methods may be developed.

Oktay. Fertility preservation. Am J Obstet Gynecol 2013 .

Reprinted, with permission, from Bedoschi and Oktay.

The awareness and access to fertility preservation was limited in the beginning. Thanks to the joint efforts from professional organizations (such as American Society of Clinical Oncology [ASCO] and the Fertility Preservation Special Interest Group at American Society of Reproductive Medicine) and patient organizations (such as Fertile Hope, BreastCancer.org , Young Survival’s Coalition and others), awareness has grown tremendously. Health care insurance plans followed suit, and an increasing number of plans are now providing coverage for fertility preservation. ASCO convened a panel in 2005 and issued fertility preservation guidelines for cancer health care providers in 2006, which was accompanied by a patient document. This was a futuristic move, given that ASCO guidelines typically are written on the basis of large prospective randomized studies, which is the standard of care in cancer. ASCO recognized the practical limitations of conducting such studies, especially when the field of fertility preservation was so new. These guidelines had significant impact on accelerating development in the field by providing credibility to the topic. Recognizing that the fertility preservation field has significantly evolved since 2006, ASCO panel recently updated these guidelines. This update now cements the idea that fertility preservation is an integral part of the approach to the young survivor and a mandate for those who render medical care to young individuals with cancer.

In this issue of the Journal, Quinn and Vadaparampil look at a different facet of fertility preservation, long-term decision-making. Authors argue that, by resorting to fertility preservation, patients enter into a long-term engagement. In very young patients, the time to use banked gametes, embryos, or ovarian tissue may come years or decades later. At that time, the patients may have experienced many changes in their lives. Among the most significant of these changes for couples is the possibility of separation post-embryo cryopreservation. In which case, unless both partners consent, the preserved embryos cannot be used by either one of them. Although this dilemma does not occur when a partner is not required (such as with oocyte and ovarian tissue in female patients and sperm or testicular tissue freezing in male patients), embryo freezing is the most common method of fertility preservation and does pose problems from time to time.

With all methods, decisions regarding long-term payment of storage fees and disposal or donation of unused material are also those that patients with cancer would not be ready to make at the time of the procedure. Is this really surprising? Although these survivors are facing a life crisis with cancer diagnosis and a multitude of treatments, they now have to become familiar with fertility treatments within days, sometimes hours, before making an important decision that could have implications many years down the line. This is a decision that a typical infertility patient takes weeks or months to make. Authors argue that patients are not always equipped to deal with such rushed decision-making and that the balance of the burden falls onto those who take care of them, which perhaps is shared equally by those who provide the medical care and the fertility preservation services. The study is unique and draws attention to an important psychosocial aspect of fertility preservation care.

However, I am less alarmed about some of the concerns. Infertility specialists are accustomed to dealing with issues that originate from long-term storage of gametes. Embryo cryopreservation has been around for decades for infertility patients who undergo in vitro fertilization treatments; most centers have dealt with separated couples and have proper consenting protocols. Likewise, oocyte cryopreservation is now considered established, and a standard discussion includes long-term decision-making in most cases. A recent individual patient data metaanalysis from thousands of oocyte thaw cycles strengthens this discussion by providing age-specific individualized oocyte freezing live birth success rates with an online estimator (Available at: http://www.i-fertility.net/index.php/probability-calc . Accessed June 5, 2013). Gonadal tissue freezing is done under institutional review board–approved protocols that typically include detailed information on the outcome of unused or discarded samples.

What may be missing, on the other hand, is the integration of the specific needs of the survivor population who undergo fertility preservation into standard procedures that are developed for patients who undergo gamete cryopreservation for infertility reasons. Oncologists or medical doctors are not charged to shoulder this burden because they need only to raise the issue and point to the right direction of expertise. The major societies in respective fields should coin joint guidelines on streamlining such communication between cancer and other medical health care professionals and fertility preservation providers.

Fertility preservation is not just for patients with cancer. Many noncancer and benign conditions may require such intervention. Recent research indicated that BRCA-mutation carriers may also be at risk for early menopause and diminished reserve in addition to the conferred cancer risks. Many similar genetic conditions (such as FMR1 permutation syndrome) will be identified in the future by predicting early ovarian failure and necessitating fertility preservation. Another such group of patients belong to Turner syndrome, especially of the mosaic type. In Turner syndrome, the ovarian reserve is depleted in an accelerated fashion, in most cases before puberty; however, pregnancy is possible approximately 2-5% of the time. Oocyte and ovarian tissue cryopreservation are also used for preserving fertility from these sometimes peripubertal children.

Finally, the uniformity in the availability and quality of care in fertility preservation awareness and services is lacking both in the United States and around the world. We should concentrate our efforts in making sure that fertility preservation is not a luxury that is available to those who happen to live close to major academic centers and in vitro fertilization programs and in certain geographic parts of the world. This is a global survivorship and quality-of-life issue and a duty for the health care professional. Many cancer interventions cannot abide by “do no harm” when it comes to future fertility. But we can amend this motto “first do no harm; second prevent harm, third reverse harm.” Open communication among medical experts, patients, and infertility specialists, long-term planning, timely referral to fertility preservation counseling, and a policy that dictates uniform access to such services will all achieve the same goal.

There is also the much debated “elective” use of fertility preservation to delay childbearing. What about women who have cryopreserved their gonadal tissues, oocytes, or embryos and have waited past the generally acceptable ages for conception, which typically is <50 years old. Cancer and other intervening medical problems and life events might not have permitted them to attempt pregnancy sooner. Many clinics limit pregnancy attempt with assisted reproduction to ≤50 years old. Should we not have a duty towards these individuals? Quinn and Vadaparampil’s article in this issue and these additional concerns all sum up for us that we are likely to encounter unforeseen challenges with the use of reproductive specimens in the future and that we are in this for a long haul.