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Fertility Preservation in Men: Overview of Current and Emerging Trends.

The continuing shifts in the global demographics and incidence of various cancers, especially in low-resource countries, are pointing to an impending hike in cancer burden over the next few decades. Worldwide, cancer has now replaced coronary heart disease or stroke as a major cause of death. Twenty million, per annum, new cancer cases are expected to further stretch the scant resources of underdeveloped and developing countries in next 7 to 10 years (Ferlay et al., 2014).

Current and evolving therapeutic regimens of chemotherapy and radiation therapy have afforded a realistic opportunity for most young adults diagnosed with a wide range of cancers to survive and lead healthy and productive lives. Unfortunately, one unintended consequence of some forms of chemotherapy is ovarian or testicular failure and loss of fertility (Jeruss & Woodruff, 2009; Shah & Keye, 2005; van Casteren, Boellaard, Romijn, & Dohle, 2010). Sixty-four percent of patients will have abnormal sperm parameters even before the initiation of cancer therapy (van Casteren et al., 2010). In the past, this loss of fertility was rarely considered by patients with cancer and their physicians because the focus was on survival, not on procreation. However, in a survey of young cancer survivors less than 35 years of age, 76% of those who were childless at the time their cancer was diagnosed wished to have a child sometime in the future (Schover, 2009; Schover, Rybicki, Martin, & Bringelsen, 1999).

A propitious confluence of improved survival rates following chemotherapy and radiation therapy, along with improving pregnancy rates using assisted reproductive technologies (ART), has contributed to widening of the scope of reproductive tissue banking. Potential candidates range from adolescents and young adults diagnosed with cancer (due to the risk of gonadotoxicity from subsequent cancer therapy) to those otherwise facing risks to their future reproductive potential.

Gonadotoxicity of Cancer Therapies

Chemotherapy in patients with testicular cancers can result in temporary or permanent loss of spermatogenesis. Men who receive cytotoxic chemotherapy with alkylating agents, such as cyclophosphamide and procarbazine, or radiotherapy to the testes are at greater risk of testicular dysfunction than those who receive other agents or modalities (Green et al., 2014; Jacob, Barker, Goodman, & Holmes, 1998). Thirty percent of childhood cancer survivors are azoospermic (Thomson et al., 2002). Besides the germinal epithelium of the testes, the hormone-producing Leydig cells are among the most radiosensitive tissues in the body. Therefore, Leydig cells may undergo significant impairment of function even with a very low dose radiation directed either at the testes (direct radiation) or at tissue adjacent to the testes (scattered radiation). Radiation produces irreversible histologic and physiologic disruption of the seminiferous tubules and Leydig cells in a dose-dependent manner (Rowley, Leach, Warner, & Heller, 1974). The gonadotoxic effects of chemotherapy and radiation therapy also increase the incidence of aneuploidy (Monteil et al., 1997) and other chromosomal abnormalities in human spermatozoa (Genesca et al., 1990), with resulting higher incidence of miscarriages.

Chemotherapy or radiation may have an even more profound effect on fertility when administered to individuals who have preexisting abnormalities of testicular function. For instance, more than half of men with testicular cancer present clinically with oligospermia or azoospermia prior to treatment (Hendry et al., 1983; Meirow & Schenker, 1995; van Casteren et al., 2010). Pathologic and pathophysiologic changes that account for reduced sperm production in men with testicular cancer include diffuse fibrosis of the seminiferous tubules, Sertoli cell-only syndrome, scrotal hyperthermia, perturbations in testicular hemodynamics, and disruption of the blood-testis barrier with the production of antisperm antibodies (Guazzieri et al., 1985). A high proportion of men (as high as 70%) with Hodgkin's disease also have compromised semen analyses before treatment (Hendry et al., 1983; Rueffer et al., 2001; Shekarriz et al., 1995).

Cancer therapies can be mutagenic, and such gene mutations can lead to transgenerational effects both in procreative abilities and oncogenesis patterns (Morris, 2002). Zini, Boman, Belzile, and Ciampi (2008) have linked sperm head DNA damage to high rates of pregnancy loss after ART treatment. Some cancers of nonreproductive organs may also be associated with marked oligo-spermia or azoospermia. For example, certain lung tumors may produce ectopic adrenocorticotropic hormone (ACTH), and adrenal tumors that can secrete androgens, which may, in turn, suppress the production of sperm.

Hypophyseal and hypothalamic tumors may be associated with hypopituitarism and secondary hypogonadism. Deficiencies of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have been demonstrated in patients receiving radiation doses of 35 to 45 Gy (Littley, Shalet, Beardwell, Robinson, & Sutton., 1989). In pediatric patients with solid central nervous system tumors, fertility disturbances may result from disruption of the hypothalamo-hypophyseal-gonadal (HPG) axis after radiation therapy to the brain. Theoretically, the treatment of hormonally active tumors, which may be inhibiting HPG function and thereby causing oligospermia or azoospermia, could restore testicular function and improve fertility (Kenney et al., 2012; Schilsky, 1989). The stress of the disease itself can suppress the function of this HPG axis, creating low or lowered sperm counts and semen quality even prior to the formal cancer diagnosis.

It is intriguing to note that male infertility per se is a significant predictor of cancer among individuals and family members (Hanson, Eisenberg, & Hotaling, 2018). Men with lower-than-normal sperm concentrations, motility, or morphology demonstrate a 20-fold increase in the incidence of testicular cancer (Hanson et al., 2016; Raman, Nobert, & Goldstein, 2005). This apparent correlation could be due to a combination of factors, including genetic, epigenetic, and environmental.

Technical Aspects of Cryopreservation Technology

Reproductive cell and tissue banking involves the collection, processing, long-term storage, and post-thaw use of spermatozoa or their precursors of testicular origin to preserve future reproductive potential. Thanks mainly to our veterinarian colleagues, the process of long-term sperm freezing in the animal industry has been in vogue for several decades. The process of cryopreservation involves incremental dehydration of any cell, including a sperm cell, and its slow- or flash-freezing in liquid nitrogen in the presence of incremental concentrations of a cryoprotectant (such as glycerol or dimethylsulfoxide [DMSO]) that prevents injury to its cellular structures. When appropriate, cells are thawed and rehydrated by exposure to decreasing concentrations of cryoprotectant, and finally, to an isotonic solution.

For decades now, commercial sperm banks have been selling frozen donor sperm to couples unable to conceive due to the male partner's inability to produce sufficient sperm required for normal conception. In the early 1990s, an accidental discovery of a technique for the injection of a single sperm into a single egg during the process of in vitro fertilization (IVF) led to a decrease in the use of third party donated sperm. This technique, known as intracytoplasmic sperm injection (ICSI) (see Figure 1), has revolutionized and enhanced IVF procedures using frozen-stored-thawed ejaculated, epididymal, or testicular sperm (Lin et al., 2004). During an attempt at IVF, frozen sperm can be thawed, and each egg can be injected with a single sperm to achieve fertilization.

ICSI has made it possible for men with low-quantity or low-quality sperm, or those with an obstructed vas deferens or epididymis, to father children of their own. With or without the aid of a surgical microscope, a urologist can retrieve and aspirate a small number of sperm cells from testicular tissue. Sperm cells, however, must exist and be viable for this treatment to be successful. A portion of sperms thus obtained can be used in the current IVF cycle, and the remainder can be cryopreserved and stored for long-term use, obviating the need for a second attempt at surgical sperm retrieval.

As embryo culture technologies progressed, IVF programs worldwide began to achieve increasing pregnancy rates using frozen embryos. The freezing and thawing of ejaculated sperm from men with normal semen parameters poses fewer technical challenges as compared to men with suboptimal semen parameters. Additionally, reported miscarriage rates are higher in suboptimal ejaculated sperm or surgically retrieved sperm (Aboulghar et al., 1997; Verza & Esteves, 2004). These challenges are further compounded when tissues are obtained from prepubertal boys whose spermatogenesis processes have not yet initiated; this remains a focus of current research.

A growing understanding of human genetics has contributed significantly into predicting success of male infertility treatments, especially regarding surgical retrieval in males with nonobstructive azoospermia. Researchers have linked select genetic factors to the etiology of male infertility in up to 15% of infertile males (Krauz, 2011). These cases would have previously been categorized as idiopathic.

Not all sperm are created equal. There can be significant individual variations among normal men in their sperm parameters, ranging from suboptimal to completely abnormal. In patients with cancer, semen parameters are likely to be affected prior to the initiation of any cancer treatments. Cryopreservation of these sperm samples is likely to further result in significant deterioration in terms of sperm numbers and motility, and is not expected to favor already poor sperm morphology, if present. These considerations are important for patient counseling in terms of long-term outcomes for conception.

Indications for Fertility Preservation

Human sperm cryopreservation is a standard of care in reproductive medicine. Interestingly, many studies have shown that a low percentage of males ultimately return to the sperm bank to attempt to conceive a child. Although there is a significant risk for gonadotoxicity, a study on semen quality prior to and after gonadotoxic treatment found that of all cancers in which men banked sperm, 60% remained fertile following cessation of cancer therapy (Bahadur et al., 2005). As the effort to minimize cancer treatment-associated toxicity continues, one could expect that sperm and testicular tissue banking could decline.

Nevertheless, the anxiety of both oncology patients and their loved ones that comes with the potential loss of fertility can impact quality of life. Additionally, in the event that fertility does not return to normal, foregoing cryopreservation can lead to feelings of regret. Cryobanking continues to remain an important and preemptive option for many men, especially those whose sperm quality has been compromised prior to the beginning of cancer therapy. As mentioned above, because spermatogenesis has not yet begun, fertility preservation in prepubertal boys continues to pose technical challenges. Whether spermatogenic tissue obtained from prepubertal testis can be successfully extracted, frozen, and grown into mature sperm remains to be seen. Regardless, there are established and emerging indications for cryopreservation of spermatozoa or testicular tissue.

Cryopreservation and Oncologic Disease

Adolescent and young adult men about to undergo chemotherapy or radiation therapy for benign or malignant diseases that could destroy testicular function should be offered cryopreservation. There is a growing trend

among men with newly diagnosed cancer to have their ejaculated sperm frozen-stored before the initiation of chemotherapy or radiation therapy. In view of the higher-than-usual rate of scrotal masses found among infertile men, routine scrotal ultrasound has been proposed as superior to a simple manual examination of the scrotum, as a means of detecting scrotal abnormalities, and for timely interventions (Pierik, Dohle, van Muiswinkel, Vreeburg, & Weber, 1999; Powell & Tarter, 2006). Such interventions could include preemptive sperm cryopreservation.

Although historically only a small number of patients (10%) have used these cryopreserved sperm, high pregnancy rates (40%) associated with use of cryo-preserved sperm for IVF are reassuring (Agarwal et al., 2004). In addition to freezing sperm obtained through ejaculation or testicular aspiration, freezing intact testicular tissue is an option. In theory, the tissue could later be transplanted back into the body of the male in the hope it would resume its production of hormones and sperm.

Prepubertal Patients

Currently, male patients between the ages of 14 to 50 years are eligible for cryopreservation. Fertility preservation in prepubertal patients who cannot produce a semen sample remains a challenge. Hopefully, in the future, when mature spermatozoa cannot be retrieved for one reason or another, testicular biopsies could be obtained, and spermatogonial stem cells from the biopsied specimens could be cultured to increase their numbers. Thus, they could subsequently be frozen and re-implanted after puberty to restore fertility or even matured in vitro and used to fertilize eggs using the technique of ICSI (Russell & Griswold, 2000; Sofikitis et al., 2003; Tanaka et al., 2003). Some animal experiments have successfully tested the technique for transplanting spermatogonial stem cells from one mouse to another, as well as a technique for freezing and thawing these cells (Kubota, Avarbock, & Brinster, 2004). Therefore, adolescent and young adult patients or guardians of young pre-pubertal patients should be counseled regarding sperm or testicular tissue banking before surgery as an additional option.

Erectile and Ejaculatory Dysfunction

Erectile dysfunction and/or ejaculatory dysfunction (inability to produce or sustain an erection or ejaculate semen) is a known risk of certain pelvic and retroperitoneal surgeries. For example, retroperitoneal lymph node dissection (RPLND), a procedure performed for some stages of testicular cancer, can result in an ejaculation due to irreversible damage to sympathetic nerves that control emission and ejaculation. This can result in difficulty conceiving even though sperm counts may return to normal or near normal after successful chemotherapy or radiation treatment. While nerve-sparing RPLND technique is an option, it is not without risk of complications (Pettus, Carver, Masterson, Stasi, & Sheinfeld, 2009), including the risk of unresected disease (Pearce, Steinberg, & Eggener, 2013) and traction injury to the nerves despite the templated dissection.

Several techniques are available to retrieve semen from anejaculatory patients. Penile vibratory stimulation involves the application of personal vibratory devices to the glans penis to induce ejaculation. Another technique is electro-ejaculation, where a probe containing electrodes is placed in the rectum and directed toward the prostate, and direct current is delivered until ejaculation occurs. Patients with spinal cord injury, psychogenic anejaculation, or severe erectile dysfunction can still provide sample for cryo-storage using this technology.

Non-Oncologic Indications

Fertility preservation can be extended beyond oncology patient. Examples are listed below.

Patients with rheumatic diseases, such as lupus, rheumatoid arthritis (RA), or Crohn's disease, as well as those facing bone marrow or stem cell transplants for hematologic diseases, can benefit from these technologies. Medications used to treat these conditions can have adverse effects on sperm production and function, as well as overall semen quality.

The outbreak of the Zika virus in certain geographical locations of the world and the identification of heavy viral loads in semen has led public health officials to declare the Zika virus as a newly emergent sexually transmitted pathogen responsible for high incidence of congenital abnormalities (Ferlay et al., 2014). Alarm bells have been sounded around the world for sexually active women and men in their reproductive years to avoid immediate conception if travelling to or from affected zones. Cryopreservation of semen samples before travelling to affected areas is a viable option if couples' personal circumstances dictate immediate conception.

Although pre-vasectomy and pre-prostatectomy semen banking is common, intraoperative retrieval and cryobanking of epididymal and testicular sperm have also been advocated at the time of vasoepididymostomy for vasectomy reversal (Glazier, Marmar, Mayer, Gibbs, & Corson, 1999). This obviates the need for a second surgery to retrieve sperm for IVF in the event of a failed vasovasostomy.

Another potential indication is the storage of sperm from a terminally ill man who wants to provide his wife with the opportunity to conceive with his sperm after his death. The posthumous birth of twin children thorough ICSI after a widow opted to use her deceased husband's cryopreserved sperm has been reported (Raziel et al., 2003). Posthumous-assisted reproduction, although invariably challenging, is ethically justifiable when written documentation from the deceased permitting the use of ART is available. State laws vary regarding whether children conceived posthumously are legally recognized as descendants of the deceased for purposes of many actual and potential legal complications, including but not limited to survivors' benefits (Ethics Committee of the American Society for Reproductive Medicine [ASRM], 2018).

Men deployed on combat missions are highly likely to face genitourinary trauma (Han, Edney, & Gonzalez, 2013), risking their potential long-term reproductive potential with devastating consequences for a deployed male soldier and his current or future spouse. Pre-deployment cryopreservation of sperm is an ideal option for these men.

Sperm storage prior to gender reassignment is an option for individuals seeking gender reassignment surgery. As the global societies continue to seek and make some progress toward recognition of sexual orientation and gender identity as a human right, lesbiangay-bisexual-transgender (LGBT) communities are likely to increasingly pursue gender reassignment surgeries. Male-to-female reassignment seekers predominate this group. Cryopreservation of sperm from these individuals with a view to preserve their reproductive potential, in the event of failed surgeries, is evolving as an attractive adjunct to these life-transforming events. Conversations about these options prior to surgical intervention are key to assuring future quality of life for this community (Ethics Committee of the ASRM, 2015).

Cryopreservation of sperm for medical causes of an ejaculation or retrograde ejaculation in multiple sclerosis (Guo, He, Zhang, Wu, & Yang, 2012) and diabetes (Fedder, Kaspersen, Brandslund, & H0jgaard, 2013) has been posited as important priorities for these patients.

Men with Klinefelter's syndrome, one of the most common chromosomal aneuploidies, make up 11% of azoospermic men. Recent advances in ART have given many of these men the opportunity to become biological fathers via surgical sperm retrieval (Vicdan et al., 2016).

Barriers to Access

Fertility preservation is still not considered a standard of care in the United States, although various special interest groups, such as the American Society of Clinical Oncology (ASCO), ASRM, the National Comprehensive Cancer Network (NCCN), and the Association of Pediatric Hematology/Oncology Nurses (see Figure 2) have all set guidelines for counseling patients with cancer about fertility preservation. An astoundingly high (30% to 50%) number of patients with cancer may not receive adequate counseling about fertility risks associated with their treatment or about different preservation options available before beginning their treatment. One study found a third of participants were dissatisfied with the quality and length of discussion with their provider about the effects cancer treatment would have on their reproductive health (Scanlon et al., 2012). Some major barriers include, but are not limited to, disparities in referral patterns; geographical access to cryobank/lab that can perform gamete freezing; shortage of time for clinical encounters; focus on cancer treatment planning concerns; provider reluctance to discuss sensitive subjects, such as sexuality and fertility; inadequate familiarity with fertility preservation techniques on part of patients or their caregivers; or a lack of insight or education associated with initiating conversations about fertility.

Historically, a major barrier in implementation of cryopreservation technology has been lack of awareness about emerging trends in fertility preservation among oncologists, pathologists, and oncology nurses. Recently, however, there is a growing awareness among these specialists of the importance of counseling patients regarding effects of treatments on infertility and available options for fertility preservation. There is also a growing recognition of the role of oncology social workers because they are often the primary source of psychosocial services and can develop long-term relationships with patients through prolonged recovery periods (King et al., 2008).

Nevertheless, unsettling disparities exist in referral rates for fertility preservation, and are often dictated by patient's age and education level, the nature of the cancer diagnosis, and the caregiver's specialization and knowledge of available options. Oncologists and their ancillary medical staff, including oncology nurses and social workers, must play a central role in navigating patients with newly diagnosed cancer, offering counseling and guidance, and initiating the referral processes across specialties, especially fertility preservation specialists. Education of all providers who interact with oncology patients and their ancillary medical staff, with respect to current and emerging progress in reproductive medicine, is likely to increase overall referral rates for patients in reproductive age groups or even prepubertal boys.
Figure 2.

Fertility Preservation Resources for Clinicians

American Society for Reproductive Medicine (ASRM)
https://www.asrm.org/

Society for Male Reproduction and Urology
https://connect.asrm.org/smru/home

Nurses' Professional Group (NPG)
Composed of nurse members of ASRM.
www.npg-asrm.org

Mental Health Professional Group
Composed of psychologists, therapists, social workers, other
reproductive health professionals with an interest in mental health
issues and the care of infertility patients, who are also members
of ASRM. https://connect.asrm.org/mhpg/home?ssopc=1
European Society of Human Reproduction and Embryology (ESHRE)
https://www.eshre.eu/

The Oncofertility Consortium
A national, interdisciplinary initiative designed to explore the
reproductive future of cancer survivors.
http://www.oncofe rtility.northwestern.edu/

LIVESTRONG

Provides free fertility medications for women in partnership with
EMD Serono, and provides access to discounted sperm, embryo, and
egg freezing services through a national network of reproductive
clinics and sperm bank partners.
https://www.livestrong.org/we-can-help/livestrong-fertility

Oncofertility: A New Medical Specialty Helping Young Cancer
Patients Have Children

https://medlineplus.gov/magazine/issues/fall14/articles/
fall14pg18-19.html


Ethical, Legal, and Religious Concerns

The convergence of ejaculated sperm or testicular tissue banking with IVF and related procedures has opened exciting new opportunities for men with life-threatening or debilitating diseases that necessitate gonadotoxic therapy. However, these reproductive options are not without caveats. Such technologies have created new social dilemmas. There are many unanswered legal, religious, and ethical questions that must be addressed (Robertson, 2005). Examples of general ethical and legal concerns include:

* Can a parent give consent for the removal of testicular tissue from a prepubertal child (Hagger, 2003)?

* Which loved one, including parents and the spouse, becomes the legal heir and assumes ownership of the frozen samples in the event of death of the patient (extensively reviewed by Sheinbach, 1999)?

* Can or should such sperm samples be used for posthumous procreation (Kindregan, 2009)?

This list is not all-inclusive, and answers to these and other questions await results of a broader conversation at a societal level. There are major differences in how various cultures, societies, and religious groups view matters of procreation. The legal complexities are not fully addressed at this time (Nangia, Kreig, & Kim, 2013; Schuster, Hickner-Cruz, Ohl, Goldman, & Smith 2003).

In view of the above, patients must be counseled properly with regard to ethical, legal, and technological challenges attendant to cryostorage of their semen samples. Where possible, recourse to legal and religious advice must be strongly encouraged. Informed consent should be given before the cryopreservation. Elements of an appropriate consent form for gamete cryopreservation should include:

* Description of the procedures involved in freezing and thawing.

* Risks (including mechanical failure of a catastrophic event leading to the loss of the frozen tissue, failure of the tissue to survive freezing and thawing, and the theoretic risk of increased congenital anomalies) and benefits (preservation of fertility).

* Disposition of the frozen tissue in the case of non-use or the death of the individual from whom the tissue was obtained.

* Final disposition of samples in the event of divorce or dissolution of a partnership if sperm samples were used at some point to create embryos, nonpayment of storage fees, and loss of contact with patients or their wards.

In most cases, a facility's legal department, especially at larger institutions, will approve this consent form.

Insurance Barriers

While 15 states in the country mandate insurance coverage for ARTs, no state laws or regulations have addressed insurance coverage for oncofertility preservation. While costs associated with sperm cryopreservation (approximately $700 to $900 in initial costs and an additional $200 to $300 in yearly storage fees) are not as high as those associated with oocyte or embryo freezing, this expense may place an additional burden on a family already facing costs and potential loss of income associated with cancer treatment, and could potentially discourage some to not opt for cryopreservation (Quinn et al., 2011).

Multidisciplinary Approach

The multidisciplinary approach to treating metastatic nonseminomatous germ cell tumors has led to a greater than 90% overall cure rate (Ehrlich, Brames, Beck, Foster, & Einhorn, 2010; van Dijk, Steyerberg, Stenning, Dusseldorp, & Habbema, 2004; van Dijk, Steyerberg, & Habbema, 2006). A greater multidisciplinary cooperation in developing diagnoses and treatment-related algorithms, standard operating procedure, and treatment algorithms is invaluable for the long-term procreative potential of males with testicular cancer (de Ziegler et al., 2010).

It is of paramount importance that specialists discuss fertility preservation with all patients in their reproductive age, as well as with those who have not yet attained reproductive maturity. Fertility preservation requires close cooperation and coordination among caregivers across multiple specialties, including non-medical groups, such as ministers or priests. Conversations about fertility preservation can be particularly difficult with prepubertal boys. Under these circumstances, specialists should have candid conversations with guardians or parents (de Vries, Bresters, Engberts, Wit, & van Leeuwen, 2009; Murphy, 2010). Two recent studies have emphasized the importance of active parental involvement in decision-making before the initiation of cancer therapies in adolescent young adults (Klosky et al., 2017; Stein et al., 2014). Specialists also need to be aware of religious and cultural nuances in these matters because there is great diversity across cultures on how matters of life and death, paternity, and posthumous procreation are viewed (Schenker, 2005). Care coordinators at oncology centers and infertility clinics are important stakeholders in this vital task of patient counseling at critical moments of cancer care delivery.

Quality Control Issues in Tissue Cryobanking of Human Tissue

In view of current and emergent indications for sperm or testicular tissue technologies, a word of caution is in order concerning the quality control issue related to reproductive banking. Reproductive tissue banks are faced with the specter of expanding inventories and potential cross-contamination of specimens that could be infected with viruses and are stored in communal liquid nitrogen tanks (Tedder et al., 1995). Storage in vapor phase nitrogen as an alternative to prevent cross-contamination is being increasingly used (Cobo et al., 2010).

The Food and Drug Administration (FDA) (2018) has mandated infectious disease screening of all tissue donors. The American Association of Tissue Banks and the ASRM have also published guidelines for patient screening before tissue cryopreservation. FDA guidelines include testing for hepatitis B, hepatitis C, HIV I and II antibodies, human T-cell lymphotropic virus type I antibody, serologic tests for syphilis (rapid plasma regain [RpR]/venereal disease research laboratory [VDRL]), Cruetzfeldt-Jacob disease, and in some cases, chlamydia and gonorrhea. Since this list is not inclusive of any unknown sources of viral or other infections, discovery of future infections from frozen samples cannot be completely ruled out.

Patients diagnosed with life-threatening cancers are often left with no time prior to initiation of therapy to complete infectious disease screening. If results of these screening tests are not available at the time the sample is obtained and ready for cryopreservation, the tissue samples may be quarantined.

Summary

The revolutionary progress in the field of reproductive medicine and ARTs over the last three decades has engendered previously inconceivable possibilities for infertile couples to conceive children of their own. Recently, these technologies, including fertility preservation technology, have extended their reach beyond infertility and now encompass many life-threatening or life-transforming disease conditions, including cancer.

Progress in cancer care has led to many surviving men and women conceiving children and starting families. While this trend is encouraging, several technical, ethical, legal, financial, and other social challenges, including barriers to access, limit the widespread use of sperm preservation technologies across various strata of the general population, especially those segments underserved in the West and most deserving patients in low resource countries. One major barrier to use remains the lower referral patterns at the time of cancer diagnosis, due mainly to lack of awareness on part of oncologists and surgeons about available options for fertility preservation. A multidisciplinary approach to this significant challenge must entail involvement of not only physicians, oncologists, and surgeons, but nurses and oncology social workers as well. Further, parental involvement of prepubertal patients and the involvement of religious and legal authority must become a part of the multidisciplinary approach in addressing the social aspects of fertility preservation.

doi: 10.7257/1053-816X.2018.38.5.221

References

Aboulghar, M.A., Mansour, R.T., Serour, G.I., Fahmy, I., Kamal, A., Tawab, N.A., & Amin, Y.M. (1997). Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm. Fertility and Sterility, 68(1), 108-111. doi:10.1016/ s0015-0282(97)81484-7

Agarwal, A., Ranganathan, P., Kattal, N., Pasqualotto, F., Hallak, J., Khayal, S., & Macha, E. (2004). Fertility after cancer: a prospective review of assisted reproductive outcome with banked semen specimens. Fertility and Sterility, 81(2), 342-348.

Bahadur, G., Ozturk, O., Muneer, A., Wafa, R., Ashraf, A., Jaman, N., ... Ralph, D.J. (2005). Semen quality before and after gonadotoxic treatment. Human Reproduction, 20(3), 774-781. doi:10. 1093/humrep/dei301

Cobo, A., Romero, J.L., Perez, S., de los Santos, M.J., Meseguer, M., & Remohi, J. (2010). Storage of human oocytes in the vapor phase of nitrogen. Fertility and Sterility, 94(5), 1903-1907. doi:10.1016/j.fertnstert. 2009.10.042

de Vries, M.C., Bresters, D., Engberts, D.P., Wit, J.M., & van Leeuwen, E. (2009). Attitudes of physicians and parents towards discussing infertility risks and semen cryopreservation with male adolescents diagnosed with cancer. Pediatric Blood & Cancer, 53(3), 386-391. doi:10.1002/pbc.22091

de Ziegler, D., Streuli, I., Vasilopoulos, I., Decanter, C., This, P., & Chapron, C. (2010). Cancer and fecundity issues mandate a multidisciplinary approach. Fertility and Sterility, 93(3), 691-696. doi:10.1016/j.fertnstert.2008. 12.028

Ehrlich, Y., Brames, M.J., Beck, S.D., Foster, R.S. & Einhorn, L.H. (2010). Long-term follow-up of cisplatin combination chemotherapy in pa tients with disseminated nonseminomatous germ cell tumors: is a postchemotherapy retroperitoneal lymph node dissection needed after complete remission? Journal of Clinical Oncology, 28(4), 531-636. doi:10.1200/JCO.2009.23.0714

Ethics Committee of the American Society for Reproductive Medicine (ASRM). (2015). Access to fertility services by transgender persons: An Ethics Committee opinion. Fertility and Sterility, 104(5), 1111-1115.

Ethics Committee of the American Society for Reproductive Medicine (ASRM). (2018). Posthumous retrieval and use of gametes or embryos: An Ethics Committee opinion. Fertility and Sterility, 110(1), 45-49.

Fedder, J., Kaspersen, M.D., Brandslund, I., & H0jgaard, A. (2013). Retrograde ejaculation and sexual dysfunction in men with diabetes mellitus: A prospective, controlled study. Andrology, 1(4), 602-606.

Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., ... Bray, F. (2014). Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, 136(5), E359-E386. doi:10.1002/ijc.29210

Food and Drug Administration (FDA). (2018). Code of Federal Regulations [Title 21, Volume 8, FDA 21CFR 1271.45]. Retrieved from https:// www.accessdata.fda.gov/scripts/cdr h/cfdocs/cfcfr/CFRSearch.cfm?CFR Part=1271

Genesca, A., Miro, R., Caballin, M.R., Benet, J., Germa, J.R., & Egozcue, J. (1990). Sperm chromosome studies in individuals treated for testicular cancer. Human Reproduction, 3, 286-290.

Glazier, D.B., Marmar, J.L., Mayer, E., Gibbs, M., & Corson, S.L. (1999). The fate of cryopreserved sperm acquired during vasectomy reversals. The Journal of Urology, 161(2), 463-466.

Green, D.M., Liu, W., Kutteh, W.H., Ke, R.W., Shelton, K.C., Sklar, C.A., ... Hudson, M.M. (2014). Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: A report from the St Jude Lifetime Cohort Study. Lancet Oncology, 15(11), 1215-1223.

Guazzieri, S., Lembo, A., Ferro, G., Artibani, W., Merlo, F., Zanchetta, R., & Pagano, F. (1985). Sperm antibodies and infertility in patients with testicular cancer. Urology, 26(2), 139-142.

Guo, Z.N., He, S.Y., Zhang, H.L., Wu, J., & Yang, Y. (2012). Multiple sclerosis and sexual dysfunction. Asian Journal of Andrology, 14, 530-535.

Hagger, L. (2003). Some implications of the Human Rights Act 1998 for the medical treatment of children. Medical Law International, 6(1), 25-51. doi:10.1177/096853320300600103

Han, J.S., Edney, M.T., & Gonzalez, C.M. (2013). Genitourinary trauma in the modern era of warfare. Journal of Men's Health, 10(4), 124-128. doi:10.1089/jomh.2013.1504

Hanson, B.M., Eisenberg, M.L., & Hotaling, J.M. (2018). Male infertility: A biomarker of individual and familial cancer risk. Fertility and Sterility, 109(1), 6-19. doi:10.1016/ j.fertnstert.2017.11.005

Hanson, H.A., Anderson, R.E., Aston, K.I., Carrell, D.T., Smith, K.R., & Hotaling, J.M. (2016). Subfertility increases risk of testicular cancer: Evidence from population-based semen samples. Fertility and Sterility, 105(2). doi:10.1016/j.fertnstert.2015.10.027

Hendry, W.F., Stedronska J., Jones, C.R., Blackmore, C.A., Barrett, A., & Peckham, M.J. (1983). Semen analysis in testicular cancer and Hodgkin's disease: Pre- and post-treatment findings and implications for cryopreservation. British Journal of Urology, 55(6), 769-773.

Jacob, A., Barker, H., Goodman, A., & Holmes, J. (1998). Recovery of spermatogenesis following bone marrow transplantation. Bone Marrow Transplantation, 22(3), 277-279. doi:10. 1038/sj.bmt.1701332

Jeruss, J.S., & Woodruff, T.K. (2009) Preservation of fertility in patients with cancer. New England Journal of Medicine, 360(9), 902-911.

Kenney, L.B., Cohen, L.E., Shnorhavorian, M. , Metzger, M.L., Lockart, B., Hijiya, N. , ... Meacham, L. (2012). Male reproductive health after childhood, adolescent, and young adult cancers: A report from the Children's Oncology Group. Journal of Clinical Oncology, 30(27), 3408-3416. doi:10. 1200/JCO.2011.38.6938

Kindrega, C.P., Jr. (2009). Dead dads: Thawing an heir from the freezer. William Mitchell Law Review, 35(2), 433.

King, L., Quinn, G.P., Vadaparampil, S.T., Miree, C.A., Wilson, C., Clayton, H., & Zebrack, B. (2008). Oncology social workers perceptions of barriers to discussing fertility preservation with cancer patients. Social Work in Health Care, 47(4), 479-501. doi:10.1080/00981380802255215

Klosky, J.L., Flynn, J.S., Lehmann, V., Russell, K.M., Wang, F., Hardin, R.N., ... Schover, L.R. (2017).

Parental influences on sperm banking attempts among adolescent males newly diagnosed with cancer. Fertility and Sterility, 108(6), 1043-1049. doi:10.1016/j.fertnstert. 2017.08.039

Krausz, C. (2011). Male infertility: Pathogenesis and clinical diagnosis. Best Practice & Research Clinical Endocrinology & Metabolism. 25(2), 217-285.

Kubota H., Avarbock, M.R., & Brinster, R.L. (2004). Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proceedings of the National Academy of Sciences of the United States of America, 101(47), 16489-16494.

Littley, M.D., Shalet, S.M., Beardwell, C.G., Robinson, E.L., & Sutton, M.L. (1989). Radiation-induced hypopituitarism is dose dependent. Clinical Endocrinology (Oxford), 31(3), 363-373.

Lin, Y.H., Huang, L.W., Seow, K.M., Huang, S.C., Hseih, M.L., & Hwang, J.L. (2004). Intentional cryopreservation of epididymal spermatozoa from percutaneous aspiration for dissociated intracytoplasmic sperm injection cycles. Acta Obstetricia et Gynecologica Scandinavica, 83(8), 745-750.

Meirow, D., & Schenker, G. (1995). Cancer and male infertility. Human Reproduction, 10(8), 2017-2022.

Monteil, M., Rousseaux, S., Chevret, E., Pelletier, R., Cozzi, J., & Sele, B. (1997). Increased aneuploid frequency in spermatozoa from a Hodgkin's disease patient after chemotherapy and radiotherapy. Cytogenetic and Genome Research, 76(3-4), 134-138. doi:10.1159/000134531

Morris, I.D. (2002). Sperm DNA damage and cancer treatment. International Journal of Andrology, 25(5), 255261. doi:10.1046/j.1365-2605.2002. 00372.x

Murphy, T.F. (2010). Parents choices in banking boys testicular tissue. Journal of Medical Ethics, 36(12), 806-809. doi:10.1136/jme.2010.037192

Nangia, A.K., Krieg, S.A., & Kim, S.S. (2013). Clinical guidelines for sperm cryopreservation in cancer patients. Fertility and Sterility, 100(5), 1203-1209.

Pearce, S., Steinberg, Z., & Eggener, S. (2013). Critical evaluation of modified templates and current trends in retroperitoneal lymph node dissection. Current Urology Reports, 14(5), 511-517. doi:10.1007/s11934-0130366-1

Pettus, J.A., Carver, B.S., Masterson, T., Stasi, J., & Sheinfeld, J. (2009). Preservation of ejaculation in patients undergoing nerve-sparing postchemotherapy retroperitoneal lymph node dissection for metastatic testicular cancer. Urology, 73(2), 328-331. doi:10.1016/j.urology.2008. 08.501

Pierik, F.H., Dohle, G.R., van Muiswinkel, J.M., Vreeburg, J.T., & Weber, R.F. (1999). Is routine scrotal ultrasound advantageous in infertile men? The Journal of Urology, 162(5), 1618-1620. doi:10.1097/00005392-19991100000012

Powell, T.M., & Tarter, T.H. (2006). Management of nonpalpable incidental testicular masses. The Journal of Urology, 176(1), 96-98.

Quinn, G.P., Vadaparampil, S.T., McGowan Lowrey, K., Eidson, S., Knapp, C., & Bukulmez, O. (2011). State laws and regulations addressing third-party reimbursement for infertility treatment: implications for cancer survivors. Fertility and Sterility, 95(1), 72-78. doi:10.1016/ j.fertnstert.2010.05.017

Raman, J.D., Nobert, C.F., & Goldstein, M. (2005). Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. The Journal of Urology, 174(5), 1819-1822. doi:10.1097/ 01.ju.0000177491.98461.aa

Raziel, A., Friedler, S., Schachter, M., Strassburger, D., Orna, B., & Ron-El, R. (2003). Birth of healthy twins resulting from donated oocytes and posthumous use of frozen-thawed spermatozoa obtained prior to chemotherapy. Journal of Assisted Reproduction and Genetics, 20(9), 382-384.

Robertson, J.A. (2005). Cancer and fertility: Ethical and legal challenges. Journal of the National Cancer Institute Monograph, 34, 104-106.

Rowley, M.J., Leach, D.R., Warner, G.A., & Heller, C.G. (1974). Effect of graded doses of ionizing radiation on the human testis. Radiation Research, 59(3), 665-678. doi:10.2307/3574084

Rueffer, U., Breuer, K., Josting, A., Lathan, B., Sieber, M., Manzke, O., ... Diehl, V. (2001). Male gonadal dysfunction in patients with Hodgkin's disease prior to treatment. Annals of Oncology, 12(9):1307-1311. doi:10. 1023/A:1012464703805

Russell, L.D., & Griswold, M.D. (2000). Spermatogonial transplantation: An update for the millennium. Molecular and Cellular Endocrinology, 161(1-2), 117-120.

Scanlon, M., Blaes, A., Geller, M., Majhail, N.S., Lindgren, B., & Haddad, T. (2012). Patient satisfaction with physician discussions of treatment impact on fertility, menopause and sexual health among pre-menopausal women with cancer. Journal of Cancer, 3, 217-225. doi:10.7150/jca.4408

Schenker, J.G. (2005). Assisted reproduction practice: Religious perspectives. Reproductive BioMedicine Online, 10(3), 310-319. doi:10.1016/ s1472-6483(10)61789-0

Schilsky, R.L. (1989). Infertility in patients with testicular cancer: Testis, tumor, or treatment? Journal of the National Cancer Institute, 81(16), 1204-1205. doi:10.1093/jnci/81.16.1204

Schover, L.R. (2009). Patient attitudes toward fertility preservation. Pediatric Blood and Cancer, 53(2), 281-284. doi:10.1002/pbc.22001

Schover, L.R., Rybicki, L.A., Martin, B.A., & Bringelsen, K.A. (1999). Having children after cancer. Cancer, 86(4), 697-709.

Schuster, T.G., Hickner-Cruz, K., Ohl, D.A., Goldman, E., & Smith, G.D. (2003). Legal considerations for cryopreservation of sperm and embryos. Fertility and Sterility, 80(1), 61-66. doi:10.1016/s00150282(03)00503-x

Shah, T.A., & Keye, W.R. (2005). Fertility: Tissue and cell banking overview. Clinics in Laboratory Medicine, 25(3), 557-569. doi:10.1016/j.cll.2005.06.007

Sheinbach, D.M. (1999). Examining disputes over ownership rights to frozen embryos: Will prior consent documents survive if challenged by state law and/or constitutional principles? Catholic University Law Review, 48(3), 989-1027.

Shekarriz, M., Tolentino, M.V., Jr., Ayzman, I., Lee, J.C., Thomas, A.J., & Agarwal, A. (1995). Cryopreservation and semen quality in patients with Hodgkin's disease. Cancer, 75(11), 2732-2736.

Sofikitis, N., Kaponis, A., Mio, Y., Makredimas, D., Giannakis, D., Yamamoto, Y., ... Miyagawa, I. (2003). Germ cell transplantation: A review and progress report on ICSI from spermatozoa generated in xenogeneic testes. Human Reproduction Update, 9(3), 291-307.

Stein, D.M., Victorson, D.E., Choy, J.T., Waimey, K.E., Pearman, T.P., Smith, K., Brannigan, R.E. (2014). Fertility preservation preferences and perspectives among adult male survivors of pediatric cancer and their parents. Journal of Adolescent and Young Adult Oncology, 3(2), 75-82. doi:10.1089/jayao.2014.0007

Tanaka, A., Nagayoshi, M., Awata, S., Mawatari, Y., Tanaka, I., & Kusunoki, H. (2003). Completion of meiosis in human primary spermatocytes through in vitro coculture with Vero cells. Fertility and Sterility, 79(Suppl. 1), 795-801.

Tedder, R.S., Zuckerman, M.A., Goldstone, A.H., Hawkins, A.E., Fielding, A.K., Briggs, E.M., ... Patterson, K.G. (1995). Hepatitis B transmission from contaminated cryopreservation tank. Lancet, 346(8968), 137-140.

Thomson, A.B., Campbell, A.J., Irvine, D.C., Anderson, R.A., Kelnar, C.J., & Wallace, W.H. (2002). Semen quality and spermatozoal DNA integrity in survivors of childhood cancer: A case-control study. The Lancet, 360(9330), 361-367. doi:10.1016/ s0140-6736(02)09606-x

van Casteren, N.J., Boellaard, W.P., Romijn, J.C., & Dohle, G.R. (2010). Gonadal dysfunction in male cancer patients before cytotoxic treatment. International Journal of Andrology, 33(1), 73-79. doi:10.1111/j.1365-2605.2009.00956.x

van Dijk, M.R., Steyerberg, E.W., Stenning, S.P., Dusseldorp, E., & Habbema, J.D. (2004). Survival of patients with nonseminomatous germ cell cancer: A review of the IGCC classification by Cox regression and recursive partitioning. British Journal of Cancer, 90(6), 1176-1183. doi:10.1038/ sj.bjc.6601665

van Dijk, M.R., Steyerberg, E.W., & Habbema, J.D. (2006). Survival of non-seminomatous germ cell cancer patients according to the IGCC classification: An update based on meta-analysis. European Journal of Cancer, 42(7), 820-826. doi:10.1016/j.ejca.2005.08.043

Verza, S., Jr., & Esteves, S.C. (2004). Sperm defect severity rather than sperm source is associated with lower fertilization rates after intracytoplasmic sperm injection. Fertility and Sterility, 82(Suppl. 2), S172-S173. doi:10.1016/j.fertnstert.2004. 07.448

Vicdan, K., Akarsu, C., Sozen, E., Bulug, B., Vicdan, A., Yilmaz, Y., & Bibero lu, K. (2016). Outcome of intracytoplasmic sperm injection using fresh and cryo-preserved-thawed testicular spermatozoa in 83 azoospermic men with Klinefelter syndrome. Journal of Obstetrics and Gynaecology Research, 42(11), 1558-1566. doi:10.1111/jog.13090

Zini, A., Boman, J.M., Belzile, E., & Ciampi, A. (2008). Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: Systematic review and meta-analysis. Human Reproduction, 23(12), 2663-2668.

Tariq A. Shah, PhD, is an Assistant Professor, Department of Urology, College of Medicine, University of Toledo, Toledo, OH.

Zane Giffen, MD, is a Resident, Department of Urology, University of Toledo Medical Center, Toledo, OH.

Peter Fredman, MS, is a Medical Student, College of Medicine, University of Toledo, Toledo, OH.

Vinaya Gogineni, BS, is a Student, College of Medicine, University of Toledo, Toledo, OH.

Puneet Sindh wani, MD, is Chairman, University of Toledo Medical Center, Toledo, OH.

Caption: Figure 1. Intracytoplasmic Sperm Injection (ICSI)
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Author:Shah, Tariq A.; Giffen, Zane; Fredman, Peter; Gogineni, Vinaya; Sindhwani, Puneet
Publication:Urologic Nursing
Date:Sep 1, 2018
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