Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2017 Jan 5.
Published in final edited form as: J Pediatr Oncol Nurs. 2014 May 5;31(4):211–222. doi: 10.1177/1043454214532025

Evidence-Based Recommendations for Fertility Preservation Options for Inclusion in Treatment Protocols for Pediatric and Adolescent Patients Diagnosed with Cancer

Alison Fernbach 1, Barbara Lockart 2, Cheryl L Armus 3, Lisa Bashore 4, Jennifer Levine 5, Leah Kroon 6, Genevieve Sylvain 7, Cheryl Rodgers 8,✉
PMCID: PMC5213740  NIHMSID: NIHMS837965  PMID: 24799444

Abstract

As survival rates improve for pediatric cancers, increased attention has been paid to late effects of cancer therapy, in particular, infertility. Fertility preservation options are available for pre- and post-pubertal cancer patients; however, many providers lack knowledge regarding options. The aim of this document is to provide a comprehensive synthesis of current evidence and recommendations regarding fertility preservation options for children, adolescent, and young adults undergoing cancer treatment. A systematic search was performed to identify fertility preservation evidence. Fifty-three studies and four clinical guidelines were used for the review. Final recommendations consisted of two strong and one weak recommendation for both female and male fertility preservation options. The treatment team should be knowledgeable about fertility preservation so that they can educate patients and families about available fertility preservation options. It is important to consider and discuss all available fertility options with patients at the time of diagnosis.

Keywords: Fertility Preservation, Cancer Treatment, Pediatric, Adolescent, Young Adult

When chemotherapy was introduced into the care of children with cancer, the goal was focused solely on achieving remission. As multimodality therapies advanced and became more refined, survival rates rose, and the long term consequences of cancer directed therapies became more apparent. Subsequently, attention shifted to identifying and minimizing these long term effects when possible. Long term complications include effects on reproductive capacity following exposure to radiation to the gonads or pituitary or from the use of chemotherapy, particularly alkylating agents (Green et al., 2010; Green et al., 2009). Patients and families have identified the threat of infertility as a major concern and conversely, knowledge that efforts have been made to preserve future fertility can serve as a stimulus of hope (Schover, 2009; Saito, Suzuki, Iwasaki, Yumura, & Kubota, 2005). In patients determined to be at risk, assisted reproductive technologies, such as cryopreservation of gonadal tissue or gametes, can be utilized to safeguard against future infertility (Levine, Canada, & Stern, 2010).

Many challenges exist in providing comprehensive fertility preservation (FP) counseling and services to children and adolescents with cancer. Specific challenges include determining who is at risk for alterations in reproductive capacity, appropriate interventions based on gender, age, risk, and available patient resources. Research focusing on FP has confirmed that oncology patients and their healthcare team are often not aware of the impact of cancer treatment on fertility or the preservation options available (Woodruff, 2007). Educating patients and families on the side-effects of treatment and interventions to minimize side effects is a primary responsibility of pediatric oncology healthcare providers. The goal of this document is to provide a comprehensive synthesis of current evidence for pediatric oncology healthcare providers about the FP options available for the pediatric, adolescent, and young adult patient undergoing treatment for a pediatric malignancy.

Evidence Review Methods

Evidence-Based Practice (EBP) Review Team Selection and Composition

A call for EBP projects was disseminated to the Children's Oncology Group (COG) Nursing Discipline membership, after EBP topic areas were developed to align with the Nursing Discipline's 5-year blueprint and organizing framework (Landier, Leonard, & Ruccione, 2013; Kelly, Hooke, Ruccione, Landier, & Haase, 2013) and vetted with COG leadership and other key stakeholders (i.e. COG committees such as Survivorship-Outcomes Committee). The project team leaders (A.F. and B.L.) applied to develop evidence-based fertility preservation recommendations for children and adolescents with cancer, and after a competitive selection process, the proposal was selected for development. The evidence based practice team for this project consists of two team leaders, five team members, and a group mentor. Members of the team include nurses, nurse practitioners, and one physician, all with interest and expertise in fertility preservation in this population. Team members are based at COG institutions across the United States. The group mentor is a doctoral prepared nurse who has experience with EBP reviews.

Question Development

The clinical concerns regarding fertility preservation were formed into PICOT questions to focus the systematic review. PICOT stands for Patient, Intervention or Issue of Interest, Comparison, Outcome, and Time (Melynk & Fineout-Overholt, 2011). Team leaders, with help from the group mentor, developed the following two PICOT questions to guide the EBP review: In pediatric and adolescent and young adult (AYA) individuals, what fertility preservation options can be utilized in pre- and post-pubertal females immediately following a cancer diagnosis, before the initiation of cancer treatment? In pediatric and AYA individuals, what fertility preservation options can be utilized in pre- and post-pubertal males immediately following a cancer diagnosis, before the initiation of cancer treatment?

Literature Search and Analysis

A systematic review of the literature was carried out by the team leaders and confirmed with a medical librarian. Databases used in the comprehensive review of the literature included: Cumulative Index of Nursing and Allied Health Literature (CINAHL), Scopus, Pubmed, OvidMedline, and the Cochrane Database of Systematic Reviews. The following search terms were used: cancer, carcinoma, neoplasm, malignant, tumor, oncology, fertility, semen, sperm, ovary, ovarian, preservation, cryopreservation, and transposition. In addition, reference lists of key articles were hand searched. Limits to the searches included the English language, any publication between the years 2002-2013, and involvement of human subjects.

A total of 1108 potential studies were identified from the searches. Articles were initially reviewed by title and 850 articles were eliminated because they were not relevant to the PICOT questions. A total of 258 abstracts were screened. Abstracts were included in the EBP review if the study met the following inclusion criteria: (a) designed as research based studies, case studies, systematic reviews, or meta analyses (b) consisted of study participants with a mean age of less than or equal to 30 years, and (c) comprised of a sample population where greater than 50% had a pediatric cancer diagnosis. Exclusion criteria included: (a) basic review article or (b) study subjects that had ovarian carcinoma or breast cancer (diagnoses typically found in the adult population). Based on these criteria, 157 of the 258 abstracts were excluded. The remaining 101 articles were reviewed in full text for inclusion and exclusion criteria, and 53 met criteria for inclusion in this EBP review. Thirty studies discussed male fertility preservation options, and 23 studies examined female fertility preservation options. Search results are shown in Figure 1.

Figure 1. Search Results.

Figure 1

Open in a new tab

The 53 studies included in the review were divided into two groups, male and female, based on the gender of the subjects studied and the fertility preservation option(s) discussed in the article. The articles were distributed amongst team members to review, summarize into matrix tables, and evaluate the evidence according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Using GRADE, literature is rated according to quality of evidence and labeled as high, moderate, low, or very low (Guyatt et al., 2011). The team leaders and mentor used summaries of the literature to create synthesized statements about the each topic and used quality ratings to determine one overall quality of the evidence. Recommendation statements were then developed from the synthesized evidence and were labeled as strong or weak, as described in the introduction article of this journal issue. The strength of each recommendation was determined by the desirable and undesirable effects of the evidence and made independently of the quality level of the evidence (Andrews et al., 2013).

Clinical Guideline Search

In addition to the database searches, a comprehensive search for clinical guidelines was conducted by one team member by searching relevant professional organizations and governmental agency websites (i.e. National Guideline Clearinghouse). Five guidelines, pertinent to both male and female fertility preservation options, were identified from the search. The clinical guidelines were reviewed using the Appraisal of Guidelines Research & Evaluation II (AGREE II) tool to assess the methodological rigor of the guidelines (Cluzeau et al., 2003). The tool's criteria evaluated six domains of the guidelines: scope and purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability, and editorial independence. Each guideline was independently reviewed by a team leader and the mentor using the AGREE II tool and significant differences of scores were discussed between the two individuals until agreement was reached. Ratings among the two individuals were then averaged for a combined score for each of the six domains. As no cut off criteria has been determined for the AGREE II tool (Cluzeau et al., 2003), the team leader and mentor discussed final score results to determine if the clinical guideline was acceptable for use. Five clinical guidelines were assessed using the AGREE II tool and four guidelines met criteria to be included. Guidelines from the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and The American Society of Reproductive Medicine (ASRM) were included in this EBP project. In 2013 ASRM updated guidelines regarding oocyte cryopreservation and these were included in the EBP review.

Review of the Evidence

Fertility Preservation Options for Females-Pre and Postpubertal

Four methods of female FP were noted in the literature – embryo/oocyte cryopreservation, oophoropexy, ovarian tissue cryopreservation, and hormone suppression. Options for FP are influenced by several factors including the patient's sexual development status, time frame to begin treatment, and the patient and family's desire to undergo FP treatments that might be time-consuming and costly (Levine, Canada, & Stern, 2010).

Embryo/oocyte cryopreservation

The literature addressing embryo and oocyte cryopreservation included five articles, three guidelines, and one amendment to clinical guidelines (Table 1). Both FP embryo and oocyte cryopreservation require medications to stimulate the ovaries to produce oocytes, which are harvested through a surgical procedure then cryopreserved. Ovarian stimulation requires days to weeks and may not be feasible if cancer treatment must be initiated emergently (Ginsberg, 2008). The expenses associated with the ovarian stimulation, surgical procedure, and annual storage fees may deter this FP option for some patients (Levine, Canada, & Stern, 2010).

Table 1. Embryo/Oocyte Cryopreservation Evidence.

Theme Findings References (first author, year) Quality of Evidence
Post-pubertal feasibility Oocytes can be retrieved with ovarian hyperstimulation and cryopreserved as fertilized (embryo) or not fertilized (oocyte) in post-pubertal females Loren, 2013; ASRM, 2005; Coccia 2012 Not applicable
4-22 oocytes have been retrieved per ovarian hyperstimulation cycle Kamath, 2011; Rossi, 2011; Huser, 2012 Very low – low
Pre- or peri-pubertal feasibility Oocyte harvesting is possible with 7-17 oocytes retrieved per ovarian hyperstimulation cycle in pre- or peri-pubertal females Revel, 2009; Reichman, 2012 Very low
Open in a new tab

Oocytes may be preserved unfertilized as an oocyte or undergo fertilization to create an embryo. Fertilization requires sperm to fertilize the oocytes prior to freezing (Agarwal & Chang, 2007), and therefore may not be a feasible option for AYA patients who do not have a life partner or for whom the use of donor sperm for fertilization is not an option. ASCO (2013), ASRM (2005), and NCCN (2012), all endorse embryo cryopreservation as a FP option for post-pubertal females at risk for infertility secondary to treatment (Loren et al., 2013; ASRM, 2005; Coccia et al., 2012).

Until recently, oocyte harvesting and cryopreservation was deemed an experimental method of FP in both the oncology and general infertility population; however, ASRM recently revised FP guidelines for cancer patients. ASRM (2013) stated that pregnancy rates following oocyte cryopreservation are similar to embryo cryopreservation; therefore, oocyte preservation is no longer experimental for post-pubertal females. The 2013 ASCO guidelines concur with the 2013 ASRM statement (Loren et al., 2013).

Oocyte harvesting and cryopreservation is a viable option in post-pubertal female patients at risk for infertility who do not wish to freeze embryos. Recent studies confirm that ovarian hyperstimulation can produce oocytes in post-pubertal females (Kamath, Londhe, Muthukumar, & George, 2011; Rossi et al., 2011). A recent study of 154 women who were newly diagnosed with cancer found that both embryo and oocyte cryopreservation are feasible methods to preserve reproductive potential prior to gonadotoxic cancer treatment (Huser et al., 2012). Two studies also report the possibility of oocyte harvesting in pre-pubertal females (Revel et al., 2009; Reichman, Davis, Zaninovic, & Rosenwaks, 2012). Successful oocyte harvesting was performed in a case report of a 13 year old pre-menarcheal female with Tanner III breast development and Tanner I pubic hair growth (Reichman et al., 2012). A 2009 cohort study of 19 patients age 5-20 years reported successful oocyte aspiration during ovarian tissue cryopreservation (Revel et al., 2009). In this study, oocytes were retrieved, matured, and cryopreserved in both pre- and post- pubertal patients.

Oophoropexy

Oophoropexy is the surgical relocation of the ovary or ovaries outside of the radiation field. This method of FP may be utilized in either pre or post pubertal females only if the ovary or ovaries are in the radiation field and do not require radiation as part of cancer therapy. To be effective, oophoropexy must be performed prior to start of radiation therapy. This method does not protect the ovaries from gonadotoxic effects due to chemotherapy (Lee, 2007).

Three articles and two clinical guidelines supported the use of oophoropexy in pediatric and AYA patients (Table 2). Fourteen pregnancies were reported in 11 women who underwent oophoropexy prior to pelvic radiation for treatment of Hodgkin lymphoma (Tereniani et al., 2009). Furthermore, a 2011 study reported three out of 11 patients had successful, full term pregnancies following oophoropexy (Gareer, Gad, & Gareer, 2011). In addition to protecting patients undergoing pelvic radiation, oophoropexy is a feasible FP option prior to craniospinal radiation with ovarian protection noted among five adolescents age 11-17 years (Kung, Chen, Huang, Ho, & Cheng, 2008). Both ASCO and NCCN endorse oophoropexy as an option for females receiving pelvic radiation (Loren et al., 2013; Coccia et al., 2012).

Table 2. Oophoropexy Evidence.

Theme Findings References (first author, year) Quality of Evidence
Clinical use Oophoropexy is an option for females receiving pelvic radiation Loren, 2013; Coccia, 2012; Tereniani, 2009 Low
Outcomes 14 pregnancies in 11 women who underwent oophoropexy as adolescents prior to Hodgkin lymphoma treatment Tereniani, 2009 Low
3 pregnancies in 11 women who underwent oophoropexy prior to radiation therapy Gareer, 2011 Low
Ovarian protection in 5 adolescents who underwent oophoropexy prior to cranio-spinal radiation Kung, 2008 Very low
Open in a new tab

Ovarian Tissue Cryopreservation

Ovarian tissue cryopreservation (OTC) is an experimental method of FP and is the only cryopreservation option available to pre-pubertal females (Gosiengfiao, 2007; Gracia & Ginsberg, 2007; Wallace, 2011). This FP method requires removal of tissue from part or all of an ovary, which is then cryopreserved for future use. One option for future use includes reimplanting part or the entire ovary back into the patient to restore either hormonal function or fertility (Lee, 2007).

A total of twelve articles and three clinical guidelines met inclusion criteria for OTC (Table 3). Because this technique requires surgery and the benefit to the patient is not yet established, ASCO and ASRM guidelines state that OTC should only be offered in research that has been approved by an Institutional Review Board (IRB) (Loren et al., 2013; ASRM, 2013). NCCN guidelines state OTC is an investigational method of FP and the possibility of re-seeding cancer through re-implanted tissue exists (Coccia et al., 2012).

Table 3. Ovarian Tissue Cryopreservation.

Theme Findings References (first author, year) Quality of Evidence
Feasibility No significant treatment delay and harvest can be bundled with other procedures Feigin, 2007; Rosendahl, 2008; Babayev, 2013; Gracia, 2012 Low
Malignancy risk 8 out of 26 ovarian tissue samples had leukemia cells Rosendahl, 2010 Low
Ovarian tissue from 24 Hodgkin lymphoma patients had no cancer cells Seshadri, 2006 Low
Outcomes Patients satisfied with ovarian tissue cryopreservation decision Rosendahl, 2008 Low
Unknown, tissue remains cryopreserved Huser, 2012 Low
Endocrine function restored after reimplantation of ovarian tissue Donnez, 2008 Very low
One live birth reported in each case study Donnez, 2011; Demeestere 2007 Very low
Retrieval of immature oocytes from ovarian tissue cryopreservation is feasible Huang, 2008 Very low
Open in a new tab

One concern for OTC is delaying the onset of treatment due to the oophorectomy procedure. Several studies show no significant delay in treatment and the ovarian tissue harvest may be bundled with other procedures such as venous port placement (Feigin, 2007; Rosendahl et al., 2008; Babayev, Arslan, Kogan, Moy, & Oktay, 2013; Gracia et al., 2012). Adult survivors of childhood cancer, younger than 18 years of age at the time of the OTC, report satisfaction with their decision to pursue OTC (Rosendahl et al., 2008).

A large descriptive study of 154 female patients with newly diagnosed cancer demonstrates that OTC is a viable option for women; however, all ovarian tissue from these women remains cryopreserved, so outcomes are unavailable (Huser et al., 2012). A 2007 observational study reports that patients who have received chemotherapy prior to OTC may still benefit from OTC if receiving gonadotoxic treatment, provided previous treatment was nonsterilizing (Meirow et al., 2007). There are two case reports of live birth following re- implantation of harvested ovarian tissue following cancer treatment. The two cases involved a 17 year old female and a 24 year old female who both underwent OTC prior to hematopoietic stem cell transplantation (Donnez et al., 2011; Demeestere, Simon, Emiliani, Delbaere, & Englert, 2007). In addition, endocrine function was restored in 5 women when ovarian tissue was re- implanted following treatment completion (Donnez et al., 2008).

If malignant cells are present in the ovary, there is a risk of re-seeding the malignancy if the ovary is reimplanted (Rosendahl et al., 2010). Thus, research is ongoing to develop techniques to mature follicles into oocytes that may be fertilized through in vitro fertilization, allowing for pregnancy to occur without the risk of re-seeding a malignancy (Gosiengfiao, 2007). In a retrospective study, polymerase chain reaction (PCR) of previously cryopreserved ovarian tissue showed that eight out of 26 samples had leukemia cells present (Rosendahl et al., 2010). However, another retrospective analysis of ovarian tissue harvested in 24 Hodgkin lymphoma patients did not show any evidence of cancer cells (Seshadri et al., 2006).

A final strategy involving OTC consists of combining OTC with retrieval of oocytes from the excised ovarian tissue. A retrospective study of 4 females reported 11 oocytes retrieved from their ovarian tissue with a greater number of oocytes retrieved from the younger patient's tissue (ages 18 and 21 years versus ages 35 and 38 years) (Huang, Tulandi, Holzer, Tan, & Ri-Ching, 2008).

Hormone Suppression

The administration of gonadotropin-releasing hormone analogs (GnRHa) to protect the ovaries from the effects of gonadotoxic treatment was evaluated in five studies and cited in two clinical guidelines (Table 4). This method of FP is thought to put the ovaries in a pre-pubertal state preventing ovulation and thus preserving the number of oocytes in the ovary. ASCO (2013) does not endorse GnRHa as a FP method. NCCN (2012) stated post treatment pregnancy rates are not improved with hormone suppression (Loren et al., 2013; Coccia et al., 2012). A phase II clinical trial was closed prematurely when an interim analysis of 23 patients did not demonstrate that GnRHa or oral contraceptives maintain ovarian reserve (Behringer, et al., 2010). Another study found that GnRHa analogues were protective only in patients receiving less gonadotoxic chemotherapy (Huser et al., 2012). Two studies examining GnRHa use in patients with Hodgkin lymphoma had conflicting results regarding efficacy. A case control study of 30 women (10 received GnRHa with chemotherapy treatment, 10 received chemotherapy without GnRHa, and 10 received GnRHa without chemotherapy) reported no ovarian protection from the GnRHa during chemotherapy (Nitzschke et al., 2010). In a retrospective study of 61 patients who all received GnRHa during their treatment for Hodgkin lymphoma, 50 women resumed menses, 22 women conceived, and 7 women developed acute ovarian failure (Falorio, Angrilli, & Fioritoni, 2008). GnRHa use in conjunction with stem cell transplantation may decrease gonadotoxicity and premature ovarian failure in patients with lymphoma, but is not shown to be effective in females with a leukemia diagnosis (Blumenfeld, Patel, Leiba, & Zuckerman, 2012).

Table 4. Hormone Suppression Evidence.

Theme Findings References (first author, year) Quality of Evidence
Outcomes Efficacy is not proven Loren, 2013; Coccia, 2012 Not applicable
No ovarian protection in patients with Hodgkin Lymphoma Behringer, 2010, Nitzschke, 2010 Very low – low
Ovarian protection only with less gonadotoxic treatment Huser, 2012 Low
Ovarian protection in women receiving treatment for Hodgkin lymphoma Falorio, 2008; Low
Decreased gonadotoxicity in patients undergoing stem cell transplant with lymphoma but not leukemia Blumenfeld, 2012 Low
Open in a new tab

Fertility Preservation Options for Females – Recommendations

Embryo/oocyte cryopreservation

The existing evidence for embryo/oocyte cryopreservation as a FP method is of moderate quality. There is a strong recommendation that embryo/oocyte cryopreservation should be offered to post-pubertal females at risk for infertility as a method of preserving fertility prior to cancer treatment.

Oophoropexy

There is a moderate quality of evidence available for oophoropexy in females receiving ovarian radiation exposure. There is a strong recommendation for the use of oophoropexy prior to radiation therapy in females who will receive ovarian radiation exposure.

Ovarian Tissue Cryopreservation

The evidence supporting ovarian tissue cryopreservation is of low quality. There is a weak recommendation that OTC, an experimental procedure, should be offered to pre and post-pubertal females as a fertility preservation method prior to treatment only as part of an IRB-approved protocol.

Hormone Suppression

There is a low quality and contradictory evidence regarding the use of hormone suppression as a FP option. Efficacy and endorsement by ASCO and ASRM is lacking. No recommendation is given regarding hormone suppression as a method of FP.

Fertility Preservation Options for Males-Pre and Post-pubertal

Sperm Banking via Masturbation

Obtaining semen for cryopreservation via masturbation is a common FP modality used for post-pubertal males undergoing treatment for cancer. The literature search yielded 28 original studies, including 16 descriptive studies, two case reports, and ten retrospective reviews that evaluated sperm banking via masturbation (Table 5). The studies indicated that post-pubertal males can effectively collect and freeze sperm via masturbation prior to starting treatment for cancer (Bahadur et al., 2002; Bashore, 2007; Chang, Chen, Chen, & Hsieh, 2006; Chong, Gupta, Punnett, & Nathan, 2010; Ginsberg et al., 2008; Hagenas et al., 2010; Kamischke, Jurgens, Hertle, Berdel, & Nieschlag, 2004; Menen et al., 2009; Mesenguer et al., 2006; Neal et al., 2007; Postovsky et al., 2003; van Casteren et al., 2008a; van Casteren, van Santbrink, van Inzen, Romijn, & Dohle, 2008b; van der Kaaij et al., 2009; Williams, Karpman, Sander, Spiess, Pisters & Lipshultz, 2009). The timing of the referral to bank sperm is critical, since there is often an urgency to start cancer treatment as soon as possible following a cancer diagnosis (Kamath et al., 2011), and sperm banking should be done prior to the initiation of any cancer treatment (Bahadur et al., 2005; Ligouri et al., 2008).

Table 5. Sperm Banking via Masturbation Evidence.
Theme Findings References (first author, year) Quality of Evidence
Collection feasibility 65-98% of pubertal males produced semen sample prior to cancer treatment ASRM, 2005; Bahadur, 2002; Bashore, 2007; Coccia, 2012; Hagenas, 2010; Kamischke, 2004; Loren, 2013; Menon, 2009; Meseguer, 2006; Postovsky, 2003; van Casteren, 2008a; van Casteren, 2008b Low – moderate
Semen collection Mean sperm count = 40-56mil/ml Median motility = 38-50% Chang, 2006; van Casteren, 2008b; van der Kaaiu, 2009; Williams, 2009 Low – moderate
Testicular volume correlates with sperm concentration and motility Hagenas, 2010 Moderate
Semen quality No difference in semen quality prior to cancer treatment based on oncology diagnosis Ginsberg, 2008; Menon, 2009; Meseguer, 2006 Low – moderate
Semen quality does differ prior to cancer treatment based on oncology diagnosis Bahadur, 2002; Chang, 2006; Neal, 2007; Postovsky, 2003 Low – moderate
Sperm banking discussions Sperm banking should occur prior initiation of cancer therapy Kamath, 2011; Bahadur, 2005; Ligouri, 2008; Nahata, 2013; Glaser, 2004; Magelssen, 2005 Very low – moderate
Majority of initial discussions occur with parents and adolescent together; many facilities use educational pamphlet Chong, 2010; Ginsberg, 2008 Low – moderate
Sperm banking outcomes Ability to sperm bank is comforting to patients Babb, 2012; Bonetti, 2009 Low – moderate
23-72% pregnancy success among use of banked sperm Babb, 2012; Bizet, 2012; Schmidt, 2004; van Casteren, 2008b Low – moderate
Open in a new tab

It is also important to consider the psychological stressors associated with being told about a new cancer diagnosis and that infertility is a potential late effect of cancer treatment. Findings from several studies support the importance of counseling patients regarding their risk for fertility issues and educating providers regarding potential fertility preservation options available (Nahata, Cohen, Lehmann, & Yu, 2013; Glaser, Phelan, Crawshaw, Jagdev, & Hale, 2004; Magelssen et al., 2005). Babb et al., 2012 indicate that fortunately, at many institutions, these conversations already take place and there is a high rate of discussion with newly diagnosed patients regarding infertility. Having the ability to bank sperm has been shown to be comforting to patients with cancer (Bonetti, Pasqualotto, Queiroz, Iaconell Jr., & Borges, 2009), and most importantly, survivors who banked sperm prior to treatment have successfully fathered children using the cryopreserved semen (Babb et al., 2012; Bizet et al., 2012; van Casteren et al., 2008a; van Casteren et al., 2008b; Schmidt, 2004). However, despite expert consensus endorsing sperm banking, as well as the relative ease and high success rates associated with sperm banking, the overall rate for referral and usage of assisted reproductive techniques in patients who cryopreserved sperm remains low (Chung et al., 2004; Ragni, 2003).

In addition, three clinical guidelines supported sperm banking as an established method of fertility preservation for post-pubertal males, and advised that sperm banking should be discussed with and offered to all post-pubertal males prior to receiving cancer treatment (Loren et al., 2013; ASRM, 2005; Coccia et al., 2012).

Sperm Banking Via Alternative Methods

Obtaining semen for cryopreservation via methods other than masturbation, such as urine collection after retrograde ejaculation, electro-ejaculation, and testicular sperm extraction (TESE), are options for post-pubertal males who are unable to ejaculate via masturbation. The evidence to support this intervention was of low quality according to the GRADE criteria. Three articles discussed this method (Table 6). Two studies were descriptive, one study was a retrospective review, and one guideline mentioned this method as a potential option. The studies showed that semen can be successfully collected and cryopreserved using alternative methods (Hagenas et al., 2010; van Casteren et al., 2008a; Glaser et al., 2004) and that these methods are available, accepted, and utilized at a number of pediatric treatment centers (Glaser, et al., 2004). One clinical guideline also recommended sperm banking via alternative methods such as electro-ejaculation and testicular sperm extraction for patients in whom ejaculation by masturbation is not possible (ASRM, 2005).

Table 6. Sperm Banking via Alternative Methods Evidence.

Theme Findings References (first author, year) Quality of Evidence
Feasibility Urine collection after retrograde ejaculation, electro-ejaculation, and testicular sperm extraction are options for post-pubertal males who are unable to ejaculate via masturbation Hagenas, 2010; van Casteren, 2008a; Glaser, 2004; ASRM, 2005 Low
Open in a new tab

Testicular Tissue Cryopreservation

Testicular tissue cryopreservation, an emerging fertility preservation method, is available for pre- and post-pubertal males. This is the only practical method for preserving sperm in pre-pubertal males, yet remains entirely experimental for this age group. This method involves surgically removing a small piece of testicular tissue, then cryopreserving and storing the specimen. In post-pubertal males, the tissue can be thawed and then mature sperm is extracted and used for in-vitro fertilization. However, the immature gametes in the testicular tissue from pre-pubertal males have yet to be matured for fertility preservation purposes (Keros et al., 2007). Similar to females, there may be a risk to re-seeding malignant cells if the malignant tissue is reimplanted (Babayev et al., 2013). Three articles discussed this method in the literature (Table 7). This procedure is feasible for tissue cryopreservation (Keros et al., 2007). This FP method can be bundled with another procedure such as a central line placement, and does not significantly increase operation or anesthesia time (Babayev et al., 2013). In addition, the testicular tissue cryopreservation is available at centers throughout the world (Glaser et al., 2004). There were three clinical guidelines that mention this method, and emphasize that it is currently experimental, but may be an alternative for fertility preservation for pre-pubertal males in the future (Loren et al., 2013; ASRM 2005; Coccia et al., 2012).

Table 7. Testicular Tissue Cryopreservation Evidence.

Theme Findings References (first author, year) Quality of Evidence
Feasibility No complications related to procedure and can be bundled with other surgical procedures Keros, 2007; Babayev, 2013 Low
Established for post-pubertal males but experimental for pre-pubertal males Loren, 2013; ASRM, 2005; Coccia, 2012 Not applicable
Malignancy risk Risk of reseeding malignant cells if malignant tissue is re-implanted Babayev, 2013 Low
Outcomes Sperm extraction from post-pubertal males' tissue but pre-pubertal males' tissue not yet used Glaser, 2004; Keros, 2007 Low – moderate
Open in a new tab

Fertility Preservation Options for Males – Recommendations

Sperm Banking

The evidence was of moderate quality, supporting sperm banking as a fertility preservation option for post-pubertal males. Thus, there is a strong recommendation that referral to a sperm bank and cryopreservation of semen obtained by masturbation should be offered to all post-pubertal adolescent and young adult males as a method of preserving fertility prior to cancer treatment.

Sperm Banking Via Alternative Methods

Obtaining sperm via alternative options is a feasible option to preserve fertility in post-pubertal males who are unable to masturbate prior to starting treatment for cancer. There is a strong recommendation that sperm banking via alternative methods be offered to post-pubertal males who are unable to sperm bank via masturbation prior to cancer therapy to preserve their fertility. Although the available evidence is of low quality, this FP method received a strong recommendation because the desirable effects clearly outweigh the undesirable effects (Guyatt et al., 2011).

Testicular Tissue Cryopreservation

Testicular tissue cryopreservation is an experimental option available for pre and post-pubertal boys to preserve fertility prior to cancer therapy. The overall evidence is very low quality. Because this method is relatively new with limited available data, there is a weak recommendation that testicular tissue cryopreservation, an experimental method to preserve fertility, should be offered to pre and post-pubertal males prior to starting cancer therapy. It should only be offered as part of an IRB-approved clinical trial.

Recommendations for Nursing Practice

Decisions regarding fertility preservation are highly personal and may be difficult to make at the time of cancer diagnosis. Families are faced with a number of concerns for the immediate and future health and well-being of the child. Nurses serve as both advocate and educator for families and the patient. Therefore, many families look to nurses for information regarding decisions such as fertility preservation.

The treatment team should be able to inform patient and families of the potential for infertility based upon treatment and the options available for FP prior to treatment. Quality improvement programs should be in place assuring that fertility preservation options are discussed with patients and their parents and appropriate fertility preservation options are made available prior to initiation of cancer treatment, according to patient and family preference.

Acknowledgments

Funding: Supported by the National Cancer Institute – Children's Oncology Group Chair's Grant (U10 CA180886) and Alex's Lemonade Stand Foundation.

Biographies

Alison Fernbach is a research nurse practitioner for the Center for Comprehensive wellness in Division of Pediatric Hematology/Oncology/Stem Cell Transplant at Columbia University Medical Center.

Barbara Lockart is a pediatric nurse practitioner for solid tumors and fertility preservation in Hematology/Oncology/Stem Cell Transplant at Ann & Robert H. Lurie Children's Hospital of Chicago.

Cheryl L. Armus is a nurse practitioner for the MACC Fund Center for Cancer and Blood Disorders located at Children's Hospital of Wisconsin through the Division of Pediatric Oncology at the Medical College of Wisconsin.

Lisa Bashore is a program manager and advanced practice nurse in the Life After Cancer Program at Cook Children's Medical Center in Fort Worth, Texas and is an associate professor at Texas Christian University.

Jennifer Levine is an attending physician and medical director of the Center for Comprehensive Wellness in the Division of Pediatric Hematology/Oncology/Stem Cell Transplant at Columbia University Medical Center.

Leah Kroon is a clinical nurse specialist for adolescent and young adult oncology patients in the Cancer and Blood Disorders Center at Seattle Children's Hospital.

Genevieve Sylvain is the nurse coordinator of the HOPE Survivorship Program and the Fertility Awareness and Education Program leader in the Center for Cancer and Blood Disorders at the Children's Hospital Colorado.

Cheryl Rodgers is an assistant professor at Duke University School of Nursing.

Footnotes

Declaration of Conflicting Interests: The authors have no potential conflicts of interest with this project or publication.

Contributor Information

Alison Fernbach, Columbia University Medical Center, 161 Fort Washington Ave, IP-7, New York, NY, 10023.

Barbara Lockart, Ann & Robert H. Lurie Children's Hospital, Box 30, 225 E Chicago Ave. Chicago IL 60611.

Cheryl L. Armus, MACC Fund Center for Cancer and Blood Disorders, Medical College of WI, 8701 Watertown Plank Road, Milwaukee, WI 53226.

Lisa Bashore, Life After Cancer Program, Cook Children's Medical Center, 801 7th Avenue, Fort Worth, TX 76104.

Jennifer Levine, Columbia University Medical Center, 161 Fort Washington Ave, IP-7, New York, NY, 10023.

Leah Kroon, Seattle Children's Hospital, 4800 Sand Point Way NE, M/S FA.7.228, Seattle, WA, 98122.

Genevieve Sylvain, Children's Hospital Colorado, 13123 E. 16th avenue, Aurora Colorado 80045.

Cheryl Rodgers, Duke University School of Nursing, 307 Trent Drive, Durham, NC, 27710.

References

  1. Agarwal SK, Change RJ. Fertility management for women with cancer. In: Woodruff TK, Snyder KA, editors. Oncofertility Fertility Preservation for Cancer Survivors. Chicago: Springer; 2007. pp. 15–27. [Google Scholar]
  2. American Society for Reproductive Medicine: Ethics Committee. Fertility preservation and reproduction in cancer patients. Fertility and Sterility. 2005;86(6):1622–1628. doi: 10.1016/j.fertnstert.2005.03.013. [DOI] [PubMed] [Google Scholar]
  3. American Society for Reproductive Medicine and Society for Assisted Reproductive Technology: Practice Committees. Mature oocyte cryopreservation: A guideline. Fertility and Sterility. 2013;99(1):37–43. doi: 10.1016/j.fertnstert.2012.09.028. [DOI] [PubMed] [Google Scholar]
  4. Andrews J, Guyatt G, Oxman A, Alderson P, Dahm P, Falck-Ytter Y, et al. Schunemann HJ. Grade guidelines: 14. Going from evidence to recommendations: the significance and presentation of recommendations. Journal of Clinical Epidemiology. 2013;66:719–725. doi: 10.1016/j.jclinepi.2012.03.013. [DOI] [PubMed] [Google Scholar]
  5. Babayev SN, Arslan E, Kogan S, Moy F, Oktay K. Evaluation of ovarian and testicular tissue cryopreservation in children undergoing gonadotoxic therapies. Journal of Assisted Reproduction and Genetics. 2013;30:3–9. doi: 10.1007/s10815-012-9909-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Babb A, Farah N, Lyons C, Lindsay K, Reddy N, Goldman J, et al. Salooja N. Uptake and outcome of assisted reproductive techniques in long-term survivors of SCT. Bone Marrow Transplantation. 2012;47:568–573. doi: 10.1038/bmt.2011.134. [DOI] [PubMed] [Google Scholar]
  7. Bahadur G, Ling KL, Hart R, Ralph D, Wafa R, Ashraf A, et al. Oyede A. Semen quality and cryopreservation in adolescent cancer patients. Human Reproduction. 2002;17(12):3157–3161. doi: 10.1093/humrep/17.12.3157. [DOI] [PubMed] [Google Scholar]
  8. Bahadur G, Ozturk O, Muneer A, Wafa R, Ashraf A, Jaman N, et al. Ralph DJ. Semen quality before and after gonadotoxic treatment. Human Reproduction. 2005;20(3):774–781. doi: 10.1093/humrep/deh671. [DOI] [PubMed] [Google Scholar]
  9. Bashore L. Semen preservation in male adolescents and young adults with cancer: one institution's experience. Clinical Journal of Oncology Nursing. 2007;11:381–386. doi: 10.1188/07.CJON.381-386. [DOI] [PubMed] [Google Scholar]
  10. Behringer K, Wildt L, Mueller H, Mattle V, Ganitis P, van den Hoonaard B, et al. Borchmann P on behalf of the German Hodgkin Study Group. No protection of the ovarian follicle pool with the use of GnRH-analogues or oral contraceptives in young women treated with escalated BEACOPP for advanced-stage Hodgkin lymphoma. Final results of a phase II trial from the German Hodgkin Study Group. Annals of Oncology. 2010;21:2052–2060. doi: 10.1093/annonc/mdq066. [DOI] [PubMed] [Google Scholar]
  11. Bizet P, Saïas-Magnan J, Jouve E, Grillo JM, Karsenty G, Metzler-Guillemain C, Perrin J. Sperm cryopreservation before cancer treatment: A 15-year monocentric experience. Reproductive Biomedicine Online. 2012;24(3):321–330. doi: 10.1016/j.rbmo.2011.11.015. [DOI] [PubMed] [Google Scholar]
  12. Blumenfeld Z, Patel B, Leiba R, Zuckerman T. Gonadotropin-releasing hormone agonist may minimize premature ovarian failure in young women undergoing autologous stem cell transplantation. Fertility and Sterility. 2012;98(5):1266–1270. doi: 10.1016/j.fertnstert.2012.07.1144. [DOI] [PubMed] [Google Scholar]
  13. Bonetti TCS, Pasqualotto FF, Queiroz P, Iaconell A, Jr, Borges E., Jr Sperm banking for male cancer patients: Social and semen profiles. International Brazilian Journal of Urology. 2009;35(2):190–198. doi: 10.1590/s1677-55382009000200009. [DOI] [PubMed] [Google Scholar]
  14. Chang HC, Chen SC, Chen J, Hsieh JT. Initial 10-year experience of sperm cryopreservation services for cancer patients. Journal of the Formosan Medical Association. 2006;105:1022–1026. doi: 10.1016/S0929-6646(09)60288-6. [DOI] [PubMed] [Google Scholar]
  15. Chen H, Li J, Cui T, Hu I. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women (review) The Cochrane Collaboration. 2011;11 doi: 10.1002/14651858.CD008018.pub2. [DOI] [PubMed] [Google Scholar]
  16. Chong AL, Gupta A, Punnett A, Nathan PC. A cross Canada survey of sperm banking practices in pediatric oncology centers. Pediatric Blood & Cancer. 2010;55:1356–1361. doi: 10.1002/pbc.22705. [DOI] [PubMed] [Google Scholar]
  17. Chung K, Irani J, Knee G, Efymow B, Blasco L, Patrizio P. Sperm cryopreservation for male patients with cancer: An epidemiological analysis at the University of Pennsylvania. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2004;113:S7–S11. doi: 10.1016/j.ejogrb.2003.11.024. [DOI] [PubMed] [Google Scholar]
  18. Cluzeau FA, Burgers JS, Brouwers M, Grol R, Mäkelä M, Littlejohns P, et al. Hunt C. Development and validation of an international appraisal instrument for assessing the quality of clinical practice guidelines: the AGREE project. Quality and Safety in Health Care. 2003;12(1):18–23. doi: 10.1136/qhc.12.1.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Coccia PF, Altman J, Bhatia S, Borenstein SC, Flynn J, George S, et al. Shead DA. Adolescent and young adult oncology. Journal of the National Comprehensive Cancer Network. 2012;10:1112–1150. doi: 10.6004/jnccn.2012.0117. [DOI] [PubMed] [Google Scholar]
  20. Demeestere I, Simon P, Emiliani S, Delbaere A, Englert Y. Fertility preservation: successful transplantation of cryopreserved ovarian tissue in a young patient previously treated for hodgkin's disease. The Oncologist. 2007;12:1437–1442. doi: 10.1634/theoncologist.12-12-1437. [DOI] [PubMed] [Google Scholar]
  21. Donnez J, Squifflet J, Van Eyck AS, Demylle D, Pascale J, Van Langendonckt A, Dolams MM. Restoration of ovarian function in orthotopically transplanted cryopreserved ovarian tissue: A pilot experience. Reproductive BioMedicine Online. 2008;16(5):694–704. doi: 10.1016/s1472-6483(10)60484-1. [DOI] [PubMed] [Google Scholar]
  22. Donnez J, Squifflet J, Jadoul P, Demylle D, Cheron A, Van Langendonckt A, Domans MM. Pregnancy and live birth after autotransplantation of frozen-thawed ovarian tissue in a patient with metastatic disease undergoing chemotherapy and hematopoietic stem cell transplantation. Fertility and Sterility. 2011;95(5):1787–1795. doi: 10.1016/j.fertnstert.2010.11.041. [DOI] [PubMed] [Google Scholar]
  23. Falorio S, Angrilli F, Fioritoni G. Gonadotropin-releasing hormone analog treatment for the prevention of treatment-related ovarian failure and infertility in women of reproductive age with Hodgkin lymphoma. Leukemia & Lymphoma. 2008;49(6):1087–1093. doi: 10.1080/10428190802035982. [DOI] [PubMed] [Google Scholar]
  24. Feigin E, Abir R, Fisch B, Kravarusic D, Steinberg R, Nitke S, et al. Freud E. Laparoscopic ovarian tissue preservation in young patients at risk for ovarian failure as a result of chemotherapy/irradiation for primary malignancy. Journal of Pediatric Surgery. 2007;42(5):862–864. doi: 10.1016/j.jpedsurg.2006.12.041. [DOI] [PubMed] [Google Scholar]
  25. Gareer W, Gad Z, Gareer H. Needle oophoropexy: a new simple technique for ovarian transposition prior to pelvic radiation. Surgical Endoscopy. 2011;25(7):2241–2246. doi: 10.1007/s00464-010-1541-9. [DOI] [PubMed] [Google Scholar]
  26. Ginsberg JP, Ogle SK, Tuchman LK, Carlson CA, Reilly MM, Hobbie WL, et al. Meadows AT. Sperm banking for adolescent and young adult cancer patients: Sperm quality, patient, and parent perspectives. Pediatric Blood & Cancer. 2008;50:594–598. doi: 10.1002/pbc.21257. [DOI] [PubMed] [Google Scholar]
  27. Glaser AW, Phelan L, Crawshaw M, Jagdev S, Hale J. Fertility preservation in adolescent males with cancer in the United Kingdom: A survey of practice. Archives in Diseases of Childhood. 2004;89:736–737. doi: 10.1136/adc.2003.042036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Gosiengfiao Y. Progress history and promise of ovarian cryopreservation and transplantation for pediatric cancer patients. In: Woodruff TK, Snyder KA, editors. Oncofertility, Fertility Preservation for Cancer Survivors. Chicago: Springer; 2007. pp. 130–134. [DOI] [PubMed] [Google Scholar]
  29. Gracia CR, Chang J, Kondapalli L, Prewitt M, Carlson CA, Mattel P, et al. Ginsberg JP. Ovarian tissues cryopreservation for fertility preservation in cancer patients: Successful establishment and feasibility of a multidisciplinary collaboration. Journal of Assisted Reproductive Genetics. 2012;29(6):495–502. doi: 10.1007/s10815-012-9753-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Gracia CR, Ginsberg JP. Fertility risk in pediatric and adolescent cancers. In: Woodruff TK, Snyder KA, editors. Oncofertility, Fertility Preservation for Cancer Survivors. Chicago: Springer; 2007. pp. 57–72. [DOI] [PubMed] [Google Scholar]
  31. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Robison L. Fertility of male survivors of childhood cancer: A report from the childhood cancer survivor study. Journal of Clinical Oncology. 2010;28(2):332–339. doi: 10.1200/JCO.2009.24.9037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, et al. Robison L. Fertility of female survivors of childhood cancer: A report from the Childhood Cancer Survivor Study. Journal of Clinical Oncology. 2009;27(16):2677–2685. doi: 10.1200/JCO.2008.20.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. Schunemann HJ. GRADE guidelines: 1. Introduction – GRADE evidence profiles and summary of findings table. Journal of Clinical Epidemiology. 2011;64:383–394. doi: 10.1016/j.jclinepi.2010.04.026. [DOI] [PubMed] [Google Scholar]
  34. Hagenas I, Jorgensen NJ, Rechnitzer C, Sommer P, Holm M, Schmiegelow K, et al. Juul A. Clinical and biochemical correlates of successful semen collection for cryopreservation from 12-18-year-old patients: A single-center study of 86 adolescents. Human Reproduction. 2010;25(8):2031–2038. doi: 10.1093/humrep/deq147. [DOI] [PubMed] [Google Scholar]
  35. Huang JY, Tulandi T, Holzer H, Tan S, Ri-Cheng C. Combining ovarian tissue cryobanking with retrieval of immature oocytes followed by in vitro maturation and vitrification: an additional strategy of fertility preservation. Fertility and Sterility. 2008;89(3):567–572. doi: 10.1016/j.fertnstert.2007.03.090. [DOI] [PubMed] [Google Scholar]
  36. Huser M, Zakova J, Smardova L, Crha I, Janku P, Hudecek R, Ventruba P. Combination of fertility preservation strategies in young women with recently diagnosed cancer. European Journal of Gynaecological Oncology. 2012;33(1):42–50. [PubMed] [Google Scholar]
  37. Kamath SM, Londhe V, Muthukumar K, George K. Fertility preservation: A case series. International Journal of Infertility and Fetal Medicine. 2011;2(3):114–117. [Google Scholar]
  38. Kamischke A, Jurgens H, Hertle L, Berdel WE, Nieschlag E. Cryopreservation of sperm from adolescents and adults with malignancies. Journal of Andrology. 2004;25(4):586–592. doi: 10.1002/j.1939-4640.2004.tb02829.x. [DOI] [PubMed] [Google Scholar]
  39. Kelly KP, Hooke MC, Ruccione K, Landier W, Haase J. Developing an organizing framework to guide nursing research in the Children's Oncology Group (COG) Seminars in Oncology Nursing. 2013 doi: 10.1016/j.soncn.2013.12.004. In press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Keros V, Hultenby K, Borgstrom B, Fridstrom M, Jahnukainen K, Hovatta O. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Human Reproduction. 2007;22(5):1384–1395. doi: 10.1093/humrep/del508. [DOI] [PubMed] [Google Scholar]
  41. Kung FT, Chen BH, Huang HC, Ho JT, Cheng B. Preservation of ovarian germinal follicles by temporary laparoscopic ovarian transposition in teenaged girls undergoing craniospinal irradiation for radiosensitive central nervous system tumors. Taiwanese Journal of Obstetrics and Gynecology. 2008;47(3):2458–2465. doi: 10.1016/S1028-4559(08)60128-X. [DOI] [PubMed] [Google Scholar]
  42. Landier W, Leonard M, Ruccione KS. Children's Oncology Group's 2013 blueprint for research: nursing discipline. Pediatric Blood & Cancer. 2013;60(6):1031–1036. doi: 10.1002/pbc.24415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lee D. Ovarian tissue cryopreservation and transplantation: banking reproductive potential for the future. In: Woodruff TK, Snyder KA, editors. Oncofertility, Fertility Preservation for Cancer Survivors. Chicago: Springer; 2007. pp. 110–129. [DOI] [PubMed] [Google Scholar]
  44. Levine J, Canada A, Stern CJ. Fertility preservation in adolescents and young adults with cancer. Journal of Clinical Oncology. 2010;28(32):4831–41. doi: 10.1200/JCO.2009.22.8312. [DOI] [PubMed] [Google Scholar]
  45. Liguori G, Trombetta C, Bucci S, Benvenuto S, Amodeo A, Ocello G, Belgrano E. Semen quality before and after orchiectomy in men with testicular cancer. Archivio Italiano di Urologia e Andrologia. 2008;80(3):99–102. [PubMed] [Google Scholar]
  46. Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge A, et al. Oktay K. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. Journal of Clinical Oncology. 2013;31(19):2500–2510. doi: 10.1200/JCO.2013.49.2678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Magelssen H, Haugen TB, Von During V, Melve KK, Sandstad B, Fossa SD. Twenty years experience with semen cryopreservation in testicular cancer patients: Who needs it? European Urology. 2005;48:779–785. doi: 10.1016/j.eururo.2005.05.002. [DOI] [PubMed] [Google Scholar]
  48. Meirow D, Baum M, Yaron R, Levron J, Hardan I, Schiff E, et al. Dor J. Ovarian tissue cryopreservation in hematologic malignancy: Ten years' experience. Leukemia & Lymphoma. 2007;48(8):1569–1576. doi: 10.1080/10428190701471957. [DOI] [PubMed] [Google Scholar]
  49. Menon S, Rives D, Mousset-Simeon N, Silbert L, Vanier JP, Mazurier S, et al. Mace B. Fertility preservation in adolescent males: Experience over 22 years at Rouen University Hospital. Human Reproduction. 2009;24(1):37–44. doi: 10.1093/humrep/den361. [DOI] [PubMed] [Google Scholar]
  50. Melynk BM, Fineout-Overholt E. Evidence-Based Practice in Nursing & Healthcare. 2nd. Philadelphia, PA: Lippincott Williams & Wilkins; 2011. [Google Scholar]
  51. Meseguer M, Molina N, García-Velasco JA, Remohí J, Pellicer A, Garrido N. Sperm cryopreservation in oncological patients: A 14-year follow-up study. Fertility and Sterility. 2006;85(3):641–645. doi: 10.1016/j.fertnstert.2005.08.022. [DOI] [PubMed] [Google Scholar]
  52. Nahata L, Cohen LE, Lehmann LE, Yu RN. Semen analysis in adolescent cancer patients prior to bone marrow transplantation: When is it too late for fertility preservation? Pediatric Blood & Cancer. 2013;60:129–132. doi: 10.1002/pbc.24172. [DOI] [PubMed] [Google Scholar]
  53. Neal MS, Nagel K, Duckworth J, Bissessar H, Fischer MA, Portwine C, et al. Barr R. Effectiveness of sperm banking in adolescents and young adults with cancer: A regional experience. Cancer. 2007;110(5):1125–1129. doi: 10.1002/cncr.22889. [DOI] [PubMed] [Google Scholar]
  54. Nitzschke M, Raddatz J, Bohlmann MK, Stute P, Strowitzki T, von Wolff M. GnRH analogs do not protect ovaries form chemotherapy-induced ultrastructural injury in Hodgkin's lymphoma patients. Gynecologic Oncology. 2010;282:83–88. doi: 10.1007/s00404-009-1308-5. [DOI] [PubMed] [Google Scholar]
  55. Postovsky S, Lightman A, Aminpour D, Elhasid R, Peretz M, Ben Arush MW. Sperm cryopreservation in adolescents with newly diagnosed cancer. Medical Pediatric Oncology. 2003;40:355–359. doi: 10.1002/mpo.10294. [DOI] [PubMed] [Google Scholar]
  56. Ragni G, Somigliana E, Restelli L, Salvi R, Arnoldi M, Paffoni A. Sperm banking and rate of assisted reproduction treatment: Insights from a 15-year cryopreservation program for male cancer patients. Cancer. 2003;97(7):1624–1629. doi: 10.1002/cncr.11229. [DOI] [PubMed] [Google Scholar]
  57. Reichman DE, Davis OK, Zaninovic N, Rosenwaks Z. Fertility preservation using controlled ovarian hyperstimulation and oocyte cryopreservation in a premenarcheal female with myelodysplastic syndrome. Fertility and Sterility. 2012;98(5):1225–1228. doi: 10.1016/j.fertnstert.2012.07.1056. [DOI] [PubMed] [Google Scholar]
  58. Revel A, Revel-Vilk S, Aizenman E, Porat-Katz A, Safran A, Ben-meir A, et al. Laufer N. At what age can human oocytes be obtained? Fertility and Sterility. 2009;92(2):458–463. doi: 10.1016/j.fertnstert.2008.07.013. [DOI] [PubMed] [Google Scholar]
  59. Rosendahl M, Andersen MT, Ralfkiaer E, Kjeldsen L, Andersen MK, Andersen CY. Evidence of residual disease in cryopreserved ovarian cortex from female patients with leukemia. Fertility and Sterility. 2010;94(6):2186–2190. doi: 10.1016/j.fertnstert.2009.11.032. [DOI] [PubMed] [Google Scholar]
  60. Rosendahl M, Anderson CY, Ernst E, Westergaard LG, Rasmussen PE, Loft A, Anderson AN. Ovarian function after removal of an entire ovary for cryopreservation of pieces of cortex prior to gonadotoxic treatment: a follow-up study. Human Reproduction. 2008;23:2475–2483. doi: 10.1093/humrep/den248. [DOI] [PubMed] [Google Scholar]
  61. Rossi BV, Ashby RK, Srouji SS. Embryo banking between induction and consolidation chemotherapy in women with leukemia. Fertility and Sterility. 2011;96(6):1412–1414. doi: 10.1016/j.fertnstert.2011.09.038. [DOI] [PubMed] [Google Scholar]
  62. Saito K, Suzuki K, Iwasaki A, Yumura Y, Kubota Y. Sperm cryopreservation before cancer chemotherapy helps in the emotional battle against cancer. Cancer. 2005;104(3):521–4. doi: 10.1002/cncr.21185. [DOI] [PubMed] [Google Scholar]
  63. Schmidt KL, Larsen E, Bangsboll S, Meinertz H, Carlsen E, Andersen AN. Assisted reproduction in male cancer survivors: Fertility treatment and outcome in 67 couples. Human Reproduction. 2004;19:2806–2810. doi: 10.1093/humrep/deh518. [DOI] [PubMed] [Google Scholar]
  64. Schover LR. Patient attitudes toward fertility preservation. Pediatric Blood & Cancer. 2009;53(2):281–4. doi: 10.1002/pbc.22001. [DOI] [PubMed] [Google Scholar]
  65. Seshadri T, Good D, Lade S, Spencer A, Grigg A, Tiedemann K, et al. Seymour JF. Lack of evidence of disease contamination in ovarian tissue lymphoma and analysis of factors predictive of oocyte yield. British Journal of Cancer. 2006;94:1007–1010. doi: 10.1038/sj.bjc.6603050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Terenziani M, Piva L, Meazza C, Gandola L, Cefalo G, Merola M. Oophoropexy: a relevant role in preservation of ovarian function after pelvic radiation. Fertility and Sterility. 2009;91(3):e15–e16. doi: 10.1016/j.fertnstert.2008.09.029. [DOI] [PubMed] [Google Scholar]
  67. van Casteren NJ, Dohle GR, Romijn JC, de Muinck Keizer Schrama SM, Weber RF, van den Heuvel-Eibrink MM. Semen cryopreservation in pubertal boys before gonadotoxic treatment and the role of endocrinologic evaluation in predicting sperm yield. Fertility and Sterility. 2008a;90(4):119–1125. doi: 10.1016/j.fertnstert.2007.08.006. [DOI] [PubMed] [Google Scholar]
  68. van Casteren NJ, van Santbrink EJ, van Inzen W, Romijn JC, Dohle GR. Use rate and assisted reproduction technologies outcome of cryopreserved semen from 629 cancer patients. Fertility and Sterility. 2008b;90(6):2245–2250. doi: 10.1016/j.fertnstert.2007.10.055. [DOI] [PubMed] [Google Scholar]
  69. van der Kaaij MA, Heutte N, van Echten-Arends J, Raemaekers JM, Carde P, Noordijk EM, et al. Kluin-Nelemans HC. Sperm quality before treatment in patients with early stage Hodgkin's lymphoma enrolled in EORTC-GELA Lymphoma Group trials. Haematologica. 2009;94(12):1691–1697. doi: 10.3324/haematol.2009.009696. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wallace WH. Oncofertility and preservation of reproductive capacity in children/young adults. Cancer. 2011;117(supp 10):2301–2310. doi: 10.1002/cncr.26045. [DOI] [PubMed] [Google Scholar]
  71. Williams DH, 4th, Karpman E, Sander JC, Spiess PE, Pisters LL, Lipshultz LI. Pretreatment semen parameters in men with cancer. Journal of Urology. 2009;181(2):736–740. doi: 10.1016/j.juro.2008.10.023. [DOI] [PubMed] [Google Scholar]

RESOURCES