Effectiveness of Sperm Banking in Adolescentsand Young Adults With CancerA Regional Experience

Michael S. Neal, MSc, PhD1

Kim Nagel, RN, BHSc (N), CCRA2

JoAnn Duckworth, RN2

Haimant Bissessar, BSc1

Marc A. Fischer, MD1

Carol Portwine, MD, PhD2

Richard Tozer, MD, PhD3

Ronald D. Barr, MB, ChB, MD2

1 Center for Reproductive Care, Hamilton, Ontario,Canada.

2 McMaster Children’s Hospital, Hamilton, Ontario,Canada.

3 Juravinski Cancer Center, Hamilton HealthSciences, Hamilton, Ontario, Canada.

BACKGROUND. Improving success in the treatment of cancer has resulted in an

increasing number of survivors. An important quality of life issue among younger

survivors is the ability to have a family. Current gonadotoxic treatments for can-

cer pose a challenge to future fertility. Preservation of fertility after gonadotoxic

therapy is an important consideration for these patients. In a regional center, the

authors evaluated efficacy and utilization of sperm banking for preservation of

male fertility in adolescents and young adults (AYA) with cancer.

METHODS. A retrospective chart review was conducted to obtain data on clinical

features, andrology, and fertility from patients (ages < 30 years) who cryopre-

served samples of semen from 1995–2005.

RESULTS. Of 821 newly diagnosed male AYA cancer patients, aged 14–30 years,

only 146 (17.8%) used sperm cryopreservation technology. Patients who used

their cryopreserved semen for attempted conception had a 36.4% success rate

with intrauterine insemination (IUI) and a 50.0% clinical pregnancy rate with in

vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).

CONCLUSIONS. Sperm cryopreservation by AYA males with cancer is an effica-

cious method for preserving future fertility. Awareness and employment of

assisted reproductive technologies needs to be implemented by an interdisciplin-

ary team of experts caring for these patients and can result in successful pater-

nity in males after treatment for cancer. Cancer 2007;110:1125–8. � 2007

American Cancer Society.

KEYWORDS: sperm preservation, adolescent, neoplasm, fertility.

C ancer in adolescents and young adults (AYA) is a unique distri-

bution of diseases with increasing incidence during the past

quarter century.1 AYA in the age group 15–29 years have a higher

risk than children (<15 years of age) of developing cancer, with the

risk directly proportional to age.1 Although cancer in these young

people is still life threatening, 5-year overall survival rates exceed

70% for both children and AYA.2 However, altered testicular function

and subsequent compromised fertility may occur with current can-

cer treatment regimens. This has contributed to a heightened

awareness of quality-of-life issues in survivors of cancer that

occurred early in life.

In AYA male cancer patients, surgery, radiation, and chemotherapy

can precipitate transient or permanent infertility by affecting either

ejaculatory or erectile function or by impairing spermatogenesis.3 Can-

cer that occurs between the ages of 15 and 30 years is 2.7 times more

common than cancer that occurs in the first 15 years of life.4 In this age

group, the incidence has increased steadily during the last 25 years.4

Address for reprints: Michael S. Neal, MSc, PhD,Centre for Reproductive Care, West End Clinic,Hamilton Health Sciences, 690 Main Street West,Hamilton, Ontario, Canada L8S 1A4; Fax: (905)521-2609; E-mail: nealm@hhsc.ca

Received March 5, 2007; revision received May9, 2007; accepted May 9, 2007.

ª 2007 American Cancer SocietyDOI 10.1002/cncr.22889Published online 23 July 2007 in Wiley InterScience (www.interscience.wiley.com).

1125

For these young men, an important question, beyond

conquering their disease, is how the malignancy or its

treatment will affect future fertility. One approach to

this challenge is to bank sample(s) of semen before

treatment. It is well established that the duration of sto-

rage of cryopreserved sperm does not impact fertility

outcome.5,6 Depending on the number and quality of

cryopreserved sperm, conception can be attempted by

thawing the sample and using it for intrauterine insem-

ination (IUI). Alternatively, patients with compromised

seminal quality, due to systemic effects of disease or

treatment, may opt for more advanced techniques such

as in vitro fertilization (IVF) with or without intracyto-

plasmic sperm injection (ICSI).

The utilization patterns of cryopreserved sperm,

and pregnancy outcomes when these sperm are

employed with IUI and IVF, are uncertain. The cur-

rent study evaluated the use of sperm banking over a

10-year period (1995–2005) in a single regional center

in Canada.

METHODSThe Research Ethics Board of McMaster University

and Hamilton Health Sciences provided approval to

conduct this study. Patients’ records were reviewed

for data on clinical features, andrology, and fertility.

All males �30 years old with cancers who had

banked their sperm between 1995 and 2005 were

included in the study. Patients were separated into 2

groups, based on age (Group A, �18 and Group B

between 18 and 30 years of age at the time of sperm

banking) for comparison. Clinical data retrieved from

the archived chart included age at diagnosis, type of

cancer, modalities of therapy, and outcome. A rou-

tine analysis of semen, based on World Health Orga-

nization (WHO) guidelines,7 was performed on each

sample before cryopreservation. Briefly, the seminal

analysis included volume, pH, viscosity, sperm con-

centration, motility, viability, and morphology. The

sample was considered normal if it met or exceeded

the 3 standard benchmark values for concentration,

motility, and strict morphology.7 After obtaining

informed consent, we froze samples according to a

standard sperm cryopreservation protocol and stored

them in liquid nitrogen. Any sample containing

sperm in the ejaculate was banked after informed

consent was obtained, because only a few sperm are

required for IVF with ICSI.

A subgroup of patients who used their samples

for assisted conception was analyzed for IUI or IVF

outcomes including number of oocytes retrieved, fer-

tilization success, embryo development and quality,

number of embryos transferred and frozen, and

implantation and pregnancy rates. The number of

normally fertilized oocytes (based on the presence of

2 pronulcei, 16–18 hours after the ICSI procedure) di-

vided by the number of oocytes injected determined

the fertilization rate. Embryo quality was quantified

by a cumulative embryo score (CES). CES was calcu-

lated as the product of blastomere number and

embryo grade. The grade assigned is based on the

degree of cellular fragmentation (descending scale of

5 to 1) observed at the 48-hour and 72-hour time-

periods of assessment. Higher CES indicates a better

morphological appearance of the embryo.8 Implanta-

tion rate was calculated by the number of fetal sacs

present at ultrasound divided by the number of

embryos transferred. Patients were considered preg-

nant when they had a positive bhCG result 17 days

after IUI or 14 days after embryo transfer, and clini-

cal pregnancy was determined by ultrasound at 6–

7 weeks of gestation.

RESULTSFrom 1995 to 2005, there were 821 newly diagnosed

male AYA patients with cancer, aged 14–30 years. Of

these, 146 (17.8%) banked semen at our facility.

Thirty-four (23.3%) of these patients were pediatric

(�18 years of age, Group A), and 112 (76.7%) were

between 18 and 30 years of age (Group B) at the

time of banking. The most common cancer diagnosis

was Hodgkin lymphoma (37.5%) for Group A and

testicular cancer (43.9%) for Group B (Fig. 1). Overall,

21.1% of patients presented with a normal semen

analysis at the time of banking. Of the pediatric

group, only 9.4% had a normal semen analysis com-

pared with 25.6% of the adult population. Volume

and concentration were not affected by the cancer

diagnosis, but reduced motility and strict morphol-

ogy appear to be the main reasons for abnormal

semen analysis (Table 1). One-third of the non-

Hodgkin lymphoma patients in Group A and half of

Hodgkin lymphoma patients in Group B had a nor-

mal seminal analysis at the time of banking (Fig. 2).

Although the sample size is small, none of the

patients diagnosed with a brain tumor had a normal

seminal analysis in either age category; the same

being true for those with a diagnosis of leukemia or

testicular cancer in Group A (Fig. 2). Despite this,

banking was undertaken, as there was adequate

sperm for a future IVF attempt with ICSI.

The majority (103, 70.5%) of sperm samples are

still being maintained in storage for future use, and

22 (15.1%) samples have been purged (10 due to

death, 12 voluntarily). There have been 21 (14.4%)

patients who have used their banked samples to

1126 CANCER September 1, 2007 / Volume 110 / Number 5

attempt conception by assisted reproductive technol-

ogies. Eleven of these patients used their samples for

IUI (range, 1 to 8 cycles per patient). Four (36.4%)

patients achieved a successful pregnancy with their

partners.

The samples from the remaining 10 patients

were used for IVF with ICSI, and the stimulation and

IVF outcome measures are summarized in Table 2.

These outcome performance measures are equal to

or better than those of other couples without cancer,

cycling during the same time period in our clinic,

and for those reported in literature.9 Two couples did

not have embryos available for transfer on Day 3.

The women were 38 and 42 years of age. Advanced

maternal age may be an important factor that contri-

butes to poor embryo development and outcome.

Seventy percent (7 of 10) of couples were successful

at initiating a pregnancy (based on a positive bhCG14 days after embryo transfer) after IVF with ICSI by

using their frozen-thawed sperm samples. One of

these conceptions was a biochemical pregnancy;

another resulted in a miscarriage at 6 weeks of preg-

nancy; and the 5 remaining are ongoing or delivered,

for a clinical pregnancy rate of 50% (5 of 10).

DISCUSSIONWhen adolescents and young adults (AYA) are diag-

nosed with cancer, every aspect of their lives is influ-

enced. This includes their physical, emotional,

economic, spiritual, interpersonal, psychosocial, and

sexual well-being.10,11 In clinical practice and qual-

ity-of-life research, sexual, interpersonal, and repro-

ductive late effects of treatment may not be

addressed adequately.10 Although cancer in AYA

remains relatively rare, it has been suggested that

better services for these young people are needed. To

afford them the opportunity to have a family (in the

FIGURE 1. Proportion of sperm samples banked by type of cancer includ-ing brain tumors (n 5 5, 4.4%); Hodgkin lymphoma (n 5 30, 26.3%); leuke-

mias (n 5 11, 9.7%); testicular cancer (n 5 40, 35.1%); Ewing sarcoma

and other solid tumors (n 5 8, 7.0%); non-Hodgkin lymphoma (n 5 11,

9.7%) and other cancer diagnosis (n 5 9, 7.9%). Gray bar represents Group

A (<18 years of age, n 5 34), and white bar represents Group B (>18

years of age, n 5 112).

TABLE 1Semen Analysis Parameters for Each Cancer Diagnosis Category

Cancer

Diagnosis

Volume,

mL

Concentration,*

million/mL

Motility,*

%

Strict

Morphology,* %

Brain tumors 3.6 � 1.0 223.4 � 162.0 41.0 � 10.0 2.0 � 1.0

Hodgkin lymphoma 2.2 � 0.3 79.5 � 15.5 48.0 � 4.0 3.0 � 1.0

Leukemias 1.4 � 0.3 46.0 � 28.3 44.0 � 7.0 3.0 � 1.0

Testicular cancers 3.0 � 0.3 38.4 � 5.1 60.0 � 3.0 4.0 � 0.0

Ewing sarcoma/

Other solid tumors 2.9 � 1.0 141.1 � 49.2 53.0 � 7.0 12.0 � 8.0

Non-Hodgkin

lymphoma 2.6 � 0.3 61.2 � 30.1 50.0 � 7.0 5.0 � 1.0

Other 2.5 � 0.9 39.5 � 28.4 32.0 � 7.0 1.0 � 0.0

Values are expressed as mean � standard error of the mean.

* Normal ranges based on WHO criteria are: > 20 million sperm/mL for concentration; > 50% motil-

ity; and > 4.0% strict morphology.7

FIGURE 2. Proportion of patients with a normal semen analysis by type ofcancer including brain tumors (n 5 0, 0.0%); Hodgkin lymphoma (n 5 10,

33.3%); leukemias (n 5 1, 9.1%); testicular cancer (n 5 9, 22.5%); Ewing

sarcoma and other solid tumors (n 5 2, 25.0%); non-Hodgkin lymphoma

(n 5 2, 18.2%) and other cancer diagnoses (n 5 0, 0.0%). Gray bar repre-

sents Group A (<18 years of age; n 5 34), and white bar represents Group

B (>18 years of age; n 5 112).

Sperm Banking for AYA Cancer Patients/Neal et al. 1127

future), after overcoming the challenge of a life-

threatening disease, would be one such service.

Because this study was a retrospective chart review,

we were unable to determine the reason behind the

low proportion of patients who banked sperm sam-

ples. However, it is evident that better education is

required for both patients and professional health

staff. Educational material should be developed spe-

cifically for AYA patients to encourage appropriate

discussion with their healthcare providers before

treatment in an effort to improve referral to a local

fertility program.

Cryopreservation of semen is an acceptable

method for fertility preservation in postpubertal males

who are about to undergo cancer therapy.12 The high

frequency of abnormal samples of sperm in this study

is unexplained, although such findings are well

described in young men with Hodgkin lymphoma

and testicular tumors before therapy.13 Newer techni-

ques for harvesting mature sperm cells for assisted

reproductive technology, such as microsurgical epi-

didymal sperm aspirations (MESA), testicular sperm

extraction (TESE), and microscopic testicular sperm

extraction (mTESE), have been implemented in cases

of obstructive and nonobstructive azoospermia,

respectively.14 Fertility-sparing measures in prepuber-

tal boys, however, still require much more research,

and the ability to preserve or restore natural fertility

in older adult cancer patients is also desirable.15

Approximately 15% to 30% of male cancer survi-

vors of reproductive age are permanently sterile after

treatment.16 Among patients in whom spermatogen-

esis recovers after treatment, the integrity of the

sperm DNA may impair future fertility. The introduc-

tion of semen cryopreservation has changed repro-

ductive prospects for AYA men who are treated for

cancer.16 Furthermore, advanced assisted reproduc-

tive technologies, such as IVF with ICSI, allow crea-

tion of in vitro embryos with only a few normal

sperm. However, because IVF and ICSI procedures

bypass natural biological control mechanisms asso-

ciated with fertilization and have been used clinically

for little more than a decade, the long-term health

implications for these offspring are unknown, espe-

cially when sperm is collected after chemotherapy

and radiotherapy. Whereas animal studies focus on

acute gonadotoxicity,17 few studies address the ques-

tion of human sperm DNA integrity in relation to

anticancer therapy.18 A recent case-control study by

Thomson et al. showed no difference in sperm DNA

integrity between sperm samples from men who

were childhood cancer survivors and age-matched

controls.19 However, because this study had a small

sample size, further investigation into the DNA frag-

mentation of sperm after potentially gonadotoxic

chemotherapy treatment is necessary. This under-

lines the importance of banking samples of semen

before fertility-damaging treatment. Moreover, the

results of this study clearly demonstrate that sperm

banking provides an excellent opportunity for

patients to father children of their own with the help

of assisted reproductive technologies.

Young adult males may be more able to accept

the idea of sperm banking, as it may preserve their

reproductive capacity in the future, whereas adoles-

cents may be more intimidated and embarrassed by

this concept.20 In a 1996 study by Kleish et al., it was

found that adolescent males, ranging in age from 14

to 17 years, were eligible for sperm banking.21 More-

over, the study by Kleish et al., found that sperm

concentration, motility, and morphology were similar

in adolescent and adult patients, thus supporting the

position that cryopreservation of semen is an option

for young male patients with cancer. In addition to

this, the American Society of Clinical Oncology

recently published recommendations on fertility

preservation in cancer patients that highlighted the

finding that more education is required to encourage

increased use of fertility preservation methods in

young cancer patients.22 Our study confirms that

sperm banking is an efficacious, but underused,

option for young men who are about to undergo

gonadotoxic treatment for malignant disease. The

use of fertility-preserving options, as part of the

treatment protocol for AYA males with cancer,

TABLE 2Information on Women Using Their Partners’ Banked Sperm for IVF

Description Mean (SEM) Range

Women’s age, y 32.6 (1.4) 28–42

*E2 at hCG, pmol/L 8614.9 (790.1) 4275.0–11122.0

No. oocytes retrieved 12.0 (2.0) 4–20

Fertilization rate, % 72.5 (7.0) 20.0–88.9yCES at 48 h 11.6 (1.5) 2.0–16.4yCES at 72 h 24.9 (3.7) 26.5–40.0yCES at embryo transfer 28.1 (5.6) 32.0–48.0

No. of embryos transferred 1.8 (0.3) 0–3.0

No. embryos frozen 3.1 (1.0) 0–10.0

Implantation rate, % 60.4 (16.0) 0–100.0{Pregnancy rate 1bhCG, % 70.0 NA§Clinical pregnancy rate, % 50.0 NA

IVF indicates in vitro fertilization; SEM, standard error of the mean; NA, not available.

* E2, estradiol measured at the time of hCG is a measure of the ovarian response to controlled ovar-

ian hyperstimulation.y CES, cumulative embryo score.{ a bhCG value greater than 10 IU/L indicated a positive pregnancy test.§ Clinical pregnancy rate was based on the presence of a fetal heart beat at the time of ultrasound

at 6.5 weeks of gestation.

1128 CANCER September 1, 2007 / Volume 110 / Number 5

requires expertise and cooperation among a multidis-

ciplinary team of experts that includes oncologists,

nurses, urologists, andrologists, and those specializing

in reproductive medicine.

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