For men

Preserving fertility before cancertreatment
For young men with cancer
who wish to have children in the futureWhat is fertility?
Fertility is defined as "the ability to reproduce".
Cancer treatment may affect your reproductivefunctions, but there are many fertility preservation
options available.

Table of contents
Introduction

1

Cancer treatment and fertility preservation2

How cancer treatment affects testicular functions

4

Fertility preservation options

6

Fertility after cancer treatment

7

Family planning after cancer treatment

8

Flow chart for fertility preservation options

9

Resources10Costs for fertility preservation

10Questions you should ask your oncologist

111

Introduction
Recent advances in cancer treatment have aided many in overcoming cancer.
Yet, despite these advances, some treatments can cause damage to testes andspermatogonia, which may lead to reduced sperm production or infertility.
This brochure will assist young male patients in making informed decisions
about their fertilitypreservation options.

Fertility Preservation Checklist
1. I understand the process and prospects of my cancer treatment, andhow they may affect my fertility.
2. I understand my fertility preservation options and what they involve.
3. I understand the commitment and costs of fertility preservation, as
well as its potential effect on my cancer treatment.
4. I should consult my oncologist and reproductive endocronologist
about my fertility preservation options.
5. I understand that fertility preservation does not guarantee futurefertility.

It is important to discuss all of these points with your partner, family, and any others
who may be affected by your decision.

2

Cancer treatment and fsertility preservation
The balance between cancer treatment and fertility preservation
Starting an appropriate cancer treatment regimen is of utmost importance.
Although fertility preservation may be an important consideration, proper
cancer treatment should be prioritized over family planning. If time allows,
effort should be made to consult with one’s partner, family, oncologist andreproductive endocrinologist so as to make an informed decision about fertility
prior to undergoing cancer treatment.

When should I start fertility preservation treatment?
You should first discuss your fertility preservation options with your doctor tounderstand both the merits and disadvantages of all preservation options. As
preservation treatments must be performed before cancer treatment can proceed,
it is sometimes necessary to adjust the treatment schedule if this is a possibility.

3How cancer treatment affects
testicular functions
Effects of chemotherapy and molecular targeted drugs
For males, gonadal dysfunction can occur due to direct toxic effects ofchemotherapy and radiation therapy on spermatogonia, the primordial germ cells
that mature into sperm during spermatogenesis. Some kinds of chemotherapy,
radiation therapy, and surgery can cause damage to the testes and spermatogonia
and reduce or stop sperm production.
Effects of chemotherapy on sperm production
Risk

Cancer treatment
Any alkylating agent + TBI
Any alkylating agent + pelvic radiation,or testicular radiation

High Risk

Cyclophosphamide >7.5 g/m 2
MOPP >3 cycles, BeACOPP >6 cycles
Protocols containing Temozolomide
BCNU ＋ Cranial/ brain radiation
Protocol containing cisplatinIntermediate Risk

BEP x 2-4 cycles
Cumulative cisplatin dose <400 mg/m 2
Cumulative carboplatin dose ≤2g/m2
ABVD, CHOP, COP

Low RiskCombination chemotherapy for leukemia
Anthracycline + cytarabine

Very Low/ No Risk

Unknown

Vincristine

Monoclonal antibody
Tyrosine kinase inhibitor

Endocrine treatment for prostate cancer may affect sperm production. While there
are reports suggesting some molecular targeted drugs may not affect male gonadal
function, the influence of molecular targeted drug on sperm production is uncertain.
4

Effects of radiation therapy
Spermatogonia are extremely sensitive to radiation. Radiation therapy can lower
sperm production when it is targeted towards the testicles, pelvis, pituitary gland,and brain, as can total body irradiation (TBI).
Effects of radiation therapy on sperm production
Risk

Cancer treatment
TBI before stem cell transplantation

High Risk>2.5Gy in men>6Gy in boys
Cranial radiation ≥40 Gy
Testicular radiation dose 1-6 Gy

Intermediate Risk

(due to scatter from abdominal/pelvic radiation)

Low Risk

Testicular radiation dose 0.2-0.7Gy

Testicular radiation due to scatter

Very Low/ No Risk

from abdominal/pelvic radiation) <2Gy

Effects of surgery
Removal of both testicles stops sperm production forever, while an orchiectomy
does not affect sperm production.

Surgery on the prostate, bladder, large intestine, spine, or rectum candamage the nerves and cause erectile dysfunction and ejaculatory
dysfunction. These surgeries often cause retrograde ejaculation or semen
backflow towards the bladder.

5

Fertility preservation options

Sperm cryopreservation before starting cancer treatment is an established clinicaloption for male fertility preservation. Masturbation is the most common semen
specimen collection method for postpubertal males.
Fertility preservation for malesAdultChildren

Establishedmethods

Spermcryopreservation

After puberty, you canselect sperm cryopreservation

Pre-clinical

Cryopreservationof testicular tissue

Cryopreservation oftesticular tissue

Nonrecommendation

Hormonal therapy

Even before treatment, testicular cancer can itself lower sperm counts. Whensperm collection for cryopreservation is not possible, sperm can be removed using
testicular sperm extraction (TESE) or microsurgical epididymal sperm aspiration(MESA) procedures. When deciding whether to go through with reproductive
medicine, it is important to know that this procedure is not covered by insurance.
If sperm preservation is not an option for you, consult with your oncologist andreproductive endocrinologist.

Sperm cryopreservation

Sperm is frozen
for later use

6

Fertility after cancer treatment

Infertility may occur immediately or within a few months after cancer treatment and canlast for months or years; in some cases, infertility is permanent. The extent and speedof recovery of spermatogenesis following a cancer treatment are dependent on theagent used and the dose received. When semen parameters are insufficient for naturalpregnancy, frozen sperm with advanced reproductive technologies (ART) such as IVF
and intracytoplasmic sperm injection (ICSI), can be used to achieve fertilization with alow number of viable sperm.

Oocytes retrieval
from ovary

ThawedspermOocyte

Sperm

When sperm collection for cryopreservation is not possible, sperm can be removed
using testicular sperm extraction (TESE) procedures. It is important to follow up yourfertility after cancer treatment with your oncologist and reproductive endocrinologist.

When should I receive reproductive medical careafter cancer treatment?
You should consult with your oncologist because the scheduling needs
to be coordinated with your cancer treatment plan.

7Family planning after cancer treatment
Ask your oncologist about fertility before cancer treatment.
Natural pregnancy is possible in some cases.
Since natural pregnancy may be difficult depending on pre-treatment fertility andcancer treatment, ask reproductive endocrinologist about fertility preservation
options.
It may be difficult to have a child in a situation of illness, health condition aftertreatment, original infertility and so on.
Even if you do not receive fer tilit y preser vation treatment before cancer
treatment, fertility after treatment may be possible, so consult your reproductive
endocrinologist.
You may have to think about a lot of things and feel burdened. Please do not hold it
alone and talk to the medical staff about your feelings.

For patients who do undergo fertility preservation treatment
Please carry out the renewal procedure for cryopreserved sperm as necessary.
If you wish to conceive using cryopreserved sperm after cancer treatment, please
consult with the reproductive medical institution.
Please be aware that it may be difficult to transfer cryopreserved sperm to othermedical institutions.
Using fertility preservation before cancer treatment does not guarantee futurefertility.

For partner
It is important that the partner is in good general health.
In case of death or divorce, preserved sperm cannot be used.
Frozen embryo, eggs or sperm cannot be used without the consent of the patient.

8

Flow chart for
fertility preservation options

1

Ask your oncologist, nurses, pharmacists, medical social worker orpsychologists about fertility preservation.

2

Ask your oncologist whether your reproductive function will be affectedby your cancer treatment.

3

Select a reproductive endocrinologist.

4

Request a letter of introduction from the oncologist to the reproductive
endocrinologist.

5

The reproductive endocrinologist will explain your current fertility andpreservation options. (Your health insurance may not cover this fee. Pleasecontact your reproductive medical institution for details.)

6

7

If you opt for fertility preservation
You will undergo treatment at a reproductive medical institution.
If you select not to pursue fertility preservation prior to treatment
You may contact a reproductive endocrinologist after cancer treatment
as needed.

After consulting about your fertility, you are ready to start cancertreatment.

9How to find reproductive medical institutions
Consult your oncologist first. Several resources are available to you.
Japan Society for Fertility Preservation（JSFP）
日本・がん生殖医療学会 https://www.j-sfp.org/
Information Center for Cancer Patients
がん・情報サービス https://ganjoho.jp/public/index.html
Oncofertility for Children and Adolescents
小児・若年がんと妊娠 https://www.j-sfp.org/ped/index.html

Costs for fertility preservation
Reproductive medicine is not covered by insurance.
Be advised that you will receive this treatment at your own expense.

Standard costs
Counseling : First visit

Thousands to 10000 yen

Oocytes cryopreservation : 200,000 yen to 400,000 yen
Embryo cryopreservation : 300,000 yen to 500,000 yen
Ovarian tissue cryopreservation 600,000 yen to 800,000 yen
Sperm cryopreservation : 50,000 yen(If testicular extraction is required 400,000 yen to 500,000 yen)
Annual storage fee for cryopreservation : 200,00 yen to 600,00 yen
Micro insemination using cryopreserved sperm : 350,000yen to 400,000 yen
Infertility treatment is covered by insurance from April 2022 in Japan, while fertility
preservation for cancer patients is not covered by insurance.
The Ministry of Health, Labour and Welfare launched the "Project to promote
Fertility Preservation for Children and AYA Cancer Patients" from April 1, 2021.
You can receive some subsidies for the fertility preservation treatment. For more
information, please contact your local government.

10

Questions you should ask your oncologist
Reproduction medical institutes will need the following information from youroncologist.

Primary site of cancer
Stage, prognosis
Scheduled start date of cancer treatment
Treatment (Chemotherapy, Operation, Radiation
therapy)
Urgency of cancer treatment (Time needed forfertility preservation)
The risk of infertility by cancer treatment
Contact information of oncologist for
reproductive endocrinologist

Please review the five checkpoints on page 2 after you talk with yourreproductive endocrinologist to check whether you now have full
information to make your own decision.

11

Reference
1

Brannigan RE. Risk of infertility in male survivors of childhood cancer. The Lancet
Oncology. 2014;15(11):1181-2. Epub 2014/09/23. doi: 10.1016/s1470-2045(14)70450-4.
PubMed PMID: 25239574.

2Johnson EK, Finlayson C, Rowell EE, Gosiengfiao Y, Pavone ME, Lockart B,Orwig KE, Brannigan RE, Woodruff TK. Fertility Preservation for PediatricPatients: Current State and Future Possibilities. The Journal of urology.
2017;198(1):186-94. Epub 2017/02/13. doi: 10.1016/j.juro.2016.09.159. PubMed
PMID: 28189577.

3Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge
AH, Quinn G, Wallace WH, Oktay K. Fertility preservation for patients withcancer: American Society of Clinical Oncology clinical practice guideline
update. Journal of clinical oncology : official journal of the American Societyof Clinical Oncology. 2013;31(19):2500-10. Epub 2013/05/30. doi: 10.1200/
jco.2013.49.2678. PubMed PMID: 23715580; PMCID: PMC5321083.

4Duncan, F. E., Brannigan, R. E. & Woodruff, T. K. (2014). Yen and Jaffe's
Reproductive Endocrinology Physiology, Pathophysiology, and ClinicalManagement, 7th Edition: Elsevier. p. 791-821 31 p

5Fertility preservation and reproduction in patients facing gonadotoxic
therapies: a committee opinion. Fertility and sterility. 2013;100(5):122431. Epub 2013/10/08. doi: 10.1016/j.fertnstert.2013.08.041. PubMed PMID:24094423.

12

Working Panel Tasked with Compiling Evidence Regarding the Fertility of Long-Term
Survivors of Cancer during Childhood or Adolescence and with Developing a
Reproductive Medicine Network (Organizer: Yoko Miyoshi)This brochure was developed with the support a research grant received from theJapanese Ministry of Health, Labour and Welfare as a cancer control promotion
project (H26-016) . (Rep: Yoko Miyoshi, MD, PhD, Department of Pediatrics, Osaka
University Graduate School of Medicine)

Authors and editors
Akitani Fumi

: Department of Integrated woman's health, St Luke's international
hospital
Tomoyasu Kato : Department of Gynecology, National Cancer Center Hospital
Atsuko Kitano: Department of Breast and Medical Oncology, National Cancer
Center Hospital
Kyouko Shioda : Department of Integrated woman's health, St Luke's international
hospital
Chikako Shimizu : Department of Breast and Medical Oncology, National Cancer
Center Hospital

English version (Ver1.2 : Revised in June 2022)
Translators
Atsuko Kusuhara : Northwestern University/ Department of Obstetrics andGynecology, The Jikei University
Yoko Miyoshi: Department of Pediatrics, Osaka University Graduate School ofMedicine
We would like to thank Chikako Shimizu and Tomoyasu Kato (National CancerHospital) and Nao Suzuki (St. Marianna University) and Duniel Tucker (NorthwesternUniverstity) .

Acknowledgment
We thank Toru Kishida (STAND Up!!) and Mie Mifune (Pink Ring) for their greatcooperation.

Production cooperation: Moonfactory,Inc