DOI: 10.1111/tog.

12753 2021;23:170–6
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Fertility on ice: an overview of fertility preservation for

children and adolescents with cancer
MBBchBAO MRCPI MRCOG, *
a b,c,d e,f,g,h
Lucia Hartigan Louise E Glover BSc PhD, Mary Wingfield MD FRCOG
a
Clinical Research Fellow, National Maternity Hospital and Merrion Fertility Clinic, Dublin 2, Ireland and University College Dublin, School of
Medicine, Dublin 4, Ireland
b
Clinical Research Officer, Merrion Fertility Clinic, Dublin 2, Ireland
c
Adjunct Assistant Clinical Professor/Clinical Lecturer, University College Dublin, School of Medicine, Dublin 4, Ireland
d
Adjunct Assistant Professor, Trinity College Dublin, School of Medicine (Immunology), Dublin 2, Ireland
e
Consultant Obstetrician Gynaecologist, National Maternity Hospital, Dublin 2, Ireland
f
Clinical Director, Merrion Fertility Clinic, Dublin 2, Ireland
g
Associate Clinical Professor/Clinical Lecturer, University College Dublin, School of Medicine, Dublin 4, Ireland
h
Adjunct Professor, Trinity College Dublin, School of Medicine, Dublin 2, Ireland
*Correspondence: Lucia Hartigan. Email: luciahartigan@hotmail.com

Accepted on 20 August 2020. Published online 15 June 2021.

Key content  To raise awareness of the importance of early discussions about FP

 Continued advances in oncology treatments have led to better with patients who are at risk of infertility from their
survival rates for children and young adults with cancer. cancer treatment.
 An important ‘late effect’ of cancer treatment is the loss of fertility.
 Although many survivors of childhood cancers go on to conceive Ethical Issues
 Autotransplantation of ovarian tissue in survivors of
without difficulty, the potential loss of fertility is a concern for
children and young adults with cancer, their parents and caregivers. haematological malignancies, particularly leukaemia, carries a
 We review current options for fertility preservation (FP) for strong risk of re-introducing the malignancy and should
prepubertal and postpubertal girls and boys, including oocyte be avoided.
 Clinicians must consider suitability of the patient for FP, taking
cryopreservation, ovarian tissue cryopreservation, sperm
cryopreservation and testicular tissue cryopreservation. into account emotional maturity, patient and parent desire for FP
and the physical fitness of the patient, including their
Learning objectives immunosuppressive state.
 To understand the different FP methods available for children and
adolescents, the barriers to FP and ethical and Keywords: child and young adult cancer / fertility preservation /
psychological considerations oocyte cryopreservation / ovarian tissue cryopreservation

Please cite this paper as: Hartigan L, Glover LE, Wingfield M. Fertility on ice: an overview of fertility preservation for children and adolescents with cancer. The
Obstetrician & Gynaecologist 2021;23:170–6. https://doi.org/10.1111/tog.12753

Fertility preservation (FP) is the preservation of an

Introduction
individual’s oocytes, sperm or gonadal tissue so that the
Continued advances in oncology treatments have led to individual may use them to have their own biological
better survival rates for children (0–14 years), adolescent (15– children in future. Consideration of FP is indicated if there is
19 years) and young adult (20–24 years) cancer patients.1 a risk of future gonadal failure for any aetiology;3 however,
Overall survival is now greater than 80%. Because of this, this review article focuses on FP options for children and
there is increasing emphasis on improving the long-term young adults with cancer.
quality of life of cancer survivors. Efforts to reduce the
downstream sequelae of treatment are increasingly a priority.
Effects of oncology treatment on
When a patient who has not yet reached their reproductive
subsequent fertility and reproductive
goals is given a cancer diagnosis, it is best practice to discuss
function
their future fertility because chemotherapy, radiotherapy and
some surgical treatments may lead to a reduction or loss of Childhood cancers are treated using various regimens, such as
gonadal function. Thus, one of the most important ‘late chemotherapy, surgery, haematopoietic stem cell transplant
effects’ of cancer treatment is the loss of fertility.2 and radiotherapy including proton therapy. More recently,

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 Hartigan et al.

immune-based therapies have also been adopted. reported pre-treatment. Sperm parameters were broadly
Conventional treatment modalities can negatively affect uniform across all cancer types, with sperm counts increasing
reproductive potential through inadvertent injury to the in an age-dependent manner.11
hypothalamic–pituitary axis and to the reproductive organs
themselves; for example, the ovary, testes, uterus and vagina.4 Oocyte cryopreservation
The effects of radiotherapy depend on the dose received, For postpubertal females, the established options for FP are
the fractionation schedule and the targeted field of radiation. embryo or oocyte cryopreservation.12 However, given the
The effects of chemotherapy are related to the type of agent young age of child and young adult patients, oocyte
used, as well as the cumulative dose received.5 cryopreservation is usually most appropriate.
Total body irradiation, radiotherapy to a field that includes Cryopreservation refers to the cooling of cells and tissues
the ovaries or testes, and the use of alkylating agents including to sub-zero temperatures, thus halting all biological activity
cyclophosphamide, busulfan and chlorambucil, pose the so that they can be preserved for future use.13 The human
greatest risk of gonadotoxicity.6 Higher accumulated doses of metaphase II oocyte is a particularly fragile cell, owing to its
alkylating agents lower anti-m€ ullerian hormone (AMH) levels large size, large cytosolic water content and chromosomal
and decrease the chance of pregnancy.7 Radiation therapy rearrangement.14 Initial oocyte freezing efforts using a ‘slow
damages granulosa cells, with subsequent damage to ovarian freezing’ technique were hampered by cellular damage, ice
follicles. Irradiation of the ovaries of 10 Gy and above is crystal formation or excessive dehydration, so this technique
associated with premature ovarian insufficiency.7 has now been replaced by vitrification. Vitrification is a
process of cryopreservation using high concentrations of
cryoprotectants and rapid cooling to avoid the formation of
Methods of fertility preservation
ice crystals. This has markedly improved the viability of
Sperm cryopreservation cryopreserved cells.13 The first human birth from a frozen
Thirty percent of male survivors of childhood cancer suffer oocyte was reported in 1986.15
from azoospermia (no sperm) and 18% suffer from Embryo and oocyte vitrification require at least one cycle
oligospermia (reduced sperm).8 Where appropriate, of ovarian stimulation with subsequent oocyte retrieval, thus
postpubertal boys who are given a cancer diagnosis should are not appropriate for prepubertal girls.
be given the option of sperm cryopreservation before Ovarian stimulation usually takes 2 weeks and involves self-
commencing treatment. This method of FP is well administration of follicle-stimulating hormone injections.
established, relatively noninvasive and, usually, does not Development of ovarian follicles, each containing an oocyte,
delay oncology treatment to any significant degree. is tracked using ultrasound scans and serum hormone levels.
However, sperm cryopreservation has its limitations. It is Ideally, the ovarian stimulation regime begins at the start of the
only suitable for postpubertal boys, some boys may suffer menstrual cycle. However, random-start protocols are
anxiety and be unable to produce a sperm sample by also used, with obvious benefits for oncology patients who
masturbation, or there may be religious or cultural concerns.9 need to commence cancer treatment as soon as possible.
Limitations may also be imposed by the nature of the disease Recently, the idea of ‘back-to-back’ stimulation protocols has
itself (for example, patients with cord compression display been introduced. This involves a double ovarian stimulation
impairment of the normal neurological pathways required during both the follicular and luteal phases, with the intention
for ejaculation) and by medication side effects (such as of achieving a greater oocyte yield in less time.16 Oocyte retrieval
analgesic narcotics required for pain control). Nevertheless, is typically performed by ultrasound-guided transvaginal
several studies have demonstrated that most adolescent needle aspiration under sedation. Increasing evidence for the
cancer patients can produce a semen sample, including safety of the procedure led oocyte vitrification to be reclassified
boys as young as 12 years of age.10,11 from experimental to nonexperimental in 2013 by both the
Sperm quantity and quality may also be adversely affected by American Society of Reproductive Medicine (ASRM) and the
the primary tumour, most notably in cases of malignant European Society for Human Reproduction and Embryology
testicular neoplasms.8 A UK study published in 200211 looked (ESHRE).17 The procedure is now in routine use in clinical
at 238 adolescent patients referred for sperm cryopreservation assisted reproduction.
before cancer treatment. Diagnoses included testicular cancer, Risks associated with ovarian stimulation for oocyte
leukaemia, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, cryopreservation in postpubertal females are 1) delayed
osteosarcoma, Ewing’s sarcoma, acute lymphoblastic initiation of cancer treatment, 2) ovarian hyperstimulation
leukaemia (ALL) and acute myeloid leukaemia (AML). Of syndrome (OHSS) in girls with high ovarian reserve and 3)
these 238 patients, 33 (13.9%) were unable to produce a the effect of stimulation protocols that increase estrogen
sample, while 205 (86.1%) successfully provided a sample levels on hormone-dependent malignancies. For estrogen-
suitable for cryopreservation. No cases of azoospermia were dependent breast and gynaecologic cancers (rare in under 25-

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 Fertility on ice

year-olds), current recommendations indicate use of tissue transplantations in 74 adult women treated for cancer
aromatase inhibitor-based protocols for ovarian in in the European FertiProtekt Network.23 Mean age at
stimulation, because these may mitigate the risk of cancer cryopreservation and transplantation was 30 years and
recurrence.18 Furthermore, it is important to take into 34 years, respectively, with the two most common
account that the process of ovarian stimulation and oocyte diagnoses being breast cancer and Hodgkin’s lymphoma.
retrieval requires ultrasound scans; these are usually Of women with premature ovarian insufficiency (POI) at the
performed transvaginally, so require a certain level of time of first transplantation, 62.5% showed evidence of
physical and psychological maturity. ovarian activity 1 year post-transplantation, 27.5% achieved
Notably, a recent large multicentre study of oocyte a pregnancy, and 22.5% had a live birth. Importantly, most of
vitrification and in vitro fertilisation (IVF) outcomes these pregnancies resulted from natural conception. The
revealed markedly lower success rates in young women potential for natural conception is a primary advantage of
(≤35 years) who used this fertility preservation method after OTC over oocyte or embryo cryopreservation. True success
cancer diagnosis compared with age-matched women seeking rates were, however, confounded by several factors, including
elective fertility preservation for non-oncological reasons.19 residual ovarian activity and transplantations for endocrine
This included significantly lower oocyte survival (81.2% function rather than fertility restoration.22
versus 91.4%), and reduced cumulative live birth rates (40% To date, there have been just two case reports of a successful
versus 70%). This important study suggests that primary live birth following autotransplantation of ovarian tissue that
malignancy may affect reproductive potential and should be was cryopreserved pre-menarche.24,25 The first case involved a
taken into consideration when counselling patients. woman, originally from the Republic of Congo, who was
diagnosed with sickle-cell anaemia at the age of five. Her right
Ovarian tissue cryopreservation ovary was laparoscopically removed and cryopreserved at the
Ovarian tissue cryopreservation (OTC) involves laparoscopic age of 13 years and 11 months, before having curative therapy
surgery to remove all or part of the ovary, followed by with haematopoetic stem cell transplant (HSCT). As expected,
cryopreservation of the excised tissue with a view to following the treatment, the patient developed primary ovarian
autotransplantation in the future. The tissue may be failure, with elevated gonadotrophins. Menarche was induced
transplanted back to the patient’s pelvic cavity at the age of 15.5 years.
(orthotopically), or to a site outside of the pelvic cavity; for Ten years later, the patient wished to become pregnant.
example, to the forearm or rectus muscle (heterotopically).20 The patient underwent ovarian tissue transplantation.
Typically, strips of ovarian cortex are laparoscopically grafted Menstruation occurred 5 months later and was followed by
back to the exposed ovarian medulla or an adjacent site, thus regular menstrual cycles thereafter.24 Two years post-
making spontaneous pregnancy or use of assisted transplantation, the patient became pregnant and delivered
reproduction techniques possible. Oocyte retrieval and a healthy boy in November 2014.24
embryo development have been demonstrated following The youngest worldwide reported case of ovarian tissue
heterotopic transplantation of ovarian tissue; however, live cryopreservation before puberty with subsequent
birth rates are very low and natural conception is not possible transplantation of the tissue was a 9-year-old girl suffering
with this technique.20 from b-thalassaemia. Her ovarian tissue was cryopreserved
A key benefit of OTC is that ovarian stimulation is not for 14 years before being transplanted back at the age of 23.
necessary, so treatment for cancer patients is not delayed. Subsequently, she conceived following IVF treatment with an
Additionally, retrieval of tissue for OTC does not require oocyte derived from the transplanted tissue and delivered a
sexual maturity, so it is suitable for prepubertal girls. A healthy baby.25
further advantage is that autotransplantation of ovarian One significant potential disadvantage of OTC is that
tissue after puberty can restore general ovarian endocrine ovarian tissue stored prior to cancer treatment may harbour
function in addition to preserving fertility.20 malignant cells.17 Numerous methods can be used to
The first successful pregnancy after replacement of determine the extent of malignant cell contamination,
cryopreserved human ovarian tissue in an adult female was including immunohistochemistry and molecular analysis.
reported in 2004.21 Since then, there have been more than However, these tests are all destructive to tissue, so cannot be
130 live births recorded using this procedure. applied to the ovarian tissue intended for transplantation. It
Ovarian activity has been reported to resume in over 90% is generally accepted that, where there is no evidence of
of women after replacement of their ovarian tissue; this metastatic disease of solid cancers, there is low risk of ovarian
occurs a median of 4 months after transplantation. Ovarian malignant contamination.22 However, in the case of
activity is sustained for a variable duration of time, but has leukaemia, several studies have indicated that the risk that
been reported to last several years in some cases.22 A recent of malignant cells in the ovary is high.20,21 The use of OTC in
publication reported on 95 orthotopic cryopreserved ovarian cases of leukaemia is therefore controversial.

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 Hartigan et al.

OTC is now considered non-experimental in some reproductive techniques. Thus, the efficacy of TTC has yet
countries (for example, Denmark and Israel). A 2018 FP to be proven; no live births from frozen tissue have been
guideline published by the American Society of Clinical reported in humans to date. In a recent milestone study,
Oncology (ASCO) indicated that the experimental status of Fayomi et al.32 reported a successful pregnancy in rhesus
OTC is under evaluation in the USA, based on accumulating macaques using transplanted prepubertal cryopreserved
evidence of successful pregnancy outcomes.18 testicular tissue in conjunction with IVF. Importantly,
complete spermatogenesis was confirmed in all transplanted
In vitro maturation testicular tissue grafts.32
In vitro maturation (IVM) of oocytes is another technique Despite the experimental nature of the technique, research
that avoids ovarian stimulation, but is classified as indicates that parents and survivors are undeterred and
experimental. This concept was first introduced to reduce remain interested in pursuing this option.9 The procedure of
risk by avoiding ovarian stimulation in patients who had testicular tissue retrieval is straightforward and can be
severe OHSS in their previous IVF treatments.26 IVM oocyte coordinated with other procedures requiring general
cryopreservation involves the retrieval of immature oocytes anaesthetic. For most cases, a 3–5-mm incision of the
from ovaries after minimal or no gonadotrophin stimulation tunica albuginea permits collection of three to four small (1–
and their subsequent maturation in the laboratory. IVM may 2 mm3) biopsies, which are placed in media and
be done at the time of oocyte collection, or immature oocytes immediately transferred to the tissue bank for processing
may be cryopreserved for use in IVM at a later stage.27 and storage.9 To generate sperm cells, suggested strategies are
Very few live births have been reported after IVM oocyte IVM or tissue transplantation, by either grafting onto an
cryopreservation. The first live birth was reported following existing testicle or injecting germ cell preparations into the
cryopreservation using the slow-cooling method of oocytes rete testes.33
retrieved at the immature germinal vesicle (GV) stage in
conventional IVF cycles.28 Subsequently, five live births were Ovarian transposition and the use of gonadotrophin-
reported following vitrification at metaphase-II (MII) stage releasing hormone agonists
after human chorionic gonadotrophin (hCG)-primed IVM Efforts to reduce the risk of gonadotoxicity include ovarian
cycles.29 Live births have also been achieved using the IVM of transposition or oophoropexy, which is an effective method
immature oocytes obtained from resected ovarian cortex.30 A of FP for both prepubertal and postpubertal girls requiring
retrospective study of 267 patients, which compared fresh pelvic radiation for non-ovarian tumours. In this technique,
and vitrified IVM-oocytes, showed that vitrification resulted one or both ovaries and fallopian tubes are separated from
in lower clinical pregnancy (36.1% versus 10.7%) and live the uterus and attached to the wall of the abdomen, away
birth rates (25.9% versus 8.9%).26 from the radiation target area.34 Barriers to success with this
IVM is particularly advantageous for oncology patients. method include scattered radiation and alterations in ovarian
As IVM does not require ovarian stimulation, it does not blood supply. Overall efficacy is thought to be around 50%.35
delay cancer treatment, and it does not carry the risk of In terms of preserving ovarian function in paediatric patients,
malignant contamination, as is the case in OTC (described success rates are difficult to establish given the limited study
above). The first live birth following IVM for a cancer number and follow-up but are estimated to be between 60%
patient was recently reported by Professor Grynberg’s group and 83%.36 Large-scale follow-up studies of clinical
in France. In brief, seven immature follicles were retrieved pregnancy and livebirth outcomes following ovarian
from a 29-year-old patient and matured in vitro for transposition in child and young adult cancer have yet to
48 hours, resulting in six MII oocytes suitable for be completed.
vitrification. After 5 years, all six oocytes were thawed and Administration of gonadotrophin-releasing hormone
fertilised (by intracytoplasmic sperm injection, ICSI), and a (GnRH) agonists during chemotherapy to suppress ovarian
single cleavage stage embryo transfer resulted in pregnancy activity is another example of a strategy to reduce the
and healthy live birth.31 negative impact of chemotherapy on ovarian reserve. Meta-
analyses have demonstrated that GnRH agonist use during
Testicular tissue cryopreservation chemotherapy in an adult population with breast cancer
For prepubertal boys, the only potential option for fertility improves return of ovarian function and pregnancy rates.37
preservation is testicular tissue cryopreservation (TTC), However, in malignancies other than breast cancer, there is
which is still considered to be an experimental technique. limited evidence to suggest their role in the prevention of
In males, puberty heralds the maturation of germinal gonadotoxicity.38,39 GnRH agonists are not useful in a
epithelium towards spermatids and mature sperm. prepubertal cohort owing to inherent hypogonadotropic
Therefore, retrieval options before puberty are unlikely to function.7 They could be considered for those who are
produce cells that can currently be used for assisted postpubertal, although the efficacy of this option remains

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 Fertility on ice

uncertain. In fact, the recently published draft of ESHRE

Box 1. The Edinburgh selection criteria41
guidance on female FP40 advises that, in malignancies other
than breast cancer, GnRH agonists should not be offered as  Age younger than 35 years
an option for ovarian function protection and  No previous chemotherapy or radiotherapy if aged 15 years or older
fertility preservation. at diagnosis, but mild, nongonadotoxic chemotherapy acceptable if
younger than 15 years
 A realistic chance of surviving for 5 years
 A high risk of premature ovarian insufficiency (>50%)
Patient selection for fertility preservation  Informed consent (from parents and, where possible, the patient)
 Negative serology results for HIV, syphilis and hepatitis B
Appropriate patient selection for FP is essential. It is not
 Not pregnant and no existing children
always appropriate for patients to take steps to preserve their
fertility. Many patients will be too unwell to consider FP
methods, or will decide that retaining fertility is not a priority overall, cancer survivors had a lower than expected number
for them. of pregnancies compared with the general population: 6627
For all FP methods, the patient must have a realistic observed compared to 10 736 expected pregnancies. Thus,
chance of survival from their disease. If a patient’s survivors of cancer were approximately 38% less likely to
condition is considered palliative, there is potential harm become pregnant, highlighting that at-risk patients should
and no benefit to preserving their fertility. Clinicians must ideally be provided timely access to fertility counselling and
consider if the patient is medically fit enough to undergo fertility preservation treatments.44
the FP procedure involved. Consent must be obtained – and
this can be a challenging ethical consideration in the case
Fertility preservation counselling and
of minors.
discussions
Another key factor to consider before invasive procedures
such as OTC, oocyte retrieval or testicular tissue freezing, is It is essential to provide patients with information about FP
the nature of the required oncology treatment; that is, in a timely fashion, as soon as possible after a cancer
whether or not the proposed treatment is of sufficiently high diagnosis. A systematic review by Taylor et al.45 summarised
risk to a patient’s fertility to justify the FP procedure. Whole that children and young adults with a new cancer diagnosis,
body, pelvic (or abdominopelvic in children) radiotherapy and their parents, value the opportunity to discuss fertility
and high-dose alkylating agents carry the greatest risk concerns and preservation options.45 Unfortunately, research
of gondadotoxicity. indicates that discussions about fertility and fertility
Wallace et al.41 developed the Edinburgh selection criteria preservation are not taking place.46–48 children and young
for suitability for OTC as outlined in Box 1. These criteria adults with cancer and their parents often report that they
have been shown to accurately predict which girls and young have no recollection of conversations about fertility options
women will or will not develop premature ovarian with their clinician.49
insufficiency. They therefore aid appropriate patient A mixed methods systematic review by Vindrola-Padros
selection for OTC before the start of cancer treatment.41 and colleagues50 studied healthcare professionals’ (HCPs)
views on discussing FP with children, adolescents and young
cancer patients (aged 0–24). Sixteen papers reporting 14
Reproductive outcomes for survivors
studies were reviewed, most of which took place in North
Research has found that most adult survivors of childhood America and Western Europe. These authors found that
cancer express the wish to have children.42,43 Many cancer HCPs had a general awareness of the risks to fertility
survivors will go on to conceive spontaneously. However, if associated with oncology treatments, but that they lacked
they have trouble conceiving and wish to proceed with use of knowledge of the various FP options. This, naturally, affected
their stored sperm, oocytes, embryos or cryopreserved the discussion about FP with children and young adults.
ovarian tissue, further treatment will be necessary to Further reported barriers to adequate discussions about FP
achieve a pregnancy. included sense of comfort, patient factors (for example, those
Anderson and colleagues44 used linkable databases of patients who had a poor prognosis or were considered too
cancer registrations and pregnancy-related outcome records young), parent factors, and the lack of availability of
in Scotland (1981–2014) to investigate whether women who written information.
have had a cancer diagnosis are as likely to achieve pregnancy In Europe, efforts to improve knowledge of oncofertility
as their age-comparable counterparts who have not had preservation options have included the establishment of a
cancer.44 Over 23 000 women aged 39 or younger at pan-European Consortium (PanCareLIFE) that aims to
diagnosis (including those treated as children) were develop FP guidelines for children and adolescents
included in their assessment. The authors found that diagnosed with cancer.51 Funding of FP represents an

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 Hartigan et al.

additional barrier in many healthcare systems. A recent study 11 Bahadur G, Ling KL, Hart R, Ralph D, Wafa R, Ashraf A, et al. Semen quality
and cryopreservation in adolescent cancer patients. Hum Reprod
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either through funding by the state or a compulsory preservation in haemato-oncology patients undergoing treatment. Br J
Haematol 2011;153:291–308.
insurance system.52 13 Iussig B, Maggiulli R, Fabozzi G, Bertelle S, Vaiarelli A, Cimadomo D, et al. A
brief history of oocyte cryopreservation: arguments and facts. Acta Obstet
Gynecol Scand 2019;98:550–8.
Conclusion 14 Bromfield JJ, Coticchio G, Hutt K, Sciajno R, Borini A, Albertini DF. Meiotic
spindle dynamics in human oocytes following slow-cooling
The impact of loss of fertility and unintended childlessness cryopreservation. Hum Reprod 2009;24:2114–23.
on young men and women who have been previously treated 15 Chen C. Pregnancy after human oocyte cryopreservation. Lancet
1986;1:884–6.
for cancer cannot be underestimated. Recent technological 16 Kuang Y, Chen Q, Hong Q, Lyu Q, Ai A, Fu Y, et al. Double stimulations
advances, such as oocyte vitrification and OTC offer during the follicular and luteal phases of poor responders in IVF/ICSI
increasing hope to this group. programmes (Shanghai protocol). Reprod Biomed Online 2014;29:
684–91.
In this era of improving survival rates of childhood cancer, 17 ESHRE Task Force on Ethics and Law, Dondorp W, de Wert G, Pennings G,
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18 Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al.
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There are no conflicts of interest. 20 Dolmans MM, Manavella DD. Recent advances in fertility preservation. J
Obstet Gynaecol Res 2019;45:266–79.
21 Donnez J, Dolmans MM, Demylle D, Jadoul P, Pirard C, Squifflet J, et al.
Contribution to authorship Livebirth after orthotopic transplantation of cryopreserved ovarian tissue.
LH researched and wrote the article. LEG and MW reviewed Lancet 2004;364:1405–10.
22 Anderson RA, Wallace WHB, Telfer EE. Ovarian tissue cryopreservation for
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2017;2017:hox001.
23 van der Ven H, Liebenthron J, Beckmann M, Toth B, Korell M, Krussel J, et al.
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