Cryopreservation of Gametes and Embryos

1. Category: Threshold

Threshold procedures and therapies are those in which a clinical threshold has been set which needs to be met before funding will be made available for treatment

For patients who DO NOT meet the eligibility criteria, the ICB will only consider funding the treatment if an Individual Funding Request (IFR) detailing the patient’s clinical presentation is submitted to the ICB

2. Background

This policy aims to provide criteria for access to and funding for cryopreservation of gametes (sperm and oocytes) and embryos for the people registered with a Coventry and Warwickshire GP practice

The policy specifically relates to cryopreservation of gametes and embryos in patient groups who are at risk of infertility due to NHS funded medical or surgical treatment including patients with gender dysphoria or for patients at risk of premature ovarian insufficiency

Patients will be offered one NHS funded treatment to recover and preserve gametes subject to the patient meeting the eligibility criteria.

Cryopreservation is the process of freezing and storing biological materials so that it can typically be used at a later date to conceive a pregnancy

3. Indication

Infertility may be an unwanted side-effect of an NHS funded medical or surgical treatment; (this is described as iatrogenic infertility)

Infertility may be the result of premature ovarian insufficiency. This can occur for several reasons such as; due to congenital disorder, as a result of medical or surgical treatment or due to autoimmune conditions

The following patient groups are covered in this policy:

• Patients who will be having NHS funded medical or surgical treatment for cancer
• Patients who will be having NHS funded medical or surgical treatment for other conditions and as a result infertility is potential risk
• Patients who are at high risk of premature ovarian insufficiency (POI). The most common genetic cause of POI is Turners syndrome

Cryopreservation is not available for any other patient group, i.e. for patients embarking on a private pathway of care likely to cause infertility or patients who wish to delay conception for non-medical reasons

In cases where there is significant likelihood of a patient becoming infertile as result of NHS funded treatment, patients must meet eligibility criteria set out in this policy in order to access cryopreservation services

Referral:

All patients about to embark on a treatment within an NHS pathway of care that might cause infertility should be offered an opportunity to discuss their circumstances with a fertility specialist, regardless of potential eligibility for cryopreservation

For patients who do not fall within the scope of this policy but where there is demonstrable evidence that the patient has clinically exceptional circumstances, an Individual Funding Request (IFR) may be considered

Approval for cryopreservation does not guarantee future funding of assisted conception treatment. For this the patient will be required to meet the criteria set out in the ICB’s Policy for Specialist Treatment of Infertility at time of application

This policy will ensure that all patients registered with a Coventry and Warwickshire GP practice who require cryopreservation services are treated according to the ICBs’ Commissioning Principles

This policy applies to Coventry and Warwickshire ICB and the principle providers of these services, NHS and private providers, irrespective of where the patient is being treated

4. Eligibility Criteria

The patient must be permanently registered with a Coventry and Warwickshire GP practice

The patient, if female born, must be of reproductive age and aged under 40 at the point of referral for treatment

On the advice of our embryology colleagues the ICB has been advised of evidence that shows that retrieved eggs are fragile to cryopreservation and chances of an egg surviving cryopreservation falls significantly with the age of the woman

The ICB has been advised that applying an age limit of under 40 has consensus agreement from the relevant embryology and fertility clinicians and is consistent with policies elsewhere in England

The patient, if male born, must have reached or else undergone adolescence. On the advice of our embryology colleagues the ICB has been advised that sperm is not especially fragile to cryopreservation and the change of sperm surviving cryopreservation does not significantly change with the age of the man

The patient must meet one of the following clinical criteria:

• The patient must be undergoing NHS funded medical or surgical treatment which is likely to lead to infertility
• Patient is at high risk of premature ovarian insufficiency*

*For the purposes of this policy POI is defined as:

o Amenorrhea of at least 12 months

o Hormonal profile in the menopausal range

o Under the age of 40

In patients born female, preparing to undergo medical treatment for cancer that is likely to render them infertile, the following should be considered:

• The patient is well enough to undergo ovarian stimulation and egg collection; AND
• This will not worsen their condition; AND
• Enough time is available before the start of their cancer treatment
• There must be written consent for treatment and gamete storage

The provider of the service must ensure that the patient receives appropriate counselling.

NHS funded cryopreservation treatment will not be available if the infertility is the result of a sterilisation procedure

The ICB does not routinely fund cryopreservation of ovarian and testicular tissues except in cases where gamete and embryo cryopreservation cannot be achieved

The ICB does not fund cryopreservation for those who wish to delay conception for non – medical reasons

5. NHS funding for storage of gametes and embryos conditions

Cryopreservation for fertility for adults may be funded for up to 10 years

If fertility is found to have returned, either through fertility testing or through conception and pregnancy, or the patient dies with no written consent regarding posthumous use, then continued storage will not be funded

The patient is able to self-fund for a further period providing that the appropriate length of storage set out by human fertilisation and embryology authority regulations is not exceeded

If storage is desired for longer than 10 years, then an application for exceptional funding could be made to the Individual Funding Request Panel and each request will be considered on its own merit and in line with Human Fertilisation and Embryology Authority (HFEA) legislation

Preferred providers:

The ICB’s local provider, the Centre of Reproductive Medicine, University Hospitals of Coventry and Warwickshire NHS Trust, is preferred; however other providers are available under Right to Choose

6. Guidance/References

NICE Clinical Guideline (CG156) Fertility: Assessment and treatment for people with fertility problems February 2013 https://www.nice.org.uk/guidance/cg156

The impact of the medical/surgical intervention on the patient’s fertility should be discussed by the relevant medical/surgical team

When deciding to offer fertility preservation to people diagnosed with cancer, the following should be taken into account:

• Diagnosis Treatment plan
• Expected outcome of subsequent fertility treatment Prognosis of the cancer treatment
• Viability of stored/post-thawed material

A lower age limit for cryopreservation fertility preservation will not be used

Patients must be informed that even though they may meet criteria for cryopreservation, it does not automatically mean they will meet criteria for using the stored material for assisted conception in an NHS setting https://www.rcr.ac.uk/our-services/all-our-publications/clinical-oncology-publications/the-effects-of-cancer-treatment-on-reproductive-functions-guidance-on-management/

This guidance makes recommendations specifically around cancer diagnosis and treatment of induced infertility. It recommends the use of cryopreservation of material prior to commencing a treatment pathway that could potentially make a patient infertile.

Possible future effects of chemotherapy or radiotherapy on fertility should be discussed with all patients with reproductive potential. It should be recognised that the prospect of infertility can be psychologically and socially damaging for both men and women by that such an outcome can, to some extent, be mitigated by gamete and embryo storage

Gametes can only be stored and used in a centre licensed by the HFEA Human Fertilisation and Embryology Authority (HFEA) Code of Practice The HFEA is the UK’s independent regulator overseeing use of gametes and embryos in fertility treatment. Its Code of Practice sets out both mandatory requirements and recommended guidance(incorporating an interpretation of mandatory guidance) for organisations involved in this area of health care

Human fertilisation and embryology authority, egg freezing in fertility treatment trends and figures. 2019. Hfeagovuk. [Online]. Available from: https://www.hfea.gov.uk/media/2656/egg-freezing-in-fertility-treatment-trends-and-figures-2010-2016-final.pdf

Fertility preservation for medical reasons in girls and women: British fertility society policy and practice guideline. Hum Fertil (Camb), 21 (1). pp. 3-26. ISSN 1742-8149 DOI: Yasmin, E and Balachandren, N and Davies, MC and Jones, GL and Lane, S and Mathur, R and Webber, L and Anderson,RA and British Fertility Society (2018) https://doi.org/10.1080/14647273.2017.1422297

The policy has made certain recommendations regarding cryopreservation. For instance, the risk of infertility, diminished ovarian reserve, and premature ovarian insufficiency should be assessed based on age, type and dose of chemotherapy

Women/couples should be advised that embryo cryopreservation is an established technique, with success rates for the transfer of frozen-thawed embryos comparable to those for the transfer of fresh embryo. Furthermore, women/couples should be advised of the length of time their oocytes/embryos can be stored and that this limit is statutory

NHS England

Gender Identity Dysphoria

NHS England commissions the gender identity dysphoria pathway. Cryopreservation is advised in the service specification of NHS England to be the responsibility of the patient’s ICB and is not commissioned by NHS England.

Human embryo and fertility act 1990 http://www.legislation.gov.uk/ukpga/1990/37/contents

Cryopreservation of gametes or embryos must meet the current legislative standards. The provider of the service must ensure that the patient receives appropriate counselling and provides full consent. Both partners must be aware of the legal position regarding embryos which have been cryopreserved, should one partner remove consent to their ongoing storage or use. The provider of the service should contact patients annually to confirm that they wish to continue storage. The patient will be responsible for ensuring the storage provider has up to date contact details. The provider must ensure that material is only stored where there is a valid consent in place.

The effects of cancer treatment on reproductive functions Guidance on management Report of a Working Party Royal College of Physicians, Royal college of Radiologists and Royal College of Obstetricians and Gynaecologists November 2007. http://www.rcr.ac.uk/docs/oncology/pdf/Cancer_fertility_effects_Jan08.pdf

Cancer treatment and survivorship statistics, 2016. Kimberly D. Miller MPH Rebecca L. Siegel MPH Chun Chieh Lin PhD, MBA Angela B. Mariotto PhD Joan L. Kramer MD Julia H. Rowland PhD Kevin D. Stein PhD Rick Alteri MD Ahmedin Jemal DVM, PhD. First published: 02 June 2016 https://doi.org/10.3322/caac.21349

Kasaven, L.S., Jones, B.P., Heath, C. et al. Reproductive outcomes from ten years of elective oocyte cryopreservation. Arch Gynecol Obstet 306, 1753–1760 (2022). https://doi.org/10.1007/s00404- 022-06711-0

Tsafrir, A., Ben-Ami, I., Eldar-Geva, T. et al. Clinical outcome of planned oocyte cryopreservation at advanced age. J Assist Reprod Genet 39, 2625–2633 (2022). https://doi.org/10.1007/s10815-022-02633-7

Lin, J et al. Effect of Maternal Age on Pregnancy or Neonatal Outcomes Among 4,958 Infertile Women Using a Freeze-All Strategy. Frontiers in Medicine, 10 January 2020 . Available Online: https://www.frontiersin.org/articles/10.3389/fmed.2019.00316/full

Joseph O. Doyle, Kevin S. Richter, Joshua Lim, Robert J. Stillman, James R. Graham, Michael J. Tucker, Successful elective and medically indicated oocyte vitrification and warming for autologous in vitro fertilization, with predicted birth probabilities for fertility preservation according to number of cryopreserved oocytes and age at retrieval, Fertility and Sterility, Volume 105, Issue 2, 2016, Pages 459-466.e2.