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Assisted Reproductive Techniques (ART) Policy

APPROVED BY: East Sussex CCG Quality & Governance Committee

EFFECTIVE FROM: June 2020

REVIEW DATE: June 2022

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Policy Category:

Commissioning

Relevant to CCG staff, GPs, providers of ART services and Patients

Version History

Version No. Date Changes Made:

0.1 January 2017 Clarifications requested by the Quality & Governance Committee on 18/1/17

0.2 March 2017

Ratified

Replaces: Intra-uterine insemination (IUI), In vitro Fertilisation (IVF) and Intra-cytoplasmic Sperm Injection ( ICSI) Policy PR 2009-07 Issued July 2009

Assisted Reproductive Techniques for Fertility Preservation for Patients Receiving Gonadotoxic Treatments Policy PR 2009-08 Issued July 2009

Surgical Sperm Retrieval Policy PR 2013-02 Issued October 2015

Assisted Conception Treatments Using Donated Genetic Materials Policy PR2011-09 Issued May 2011

Template Criteria for Fertility Preservation and Assisted Conception Treatments Using Cryopreserved Embryos and Sperm. Health Policy Support Unit. Issued July 2009.

Template Criteria for NHS Funded Assisted Conception Treatments for Sub Fertility For the CCGs within East Sussex. Issued May 2016

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Page

Introduction, purpose and scope of this policy

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Staff quick reference guide

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Definitions

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Eligibility Criteria

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Funded Cycles

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Surgical Sperm Retrieval

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Sperm Washing

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Intra-uterine insemination (IUI) using partner sperm

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Donated Genetic Materials

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Use of Surrogates

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Fertility Preservation For Patients Receiving Gonadotoxic Treatments

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References

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Contents

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1. Introduction Prior to 2013, the East Sussex CCG were party to the Brighton & Hove Assisted Reproductive Technologies Commissioning Group’s consideration of current guidance and legislation. The group also conducted an assessment of the baseline position and the views and opinions of stakeholders. Following this exercise, Brighton and Hove policies were reviewed and updated but the East Sussex policies were not reviewed at the time and the CCGs have continued to use the inherited policies from the predecessor PCTs. This has led to some inequality of access to the tertiary fertility centres in Sussex. This policy has now been drafted in order to achieve alignment of the Sussex CCG policies.

2. Purpose

It is estimated that infertility affects 1 in 7 heterosexual couples in the UK (National Institute for Health and Care Excellence (NICE) (2013) Clinical guideline 156). Since the original NICE guideline on fertility was published in 2004 there has been a small increase in the prevalence of fertility problems, and a greater proportion of people now seeking help for such problems. This policy is informed by NICE guidance GL156 (2013) and it establishes the eligibility criteria for access to assisted reproductive technologies and the range of procedures funded by the CCGs in order to ensure there is a focus of resources on groups of patients most likely to have successful outcomes, and to prioritise groups of patients who are most likely to have the greatest need.

3. Scope This policy will apply to all forms of Assisted Reproductive Techniques in eligible patients. This policy will apply to all patients registered with a GP in East Sussex CCG.

4. Staff Quick Reference Guide This policy covers the East Sussex CCG. This policy describes the eligibility criteria and Assisted Reproductive

Techniques that will be funded by the CCG. The policy describes the ways in which the CCG will commission and provide

care in a manner that reflects the choice and preferences of individuals and yet balances the need for the CCG to commission care that is safe and effective and makes the best use of available resources.

5. Definitions

Assisted Reproductive Techniques (ART) Any treatment that deals with means of conception other than by vaginal intercourse. Cryopreservation

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The process of placing cells, organs or even whole organisms at low temperatures so that they remain in a state of suspended animation and viability is preserved. Expectant management A formal approach that encourages conception through unprotected vaginal intercourse by offering advice and information to the couple to improve their chances of conceiving; it does not involve active clinical or therapeutic interventions. In vitro fertilisation (IVF) A process by which an egg is fertilised by sperm outside the body. Intra-cytoplasmic sperm injection (ICSI) An IVF procedure in which a single sperm is injected directly into an egg. Anti-mullerian hormone (AMH) and Follicle-stimulating Hormone (FSH) Hormones that indicate the level of a woman’s ovarian reserve.

Azoospermia Sperm count is equal or less than 15 million/ml. Intra-uterine insemination (IUI) A fertility treatment that involves placing sperm inside a woman’s uterus to facilitate fertilisation. Oocyte An immature female sex cell. Gonadotoxic Gonadotoxicity is the temporary or permanent damage to ovaries or testes after exposure to certain substances or drugs.

Full Cycle NICE guidance defines a full cycle of IVF treatment as comprising one episode of ovarian stimulation and the transfer of resultant fresh or frozen embryo(s).

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6. Eligibility Criteria In order to access NHS funded treatments patients must be registered with an East Sussex CCG and are required to meet the relevant eligibility criteria. Visitors and migrants who are entitled to an exemption from charge for NHS services under Immigration Health Surcharge arrangements are not eligible to receive free NHS-funded assisted reproduction services (such as IVF) as part of their exemption*.

Criterion Description Rationale

Duration of sub-fertility

Funding will be available for couples with unexplained infertility, endometriosis or mild male factor infertility (two or more semen analyses have one or more variables below the fifth centile), who have been having regular unprotected sexual intercourse and attempting to conceive for at least 24 months (this can include up to 12 months before their fertility investigations began). Where investigations show there is no chance of pregnancy with expectant management (i.e

through unprotected vaginal intercourse with clinical advice and information to the couple to improve their chances of conceiving and where IVF is the only effective treatment, patients can be referred directly for IVF treatment, with or without ICSI.

NICE Clinical Guideline 156 (CG156) recommends couples with unexplained infertility try to conceive for a total of two years before IVF, with or without ICSI, is considered. There is good evidence that waiting for three years will not be beneficial to the vast majority of patients who have not conceived after two years. In addition, waiting a third year may reduce the success rates for couples who go on to have IVF because the chance of a live birth following IVF treatment falls with rising female age.

Age of woman Funding is available where the woman is aged less than 40 years. If the woman reaches the age of 40 during treatment, the current full cycle will be completed but no further full cycles will be available. A full cycle of IVF treatment, with or without ICSI, will comprise one episode of ovarian stimulation and the transfer of resultant fresh and frozen embryo(s).

NICE CG156 concludes that treatment with IVF is cost effective for women aged under 40 years. There is considerable uncertainty about whether IVF is cost effective in any sub-groups of women aged between 40 and 42. The clinical and health economic evidence is overwhelming in indicating that IVF should not be offered to women aged 43 years or older. Analysis of local data confirms that IVF is less cost effective for couples where the woman is aged between 40 and 42 than those aged 39 and under.

Female Hormone Levels

Women must have an AMH level of >4.9 pmol/l

NICE CG156 states that ovarian reserve is effective in predicting response to IVF. The anti-Müllerian hormone (AMH) test has significantly less inter- and intra-menstrual cycle

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variability compared with follicle-stimulating hormone (FSH) testing. AMH can be measured at any point of the menstrual cycle.

Body Mass Index

Women must have a Body Mass Index (BMI) within the range 19-29.9 kg/m2.

NICE CG156 states that low body weight is recognised as an important cause of hypo-oestrogenic amenorrhoea. In women, weight loss of over 15% of ideal body weight is associated with menstrual dysfunction and secondary amenorrhoea when over 30% of body fat is lost. Women with BMI over 30 kg/m2 take longer to conceive, compared with women with lower BMI, even after adjusting for other factors.

Previous children

Neither partner in a couple should have a living child from their relationship or any previous relationship. A child adopted by the couple or adopted in a previous relationship is considered as having the same status as a biological child. ‘Child’ refers to a living son or daughter irrespective of their age or place of abode.

It is recognised nationally that NHS organisations need to focus their budgets on patients who have the most need and can obtain the maximum health gain. Local priority is therefore being given to those couples who are completely childless. This is in line with all other CCGs in Sussex, Surrey and Kent **

Previous sterilisation

ART will not be funded for couples if their sub-fertility is the result of sterilisation in either partner.

Sterilisation is offered within the NHS as an irreversible method of contraception. Considerable time and expertise are expended in ensuring that individuals are made aware of this at the time of the procedure. Since the majority of requests arise for non-medical reasons, CCGs consider that it is inappropriate that NHS funds are used in reversing these procedures. This position is reflected in the information and documentation that accompanies sterilisation procedures.

Lifestyle Factors Couples should be aware of, and acting upon, current advice contained in NICE GL 156 regarding the effect of smoking on fertility and of caffeine and alcohol consumption on the success rates of assisted reproductive procedures.

NICE CG156 states that smoking is likely to reduce female fertility. In addition, maternal and paternal smoking can adversely affect the success rates of assisted reproduction

* DOH NHS visitor and migrant cost recovery programme update February 2017

** http://www.fertilityfairness.co.uk/nhs-fertility-services/ivf-provision-in-england/south-england

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These criteria are applicable to patients who require assisted reproductive technologies listed above. They do not apply to:

Investigations for general fertility problems and the primary treatment of conditions found during such investigation.

Medical treatment to restore fertility (for example, the use of drugs for ovulation induction)

Surgical treatment to restore fertility (for example, laparoscopy for ablation of endometriosis)

Pre-implantation genetic diagnosis and services for members of the armed forces and some veterans, commissioning of which fall under the remit of NHS England.

Other forms of assisted reproductive technologies are not included. Any new treatments or research trial treatments are not included – patients taking part in trials of new treatments will be considered separately and will be within the governance arrangements of that research trial. New developments in assisted reproductive technologies will be dealt with through the agreed local processes. Future updates of these criteria will take these into account national reviews of evidence and revisions to NICE clinical guidelines where appropriate.

7. Funded Cycles of Intra-uterine insemination (IUI) and In vitro Fertilisation

(IVF) Eligible couples will be funded:

for up to six cycles of IUI using partner sperm as a treatment option for people who are unable to, or would find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem or for people with conditions that require specific consideration in relation to methods of conception (for example, after sperm washing where the man is HIV positive),or where a person has specific cultural or religious objections to IVF and at the discretion of the referring gynaecologist;

for two fresh cycles of IVF with or without ICSI if no previous fresh cycles have been undertaken;

for one fresh cycle of IVF with or without ICSI if the couple has already received one fresh cycle, irrespective of how this was funded;

couples will not be funded if either partner has already had two or more previous fresh cycles of IVF with or without ICSI, irrespective of how these were funded; and

overall, eligible couples will be funded for a maximum of four embryo transfers (including no more than two transfers from fresh cycles).

7.1 Key Points and Rationale What is in vitro fertilisation (IVF)?

During IVF, eggs are removed from the woman’s ovaries and fertilised with sperm in a dish. The best one or two embryos that are created are then placed in the woman’s womb a few days later. If there are a number of unused good quality embryos left following a treatment cycle, these may be cryopreserved (frozen) for use in later cycles, called frozen embryo transfers.

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What is intra-cytoplasmic sperm injection (ICSI)? The procedure for ICSI is similar to that for IVF, but instead of fertilisation taking place in a dish, the embryologist selects sperm from the sample and a single sperm is injected directly into each egg. The fertilised egg (embryo) is then transferred to the woman’s womb. The development of ICSI means that as long as some sperm can be obtained (even in very low numbers), fertilisation is possible. What does National Institute for Health and Care Excellence (NICE) currently recommend? NICE CG156 recommends that eligible women aged under 40 years should be offered three full cycles of IVF, with or without ICSI. NICE defines a full cycle of IVF treatment as comprising one episode of ovarian stimulation and the transfer of any resultant fresh and frozen embryo(s). Why are three full cycles of IVF/ICSI not available on the NHS? When making resource allocation decisions in this context, the CCG needs to take into account the needs of the populations suitable for ART, and their wider population. In 2015/16 the EHS and HR CCGs committed £835,000 to funding 2 cycles of IVF for eligible couples. The CCG has concluded that extending provision of IVF/ICSI to three full cycles for eligible couples is currently unaffordable in the context of local priorities.

8. Surgical Sperm Retrieval Eligible couples where the male has obstructive azoospermia will have one surgical

sperm retrieval procedure funded. Surgical sperm retrieval will not be available if sub-fertility is the result of sterilisation. Where the procedure is successful, eligible couples can access IVF with ICSI, in line with policy. Cryopreservation of surgically retrieved sperm will be funded for a maximum of two years

8.1 Key points and rationale

What is surgical sperm retrieval? Surgical sperm retrieval is a set of techniques for collecting sperm from within the male reproductive organs for use in ICSI. ICSI involves an embryologist selecting a single sperm from the sample and injecting it directly into an egg. The fertilised egg (embryo) is then transferred to the woman’s womb. The development of ICSI means that as long as some sperm can be obtained (even in very low numbers), fertilisation is possible.

What are the indications for surgical sperm retrieval? Surgical sperm retrieval is indicated in cases of male sub-fertility where there is testicular sperm production but an absence of sperm in the semen (azoospermia).

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What does National Institute for Health and Care Excellence (NICE) currently recommend? NICE CG156 recommends surgical sperm recovery before ICSI may be performed using several different techniques depending on the pathology and wishes of the man. In all cases, facilities for cryopreservation of spermatozoa should be available.

Why is NHS funded surgical sperm retrieval only available to East Sussex patients with obstructive azoospermia? The available evidence suggests that the success rate for surgical sperm retrieval is good for men with obstructive azoospermia (between 85% and 100% depending on the procedure). Success rates are lower for men with non-obstructive azoospermia (between 44% and 88% depending on procedure). Furthermore studies have found that outcomes of ICSI using testicular sperm from men with non-obstructive azoospermia are generally inferior compared to those with obstructive azoospermia.

9. Sperm Washing

One sperm washing procedure will be funded within the NHS for couples where the man is Human Immunodeficiency Virus (HIV) positive and either he is not compliant with Highly Active Antiretroviral Therapy (HAART) or his plasma viral load is 50 copies/ml or greater and where the female partner is HIV negative.

9.1 Key findings and rationale

What is sperm washing? The purported utility of sperm washing rests on the premise that HIV-infected material is carried primarily in the seminal fluid rather than in the sperm itself. The technique involves purifying sperm from seminal fluid. The sperm is then used in assisted reproductive techniques such as IUI or IVF, with or without ICSI. What are the indications for sperm washing? Sperm washing is normally indicated for couples who wish to have a child where the male is HIV positive and the female is HIV-negative, or to minimise the risk of transmission of resistant virus in couples with the same HIV status. The use of sperm washing has also been proposed in couples where the male is hepatitis C positive and the female is negative. What does National Institute for Health and Care Excellence (NICE) currently recommend with regard to NHS provision of sperm washing for couples where the male is Human Immunodeficiency Virus (HIV) positive? CG156 recommends offering sperm washing to couples where the man is HIV positive and either he is not compliant with HAART or his plasma viral load is 50 copies/ml or greater. What is the safety and clinical efficacy of sperm washing for couples where the male is Human Immunodeficiency Virus (HIV) positive? NICE undertook a review of the research literature and the evidence showed that the procedure appears to be very effective in reducing viral transmission; no cases of transmission to the woman or the baby have been documented. In comparison

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with pregnancy outcomes following ART without sperm washing, higher live full-term singleton birth rates are seen with IVF following sperm washing. This is likely to be because couples undergoing sperm washing were having treatment to avoid HIV transmission rather than for fertility problems. A comparison of pregnancy outcomes for different Assisted Conception Treatments (ACT) methods using washed sperm was also undertaken. Consistent with other studies, IUI cycles had fewer singleton live births than both IVF cycles with and without ICSI, but it also had fewer multiple births. This may reflect the transfer of more than one embryo in IVF cycles.

Why is sperm washing unavailable on the NHS for couples where the male is hepatitis C positive? NICE CG156 recommends that couples who want to conceive and where the man has hepatitis C should be advised that the risk of transmission through unprotected sexual intercourse is thought to be low. What are the eligibility criteria for access to sperm washing? In order to access NHS funded treatment patients will be required to fulfil the relevant eligibility criteria.

10. Intra-uterine insemination (IUI) using partner sperm Up to six cycles of IUI with partner sperm will be funded as a treatment option for

eligible couples who:

are unable to, or would find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psycho sexual problem;

are clinically indicated to receive IUI following a successful sperm washing procedure where the man is HIV positive.

10.1 Key findings and rationale

What is intra-uterine insemination (IUI)? IUI is a form of treatment where sperm are inserted into the uterine cavity around the time of ovulation. IUI can be carried out in a natural cycle, without the use of drugs, or the ovaries may be stimulated with medications. IUI can be undertaken using partner or donor sperm; this policy recommendation addresses the former circumstances only.

What does National Institute for Health and Care Excellence (NICE) currently recommend with regard to NHS provision of IUI using partner sperm? CG156 recommends IUI using partner sperm as a treatment option for people who are unable to, or would find it very difficult to, have vaginal intercourse because of a clinically diagnosed physical disability or psychosexual problem or for people with conditions that require specific consideration in relation to methods of conception (for example, after sperm washing where the man is HIV positive) or where a person has specific religious or cultural objections to IVF.

Why is IUI no longer recommended by National Institute for Health and Care Excellence (NICE) for couples with fertility problems?

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NICE no longer recommends IUI for people with unexplained infertility, mild endometriosis or mild male factor infertility because a review of the literature concluded that IUI without stimulation is no better than expectant management. It is unclear if IUI with stimulation is more effective than expectant management for these groups; however it is likely to increase the risk of multiple pregnancies, which is the single biggest risk of fertility treatment.

11. Donated Genetic Materials Procedures involving donor genetic materials are not funded for any patient group.

Funding of procedures involving donor genetic materials abroad will not be reimbursed by the local NHS.

11.1 Key findings and rationale

What does National Institute for Health and Care Excellence (NICE) currently recommend with regard to NHS provision of assisted reproductive technologies using donated genetic materials? NICE recommends donor insemination and use of donor oocytes should be considered for managing a range of fertility problems. NICE CG156 also recommends consideration of unstimulated IUI as a treatment option, as an alternative to vaginal sexual intercourse, for patients in same sex relationships; this would necessitate the use of donated genetic materials. The above were not considered by NICE to be key priorities for implementation. NICE does not address use of donated embryos or funding of assisted reproductive technologies using surrogates.

Why are Assisted Reproductive Techniques (ART) using donated genetic materials, not available on the NHS for East Sussex patients? When making resource allocation decisions in this context, the CCGs need to take into account the needs of the populations suitable for assisted reproductive technologies, and their wider population. In general resources are focused on groups of patients most likely to have successful outcomes. In the UK, donated genetic materials are in short supply, with demand commonly exceeding supply. The purchase of donor sperm from an independent sperm bank would increase the cost of each cycle of IVF by a minimum of £1,000; costs are variable according to the specification of the purchaser with regard to compatibility and validation of donors. The cost of a donated ovum is around £8,000.

What about NHS funded treatment abroad? An unintended consequence of any policy making ART using donated genetic materials available on the NHS locally may be that patients could seek NHS funded treatments abroad. This is undesirable as clinics may be unregulated and treatments undertaken could pose significant health risks to patients.

12. Use of Surrogates Assisted reproduction techniques involving surrogates are not funded within the

local NHS for any patient group.

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12.1 Key findings and rationale What is surrogacy? Surrogacy is when a woman who is not the intended mother carries and gives birth to a baby for a couple or individual who want to have a child. Partial surrogacy uses sperm from the intended father and an egg from the surrogate. Here fertilisation is usually facilitated by artificial insemination or IUI. Full surrogacy involves IVF, with or without ICSI, and the implantation of an embryo which is not created using the surrogate’s eggs. What are the indications for Assisted Reproductive Techniques (ART) using surrogates? Full or partial surrogacy may be considered an option for women who have a medical condition that makes it impossible or dangerous to get pregnant and/or give birth. Partial surrogacy can also be considered an option for single men and male same sex couples.

What national guidance exists on fertility? In February 2013 NICE issued Clinical Guideline 156 (CG156), Fertility: assessment and treatment for people with fertility problems. Surrogacy was not included within the scope of CG156. How are surrogacy arrangements made in the UK? The Surrogacy Arrangements Act 1985 states that commercial surrogacy is illegal in the UK. However, the surrogate can be paid reasonable expenses such as travel expenses and loss of earnings. The Human Fertilisation and Embryology Authority (HFEA) states that fertility clinics cannot identify surrogates for their patients.

What are the legal issues around surrogacy? Surrogacy arrangements are not legally enforceable, even if a contract has been signed and the expenses of the surrogate have been paid. The surrogate will be the legal mother of the child unless or until parenthood is transferred to the intended mother through a parental order or adoption after the birth of the child. This is because, in law, the woman who gives birth is always treated as the mother. There is an absence of evidence on the long-term psychological impact or social consequences for commissioning couples, surrogates or children born to surrogates. Why are assisted conception treatments using surrogates not available on the NHS for East Sussex patients? There are significant medico-legal issues involved in surrogacy arrangements that would pose risks to an NHS organisation funding this intervention.

13. Fertility Preservation For Patients Receiving Gonadotoxic Treatments Cryopreservation of sperm, oocytes or embryos will be available for fertility

preservation for eligible patients due to receive gonadotoxic treatments. Women undergoing gonadotoxic treatment should have access to a consultation with an NHS fertility specialist before and after undergoing gonadotoxic treatment.

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Storage of embryos, oocytes and sperm will be funded for up to ten years after cryopreservation. NHS funding of cryopreservation of materials will cease where:

fertility is established through tests or conception;

a live birth has occurred;

the patient dies and no written consent has been left permitting posthumous use.

13.1 Key findings and rationale

What treatments can affect fertility? The treatment of cancer frequently involves the use of radiotherapy and/or chemotherapy. These treatments can impact on fertility, either by direct injury to the ovaries or testes from radiotherapy or via systemically administered chemotherapeutic agents. Some treatments for autoimmune disorders such as systemic lupus erythematous, multiple sclerosis and Crohn’s disease can also have gonadotoxic effects. In some cases the individual’s fertility will return after their treatment is completed but in other cases fertility never returns, or is severely impaired. What does fertility preservation involve? It normally involves cryopreservation of semen, oocytes or embryos. Following completion of the potentially gonadotoxic treatment, patients can undergo assisted reproductive procedures using their cryopreserved materials so long as they meet the CCGs’ eligibility criteria. What does National Institute for Health and Care Excellence (NICE) currently recommend with regard to NHS provision of Assisted Reproductive Techniques (ART) for fertility preservation? NICE CG156 recommends offering sperm cryopreservation to men and adolescent boys who are preparing for medical treatment for cancer that is likely to make them infertile and to women of reproductive age who are preparing for medical treatment for cancer that is likely to make them infertile, CG156 recommends offering oocyte or embryo cryopreservation as appropriate if they are 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. Storage of cryopreserved material is recommended for an initial period of 10 years. What are the eligibility criteria for access to Assisted Reproductive Techniques (ART) for fertility preservation? In order to access NHS funded treatment patients will be required to fulfil relevant eligibility criteria set out in this policy prior to accessing cryopreservation of genetic materials and prior to using the cryopreserved materials.

References: NICE (2013) Clinical guideline 156 and 2016 update: – Fertility: Assessment and treatment for people with fertility problems, Online: http://www.nice.org.uk/cg156 ART Template Eligibility Criteria – B&H CCG

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KMCS HPSU October 2013 Amended by B&H CCG March 2015