Rationale and impact
These sections briefly explain why the committee made the recommendations and how they might affect services.
Advice about conception using donor sperm
Why the committee made the recommendation
The committee noted that some people seek donor insemination through unregulated routes such as websites, social media, or friends or family members, instead of through a regulated, licensed fertility clinic. This may be because of limited access to NHS-funded donor insemination or the cost of self-funded care, or factors such as shorter waiting times, better availability of sperm, or previous healthcare experiences. However, the committee agreed that using donor sperm through unregulated routes carries health and other risks. Licensed fertility clinics provide essential safeguards by following strict standards for donor screening, infectious disease testing and genetic evaluation, which reduces the health risks associated with unregulated donations. Licensed fertility clinics also ensure legal parenthood by formalising consent and guaranteeing that donors relinquish parental rights – protections not guaranteed in informal arrangements, which can lead to legal disputes.
The committee agreed that these measures uphold safety, legality and accountability, making treatment in a licensed fertility clinic their recommended approach, and that this should be discussed with couples who are planning conception using donor sperm.
How the recommendation might affect practice
Advising people about the potential risks and harms of using unregulated donor insemination could lead to more people seeking safer donor insemination in licensed fertility clinics. However, the committee were aware that current restrictions on access to NHS-funded donor insemination and the cost of treatment in licensed fertility clinics may pose challenges for some people.
Miscarriage or ectopic pregnancy when trying to conceive
Why the committee made the recommendation
The committee were aware that some people have a miscarriage or an ectopic pregnancy during the year of unprotected vaginal sexual intercourse before they are eligible to have investigations for infertility. Similarly, this can occur during the second year of expectant management for unexplained infertility, or during the 12 cycles of artificial insemination. The committee were aware that in practice, this sometimes means that people are made to restart the eligibility period from the date of the miscarriage or ectopic pregnancy. The committee agreed that such decisions are unjustified. To address this, the committee agreed a new recommendation to clarify this issue and ensure that people do not have to restart the eligibility timeframe after having a miscarriage or an ectopic pregnancy. The same principle also applies to people who are using artificial insemination to conceive.
How the recommendation might affect practice
The recommendation will standardise good practice and reduce variation in service provision. It will reduce unnecessary delays in access to clinical assessment, investigations and treatment for fertility problems in some areas for people who may be subfertile and experience a miscarriage or an ectopic pregnancy.
Testing for male factor fertility problems
Recommendations 1.17.5 to 1.17.11
Why the committee made the recommendations
The committee highlighted the variation in clinical practice in terms of investigations for male factor fertility problems. They also discussed how explorations of couples' fertility problems often focus on the partner with female reproductive organs, and emphasised the importance of assessing male factors as well. Investigations for male factor infertility may have wider implications for the health of the partner with male reproductive organs.
Physical examination and measuring serum testosterone and gonadotrophin levels
Based on their knowledge and experience, the committee agreed that carrying out a physical examination of the scrotum and testes is an essential part of assessing male infertility after 2 or more abnormal semen analyses. It can help detect the underlying causes of semen abnormalities, such as varicocele and testicular cancer, and inform treatment, and is a simple and low-cost procedure. In addition, testing serum testosterone and gonadotrophin levels may reveal an underlying hormonal issue that could be treated.
Sperm DNA integrity (fragmentation) testing
The evidence on treating sperm DNA fragmentation did not show a convincing benefit. Without effective treatments, and given that sperm DNA assays are expensive tests that can take weeks to obtain results, the committee recommended against testing for sperm DNA integrity (fragmentation). They agreed that the link between elevated DNA fragmentation and subfertility has not yet been established. It is also not clear which type of test and what threshold should be used for defining elevated DNA fragmentation. Given these uncertainties, the committee agreed that testing for sperm DNA integrity is not appropriate.
Y chromosome microdeletion testing
According to the evidence and the committee's knowledge and experience, it is almost impossible to extract sperm through surgical sperm retrieval for people with Y chromosome AFZa and AFZb microdeletions. To avoid unnecessary surgical sperm retrieval with no chance of success, the committee agreed the importance of testing for Y chromosome microdeletions in those with azoospermia or a sperm concentration of less than 1 million per ml. This cut-off was agreed through committee consensus, based on their knowledge that the vast majority of microdeletions occur in those with sperm concentrations less than or equal to 1 million per ml. Therefore, testing in those with higher sperm concentrations might not be cost effective.
Testing for cystic fibrosis transmembrane conductance regulator genetic mutations, and karyotype abnormalities and genetic counselling
The committee also reviewed the 2004 recommendations around genetic testing before intracytoplasmic sperm injection (ICSI) for male factor fertility problems, and agreed the need for clearer guidance on tests for cystic fibrosis transmembrane conductance regulator genetic mutations, karyotype abnormalities and genetic counselling. They made recommendations based on consensus to clarify what to test and in whom, and to reflect current best practice.
How the recommendations might affect practice
Physical examination of the scrotum and testes is a low-cost and simple intervention. There may be an increase in offering this, which should lead to improved identification of underlying causes of fertility problems or wider health issues.
Testosterone and gonadotrophin tests are relatively low cost and can support appropriate management of male factor fertility problems by identifying hormonal abnormalities that may be treatable.
Not testing for DNA integrity (fragmentation) reflects current NHS practice.
There may be an increase in testing for Y chromosome microdeletions, but any cost should be offset by reduction in surgical sperm retrieval procedures where it is unlikely to be successful.
The recommendations on genetic testing will use resources more efficiently by clarifying the populations who should be tested for cystic fibrosis transmembrane conductance regulator genetic mutations and karyotype.
Ovarian reserve testing
Recommendations 1.18.3 to 1.18.5
Why the committee made the recommendations
There was a lack of good evidence showing any association between anti-Müllerian hormone (AMH) levels and spontaneous clinical pregnancy. The committee agreed that measuring AMH levels should not be used to predict the chance of spontaneous conception.
There was some evidence of an association between AMH levels and rates of live births and clinical pregnancy after assisted conception, so the committee agreed that AMH could be used as a prognostic indicator for outcomes of assisted conception. Although there was less evidence for antral follicle count (AFC), the committee agreed that AFC has a similar ability to AMH to predict ovarian response in conjunction with assisted conception. Overall, there was sufficient evidence to recommend using either AMH or AFC to form part of the clinical considerations regarding the best possible treatment regimen, and to aid individualised discussions about the chance of live birth following assisted conception.
There was evidence that follicle-stimulating hormone (FSH) levels do not predict clinical pregnancy or ovarian response.
The committee agreed that there may be other indications for using these tests if not for ovarian reserve testing, such as investigating ovulatory disorders.
How the recommendations might affect practice
The use of AMH or AFC in conjunction with assisted conception will likely be increased. Although FSH is now rarely used as an ovarian reserve marker, it is still occasionally offered as a cheaper alternative to an AMH test despite its lack of predictive ability, so the recommendations will change this practice.
Subclinical hypothyroidism
Why the committee only made a recommendation for research
The committee looked for evidence on whether treating subclinical hypothyroidism would have an impact on fertility outcomes, but no evidence from randomised controlled trials was found. The committee agreed that subclinical hypothyroidism would not normally be picked up because it is often asymptomatic; therefore, if treating it would be beneficial, people with fertility problems should also be screened for it. Taking into account the lack of evidence on treating subclinical hypothyroidism and the potential costs of unnecessary screening, the committee agreed that the 2004 recommendations about not offering routine measurement of thyroid function to those without symptoms of thyroid disease are still valid. However, to address the lack of evidence and uncertainty about potential benefits or harms associated with treatment for subclinical hypothyroidism, the committee agreed to make a recommendation for research on the benefits and harms of levothyroxine for the treatment of subclinical hypothyroidism in women, and trans men and non-binary people with female reproductive organs who are receiving fertility treatment.
Coeliac disease testing
Why the committee made the recommendation
The NICE guideline on coeliac disease has a recommendation relevant to people with unexplained subfertility so the committee agreed to cross-refer to it.
How the recommendation might affect practice
The recommendation is already included in the NICE guideline on coeliac disease, but it is not common practice in fertility services. Including it in this guideline may lead to some increase in serological testing for coeliac disease.
Medical management of male factor fertility problems
Recommendations 1.24.1 to 1.24.3, and 1.24.6
Why the committee made the recommendations
The committee agreed, based on their knowledge and experience, that replacement therapy with gonadotrophins is necessary to treat hypogonadotropic hypogonadism.
However, if azoospermia or non-azoospermia is not associated with hypogonadotropic hypogonadism, the effectiveness of treatment is less certain. There was some evidence of benefit for anti-oestrogens and gonadotrophins in improving pregnancy rates and live births, but the evidence had serious limitations, including very small study sizes, a lack of information on the ages of the women involved, as well as confounding factors such as varicocele surgery. Because of the uncertainty of the evidence, and based on their knowledge and experience, the committee agreed that these treatments should only be used as part of a clinical trial in people with impaired semen parameters and no hypogonadotropic hypogonadism. As the evidence was unclear, the committee also made a recommendation for research about the effectiveness of anti-oestrogens or gonadotrophins.
There was no evidence of improved pregnancy rates with the use of androgens, and the committee discussed that, based on their knowledge and experience, taking androgens may even harm fertility.
There was no standardised treatment for sperm DNA fragmentation with different types, doses and combinations of antioxidants, supplements and medical treatments used across studies, and no convincing evidence of benefit because antioxidants showed equivocal effects on live birth and sperm DNA fragmentation. There were also no benefits in relation to clinical pregnancy, miscarriage, stillbirth, and embryo quality or grading. The committee agreed that currently there is too much uncertainty about the relationship between sperm DNA fragmentation and subfertility, about the best way to test and define this, and if and how this should be treated. Before these uncertainties are resolved, they agreed that testing and treating sperm DNA integrity is not appropriate.
How the recommendations might affect practice
The recommendations may decrease the use of gonadotrophins and anti-oestrogens to treat semen abnormalities, except to treat hypogonadotropic hypogonadism, and may decrease the use of androgens to treat semen abnormalities.
The recommendation on treatment for DNA fragmentation reflects current best practice.
Azoospermia
Recommendations 1.25.1 to 1.25.3
Why the committee made the recommendations
There was evidence that vasovasostomy, vasoepididymostomy and epididymovasostomy (all forms of surgical correction) and surgical sperm retrieval all increase chance of live birth and clinical pregnancy. The committee agreed that vasovasostomy is a simpler surgical technique but is not possible in all cases because it depends on the presentation of the obstruction, so the surgeon may need to decide which technique to use during the procedure. Likewise, the committee agreed that the decision whether to use surgical reconstruction or surgical sperm retrieval would depend on other factors including female factors, time since the obstruction and personal preference.
There was no evidence on the techniques for surgical sperm retrieval in obstructive azoospermia, so the committee did not specify a technique.
For non-obstructive azoospermia, there was very limited evidence showing that microscopic testicular sperm extraction (micro-TESE) leads to a greater rate of sperm retrieval (suitable for in vitro fertilisation [IVF] or ICSI) compared to testicular sperm aspiration (TESA). The committee noted that this finding was consistent with their own experience and in clinical practice, micro-TESE would be the preferred method of surgical sperm retrieval. There was evidence that micro-TESE does not increase adverse effects including testicular pain, atrophy, haematoma and infection compared to TESA plus salvage micro-TESE. However, the evidence base was limited and of low quality, and there was no evidence for live birth, clinical pregnancy and miscarriage so the committee agreed that they could only recommend micro-TESE as an option for sperm retrieval.
How the recommendations might affect practice
The recommendation for obstructive azoospermia will standardise practice across the NHS by offering a choice of treatment options.
The recommendations will increase the use of micro-TESE to retrieve sperm for IVF or ICSI for non-obstructive azoospermia.
Y chromosome microdeletions
Why the committee made the recommendation
The evidence, although of poor quality, showed that the rate of successful surgical sperm retrieval in people with Y chromosome AZFa or AZFb microdeletions was very low. This was even lower compared with people with Y chromosome AZFc microdeletions and those without Y chromosome microdeletions. These findings aligned with the committee's experience. The committee noted that the presence of a Y chromosome AZFc microdeletion does not affect the success of surgical sperm retrieval.
How the recommendation might affect practice
The recommendation reflects current best practice.
Reduced sperm DNA integrity
Why the committee made the recommendation
There was limited evidence on testicular sperm extraction as a treatment for sperm DNA fragmentation, and no benefits were shown in terms of pregnancy or miscarriage rates when comparing ICSI using extracted sperm and ICSI using ejaculated sperm. The committee also acknowledged the wider uncertainties about the relationship between sperm DNA fragmentation and subfertility, and the best way to test and define this. Based on this evidence, the committee recommended against surgical sperm retrieval as a way of improving outcomes for people with reduced sperm DNA integrity.
How the recommendation might affect practice
The recommendation reflects current best practice.
Varicocele
Why the committee made the recommendation
There was evidence of higher pregnancy rates following surgical or radiological treatment for varicocele for a subgroup with clinically detected varicocele and abnormal semen analysis, compared with no treatment. Very few studies reported on the outcome of live birth and those that did reported mixed results. Based on the evidence, the committee agreed that treatment for varicocele should be considered for those with clinically detected varicocele and abnormal semen analysis. The committee agreed that female factors should be taken into account because, where there is no chance of spontaneous conception because of female factor fertility problems, treating varicocele in the partner with male reproductive organs would not be needed.
The evidence showed no important difference between surgical and radiological treatment, but the committee noted that no evidence was identified for the important adverse outcome of testicular atrophy for this comparison. A small and statistically significant benefit of microscopic subinguinal surgical treatment relative to other surgical treatments was also observed. The committee noted that, although this option would be likely to be the preferred approach in specialist clinics, it is not universally available.
Because of the limited evidence and uncertainty in terms of the relative clinical and cost effectiveness of different radiological and surgical treatments, the committee made a recommendation for research to compare the clinical and cost effectiveness of radiological, surgical and microsurgical treatment for varicocele.
The evidence review only included couples attempting spontaneous conception. Based on their knowledge and experience, the committee discussed the potential benefits of treating varicocele before assisted conception but they were not aware of any evidence from randomised controlled trials on this topic. Therefore, they agreed that it was not appropriate to make any recommendations for this population.
How the recommendation might affect practice
The recommendation for varicocele might increase the use of this treatment, but this should lower the need for IVF and ICSI because couples could conceive spontaneously without the need for assisted conception. On the other hand, there could be a decrease in unnecessary treatment of varicocele for people in whom the varicocele is only detectable on ultrasound and not on examination.
Management of ejaculatory failure
Why the committee made the recommendation
No evidence from randomised controlled trials was identified so the recommendation was made based on the committee's knowledge and experience. Because there are many different causes of ejaculatory failure, such as retrograde ejaculation, diabetic neuropathy, spinal cord injury and ejaculatory duct obstruction, it is important to identify the cause to determine the most appropriate and least invasive approach to manage the issue. The committee agree that the standard male infertility assessment would usually help identify the cause.
How the recommendation might affect practice
The recommendation reflects current best practice and can lead to more effective use of resources.
Hypogonadotropic hypogonadism
Recommendations 1.30.1 and 1.30.2
Why the committee made the recommendations
The committee discussed that anovulatory infertility may be due to reduced body weight, so increasing weight or reducing excessive exercise, or both, may improve fertility. However, in some cases, the lack of gonadotrophin-releasing hormone from the hypothalamus or gonadotrophins from the pituitary gland leads to failure of ovulation, so replacement therapy with gonadotrophin-releasing hormone or gonadotrophins with luteinising hormone activity is needed to induce ovulation.
The committee noted that there was very limited evidence for increased clinical pregnancy rates with a recombinant follicle-stimulating hormone or luteinising hormone product compared with human menopausal gonadotrophin, but no evidence of a difference in the live birth rate. Because the evidence was so limited, the committee agreed not to recommend a specific type of gonadotrophin.
How the recommendations might affect practice
The recommendations will reinforce current practice to treat hypogonadotropic hypogonadism with gonadotrophins or gonadotrophin-releasing hormones.
Ovulatory disorders due to hyperprolactinaemia
Why the committee made the recommendation
There was some evidence that cabergoline resolves amenorrhoea and improves pregnancy rates. The committee noted that the 2013 guideline had recommended bromocriptine but they were aware, based on their knowledge and experience, that cabergoline is associated with fewer side effects than bromocriptine, is less expensive and only needs to be taken once a week. They therefore agreed that cabergoline should be used to treat hyperprolactinaemia instead of bromocriptine.
How the recommendation might affect practice
The recommendation will increase the use of cabergoline for ovulatory disorders due to hyperprolactinaemia and reduce the use of bromocriptine. This will reduce costs for the NHS.
Tubal surgery for mild tubal disease
Why the committee made the recommendation
The committee based the recommendation on their clinical knowledge and experience as no relevant randomised controlled trials were found. The committee agreed that tubal surgery should be considered as a treatment option for those with mild tubal disease who do not wish to have IVF because of, for example, their preferences, or moral or religious beliefs. The committee drew on current clinical practice and their knowledge of older cohort studies that suggest that tubal surgery may not be effective for more damaged fallopian tubes, so agreed not to recommend it for those with moderate or severe tubal disease. The committee wanted to emphasise that tubal surgery should be performed in centres where appropriate expertise is available, to ensure patient safety.
How the recommendation might affect practice
The recommendation reinforces current best practice.
Tubal catheterisation
Why the committee made the recommendation
Evidence from non-comparative and very-low-quality studies showed some benefit of tubal catheterisation. For example, for women, trans men and non-binary people with bilateral obstruction who would not be able to conceive without the procedure, a live birth rate of 16% and clinical pregnancy rate of 19% could be considered as an appreciable potential benefit. However, the committee noted the considerable heterogeneity and uncertainty in the evidence. The evidence on outcomes of ectopic pregnancy, miscarriage, or tubal perforation following tubal catheterisation was more consistent and showed low rates.
Without comparative trials comparing tubal catheterisation with other treatments, it was difficult to make a strong recommendation. In practice, IVF is often offered to those with proximal tubal obstruction. However, for some people, tubal catheterisation may be the preferred treatment option, particularly where there might be religious or other objections to IVF, or where IVF might not be expected to have a significantly higher success rate relative to spontaneous conception – as in the case of those with diminished ovarian reserve.
Given the uncertainties around the potential benefits, the low rates of harm, and the importance of patient preference and shared decision making, the committee agreed that fallopian tube catheterisation should be considered for those with proximal tubal obstruction. However, this should be in the context of a full treatment discussion that covers the risks and benefits of other treatments, including IVF.
How the recommendation might affect practice
The recommendation reinforces current best practice.
Surgery for hydrosalpinges before IVF
Recommendations 1.34.3 and 1.34.4
Why the committee made the recommendations
There was evidence that salpingectomy before IVF compared with no surgery improves clinical pregnancy rates. No evidence was available on its effectiveness on improving live birth rates. There was also evidence that tubal occlusion before IVF improves clinical pregnancy rates when compared with no surgery. Evidence comparing salpingectomy and tubal occlusion found no clinically important difference between the 2 treatments. The committee noted that salpingectomy is a more invasive procedure but may help those who have chronic pelvic pain in addition to hydrosalpinges. Based on the evidence, the committee agreed that both treatments are options for treating hydrosalpinges before IVF.
There was some evidence that transvaginal aspiration of hydrosalpinges before IVF is effective in improving clinical pregnancy rates compared with no treatment. The committee noted that aspiration does not provide a permanent solution, and that fluid often re-accumulates. Based on the evidence, the committee agreed that aspiration can be considered for those for whom laparoscopic surgery is not advised.
How the recommendations might affect practice
Recommendation on salpingectomy and tubal occlusion reflect current practice. The recommendation on aspiration to treat hydrosalpinges may lead to an increase in this procedure as it is not currently common practice. If it is done at the time of egg collection, no extra procedure would be needed. There could indeed be an overall resource saving through reduced need for further IVF cycles if people who would otherwise not have treatment for their hydrosalpinges (because laparoscopy would be risky) would increase their chances of pregnancy through aspiration treatment.
Unexplained fertility problems in people trying to conceive through unprotected vaginal sexual intercourse
Recommendations 1.38.2 and 1.38.3
Why the committee made the recommendations
A network meta-analysis (NMA) compared the following options for people with unexplained fertility problems:
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expectant management (no treatment)
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different ovarian stimulation regimens
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intrauterine insemination (IUI) with or without ovarian stimulation
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IVF.
The NMA compared these with their effect on live birth rate, clinical pregnancy rate and multiple gestation. An economic model was developed based on the NMA. Based on the clinical- and cost-effectiveness evidence, the committee concluded that IVF is the most cost-effective first-line treatment, and ovarian stimulation alone is not effective or cost effective. There was sufficient evidence that IUI with ovarian stimulation with a gonadotrophin could be cost effective, so the committee agreed that it could be considered as an alternative first‑line treatment option before IVF. The committee acknowledged that some people may prefer the less invasive treatment of IUI to IVF.
Most of the evidence reviewed focused on people with unexplained fertility problems, although some of the studies extended the population to include those with 'mild endometriosis' and 'mild male factor fertility problems'. However, because these were not distinct population groups in the evidence and no standard definitions exist, the committee did not refer to these in the recommendations.
How the recommendations might affect practice
More people might opt for IUI (with a gonadotrophin) as first-line treatment before IVF. This could result in some increase in costs, but the committee agreed that this should be limited as it would likely only affect a small proportion of the relevant population and would avoid the need for IVF for some. Otherwise, the recommendations are not expected to have a significant resource impact as the 2013 guideline also recommended IVF as a first-line treatment.
Endometriosis
Recommendations 1.36.1 to 1.36.3
Why the committee made the recommendations
The committee reviewed the evidence comparing the clinical and cost effectiveness of expectant management (no treatment), different ovarian stimulation regimens, IUI with or without ovarian stimulation, and IVF. Most of the populations in the studies were people with unexplained fertility problems, although some of the studies extended the population to include those with 'mild endometriosis' and 'mild male factor fertility problems'. 'Mild endometriosis' in the studies was typically defined as the revised American Society for Reproductive Medicine (rASRM) stage 1 or 2. However, these were not distinct population groups in the evidence, so the committee did not to refer to these in the recommendations.
Endometriosis can cause infertility, and first-line treatment – such as hormone treatment with the oral contraceptive pill – is not appropriate for women, trans men and non-binary people with female reproductive organs who are trying to conceive. Surgical treatment for endometriosis may be an option, and the committee acknowledged that NICE's endometriosis guideline provides recommendations for situations where fertility is a priority.
The committee agreed that fertility management options for endometriosis include expectant management, surgical treatment or assisted reproductive techniques. The most appropriate option depends on various factors, such as how long the person has been trying to conceive, the symptoms and severity of the endometriosis, their age and ovarian reserve, and the presence of any male factor fertility issues.
In some cases, expectant management would not be an option where, for example, there is considered to be little chance of spontaneous conception because of the extent or severity of the endometriosis, or where the endometriosis symptoms have such an impact that the person could not stop taking symptom-relieving hormone treatment for an extended period. The committee also noted that the severity of endometriosis based on imaging (using, for example, rASRM staging) does not necessarily correspond with the impact of the endometriosis on the person's fertility or quality of life. The committee were aware of the Endometriosis Fertility Index (EFI), which is a validated tool that can help with advising on the chances of pregnancy following surgery, and identify those who would benefit from assisted reproductive techniques.
Based on the clinical- and cost-effectiveness evidence, compared to IUI (with or without stimulation) or ovarian stimulation alone, IVF is the most cost-effective first-line treatment, and ovarian stimulation alone is not effective or cost effective. There was sufficient evidence that IUI with ovarian stimulation with a gonadotrophin could be cost effective, so the committee agreed that it could be considered as a treatment option. The committee discussed that in practice, this option could be appropriate for those without deep endometriosis and with patent fallopian tubes. They also acknowledged that some may prefer the less invasive treatment of IUI to IVF.
How the recommendations might affect practice
The recommendations should improve care for couples with fertility problems related to endometriosis. They reinforce the need to assess the couple's overall fertility potential and consider treatment options based on multiple factors including symptom severity, recognising that the physical extent of endometriosis does not always correlate with fertility outcomes. The recommendations may increase the use of stimulated IUI as a treatment option before IVF, and will reinforce the option of surgery as a treatment option.
Access criteria for IVF
Recommendations 1.39.2 and 1.39.3, 1.39.6 and 1.39.7, and 1.39.9
Why the committee made the recommendations
Evidence supported using ovarian reserve (using anti-Müllerian hormone or antral follicle count) as a prognostic indicator for outcomes of assisted conception, so the committee agreed that ovarian reserve should be taken into account when discussing IVF as a treatment option.
The recommendations on IVF access criteria are based on an economic analysis that used validated prediction models to estimate the effectiveness and cost effectiveness of IVF in different clinical scenarios. The committee agreed that the economic analysis, despite some limitations, provides stronger evidence than the 2013 guideline that 3 full cycles of IVF is a cost-effective treatment for the NHS to provide for those under 40 years. This is manifested by much lower incremental cost-effectiveness ratios (ICERs) than observed in the 2013 guideline, typically falling below a cost-effectiveness threshold of £20,000 per quality-adjusted life year (QALY). The 2013 guideline had used a less stringent cost-effectiveness threshold of £30,000 per QALY.
The analysis suggested that up to 6 cycles could be cost effective using a threshold of £20,000 per QALY. However, there were some uncertainties in the evidence, particularly for cycles 4 to 6. These uncertainties relate to concerns about increasing selection bias in the datasets informing the prediction models and the very small numbers of women in these datasets having 4 or more cycles, resulting in considerable sampling uncertainty around the point estimates for predicted live birth rates for these higher order IVF cycles. The committee agreed that the evidence was not sufficiently robust to justify increasing the number of cycles initially being offered because of its potentially significant resource impact, but agreed that further cycles, beyond the initial 3, could be considered.
For those aged 40 or 41 years, the cost-effectiveness evidence for IVF was less clear cut, and in some model scenarios, was not found to be cost effective. However, the committee did note that a limited number of IVF cycles was often cost effective, especially if the inherent uncertainty in the model parameters was taken into account. Therefore, the committee agreed that the evidence did not support removing the provision of IVF altogether for this age group and recommended that 1 cycle of IVF be offered.
However, the committee agreed that the cost-effectiveness analysis did not provide sufficiently strong evidence to support the provision of IVF to 42‑year‑olds. The committee agreed on the need to produce pragmatic recommendations that reflected the totality of the cost-effectiveness evidence and the limitations of the data. In women aged 42 years, no cycles of IVF were ever cost effective at an ICER of £20,000 per QALY in any of the scenarios in the base-case analyses. And for most clinical scenarios included in the analysis, IVF was not cost effective even when using the less stringent £30,000 per QALY decision threshold. In the limited scenarios where borderline cost effectiveness was suggested, limitations in the data, likely overestimation of IVF effectiveness or other factors, led to the committee to conclude that IVF is not a cost-effective treatment for people aged 42 or over.
How the recommendations might affect practice
In current practice, very few areas in England offer IVF treatment according to NICE recommendations. The cost-effectiveness evidence for IVF for those under 40 is now stronger, which could lead to an increase in the number of IVF cycles provided by the NHS. This would have a resource impact, although, based on their knowledge of localised data where more cycles are offered, the committee agreed that the provision of IVF would likely not increase that much. Areas that currently offer IVF to 42‑year‑olds would be expected to change practice, so there could be some modest cost savings in those areas.
Pre-treatment
Recommendations 1.40.1 and 1.40.2
Why the committee made the recommendations
The evidence on endometrial scratch was inconclusive. There were mixed findings across different studies, including potential harm, potential benefit, or no effect. Endometrial scratch is an invasive procedure that has time, resource and financial costs because it is not possible to combine it with another procedure. Because of the uncertainty and inconsistency in the evidence, and the potential for endometrial scratch to have a negative impact on IVF outcomes or no impact at all, the committee agreed that it should not be offered.
There was conflicting evidence from randomised controlled trials (RCTs) on the effectiveness of screening hysteroscopy before assisted conception for those without known or suspected uterine abnormalities on outcomes of live birth and clinical pregnancy. Larger, better quality, multicentre RCTs showed no benefit on these outcomes, whereas several smaller RCTs with a higher risk of bias showed there to be an important benefit. Balancing the uncertainty in the evidence around any benefit against the invasiveness and cost of the procedure, the committee concluded that hysteroscopy should not be offered as a way to improve IVF outcomes. However, the committee recognised the importance of hysteroscopy when uterine or endometrial abnormality is suspected.
How the recommendations might affect practice
There may be a reduction in unnecessary procedures because endometrial scratch, and hysteroscopy are sometimes done in current clinical practice.
Endometrial receptivity testing
Why the committee made the recommendation
The evidence showed no difference in clinical pregnancy and live birth rates between gene expression analysis using endometrial receptivity array (ERA)-timed frozen embryo transfer and standard frozen or fresh embryo transfer. There was also evidence that ERA-timed frozen embryo transfer had a lower risk of multiple gestation compared with standard fresh embryo transfer but led to an increased rate of clinical pregnancy loss.
There was no evidence on treatment of endometrial abnormalities related to the microbiome or microbiological analysis, so the committee made a recommendation for research on treatments based on endometrial receptivity testing.
How the recommendation might affect practice
The recommendation will decrease the use of endometrial receptivity testing.
Immunological treatments
Why the committee made the recommendation
Overall, there was no convincing evidence that immunological treatments are effective in improving fertility outcomes, and there are various safety concerns associated with their use. The committee agreed that they should not be used as part of fertility treatment.
The evidence on intralipids was inconclusive and studies had a high risk of bias. One RCT showed an increase in live birth rate in the intralipids arm, the other studies showed no important difference between groups either for live birth or for miscarriage rates. The committee also discussed the risks of intralipid use, including the potential for congenital malformations, common, minor side effects (such as headache and nausea), and rarer, more serious side effects (such as bone pain and muscle weakness). The committee agreed that the existing evidence does not justify its use.
The evidence on intravenous immunoglobulins (IVIG) came from small studies and showed no effect on live birth or miscarriage rates. In addition, there are potential safety concerns, including risks associated with any blood products as well as common side effects such as headache and muscle pain, and more serious adverse events such as thrombosis and kidney failure. The committee noted that IVIG is an invasive and expensive treatment, and agreed that the existing effectiveness evidence and potential risks do not justify its use.
In terms of steroids (glucocorticoids), there was poor-quality evidence that showed some mixed findings, but overall did not find steroids to have an effect on fertility outcomes, including live birth, clinical pregnancy and miscarriage. Some of the studies showed a benefit of steroids for live birth and miscarriage rates but others showed no difference between groups who received steroids or no steroids for these outcomes. The committee discussed the significant safety concerns associated with the use of steroids, most importantly that they suppress the immune system, which puts patients at risk of infections, and other side effects. Due to the lack of convincing evidence of effectiveness and serious safety concerns, the committee agreed that steroids should not be used as part of fertility treatment.
How the recommendation might affect practice
The recommendation will reinforce current best practice.
Embryo selection strategies
Why the committee made the recommendation
Pre-implantation genetic testing for aneuploidy (PGT‑A)
Evidence on the effectiveness of pre-implantation genetic testing for aneuploidy (PGT‑A) on improving live birth rates was inconclusive and there are potential risks associated with its use. PGT‑A has the potential to reduce the number of viable embryos available for transfer, which can mean that embryo transfer cannot take place in that IVF cycle. Emerging evidence shows a potential benefit of PGT‑A in terms of reducing miscarriage; however, there are still significant uncertainties around PGT‑A's overall effectiveness for improving live birth and pregnancy rates. Based on the evidence, the committee agreed that PGT‑A should not be offered as part of fertility treatment to improve live birth rates.
Time-lapse imaging
Evidence on embryo selection using time-lapse imaging compared with conventional embryo selection showed no benefit on ongoing pregnancy, clinical pregnancy or live birth. The evidence for all outcomes was of very low certainty. The committee were also aware of a 2024 randomised controlled trial (RCT) that showed no important difference in live birth rates for time-lapse imaging compared with standard care. Although the committee agreed that current evidence does not show embryo selection using time-lapse imaging to be better than conventional embryo selection, time-lapse systems may have other benefits, including undisturbed incubation, and more research is needed to understand the full potential of these technologies.
The committee did not make a recommendation about the use of time-lapse imaging for embryo selection because there is no evidence of clinical benefit relative to conventional embryo selection. However, the committee did not want to preclude the use of time-lapse imaging because these systems are widely used and may have benefits in terms of incubation, such as providing a more stable environment than conventional systems, even if benefits in terms of embryo selection are less clear. The committee agreed that further research would be needed but that it would be premature to draft a fully specified and implementable research recommendation that would be able to deliver conclusive results about the potential benefits of time-lapse imaging for embryo selection.
How the recommendation might affect practice
The recommendation on PGT‑A should reinforce current best practice. Time-lapse systems are used in practice. No recommendation was made on time-lapse imaging for embryo selection and this should not have an impact on current practice.
Intracytoplasmic sperm injection
Recommendations 1.50.1 to 1.50.5
Why the committee made the recommendations
The committee made recommendations based on their knowledge, experience and current best practice because the original 2004 recommendation on indications for ICSI was outdated and no longer helpful.
The committee reviewed evidence on the effectiveness of ICSI for non-male factor fertility problems. The evidence showed that ICSI does not have an impact on live birth rates, clinical pregnancy rates or any other outcomes. The committee agreed that ICSI should not be used for non-male factor fertility problems. However, in line with the original 2004 recommendation on ICSI, the committee agreed that ICSI could be considered if previous standard IVF cycles have resulted in failed or very poor fertilisation.
There was insufficient evidence on the effectiveness of intracytoplasmic morphologically selected sperm injection (IMSI) as an adjunct to ICSI in terms of improving live birth rate compared with standard ICSI, so the committee agreed that it should not be used, because it is unlikely to provide any benefit over standard ICSI.
Evidence on physiological intracytoplasmic sperm injection (PICSI) showed no difference in rate of live births when compared with standard ICSI, therefore the committee agreed that it should not be used.
How the recommendations might affect practice
The recommendations will decrease the use of ICSI for non-male factor fertility problems and could therefore result in cost savings.
The recommendations on IMSI and PICSI should reinforce current best practice.
Fertility preservation for medical indications
Recommendations 1.53.1, and 1.53.5 to 1.53.8
Why the committee made the recommendations
The 2013 guideline recommendations on fertility preservation only covered people with cancer who wish to preserve their fertility. For the 2025 update, the population was expanded to cover anyone with a medical indication likely to impair their reproductive potential, including medical or surgical treatments or medical conditions. Most of the evidence was among people with cancer; however, there was evidence that fertility preservation can be successful for other medical indications. While the need for fertility preservation often arises in the context of planned gonadotoxic cancer treatment, the committee acknowledged that numerous other medical conditions and medical or surgical interventions may lead to a high risk of fertility problems. The committee agreed that fertility preservation should be discussed as an option for anyone with an appropriate medical indication. In some cases, the need for treatments that will impact fertility is urgent, so it is important that discussions around preserving fertility are held at the earliest opportunity.
Cryopreservation of sperm is established practice and supported by evidence, but cryopreservation of testicular tissue is still experimental and very limited evidence was available. This is particularly relevant for boys before and during puberty. Therefore, the committee made a recommendation for research about testicular tissue cryopreservation among prepubertal and peripubertal boys undergoing treatment for cancer or other conditions, or in situations that are likely to impair their fertility.
The committee also reviewed the evidence on oocyte and embryo cryopreservation and ovarian tissue cryopreservation. Given the larger evidence base, higher live birth and clinical pregnancy rates, and more established retrieval procedures, the committee agreed that oocyte or embryo cryopreservation should be offered for medical indications. The evidence on ovarian tissue retrieval and cryopreservation was more limited but showed it is feasible and effective. There is also NICE interventional procedures guidance about this. This option is particularly relevant for girls before puberty, when oocyte and embryo retrieval would not be possible.
Consent to store cryopreserved material must be renewed with the person every 10 years for storage to lawfully continue. In addition to the legal requirement, the committee emphasised the importance of more robust follow-up procedures to discuss the need for continued storage. Balancing considerations such as minimising unnecessary storage time, the resources needed to organise follow-ups, and risk of losing touch with people, the committee agreed follow-ups at least every 5 years would be reasonable but leaving flexibility.
How the recommendations might affect practice
There may be some variation in the provision of NHS-funded fertility preservation for the range of medical indications, but the recommendations broadly reflect current practice and therefore are not expected to result in a significant resource impact for the NHS. The recommendation on regular follow-ups could have some resource implications but ultimately could lead to cost savings as unnecessary storage would be avoided.