In vitro fertilisation: eligibility, processes and technologies

Introduction

Approximately 1 in 7 UK couples are unable to achieve a pregnancy after 12 months or more of regular, unprotected sexual intercourse^​1​. This phenomenon is classified as infertility and includes individuals who have never conceived successfully (i.e. primary infertility), as well as those who have previously conceived but are now unable to do so (i.e. secondary infertility)^​2​. Infertility can be ascribed to various aetiologies (see Table 1)^​1,3,4​.

Table 1: Causes of infertility

While aetiology largely corresponds to anatomical, genetic and disease predisposition, modifiable lifestyle factors are increasingly blamed for infertility issues^​1–5​.

Assisted reproductive technology revolutionised the fertilisation of gametes outside the human body, succeeding in the birth of the world’s first ‘test-tube baby’, Louise Brown, in 1978^​6​. In vitro fertilisation (IVF) is an innovative technology that has rapidly evolved to become accessible worldwide, producing nearly 400,000 live births in the UK since the Human Fertilisation and Embryology Authority (HFEA) — the UK’s independent regulator for fertility treatment — began monitoring, licensing and inspecting clinics in 1991^​7​. Beyond infertility, assisted reproductive technologies have expanded scope to protect reproductive potential through cryopreservation, benefiting patients undergoing cancer treatment^​8​, sickle cell anaemia, thalassaemia, pelvic surgeries or gender dysphoria therapy^​9​. This has created a novel path towards parenthood, where gametes and embryos can be frozen with the intention of starting a family later in life. IVF has also become more accessible, with increased uptake among same-sex female couples and single patients. This has resulted in increased popularity for donor eggs or sperm, while surrogacy has declined^​10​. Today, approximately one child in every classroom is born from IVF^​10​.

Although not without established or potential physical risk^{​11–20​} and psychological challenges^{​19–21​}, the HFEA’s 30-year report, published in June 2026, found that IVF is at its most successful and safest to date^​7​, with birth rates for under 44-year-olds improving year on year. Success is influenced by a myriad of predictors^​22​, where age is an important factor affecting fertility^​23​ (see Tables 2^​10​ and 3^​24​) and the overall chance of pregnancy success^​1​. However, a growing population of patients continues to be aged over 40 years^​10​.

Table 2: IVF success rates by maternal age

Table 3: IVF success rates by paternal age

Cost of IVF

IVF is offered on the NHS under specific criteria, leaving self-funding as the alternative option for non-qualifiers (see Table 4)^​1​. While governments define NHS eligibility guidance in Scotland and Wales, in England, it is the National Institute for Health and Care Excellence (NICE) that provides guidance (see Table 4)^​1​. Ultimately, local integrated care boards make the final decision and can stipulate additional criteria for approval (e.g. ideal weight, non-smoker status, aged under 35 years or no previous offspring of either partner)^​25​.

Table 4: National Institute for Health and Care Excellence IVF access criteria

A typical three to six-week cycle of IVF costs at least £5,000^​25​, with additional costs of medication and storage also needing to be factored in^​26​. Equitable access to fertility care remains a challenge, as shown by the growing reliance on privately funded IVF. The proportion of IVF cycles funded by the NHS has fallen from 35% in 2019, to 28% in 2024, meaning that 72% of all IVF treatments in 2024 were privately funded. Geographically, accessibility also varies significantly. For example, NHS funding accounts for 54% of cycles in Scotland, compared with 50% in Northern Ireland, 35% in Wales and just 25% in England, where it is the highest in the north east of England (51%) and lowest in the south west of England (20%)^​10​. 

Mechanisms of natural fertility

Natural conception follows sexual intercourse, as sperm travel through the cervix and uterus into the fallopian tubes to fertilise an awaiting egg^​27​. The hypothalamic-pituitary axis orchestrates both male and female natural fertility (see Figure 1^{​27–34​}). In female fertility, this takes place in timed phases within an average 28-day follicular, ovulation and luteal menstrual cycle (see Figure 2), through a coordinated rise and fall of gonadotrophin hormones (e.g. LH, FSH) and sex-steroids (e.g. oestrogen and progesterone). 

Figure 1: Role of key fertility hormones in females and males

Gonadotrophin releasing hormone (GnRH) plays a central regulatory role in regulating the fertility axis^​28​. The hypothalamus secretes GnRH in a pulsatile fashion to stimulate the anterior pituitary to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), working in synergy to develop follicles (in female fertility) and sperm (in male fertility). 

In female fertility, FSH is crucial for follicular recruitment in the early follicular phase and leads to a rise in oestrogen, propelling luteinising hormone in the late follicular phase (see Figures 2 and 3)^​28,29​. A mid-cycle surge (approximately day 14) of LH forces the dominant mature follicle in the ovaries to burst and release an egg. The LH surge also triggers the formation of a corpus luteum. This structure secretes progesterone and oestradiol in the luteal phase^{​27–29​}. Figure 2 describes the female menstrual cycle in more detail.

Figure 2: menstrual cycle interactive figure

In male fertility, LH from the pituitary stimulates testosterone production in the testes, which is essential for spermatogenesis. Meanwhile, FSH synergistically supports the regulation, nourishment and protection of developing sperm^​28​. A blastocyst (i.e. an early-stage embryo) implants into the uterine wall six to ten days post-fertilisation, through apposition (i.e. contact), adhesion (i.e. attachment) and invasion (i.e. penetration)^​27,30​. Successful implantation depends on harmony between the blastocyst and endometrium, regardless of natural or artificial fertilisation^​30​. This encompasses optimal egg^​31​, sperm^​32​ and thus embryo quality^​30​, which is a primed uterus that is receptive to an embryo^​30​ and hormones (see Figure 2) that promote implantation and sustain early pregnancy^{​27–30​}.

The feedback loops that govern hormonal control in both males and females are displayed in Figure 3 below. 

Figure 3: Hormonal control of female and male fertility

IVF process and protocols

An IVF cycle takes control of the hypothalamic–pituitary–adrenal axis to prevent women from having their own LH surge and subsequent ovulation^​35,36​. Egg maturation, ovulation and collection must be planned in a controlled manner (see Figure 4).

Figure 4: IVF process

IVF protocols

A crucial element of IVF involves preventing a premature LH surge, thereby offering a predictable opportunity for oocyte retrieval^​1​. Dominating IVF regimens are the GnRH agonist and antagonist protocols (see Table 5^​37,38​), with differing modes of action to suppress the natural LH surge^{​1,37,38​}. The shorter GnRH antagonist protocol is increasingly recognised as a more patient-friendly and contemporary alternative to the conventional long GnRH agonist regimen. Several variations of both protocols exist, reflecting ongoing refinements in clinical practice to optimise patient outcomes. In 2025, the European Society of Human Reproduction and Embryology (ESHRE) updated evidence-based guidance and best-practice recommendations for ovarian stimulation^​38​. 

Table 5: Comparison of agonist and antagonist IVF protocols

It is important to note that for both the long and short protocols, many drugs are used off-label, thus doses do not exist in product licences and vary in drug literature. Long-standing experience has established anecdotal doses that vary between clinics.

Pharmacological adjuvants and add-ons

Clinics offer pharmacological adjuvants or add-ons on an empirical basis to support evidence-based treatments^{​39–41​}. The rationale behind many adjuvants in IVF is based on mechanisms of action and off-label indications^​41​. However, many lack evidence of improved IVF success in randomised controlled trials, as reflected in HFEA traffic-light ratings^​39​. NICE also advises that further research is required to determine their efficacy^​1​, while some even have serious side effects^​39​. Patients must therefore be informed of the limited evidence and potential risks. 

Male treatment during IVF

Male infertility treatments are aimed to improve sperm parameters: sperm concentration, semen volume and total sperm per ejaculate. Pharmacological treatment will be indicated for specific causes of infertility (e.g. in men with congenital or acquired hypogonadotrophic hypogonadism or oligozoospermia) with lifestyle change recommended to optimise sperm health (e.g. smoking cessation, reduced alcohol intake and maintaining a healthy BMI). For more information on treatment for male infertility see ‘Infertility in men: assessment and treatment’. 

Intracytoplasmic sperm injection

Some sperm may fail to penetrate the zona pellucida (i.e. the glycoprotein coat surrounding the egg) for a variety of reasons. For example, they may not move in a typical fashion or may lack the inclination to swim towards the egg. Others may be sub-optimal quality, an abnormal morphology or find the egg exterior too thick to penetrate^​42​. Intracytoplasmic sperm injection (ICSI) can overcome the challenges posed by male infertility by identifying an optimal single sperm and manually fusing gametes. This approach is also advantageous when men cannot produce sufficient sperm for traditional IVF or when a physical impediment prevents sperm release^​42​.  

Intracytoplasmic morphologic sperm injection

Intracytoplasmic morphologic sperm injection (IMSI) allows visualisation of sperm under high magnification (over x6000), providing detailed images of sperm defects that cannot be achieved with the magnification in ICSI alone^​43​. However, the results of randomised controlled trials show no evidence that IMSI improves pregnancy rates.

Intrauterine insemination

Intrauterine insemination (IUI) is less invasive than IVF, as sperm are injected directly into the womb to naturally fertilise an egg, with or without follicle stimulation drugs^​44​. This approach skips several IVF steps, avoiding egg retrievals and the need to artificially create embryos. Donor sperm may be utilised in the absence of female fertility issues, when sperm is too poor in quality to achieve successful fertilisation, or for single women or same-sex female couples. IUI can also help those with physical or psychological barriers to intercourse. Although less invasive and approximately 25% cheaper, success rates are 66% lower for IUI than IVF cycles^​44​. Other disadvantages include the inability to create an optimal embryo or monitor fertilisation, and a reliance on the reproductive system playing its part. Without the same level of control, several IUI attempts are common before a successful pregnancy is achieved. 

Alternative and less invasive IVF options

It is important to appreciate that IVF does not always pertain to medication, with alternative approaches that involve fewer or no drugs. This can benefit patients who do not want, need or cannot choose traditional IVF^​45​. For example, cancer treatments can risk fertility damage, making gamete freezing invaluable in preserving fertility^​8,9​. For others, freezing or discarding embryos may conflict with personal or religious beliefs, and so natural IVF may be preferred^​45​. With respect to medication, potential side effects and allergic reactions can risk terminating cycles. Hence, individuals with strong responses to stimulation (i.e. ovarian hyperstimulation syndrome (OHSS)) or susceptibility to oestrogen-sensitive cancers may need to opt for modified approaches^​38,45​. A selection of the most common alternative and less invasive options is summarised below. 

Natural IVF

Rather than aiming to boost egg production, natural IVF works with the menstrual cycle without drug intervention and therefore relies on the body’s ability to ovulate naturally. The natural leading follicle is closely monitored, with IVF ensuing the collection of one naturally matured egg. With this approach, there is a risk of missing the LH surge and subsequent egg release, so modified natural cycles integrate drugs to control final oocyte maturation to mitigate this risk^​45​.

Mild stimulation IVF

This approach works in synchronisation with a natural menstrual cycle, though by combined action with low dose follicle stimulating drugs over a short stimulation phase^​45​. This reduces costs and treatment time to two weeks; minimising stress and the severity of side effects associated with higher doses and longer stimulation periods. It aims for fewer oocytes, whilst significantly reducing OHSS^​38​. 

In vitro maturation

In vitro maturation (IVM) is a relatively novel technique. Uniquely, immature eggs are removed before maturation, which instead occurs in the laboratory, bypassing follicle stimulating drugs and eliminating OHSS risk. This can be advantageous in oestrogen-sensitive cancers, since IVM avoids the oestrogen output linked to ovarian stimulation. It also enables immediate cryopreservation to preserve fertility before urgent cancer therapy. However, eggs matured in vitro are lower in quality than eggs matured via ovarian stimulation. In addition, the technique is limited to ICSI^​45​.

Considerations or interactions with other medicines 

Pharmacists play a vital role in navigating the pharmacological complexities of infertility treatment^​46​. Their expert knowledge of drug actions, pharmacokinetics, interactions, stability and safety is essential to clinical decision-making, guiding drug choices based on pre-existing conditions or allergies, adjusting treatment, or managing adverse effects requiring urgent attention. They also review the patient’s own drugs, herbal and over-the-counter remedies and supplements, to assess their impact on fertility, compatibility with treatment and teratogenicity in early pregnancy. Given that infertility regimens often involve multiple, precisely timed oral and injectable medications, pharmacists can oversee procurement and advise on preparation and administration. They also help prevent medication errors, reduce risks and minimise patient costs. Following successful treatment, pharmacists are well-positioned to recommend safe treatments for common early pregnancy symptoms (e.g. nausea, constipation and reflux), assess the suitability of prescribed medicines, make interventions, screen pre-conception and pregnancy supplements, provide emotional support, and refer to early pregnancy services and infertility support groups. Ultimately, pharmacists can support a safe and successful IVF journey through to early pregnancy.

For a summary of interactions and considerations with other medication, see Box^{​47–54​}.

Improving fertility: lifestyle advice 

It is widely acknowledged that modifiable lifestyle factors influence fertility status^{​1,2,4,5​}. Factors including weight, smoking, alcohol consumption, mental health, nutrition, occupational exposures and recreational drug use can negatively impact reproductive outcomes^​5​. 

BMI plays a significant role in optimising fertility^{​1,5,55–58​} and IVF outcomes in both genders^​56​. Both high and low BMIs can disrupt hormonal balance and delay conception^{​57–60​}. In women, obesity induced oestrogen production can interfere with menstrual cycles, hinder ovulation and promote hyperplasia^​58​. High BMIs also increase the risk of suboptimal embryos, foetal congenital anomalies, and miscarriage^{​1,57,58​}. In IVF, a reduced response to gonadotropin medication and challenging egg retrieval may be experienced^​56​. 

Additionally, higher BMIs are closely linked to polycystic ovary syndrome (PCOS)^​56,59​, where weight gain is often compounded by insulin resistance^​1​. As PCOS is the most common cause of infertility in young women, first-line treatment emphasises diet, exercise and behavioural interventions for weight management^​59​. Conversely, very low BMIs can reduce oestrogen levels until ovulation ceases altogether^​60​. In men, high BMI can increase scrotal temperatures, contribute to erectile dysfunction and, as with low BMI, is associated with lower testosterone and poor sperm quality^​61,62​. The ideal female BMI for fertility lies between 18.5 and 24.9 kg/m², while just a 5–10% weight reduction can be sufficient to restore fertility in women^​55​.

Smoking is detrimental to fertility, as people who smoke are twice as likely to be infertile as non-smokers^​63​. It increases the risks of spontaneous miscarriage and ectopic pregnancies, while reducing live birth rates^{​3,63,64​}. Several hypotheses, including inflammation, disruption of the hypothalamus-pituitary-axis and thus alteration of spermatogenesis, have been attributed to tobacco-inflicted abnormal semen parameters^​65​. Smoking-induced oxidative stress reduces quality, motility and sperm count^​4,32​. Moreover, smoking is predominantly blamed for sperm DNA fragmentation aetiology, which has been identified as a major cause of male infertility, compromising successful fertilisation and embryo development^​4,32​. Female smokers have lower ovarian reserves, hindered uterine blood flow and compromised endometrial linings^​4,5​. As well as smoking, drugs can hinder ejaculation^​4,5,63​. Recreational drugs (e.g. cannabis) can dysregulate fertility hormones and cause serious, irreversible damage, possibly rendering men and women infertile^​5,65​.

There is strong evidence showing that excess alcohol causes testicular damage and hinders spermatogenesis^{​5,65,66​}. It also disrupts menstrual cycles, ovulation and implantation, owing to oestrogen elevation^​5​. It is important to note that negative effects are dose dependent. As a result, reducing or quitting alcohol consumption can reverse damage^​66​. 

Endocrine disruption is well documented for its detriment to male fertility, where semen quality is particularly vulnerable to pesticides, metals and chemicals^​65​. Additionally, bisphenols commonly found in plastics and cosmetics can cause testicular atrophy and mimic oestrogen, lowering natural levels in women. This is linked to lower oocyte quality, oocyte retrieval rates and embryo implantation success in IVF^​67​.

The effects of temperature on male fertility are also well established. Testicular temperature is maintained lower than core body temperature to ensure normal spermatogenesis. This is compromised by excess heat from laptops, tight clothing, driving and hot tubs, which raises scrotum temperature and impairs normal sperm parameters^​5​.

Several medications have the potential to impair reproductive mechanisms, so it is advisable to assess this prenatally, considering sperm and egg development take approximately two and three months, respectively^​28​. Medications may induce impotence (e.g. alpha blockers, beta blockers, selective serotonin reuptake inhibitors)^​5,68​, suppress the male HP axis (i.e. anabolic steroids^​68​ and testosterone supplements^​69​) or impair spermatogenesis (i.e. sulfasalazine^​68​ and methotrexate^​70​ ). Additionally, cytotoxics (e.g. methotrexate) affect egg development^​70​, long-term non-steroidal anti-inflammatory drugs use can impact fertility^​54​, and excessive thyroid medications (levothyroxine) can disrupt ovulation^​71​. 

Pre-conception nutrition is paramount to fertility outcomes^​72​. The British Dietetic Association (BDA)’s recommendations on diet and fertility place emphasis on both partners optimising their nutritional status before conception^{​72–74​}. The updates recommend an increased intake of fertility enhancing dietary components, alongside a reduction of those linked to diminished reproductive potential at least three months pre-conception (see Table 6). Although not currently recommended by the BDA for female fertility, coenzyme Q10 has been widely researched for its potential role in improving reproductive outcomes and is commonly recommended across fertility clinics^​75​. Diets linked to improved IVF outcomes are similar in composition to Mediterranean diets, encompassing fresh fruit, vegetables, grains, dairy, fish and meat (see Table 6^{​72–74,76​}).

Table 6: The British Dietetic Association’s recommendations on diet and fertility

Finally, the significance of managing heightened emotional and excessive physical stress should not be underestimated in optimising fertility outcomes. Both negatively affect the hypothalamus and its associated cascade of reproductive hormones^​77​. Psychological interventions for individuals experiencing infertility may help reduce stress and are associated with improved treatment outcomes^​1​.

Safety considerations during IVF

Beyond medication side effects, artificial reproduction processes carry risks^​11​. However, the HFEA emphasises that most individuals do not experience issues, while IVF is generally considered ‘very safe’^​25​.  
 
Short-term risks involve the processes of egg collection and embryo transfer, which commonly cause pelvic and abdominal pain, as well as bleeding^​78​. Although uncommon, pelvic and uterine infections can arise from needles and catheters during procedures, though antibiotic prophylaxis may reduce this risk. Furthermore, the ovaries are surrounded by critical organs and structures, including vessels, ureters, the bladder and bowel. Although rare, puncture can necessitate surgical removal^​11​.
 
OHSS is a critical complication of ovarian stimulation (see Table 7)^{​12–14​}, which is exacerbated by existing PCOS^​13​. Several enlarged follicles increase ovarian vascular permeability, causing fluid to shift from the intravascular compartments into third spaces, affecting the abdomen (i.e. ascites), heart and lungs. Ovarian enlargement can also cause torsion^​14​. Treatment for OHSS focuses on pain relief for mild symptoms and prevention of exacerbation and serious OHSS complications^​14​. Should monitoring indicate excessive follicle development before human chorionic gonadotropin trigger, a short course of dopamine agonist, alternative agonist trigger and freeze all embryos option can mitigate risk by preventing hormone-induced intensification and prolongation of OHSS^​38​.  

Table 7: Symptoms of ovarian hyperstimulation syndrome

Multiple pregnancies resulting from IVF are considered the single biggest health risk to both mothers and babies in fertility treatment^​17​. While the goal of IVF is to achieve a healthy pregnancy, transferring multiple embryos significantly increases the likelihood of twins or triplets^​17​. Multiple pregnancies increase the risk of complications, including gestational anaemia, diabetes, pre-eclampsia and mortality in mothers. Babies may face preterm birth, learning difficulties, a six-fold higher risk of cerebral palsy and a ten-fold greater need for specialist neonatal care^​79​. Embryo transfer also increases the chances of ectopic pregnancies^​11​. However, incidents are rare and unsurprisingly, single-embryo transfer is recommended^​1​, reflecting continued success in a 3.2% multiple birth rate in 2024, in the UK^​10​. Furthermore, research by The Twin’s Trust shows postnatal depression doubles in mothers of twins and worsens with triplets^​21​. It is therefore encouraging that multiple pregnancies following IVF continue to decline^​10​.
 
While concerns exist about the long-term health of babies born from IVF treatment, evidence of causal links to negative health outcomes remains inconclusive. Initial apprehensions regarding low growth and birth weight have been proven insignificant by adolescence, whether IVF increases susceptibility to genetic defects remains uncertain^​80​. While follow-up studies provide reassuring results, long-term investigations with moderate- to high-quality evidence remain limited. In collaboration with the HFEA, the University of Oxford launched “PEARL”, a comprehensive investigation of long-term effects on mothers and babies born via artificial reproductive technology in England between 1991-2018. The study is aimed to deepen understanding of IVF implications and improve outcomes^​81​.

Post-IVF treatment, if treatment fails

For IVF to succeed, an optimal embryo must be placed into a receptive endometrium, followed by successful implantation and growth, sustained by the mother^​22,30​. If these factors are compromised, IVF can fail. Pre-implantation genetic testing can help identify suboptimal embryos in cases of recurrent failure^​82​. While IVF can help achieve pregnancy, it cannot fully overcome age-related barriers, such as diminished ovarian reserve and DNA damage.

Should IVF fail, treatment should be reviewed to identify the likely reason for failure and opportunities to improve the chances of success. Patients may opt for further cycles after discussing their chances of conceiving, while adjustments may include optimising medication doses, switching protocols, adjuvants or exploring options including donor gametes or surrogacy. 

IVF is a mentally, physically and emotionally taxing process^​19​. Supporting patients throughout their IVF journeys can restore a sense of control. NICE advises all patients should be offered counselling services before, throughout and after treatment, irrespective of treatment outcomes^​1​. Counselling provides a confidential and safe space to explore infertility-related issues with an impartial professional, who can help patients navigate challenging thoughts and emotions about medications, procedures and outcomes^​83​. Many fertility clinics have in-house counsellors to meet this requirement, and counselling services are also available through NHS therapy^​1​. Alternatively, patients can access a directory of accredited counsellors with specialist training through the British Infertility Counselling Association, for trustworthy self-funded therapy^​83​. 

While professional support is valuable, it can also help to connect to a community that has been through similar experiences through fertility apps, online forums and support groups. In addition, the emergence of male support groups has actively addressed the issue of men being overlooked in fertility^​84​. Patients should be directed to vetted groups to guarantee confidence in information accuracy^​85​. 

However, workplace support is lacking, with 46% of UK employees feeling neither supported nor unsupported at work during fertility challenges, though recent initiatives have encouraged employers to create fertility policies^​86​. Finally, all healthcare professionals involved in the care of IVF patients would benefit from integrating the ESHRE’s guidelines on psychosocial care in fertility into clinical practice to improve the IVF experience with a holistic perspective^​87​.