Assisted reproduction and fertility preservation

• Assisted reproduction is a set of techniques that handle gametes or embryos outside the body to help people with fertility problems, or to preserve fertility before treatment that may damage it.
• The simplest assisted step is ovulation induction with monitored oral or injectable drugs; the next step is intrauterine insemination (IUI) with sperm placed into the uterus at ovulation.
• Full in vitro fertilisation (IVF) retrieves oocytes, fertilises them in the laboratory, and transfers an embryo into the uterus; intracytoplasmic sperm injection (ICSI) is the same process with a single sperm injected into each oocyte.
• The most serious immediate complication of ovarian stimulation is ovarian hyperstimulation syndrome (OHSS), driven by vascular endothelial growth factor (VEGF) after exposure to human chorionic gonadotrophin (hCG). ^[3]
• Fertility preservation uses sperm freezing, oocyte or embryo cryopreservation, or ovarian tissue freezing, ideally before gonadotoxic treatment; donation of gametes and embryos is tightly regulated, including a 10-family limit in the United Kingdom and storage for up to 55 years with renewed consent.
• Every decision must follow local protocols and guidelines; this page names the current editions used: NICE NG257 (2026, which updates NICE CG156 from 2013), the ESHRE female fertility preservation guideline (2020), and the Human Fertilisation and Embryology Authority (HFEA) framework for donation and storage. ^[2]

By the end of this page you should be able to:

1. Explain ovulation induction, what it aims to achieve, and how it is monitored.
2. Describe IUI, its indications, and the evidence for its use in unexplained infertility.
3. Outline the stages of IVF, from ovarian stimulation to embryo transfer.
4. State when ICSI is and is not indicated.
5. Recognise ovarian hyperstimulation syndrome, explain its pathophysiology, and list prevention strategies.
6. Describe options for oocyte freezing, embryo freezing, and ovarian tissue cryopreservation, including oncofertility.
7. Explain donor gamete treatment and the legal rules that govern donation and storage.
8. Apply a clear flowchart when deciding which assisted pathway to use.

Assisted reproduction is best understood as a ladder rather than a single treatment. At the bottom is careful timing and preconception care. Above that comes restoration of normal ovulation. Then comes intrauterine insemination, which brings gametes together inside the body but in the right place at the right time. At the top are in vitro fertilisation and ICSI, which move fertilisation into the laboratory so that fertilisation can be checked directly and embryos can be selected before transfer. The same technologies also allow preservation of fertility and donation between people.

Two ideas run through the whole page. The first is that assisted reproduction is a couple's treatment, not a woman's treatment, because the cause of difficulty may be female, male, combined, or unexplained. The second is that the hormones used to stimulate the ovary are powerful drugs with a serious, sometimes life-threatening complication, so monitoring and prevention matter as much as the treatment itself.

This topic covers a curriculum area with no single agreed book chapter heading; it brings together ovulation induction, IUI, IVF and ICSI, ovarian hyperstimulation syndrome, oocyte and embryo freezing, oncofertility, and donor gametes in one place. It replaces the older framing of NICE clinical guideline CG156 (2013, last updated 2017) with the current NICE guideline NG257 (published 31 March 2026), which covers the same ground and updates many recommendations. ^[1]

Ovulation induction is the pharmacological restoration of a cycle in which a mature egg is released. It is used when a woman does not ovulate, or ovulates irregularly, and wants to conceive. The aim is not to make the ovary work harder than normal, but to create a single dominant follicle rather than none, or several uncontrolled follicles. The clinical goal is one egg per cycle whenever possible, because the main danger of unmonitored stimulation is multiple pregnancy and ovarian hyperstimulation syndrome.

The clearest group is anovulatory women who want to conceive, including women with polycystic ovary syndrome and those with hypothalamic amenorrhoea. A woman with regular cycles is already likely to be ovulating, so induction is not needed in that situation. In unexplained infertility, oral ovulation agents alone are not offered, because they do not improve the chance of pregnancy in that group; instead IUI with stimulation or IVF is used. ^[1]

• Clomiphene citrate is an oral selective oestrogen receptor modulator that increases pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) release. A block of treatment is usually given early in the cycle, and monitoring is essential after early cycles.
• Letrozole, an aromatase inhibitor, lowers oestradiol and thereby lifts the brake on hypothalamic gonadotrophin-releasing hormone. It is widely used, especially in polycystic ovary syndrome, and is generally regarded as an alternative first-line oral agent.
• Exogenous gonadotrophins (FSH, with or without LH) are injectable and are used when oral agents fail or when the ovaries need more powerful stimulation for IVF. They require ultrasound monitoring and estradiol measurement.
• Gonadotrophin-releasing hormone (GnRH) agonists and antagonists are not ovulation inducers on their own; they are used to control the timing of the LH surge during an IVF cycle.

For women treated for cancer, there is a specific timing problem. The GnRH antagonist protocol is favoured for fertility preservation because it is short, can be started at any point in the cycle, and allows the cycle to be completed quickly. Random-start stimulation and double stimulation (two rounds in one cycle with retrieval after each) are also options when there is little time before treatment must begin. In oestrogen-sensitive disease such as breast cancer, letrozole may be used alongside gonadotrophins to limit oestradiol exposure. ^[2]

Monitoring by ultrasound, with or without serum oestradiol, is the safety net of induction. It confirms that a follicle is growing, shows whether several follicles are developing, and allows the cycle to be cancelled before triggering when the response is too strong. Gonadotrophins combined with clomiphene or letrozole in an unmonitored setting are discouraged for the same reason. ^[1]

If the cause is tubal damage, significant male factor, or age-related decline in ovarian reserve, induction alone will not succeed. In those cases the pathway moves to IUI or IVF, described below. ^[1]

Intrauterine insemination is the placement of prepared sperm directly into the uterine cavity through a thin catheter, timed around ovulation. It bypasses the cervix, shortens the distance sperm must travel, and ensures that sperm are present when the egg is released. It is most often combined with ovarian stimulation at low dose so that the number of ovulating follicles and the timing of insemination are controlled. IUI is technically simple, can be done in an outpatient clinic, and does not involve egg retrieval.

Common indications include unexplained infertility, mild male factor, cervical factor, and donor sperm treatment. IUI is particularly valuable when intercourse is very difficult or impossible, for example because of a physical disability or psychosexual problem. For these situations NICE offers up to 12 cycles of unstimulated IUI before moving to IVF. ^[1]

For donor insemination (using sperm from someone other than the male partner), ovulation should be confirmed first, and tubal assessment offered where the history suggests tubal damage. IUI with donor sperm is recommended in preference to intracervical insemination because pregnancy rates are higher. ^[1]

In unexplained infertility the European Society of Human Reproduction and Embryology (ESHRE) guideline is explicit: first-line treatment is IUI with low-dose monitored ovarian stimulation, with oil-soluble contrast at hysterosalpingography preferred where tubal patency is being assessed. IVF is probably not superior overall, but decisions are individualised by age, duration of infertility, and previous treatment. Oral ovulation agents for unexplained infertility are not offered, because they have not been shown to help. ^{[1] [2]}

For women using donor insemination who have not conceived after 6 cycles and have no suspected or known cause of infertility, NICE advises a further 6 cycles of unstimulated donor IUI before considering IVF. ^[1]

IUI gives only a modest increase in monthly fecundability, it does not overcome significant tubal disease or severe male factor, and it adds a small risk of multiple pregnancy and of OHSS whenever stimulation is used. For strong male factor, severe tubal disease, or older women with limited time, IVF or ICSI becomes the better next step.

IVF is the entire sequence of ovarian stimulation, egg retrieval, fertilisation outside the body, embryo culture, and transfer of one or more embryos into the uterus. A standard cycle has the following stages.

1. Ovarian stimulation. Exogenous gonadotrophins drive the growth of several follicles at once. A GnRH agonist or antagonist protocol suppresses the natural LH surge so that ovulation does not occur before eggs are ready.
2. Triggering. Final maturation of the eggs is triggered with hCG, or with a GnRH agonist in an antagonist protocol.
3. Oocyte retrieval. Eggs are collected transvaginally under ultrasound guidance, usually with conscious sedation. Follicle flushing is not recommended when at least 3 follicles are present, because it does not increase retrieval or pregnancy rates and increases pain. ^[1]
4. Fertilisation. Eggs are mixed with prepared sperm in the laboratory and left overnight. Semen preparation concentrates motile, morphologically normal sperm.
5. Embryo culture. Embryos are monitored for two to six days. Assessment uses standard grading criteria; preimplantation genetic testing for aneuploidy (PGT-A) is not offered to improve live birth rates. ^[1]
6. Embryo transfer. One or two embryos are placed into the uterus through the cervix under ultrasound guidance. Ultrasound-guided transfer improves pregnancy rates. ^[1]
7. Luteal support and storage. Progesterone supports the endometrium. Any remaining good-quality embryos are cryopreserved. ^[1]

NICE advises that the endometrium should be at least about the thickness of 5 millimetres for transfer, with very low pregnancy rates below that; bed rest beyond 20 minutes after transfer does not improve outcome. ^[1]

The number of embryos transferred is the main lever for both success and safety. In younger women single embryo transfer is preferred in the first and often the second cycle; double transfer may be considered if no top-quality embryo is available, and never more than 2 embryos are transferred in one cycle. At 40 to 41 years double transfer may be considered. Each extra embryo raises the chance of multiple pregnancy, preterm birth, and obstetric risk. ^[1]

Intracytoplasmic sperm injection is the microinjection of a single selected sperm into a mature oocyte. It bypasses problems with sperm number, motility, and binding to the egg, and it is the route by which surgically retrieved sperm (from obstructed or non-obstructed azoospermia) or frozen-thawed eggs can be used. ^[1]

NICE recommendations are clear and worth memorising:

• Offer ICSI using surgically retrieved sperm or frozen-thawed oocytes. ^[1]
• Consider ICSI when semen parameters are abnormal, or when a previous IVF cycle had failed fertilisation or a very low fertilisation rate. ^[1]
• Do not use ICSI for non-male factor infertility with normal semen parameters; it does not add benefit in that setting. ^[1]
• Do not use intracytoplasmic morphologically selected sperm injection (IMSI) as an adjunct, and do not prefer physiological ICSI (PICSI) over standard ICSI. ^[1]

In other words, ICSI is a treatment for a sperm problem or for a fertilisation problem, not a default upgrade for every cycle.

NICE sets auditable criteria for offering IVF on the health system, although local funding differs. Women under 40 are offered 3 full cycles where there is 2 years of regular unprotected intercourse without conception, or 12 cycles of artificial insemination of which at least 6 were IUI. Women aged 40 to 42 who have never had IVF and who do not show evidence of low ovarian reserve are offered one full cycle. A full cycle is defined as one episode of ovarian stimulation and transfer of any resulting good-quality embryos. Any previous full cycle, self-funded or publicly funded, counts towards the total. These rules change over time, and clinicians should always use the current edition. ^[1]

Ovarian hyperstimulation syndrome is the most serious complication of controlled ovarian stimulation. It is driven by an excessive ovarian response followed by exposure to hCG, which increases vascular endothelial growth factor production in granulosa-luteal cells and raises capillary permeability. Fluid then leaks into the peritoneal, pleural, and sometimes pericardial spaces, producing hypovolaemia, haemoconcentration, and ascites. It presents a spectrum from mild discomfort to life-threatening disease.

The incidence figures, taken from a major review, are moderate OHSS in 3 to 6 percent of all cycles, severe OHSS in 0.1 to 3 percent, and a risk approaching 20 percent in high-risk women. ^[3] Mild OHSS is more common than the severe form but figures vary by definition. It occurs almost exclusively during assisted reproduction, although it has been described after clomiphene stimulation and in spontaneous pregnancy. ^[3]

Risk factors include young age, low body mass index, higher doses of gonadotrophins, very high or rapidly rising estradiol, polycystic ovary syndrome, a high antral follicle count or anti-Mullerian hormone, and any previous episode of OHSS. ^[3]

• Mild. Abdominal discomfort, nausea, mild bloating, ovarian enlargement. Managed at home with analgesia, adequate (not excessive) fluids, and avoidance of strenuous exercise.
• Moderate. Pain, nausea, vomiting, ultrasound evidence of ascites, ovarian enlargement. Close outpatient follow-up.
• Severe. Tense ascites or hydrothorax, oliguria, haematocrit above 45 percent, low albumin, ovarian enlargement beyond about 12 centimetres, or thromboembolism.
• Critical. Tense ascites or large hydrothorax, haematocrit above 55 percent, white cell count above 25, anuria, thrombosis, or acute respiratory distress syndrome. Admission and multidisciplinary care.

These thresholds come from clinical pathways in common use; local protocols may set slightly different values. Oestrogen and hCG are key mediators, but hCG alone is not sufficient to produce the syndrome; VEGF and the renin-angiotensin system are involved, and interleukin 6 is associated with increased vascular permeability. ^[3]

Prevention is always more effective than treatment. The most important step is sound clinical judgement: choose stimulation protocols that match ovarian reserve, and cancel or freeze the cycle when the response is excessive. Evidence-based strategies include:

• GnRH antagonist protocols reduce severe OHSS compared with long GnRH agonist protocols, with an odds ratio of 0.60 in one meta-analysis, at a small cost in pregnancy rate. ^[3]
• Replacing hCG with a GnRH agonist to trigger final maturation, within an antagonist protocol, virtually eliminates moderate and severe early OHSS and is one of the safest approaches. ^[3]
• In vitro maturation of oocytes avoids stimulation altogether and eliminates OHSS risk, although it remains less efficient than conventional IVF and is not mainstream. ^[3]
• Coasting, delaying the trigger while withholding gonadotrophins, lowers estradiol but its preventive value is uncertain, and OHSS can still occur in up to 9.4 percent of coasted cycles. ^[3]
• Cabergoline reduces early OHSS by antagonising VEGF receptor signalling. ^[3]
• Low-dose aspirin given from the start of stimulation reduced OHSS from 8.4 to 0.25 percent in one large trial of high-risk women. ^[3]
• Reducing or tailoring hCG dose, embryo cryopreservation with later transfer (freeze-all), cycle cancellation, and choosing single embryo transfer all reduce risk.
• Albumin given at retrieval has not shown benefit, and renin-angiotensin blockade has potentially harmful fetal effects and is not recommended as prevention. ^[3]

Every clinic that stimulates ovaries with gonadotrophins should have a written protocol for preventing, diagnosing, and managing OHSS. ^[1] Management is mainly supportive: analgesia with paracetamol-based regimens (avoiding non-steroidal anti-inflammatory drugs), maintenance of fluid balance, thromboprophylaxis with low molecular weight heparin, drainage of tense ascites by paracentesis, careful monitoring of renal function, and early involvement of a specialist team. Critical disease requires multidisciplinary care in hospital.

Oocyte cryopreservation (egg freezing) is the process of retrieving mature oocytes and freezing them for future use. Since the development of vitrification, slow-freezing methods have been largely replaced: vitrification is fast and produces very high oocyte survival rates, and the ESHRE female fertility preservation guideline now describes oocyte cryopreservation as the method of choice for age-related fertility loss and for most women seeking medical fertility preservation. ^[2]

Oocyte freezing has two very different indications.

• Elective (social) fertility preservation. Women who wish to defer childbearing freeze oocytes while their ovarian reserve is better. Success depends almost entirely on age at freezing and the number of eggs stored; live birth rates per egg used are not high, and couples should be counselled on the limits of the technology.
• Oncofertility. Women facing gonadotoxic treatment freeze oocytes or embryos before treatment so that a future pregnancy is still possible.

Embryo freezing is technically easier and better established than oocyte freezing, with higher survival after thaw. Its main drawback in women without a partner is that embryos created with donor sperm belong jointly to both genetic contributors in law, which can lead to disputes about use and storage long after treatment. Oocyte freezing avoids this.

Ovarian tissue cryopreservation (removal and freezing of cortical strips) is the only option for girls before puberty, and it is important when there is not enough time for ovarian stimulation. The tissue is later grafted back to restore some ovarian activity. It still sits closer to experimental practice than to routine care, and outcomes data are limited; it is best performed in experienced centres. ^{[2] [1]}

Oncofertility is the integration of cancer care with fertility care. The clinical pathway is:

1. Raise fertility preservation at the earliest possible opportunity for anyone whose condition or treatment is likely to impair fertility. ^[1]
2. Assess the person individually, taking into account the diagnosis, the planned treatment, the likely fertility outcome, the prognosis, and the viability of stored material. ^[1]
3. Offer sperm cryopreservation to men and to trans women and non-binary people with male reproductive organs who are of reproductive age. ^[1]
4. Offer oocyte or embryo cryopreservation to women and to trans men and non-binary people with female reproductive organs who are of reproductive age. ^[1]
5. Consider ovarian tissue cryopreservation when oocyte or embryo cryopreservation is not feasible, such as in prepubertal girls. ^[1]
6. Use GnRH antagonist random-start stimulation with or without double stimulation so that fertility preservation fits around urgent treatment; in oestrogen-sensitive cancer use letrozole alongside stimulation. ^[2]
7. Check ovarian reserve with antral follicle count or anti-Mullerian hormone, which are preferred over other tests for predicting response. In breast cancer and haematological malignancy, pre-treatment anti-Mullerian hormone helps predict ovarian recovery, although it should not be used alone as a predictor of later fertility. ^[2]
8. Arrange follow-up at least every 5 years for people with preserved material to decide whether storage should continue, and continue funded storage while significant risk of infertility remains, in line with consent law. ^[1]

For fertility preservation, the usual eligibility rules for NHS-funded treatment are waived, including the lower age limit, but eligibility rules apply again when the stored material is used. ^[1]

GnRH agonists are sometimes given during chemotherapy to suppress ovarian function; the evidence for protection of future fertility is strongest in breast cancer, but the evidence base is mixed and this is supplementary to cryopreservation. Ovarian transposition, moving the ovaries out of a planned radiotherapy field, is the surgical analogue.

Transgender men who wish to preserve oocytes should be counselled before starting gender-affirming testosterone, because ovarian stimulation can still be carried out after testosterone is stopped. Transgender women may bank sperm before feminising hormone therapy or surgery. Care must follow protocols for these groups and include psychological support.

Donor treatment uses eggs, sperm, or embryos from someone other than the person or couple seeking treatment. It is indicated for conditions such as premature ovarian insufficiency (including after treatment), gonadal dysgenesis (including Turner syndrome), severe male factor where ICSI is not possible or chosen, obstructive and non-obstructive azoospermia, severe semen deficits, a high risk of transmitting a genetic or infectious disease, or failure of previous IVF. ^[1][4]

Donor insemination is offered with IUI rather than intracervical insemination because pregnancy rates are higher. ^[1] Oocyte donors should be given information about the potential risks of ovarian stimulation and egg collection. ^[1]

In the United Kingdom, a donor's eggs, sperm, or embryos may be used to create children in up to 10 families, a limit that does not include the donor's own family. Donor material imported into the UK may be used in additional families in its country of origin or elsewhere, so children conceived with imported gametes may have more genetic half-siblings than the UK limit suggests. ^[4]

Licensed clinics must carry out infection screening and tests for donors, include counselling for donors and recipients, and register donor and treatment outcomes with the regulator. Consent can be changed or withdrawn at any time before the gametes or embryos are used. ^[4]

Compensation for donation is fixed by the regulator: up to £45 per clinic visit for sperm and embryo donors, and up to £985 per cycle for egg donors. Donation is altruistic rather than a commercial transaction. Donors are anonymous at the time of treatment, but children born from donation can apply to the regulator for identifying information about their donor once they reach 18 years. Donor-conceived children, and their relatives, can therefore discover their genetic origins as adults. ^[4]

Storage law is important in counselling anyone who freezes gametes, particularly before cancer treatment. From July 2022 (Health and Social Care Act 2022) all patients may store their own eggs, sperm, and embryos for treatment for up to 55 years, provided they reconsent every 10 years; donors may store gametes for up to 55 years without reconsenting; and material may be stored for up to 10 years after death if valid posthumous consent exists. For people who preserved fertility ahead of chemotherapy, radiotherapy, or hormone therapy, reconsenting every 10 years is now required, and contact details must be kept up to date so that clinics can reach them. ^[5]

The NICE IVF access criteria (see above) are one example of how assisted reproduction is rationed and audited. Local funding differs, and couples should be given full information about costs, success rates by age, and the possibility of self-funded treatment. ^[1]

Because multiple pregnancy is the most common serious outcome of assisted reproduction, every clinic has an embryo transfer strategy. Single embryo transfer is the default for a good-prognosis first cycle in a woman under 37; double transfer is reserved for specified situations; more than 2 embryos are never transferred in one cycle. ^[1]

Consent is the thread that runs through fertility treatment. Consent to storage must be written, must specify what the material may be used for, and can be changed or withdrawn up to the point of use. Donors must consent in writing, children born after mitochondrial donation have special rules, and ovarian tissue removal and storage fall under tissue and cell quality regulations as well.

• Multiple pregnancy, the commonest serious outcome, from transferring more than one embryo or from excessive stimulation.
• Ovarian hyperstimulation syndrome, described above.
• Ectopic pregnancy, more likely after tubal surgery and in assisted cycles.
• Ovarian torsion or bleeding after egg collection.
• Thrombosis in the setting of OHSS.
• Cumulative pregnancy rates that fall sharply with age, so counselling must be realistic.
• Psychological burden of repeated treatment and of unsuccessful cycles, which should be acknowledged and supported. ^[1]
• Long-term safety: follow-up of children born after assisted reproduction is reassuring for the techniques in common use; ICSI with surgically retrieved sperm raises the question of passing on underlying genetic causes of male infertility to sons, so genetic counselling is part of male infertility care.

• Ovulation induction with oral agents and timed intercourse can be delivered in most clinics; the limiting step is monitoring for multiple follicles and OHSS.
• IUI requires only a simple laboratory set-up (sperm preparation and a speculum and catheter) and is feasible in district-level hospitals.
• IVF depends on expensive laboratory equipment, quality control, and staff; where it is not available, referral to a higher centre or a regional programme is the honest advice.
• Fertility preservation for cancer patients should at least include counselling and, where possible, simple sperm freezing; oocyte freezing needs IVF laboratory capability.
• The hepatitis B and HIV status of donor material must be handled under local regulations; donor treatment in many low-resource settings depends on imported sperm or embryos.

• Age over 35. Investigation begins earlier (6 months after a defined period of trying rather than 12), and IVF access is more restrictive after 42. ^[1]
• Women with cancer. Fertility preservation should be discussed at diagnosis, before treatment. ^[1]
• Transgender people. Fertility preservation must be offered before irreversible treatment. ^[1]
• Single people and same-sex couples. Modern definitions of infertility recognise the need for medical intervention as qualifying; donation of sperm or eggs is the route. ^[4]
• Religious and cultural contexts. Consent, donor identity, and the acceptability of third-party reproduction differ; counselling should be individual and non-directive.

This page sits alongside the companion topic on infertility and Bartholin gland disease, which covers causes, work-up and IVF access criteria in more detail, as well as polycystic ovary syndrome, premature ovarian insufficiency, tubal and peritoneal disease, endometriosis, uterine fibroids, varicocele, and male infertility. Until those pages are verified they are listed here as plain text. Fertility preservation in cancer care should also be read with the relevant oncology pages.