IVF (In Vitro Fertilisation)

01 — Investigation and protocol planning

Before a cycle begins, both partners undergo a thorough assessment. For women, this includes baseline hormone testing — anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinising hormone (LH), and oestradiol — along with a transvaginal ultrasound to assess the antral follicle count, which gives an indication of ovarian reserve. A uterine cavity assessment is usually performed to rule out structural issues such as fibroids, polyps, or adhesions that could impair implantation. For the male partner, a full semen analysis is conducted against WHO criteria, examining count, motility, and morphology. In some cases, genetic screening — including karyotyping and testing for specific heritable conditions such as cystic fibrosis — is also recommended.

Based on these findings, the clinic selects a stimulation protocol. There are two main approaches: the long protocol and the short protocol. The difference lies in how and when the ovaries are suppressed before stimulation begins.

02 — Stimulation: the long protocol

In the long protocol, the first step is down-regulation — temporarily switching off the body's natural hormone cycle before stimulation begins. A GnRH agonist is administered for two to three weeks, either as a nasal spray or a subcutaneous injection. This renders the ovaries temporarily inactive, which serves two purposes: it prevents the ovaries from releasing eggs prematurely before retrieval, and it allows the follicles to grow in a more uniform, synchronised pattern once stimulation starts.

Down-regulation can produce side effects that resemble early menopause — hot flushes, night sweats, headaches, mood shifts, and difficulty concentrating — because oestrogen levels drop sharply during this phase. These symptoms typically resolve once the FSH injections begin and oestrogen rises again.

After two to three weeks, a transvaginal ultrasound confirms that the ovaries are inactive and contain no large follicles or cysts before stimulation proceeds.

03 — Stimulation: the short protocol

In the short protocol, down-regulation is not carried out in advance. Instead, FSH injections begin from the start of the cycle, with a GnRH antagonist added from approximately day six of stimulation to prevent premature ovulation. Some clinics ask patients to take the oral contraceptive pill in the preceding cycle to synchronise the start date. The short protocol is often preferred for women identified as being at higher risk of ovarian hyperstimulation syndrome (OHSS), as dose adjustments can be made more flexibly.

Both protocols carry comparable pregnancy rates; the choice is made on individual clinical grounds.

04 — Ovarian stimulation and monitoring

Whichever protocol is used, the stimulation phase involves daily subcutaneous injections of FSH — and sometimes additional LH — for ten to fourteen days. The aim is to encourage the ovaries to develop multiple follicles simultaneously rather than the single follicle a natural cycle would produce. Around fifteen mature eggs per retrieval is considered optimal; too few limits the chances of producing a viable embryo, while too many increases the risk of hyperstimulation.

Throughout this phase, follicle growth and number are monitored by transvaginal ultrasound at intervals, with blood tests tracking oestrogen levels. Doses may be adjusted based on the response. The target is follicles measuring approximately 18–20 mm in diameter before triggering. Side effects of FSH stimulation include bloating, breast tenderness, nausea, and heightened emotionality — all driven by the significant hormonal changes the body is undergoing.

05 — The trigger injection and egg retrieval

Once the follicles reach target size, a trigger injection is administered — usually human chorionic gonadotropin (hCG) or a GnRH agonist — to prompt the final maturation of the eggs. The timing of this injection is critical: egg retrieval is scheduled precisely 34 to 36 hours later, and errors in timing can result in eggs that are too immature to fertilise. Patients receive clear, written instructions on when to take the trigger.

Egg retrieval takes place under light intravenous sedation and typically lasts around twenty minutes. A fine needle, guided by transvaginal ultrasound, is passed through the vaginal wall into each follicle in turn, and the fluid — containing the egg — is drawn out. Both ovaries are treated in the same session. Not every follicle will yield an egg, and the total number retrieved is reported immediately after the procedure. Around one in twenty cycles (5%) has to be cancelled before retrieval, usually because the ovaries have not responded adequately or have over-responded to the point where proceeding would carry unacceptable risk.

Patients should fast for seven hours beforehand, avoid makeup, nail varnish, jewellery, and perfume, and arrange to be accompanied home. Driving, alcohol, and operating machinery are not permitted for the rest of that day.

06 — Sperm collection

On the same day as egg retrieval, a semen sample is produced by the male partner and assessed in the laboratory. For optimal quality, ejaculation is generally avoided for two to three days beforehand.

Where the standard ejaculated sample is of insufficient quality, or where sperm cannot be produced through ejaculation, surgical sperm retrieval may be used. Testicular sperm extraction (TESE) involves a biopsy of testicular tissue from which sperm are isolated. Microsurgical epididymal sperm aspiration (MESA) retrieves sperm directly from the epididymis using an operating microscope. Both procedures are used when azoospermia (complete absence of sperm in the ejaculate) is due to obstruction or to impaired production. They are performed under local or general anaesthesia and always paired with ICSI rather than conventional IVF, since the numbers of sperm retrieved are typically very small.

07 — Fertilisation: IVF and ICSI

In standard IVF, prepared sperm are placed in a laboratory dish alongside the retrieved eggs and left overnight in an incubator at body temperature. Fertilisation is spontaneous, with the faster and more motile sperm competing naturally. Fertilisation success rates typically fall in the range of 50–70%.

Where the sperm quality is poor — low count, impaired motility, or abnormal morphology — or where previous IVF cycles have failed to achieve fertilisation despite apparently normal sperm parameters, intracytoplasmic sperm injection (ICSI) is used instead. A single sperm is selected and injected directly into the egg under high-powered microscopy. ICSI is also recommended when sperm has been surgically retrieved or when the male partner is a carrier of a transmissible infection such as HIV or hepatitis that requires the sample to be processed specially.

A variant called IMSI (intracytoplasmic morphologically selected sperm injection) uses even higher magnification to select sperm based on detailed structural assessment. Early studies suggested improved outcomes in couples with repeated ICSI failures, but subsequent Cochrane reviews have found insufficient high-quality evidence to confirm a benefit in live birth rates. It is not currently considered standard practice.

The embryologist will also investigate in vitro maturation (IVM) for a small subset of patients — particularly those at high risk of OHSS — in which immature eggs are retrieved with minimal or no hormonal stimulation and matured in the laboratory before fertilisation. The technique remains experimental and is not widely available.

All dishes, tubes, and embryos are labelled with the patient's name and a unique identifier. Most accredited units use electronic witnessing systems to verify sample identity at each handling stage, a safeguard that exists because embryo or gamete mix-ups, while rare, have been documented and have serious legal and personal consequences.

08 — Embryo development

Fertilised eggs are called embryos from the moment fertilisation is confirmed. The embryologist checks each one the morning after retrieval and reports the results to the patient. Embryos are then cultured in the incubator and assessed at intervals:

Transfer can take place on day 2, 3, or 5. Blastocyst-stage transfer is generally preferred where embryo quality allows, because it permits better selection — only embryos that have reached blastocyst are considered to have demonstrated the developmental potential likely to result in implantation. However, not all embryos survive to blastocyst, so in some cases earlier transfer is chosen to avoid losing all embryos in the laboratory.

Any additional blastocysts of sufficient quality can be vitrified (rapidly frozen) for future use. Freezing is possible in approximately 40% of cycles; around 85% of vitrified blastocysts survive the thaw.

By day 2: typically 2–4 cells

By day 3: typically 6–8 cells

By day 5: more than 100 cells, at the blastocyst stage

09 — Embryo transfer

Transfer is a straightforward outpatient procedure that requires no sedation. The patient attends with a full bladder, which improves ultrasound visibility of the uterus. A soft catheter is passed through the cervix, and the selected embryo or embryos are deposited at the optimal position in the uterine cavity. The procedure takes a few minutes and causes minimal discomfort — broadly comparable to a cervical smear.

The number of embryos transferred is decided on clinical grounds and is one of the most important decisions in the cycle. Current guidance from most regulatory bodies limits transfer to one embryo in most circumstances, reflecting the serious risks associated with multiple pregnancy. In practice:

The bladder can be emptied immediately after transfer without any effect on the embryos. The old advice to remain horizontal for hours post-transfer has no scientific basis.

Progesterone supplements — usually administered as vaginal pessaries — are prescribed from the day of egg retrieval and continued for 17 days. Their role is to support the uterine lining during the implantation window.

Women under 35 in their first cycle, especially with spare embryos for freezing, are typically offered single embryo transfer, which gives a strong chance of pregnancy alongside a low rate of twins.

Women over 35 or those with poorer-quality embryos may be offered two embryos.

Women over 40 may discuss three embryos in specific circumstances, though the risks of multiple pregnancy in this age group also carry additional complexity.

10 — The pregnancy test

A urine pregnancy test is taken 16 days after egg retrieval — not immediately after the two-week wait, and not before the specified date. The trigger injection contains hCG, which can remain in the bloodstream for 8–10 days and will produce a false positive if the test is taken too early.

Any bleeding before the test date does not mean the cycle has failed; it should not prompt early testing, because an ectopic pregnancy — in which the embryo implants outside the uterus — can initially present with bleeding and may give a positive result. Ectopic pregnancies occur in approximately 1–3% of IVF cycles and require prompt medical assessment. If there is significant pain, particularly on one side, heavy bleeding, or shoulder tip pain, a clinic or emergency department should be contacted without waiting for the test date.

A positive result is followed by an ultrasound scan at approximately seven weeks to confirm a fetal heartbeat. Miscarriage occurs in roughly 10–20% of clinical pregnancies following IVF, with risk rising with age and influenced by other factors including embryo quality.

If the result is negative, progesterone is stopped and menstruation usually follows within a few days. A review appointment with a senior clinician should be arranged to discuss the cycle outcome, review the quality and number of embryos produced, and consider adjustments for any future cycle. At least two months' rest between cycles is generally advised to allow physical and emotional recovery.