IVF Drugs and Their Side Effects, Protocol by Protocol

The honest picture

The drug part of IVF looks more complicated than it is, because every clinic uses different brand names for the same four jobs. Strip the branding away and a cycle needs to do four things: stop your body ovulating on its own schedule, grow several follicles instead of one, mature those eggs at a chosen moment, and support the uterine lining afterwards.

This page describes what each group is for. It deliberately gives no doses. Doses in IVF are set individually from your age, ovarian reserve markers, antral follicle count, weight and previous response, and a number that is right for one person is unsafe for another. NG257 recommendations 1.54.3 and 1.55.4 tell clinicians to limit ovulation induction and ovarian stimulation agents, and drugs used for controlled ovarian stimulation in IVF, to the lowest effective dose and duration of use.

The four jobs

1. Suppressing your own cycle

The NHS describes the first step of a standard cycle as using an injection or nasal spray every day for 2 to 3 weeks to stop your ovaries producing eggs naturally, followed by an ultrasound scan to check the medicine has worked. This is the long protocol, and the HFEA describes it the same way: suppress the natural hormones, scan to confirm suppression is complete, then start stimulation.

The alternative is the antagonist protocol. The HFEA describes it as taking an antagonist medication to suppress your hormones for a few days after you have already started the hormone medication that boosts egg numbers. The practical difference is that the antagonist protocol is shorter, because the suppression phase is folded into stimulation rather than preceding it.

2. Stimulating the ovaries

Gonadotrophins are injected daily to grow multiple follicles. The NHS puts this at around two weeks of daily injections with tests or scans to check how well it is working; the HFEA describes close monitoring for several days, which may involve blood tests or ultrasound scans.

The HFEA is explicit that women taking gonadotrophins can develop ovarian hyperstimulation syndrome, which in rare cases can be fatal, and that it is essential to know the symptoms. That is why the monitoring exists — it is not administrative.

3. The trigger

A final injection matures the eggs and sets the timing of collection. NG257 does not write its own recommendations here: it directs clinicians to the part of the ESHRE guideline on ovarian stimulation for IVF and ICSI covering triggering ovulation and luteal support. Your clinic will give you an exact time to take it, and that time is the reason collection is booked when it is.

4. Luteal support

After transfer, medication supports the uterine lining. The HFEA describes this as medication to help prepare the lining of the womb, usually taken as a pessary or gel inserted vaginally or rectally. NG257 again defers to ESHRE for the detailed recommendations.

Where NICE hands over to ESHRE

This is worth understanding, because it explains why NG257 looks thin on drug detail. For pre-treatment therapies, for pituitary suppression and controlled ovarian stimulation, for monitoring during stimulation, for triggering ovulation and luteal phase support, and for the prevention of OHSS, NG257 explicitly points to the corresponding parts of the ESHRE guideline on ovarian stimulation for IVF and ICSI, updated in 2025. The UK guideline has adopted the European one for the pharmacology rather than duplicating it.

If you want the underlying rationale for your protocol, that is the document your clinician is working from.

Side effects, and the ones that are not side effects

The HFEA groups the risks of stimulation into ovarian hyperstimulation syndrome, multiple pregnancy where more than one embryo is transferred, and ectopic pregnancy, alongside the ordinary discomforts of daily injections. Injection-site soreness, bloating as the ovaries enlarge, and mood change are commonly reported during stimulation.

What matters is distinguishing expected discomfort from a warning sign, and the discriminator is the same as for OHSS generally: expected discomfort plateaus and settles, whereas swelling that keeps increasing, breathlessness, vomiting and reduced urine output escalate. Report the second group the day you notice it.

The long-term risk questions, answered as the guideline answers them

Two questions come up constantly, and NG257 addresses both in section 1.54 and 1.55.

On cancer: people offered ovulation induction or ovarian stimulation should be informed that no direct association has been found between these treatments and invasive cancer, that no association has been found in the short to medium term between these treatments and adverse outcomes including cancer in children born from them, and that information about long-term health outcomes is still awaited. For IVF specifically, NICE says people should be told that while the absolute risks of long-term adverse outcomes are low, a small increased risk of borderline ovarian tumours cannot be excluded.

On children: NICE says people considering IVF should be informed that the absolute risks of long-term adverse outcomes in children born as a result of IVF are low.

Those are careful sentences and they are the honest state of the evidence. They are neither a clean bill of health nor a warning.

Doing it with fewer drugs

The HFEA notes it is possible to have IVF with no fertility drugs at all, called natural cycle IVF, or with fewer drugs, in mild stimulation IVF and in vitro maturation. These may suit people who cannot take the drugs because of an existing medical condition or who prefer not to. It is equally clear about the trade: success rates tend to be lower without fertility drugs, and in the case of natural cycle IVF are significantly lower.

What to do next

1. Ask which protocol you are on and why — long, antagonist or something else — and what would make the clinic switch.
2. Ask for your drug schedule in writing, with the name, route and timing of each medicine, and who to call out of hours if a dose goes wrong.
3. Ask what your monitoring plan is: how many scans, which blood tests, and what result would trigger a change or cancellation.
4. Ask what your OHSS risk is and what is being done about it.
5. Get drug costs itemised separately from treatment costs. The HFEA warns that quoted prices often exclude fertility drugs.
6. Ask whether a milder protocol is reasonable for you, and what it would cost in success terms.

When to seek help

Contact your clinic the same day for increasing abdominal swelling, severe pain, persistent vomiting, breathlessness or a noticeable drop in urine output during or after stimulation. The NHS advises calling 999 or going to A and E for difficulty breathing, chest or upper back pain, dehydration with much reduced urination, swelling anywhere on the body, low one-sided tummy pain, or shoulder-tip pain. Also tell the clinic promptly about a severe reaction at an injection site, or if you have missed or mistimed a dose — particularly the trigger, where timing determines whether the collection works at all.