IVF add-ons: what the new guideline says about taking “something extra”

The ESHRE working group reviewed the literature for every step of ovarian stimulation: how the protocol is chosen, how the starting dose is set, what is monitored during the cycle, when the trigger is given and which additions have been studied. The result is 46 new and 29 updated recommendations which, together with the existing ones, cover practically the whole cycle. What stands out on reading the document is that behind most recommendations sits evidence graded as low or very low quality, meaning small studies, differing methods, or results that do not replicate. That is the real state of the field rather than a weakness of the guideline.

For a patient this has a practical meaning. When a doctor says “there is not enough evidence”, they are not withholding an option; they are describing precisely what is known. Strong recommendations are few and concern safety and protocol choice rather than add-ons. A good treatment plan is therefore not recognised by how many things it contains, but by how well the things it does contain are justified.

Several substances have been studied for years as ways to improve ovarian response or egg quality. Growth hormone, DHEA and testosterone pre-treatment are not recommended for improving live birth; for some of them the evidence is uncertain and study results conflict. The same applies to aspirin, sildenafil and myo-inositol: none has shown a consistent live birth benefit when given routinely during an IVF cycle.

This does not mean these medicines are worthless in medicine; each has its own other indications, and some are used with good reason in specific situations defined by a doctor. It only means they should not be taken in the expectation that they will change the outcome of IVF. Taking them without an indication adds cost, possible side effects and, sometimes, a sense of guilt when the cycle does not end in a pregnancy.

Where the evidence is clearest, it often concerns safety. GnRH antagonist protocols are preferred over the long agonist protocol because they give similar live birth results with a markedly lower risk of ovarian hyperstimulation syndrome (OHSS). In women with a high response, freezing all embryos and deferring transfer to a later cycle is an established way of lowering that risk further. These are decisions the team makes with you, based on AMH, the antral follicle count and the response actually observed.

On the other hand, some things that look like extra care have not shown a benefit. Routine measurement of serum oestradiol or LH on the day of the trigger, for example, has not been shown to add information that improves the outcome when ultrasound monitoring is good. Fewer tests does not mean less care; it means care is directed to where it changes decisions.

Beyond medicines there is a group of laboratory and clinical procedures offered as add-ons: endometrial scratch, PGT-A, assisted hatching, immune therapies, PRP and intralipid. The UK regulator HFEA rates these with a traffic-light system according to the evidence for live birth in a typical patient, and most of them currently sit at red or amber, meaning the evidence is absent or unclear. Some have a place in research or in very specific situations; none is a guarantee.

The same logic applies to supplements. Coenzyme Q10, vitamin D and antioxidants have been studied, but the evidence for live birth remains insufficient. Folic acid is the exception, recommended for pregnancy and the prevention of neural tube defects rather than as an add-on to improve IVF success. If something is sold as a guaranteed improvement, ask for the evidence; a good clinic is not offended by that question.