Time-lapse imaging, embryo glue, endometrial scratch, reproductive immunology… These are just some of the many extras you may be offered alongside your fertility treatment. Of course, you want to do anything you can to increase your chances of success, but are these extras, often known as ‘add ons’, worth paying for? Different clinics and different specialists may give conflicting advice about which add ons can improve the likelihood of pregnancy, and it is not easy to know what to believe when the experts seem to disagree.
Perhaps the best place to start is by understanding what add ons are. It ought to be straightforward, but it is not always clear as fertility clinics may include some of them as part of their standard IVF or ICSI treatment. Other clinics may present you with what looks like a shopping list of extras to consider. Although they may be offered in different ways, add ons are all additions to IVF or ICSI, and most are relatively new so there is little or no clear evidence about how effective they are.
Some clinics may offer every add on available giving you a huge range of extras to choose from, while others provide very few, or none at all. Patients sometimes assume that a clinic offering lots of add ons must be better, but that is not always the case. Clinics that don’t provide them may have looked at the evidence and decided they cannot justify charging patients for a treatment which they do not believe will increase success and may even be risky.
Assessing the evidence is not easy, and the Human Fertilisation and Embryology Authority (HFEA) recently carried out a patient survey to find out what people think about add ons. Some patients were very much in favour and felt that the lack of scientific evidence did not necessarily mean that add ons did not work. They were concerned that patients might miss out if clinics could only provide treatments that have been proven to work. Others were more sceptical, and felt it was too difficult for patients to be faced with an array of extras without clear evidence. Some felt that people could feel pressured into paying for add ons because they would do anything that had any possibility of increasing the chances of success.
So how can you decide whether an add on is right for you? The first thing to look into is whether there is any evidence that the add on works. You may come across research which seems promising, but there are many different types of evidence, and the gold standard is the randomised controlled study. This takes a large group of people who are randomly placed into two separate groups. The people in one group have the add on and those in the other group don’t and the outcomes are then compared. The majority of add ons have not been through this kind of testing.
The HFEA decided to help patients by assessing the evidence about add ons and got together a group of leading scientists and fertility experts to look at all the existing research. They introduced a traffic light system for add ons to help patients when considering possible risks and benefits. When there is more than one good quality study which shows that the procedure is effective and safe, they have given the add on a green light. A yellow light indicates that there is some evidence or some potentially promising results but further research is still required, and a red light indicates that there is no evidence to show that an add on is effective and safe. Once they had made their own assessments, they brought in an expert in the validity of evidence who double checked every traffic light to make sure the ranking was right.
You may be surprised to learn that there are currently no green lights. The majority of add ons fall into amber, with a few red lights. One red-lighted add on is assisted hatching, which involves making a hole in the thick layer of protein which surrounds human eggs and early embryos in order to help an embryo break out of the layer, or “hatch”. Another red light has been given to intrauterine culture, which involves putting fertilised eggs into a device which is inserted into the woman’s womb and left there for several hours. This treatment is rarely offered as there is no evidence to show it works and not enough is known about potential risks. What’s more, the womb would not be the right environment for an embryo at this stage of development as it would usually still be in the tube which connects the ovary to the womb.
Pre-implantation genetic screening, or PGS, has two different lights. It gets a red light if it is carried out on day 3 after egg collection and is offered to women over the age of 37, to couples who had had several miscarriages or failed IVF cycles or to people who may be at risk of chromosomal problems. During PGS, a cell is taken from the embryo to test the chromosomes, but there is no evidence to show that this type of PGS is beneficial. In fact, studies have shown that it can actually reduce success rates, probably because of damage to the embryo. There is, however, some limited evidence that carrying out PGS on a blastocyst on day 5 or 6 may be helpful in finding the best embryo to transfer for younger women with no history of unsuccessful IVF or miscarriage, so PGS at this stage of treatment gets an amber light.
The final red light is for reproductive immunology, which is based on the idea that a woman’s immune system may not accept an embryo due to differences in their genetic codes. There are a variety of treatments which may be offered for this including steroids, intravenous immunoglobulin (IVIg), ‘TNF-a’ blocking agents, and intralipid infusions. There is no convincing evidence for the theory behind reproductive immunology, and not only do these treatments not improve your chances of getting pregnant, there may be very serious risks to using some of them.
Most of the other add ons get an amber light which means more research is needed. For example, there may be inconsistencies in existing evidence about the add on, or there may just be one trial or small studies. The add ons with amber lights include embryo glue, a substance which is added to the dish embryos are stored in before transfer to try to improve the chances of them implanting when they are transferred to the womb, and endometrial scratch, which involves scratching the womb using a small plastic tube. The theory behind endometrial scratch is that it may trigger the body to repair the area where the womb was scratched, sending out chemicals and hormones which can make the lining of the womb more receptive to an embryo implanting. There is currently a large multi-centre trial for endometrial scratch and if you sign up at one of the participating clinics, you may be randomised to get the scratch without having to pay for it.
There is also a national trial (E-Freeze) for elective freeze-all cycles, which involves freezing all the embryos created in an IVF or ICSI cycle for transfer at a later date once the effects of the drugs used to stimulate the ovaries have worn off. Some believe it may be easier for embryos to implant if they are transferred later, and it also reduces the risk of getting ovarian hyperstimulation syndrome (OHSS) when the ovaries become overstimulated after IVF/ICSI treatment.
Finally, the last amber light is for time-lapse imagining, a widely-offered add on which is used to help to choose which embryo to transfer. It allows the embryologist to view regular images of the developing embryos without having to take them out of the incubator to look at them. It means the embryos are undisturbed while they grow and the embryologist can select one based on how they have developed. Although initial research has shown some promise, there is not yet enough evidence to prove that time-lapse imaging improves birth rates.
We have seen that there is no certainty that any of these add ons will increase the chances of successful treatment. Some clinics offer some add ons as part of a standard IVF cycle, and do not charge extra for this. The majority of clinics do charge for add ons and you will want to think carefully about whether you want to pay for something which you are not sure will make a difference.
If you decide to go ahead, you should check how much your clinic charges for the add on and whether this is in line with what other clinics are charging. The prices can vary hugely, and if you are going to pay for an add on, you want to be sure you know what the average price is. For example, some clinics now include embryo glue in a standard cycle, others may charge £75, or £150, or even £350. The embryo glue isn’t different, but the prices are.
Before going ahead with any add on, make sure you are happy with the evidence that your clinic has given you about it and that you have read the information on the HFEA website. Check the price, and think carefully about whether you can afford it. Think about whether paying for add ons would have an impact on your chances of affording another cycle if you need it.
Going ahead with an add on is fine as long as you are fully aware of the evidence about any risks and benefits, and have made an informed decision. It may be worth bearing in mind that there have been no huge leaps in national success rates since add ons were introduced, and any differences they make to treatment outcomes may be relatively small.
You can find the evidence about all the main add ons and their risks and benefits on the HFEA website (https://www.hfea.gov.uk/treatments/explore-all-treatments/treatment-add-ons/).
To find out more about the E-Freeze trial, visit https://www.npeu.ox.ac.uk/e-freeze and for more information about the Endometrial Scratch trial, visit https://www.sheffield.ac.uk/scratchtrial/patients