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Treatment add ons

Your clinic may offer you additional treatments on top of your main treatment such as IVF or ICSI. This page explains what some of the most common treatment add ons are and how effective they are. For more detailed information, you may want to contact a clinic to discuss this further with a specialist. Some of these add ons are also offered on the NHS.

What are add ons?

Add ons are optional extras that you may be offered on top of your normal fertility treatment, often at an additional cost. They’re typically emerging techniques that may have shown some promising results in initial studies but haven’t necessarily been proven to improve pregnancy or birth rates.

Some clinics may include certain add ons with their treatment packages as standard whilst others charge separately. To make it easier to identify which add ons have a lot of evidence supporting their effectiveness and safety and which have very little evidence, or should be considered experimental, look for these symbols:

What do the ratings mean?

The only way to be confident that a treatment is effective in humans is to carry out a randomised controlled trial (RCT). In an RCT, patients are assigned randomly to two groups: a treatment group, given the new treatment and a control group, given either a well-tried treatment or a placebo. The number of patients included is very important, with more patients giving more accurate results.

Ideally, several different groups of researchers or scientists should have performed high quality RCTs and follow up studies to be sure a new procedure is effective and safe. We have given a green symbol where there is more than one good quality study which shows that the procedure is effective and safe.

We have used a yellow symbol where there is a growing body of evidence which is showing promising results but where further research is still required. A treatment is red if there is no evidence to show that it is effective and safe.

Assisted hatching - Red

What is assisted hatching?

The egg and early embryo are surrounded by a thick layer of special proteins called the zona pellucida. Before an embryo can implant in the womb it has to break out or ‘hatch’ from its zona pellucida.
Some people think that assisted hatching - using acid, lasers or other tools to thin or make a hole in the zona pellucida - helps the embryo to hatch.

Are there any risks?

There is always some risk of damaging embryos with these types of procedures.

What’s the evidence for assisted hatching?

The National Institute for Clinical Excellence (NICE) is the national body advising doctors on treatments. It says:

“Assisted hatching is not recommended because it has not been shown to improve pregnancy rates.”

NICE also says that further research is needed to find out whether assisted hatching has an effect on birth rates and to examine the consequences for children born as a result of this procedure.

Some clinics believe assisted hatching can lead to higher birth rates in very select cases. For example, it has been noted that the zona pellucida may be thicker in some older women, so weakening or thinning it may help the embryos hatch, but this hasn’t been proven.

Early results are promising but more evidence is needed.

Early results are promising but more evidence is needed.

Artificial egg activation calcium ionophore - Amber

What is egg activation?

When a sperm meets an egg, it triggers a process called ‘egg activation’ which starts off the process of embryo development, while at the same time allowing only one sperm to fertilise the egg. If the egg doesn’t activate, then it won’t develop.
Egg (or oocyte) activation may be stimulated by chemicals called calcium ionophores. These chemicals can be added to the embryo in the lab.

Are there any risks?

In theory, egg activation using calcium ionophores could cause embryos to have abnormal numbers of chromosomes, which would cause the pregnancy to miscarry. As yet there’s not enough evidence to decide whether these risks are a serious concern.

Given the possible risks, clinics offering this treatment are expected to do so only in selected patients who have had failed fertilisation and to justify their reasons for doing so.

What’s the evidence for egg activation?

In the few studies done to date, egg activation using calcium ionophores may improve fertilisation rates in ICSI cycles where the egg and sperm have failed to activate in previous treatment cycles. However, there are no RCTs to show that it is effective or follow up studies on the safety of this technique.

Early results are promising but more evidence is needed.

Early results are promising but more evidence is needed.

Elective freeze all cycles - Amber

What are elective freeze all cycles?

In a normal IVF cycle, one to two fresh embryos are transferred a few days after the egg collection and any remaining suitable embryos are frozen.

Elective freeze all cycles involve creating embryos using IVF or ICSI and then freezing all of them so no embryos are transferred in the ‘fresh’ cycle. The embryos are thawed a few months later and transferred to the woman’s womb as part of a frozen embryo transfer (FET) cycle.

There is some evidence that the body’s hormonal response to fertility drugs can affect the lining of the womb, which makes it more difficult for the embryos to implant. Freezing the embryos means they can be transferred back into the woman when the womb lining is well developed.

It’s also thought by having all their embryos frozen, women are at lower risk of suffering from ovarian hyperstimulation syndrome (OHSS), an overreaction to fertility drugs. This is because OHSS is more common and more severe when it occurs during a pregnancy.

Find out more about the risks of fertility treatment

There is also evidence that while the birthweight of babies born from normal fresh IVF cycles is lower, from FET cycles it is higher, closer to naturally conceived babies. Since birthweight is associated with risk of disease in later life, freeze all cycles may be safer for the baby.

Are there any risks of elective freeze all?

The freezing process is generally thought to be safe for the embryo, although there’s always a risk that one or more embryos may not survive.

Find out more about embryo freezing

What’s the evidence for freeze all cycles?

Research into freeze all cycles is progressing quickly. Some research suggests that pregnancy rates are increased by using frozen embryo transfers (FETs) rather than fresh transfers, and that the risks to mother and baby are lower. These include the risk of OHSS (above) and of low birthweight.

However, at the moment, doctors don’t know with enough confidence whether freeze all cycles are safer and more effective than conventional IVF or ICSI. There’s currently a large clinical trial of freeze all cycles called E-Freeze, which you may be invited to join by your clinic.

Research consistently shows benefit, however further evidence is needed.

Research consistently shows benefit, however further evidence is needed.

Embryo glue - Amber

What is embryo glue?

Embryo glue contains a natural substance called hyaluronan, which may improve the chance of the embryo implanting in the womb. It is added to the solution in the dish in which the embryos are kept before being transferred to the woman.

Are there any risks?

There are no known risks from using embryo glue.

What’s the evidence for embryo glue?

Research from the Cochrane review shows that embryo glue containing hyaluronan increases pregnancy and live birth rates by around 10%. There is one high quality study in this review which shows that the use of embryo glue improves pregnancy and live birth rates. Other studies in the review were of moderate quality. Further high quality studies are needed before doctors can be confident of the benefits of embryo glue.

Research consistently shows benefit, however further evidence is needed.

Research consistently shows benefit, however further evidence is needed.

Endometrial scratching - Amber

What is endometrial scratching?

In order to have a successful pregnancy, an embryo needs to ‘implant’ in the womb; if it doesn’t, the woman will need to start her cycle again.

Most embryos don’t implant because they’ve been unable to develop fully to the implantation stage or because of a developmental mismatch between the stage of the embryo and the lining of the womb.

However, in a small number of cases an embryo won’t implant because the lining of the womb isn’t providing them with the right environment.

Endometrial scratching is carried out before IVF and is intended to correct problems with the womb lining. During the procedure the lining of the womb (the endometrium) is ‘scratched’ using a small sterile plastic tube.

The theory is that this procedure triggers the body to repair the site of the scratch, releasing chemicals and hormones that make the womb lining more receptive to an embryo implanting.

Some also suggest the treatment may activate genes that make the womb lining more receptive to an embryo implanting.

Are there any risks?

There is a small risk that if you have an infection within your cervix before ‘scratching’, this may cause the infection to spread up into the uterus. Your clinic can treat this if necessary.

What’s the evidence for endometrial scratching?

Early results suggest that endometrial scratching could increase pregnancy rates, although stronger evidence is needed to prove this. There’s currently a large clinical trial underway in the UK called Endometrial Scratch Trial, which you may be invited to join by your clinic.

Intrauterine culture - Red

What is intrauterine culture?

During a conventional IVF cycle, eggs are fertilised and allowed to develop in a special culture fluid inside an incubator. Intrauterine culture differs in that it allows the early stages of embryo development to take place within the patient’s womb. As with conventional IVF, eggs and sperm are collected and prepared. The eggs are fertilised and placed in an intrauterine culture device, which is inserted into the woman’s womb.

The device stays in place for several hours during the initial stages of embryo development. When the device is removed, the embryos are put in an incubator until they are ready to be transferred back to the womb or frozen for use in future treatment.

Are there any risks?

There is currently very little evidence exploring the potential risks in using this device. It’s worth noting that the womb is not the right place in the body for the embryo to develop at this stage. Normally it would be living in the ‘fallopian’ tube which connects the ovary to the womb.

What’s the evidence for intrauterine culture?

There’s currently no evidence to show that intrauterine culture improves birth rates and is safe. This is something you may wish to consider if you are offered this technique at an additional cost.

Early results for PGS carried out on day five embryos are promising but further evidence is needed.

Early results for PGS carried out on day five embryos are promising but further evidence is needed.

No evidence to show that PGS carried out on day three embryos is of benefit.

No evidence to show that PGS carried out on day three embryos is of benefit.

Pre-implantation genetic screening (PGS) - Amber for day five embryos, Red for day three embryos

What is PGS?

PGS (also known as aneuploidy screening) involves checking embryos for abnormalities in the number of chromosomes. Embryos with an abnormal number of chromosomes may stop developing very early on, end in a miscarriage or a still birth, or the child may be born with a disorder such as Down’s Syndrome.
To do PGS, embryologists remove a cell, or if at a later stage, several cells, from the embryo, which is then tested for any chromosomal abnormalities. The embryo can still develop with fewer cells, as long as this is done carefully.

Are there any risks?

PGS carries the same risks as PGD, which you can read about here. However, PGS may have some additional risks:

  • Although current PGS techniques are mostly very accurate, the test may give the wrong result (it may miss an abnormality or detect one that isn’t there).
  • Removing a cell from the embryo may damage it and prevent it from successfully developing once it’s been transferred to the womb.
  • Removing part of the embryo may cause changes in later growth in the womb, which may cause problems in later life.
  • In some cases, cells within the same embryo are not chromosomally identical (known as ‘mosaic’), which means that PGS may show that the embryo has chromosome abnormalities when in fact it’s capable of producing a normal pregnancy or vice versa. In some clinics, mosaic embryos are considered for transfer, even though they show some abnormality.

What’s the evidence for PGS?

In the past PGS was traditionally offered to women over 37, couples who had had several miscarriages or failed IVF cycles, people with a family history of chromosome problems, and men whose sperm may carry abnormal chromosomes. The cells were removed from the embryo at the 8-cell stage on day 3.

There is no evidence to show that this type of PGS is beneficial for these groups. In fact studies have shown that this type of PGS can actually reduce success rates, probably because of damage to the embryo.

Three small studies have now shown that PGS carried out at a later stage, the blastocyst embryo on day 5 or 6, might be helpful in selecting a viable embryo to transfer in younger patients who are typically under 37 with no history of miscarriage or failed IVF cycles. However, more evidence is needed to confirm these findings.

Find out more about PGS 

Find out more about blastocyst embryos

Reproductive immunology tests and treatment - Red

What is reproductive immunology?

Reproductive immunology is a field of study that looks at how a woman’s immune system reacts when she becomes pregnant.
Usually, your immune system works by fighting off any invading cells that it doesn't recognise because they don't share your genetic code. In the case of an embryo, the immune system learns to tolerate it even though it has a different genetic code from the mother.

Some scientists believe that in some cases of miscarriage or infertility, the mother’s immune system may fail to accept the embryo due to these differences in their genetic codes.

Are there any risks?

There are various different treatments associated with reproductive immunology, which are used to suppress the body’s natural immunity, and all of which have risks:

  • Steroids (e.g. prednisolone): Risks include high blood pressure, diabetes and premature birth.
  • Intravenous immunoglobulin (IVIg): Side effects can include headache, muscle pain, fever, chills, low back pain, and rarely thrombosis (blood clots), kidney failure and anaphylaxis (a bad allergic reaction to the drug).
  • TNF-a blocking agents (eg adalimumab, infliximab): Remicade is not recommended for use during pregnancy. Side effects can include infections including septicaemia, chronic infections such as tuberculosis, and severe allergic reactions to the drug.
  • Intralipid infusions: Side effects include headache, dizziness, flushing, nausea and the possibility of clotting or infection.

What’s the evidence for reproductive immunology?

There is no convincing evidence that a woman’s immune system will fail to accept an embryo due to differences in their genetic codes. In fact, scientists now know that during pregnancy the mother’s immune system works with the embryo to support its development.

Not only will reproductive immunology treatments not improve your chances of getting pregnant, there are risks attached to all these treatments, some of which are very serious.

Early results are promising but more evidence is needed.

Early results are promising but more evidence is needed.

Time-lapse imaging - Amber

What is time-lapse imaging?

In IVF, time-lapse imaging is used to help select the embryos most likely to successfully develop into a baby.

In conventional IVF, the embryologist will check the developing embryos each day under a microscope, which involves removing them from the incubator for a brief period.

Time-lapse imaging allows the embryologist to take thousands of images of the embryos as they grow without disturbing them. Not only does this mean the embryos do not have to be removed from the incubator, it also allows the embryologist to get a continuous view of each embryo as it develops, rather than just viewing them once a day.

The embryologist can then choose a specific embryo for implantation based on criteria such as rate of development and the number and appearance of cells. Indeed, being undisturbed while they grow may improve the quality of the embryos.

Are there any risks?

No, there are no known risks to the woman or her embryos from time-lapse imaging.

What’s the evidence for time-lapse imaging?

There have been various studies to try and see if time-lapse imaging can improve birth rates. Initial research has shown some promise, but it’s still very early days.
There’s certainly not enough evidence to show that time-lapse imaging improves birth rates, which is something you may want to consider if it’s being offered to you at an extra cost.

The NHS has further information on the evidence for time-lapse imaging.


Review date: 9 November 2020

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