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Treatment add-ons

Your clinic may offer you additional treatments on top of your main treatment such as in vitro fertilisation (IVF). or intracytoplasmic sperm injection (ICSI). This page will explain 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.

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 sometimes emerging techniques that may have shown some promising results in initial studies, or they may have been around for a number of years, 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 been shown to be effective, we’ve developed a traffic light rating system.

What do the ratings mean?

The only way to be confident that a treatment is effective enough to be used routinely 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 give a green symbol where there is more than one good quality RCT which shows that the procedure is effective and safe.

We use an amber symbol where there is a small or conflicting body of evidence, which means further research is still required and the technique cannot be recommended for routine use.

A treatment is red if there is no evidence to show that it is effective and safe.

Currently none of the treatment add-ons we have assessed have been rated green. This means that we don’t think any of these techniques should be used routinely.

Red - There is no evidence that this add-on is effective and safe

Red - There is no evidence that this add-on 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.

Amber - There is a conflicting body of evidence for this add-on, further research is required

Amber - There is a conflicting body of evidence for this add-on, further research is required

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.

Amber - There is a conflicting body of evidence for this add-on, further research is required

Amber - There is a conflicting body of evidence for this add-on, further research is required

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.

Amber - There is a conflicting body of evidence for this add-on, further research is required

Amber - There is a conflicting body of evidence for this add-on, further research is required

Embryo glue - Amber

What is embryo glue?

Embryo glue contains a 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.

Amber - There is a conflicting body of evidence for this add-on, further research is required

Amber - There is a conflicting body of evidence for this add-on, further research is required

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. 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?

The current amber rating for endometrial scratching is based on a small number of moderate quality studies. There are currently three large clinical trials looking into endometrial scratching and the early findings suggest that the benefits of using this procedure may be less certain than initially thought. We will update our information when the data from these clinical trials becomes available.

Red - There is no evidence that this add-on is effective and safe

Red - There is no evidence that this add-on is effective and safe

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 developing 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 intrauterine culture at an additional cost.

Amber - For day 5 screening there is a conflicting body of evidence for this add-on, further research is required

Amber - For day 5 screening there is a conflicting body of evidence for this add-on, further research is required

Red - For day 3 screening there is no evidence that this add-on is effective and safe

Red - For day 3 screening there is no evidence that this add-on is effective and safe

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

What is PGS?

PGS (also known as aneuploidy screening or PGT-A) involves checking embryos for abnormalities in the number of chromosomes. Embryos with an abnormal number of chromosomes (known as aneuploid embryos) have less chance of developing into a baby or, less commonly, may result in a baby being born with a genetic condition. PGS identifies aneuploid embryos that are unsuitable for fertility treatment.

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 the removal of cells is done carefully.

Are there any risks?

PGS carries some 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).
  • Using PGS may mean you have fewer embryos to use in treatment, or for freezing to use in treatment at a later date. If any healthy embryos are discarded in this process, you may have fewer chances to transfer an embryo which could develop into a healthy baby.
  • 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 chromosomal 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.

Some small studies have shown that PGS carried out at a later stage, the blastocyst embryo on day five or six, 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.  It is important to understand that PGS will not increase your overall chances of having a baby. It may help to reduce the likelihood of having a miscarriage, but more evidence is needed to confirm these findings. When considering whether to have PGS, you should also think about the cost as it is usually very expensive.

Find out more about PGS  

Find out more about blastocyst embryos

Red - There is no evidence that this add-on is effective and safe

Red - There is no evidence that this add-on is effective and safe

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 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 these treatments, some of which are very serious.

Amber - There is a conflicting body of evidence for this add-on, further research is required

Amber - There is a conflicting body of evidence for this add-on, further research is required

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.

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.

Indeed, being undisturbed while they grow may improve the quality of the embryos but 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. 

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

Red - There is no evidence that this add-on is effective and safe

Red - There is no evidence that this add-on is effective and safe

Intracytoplasmic morphologic sperm injection (IMSI) - Red

What is IMSI?

Intracytoplasmic morphologically selected sperm injection (IMSI) is a sperm selection method used in intracytoplasmic sperm injection (ICSI). The technique involves using a microscope to view sperm under very high magnification (over x6000). This allows clinics to view detailed images of sperm.

Are there any risks?

IMSI is a non-invasive test performed on a semen sample as an additional step in the ICSI process. The risks associated with the use of ICSI also apply to IMSI; there are no significant additional risks to the patient or embryo.

Find out more about ICSI

What’s the evidence for IMSI?

There have been several RCTs within the last decade. Systematic reviews suggest that IMSI could be beneficial in specific situations such as previously failed ICSI attempts. The research that has been carried out does not support the use of IMSI over standard ICSI for infertile men. One small study found that IMSI had improved pregnancy outcomes in older women, however this study was carried out with a small number of women and the link, if any, between IMSI and older eggs is not fully understood.

Red - There is no evidence that this add-on is effective and safe

Red - There is no evidence that this add-on is effective and safe

Physiological intracytoplasmic sperm injection (PICSI) - Red

What is PICSI?

Physiological intracytoplasmic sperm injection (PICSI) is a technique used to select sperm to use in ICSI treatment. It involves placing sperm with hyaluronic acid (HA), a natural compound in the body. PICSI identifies sperm that can bind to HA and these sperm are selected for use in treatment.

Are there any risks?

PICSI is a non-invasive procedure performed on a semen sample as an additional step in the ICSI process. Risks associated with the use of ICSI also apply to PICSI; there are no significant additional risks to the patient or embryo.

Find out more about ICSI

What’s the evidence for PICSI?

There have been a number of studies comparing PICSI with standard ICSI, however there is very little evidence to suggest any benefit of using it. A large randomized study was recently carried out which showed that using PICSI did not increase the chances of having a baby.

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Additional information - Sperm DNA damage

What is sperm DNA damage?

Half of the genetic information to make us is delivered by the sperm to the egg. It takes around two months for a mature sperm to be made and during this time the DNA of the sperm may become damaged.

A number of different tests might be used by your clinic to assess the level of DNA damage in your sperm. There is some evidence for a relationship between sperm DNA damage and the outcome of fertility treatment. However, the evidence is conflicting and depends on the type of test used by the clinic. The results of a sperm DNA damage test are unlikely to impact on the management of your treatment.

There is currently no traffic light rating for treatments relating to sperm DNA damage.

Are there any risks?

Sperm DNA damage testing is a non-invasive procedure performed on a semen sample, usually before treatment as an additional diagnostic test. There are no significant additional risks to the patient.

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Review date: 18 January 2021

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