IVF add-ons: the latest Cochrane evidence

In this blog for people undergoing IVF, Sarah Lensen (Cochrane editor) and Noortje Uphoff (IVF patient) look at the latest Cochrane evidence on IVF add-ons, as part of the new Cochrane Special Collection: In vitro fertilisation – effectiveness of add-ons.

Page last checked 26 June 2023

Take-home points

Although many different IVF add-ons are available, none have been evaluated in high-quality studies to show that they actually help people to get pregnant and have a baby, and are safe to use. There is some evidence, but it is not high-quality, that three of these add-ons may benefit people having IVF: addition of hyaluronic acid to embryo transfer media, using an advanced sperm selection technique known as hyaluronic acid binding, and injection of high doses of a pregnancy hormone (hCG) into the womb near the time of embryo transfer. People undergoing IVF might like to read the summaries of these Cochrane Reviews, and even take them along to IVF consultations to discuss the evidence with the fertility specialist, to help them make decisions about using IVF add-ons.

“During our first round of IVF, we were given the option to use embryo glue to help the embryo ‘stick’. We could also opt for ‘embryo time lapse imaging’ so that the embryologist could make detailed observations of embryos as they developed each day in the lab, without disturbing them. We looked at the evidence from Cochrane Reviews to help our decision making. It was important to us to know whether these optional extras would do no harm. Making these decisions was difficult. We had to weigh up the additional costs and our wish to do everything we could to make IVF work for us. We were successful after three IVF treatment cycles and our baby is due to arrive in a few weeks. If we use IVF again in the future, I hope to look at the Cochrane Library and find that more robust evidence on the effectiveness and safety of add-ons has emerged!” –  Noortje Uphoff.

In vitro fertilization (IVF)

Many couples have trouble getting pregnant and may turn to IVF for help. People also undergo IVF for other reasons, such as needing genetic testing of their embryos for a known inherited disorder or single women who wish to have a baby. Unfortunately, the success rate of IVF is mediocre. Although the success of IVF depends on many factors, including the age of the women, the overall chance of getting pregnant and having a baby from IVF is approximately 20-30% per IVF cycle.

In 1978, Louise Brown was the first baby born using IVF. In the last 40 years IVF technology has undergone many important advancements, including ovarian stimulation to allow the collection of multiple eggs in a single cycle instead of just one, injection of sperm directly into eggs to allow IVF to treat couples with male-factor infertility, and freezing of embryos and eggs so they can be used in the future. The field of IVF is constantly advancing and introducing new techniques or treatment options, with the hopes that they will improve the chances of having a baby for the 1 million people who undergo IVF across the world every year.

What are IVF add-ons?

When people undergo IVF, they are often provided with additional options to consider as part of their IVF treatment. This might include extra procedures, medicines, or laboratory techniques. We call these optional extras IVF ‘add-ons’. Examples include taking extra medications such as steroids or aspirin, dipping the embryo into an extra solution known as embryo glue just before it is transferred into the womb, or genetic testing of embryos for extra chromosomes when there is no known inherited disorder present. IVF add-ons are normally offered or available at IVF clinics with the aim or hope that they may help people to conceive and have a baby from IVF. Because they are additional to standard IVF, add-ons usually come at an extra cost to patients. The cost will vary depending on the add-on, but can be anywhere between a few pounds and thousands of extra pounds. Different IVF clinics may choose to make different add-ons available, and some IVF clinics don’t use any add-ons.

The evidence for IVF add-ons

Just like every intervention in health care, it is important that new treatment options are robustly evaluated in scientific studies to confirm that they are effective and safe. People having IVF should have access to information about the evidence of risks and benefits of IVF add-ons when making decisions about whether to use them. This may be especially important in the setting of IVF where concerns about safety include the patient but also a potential pregnancy.

In this Special Collection, we have collated all the Cochrane Reviews that evaluate different IVF add-ons. We have only included reviews that were completed in the last 5 years, to make sure the evidence is up-to-date.

These Cochrane reviews found that none of the IVF add-ons are supported by high-quality evidence that the add-on is effective and safe. In most cases, the included studies suffered from limitations, such as risk of bias and small sample size, which result in uncertainty about whether the add-on is beneficial, harmful or has no effect – it was not possible to tell.

For three add-ons, there was some evidence of possible benefit, however the evidence was not high quality:

People having IVF should have access to information about the evidence of risks and benefits of IVF add-ons when making decisions about whether to use them. This may be especially important because concerns about safety include the patient but also a potential pregnancy.

Making decisions about using IVF add-ons

Most IVF add-ons tend to be offered as optional extras, that people can choose whether to use on top of their standard IVF care. We hope the evidence summarized in this Special Collection will help people to make these decisions. You can also read a blog about endometrial scratching (or endometrial injury). If you are considering whether to use an IVF add-on, discuss the evidence, and your options, with your IVF doctor.

You might want to ask:

  • What is the benefit?
  • What are the risks?
  • What does it cost?

The future

People undergoing IVF should be able to presume that the treatment options they are offered or recommended, such as IVF add-ons, are safe to use and are likely to offer them some benefit, such as an increased chance of having a baby. This is especially so if the add-on is costing patients extra money, which they could otherwise save for a potential further IVF cycle or put towards treatment options that have good evidence. The best way to know whether IVF add-ons are effective and safe is to evaluate them in large randomised controlled trials. We need more of these studies so we can test new add-ons and make sure they work and don’t cause harm, to help people make informed decisions about their IVF treatment options.

Noortje Uphoff
Noortje Uphoff has received three IVF treatments to help her get pregnant. Noortje shares her experience of fertility treatments to raise awareness of infertility and to bring a patient perspective to the research. She is also a mental health researcher and works for the Cochrane Common Mental Disorders group at the University of York.

Join in the conversation on Twitter with @CochraneUK and @CochraneCGF or leave a comment on the blog. Please note, we will not publish comments that link to commercial sites or appear to endorse commercial products. We welcome diverse views and encourage discussion but ask that comments are respectful and reserve the right to not publish comments we consider offensive.

References (pdf)

Dr. Lensen reports being a Cochrane Review author including reviews on IVF add-on endometrial scratching. Sarah’s biography appears below.

Dr. Noortje Uphoff has nothing to disclose.

IVF add-ons: the latest Cochrane evidence by Sarah Lensen

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

1 Comments on this post

  1. How big of a difference do these IVF treatment add-ons make in terms of success? There are facilities and physicians all over the globe promising high IVF treatment success rates. The significance of add-ons for a successful IVF treatment procedure, on the other hand, is not highlighted. Thank you for sharing this useful information.

    IVF Treatment in Turkey / Reply

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