IVF to treat infertility associated with endometriosis: the latest evidence

In this blog for people with endometriosis, Dr Ippokratis Sarris, Consultant in Reproductive Medicine and the Director of King’s Fertility, and Dr James Duffy, Clinical Fellow at King’s Fertility, discuss the reasons why endometriosis causes fertility problems, potential treatment options, and the latest Cochrane evidence on IVF for endometriosis.

This blog is the fifth in our #MyEndometriosisQuestion series running throughout March, with blogs about endometriosis and an invitation to ask your questions, which will be addressed by a panel of experts. More details at the end of this blog.

Featured image: ‘Brave face of endometriosis pain’ by Margaret Kalms* http://www.endowomanart.com

Take home messages •	Not all people with endometriosis will have problems, and many will eventually be able to get pregnant without fertility treatment. •	There are several types of fertility treatment available. Treatment should be individualised for each person’s circumstances and preferences. •	A Cochrane Review has highlighted uncertainty about whether pre-treatment with GnRH agonist before IVF affects pregnancy or live birth rates. •	For some people, IVF may be more appropriate than trying to conceive naturally, IUI, or keyhole surgery, especially if the fallopian tubes are found to be blocked or if there are other fertility problems such as abnormalities with the sperm.

What is endometriosis?

In the video below, Dr Kuhan Rajah explains what endometriosis is. Dr Rajah is a consultant obstetrician and a sub-specialist in reproductive medicine at King’s Fertility. His areas of expertise are gynaecological and early pregnancy ultrasound, minimally invasive surgery, and all aspects of fertility medicine.

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Why does endometriosis cause fertility problems?

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It is not fully understood why it may be more difficult for some people with endometriosis to become pregnant. Depending on the severity of the endometriosis, between 30% to 50% of people with endometriosis may experience fertility problems. Endometriosis can influence fertility in several ways:

  • distorted anatomy of the pelvis
  • adhesions (bands of scar-like tissue)
  • damage to the fallopian tubes or ovaries
  • inflammation of the pelvic structures
  • altered immune system functioning
  • changes in the hormonal environment of the eggs
  • impaired implantation of a pregnancy
  • altered egg quality

The exact nature of the link between fertility problems and endometriosis is unclear but the severity of the condition and location of the tissue appears to have an effect. It is not fully known why and how mild endometriosis affects the chances of getting pregnant. But people with severe endometriosis, which causes considerable scarring, blocked fallopian tubes, and damaged ovaries, experience the most difficulty becoming pregnant and often require Assisted Reproductive Techniques (ART) treatment, including in-vitro fertilisation (IVF). However, even with severe endometriosis natural conception is still possible.

It is also important to remember that not all people with endometriosis will have problems, and many will eventually be able to get pregnant without treatment.

What are my treatment options?

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There is no such thing as ‘the best fertility treatment’. There are several types of fertility treatment available. What type of fertility treatment you might want to pursue depends on the severity of endometriosis, your age, other medical conditions, past pregnancies, and whether there are other identified fertility problems such as blocked tubes or sperm problems. Your preferences, for example, continuing trying to conceive without fertility treatment or favouring a less invasive fertility treatment, and circumstances, for example, your individual work circumstances or family and carer obligations, should be considered when developing a treatment plan.

Medical treatments

Currently, there is no evidence that taking medicines can improve a person’s chances of getting pregnant.

Keyhole surgery

One treatment option is keyhole surgery which aims to remove deposits of endometriosis and scar tissue from the surface of the womb, fallopian tubes, and ovaries. This is a popular treatment choice for women with infertility associated with endometriosis.

James was part of the research team which prepared a systematic review, Laparoscopic surgery for endometriosis, published in October 2020, on behalf of the Cochrane Gynaecology and Fertility Group. They brought together the evidence from all published research studies evaluating keyhole surgery for the treatment of infertility associated with endometriosis. After systematically reviewing the evidence, they concluded there was moderate-certainty evidence that laparoscopic surgery probably increases pregnancy rates compared to diagnostic laparoscopy in women with mild to moderate endometriosis. Unfortunately, there was insufficient evidence concerning adverse events to allow them to draw any conclusions regarding safety.

Unfortunately, there is currently no high-quality evidence comparing surgery before IVF or comparing keyhole surgery with IVF directly.

You can read more in the Evidently Cochrane blog Keyhole surgery to treat infertility associated with endometriosis: the latest evidence.

Assisted reproductive techniques (ART)

ART treatments, such as Intrauterine Insemination (IUI) or In Vitro Fertilisation (IVF) are established treatments for endometriosis-related infertility.

Intrauterine Insemination (IUI)

Taking into account the available evidence and our experience, we tend to recommend that IUI is only suitable for milder forms of endometriosis (stage I-II) and for women that have normal fallopian tubes and whose partner’s sperm is of sufficiently good quality. In order to improve the likelihood of pregnancy, fertility medication can be used to mildly stimulate the ovaries. Around the time that the egg is released from the ovary (ovulation), a sperm sample is processed in the laboratory. The sperm is then placed into the womb with a thin tube. This is done using a speculum, which is the same instrument which is used when performing a smear test. IUI is currently not recommended routinely by NICE, although it is still widely used throughout the world.

In Vitro Fertilisation (IVF)

IVF is a process of collecting eggs from a woman’s ovaries, fertilising them with sperm (her partner’s or donor sperm), to create embryos and then replacing the embryos in her womb. Donor eggs and sperm can also be used for IVF.

Cochrane evidence regarding pre-treatment before IVF

One treatment option is to treat people with endometriosis with gonadotrophin‐releasing hormone (GnRH) agonist medication for a period of three to six months prior to in IVF. This is a modified version of a naturally occurring hormone known as gonadotropin releasing hormone. Through its effect, it stops the activity of the ovaries and consequently the production of oestrogen. This is thought to cause regression of the endometriosis and could be effective in improving fertility. Practice varies across the world and GnRH agonist medication prior to IVF is sometimes offered, as colleagues believe it could be effective in improving pregnancy and live birth rates.

A research team has prepared a systematic review, Long‐term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis, published in November 2019, on behalf of the Cochrane Gynaecology and Fertility Group. They brought together the evidence from all published research studies evaluating a minimum of three months of GnRH agonist therapy before IVF. They included research studies that randomly allocated women with infertility associated with endometriosis to undergo GnRH agonist therapy before IVF or no pre-treatment. They identified eight research studies which included 640 women. There were no studies comparing long-term GnRH agonist therapy with other types of pretreatment.

After systematically reviewing the evidence, they were uncertain whether pre-treatment with GnRH agonist before IVF affected the pregnancy or live birth rates. Currently, the evidence is also very uncertain about the likelihood that people may experience complications of GnRH agonist therapy.

The main limitations in the evidence were lack of blinding (the process where the women participating in the trial, as well as the research staff, are not aware of the medication used), inconsistency (differences between different studies), and imprecision (small size of each study).

This is disappointing because although we think medical or surgical treatment of endometriosis before IVF has the potential to improve pregnancy and live birth rates, reliable evidence on its effectiveness and safety would better inform decisions about treatment. Further high-quality research is urgently required.

Role of IVF

Assuming that other factors, such as semen quality, fallopian tubes, and ovulation, are normal then NICE recommends that IVF is offered to women with endometriosis after two years of trying for a baby unsuccessfully.

Taking into account the available evidence and our experience, we tend to recommend that, some people with endometriosis go straight to fertility treatment with IVF. For example, if pregnancy does not occur within six to 12 months after surgical treatment of endometriosis, if the fallopian tubes are found to be blocked, or if there are other fertility problems such as abnormalities with the sperm.

Questions to ask your fertility specialist

  • What are my fertility treatment options?
  • What are the chances of success?
  • What are the risks?
  • What are the chances of me becoming pregnant if I do not seek fertility treatment?
  • Should I consider having keyhole surgery before embarking on IVF treatment?
  • How will keyhole surgery affect my egg count (ovarian reserve) and future fertility potential?

More about #MyEndometriosisQuestion – and ask yours

You can find out more in the blog Endometriosis: #MyEndometriosisQuestion – a special series, including how to ask your question on our social media platforms, or you can post your question below this blog. While our experts cannot give specific medical advice, they can provide information about endometriosis, relevant evidence and guidelines, and tips for discussing endometriosis with your own health professional. Our expert panel will do their best to answer your questions individually. They will also reflect on some of the submitted questions in a blog to be published at the end of the month. No individuals will be named or identified in this blog. 

Support for people with fertility problems

There is an online community of people with fertility problems who share knowledge and offer support. There are also charities such as Fertility Network UK, Fertility Europe, and RESOLVE: The National Infertility Association, and grassroots organisations such as Fair Treatment for the Women of Wales.

Support for people with endometriosis

There is a vibrant online community of women with endometriosis, commonly known as #endosisters, who share knowledge and offer support, along with charities such as Endometriosis UK and grassroots organisations such as Fair Treatment for the Women of Wales.

Further information about endometriosis

Join in the conversation on Twitter with @KingsFertility @JamesMNDuffy @CochraneUK and @CochraneCGF or leave a comment on the blog. Comments are checked by the Editors before they are made public on the blog.

Please note, we cannot give specific medical advice and do not publish comments that link to individual pages requesting donations or to commercial sites, or appear to endorse commercial products. We welcome diverse views and encourage discussion but we ask that comments are respectful and reserve the right to not publish any we consider offensive. Cochrane UK does not fact check – or endorse – readers’ comments, including any treatments mentioned.

Ippokratis Sarris and James Duffy have nothing to disclose.

References and further reading (pdf)

*Image used with permission and cannot be reused without permission from the artist.



IVF to treat infertility associated with endometriosis: the latest evidence by Ippokratis Sarris

is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International

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