While endometriosis is found in both fertile and sub-fertile women and people assigned female at birth, it is three times more likely in the latter (14% cf. 4%). Endometriosis is also more likely to be severe in sub-fertile women, compared to their fertile counterparts. In this blog post, Maven Centre’s Dr Alison Bryant-Smith and Dr Melissa Cameron discuss some of the factors that are considered, when helping patients navigate the complicated combination of “endometriosis + subfertility”.

Does endometriosis cause subfertility?

The Venn diagrams of ‘endometriosis’ and ‘subfertility’ have significant overlap. It is estimated that approximately:

• 10% of the female population have endometriosis
• 25% – 50% of women with subfertility have endometriosis
• 30% – 50% of women with endometriosis are impacted by subfertility

However, subfertility is often multifactorial: endometriosis is only one of numerous possible causes for a couple’s subfertility. 

How does endometriosis cause fertility? 

There are several ways in which endometriosis may reduce fertility, including: 

• Endometriosis often causes pain during insertive sex (known as ‘dyspareunia’). This can lead to couples having sex less often, which reduces their chances of conceiving spontaneously 
• Endometriosis can lead to persistent pelvic pain, which can limit sexual activity for those whose partners have sperm 
• Endometriosis often leads to internal scarring, which can distort the anatomy of the Fallopian tubes and ovaries. This may impair the Fallopian tubes’ ability to ‘catch’ an egg. Up to 30% of women with endometriosis have some sort of Fallopian tube problem 
• Reduced ability of eggs to mature and only mature eggs have the ability to fertilise and become an embryo 
• Impaired fertilisation (when egg and sperm combine to create an embryo) 
• Interference with an embryo’s early development
• Reduced ‘endometrial receptivity’ (ie. the uterine lining is not as welcoming to an embryo which is trying to implant and grow) 

Unfortunately, it often occurs that several of these mechanisms are occurring at once. This explains why up to 50% of women with endometriosis are impacted by subfertility. 

Do all stages endometriosis lead to sub-fertility? 

As outlined in our first blog post in this series, there are four stages of endometriosis, from minimal to severe. Broadly speaking, the more severe your endometriosis is, the more likely it is that your fertility will be impaired. However, even women with mild endometriosis have lower fertility rates (when compared to women who don’t have any endometriosis at all).  

Adenomyosis often co-exists with endometriosis and can also contribute to subfertility. 

Can the presence of endometriosis impair IVF outcomes? 

Compared to women without endometriosis who are undergoing in vitro fertilisation (IVF), women with: 

• Stage I (minimal) or II (mild) endometriosis who undergo IVF have lower fertilisation rates, but similar pregnancy and live-birth rates
• Stage III (moderate) or IV (severe) endometriosis who undergo IVF have reduced embryo implantation and pregnancy rates, and reduced live birth rates

If you are suspected of having moderate or severe endometriosis, IVF is less likely to be successful. This is likely related to the fact that endometriosis can impair both the embryo’s early development, and the likelihood of a developing embryo successfully attaching to the uterine lining. 

Surgical management when you have both endometriosis and fertility issues 

Broadly speaking, endometriosis exists as three entities: 

• Peritoneal (shallow) endometriosis 
• Ovarian endometriosis (eg. endometriotic ovarian cysts, or ‘endometriomas’) 
• Deeply infiltrative endometriosis (DIE) 

Many patients have more than one of the above forms of endometriosis. Surgical management should be aimed at improving your chances of pregnancy and reducing any symptoms you may have.  

Stage I (minimal) and stage 2 (mild) endometriosis 

If you’ve had a high-quality transvaginal ultrasound which hasn’t shown any signs of moderate / severe endometriosis, you may be suspected of having mild endometriosis. (These more subtle, shallow blisters of endometriosis can’t yet be seen using ultrasound or MRI.) If so, there is some evidence that having keyhole surgery to cut it out will improve your chances of conceiving – either spontaneously, or with the help of assisted reproductive technologies (ART, like IVF). One recent Cochrane review (the highest level of evidence) concluded that having keyhole surgery to cut out mild endometriosis almost doubles the rate of natural pregnancy thereafter. Hence, many guidelines conclude that keyhole surgery to cut out mild endometriosis may improve fertility. 

Keyhole surgery may also be warranted to improve your symptoms (such as bad period pain). Your gynaecologist may recommend that you have a ‘tubal patency test’ (flushing the Fallopian tubes with blue dye) during your keyhole surgery, to confirm that at least one Fallopian tube is open.  

Following keyhole surgery to cut out mild endometriosis, your gynaecologist may suggest trying to conceive naturally, or may suggest proceeding with IVF: many factors are taken into consideration to guide such decision-making. 

Endometriotic ovarian cysts (‘endometriomas’) 

Endometriotic ovarian cysts (or ‘endometriomas’) are found in approximately 30% of women with endometriosis: one third of these women have endometriomas in both the left and right ovary. Endometriomas are considered a marker of more severe endometriosis; 50% of women with deeply infiltrative endometriosis (DIE) will have an endometrioma. 

Endometriomas cause particular challenges for both women and clinicians, in several ways: 

• Endometriomas (esp. if > 3cm in size) can impair ovarian function and reserve, making it less likely that a good quality egg is released every month 
• Endometriomas often cause thick internal scarring and distorted anatomy, which require  the skills of an advanced laparoscopic gynaecological surgeon 
• Surgically cutting out an endometrioma involves cutting stripping it out from the surrounding ovary. This process can further impair ovarian function 
• Having egg pick-up (as part of the IVF process) in the presence of endometriomas may accidentally introduce an infection into the ovarian cyst. If an ovarian abscess forms, ovarian function will be further impaired. 

Pooling together the results of relevant research trials favours cutting out endometriomas (rather than simply surgically draining them), in order to: 

• Improve the chances of natural conception 
• Reduce endometriosis recurrence (ie. reduce the chances that the endometriosis happens again) 
• Reduce recurrence of dysmenorrhoea (bad period pain), dyspareunia (painful sex) and non-cyclic pelvic pain (pain between your periods) 

Because of the above inter-related factors, navigating a safe course through the minefield that is the “endometriomas + infertility” combination requires the knowledge and skills of a gynaecologist with fertility expertise, such as Maven Centre’s Dr Melissa Cameron. It may also involve a staged approach, such as: 

• IVF and egg pick-up from the ‘better’ of the two ovaries (ie. the ovary without the endometrioma) 
• Then keyhole surgery to remove the endometrioma 
• Then ‘embryo transfer’ to place the fertilised egg + sperm combination inside the uterus, in the hopes that it attaches to the uterine lining and grows into a healthy, happy baby 

An alternative approach is: 

• Keyhole surgery to drain (but not surgically remove) the endometrioma 
• IVF 
• Then another keyhole surgery to remove the endometrioma entirely 

Multi-disciplinary teams of outstanding clinicians (such as that at Maven Centre) are well-placed to discuss your options. We often chat about challenging clinical situations amongst ourselves, and even refer patients amongst ourselves, to ensure that (as a team) we are optimising your chances of both symptomatic relief, and taking a baby home. 

Deeply infiltrative endometriosis (DIE) 

Deeply infiltrative endometriosis (DIE) is when an endometriotic nodule grows more than 5mm under the layer of cells that lines the inside of your abdomen and pelvis, which is called the ‘peritoneum’. These deeper nodules may be found growing deeply through the peritoneal lining that overlies your bladder, bowel (esp. rectum), and / or pelvic side walls. DIE is the most severe form of endometriosis, and is a sub-type of stage IV (severe) endometriosis. Fortunately, DIE only occurs in approximately 1 – 2 % of all women with endometriosis.  

There is mixed evidence regarding whether or not surgical excision of stage III (moderate) endometriosis, stage IV (severe) endometriosis, or DIE improves fertility or IVF outcomes. However, surgical excision of DIE should lead to a significant improvement in dyspareunia (pain with sex) and endometriosis recurrence. 

In women with current severe endometriosis who have previously experienced failed IVF cycles, having their severe endometriosis surgical excised will lead to up approximately 42% achieving a pregnancy. 

The current guidance from the world’s leading fertility authority (the European Society of Human Reproduction and Embryology) states that while surgery for DIE does not definitely improve fertility, it is an option in symptomatic women wanting to conceive (particularly if IVF has not been successful previously). 

ART in the context of endometriosis 

For many women who have both endometriosis and subfertility, assisted reproductive technologies (ART) will provide their best chance of achieving parenthood. Unfortunately there are no high-quality randomised controlled trials comparing the success of ART with expectant management (ie. a ‘wait and see’ approach), for women with either mild or severe endometriosis. 

Mild endometriosis appears not to have any impact on ART success rates. In contrast, the presence of moderate or severe endometriosis significantly lowers both the number of eggs collected, and live birth rates. Patients with severe endometriosis, particularly when the bowel is involved, have higher risks of inadvertent complications such as bowel injury, during the egg collection procedure. They may also experience more discomfort throughout the cycle.  

Reasons to consider IVF if you have both endometriosis and fertility issues 

There are several key reasons to consider IVF, if you’re struggling with both endometriosis and subfertility. These include: 

• Fallopian tube dysfunction (eg. blockage) 
• Male contributing factors (eg. abnormal sperm test results) 
• Significant anatomical distortion due to endometriosis, which can’t be fixed with keyhole surgery (eg. severe Fallopian tube distortion, non-functional or absent ovary) 
• Advanced age (eg. maternal age ≥ 40 yo) 
• Over 3 years of trying to conceive naturally 
• If other fertility treatments (including keyhole surgery) have not been successful 

Impact of endometriosis on pregnancy outcomes 

Even if you have endometriosis and manage to fall pregnant, unfortunately endometriosis is associated with an increased risk of: 

• Miscarriage (if severe endometriosis) 
• Having a small baby (‘intrauterine growth restriction’) 
• Pre-eclampsia (a combination of high blood pressure and excess protein in the urine) 
• Premature labour 
• Bleeding after birth (or ‘post-partum haemorrhage’) 
• Caesarean section 

When you book in for antenatal care, let your midwifery and obstetric team know that you’ve previously been diagnosed with endometriosis. 

Topic area frequently asked questions (FAQs) 

I’ve had keyhole surgery to excise my endometriosis. How do I know whether to try to conceive spontaneously, or to go straight to IVF? 

Speak to your gynaecologist and / or fertility specialist! Fertility is complex involving many factors that can affect the eggs, sperm and uterus. Your specialist will work with you to recommend an individual plan tailored to your unique situation. Some clinicians use the Endometriosis Fertility Index (EFI), which is a scoring system that may guide this decision. We are able to estimate your likelihood of conceiving spontaneously, by plugging into the scoring system several variables, such as: 

• The level of function of your Fallopian tubes and ovaries at the end of your keyhole surgery 
• Your age 
• How many years you have been trying to conceive 
• If you have been pregnant previously 

IVF is likely to be needed to manage endometriosis-related infertility if: 

• Fallopian tube function remains compromised despite high-quality surgery 
• There is ‘male factor’ infertility (eg. abnormal sperm test results) 
• The calculated EFI score is low 
• Other treatments have not been successful 

Will the hormones I need to take as part of IVF make my endometriosis worse? 

One systematic review (the highest level of medical evidence) found that undergoing IVF does not increase endometriosis-related pain; nor does IVF increase the risk of endometriosis recurrence. Other studies have shown that IVF has minimal impact on endometrioma size. Some patients experience more discomfort throughout a cycle but this is not always the case. 

Conclusion  

The combination of endometriosis plus subfertility can present many and various challenges, for both patients, gynaecologists, and fertility specialists alike. Individualised patient management is needed, which takes into account factors such as: your age; other factors that might impact on your fertility (eg. abnormal sperm test results); endometriosis severity; the presence / absence of endometriomas; your symptoms; and the length of time you’ve been trying to conceive. Multidisciplinary teams such as that at Maven Centre are well-placed to help you navigate these discussions, to optimise your chances of taking home a healthy baby.