The effect of endometriosis and its IVF/ICSI outcome?

Elias Tsakos, FRCOG
Medical Director , Embryoclinic

From this video you will find out:

What is endometriosis, what are its symptoms, and how is it diagnosed?
How does endometriosis affect fertility?
How does endometriosis affect IVF/ICSI outcome?
What are the medical and surgical treatment options available?

The effect of endometriosis and its IVF/ICSI outcome?

During this session, Dr Elias Tsakos, FRCOG, Medical Director of Embryoclinic – Assisted Reproduction Clinic in Thessaloniki discussed the impact of endometriosis on IVF results, ways to treat it and outcomes.

Endometriosis – what is it?

Endometriosis is a condition in which tissue from the lining of the uterus, known as endometrial tissue, grows in ectopic locations. These locations can include the tubes, ovaries, uterus, peritoneum, intestines, bladder, and even remote areas like the diaphragm, chest, surgical scars, and eyelids. The presence of endometrial cells in these ectopic sites can lead to small bleeding areas and inflammation, causing various symptoms such as pain and infertility.

How common is endometriosis?

Endometriosis affects approximately 10% of women, making it quite common. It has been estimated that around 200 million women worldwide suffer from endometriosis. While it mainly affects women of reproductive age, it can also be found in women older than 50 or 60 years old. The most common age range affected by endometriosis is between 30 and 40, and the diagnosis is often delayed by about 7 years or more. Endometriosis and fibroids are more common in African and Asian populations, but they can be found worldwide, including in the Americas and Europe. The age distribution of endometriosis shows that the highest prevalence is between 30 and 40. However, considering the potential delay in diagnosis, the disease may have started much earlier but remained undetected until that age range.

Clinical symptoms of endometriosis

Common symptoms of endometriosis include tiredness, low energy, abdominal pain, painful periods (dysmenorrhea), pelvic pain, back pain, and abdominal bloating. Additional symptoms may include painful intercourse, painful passage of stools, and painful urination. These symptoms arise due to chronic inflammation, chronic pain, and irritation affecting various organs.

Endometriosis & Infertility

Endometriosis is associated with infertility in about 30% to 50% of women. The presence of endometriosis increases the chance of coexisting infertility, and the effect on fertility can be five times higher than in the general population. Endometriosis can affect fertility through various mechanisms, including damage to the fallopian tubes, impaired ovarian function, effects on the uterus and implantation, and potential effects on sperm.

Endometriosis – outcomes and challenges

Endometriosis can affect pregnancy outcomes, with higher rates of placenta previa and increased bleeding risks. However, there are no significant differences in live birth rates, low birth weight rates, or neonatal complications. The challenges in treating endometriosis lie in the chronic nature of the disease, delayed diagnosis, extensive organ damage, and the complexity of managing both fertility and symptoms. The responsibility of managing endometriosis in fertility patients requires careful consideration, individualized treatment plans, and comprehensive support from a multidisciplinary team. When undergoing assisted reproductive techniques like in vitro fertilization (IVF), women with endometriosis have lower implantation rates and fewer eggs retrieved. This can be attributed to the effects of endometriosis on the ovaries. Furthermore, the chance of multiple pregnancies and ectopic pregnancies is higher in women with endometriosis, making it more challenging to achieve successful outcomes in IVF. During pregnancy, women with endometriosis have a higher risk of placenta previa (abnormal location of the placenta) and increased bleeding rates. However, there are no significant differences in live birth rates, low birth weight rates, or neonatal complications. Proper management can help mitigate these risks and ensure the well-being of both the mother and the baby.

Endometriosis – treatment options

Treatment for endometriosis and fertility aims to balance preservation and enhancement of fertility while alleviating symptoms. It often requires a multidisciplinary team, including gynaecologists, fertility specialists, minimal access gynaecologists, pain management specialists, and more. Treatment options can include surgery, medical management, hormonal manipulation, and fertility treatments such as in vitro fertilization (IVF) or oocyte cryopreservation (egg freezing). The choice of treatment depends on factors such as the patient’s age, physical condition, extent and severity of the disease, additional infertility factors, and severity of pain. Treating endometriosis in the context of fertility is a challenging task, and its treatment becomes even more challenging for fertility patients. The primary goals in such cases are to strike a balance between preserving and enhancing fertility while also alleviating symptoms. Radical surgery is not desired, but effective surgery, such as plasma minus effective medical management, can be considered. It is crucial to consider various factors when making decisions about endometriosis and fertility treatment. The age and physical condition of the patient are significant determinants. For young patients not planning to have a family yet, fertility preservation options like oocyte or embryo cryopreservation may be considered. For symptomatic patients, a combination of surgery and medical management can be used. It’s important to note that managing endometriosis requires a multidisciplinary team, as no gynaecologist alone should be solely responsible for the treatment. The team should include a fertility gynaecologist, minimal access gynaecologist, robotic surgeon, imaging specialist, pain management specialist, psychologists, colorectal surgeons, and nurses. The extent and severity of the disease also play a crucial role. Balancing symptom alleviation and fertility enhancement becomes challenging. Surgical excision, especially through laparoscopy or robotic surgery, has shown improvement in pregnancy rates, even in cases classified as unexplained infertility. Therefore, considering laparoscopy for younger women with suspected endometriosis and unexplained infertility may be beneficial. Infertility factors beyond endometriosis are also important to consider. Complex cases involving deep endometriosis, ovarian endometriosis, and additional male factor problems require careful evaluation and discussion with the patient to determine the best course of action. Depending on the circumstances, options like oocyte donation, surrogacy, or advanced fertility treatments like IVF or ICSI may be considered. Medical treatments for endometriosis include various hormonal manipulation, suppression, contraceptives, and anti-inflammatory or antioxidant agents. Surgical options have advanced with minimally invasive solutions, such as laparoscopy and robotic surgery. Robotic surgery provides improved control, precise movements, safer excision, and minimal complications, allowing for careful sparing and protection of healthy tissues, including reproductive organs, vessels, and nerves. In addition to traditional treatments, emerging options like molecular targeting in gene expression, prostaglandin inhibitors, and stem cells are being explored, although they are still considered experimental.

The key take-home messages are:

Endometriosis is a common condition with a significant impact on quality of life and fertility.
It negatively affects IVF outcomes, making its treatment within the context of fertility challenging.
Specialized centres with multidisciplinary teams are required for optimal management.
A combination of surgical and fertility treatments is often necessary.
Robotic surgery is a safe and effective solution for endometriosis.

You’ve mentioned oxidative stress. Would you recommend supplements like ubiquinol to help? Should these be continued after the embryo transfer?

Although it’s recognized that oxidative stress is one of the mechanisms through which endometriosis affects the ovaries, it’s not clear whether supplements can reverse this effect. The usefulness, extent, and specific supplements to be used are still uncertain. In general, I would say that taking supplements wouldn’t harm you, but I can’t provide a defined protocol to suggest.

Can long-term use of hormonal birth control mask the symptoms of endometriosis?

Yes, unfortunately, long-term use of hormonal birth control can mask the symptoms of endometriosis. Endometriosis can present itself in different ways, and using birth control can suppress or alleviate some of its symptoms. This makes it challenging to diagnose the condition accurately, as endometriosis can resemble other conditions or even disappear temporarily. It may present as painful periods initially, then shift to painful intercourse, and the symptoms can come and go over time. Furthermore, endometriosis can be deceptive, like a chameleon, as it can look like different diseases in different women or even within the same woman. It can also be compared to an iceberg, where what is visible on the surface is only a fraction of what lies beneath. Sometimes, endometriosis can go undetected during laparoscopy or be missed entirely. It can remain silent like a time bomb until it manifests as severe symptoms or infertility.

Is endometriosis fed by estrogen only, or does progesterone also feed it?

I can’t provide a definitive answer to this question. What I can say is that endometriosis occurs when the tissue resembling the lining of the uterus is present in areas outside the uterus. The bleeding during periods, caused by hormonal changes, leads to internal bleeding in these abnormal locations. Both estrogen and progesterone, which regulate the menstrual cycle, contribute to the growth and maintenance of this misplaced tissue. As part of the management and treatment of endometriosis, hormonal medications may be used to suppress periods temporarily or long-term. This approach aims to reduce the symptoms associated with endometriosis. In some cases, stopping the menstrual cycle through hormonal manipulation can provide relief and potentially serve as a diagnostic tool for identifying endometriosis.

Does the implementation rate of all retrieved oocytes decrease with age in women with endometriosis?

Unfortunately, yes. Endometriosis can be seen as a local inflammation factor that affects the oocytes and ovaries. With advanced age, we have two effects: the direct impact of age on the number and quality of oocytes, and the effect of endometriosis on the number and quality of oocytes. Additionally, endometriosis affects IVF success through other factors, including the implantation factor that directly influences the quality of implantation in the uterus.

You’ve mentioned oxidative stress. Would you recommend supplements like ubiquinol to help? Should these be continued after the embryo transfer?

Can long-term use of hormonal birth control mask the symptoms of endometriosis?

Do you normally drain endometrial cysts before IVF stimulation starts? What is the effect of endometrial cysts on IVF outcomes?

I never drain an endometrioma. I do not like to drain endometriomas, especially in the context of IVF or imminent IVF. Firstly, when we see a cyst in the ovary with blood in it, it is often mislabelled as an endometrioma. The chance of it being an endometrioma is probably 50% because what we see on the scan is not definitive. Unless we remove the cyst and perform a biopsy to find endometrial tissue, we cannot confirm if it is endometriosis. Sometimes, even when it appears to be endometriosis, it turns out to be something else entirely. Therefore, I don’t drain the cyst because it could be any kind of cyst. Secondly, if the cyst contains old blood, it is often difficult to drain it due to blood clotting. Attempting to drain it can lead to complications such as infections. Even with precautions, there is still a risk of introducing infection. Additionally, there is always the possibility of cancer, especially if the cyst is in a 40-year-old woman with an elevated CA15 marker. Therefore, I never drain the cysts, even if they are confirmed endometriomas through laparoscopy.

Can endometriosis be prevented?

Unfortunately, no. However, increased awareness and knowledge about endometriosis among both patients and doctors can help with early detection and diagnosis. Collaboration among specialists from different fields, such as radiologists, MRI specialists, geneticists, etc., can improve our understanding of the disease and potentially lead to better prevention or early intervention.

If I have endometriosis only on one ovary, can I assume the other ovary is not damaged?

Yes, it is possible. Localized endometriosis on one ovary is not uncommon. Superficial endometriosis can present as an ovarian cyst. However, it is important to undergo imaging and possibly laparoscopy to confirm the absence of endometriosis on the other ovary. Regular clinical and ultrasound follow-ups are recommended to ensure the health of both ovaries.

I have endometriosis, diminished ovarian reserve, low AMH, and recurrent implantation failure. Should I undergo an immune investigation and treatment or opt for suppressive therapy before embryo transfer?

Given your circumstances, I would recommend immune investigation and treatment, as there is an ongoing discussion about a potential link between endometriosis and autoimmune issues. Considering your age, diminished ovarian reserve, low AMH, and recurrent implantation failure, it would be beneficial to explore immune factors. Suppressive therapy before embryo transfer can help reduce local inflammation and improve the chances of successful implantation. Additionally, using steroids with anti-inflammatory and immunosuppressive effects may be considered. However, there is no clear evidence regarding the effectiveness of these approaches. It is crucial to work closely with your healthcare provider to determine the best course of action based on your situation.

I’m a 41-year-old woman diagnosed with stage 4 endometriosis in 2021 following laparoscopy. I’ve had 3 failed embryo transfers and now have low AMH. What are my options for fertility treatment?

Based on your history and assuming you have no obvious endometriosis or serious symptoms now, it is normal to have low AMH at 41 years old. Considering this, I suggest continuing with IVF. As long as you produce at least one healthy embryo, I would recommend continuing with embryo transfers, preferably with one that looks normal or has been tested through PGT. The specific protocols may vary among doctors, including factors like downregulation, use of anti-inflammatory agents, and steroids, and whether to perform the transfer in a fresh or frozen cycle. But as long as you still produce eggs and embryos, it is reasonable to continue with the embryo transfers.

Can endometriosis be prevented?

If I have endometriosis only on one ovary, can I assume the other ovary is not damaged?

I have endometriosis, diminished ovarian reserve, low AMH, and recurrent implantation failure. Should I undergo an immune investigation and treatment or opt for suppressive therapy before embryo transfer?

There is a lot of discussion about a possible link between endometriosis and autoimmune issues. Do you think someone with endometriosis at age 35, diminished ovarian reserve, low AMH, and recurrent implantation failure should undergo immune investigation and treatment? Or is there value in suppressing the immune system before transfer, or is it just wasting precious time given the ticking clock of ovarian reserve?

In your case, since you have diminished ovarian reserve and low AMH, I would agree with your decision not to undergo excision surgery, especially if you have no serious symptoms or if your symptoms are being managed conservatively. As long as you have good-quality blastocysts, I would suggest continuing with the implantation. In terms of immune suppression, using lupron suppression for a longer duration before the transfer could be beneficial. This approach aims to reduce local inflammation. Additionally, although there is no clear evidence, considering the use of low-dose steroids might be worth discussing with your doctor. Steroids can have anti-inflammatory and immunosuppressive effects. Keep moving forward and have the implantations if you have viable blastocysts. Discuss with your doctors the option of using GnRH analogues for a longer duration, possibly with the addition of steroids.

Can endometriomas cause high CA-125 levels?

No, endometriomas typically do not cause high CA-125 levels. CA-125 is a biomarker that can be elevated in various conditions, including endometriosis. However, the presence of an endometrioma alone is not likely to cause a significant increase in CA-125 levels. Other factors, such as the extent of endometriosis, inflammation, or other coexisting conditions, may contribute to elevated CA-125 levels. It is essential to consult with your healthcare provider to evaluate the specific circumstances and interpret CA-125 levels accurately.

I’m 47 and still hoping to become your IVF patient soon. I got my first ovarian cyst after social freezing, following social freezing. I am currently on medication to suppress the cysts. Does being overweight encourage endometriosis?

I am not aware of a direct association between obesity and endometriosis. I cannot provide a definitive answer regarding the link between being overweight and endometriosis. However, in some cases, ovarian stimulation during IVF can lead to the formation of multiple corpus luteum cysts, which may resemble the appearance of endometriosis. Without a biopsy, it is difficult to determine whether it is indeed endometriosis. If you have undergone social freezing at 42 and have preserved good-quality eggs, I would suggest not waiting much longer before proceeding with implantation. Regarding your weight, if you feel the need to optimize it, I recommend seeking advice from a friendly dietitian or a physician specializing in diet and nutrition. Once you have achieved your desired weight, proceed with implantation and hopefully achieve a positive outcome.

I had a positive Receptiva test but have no symptoms. I was told it could be possible adenomyosis but maybe endometriosis. I’m going through three months of Lupron Depot and Letrozole. Would you recommend anything else before the transfer?

I recommend a hysteroscopy before the transfer. It would be valuable to know if there is suspicion of adenomyosis or endometriosis before the embryo transfer. Although endometriosis can be challenging to diagnose through a scan, adenomyosis is usually recognizable on a good-quality ultrasound scan. Therefore, it would be beneficial to understand what’s happening in terms of adenomyosis or endometriosis before proceeding with the embryo transfer. Regarding the three months of Lupron Depot, it could be an option, but it’s important to be aware of the potential side effects. I suggest insisting on a firm diagnosis, which can be achieved through a good-quality ultrasound scan. In approximately 85-90% of cases, an accurate diagnosis can be made through ultrasound. If there are any doubts, an MRI scan may be indicated as well. Focus on confirming the diagnosis before proceeding with any specific treatment, as the treatment you described may be suitable for endometriosis or adenomyosis, but it’s essential to have the diagnosis confirmed.

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Authors

Elias Tsakos, FRCOG

Dr Elias Tsakos, FRCOG, is a Medical Director of Embryoclinic - Assisted Reproduction Clinic in Thessaloniki, Greece. He has received extensive and certified training in the United Kingdom and is a Fellow of the Royal College of Obstetrics & Gynaecology. Dr Tsakos is also a Board Member Representative of the Royal College for Greece and Cyprus and a Board Member of the Hellenic Society of Assisted Reproduction. He is a Member of the British, European and American Fertility Societies (BFS, ESHRE, ASRM). Dr Tsakos has been living and working in Thessaloniki, Greece, since 1999.

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Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.

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