The diagnosis and management of endometriosis

Recommendation

Strength

Diagnosis of endometriosis

Symptoms:

Clinicians should consider the diagnosis of endometriosis in individuals presenting with the following cyclical and non-cyclical signs and symptoms: dysmenorrhea, deep dyspareunia, dysuria, dyschezia, painful rectal bleeding or haematuria, shoulder tip pain, catamenial pneumothorax, cyclical cough/haemoptysis/ chest pain, cyclical scar swelling and pain, fatigue, and infertility

GPS

Signs:

 Offer an abdominal and pelvic examination to people with suspected endometriosis to identify abdominal masses and pelvic signs, such as reduced organ mobility and enlargement, tender nodularity in the posterior vaginal fornix, and visible vaginal endometriotic lesions.

GPS

If rectal endometriosis is suspected, a rectal examination may also be proactively performed to confirm the status of the bowel wall.

GPS

Diagnostic imaging

Women with suspected endometriosis, further diagnostic steps, including imaging, should be considered even if the clinical examination is normal

Strong

Clinicians are recommended to use imaging (US or MRI) in the diagnostic work-up for endometriosis, but they need to be aware that a negative finding does not exclude endometriosis, particularly superficial peritoneal disease

Strong

Offer a transvaginal ultrasound scan to all women with suspected endometriosis, even if pelvic or abdominal examination is normal, to: identify ovarian endometriomas and deep endometriosis

Conditional

If a transvaginal scan is declined or not appropriate, consider transabdominal ultrasound scan of the pelvis

GPS

Do not use pelvic MRI as the primary investigation to diagnose endometriosis in people with symptoms or signs suggestive of endometriosis.

Conditional

Consider pelvic MRI to assess the extent of deep endometriosis involving the bowel, bladder or ureter

Conditional

Laparoscopy: surgical diagnosis

In patients with negative imaging results, or where empirical treatment (hormonal contraceptives or progestogens) was unsuccessful, consider offering laparoscopy for the diagnosis and treatment of suspected endometriosis

GPS

Laparoscopic identification of endometriotic lesions should be confirmed by histopathologic examination of the lesions. However, a negative histology does not entirely rule out the disease

GPS

The procedure should be performed by a trained laparoscopic surgeon, who should perform and document a systematic inspection of the pelvis and abdomen

GPS

Biomarker:

Do not use serum CA125 to diagnose endometriosis.

Strong

Treatment of endometriosis associated pain

Pain control in endometriosis

For women with pain associated with endometriosis-, consider a short trial (for example, 3 months) of a non-steroidal anti-inflammatory drug (NSAID) alone or in combination with paracetamol, if not contraindicated. If such a trial does not provide adequate pain relief, consider other forms of pain management and referral for secondary or tertiary care center.

GPS

Advise patients that there is no evidence for or against the use of anti-neuropathic medications for pain associated with endometriosis

GPS

Women with endometriosis should be referred to a pain specialist and/or a condition-specific specialist at any stage if:

• pain is severe and unresponsive to simple analgesics.

• the pain substantially limits daily activities.

• any underlying health condition has deteriorated.

Conditional

Hormonal treatment for endometriosis

It is recommended to offer women hormone treatment (combined hormonal contraceptives, progestogens, GnRH agonists or GnRH antagonists) as one of the options to reduce endometriosis-associated pain

Strong

The GDG recommends that clinicians take a shared decision-making approach and take individual preferences, side effects, individual efficacy, costs, and availability into consideration when choosing hormone treatments for endometriosis-associated pain

GPS

When appropriate a levonorgestrel-releasing intrauterine system or an etonogestrel-releasing subdermal implant to reduce endometriosis-associated pain can be used

Strong

It is recommended to prescribe women GnRH agonists to reduce endometriosis-associated pain, although evidence is limited regarding dosage or duration of treatment

Strong

The GDG recommends that GnRH agonists are prescribed as second line (for example if hormonal contraceptives or progestogens have been ineffective) due to their side-effect profile

GPS

Clinicians should consider prescribing combined hormonal add-back therapy alongside GnRH agonist therapy to prevent bone loss and hypoestrogenic symptoms

Strong

In women with endometriosis-associated pain refractory to other medical or surgical treatment, it is recommended to prescribe aromatase inhibitors, as they reduce endometriosis-associated pain. Aromatase inhibitors may be prescribed in combination with oral contraceptives, progestogens, GnRH agonists or GnRH antagonists

Strong

Surgical management for endometriosis

Laparoscopic management should be done by an expert in laparoscopic surgery

GPS

When surgery is performed, clinicians may consider excision instead of ablation of endometriosis to reduce endometriosis-associated pain

Conditional

It can be concluded that LUNA is not beneficial as an additional procedure to conventional laparoscopic surgery for endometriosis, PSN is beneficial for treatment of endometriosis-associated midline pain as an adjunct to conventional laparoscopic surgery

GPS

When performing surgery in women with ovarian endometrioma, clinicians should perform cystectomy instead of drainage and coagulation,

Strong

When performing surgery for ovarian endometrioma, specific caution should be used to minimize ovarian damage

Strong

Clinicians can consider performing surgical removal of deep endometriosis, as it may reduce endometriosis-associated pain and improves quality of life

Conditional

The GDG recommends that patients undergoing surgery particularly for deep endometriosis are informed on potential risks, benefits, and long-term effect on quality of life

GPS

Due to the heterogeneity of patient population, presentation, surgical approaches and techniques, it is difficult to make definitive recommendations on the specific techniques to be applied for the treatment of pain associated with deep endometriosis

GPS

In case of bowel endometriosis, a conservative approach should be chosen whenever possible.

GPS

Hysterectomy for endometriosis associated pain

Clinicians can consider hysterectomy (with or without removal of the ovaries) with removal of all visible endometriosis lesions, in those women who no longer wish to conceive and failed to respond to more conservative treatments.

Conditional

The GDG recommends that when hysterectomy is performed, a total hysterectomy is preferred

GPS

When a decision is made whether to remove the ovaries, the long-term consequences of early menopause and possible need for hormone replacement therapy should be considered

GPS

Studies should evaluate factors that can be assessed prior to surgery and can predict a clinically meaningful improvement of pain symptoms. Such prognostic markers can be used to select patients that may benefit from endometriosis surgery

GPS

Women may be offered postoperative hormone treatment to improve the immediate outcome of surgery for pain in women with endometriosis if not desiring immediate pregnancy

Conditional

Non-medical interventions in endometriosis

No recommendations can be made for any specific non-medical intervention (Chinese medicine, nutrition, electrotherapy, acupuncture, physiotherapy, exercise, and psychological interventions) to reduce pain or improve quality of life measures in women with endometriosis, as the potential benefits and harms are unclear.

GPS

Treatment of endometriosis associated infertility

Ovarian suppression

In infertile women with endometriosis, clinicians should not prescribe ovarian suppression treatment to improve fertility.

Strong

Women seeking pregnancy should not be prescribed postoperative hormone suppression with the sole purpose to enhance future pregnancy rates.

strong

Those women who cannot attempt to or decide not to conceive immediately after surgery may be offered hormone therapy as it does not negatively impact their fertility and improves the immediate outcome of surgery for pain

Conditional

In infertile women with endometriosis, clinicians should not prescribe pentoxifylline, other anti-inflammatory drugs or letrozole outside ovulation-induction to improve natural pregnancy rates.

Strong

Surgical treatment

The GDG recommends that the decision to perform surgery should be guided by the presence or absence of pain symptoms, patient age and preferences, history of previous surgery, presence of other infertility factors, ovarian reserve, and estimated Endometriosis Fertility Index (EFI).

GPS

Operative laparoscopy could be offered as a treatment option for endometriosis-associated infertility in rASRM stage I/II endometriosis as it improves the rate of ongoing pregnancy.

Conditional

Clinicians may consider operative laparoscopy for the treatment of endometrioma-associated infertility as it may increase their chance of natural pregnancy, although no data from comparative studies exist.

Conditional

Although no compelling evidence exists that operative laparoscopy for deep endometriosis improves fertility, operative laparoscopy may represent a treatment option in symptomatic patients wishing to conceive.

Conditional

Assessing the need for assisted reproduction after surgery

Women should be counselled of their chances of becoming pregnant after surgery. To identify patients that may benefit from ART after surgery, the Endometriosis Fertility Index (EFI) should be used as it is validated, reproducible and cost-effective. The results of other fertility investigations such as their partner’s sperm analysis should be taken into account.

GPS

Medically assisted reproduction

IUI with endometriosis

In infertile women with rASRM stage I/II endometriosis, clinicians may perform intrauterine insemination (IUI) with ovarian stimulation, instead of expectant management or IUI alone, as it increases pregnancy rates.

Conditional

Although the value of IUI in infertile women with rASRM stage III/IV endometriosis with tubal patency is uncertain, the use of IUI with ovarian stimulation could be considered.

Conditional

ART in women with endometriosis

ART can be performed for infertility associated with endometriosis, especially if tubal function is compromised, if there is male factor infertility, in case of low EFI and/or if other treatments have failed

Conditional

A specific protocol for ART in women with endometriosis cannot be recommended. Both GnRH antagonist and agonist protocols can be offered based on patients’ and physicians’ preferences as no difference in pregnancy or live birth rate has been demonstrated

Conditional

Women with endometriosis can be reassured regarding the safety of ART since the recurrence rates are not increased compared to those women not undergoing ART.

Conditional

In women with endometrioma, clinicians may use antibiotic prophylaxis at the time of oocyte retrieval, although the risk of ovarian abscess formation following follicle aspiration is low.

GPS

Medical therapies as an adjunct to MAR

The extended administration of GnRH agonist prior to ART treatment to improve live birth rate in infertile women with endometriosis is not recommended, as the benefit is uncertain.

Strong

There is insufficient evidence to recommend prolonged administration of the COC/progestogens as a pre-treatment to ART to increase live birth rates.

Conditional

Surgical therapies as an adjunct to MAR

Clinicians are not recommended to routinely perform surgery prior to ART to improve live birth rates in women with rASRM stage I/II endometriosis, as the potential benefits are unclear.

Strong

Clinicians are not recommended to routinely perform surgery for ovarian endometrioma prior to ART to improve live birth rates, as the current evidence shows no benefit and surgery is likely to have a negative impact on ovarian reserve.

Strong

Surgery for endometrioma prior to ART can be considered to improve endometriosis-associated pain or accessibility of follicles.

GPS

The decision to offer surgical excision of deep endometriosis lesions prior to ART should be guided mainly by pain symptoms and patient preference as its effectiveness on reproductive outcome is uncertain due to lack of randomised studies

Strong

Non-medical management strategies for infertility

No recommendation can be made to support any non-medical interventions (nutrition, Chinese medicine, electrotherapy, acupuncture, physiotherapy, exercise, and psychological interventions) to increase fertility in women with endometriosis. The potential benefits and harms are unclear.

GPS

Fertility Preservation

In case of extensive ovarian endometriosis, clinicians should discuss the pros and cons of fertility preservation with women with endometriosis. The true benefit of fertility preservation in women with endometriosis remains unknown

Strong

Impact of endometriosis on pregnancy and pregnancy outcome

Patients should not be advised to become pregnant with the sole purpose of treating endometriosis, as pregnancy does not always lead to improvement of symptoms or reduction of disease progression.

strong

Complications related directly to pre-existing endometriosis lesions are rare, but probably under-reported. Such complications may be related to their decidualization, adhesion formation/stretching and endometriosis-related chronic inflammation. Although rare, they may represent life-threatening situations that may require surgical management.

GPS

Clinicians should be aware that there may be an increased risk of first trimester miscarriage and ectopic pregnancy in women with endometriosis.

Strong

Clinicians should be aware of endometriosis-associated complications in pregnancy, although these are rare. As these findings are based on low/moderate quality studies, these results should be interpreted with caution and currently do not warrant increased antenatal monitoring or dissuade women from becoming pregnant.

Strong

Endometriosis recurrence

Prevention of endometriosis recurrence

When surgery is indicated in women with an endometrioma, clinicians should perform ovarian cystectomy, instead of drainage and electrocoagulation, for the secondary prevention of endometriosis-associated dysmenorrhea, dyspareunia, and non-menstrual pelvic pain. However, the risk of reduced ovarian reserve should be taken into account

Strong

Clinicians should consider prescribing the postoperative use of a levonorgestrel-releasing intrauterine system (52 mg LNG-IUS) or a combined hormonal contraceptive for at least 18–24 months for the secondary prevention of endometriosis-associated dysmenorrhea

Strong

After surgical management of ovarian endometrioma in women not immediately seeking conception, clinicians are recommended to offer long-term hormone treatment (e.g. combined hormonal contraceptives) for the secondary prevention of endometrioma and endometriosis-associated related symptom recurrence.

Strong

For the prevention of recurrence of deep endometriosis and associated symptoms, long-term administration of postoperative hormone treatment can be considered

Conditional

Long-term administration of progestogen may reduce the recurrence of ovarian endometriotic cysts.

Conditional

Treatment of recurrent endometriosis

Any hormone treatment or surgery can be offered to treat recurring pain symptoms in women with endometriosis

Conditional

Adolescent Endometriosis

Clinical symptoms:

In adolescents, clinicians should take a careful history and consider the following symptoms as suggestive of the presence of endometriosis:

-chronic or a-cyclical pelvic pain, particularly combined with nausea, dysmenorrhea, dyschezia, dysuria, dyspareunia

-cyclical pelvic pain

Strong

Clinical examination

In case of virgin written informed consent from the patient and her parents before rectal examination

GPS

The recommendations for clinical examination in adults can be applied.

GPS

Imaging

In case of virgin written informed consent from the patient and her parents before rectal u/s

GPS

Pelvic imaging with ultrasonography, regardless of findings on pelvic examination, also should be considered during evaluation for secondary dysmenorrhea.

GPS

Transvaginal ultrasound is recommended to be used in adolescents in whom it is appropriate non virgin, as it is effective in diagnosing ovarian endometriosis.

Strong

If a transvaginal scan is not appropriate, MRI, trans abdominal, trans-perineal, or trans rectal scan may be considered.

Conditional

Laboratory parameters

Serum biomarkers (e.g., CA-125) are not recommended for diagnosing or ruling out endometriosis in adolescents.

Strong

Diagnostic laparoscopy

In adolescents with suspected endometriosis where imaging is negative and imperical medical treatments (with NSAIDs and/or hormonal contraceptives) have not been successful, diagnostic laparoscopy may be considered.

Conditional

The appearance of endometriosis may be different in an adolescent than in an adult woman. In adolescents, endometriotic lesions are typically clear or red and can be difficult to identify for gynecologists unfamiliar with endometriosis in adolescents.

GPS

If a laparoscopy is performed, clinicians may consider taking biopsies to confirm the diagnosis histologically, although negative histology does not entirely rule out the disease.

Strong

Medical treatment

Nonsteroidal anti-inflammatory drugs should be the mainstay of pain relief for adolescents with endometriosis.

GPS

In adolescents with severe dysmenorrhea and/or endometriosis-associated pain, Clinicians should prescribe hormonal contraceptives or progestogens

Strong

In adolescents with laparoscopically confirmed endometriosis and associated pain in whom hormonal contraceptives or progestogen therapy failed, clinicians may consider prescribing GnRH agonists combined with add-back therapy for up to 1 year, as they are effective and safe.

Conditional

If GnRH agonist treatment is considered, it should be used only after careful consideration and discussion of potential side effects and potential long-term health risks with a practitioner in a secondary or tertiary care setting

GPS

Combined medical and surgical treatment.

In adolescents with endometriosis, clinicians should consider postoperative hormone therapy, as this may suppress recurrence of symptoms

Strong

Menopause and Endometriosis

Treatment of endometriosis in postmenopausal women

Clinicians may consider surgical treatment for postmenopausal women presenting with signs of endometriosis and/or pain to enable histological confirmation of the diagnosis of endometriosis

conditional

Clinicians should acknowledge the uncertainty towards the risk of malignancy in postmenopausal women. If a pelvic mass is detected, the work-up and treatment should be performed according to national oncology guidelines

GPS

For postmenopausal women with endometriosis-associated pain, clinicians may consider aromatase inhibitors as a treatment option especially if surgery is not feasible.

Conditional

Menopausal symptoms in women with a history of endometriosis

Clinicians may consider combined menopausal hormone therapy (MHT) for the treatment of postmenopausal symptoms in women (both after natural and surgical menopause) with a history of endometriosis

Conditional

Clinicians should avoid prescribing estrogen-only regimens for the treatment of vasomotor symptoms in postmenopausal women with a history of endometriosis, as these regimens may be associated with a higher risk of malignant transformation

Strong

Clinicians should continue to treat women with a history of endometriosis after surgical menopause with combined estrogen-progestogen at least up to the age of natural menopause.

GPS

Menopause-related major health concerns in women with endometriosis

Clinicians should be aware that women with endometriosis who have undergone an early bilateral salpingo-oophorectomy as part of their treatment have an increased risk of diminished bone density, dementia, and cardiovascular disease. It is also important to note that women with endometriosis have an increased risk of cardiovascular disease, irrespective of whether they have had an early surgical menopause

GPS

Extra pelvic endometriosis

Clinicians should be aware of symptoms of extra-pelvic thoracic endometriosis, such as cyclical shoulder pain, cyclical spontaneous pneumothorax, cyclical cough, or nodules which enlarge during menses.

GPS

It is advisable to discuss diagnosis and management of extra-pelvic & thoracic endometriosis in a multidisciplinary team in a center with sufficient expertise

GPS

For abdominal extra-pelvic endometriosis, surgical removal is the preferred treatment, when possible, to relieve symptoms. Hormone treatment may also be an option when surgery is not possible or acceptable

Conditional

Asymptomatic endometriosis

Treatment

Clinicians should inform and counsel women about any incidental finding of endometriosis

GPS

Clinicians should not routinely perform surgical excision/ablation for an incidental finding of asymptomatic endometriosis at the time of surgery

Strong

Clinicians should not prescribe medical treatment in women with incidental finding of endometriosis

Strong

Monitoring

Routine ultrasound monitoring of asymptomatic endometriosis can be considered.

Conditional

Primary prevention of endometriosis

Although there is no direct evidence of benefit in preventing endometriosis in the future, women can be advised of aiming for a healthy lifestyle and diet, with reduced alcohol intake and regular physical activity

Conditional

The usefulness of hormonal contraceptives for the primary prevention of endometriosis is uncertain

Conditional