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Diagnosing endometriosis
ENDOMETRIOSIS: DIAGNOSIS
The clinical manifestation of endometriosis is quite diverse and there is no fixed symptom complex which is diagnostic. There are some clinical symptoms that seem to be more crucial, because subsequent diagnostic tests are more likely to be positive when these symptoms are present, but they are not inevitably so.
Pathogenesis of infertility in endometriosis is discussed on pages 15–17. Risk factors are discussed further on pages 18–19. • Almost all cases of endometriosis occur in women of reproductive age, although endometriosis can be found in early adolescence in patients with partial/complete obstructive Müllerian anomalies. • A family history of endometriosis is relevant, as this increases the incidence seven-fold. • Endometriosis is more common in women with short menstrual cycles (less than 27 days), longer menstrual flow (greater than 7 days) and pre-menstrual spotting. • Some constitutional factors carry an interesting increased risk for endometriosis. Tall women with low body mass and women who have voluntarily delayed child bearing, have an increased risk of endometriosis. • Asian women have a higher incidence than Caucasian women.
History
Physical examination
The most important pointers towards a diagnosis of endometriosis are chronic pelvic pain and infertility. Chronic pelvic pain – endometriosis is detected at the time of surgery in approximately 20% of women who are operated on. The pelvic pain may be dysmenorrhoea, intermenstrual pain or dyspareunia (pain on intercourse). • Dyspareunia occurs in 77% of women with endometriomas (see below), 88% of women with peritoneal disease and 100% of women with recto-vaginal disease. The pain is usually positional and most intense on deep penetration and in some severe cases it may preclude intercourse. • The dysmenorrhoea is usually progressive (i.e. each menstruation is more painful than the last), often preceding the onset of menstrual flow. It continues throughout menses and occasionally persists afterwards. It is most often localized to the lower abdomen and deep in the pelvis, is often bilateral and may radiate to the back and thighs. It may be associated with rectal pressure, nausea and episodes of diarrhoea. • Pain between the periods is reported in up to 68% of women with endometriosis and this pain may not be directly due to endometriosis. Of course, intermenstrual pain may also be caused by other conditions, such as irritable bowel syndrome. The relationship between pain and endometriosis severity remains controversial. Overall, there seems little correlation between the severity of the disease and severity of pelvic pain. Infertility – in infertile women undergoing laparoscopic evaluation of a cause for their infertility, incidence of endometriosis was found on average to be 14% higher than in controls.
The findings of physical examination can be as diverse as the symptom complex of the history. In some cases of mild endometriosis, clinical examination may not reveal any abnormality at all. Ideally, the woman should be examined when symptoms are at their worst, as it is then easier to detect and localize areas of suspected endometriosis. Abdominal examination is often of little value and bi-manual vaginal examination is usually required. Deeply infiltrating endometriosis is diagnosed clinically in approximately 40% of those patients who are subsequently found to have deeply infiltrating disease at laparoscopy. • The uterus itself may be retroverted, due to decreased mobility and peri-uterine adhesions. • Endometriomas (see below) may be detected as either tender or non-tender adnexal masses. • Nodules or fibrosis may be palpable on the uterosacral ligaments or the rectovaginal septum. A normal clinical examination, however, does not rule out the diagnosis of endometriosis. It is possible that on speculum examination endometrial implants may be seen on the cervix or the posterior fornix. A recent study suggested that pelvic examination was a reliable predictor of endometriomas, but a poor predictor of non-ovarian lesions.1
Diagnosing endometriosis Gillian L Rose
Laboratory tests Although many attempts have been made to identify serum markers as a way of screening for endometriosis, there has yet to be an adequately sensitive and specific test for this purpose. CA125 has been evaluated in a number of studies and has a sensitivity ranging from 13–60%, although the specificity is between 93–100%.2 The poor sensitivity of CA125 in diagnosing endometriosis means that it is not valuable as a screening test. In severe disease, CA125 levels may be used to predict the response to medical or surgical treatment in some women.
Gillian L Rose is a Consultant Gynaecologist at the Queen Charlotte’s and Chelsea Hospital for Women, London, UK. She qualified from the Royal Free Hospital School of Medicine and trained in obstetrics and gynaecology in London. She established the first dedicated endometriosis clinic in the UK and continues to have a research interest in the treatment of endometriosis.
WOMEN’S HEALTH MEDICINE 2:1
Imaging Imaging using transvaginal ultrasound and MRI have been useful adjuncts to the monitoring and diagnosis of endometriosis.
20
© 2005 The Medicine Publishing Company Ltd
ENDOMETRIOSIS: DIAGNOSIS
Endometrioma – ultrasound scan Endometrium Fundus of uterus Cervix
Endometrioma containing altered blood Rim of normal ovary 1
Multiloculated endometrioma – ultrasound Compressed vessel
Locule of cyst – appearance of old cyst containing clear fluid Locule of cyst containing altered blood typical appearance of more recent bleed 2
Ultrasound (Figures 1 & 2) Ultrasound is particularly helpful in: • the evaluation of endometriotic cysts. It has not proved to be valuable in: • detection of adhesions • detection of peritoneal implants. The appearance on ultrasound is usually of cystic structures with diffuse, low-level, internal echoes and endometriotic cysts may be septate and have thick walls. Ultrasound has very high sensitivity and specificity for endometriosis, about 92% and 99%, respectively. The addition of colour Doppler flow increases sensitivity, as endometriomas usually manifest peri-cystic blood.3 Differential diagnoses for endometriomas include dermoid cysts, haemorrhagic corpus lutei and other cystic tumours of the ovary. The use of three-dimensional ultrasound for the detection of endometriomas has yet to be evaluated.
MRI scan of endometrioma
Endometrioma
Magnetic resonance imaging (MRI) MRI is very helpful in: • detection of endometriomas • visualization of rectovaginal disease and adhesions. MRI is equally comparable to ultrasound in its sensitivity and specificity in the diagnosis of endometriomas. Figure 3 is an example of an MRI scan taken of a woman with endometriosis.
WOMEN’S HEALTH MEDICINE 2:1
3
Laparoscopy Laparoscopic assessment of the pelvis in patients with suitable clinical findings remains the standard way of diagnosing endometriosis. The laparoscopist must be familiar with the
21
© 2005 The Medicine Publishing Company Ltd
ENDOMETRIOSIS: DIAGNOSIS
American Society for Reproductive Medicine revised classification of endometriosis at laparoscopy Patient's Name: Stage I (minimal): 1–5 Stage II (mild): 6–15 Stage III (moderate): 16–40 Stage IV (severe): > 40 Total: Peritoneum
Ovary
Date: Laparoscopy: Laparotomy: Recommended treatment: Prognosis:
Endometriosis
<1 cm
1.3 cm
>3 cm
Superficial
1
2
4
Deep
2
4
6
Right superficial
1
2
4
Right deep
4
16
20
Left superficial
1
2
4
Left deep
4
16
20
Partial
Complete
4
40
<1/3 enclosure
1/3–2/3 enclosure
Posterior culdesac obliteration
Ovary
Tube
Photography:
ADHESIONS
>2/3 enclosure
Right filmy
1
2
4
Right dense
4
8
16
Left filmy
1
2
4
Left dense
4
8
Right filmy
1
2
4
Right dense
4*
8*
16
Left filmy
1
2
4
Left dense
4*
8*
16
*If the fimbriated end of the fallopian tube is completely enclosed, change the point assignment to 16.
4
common locations of endometriosis, so that an accurate inspection of the pelvis can be carried out. The surgeon must be familiar with the appearances of peritoneal implants, endometriomas and deep infiltrating lesions of the rectovaginal septum. Surgeons appropriately trained in diagnostic laparoscopy for endometriosis make the diagnosis twice as often as those who do not perform this procedure regularly. The endometriosis classification system, devised by the American Society for Reproductive Medicine (formerly the American Fertility Society) contains four stages of disease severity. The purpose of the classification system is to identify the relative severity of the disease process. Figure 4 shows the criteria for each stage of severity of endometriosis in the form of a table which the doctor completes at laparoscopy.
Peritoneum with a gland surrounded with endometrial epithelium
Peritoneal implants (Figure 5) Peritoneal implants are most commonly localized in the: • uterosacral ligaments • pouch of Douglas • ovarian fossa • adjacent pelvic side walls. They are less frequently seen in association with the surface of the bladder and the bowel, but it is important that the surgeon
WOMEN’S HEALTH MEDICINE 2:1
5
22
© 2005 The Medicine Publishing Company Ltd
ENDOMETRIOSIS: DIAGNOSIS
Severe endometriosis, bilateral endometriomas
Learning points • There is no doubt that laparoscopy remains the definitive diagnostic tool to assess and diagnose endometriosis. The best strategy is clinical history, examination and then laparoscopy. • Clinical history and examination is extremely important in differentiating those patients who may or may not have endometriosis, but these techniques have limitations. • Ultrasound and MRI may be useful in diagnosing endometriomas, but are of limited value in diagnosing peritoneal disease. • The differentiation between physiological isolated ectopic endometrium and endometriosis is difficult. The clinical history and examination findings are considered with the findings at laparoscopy to decide if there truly is an association between the symptoms and the endometriosis seen. • Misdiagnosis of endometriosis as the cause of pelvic pain is a dangerous clinical trap, as patients labelled as having endometriosis cling to this diagnosis as the aetiology to their problem for evermore. • The future development of serum markers for endometriosis is extremely important for diagnosis and management of the disease. Clinicians involved in the management of these cases await this next scientific step with bated breath.
6
carries out a wide-ranging inspection of the pelvis in order not to miss sites of the implants. Colour: peritoneal implants are classically described as bluish/ black powder-burn lesions, with varying degrees of surrounding pigmentation and fibrosis. The dark coloration is a result of haemosiderin deposition from entrapped menstrual debris, but it is important to realize that most peritoneal implants are not black and may be red, white, yellow/brown or clear. White, opacified areas and red, flame-like lesions contain endometriosis in around 80% of cases, while brown patches have endometriosis in approximately 50% of cases. However, white peritoneal implants are associated with less pain than black or red ones, and it is believed that the black/red lesions produce prostaglandin F2α, which is the cause of the pelvic pain. It has been proposed that endometrial implants undergo a process of natural evolution through a number of phases, finally becoming black; all colours can co-exist in the same patient, presumably due to ages of the various lesions. Microscopic endometriosis, diagnosed following peritoneal biopsy, may occur in up to 50% of specimens, but has a similar prevalence in non-symptomatic and symptomatic women. It is therefore very difficult to ascertain its significance. Microscopic endometriosis may be a normal physiological process.
brown, dense, chocolate-like fluid and endometriomas larger than 3 cm are often multi-locular (more than one cavity). Deep infiltrating endometriosis Deep infiltrating endometriosis is usually localized to the rectovaginal septum and is probably a distinct entity, as opposed to peritoneal and ovarian endometriosis. It is suggested that it originates from Müllerian rest cells, which have remained in the rectovaginal septum. Histologically, it is often similar in appearance to adenomyosis (endometriosis in the uterine myometrium). It is important to ensure that the bowel can be manoeuvred adequately during the laparoscopy procedure, in order to make sure that the laparoscopist can meticulously examine the rectovaginal septum, to exclude these lesions.
Endometriomas (Figures 6 and 7) Endometriomas are smooth, dark brownish cysts, often associated with adhesions, that lie on the surface of the ovary. They contain
Endometriomas
Acknowledgement The author would like to thank Dr J Hollway, Consultant Radiologist at Queen Charlotte’s and Chelsea and Hammersmith Hospitals for providing the ultrasound and MRI images.
REFERENCES 1 Eskenazi B, Warner M, Bonsignore L. Validation study of non-surgical diagnosis of endometriosis. Fertil Steril 2001; 76: 929–35. 2 Chen F P, Soong Y K, Lee N, Lo S K. The use of serum Ca-125 as a marker for endometriosis in patients with dysmenorrhoea for monitoring therapy and for recurrence of endometriosis. Acta Obstet Gynecol Scand 1998; 77: 665–70. 3 Pascual M A, Tresserra F, Lopez-Marin L, Ubeda A, Grases P J, Dexeus S. Role of color Doppler ultrasound in the diagnosis of endometriotic cyst. J Ultrasound Med 2000; 19: 695–99.
7
WOMEN’S HEALTH MEDICINE 2:1
23
© 2005 The Medicine Publishing Company Ltd
The clinical manifestation of endometriosis is quite diverse and there is no fixed symptom complex which is diagnostic. There are some clinical symptoms that seem to be more crucial, because subsequent diagnostic tests are more likely to be positive when these symptoms are present, but they are not inevitably so.
Pathogenesis of infertility in endometriosis is discussed on pages 15–17. Risk factors are discussed further on pages 18–19. • Almost all cases of endometriosis occur in women of reproductive age, although endometriosis can be found in early adolescence in patients with partial/complete obstructive Müllerian anomalies. • A family history of endometriosis is relevant, as this increases the incidence seven-fold. • Endometriosis is more common in women with short menstrual cycles (less than 27 days), longer menstrual flow (greater than 7 days) and pre-menstrual spotting. • Some constitutional factors carry an interesting increased risk for endometriosis. Tall women with low body mass and women who have voluntarily delayed child bearing, have an increased risk of endometriosis. • Asian women have a higher incidence than Caucasian women.
History
Physical examination
The most important pointers towards a diagnosis of endometriosis are chronic pelvic pain and infertility. Chronic pelvic pain – endometriosis is detected at the time of surgery in approximately 20% of women who are operated on. The pelvic pain may be dysmenorrhoea, intermenstrual pain or dyspareunia (pain on intercourse). • Dyspareunia occurs in 77% of women with endometriomas (see below), 88% of women with peritoneal disease and 100% of women with recto-vaginal disease. The pain is usually positional and most intense on deep penetration and in some severe cases it may preclude intercourse. • The dysmenorrhoea is usually progressive (i.e. each menstruation is more painful than the last), often preceding the onset of menstrual flow. It continues throughout menses and occasionally persists afterwards. It is most often localized to the lower abdomen and deep in the pelvis, is often bilateral and may radiate to the back and thighs. It may be associated with rectal pressure, nausea and episodes of diarrhoea. • Pain between the periods is reported in up to 68% of women with endometriosis and this pain may not be directly due to endometriosis. Of course, intermenstrual pain may also be caused by other conditions, such as irritable bowel syndrome. The relationship between pain and endometriosis severity remains controversial. Overall, there seems little correlation between the severity of the disease and severity of pelvic pain. Infertility – in infertile women undergoing laparoscopic evaluation of a cause for their infertility, incidence of endometriosis was found on average to be 14% higher than in controls.
The findings of physical examination can be as diverse as the symptom complex of the history. In some cases of mild endometriosis, clinical examination may not reveal any abnormality at all. Ideally, the woman should be examined when symptoms are at their worst, as it is then easier to detect and localize areas of suspected endometriosis. Abdominal examination is often of little value and bi-manual vaginal examination is usually required. Deeply infiltrating endometriosis is diagnosed clinically in approximately 40% of those patients who are subsequently found to have deeply infiltrating disease at laparoscopy. • The uterus itself may be retroverted, due to decreased mobility and peri-uterine adhesions. • Endometriomas (see below) may be detected as either tender or non-tender adnexal masses. • Nodules or fibrosis may be palpable on the uterosacral ligaments or the rectovaginal septum. A normal clinical examination, however, does not rule out the diagnosis of endometriosis. It is possible that on speculum examination endometrial implants may be seen on the cervix or the posterior fornix. A recent study suggested that pelvic examination was a reliable predictor of endometriomas, but a poor predictor of non-ovarian lesions.1
Diagnosing endometriosis Gillian L Rose
Laboratory tests Although many attempts have been made to identify serum markers as a way of screening for endometriosis, there has yet to be an adequately sensitive and specific test for this purpose. CA125 has been evaluated in a number of studies and has a sensitivity ranging from 13–60%, although the specificity is between 93–100%.2 The poor sensitivity of CA125 in diagnosing endometriosis means that it is not valuable as a screening test. In severe disease, CA125 levels may be used to predict the response to medical or surgical treatment in some women.
Gillian L Rose is a Consultant Gynaecologist at the Queen Charlotte’s and Chelsea Hospital for Women, London, UK. She qualified from the Royal Free Hospital School of Medicine and trained in obstetrics and gynaecology in London. She established the first dedicated endometriosis clinic in the UK and continues to have a research interest in the treatment of endometriosis.
WOMEN’S HEALTH MEDICINE 2:1
Imaging Imaging using transvaginal ultrasound and MRI have been useful adjuncts to the monitoring and diagnosis of endometriosis.
20
© 2005 The Medicine Publishing Company Ltd
ENDOMETRIOSIS: DIAGNOSIS
Endometrioma – ultrasound scan Endometrium Fundus of uterus Cervix
Endometrioma containing altered blood Rim of normal ovary 1
Multiloculated endometrioma – ultrasound Compressed vessel
Locule of cyst – appearance of old cyst containing clear fluid Locule of cyst containing altered blood typical appearance of more recent bleed 2
Ultrasound (Figures 1 & 2) Ultrasound is particularly helpful in: • the evaluation of endometriotic cysts. It has not proved to be valuable in: • detection of adhesions • detection of peritoneal implants. The appearance on ultrasound is usually of cystic structures with diffuse, low-level, internal echoes and endometriotic cysts may be septate and have thick walls. Ultrasound has very high sensitivity and specificity for endometriosis, about 92% and 99%, respectively. The addition of colour Doppler flow increases sensitivity, as endometriomas usually manifest peri-cystic blood.3 Differential diagnoses for endometriomas include dermoid cysts, haemorrhagic corpus lutei and other cystic tumours of the ovary. The use of three-dimensional ultrasound for the detection of endometriomas has yet to be evaluated.
MRI scan of endometrioma
Endometrioma
Magnetic resonance imaging (MRI) MRI is very helpful in: • detection of endometriomas • visualization of rectovaginal disease and adhesions. MRI is equally comparable to ultrasound in its sensitivity and specificity in the diagnosis of endometriomas. Figure 3 is an example of an MRI scan taken of a woman with endometriosis.
WOMEN’S HEALTH MEDICINE 2:1
3
Laparoscopy Laparoscopic assessment of the pelvis in patients with suitable clinical findings remains the standard way of diagnosing endometriosis. The laparoscopist must be familiar with the
21
© 2005 The Medicine Publishing Company Ltd
ENDOMETRIOSIS: DIAGNOSIS
American Society for Reproductive Medicine revised classification of endometriosis at laparoscopy Patient's Name: Stage I (minimal): 1–5 Stage II (mild): 6–15 Stage III (moderate): 16–40 Stage IV (severe): > 40 Total: Peritoneum
Ovary
Date: Laparoscopy: Laparotomy: Recommended treatment: Prognosis:
Endometriosis
<1 cm
1.3 cm
>3 cm
Superficial
1
2
4
Deep
2
4
6
Right superficial
1
2
4
Right deep
4
16
20
Left superficial
1
2
4
Left deep
4
16
20
Partial
Complete
4
40
<1/3 enclosure
1/3–2/3 enclosure
Posterior culdesac obliteration
Ovary
Tube
Photography:
ADHESIONS
>2/3 enclosure
Right filmy
1
2
4
Right dense
4
8
16
Left filmy
1
2
4
Left dense
4
8
Right filmy
1
2
4
Right dense
4*
8*
16
Left filmy
1
2
4
Left dense
4*
8*
16
*If the fimbriated end of the fallopian tube is completely enclosed, change the point assignment to 16.
4
common locations of endometriosis, so that an accurate inspection of the pelvis can be carried out. The surgeon must be familiar with the appearances of peritoneal implants, endometriomas and deep infiltrating lesions of the rectovaginal septum. Surgeons appropriately trained in diagnostic laparoscopy for endometriosis make the diagnosis twice as often as those who do not perform this procedure regularly. The endometriosis classification system, devised by the American Society for Reproductive Medicine (formerly the American Fertility Society) contains four stages of disease severity. The purpose of the classification system is to identify the relative severity of the disease process. Figure 4 shows the criteria for each stage of severity of endometriosis in the form of a table which the doctor completes at laparoscopy.
Peritoneum with a gland surrounded with endometrial epithelium
Peritoneal implants (Figure 5) Peritoneal implants are most commonly localized in the: • uterosacral ligaments • pouch of Douglas • ovarian fossa • adjacent pelvic side walls. They are less frequently seen in association with the surface of the bladder and the bowel, but it is important that the surgeon
WOMEN’S HEALTH MEDICINE 2:1
5
22
© 2005 The Medicine Publishing Company Ltd
ENDOMETRIOSIS: DIAGNOSIS
Severe endometriosis, bilateral endometriomas
Learning points • There is no doubt that laparoscopy remains the definitive diagnostic tool to assess and diagnose endometriosis. The best strategy is clinical history, examination and then laparoscopy. • Clinical history and examination is extremely important in differentiating those patients who may or may not have endometriosis, but these techniques have limitations. • Ultrasound and MRI may be useful in diagnosing endometriomas, but are of limited value in diagnosing peritoneal disease. • The differentiation between physiological isolated ectopic endometrium and endometriosis is difficult. The clinical history and examination findings are considered with the findings at laparoscopy to decide if there truly is an association between the symptoms and the endometriosis seen. • Misdiagnosis of endometriosis as the cause of pelvic pain is a dangerous clinical trap, as patients labelled as having endometriosis cling to this diagnosis as the aetiology to their problem for evermore. • The future development of serum markers for endometriosis is extremely important for diagnosis and management of the disease. Clinicians involved in the management of these cases await this next scientific step with bated breath.
6
carries out a wide-ranging inspection of the pelvis in order not to miss sites of the implants. Colour: peritoneal implants are classically described as bluish/ black powder-burn lesions, with varying degrees of surrounding pigmentation and fibrosis. The dark coloration is a result of haemosiderin deposition from entrapped menstrual debris, but it is important to realize that most peritoneal implants are not black and may be red, white, yellow/brown or clear. White, opacified areas and red, flame-like lesions contain endometriosis in around 80% of cases, while brown patches have endometriosis in approximately 50% of cases. However, white peritoneal implants are associated with less pain than black or red ones, and it is believed that the black/red lesions produce prostaglandin F2α, which is the cause of the pelvic pain. It has been proposed that endometrial implants undergo a process of natural evolution through a number of phases, finally becoming black; all colours can co-exist in the same patient, presumably due to ages of the various lesions. Microscopic endometriosis, diagnosed following peritoneal biopsy, may occur in up to 50% of specimens, but has a similar prevalence in non-symptomatic and symptomatic women. It is therefore very difficult to ascertain its significance. Microscopic endometriosis may be a normal physiological process.
brown, dense, chocolate-like fluid and endometriomas larger than 3 cm are often multi-locular (more than one cavity). Deep infiltrating endometriosis Deep infiltrating endometriosis is usually localized to the rectovaginal septum and is probably a distinct entity, as opposed to peritoneal and ovarian endometriosis. It is suggested that it originates from Müllerian rest cells, which have remained in the rectovaginal septum. Histologically, it is often similar in appearance to adenomyosis (endometriosis in the uterine myometrium). It is important to ensure that the bowel can be manoeuvred adequately during the laparoscopy procedure, in order to make sure that the laparoscopist can meticulously examine the rectovaginal septum, to exclude these lesions.
Endometriomas (Figures 6 and 7) Endometriomas are smooth, dark brownish cysts, often associated with adhesions, that lie on the surface of the ovary. They contain
Endometriomas
Acknowledgement The author would like to thank Dr J Hollway, Consultant Radiologist at Queen Charlotte’s and Chelsea and Hammersmith Hospitals for providing the ultrasound and MRI images.
REFERENCES 1 Eskenazi B, Warner M, Bonsignore L. Validation study of non-surgical diagnosis of endometriosis. Fertil Steril 2001; 76: 929–35. 2 Chen F P, Soong Y K, Lee N, Lo S K. The use of serum Ca-125 as a marker for endometriosis in patients with dysmenorrhoea for monitoring therapy and for recurrence of endometriosis. Acta Obstet Gynecol Scand 1998; 77: 665–70. 3 Pascual M A, Tresserra F, Lopez-Marin L, Ubeda A, Grases P J, Dexeus S. Role of color Doppler ultrasound in the diagnosis of endometriotic cyst. J Ultrasound Med 2000; 19: 695–99.
7
WOMEN’S HEALTH MEDICINE 2:1
23
© 2005 The Medicine Publishing Company Ltd