Endometriosis is a condition in which the endometrial tissue (glands and mesenchyme) appears outside the body of the uterus and is characterized by the following features: frequent in women of childbearing age, mainly causing pain and infertility; a marked increase in incidence; disproportionate symptoms to signs and severity of disease; widespread lesions with a variety of morphologies; highly invasive, forming extensive, severe adhesions; hormone-dependent, prone to Hormone-dependent and prone to recurrence.
I. Clinicopathological types of endometriosis
1. Peritoneal endometriosis: It refers to various endometriosis lesions in the pelvic peritoneum, mainly including red lesions (early lesions), blue lesions (typical lesions) and white lesions (old lesions).
2. Ovarian endometriosis: cysts can be formed, which are called endometriotic cysts (customarily called “chocolate cysts”). According to the size of the cyst and the degree of infiltration of the ectopic lesion, it is divided into:
Type I: the diameter of the cyst is less than 2 cm, the wall of the cyst has adhesions and the level of p is unclear, so it is not easy to peel off surgically.
Type II: It is also divided into three types of ABC.
Type IIA: endoimplantation foci are superficial, involving the ovarian cortex, not reaching the cyst wall, often combined with functional cysts, and easy to peel off during surgery.
ⅡB: The ectopic implantation foci have involved the wall of the chocolate cyst, but the boundary with the ovarian cortex is clear, and it is easy to peel off during surgery.
ⅡC: The ectopic implant foci have penetrated into the cyst wall and extended to the surrounding area. The cyst wall is tightly adherent to the ovarian cortex and is associated with fibrosis or multiple atria. The ovary is adherent to the lateral pelvic wall and is large in size, so it is not easy to peel off surgically.
3, Deep Infiltrating Endometriosis (DIE): the depth of infiltration of lesions ≥5 mm is common in the uterosacral ligament p recto-uterine sink p vaginal vault p recto-vaginal septum. The rectovaginal septum includes two cases, one is pseudo-vaginal rectal septal endometriosis, that is, the adhesions of the rectal fossa are closed, and the lesion is located below the adhesions; the other is true rectovaginal septal endometriosis, that is, the lesion is located outside the peritoneum, in the rectovaginal septum, and there is no obvious anatomical abnormality in the rectal uterine sulcus.
4, other parts of endometriosis: can involve the digestive, urinary (U), respiratory (R) system, can form scar endometriosis (S), as well as other rare distant endometriosis, etc.
II. Pathogenesis of endoheterotaxy
1.The pathogenesis of endometriosis is not fully understood, but Sampson’s theory of epithelial metaplasia and induction is the leading theory.
2. The endometrium needs to undergo the process of adhesion, invasion and vascular formation outside the uterine cavity, and develops after implantation and growth, and the characteristics of the in situ endometrium may play a decisive role.
3. The systemic and local immune status and function, hormones, cytokines and enzymes of the body play an important role in the completion of the above process of ectopic endometrium.
4. There is family aggregation of endometriosis.
5. External environmental pollution (such as dioxin) may have some influence.
Clinical manifestations and auxiliary examination methods
Pain: 70%~80% have different degrees of pelvic pain, not exactly parallel to the degree of lesion, including {1} dysmenorrhea: typically secondary and progressively aggravated; {2} non-menstrual abdominal pain: chronic pelvic pain); {3} painful intercourse and painful defecation; {4} rupture of ovarian endometriosis cysts can cause acute abdominal pain.
2, infertility: about 50% of patients combined with infertility.
3, abnormal menstruation.
4. Pelvic mass.
5.Special site endometriosis: various symptoms often have cyclic changes and can be combined with clinical manifestations of pelvic endometriosis. For example, (1) gastrointestinal endoheterosis: symptoms such as increased frequency of stool or constipation, blood in stool and painful defecation. (2) Urinary tract endoheterosis: urinary frequency, painful urination, hematuria and lumbar pain, even causing urinary obstruction and renal dysfunction. (3) Respiratory tract endografts: menstrual hemoptysis and pneumothorax. (4) scar endoheterosis including {1} abdominal wall: nodules at the incision scar after surgery such as cesarean section, increasing in size and pain during menstruation; {2} perineum: nodules at the perineal incision or wound scar, increasing in size and pain during menstruation.
6, gynecological examination: typical cases of the uterus is often posterior p poor mobility; uterosacral ligament p rectal uterine sink or posterior fornix painful nodules; may be accompanied by cystic inactive adnexal masses.
7. Blood carcinoembryonic antigen 125 (CA125) test: CA125 level is mostly mild to moderately elevated.
8. Imaging: Ultrasound scan is mainly meaningful for the diagnosis of ovarian endometriosis cysts. The typical ultrasound image is an anechoic mass in the adnexal region with a strong light spot inside. Magnetic resonance imaging (MRI) is useful for the diagnosis and evaluation of ovarian endometriosis cysts p pelvic extranodal heterotrophy and deep invasive lesions.
9. Other: other ancillary tests such as intravenous pyelogram (IVP), cystoscopy, colonoscopy, etc. are feasible if necessary.
IV. Diagnosis
1, pain (dysmenorrhea, chronic pelvic pain, painful intercourse, etc.), infertility, pelvic examination, imaging and serum CA125 test are important clinical diagnostic indicators.
2. Laparoscopy is currently a common method for the diagnosis of endometriosis. The diagnosis is mainly based on the morphology of the lesion under laparoscopy, but it is difficult to confirm all of them by pathology.
3.Special sites: according to the symptoms and the corresponding examination.
V. Clinical staging
The commonly used staging method for endometriosis is the 1985 revised rAFS staging method, which is mainly based on the size and depth of peritoneal p-ovarian lesions, the extent of ovarian-fallopian tube adhesions and the thickness of adhesions, and the degree of closure of the recto-uterine sink to score. The staging method is divided into 4 stages: stage I (micro lesions): 1~5 points; stage II (mild): 6~15 points; stage III (moderate): 16~40 points; stage IV (severe): >40 points.
VI. Treatment
The objectives of treatment are: to reduce and eliminate lesions, to relieve and relieve pain, to improve and promote fertility, and to reduce and avoid recurrence. The main factors to be considered in treatment are: age, fertility requirements, severity of symptoms, extent of lesions, previous treatment history and the patient’s wishes. Treatment should be standardized and individualized. The treatment of pelvic pain, infertility and pelvic masses should be treated separately. The treatment methods can be divided into: surgical treatment, pharmacological treatment, interventional treatment, and assisted reproduction treatment.
1.Surgical treatment
-The purpose of surgery is to remove the lesion and restore the anatomy. The procedure is divided into conservative surgery, semi-curative surgery and curative surgery.
-Types of surgery and principles of selection:
Conservative surgery: to preserve the patient’s reproductive function, the surgery tries to remove the lesions visible to the naked eye, remove the ovarian endometriosis cysts and separate the adhesions, suitable for young people or those who need to preserve their reproductive function.
Semi-radical surgery: Removal of the uterus and the lesions, but preservation of the ovaries, mainly for those who do not want to have children but want to preserve the endocrine function of the ovaries.
Radical surgery: Removal of the entire uterus and both adnexa, as well as all lesions visible to the naked eye. It is suitable for those who are older, have no fertility requirements, have severe symptoms, or have failed multiple treatments.
-Adjunctive procedures: such as LUNA and PSN for pain in the midline.
Preoperative preparation: adequate preoperative preparation and evaluation; adequate understanding and informed consent, such as the risk of surgical injury, especially the possibility of urological and intestinal injury, and the possibility of conversion of laparoscopic surgery to open surgery; adequate bowel preparation for deep infiltrative endometriosis, especially if the lesion involves the vaginal-rectal region; and the presence of significant deep infiltrative parametrial lesions. The ureter and kidneys should be checked for abnormalities before surgery; if necessary, urology and general surgery should be used.
-The main points of surgery are: firstly, pelvic adhesions should be separated to restore the anatomy; peritoneal endometriosis lesions should be removed or destroyed as much as possible to achieve reduction; smaller and superficial lesions can be cauterized or vaporized; deep infiltrating lesions should be excised.
In ovarian endometriosis cyst removal, the adhesions with the surrounding area should be separated, the chocolate like fluid inside the cyst should be aspirated and the cyst wall should be flushed out, then the fibrous tissue ring around the cyst rupture should be removed and the cyst wall should be peeled off completely to protect the normal ovarian tissue as much as possible. In cases of combined infertility, hysteroscopy and tubal lavage can be performed at the same time.
Deeply infiltrating endometriosis is more difficult to manage. If the lesion does not invade the rectum or colon wall, the lesion should be removed as much as possible; if there is intestinal wall infiltration but no intestinal stricture, it is generally not recommended to remove the intestinal wall or intestinal segment, and it is appropriate to reduce the lesion; if the lesion is large and causes intestinal stricture or even intestinal obstruction, intestinal segment resection and anastomosis should be performed as appropriate.
If the lesion is large and causes intestinal stricture or even intestinal obstruction, resection of the intestinal segment and anastomosis will be performed as appropriate.
For ureteral endoanomalies, adhesiolysis or partial ureteral resection and anastomosis are performed depending on the lesion and the degree of ureteral obstruction.
For scar endoheteropathy, surgery is the main treatment, and drugs are mostly insensitive.
For lesions of endometriosis that are difficult to remove surgically or may damage important organs and tissues, drugs such as gonadotropin-releasing hormone agonist (GnRH-a) can be used for 3 to 6 months before surgery.
When separating adhesions or removing the uterus to deal with the uterine vessels and ligaments, attention should be paid to the ureteral anatomy, and if necessary, a ureteral catheter should be placed in the ureter before surgery as an indication. In addition, postoperative patients can apply anti-adhesion preparations.
2.Drug treatment
The purpose of treatment is to inhibit ovarian function, stop the progression of endometriosis, reduce the activity of endometriosis lesions and reduce the formation of adhesions.
The principles of selection are: (1) the treatment should be used in basic diagnosed cases, and long-term “experimental treatment” is not recommended; (2) there is no standardized program; (3) the efficacy of various programs is basically the same, but the side effects are different, so the side effects of drugs should be considered when selecting drugs; (4) the patient’s wishes and financial ability should also be considered.
The four main categories of drugs available are: oral contraceptives, highly effective progestins, androgen derivatives and GnRH-a. Commonly used medication regimens, mechanisms of action and side effects are as follows:
Oral contraceptives: continuous or cyclic use for a total of 6 months, can inhibit ovulation, with fewer side effects, such as gastrointestinal symptoms or liver function abnormalities.
MPA can synthesize highly effective progesterone, causing metaplastic changes in the endometrial tissue, which eventually leads to atrophy, as well as negative feedback to inhibit the hypothalamic-pituitary-ovarian axis. The side effects are mainly breakthrough bleeding, breast pain, weight gain, gastrointestinal symptoms and abnormal liver function.
Danazol: 600~800 mg per day, divided into 2~3 oral doses, for 6 months. Danazol is an androgenic derivative that inhibits mid-menstrual luteinizing hormone (LH) peak and thus suppresses ovulation; it also inhibits various enzymes involved in steroid synthesis and increases the level of free testosterone in the blood. Side effects are mainly masculine manifestations, such as increased hair, mood changes, and thickening of the voice, in addition to possible effects on lipoprotein metabolism, liver damage, and weight gain.
Pregnatrienone: 2 or 5 mg orally, 2-3 times/week for 6 months. Pregnenolone is a synthetic derivative of 19-nortestosterone, which can antagonize progesterone and estrogen, reduce the level of sex hormone binding protein, and increase the level of free testosterone in blood. The side effects are mainly anti-estrogenic and androgenic, basically the same as Danazol, but less severe.
GnRH-a: Depending on the formulation, it is administered subcutaneously and intramuscularly once a month for 3 to 6 months.
GnRH-a can down-regulate pituitary function, resulting in a temporary depot of the drug and a low estrogenic state in the body. The side effects are mainly menopausal symptoms caused by hypoestrogenemia, such as hot flashes, vaginal dryness, decreased libido, insomnia and depression, etc. Long-term use may cause bone loss.
GnRH-a + Add-back: Based on the theory of “estrogen window dose”, the sensitivity of different tissues to estrogen varies, the estrogen level in the body is maintained in a range that does not stimulate the growth of ectopic endometrium without causing menopausal symptoms and bone loss (estradiol level between 30-40 pg/ml). ml), which can reduce side effects and prolong the treatment time without affecting the therapeutic effect.
-Add-back regimen:
Combined estrogen and progestin regimen: Combined estrogen (CEE, Pemetil) 0.3-0.625 mg + MPA 2-4 mg daily.
Tiberone (Levitra): 1,25 mg daily.
Add-back precautions: Add-back is recommended after more than 3 months of GnRH-a use and can be started from the second month of use depending on the severity of symptoms; the treatment dose should be individualized and estrogen levels should be monitored when available.
3. Treatment of dysmenorrhea
Treatment principles: ① surgery is preferred in cases of combined infertility and nodules or adnexal masses; ② medication is preferred in cases of uncomplicated infertility and adnexal masses; ③ surgery can be considered if medication is not effective.
Treatment: Surgery: conservative surgery, semi-radical surgery or radical surgery according to the patient’s specific situation; LUNA and PSN may be performed as appropriate.
Commonly used drug treatments:
-First-line medications:Non-steroidal anti-inflammatory drugs (NSAIDs) or oral contraceptives are available. Oral contraceptives can be used cyclically or continuously, and can be continued if effective, or switched to second-line drugs if ineffective.
Second-line regimen: Progestin p androgen derivatives and GnRH-a can be used, with GnRH-a+Add-back being the first choice,
GnRH-a+Add-back is the first choice to control the adverse effects of long-term use.
If second-line drugs are not effective, surgical treatment should be considered.
Pre-operative medication: For those who have severe lesions, it is estimated that it is difficult to cut or surgery may damage important organs, pre-operative medication can be used briefly for 3 months to reduce the difficulty of surgery.
Postoperative medication: according to the specific situation, if the lesion is light or the surgery is complete, no medication can be temporarily used; if the pelvic lesion is serious or the lesion cannot be completely cut, medication can be used for 3-6 months depending on the presence of pain symptoms.
4.Treatment of infertility
Treatment principles: ① comprehensive infertility examination to exclude other infertility factors; ② medication alone is ineffective; ③ laparoscopic examination can be used to assess the lesion and stage of endoheterosis; ④ young patients with mild to moderate endoheterosis should expect natural conception for six months after surgery and be given fertility guidance; ⑤ those with high risk factors (age 35 years or older, adhesions in the oviduct, low functional score, infertility for more than 3 years, especially primary infertility), (5) Assisted reproductive technology should be actively used to help pregnancy in patients with high risk factors (age 35 years or older, adhesions in the fallopian tubes, low functional score, infertility for more than 3 years, especially in primary infertility, moderate to severe endometriosis, pelvic adhesions, incomplete excision of lesions).
Surgical approach: Conservative laparoscopic surgery should be performed to remove as many lesions as possible and to separate adhesions to restore anatomy. Special care should be taken to protect normal ovarian tissue when removing endometriotic cysts. Intraoperative tubal lavage is performed simultaneously to understand the patency of the fallopian tubes and hysteroscopy is performed to understand the condition of the uterine cavity.
Assisted reproductive techniques: Controlled ovulation/IUI (COH/IUI), IVF-ET, depending on the patient’s condition.
-IUI:
Indications for COH/IUI: mild or moderate endometriosis; mild male factor (mild oligozoospermia, etc.); cervical factor and unexplained infertility.
The success rate of IUI and the course of treatment: the pregnancy rate of a single cycle is about 15%, and if the pregnancy is unsuccessful after 3-4 courses of treatment, the mode of pregnancy assistance will be adjusted.
-IVF-ET:
Indications for IVF-ET: severe endometriosis, failure of other methods (including natural conception, ovulation induction, artificial insemination and surgical treatment); long duration and advanced infertility.
Pre-IVF-ET GnRH-a treatment: It is recommended to pretreat with GnRH-a for 2-6 months before IVF-ET to help improve the success rate of pregnancy. The duration of drug use is adjusted according to the severity of endometriosis p ovarian reserve of the patient (Figure 1).
VII. Hormone replacement therapy in patients with endometriosis
Hormone replacement therapy can be performed after menopause or radical surgery to improve the patient’s quality of life; hormone replacement therapy is individualized according to the patient’s symptoms; even if the uterus has been removed, if there are residual endometriosis foci, estrogen replacement therapy (ERT) along with progestin is recommended; ERT can also be applied only if there are no residual foci; blood E2 levels should be monitored when available so that estrogen levels are in line with The level of estrogen should be monitored so that the level of estrogen meets the principle of “two highs and one low”, that is, high enough not to show the symptoms of endometriosis and not to recur, and low enough not to cause bone loss.
VIII. Recurrence of endometriosis
After surgery and standard drug treatment, the lesion shrinks or disappears and the symptoms are relieved, the clinical symptoms reappear and return to the level before treatment or worsen, or the endometriosis lesion appears again.
Treatment principles: The basic principles of primary treatment should be followed, but should be individualized. Ovarian endometriosis cysts can be treated with surgery or ultrasound-guided puncture and postoperative medication. If recurrence occurs after medication for dysmenorrhea, surgery should be performed; if recurrence occurs after surgery, surgery should be considered if medication is still ineffective; if the patient is older and does not require fertility and has severe symptoms, radical surgery may be considered. Infertile patients with combined endometriosis cysts can be treated surgically or by ultrasound-guided puncture and IVF-ET after 3 months of GnRH-a; those without combined ovarian endometriosis cysts can undergo IVF-ET after 3 months of GnRH-a.
Nine p endometriosis malignant change
Malignancy can occur in endometriosis, with an incidence of about 1%. The following conditions should be alerted for malignant change: ① cyst diameter >10 cm or significantly increased within a short period of time; ② recurrence after menopause; ③ change in pain rhythm, progressive or persistent dysmenorrhea; ④ solid or papillary structures on imaging, color Doppler ultrasound shows rich blood flow in the lesion and low resistance index (RI); ⑤ significant increase in serum CA125 (>200 U/ml)
1.Diagnostic criteria:{1}Cancerous tissue and endometriosis tissue coexist in the same lesion site;{2}There is histological correlation between the two, similar to endometrial interstitium and glands, or there is old bleeding;{3}The presence of other primary tumors is excluded, or cancerous tissue occurs in the endometriosis lesion, rather than metastasis from other sites;{4}There is morphological evidence of endometriosis to malignant migration, or benign endometriosis and The endometriosis is not metastatic from other sites.
2.Atypical endoheterosis: {1}The pathological histological diagnosis refers to atypical or nuclear heterotypic changes of ectopic endothelial glandular epithelium, but does not break through the basement membrane. {2}The diagnostic criteria are darkly stained or pale, pale nuclei with moderate to severe heterogeneity; increased nuclear/pulp ratio; and dense, compound or clustered cells in ectopic endothelial glandular epithelium. The significance of {3} atypical endothelial disease may be precancerous, or junctional tumor status.
The site of malignancy is mainly in the ovary, other sites such as vaginal-rectal compartment p abdomen or perineal incision are less common.
4. Treatment: follow the principles of ovarian cancer treatment.
Adenomyosis of the uterus
The endometrial glands and mesenchyme are present in the myometrium, and under the influence of hormones, bleeding and proliferation of myofibrous connective tissue occur, resulting in diffuse lesions or limited lesions, or adenomyoma.
1, the etiology is unclear, mainly endometrial invasion theory, others include vascular lymphatic dissemination, epithelial metaplasia and hormonal effects.
2, clinical manifestations: {1} dysmenorrhea: more than half of the patients have secondary dysmenorrhea, progressive aggravation; {2} menstrual abnormalities: excessive menstruation p prolonged periods and irregular bleeding; {3} infertility; {4} uterine enlargement, mostly homogeneous enlargement, spherical, can also be raised uneven, hard.
3, diagnosis: according to the symptoms, pelvic examination and the following auxiliary tests can make a preliminary diagnosis: {1} ultrasound scan shows an enlarged uterus, myometrial thickening, the posterior wall is more pronounced, the endometrial line is shifted forward. The lesion is isoechoic or echogenic with dotted hypoechogenicity between them. MRI shows the presence of poorly defined lesions with low p-signal intensity in the uterus, and T2 enhanced images may show lesions with high signal intensity and a widening of the endometrium-myometrium junction area, greater than 12 mm. {The pathological examination is the gold standard for diagnosis.
4, Treatment: {1}Expectant treatment: asymptomatic p without fertility requirements can receive observation. {Surgical treatment is the main treatment, with hysterectomy being the radical procedure. In young people who need to preserve their reproductive function, focal resection or wedge hysterectomy can be performed, as well as adjuvant LUNA, PSN or uterine artery blockade. For those who do not require fertility and have increased menstrual flow, endometrial removal can be performed. {3}Medication: Same as endometriosis. {4}Interventional treatment (DSA). {For infertile patients, treatment with GnRH-a for 3-6 months can be followed by fertility treatment; for patients with limited lesions or adenomyoma, surgery + GnRH-a treatment can be followed by fertility treatment.