Endometriosis and infertility: management of patients from the perspective of evidence-based medicine. Endometriosis and infertility: patient management from the perspective of evidence-based medicine Presentation on the topic of endometriosis, modern methods of treatment

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Thank you for your attention.

Literature. 1. Serov V.N. Kira E.F. Gynecology. Guide for doctors. Moscow 2008 2 Strizhakov A.N. Davydov A.I.

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General characteristics of endometriosis. Description of endometriosis in the uterus and external genital. Consideration of the stages of the pathological process in the mucous membrane of the uterine body. Risk factors for this disease. Symptoms, differential diagnosis, treatment.

Relevance of the problem. Over the past decades, the problem of endometriosis has acquired particular significance. The reasons for this are the increasing frequency of this pathology. It ranks 3rd after inflammatory diseases of the gastrointestinal tract and uterine fibroids (8-15% of menstruating women) - in recent years, with improved diagnosis of the disease, especially in young patients with algodysmenorrhea, the frequency of endometrioid disease is 17 % and reaches 30% in those in need of gynecological operations






















The main theories of the development of endometriosis are the origin of the pathological substrate from the endometrium (implantation, lymphogenous, hematogenous, iatrogenic dissemination) metaplasia of the epithelium (peritoneum) disturbance of embryogenesis with abnormal residues disturbance of hormonal homeostasis changes in the immune balance features of intercellular interaction





Pathogenesis The main pathogenetic factors of endometriosis include the retrograde flow of menstrual blood containing viable endometrial elements through the fallopian tubes into the pelvic cavity, the introduction of endometrial cells into various organs and their proliferation lead to the formation of foci and implants of endometriosis.





Hormonal disorders (high estrogen stimulation, anovulation, hypofunction of the corpus luteum) - dysfunction of the immune system and impaired biological response of endometrial cells to sex hormones, constitutional - hereditary features that are associated with the occurrence of congenital forms of endometriosis in young and young people





Prolonged tension of protective-adaptive reactions and a decrease in the nonspecific resistance of the body (in women with chronic hepatitis of various etiologies and localizations, morphological changes in the myometrium that occur in connection with frequent intrauterine interventions and surgical operations on the genital organs - insufficiency of the body's antioxidant system - dysfunction of the liver and pancreas .

















According to the distribution and depth of tissue damage by endometriosis, they are distinguished: I degree - single superficial lesions. Grade II: slightly deeper lesions. III degree: many deep foci of endometriosis, small endometrioid cysts of one or both ovaries, thin peritoneal adhesions. IV degree Many deep lesions, large bilateral endometrioid ovarian cysts, dense adhesions of organs, invasion of the vagina or rectum.





MAIN CLINICAL SYMPTOMS OF ENDOMETRIOSIS I. The main symptom of endometriosis is pain during menstruation dyspareunia (pain during sexual activity) - 26-70% pain radiates to the vagina, rectum, perineum pain during bowel movements pain reduces ability to work There is not always a correlation between the size of the lesion and pain syndrome.





MAIN CLINICAL SYMPTOMS OF ENDOMETRIOSIS II. Menstrual dysfunction, algodismenorrhea, menorrhagia, pre- and postmenstrual bleeding. MF disorders depending on the location of endometriosis foci Progressive algodysmenorrhea (with intrauterine endometriosis with damage to the isthmus, endometriosis of the ovaries, pelvic peritoneum, uterosacral ligaments, retrocervical endometriosis with damage to the perirectal tissue and rectal wall). Menometrorrhagia (with intrauterine endometriosis and adenomyosis in combination with uterine fibroids). Bleeding before and after menstruation, contact bleeding (with ovarian endometriosis and uterine adenomyosis). Irregular menstruation (with a combination of ovarian endometriosis and sclerocystic disease).





MAIN CLINICAL SYMPTOMS OF ENDOMETRIOSIS III. There is a slight increase in the size of the affected organs (uterus and ovary) or extragenital foci of endometriosis on the eve of and during menstruation. The disease is characterized by a long, often progressive course. Spontaneous regression is possible in the postmenopausal period.





MAIN CLINICAL SYMPTOMS OF ENDOMETRIOSIS IV Infertility (detected with a frequency of % during laparoscopic examination of patients suffering from infertility and with a frequency of 6-7% in fertile women).











The functional state of the pituitary-ovarian system in endometriosis is an increase in basal levels and peak-free secretion of LH; - normal or elevated basal FSH levels; - LH/FSH ratio from 2.37 to 2.63; - hyperestradiolemia; - hypoprogesteronemia; - hypertestosteronemia in patients with a hirsute score of more than 8 points; - a 2-fold decrease in the estradiol/testosterone index.











Endometriosis of the uterus (adenomyosis) stage 1 - germination of endometriosis to a shallow depth, the process is limited to the submucosa of the uterine body. Stage 2: the process spreads to the middle of the myometrial thickness. 3rd degree - spread of the pathological process throughout the entire thickness of the myometrium to its serous cover. 4th degree involvement of the parietal peritoneum and neighboring organs in the process.





Ovarian endometriosis. Grade 1: small, pinpoint foci of endometriosis on the surface of the ovaries and on the peritoneum of the posterior pouch of Douglas. Grade 2 unilateral endometrioid cyst with a diameter of up to 5-6 cm, adhesions in the area of ​​the uterine appendages. Grade 3 endometrioid cysts of both ovaries (diameter more than 5-6 cm), foci of endometriosis on the serous surface of the uterus, fallopian tubes, pelvic peritoneum, pronounced adhesions. 4th degree bilateral cysts of large sizes with the transition of the process to neighboring organs.





























Diagnosis of endometriosis Gynecological examination over time during and outside of menstruation; General clinical blood test; Biochemical blood test and determination of hormones (FSH, LH, PL, E); Oncocolpocytological study; Immunogram; Hysteroscopy, colposcopy, cystoscopy, irrigoscopy, sigmoidoscopy; Ultrasound of the pelvic organs; Histological examination; X-ray of the lumbar spine; Determination of tumor markers; CT and SCT of the pelvic organs; Laparoscopy with chromotubation; Laparotomy in selected cases. Final list of studies for endometriosis





Determination of oncoantigens CA 19-9, CEA and CA 125 (RAMS) In healthy individuals, the concentration of CA is on average 13.1 U/ml, in patients with endometriosis - on average 29.5 U/ml; The concentration of CA 125 in healthy individuals is 8.3 U/ml, with endometriosis - on average 27.2 U/ml; The content of CEA (carcinoembryonic antigen) in the blood serum of healthy individuals is 1.3 ng/ml, with endometriosis – 4.3 ng/ml.





The main symptom of endometriosis is pain; Other causes of pelvic pain should be excluded; During a gynecological examination, sensitivity and soreness of the retrouterine space with or without compactions is observed. Ultrasound research methods are not always informative; Tumor marker CA 125 may increase in other benign and malignant tumors. Therefore, one of the main methods for the final diagnosis of endometriosis today is laparoscopy.












Treatment of endometriosis The surgical method of treating endometriosis was and remains the only one that allows you to remove mechanically or destroy using energy (laser, electro-, cryo-, ultrasound) the morphological substrate of endometriosis itself. A combination of surgical method and hormone-modulating therapy for common forms of the disease, uncertainty about complete removal of the lesion or a high risk of recurrence. immunomodulators





Hormone therapy The main principle of drug therapy for endometriosis is the suppression of estradiol secretion by the ovaries. The degree and duration of suppression of ovarian function determine the effectiveness of hormonal therapy. A decrease in the level of estradiol in peripheral blood below 40 picograms/ml indicates adequate suppression of ovarian function. Progestogens: norethisterone, duphaston, orgametril Antigestagens: mefepristone, geststrinone (nemestran).











Efficiency: Atrophic changes in endometrioid lesions occur due to decreased blood circulation, which is confirmed by histological examination of biopsies taken before and after treatment. Of the clinical symptoms, dysmenorrhea disappears first, then pain not associated with menstruation, and after 3-4 months. and dyspareunia. By the end of the course of treatment, the intensity of the pain syndrome decreases by 4 times. The treatment is effective for peritoneal endometriosis and superficial ovarian endometriosis in combination with the main surgical method.














Prof. A.A. Popov Moscow Regional Research Institute of Obstetrics and Gynecology

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Endometriosis in numbers

1 in 10 women of reproductive age suffers from endometriosis Rogers et al. Reprod.Sci 2009 16:335-346 1,761,687,000 women aged 15 - 49 years World Bank Population Protection Tables by Country and Group, 2010 176 million women today suffer from endometriosis

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Infertility and endometriosis

The most common cause of infertility Endometriosis as a cause of infertility is registered in 38% of infertile couples. There is no correlation between the extent of endometriosis and the incidence of fertility disorders. The success of treatment does not exceed 45-58%

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Endometriosis is one of the main causes of female infertility.

After surgical and hormonal treatment, pregnancy occurs in 30-52% of patients. Repeated laparoscopy as a method of restoring fertility is not effective Koga K et al., Hum Reprod 2006, Ragni G et al., Am J Obstet Gynecol 2005, Kulakov V.A. co-author, 2002, Volkov N.I., 1996

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Surgery for endometriosis-associated infertility: a pragmatic approachP.Vercellini, E.Somigliana, P.Vigano, A.Abbiati, G.Barbara, P.G.CrosignaniHuman Reproduction, Vol.24, N2, 2009

The actual pregnancy rate during surgical treatment does not exceed 25% and depends little on the type of lesion. The effectiveness of surgery for peritoneal endometriosis is also low. The outcome of excision of rectovaginal lesions is questionable and is associated with a higher incidence of complications.

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ESHRE guidelines for the diagnosis and treatment of endometriosis (2005)

www.endometriosis.org/guidelines.html Laparoscopy is the “gold standard” in the diagnosis and treatment of endometriosis. With minimal endometriosis, ovarian suppression alone is not effective enough to restore eating. fertility. Ablation of heteropopias and dissection of adhesions is more effective in restoring natural fertility compared to a diagnostic procedure. There is insufficient evidence whether surgical ablation for severe endometriosis increases pregnancy rates. IVF is the best treatment for patients suffering from infertility, but the effectiveness of IVF in these patients is lower than in patients with TBI. Treatment of endometriosis is complex and should be carried out in clinics where there is extensive experience and capabilities in treating this disease.

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Ablation or excision of endometrioid heterotopias?

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  Genital endometriosis and infertility

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  Peritoneal endometriosis I-II degrees.

  Laparoscopy Watchful waiting for 6 months. CIO (3-4 cycles) If there is no effect - IVF

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  Peritoneal endometriosis stage III-IV

  Laparoscopy Expectation of pregnancy 6 months. If there is no effect - IVF

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  Rationale for perioperative use of hormones.

  Persistent hypoestrogenism. Reducing blood loss during surgery. Reducing the size of formations Treatment of anemia (elimination of menstrual losses). Improvement of the postoperative period. Reducing the recurrence rate of endometriosis.

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  Laureates NP (1977) for the discovery of GnRH R.Guillemin and A.Schally

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  Tactics for endometrioid ovarian cysts

  History (presence of endometriosis during surgical interventions) Size of the cyst (more or less 4 cm) Localization (unilateral or bilateral) Age of the woman State of ovarian reserve Any ovarian formation - oncological alert!

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  Effect of endometrioma surgery on ovarian function

  Endometrioma is a true ovarian tumor that requires removal and histological verification. Surgery for extensive ovarian endometriosis provides the most favorable balance of effectiveness and possible harm (P. Vercellini, 2009) Laparoscopic surgery is the “gold” standard. The technique of mechanical removal of the cyst pseudocapsule with subsequent hemostasis (V. Cela, 2005, N. Volkov, 2004)

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  PR after IVF (n=104, data from OR MONIIAG) 23

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  “Gentle” hemostasis after endometrioma removal

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  Unilateral ovarian cysts in women under 38 years of age Newly detected Recurrence EOC > 4 cm

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  Bilateral ovarian cysts Laparoscopy Maximum care for ovarian tissue! Urgent IVF

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  Results of surgical treatment of infertility for endometriosis PE 1-2 PE 3-4 EKY 1st EKY 2nd 34.3% 14.9% 11.9% 32.0% - % of patients with pregnancy within 1 year (after surgical treatment)

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  Infiltrative endometriosis

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  MONIIAG + MC "Moskvorechye" 2004-2010

  Infiltrative endometriosis 123+1 Excision of infiltrate 63 Segmental resection 8 Circular resection 7+1 Ureterolysis 24 Resection of the bladder 1 Ureterocystoanastomosis 1+1

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  Circular resection

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  Is recto-vaginal endometriosis a progressive disease?

  Only 6 out of 88 women (6.8%) noted progression of the disease during follow-up periods of more than 68 months. Fedele at al, Am.J.Obstet.Gynecology, 2004

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  Infiltrative endometriosis

  Does “asymptomatic” infiltrative endometriosis require surgical treatment? Is it advisable to use perioperative hormone therapy? Is it the cause of fertility problems? Does IVF affect the results? V.Bianchi (2009) PR (IVF) 40 vs 22

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  Fertility in infiltrative endometriosis: spontaneous pregnancy rates after surgery

  Vircellini at al. 2006 15/44 34% 20-50 Landi at al. 2008 11/4425% 13-40 Stepniewska at al.2009 43/133 32% 24-41 Darai at al. 2010 12/3931% 17-48 Cumulative 31% 26-37

  Adequate preoperative diagnostics (MRI, FCS, cystoscopy) Adequate intraoperative diagnostics Adequate surgical intervention As an alternative: diagnostic Ls>expert department

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  Basic principles of treatment tactics for external-internal endometriosis.

  Hormonal therapy in long courses over a long period of time has no effect and leads to advanced, widespread forms. Prescribing a long course of hormone therapy for initially severe forms of endometriosis without subsequent surgical treatment is ineffective. Surgery is the main treatment for endometriosis.

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  4. In the absence of pronounced adhesions, damage to the intestines and urinary system, laparoscopic surgery is preferable.

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  5. The basis of prevention is early diagnosis of mild and moderate forms of endometriosis and active combined tactics (surgery + drug therapy). Performing reconstructive operations against the background of perioperative use of hormones.

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