Philippe Koninckx

Deep endometriosis: a consequence of infiltration or retraction or possibly adenomyosis externa? *

OBJECTIVE To analyze the incidence and occurrence of subtypes of deep endometriosis. DESIGN Deep endometriotic lesions (> 5 mm) were retrospectively analyzed, using our data base and slides taken systematically during surgery. SETTING University Hospital Gasthuisberg (University of Leuven) which is a referral center for infertility and endoscopic surgery. PATIENTS All women with deep endometriosis (n = 136) were selected from a consecutive series of 1,252 laparoscopies for infertility, pain, or both. INTERVENTIONS AND MAIN OUTCOME MEASUREMENTS Deep endometriosis was excised by CO2 laser and the depth of infiltration and the pelvic area measured. As part of an ongoing study, most lesions were photographed. RESULTS Deep endometriosis is suggested to contain three subgroups. Type I is conical shaped and suggested to be formed by infiltration. Type II is deeply located and covered by extensive adhesions and probably formed by retraction. Type III is a spherical nodule with its largest dimension under the peritoneum. Types I, II, and III are found in 4.1%, 0.8%, and 0.9% of women with infertility (n = 759) and in 10.4%, 3.2%, and 3.2% of women with pelvic pain (n = 374). Types I, II, and III are most frequently found in the revised American Fertility Society classes II, III to IV, and I, respectively. CONCLUSIONS Three subtypes of deep endometriosis can be distinguished. Type III, which is a spherical nodule located in the recto vaginal septum is the most severe and largest lesion. This is, however, easily missed clinically because these lesions are generally scored as revised American Fertility Society class I.

Correlation between endometriosis and pelvic pain

STUDY OBJECTIVE To evaluate the relationship between prevalence and severity of chronic pelvic pain (CPP) and stage, site, and type of endometriosis. DESIGN Prospective, observational study (Canadian Task Force classification II-2). SETTING University Hospital. PATIENTS Of 90 consecutive women with biopsy-proved endometriosis, laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis. INTERVENTION Preoperatively, using a 10-point visual analog scale, the severity of dysmenorrhea, CPP, and deep dyspareunia was assessed. During laparoscopy all visible endometriotic lesions were recorded and treated. MEASUREMENTS AND MAIN RESULTS Ten women (11.1%) had no pain; 72 had dysmenorrhea (mild in 13, moderate in 37, severe in 22); 55 had CPP (mild in 11, moderate in 25, severe in 19); and 39 deep dyspareunia (mild in 5, moderate in 31, severe in 3). The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions (p = 0.004); the severity of CPP correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001) and extent of pelvic adhesions (p = 0.02); and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments (p = 0.04). Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001), peritoneal adhesions (p = 0.01), and extent of adnexal adhesions (p = 0.01). No significant correlation was found among revised American Fertility Society stage of endometriosis; presence and size of ovarian endometriomas; extent, type, and site of peritoneal lesions; and pain scores. By logistic regression analysis, the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis (p = 0.0001) and presence and extent of adnexal adhesions without cystic endometriosis (p = 0.01), and by the presence of ovarian endometrioma with periovarian adhesions (p = 0.03). Chronic pelvic pain was predicted by both deep endometriosis (p = 0.0001) and ovarian endometriomas with adnexal adhesions (p = 0.03). Deep dyspareunia was predicted simultaneously by deep endometriosis (p = 0.01) and an ovarian endometrioma with periovarian adhesions (p = 0. 008). Conclusion. Deep endometriosis, pelvic adhesions, and ovarian cystic endometriosis were independent predictors of pelvic pain. These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain.

A STUDY OF PLASMA PROGESTERONE, OESTRADIOL‐l7β, PROLACTIN AND LH LEVELS, AND OF THE LUTEAL PHASE APPEARANCE OF THE OVARIES IN PATIENTS WITH ENDOMETRIOSIS AND INFERTILITY

Thirty‐four infertile patients with regular cycles and endometriosis were studied and compared to a control group of 28 women. The endometriosis was classified as mild (n = 16), moderate (n = 9) and severe (n = 9) according to Acosta et a1 (1973). The interval between the LH peak and the onset of subsequent menstruation was shorter (P = 0.024) in patients with endometriosis than in the control group. In mild endometriosis, oestradiol‐17β levels fell on the day after the LH peak, but this was not the case in moderate and severe endometriosis. In mild, moderate and severe endometriosis the plasma progesterone concentration did not rise on the first day following the LH peak, and at laparoscopy significantly (P<0.005) less ovulation stigmata were present. We conclude that endometriosis is associated with luteinization in situ and that this may explain the associated infertility.

Treatment of deeply infiltrating endometriosis.

Deep endometriosis has been defined as endometriosis infiltrating deeper than 5 mm under the peritoneum. A model for the development and propagation of endometriosis is presented. Subtle and non-pigmented lesions are suggested to occur intermittently in all women. Infiltration occurs generally to a few millimeters of depth only, and these lesions become typical, burnt out lesions. In some 20% of women, severe endometriosis develops either as deeply infiltrating disease or as cystic ovarian disease. Arguments are given to consider deep endometriosis and cystic ovarian endometriosis as two specific entities of endometriotic disease. A possible causal relationship with dioxin pollution is discussed. Diagnosis of deep endometriosis is made by clinical examination and palpation during surgery. Clinical examination during menstruation and CA-125 concentrations in plasma are useful to help in the diagnosis of smaller deep lesions. Surgical excision can be carried out by laparoscopy, laparotomy or vaginally using sharp dissection, electrosurgery or with the use of a CO2 laser. Excision is the treatment of choice because of a high pregnancy rate, a complete cure of pain in most women, and a low recurrence rate. Medical treatment is probably less effective to treat infertility, but highly effective in relieving pelvic pain. Medical therapy, by luteinizing hormone-releasing hormone agonists, danazol, or gestrinone, also seems useful as a pretreatment for surgery. The choice of treatment will therefore depend on the local expertise with minimal invasive surgery, certainly if a first excision has been incomplete and pain symptoms recur.

ORIGIN OF PERITONEAL FLUID IN WOMEN: AN OVARIAN EXUDATION PRODUCT

The volume of peritoneal fluid was measured after laparoscopic aspiration in 303 women. Contamination with blood was estimated at 4.2 per cent by haemoglobin assay. In 120 women with regular menstrual cycles, the volume of peritoneal fluid increased progressively during the follicular phase, was highest during the early luteal phase (20.0±6.3 ml) and declined thereafter. In 89 women with moderate and mild endometriosis the amounts of peritoneal fluid were similar, but 9 women with severe endometriosis had lower (P<0.05) volumes during the luteal phase. Women with inactive ovaries had uniformly low amounts of peritoneal fluid: 4.2±2.3 ml in 31 women taking combined oral contraceptive pills; 4.7±5.8 ml in 17 women taking 5 mg of lynoestrenol daily and 1.2±1.9 ml in 20 postmenopausal women with an inactive endometrium. In contrast, two postmenopausal women with proliferative endometrium had 7 and 10 ml of peritoneal fluid. Women with active ovaries, 5 with absent or distally occluded Fallopian tubes and 7 without a uterus had normal amounts of peritoneal fluid. The volume of peritoneal fluid was not affected by pelvic varicose veins, a visible corpus luteum or an ovulation stigma. Peritoneal fluid appears to be predominantly an ovarian exudate, neither an exudate from the pelvic peritoneum nor a tubal secretion.

Bowel resection for deep endometriosis: a systematic review

Please cite this paper as: De Cicco C, Corona R, Schonman R, Mailova K, Ussia A, Koninckx P. Bowel resection for deep endometriosis: a systematic review. BJOG 2011;118:285–291.

Diagnosis of deep endometriosis by clinical examination during menstruation and plasma CA-125 concentration * †

OBJECTIVES To evaluate a clinical examination during menstruation and plasma CA-125 concentrations to diagnose deep endometriosis. DESIGN Prospective study in 61 women scheduled for a laparoscopy, a retrospective study in 140 women with deep endometriosis, and a clinical validation study in 16 women with painful pelvic nodularities during menstruation. SETTING University Hospital Gasthuisberg, a tertiary referral center. RESULTS In the retrospective study, deep endometriosis was detected by routine clinical examination in only 36% of women. Lesions infiltrating deeper than 15 mm were detected in 50%. In the prospective study pelvic nodularities were detected by routine clinical examination in 4 women but were detected in 22 by clinical examination during menstruation. The latter was highly reliable to diagnose deep endometriosis, cystic ovarian endometriosis, and cul-de-sac obliteration. CA-125 concentrations were higher during menstruation and correlated with deep endometriosis and with deep and cystic ovarian endometriosis. Nodularities at clinical examination or follicular phase CA-125 concentrations > 35 U/mL are useful to decide that a bowel preparation should be given, achieving a sensitivity of 87% and a specificity of 83%. In the clinical validation study, deep endometriosis was found in 14 of 16 women. CONCLUSION Clinical examination during menstruation can diagnose reliably deep endometriosis, cystic ovarian endometriosis, or cul-de-sac adhesions. This test, preferentially combined with a follicular phase CA-125 assay, should be used to decide whether a preparation for bowel surgery should be given.

Intrapelvic injection of menstrual endometrium causes endometriosis in baboons (Papio cynocephalus and Papio anubis)

OBJECTIVE The Sampson hypothesis of retrograde menstruation as a cause of endometriosis was tested by determining the effect of intrapelvic injection of menstrual versus luteal endometrium on the incidence, peritoneal involvement, and stage of endometriosis. STUDY DESIGN Seventeen baboons were injected retroperitoneally with luteal (n = 6) or menstrual (n = 7) endometrium and intraperitoneally with menstrual endometrium (n = 4). Laparoscopies were performed after 2 months in all animals and after 5 and 12 months in six and five primates injected with luteal and menstrual endometrium, respectively. RESULTS The peritoneal endometriosis surface area, number of implants, and incidence of typical and red subtle lesions were significantly higher after retroperitoneal injection of menstrual than of luteal endometrium. By use of menstrual endometrium intraperitoneal seeding was more successful in causing endometriosis than was retroperitoneal injection. No significant changes in number or surface area of endometriotic lesions induced with retroperitoneal injection of luteal endometrium after 5 months were observed in the six baboons. At repeat laparoscopy 12 months after intrapelvic injection of menstrual endometrium progression was recorded in three of four regularly cycling animals, whereas regression was evident in one baboon that had become amenorrheic after induction. CONCLUSION Intrapelvic injection of menstrual endometrium can cause peritoneal endometriosis and offers experimental evidence supporting the Sampson hypothesis.

Peritoneal mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation in a laparoscopic mouse model

OBJECTIVE To develop a laparoscopic mouse model to evaluate the hypothesis that mesothelial hypoxia during pneumoperitoneum is a cofactor in adhesion formation. DESIGN Prospective randomized trials. SETTING Academic research center. ANIMAL(S) One hundred thirty female Naval Medical Research Institute (NMRI) mice. INTERVENTION(S) Adhesions were induced by opposing monopolar lesions in uterine horns and pelvic side walls during laparoscopy and evaluated after 7 or 28 days under microscopic vision during laparotomy. The following pneumoperitoneum variables were assessed: duration (10 or 60 minutes), insufflation pressure (5 or 15 cm of water), insufflation gas (CO(2) or helium), and addition of oxygen (0-12%). MAIN OUTCOME MEASURE(S) Adhesions were scored quantitatively and qualitatively for extent, type, and tenacity. RESULT(S) Scoring of adhesions 7 or 28 days after laparoscopic surgery was comparable. Adhesions increased with duration of pneumoperitoneum and with insufflation pressure and decreased with the addition of oxygen. Half-maximal reduction of adhesions was obtained at 1.5% oxygen, whereas a maximal reduction required only 2%-3%. The effect of CO(2) and helium was similar. CONCLUSION(S) These data demonstrate the feasibility of the intubated laparoscopic mouse model and confirm previous observations in rabbits, indicating that mesothelial hypoxia plays a key role in adhesion formation.

DIAGNOSIS OF THE LUTEINIZED UNRUPTURED FOLLICLE SYNDROME BY STEROID HORMONE ASSAYS ON PERITONEAL FLUID

The luteinized unruptured follicle syndrome is a frequent phenomenon, occurring in half of our women with regular cycles and infertility. Progesterone concentrations and 17p‐oestradiol concentrations were assayed in peritoneal fluid of women during the luteal phase. Up to day 20 of the cycle, the concentrations were significantly higher in women with an ovulation stigma than in women without an ovulation stigma on their corpus luteum. The range of concentrations was sufficiently different in the early luteal phase to be used diagnostically, the only limitation being the presence of a cystic corpus luteum. We suggest that the assay of progesterone and 17β‐oestradiol in peritoneal fluid should be done in all women with infertility and biphasic basal body temperature charts in order to diagnose the luteinized unruptured follicle syndrome.