Human Reproduction, Vol. 16, No. 12, 2676-2679,
December 2001
© 2001 European Society of Human Reproduction and Embryology
Endometriosis: absence of recurrence in patients after endometrial ablation
1 Department of Obstetrics, Gynaecology and Physiopathology of Reproduction, Rimini's General Hospital `Infermi', 2 First Institute of Obstetrics and Gynaecology, University of Bologna, 3 Department of Obstetrics and Gynaecology, University of Bari, Bari, Italy and 4 Nyon Medical Centre, Nyon, Switzerland
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Abstract |
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BACKGROUND: The present study was undertaken to evaluate differences between patients with and without eutopic endometrium in the recurrence of ectopic endometriotic implants. METHODS: Endometrial ablation (EA) was carried out in 14 women out of 28 laparoscopically treated for endometriosis and recurrence of the disease was evaluated 24 months later. Data were compared using paired Student's t-test and
2 test. RESULTS: Patients undergoing EA procedures did not exhibit recurrence of endometriosis while nine patients without that procedure had recurrence of the disease (P < 0.001). The endometrial cells found in the debris of the cul de sac of eight patients who did not undergo EA were both stromal and epithelial cells. No blood or blood cells were found in the cul de sac of patients undergoing EA. CONCLUSIONS: The present study supports a role of eutopic endometrium in the recurrence of endometriosis through tubal dissemination of endometrial debris and implantation of endometrial cells into the abdomen.
Key words: dysmenorrhoea/endometrial ablation/endometriosis/infertility/uterine contractility
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Introduction |
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Endometriosis is a very common debilitating disease occurring in 1–50% of premenopausal women (Weeler, 1989
) with a prevalence of 38.5% in infertile women and 5.2% in fertile women (Verkauf, 1987). Patients with endometriosis seek medical care because of pelvic pain, dysmenorrhoea and dyspareunia (Rock and Markham, 1992). The goals of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Controlled trials on the use of medical (Reichel and Schweppe, 1992; Rock et al., 1993) and surgical (Adamson et al., 1993) treatments reported both a reduction/complete resolution of ectopic endometrial deposits and an improvement in the subjective symptoms associated with endometriosis. Yet despite these improvements, the disease still awaits optimal therapy (Bulletti et al., 1996a) as high recurrence rates are still reported (Puleo and Hammond, 1983). Patterns of uterine contractility were extensively studied in the non-pregnant uterus with special attention to the effects of contractility in infertility and endometriosis (Leyendecker et al., 1996) and to the effects of steroids (Kunz et al., 1988) and other substances active in the pharmacological control of contractions (Makarainen and Ylikorkala, 1982) and dysmenorrhoea (Makarainen and Ylikorkala, 1983).
Theories on the pathogenesis of endometriosis include the abdominal dissemination of endometrium due to abnormal uterine contractility (Sampson, 1922; Sampson and Albany, 1927) and enhanced uterine contractility (Halme et al., 1984; Sanfilippo et al., 1986; Salamanca and Beltran, 1995; Bulletti et al., 1996a,1996b). More recently enhanced uterine contractility was established in close relationships with the finding of viable endometrial cells in the cul de sac and with the presence of endometriotic implants (Bulletti et al., 2000).
Endometrial ablation (Cooper and Erickson, 2000; Sowter et al., 2000) is a well known surgical procedure that aims at removing the eutopic endometrium (basalis and functionalis) thus avoiding further menstrual bleedings. The present study was undertaken to evaluate differences in recurrence of ectopic endometriotic implants between patients treated for endometriosis and left with or without eutopic endometrium.
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Materials and methods |
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Patients and design
Twenty-eight women (mean age ± SD: 30.4 ± 4.6 years; range 24–40) with at least one child, who underwent laparoscopy for uncontrollable dysmenorrhoea, with diagnosis of endometriosis stage II to IV (American Fertility Society, 1985
) and retrograde bleeding, were enrolled in the present study after their informed consent was obtained. The study was approved by our internal review board (IRB). Fourteen patients underwent laparoscopy with endometriosis treatment and endometrial ablation (EA) with roller ball at 50 watt to avoid recurrence of abdominal dissemination of endometrial debris and possible recurrence of endometriosis (group 1) (mean age ± SD: 31.6 ± 3.7 years) (mean length of cycles ± SD: 29 ± 2 days). Fourteen other patients (group 2) (mean age ± SD: 29.3 ± 5.3 years) (mean length of cycles ± SD: 28 ± 2 days) underwent laparoscopy and treatment of endometriosis only. Twenty-four months later all patients underwent a second laparoscopy to establish possible recurrences of ectopic implants and to treat them. Laparoscopies were performed on day 3–5 of the menstrual cycle as detected by bleeding and/or basal temperature. Dysmenorrhoea and endometriosis symptoms were evaluated before and 3 months after the first laparoscopy, and before the second laparoscopy, using a self-modified non-continuous five point verbal score (Vercellini et al., 1996).
Laparoscopic treatment
Endometriotic implants were treated during laparoscopies by using surgical equipment including bipolar instruments (Storz, Germany) or by excision of the implants themselves. Endometrial ablation was performed by hysteroscopy (Cooper and Erickson, 2000; Sowter et al., 2000). Endometrial implants were carefully identified, as well as evidence of retrograde bleeding at the time of the first and second laparoscopies in all patients studied. Diagnosis of endometriosis and its recurrence were correlated with clinical evidence of dysmenorrhoea. Blood in the cul de sac was collected after washing with 50–100 ml of saline and endometrial cells were isolated, fixed in 10% buffered formalin, paraffin-embedded and analysed as previously reported (Hedley et al., 1985; Bulletti et al., 1994). Endometriotic implants were considered as recurrence when they were found in at least three active foci.
Analysis
Data were compared using paired Student's t-test and 2 test as for dysmenorrhoea scores, the presence or absence of retrograde bleeding, endometrial cell contents and endometriotic implants.
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Results |
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Nine of the 14 patients who underwent laparoscopy and endometrial ablation (Figure 1
) reported a disappearance and three a significant reduction of the dysmenorrhoea after 3 months (median scores 4 versus 1, P < 0.0001), while only three of the other group (group 2) had significant amelioration of their symptoms (median scores 4 versus 3, P = NS) (Table I). Dysmenorrhoea symptoms increased up to 24 months but not so significantly as compared with presurgical evaluation (medians group 1: 3 versus 4, P = NS; group 2: 4 versus 4, P = NS). At the second laparoscopy no retrograde bleeding was found in patients who had EA, while nine of 14 patients who did not have EA exhibited retrograde bleeding at the time of the second laparoscopy (P < 0.001). Patients who underwent EA procedures did not exhibit recurrences of endometriosis at the second laparoscopy, while nine patients who did not have EA exhibited significant recurrences of the disease (P < 0.001) (Table I). Endometrial cells were found in the debris of the cul de sac of eight patients who did not undergo EA and both stromal and epithelial cells were found. Blood and cells were found in the cul-de-sac in two patients without dysmenorrhoea. No blood or cells were found in the cul de sac of patients who underwent EA.
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Discussion |
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Endometriosis is a debilitating condition characterized by high recurrence rates after surgery (Puleo et al., 1983) and uncertain aetiology and pathogenesis. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants and prevention of new foci of ectopic endometrial tissue.
Today medical treatments focus on reducing the production and/or effects of oestrogens which are well known promoters of the growth and maintenance of the eutopic and ectopic endometrium. Instead, if we take into account the prevailing theories on the pathogenesis of endometriosis, treatments should rather administer molecules that block the migration of endometrial cells throughout the tubes as well as their development as endometriotic foci in the abdomen. Unfortunately, optimal therapy for this disease still awaits the identification of these ideal molecules.
The present study was conceived in accordance with the theory of retrograde menstruation originally proposed by Sampson (Sampson and Albany, 1927). This author proposed that endometriosis develops as a consequence of abdominal dissemination of endometrium at the time of menses (retrograde bleeding/menstruation).
The study was thus conceived to inhibit retrograde menstruation and transtubal migration of viable endometrial cells, shed by the process of menses, that can successfully attach and implant in the pelvic cavity and cause endometriosis.
In the uterus, contractility controls the process of endometrial shedding at the time of menstruation, as well as the transport of gametes, implantation and the maintenance of the developing pregnancy (Kunz et al., 1996; Bulletti et al., 1998) through normal (Bulletti et al., 2000) or abnormal (Ijland et al., 1997, 1998) patterns of myometrial activity.
Abnormal patterns of uterine contractions (UC) are mainly associated with three medical entities: dysmenorrhoea (Dawood, 1990), endometriosis (Ishimaru and Masuzaki, 1991; Salamanca and Beltran, 1995) and infertility (Ijland et al., 1997; Fanchin et al., 1998). The abnormal contractility of this organ has long been suspected to cause pelvic pain including dysmenorrhoea, as well as preterm labour (Kelly, 1962; Bulletti and Flamigni, 1994b; Bulletti et al., 1997).
Endometriosis and presence of endometrial cells in the abdomen was recently related to specific pattern of uterine contractility (Bulletti et al., 2000). An increase in retrograde peristaltic-like contractions during menses may have an important `pumping-like effect' and transport and disseminate endometrial debris into the abdomen (Bulletti et al., 2000). The increased uterine contractility is a general term which includes specific patterns such as: (i) higher intraluminal pressure and (ii) higher peristaltic waves, these last with cervical to fundus and fundus to cervical displacement of the uterine contents. Retrograde bleeding may provide blood and endometrial debris including stromal and epithelial cells, which under the influence of UC arrive in the peritoneum. The peritoneal receptivity for their implantation and the subsequent biological response to hormones resulting in the classical endometriotic response of this tissue is still poorly understood. The different environments of peritoneal and uterine intraluminal cavities may trigger different responses in ectopic and eutopic endometrium as well as in individual active and inactive foci during menstrual cycles. However, there is evidence of a close association between UC and dysmenorrhoea (Halme et al., 1984), between UC and retrograde bleeding (Bulletti et al., 1996b, 1997) and between retrograde bleeding and endometriosis (Ishimaru and Masuzaki, 1991). In the absence of a dedicated pharmacology aimed at controlling uterine contractility and tubal efflux of endometrial debris, we attempted to avoid recurrences of endometriosis by physically removing the damaged endometrium in patients who had already had their children and now had unacceptable dysmenorrhoea. Surprisingly, we observed a prompt and significant reduction of dysmenorrhoea in patients who underwent hysteroscopic EA with no other clear explanation than the inhibition of retrograde bleeding and dissemination of endometriotic implants in these patients. This evidence supports the hypothesis on the role of the endometrium with its cyclical function as a source for prostaglandins that may enhance UC and their possible related pain. From this study we cannot exclude the occurrence of adenomyosis reported by McCausland (McCausland and McCausland, 1998) as a consequence of EA but the recurrence of symptoms after 24 months in some patients without evidence of endometriosis may indirectly support these data.
Evidence of high recurrence rates of endometriosis within 24 months in patients who did not undergo EA supports Sampson's theory (Sampson and Albany, 1927) at least for the recurrence of this disease. Obviously, this procedure cannot be proposed to all women who have aggressive endometriosis but may be reserved for those who have completed their child plan and suffer from severe endometriosis and unacceptable dysmenorrhoea.
We here reported the high frequency of the presence of endometrial cell aggregates in the cul de sac of patients with endometriosis, when laparoscopy is performed during menses. It is difficult to establish why only a few but not all women with retrograde bleeding have endometriotic implantation, but a possible permissive role of the peritoneal environment in determining the attachment of viable endometrial cells should be taken into account. Infections, inflammatory reaction to the blood's peritoneal stimulation, may be causes of the loss of peritoneal integrity which in turn leave the surface epithelium disrupted and thus prepared for endometriotic implants.
In conclusion, the present study supports the crucial role of eutopic endometrial removal in the recurrence of endometriosis: the eutopic endometrium may cause, in patients with endometriosis, abnormal UC throughout its cyclical tissue changes and tubal dissemination of endometrial debris with implantation of endometrial cells into abdomen may complete the vicious circle. Tubal ligation may provide for similar effects, but the reduction of dysmenorrhoea obtained immediately after the endometrial procedure in this study may be associated with the ablation of the source of biochemical environment that may contribute to enhance UC and pain, and this last should be evaluated in a study with tubal ligation procedures. The recurrence of endometriosis after medical and surgical therapies is possibly due to treatments, mostly directed to delete endometriotic implants and to reduce/antagonize its promoters rather then to stop the retrograde uterine contractility during menses, that may be the primary cause of its recurrence throughout ectopic endometrial dissemination.
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Notes |
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5 To whom correspondence should be addressed at: Rimini's General Hospital and University of Bologna, Centre for Special Pelvic Surgery, Operative Laparoscopy and Hysteroscopy of the University of Bologna, Via Settembrini 2, 47900 Rimini, Italy. E-mail: bull{at}infotel.it
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Submitted on May 22, 2001; accepted on September 4, 2001.
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