- Email: [email protected]
Resectoscopic treatment of atypical endometrial polyps in fertile women
Research
www. AJOG.org
BASIC SCIENCE: GYNECOLOGY
Resectoscopic treatment of atypical endometrial polyps in fertile women Federica Scrimin, MD; Uri Wiesenfeld, MD; Alberto Candiotto, MD; Stefania Inglese, MD; Luca Ronfani, MD; Secondo Guaschino, MD OBJECTIVE: The purpose of this study was to evaluate the long-term efficacy and prognosis of hysteroscopic resection and coagulation of the base of endometrial polyps with focal atypia in fertile women with or without progestin suppression. STUDY DESIGN: We conducted a quasi-randomized trial in which con-
servative treatment was offered to 21 patients who had endometrial polyps with focal atypia and a surrounding normal endometrium. The polyps were analyzed separately from their bases. Random biopsy specimens were taken from 4 standard places of the endometrium. RESULTS: Eighteen women (10 women with an intrauterine device and
8 women with no intrauterine device) completed the follow-up proce-
dure. After 5 years, we found no difference in the 2 groups regarding recurrence of atypical polyps. CONCLUSION: Conservative resectoscopic treatment may be considered in fertile women with atypical polyps if polyp base and surrounding endometrium are benign. If women want to become pregnant at short term, the use of progestins can be delayed, with a strict follow-up procedure. Larger studies should be encouraged.
Key words: atypical endometrial polyp, fertile women, hysteroscopic resection, levonorgestrel IUD
Cite this article as: Scrimin F, Wiesenfeld U, Candiotto A, Inglese S, Ronfani L, Guaschino S. Resectoscopic treatment of atypical endometrial polyps in fertile women. Am J Obstet Gynecol 2008;199:365.e1-365.e3.
T
his study started 1 year after a preliminary study of the conservative treatment of postmenopausal women with high anesthesiologic risk who had endometrial polyps with atypia and no involvement of the base.1 The good initial results and the request of conservative treatments by some women who wanted to become pregnant encouraged us to start this preliminary quasirandomised controlled trial to evaluate the long-term efficacy and prognosis of hys-
From the Department of Obstetrics and Gynecology (Drs Scrimin, Wiesenfeld, Candiotto, Inglese, and Guaschino) and the Epidemiology and Biostatistics Unit, Institute of Child Health, IRCCS Burlo Garofolo, Trieste, Italy (Dr Ronfani). Received Oct. 6, 2007; accepted March 17, 2008 Reprints: Federica Scrimin, MD, Department of Obstetrics and Gynecology, IRCCS “Burlo Garofolo” University of Trieste, Via dell’Istria 65/1-34137 Trieste, Italy. [email protected]. 0002-9378/$34.00 © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.03.041
teroscopic resection and coagulation of the base of endometrial polyps, with focal atypia in fertile women with or without progestin suppression. No experiences are described in the literature. Other authors reported progestin treatment of well-differentiated carcinoma in young women who wanted to preserve fertility.2 There is no evidence of a correlation between the tendency to develop endometrial polyps and the risk of endometrial carcinoma. The risk of malignant degeneration of endometrial polyps is not well-known but seems to range between 0.5% and 6%.3 Savelli et al4 reported 0.8% of malignant degeneration. We decided to study also the possible effect of levonorgestrel- releasing intrauterine device (IUD).
M ATERIALS AND M ETHODS This open-label quasirandomized controlled trial was carried out in Friuli Venezia Giulia, a region of North East Italy, with approximately 1,000,000 people. After a discussion in a regional meeting of our previous study, some obstetrics and gynecologic departments referred
patients to our center. Women were evaluated at the Hysteroscopy Service of the Department of Obstetrics and Gynecology at Trieste University (Italy), between 1999 and 2002. Inclusion criteria were fertile women with atypical polyps without atypia in the base and want to preserve their uterus. The hysteroscopic and histologic criteria for inclusion in the study were proliferative, secretive, dysfunctional endometrium or simple hyperplasia in 4 random biopsy specimens that were taken under tubal orifices, in fundus, and in isthmus. All the hysteroscopic pictures were photographed. Women who were referred by other centers underwent a second hysteroscopy in our Service before entering the study. All histologic diagnoses and evaluations of polyp bases were made by the Service of Pathological Anatomy of the University of Trieste. The histologic examination was carried out according to the criteria suggested by Kurman.5,6 An open- label quasirandomized controlled trial was carried out in the following manner: women who were assigned to odd numbers underwent polyp resec-
OCTOBER 2008 American Journal of Obstetrics & Gynecology
365.e1
Research
Basic Science: Gynecology
www.AJOG.org
TABLE
Characteristics of the women who completed the study Characteristic a
Age (y)
Group Control (n ⴝ 8)
IUD (n ⴝ 10)
40 (29-48)
43 (26-50)
All (n ⴝ 18) 41.5 (26-50)
.............................................................................................................................................................................................................................................. a
Weight (kg)
63.5 (56-81)
63.5 (55-80)
63.5 (55-81)
Height (cm)
167 (160-178)
166 (158-180)
167 (158-180)
.............................................................................................................................................................................................................................................. a .............................................................................................................................................................................................................................................. a
Blood pressure (mm Hg)
.....................................................................................................................................................................................................................................
Maximum
125 (110-150)
120 (110-150)
120 (110-150)
Minimum
70 (60-95)
70 (70-95)
70 (60-95)
..................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................
Parity (n)
.....................................................................................................................................................................................................................................
No previous pregnancy
4 (50%)
3 (30%)
7 (39%)
1 previous pregnancy
2 (25%)
4 (40%)
6 (33%)
ⱖ2 previous pregnancies
2 (25%)
3 (30%)
5 (28%)
In treatment for sterility (n)
1 (13%)
2 (20%)
3 (17%)
..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................
Histologic data (n)
.....................................................................................................................................................................................................................................
Simple adenomatous polyp
5 (62%)
6 (60%)
11 (61%)
Atypical glandular polyp
3 (38%)
4 (40%)
7 (39%)
..................................................................................................................................................................................................................................... .............................................................................................................................................................................................................................................. a
Data are given as median (range).
Scrimin. Resectoscopic treatment of atypical endometrial polyps in fertile women. Am J Obstet Gynecol 2008.
tion and endometrial surveillance with insertion of levonorgestrel intrauterine system (IUD group); women who were assigned to even numbers underwent polyp resection and endometrial surveillance without insertion of levonorgestrel intrauterine system (control [no IUD] group). Resections were carried out under mild sedation in the operating room with resectoscopes or office hysteroscopes with diameter of 3.2 mm. Bipolar electrodes and an electric intensity of 170 W for vaporization and 80 W for coagulation with resectoscopes, or with electrode twizzle in office, were used. Levonorgestrel intrauterine system was inserted after polyp resection. The main outcome of the study was the evaluation of the long-term efficacy and prognosis of hysteroscopic resection of polyps with focal atypia in fertile women. The second end point was to evaluate the recurrence rate of polyps in the 2 groups. The follow-up period was 5 years after inclusion in the study. We did an outpatient hysteroscopic assessment with endometrial sampling every 6 months in the first 2 years and every years subsequently. 365.e2
The study was approved by the hospital’s Ethics Committee. The patients gave their consent to the study at which time they were informed that the guidelines of main scientific societies recommend hysterectomy for their pathologic condition.7,8 Furthermore, the women were informed regarding the importance of regular hysteroscopic follow-up examinations because only direct observation of the uterine cavity could ensure their health.
Statistical methods Categoric data are presented as numbers and percentages; continuous variables are presented as median and ranges. Differences between categoric variables were evaluated with the chi-square test. Differences between continuous variables were evaluated with a nonparametric test for independent data (Mann-Whitney U test), assuming a nonnormal distribution of data. Statistical analysis was carried out with SPSS statistical software (version 11.0; SPSS Inc, Chicago, IL).
R ESULTS There were 21 women who were assigned randomly in the study. Eleven of
American Journal of Obstetrics & Gynecology OCTOBER 2008
the women were recruited in our service, and 10 of the women were sent us from other hospitals. We performed 18 resections with resectoscopes and 3 with office hysteroscopes. The diagnoses were 13 adenomatous polyps (complex hyperplasia) with focal atypia, 8 glandulocystic polyps with foci of atypia. Polyp sizes varied between 0.3 and 3 cm of maximum diameter. Eighteen patients completed 5 years of follow-up evaluation. Three patients withdrew: 2 from the control group because of pregnancy, 1 from the IUD group because the woman requested its removal because she wanted to get pregnant. The patients were white, with a mean age of 41.5 years (range, 26-50 years). The Table shows the baseline characteristics of the 18 women who completed the study. There was no significant difference between women in the 2 groups. At the end of the trial, there were no recurrences of atypical polyps in the 2 groups. However, in the control group, there were 3 recurrences (38%) of glandular cystic polyps vs no recurrence in the IUD group (P ⫽ .07). In all 3 cases, the histologic finding of polyp was benign. During the follow-up period, 8 patients in the IUD group gained weight (80%) vs 2 patients (25%) in the control group (P ⫽ .05). The mean weight gain was 3 kg (range, 2-6) in IUD group vs 1 kg in the control group (P ⫽ .03). Blood pressure increased in only 1 woman in IUD group (10%) vs no increase in control group (P ⫽ 1). This was a woman with hypertension before treatment was started. The 3 women who withdrew were followed for 2 years. At inclusion, there was no significant difference with the 18 patients who completed the trial regarding polyp histologic findings (2 cases of simple adenomatous and 1 case glandular with atypia), mean age (36 years; range, 32-38 years), weight (63 kg; range, 60-70 kg), height (168 cm; range, 164-170 cm), blood pressure (minimal, 70 mm Hg [range, 70-90 mm Hg]; maximal, 120 mm Hg [range, 120-140 mm Hg]), and parity. One patient was nulliparous (33%), and 2 patients were primiparous
www.AJOG.org (67%). Two patients were assigned to the control group, and 1 patient was assigned to the IUD group. Available follow-up data show that there were no recurrences in these 3 women.
C OMMENT Hysteroscopy has changed our approach to the endometrium, which allows us more accurate diagnoses. With this background in a previous study, we studied conservative treatment in 13 postmenopausal patients with high anesthesiologic risk, who had endometrial polyps with atypia. These patients were followed for 5 years with encouraging results.1 Therefore, 1 year after starting the previous study, we decided to treat conservatively some patients (3 of whom were physicians) who requested that option. The risk of malignant degeneration or appearance of atypias in endometrial polyps is not well-known but seems low (0.5%-6%) according to previous studies.3,4 In our study, all polyps that were seen in follow-up examinations immediately were removed resectoscopically. Therefore, we were not able to evaluate the risk of appearance of atypias; on the other hand, the removal was essential for histologic examination. Finding an atypical polyp in a premenopausal woman usually is indicative of a predisposition to endometrial cancer and an anovulatory state. Our sample was too small, however, to have 2 treatment groups for ovulatory and anovulatory conditions and to draw significant conclusions. It was interesting to observe that no woman in the treatment group experienced polyps. This finding is in agreement with Gardner et al9 who followed women who were treated with tamoxifen. This study compared women who were assigned to endometrial surveillance or to surveillance with insertion of the levonorgestrel device and showed a
Basic Science: Gynecology significant difference (P ⫽ .05) in polyp development, which supports the role of the levonorgestrel device in the prevention of endometrial polyps. This observation is confirmed in other studies on fertile and postmenopausal women who received hormone replacement therapy.10-12 Some studies, although with a limited number of cases, suggest that treatment with progestins of atypical hyperplasia and well-differentiated carcinoma of the endometrium appears to be a safe alternative to hysterectomy in women ⬍40 years old.2 Our study regarded a selected population from histologic and hysteroscopic points of view and differs from the studies that were made with a curettage background. To date, the diagnosis of endometrial disease by curettage has led gynecologists to consider the diagnoses of diffuse atypical hyperplasia and atypical adenomatous polyp as being the same disease that, according to available guidelines, has to be treated by hysterectomy.12 Hysteroscopy changed our approach and allowed us to perform follow-up evaluations in a very safe way of the eventual evolution of polyp disease and to treat it with an easy conservative procedure: resectoscopic polypectomy. This may be very useful in young women who have not had children yet. By sending the polyp and its base in separate vases to the histologist, there was a more accurate grading of the disease. If the polyp base does not show atypias, according to surgical approach with other organs, the uterus can be conserved. This was a small study and was limited, but this trial wanted to evaluate the need of starting a big multicentric study regarding conservative treatments of atypical endometrial lesions; our conclusion was that it is necessary. The open question is how long should the follow-up period be to allow conclusions about the outcome. Familiarity, anovulatory state,
Research
and body mass index are risk factors that will be evaluated necessarily in a larger f study before drawing conclusions. REFERENCES 1. Scrimin F, Mangino F, Wiesenfeld U, Candiotto A, Guaschino S. Is resectoscopic treatment of atypical endometrial polyps a safe option? Am J Obstet Gynecol 2006;195: 1328-30. 2. Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997;90:434-40. 3. Scott RB. The elusive endometrial polyp. Obstet Gynecol 1953;1:212-8. 4. Savelli L, De Iaco P, Santini D, et al. Histopathologic features of and risk factors for benignity, hyperplasia and cancer in endometrial polyps. Am J Obstet Gynecol 2003;188: 927-31. 5. Kurman RJ, Kaminski PF, Norris HG. The behavior of endometrial hyperplasia: a long-term study of “untreated” hyperplasia in 170 patients. Cancer 1985;56:403-12. 6. Kurman RJ, Norris HG. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer 1982:49:2547-59. 7. Broder MS, Kanouse DE, Mittman BS, Bernstein SJ. The appropriateness of recommendations for hysterectomy. Obstet Gynecol 2000;95:199-205. 8. Lefebvre G, Allaire C, Jeffrey J, et al. SOGC clinical guidelines: hysterectomy. J Obstet Gynaecol Can 2002;24:37-61. 9. Gardner FJE, Konje JC, Abrams KR, et al. Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel- releasing intrauterine system: a randomised controlled trial. Lancet 2000;356:1711-7. 10. Luukkainen T, Toivonen J. Levonorgestrelreleasing IUD as a method of contraception with therapeutic properties. Contraception 1995;52: 269-76. 11. Andersson K, Mattsson LA, Rybo G, Stradberg E. Intrauterine release of levonorgestrel: a new way of adding progesterone in hormone replacement therapy. Obstet Gynecol 1992;79: 963-7. 12. Bernstein SJ, Fiske ME, McGlynn EA, Glifford DS, Southern California Health Policy Research Consortium. Hysterectomy: a review of the literature on indications, effectiveness and risks. Santa Monica (CA); Rand Corp; 1997: MR-592/2.
OCTOBER 2008 American Journal of Obstetrics & Gynecology
365.e3
www. AJOG.org
BASIC SCIENCE: GYNECOLOGY
Resectoscopic treatment of atypical endometrial polyps in fertile women Federica Scrimin, MD; Uri Wiesenfeld, MD; Alberto Candiotto, MD; Stefania Inglese, MD; Luca Ronfani, MD; Secondo Guaschino, MD OBJECTIVE: The purpose of this study was to evaluate the long-term efficacy and prognosis of hysteroscopic resection and coagulation of the base of endometrial polyps with focal atypia in fertile women with or without progestin suppression. STUDY DESIGN: We conducted a quasi-randomized trial in which con-
servative treatment was offered to 21 patients who had endometrial polyps with focal atypia and a surrounding normal endometrium. The polyps were analyzed separately from their bases. Random biopsy specimens were taken from 4 standard places of the endometrium. RESULTS: Eighteen women (10 women with an intrauterine device and
8 women with no intrauterine device) completed the follow-up proce-
dure. After 5 years, we found no difference in the 2 groups regarding recurrence of atypical polyps. CONCLUSION: Conservative resectoscopic treatment may be considered in fertile women with atypical polyps if polyp base and surrounding endometrium are benign. If women want to become pregnant at short term, the use of progestins can be delayed, with a strict follow-up procedure. Larger studies should be encouraged.
Key words: atypical endometrial polyp, fertile women, hysteroscopic resection, levonorgestrel IUD
Cite this article as: Scrimin F, Wiesenfeld U, Candiotto A, Inglese S, Ronfani L, Guaschino S. Resectoscopic treatment of atypical endometrial polyps in fertile women. Am J Obstet Gynecol 2008;199:365.e1-365.e3.
T
his study started 1 year after a preliminary study of the conservative treatment of postmenopausal women with high anesthesiologic risk who had endometrial polyps with atypia and no involvement of the base.1 The good initial results and the request of conservative treatments by some women who wanted to become pregnant encouraged us to start this preliminary quasirandomised controlled trial to evaluate the long-term efficacy and prognosis of hys-
From the Department of Obstetrics and Gynecology (Drs Scrimin, Wiesenfeld, Candiotto, Inglese, and Guaschino) and the Epidemiology and Biostatistics Unit, Institute of Child Health, IRCCS Burlo Garofolo, Trieste, Italy (Dr Ronfani). Received Oct. 6, 2007; accepted March 17, 2008 Reprints: Federica Scrimin, MD, Department of Obstetrics and Gynecology, IRCCS “Burlo Garofolo” University of Trieste, Via dell’Istria 65/1-34137 Trieste, Italy. [email protected]. 0002-9378/$34.00 © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.03.041
teroscopic resection and coagulation of the base of endometrial polyps, with focal atypia in fertile women with or without progestin suppression. No experiences are described in the literature. Other authors reported progestin treatment of well-differentiated carcinoma in young women who wanted to preserve fertility.2 There is no evidence of a correlation between the tendency to develop endometrial polyps and the risk of endometrial carcinoma. The risk of malignant degeneration of endometrial polyps is not well-known but seems to range between 0.5% and 6%.3 Savelli et al4 reported 0.8% of malignant degeneration. We decided to study also the possible effect of levonorgestrel- releasing intrauterine device (IUD).
M ATERIALS AND M ETHODS This open-label quasirandomized controlled trial was carried out in Friuli Venezia Giulia, a region of North East Italy, with approximately 1,000,000 people. After a discussion in a regional meeting of our previous study, some obstetrics and gynecologic departments referred
patients to our center. Women were evaluated at the Hysteroscopy Service of the Department of Obstetrics and Gynecology at Trieste University (Italy), between 1999 and 2002. Inclusion criteria were fertile women with atypical polyps without atypia in the base and want to preserve their uterus. The hysteroscopic and histologic criteria for inclusion in the study were proliferative, secretive, dysfunctional endometrium or simple hyperplasia in 4 random biopsy specimens that were taken under tubal orifices, in fundus, and in isthmus. All the hysteroscopic pictures were photographed. Women who were referred by other centers underwent a second hysteroscopy in our Service before entering the study. All histologic diagnoses and evaluations of polyp bases were made by the Service of Pathological Anatomy of the University of Trieste. The histologic examination was carried out according to the criteria suggested by Kurman.5,6 An open- label quasirandomized controlled trial was carried out in the following manner: women who were assigned to odd numbers underwent polyp resec-
OCTOBER 2008 American Journal of Obstetrics & Gynecology
365.e1
Research
Basic Science: Gynecology
www.AJOG.org
TABLE
Characteristics of the women who completed the study Characteristic a
Age (y)
Group Control (n ⴝ 8)
IUD (n ⴝ 10)
40 (29-48)
43 (26-50)
All (n ⴝ 18) 41.5 (26-50)
.............................................................................................................................................................................................................................................. a
Weight (kg)
63.5 (56-81)
63.5 (55-80)
63.5 (55-81)
Height (cm)
167 (160-178)
166 (158-180)
167 (158-180)
.............................................................................................................................................................................................................................................. a .............................................................................................................................................................................................................................................. a
Blood pressure (mm Hg)
.....................................................................................................................................................................................................................................
Maximum
125 (110-150)
120 (110-150)
120 (110-150)
Minimum
70 (60-95)
70 (70-95)
70 (60-95)
..................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................
Parity (n)
.....................................................................................................................................................................................................................................
No previous pregnancy
4 (50%)
3 (30%)
7 (39%)
1 previous pregnancy
2 (25%)
4 (40%)
6 (33%)
ⱖ2 previous pregnancies
2 (25%)
3 (30%)
5 (28%)
In treatment for sterility (n)
1 (13%)
2 (20%)
3 (17%)
..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................
Histologic data (n)
.....................................................................................................................................................................................................................................
Simple adenomatous polyp
5 (62%)
6 (60%)
11 (61%)
Atypical glandular polyp
3 (38%)
4 (40%)
7 (39%)
..................................................................................................................................................................................................................................... .............................................................................................................................................................................................................................................. a
Data are given as median (range).
Scrimin. Resectoscopic treatment of atypical endometrial polyps in fertile women. Am J Obstet Gynecol 2008.
tion and endometrial surveillance with insertion of levonorgestrel intrauterine system (IUD group); women who were assigned to even numbers underwent polyp resection and endometrial surveillance without insertion of levonorgestrel intrauterine system (control [no IUD] group). Resections were carried out under mild sedation in the operating room with resectoscopes or office hysteroscopes with diameter of 3.2 mm. Bipolar electrodes and an electric intensity of 170 W for vaporization and 80 W for coagulation with resectoscopes, or with electrode twizzle in office, were used. Levonorgestrel intrauterine system was inserted after polyp resection. The main outcome of the study was the evaluation of the long-term efficacy and prognosis of hysteroscopic resection of polyps with focal atypia in fertile women. The second end point was to evaluate the recurrence rate of polyps in the 2 groups. The follow-up period was 5 years after inclusion in the study. We did an outpatient hysteroscopic assessment with endometrial sampling every 6 months in the first 2 years and every years subsequently. 365.e2
The study was approved by the hospital’s Ethics Committee. The patients gave their consent to the study at which time they were informed that the guidelines of main scientific societies recommend hysterectomy for their pathologic condition.7,8 Furthermore, the women were informed regarding the importance of regular hysteroscopic follow-up examinations because only direct observation of the uterine cavity could ensure their health.
Statistical methods Categoric data are presented as numbers and percentages; continuous variables are presented as median and ranges. Differences between categoric variables were evaluated with the chi-square test. Differences between continuous variables were evaluated with a nonparametric test for independent data (Mann-Whitney U test), assuming a nonnormal distribution of data. Statistical analysis was carried out with SPSS statistical software (version 11.0; SPSS Inc, Chicago, IL).
R ESULTS There were 21 women who were assigned randomly in the study. Eleven of
American Journal of Obstetrics & Gynecology OCTOBER 2008
the women were recruited in our service, and 10 of the women were sent us from other hospitals. We performed 18 resections with resectoscopes and 3 with office hysteroscopes. The diagnoses were 13 adenomatous polyps (complex hyperplasia) with focal atypia, 8 glandulocystic polyps with foci of atypia. Polyp sizes varied between 0.3 and 3 cm of maximum diameter. Eighteen patients completed 5 years of follow-up evaluation. Three patients withdrew: 2 from the control group because of pregnancy, 1 from the IUD group because the woman requested its removal because she wanted to get pregnant. The patients were white, with a mean age of 41.5 years (range, 26-50 years). The Table shows the baseline characteristics of the 18 women who completed the study. There was no significant difference between women in the 2 groups. At the end of the trial, there were no recurrences of atypical polyps in the 2 groups. However, in the control group, there were 3 recurrences (38%) of glandular cystic polyps vs no recurrence in the IUD group (P ⫽ .07). In all 3 cases, the histologic finding of polyp was benign. During the follow-up period, 8 patients in the IUD group gained weight (80%) vs 2 patients (25%) in the control group (P ⫽ .05). The mean weight gain was 3 kg (range, 2-6) in IUD group vs 1 kg in the control group (P ⫽ .03). Blood pressure increased in only 1 woman in IUD group (10%) vs no increase in control group (P ⫽ 1). This was a woman with hypertension before treatment was started. The 3 women who withdrew were followed for 2 years. At inclusion, there was no significant difference with the 18 patients who completed the trial regarding polyp histologic findings (2 cases of simple adenomatous and 1 case glandular with atypia), mean age (36 years; range, 32-38 years), weight (63 kg; range, 60-70 kg), height (168 cm; range, 164-170 cm), blood pressure (minimal, 70 mm Hg [range, 70-90 mm Hg]; maximal, 120 mm Hg [range, 120-140 mm Hg]), and parity. One patient was nulliparous (33%), and 2 patients were primiparous
www.AJOG.org (67%). Two patients were assigned to the control group, and 1 patient was assigned to the IUD group. Available follow-up data show that there were no recurrences in these 3 women.
C OMMENT Hysteroscopy has changed our approach to the endometrium, which allows us more accurate diagnoses. With this background in a previous study, we studied conservative treatment in 13 postmenopausal patients with high anesthesiologic risk, who had endometrial polyps with atypia. These patients were followed for 5 years with encouraging results.1 Therefore, 1 year after starting the previous study, we decided to treat conservatively some patients (3 of whom were physicians) who requested that option. The risk of malignant degeneration or appearance of atypias in endometrial polyps is not well-known but seems low (0.5%-6%) according to previous studies.3,4 In our study, all polyps that were seen in follow-up examinations immediately were removed resectoscopically. Therefore, we were not able to evaluate the risk of appearance of atypias; on the other hand, the removal was essential for histologic examination. Finding an atypical polyp in a premenopausal woman usually is indicative of a predisposition to endometrial cancer and an anovulatory state. Our sample was too small, however, to have 2 treatment groups for ovulatory and anovulatory conditions and to draw significant conclusions. It was interesting to observe that no woman in the treatment group experienced polyps. This finding is in agreement with Gardner et al9 who followed women who were treated with tamoxifen. This study compared women who were assigned to endometrial surveillance or to surveillance with insertion of the levonorgestrel device and showed a
Basic Science: Gynecology significant difference (P ⫽ .05) in polyp development, which supports the role of the levonorgestrel device in the prevention of endometrial polyps. This observation is confirmed in other studies on fertile and postmenopausal women who received hormone replacement therapy.10-12 Some studies, although with a limited number of cases, suggest that treatment with progestins of atypical hyperplasia and well-differentiated carcinoma of the endometrium appears to be a safe alternative to hysterectomy in women ⬍40 years old.2 Our study regarded a selected population from histologic and hysteroscopic points of view and differs from the studies that were made with a curettage background. To date, the diagnosis of endometrial disease by curettage has led gynecologists to consider the diagnoses of diffuse atypical hyperplasia and atypical adenomatous polyp as being the same disease that, according to available guidelines, has to be treated by hysterectomy.12 Hysteroscopy changed our approach and allowed us to perform follow-up evaluations in a very safe way of the eventual evolution of polyp disease and to treat it with an easy conservative procedure: resectoscopic polypectomy. This may be very useful in young women who have not had children yet. By sending the polyp and its base in separate vases to the histologist, there was a more accurate grading of the disease. If the polyp base does not show atypias, according to surgical approach with other organs, the uterus can be conserved. This was a small study and was limited, but this trial wanted to evaluate the need of starting a big multicentric study regarding conservative treatments of atypical endometrial lesions; our conclusion was that it is necessary. The open question is how long should the follow-up period be to allow conclusions about the outcome. Familiarity, anovulatory state,
Research
and body mass index are risk factors that will be evaluated necessarily in a larger f study before drawing conclusions. REFERENCES 1. Scrimin F, Mangino F, Wiesenfeld U, Candiotto A, Guaschino S. Is resectoscopic treatment of atypical endometrial polyps a safe option? Am J Obstet Gynecol 2006;195: 1328-30. 2. Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997;90:434-40. 3. Scott RB. The elusive endometrial polyp. Obstet Gynecol 1953;1:212-8. 4. Savelli L, De Iaco P, Santini D, et al. Histopathologic features of and risk factors for benignity, hyperplasia and cancer in endometrial polyps. Am J Obstet Gynecol 2003;188: 927-31. 5. Kurman RJ, Kaminski PF, Norris HG. The behavior of endometrial hyperplasia: a long-term study of “untreated” hyperplasia in 170 patients. Cancer 1985;56:403-12. 6. Kurman RJ, Norris HG. Evaluation of criteria for distinguishing atypical endometrial hyperplasia from well-differentiated carcinoma. Cancer 1982:49:2547-59. 7. Broder MS, Kanouse DE, Mittman BS, Bernstein SJ. The appropriateness of recommendations for hysterectomy. Obstet Gynecol 2000;95:199-205. 8. Lefebvre G, Allaire C, Jeffrey J, et al. SOGC clinical guidelines: hysterectomy. J Obstet Gynaecol Can 2002;24:37-61. 9. Gardner FJE, Konje JC, Abrams KR, et al. Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel- releasing intrauterine system: a randomised controlled trial. Lancet 2000;356:1711-7. 10. Luukkainen T, Toivonen J. Levonorgestrelreleasing IUD as a method of contraception with therapeutic properties. Contraception 1995;52: 269-76. 11. Andersson K, Mattsson LA, Rybo G, Stradberg E. Intrauterine release of levonorgestrel: a new way of adding progesterone in hormone replacement therapy. Obstet Gynecol 1992;79: 963-7. 12. Bernstein SJ, Fiske ME, McGlynn EA, Glifford DS, Southern California Health Policy Research Consortium. Hysterectomy: a review of the literature on indications, effectiveness and risks. Santa Monica (CA); Rand Corp; 1997: MR-592/2.
OCTOBER 2008 American Journal of Obstetrics & Gynecology
365.e3