ORIGINAL ARTICLE
Uterine remodelling following conservative myomectomy Ultrasonographic evaluation YORAM
BEYTH,RICHARDJAFFE,AND SHMUEL GOLDBERQER
From the Department of Obstetrics and Gynecology. Sapir Medical Center, Kfar Saba, Israel
Acta Obstet Gynecol Scand 1992; 71: 632-635
Uterine leiomyomata develop during the reproductive years and may interfere with fertility through mechanisms as yet not fully understood. A developing intramural or large submucosal leiomyoma causes hypertrophy of the myometrium. Conservative myomectomy , as opposed to hysterectomy, is the preferred surgical procedure for patients who wish to preserve their fertility. Ten patients were ultrasonographically evaluated at monthly intervals foltowing myomectomy and the changes in uterine (myometrial) volume were assessed. There was a gradual decrease in uterine volume in all patients during the six months following removal of intramural and submucosal leiomyomata. The most remarkable decrease in size occurred during the initial two to three months for the majority of the patients. The impact of this process on fertility should be further evaluated. One of the intriguing questions is whether the period of uterine shrinkage represents the time of the healing process during which conception should be prevented. Key words: fertility; leiomyoma; myomectomy; ultrasound Submitted March 13, 1992 Accepted June 7, 1992
Uterine leiomyomata are the most common tumors of the uterus and pelvis. Their incidence is quoted as 50% at postmortem examinations, however the true incidence during the fertile years is difficult to determine (1). Leiomyomata develop during the reproductive years and are not uncommon before the age of 30 in the black woman. They are frequently associated with gynecological and obstetrical complications and may cause infertility. The mechanisms by which leiomyoma interferes with fertility are not fully understood but it is well established that conservative myomectomy may improve fertility (1). Conservative myomectomy is the surgical procedure of choice (as opposed to hysterectomy) in women who wish to preserve fertility. Following myomectomy of an intramural or submucosal leiomyoma, the distorted uterine cavity often returns to its normal shape (2). The surgical procedure of removing 0 Aria Obsrer Gynecol Scand 71 (1992)
intramural or submucosal leiomyomata usually leaves the patient with a uterus whose size is larger than the normal intact one. Repeated pelvic examinations after surgery reveal a gradual decrease in uterine size, often with a return to its normal size. This study was performed in order to evaluate the changes occurring in the uterine volume during the initial few months following conservative myomectomy.
Materlals and methods Ten women, who underwent conservative myomectomy between April 1989 and February 1990, were included in this study. Large or rapidly growing leiomyomata were indications for surgery. All operations were performed by one surgeon (YB).The
Uterine remodelling after myomectomy
633
Table 1. Clinical and surgical data of the patients Patient no . I 2 3 4 5 6 7 8 9 10
Age (yrs)
Single/ Married
Uterine size (gestational weeks)
No. intramural myomata removed
18 37
S S S
3
0
3 1
0
M
18 9 9 Normal
S S
18 12
M M S S
23 20
35 32
35 36 36 25 28 39
Blood transfusion (units packed cells)
0 0
oa 5 12 2 10
10
0 1 0
3 0 0
1 10
16
“One large pedunculated subserous leiomyoma was removed.
patients’ ages at the time of surgery ranged from 18 to 39 years. All patients, except for one NO.^), were nulligravidae. The uterine size on clinical examination ranged from the equivalent of 9 weeks to 23 weeks of pregnancy. Only one patient had a large pedunculated leiomyoma and her uterus was described as normal in size. The maximal number of tumors removed from one patient was 12. None of the uterine cavities were penetrated during the surgical procedures and only two patients required blood transfusions (Table I). Following the removal of the
leiomyoma, the myometrium was sutured with chromic catgut No. 1 interrupted sutures and the serosa was closed with a running vicryl 4-0 gauge suture. Three Cushing clips were applied after removal of the intramural leiomyoma and prior to repairing the myometrium (to the depth of the incision). An additional three clips were located subserous. These were used in order to enable the hysterosalpingographic evaluation of the scar depth in the myometrium and the total uterine wall thickness at the incision site (3). The only postoperative com-
Table 11. Uterine volume (and percentage of decrease) before surgery and on monthly intervals following myomectomy: ultrasonographic evaluation Patient no.
Volume (cm’) before surgery
Uterine volume at intervals following surgery (cm”).
1 weekh I
690 230
200
3
575
180
4
83
83
377
6
452
183
7
1160
800 1051
8
130 (65) 140 (78) 201 (53) 158 (86) 455 (57) 895 (85)
9
234
154
91 (59)
10
I’
290
2 months
3 months
49 1
2
5
1 month
109
76 (69)
81 (411 125 (62) 82 (99)
4 months
6 months
108 (22) 80 (40)
(15)
12
81 (45)
78 (94)
107 (28)
119 (65) 328 (41) 738 (70)
80 (52) 62 (57)
348
(44)
125 (68) 240 (30) 768 (73) 57 (37) 61
22 1 (27) 769
(73)
(55)
values in parentheses are percents.
’’ uterine volume measured one week following surgery is considered 100%.
0 Acra Obsret Gynecol Scand 71 (1992)
634
2
0
Y . Beyth, R. Jaffe and S. Goldberger Fig. 1 . Post myomectomy reduction in uterine size. evaluated ultrasonically at monthly intervals. * uterine volume as measured at the initial examination, one week following surgery.
100%.
=I
I
' 0
80%.
.-c
P)
'
5
.-aE
8
60%
40%
0
c
7
0
6
20% 1
I
I
I
I
I
I
I
0
4
8
12
16
24
1
Weeks Following Surgery plication was a low grade temperature, which gradually subsided and did not lengthen the duration of postoperative hospitalization nor require antibiotic treatment. Sonographic follow-ups were performed by one author (RJ) during the first postoperative week and at four week intervals for four to six months thereafter. Uterine volume was calculated according to the equation for estimation of an ellipsoid, where volume equals 1/6 II multiplied by length, anterioposterior and transverse diameters (0.523 x length x A-P x transverse).
Results Uterine sizes before operation, during the week following operation and on subsequent sonograms are depicted in Table 11. nVo patients did not have an ultrasonographic (U/S) evaluation prior to surgery by the author. In all but one patient, there was a gradual decrease in uterine volume during the four to six months (Fig. 1). Only one patient NO.^), whose pedunculated subserous fibroid attached to the uterus by a narrow pedicle was removed, had a normal size uterus prior to surgery. It is noteworthy that the most remarkable decrease in uterine size occurred within the first two to three months for most patients. The normal uterine size ranges between W 8 0 cm (3). In six out of ten patients, the uterus reached normal size. Uterine size in two patients reached the volume of 107 and 125 cm3 four months after surgery and in two additional patients (Nos 7 and 8) who had very large leiomyomata, the uterus gradually shrank but remained large and bulky (220 cm3and 769 cm' respectively) six months @ Arra Obsier Gynerol Scand 71 (1992)
following surgery. Prior to surgery, patient No. 8 had a uterus equivalent to 20 weeks gestation. Ten intramural leiomyomata were removed from this patient during surgery, however many very small leiomyomata buds were noticed and left untouched.
Discussion Conservative myomectomy is performed instead of hysterectomy when surgery is indicated, and the patient wants to preserve her fertility potential. Leiomyomata may cause a wide scale of clinical symptoms necessitating surgery. Infertility is but one of these symptoms which may even be caused by an otherwise asymptomatic leiomyoma. The mechanism by which leiomyoma interferes with infertility is not fully understood; anovulatory cycles, interference with sperm transport, impingement of the tumor on the endocervical canal or an interstitial portion of the fallopian tube, interference with prostaglandin induced uterine contractions, endometrial and vascular changes are all just a few of the speculations. Clinically, it is well documented that when leiomyomata are intramural or submucosal and of significant size, they may well be factors causing infertility (4). Conservative myomectomy in such cases may restore fertility (5). A developing intramural or large submucosal myoma causes hypertrophy of the entire uterine wall. Schlaff et al. studied changes in total uterine volume, myoma volume and nonmyoma (myometrium) volume of patients exposed to gonadotropinreleasing hormone analogue following therapy and 24 weeks after cessation of treatment (6). The in'
Uterine remodelling after myomectomy
crease in nonmyoma (myometrial) volume, 24 weeks after completion of treatment, was 168% while the increase in myoma volume was only 27% (6). Pollow et al. found significantly lower conversion of estradiol into estrone in leiomyomata than in myometrium. This difference in conversion rate could result in a relative accumulation of estrogen in a leiomyoma, resulting in hyperestrogenic state within the tumor and surrounding tissues (7). Such hormonal milieu may explain the myometrial hypertrophy so that after removal of the myoma and reconstruction of the uterus the myometrium, at the site of the operation, remains thicker compared with the remaining intact myometrium. It has been shown, by hysterographic studies, that the distended and deformed uterine cavity returns to normal shape following conservative myomectomy of submucosal or intramural leiomyoma (2). At the sonographic screening a week post surgery, we found a very thick uterine wall, especially at the site close to the myomectomy. The myometrium at this site was occasionally thickened to such an extent that it could be misleading by its ecogenic similarity to leiomyoma. We followed the change in uterine volume after the myomectomy using ultrasound. The uterine shrinkage process lasts between four and six months, and in all cases there was a significant decrease in the final uterine size as compared with the first postoperative sonogram (Fig. 1). This study also clearly demonstrates that the larger the presurgery uterus, the more significant is the decrease in size during remodelling. At the end of this process, most uteri achieve an almost normal volume. In patient No. 8, the uterus remained very bulky two months after surgery and did not continue to shrink. This may possibly be due to the presence of many small leiomyomata, which eventually continued to exert their estrogenic effect on the surrounding myometrium, thus stimulating its hypertrophy and preventing the continuous volume reduction. There are still several unanswered questions: is there any relationship between future fertility and the size of the uterus immediately after surgery? Does the extent of change in uterine volume during
635
the remodelling period affect future fertility? Does the period of uterine volume shrinkage represent a healing process during which conception should be avoided? In conclusion, it appears that the uterus is a dynamic organ, with the myometrium undergoing a process of hypertrophy not only during pregnancy and direct estrogenic effect, but also concomitant with the growth of the leiomyomata. This process is reversible following myomectomy; over a period of four to six months, the uterus can reduce its volume and regain its normal shape. The impact of this process on fertility has yet to be determined.
References 1. Vollenhoven BJ, Lawrence AS, Healy DL. Uterine fibroids: A clinical review. Br J Obstet Gynaecol 1990; 97: 285-98. 2. Weinstein D, Aviad Y, Polishuk WZ. Hystography before and after myomectomy. Am J Roentgen01 1977; 129: 899-902. 3. Beyth Y, Ohel G. Postmyomectomy evaluation of uterine scar - a new hysterographicmethod. Fertil Steril 1983; 39: 564-5. 4. Buttram VC, Reiter RC. Uterine leiomyomata - etiology, symptomatology and management. Fertil Steril 1981; 36: 43345. 5. Garcia CR, 'hrech RW. Submucosal leiomyomas and fertility. Fertil Steril 1984; 42: 16-19. 6. Schlaff W, Zerhouni EA, Huth JAM, Chen J, Damewood MD, Rock JA. A placebo-controlled trial of a depot gonadotropin-releasing hormone analogue (leuprolide) in the treatment of uterine leiomyomata. Obstet Gynecol 1989; 74: 856-62. 7. Pollow K, Geilfuss J, Boquoi E, Pollow B. Estrogen and progesterone binding proteins in normal human myometrium and leiomyoma tissue. J Clin Chem Biochem 1978; 16: 503-11. Address for correspondence:
Yoram Beyth, M.D., FACOG Department of Obstetrics & Gynecology Sapir Medical Center Kfar Saba 44281 Israel
@ Acta Obsret Gynecol Scand 71 (1992)
Uterine remodelling following conservative myomectomy Ultrasonographic evaluation YORAM
BEYTH,RICHARDJAFFE,AND SHMUEL GOLDBERQER
From the Department of Obstetrics and Gynecology. Sapir Medical Center, Kfar Saba, Israel
Acta Obstet Gynecol Scand 1992; 71: 632-635
Uterine leiomyomata develop during the reproductive years and may interfere with fertility through mechanisms as yet not fully understood. A developing intramural or large submucosal leiomyoma causes hypertrophy of the myometrium. Conservative myomectomy , as opposed to hysterectomy, is the preferred surgical procedure for patients who wish to preserve their fertility. Ten patients were ultrasonographically evaluated at monthly intervals foltowing myomectomy and the changes in uterine (myometrial) volume were assessed. There was a gradual decrease in uterine volume in all patients during the six months following removal of intramural and submucosal leiomyomata. The most remarkable decrease in size occurred during the initial two to three months for the majority of the patients. The impact of this process on fertility should be further evaluated. One of the intriguing questions is whether the period of uterine shrinkage represents the time of the healing process during which conception should be prevented. Key words: fertility; leiomyoma; myomectomy; ultrasound Submitted March 13, 1992 Accepted June 7, 1992
Uterine leiomyomata are the most common tumors of the uterus and pelvis. Their incidence is quoted as 50% at postmortem examinations, however the true incidence during the fertile years is difficult to determine (1). Leiomyomata develop during the reproductive years and are not uncommon before the age of 30 in the black woman. They are frequently associated with gynecological and obstetrical complications and may cause infertility. The mechanisms by which leiomyoma interferes with fertility are not fully understood but it is well established that conservative myomectomy may improve fertility (1). Conservative myomectomy is the surgical procedure of choice (as opposed to hysterectomy) in women who wish to preserve fertility. Following myomectomy of an intramural or submucosal leiomyoma, the distorted uterine cavity often returns to its normal shape (2). The surgical procedure of removing 0 Aria Obsrer Gynecol Scand 71 (1992)
intramural or submucosal leiomyomata usually leaves the patient with a uterus whose size is larger than the normal intact one. Repeated pelvic examinations after surgery reveal a gradual decrease in uterine size, often with a return to its normal size. This study was performed in order to evaluate the changes occurring in the uterine volume during the initial few months following conservative myomectomy.
Materlals and methods Ten women, who underwent conservative myomectomy between April 1989 and February 1990, were included in this study. Large or rapidly growing leiomyomata were indications for surgery. All operations were performed by one surgeon (YB).The
Uterine remodelling after myomectomy
633
Table 1. Clinical and surgical data of the patients Patient no . I 2 3 4 5 6 7 8 9 10
Age (yrs)
Single/ Married
Uterine size (gestational weeks)
No. intramural myomata removed
18 37
S S S
3
0
3 1
0
M
18 9 9 Normal
S S
18 12
M M S S
23 20
35 32
35 36 36 25 28 39
Blood transfusion (units packed cells)
0 0
oa 5 12 2 10
10
0 1 0
3 0 0
1 10
16
“One large pedunculated subserous leiomyoma was removed.
patients’ ages at the time of surgery ranged from 18 to 39 years. All patients, except for one NO.^), were nulligravidae. The uterine size on clinical examination ranged from the equivalent of 9 weeks to 23 weeks of pregnancy. Only one patient had a large pedunculated leiomyoma and her uterus was described as normal in size. The maximal number of tumors removed from one patient was 12. None of the uterine cavities were penetrated during the surgical procedures and only two patients required blood transfusions (Table I). Following the removal of the
leiomyoma, the myometrium was sutured with chromic catgut No. 1 interrupted sutures and the serosa was closed with a running vicryl 4-0 gauge suture. Three Cushing clips were applied after removal of the intramural leiomyoma and prior to repairing the myometrium (to the depth of the incision). An additional three clips were located subserous. These were used in order to enable the hysterosalpingographic evaluation of the scar depth in the myometrium and the total uterine wall thickness at the incision site (3). The only postoperative com-
Table 11. Uterine volume (and percentage of decrease) before surgery and on monthly intervals following myomectomy: ultrasonographic evaluation Patient no.
Volume (cm’) before surgery
Uterine volume at intervals following surgery (cm”).
1 weekh I
690 230
200
3
575
180
4
83
83
377
6
452
183
7
1160
800 1051
8
130 (65) 140 (78) 201 (53) 158 (86) 455 (57) 895 (85)
9
234
154
91 (59)
10
I’
290
2 months
3 months
49 1
2
5
1 month
109
76 (69)
81 (411 125 (62) 82 (99)
4 months
6 months
108 (22) 80 (40)
(15)
12
81 (45)
78 (94)
107 (28)
119 (65) 328 (41) 738 (70)
80 (52) 62 (57)
348
(44)
125 (68) 240 (30) 768 (73) 57 (37) 61
22 1 (27) 769
(73)
(55)
values in parentheses are percents.
’’ uterine volume measured one week following surgery is considered 100%.
0 Acra Obsret Gynecol Scand 71 (1992)
634
2
0
Y . Beyth, R. Jaffe and S. Goldberger Fig. 1 . Post myomectomy reduction in uterine size. evaluated ultrasonically at monthly intervals. * uterine volume as measured at the initial examination, one week following surgery.
100%.
=I
I
' 0
80%.
.-c
P)
'
5
.-aE
8
60%
40%
0
c
7
0
6
20% 1
I
I
I
I
I
I
I
0
4
8
12
16
24
1
Weeks Following Surgery plication was a low grade temperature, which gradually subsided and did not lengthen the duration of postoperative hospitalization nor require antibiotic treatment. Sonographic follow-ups were performed by one author (RJ) during the first postoperative week and at four week intervals for four to six months thereafter. Uterine volume was calculated according to the equation for estimation of an ellipsoid, where volume equals 1/6 II multiplied by length, anterioposterior and transverse diameters (0.523 x length x A-P x transverse).
Results Uterine sizes before operation, during the week following operation and on subsequent sonograms are depicted in Table 11. nVo patients did not have an ultrasonographic (U/S) evaluation prior to surgery by the author. In all but one patient, there was a gradual decrease in uterine volume during the four to six months (Fig. 1). Only one patient NO.^), whose pedunculated subserous fibroid attached to the uterus by a narrow pedicle was removed, had a normal size uterus prior to surgery. It is noteworthy that the most remarkable decrease in uterine size occurred within the first two to three months for most patients. The normal uterine size ranges between W 8 0 cm (3). In six out of ten patients, the uterus reached normal size. Uterine size in two patients reached the volume of 107 and 125 cm3 four months after surgery and in two additional patients (Nos 7 and 8) who had very large leiomyomata, the uterus gradually shrank but remained large and bulky (220 cm3and 769 cm' respectively) six months @ Arra Obsier Gynerol Scand 71 (1992)
following surgery. Prior to surgery, patient No. 8 had a uterus equivalent to 20 weeks gestation. Ten intramural leiomyomata were removed from this patient during surgery, however many very small leiomyomata buds were noticed and left untouched.
Discussion Conservative myomectomy is performed instead of hysterectomy when surgery is indicated, and the patient wants to preserve her fertility potential. Leiomyomata may cause a wide scale of clinical symptoms necessitating surgery. Infertility is but one of these symptoms which may even be caused by an otherwise asymptomatic leiomyoma. The mechanism by which leiomyoma interferes with infertility is not fully understood; anovulatory cycles, interference with sperm transport, impingement of the tumor on the endocervical canal or an interstitial portion of the fallopian tube, interference with prostaglandin induced uterine contractions, endometrial and vascular changes are all just a few of the speculations. Clinically, it is well documented that when leiomyomata are intramural or submucosal and of significant size, they may well be factors causing infertility (4). Conservative myomectomy in such cases may restore fertility (5). A developing intramural or large submucosal myoma causes hypertrophy of the entire uterine wall. Schlaff et al. studied changes in total uterine volume, myoma volume and nonmyoma (myometrium) volume of patients exposed to gonadotropinreleasing hormone analogue following therapy and 24 weeks after cessation of treatment (6). The in'
Uterine remodelling after myomectomy
crease in nonmyoma (myometrial) volume, 24 weeks after completion of treatment, was 168% while the increase in myoma volume was only 27% (6). Pollow et al. found significantly lower conversion of estradiol into estrone in leiomyomata than in myometrium. This difference in conversion rate could result in a relative accumulation of estrogen in a leiomyoma, resulting in hyperestrogenic state within the tumor and surrounding tissues (7). Such hormonal milieu may explain the myometrial hypertrophy so that after removal of the myoma and reconstruction of the uterus the myometrium, at the site of the operation, remains thicker compared with the remaining intact myometrium. It has been shown, by hysterographic studies, that the distended and deformed uterine cavity returns to normal shape following conservative myomectomy of submucosal or intramural leiomyoma (2). At the sonographic screening a week post surgery, we found a very thick uterine wall, especially at the site close to the myomectomy. The myometrium at this site was occasionally thickened to such an extent that it could be misleading by its ecogenic similarity to leiomyoma. We followed the change in uterine volume after the myomectomy using ultrasound. The uterine shrinkage process lasts between four and six months, and in all cases there was a significant decrease in the final uterine size as compared with the first postoperative sonogram (Fig. 1). This study also clearly demonstrates that the larger the presurgery uterus, the more significant is the decrease in size during remodelling. At the end of this process, most uteri achieve an almost normal volume. In patient No. 8, the uterus remained very bulky two months after surgery and did not continue to shrink. This may possibly be due to the presence of many small leiomyomata, which eventually continued to exert their estrogenic effect on the surrounding myometrium, thus stimulating its hypertrophy and preventing the continuous volume reduction. There are still several unanswered questions: is there any relationship between future fertility and the size of the uterus immediately after surgery? Does the extent of change in uterine volume during
635
the remodelling period affect future fertility? Does the period of uterine volume shrinkage represent a healing process during which conception should be avoided? In conclusion, it appears that the uterus is a dynamic organ, with the myometrium undergoing a process of hypertrophy not only during pregnancy and direct estrogenic effect, but also concomitant with the growth of the leiomyomata. This process is reversible following myomectomy; over a period of four to six months, the uterus can reduce its volume and regain its normal shape. The impact of this process on fertility has yet to be determined.
References 1. Vollenhoven BJ, Lawrence AS, Healy DL. Uterine fibroids: A clinical review. Br J Obstet Gynaecol 1990; 97: 285-98. 2. Weinstein D, Aviad Y, Polishuk WZ. Hystography before and after myomectomy. Am J Roentgen01 1977; 129: 899-902. 3. Beyth Y, Ohel G. Postmyomectomy evaluation of uterine scar - a new hysterographicmethod. Fertil Steril 1983; 39: 564-5. 4. Buttram VC, Reiter RC. Uterine leiomyomata - etiology, symptomatology and management. Fertil Steril 1981; 36: 43345. 5. Garcia CR, 'hrech RW. Submucosal leiomyomas and fertility. Fertil Steril 1984; 42: 16-19. 6. Schlaff W, Zerhouni EA, Huth JAM, Chen J, Damewood MD, Rock JA. A placebo-controlled trial of a depot gonadotropin-releasing hormone analogue (leuprolide) in the treatment of uterine leiomyomata. Obstet Gynecol 1989; 74: 856-62. 7. Pollow K, Geilfuss J, Boquoi E, Pollow B. Estrogen and progesterone binding proteins in normal human myometrium and leiomyoma tissue. J Clin Chem Biochem 1978; 16: 503-11. Address for correspondence:
Yoram Beyth, M.D., FACOG Department of Obstetrics & Gynecology Sapir Medical Center Kfar Saba 44281 Israel
@ Acta Obsret Gynecol Scand 71 (1992)
