Hysteroscopy is the standard surgical approach for leiomyomas entirely or mostly within the uterine cavity,1–7 but there is no consensus with regard to largely intramural tumors. In those circumstances, the operation might be more difficult and could have an increased risk of complications and nonradical interventions.8–12 Hysteroscopy is being proposed for the latter type of lesion as experience increases.13,14 Systematic use of transvaginal ultrasound and diagnostic hysteroscopy in women with menorrhagia has shown that submucous myomas are a frequent cause of excessive uterine bleeding,15–18 whereas information on their effects on infertility and pregnancy loss is more limited and inconsistent.19,20 We analyzed data from a large series of hysteroscopic myomectomies done over 7 years at the First Department of Obstetrics and Gynecology of the University of Milan, Italy. The main objective of the study was to determine the procedure's effects on menstrual patterns in menorrhagic women and on reproductive outcomes in women with infertility or histories of abortion, in relation to the degree of intramural extension of the myoma. We also assessed operating time, distension fluid absorption, the number of interventions required for complete removal, and disease recurrence.
Materials and Methods
Women referred to a tertiary care academic center specializing in operative hysteroscopy for symptomatic submucous leiomyomas from 1991 to 1997 were evaluated, treated, and followed up. The following data were collected: demographics; outcome of pregnancies before surgery; menstrual patterns; indications for the intervention; duration of infertility when present; associated infertility factors; number, size, and location of myomas; intraoperative and postoperative morbidity; number of hysteroscopic procedures; variations in uterine bleeding; reproductive outcome; and myoma recurrences. To evaluate specifically the effect of removal of submucous myomas on bleeding pattern and fertility, we excluded women with completely extracavitary myomas with diameters of more than 2 cm.
Excessive uterine bleeding was diagnosed on the basis of history; serum hemoglobin, hematocrit, and iron levels; and scores on a pictorial blood loss assessment chart devised by Higham et al21 for evaluating menstrual flow. A monthly score of 100 or higher on that chart was significantly associated with a uterine blood loss of more than 80 mL as measured by the alkaline hematin method. Women completed at least one menstrual diary card before surgery.
Women who had tried to conceive for at least 12 months, without success, had routine infertility evaluations, including luteal phase plasma progesterone determinations, hysterosalpingography, and partner semen analyses. Women with persistent anovulation, bilateral tubal occlusion, or severe partner dyspermia (sperm concentration less than 10 × 106/mL, less than 30% progressive motility at the third hour, and less than 30% typical forms) were excluded from fertility evaluation. To avoid confounding in the assessment of the effect of hysteroscopic myomectomy on otherwise unexplained infertility, subjects who had in vitro fertilization-embryo transfer postoperatively also were excluded.
Preoperative transvaginal ultrasonography and diagnostic hysteroscopy were done in all cases. A submucous myoma was considered pedunculated when it had no intramural extension, sessile when it had an intramural extension of less than 50%, and intramural if its greatest diameter lay outside the uterine cavity. In the case of multiple myomas, classification was based on the largest one. Hysteroscopic resection was deemed possible only if the largest diameter was less than 5 cm and the distance between the outer margin of the myoma and the perimetrium as determined by transvaginal ultrasonography was more than 5 mm. Preoperative treatment was prescribed usually for 2 months to women with iron deficiency anemia; otherwise, intervention took place in the early postmenstrual phase.
Hysteroscopic myomectomy was done under general anesthesia using a rigid resectoscope (model G25-ST-CFR; Circon Acmi, Stamford, CT; or model 26050 EG; Storz GmbH & Co., Tuttlingen, Germany) and a 12° fore-oblique telescope (model M3–12; Circon Acmi; or model 27005 FA; Storz) equipped with standard rightangle cutting loop electrodes. After introduction of the resectoscope, the uterine cavity was distended with a nonconductive, hypoosmolar solution of 2.7% sorbitol and 0.54% mannitol, instilled under manometric control, with a pressure of 100–120 rnmHg generated by a pneumatic cuff for intrauterine irrigation and a vacuum of −30 to −40 mmHg applied for suction. First a coagulating waveform current set at 50 watts was used to seal large superficial vessels, and then resection was done with pure cutting current set at 100 watts. The entire pedunculated myoma and the intracavitary portion of sessile and intramural tumors were shaved gradually, the wire loop being brought behind the lesion and the electrode being withdrawn toward the surgeon until the resected chip was released completely. Only after substantial reduction of the myoma was the pedicle or base cut. To remove the extracavitary part, the wire loop was driven between the myoma and the myometrium, first developing the cleavage plane with tractions of the deactivated electrode and then progressively resecting small portions of the lesion until normal myometrium was seen. For removal of small fundal or cornual myomas, a 45° wire loop was sometimes used, with caution. Complete resection was attempted in all subjects. Myoma fragments were removed with polyps or ovum forceps and sent for pathologic examination.
Operating time was defined as the interval between initial insertion and final removal of the instrument. Fluid deficit was calculated as the difference between the total amount of solution instilled into the uterus and the amount of fluid recovered from the suction bottle and the plastic draping that funneled escaping fluid through the cervix into a calibrated pouch. The procedure was stopped if the estimated fluid deficit was more than 1 L.
Women were scheduled for transvaginal ultrasonography 2 months after their procedures. For residual myoma persistence, repeat resections were advised. It was deemed reasonable to limit the number of procedures to three. After surgery, most subjects were evaluated twice a year.
At each follow-up visit, a standard gynecologic examination was done, menstrual pattern was assessed, occurrence and outcome of pregnancy were noted, and a transvaginal ultrasound scan was done. Disease recurrence was recorded in terms of ultrasonographic evidence of uterine leiomyomas and need for reoperation. Follow-up of women not examined regularly at our institution was by telephone. Women gave informed consent to participate in follow-up and data collection, but because of the nonexperimental nature of the study, a formal evaluation of the research protocol by the local ethics committee was not requested.
We used the Kaplan-Meier method to calculate the cumulative proportion of women, according to myoma type, who developed recurrence of menorrhagia and submucous myomas or who became pregnant, and curves were compared by the log-rank test. Event dates used in the computation of cumulative probability of becoming pregnant were the date of surgery and the date of the last menstrual period (LMP) or last follow-up visit. Event dates used in the computation of cumulative probability of menorrhagia or myoma recurrence were the date of surgery; the date of symptom recurrence, according to the pictorial blood loss assessment chart; the date of ultrasonographic diagnosis of submucous myoma recurrence; and the date of the last follow-up visit, or LMP in cases of conception. Because the Kaplan-Meier method allows comparison of subjects with different lengths of follow-up, women who became pregnant postoperarively were not excluded from menorrhagia or disease recurrence evaluations. Differences in mean operating time and fluid absorption were evaluated by one-way analysis of variance, and the χ2 test for heterogeneity was used to analyze the number of interventions required for complete removal according to myoma type. Continuous and dichotomous variables before and after surgery were compared using the paired t test and the Fisher exact test, respectively. All statistical tests were two-sided. Probability values less than 5% were considered statistically significant.
In the period studied, 108 eligible women had hysteroscopic myomectomies at our institution and were followed up regularly. Twelve women (11%) were followed up by phone after early postoperative examinations. Thirteen others with similar baseline characteristics were lost to follow-up and were not included in analyses (Table 1). Menorrhagia was the main surgical indication for two-thirds of the subjects. A completely intracavitary myoma was the most frequent type of lesion, and in 14% of cases more than one submucous lesion was present (Table 1). Fifteen women (14%) had small intramural or subserosal completely extracavitary myomas (one in eight subjects, two in five subjects, and three or more in two subjects) in addition to the submucous tumors. Preoperative medical treatment was prescribed to 89 (82%) of 108 women (GnRH agonists, 66; oral estrogen-progestogen combinations, 11; progestogens, nine; danazol, three).
The only intraoperative complication observed was a brisk hemorrhage, which required interruption of the intervention and was controlled by manual uterine massage and intravenous administration of methylergonovine maleate. One procedure was stopped when the fluid deficit was more than 1 L. Postoperative courses were always uneventful, and all women were discharged within 24 hours.
In subjects with tumors with more than 50% intramural extension, operating times were 78% longer and fluid deficits 64% higher than in those with completely intracavitary lesions. Intermediate values were noted in women with submucous sessile myomas; however, only differences in distension fluid absorption were statistically significant (Table 2). The aforementioned variables were not influenced significantly by preoperative medical treatment (data not shown). There was a trend toward need for repeated surgery when myoma intramural extension was more than 50%, because submucous pedunculated and sessile lesions required more than one operation for complete removal in 26% of cases, compared with half of cases of intramural tumors (Table 2). The reason for repeat operations was always incomplete myoma removal during the first surgical procedure, confirmed by postoperative transvaginal ultrasonography.
After a mean (± standard deviation [SD]) follow-up of 41 ± 23 months, there was myoma recurrence in 27 subjects (12 of 54 with pedunculated lesions, seven of 30 with sessile lesions, and eight of 24 with intramural lesions), with a corresponding overall 3-year cumulative myoma recurrence rate of 34%. There were no significant differences in myoma recurrence rates between the three study groups (Figure 1A). During the same period, the mean (±SD) pictorial blood loss assessment chart score decreased from 187 ± 92 to 65 ± 41 in women with pedunculated myomas, from 165 ± 86 to 62 ± 34 in those with sessile myomas, and from 182 ± 92 to 74 ± 43 in those with intramural myomas, and the mean (± SD) serum hemoglobin levels increased from 10.2 ± 2.0 to 12.4 ± 2.1 g/dL in women with pedunculated lesions, from 10.7 ± 1.8 to 12.3 ± 1.8 g/dL in women with sessile lesions, and from 10.3 ± 1.6 to 12.1 ± 2.3 g/dL in women with intramural lesions. Those variations were all statistically significant (paired t test, P < .01).
Twenty of the 101 women who were menorrhagic at baseline (72 menorrhagic and 29 infertile and menorrhagic) had recurrent excessive uterine bleeding, based on history, blood chemistries, and pictorial blood loss assessment chart scores (nine of 51 women with pedunculated myomas, four of 28 with sessile myomas, and seven of 22 with intramural myomas), with an overall 3-year cumulative menorrhagia recurrence rate of 30% not influenced significantly by the type of myoma removed (Figure 1B). Seven of the 20 women with recurrent menorrhagia had hysterectomies, three had abdominal myomectomies, one had endometrial ablation, and seven underwent various successful medical therapies (cyclic norethindrone acetate in four cases, danazol in two, and GnRH agonist plus add-back therapy in one). The remaining two women refused further surgical or hormonal treatments, preferring to rely on continuous oral iron supplementation.
Fifteen of the 40 infertile women achieved pregnancies (10 of 22 with pedunculated myomas, four of 12 with sessile myomas, and one of six with intramural myomas), with an overall 3-year cumulative conception rate of 43%, which was not affected significantly by the type of myoma resected (Figure 1C). One woman conceived twice, bringing the total number of pregnancies to 16. Nine pregnancies ended with term vaginal deliveries, five with cesarean deliveries (one because of placenta previa, one because of disproportion, and three because of previous myomectomies), and one with a first-trimester miscarriage and one pregnancy was terminated voluntarily. Five women not included among the infertile subjects had myoma resections because of two or more abortions. Before surgery, those women had 15 pregnancies that ended in first-trimester miscarriages in nine cases, second-trimester loss in two, and term vaginal deliveries in four. Postoperatively, four of the 15 women achieved six pregnancies, which were carried to term in five cases and ended with first-trimester abortion in only one instance. The abortion rate decreased from 73% (11 of 15) preoperatively to 17% (one of six) postoperatively (P = .046, Fisher exact test). Nine other women who had hysteroscopic myomectomies for menorrhagia and did not want to conceive in the period before surgery tried to become pregnant postoperatively. Five of them did become pregnant; four delivered at term and one miscarried.
Hysteroscopic resection of submucous myomas has been reported to be feasible, efficacious, and safe by many authors.1–14 We studied a large number of women operated on consecutively using a standard surgical technique and followed up prospectively by trained interviewers. The number of subjects lost to follow-up was limited (13 of 121) and the baseline characteristics of these women did not differ from the characteristics of the women who remained in the study. Our main objective was to assess the long-term outcomes of the procedure with survival analysis, in terms of relief from menorrhagia and conception rate, according to degree of intramural extension of lesions. Wamsteker et al14 observed that tumors that develop mainly into the myometrium are associated with increased need for repeat resections and reduced chance of definitive bleeding control. They14 also stressed the importance of detailed preoperative assessment of intracavitary conditions and described the surgical difficulties that could be encountered when the myoma is only partly submucosal. In our series, myomas with their greatest diameter within the uterine wall were associated with increased operating time, fluid absorption, and need for repeat operation for complete removal, although only operating time varied significantly. In the above circumstances, half of the subjects needed more than one intervention, which is important with regard to preoperative counseling. This does not mean that an endoscopic approach should not be adopted, but it does imply that an expert hysteroscopist should be available, especially if lesions are not small (usually more than 3cm).
About one-fourth of the women had submucous myoma recurrence within 3 years of resection, which should not have been the result of lesion persistence, because operations were deemed radical on the basis of hysteroscopic and ultrasonographic findings. That figure is similar to the recurrence rate after abdominal myomectomy for subserous and intramural tumors.20 Some women had multiple small myomas throughout the uterine body, showing an increased risk for new tumor growth independent of lesion site and surgical method. Twelve women had late follow-up pelvic ultrasonography in other hospitals, which could have had an effect on the estimate of submucous myoma recurrence, given that identification of intrauterine lesions can be operator-dependent. Our institution treats a nationally based referral population, and many women living in distant regions find it inconvenient to return for periodic examinations after intervention.
Menorrhagia was by far the most frequent indication for surgery, and the rate of recurrence of menorrhagia was lower than that of submucous myomas, which is not surprising because we considered very small tumors, which may not cause excessive uterine bleeding, to be examples of lesion recurrence. Long-term control of menorrhagia was achieved in 80% of cases, confirming the satisfactory results obtained by other surgeons.1–14 Myoma and menorrhagia recurrence rates were not significantly different among the three groups of women with various submucous myoma types, further evidence that the operations, whether single or multiple, were finally complete, limiting the influence of the original location of the tumor on long-term outcomes. The probability of pregnancy after intervention was not influenced by the type of myoma removed. According to post hoc calculations, the study had 80% power to detect no less than five- and three-fold increases in menorrhagia recurrence and conception rates, respectively, in the mainly intramural myoma group compared with the completely or mainly intracavitary myoma group. However, our original decision to perform an exploratory analysis was predicated on the almost complete lack of relevant information available in the literature on which to base an a priori calculation of the sample.
Several hypotheses have been suggested to explain how submucous myomas cause infertility,19 but none is definitive. According to our results, the effect of hysteroscopic myomectomy on infertility is not negligible but seems limited compared with that of abdominal myomectomy for subserous and intramural tumors. The crude postoperative pregnancy rate in our series was 38% (15 of 40), compared with 61% in seven prospective studies involving 112 women with otherwise unexplained infertility.20 The corresponding cumulative conception rate after resection was 43%, whereas it was 65% 2 years after abdominal myomectomy in 138 infertile women operated on at our institution in the same study period (unpublished data). That seems in line with the findings of Hallez22 but at odds with those of Goldenberg et al,23 who noted seven pregnancies among 15 infertile women (crude rate 47%). Eldar-Geva et al24 recently found that submucous myomas significantly worsen the outcome of assisted reproductive technology treatment, which strongly suggests that intracavitary tumors are implicated in infertility and supports surgical intervention regardless of menstrual pattern. We wonder whether it would be opportune to combine laparoscopy with hysteroscopic myomectomy for infertility, to investigate the presence of any additional factors that could delay conception. Some women whose main indication for hysteroscopic myomectomy was menorrhagia tried to become pregnant postoperatively. Interpretation of data from this small subgroup is problematic because these women did not attempt to conceive before surgery.
It is known that submucous myomas can cause repeated abortions and that surgery can increase the chances of a viable pregnancy.25 Only five women had hysteroscopies for repeated abortions in our series, but the effect on pregnancy losses was substantial and statistically significant.
Hysteroscopic resection of submucous myomas proved safe and resulted in satisfactory menorrhagia control and limited lesion recurrence rates. The effect on infertility was less impressive and suggests that a concomitant laparoscopy might be appropriate when pregnancy delay is the main indication for surgery. The degree of intramural extension of the lesion had no significant influence on any of the long-term outcomes. Resection of myomas whose greatest diameters were outside the uterine cavity was associated with longer operating time, more fluid absorption, and increased need for multiple resections for complete tumor removal. An accurate preoperative assessment of the uterine condition by sonohysterography or diagnostic hysteroscopy is required for proper counseling and so that a surgeon with adequate experience can be chosen.10,14,18
1. Neuwirth RS. A new technique for an additional experience with hysteroscopic resection of submucous fibroids. Am J Obstet Gynecol 1978;131:91–4.
2. Neuwirth RS. Hysteroscopic management of symptomatic submucous fibroids. Obstet Gynecol 1983;62:509–11.
3. DeCherney A, Polan ML. Hysteroscopic management of intrauterine lesions and intractable uterine bleeding. Obstet Gynecol 1983; 61:392–7.
4. Hallez JP, Netter A, Carder R. Methodical intrauterine resection. Am J Obstet Gynecol 1987;156:1080–4.
5. Brooks PG, Loffer FD, Serden SP. Resectoscopic removal of symptomatic intrauterine lesions. J Reprod Med 1989;34:435–7.
6. Loffer FD. Removal of large symptomatic intrauterine growths by the hysteroscopic resectoscope. Obstet Gynecol 1990;76:836–40.
7. Valle RF. Hysteroscopic removal of submucous leiomyomas. J Gynecol Surg 1990;6:89–93.
8. Derman SG, Rehnstrom J, Neuwirth RS. The long-term effectiveness of hysteroscopic treatment of menorrhagia and leiomyomas. Obstet Gynecol 1991;77:591–4.
9. Corson SL, Brooks PG. Resectoscopic myomectomy. Fertil Steril 1991;5:1041–4.
10. Wamsteker K, de Blok S, Gallinat A, Lueken RP. Fibroids. In: Lewis BV, Magos AL, eds. Endometrial ablation. Edinburgh, UK: Churchill Livingstone, 1993:161–81.
11. Indman PD. Hysteroscopic treatment of menorrhagia associated with uterine leiomyomas. Obstet Gynecol 1993;81:716–20.
12. Neuwirth RS. Hysteroscopic submucous myomectomy. Obstet Gynecol Clin North Am 1995;22:541–58.
13. Donnez J, Gillerot S, Bourgonjon D, Clerckx F, Nisolle M. Neodymium: YAG laser hysteroscopy in large submucous fibroids. Fertil Steril 1990;54:999–1003.
14. Wamsteker K, Emanuel MH, de Kruif JH. Transcervical hysteroscopic resection of submucous fibroids for abnormal uterine bleeding: Results regarding the degree of intramural extension. Obstet Gynecol 1993;82:736–40.
15. Fedele L, Bianchi S, Dorta M, Brioschi D, Zanotti F, Vercellini P. Transvaginal ultrasonography versus hysteroscopy in the diagnosis of uterine submucous myomas. Obstet Gynecol 1991;77:745–8.
16. Vercellini P, Vendola N, Ragni G, Trespidi L, Oldani S, Crosignani PG. Abnormal uterine bleeding associated with iron-deficiency anemia: Etiologic diagnosis and role of hysteroscopy. J Reprod Med 1993;38:502–4.
17. Vercellini P, Cortesi I, Oldani S, Moschetta M, De Giorgi O, Crosignani PG. The role of transvaginal ultrasonography and outpatient diagnostic hysteroscopy in the evaluation of patients with menorrhagia. Hum Reprod 1997;12:1768–71.
18. Corson SL. Hysteroscopic diagnosis and operative therapy of submucous myoma. Obstet Gynecol Clin North Am 1995;22:739–55.
19. Vercellini P, Bocciolone L, Rognoni MT, Bolis G. Fibroids and infertility. In: Shaw RW, ed. Uterine fibroids. Carnforth, UK: Parthenon, 1992:47–56.
20. Vercellini P, Maddalena S, De Giorgi O, Aimo G, Crosignani PG. Abdominal myomectomy for infertility: A comprehensive review. Hum Reprod 1998;13:873–9.
21. Higham JM, O'Brien PMS, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol 1990;97:734–9.
22. JP Hallez. Single-stage total hysteroscopic myomectomies: Indications, techniques, and results. Fertil Steril 1995;63:703–8.
23. Goldenberg M, Sivan E, Sharabi Z, Bider D, Rabinovici J, Seidman DS. Outcome of hysteroscopic resection of submucous myomas for infertility. Fertil Steril 1995;64:714–6.
24. Eldar-Geva T, Meagher S, Healy DL, MacLachlan V, Breheny S, Wood C. Effect of intramural, subserosal, and submucosal uterine fibroids on the outcome of assisted reproductive technology treatment. Fertil Steril 1998;70:687–91.
25. Buttram VC, Reiter RC. Uterine leiomyomata: Etiology, symptomatology, and management. Fertil Steril 1981;36:433–45.