Neodymium: VAG laser hysteroscopy in large submucous fibroids

FERTILITY AND STERILITY Copyright <> 1990 The American Fertility Society Printed on acid-free paper in U.S.A. Neodymium: VAG laser hysteroscopy in large submucous fibroids Jacques Donnez, M.D., Ph.D.* Stephane Gillerot, M.D. Damieri Bourgonjon, M.D. Franc;:oise Clerckx, B.S. Michelle Nisolle, M.D. Infertility Research Unit, Department of Gynecology, University of Louvain, Brussels, Belgium The preoperative use of a potent, subcutaneously injected gonadotropin-releasing hormone agonist ( GnRH -a) was evaluated in a series of 60 women with large submucosal fibroids. Myomectomy by hysteroscopy and Nd:YAG laser was easily performed. In 12 cases, the largest portion of the myoma was not inside the uterine cavity and myomectomy was carried by a two-step hysteroscopy. In women who wished to become pregnant, a pregnancy rate of 66% was achieved. Advantages of preoperative use of a GnRH-a are (1) the significant decrease of the fibroid size, (2) a lower fluid absorption, and (3) the restoration of a normal hemoglobin concentration. Fertil Steril54:999, 1990 Submucous uterine fibroids are common benign solid tumors of the genital tract, that may produce menorrhagia and/or infertility. The effect of a potent agonist gonadotropin-releasing hormone agonist (GnRH-a) on the size of uterine leiomyomas has been previously described. 1-6 In women with uterine fibroid associated infertility, use of GnRH-a represented an adjunct for preoperative reduction of tumor size 2 5 and permitted the surgical treatment by hysteroscopy if the greatest diameter of the fibroma was inside the uterine cavity. 5 The purpose of the current study was to describe the technique used by the authors in cases of very large submucous fibroids. MATERIALS AND METHODS Sixty women aged 23 to 40 years (mean 34 years) with symptomatic submucous uterine fibroids were treated with a biodegradable GnRH-a (Zoladex Implant ICI; Cambridge, United Kingdom). The implant was injected subcutaneously at the end of the Received March 19, 1990; revised and accepted July 25, 1990. * Reprint requests: Jacques Donnez, M.D., Ph.D., Infertility Research Unit, Department of Gynecology, University of Louvain, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, B-1200 Brussels, Belgium. luteal phase to curtail the initial gonadotropin stimulation phase always associated with a rise in estrogen. One implant was systematically injected at weeks 0, 4, and 8. Blood samples were drawn the day of the first implant injection, 7 days after, and every 2 weeks until the recovery of menstruation. Samples were assayed by radioimmuassay (RIA) for concentrations of gonadotropins (luteinizing hormone [LH], follicle-stimulating hormone [FSH], and estradiol [E 2]). Endometrial biopsy, hysterography, and hysteroscopy were performed before treatment and at 8 weeks. The uterine cavity area and the fibroid area were calculated as previously described 5 on the hysterography images using the short-line "multipurpose test system" described by Weibel. 6 Care was taken to carry out the hysterosalpingography in a standard fashion and to compare images of hysterography at the same degree of uterine and tubal filling by contrast and with the same reference marks to the pelvic bones. In cases of very large fibroids, transabdominal and transvaginal echography were performed to evaluate the depth of the intramural portion of the fibroids. At 8 weeks, hysteroscopic myomectomy was carried out with the help of the neodymium Y AG (N d: Y AG) laser. A Sharplan 2100 apparatus (Sharplan; Donnez et al. Hysteroscopy in submucous fibroids 999

' - A l l cases... Myomas> 10 cm2..., Myomas> 5 < 10 cm2... Myomas< 5 cm2 20 15 15.4 ± 7.6 10 9.5 ± 6.4 7.5±6.7~ 6.9 ± 1.2 4.6 ± 4.8 4.0 ± 1.7 5 the treatment period, LH and FSH concentrations were significantly suppressed by 2 weeks of treatment. Recovery of ovarian secretion occurred, on average ±10 weeks after the last injection, as proved by the significant increase of E 2 secretion observed 10 weeks after the last implant injection (58± 32 pg/ml). Evaluation of Hormonal Therapy 2.5 ± 1. 2 - - - - - - - - - - 1. 6 ± 1.0 0 ~------~--------------~-------Weeks of therapy 0 8 Figure 1 Submucosal fibroid areas as assessed by hysterosalpingography before and after an 8-week GnRH -a therapy: B, all cases; A, women with initial fibroid area > 10 cm2 (n = 17); C, women with initial fibroid area> 5 cm2 < 10 cm2 (n = 22); and D, women with initial fibroid area< 5 cm 2 (n = 21). Tel-Aviv, Israel) was used for generating the laser. A power output of 80 W was used. The instrument used in our series was the operative hysteroscope with a deflecting arm (Storz; Tuttlingen, West Germany). The technique that the senior author (J.D.) used to provide constant distention involved attaching one 300-mL plastic bag of glycine solution (Travenol; Baxter, Brussels, Belgium) to blood infusion tubing. The bag was then wrapped in a pressure infusion cuff similar to that used to infuse blood under pressure. The tubing was connected to the hysteroscope. In case of bleeding during the intervention, the pressure infusion was increased so that the intrauterine pressure was above the arterial pressure until the blood vessel provoking the bleeding was coagulated with the help of the Nd:YAG laser. At the end of the procedure, no intrauterine stent was placed in the uterine cavity. No hormonal therapy, such as estrogens and progesterone, was given. The operating time varied from 10 to 50 minutes (mean 24 ± 6 minutes). Blood loss was minimal. Indeed, when blood loss was controlled, the difference between preoperative and postoperative (2 days) hemoglobin concentration was never > 1 g/l. Analysis of data from hysterosalpingography before and after treatment was performed with the Wilcoxon's rank sum test for matched pairs and Student's t-test. All data are expressed as the mean± SD. All patients had a pretreatment uterine cavity area > 10 cm 2 In all patients, the uterine cavity area was decreased, with an average decrease of 36%. The area decreased significantly (P < 0.01) from the baseline area (14.5 ± 5.1 cm 2 ) to 9.2 ± 3.4 cm 2 by 8 weeks of therapy. Using the same method, the decrease of very large submucous fibroid area was also calculated. When more than one fibroid was present, only the largest was evaluated. In all cases except two, the fibroid area was decreased by an average of 38%. However, the response was variable, ranging from 4% to 90%. Fibroid area decreased significantly (P < 0.01) from the baseline area (7.5 ± 6.7 cm 2 ) to 4.6 ± 4.8 cm 2 by 8 weeks of therapy. Figure 1 shows the mean fibroid areas in patients with a pretreatment fibroid area < 5 cm 2 (2.5 ± 1.2 to 1.6 ± 1.0 cm 2 ) versus those with an area > 5 cm 2 to <10 cm 2 (6.9 ± 1.2 to 4.0 ± 1.7 cm 2 ) and those with an area> 10 cm 2 (15.4 ± 7.6 to 9.5 ± 6.4 cm 2 ). In all subgroups, a signifi- RESULTS After a well-known initial stimulation of E 2 secretion, GnRH -a administration resulted in a postmenopausal E 2 range (16 ± 11 pg/ml). Throughout 1000 Donnez et al. Hysteroscopy in submucous fibroids Figure 2 A, Technique used for submucosal fibroid of which the greatest diameter is inside the uterine cavity; B, technique used for submucosal fibroid of which the greatest diameter is in the uterine wall. Fertility and Sterility

cant decrease (P < 0.005) was noted. There was no significant difference between the different subgroups. In patients with menorrhagia complaints (n = 38) the initial hemoglobin measurement was 11.3 ± 0.9 mg/l. Significant increase (13.8 ± 0.8 g/100 ml) (P < 0.005) was observed by the end of the 8-week treatment period. Moreover, the endometrium is atrophic. The amount of fluid absorbed was significantly (P < 0.05) lower in patients preoperatively treated with a GnRH-a (330 ± 210 ml) than in patients without any hormonal therapy 7-9 (750 ± 340 ml). Side effects of GnRH-a treatment, including hot flushes (58/60) and vaginal dryness (34/60), appeared the second week of therapy but were well tolerated. Hysteroscopic Myomectomy Submucosal Fibroid of Which the Greatest Diameter Was Inside the Uterine Cavity All patients underwent myomectomy by hysteroscopy and Nd:YAG laser. In all cases (n = 48), the operation was easily performed. The myometrium overlying the myoma was less vascular and the "shrinkage" of the uterine cavity may have accounted for the relative ease of separating the myoma from the surrounding myometrium (Fig. 2). The myoma was left in the uterine cavity. No complications such as infection, bleeding, or uterine contractions occurred. Office hysteroscopy done with C0 2 and carried out 2 to 3 months after myomectomy confirmed the complete disappearance of the myoma, which was probably "ejected" during the first menstruation occurring after the procedure. Large Submucosal Fibroid of Which the Largest Portion Was Located in the Uterine Wall In cases of very large submucous fibroids of which the largest portion was not inside the uterine cavity but well inside the uterine wall (n = 12) (Fig. 3), a two-step operative hysteroscopy was proposed (Fig. 2B). After 8 weeks preoperative GnRH therapy, a partial myomectomy was carried out by resecting the protruded portion of the myoma. Thereafter, the laser fiber was directed as perpendicularly as possible to the remaining (intramural) fibroid portion and was introduced in the fibroid on a length of 5 to 10 mm. During the application of laser energy, the fiber was removed slowly so that the deeper areas were coagulated. The end point of fibroid coagulation with this technique was identi- fied by distinct "craters" with brown borders on all fibroid area. The depth of the intramural fibroid portion was well known by echographic examination performed the day before surgery. The aim of this procedure was to decrease the size of the remaining myoma by decreasing the vascularity. A GnRH-a therapy was given for another 8 weeks and the second-look hysteroscopy was then performed. In all cases, the myoma was found to protrude again inside the uterine cavity and appeared very white and without any apparent vessel on its surface (Fig. 3). Myomectomy was then carried out as described for myomas in which the largest portion was inside the uterine cavity. The shrinkage of the uterine cavity allowed the residual myoma portion to be easily separated from the surrounding myometrium and dissected off the myometrium. At the end of the procedure, the myoma was left in the uterine cavity. No concomitant lap a roscopy was carried out, but should be suggested as the safest approach in some cases. In all cases, hysterography and hysteroscopy, carried out 2 to 3 months after myomectomy, confirms the disappearance of the myoma. The uterine cavity was normal. Long-Term Results In all cases, myomectomy permits the restoration of normal flow. Among the 60 women, 24 desired to become pregnant and had no other fertility factors. Sixteen (66%) of them became pregnant during the first 8 months after the recovery of menstruation. No miscarriage or premature labor was observed in this series; one cesarean section was mandatory because of fetal distress. DISCUSSION Because most leiomyomata return to near pretreatment size within 4 months after cessation of GnRH -a therapy 2, these agents cannot be used as definitive medical therapy. Several reports have demonstrated reductions in uterine and fibroid volumes by 52% to 77% after 6 months of GnRH-a therapy, as assessed by ultrasound imaging. 2 3-10 In a recent study, 5 as documented by hysterography imaging, an average decrease of 35% in the uterine cavity area was found. The current study demonstrated reductions in fibroid volume by 38% after 8 weeks of GnRH-a therapy. However, the response was variable ranging from 4% to 90%. There was no difference in the Donnez et al. Hysteroscopy in submucous fibroids 1001

, Figure 3 Submucosal fibroid of which the greatest diameter is in the myometrium. A, B, hysterosalpingography after GnRH-a therapy; C, D, hysterosalpingography before the "second" myomectomy (Note the protrusion of the earlier intramural portion). extent of decrease according to the pretreatment fibroid area. A treatment duration of 8 weeks was adapted before hysteroscopic myomectomy. Indeed, in a previous study,5 10 a significant uterine shrinkage was observed at 8 weeks of therapy, and uterine cavity area at 12 weeks was not significantly different from that found after 8 weeks of therapy. In cases of submucosal uterine fibroids, hysteroscopic myomectomy was carried out if the greater diameter of leiomyoma, as assessed by hysterography, was inside the uterine cavity. Myomas were easily separated from the surrounding myometrium with the help of the Nd:YAG laser. The preoperative blood loss was minimal, possibly because of decreased vascularity of the myometrium, which was demonstrated by a significant reduction in the 1002 Donnez et al. Hysteroscopy in submucous fibroids uterine arterial blood flow (Doppler), after treatment with a GnRH -a. 10 11 In all cases, the myoma was left in the uterine cavity and there were no complications. Office hysteroscopy performed after the first postoperative menstruation confirmed the disappearance of the myoma. Probably after a necrosis phase, it was ejected with the menstrual blood. In cases of very large fibroids of which the largest diameter was not inside the uterine cavity, the myomectomy was carried out in two steps. During the first surgical procedure, the protruding portion was removed and the intramural portion was devascularized by introducing the laser fiber in the myoma, on a length of 5 to 10 mm, depending on the depth of the remaining intramural portion, which was evaluated by echography performed before surgery. Fertility and Sterility

A very interesting finding was that this intramural portion of the myoma became submucosal and protruded again inside the uterine cavity, possibly because of the GnRH-a-induced uterine shrinkage, which provokes the protrusion of the remaining portion. In all cases, the largest diameter of the remaining portion was inside the uterine cavity so that myomectomy was easily performed by separating it from the surrounding myometrium with the help ofthe Nd:YAG laser. As previously evaluated by Goldrath/ 2 a temperature< 50oC was measured 1 em below the endometrial surface when the laser beam was set at 55 W and directed for 5 seconds at the tissue over the thermocouples. There is no risk of damage to the bowel or the bladder by transmural Nd:YAG energy effect. Indeed, in all cases, the distance between the deepest portion of the myoma and the uterine serosa was evaluated by echography. The pelvic structures were protected from injury because the distance between the top of the fiber and the external surface of the uterus was never <1.5 em. There was no risk to push a laser fiber as much as 1 em into the remaining portion if the diameter of the fibroid was >3 to 4 em. The procedure was never done under laparoscopic control, but concomitant laparoscopy must be suggested as the safest approach because.of the potential risks of bowel injury by doing this blindly. Because of the cessation of uterine bleeding, preoperative therapy resulted in the restoration of a normal hemoglobin concentration, which makes possible donation of blood for later transfusion. The decreased risk of transfusion-acquired infections could be substantial. The hormonal endometrial status is one of the factors affecting fluid absorption, 7 8 which is also a function of uterine distention pressure, length of anesthesia time, and amount of open uterine bed that is developed during the procedure. The endometrium vascularization may account for liquid resorption. During the menstrual cycle, the endometrium is well developed and there is an important vascularization. This important vascularization was reduced by a preoperative GnRH -a therapy. The amount of fluid absorbea was lower if the endometrium was atrophic. By reducing the amount of fluid absorbed, the preoperative GnRH -a therapy reduced the risk of fluid overload and this represents another advantage. In women with uterine fibroid-associated infertility, a pregnancy rate of 66% was achieved. Hysteroscopic myomectomy seems thus to improve fertility without affecting the mode of delivery. In conclusion, use of GnRH-a represents an adjunct for preoperative reduction of tumor size so that surgical treatment by hysteroscopy is possible. Even when the largest diameter is in the myometrium, the two-step hysteroscopic therapy combined with a GnRH -a therapy represents an ideal management of large submucous myomas and decreases the chance of myomectomy by laparotomy, which is often accompanied by operative blood loss and postoperative adhesion formation. REFERENCES 1. Healy DL, Fraser HM, Lawson SL: Shrinkage of a uterine fibroid after subcutaneous infusion of a LH-RH agonist. Br MedJ 209:267, 1984 2. Maheux R, Guilloteau C, Lemay A, Bastide A, Fazekas ATA: Luteinizing hormone-releasing hormone agonist and uterine leiomyoma: pilot study. Am J Obstet Gynecol 152: 1034,1985 3. Friedman AJ, Barbieri RL, Doubilet PM, Fine C, Schiff I: A randomized, double-blind trial of a gonadotropin releasinghormone agonist (leuprolide) with or without medroxyprogesterone acetate in the treatment ofleiomyomata uteri. Fertil Steril 49:404, 1988 4. Andreyko JL, Blumenfeld Z, Marschall LA, Monroe SE, Hricak H, Jaffe RB: Use of an agonistic analog of gonadotropin-releasing hormcne (nafarelin) to treat leiomyomas: assessment by magnetic resonance imaging. Am J Obstet Gynecol158:903, 1988 5. Donnez J, Schrurs B, Gillerot S, Sandow J, Clerckx F: Treatment of uterine fibroids with implants of gonadotropin-releasing hormone agonist: assessment by hysterography. Fertil Steri151:947, 1989 6. Weibel ER: Practical methods for biological morphometry. In Stereogical methods, Vol. 1, Edited by ER Weibel. Bern, Switzerland, Academic Press, 1979, p 101 7. Van Boven M, Singelyn F, Donnez J, Gribomont BF: Dilutional hyponatremia associated with intrauterine endoscopic laser surgery. Anesthesiology 3:71, 1989 8. Donnez J: unpublished data 9. Van Boven M, Singelyn F, Gribomont B: Complications and precautions in operative hysteroscopic surgery. In Laser Operative Laparoscopy and Hysteroscopy, Edited by J, Donnez. Leuven, Nauwelaerts Printing, 1989 p 299 10. Donnez J, Schrurs B, Clerckx F, Nisolle M: Les agonistes de Ia LH-RH: une alternative dans le traitement de Ia myomatose uterine. Contrac Fertil Sex 17:47, 1989 11. Matta WHM, Stabile I, Shaw RS, Campbell S: Doppler assessment of uterine blood flow changes in patients with fibroids receiving the gonadotropin-releasing hormone agonist Buserelin. Fertil Steril49:1083, 1988 12. Goldrath MH: Hysteroscopic laser surgery. In Basic and Advanced Laser Surgery in Gynecology, Edited by MH Baggish. Norwalk, Appleton-Century-Crofts, 1985, p 357 Donnez et al. Hysteroscopy in submucous fibroids 1003