Determinants of pregnancy rate and obstetric outcome after laparoscopic myomectomy for infertility

Transcription

1 FERTILITY AND STERILITY VOL. 76, NO. 2, AUGUST 2001 Copyright 2001 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A. Determinants of pregnancy rate and obstetric outcome after laparoscopic myomectomy for infertility Lionel Dessolle, M.D., a David Soriano, M.D., a Christophe Poncelet, M.D., b Jean-Louis Benifla, M.D., b Patrick Madelenat, M.D., b and Emile Daraï, M.D., Ph.D. a Hôpital Hôtel-Dieu de Paris and Hôpital Bichat-Claude Bernard, Paris, France Objective: To determine the effect of myomectomy on infertility and to assess the factors influencing reproductive outcome. Design: Retrospective study. Setting: Tertiary care center. Patient(s): One hundred and three infertile women with uterine leiomyoma who had had infertility 2 years and a follow-up time 12 months were enrolled. Follow-up was complete for 88 patients, including 28 (31.8%) with primary infertility and 44 (50%) with unexplained infertility. The mean ( SD) age of the patients was years. Intervention(s): Laparoscopic myomectomy. Main Outcome Measure(s): Pregnancy rate according to patient and fibroid characteristics. Result(s): Forty-two patients became pregnant (40.7%). The mean ( SD) delay in conception was months. Nearly 80% of the women conceived spontaneously. Of 44 pregnancies in 42 women, 36 live newborns were delivered. No dehiscence of uterine scar occurred. The pregnancy rate was significantly higher in women 35 years of age or 3 years of infertility. Women with unexplained infertility had higher pregnancy rate than did women with multifactorial infertility (P.001). No difference was noted in pregnancy rates according to fibroid characteristics. Conclusion(s): Fertility and pregnancy after laparoscopic myomectomy depend primarily on patient age, duration of infertility before myomectomy, and existence of associated infertility factors. (Fertil Steril 2001; 76: by American Society for Reproductive Medicine.) Key Words: Infertility, laparoscopy myomectomy, leiomyomas, fibroids. Received October 30, 2000; revised and accepted February 16, Reprint requests: Emile Daraï, M.D., Ph.D., Service de Gynécologie, Hôpital Hôtel-Dieu de Paris, 2 rue d Arcole, 75004, Paris, France (FAX: ; emile.darai@htd.ap-hopparis.fr). a Service de Gynécologie, Hôpital Hôtel-Dieu de Paris. b Service de Gynécologie, Hôpital Bichat-Claude Bernard /01/$20.00 PII S (01) Uterine fibroids are the most common tumors of the female genital tract. These benign neoplasms are estimated to occur in 20% to 50% of women, with increased frequency during the later reproductive years (1). A causal relationship between uterine fibroids and infertility has been proposed (2) but not definitively demonstrated. The role of uterine fibroids in infertility was evaluated indirectly by assessment of fertility after myomectomy in women with unexplained infertility. The pregnancy rate ranged from 45% to 64.3% within 1 year of surgery (1 5). This value is higher than that observed in couples with untreated unexplained infertility (6). Infertile women with fibroids undergoing assisted reproductive treatment have lower pregnancy rates than do age-matched women with no fibroid (7). However, the characteristics of infertile patients suitable for myomectomy and of the fibroids, which should be removed, are still controversial. We sought to evaluate the effect of myomectomy as therapy for infertility and to define the factors that influence reproductive success after laparoscopic myomectomy. MATERIALS AND METHODS From January 1990 to October 1998, 298 women with uterine fibroids underwent laparoscopic myomectomy in our department; of these, 121 were infertile. Inclusion criteria were patient age years, infertility 24 months, presence of intramural or subserous 370

2 fibroids 3 cm, 4 myomas, and size of the largest fibroid 10 cm. Fibroids were classified as intramural when more than 50% of the fibroid developed in the uterine wall and subserous when more than 50% of the fibroid was covered by the serosal layer. Exclusion criteria were contraindication to anesthesia for laparoscopy. with only submucous fibroids were excluded because myomectomy was performed by hysteroscopy. with pedunculated subserous fibroids were also excluded. Eighteen of 121 infertile women (14.8%) had laparoconversion. All patients gave fully informed consent and were informed of the possible complications of general anesthesia, laparoscopy, and myomectomy. All women had preoperative infertility evaluation that included ovulation studies, postcoital testing, sonographic examination, hysterosalpingography, and diagnostic hysteroscopy. Sperm characteristics of the partner were also evaluated. with no other explanation for infertility than uterine fibroids and those with multifactorial infertility due to associated infertility factors were included. Forty-four patients (50%) had multifactorial infertility. Most of the patients with multifactorial infertility presented with more than one additional factor; 44 had tubal factor, 13 had mild endometriosis, 12 had male infertility, and 5 had ovulation dysfunction. The duration of infertility ranged from 24 to 120 months (mean, 42 months). All procedures were performed, as reported elsewhere (8). In brief, all myomectomies were performed under general anesthesia. Three stab incisions were made in the suprapubic area: one in the midline of 10 or 12 mm and one in each iliac fossa of 5.5 mm. A 10-mm laparoscope was inserted through an umbilical or supraumbilical incision and connected to a video monitor (Stortz, Tuttlingen, Germany). An incision was made through the uterine wall and pseudocapsule of the myoma was performed according to the location of the fibroids. Traction on the myoma associated with electrodissection allowed cleavage of the leiomyoma. Uterine incision was closed by myometrial and serosal layers of interrupted absorbable sutures of Vicryl, 2-0 or 3-0 caliber (Polyglactine; Ethicon, Neuilly, France). Postoperative fever was defined as body temperature 38 C on two consecutive measurements obtained at least 6 hours apart, excluding the first 24 hours. The incidence of intraoperative and postoperative complications, febrile morbidity, analgesia requirements, and postoperative hospital stay were recorded for all patients. Information on subsequent fertility was obtained from hospital records, physicians, and direct patient reports. Only patients with follow-up of at least 12 months are discussed here. Statistical analysis was performed by using the Student t-test for parametric and nonparametric continuous variables; the 2 test or Fisher exact test was used to assess categorical variables. The log-rank test was used to calculate cumulative pregnancy rates. P.05 was considered statistically significant. RESULTS During the study period, 103 patients underwent myomectomy exclusively by laparoscopy; of these, 15 (12.4%) women were lost during follow-up. Therefore, the study population included 88 patients. Sixty-five women were white (73.8%) and 23 (26.2%) were of African origin. The mean ( SD) age was years (range, years). Twenty-two patients (25.1%) were 40 years, 32 (36.3%) were years, 31 (35.2%) were years and 3 (3.4%) were 30 years. In the full study population, 28 (31.8%) women presented with primary infertility and 44 (50%) presented with unexplained infertility. The mean ( SD) duration of infertility was years (range, 2 10 years). The mean ( SD) number of fibroids per patient was (range, 1 4). Forty-six women (52.3%) had one fibroid, 27 (30.6%) had two fibroids, 13 (14.7%) had three fibroids, and 2 (2.4%) had four fibroids. Forty-two women (47.7%) had two or more uterine fibroids. The mean ( SD) size of the largest fibroid was cm (range, 3 11 cm). Most fibroids (64.7%) were intramural; the remainder were subserosal. The distribution of the locations of the largest fibroid in the uterus was 43 (48.8%) in the posterior wall, 37 (42.2%) in an anterior/fundal location, and 8 (9%) in intraligamentary locations. Hysteroscopy revealed distortion of the uterine cavity in 20.5% of patients. The mean ( SD) operative time was minutes (range, minutes). Opening of the uterine cavity occurred in 3 patients (3.4%). No major complications occurred. No patient needed a blood transfusion during or after surgery. Two complications occurred during the procedure: one case of subcutaneous emphysema and one case of bowel puncture by the Veress needle. Two postoperative complications were noted: one case of fever and one case of phlebitis. The mean ( SD) hospital stay was days (range, 1 10 days). Fertility after laparoscopic myomectomy is shown in Table 1. The mean ( SD) duration of follow-up was months. Forty-two of 103 patients who had laparoscopic myomectomy conceived (40.7%). The pregnancy rate among patients with complete follow-up was 47.7% (42 of 88). Two women conceived twice and 2 women had a twin pregnancy. The mean ( SD) time to conception was months. Nearly 80% of the women conceived spontaneously. Pregnancy outcome is shown in Table 1. Of the 44 pregnancies in 42 women, 36 live newborns were delivered, of which 32 were singletons and 2 were twins. Of the 34 deliveries, 24 (76.5%) were vaginal deliveries. Indications for cesarean deliveries included 4 elective surgery and 6 FERTILITY & STERILITY 371

3 TABLE 1 Pregnancy outcome in women undergoing laparoscopic myomectomy. Characteristic obstetrical indications during labor. No dehiscence of uterine scar was observed. Fertility according to patient characteristics in women undergoing laparoscopic myomectomy for whom follow-up TABLE 2 Factors influencing pregnancy rates after myomectomy. Patient characteristic who conceived (n 42) who did not conceive (n 46) P value Mean follow-up ( SD) (range) (mo) (14 55) (13 45) age 40 y 0 (0) 22 (100) 40 y 42 (63.6) 24 (36.4) y 14 (25.9) 40 (74.1) 35 y 28 (82.4) 6 (17.6).001 Duration of infertility 3 y 6 (15) 34 (85) 3 y 36 (75) 12 (25).001 Type of infertility Unexplained 32 (72.7) 12 (27.3) Multifactorial 10 (22.7) 34 (77.3).001 Primary 14 (50) 15 (50) NS Secondary 28 (46.7) 32 (53.3) Note: Unless otherwise indicated, data are the number (percentage) of patients. NS not significant. Data who conceived 42 Pregnancies 44 Mean delay in conception (range) (mo) (3 15) No. of spontaneous pregnancies 36 Induction of ovulation plus IUI 2 IVF-ET 6 Ectopic pregnancy 1 First-trimester abortion 6 Artificial abortion 2 Termination of pregnancy because of 1 chromosomal abnormalities Dehiscence of uterine scar 0 Live newborn 36 Singleton 32 Twins 2 Vaginal delivery (%) 24/34 (67.6) Adhesions after myomectomy in 12/16 (75) evaluated women (%) Note: Unless otherwise indicated, data are numbers of patients or events. TABLE 3 Fibroid characteristics according to fertility in women undergoing laparoscopic myomectomy. Characteristic who conceived (n 42) was complete is shown in Table 2. All 42 pregnancies were achieved in women 40 years of age. The pregnancy rate was significantly higher in women 35 years of age compared with women 35 years of age. Women with 3 years of infertility duration had significantly higher pregnancy rate than those who had been infertile 3 years. Women with unexplained infertility had higher pregnancy rates than did women with multifactorial infertility (32 vs. 10; P.001). No difference in pregnancy rate was noted between women with primary infertility and those with secondary infertility. Fertility according to fibroid characteristics in women undergoing laparoscopic myomectomy for whom follow-up was complete is shown in Table 3. Pregnancy rates did not differ according to the size of the largest fibroid, the number of fibroids, and the location of the fibroid in the uterus. Among women who underwent laparoscopic myomectomy, 18 had distortion of the uterine cavity by the fibroid and 70 had a normal cavity. The pregnancy rate in women with a distorted cavity was 66.7% compared with 42.8% in women with a normal cavity (P.12). Evaluation of adhesion formation after laparoscopic myomectomy could be done in 16 patients. Evaluation was performed during cesarean deliveries (n 8), elective second-look laparoscopy (n 7), or laparoscopic treatment of ectopic pregnancy (n 1). Pelvic adhesions were seen in 12 of 16 patients. DISCUSSION who did not conceive (n 46) P value Size of fibroid At least one fibroid 5 cm 28 (56) 22 (44) NS No 14 (36.8) 24 (63.2) Number of fibroids 1 26 (56.5) 20 (43.5) NS 2 18 (42.9) 24 (57.1) Location of the largest fibroid Posterior wall 20 (46.5) 23 (53.5) NS Other 22 (48.9) 23 (51.1) Distortion of uterine cavity Yes 12 (66.7) 6 (33.3) 0.12 No 30 (42.8) 40 (57.2) Note: Values are the number (percentage) of patients. NS not significant. Physicians who have female patients with uterine fibroids who want to become pregnant face a clinical quandary 372 Dessolle et al. Fertility after laparoscopic myomectomy Vol. 76, No. 2, August 2001

4 regarding the best management of fibroids. The main argument against conservative myomectomy is the lack of definite evidence of a causal association between uterine fibroids and infertility (1, 3, 9, 10). Concerns remain about potential adverse consequences, such as morbidity, complications, adhesion formation, and increased risk for uterine scar dehiscence, as well as postoperative need for cesarean delivery. However, indirect evidence suggests that the pregnancy rate in women with unexplained infertility is fairly good, and more than half of patients become pregnant after surgery (9 13). Our study supports these findings; the pregnancy rate was relatively high in women with prolonged duration of infertility. Pregnancies were achieved after a relatively short delay in conception ( months), and the rate of spontaneous conception was remarkably high (81.8%). We found that the main factors determining fertility after myomectomy were patient characteristics. Patient age, presence of additional infertility factors, and duration of infertility before surgery are the most important factors. All pregnancies were achieved in women 40 years of age, suggesting the potential role of associated infertility factors such as dysovulation. Rosenfeld (14) observed that adverse prognostic factors for infertility after laparotomic myomectomy included increased patient age, long duration of infertility and large size or high number of fibroids removed. In contrast, we found that fibroid characteristics, including number, size, and location, were not decisive. Our findings agree with those of the meta-analysis by Vercellini et al. (15), who arrived at the same conclusions regarding abdominal myomectomy. Furthermore, we found that the pregnancy rate was higher (but significantly so) among women with fibroids that distorted the uterine cavity than among those with a normal cavity. These results are also in agreement with those of Farhi et al. (16). In contrast, Fauconnier et al. (17) did not find patient age to be related to a lower rate of pregnancy after laparoscopic myomectomy. However, they also found that neither the size of the fibroids nor distortion of the uterine cavity played a role. A possible explanation for these results is that the effect of the fibroid is not only mechanical. Few studies (7, 16, 18) have evaluated the effect of myoma uteri on the pregnancy rate after ART. Assisted reproductive treatment provides a unique setting because such factors as mechanical factors, greater distance for the gametes to travel, position of the cervix, or menometrorrhagia can be excluded as possible causes for infertility. Stovall et al. (18) showed that even after patients with submucosal fibroids are excluded, the presence of fibroids reduces the efficacy of ART. Eldar-Geva et al. (7) compared 106 ART cycles in patients with uterine fibroids with 318 ART cycles in age-matched patients without fibroids and concluded that implantation and pregnancy rates were significantly lower in patients with intramural or submucosal fibroids, even those with no deformation of the uterine cavity. Therefore, if women with unexplained infertility have a better chance of conception after myomectomy and if the main factors in treatment success are patient age and duration of infertility, this conservative operation should not be postponed for too long. In our study, myomectomy was performed exclusively by laparoscopy, a well-established method (8, 19 23). Laparoscopic myomectomy, as well as other laparoscopic procedures, has less morbidity, rapid recovery, and potentially less risk for adhesion formation (24, 25). However, in our limited experience, the rate of postmyomectomy adhesion remains high despite use of the laparoscopic approach. Some of the main concerns after laparoscopic myomectomy are obstetric complications, including uterine rupture during pregnancy and the need for elective cesarean delivery. The few published case reports of this complication occurred during the second trimester (26 30). We observed no scar dehiscence or uterine rupture, and 67.6% of the patients delivered vaginally. However, our sample is too small to permit definitive conclusions about this complication. Our study has limitations. First, it was observational and did not include a control group; moreover, data on postoperative fertility were collected retrospectively. Second, some of the factors studied were closely associated, such as the presence of additional infertility factors and long duration of infertility duration. Third, the outcomes may have been influenced by the fact that the procedures were performed by different operators and that the infertility treatment protocol after myomectomy was not standardized. However, no randomized controlled studies have evaluated the role of myomectomy in the management of infertile women. Thus, the criteria for selecting the patient most likely to benefit from laparoscopic myomectomy must be better defined. On the basis of our experience, we suggest that myomectomy should be restricted to women with unexplained infertility who have intramural fibroids, especially intramural fibroids that distort the uterine cavity. Patient age and the duration of infertility also seem to be important factors that influence the pregnancy rate after myomectomy. In countries that limit the number of IVF attempts, performing myomectomy before the beginning of IVF treatment could be beneficial. Randomized controlled studies are needed to identify more conclusively in whom and when to perform myomectomy. In conclusion, pregnancy rates and obstetric outcomes are relatively good after laparoscopic myomectomy. 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