A comparative analysis of the impact of three distinct laparoscopic myomectomy techniques on ovarian reserve: a randomized clinical trial.

This study demonstrates that temporary uterine artery occlusion, permanent uterine artery occlusion, and vasopressin injection during laparoscopic myomectomy have comparable effects on ovarian reserve. These findings enable clinicians to select the most appropriate surgical technique based on surgeon preference and patient-specific factors without adversely impacting ovarian function.

This clinical trial compared three different methods of laparoscopic myomectomy (LM) on ovarian reserve in women with symptomatic uterine leiomyomas. The study was conducted at Shahid Beheshti and Al-Zahra Hospitals in Isfahan, Iran, from January 2024 to July 2024. The research flow diagram based on the CONSORT statement is shown in Fig.  1 . Fig. 1 Research flow diagram based on Consort statement Research flow diagram based on Consort statement Women under 45, referred for LM, with symptomatic uterine leiomyomas, a maximum of three myomas, and individual myoma size smaller than 10 cm were considered for participation. Using G-Power software, a sample size of 54 was calculated to achieve 90% power with a 95% confidence level and a 5% margin of error, considering 10 independent variables. Inclusion criteria were: women under 45 with symptomatic uterine leiomyomas suitable for LM. Exclusion criteria were: other medical conditions affecting ovarian reserve, history of infertility, ovarian pathology, endometriosis, or any other condition potentially impacting ovarian reserve. Participants referred for LM at the two hospitals were screened according to the inclusion/exclusion criteria. Eligible participants were then randomly assigned to one of three treatment groups: TUAO (Temporary Uterine Artery Occlusion): LM performed with temporary occlusion of the uterine arteries. PUAO (Permanent Uterine Artery Occlusion): LM performed with permanent occlusion of the uterine arteries. VPI (Vasopressin Injection): LM performed after injecting 1 mL of vasopressin (20 units/mL) into each myoma before resection. TUAO (Temporary Uterine Artery Occlusion): LM performed with temporary occlusion of the uterine arteries. PUAO (Permanent Uterine Artery Occlusion): LM performed with permanent occlusion of the uterine arteries. VPI (Vasopressin Injection): LM performed after injecting 1 mL of vasopressin (20 units/mL) into each myoma before resection. After identification and eligibility confirmation, potential participants received detailed information about the study objectives, methods, risks, and benefits. Written informed consent was obtained from all participants prior to enrollment. Demographic data, medical history, preoperative and postoperative (3 months) ovarian reserve markers (AMH and Hb), and surgical details (including operative time) were collected. Serum AMH levels were drawn during the early follicular phase (days 2–5 of the menstrual cycle) to standardize measurements and minimize hormonal variability. Hemoglobin levels were measured preoperatively and postoperatively. The primary outcome measures were the changes in AMH and Hb levels from preoperative to three months postoperative. All LM procedures were performed using the Alexis retractor and the laparoscopic-assisted myomectomy (LAM) method. A laparoscope was inserted through small abdominal incisions, and the uterus and fibroids were visualized on a monitor. LigaSure vessel sealer was used for hemostasis in all procedures. The specific interventions for each group were as described above (TUAO, PUAO, VPI). [Optional: You can add more details about the surgical techniques if necessary, but keep it concise and relevant.] Descriptive statistics, Mann–Whitney U test, Chi-Square test, Fisher's exact test, and multiple regression analysis were performed using SPSS version 26. A significance level of p < 0.05 was considered statistically significant.

The mean age of women in TUAO, PUAO, and VPI groups was reported to be 35.17, 35.22, and 35.28 years, respectively. The mean body mass index (BMI) was obtained 25.01 kg/m 2 , 26.46 kg/m 2 and 26.87 kg/m 2 , respectively (Table  1 ). The results showed that there was no statistically significant difference between the mean ages of the different studied groups (P = 0.872). In addition, the results showed that there was no statistically significant difference between the mean BMI (P = 0.542). The diagnosis of uterine fibroids was made based on transvaginal ultrasound and pelvic magnetic resonance imaging (MRI). The results indicated that the number of women whose fibroid diameter was smaller than 5 cm was 1, 2, and 2 women in the TUAO, PUAO, and VPI groups, respectively. In addition, the number of women who had a fibroid diameter of 5–10 cm in the TUAO, PUAO, and VPI groups was 17, 16, and 16, respectively (Table  1 ). The results showed that there was no statistically significant difference between the number of women in the different groups studied in terms of fibroid diameter (P = 0.942). In terms of predominant myoma, the FIGO (International Federation of Gynecology and Obstetrics) grading system was used to classify the fibroids [ 20 ]. The number of FIGO 3–8 in TUAO, PUAO, and VPI groups was reported as 7, 6, and 8, respectively. Besides, the number of hybrid fig 2–5 in TUAO, PUAO, VPI groups was 11, 12 and 10, respectively. The results showed that there was no statistically significant difference in the number of FIGO types in the different studied groups (P = 0.984). In this study, the location of the myoma was also evaluated. The number of women with anterior myoma in TUAO, PUAO, and VPI groups was 4, 5, and 5, respectively (Table  1 ). Also, the number of women with posterior myoma in TUAO, PUAO, and VPI groups was reported as 6, 6, and 7, respectively. The number of women with fundal myoma in these groups was 2, 3 and 3, respectively. In addition, the number of women with lateral lymphoma was reported as 4, 4 and 0 respectively (Table  1 ). Finally, the number of women with cervical myoma in TUAO, PUAO, and VPI groups was 2, 0, and 0, respectively. The results showed that there was no significant statistical difference between the number of women in different groups in terms of the location of the predominant myoma (P = 0.791). The results demonstrated that the mean concentration of Hb before the surgery in TUAO, PUAO, VPI groups was 11.23 g/dL, 11.55 g/dL and 11.67 g/dL, respectively. In addition, the mean concentration of Hb after the operation (3 months) was reported as 10.95 g/dL, 11.31 g/dL and 11.25 g/dL, respectively (Table  2 ). Additionally, the results showed that the mean difference of Hb levels among different groups was not statistically significant (P = 342). Also, no statistically significant difference was reported between the mean Hb levels in different groups (P = 0.567). Moreover, the results showed that the difference in the mean concentration of Hb before and after the surgery of all groups was not statistically significant. The P-value in TUAO, PUAO, and VPI groups before and after operation was 0.36, 0.31, and 0.13, respectively (Table  2 ). Furthermore, the mean serum AMH concentration of women before surgery in TUAO, PUAO, and VPI groups was reported as 3.87 ng/mL, 3.42 ng/mL, and 3.57 ng/mL, respectively. The mean concentration of serum AMH in women after surgery was 3.78 ng/mL, 3.34 ng/mL and 3.48 ng/mL in TUAO, PUAO, and VPI groups, respectively. The results showed that the difference in the mean concentration of AMH among the groups before surgery was not statistically significant (P = 0.234). Besides, the results indicated that the difference in the mean concentration of AMH among the groups after surgery was not statistically significant (P = 0.145). The results indicated that the difference in the mean concentration of AMH before and after the surgery in all three groups was not statistically significant (Table  2 ). In addition, surgery time in TUAO, PUAO, and VPI groups was reported as 120.27, 135.83, and 98.61 min, respectively (Table  2 ). The results showed that the difference in surgery time between the studied groups was not statistically significant (P = 0.357). Table 1 Characteristics of women participating in this study Variables Laparoscopic myomectomy procedure P-value Group 1 TUAO Group 2 PUAO Group 3 VPI Age 35.17 ± 4.10 35.22 ± 4.13 35.28 ± 5.59 0.872 BMI 25.01 ± 6.60 26.46 ± 1.74 26.87 ± 2.45 0.542 Parity 0 11 0 11 0.000 1 4 6 5 2 3 8 2 3 0 4 0 Maximum diameter of the largest myoma (cm)  < 5 cm 1 2 2 0.942 5–10 cm 17 16 16 Dominant myoma FIGO type 3–8 7 6 8 0.984 Hybrid ( FIGO type 2–5) 11 12 10 Location of dominant myoma Anterior 4 5 5 0.791 Posterior 6 6 7 Fundal 2 3 3 Lateral 4 4 0 Cervix 2 0 0 International Federation of Gynecology and Obstetrics (FIGO) grading. Fibroid types range from 0 to 8: 0 = pedunculated (intracavitary); 1 = submucosal (< 50% intramural); 2 = submucosal (≥ 50% intramural); 3 = contact with endometrium (100% intramural); 4 = intramural; 5 = subserosal (≥ 50% intramural); 6 = subserosal (< 50% intramural); 7 = subserosal (pedunculated); and 8 = other (cervical, parasitic). Where two numbers are given (2–5), the first number pertains to the relationship with the endometrium, and the second with the serosa, so 2–5 is both submucosal and subserosal, with less than half of its diameter in the endometrial and peritoneal cavities respectively [ 21 ]. Hybrid is between a submucous and an intramural uterine leiomyomas (ULs) Chi-Square test Table 2 The HB changes, ovarian reserve markers levels pre and post operation and the surgery time of the women Variable Laparoscopic myomectomy procedure P-value Group 1 TUAO Group 2 PUAO Group 3 VPI Hb ( g/dL ) Pre operation 11.23 ± 1.12 11.55 ± 1.43 11.67 ± 1.56 0.342 Post operation 10.95 ± 0.98 11.31 ± 2.32 11.25 ± 1.67 0.567 P-value 0.36 0.31 0.13 – AMH ( ng/mL ) Pre operation 3.87 ± 1.19 3.42 ± 1.38 3.57 ± 2.23 0.234 Post operation 3.78 ± 1.08 3.34 ± 1.50 3.48 ± 1.06 0.145 P-value 0.27 0.12 0. 29 – Surgery or operation time (min) 120.27 ± 32.09 135.83 ± 40.81 98.61 ± 28.83 0.357 Mann–Whitney U test Characteristics of women participating in this study International Federation of Gynecology and Obstetrics (FIGO) grading. Fibroid types range from 0 to 8: 0 = pedunculated (intracavitary); 1 = submucosal (< 50% intramural); 2 = submucosal (≥ 50% intramural); 3 = contact with endometrium (100% intramural); 4 = intramural; 5 = subserosal (≥ 50% intramural); 6 = subserosal (< 50% intramural); 7 = subserosal (pedunculated); and 8 = other (cervical, parasitic). Where two numbers are given (2–5), the first number pertains to the relationship with the endometrium, and the second with the serosa, so 2–5 is both submucosal and subserosal, with less than half of its diameter in the endometrial and peritoneal cavities respectively [ 21 ]. Hybrid is between a submucous and an intramural uterine leiomyomas (ULs) Chi-Square test The HB changes, ovarian reserve markers levels pre and post operation and the surgery time of the women Mann–Whitney U test

This study revealed that TUAO, PUAO and VPI laparoscopic myomectomy techniques had similar effects on ovarian reserve as indicated by hemoglobin and AMH concentrations. The results showed that these techniques were equally effective in terms of surgical efficiency and did not significantly affect key parameters such as hemoglobin levels and AMH concentration. Therefore, physicians can choose any of these techniques based on their preference and expertise without compromising ovarian reserve. However, further studies with larger sample sizes and longer follow-up periods are recommended to confirm these results. Future perspectives for this study include potential implications for clinicians in choosing the most appropriate surgical approach for myomectomy in patients who wish to preserve their fertility. The results could also lead to further research on the long-term effects of different myomectomy techniques on ovarian reserve and fertility outcomes. The strengths of this study included its randomized clinical trial design, which is considered the gold standard for determining causal relationships. The inclusion of measurement of AMH levels as a marker of ovarian reserve was also a strength, as it provided objective data on the effect of different techniques. Study weaknesses include the relatively small sample size, which may limit the statistical power to detect subtle differences between the groups. The study's findings may also have limited generalizability to different populations or surgical settings due to the specific characteristics of the participants and the hospitals where the study was conducted. Potential confounding variables that were not controlled for in the analysis could also influence the results. Additionally, the lack of long-term follow-up restricts our ability to assess the lasting effects of the different LM techniques on ovarian reserve. Finally, potential variations in surgical skill and technique across the two centers could have introduced variability in the outcomes. The corresponding author (Safoura Rouholamin) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. All authors have read and approved the final version of the manuscript. The corresponding author had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

In this study, the impact of three distinct laparoscopic myomectomy techniques on ovarian reserve was assessed through various parameters such as age, BMI, fibroid characteristics, hemoglobin concentrations, AMH concentrations, and surgery time. This study was unique because it compared the TUAO, PUAO, and VPI methods. The results showed that there were no significant differences in age, BMI, fibroid characteristics, and operation time among the three groups, indicating that the groups were well-matched at baseline. One of the key results of this study was the evaluation of hemoglobin concentrations before and after the operation. The results indicated that there were no significant differences in hemoglobin concentrations before and after the operation in all three groups. This suggests that the laparoscopic myomectomy techniques did not have a significant impact on hemoglobin levels, which is an important indicator of postoperative recovery and risk of complications. Another important parameter assessed in this study was the AMH concentrations before and after the operation. The results demonstrated that there were no significant differences in AMH concentrations before the operation among the three groups. However, there were slight decreases in AMH concentrations after the operation in all three groups, although these differences were not statistically significant. The results also showed that the biggest difference in Hb level before and after the operation was in the VPI technique. In addition, the greatest difference in AMH level before and after the operation was observed in the PUAO technique. However, none of these differences were statistically significant. This indicated that the laparoscopic myomectomy techniques used in this study had a minimal impact on ovarian reserve. The results of the study revealed that the three laparoscopic myomectomy techniques were equally effective in terms of surgical efficiency. Studies on the impact of LM on ovarian reserve are limited and inconclusive. Some studies suggested that LM may have a negative impact on ovarian reserve, while others showed no significant effect. In a study, Qu et al. showed that in the short-term follow-up, no significant effect on ovarian reserve was found in myoma patients who underwent laparoscopic uterine artery occlusion (LUAO) [ 22 ]. The results obtained from their study confirmed the results of the present study. Cho and Kyung also reported AMH0 (reoperation), AMH1 (7 days), AMH2 (2 months), and AMH3 (6 months) were significantly higher in the LM group than in the LH group (p = 0.012, 0.001, 0.001, and 0.015, respectively). The results of their study showed that serum AMH levels decreased significantly directly after LH, which indicated that LH had adverse effects on ovarian reserve. Also, mid-term follow-up showed that the damaged ovarian reserve in women who underwent LH may be partially restored at 6 months [ 23 ]. The results of their study, like this study, showed that in the LM method, the concentration of hemoglobin after the operation did not change significantly compared to before the operation. Furthermore, Aharon et al. revealed a significant decline in mean serum AMH levels in the open myomectomy group at 2 weeks after surgery compared with minimally invasive myomectomy (mean change − 0.46 ng/mL, 95% CI − 0.69 to − 0.25 ng/mL, P  < 0.001). Their results showed that in the minimally invasive myomectomy group, no significant differences in mean AMH levels were detected between baseline and any postoperative time point [ 14 ]. The results of their study, like the present study, showed that in closed myomectomy, the changes in AMH levels are not statistically significant. Although, Diab et al. showed that open myomectomy had no significant effect on ovarian reserve parameters such as antral follicle count (AFC) and AMH [ 18 ]. This shows that the time of measuring ovarian reserve markers has an effect on the concentration of these parameters such as Hb and AMH. For example, studies have shown that levels of AMH can vary throughout the menstrual cycle, with the highest levels typically seen in the early follicular phase (days 2–4 of the cycle) and the lowest levels in the late luteal phase (days 18–28) [ 24 ]. Additionally, AMH levels have been shown to decrease with age, so it is important to take into consideration the age of the individual when interpreting AMH results [ 25 ]. Similarly, Hb levels can also fluctuate throughout the menstrual cycle, with levels typically being lower during the menstrual phase and higher during the follicular phase. Moreover, factors such as iron deficiency or blood loss can affect Hb levels, so it is important to consider these factors when interpreting Hb results [ 26 , 27 ]. However, Mube et al. reported that there was no statistically significant change in AMH levels and there was no significant relationship between blood loss and tourniquet time and AMH after open abdominal myomectomy. Their results showed that the use of uterine tourniquet and blood loss during open myomectomy did not affect ovarian reserve [ 17 ]. In this study, operation time was also evaluated, and the results showed that there were no significant differences in operation time among the three groups. According to the obtained results, the longest and shortest operation time was related to PUAO and VPI methods, respectively. Albarzi et al. revealed that the mean operation time and blood loss for the interventional group was 112 ± 18 min and 173 ± 91 mL and for the control group was 95 ± 14 min and 402 ± 131 mL, respectively. The difference in these two groups was statistically significant. The results of this study highlighted the superiority of laparoscopic uterine artery ligation combined with myomectomy in the treatment of symptomatic myomas [ 19 ]. The operation time is typically shorter in TUAO compared to the PUAO and VPI methods. TUAO involves temporarily occluding the uterine arteries during the surgery to reduce blood loss, while PUAO involves permanent occlusion of the arteries. VPI involves the injection of vasopressin to constrict blood vessels and reduce bleeding during the procedure. In general, TUAO is associated with a shorter operation time because it allows for better visualization of the surgical field and reduces blood loss, making the procedure more efficient. PUAO may take longer due to the permanent nature of the artery occlusion, which requires more precise surgical techniques. VPI may also prolong the operation time due to the time needed for the vasopressin to take effect and reduce bleeding [ 28 ]. In general, the results of the present study were different from the results of these studies regarding the effect of different surgical methods on ovarian reserve. The current study focused on the effect of different surgical procedures on various parameters including fibroid size, myoma grading, myoma location, Hb and AMH levels. The results demonstrated no significant differences in these parameters among the different surgical groups. In contrast, the studies by Cho and Kyung, Aharon et al., Mube et al., and Alborzi et al. specifically evaluated the impact of myomectomy or uterine artery occlusion on ovarian reserve through changes in AMH levels and AFC values [ 14 , 17 , 19 , 23 ]. The current study did not find any significant differences in Hb levels, AMH levels, operation times, or other parameters among the surgical groups. In contrast, the studies by Aharon et al., Farag et al., and Diab et al. reported changes in AMH levels postoperatively, with some studies showing a decline in AMH levels after open myomectomy but not after minimally invasive myomectomy [ 14 , 16 , 18 ]. The current study included various surgical procedures and compared their impact on fibroid size, myoma grading, myoma location, hemoglobin concentration, and AMH levels, while the given studies focused primarily on myomectomy or uterine artery occlusion and their effects on ovarian reserve. Ovarian reserve refers to the number and quality of a woman's eggs that are available for fertilization. It represents a woman's reproductive potential and can indicate her chances of conceiving naturally or through assisted reproductive technologies such as in vitro fertilization (IVF). Ovarian reserve is typically determined through various tests such as blood tests for hormonal levels (such as follicle-stimulating hormone, AMH, and estradiol), ultrasounds to count the number of follicles in the ovaries, and sometimes a clomiphene citrate challenge test. A low ovarian reserve can indicate a decrease in fertility and may suggest that a woman is approaching menopause [ 29 , 30 ]. Uterine leiomyomas, also known as uterine fibroids, are non-cancerous growths that develop in or on the uterus. Research suggests that uterine leiomyomas may have an impact on ovarian reserve, which refers to the number and quality of a woman's eggs [ 31 ]. One way in which uterine leiomyomas can affect ovarian reserve is through compression of the ovaries. Large fibroids that grow in close proximity to the ovaries can put pressure on them, potentially affecting blood flow and hormone production. This can lead to a decrease in ovarian function and a reduction in egg quality. Additionally, the presence of uterine fibroids can disrupt the normal hormonal balance in the body, which can also negatively impact ovarian function [ 32 ]. Imbalances in hormones such as estrogen and progesterone can interfere with the process of ovulation and egg development. Furthermore, the surgical removal of uterine fibroids, particularly through procedures like myomectomy, can sometimes result in damage to the ovaries or their blood supply. This can potentially reduce ovarian reserve and impact a woman's fertility [ 33 ]. Laparoscopic myomectomy is a minimally invasive surgical procedure used to remove uterine leiomyomas. There are different methods of laparoscopic myomectomy, including the intramural myomectomy, subserosal myomectomy, and pedunculated myomectomy. Studies have shown that laparoscopic myomectomy, regardless of the method used, can have varying effects on ovarian reserve [ 34 , 35 ]. Some studies have suggested that laparoscopic myomectomy may result in a temporary decrease in ovarian reserve, potentially due to the surgical trauma and disruption of blood supply to the ovaries during the procedure [ 36 ]. However, other studies have shown that laparoscopic myomectomy does not significantly impact ovarian reserve in women, especially when performed by experienced surgeons using minimally invasive techniques [ 37 ]. Therefore, for women considering laparoscopic myomectomy, it is important to be aware of the potential effects on ovarian reserve and to evaluate the risks and benefits of the procedure.

Uterine leiomyomas, also known as uterine fibroids, are noncancerous growths that develop in the muscle tissue of the uterus. They are very common, with up to 70–80% of women developing fibroids by the age of 50 [ 1 ]. While many women with fibroids do not experience any symptoms, some may have heavy menstrual bleeding, painful periods, pelvic pressure or pain, frequent urination, or difficulty emptying the bladder [ 2 ]. Uterine fibroids can vary in size, number, and location, and in some cases, they can cause complications such as infertility, miscarriage, or problems during pregnancy and delivery. Treatment options for fibroids depend on the size, location, and severity of symptoms, and may include medication, noninvasive procedures, or surgery [ 3 , 4 ]. Laparoscopic myomectomy (LM) and laparoscopic assisted myomectomy (LAM) are minimally invasive surgical procedures that involves removing fibroids from the uterus through small incisions in the abdomen. There are three main types of LM surgery: conventional laparoscopic myomectomy, myomectomy with morcellation, and myomectomy with enucleation [ 5 , 6 ]. Conventional laparoscopic myomectomy and LAM involves removal of intact fibroids from the uterus without the use of an electric morcellator. This technique is considered safe and effective, but may be more time-consuming and challenging [ 7 ]. On the other hand, laparoscopic myomectomy with morcellation involves dividing the fibroids into smaller pieces for removal. While this technique is faster and easier, there are concerns about the potential spread of uterine tissue into the abdominal cavity. [ 8 , 9 ]. Each of these techniques has its own advantages and disadvantages. For example, conventional laparoscopic myomectomy may be associated with a lower risk of tissue dissemination, but may require a longer operative time [ 10 ]. Laparoscopic myomectomy with enucleation may provide a balance between other techniques [ 11 , 12 ]. Global organizations such as the American College of Obstetricians and Gynecologists (ACOG) and the Society of Gynecologic Surgeons (SGS) have issued guidelines on the management of uterine fibroids, including the use of minimally invasive surgical techniques such as LM. However, there is still debate among experts about the best technique for performing LM [ 13 ]. Studies on the impact of LM on ovarian reserve are limited and inconclusive. Some studies suggest that LM may have a negative impact on ovarian reserve, while others show no significant effect. In a study, Aharon et al. evaluated the effect of open and minimally invasive myomectomy on ovarian reserve changes as measured by serum levels of anti-Müllerian hormone (AMH). The results revealed a significant decline in mean serum AMH levels in the open myomectomy group and also no significant differences in mean AMH levels were detected between baseline and any postoperative time point [ 14 ]. Similarly, Shi, Xiaolong et al. evaluated the effect of laparoscopic surgery in the treatment of benign female diseases on ovarian reserve. The results indicated that these 4 laparoscopic surgeries all decreased the AMH level one month after the operation [ 15 ]. Moreover, Farag et al. investigated the effect of open myomectomy on ovarian reserve. The results showed that there were no significant changes in AMH and AFC values after the operation [ 16 ]. Mube et al. also evaluated the effect of uterine artery occlusion with tourniquet during open myomectomy on ovarian reserve using serial antimüllerian hormone (AMH) measurements. The results demonstrated that there was no statistically significant change in AMH levels and there was no significant relationship between blood loss and tourniquet time and AMH after open abdominal myomectomy [ 17 ]. Further, Diab et al. investigated the effect of open myomectomy on ovarian reserve in women of reproductive age. The results of their study showed that open myomectomy had no significant effect on ovarian reserve parameters [ 18 ]. In Iran, Albarzi et al. also investigated the effectiveness of uterine artery ligation before laparoscopic myomectomy compared to myomectomy alone in a prospective controlled clinical trial. The results of this study revealed the superiority of laparoscopic uterine artery ligation combined with myomectomy in the treatment of symptomatic myomas [ 19 ]. Due to the lack of consensus in the literature, there is a need for further research to clarify the effects of LM on ovarian reserve. Therefore, the aim of this study was to compare the effects of three different methods of LM on ovarian reserve in women with symptomatic uterine fibroids.