Long-term follow-up of patients with uterine fibroids after treatment with the LHRH agonist buserelin

Summary. Ten patients with uterine fibroids palpable abdominally were treated with the luteinizing hormone-releasing hormone (LHRH) agonist buserelin, administered intransally, 300 μg three times daily, for 6 months, and were then followed for a further 12 months. Oestrogen levels were markedly reduced in all patients during treatment. At the end of treatment the mean volume reductions were 44·4% (SEM 3·5) for total uterine volume and 57·3% (SEM 7·4) for volume of discrete fibroids as assessed ultrasonically. There was also marked improvement in associated symptoms. After buserelin therapy was stopped, the total uterine and discrete fibroid volumes returned to, or slightly exceeded, pretreatment volumes within 6 months in five patients, and by 12 months in two patients. Three other patients who underwent surgery for their fibroids during the first 4 months after treatment showed regrowth of fibroids to pretreatment size, Four comparable asymptomtic untreated patients showed no significant change in the total uterine or fibroid volume during six monthly ultrasonic assessments. Buserelin therapy may facilitate rather than replace surgery in the management of uterine fibroids.     

Medical treatment of uterine fibroids with the LHRH antagonist: Cetrorelix

A depot preparation of the LHRH-antagonist Cetrorelix was used for the preoperative treatment of 20 premenopausal women with symptomatic uterine fibroids to undergo surgery. In an open, prospective and randomised study, 60 mg of this depot preparation were administered i.m. at the second day of cycle. Patients were randomised for a second dosage of 60 mg or 30 mg to be injected on day 21 or day 28 of treatment according to the degree of estradiols' suppression (< 50 pg/mL). The operation was carried out after six or eight weeks of treatment according to the timing of second dosages administration. Weekly transvaginal sonography as well as MRI before and after Cetrorelix treatment were performed for fibroids volume assessment; 16 patients showed satisfactory suppression of gonadotrophins and sexual steroids. No flare up effect was to be observed. In this group of patients the maximum reduction in fibroids size was of 33.5% at the end of treatment. After 14 days of treatment the reduction was of 31.3%. Within the group of good responders (reduction of fibroids size > 20%) the volume of the biggest fibroid after 14 days of treatment was of 56.7% of the initial assessment. Although MRI showed minor mean shrinkage rates of only 25.4% of the initial volume, these differences in comparison to transvaginal sonography were not statistically significant. The avoidance of any flare up phenomenon by the LHRH-antagonist may explain this fast reduction in size. The basic advantages of this treatment modality are the reduction of treatment time with a fast restoration of the ovarian function. The rate of poor responders may be reduced by improving the galenic preparation.     

Effect of LHRH agonist (buserelin) on pulsatile secretion of LHRH and LH

The LHRH agonist buserelin was administered intranasally to eight patients with endometriosis in doses of 300, 600 or 900 micrograms/day for six months. In all patients buserelin clearly suppressed ovulation. In the patients treated with 900 micrograms/day, estradiol levels declined to less than 30pg/ml, and LH release in response to LHRH testing decreased markedly after 2 months of treatment. A mild decrease in LH release was noted in the premarin test at the end of the treatment. At the end of buserelin treatment baseline levels of plasma LHRH, LHRH pulse amplitude and frequency were not lowered. However, baseline levels of plasma LH and LH pulse amplitude decreased. These results indicate that buserelin may act to decrease pituitary response to LHRH.     

Intranasal buserelin versus surgery in the treatment of uterine leiomyomata: long-term follow-up

Forty-two women with symptomatic uterine myomas, candidates for myomectomy or hysterectomy, were randomized to 6 months' treatment with buserelin 1200 micrograms/day intranasally (n = 22) or immediate surgery (n = 20). After buserelin treatment or operation the patients were followed for at least 12 months. Buserelin was well tolerated, the uterine volume fell from 465 +/- 168 to 273 +/- 88 cm3, and hemoglobin values normalized in all anemic patients. Rapid myoma regrowth was observed in all patients in the buserelin group after treatment withdrawal. Pregnancy occurred during follow-up in one of five buserelin-treated myomectomy candidates. Menorrhagia recurred in eight of 15 buserelin-treated hysterectomy candidates, and a hysterectomy was required but no transfusion was needed. Two women entered natural menopause and were considered cured. In the surgery group all operations were uneventful: three women conceived after myomectomy, whereas four of the patients that underwent hysterectomy required transfusions. Thus buserelin treatment appears to be indicated for infertile patients when surgery is contra-indicated or could cause adhesions, and for hysterectomy candidates in perimenopausal age and/or with secondary anemia.     

Treatment of uterine fibroids with agonist analogs of gonadotropin-releasing hormone

Agonist analogs of GnRH were used to effect a "medical castration" in 14 patients with uterine fibroids, presenting with either an enlarged uterus, recurrent menometrorrhagia, and/or infertility. This study confirms prior reports of a reduction in uterine size and cessation of menometrorrhagia in patients with fibroids following treatment with GnRHa. Of interest, however, was the successful use of GnRHa as either the sole treatment for uterine fibroid-associated infertility, or as a preoperative adjunct in infertility patients scheduled for myomectomy. Three of the five infertility patients in this study achieved intrauterine pregnancies. Further study of the role of GnRHa treatment in infertility patients with uterine fibroids appears warranted.     

Clinical predictors for buserelin acetate treatment of uterine fibroids: a prospective study of 40 women

Buserelin acetate, a luteinizing hormone-releasing hormone agonist, is known to be effective in the shrinkage of uterine fibroids. A prospective trial was undertaken (1) to compare the efficacy of intranasal (IN) and subcutaneous (SC) administration of buserelin acetate and (2) to assess if tumor regression correlated with fibroid size and/or patient age. Forty patients were randomly allocated to receive 6 months of either IN buserelin acetate (n = 21) or SC buserelin acetate (n = 19). Four patients did not complete the study and were excluded from statistical analysis. Fibroid regression occurred in all 36 patients. Overall regression to 66% or less of the initial fibroid volume occurred in 70% of subjects. There was no significant difference in fibroid shrinkage between the two administration routes. A significant positive correlation was found between initial fibroid size and subsequent fibroid regression, with larger tumors being more likely to shrink than smaller fibroids. No correlation was found between the patient's age and the extent of fibroid regression.     

Endoscopic treatment of uterine fibroids

Endoscopic surgery is able to replace most abdominal operations in the surgical treatment of uterine leiomyomas. The use of gonadotrophin hormone-releasing hormone analogues, arterial embolization, hysteroscopy, new techniques of morcellation, laparo-vaginal gasless laparoscopy and laparoscopic mini-laparotomy have enabled the avoidance of laparotomy incisions in most patients. The previous disadvantages of laparoscopy, namely a prolonged operating time, excessive bleeding and inadequate closure, have been overcome. Case and controlled studies have demonstrated the effectiveness of endoscopy in fibroid treatment. The surgical techniques require advanced endoscopic training.     

Doppler assessment of uterine blood flow changes in patients with fibroids receiving the gonadotropin-releasing hormone agonist Buserelin

Uterine arterial blood FVWs were studied by doppler ultrasound in eight patients with large uterine fibroids who were treated with the GnRH agonist Buserelin intranasally for 4 months. At the end of treatment, reductions in the uterine and discrete fibroid volumes were associated with significant increases in the mean RI values for the uterine (P less than 0.01) and fibroid (P less than 0.001) vasculature, thus indicating reduction in blood flow.     

Long-term follow up of uterine artery embolisation--an effective alternative in the treatment of fibroids

OBJECTIVES: To evaluate the long-term efficacy and complications of uterine artery embolisation (UAE) for treatment of symptomatic uterine fibroids. DESIGN: A prospective observational study. SETTING: A district general hospital and two private hospitals in the southeast of England. POPULATION: Women with symptomatic fibroids who had been offered surgical options for treatment. METHODS: Postal questionnaire follow up at 5-7 years to assess long-term clinical effects among women who had undergone UAE. MAIN OUTCOME MEASURES: The questionnaire was subdivided into sections dealing with menstrual flow, amenorrhoea and menopause, fibroid-related symptoms, fertility, vaginal discharge, sexual function, subsequent treatments for fibroids and satisfaction with the procedure. RESULTS: A total of 258 women were identified as being between 5 and 7 years post-UAE and suitable for long-term follow up in October 2004. One hundred seventy-two completed questionnaires were analysed (67% response rate). Seventy-five percent of women still had either a return to normal or an improvement in menstrual flow compared with how they were prior to UAE. More than 80% of fibroid-related symptoms were still resolved or improved. Sixteen percent of women required further treatment for fibroids. Premature menopause directly following UAE occurred in only one woman in the study group. Eighty-eight percent of women were satisfied with the outcome of the procedure at 5-7 years and would choose it again or recommend it to others. CONCLUSIONS: These findings show that UAE is of benefit to women wishing to avoid hysterectomy and it carries a low risk of complications.     

Radiological treatment of symptomatic uterine fibroids

Uterine artery embolization (UAE) is a relatively new alternative treatment for symptomatic fibroids. Recent Level 1 evidence from two major randomized controlled trials has established UAE as a safe and effective alternative to hysterectomy. Technical aspects, choice of embolic agent, safety, contra-indications and complications of the procedure will be reviewed. The available data on the effects on ovarian function, fertility and pregnancy outcomes following UAE will be presented.     

Systematic review of pregnancy outcomes after fertility-preserving treatment of uterine fibroids

The aim of this study was to compare pregnancy outcomes after medical (ulipristal acetate [UPA]), surgical (myomectomy) and radiological (uterine artery embolization [UAE] or thermal ablation) therapy for fibroids in women. A systematic review was conducted and ScienceDirect, PubMed, Web of Science and Cochrane Library databases were thoroughly searched from 2000 to 2018. Only primary research was included with independent extraction of articles by two reviewers, using a standardized form. Data were available on 12 pregnancies after treatment with UPA, 1575 after myomectomy, 424 after UAE and 420 after fibroid ablation. Results after UPA therapy were not included in the statistical analysis owing to the limited number of cases; most were ongoing pregnancies. High rates of successful pregnancy were seen after myomectomy (75.6%) and fibroid ablation (70.5%), whereas pregnancies after UAE had the lowest live birth rates (60.6%) and highest miscarriage rates (27.4%) (both P < 0.001 versus other treatments). In conclusion, myomectomy is associated with better pregnancy outcomes than other fertility-preserving treatments for fibroids. At present, UPA is the only medical treatment for fibroids; however, the evidence on pregnancy outcome is limited. In the absence of randomized controlled trials, these data may be of benefit in advising patients about future pregnancy.     

Treatment of uterine fibroids with implants of gonadotropin-releasing hormone agonist: assessment by hysterography

The effect of a potent, subcutaneously injected gonadotropin-releasing hormone (GnRH analog) (Buserelin, Hoechst, Frankfurt/Main West Germany) on the size of uterine leiomyomas and the uterine cavity area was studied in a group of 20 women. In all patients except 1, the uterine cavity area calculated by hysterosalpingography was decreased, with an average decrease of 35% (from 12.0 +/- 5.4 cm2 to 7.8 +/- 3.3 cm2) by 8 weeks of therapy. Significant decrease was observed in the group of women with initial uterine cavity area greater than 10 cm2. In patients with very large submucous fibroids, myomectomy by hysteroscopy and neodymium:YAG laser was easily performed. Rapid relief of symptoms such as menometrorrhagia permits the restoration of a normal hemoglobin concentration. In conclusion, use of GnRH analog represents an adjunct for preoperative reduction of tumor size and may permit surgical treatment by hysteroscopy.     

Symptom-free interval after triptorelin treatment of uterine fibroids: long-term results.

An increasing number of publications document regression of fibroids under treatment with gonadotropin releasing hormone (GnRH) agonists. However, recurrence after stopping treatment regularly counterbalances its benefit. We now report on 28 patients with intramural myomas, treated with triptorelin for 4-6 months and followed for 42-56 months. During or shortly after treatment, six patients entered menopause. In this group, a volume reduction of 71% was achieved and no surgery was needed thereafter. In 22 premenopausal women, a 64% decrease of uterine volumes was obtained at the end of treatment; the long-term reductive effect was 31%. When compared with initial values, a significant decrease was observed at the end of treatment (p = 0.0001) and of follow-up (p < 0.0005). In 13 (of 22) premenopausal patients, surgery was needed after triptorelin treatment for permanent control of fibroids. The remaining nine patients were free of symptoms after 42-56 months, having uteri in situ. These two groups differ significantly in pretreatment uterine volume (p < 0.001) and in reduction rate after therapy (p < 0.01), both parameters being higher in patients who finally needed surgery. In conclusion, triptorelin treatment is definitely beneficial in perimenopausal women and in nearly half of premenopausal women, in whom hysterectomy can be prevented. In the other half, surgery is necessary, despite significant volume reduction. These results need to be corroborated on larger groups of patients. More research is needed to explain different responses to treatment in premenopausal patients.     

Long-term compliance with follow-up after treatment for cervical intra-epithelial neoplasia

Objective. To assess the level of compliance with follow-up over time after treatment for preinvasive and Stage Ia1 lesions of the cervix. To compare the average interval between visits with the interval prescribed by protocol and to evaluate the use of this difference as a measure of compliance. Design. Retrospective observational study. Setting. London university hospital. Population. Women who received treatment for preinvasive (CINI-III, AIS) or Stage Ia1 cervical lesions. Methods. Attendance data were obtained from hospital-based colposcopy and community-based databases. Main outcome measures. The average interval between the appointments attended by each woman was compared with the planned interval between visits. The time that elapsed since the previous appointment attended was calculated for each visit and correlated with the time since treatment. Results. 1013 women attended 4128 follow-up visits in the colposcopy clinic and in the community. Twenty-two (2.2%) women never attended any post-treatment appointment and 209 (21.0%) of the 991 women who attended at least once, did so on average more than 12 months later than specified by the follow-up protocol. There was a highly significant correlation between the interval since the previous appointment and the time since treatment (Kendall's tau b = 0.529614, two-sided p < 0.0001), showing that compliance deteriorates with increasing time since treatment. Conclusions. Comparing the average interval between attendances with the planned interval prescribed by protocol is a sensitive measure of compliance. Compliance with follow-up deteriorates significantly with time since treatment. This decline in compliance may contribute to the increased risk of invasive disease after treatment.     

子宫肌瘤子宫动脉栓塞术后妊娠情况及影响因素分析

目的:探讨子宫肌瘤患者行子宫动脉栓塞术(UAE)后的妊娠结局,以及肌瘤位置对妊娠率和结局的影响。方法:对行子宫动脉栓塞术的84例有生育要求和497例无生育要求的子宫肌瘤患者进行随访,了解其术后妊娠和产科并发症的发生情况。结果:(1)截止2011年4月,本研究中有50例患者60次妊娠。其中有妊娠要求组共30例39次妊娠,无妊娠要求组共20例21次妊娠。(2)有妊娠要求组妊娠结局为分娩26次(自然分娩9次,剖宫产17次),人工流产4次,自然流产5次,异位妊娠1次,宫内死胎3次(同1人);无妊娠要求组均行人工流产;(2)分娩的26例患者中,发现产科并发症7例26.92%(7/26),其中子痫前期1例3.85%(1/26)、胎盘前置状态1例3.85%(1/26)、早产4例15.38%(4/26)、中央性前置胎盘1例3.85%(1/26);(4)有妊娠要求的单发性肌瘤组(黏膜下、肌壁间、浆膜下、不明)和多发性肌瘤组的妊娠率分别为25.00%、59.09%、62.50%、14.29%和27.58%;单发浆膜下肌瘤组无产科并发症发生,黏膜下子宫肌瘤患者的产科并发症发生率高达75%。结论:子宫肌瘤患者在UAE后可正常妊娠,但自然流产率、胎盘异常等的发生率明显增高,特别是黏膜下和多发性子宫肌瘤患者。