Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata. Treatment with a gonadotrophin releasing hormone agonist before hysterectomy for leiomyomas: results of a multicentre, randomised controlled trial. Gonadotropin-releasing hormone agonist use before hysterectomy. [Preoperative management of uterine leiomyomatosis using pituitary gonadotropin-releasing hormone analogues]. Treatment with the gonadotrophin releasing hormone-agonist goserelin before hysterectomy for uterine fibroids. Short-term postoperative GnRH analogue or danazol treatment after conservative surgery for stage III or IV endometriosis before ovarian stimulation: a prospective, randomized study. A comparative randomized trial to assess the impact of oral contraceptive pretreatment on follicular growth and hormone profiles in GnRH antagonist-treated patients. Post-operative GnRH analogue treatment after conservative surgery for symptomatic endometriosis stage III-IV: a randomized controlled trial. Treatment with GnRH agonists before myomectomy and the risk of short-term myoma recurrence.
To determine whether pre-operative treatment with gonadotrophin-releasing hormone (GnRH) analogue may have a beneficial effect on surgery outcome, 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy (TAH), were randomly divided into a study group (n = 29) and a control group (n = 24). The study group of patients were treated by an i.m. injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery. The control group had no pre-operative treatment. Haemoglobin concentration and oestradiol, follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery, and at surgery. The duration of surgery was shorter in the study group (49 versus 70 min in the hysterectomy group) and intra-operative blood loss was less (208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies). Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery, and diminishing the intra-operative blood loss in surgery for fibroid uteri. Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri. To ascertain whether uterine shrinkage induced by a gonadotrophin releasing hormone agonist before hysterectomy for fibroids increases the possibility of a vaginal procedure.
                A multicentre, prospective, randomised, controlled study.
                One hundred and twenty-seven premenopausal women with a uterine volume of 12 to 16 gestational weeks.
                Twelve weeks of triptorelin depot treatment before hysterectomy or immediate surgery.
                Number of vaginal and abdominal hysterectomies, operating time, blood loss, degree of difficulty of the procedure, perioperative serum haemoglobin and haematocrit levels, hospital stay, and patients' overall satisfaction with treatment.
                After randomisation, four women withdrew from the study, leaving 60 women in the triptorelin arm and 63 in the immediate surgery arm. At baseline evaluation a vaginal hysterectomy was indicated in seven women allocated to pre-operative medical therapy (12%), and in 10 of those allocated to immediate surgery (16%). Clinical assessment after the 12-week GnRH agonist course showed that abdominal hysterectomy was no longer indicated in 25/53 women (47%) as a vaginal procedure appeared appropriate. Thus the overall rate of indication for a vaginal procedure in the pre-operative medical treatment arm was 32/60 cases (53%), with a between-group difference of 37% (95% CI, 26% to 51%; chi2(1) = 19.18, P < 0.0001; OR 6.06; 95% CI, 2.60 to 14.10). Pre- and post-operative serum haemoglobin and haematocrit levels were significantly higher in the GnRH agonist than in the immediate surgery arm. No appreciable difference was observed between the groups in the other intra- and post-operative variables, including patients' satisfaction.
                Pre-operative GnRH agonist therapy increased the rate of vaginal hysterectomy in selected women with fibroids and uterine volume of 12 to 16 gestational weeks. Our purpose was to compare the effects of leuprolide acetate in patients with symptomatic uterine leiomyoma before hysterectomy.
                Group I (n = 90) included patients with a pretreatment uterine size of 14 to 18 gestational weeks and group II (n = 60) included patients with uteri > 18 weeks' gestational size. Patients in both groups were randomized to either immediate hysterectomy or 2 months of preoperative gonadotropin-releasing hormone agonist.
                All patients in the two groups with a pretreatment hemoglobin < 11.0 gm/dl randomized to agonist had a significant (p < 0.05) increase (> or = 1.5 gm/dl) in hemoglobin level. Patients in group I who received preoperative agonist were more likely to undergo vaginal hysterectomy (80% vs 13%, p < 0.05) than were patients who did not receive preoperative agonist. Patients undergoing vaginal hysterectomy had a shorter hospital stay, decreased operative blood loss, and a shorter convalescence period than did those undergoing abdominal hysterectomy. In group II, in spite of a mean uterine volume reduction of 51.3%, intraoperative morbidity, operative blood loss, hospital stay, and postoperative convalescence period did not differ between treatment arms.
                The preoperative administration of gonadotropin-releasing hormone agonist in patients with a uterus of 14 to 18 weeks' size increases the use of vaginal hysterectomy, decreases intraoperative blood loss, and shortens hospital stay and convalescence. Preoperative gonadotropin-releasing hormone agonist for patients with a preoperative hemoglobin < 11.0 gm/dl reduces the risk of preoperative transfusion. Preoperative gonadotropin-releasing hormone use in the nonanemic patient with a uterine size > or = 18 weeks' gestational size doses not appear to lower operative morbidity. Uterine leiomyomatosis shows a frequency from 25 to 30% in reproductive age women. Traditional treatment is hysterectomy or myomectomy independently from fertility wishes of the woman. Its growth has been associated to estrogenic activity. Because of this, several substances have been used to diminish tumour size, pre-operatively. The use of analogues of liberating hormone of hypophysiary gonadotropins (GnRH), given to favor surgical technique, to diminish trans-operative bleeding and to avoid blood transfusions. Clinical efficiency of the use of nafarelin acetate in women with uterine leyomiomatosis, pre-operatively during three months, was studied in this paper. The study was prospective, comparative, blind and with longitudinal measurements. Twenty eight women were included. Group I (n = 13) and Group II (n = 15) control without treatment. Observation units included FSH, LH, E2, BHC, HCT, USG basal, 30, 60, 90 days. Results showed a diminution of more than 80% of the initial uterine volume, and of 30% of the myomas independently measured. Side effects, tolerance and efficacy of the used compound, are mentioned. To investigate the effect of the gonadotrophin releasing hormone (GnRH)-agonist goserelin, given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata, on the pre-operative symptoms, difficulty of operation and operative blood loss.
                Randomised placebo-controlled study.
                Patients were recruited from the gynaecological outpatient departments from hospitals in Edinburgh, Glasgow and Newcastle.
                Seventy-one premenopausal women with uterine leiomyomata who were on the waiting list for hysterectomy.
                After the presence of leiomyomata was confirmed using ultrasonography, the women were randomised to receive either the GnRH-agonist goserelin by monthly subcutaneous injection or a sham injection for three months prior to operation. At the monthly visits, patients were asked about treatment related symptoms, fibroid related symptoms, and their bleeding patterns. Blood was taken for haematological assessment.
                Haemoglobin concentrations at recruitment, at operation and post-operatively, pre-operative symptoms, operative difficulty and blood loss and post-operative complications.
                Treatment with goserelin induced amenorrhoea in over 80% of the women, and this was associated with a significant rise in haemoglobin level. At the time of operation, fibroid related symptoms were less in the goserelin group than in the placebo group. The hysterectomy was technically easier and the median (range) operative blood loss was significantly lower in the goserelin group compared with the placebo group (187 (60-600) ml vs 308 (118-1000) ml respectively; P < 0.05, Wilcoxon signed rank test). There was no difference between the two groups in the duration of hospital stay or the frequency of post-operative complications. The fibroids were smaller at the time of operation in the goserelin group, and more women treated with goserelin were able to have their operations through a transverse incision.
                This study demonstrates the benefits of goserelin in women having total abdominal hysterectomy for uterine leiomyomata. To assess the effect of short-term use of a gonadotropin releasing hormone (GnRH) analogue for 3 months before ovarian stimulation in patients with stage III and IV endometriosis after conservative surgery.
                Eleven patients were randomly selected to receive intramuscular injections of GnRH analogue, leuprolide acetate (3.75 mg), every 28 days, or 400 mg danazol orally 2 times per day for 3 months before ovarian stimulation after conservative laparoscopic or laparotomy surgeryfor stage III and IV symptomatic endometriosis (group 1), as compared with 30 patients who had received no postoperative treatment with GnRH analogue or danazol but underwent ovarian stimulation immediately after thefirst menses within 3 months postoperatively (group 2).
                Although the number of oocytes retrieved and number of embryos per cycle were significantly higher in group 1, the pregnancy rate per cycle in group 1 was not significantly different from that in group 2 (18% vs. 20%). The cumulative pregnancy rate at 12 months was 54.5% and 56.7% in group 1 and group 2, respectively. With regard to recurrence of disease after 24 months of follow-up, group 2 had a statistically significantly higher recurrence rate (13.3%) than did group 1 (0%).
                Short-term use of GnRH analogue before ovarian stimulation in women with stage III or IV endometriosis confers no definite benefits on pregnancy rates per cycle when compared with patients who received ovarian stimulation within 3 months after conservative surgery. This randomized controlled trial was designed to assess the impact of oral contraceptive (OC) scheduling with a GnRH antagonist (ganirelix) regimen on the ovarian response of women undergoing recombinant FSH (rFSH) stimulation for IVF, compared with a non-scheduled ganirelix regimen and a long GnRH agonist (nafarelin) protocol.
                A total of 110 women was treated with an OC and ganirelix, 111 with ganirelix alone and 111 with nafarelin. The OC (containing 30 microg ethinylestradiol/150 microg desogestrel) was taken for 14-28 days and stopped 2 days prior to the start of rFSH treatment. Primary efficiency parameters were the number of cumulus-oocyte complexes (per attempt) and the number of grade 1 or 2 embryos (per attempt).
                In terms of follicular growth and hormone profiles, the OC-scheduled antagonist regimen mimicked the agonist regimen rather than the (non-scheduled) GnRH antagonist regimen. In the OC-scheduled GnRH antagonist group and the nafarelin group (versus the non-scheduled antagonist group), pituitary suppression was more profound at the start of stimulation (P < or = 0.001), there was a slower start of follicular growth (P < or = 0.001), longer stimulation was required (11.7 and 10.3 days respectively versus 9.4; P < or = 0.001), and more rFSH was used (2667 and 2222 IU versus 1966 IU; P < or = 0.001). In the three groups, the number of oocytes was similar (13.1, 12.9 and 11.5 respectively; not significant) as well as the number of good quality embryos (5.1, 5.7 and 5.0 respectively; not significant).
                OC treatment prior to the rFSH/ganirelix regimen can be successfully applied to schedule patients, although more days of stimulation and more rFSH are required than with a non-scheduled GnRH antagonist regimen. In order to decrease endometriosis recurrence after surgical therapy, it has been proposed to use a post-surgical oestrogen-lowering medical treatment. Results from previous trials on this topic are contradictory.
                A total of 89 women were randomized, by computer-generated list, after laparoscopic conservative surgery for symptomatic endometriosis stage III-IV to receive monthly i.m. injections of gonadotrophin-releasing hormone (GnRH) analogue, leuprolide acetate depot (3.75 mg) for 3 months (n = 44) or to an expectant management (n = 45). All patients were followed up every 6 months for evaluation of pain symptoms, fertility and objective disease recurrence.
                During the follow-up, which ranged from 6-36 months, five (33%) of the 15 women who wanted children and who were allocated the GnRH analogue and six (40%) of the 15 given no treatment became pregnant (not significant). Moderate/severe pelvic pain recurred during the follow-up in 10 (23%) of the women allocated the GnRH analogue and 11 (24%) of those allocated no treatment; the cumulative pain recurrence rates at 18 months were 23 and 29% respectively (not significant). Four women (9%) treated with GnRH analogue and four women (9%) who received no treatment had objective disease recurrence as demonstrated by gynaecological examination and/or pelvic ultrasonography.
                This study does not support the routine post-operative use of a 3 month course of GnRH analogue in women with symptomatic endometriosis stage III-IV. Twenty-four women with symptomatic multiple uterine myomas were allocated randomly to treatment with buserelin, 1200 micrograms/day intranasally, for 3 months followed by myomectomy (n = 8) or to immediate myomectomy (n = 16). Pre-operative treatment with buserelin reduced the mean uterine volume from 432 (SD 165) to 242 (SD 82) ml (P less than 0.01) but intra-operative blood loss and postoperative morbidity were not significantly less in this group. Six months after operation, pelvic examination was normal in all the patients. However, ultrasonography with transvaginal probe demonstrated the presence of myomas of less than 1.5 cm in five women (63%) treated pre-operatively with the analogue and in two women (13%) who underwent immediate surgery (P less than 0.05). Induction of a period of hypo-oestrogenism before myomectomy seems to favour short-term recurrence of uterine myomas, limiting the efficacy of surgery.
The use of GnRH analogues for 3 to 4 months prior to fibroid surgery reduce both uterine volume and fibroid size. They are beneficial in the correction of pre-operative iron deficiency anaemia, if present, and reduce intra-operative blood loss. If uterine size is such that a mid-line incision is planned, this can be avoided in many women with the use of GnRH analogues. For patients undergoing hysterectomy, a vaginal procedure is more likely following the use of these agents.