A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy.

OBJECTIVE: To compare single dose systemic methotrexate (50 mg/m2) with laparoscopic surgery for the treatment of unruptured tubal pregnancy. DESIGN: An open, pragmatic, prospective randomised trial. SETTING: Departments of obstetrics and gynaecology at three hospitals in Auckland, New Zealand. PARTICIPANTS: Clinically stable women with an unruptured tubal pregnancy diagnosed by transvaginal ultrasound and quantitative serum beta-hCG measurement. Inclusion criteria included a serum beta-hCG concentration < 5,000 IU/L, and a tubal pregnancy of < 3.5 cm diameter. MAIN OUTCOME MEASURES: Treatment success, physical and psychological functioning, side effects, and subsequent ipsilateral tubal patency. RESULTS: Two hundred and eighteen women with ectopic pregnancies were seen at the three hospitals. 79 women (36% eligibility rate) were eligible for trial entry and 62 women (78% recruitment rate) were recruited. Twenty-six of the 28 women (93%) randomised to laparoscopic surgery required no further treatment, compared with 22 of the 34 women (65%) randomised to methotrexate (95% CI of difference in success rate 10 - 47%; P < 0.01). Two women (7%) in the laparoscopic surgery group had persistent trophoblast. Nine women (26%) in the methotrexate group required more than one dose of methotrexate and five women (15%) underwent laparoscopy during follow up. In the laparoscopy group three women (11%) had negative laparoscopies and two women (7%) had were found to have a ruptured fallopian tube at the time of surgery. Women treated with methotrexate had significantly better objective physical functioning scores but there were no differences in any other psychological outcomes. Women treated with methotrexate experienced greater and more prolonged vaginal bleeding. The likelihood of methotrexate treatment failure was greater at higher serum beta-hCG concentrations. Ipsilateral tubal patency rates were similar in each group. CONCLUSION: This trial shows that in the treatment of tubal pregnancy single dose systemic methotrexate is a less effective treatment than laparoscopic salpingotomy. It is well tolerated, but should only be offered as an alternative to surgery to women who have mild symptoms and present at low serum beta-hCG concentrations. In our population this likely to be no more than a quarter of women presenting with a tubal pregnancy.

An economic evaluation of single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured ectopic pregnancy.

OBJECTIVE: To compare the direct and indirect costs of single dose systemic methotrexate with laparoscopic surgery for the treatment of unruptured ectopic pregnancy. DESIGN: A cost minimisation study undertaken alongside a randomised trial. SETTING: Departments of Obstetrics and Gynaecology in three hospitals in Auckland, New Zealand. PARTICIPANTS: Sixty-two women with an ectopic pregnancy randomised to treatment with either a single dose of methotrexate (50 mg/m2) or laparoscopic surgery. MAIN OUTCOME MEASURES: Direct and indirect costs based on the results of the randomised trial. RESULTS: Direct costs per case were significantly lower in the methotrexate group (mean $NZ 1,470) than in the laparoscopy group (mean $NZ 3,083) with a mean difference of $NZ 1,613 (95% CI $NZ 1,166 - $NZ 2,061). These significant differences existed under a wide range of alternative assumptions about unit costs. The difference in direct costs in favour of methotrexate was greatest for women presenting with low pretreatment serum beta-hCG concentrations. Mean indirect costs were also significantly lower in the methotrexate group (mean $NZ 1,141) than in the laparoscopy group (mean $NZ 1899) with a mean difference of $NZ 758 (95% CI $NZ 277 - $NZ 1,240). For women presenting with pretreatment serum beta-hCG concentrations of over 1,500 IU/ L this difference in indirect costs is lost due to the prolonged follow up required and a higher rate of surgical intervention in women receiving methotrexate. CONCLUSION: This economic evaluation shows that treating suitable women with an ectopic pregnancy using systemic methotrexate therapy results in a significant reduction in direct costs. The indirect costs borne by the woman and her carers are only likely to be reduced in women with pretreatment serum beta-hCG concentrations under 1,500 IU/L.

Adnexal torsion.

We performed a retrospective audit of 24 cases of adnexal torsion managed at National Women's Hospital from 1996 to 1997 inclusive. There have been several reports in the recent literature of ovarian conservation in cases of ovarian infarction secondary to torsion in women desiring further fertility (1-3). In our review 50% (12 of 24) of patients were treated by oophorectomy or salpingo-oophorectomy and most of these women desired further fertility. In spite of torsion being suspected in 73% (17 of 24), the time interval between admission and operation varied from 0.5 to 52 hours with a mean of 8 hours; 46% (11 of 24) were treated laparoscopically without recourse to laparotomy. As expertise increases, we consider that adnexal torsion will be increasingly managed laparoscopically. These results suggest that more urgent surgery should be scheduled if ovarian torsion is suspected, and in view of recent reports in the literature greater consideration should be given to conservation of infarcted ovaries if further fertility is required.

Heterotopic pregnancy complicating in vitro fertilization.

A review was undertaken of the cases of heterotopic pregnancy resulting from in vitro fertilization/embryo transfer (IVF/ET) and frozen embryo replacement (FER) in a 6-year cohort of women at National Women's Hospital in Auckland. The incidence of heterotopic pregnancy was 2.9% (5 cases) in 173 clinical pregnancies resulting from 901 embryo replacements. Of the 5 women with heterotopic pregnancy, 1 had unilateral tubal patency and 4 had bilateral tubal blockage; 3 had 'high responder' peak serum oestradiol levels (greater than 9,000 pmol/L) prior to oocyte pick-up (OPU); 3 had a serum human chorionic gonadotrophin beta subunit (beta-HCG) level greater than 600 IU/L on Day 14 following embryo transfer (ET) in the absence of a multiple intrauterine gestation on subsequent ultrasound scan. In the 4 women in whom unequivocal diagnosis of heterotopic pregnancy was not made on the initial ultrasound scan, there was delay in appropriate management, in 1 for more than 5 months. In conclusion, early IVF pregnancies require a transvaginal ultrasound scan performed by a sonographer experienced in the diagnosis of ectopic pregnancy and management of early pregnancy complications by clinicians in close consultation with the IVF centre itself. No single risk factor, laboratory test or combination of these is sensitive or specific enough to predict the occurrence of heterotopic pregnancy. The first-line surgical treatment of heterotopic pregnancy should be laparoscopic salpingectomy with excision of all except the intramural portion of the affected Fallopian tube.