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Objective: This study was undertaken to compare from a societal perspective the costs of systemic methotrexate administration with those of laparoscopic salpingostomy for the treatment of patients with tubal pregnancy.Study Design: An economic evaluation was set up in tandem with a multicenter randomized clinical trial that compared systemic methotrexate administration and laparoscopic salpingostomy for the treatment of 100 hemodynamically stable patients with laparoscopically confirmed unruptured tubal pregnancy. Data on resources used for treatment and lost production time were prospectively collected and costs of both treatments were calculated by multiplying actual expenses for resource units at a single center and resource unit use measured in all centers. Costs were originally calculated in Dutch guilders and converted to US dollars at a rate of 1.67 guilders/$1.Results: Because clinical outcomes of the trial were equivalent for the 2 strategies a cost-minimization analysis was done. Mean total costs per patient were $5721 for systemic methotrexate administration and $4066 for laparoscopic salpingostomy, with a mean difference of $1655 (95% confidence interval, $906-$2414). Costs of systemic methotrexate administration were similar to those of salpingostomy for patients in whom the initial serum human chorionic gonadotropin concentration was <1500 IU/L, a cutoff value that had not been previously hypothesized. In a scenario without a confirmatory laparoscopy, in which transvaginal ultrasonography and serial repeated serum human chorionic gonadotropin measurements were assumed to be as accurate as laparoscopy, systemic methotrexate therapy would have reduced total cost by $1500 for a patient with an initial serum human chorionic gonadotropin concentration of <1500 IU/L. In such a scenario total costs would have been similar for a patient with an initial serum human chorionic gonadotropin concentration in the range of 1500 to 3000 IU/L, whereas systemic methotrexate administration would be more costly for a patient with an initial serum human chorionic gonadotropin concentration of >3000 IU/L.Conclusions: Although systemic methotrexate administration is safe and effective for the treatment of tubal pregnancy, it does not necessarily reduce costs. Systemic methotrexate therapy could reduce costs if administered to patients with low initial serum human chorionic gonadotropin concentrations without confirmatory laparoscopy. [ABSTRACT FROM AUTHOR]

The guideline 'Indications for in vitro fertilisation (IVF)' of the Dutch Society for Obstetrics and Gynaecology (Dutch acronym: NVOG) reports limited international evidence on this subject. A review of the published studies of effectiveness and cost-effectiveness shows that the possibilities to compare the studies and to translate the results to the diagnostic indications according to the Dutch guideline are indeed limited. This is due to differences in the study-populations, different outcome measures and differences in the severity of the underlying pathology. The results of foreign cost-effectiveness studies cannot easily be generalised to the Dutch situation due to differences in the consumption of medical care, the policy as to indications and the price-structure. For the indications inoperable tubal pathology and, to a lesser extent, severe male subfertility there is sufficient evidence-based support for the (cost-)effectiveness of IVF or intracytoplasmic sperm injection (ICSI) in comparison to waiting for spontaneous pregnancy to occur. There is insufficient current literature to support recommendations for the other causes of infertility as given in the Dutch guideline.

Objective: To investigate if implementation of a non-invasive diagnostic work up of patients with suspected ectopic pregnancy, involving transvaginal sonography and serum human chorionic gonadotrophin (hCG) measurement decreases the likelihood of performing diagnostic laparoscopies., Study Design: We interviewed 27 Dutch gynaecologists using 16 structured case summaries in a fractional factorial design. Each case summary concerned a hypothetical patient with suspected ectopic pregnancy. For each case presentation, the gynaecologists were asked for their inclination to perform laparoscopy., Results: There were substantial differences in the degree to which data from a non-invasive work-up influenced the decision to perform a laparoscopy. Some gynaecologists would perform laparoscopy in all 16 patients at the first visit, whereas others would initially admit none of them., Conclusion: Dutch gynaecologists seem to be familiar with a non-invasive diagnostic approach in women with suspected ectopic pregnancy. However, there are considerable differences in management approach probably due to individual variability in weighing the risks and benefits of expectant management.

Objective: To compare gestational age and endometrial stripe thickness measurement with serum hCG measurement as criteria for the diagnosis of ectopic pregnancy (EP)., Design: Prospective study., Setting: Two large teaching hospitals in Amsterdam, The Netherlands., Patient(s): Three hundred fifty-four consecutively seen pregnant patients who presented between September 1993 and April 1996 with suspected EP and in whom transvaginal ultrasonogram showed no intrauterine pregnancy or EP. Ultrasonography was performed by one of the study investigators or, during shifts, by the resident on call., Intervention(s): None., Main Outcome Measure(s): The accuracy of gestational age, endometrial stripe thickness, and serum hCG measurement in the diagnosis of EP was evaluated with receiver operating characteristic curve analysis., Result(s): Gestational age and endometrial stripe thickness could not discriminate between patients with EP and patients without EP, whereas serum hCG had an acceptable area under the receiver operating characteristic curve., Conclusion(s): Gestational age and endometrial thickness are not useful in the diagnosis of EP. Serum hCG measurement is the diagnostic instrument of choice in patients with suspected EP when transvaginal ultrasonography does not reveal a diagnosis.

Objective: To determine the effect of corticosteroids on ovarian responsiveness to exogenous gonadotropins in patients with idiopathic premature ovarian failure (POF)., Design: Placebo-controlled, randomized, double-blind, multicenter study., Setting: Two tertiary care academic centers for reproductive endocrinology and fertility and two general teaching hospitals., Patient(s): One hundred patients with idiopathic POF intended to enter the study. The study was discontinued after 36 patients failed to ovulate., Intervention(s): Endocrine and immune parameters were tested on days 1 and 15. On day 1, subjects were randomized to receive either 9 mg of dexamethasone daily or placebo. From day 5 onward, 300 IU of hMG daily was added for 10 days in both groups. The dosage of dexamethasone was decreased stepwise in the second week and discontinued after day 15. Patients were monitored by transvaginal ultrasonography and by determining serum E2 levels., Main Outcome Measure(s): Ovulation rate. Fifty patients would have to be included in each study group to detect a statistically significant difference of 20% in the ovulation rate between the two groups with alpha = 0.05 and beta = 0.1 (one-tailed test)., Result(s): No ovulation was recorded in the first 36 patients. Interim analysis showed that the 95% confidence intervals of an ovulation rate of 0 were 0-17% for the dexamethasone arm (n = 19) and 0-19% for the placebo arm (n = 17). Because the preset objective (a difference of 20%) would never be reached, the study was discontinued., Conclusion(s): Corticosteroids do not influence ovarian responsiveness to gonadotropins in patients with idiopathic POF.

Background: Laparoscopy has generally replaced open surgery in the treatment of ectopic pregnancy. This study assesses the impact of the introduction of laparoscopy in the surgical treatment of tubal pregnancy on costs., Methods: Consecutive patients undergoing primary surgery for tubal pregnancy between January 1992 and December 1995 were included in the study. Surgery was performed laparoscopically or by open surgery. Cost for each treatment was calculated by multiplying resources used with calculated resource unit prices. The analysis was stratified for radical and conservative surgery., Results: Data of 255 patients were analysed. Tubal pregnancy was successfully treated in all patients. Costs per patient were US$ 3,490 for radical open surgery, US$ 1,872 for radical laparoscopic surgery, US$ 3420 for conservative open surgery and US$ 2,125 for conservative laparoscopic surgery. Differences in costs were caused by a decreased duration of hospital stay after laparoscopy, and, in case of conservative surgery, by an increased persistent trophoblast rate after laparoscopy., Conclusions: Laparoscopy is equally effective as open surgery in the treatment of tubal pregnancy, and considerably reduces costs.

Objective: The traditional treatment of ectopic pregnancy is salpingectomy, while conservative surgery aims to save the function of the uterine tube. This study compares the effectiveness and the economic costs of salpingectomy and conservative tubal surgery in women with a tubal pregnancy., Methods: Salpingectomy and conservative tubal surgery were compared economically, based on a combined retrospective and prospective cohort study and a review of the literature. A model was developed in which conservative surgery and salpingectomy with in vitro fertilisation and embryo-transfer (IVF-ET) were compared with salpingectomy alone., Participants: One hundred and fifteen consecutive women treated laparoscopically for tubal pregnancy., Main Outcome Measures: Complete removal of the tubal pregnancy; subsequent intrauterine pregnancy rate; economic analysis., Results: Tubal pregnancy was always treated successfully by both methods, sometimes with additional treatment for persistent trophoblast. In the short term costs per patient were 1554 pounds (95% confidence interval [CI] 1501 pounds-1656 pounds) for salpingectomy and 1787 pounds (95% CI 1683 pounds-1930 pounds) for conservative surgery. The mean difference between costs of salpingectomy and costs of conservative surgery was 233 pounds (95% CI 80 pounds-371 pounds). Concerning subsequent intrauterine pregnancy, conservative surgery is slightly more effective than salpingectomy but is more expensive. Costs per subsequent intrauterine pregnancy are 4063 pounds. If IVF-ET is performed in all women who are not pregnant within three years after salpingectomy, costs per subsequent intrauterine pregnancy are 15,629 pounds., Conclusions: Salpingectomy is the treatment of choice in women not desiring future pregnancy. Salpingectomy seems less effective than conservative surgery when future pregnancy is desired, but is less costly. Conservative surgery seems more cost effective than salpingectomy with additional IVF-ET.

Objective: To evaluate short-term effectiveness of systemic methotrexate (MTX) in interstitial pregnancy., Design: Case series., Setting: Two Dutch teaching hospitals., Patient(s): Eight consecutive patients with an unruptured interstitial pregnancy., Intervention(s): Four doses of 1.0 mg/kg IM MTX alternated with 0.1 mg/kg oral folinic acid. Serum hCG concentrations were determined before the first MTX injection and followed until levels were undetectable. A second MTX course was started on day 14, if by then serum hCG concentrations were > 40% of the initial value. Serum hCG clearance curves of all patients in the present study were compared with those from our earlier studies, in which a different folinic acid regimen (15 mg orally) was used., Main Outcome Measure(s): Serum hCG clearance curves., Result(s): All patients were treated successfully: five with one course and three with two courses. Serum hCG clearance curves of these patients tended to decline more rapidly than those successfully treated with the 15 mg folinic acid regimen., Conclusion(s): Systemic MTX is an attractive therapeutic option in the conservative treatment of unruptured interstitial pregnancy. The regimen of four doses of 1.0 mg/kg IM MTX alternated with 0.1 mg/kg folinic acid is effective. Serum hCG clearance curves may serve as a guideline for monitoring MTX treatment, thus enabling a timely detection of impending treatment failure.

Objective: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives., Study Design: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 micrograms of ethinyl estradiol and 150 micrograms of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 micrograms gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed., Results: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 micrograms bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change., Conclusion: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level.

Objective: To study the effects of preoperative naproxen on postoperative and post-discharge outcome and consumption of analgesics in patients undergoing diagnostic hysteroscopy and laparoscopy for infertility., Methods: A double-blind, placebo-controlled study was conducted in 60 healthy women scheduled for day-case hysteroscopy and laparoscopy. Subjects were randomized to receive either 500-mg naproxen suppositories (n = 30) or placebo (n = 30) preoperatively. Following discharge, each patient was given two naproxen suppositories for treatment of pain at home. Pain was scored on the Visual Analogue Scale, and the postoperative and post-discharge use of analgesics was determined, recorded, and analyzed., Results: Patients premedicated with naproxen had significantly less postoperative pain, showed more rapid ambulation, could be discharged earlier, and had less post-discharge pain. On the day after surgery, only six of 28 naproxen-treated patients needed analgesics, compared to 18 of 30 placebo patients., Conclusion: Day-case diagnostic hysteroscopy and laparoscopy for evaluation of infertility is potentially painful and stressful. Preoperative naproxen contributed to postoperative pain prevention, reduced hospital stay and consumption of analgesics, and shortened the period of post-discharge abdominal discomfort.

Oral contraceptives inhibit ovarian follicular growth by suppressing the release of gonadotropins from the pituitary. We studied basal and gonadotropin-releasing hormone-stimulated gonadotropin release, as well as pulsatile luteinizing hormone (LH) secretion, in ten healthy volunteers who had not used oral contraceptives before. Subjects received either a monophasic preparation containing 30 micrograms of ethinylestradiol and 75 micrograms of gestodene (group 1) or a triphasic formulation containing 30-40 micrograms of ethinylestradiol and 50, 70 and 100 micrograms of gestodene (group 2). Blood sampling at 10-min intervals during 6-h periods was performed on days 1, 8, 15 and 21 of both the first and fourth pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. Both LH and follicle-stimulating hormone (FSH) were measured by a sensitive immunoradiometric assay. Pulsatile LH secretion was observed in all oral contraceptive users. Mean serum LH and FSH levels, number of pulses/6 h and the amplitude of LH pulses on day 1 in both the first and fourth pill cycle did not differ from early follicular phase controls in both groups. The FSH levels were suppressed rapidly in both groups, even in first cycles, while LH serum levels progressively declined in all cycles studied. In both groups, amplitudes of LH pulses decreased from day 8 onwards, with a substantial number of low-amplitude pulses (< 0.75 U/l) interspersed between large-amplitude pulses. On day 1 of the fourth pill cycle a significant number of pulses were of low amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the feasibility of detecting Chlamydia trachomatis in cryopreserved donor semen by a specific, direct polymerase chain reaction (PCR)., Design: Cryopreserved donor semen was tested for the presence of C. trachomatis by a specific PCR, directly applied to semen without prior DNA purification., Setting: Tertiary care fertility center in a teaching hospital and university-based laboratory for molecular pathology., Participants: Cryopreserved semen from 30 donors was investigated. These semen samples had previously given negative results in cell culture for C. trachomatis. Two different ejaculates of each donor, cryopreserved with an interval of 2 years, were retrospectively analyzed., Interventions: None., Main Outcome Measure: The presence of C. trachomatis as demonstrated by PCR., Results: In 3 of 30 donors C. trachomatis was detected in both ejaculates, whereas in 2 additional donors only one of the two samples tested positive. Additional samples from 2 positive donors, together with samples from 3 negative donors, were studied more extensively, to test the reproducibility and reliability of PCR results. All ejaculates of the donors, previously positive for C. trachomatis by PCR, indeed appeared to be positive, whereas the samples of the negative donors remained negative., Conclusions: The direct PCR is a reliable, sensitive, and valuable method for detection of C. trachomatis in semen. The incidence of contamination of donor semen with C. trachomatis in the donor population in this study stresses the need for rigorous screening of donor semen before artificial insemination, preferably using a sensitive method such as the PCR.

Three patients with genital herpes simplex type II primoinfection and acute urinary retention are described. All patients showed pleocytosis of the cerebrospinal fluid, substantiating central nervous involvement. The association of genital herpes and sacral (myelo-) radiculitis has gained little attention in gynecologic literature, yet it is not an uncommon finding in female patients suffering from herpes. The present report emphasizes the importance of urinary symptoms in genital herpes and reviews the literature on similar cases.

The birthweights and placental weights of 3000 singletons, 1500 twin pairs and 67 triplets are studied in relation to the gestational age. From 30-32 weeks onwards, newborns of twin- and triplet gestation show lower birthweight as compared to singleton newborns. Placental indices (placental weights related to birthweights) are about alike in singletons, twins and triplets. From about 24 weeks onwards placental weights of twin and triplet newborns are smaller as compared to those of singletons. Obviously, children in multiple gestations become growth retarded, preceded by and very likely due to poor early placental development (placental crowding of the uterus).