Cost-effectiveness of salpingotomy and salpingectomy in women with tubal pregnancy (a randomized controlled trial).

STUDY QUESTION: Is salpingotomy cost effective compared with salpingectomy in women with tubal pregnancy and a healthy contralateral tube? SUMMARY ANSWER: Salpingotomy is not cost effective over salpingectomy as a surgical procedure for tubal pregnancy, as its costs are higher without a better ongoing pregnancy rate while risks of persistent trophoblast are higher. WHAT IS KNOWN ALREADY: Women with a tubal pregnancy treated by salpingotomy or salpingectomy in the presence of a healthy contralateral tube have comparable ongoing pregnancy rates by natural conception. Salpingotomy bears the risk of persistent trophoblast necessitating additional medical or surgical treatment. Repeat ectopic pregnancy occurs slightly more often after salpingotomy compared with salpingectomy. Both consequences imply potentially higher costs after salpingotomy. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation of salpingotomy compared with salpingectomy in an international multicentre randomized controlled trial in women with a tubal pregnancy and a healthy contralateral tube. Between 24 September 2004 and 29 November 2011, women were allocated to salpingotomy (n = 215) or salpingectomy (n = 231). Fertility follow-up was done up to 36 months post-operatively. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: We performed a cost-effectiveness analysis from a hospital perspective. We compared the direct medical costs of salpingotomy and salpingectomy until an ongoing pregnancy occurred by natural conception within a time horizon of 36 months. Direct medical costs included the surgical treatment of the initial tubal pregnancy, readmissions including reinterventions, treatment for persistent trophoblast and interventions for repeat ectopic pregnancy. The analysis was performed according to the intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Mean direct medical costs per woman in the salpingotomy group and in the salpingectomy group were €3319 versus €2958, respectively, with a mean difference of €361 (95% confidence interval €217 to €515). Salpingotomy resulted in a marginally higher ongoing pregnancy rate by natural conception compared with salpingectomy leading to an incremental cost-effectiveness ratio €40 982 (95% confidence interval -€130 319 to €145 491) per ongoing pregnancy. Since salpingotomy resulted in more additional treatments for persistent trophoblast and interventions for repeat ectopic pregnancy, the incremental cost-effectiveness ratio was not informative. LIMITATIONS, REASONS FOR CAUTION: Costs of any subsequent IVF cycles were not included in this analysis. The analysis was limited to the perspective of the hospital. WIDER IMPLICATIONS OF THE FINDINGS: However, a small treatment benefit of salpingotomy might be enough to cover the costs of subsequent IVF. This uncertainty should be incorporated in shared decision-making. Whether salpingotomy should be offered depends on society's willingness to pay for an additional child. STUDY FUNDING/COMPETING INTERESTS: Netherlands Organisation for Health Research and Development, Region Västra Götaland Health & Medical Care Committee. TRIAL REGISTRATION NUMBER: ISRCTN37002267.

A mechanism for virilization of female spotted hyenas in utero.

Female spotted hyenas exhibit male-like genitalia and dominance over males. Hyena ovarian tissues incubated in vitro produced large quantities of the steroid hormone precursor androstenedione. The activity of aromatase, which converts androstenedione to estrogen, was one-twentieth as great in hyena versus human placental homogenates. In comparison, the activity of 17 beta-hydroxysteroid dehydrogenase, which converts androstenedione to testosterone, was equal in the two homogenates. The limited aromatase activity may allow the hyena placenta to convert high circulating concentrations of androstenedione to testosterone, which results in virilization of the fetal external genitalia and possibly destruction of fetal ovarian follicles. Androstenedione production by residual ovarian stromal cells during reproductive life accounts for the epigenetic transmission of virilization in female spotted hyenas.

Androgen receptor expression and 5 alpha-reductase activity along the proximal-distal axis of the rat prostatic duct.

The rat prostate consists of a series of branched ducts that eminate from the urethra. Heterogeneity of rat prostatic growth, secretory activity, and cell turnover has been observed along the proximal-distal axis of the branched ductal network. In addition, there are regional differences in androgen sensitivity along the ducts, with the distal ductal tips being highly androgen dependent and the proximal regions being relatively androgen independent. To determine the underlying mechanisms that may regulate these regional differences in androgen responsiveness, androgen receptor (AR) levels and 5 alpha-reductase activity were examined along the proximal-distal axis of microdissected ventral prostatic ducts from 15-, 30-, and 100-day-old rats. As in the murine prostate, DNA synthetic activity was concentrated in the distal tip region of the 15- and 30-day ducts. Immunocytochemistry and autoradiography with [3H] dihydrotestosterone were used to examine AR expression and functional ability to bind ligand, respectively. The results revealed no discernable differences in AR levels or binding activity in any cell type along the ductal length in prepubertal, pubertal, or adult rats. In addition, 5 alpha-reductase activity was the same in the distal and proximal ductal regions. We conclude that regional heterogeneity in prostatic growth and function is not a result of differences in levels of AR and 5 alpha-reductase. Rather, other region-specific structural, intracellular, or paracrine factors may be responsible for the differences in androgen responsiveness along the prostatic duct.

Early diagnosis of ectopic pregnancy. Does use of a strict algorithm decrease the incidence of tubal rupture?

OBJECTIVE: To determine if tubal rupture rates are decreased when a strict diagnostic algorithm is employed in the evaluation of women with suspected ectopic pregnancy as compared to individualized diagnostic methods. STUDY DESIGN: Between 1994 and 1996, a group of investigators at Charleston Area Medical Center employed a strict diagnostic algorithm consisting of serum quantitative human chorionic gonadotropin (hCG) levels, progesterone levels, ultrasound and endometrial curettage in order to expedite diagnosis when ectopic pregnancy was suspected (group A patients). Other practitioners employed traditional criteria in similar clinical situations (group B patients). Medical records of patients diagnosed with ectopic pregnancy in this period were retrospectively reviewed. Demographic data, clinical and laboratory characteristics, and rate of tubal rupture were compared. RESULTS: Sixty-one of 122 patients were diagnosed with ectopic pregnancy by strict criteria. These patients did not differ significantly from those evaluated by an individualized approach in regard to age, gravidity, parity or risk factors for ectopic pregnancy. Menstrual age, hCG levels and progesterone levels were similar as well. Group A patients had a median diagnostic interval of 2 days, with a range of 0-16. Group B patients had a median diagnostic interval of 8 days, with a range of 0-44 (P < .001). Of patients evaluated by this strict algorithm, 3.3% experienced rupture as compared to 23% of patients in group B (P < .001). CONCLUSION: Use of a strict diagnostic algorithm in the evaluation of patients with suspected ectopic pregnancy resulted in decreased tubal rupture rates. Such an algorithm could be disseminated to all locations for triage of patients and use in a standardized manner. This practice could result in a reduction in loss of reproductive function and mortality secondary to ectopic pregnancy.

High ovulatory rates with use of troglitazone in clomiphene-resistant women with polycystic ovary syndrome.

This preliminary report reviews our experience with 18 infertile patients with clomiphene-resistant polycystic ovary syndrome (PCOS). In the first treatment cycle, troglitazone was administered alone. During cycles 2-5, clomiphene was added with increments of 50 mg (up to 200 mg/day) if the previous cycle was anovulatory. Basal body temperature charts and serum progesterone were obtained to confirm ovulation. In a total of 66 treatment cycles, ovulation occurred in 44 (67%) and pregnancy in seven (11%). There were no significant changes in body weight, waist:hip ratio or liver enzymes during treatment. Troglitazone, alone or with clomiphene, induced ovulation in 15 of 18 patients (83%) and seven (39%) of them achieved pregnancy. This is the first report on ovulatory rates in clomiphene-resistant women with PCOS when troglitazone was used alone or with clomiphene. Recently, metformin and clomiphene were successfully used in women with PCOS. However, our patients represent a more resistant population of women with PCOS, with each patient serving as her own historical control by previous resistance to clomiphene. Although the pregnancy rate (39%) was promising for clomiphene-resistant women with polycystic ovary syndrome, it does not seem to have a definite advantage over gonadotrophins.

Hormonal correlates of 'masculinization' in female spotted hyaenas (Crocuta crocuta). 2. Maternal and fetal steroids.

Concentrations of androgens (androstenedione, testosterone, 5 alpha-dihydrotestosterone), oestrogen and progesterone were measured in relation to pregnancy in the spotted hyaena (Crocuta crocuta). The gestation period was estimated to be about 110 days. There was a marked progressive rise in all the steroids starting in the first third of gestation. Chromatographic separation of plasma showed that much of the oestrogen is not oestradiol (only 12% of total measured) and that a significant fraction of the 'testosterone' may be dihydrotestosterone. In the final third of pregnancy, concentrations of androgen (especially testosterone plus dihydrotestosterone) in the female circulation reached the maximal values of adult males; the percentage of dihydrotestosterone relative to total testosterone plus dihydrotestosterone was higher in females (44 +/- 3.9%, n = 20) than in males (29.5 +/- 3.5%, n = 17). Plasma androstenedione was also significantly higher in females, but the increment was less than for oestrogen, testosterone and progesterone, and the temporal pattern was less clear. Samples from the maternal uterine and ovarian circulation showed that androstenedione is largely of ovarian origin and metabolized by the placenta, while testosterone, progesterone and oestrogen are primarily of placental or uterine origin. Fetal samples were taken from two mixed-sex sets of twins and one male singleton. Gradients across the placenta measured in the fetal circulation confirmed that the placenta metabolizes androstenedione and is a source of testosterone for the female fetus; there were no consistent differences in androgens between male and female fetuses. It is suggested that the conspicuous masculinization of the female spotted hyaena, especially evident in the external genitalia at birth, is a result, at least in part, of high placental production of testosterone or dihydrotestosterone derived from the metabolism of high maternal androstenedione.