Hysteroscopy versus hysterectomy for the treatment of abnormal uterine bleeding: a comparison of cost.

OBJECTIVE: To compare the costs of hysteroscopic treatment of abnormal uterine bleeding with the costs associated with abdominal and vaginal hysterectomy. DESIGN: Retrospective review. SETTING: Academic medical center and outpatient gynecology practice. PATIENTS: A list of all women undergoing an endometrial ablation (n = 60), hysteroscopic myomectomy (n = 14), abdominal (n = 192), or vaginal (n = 37) hysterectomy between June 1, 1987 and June 1, 1992 for the treatment of abnormal uterine bleeding was generated by a computer search of billing records using the appropriate ICD-9-CM codes. MAIN OUTCOME MEASURE: The direct cost per case for each patient were defined as the sum of the surgeon's fee, all related hospital and operating room charges, the anesthesiologist's fee, and the cost of preoperative medications. When the initial procedure failed, the cost associated with any additional surgery was accounted for in the determination of the direct cost per case. Indirect costs per case were calculated based on known demographic data, recovery time, and the cost in lost productivity during recuperation. Mean direct and indirect costs per case were determined for each procedure and compared. RESULTS: The mean direct cost per case for endometrial ablation was $5,159 and for myomectomy and ablation was $5,525. The direct cost per case was not different between the hysteroscopic procedures but both were significantly less expensive than either vaginal ($8,132) or abdominal ($8,833) hysterectomy. Total hospital cost also was significantly less for the hysteroscopic procedures than for hysterectomy by either technique. The indirect costs associated with the hysteroscopic procedures were significantly less than those incurred by abdominal and vaginal hysterectomy. CONCLUSIONS: The total direct and indirect cost per case of an hysteroscopic approach to the treatment of abnormal uterine bleeding is significantly less than that associated with vaginal or abdominal hysterectomy. This difference persists when the cost of failure of an hysteroscopic procedure is accounted for.

CA-125 levels in human uterine fluid.

OBJECTIVE: To measure uterine fluid CA-125 concentration and to determine if any menstrual cycle phase dependent changes exist in its level. Serum levels are measured for comparison. DESIGN: CA-125 levels in uterine fluid were measured during the follicular and luteal phases of the menstrual cycle. In a sequential study, paired uterine fluid and serum samples were obtained once in both midfollicular and midluteal phases of the same menstrual cycle. RESULTS: CA-125 in uterine fluid during the follicular phase (n = 14) ranged from 16.4 x 10(3) to 616.5 x 10(3) U/mL, and from 6.2 x 10(3) to 567.3 x 10(3) U/mL in the luteal phase (n = 11). In the paired sequential uterine fluid and serum samples, (1) the means (+/- SEM) CA-125 in uterine fluid were 81.5 x 10(3) +/- 37.9 x 10(3) U/mL and 91.4 x 10(3) +/- 56.8 x 10(3) U/mL in the midfollicular and midluteal phases, respectively (P = 0.75); (2) the CA-125 levels in serum increased in the midluteal phase (P less than 0.05); and (3) compared with serum, uterine fluid levels were greater with a wider range. CONCLUSIONS: When compared with serum CA-125, uterine fluid contains high concentrations varying over a wide range without fluctuation between the follicular and luteal phases of the menstrual cycle.

Serum concentration of CA-125 during the first trimester of normal and abnormal pregnancies.

A prospective study was initiated to closely examine maternal serum concentrations of CA-125 during the early first trimester of normal and abnormal pregnancies. Sequential serum specimens were obtained from 43 women with a normal intrauterine pregnancy, 20 with a surgically confirmed ectopic gestation and 10 whose pregnancies ended in spontaneous abortion. In normal pregnancies the CA-125 levels increased significantly from the first week after the missed menses (39.9 +/- 8.2 U/mL [mean +/- SEM]) to the second week (48.3 +/- 6.9 U/mL) (P less than .05) and from the second to the third week (62.5 +/- 9.8) (P less than .05). After the third week after the missed menses the mean CA-125 serum concentrations plateaued, but levels observed during the fourth (59.6 +/- 8.8 U/mL) and fifth (48.8 +/- 7.2 U/mL) weeks were still significantly greater than at week 1. In addition, the mean CA-125 concentrations were significantly higher in normal pregnancies than in ectopic gestations during the second, third and fourth weeks after the missed menses. Although there was a tendency for the CA-125 levels to be lower in women who had a spontaneous abortion when compared to normals, these differences were not statistically significant. Serum levels of CA-125 may prove useful in monitoring early pregnancy.

Postoperative adhesion formation after ovarian wedge resection with and without ovarian reconstruction in the rabbit.

A rabbit model was used to examine adhesion formation after ovarian wedge resection with and without reapproximation of the ovarian cortex. A wedge resection was completed on one ovary with a scalpel, and the ovarian cortex was reapproximated using microsurgical technique. In the contralateral ovary, a wedge resection was performed using the Nd:YAG laser and the cortex was left to heal by secondary intention. A second laparotomy was performed and the adhesion scores were compared between the two adnexa. In 17 of 19 rabbits, the adhesion score was greater on the side where ovarian reconstruction had been performed. No difference was noted in adhesion scores when, in our preliminary studies presented herein, laser and scalpel wedge resections were both followed by reapproximation of the cortex. These data have ramifications for conservative ovarian surgery performed both at laparotomy and laparoscopy.

Diagnosis and treatment of cornual obstruction using a flexible tip guidewire.

Proximal tubal obstruction, either unilateral or bilateral, is a frequent finding on hysterosalpingogram (HSG). Approximately two-thirds of the fallopian tubes resected for proximal tubal obstruction reveal an absence of luminal occlusion. The distinction between true pathologic occlusion and either spasm or plugging is crucial in determining therapy. We combined hysteroscopic cannulation of the proximal fallopian tube with laparoscopy in 11 patients with proximal tubal obstruction diagnosed by HSG and confirmed at laparoscopy. Hysteroscopic cannulation was able to be performed in 72% of the fallopian tubes attempted, and there was a postcannulation patency rate by HSG of 73%. Six of the 11 patients became pregnant after tubal cannulation and adjunctive distal tubal surgery. Hysteroscopic cannulation of the fallopian tube is a safe diagnostic procedure that can be used to identify those patients with true proximal occlusion, and may also serve as a therapeutic procedure in some of these patients.

Prostaglandin F2 alpha synthesis and metabolism by luteal phase endometrium in vitro.

Differences in prostaglandin (PG) F2 alpha synthesis and degradation were sought between early luteal endometrium (histology day 15 to 22, n = 6) and late luteal endometrium (histology day 23 to 28, n = 6). In addition, alterations in PGF2 alpha synthesis and degradation in response to 17 beta-estradiol (E2) and progesterone (P) were examined to clarify the mechanism of steroid modulation of endometrial PG production (n = 12). Endometrium was maintained in tissue culture and the concentration of PGF2 alpha and 13,14 dehydro-15 keto F2 alpha (DHKF2 alpha) was determined in spent media by radioimmunoassay. Prostaglandin F2 alpha and DHKF2 alpha output from luteal endometrium exposed to P and E2 + P were both significantly reduced when compared with no addition or E2 treatments. This implies that the modulation of PGF2 alpha output by P in vitro is secondary to altered synthesis. There was an increase in PGF2 alpha output from late luteal endometrium when compared with early luteal endometrium in the P and E2 + P treatments, but DHKF2 alpha remained unchanged. These data imply that the temporal increase in PGF2 alpha output is the result of alterations in both PG synthesis and catabolism.

Absence of progestational activity of oral spironolactone.

Menstrual irregularity is a recognized side effect of spironolactone when used as a treatment for hirsutism in women. This effect has been attributed to the progestational activity of spironolactone observed in animal models. However, when oral spironolactone was given to women with appropriately estrogen-primed endometrium, secretory transformation of the endometrium was absent in comparison with control cycles. When control cycles were repeated with the addition of spironolactone, a decidualized endometrial response was seen. These findings suggest that spironolactone at clinically used dosages does not act as a progestin or an antiprogestin on the human endometrium.

Observation of production of immunoactive prolactin by normal human connective tissue in cell culture.

Data from our in vitro studies indicate a new source of prolactin (PRL)-like activity, normal human connective tissue. Fascial cells from primary culture and subsequent passages produced an extracellular antigen which specifically reacted in a radioimmunoassay RIA developed to detect human pituitary PRL. An initial peak or first surge of fascial PRL-like activity occurred between 4 and 15 d in primary culture. Ibuprofen, cytotoxic levels of 0.01% azide, or 7.5 mM EDTA and medium lacking serum [fetal bovine serum (FBS)] significantly (P less than or equal to 0.05) reduced PRL-like activity levels, whereas female steroids, 257 to 342 milliosmolarity, 1 to 3.6 mg/ml glucose, 2 to 20% FBS, and dialyzed FBS (MWCO approximately 1 kDa) were without effect. Optimum production of PRL-like activity occurred at pH 7.3. A second surge began after 18 d and continued until passage indicating that perhaps two populations of cells produced PRL-like activity in primary culture. Production of PRL-like activity by cells from early passages (1 and 2) became detectable at confluence, was serum-dependent, showed two patterns (tonic, rising to plateau), and averaged 3.2 fg.cell-1.3 d-1 feed interval. Cells from late passages showed morphologic damage from repetitive trypsinization, aging, and reduced production of PRL-like activity with aberrant production pattern. Production of PRL-like activity was maintained in an unusual long-term culture. These in vitro studies demonstrate the most recently recognized and ubiquitous source of human extrapituitary PRL or PRL-like activity, normal connective tissue (fascia).

Stimulation of uterine prolactin secretion by human chorionic gonadotropin and progesterone in the cynomolgus monkey.

The ovulating cynomolgus monkey secretes immunoreactive prolactin (PRL) into the uterine cavity. Consistent with human endometrial explant data, uterine PRL is undetectable in the early secretory phase, then increases from the mid to late secretory phase, peaking premenstrually. The anovulatory monkey does not produce detectable uterine PRL. Human chorionic gonadotropin given repeatedly fails to induce PRL secretion in anovulatory monkeys but prolongs the luteal phase and thereby PRL secretion in ovulatory monkeys. Progesterone (P) induces PRL secretion in anovulatory monkeys after estrogen priming with a time delay of several days, indicating probable de novo synthesis. P appears to be an important stimulating factor in the control of uterine PRL secretion.

A comparison of laparoscopy and laparotomy for the treatment of ectopic pregnancy.

A case-control method was used to examine differences in outcome between laparoscopy and laparotomy for the treatment of ectopic pregnancy. Cases and controls, 25 each, were matched by criteria selected to minimize differences in preoperative morbidity and technical difficulty. Patients treated laparoscopically had significantly shorter hospital stays (1.34 +/- 0.8 versus 3.92 +/- 1.1 days; mean +/- SD; P less than .01) and less operating time (77.5 +/- 26.1 versus 103.6 +/- 26.7 minutes; P less than .05). In addition, a laparoscopic approach resulted in a shorter convalescence (8.7 +/- 7.8 versus 25.7 +/- 16.2 days; P less than .01) and reduced postoperative analgesia requirements (0.84 +/- 2.3 versus 4.64 +/- 2.9 doses; P less than .01). We conclude that laparoscopic treatment of ectopic pregnancy is well tolerated by patients and, in comparison with laparotomy, requires fewer medical resources, thereby significantly reducing cost.

Physicochemical characterization and functional activity of fibroid prolactin produced in cell culture.

Evidence from our laboratory with the use of cultured (primary and passaged) cells has extended our initial observation that human uterine fibroid is an extrapituitary source of prolactin. Fibroid prolactin antigen in conditioned medium reacted specifically in radioimmunoassay for human pituitary prolactin. Control experiments demonstrated that the radioimmunoassay results were not spurious due to degradation of tracer 125I-labeled prolactin. Immunoparallel dilution curves indicated antigenic relatedness of pituitary and fibroid prolactin. In a calibrated Sephadex G-100 column, fibroid prolactin eluted in the same region (20.3 to 20.9 kd) as purified pituitary prolactin. Glycosylated prolactin, detected by concanavalin A affinity column chromatography, appeared to constitute only a small percentage of fibroid prolactin made in culture. The ratio of fibroid prolactin bioactivity (lactogen Nb2 lymphoma bioassay) to antigen (radioimmunoassay) was 0.77. These data indicate that human uterine fibroid tissue produces a molecule similar to or, perhaps, identical with pituitary prolactin.

Ultrasonographic monitoring of follicular growth for luteal phase defects.

In the evaluation of 39 patients with untreated and treated luteal phase defect (LPD), serial ultrasonographic monitoring of follicular development identified three morphologically distinct growth patterns: normal-sized follicles, small follicles, and luteinized-unruptured follicles. All three patterns were observed in both untreated (46% had normal-sized follicles, 39% had small follicles, 15% had luteinized-unruptured follicles) and treated patients. A small follicle was observed uncommonly in histologically corrected LPD patients (6%). However, a luteinized-unruptured follicle (38%) may persist or be induced in situations where clomiphene citrate has been used to correct LPD or induce ovulation. Ultrasonographic evaluations of follicular growth in luteal phase defect support the theory that luteal phase defect represents a spectrum of normal and abnormal ovarian cycle events.

Medical management of hyperprolactinemia: a lower dose of bromocriptine may be effective.

This prospective study includes 31 women with a prolactin (PRL) level greater than 20 ng/ml (upper limits of normal in our laboratory) on at least three different occasions and chemically euthyroid. Each woman received bromocriptine mesylate (BRC) 1.25 mg (1/2 tablet)/day for 2 weeks, at which time a repeat PRL level was obtained. If needed, the dose was increased in a stepwise fashion until the PRL level was in the normal range. Results show that 12 of 15 patients with an initial PRL greater than 20 but less than 50 ng/ml required 2.5 mg or less of BRC daily. Of 9 patients with a PRL greater than 50 but less than 100 ng/ml, 5 required 2.5 mg daily with the remaining 4 needing 5.0 mg. Five of 7 patients with a PRL greater than 100 ng/ml required 5.0 mg or more, while one responded to 1.25 mg. These findings confirm that a lower than manufacturer-recommended dose of BRC is usually effective in normalizing PRL levels, especially when the initial PRL is less than 100 ng/ml.

Successful pregnancy outcome after therapy for a müllerian anomaly with concomitant sex chromosomal mosaicism. A case report.

Recurrent abortion associated with both a chromosomal abnormality and a müllerian anomaly has been reported previously only once. A 31-year-old woman was referred for secondary habitual abortion and found to have sex chromosome mosaicism, subseptate uterus and chronic endometritis. Following hysteroscopic resection of the subseptum and antibiotic therapy for the endometritis, a term pregnancy ensued. Complete evaluation and treatment of all correctable etiologies of recurrent pregnancy loss are essential in such cases.

Luteal phase defect and premenstrual syndrome in an infertile population.

To test the hypothesis that an abnormal luteal phase is associated with significant symptoms of premenstrual syndrome, psychologic and somatic premenstrual syndrome symptoms were evaluated in a group of 83 infertile patients undergoing timed endometrial biopsy for the assessment of luteal phase adequacy. The severity of psychologic and somatic symptoms was evaluated separately. It was found that luteal phase defect, defined by endometrial biopsy, was associated with less severe psychologic and no more severe somatic symptoms of premenstrual syndrome in comparison with normal luteal phase controls. The data suggest that the hormonal milieu associated with luteal phase defects does not correlate with premenstrual syndrome symptoms and do not support the hypothesis that suboptimal ovarian function causes premenstrual syndrome.

Comparison of real-time ultrasonography, hysterosalpingography, and laparoscopy/hysteroscopy in the evaluation of uterine abnormalities and tubal patency.

In a study to assess real-time ultrasonography (US) as an alternative to hysterosalpingography (HSG) in the evaluation of uterine abnormalities and tubal patency, 61 women underwent US immediately before hysteroscopy/laparoscopy. Saline was instilled into the uterus to provide contrast during US. The findings were compared with surgical and preoperative HSG findings. With surgical findings as the standard, US was as accurate (sensitivity 98%, specificity 100%) as HSG (sensitivity 98%, specificity 92%) in demonstrating uterine abnormalities and provided a more complete assessment of the abnormality. US was as accurate (sensitivity 100%, specificity 91%) as HSG (sensitivity 96%, specificity 94%) in demonstrating the presence of tubal patency but less accurate in establishing which tubes were patent. Thus real-time US with fluid instillation provides an accurate alternative to HSG in screening for uterine abnormalities and tubal patency.

Uterine fluid and prolactin secretion in the ovulating cynomolgus monkey.

Immunoreactive prolactin is produced by late secretory human endometrium in vitro. Human myometrium in explant culture also produces prolactin. A primate model with the use of the cynomolgus monkey is described that allowed repeated samplings of uterine secretions in vivo. The uterine secretory prolactin thus measured appears immunoreactively similar to human serum prolactin, and the pattern of secretions reflects the previously described pattern of endometrial prolactin production in vitro.

Evidence of short-loop inhibition of decidual prolactin synthesis by decidual proteins. Part I.

Induction of uterine endometrial prolactin synthesis is dependent on progesterone-induced decidualization of stromal cells. These decidual cells are not dependent on progesterone for continued prolactin synthesis. The factors modifying decidual prolactin synthesis remain largely unknown. To test the hypothesis that a decidual protein is the major modulator of new prolactin synthesis, decidua were cultured within dialysis membranes allowing the accumulation of proteins greater than 12,000 molecular weight in a metabolically neutral environment, and the rate of new synthesis was compared with prolactin synthesis from samples cultured in 10 times the available volume for protein distribution. The rate of new prolactin synthesis at 48-hour intervals up to 144 hours was compared. Initial and postculture decidual prolactin content was obtained and was found not to vary significantly between groups (0.05 less than p less than 0.10). At 48 hours significant suppression of decidual prolactin synthesis was apparent (p less than 0.05) within the dialysis membranes. As prolactin concentration increased during in vitro culture this suppression was enhanced (p less than 0.005). Gel chromatography and immunoprecipitation of iodine 125-labeled prolactin added at time 0 revealed no significant degradation of the 125I-labeled prolactin and maintenance of its immunoactivity even at 144 hours. This confirms that the plateauing of prolactin concentration within the dialysis membranes is due to suppression of new synthesis rather than metabolism of previously synthesized prolactin.

Prolactin production by explants of normal, luteal phase defective, and corrected luteal phase defective late secretory endometrium.

The production of prolactin by explants of late secretory endometrium has been correlated with the extent of decidual differentiation. This correlation is strengthened by the observation that luteal phase defective endometrium produces less prolactin than normal control endometrium in a 24-hour in vitro culture system. In the present study the prolactin production by explants of normal, luteal phase defective, progesterone-corrected luteal phase defective, and clomiphene- or follicle-stimulating hormone/luteinizing hormone-corrected luteal phase defective late secretory endometrium was measured over 96 hours at 24-hour intervals. Progesterone in physiologic concentrations was added to the culture medium to maintain tissue integrity and prolactin synthesis. The prolactin production of normal late secretory endometrium rose over 96 hours under progesterone stimulation. The luteal phase defective endometrium produced significantly less prolactin under the same conditions. Histologically proven corrected luteal phase defective endometrium, regardless of treatment method, produced prolactin not different from the normal controls of the same dates. From these results it is concluded that histologic correction of luteal phase defective endometrium is associated with a corresponding biochemical correction with use of prolactin as a metabolic marker. The findings also strongly support timed endometrial biopsy as the method of diagnosis and evaluation of treatment of luteal phase defect.