Estrogen and progesterone effects on transcapillary fluid dynamics.

The purpose of this study was to determine estrogen (E(2)) and progesterone (P(4)) effects on atrial natriuretic peptide (ANP) control of plasma volume (PV) and transcapillary fluid dynamics. To this end, we suppressed reproductive function in 12 women (age 21-35 yr) using a gonadotropin releasing-hormone (GnRH) analog (leuprolide acetate) for 5 wk. During the 5th week, the women either received 4 days of E(2) administration (17beta-estradiol, transdermal patch, 0.1 mg/day) or 4 days of E(2) with P(4) administration (vaginal gel, 90 mg P(4) twice per day). At the end of the 4th and 5th week of GnRH analog and hormone administration, we determined PV (Evans blue dye) and changes in PV and forearm capillary filtration coefficient (CFC) during a 120-min infusion of ANP (5 ng x kg body wt(-1) x min(-1)). Preinfusion PV was estimated from Evans blue dye measurement taken over the last 30 min of infusion based on changes in hematocrit. E(2) treatment did not affect preinfusion PV relative to GnRH analog alone (45.3 +/- 3.1 vs. 45.4 +/- 3.1 ml/kg). During ANP infusion CFC was greater during E(2) treatment compared with GnRH analog alone (6.5 +/- 1.4 vs. 4.9 +/- 1.4 microl. 100 g(-1) x min(-1) mmHg(-1), P < 0.05). The %PV loss during ANP infusion was similar for E(2) and GnRH analog-alone treatments (-0.8 +/- 0.2 and -1.0 +/- 0.2 ml/kg, respectively), indicating the change in CFC had little systemic effect on ANP-related changes in PV. Estimated baseline PV was reduced by E(2)-P(4) treatment. During ANP infusion CFC was approximately 30% lower during E(2)-P(4) (6.0 +/- 0.5 vs. 4.3 +/- 4.3 microl. 100 g(-1) x min(-1) mm Hg(-1), P < 0.05), and the PV loss during ANP infusion was attenuated (-0.9 +/- 0.2 and -0.2 +/- 0.2 ml/kg for GnRH analog-alone and E(2)-P(4) treatments, respectively). Thus the E(2)-P(4) treatment lowered CFC and reduced PV loss during ANP infusion.

The Endosquid, a new device for laparoscopic Pomeroy tubal ligation.

The Pomeroy method is a most widely practiced and most familiar form of tubal ligation. It traditionally requires laparotomy or multiple-puncture laparoscopic suturing, which is not a realistic option for the average endoscopist. We designed a 5-mm device, the Endosquid, to reproduce Pomeroy tubal ligation laparoscopically using a single 5-mm accessory puncture site. It is able to ligate, transect, and remove a loop of isthmic tube. We tested the Endosquid in a porcine model by ligating 25 bicornuate uterine horns and aortas. Ligation times averaged less than 5 minutes for each application. Gross and histologic evaluation of ligation specimens performed at necropsy confirmed correct placement. Blood loss was negligible and there were no operative complications.

Is tubal embryo transfer of any value? A meta-analysis and comparison with the Society for Assisted Reproductive Technology database.

OBJECTIVE: To analyze published randomized trials of ZIFT and ET via meta-analysis and compare the results with those of the Society for Assisted Reproductive Technology database. DESIGN: Meta-analysis and comparison to SART data sets for 1991-1996. SETTING: University medical center. PATIENT(S): Patients from the literature with infertility, randomized to either tubal or uterine embryo transfer. INTERVENTION(S): All published articles in English were identified using an electronic database spanning January 1966 to December 1998 by keyword and text word searches, supplemented with a hand search through the references of original studies, review articles, and conference abstracts to identify randomized trials comparing ZIFT and IVF-ET. Additional data was obtained through correspondence with authors. MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rates were compared. Ectopic pregnancy rate was a secondary outcome measure. RESULT(S): Six randomized controlled trials including 548 cycles, 514 retrievals, and 388 transfers were reviewed. Demographic and stimulation and transfer details were comparable between the groups. Implantation and pregnancy rates did not differ significantly, and there was a trend toward increased risk of ectopic pregnancy with ZIFT. CONCLUSION(S): Published randomized trials suggest that there is no difference in implantation and pregnancy rates between women undergoing ZIFT and IVF-ET.

Are estrogens of import to primate/human ovarian folliculogenesis?

The notion that estrogens play a meaningful role in ovarian folliculogenesis stems from a large body of in vitro and in vivo experiments carried out in certain rodent models, (e.g., rats) wherein the stimulatory role of estrogen on granulosa cell growth and differentiation is undisputed. However, evidence derived from these polyovulatory species may not be readily generalizable to the monoovulatory subhuman primates, let alone the human. Only recently, significant observations on the ovarian role(s) of estrogen have been reported for the primate/human. It is thus the objective of this communication to review the evidence for and against a role for estrogens in primate/human ovarian follicular development with an emphasis toward the application of the concepts so developed to contemporary reproductive physiology and to the practice of reproductive medicine. The role(s) of estrogens will be examined not only by analyzing the physiological evidence to the effect that these hormones control ovarian function and follicular growth, but also by summarizing the molecular evidence for the existence and distribution of the cognate receptors.

Interleukin-8 in the human fallopian tube.

The human fallopian tube is a dynamic structure that undergoes cyclic variation in its functional epithelium. This epithelium contains both secretory and ciliated cells. The mechanisms regulating the growth and function of the tubal epithelium are not fully understood. Interleukin-8 (IL-8) is one potential local regulatory factor. We therefore characterized the IL-8 system, which includes IL-8, its receptors A and B, and its degradative enzyme aminopeptidase N, in the human fallopian tube by immunohistochemistry. Immunohistochemistry was performed on isthmic, ampullary, and fimbrial fallopian tubal segments obtained from women undergoing gynecological surgical procedures for benign conditions (n = 52). IL-8 was found in the human fallopian tube predominantly in the epithelial cells. It was present in greater amounts in the distal compared with the proximal tube. IL-8 receptors A and B localized in the tube in similar patterns. The degradative enzyme aminopeptidase N is found in tubal stromal tissue at the epithelial stromal border and perivascularly and may limit the systemic effects of epithelial IL-8. The IL-8 system seems to be an active component of tubal physiology.

Outpatient evaluation and treatment of tubal obstruction with selective salpingography and balloon tuboplasty.

OBJECTIVE: To compare selective salpingography and balloon tuboplasty for the treatment of tubal obstruction. DESIGN: A retrospective evaluation of results of women treated for tubal obstruction by outpatient methods at a single center. SETTING: Tertiary-care, university-affiliated hospital. PATIENT(S): A total of 3,424 infertile women, of whom 418 had bilateral tubal obstruction by hysterosalpingography, treated at Nihon Medical Center from 1982 to 1997. INTERVENTION(S): Women with tubal obstructions who had visual evidence of an intact uterine tubal ostium at hysteroscopy were treated by selective salpingography. If selective salpingography could not establish patency, then transcervical balloon tuboplasty was performed with one of three catheter systems. Patients were followed expectantly for 1 year after treatment. MAIN OUTCOME MEASURE(S): Postoperative tubal patency and overall pregnancy rates (PRs) at 1-year of follow-up. RESULT(S): The overall patency rate was 67.5%, with 30% of these patients conceiving (20.2% of all subjects). Selective salpingography was associated with a 35. 7% patency rate, and 27.3% of these patients conceived. Of the subjects who failed selective salpingography and underwent balloon tuboplasty, 66.2% achieved patency, of whom 33% spontaneously conceived. Balloon tuboplasty was effective in restoring patency in many cases after selective salpingography had failed. Statistically significant differences were found between selective salpingography and balloon tuboplasty and for the different balloon tuboplasty catheters in terms of patency rates, while a trend was seen for PRs. CONCLUSION(S): Many women diagnosed as having tubal obstruction can be treated by outpatient methods that do not require general anesthesia. Achieving patency by these methods is associated with high PRs and avoids the need for assisted reproductive technologies in some cases. Balloon tuboplasty is a more effective treatment than selective salpingography. The choice of balloon tuboplasty catheter system may affect success rates.

Microlaparoscopy under local anesthesia and conscious pain mapping for the diagnosis and management of pelvic pain.

Chronic pelvic pain is a complex disorder with multiple etiologies. Recently, the technique of microlaparoscopy under local anesthesia has been applied to chronic pelvic pain. The specialized technique of conscious pain mapping has been developed to aid in the diagnosis of these patients. This paper will review the history and usage of office and microlaparoscopy in general. It will then discuss specific applications for patients with acute or chronic pelvic pain.

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Anesthesia for office endoscopy.

A trend is emerging in the United States whereby surgical procedures are gradually migrating to less complex environments. The demands of cost containment, pressures to limit unnecessary time delays, and desires for increased control have all conspired to promote ambulatory surgicenters, minor procedure center, and office surgical suites. Concomitant with this shift is a differing attitude toward anesthesia, with an increasing number of procedures using alternatives to general anesthesia, such as regional blocks and conscious sedation.

Office microlaparoscopy under local anesthesia.

Office laparoscopy under local anesthesia is especially suited to meet the current pressures of quality versus cost in an era of managed care. It is likely that this technique will soon become a major part of the practicing gynecologist's diagnostic operative armamentarium. Advantages of office microlaparoscopy under local anesthesia are realized by the practitioner, the patient, and the managed care provider. Office microlaparoscopy under local anesthesia is a safe, effective, and less costly tool for the evaluation of patients with many different indications. To date, the procedure has been primarily used for patients with infertility, chronic pelvic pain, and tubal ligation. The ease of scheduling, reduced costs, and rapid recovery suggest that it may be the preferred initial procedure for these patients.

Endometrial cryoablation, a minimally invasive procedure for abnormal uterine bleeding.

STUDY OBJECTIVE: To evaluate the effectiveness of endometrial cyroablation for abnormal uterine bleeding. DESIGN: Prospective study with 22 months follow-up (Canadian Task Force classification II-2). SETTING: University Medical Center. PATIENTS: Fifteen consecutive patients treated for metrorrhagia or menorrhagia refractory to medical or surgical therapy, and who were either not operative candidates or did not desire hysterectomy. INTERVENTION: Cyroablation of the endometrium. MEASUREMENTS AND MAIN RESULTS: Fifteen patients underwent 16 procedures for dysfunctional uterine bleeding. Uterine sounding depth was 6 to 15 cm. One patient had spinal anesthesia, seven had general anesthesia, and seven had intravenous conscious sedation with a cervical block. Eight patients underwent cryosurgery while fully anticoagulated. Posttreatment endometrial biopsies were performed on three patients and showed only granulation tissue. Life table calculations give amenorrhea rates of 75.5% at 6 months and 50.3% at 22 months. One woman underwent a repeat procedure, resulting in hypomenorrhea at 7-month follow-up. CONCLUSION: This pilot study suggests that endometrial cryoablation may be performed simply and effectively. Future studies should be designed to optimize the technical aspects of the procedure, determine its relative efficacy, and investigate the indications.

Cryomyolysis, a new procedure for the conservative treatment of uterine fibroids.

Conservative surgical options for uterine myomata traditionally were abdominal myomectomy, laparoscopic myomectomy, and, more recently, myolysis. Each of these procedures has distinct advantages, but also apparent disadvantages. We attempted to introduce an additional option for conservative surgical treatment of fibroids by freezing the structures, a procedure termed cryomyolysis. In this pilot study, 14 women were pretreated with a gonadotropin-releasing hormone (GnRH) agonist for a minimum of 2 months preoperatively to minimize uterine and myoma size. Cryomyolysis was performed and the GnRH agonist was discontinued. Magnetic resonance imaging scans were performed in 10 of the 14 women after GnRH agonist treatment but before surgery, and 4 months postoperatively. Total uterine volume ranged from 41.3 to 1134.8 ml preoperatively, and 49.5 to 1320 ml postoperatively (mean increase 22% after discontinuation of GnRH agonist). Normal uterine volume ranged from 35.6 to 548.7 ml preoperatively and 45.1 to 729.6 ml postoperatively (mean increase 40%); however, myoma volume showed a mean decrease of 6% (range -87-28%). Analysis of only frozen myomata revealed a mean volume decrease of 10%. Cryomyolysis maintains at or slightly reduces these lesions to post-GnRH agonist size, and all other uterine tissue returns to pretreatment size. We believe cryomyolysis may be an effective conservative surgical approach to uterine fibroids.

Estrogen influences osmotic secretion of AVP and body water balance in postmenopausal women.

To determine if estrogen upregulates osmotic secretion of arginine vasopressin (AVP) and alters body water balance, we infused hypertonic (3% NaCl) saline in 6 women (68 +/- 3 yr) after 14 days of 17 beta-estradiol (transdermal patch, approximately 0.1 mg/day, E2) and placebo (control) administration. Hypertonic saline was infused at 0.1 ml.kg-1.min-1 for 120 min, and after a 30-min equilibration period, the subjects drank water ad libitum for 180 min. E2 increased basal plasma estradiol concentration from < or = 12 to 80 +/- 12 pg/ml and plasma AVP concentration (P[AVP]) from 2.1 +/- 0.7 to 3.1 +/- 0.8 pg/ml (P < 0.05), but not plasma osmolality (Posm, 288 +/- 1 and 287 +/- 1, for control and E2, respectively). Hypertonic saline infusion increased Posm by 18 +/- 1 and 17 +/- 1 mosmol/kgH2O and P[AVP] by 5.2 +/- 0.5 and 4.9 +/- 0.4 pg/ml for control and E2 treatments, respectively. The P[AVP]-Posm relationship shifted upward after E2, with no change in sensitivity (slope, 0.36 +/- 0.02 and 0.33 +/- 0.03 pg.ml-1.mosmol-1 for control and E2, respectively). Water intake was similar between control and E2 (24 vs. 22 ml/kg), but by 180 min of drinking, urine output and free water clearance (CH2O) were reduced by 5.6 +/- 2.3 ml/kg and 2.6 +/- 2.0 ml/min, respectively (P < 0.05) after E2. Plasma aldosterone concentration was unaffected by E2, but fractional sodium excretion was reduced from 2.7 +/- 0.5 to 1.7 +/- 0.4% (P < 0.05) at 180 min of drinking. Our data suggest that E2 augments osmotic AVP secretion, thereby implicating elevated AVP as a contributor to water retention in high E2 states; however, an increase in renal sodium reabsorption was a major component of the enhanced fluid retention.

Minilaparoscopy without general anesthesia for the diagnosis of acute appendicitis.

The timely diagnosis of intra-abdominal pathology continues to be an elusive problem. Delays in diagnosis and therapeutic decision making are continuing dilemmas in patients who are females of childbearing age, elderly, obese or immunosuppressed. Minilaparoscopy without general anesthesia potentially can provide an accurate, cost-effective method to assist in the evaluation of patients with acute abdominal pain. Laparoscopy without general anesthesia is not a new technique, but with the combination of two emerging factors--1) the introduction of new technology with the development of improved, smaller laparoscopes and instruments, and 2) the shifting of emphasis on healthcare to a more cost-effective managed care environment--its value and widespread utilization is being reconsidered. We report the case of a 22 year old female with an acute onset of increasing abdominal and pelvic pain. Despite evaluation by general surgery, gynecology, emergency room staff, as well as, non-invasive testing, a clear diagnosis could not be made. In view of this, minilaparoscopy without general anesthesia was performed and revealed an acute, retrocecal appendicitis. The diagnosis was made with the assistance from the conscious patient. The utilization of this technique greatly expedited the treatment of this patient. Full-sized laparoscopic equipment was then used to minimally invasively remove the diseased appendix under general anesthesia. Both procedures were well tolerated by the patient.

Office microlaparoscopy under local anesthesia.

Laparoscopic surgery has been at the forefront of gynecologic surgical innovation in the past decade. Significant benefits which have been realized by the utilization of laparoscopy include: 1) a reduced size of surgical incisions 2) reduced length of hospital stays 3) increased utilization of outpatient surgery 4) a more rapid postoperative recovery period 5) reduced morbidity and 6) reduced total costs of treatment. Recent refinements in surgical technique and instrumentation have allowed for the development of a new incarnation of laparoscopy which has the potential to further realize each of these goals. Office microlaparoscopy under local anesthesia is the most recent advance in gynecologic minimally invasive surgery.

Cryomyolysis in the Conservative Treatment of Uterine Fibroids

Conservative surgical options for uterine fibroids are abdominal myomectomy, laparoscopic myomectomy, and, more recently, myolysis. Another option for the conservative surgical treatment of fibroids is freezing the structures. This procedure, cryomyolysis, can be performed rapidly by laparoscopic or hysteroscopic access. We performed a pilot study of 14 women with uterine fibroids. All were pretreated with a gonadotropin-releasing hormone (GnRH) agonist for 3 months to reduce uterine and myoma size. Cryomyolysis was performed in each, and the GnRH agonist was discontinued. Magnetic resonance imaging scans were performed in 10 of the 14 women after GnRH agonist treatment before surgery and 4 months postoperatively. Total uterine volume ranged from 41.3 to 1134.8 ml preoperatively and 49.5 to 1320 ml postoperatively, for a mean increase of 22%. Normal uterine volume ranged from 35.6 to 548.7 ml preoperatively and 45.1 to 729.6 ml postoperatively, for a mean increase of 40%. Myoma volume showed a mean decrease of 6% (range 87-28%). Analysis of frozen fibroids revealed a mean volume decrease of 10%. We conclude that cryomyolysis is able to maintain (or slightly reduce) the uterine fibroid at its post-GnRH agonist size, whereas all other uterine tissues return to pretreatment size.

Ethics of clinical trials.

The modern clinical trial is a form of human experimentation. There is a long history of disregard for individual rights of the patient in this context, and special attention must be paid to ethical guidelines for these studies. Clinical trials differ in basic ways from clinical practice. Foremost is the introduction of outside interests, beyond those of the patient's health, into the doctor-patient therapeutic alliance. Steps must be taken to protect the interests of the patient when such outside influence exists. Kantian moral theory and the Hippocratic oath dictate that the physician must respect the individual patient's rights and hold such interests paramount. These principles are the basis for informed consent. Randomization of patients is justified when a condition of equipoise exists. The changing nature of health care delivery in the United States introduces new outside interests into the doctor-patient relationship.

Office microlaparoscopy under local anesthesia for chronic pelvic pain.

STUDY OBJECTIVE: To investigate the utility, tolerance, and costs associated with a program of office laparoscopy under local anesthesia using fiberoptic microlaparoscopes (<2 mm) and accessory instrumentation (<2 mm) for the evaluation of patients with chronic pelvic pain (CPP). DESIGN: Prospective, nonselected cohort study. SETTING: Office-based free-standing faculty practice at a tertiary care referral center. PATIENTS: All women with a history of CPP from February to June 1995 who required diagnostic laparoscopy were compared with a cohort of patients undergoing in office diagnostic laparoscopy for the evaluation of infertility during the same period. INTERVENTIONS: All patients underwent diagnostic office microlaparoscopy under local anesthesia (OLULA) with supplemental intravenous sedation, as well as conscious pain mapping. MEASUREMENTS AND MAIN RESULTS: A specific questionnaire was developed to follow all aspects of patient acceptance and tolerance of the procedures, and all patients were queried preoperatively, and 30 minutes and 1 week postoperatively. Pain was evaluated with a modification of the McGill pain inventory. A subset of questions evaluated the length of time until usual activities were resumed, anxiety level, and general acceptance of the procedure including set-up, operative time, and recovery time until discharge. Overall, there was a high degree of patient acceptance and satisfaction with OLULA; however, women with CPP experienced greater intraoperative and postoperative pain than those with infertility. Some patients with CPP had a generalized visceral hypersensitivity to pain; all areas of the pelvis and bowel were sensitive, and pain was not completely blocked with local anesthesia. Average procedure length was similar for the two groups. Patients with CPP required greater postoperative analgesia and took longer to return to work. Conscious pain mapping identified a focal source of pain in three patients and generalized visceral hypersensitivity in a majority of patients with CPP. Neither of these were found in patients with infertility. Compared with traditional laparoscopy there was almost an 80% reduction in costs. CONCLUSION: Office laparoscopy under local anesthesia is safe and effective for the evaluation of patients with CPP and is less expensive than traditional laparoscopy. Although the procedure is better tolerated by women undergoing infertility evaluation, it was well tolerated by both groups. Conscious pain mapping helps identify potential areas of pelvic pain and helps further characterize patients with CPP.

Bilateral laparoscopic gonadectomy in a patient with complete androgen insensitivity. A case report.

BACKGROUND: Complete androgen insensitivity (CAI) is the most common cause of male pseudohermaphroditism. Affected individuals are advised to have bilateral gonadectomies to prevent the development of germ cell tumors. CASE: A 19-year-old phenotypic female presented for the evaluation of primary amenorrhea and was diagnosed with CAI. Operative videolaparoscopy was performed, and the intraabdominal gonads were resected; the patient was discharged in < 24 hours. CONCLUSION: Laparoscopic gonadectomy can be performed in individuals with CAI. This approach eliminates the need for laparotomy and results in rapid recovery with minimal blood loss. This approach should be considered for all patients with CAI and intraabdominal gonads.

Accelerated osteoporosis in psychiatric patients: possible pathophysiological processes.

Osteoporosis, a very prevalent, potentially debilitating disease, is characterized by decreased bone mineral density (BMD). Decreased BMD has recently been reported in patients suffering from several mental disorders, including schizophrenia and major depression. In these patients the accelerated decrease in BMD can be attributed to drug-induced decreases in levels of estrogen and testosterone, to polydipsia and decreased calcium to smoking and alcoholism, and to increased activity of several interleukins as well as to hyperprolactinemia and hypercortisolemia. Several of these processes may be prevented or altered in order to prevent or delay decreased BMD.