Saline contrast sonohysterography and directed extraction, resection and biopsy of intrauterine pathology using a Uterine Explora Curette.

OBJECTIVE: To assess the utility of an endometrial sampling device, the Uterine Explora Curette, with concomitant saline contrast sonohysterography (SCSH) for ultrasound-directed extraction, resection and biopsy of endometrial pathology. METHODS: Use of the Uterine Explora Curette was prospectively evaluated in 20 women with either infertility (n = 14), recurrent miscarriage (n = 2) or peri-/postmenopausal bleeding (n = 4). Findings on SCSH were compared with those on pathological analysis. RESULTS: In all 20 cases the Uterine Explora Curette was used successfully during SCSH to treat endometrial filling defects. The procedure was well tolerated, with an average time from start to finish of 10 (range, 2-23) min. It was without complications, and appeared to remove or biopsy adequately endometrial filling defects in most patients, obviating the need for hysteroscopy. CONCLUSIONS: In properly selected patients, directed extraction, resection and biopsy using the Uterine Explora Curette during SCSH appears to be an effective and easy method for treating intrauterine pathology and provides a cost-effective alternative to operative hysteroscopy.

Review of the evidence for treatment of leiomyomata.

Leiomyomata of the uterus are common tumors of women, and a number of treatments are now available for symptoms of this disorder. Surgical treatments include hysterectomy, abdominal myomectomy, laparoscopic myomectomy, and myolysis. Nonsurgical treatments include uterine artery embolization and medical therapy. All have a small amount of accumulated data, but existing studies are generally small and of poor quality. There is a strong need for appropriately designed and analyzed randomized clinical trials, and surgical trials should preferably be multicenter/multisurgeon. In summary, although a large array of options exist, there are still little data upon which to base decisions regarding optimal treatment approaches.

New approaches to the management of fibroids.

New and innovative treatments are available for the control of uterine leiomyomata, each with advantages and disadvantages. Most of these techniques have few data to support their use; they are generally poorly studied, with brief follow-up. Not much is known regarding risks, costs, and comparative value. Furthermore, many of these procedures are in a state of evolution, with current investigative results having little applicability to the future use of such tools. Given the increasing number of options available to the patient with fibroids, further investigation is needed. A series of high-quality, randomized, comparative trials are needed to assess the relative merits of these new alternatives to treatment.

Endometriosis and assisted reproductive technologies.

The association between endometriosis and infertility is well established, and different mechanisms have been postulated to cause infertility depending on the stage of endometriosis. Controlled ovarian hyperstimulation improves pregnancy outcome for minimal to mild endometriosis; however, there are no randomized controlled studies of this technique in patients with severe disease. Further, ART appears to have an overall beneficial effect for all stages of endometriosis. Based on the current staging system, several studies have not been able to demonstrate a significant difference in true outcomes for different stages of the disease. The limitations of these studies have been discussed above. Similarly, the effect of endometriomas when considered independent of the stage is still unclear. In addition to ART, pretreatment with GnRH analogues or surgical intervention may be beneficial and needs to be addressed in randomized controlled studies. It is evident that we urgently need large randomized studies to answer several questions about the treatment of endometriosis-associated infertility with ART. Although our current practice is based primarily on retrospective observational studies and small randomized studies, the overall impact on pregnancy outcome is beneficial.

Prospective, randomized, crossover study to evaluate the benefit of human chorionic gonadotropin-timed versus urinary luteinizing hormone-timed intrauterine inseminations in clomiphene citrate-stimulated treatment cycles.

OBJECTIVE: To compare two methods of timing IUI, urinary LH monitoring and transvaginal ultrasonography/ hCG timing of ovulation, in patients receiving clomiphene citrate. DESIGN: Prospective, randomized, crossover study. SETTING: Yale University Reproductive Medicine Center. PATIENT(S): Infertile couples undergoing IUI because of unexplained infertility, anovulation, or male factor infertility. INTERVENTION(S): Patients received clomiphene citrate on days 3-7 of the menstrual cycle and were randomized initially to one of two monitoring protocols. In protocol A, urinary LH monitoring was used to time IUI. Urinary LH levels were determined daily with the use of commercial kits, starting on day 10 of the cycle. When urinary LH was detected, IUIs were performed daily for the next 2 days. In protocol B, ultrasound monitoring of folliculogenesis was performed until a leading follicle of > or = 18 mm was noted, at which time hCG (10,000 IU) was given intramuscularly and IUIs were performed daily for the next 2 days. If no pregnancy occurred, the couple crossed over to the alternate protocol for the next cycle and continued this alternating therapy for a total of four cycles. MAIN OUTCOME MEASURE(S): Pregnancy rate per cycle. RESULT(S): One hundred forty-one cycles were completed. In these cycles, six pregnancies occurred, for an overall pregnancy rate of 4.26% per cycle. The pregnancy rate with LH-timed IUI was 4.29% (3/70) and that with hCG-induced ovulation was 4.23% (3/71); the difference was not statistically significant. CONCLUSION(S): Timing IUI with the use of a relatively expensive and time-consuming method such as ultrasound monitoring of folliculogenesis and hCG induction of ovulation does not appear to produce an increased pregnancy rate over urinary LH monitoring of ovulation.

Divergent mechanisms regulate proliferation/survival and steroidogenesis of theca-interstitial cells.

Luteinizing hormone (LH) and insulin-like growth factor I (IGF-I) are recognized as major regulators of ovarian theca-interstitial (T-I) function. This study was designed to compare the effects of LH and IGF-I on T-I proliferation and steroidogenesis. Purified rat T-I cells were cultured in chemically-defined media. DNA synthesis was evaluated by a radiolabelled thymidine incorporation assay. The cells were also directly counted. Progesterone production was assessed using a specific radioimmunoassay. DNA synthesis of T-I cells was stimulated by IGF-I (10 nM) but modestly inhibited by LH (100 ng/ml). The inhibitory effect of LH was mimicked by 8Br-cAMP (10(-4) to 10(-3) M); forskolin (10(-5) M), cholera toxin (10 ng/ml) and 3-isobutyl-methylxanthine (10(-5) M). Stimulation of protein kinase C with phorbol 12-myristate 13-acetate (10(-7) M) had no significant effect on DNA synthesis. Furthermore, DNA synthesis was not affected by testosterone (10(-10) to 10(-9) M) or progesterone (10(-9) to 10(-8) M). Accumulation of progesterone was co-operatively stimulated by LH and IGF-I. These results suggest that LH-induced inhibition of T-I proliferation and/or survival is mediated via the cAMP system. IGF-I may be viewed as a co-gonadotrophin with respect to steroidogenesis but not with respect to proliferation/survival. The divergence of the effects on proliferation/survival versus steroidogenesis underscores the complexity of the interactions between LH and IGF-I signalling pathways.

Problems with evidence-based medicine.

Evidence-based medicine is a modern paradigm by which to practice clinical medicine. It is rapidly gaining acceptance among academicians and clinicians as the optimal way to care for patients. Modern technology has facilitated easy access to information, improving the ability to put evidence-based medicine into practice. Data demonstrating its value are accumulating; however, like any innovation, evidence-based medicine has come under attack for a variety of shortcomings. These problems are both secondary to misapplication of basic principles inherent to the concept. (J Am Assoc Gynecol Laparosc 6(2):237-240, 1999)

Identification and characterization of an ascorbic acid transporter in human granulosa-lutein cells.

Ascorbic acid serves a vital role as a pre-eminent antioxidant. In animals, it has been shown to be concentrated in granulosa and theca cells of the follicle, in luteal cells of the corpus luteum, and in the peripheral cytoplasm of the oocyte. We have previously identified hormonally-regulated ascorbic acid transporters in rat granulosa and luteal cells, and herein present preliminary evidence for the presence of a transporter for ascorbic acid in human granulosa-lutein cells. Granulosa-lutein cells were obtained from the follicular fluid of patients undergoing in-vitro fertilization. Following an overnight incubation, the cells were incubated with [14C]-ascorbic acid (0.15 microCi; 150 microM) and ascorbic acid uptake was determined. The uptake of ascorbic acid was saturable with a Michaeli's constant (Km) and maximum velocity (Vmax) of 21 microM and 3 pmol/10(6) cells/min respectively. Ouabain, low Na+ medium, and dinitrophenol significantly inhibited ascorbic acid uptake (P<0.05). Neither the presence of insulin, human chorionic gonadotrophin (HCG), insulin-like growth factor (IGF)-I, nor IGF-II affected the uptake of ascorbic acid in a statistically significant fashion. Following saturation of cellular uptake, the ascorbic acid level was estimated to be 1.04 pmoles/10(6) cells or approximately 1 mM, a high concentration similar to that seen in rat luteal cells. Active ascorbic acid transport in human granulosa-lutein cells appears to occur via a Na+ - and energy-dependent transporter, with high levels of ascorbic acid being accumulated in these cells.

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.

Sex steroids mediate HOXA11 expression in the human peri-implantation endometrium.

Under the influence of sex steroids, human endometrium undergoes sequential development in preparation for implantation. Hoxa11 is essential for implantation in the mouse. Here we describe a potential role for HOXA11 in human endometrial development and implantation. Northern analysis demonstrates that HOXA11 is expressed in a menstrual cycle phase-dependent fashion in adult human endometrium. HOXA11 messenger RNA levels dramatically increase at the time of implantation and remain increased in pregnancy. In vitro, HOXA11 expression is increased in response to estrogen or progesterone. There is a dose-responsive increase over the physiologic range of progesterone concentration. Pretreatment with Cyclohexamide does not decrease the response to estrogen. Steroids are novel regulators HOX gene expression. The spatial and temporal pattern of HOXA11 expression in the human endometrium suggests a role in endometrial development, implantation, and maintenance of pregnancy.

Evidence-based medicine: evaluating diagnostic tests.

Physicians have at their disposal a great number of established diagnostic tests, and new ones continue to be developed that are potentially helpful in diagnosing and establishing the prognosis of disease. Many of these tests were either inadequately evaluated or were found, on more careful scrutiny, to be less helpful than first believed. To ensure optimal patient care as well as appropriate use of health care resources, practitioners must be adept in understanding the true efficacy of diagnostic tests that they ask patients to undergo. They must be able to understand the basic language applied in evaluating tests and be able to determine if and when tests are applicable. (J Am Assoc Gynecol Laparosc 6(1):105-112, 1999)

Operative hysteroscopy in physiologic distention media.

Distention media are essential in operative hysteroscopy to ensure good visualization within the uterine cavity. Carbon dioxide, dextran-70, glycine, sorbitol, mannitol, saline, and Ringer's lactate solution have all been used, but are associated with difficulties that prevent their use with instruments that achieve appropriate current densities. Three new distention media are now available that correct problems associated with the earlier products. (J Am Assoc Gynecol Laparosc 6(1):113-118, 1999)

A case of fatal pulmonary thromboembolism associated with the use of intravenous estrogen therapy.

OBJECTIVE: To report a case of fatal pulmonary embolism associated with the use of i.v. estrogen therapy for menometrorrhagia. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 52-year-old woman with fibroid uterus treated with GnRH analogues with add-back therapy who presented with excessive vaginal bleeding. INTERVENTION(S): Intravenous conjugated estrogens were administered for a total of six doses. MAIN OUTCOME MEASURE(S): Fatal thromboembolic event. RESULT(S): The day after i.v. conjugated estrogens were administered, the patient had only scant vaginal bleeding, but she experienced the sudden onset of respiratory distress, became comatose, and subsequently had ventricular fibrillation leading to asystole. All resuscitative efforts failed. Postmortem examination revealed bilateral pulmonary artery thromboembolism (saddle embolus). CONCLUSION(S): Intravenous conjugated estrogen therapy may be complicated by fatal thromboembolic events. This potential adverse effect must be considered in the use of such therapy for severe menometrorrhagia, especially when treating a patient at increased risk.

Unicornuate uterus with a rudimentary horn and ovarian dysgerminoma. A case report.

BACKGROUND: Several documented cases of endometrial and cervical carcinoma arising in unicornuate uteri have been described; however, ovarian malignancy occurring in conjunction with this müllerian anomaly has not been reported. CASE: An 18-year-old woman had a unicornuate uterus, noncommunicating rudimentary horn and homogeneous, solid, right ovarian mass found to be a dysgerminoma at surgery. CONCLUSION: Müllerian anomalies are unlikely to predispose women to ovarian malignancies. However, it is essential to keep in mind that women with such anomalies, though presenting at a young age, could still have cervical, uterine or even ovarian malignancies.