Evaluation of real-time imaging using a laparoscopic ultrasound probe during operative endoscopic procedures.

OBJECTIVES: To evaluate rigid and flexible ultrasound transducers introduced through a laparoscopic port to image pelvic anatomy during operative endoscopy as a means of mapping the pelvic anatomy, detecting pathology, and for real-time tracking of intra-uterine procedures. DESIGN: Prospective, descriptive, non-comparative. MATERIALS AND METHODS: Laparoscopy, hysteroscopy and real-time, gray-scale ultrasonography were performed simultaneously in 36 patients. Laparoscopic ultrasound was performed using 10 mm diameter, 7.5 MHz gray-scale rigid and steerable transducers for imaging of the ovaries and uterus during operative endoscopy (Aloka, Wallingford, CT, USA). All patients underwent intra-operative evaluation using this probe to assess uterine and ovarian structures and to track instruments intra-operatively during complex intra-uterine hysteroscopic procedures and for intra-operative sonohysterography. RESULTS: Laparoscopic ultrasound provided visualization of structures and delineation of ovarian anatomy needle placement for tracking microscissors and intra-operative sonohysterography. The ultrasonography provided information useful for determining the configuration of normal anatomic structures, the localization of and more precise incision placement for anatomic abnormalities and for intra-operative guidance during hysteroscopic resection of intra-uterine adhesions. The imaging also provided details of intra-uterine anatomy through sonohysterography performed during chromotubation. However, no additional information regarding ovarian or uterine abnormalities was noted beyond that detected on pre-operative transvaginal ultrasonography. No technical problems were encountered. No additional operative time was required. CONCLUSIONS: Real-time laparoscopic ultrasound imaging is useful in monitoring complex intra-uterine operative procedures and in detailing intra-uterine anatomy during intra-operative sonohysterography. However, it did not provide more enhanced imaging of ovarian anatomy beyond images obtained with pre-operative transvaginal imaging. This imaging technique may have broad application for a variety of endoscopic operative procedures with the potential to impact on operative decision-making and requires further evaluation.

Impact of subdermal norgestrel on hepatic acyl-coenzyme A:cholesterol- acyltransferase (ACAT) activity: possible antiatherogenic effect.

The impact of subdermally placed ethinyl estradiol, norgestrel, and the combination of the two on cholesterol metabolism as measured by hepatic acyl:cholesterol-acyltransferase (ACAT) activity was examined in the rat model. A total of 48 rats were assigned to one of 6 groups, receiving either 0.1 mg or 1.0 mg of ethinyl estradiol daily, 1.0 or 10 mg of norgestrel daily, and combinations of either 0.1 mg ethinyl estradiol/1.0 mg norgestrel or 1.0 mg ethinyl estradiol/10 mg norgestrel daily. All drugs were administered through subdermally placed time release capsules. The administration of norgestrel only in either 1.0 mg or 10 mg resulted in significantly lower rates of ACAT activity (0.77 +/- 0.566 and 0.91 +/- 0.239 pmol/mg/min, respectively). The combination of 1.0 ethinyl estradiol and 10 mg norgestrel resulted in a significant increase in ACAT activity to 2.17 +/- 0.873. This combination also resulted in significantly greater weight loss at the conclusion of treatment [247.83 +/- 6.2 g (pre) vs. 205.50 +/- 10.6 (post)]. There were no other differences in ACAT activity between groups and no other differences in weight, both between groups and pre- and post-treatment within groups. In summary, subdermally placed norgestrel resulted in a significant lowering of ACAT activity not seen with either administration of ethinyl estradiol alone or the combination of ethinyl estradiol and norgestrel in doses ranging from 0.1 to 1.0 mg of ethinyl estradiol and 1.0 to 10.0 mg of norgestrel. Significantly increased ACAT activity for the combination of 1.0 ethinyl estradiol and 10 mg norgestrel over either ethinyl estradiol or norgestrel alone or a lower dose combination suggests a dose-related threshold and drug-drug interaction for this effect. These results suggest that subdermally placed norgestrel may result in significantly lower ACAT activity and may have a potential role as an antiatherogenic treatment.

Serial serum human chorionic gonadotropin (hCG) levels in ectopic pregnancy and first trimester miscarriage.

Serial serum hCG levels were measured in 50 patients with a tubal ectopic pregnancy and 50 patients with spontaneous miscarriage of an intrauterine pregnancy. Serum samples were obtained at intervals of 3-5 d and more frequently if clinically indicated. The final diagnosis was confirmed by laparoscopy and/or dilatation and curettage. Data were analyzed using a linear regression model. Initial hCG concentrations ranged from 91 to 3,050 mIU/mL. Eighty percent of ectopic pregnancies and 35% of miscarriages were associated with rising hCG concentrations and no significant differences were noted in daily increments of hCG in the two groups (210 +/- 30 mIU/mL/day for ectopic pregnancies versus 311 +/- 55 mIU/mL/d for miscarriages). Twenty percent of ectopic pregnancies and 65% of miscarriages had falling hCG concentrations and significant differences were noted in the daily decrements of hCG for EP and AB (270 +/- 52 mIU/mL/day for ectopic pregnancies versus 578 +/- 28 mIU/mL/d for miscarriages (P < or = 0.05).

The journal club. Teaching critical evaluation of clinical literature in an evidence-based environment.

OBJECTIVE: To develop a curriculum in epidemiology, biostatistics and experimental design that uses a journal club format for resident instruction and to assess participants' response to this format. STUDY DESIGN: A curriculum over 12 months included 24 concepts descriptive of topics considered critical in the assessment and evaluation of literature descriptive of clinical practice and patient care. There was one two-hour session per month for 12 months. Two sets of articles were distributed for each session. The first set consisted of literature on the topics of epidemiology, biostatistics and experimental design. These concepts increased in complexity throughout the academic year, starting from simple concepts, such as P values, and progressing to more-involved and complicated concepts, such as meta-analysis. The second set of articles consisted of literature on clinical topics. It was intended to illustrate and emphasize the concepts of experimental design and statistical analysis presented in the first set of articles. These clinical articles were both contemporary and historical and were from a variety of medical disciplines, including internal medicine, obstetrics and gynecology, orthopedics, infectious disease, anesthesiology, pediatrics and psychiatry. A questionnaire was distributed to the students at the conclusion of the curriculum. RESULTS: This format was well received by both residents and staff. Eighty-five percent of the residents expressed interest in continuing the format without a major change. Fifteen percent requested restricting the clinical literature to obstetrics and gynecology. CONCLUSION: This format proved an excellent method of training residents in evaluating clinical literature and providing familiarity with concepts in epidemiology, biostatistics and experimental design.

Inhibition of gonadotropin surge by a brief mid-cycle regimen of ethinyl estradiol and norethindrone: possible role in in vitro fertilization.

Various methods to prevent premature luteinizing hormone (LH) surge and improve cycle control during hyperstimulation for in vitro fertilization (IVF) are standard of care. The purpose of the present study was to determine the influence of a 5-day regimen of ethinyl estradiol (EE) and norethindrone (NET) on folliculogenesis, gonadotropin surge, and ovulation. In a prospective randomized and comparative study, ten patients were assigned to two groups. A combination of 50 micrograms of EE and 1 mg of NET was used in groups I and II from days 6 through 10, and days 8 through 12, respectively. Blood samples and transvaginal ultrasound imaging were carried out throughout a 28-day cycle. Follicular diameter, plasma levels of LH, follicle-stimulating hormone (FSH), estradiol and progesterone, and endometrial thickness were determined. No LH surge or ovulation was detected in any patient studied. Peak estradiol concentrations were not significantly different between the groups (152.04 +/- 107.1 pg/ml vs 162.1 +/- 56.1 pg/ml [mean +/- SD] for groups I and II, respectively). No differences were noted between the groups for serum concentrations of FSH (range: 2-9 mIU/ml) or LH (range: 2-10 mIU/ml) for any given cycle day. Mean follicular diameters were not different between groups I and II (20.5 +/- 8.1 mm2 vs 20.6 +/- 14.2 mm2). Ultrasound assessment of mid-cycle follicular growth revealed diameters ranging from 18.5 mm2 to 34.0 mm2. Endometrial thickness ranged from 8 to 10 mm. There was no evidence of ovulation on ultrasound examination and either persistence or gradual resolution of follicles through the luteal phase. Peak serum concentrations at mid-luteal phase were < or = 2 ng/ml. In this pilot study, the combination of EE and NET restricted to a 5-day course beginning on day 6 or 8 permitted folliculogenesis but effectively inhibited midcycle LH surge and ovulation. Such regimens may have a role in IVF cycles for prevention of premature LH surges, especially as stimulation regimens evolve toward decreased gonadotropin use for stimulation and strict FSH preparations with the potential need for less complete pituitary suppression.

A new coaxial catheter system with an echodense tip for ultrasonographically guided embryo transfer.

OBJECTIVES: To determine performance of a new coaxial catheter system with an echodense tip for imaging during transabdominal ultrasonographically guided catheter passage. DESIGN: Prospective, descriptive, noncomparative study. SETTING: Fertility center within a tertiary care center. PATIENT(S): Twenty-five patients who were undergoing ET. INTERVENTION(S): The catheter was passed transcervically under transabdominal ultrasonographic guidance. MAIN OUTCOME MEASURE(S): The catheter was assessed for ease of placement and immediacy of identification of the outer and inner sheaths and the degree of catheter movement (if any) needed for identification. RESULTS: The outer sheath of the system was well visualized through the cervix and into the lower uterine segment due to its thickness. Immediate recognition of the echodense tip of the inner sheath was achieved in all patients. With minimal movement of the catheter or ultrasonographic transducer, the tip could be easily tracked during passage through the entire uterine cavity into the fundal region. CONCLUSIONS: In this preliminary study, the echodense tip was immediately identified by transabdominal imaging, reducing the need to move the catheter for identification. Previous investigations have not conclusively shown improved pregnancy rates with ultrasonographic guidance, possibly because of the need for catheter movement for identification of the tip and resultant disruption of the endometrium. The immediate identification of the catheter may provide a method for precise, atraumatic ET.

Ultrasound guidance during endoscopic procedures.

The use of laparoscopic ultrasound probes has been shown to improve outcomes and facilitate surgery for hepatobiliary and pancreatic cancers. It is a useful, inexpensive, and safe imaging technique that should also supplement operative laparoscopy for gynecologic indications. These techniques are new, and their use in gynecologic surgery has not been adequately evaluated to recommend widespread use. The principal benefit of ultrasound monitoring during operative laparoscopy is its potential impact on operative management and decision making. Theoretically, the intentions would be to reduce the amount of tissue dissection, for example, by more precisely locating an ovarian endometrioma; to reduce operating time; and to monitor more closely intrauterine procedures. Further prospective randomized studies are needed to define the exact role of ultrasound monitoring in gynecologic surgery. An exciting possibility is its use to define intraovarian anatomy more definitively in the hope of minimizing the amount of ovarian dissection and, in select circumstances, guiding further intrauterine surgery. With the use of steerable probes, an assessment could be made of the pelvic side wall in oncologic surgery to select specifically nodes that are highly suspicious for malignancies, thereby minimizing the amount of dissection necessary in staging procedures. Intraoperative ultrasound guidance in intrauterine endoscopic procedures offers a noninvasive means of assessing the precision of such procedures and provides information regarding the exact location of instruments within the uterine cavity and uterine wall. It has been used for almost 15 years, and adequate clinical experience has been accrued. It offers an alternative to more invasive laparoscopy and may be considered as an adjunct to any complicated intrauterine procedure.

Combined congenital absence of the vagina and cervix. Diagnosis with magnetic resonance imaging and surgical management.

The combination of congenital absence of the cervix and vagina is an extremely infrequent anatomic abnormality. We report a patient in whom this combination was diagnosed preoperatively by magnetic resonance imaging and managed surgically in a two-stage procedure using a modified McIndoe vaginoplasty followed by the creation of a uterovaginal fistula.

The antiestrogen tamoxifen in the treatment of recurrent benign cystic mesothelioma.

Benign cystic mesothelioma is a tumor characteristically found in women during the reproductive years. These tumors are infrequently found after castration or menopause, suggesting some degree of hormonal sensitivity. Such aspects of the tumor suggest a potential role for antiestrogens as medical management and an alternative to radical surgery. We treated a 19-year-old woman with a symptomatic pelvic mass secondary to a recurrent benign cystic mesothelioma 2 years after radical surgery with the antiestrogen tamoxifen. An initial reduction in volume and arrest of growth was followed by stabilization in size and disappearance of symptoms. Therapy was continued for 18 months with no change in the volume of the cystic structure. The patient continued to be asymptomatic. Periodic surveillance with quantitative digital radiography for bone density showed no change in bone mineral density. Serum testing for liver function studies was normal throughout treatment. This case suggests that antiestrogens may have a role in the medical management of these rare estrogen-dependent neoplasms. The initial reduction in size and arrest in growth further suggest extreme sensitivity of this tumor to manipulation of the hormonal milieu. Therapy with the antiestrogen tamoxifen in this setting may provide an option for long-term medical management in cases of symptomatic recurrent cystic mesotheliomas.

A regimen of oral contraceptives restricted to the periovulatory period may permit folliculogenesis but inhibit ovulation.

Increased safety of oral contraceptives (OC) has resulted from a reduction in the estrogen and progestin content per tablet. A reduction in the number of hormonally active pills and their placement at critical points within the cycle may provide a novel regimen for further reducing the hormonal content of OC per cycle and their attendant side effects without compromising efficacy. The objective of this study was to determine the effectiveness of two OC regimens that incorporate a delayed start and limited midcycle use of the combination of ethinyl estradiol and norethindrone, and limited use of norethindrone only during the second half of the cycle. Main outcome measures were defined as ovulation, serum concentrations of estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone (P), follicular diameters, and endometrial thickness. Volunteers were issued blister packs containing 28 pills and randomized to one of two groups. Group 1 used a combination of 50 micrograms ethinyl estradiol and 1 mg norethindrone per tablet day 6-10, and 0.70 mg norethindrone only day 11-19. Placebo tablets were used on days 1-5 and day 20-28. Group 2 used a combination of 50 micrograms ethinyl estradiol and 1 mg norethindrone per tablet on day 8-12, and 0.70 mg norethindrone only on day 13-21. Placebo tablets were used on day 1-7 and day 22-28. A total of 20 cycles were studied using 10 volunteers. To assess any possible carryover effect, two successive cycles were studied for each subject. Serum sampling for E2, FSH, LH, and P, and transvaginal ultrasound imaging to assess endometrial thickness and follicle diameter were carried out at 4 day intervals throughout the cycle. One ovulation occurred in 10 cycles in group 1. Five ovulations occurred in 10 cycles in group 2. All ovulations, regardless of group, occurred in the second cycle. Peak E2 concentrations were not significantly different between groups (152.04 +/- 107.1 pg/mL vs 162.1 +/- 56.1 pg/mL [mean +/- SD] for groups 1 and 2, respectively] but occurred earlier in the cycle in group 1. No differences were noted between the groups in serum concentrations of FSH or LH for any given cycle day. Maximum follicle diameters were not different between groups 1 and 2, regardless of ovulatory status (20.5 +/- 8.1 mm2 vs 20.6 +/- 14.2 mm2, respectively). Ultrasound imaging assessment of midcycle follicle growth revealed diameters ranging from 18.5 mm2 to 34.0 mm2 with gradual resolution through the second half of the cycle in anovulatory cycles, and 16.0 mm2 to 23.5 mm2 with abrupt disappearance in ovulatory cycles. Endometrial thickness did not exceed 10 mm for any anovulatory cycle regardless of group, but ranged from 6 to 9 and 6 to 11 during the luteal phase of ovulatory cycles of groups 1 and 2, respectively. Peak serum P concentrations at midluteal phase in ovulatory cycles ranged from 9.2 ng/ml to 18.2 ng/ml. Data from this preliminary study suggest that ovulation may be prevented with a combination of ethinyl estradiol and norethindrone started as late as cycle day 6 and limited to 5 days' duration using norethindrone only for 9 days during the second half of the cycle. Such a restricted regimen may offer both an effective method of contraception and a means of further reducing both estrogen and progestin content per cycle and the possible short and long term adverse side effects of these hormones.

PIP: A reduction in the number of hormonally active oral contraceptive (OC) pills and their placement at critical points within the cycle represents a novel potential regimen for further reducing the hormonal load of OCs per cycle and the attendant side effects without compromising efficacy. The present study evaluated the effectiveness of two such OC regimens: group 1--placebo tablet on days 1-5, 50 mcg of ethinyl estradiol and 1 mg of norethindrone per tablet on days 6-10, 0.70 mg of norethindrone only on days 11-19, and placebo tablets on days 20-28; and group 2--placebo tablet on days 1-7, 50 mcg of ethinyl estradiol and 1 mg of norethindrone per tablet on days 8-12, 0.70 mg of norethindrone only on days 13-21, and placebo on days 22-28. 10 volunteers were randomized to one of the two groups for two cycles. There was 1 ovulation in the 10 cycles completed in group 1 and 5 ovulations in the 10 cycles in group 2. All ovulations occurred in the second cycle. Peak estradiol concentrations occurred earlier in the cycle in group 1, but were not significantly different between groups. Serum concentrations of follicle-stimulating hormone or luteinizing hormone and mean follicle diameters were not different between groups. Folliculogenesis occurred in all 20 cycles. Mid-cycle follicular growth resolved gradually during the second half of the cycle in anovulatory cycles and abruptly in ovulatory cycles. The length of the luteal phase for ovulatory cycles was 7 days in group 1 and 8-12 days in group 2. These findings suggest ovulation may be prevented with a combination of ethinyl estradiol and norethindrone started as late as cycle day 6 and limited to 5 days' duration, using norethindrone only for 9 days during the second half of the cycle.

AN electronic bulletin board for instruction in reproductive endocrinology in a residency in obstetrics and gynecology.

OBJECTIVE: To explore the role of an electronic bulletin board as a means of computer-based learning in reproductive endocrinology for residents in obstetrics and gynecology. DESIGN: An electronic bulletin board was networked to all residents to present a formal lecture series in reproductive endocrinology and an informal question, answer, and discussion session after each lecture. Ten lectures were presented, one each month, throughout the academic year followed by question, answer, and discussion sessions. All lectures could be stored in an electronic file folder or printed as hard copy for review. A questionnaire was distributed at the conclusion of the project to assess previous resident experience with computers, resident response to, and utilization of the bulletin board. SETTING: A residency program in obstetrics and gynecology in a major medical center. PARTICIPANTS: Twenty-four residents in a 4-year program. MAIN OUTCOME MEASURES: Previous computer experience, ease of use, resident participation, and satisfaction with the bulletin board. RESULTS: Sixty-five percent of the residents considered themselves computer literate and 33 percent previously had taken a course in computer technology. Computer experience in word processing, spreadsheet, and database management was related by 55 percent, 40 percent, and 25 percent of the residents, respectively. Ninety-five percent of the residents accessed the bulletin board for the lectures and found this system a convenient means of review. Sixty percent reviewed the lectures and stored them in an electronic file folder for later review. Forty percent printed the lecture on hard copy. On a scale of 1 to 5 (1 = lowest; 5 = highest), overall resident satisfaction was high at 4.5. CONCLUSION: Our data suggest a potential role for electronic bulletin boards as a complement to standard teaching protocols in resident education. The relative ease of use and satisfaction suggest that these techniques are feasible and offer an effective method of on-line instruction.

Ovulation induction using s.c. pulsatile gonadotrophin-releasing hormone: effectiveness of different pulse frequencies.

To determine the ovarian response to a fixed dose of gonadotrophin-releasing hormone (GnRH) administered s.c. at four different pulse frequencies, 20 patients with hypothalamic amenorrhoea were treated over 41 cycles using a dose of 20 ng/kg/pulse. These patients were randomly assigned to receive GnRH at pulse frequencies of 60, 90, 120 or 180 min. GnRH was administered s.c. using portable infusion pumps. Subjects were paid volunteers with a diagnosis of hypothalamic amenorrhoea. All patients had low to less than detectable serum concentrations of luteinizing hormone and follicle stimulating hormone on 8 h serial sampling, and normal serum concentrations of prolactin and androgen, including androstenedione, testosterone and dihydroepiandrosterone sulphate. Six of the 20 patients were enrolled in the protocol to achieve a pregnancy, while 14 were volunteers using a barrier method of contraception. Highest ovulation rates were achieved using pulse frequencies of 90 and 120 min (60 and 88% of cycles respectively). Ovulation occurred significantly less often with frequencies of 60 and 180 min (12 and 38% respectively; P

Unique unbalanced X;X translocation (Xq22;p11.2) in a woman with primary amenorrhea but without Ullrich-Turner syndrome.

This is a report of a patient with delayed puberty and a previously unreported translocation 46,X -X, +der(X),t(X;X) (q22;p11.2) without any manifestations of Ullrich-Turner syndrome. The relationship of this unbalanced translocation to the critical region hypothesis is discussed.

Dysgerminoma and gonadal dysgenesis in a 46,XX female with no evidence of Y chromosomal DNA.

The occurrence of dysgerminoma in dysgenetic gonads without Y chromosomal influence is exceptionally rare. We used Southern blot hybridization of Y-DNA probes to genomic DNA to search for any Y-related influence in a patient with a dysgerminoma, dysgenetic gonads, and a 46,XX karyotype. No Y-specific DNA was found at 11 loci representing the short arm, centromere, and long arm. This absence of any Y-DNA leaves open to question the absolute requirement of Y-related influence in the development of dysgerminoma in dysgenetic gonads.

Localization of "lost" Norplant capsules using compression film screen mammography.

BACKGROUND: The complications of Norplant removal relate primarily to the length of time and amount of dissection required for removal of the capsules. Complications include swelling and pain at the removal site and, at times, capsule fracture. The inability to locate one or more of the capsules is a rare complication. Recommended methods for locating the capsules include plain film radiography and ultrasound imaging. However, in circumstances where neither of these techniques succeeds, no specific recommendations exist to enhance visibility of the capsules. CASE: We used compression film screen mammographic techniques of the soft tissue at the site of insertion to locate a "lost" Norplant capsule after both plain films and ultrasound images failed to reveal the location of the capsule. CONCLUSION: Film screen mammographic techniques may help locate "lost" Norplant capsules that are not visualized with either plain film radiography or ultrasound imaging of the insertion site.

Use of a long-acting GnRH agonist for benign cystic mesothelioma.

BACKGROUND: Benign cystic mesothelioma, a tumor characteristically found in women during the reproductive years, is rare after bilateral oophorectomy or menopause, suggesting hormonal sensitivity. CASE: We treated a 17-year-old woman with a rapidly increasing and symptomatic benign cystic mesothelioma with a long-acting GnRH agonist. A rapid and continued reduction in volume corresponded to the induction and maintenance of a hypoestrogenic state over a 6-month period. However, the subsequent addition of a combination of estrogen and progestin (known as add-back therapy) resulted in a gradual increase in cyst volume, which progressed after discontinuation of all therapy. Resumption of GnRH-analog therapy alone reduced cyst volume again, and the patient underwent surgical removal. CONCLUSION: Long-acting GnRH agonists may have a role in the conservative management of these rare neoplasms. The reduction in volume concomitant with a hypoestrogenic state and regrowth with addition of add-back therapy further suggest extreme sensitivity of this tumor to one or both hormones.