Grace M. Couchman

Management of uterine leiomyomata: what do we really know?,

OBJECTIVE To systematically review the literature on the surgical and nonsurgical management of uterine leiomyomata. DATA SOURCES Published literature in English on the management of uterine leiomyomata published from 1975 through 2000 was identified in MEDLINE, CINAHL, CancerLit, EMBASE, HealthSTAR, and the Cochrane Database of Systematic Reviews. Search terms included “leiomyomata,” “fibroids,” “hysterectomy,” and “myomectomy.” STUDY SELECTION Study designs considered included controlled trials, prospective trials with historical controls, prospective or retrospective cohort studies, and series with at least 20 cases. Original research studies or relevant reviews were included if the study population included women with uterine leiomyomata, and data were provided relevant to one or more of nine prespecified research questions. TABULATION, INTEGRATION, AND RESULTS Inconsistency in reporting of severity of symptoms, uterine anatomy, and response to therapy prevented meaningful comparison of studies in most cases, and prevented performance of meta‐analysis in all cases. This was true of both surgical and nonsurgical treatments. CONCLUSION The available evidence on the management of uterine leiomyomata is of poor quality. Patients, clinicians, and policymakers do not have the data needed to make informed decisions about appropriate treatment. Given the prevalence of this condition and its substantial impact on womens lives, obtaining these data should be a high research priority.

ReviewManagement of uterine leiomyomata: what do we really know?1,2

OBJECTIVE To systematically review the literature on the surgical and nonsurgical management of uterine leiomyomata. DATA SOURCES Published literature in English on the management of uterine leiomyomata published from 1975 through 2000 was identified in MEDLINE, CINAHL, CancerLit, EMBASE, HealthSTAR, and the Cochrane Database of Systematic Reviews. Search terms included “leiomyomata,” “fibroids,” “hysterectomy,” and “myomectomy.” STUDY SELECTION Study designs considered included controlled trials, prospective trials with historical controls, prospective or retrospective cohort studies, and series with at least 20 cases. Original research studies or relevant reviews were included if the study population included women with uterine leiomyomata, and data were provided relevant to one or more of nine prespecified research questions. TABULATION, INTEGRATION, AND RESULTS Inconsistency in reporting of severity of symptoms, uterine anatomy, and response to therapy prevented meaningful comparison of studies in most cases, and prevented performance of meta‐analysis in all cases. This was true of both surgical and nonsurgical treatments. CONCLUSION The available evidence on the management of uterine leiomyomata is of poor quality. Patients, clinicians, and policymakers do not have the data needed to make informed decisions about appropriate treatment. Given the prevalence of this condition and its substantial impact on womens lives, obtaining these data should be a high research priority.

The role of partial sigmoid colectomy for debulking epithelial ovarian carcinoma

Forty women underwent partial sigmoid colectomy during cytoreductive surgery for advanced epithelial ovarian carcinoma. Twenty-one (53%) and nineteen (47%) received this as part of primary or secondary debulking procedures, respectively. Fifty-four percent had postoperative residual disease less than 1 cm in largest diameter. Even though multiple surgical procedures were performed in conjunction with sigmoid colectomy, 75% of the patients had no significant postoperative morbidity. Postoperative mortality was 2.5%. Seventy-eight percent avoided permanent colostomy. Despite the above morbidity rate and aggressive postoperative therapy, the median survival for the entire group was only 14.5 months, with no significant differences between groups of patients who were categorized by primary or secondary debulking, histologic grade, amount of preoperative disease, ascites, or extent of postoperative residual disease. Although a partial sigmoid colectomy can be performed with a reasonable morbidity rate as part of debulking for ovarian cancer, and probably provides significant palliation of symptoms from large pelvic tumors, it must be used judiciously in selected patients.

Mullerian agenesis and thrombocytopenia absent radius syndrome : A case report and review of syndromes associated with mullerian agenesis

Mullerian agenesis, commonly referred to as Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS), is a congenital defect that is most commonly associated with renal and spinal malformations. It is very rare for Mullerian agenesis to be accompanied by malformations of the extremities. In this report, we describe a 22-year-old woman with Mullerian agenesis and thrombocytopenia absent radius syndrome (TARS). We also review rare syndromes associated with Mullerian anomalies, including Mullerian hypoplasia/aplasia–renal agenesis–cervicothoracic somite dysplasia (MURCS), Roberts syndrome, Bardet-Biedl syndrome (BBS), McKusick-Kaufman syndrome (MKS), Wolf-Hirschhorn syndrome, and others. The pathogenesis of these complex malformation syndromes is not well understood as a result of their sporadic occurrence. However, some of these syndromes do follow a pattern of inheritance, suggesting that they could provide insights into our understanding of their origins. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader should be able to review the rare congenital defects associated with Mullerian agenesis, to determine the genetic etiologies of the associated syndromes with Mullerian agenesis, and to discuss information for parental counseling related to inheritance patterns and growth and development of the affected child.

Optical instrument for measurement of vaginal coating thickness by drug delivery formulations

An optical device has been developed for imaging the human vaginal epithelial surfaces, and quantitatively measuring distributions of coating thickness of drug delivery formulations—such as gels—applied for prophylaxis, contraception or therapy. The device consists of a rigid endoscope contained within a 27-mm-diam hollow, polished-transparent polycarbonate tube (150mm long) with a hemispherical cap. Illumination is from a xenon arc. The device is inserted into, and remains stationary within the vagina. A custom gearing mechanism moves the endoscope relative to the tube, so that it views epithelial surfaces immediately apposing its outer surface (i.e., 150mm long by 360° azimuthal angle). Thus, with the tube fixed relative to the vagina, the endoscope sites local regions at distinct and measurable locations that span the vaginal epithelium. The returning light path is split between a video camera and photomultiplier. Excitation and emission filters in the light path enable measurement of fluorescence of t...

Osteoporosis risk factors: association with use of hormone replacement therapy and with worry about osteoporosis

Abstract Among risk factors for osteoporosis, only family history was associated with worry about osteoporosis, while white race was the only factor associated with hormone replacement therapy use. Objectives: To determine whether postmenopausal women with risk factors for osteoporosis are more likely to use hormone replacement therapy (HRT) or to worry about osteoporosis than women without risk factors. Method: Cross-sectional survey of postmenopausal women at the Women Veteran Comprehensive Health Center. Statistical analysis was performed using the chi-square test and logistic regression analysis. Results: Of the 230 postmenopausal women who answered the questionnaire (mean age 55.7 years), 167 (72%) reported ever having used HRT and 113 (49%) worried about osteoporosis. Factors that were significantly associated ( P P Conclusions: Among risk factors for osteoporosis, only family history was associated with worry about osteoporosis, while white race was the only risk factor associated with HRT use in our cohort of postmenopausal woman veterans. This may represent a lack of awareness and knowledge about osteoporosis and its sequelae and about the benefits of HRT. An understanding of patient awareness of risk factors for osteoporosis and their motivations to take HRT can be valuable when counseling women on their decision to use HRT or other medications to prevent osteoporosis.

Successful Pregnancies in Patients with Estrogenic Anovulation After Low-Dose Human Chorionic Gonadotropin Therapy Alone Following hMG for Controlled Ovarian Hyperstimulation

Objective: To demonstrate that folliculogenesis can be sustained with 200 IU human chorionic gonadotropins (hCG) after FSH-priming and result in pregnancy in women with estrogenic ovulatory dysfunction and risk factors for severe ovarian hyperstimulation syndrome (OHSS).Design:Case report: Three women with infertility associated with estrogenic ovulatory dysfunction and hyperinsulinemia who appeared to be at high risk for severe OHSS during gonadotropin therapy.Interventions: After 10 days of receiving either 150 IU hMG or recombinant FSH, patients were switched to 200 IU hCG/day alone for 2–3 days. 5,000 IU of hCG was then administered followed by either home intercourse, intrauterine insemination or transvaginal oocyte retrieval-embryo transfer.Main Outcome Measures: Endovaginal ultrasound measurement of follicle number and size, serum estradiol levels, symptoms of ovarian hyperstimulation, pregnancy test, and evaluation of pregnancy by transvaginal ultrasound.Results: After discontinuation of hMG or recombinant FSH, serum estradiol concentrations continued to rise, and follicles > 14 mm continued to grow during low-dose hCG administration. All women conceived without developing symptoms of OHSS. Pregnancy outcomes achieved include a term singleton delivery, a term twin delivery, and triplets delivered at 31 weeks gestation.Conclusion: The use of low-dose hCG alone is sufficient for supporting the late stages of folliculogenesis in women with estrogenic ovulatory dysfunction. This ovulation induction regimen appears to support the follicular growth of larger follicles while decreasing the number of smaller preovulatory follicles, thereby reducing a known risk factor for OHSS. We report on the positive pregnancy outcomes in 3 women with estrogenic ovulatory dysfunction and clinically appeared to be at high risk for developing severe OHSS who safely underwent this protocol.

p53lyn and p56lyn: A New Signaling Pathway in Human Endometrium and Endometrial Adenocarcinomas

Objective: To identify specific tyrosine kinases that are involved in endometrial signaling and to study their in vivo expression in normal and abnormal endometrium. We hypothesized that proteins that are differentially expressed would be mor likely to be important in regulated cellular events. Methods: Complementary DNA libraries, constructed from human secretory (n = 5) and proliferative (n = 5) endomentrial specimens, were screened with a polyclonal anti-phosphotyrosine antibody. Positive clones were sequenced and screened for differential expression using immunoblotting and Northern analysis of samples from proliferative and secretory endometrium. The expression of one identified clone, lyn, a Src family member, was characterized further with Western and Northern blot analyses and immunolocalization. Results: One protein identified by the above method was lyn, a member of the src family of protein tyrosine kinases, never described in the human endometrium. Western blot analysis revealed two forms of lyn protein p53lyn and p56lyn, that were most abundant in the late secretory phase. Immunohistochemistry demonstrated uniform protein expression by all cells in normal glandular epithelium and suggesed a correlation between lyn protein expression and cell differentiation for human endometrial adenocarcinomas, with markedly elevated levels noted in poorly differentiated adenocarcinomas compared with well-differentiated tumors (n = 3). Northern hybridization confirmed the presence of the expected 3.5-kb lyn transcript in normal and abnormal endometrium. Conclusions: Our data demonstrate that human cDNA libraries created from different phases of the menstrual cycle can be screened successfully using anti-phosphotyrosine antibodies to identify differentially expressed protein tyrosine kinases. Although p53lyn and p56lyn expression has been thought of as a predominantly lymphoid-specific tyrosine kinase, we show prominent expression of lyn protein and mRNA by normal and malignant epithelium of the human endometrium, suggesting a role in endometrial signaling and human reproduction.

Evaluation of the postcoital test in cycles involving exogenous gonadotropins

Objective To evaluate the hypothesis that a postcoital test, optimally performed in the periovulatory period of cycles in which gonadotropin-induced superovulation was used, correlates with cycle fecundity. Methods Of 1135 total consecutive cycles, 367 first cycles were analyzed from the reproductive endocrinology and infertility service of a university medical center. This referral population had a mean age of 34.6 years for the female partner, a nulliparity rate of 81%, and a mean length of infertility of 4.8 years. Postcoital tests were performed 36–40 hours after hCG administration in gonadotropin-stimulated cycles. Clinical pregnancy was defined as fetal cardiac activity as seen on transvaginal ultrasound examination. Results Couples with no sperm observed per high-power field in the cervical mucus achieved a 16% fecundity rate (21 pregnancies in 129 cycles), one to ten sperm a 18% fecundity rate (28 pregnancies in 154 cycles), and more than ten sperm a 15% fecundity rate (13 pregnancies in 84 cycles). There was no significant difference between groups (n = 367, P = .85); the power to detect a statistically significant difference was .82. As validation of optimal cervical mucus, fecundity rates were compared with these postcoital test values across the entire range of peak periovulatory serum estrogen levels, and no correlation was seen (P = .61, .86, and .96 for estrogen levels of 201-500, 501-1500, and 1501-3433 pg/mL, respectively). Conclusion With precise periovulatory timing and supraphysiologic estrogen levels optimizing qualitative cervical mucus characteristics in gonadotropin-induced cycles, the number of sperm observed per high-power field does not correlate with cycle fecundity.

p53(lyn) and p56(lyn)

TO identify specific tyrosine kinases that are involved in endometrial signaling and to study their in vivo expression in normal and abnormal endometrium. We hypothesized that proteins that are differentially expressed would be more likely to be important in regulated cellular events. Complementary DNA libraries, constructed from human secretory (n = 5) and proliferative (n = 5) endometrial specimens, were screened with a polyclonal anti-phosphotyrosine antibody. Positive clones were sequenced and screened for differential expression using immunoblotting and Northern analysis of samples from proliferative and secretory endometrium. The expression of one identified clone, lyn, a Src family member, was characterized further with Western and Northern blot analyses and immunolocalization. One protein identified by the above method was lyn, a member of the src family of protein tyrosine kinases, never before described in the human endometrium. Western blot analysis revealed two forms of lyn protein, p53lyn and p56lyn, that were most abundant in the late secretory phase. Immunohistochem-istry demonstrated uniform protein expression by all cells in normal glandular epithelium and suggested a correlation between lyn protein expression and cell differentiation for human endometrial adenocarcinomas, with markedly elevated levels noted in poorly differentiated adenocarcinomas compared with well-differentiated tumors (n = 3). Northern hybridization confirmed the presence of the expected 3.5-kb lyn transcript in normal and abnormal endometrium. Our data demonstrate that human cDNA libraries created from different phases of the menstrual cycle can be screened successfully using anti-phosphotyrosine antibodies to identify differentially expressed protein tyrosine kinases. Although p53lyn and p56lyn expression has been thought of as a predominantly lymphoid-specific tyrosine kinase, we show prominent expression of lyn protein and mRNA by normal and malignant epithelium if the human endometrium, suggesting a role in endometrial signaling and human reproduction.