Endometrial microstructure after long-term use of a 91-day extended-cycle oral contraceptive regimen.

Objective: To assess the effect on the endometrial microstructure of an extended-cycle oral contraceptive (OC) regimen containing ethinyl estradiol (EE) and levonorgestrel (LNG).

Methodology: Subjects received up to four cycles of a 91-day extended-cycle OC regimen (84 consecutive days of monophasic 30 microg EE/150 microg LNG followed by 7 days of placebo). Endometrial biopsies were performed prior to the initiation and at the completion of therapy.

Gene expression profiles and structural/functional features of the peri-implantation endometrium in natural and gonadotropin-stimulated cycles.

It has been speculated that controlled ovarian hyperstimulation (COH), as performed during in vitro fertilization therapy, may negatively affect embryo implantation. The objective of this prospective and randomized study was to investigate gene expression profiles of the human endometrium during the window of implantation of gonadotropin-stimulated COH cycles compared with temporally matched natural cycles (d 21). Analysis was performed with high-density oligonucleotide microarrays.

Interleukin (IL)-1, IL-6, and IL-8 predict mucosal toxicity of vaginal microbicidal contraceptives.

Inflammation of the female reproductive tract increases susceptibility to HIV-1 and other viral infections and, thus, it becomes a serious liability for vaginal products. Excessive release of proinflammatory cytokines may alter the mucosal balance between tissue destruction and repair and be linked to enhanced penetration and replication of viral pathogens upon chemical insult. The present study evaluates four surface-active microbicide candidates, nonoxynol-9 (N-9), benzalkonium chloride (BZK), sodium dodecyl sulfate, and sodium monolaurate for their activity against human sperm and HIV, and their capacity to induce an inflammatory response on human vaginal epithelial cells and by the rabbit vaginal mucosa.

Functional studies of subcutaneous ovarian transplants in non-human primates: steroidogenesis, endometrial development, ovulation, menstrual patterns and gamete morphology.

Background: The study objective was to determine if ovarian function would be restored following fresh and cryopreserved extrapelvic autologous ovarian transplantation and if vascular endothelial growth factor (VEGF) administration would augment the success rate.

Methods: Sixteen regularly cycling female cynomolgus monkeys underwent bilateral oophorectomy and were randomly assigned to one of three treatment groups: (i) sham transplant group (n = 5) underwent transplantation of pieces of adipose tissue; (ii) fresh autologous ovarian transplantation without VEGF administration (n = 6) and (iii) fresh autologous ovarian transplantation with 1 microg of VEGF (n = 5) administered at the transplantation site daily for 14 days after transplantation. The ovarian tissue from the sham transplanted group was cryopreserved.

Preclinical experience with two selective progesterone receptor modulators on breast and endometrium.

Org 31710 and Org 33628 are two highly selective progesterone receptor modulators (PRMs) with respect to their anti-progestational and anti-glucocorticoid activity. The compounds have been studied both in vitro and in vivo. Org 33628 has approximately four times stronger anti-progestational activity in vitro than does Org 31710, and in rats it is about 15 times more potent in the pregnancy interruption test.

A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study.

Objective: The aims of this study were to substantiate the previously reported activity of ifosfamide in patients with advanced, persistent, or recurrent carcinosarcoma (mixed mesodermal sarcoma) of the uterus, and to determine whether the addition of cisplatin results in an improved response or survival. Secondarily, we sought to determine the toxicity of ifosfamide-cisplatin in this patient population.

Methods: Patients were randomized to receive ifosfamide (1.

Detection of endometrial pinopodes by light microscopy.

Objective: To study the value of light microscopy (LM) in the assessment of endometrial pinopodes.

Design: Comparative histologic study.

Setting: Outpatient infertility clinic in an academic teaching institution.

Screening for antiproliferative actions of mifepristone. Differential endometrial responses of primates versus rats.

This laboratory has previously shown the capability of the antiprogestin, mifepristone, to noncompetitively inhibit estrogen-induced endometrial proliferation in nonhuman primates. In the following study, use of the rat uterine weight bioassay was compared against a primate (Macaca fascicularis) uterine bioassay to identify the noncompetitive/antiproliferative effects of mifepristone. These uterine bioassays were contrasted for reasons of identifying a comparative laboratory rodent model that could substitute for the need to use primate models in the screening of potential antiprogestins, thereby saving time, cost, and primate resources.

Chronic antiprogestin therapy produces a stable atrophic endometrium with decreased fibroblast growth factor: a 1-year primate study on contraception and amenorrhea.

Objective: To describe the efficacy of mifepristone in the prevention of menstrual bleeding and ovulation, with similar observations in comparison groups.

Design: Prospective experimental study. Thirty-two cynomolgus monkeys were divided equally into four treatment groups (n = 8).

p53 protein accumulation and genetic alterations in human giant cell tumors of bone (osteoclastomas).

Inactivation of tumor suppressor genes represents a critical determinant in the development of a large proportion of human cancers. The tumor suppressor gene p53 is the most frequently altered gene in human cancers. In the present study, p53 protein accumulation, gene mutation and the association between p53 alteration and clinicopathological parameters was analyzed in 29 giant cell tumors of bone.

Endometrial effects of RU486 in primates--antiproliferative action despite signs of estrogen action and increased cyclin-B expression.

Continuous antiprogestin administration to hormone replaced, castrate monkeys inhibits estrogen-induced endometrial proliferation through mechanisms which remains unclear. To elucidate the molecular mechanisms of RU486-induced endometrial suppression, we treated six intact female cynomolgus monkeys on cycle days 2-22 sequentially with placebo, RU486 (1 mg/kg/day) and levonorgestrel (LNG) (2 microg/kg/day) intramuscularly (i.m.

Role of hypoestrogenism or sex steroid antagonism in adhesion formation after myometrial surgery in primates.

Objective: To determine the contribution of estrogen in the development of pelvic adhesions during myometrial surgery.

Design: A randomized, prospective study in the nonhuman primate.

Setting: A primate colony, Department of Obstetrics and Gynecology, Eastern Virginia Medical School.

Antiprogestin and/or gonadotropin-releasing hormone agonist for endometriosis treatment and bone maintenance: a 1-year primate study.

The fact that RU 486 curtailed estrogen-induced endometrial proliferation in primates and relieved pelvic pain in women with endometriosis is the reason for continuing research on antiprogestins. Thirty-two adult female cynomolgus monkeys demonstrating menstrual regularity had surgery for the induction of endometriosis. After lesion staging, four treatment groups (n = 8), each of 1-yr duration, were made.

Estrogen and progesterone receptor mRNA are expressed in distinct pattern in male primate reproductive organs.

Purpose: The role(s) of estrogens (E) and progesterone (P) in male reproductive physiology remain unclear. Estrogens are used in the treatment of prostatic cancer. Progestins have been used to control excessive sexual behavior in men, and proposed as a male contraceptive.

The effect of progesterone on the accumulation of leukocytes in the human endometrium.

Objective: Our purpose was to determine the role of progesterone on the number and type of leukocytes found in human endometrium.

Study Design: Endometrial tissue was obtained from normally cycling women and from women receiving hormone replacement therapy for premature ovarian failure. All tissues were formalin fixed, sectioned, and stained with specific antibodies to leukocytes, T cells, B cells, and macrophages.

A prospective evaluation of transvaginal sonography for detection of ovarian disease.

Objective: Despite the expanding role of transvaginal sonography in routine gynecologic examinations, as well as in screening for ovarian cancer, recent reports have noted problems when using the procedure for detecting ovarian masses and visualizing the ovaries in postmenopausal women. Our study was designed to assess prospectively the capability of transvaginal sonography in evaluating the ovary and detecting adnexal masses.

Subjects And Methods: Transvaginal sonography was used to examine 113 ovaries in 59 women within 72 hr before gynecologic surgery.

Phyllodes tumors.

Phyllodes tumors are rare lesions of the breast with unpredictable behavior. A review of 18 patients with phyllodes tumors was performed to determine if pathologic and cellular characteristics correlated with clinical behavior and to determine the influence of the extent of the operation performed on clinical outcome. Local excision, primarily breast biopsy, was performed in 14 of the 18 patients.

Papillary peritoneal carcinomatosis after prophylactic oophorectomy.

Prophylactic oophorectomy has been recommended in patients with a strongly positive family history for ovarian carcinoma. A patient with a strongly positive family history underwent a prophylactic oophorectomy and, 5 years later, developed a primary peritoneal papillary serous adenocarcinoma. A prophylactic oophorectomy does not afford complete protection in some patients with familial ovarian cancer syndrome.

Transitional cell carcinoma of the renal pelvis with ovarian metastasis.

This article describes the first reported case of a primary transitional cell carcinoma of the renal pelvis metastatic to the ovary. The clinical presentation in our patient was similar to that of a primary ovarian carcinoma. The differential diagnosis of a primary or metastatic transitional cell carcinoma in the ovary is important and has therapeutic as well as prognostic implications.

Endometrial receptivities after leuprolide suppression and gonadotropin stimulation: histology, steroid receptor concentrations, and implantation rates.

The effect of markedly supraphysiologic levels of E2 and P4 on the endometrium was assessed by examining endometrial histology, E2 and P4 receptor concentrations, and embryo implantation rates in IVF cycles with and without leuprolide use. Results suggest that 1) the high ovarian response common in leuprolide pretreated cycles can advance endometrial histology, but only up to a certain limit, 2) P4 greater than 25ng/ml or E2 greater than 200pg/ml on the day of transfer was associated with non-lagging endometria, 3) implantation rate in high response cycles is not impaired and may be increased, 4) earlier P4 supplementation in low response cycles may be beneficial, 5) extraordinarily high response (E2 greater than 5000pg/ml) may be detrimental to implantation, and 6) the optimal histology for implantation appears to be at least day 16.

Intermittent GnRH antagonist plus progestin contraception conserving tonic ovarian estrogen secretion and reducing progestin exposure.

The present study was designed to evaluate the effectiveness of a once-weekly regimen of GnRH antagonist followed by a progestin as a potential new contraceptive method. On menstrual cycle days 2, 9, 16, and 23 (onset of menses = Day 1) monkeys were divided into two groups: 1) those injected sc with 0.1 mg/kg Nal-Glu GnRH antagonist in saline and those given only vehicle (control).

Prospective evaluation of the role of fine-needle aspiration biopsy in the diagnosis and management of patients with palpable solid breast lesions.

To evaluate the role of fine-needle aspiration biopsy (FNAB) in the diagnosis and management of patients with palpable, solid and suspicious breast lesions, a total of 107 FNABs were performed on 98 patients under the prospective FNAB protocol. Eight-four FNABs were positive for breast carcinomas; of these 84 positive FNABs, 80 underwent mastectomy without open biopsy or frozen section. Our data showed a sensitivity of 95 per cent and a specificity of 100 per cent for diagnosis of breast malignancies on these patients.