Endometrioma of uterine serosa in a woman with mosaic Turner's syndrome receiving hormone replacement therapy: case report.

Endometriosis in Turner's syndrome patients has only been reported in five isolated cases. We present here an endometrioma on the uterine serosa and pelvic endometriosis arising in a mosaic Turner's patient receiving hormone replacement therapy (HRT). The 24 year old patient with mosaic Turner's syndrome [45,X; 46,X pseudo dicentric Y (q11.23)], on cyclic HRT after laparoscopic gonadectomy 5 years previously, was found to have an adnexal mass on routine examination. Given her history, due to the fear of a malignant process arising from a potential gonadal remnant, she underwent a laparoscopy and was found to have a 5 cm serosal endometrioma arising on a stalk from the uterine fundal surface as well as pelvic endometriosis. De-novo endometrioma and endometriosis occurred in a mosaic Turner's patient after gonadectomy on cyclic HRT. The presentation was also unusual with a pedunculated endometrioma arising from the uterine serosa. Due to the fact that the patient did have cyclic menstrual flow, her endometriosis may have arisen from retrograde menstruation or coelomic metaplasia induced by exogenous hormones.

Regulation of insulin-like growth factor-binding protein 1 by hypoxia and 3',5'-cyclic adenosine monophosphate is additive in HepG2 cells.

Insulin-like growth factor-binding protein 1 (IGFBP-1) is important in regulating minute-to-minute IGF bioavailability in the circulation and is primarily an inhibitor of IGF action systemically and in most cellular systems. Understanding regulation of IGFBP-1 is, thus, important in understanding regulation of IGF actions. The IGFBP-1 promoter contains a cAMP response element, and cAMP stimulates IGFBP-1 gene expression at the transcriptional level. Recently, we have found three consensus sequences for the hypoxia response element in intron 1 of the IGFBP-1 gene. Herein, we have investigated the effects of hypoxia and a cAMP analog, 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP), on IGFBP-1 expression in HepG2 cells, a model system for IGFBP-1 gene regulation. HepG2 cells were exposed to normoxia (20% pO2) or hypoxia (2% pO2) for 24 h in the absence or presence of 8-Br-cAMP (0.1, 0.5, and 1 mM). Western ligand blotting revealed IGFBP-1 as the predominant IGFBP in HepG2-conditioned media, which increased in a dose-dependent manner after incubation with 8-Br-cAMP in normoxia and hypoxia (3-fold and 7-fold at 1 mM, respectively). Under hypoxic, compared with normoxic, conditions, IGFBP-1 protein and messenger RNA (mRNA) levels increased approximately 10-fold and 20-fold, respectively. In normoxia, 8-Br-cAMP stimulated IGFBP-1 protein and mRNA levels in a dose-dependent manner (7-fold and 10-fold at 1 mM). Hypoxia and 8-Br-cAMP showed additive stimulatory effects on IGFBP-1 protein and mRNA levels (35-fold and 50-fold at 1 mM) that were time and dose dependent. Primary transcripts of IGFBP-1 mRNA were increased concordantly with IGFBP-1 mRNA. The half-life of the IGFBP-1 mRNA was markedly increased (approximately 6-fold) by hypoxia, and cAMP minimally enhanced this effect. These results demonstrate that hypoxia and compounds that increase intracellular cAMP additively regulate IGFBP-1 gene expression by transcriptional and posttranscriptional mechanisms. Regulation of IGFBP-1 mRNA and protein by cAMP and hypoxia may be important for understanding the physiologic and pathophysiologic roles of IGFBP-1.

Pregnancy following laparoscopic myomectomy: preliminary results.

The objective of this study was to assess the outcome of pregnancy in a series of women who underwent laparoscopic myomectomy. A total of 115 women underwent laparoscopic myomectomy for pressure and pain (76.5%), abnormal bleeding (52.2%) and/or infertility (29.6%). Follow up data were obtained either by reviewing the patient's chart or returned questionnaire. Of the 115 women, there were 42 pregnancies in 31 patients. Two women were lost to follow-up. Of the remaining 40 pregnancies, six ended with vaginal delivery at term. Caesareans were performed in 22 cases, including 21 at term and one at 26 weeks gestation. Two pregnancies were associated with a normal delivery, but the mode of delivery is unknown. Eight resulted in first trimester pregnancy loss, one was an ectopic pregnancy, and one patient underwent elective termination. Spontaneous uterine rupture was not noted during pregnancy or at term in any of the cases. Average length of follow-up from the date of surgery was 43 months, with a range of 9-99 months. Our series did not confirm the hypothesis that laparoscopic myomectomy is associated with an increased risk for uterine dehiscence during pregnancy. However, a larger series is needed to make a conclusive judgement.

Medical management of interstitial ectopic pregnancy: a case report and literature review.

Recent reports describe successful treatment of interstitial ectopic pregnancies using methotrexate. While the number of reported cases is increasing, no consensus exists regarding the management of this complication of pregnancy. We present the successful use of combined systemic and direct intrasac injection of methotrexate for an interstitial pregnancy with the highest yet reported initial beta-human chorionic gonadotrophin concentration (102,000 mIU/ml). We also describe the use of Doppler ultrasound for monitoring treatment progression. Through a review of the current literature, we propose to facilitate management decisions and increase outcome success by summarizing previously reported treatment regimens and by describing enhanced parameters for patient selection and monitoring.

Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia.

IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that hypoxia regulates IGFBP-1 in the human fetus in vivo and IGFBP-1 gene expression and protein in vitro. Umbilical artery IGFBP-1 levels (mean +/- SEM) from term babies with respiratory acidosis (acute hypoxia), normal babies, and those with mixed respiratory/metabolic acidosis (more profound and prolonged hypoxia) were measured using an immunoradiometric assay. IGFBP-1 levels were similar in normal (n = 12) and acutely hypoxic (n = 6) babies (189.1 +/- 71.8 vs. 175.8 +/- 45.9 ng /ml, respectively, P = 0.789). However, with more profound and prolonged hypoxia (n = 19), IGFBP-1 levels were markedly elevated (470.6 +/- 80.0 ng /ml, P = 0.044). To investigate IGFBP-1 regulation by hypoxia in vitro, HepG2 cells were incubated under hypoxia (pO2 = 2%) and normoxia (pO2 = 20%). IGFBP-1 protein and mRNA increased 8- and 12-fold, respectively, under hypoxic conditions. Hypoxia did not affect protein or mRNA levels of IGFBP-2 or -4. IGFBP-5 and -6 mRNAs, undetectable in control cells, were not induced by hypoxia, whereas minimally expressed IGFBP-3 mRNA increased twofold. Investigation into IGFBP-1 gene structure revealed three potential consensus sequences for the hypoxia response element (HRE) in the first intron. To investigate functionality, a 372-bp fragment of IGFBP-1 intron 1, containing putative HREs, was placed 5' to a heterologous hsp70 promoter in a plasmid using luciferase as a reporter gene. Under hypoxia, reporter gene activity increased up to 30-fold. Mutations in the middle HRE abolished reporter activity in response to hypoxia, suggesting that this HRE is functional in the IGFBP-1 hypoxia response. Cotransfection of HRE reporter genes with a constitutively expressing hypoxia-inducible factor 1 plasmid in HepG2 cells resulted in a fourfold induction of reporter activity, suggesting a role for hypoxia-inducible factor 1 in hypoxia induction of IGFBP-1 gene expression. These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability.

Status of current research on endometriosis.

Endometriosis, a benign gynecologic disorder, occurs in about 10% of women of reproductive age and in up to 50% of women with infertility. Endometriosis is defined as the presence of endometrial glandular and stromal cells outside their normal location in the uterus. Commonly affected areas in the abdominopelvic cavity include the ovaries, the cul-desac and other kinds of pelvic peritoneum, bowel and diaphragm. Rarely is it found in extraabdominal sites, including the pleura and pericardium. While it is not a malignant disorder, endometriosis exhibits cellular proliferation, cellular invasion and neoangiogenesis. The steroid hormone dependence of endometriosis is underscored by its appearance during the reproductive years. Furthermore, the progress of this enigmatic disease can be tempered by administration of antiestrogens, inhibitors of endogenous estradiol production, and hormonal and surgical castration. It is a disorder that markedly affects well-being and physical and emotional health in women. Research on the pathogenesis of endometriosis currently interfaces with four areas of basic research, including the fields of genetics, environmental science, cancer biology and immunology. Here we focus on current research in the latter two disciplines and their relevance to endometriosis research.

Comparison of carbon dioxide and air pneumoperitoneum for gamete intrafallopian transfer under conscious sedation and local anesthesia.

OBJECTIVE: To compare patient tolerance and pregnancy rates (PRs) between two cohorts that underwent GIFT under local anesthesia with air versus carbon dioxide (CO2) pneumoperitoneum. DESIGN: Retrospective study. SETTING: University clinic. PATIENT(S): Eighty-five patients who underwent 125 laparoscopies under conscious sedation for GIFT using air pneumoperitoneum were compared with 42 patients who had 70 GIFT procedures with CO2 pneumoperitoneum. INTERVENTION(S): Transvaginal ultrasound-guided egg retrieval followed by GIFT with compressed air or CO2 for pneumoperitoneum under local anesthesia and i.v. sedation. MAIN OUTCOME MEASURE(S): Patient tolerance and viable PR. RESULT(S): The percentage of patients scoring "very good" was lower in the CO2 group (73% for air versus 57% for CO2), but the combined percentage of those scoring "very good" or "good" was comparable at 89% and 87%. The difference in the viable PRs between the two groups (43% versus 37%) for patients < 40 years old was not statistically significant. CONCLUSION(S): Patient tolerance and PRs are similar for air and CO2 pneumoperitoneum during GIFT under local anesthesia. Given the theoretical risk of air embolus and lack of detrimental effect of CO2 on patient tolerance and success rate, it seems prudent to use CO2 in such a setting.

Laparoscopic management of pelvic pathology during pregnancy.

Advanced operative laparoscopy is being performed increasingly for various indications and in diverse patient populations, including gravid women. In the United States approximately 1.6% to 2.2% of pregnant women require nonobstetric surgery for abdominal and pelvic pathology. Increasing numbers of case reports suggest the feasibility and safety of operative laparoscopy during pregnancy. We identified certain management issues specific to these procedures based on our experience with nine cases of operative laparoscopy in women with gestations up to 22 weeks.

Office laparoscopy under local anesthesia for gamete intrafallopian transfer: technique and tolerance.

OBJECTIVE: To describe our technique for laparoscopic GIFT under local anesthesia and to evaluate patient tolerance and surgeon satisfaction in 175 consecutive procedures. DESIGN: Prospective cohort study. SETTING: University infertility practice. PATIENT(S): All GIFT candidates from 1992 to 1996 were offered the procedure. Of 119 patients, 119 chose local anesthesia for 175 procedures and 1 patient elected to have general anesthesia. INTERVENTION(S): Transvaginal ultrasound-guided egg retrieval followed by GIFT in the clinic procedure room with a 5-mm laparoscope and two accessory 3-mm trocars with local anesthesia and i.v. sedation. MAIN OUTCOME MEASURE(S): Patient tolerance and acceptance, duration of the procedure, amount of analgesics, surgeon satisfaction, and pregnancy rate (PR). RESULT(S): The laparoscopic portion lasted an average of 27 minutes, with a mean dose of 1.41 mg of midazolam and 68 micrograms of fentanyl used. Sixty-nine percent of the patients scored "very good," 20% "good," 9% "acceptable," and 2% "poor." All 38 patients undergoing 97 repeat procedures selected local anesthesia again. For women < 40 years of age, clinical PR and delivery rate were 43% and 38%, respectively. CONCLUSION(S): Routine office GIFT under local anesthesia is effective and well accepted by the surgeon and is preferred by patients. It offers a significant cost containment and scheduling flexibility in addition to high success rates.

Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells.

OBJECTIVE: To investigate monocyte chemotactic protein-1 concentrations in the peritoneal fluid (PF) of women with or without endometriosis, then assess peritoneal mesothelial cells as a potential source of monocyte chemotactic protein-1. DESIGN: Prospective study. SETTING: University medical center. PATIENT(S): Women with (n = 60) or without (n = 18) endometriosis. INTERVENTION(S): First monocyte chemotactic protein-1 levels in PF were measured, then mesothelial cells in culture were treated with cytokines. MAIN OUTCOME MEASURE(S): In PF and culture supernatants, monocyte chemotactic protein-1 was measured by ELISA. In vitro monocyte chemotactic protein-1 messenger RNA expression was evaluated by Northern analysis. RESULT(S): The median concentration of monocyte chemotactic protein-1 in PF of control women was 137 pg/mL (conversion factor to SI unit, 0.115; range, 12 to 418 pg/mL); that of women with moderate endometriosis was 205 pg/mL (range 65 to 6,000 pg/mL); and that of those with severe endometriosis was 1,165 pg/mL (0 to 2,602 pg/mL). Within the moderate to severe endometriosis group, monocyte chemotactic protein-1 levels were higher in women with untreated endometriosis (354 pg/mL range 0 to 6,000 pg/mL) than in women receiving GnRH agonist (128 pg/mL, range 0 to 216 pg/mL). In the control group, monocyte chemotactic protein-1 levels were higher in the proliferative phase than in the secretory phase. Mesothelial cells produced constitutively monocyte chemotactic protein-1; moreover, both interleukin-1 alpha and tumor necrosis factor-alpha induced higher levels of monocyte chemotactic protein-1. CONCLUSION(S): Levels of monocyte chemotactic protein-1 in PF were higher during the proliferative phase than secretory phase of control women and increased in moderate to severe endometriosis. The regulated expression of monocyte chemotactic protein-1 may recruit macrophages into PF and contribute to the pathogenesis of endometriosis.

Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells.

Interleukin-8 (IL-8) is a chemoattractant and activating factor for human neutrophlls and a potent angiogenic agent. The peritoneal fluid of women with endometriosis has been shown to have increased neutrophil chemotactic activity. We postulate that IL-8 may be an important modulator in the pathogenesis of endometriosis and adhesion formation. We first investigated IL-8 concentrations in the peritoneal fluid of women with or without endometriosis, then assessed peritoneal mesothelial cells as a potential source of peritoneal fluid IL-8. Northern blot analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate IL-8 mRNA and protein modulation. The mean concentration of IL-8 in samples obtained from control patients (n = 28) was 4.8 +/- 0.5 pg/ml; from patients with minimal-mild endometriosis (n = 24) was 27.5 +/- 2.6 pg/ml; and from patients with moderate-severe endometriosis (n = 21) was 530.2 +/- 65.1 pg/ml. Confluent mesothelial cells were incubated with human recombinant IL-1 alpha (0.01-100 IU/ml) or tumour necrosis factor (TNF)-alpha (0.01 to 100 ng/ml) for 2-24 h. IL-8 mRNA was detectable in non-treated cells, however both IL-1 alpha and TNF-alpha induced higher amounts of IL-8 mRNA in a dose- and time-dependent manner. Non-treated mesothelial cells in culture also produced and secreted IL-8 protein quantified by ELISA, but again higher concentrations were induced by IL-1 alpha and TNF-alpha treatment. In conclusion, we found that IL-8 concentrations were elevated in peritoneal fluids from women with endometriosis. Cultured mesothelial cells expressed cytokine-inducible IL-8 mRNA and secreted IL-8 protein. The regulated expression of this angiogenic factor may play a role in pathogenesis of endometriosis.