Laparoscopically assisted uterine fibroid cryoablation.

OBJECTIVE: The objective of the study was to develop a safe and effective cryoablation technique for the treatment of uterine fibroids. STUDY DESIGN: This was a multicenter pilot case series to evaluate cryoablation of uterine fibroids using laparoscopically assisted placement of 17-gauge cryoablation needles. Patient satisfaction was documented with a validated Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire. Procedural efficacy was evaluated by assessing fibroid shrinkage. Treatment was followed by assessments at 3, 6, and 12 months. RESULTS: Median fibroid volume reduction was 43.3% (19 patients) and 66.4% (15 patients) at 6 and 12 months, respectively. Median UFS-QOL score improvement was 61.9% and 66.7% at 6 and 12 months, respectively. Additionally, patients experienced marked improvement of bleeding and fibroid bulk symptoms. The median Symptom Severity Score at baseline was 50, 25.0 (-59%) at 6 months, and 12.5 (-66.7%) at 12 months. CONCLUSION: These pilot data indicate that uterine fibroid cryoablation is a safe and effective minimally invasive alternative to treat symptomatic uterine fibroids.

Veracity in in vitro fertilization Web pages.

Huang et al. described compliance of IVF websites against the American Medical Association online health information guidelines and reported that IVF websites scored poorly. We describe a protocol for IVF websites that would inform readers about truthfulness of the page, develop standards for page construction, and establish a review process.

Myomectomy and MRI-directed cryotherapy.

The purpose of this study was to identify alternatives to hysterectomy by transabdominal interventional magnetic resonance imaging-guided cryoablation. This represents a report of a prospective institutional review board-approved protocol to study interventional magnetic resonance imaging-guided cryoablation of uterine fibroid tumors. Women were selected on the basis of symptoms that were related to uterine fibroid tumors (bleeding, uterine pain, pelvic congestion, compression symptoms) and the absence of any desire for childbearing. Magnetic resonance imaging was performed before the procedure to measure the size and number of fibroid tumors, and follow-up magnetic resonance imaging determined the reduction of the lesion. Ten patients were originally included, and nine were treated and had substantial reduction in the uterine size (average, 65% volume reduction). The primary symptoms have either improved or resolved in eight of the nine women. This is the first reported review of interventional magnetic resonance imaging-directed cryotherapy of uterine fibroid tumors. This minimally invasive therapy produced shrinkage of the tumor in nine of our first ten patients.

Telomerase expression abrogates rapamycin-induced irreversible growth arrest of uterine fibroid smooth muscle cells.

Uterine fibroids are the most common solid tumors found in women of reproductive age. It has been reported that deregulation of the mammalian target of rapamycin (mTOR) pathway plays an important role in the etiology of leiomyoma. Here, we investigated the effect of rapamycin, an inhibitor of mTORC1, on the growth of primary fibroid smooth muscle cells (fSMCs) and human telomerase reverse transcriptase (hTERT)-transduced and immortalized fSMCs. With the primary fSMCs, a 24-hour treatment with rapamycin was sufficient to trigger a growth arrest that was not reversible upon drug removal. By contrast, the growth inhibitory effect of rapamycin on the hTERT-transduced fSMCs was readily reversible, as these cells resumed proliferation upon the withdrawal of the drug. These results suggest that rapamycin-induced irreversible growth arrest of fSMCs is dependent on the senescence barrier that is abrogated by the ectopic expression of telomerase.

Expression profile of several genes in human myometrium and uterine leiomyoma.

OBJECTIVE: To screen several genes that are differentially expressed in uterine leiomyoma and matched unaffected myometrium by using microarray-based hybridization and real-time polymerase chain reaction analyses. DESIGN: Screen by arrays for < or =2,400 known genes in leiomyoma and control myometrium. SETTING: University clinical research laboratory. PATIENT(S): Four patients with leiomyoma scheduled for surgery during the proliferative phase. INTERVENTION(S): Four paired samples of leiomyoma and adjacent myometrium were obtained from patients undergoing hysterectomy. MAIN OUTCOME MEASURE(S): Fold-changes in expression of leiomyoma and matched myometrium (L/M). RESULT(S): A comparison of expression patterns revealed 73 genes significantly up- or down-regulated in each paired tissue sample, of which 30 genes showed increased expression (mean L/M of >2) and 43 showed decreased expression (mean L/M of <0.5) in leiomyoma compared with normal myometrium. When considering only growth factors, pleiotropin (PTN) was expressed 3.5-fold more in leiomyomas compared with in myometrium. No other growth factors were similarly affected. In addition, real-time polymerase chain reaction analysis correlated well with microarray data. CONCLUSION(S): Data obtained from the present study suggest that several genes are selectively overexpressed in leiomyomas compared with in myometrium. Increased expression of growth factor PTN may represent a promising target for therapy.

Professional liability claims and Central Association of Obstetricians and Gynecologists members: myth versus reality.

OBJECTIVE: The purpose of this study was to survey members of the Central Association of Obstetricians and Gynecologists about professional liability claims. STUDY DESIGN: A survey was mailed to Central Association of Obstetricians and Gynecologists members regarding medical liability experience. RESULTS: Of the 897 surveys mailed, 73% were completed. The responding 658 clinicians had been in practice for 17,136 years and had 1507 closed claims. The respondents had a claim every 11 years of practice and a trial every 69 years. Matched for years of practice, a case control comparison indicated that the litigation is significantly lower for female physicians (1.5 +/- 1.8) than for male physicians (2.2 +/- 2.0; P = .019) although the mean cases that were dropped or dismissed were higher for men (1.3 +/- 1.7 vs 0.8 +/- 1.4; P = .022). However, the mean number of trials, defense trial verdicts, and the settlement amounts were similar for both genders. CONCLUSION: We found that professional liability claims are uncommon and that the gender of the obstetrician-gynecologist influences the litigation profile.

FEM1A is a candidate gene for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, and is characterized by infertility, hyperandrogenism and insulin resistance in skeletal muscle. There is evidence for a PCOS gene localized to chromosome 19p13.3. The FEMIA gene maps to chromosome 19p13.3 and is highly expressed in skeletal muscle. FEMIA is a homolog of fem-1, a sex-determination gene of Caenorhabditis elegans that controls masculinization. In a pilot study of Caucasian PCOS patients from our local clinic, we found that one of these five patients exhibited a heterozygous germline missense mutation in FEM1A, designated FEM1A*H500Y. This mutation alters an amino acid conserved from human to C. elegans, and was not found in any of 198 control chromosomes. This missense allele was not found in any of a separate group of 30 PCOS patients from a different regional/ethnic background. Immunostaining of mouse ovary demonstrated that the mouse homolog of FEM1A is expressed in androgen-producing secondary interstitial cells, with a marked increase in expression after puberty, consistent with a key feature of PCOS -- ovarian hyperandrogenism. In conclusion, FEM1A should be considered a candidate gene for PCOS, and more extensive analysis of FEM1A, both coding and regulatory sequences, is warranted in patients and families with PCOS.

Leukemia inhibitory factor and homeobox a10 gene expression in an ectopic pregnancy model for implantation.

OBJECTIVE: We investigated the expression of leukemia inhibitory factor and homeobox a10 in endometrium that was derived from patients with concurrent ectopic pregnancies compared with nonpregnant luteal phase endometrium from the same patients. STUDY DESIGN: Endometrial biopsy specimens that were obtained from women (n=3) who underwent surgery for ectopic pregnancy were matched with biopsy specimens in a nonpregnant luteal phase from the same patients. Quantitative reverse transcription polymerase chain reaction for leukemia inhibitory factor and homeobox a10 was performed. Polymerase chain reaction products were assayed with laser detection of nanogram quantities of complementary deoxyribonucleic acid. Ratios of each implantation marker to glyceraldehyde-3-phosphate dehydrogenase as an internal standard were compared for quantification. RESULTS: Leukemia inhibitory factor expression is increased in endometrium from ectopic pregnancy; homeobox a10 is increased in luteal phase endometrium. CONCLUSION: Leukemia inhibitory factor appears to be regulated by human chorionic gonadotropin or other factors of pregnancy; homeobox a10 is regulated by ovarian steroids of the luteal phase.

Interventional magnetic resonance imaging cryotherapy of uterine fibroid tumors: preliminary observation.

OBJECTIVE: The purpose of this study was to identify alternatives to hysterectomy. We have developed a transabdominal interventional magnetic resonance imaging-guided cryoablation procedure and report this novel approach. STUDY DESIGN: This represents the preliminary and first report of a prospective Institutional Review Board-approved protocol to study interventional magnetic resonance imaging-guided cryoablation of uterine fibroid tumors. Women were selected on the basis of symptoms that were related to uterine fibroid tumors (bleeding, uterine pain, pelvic congestion, compression symptoms) and the absence of any desire for child bearing. A physical examination confirmed the presence of fibroid tumors, and magnetic resonance imaging was performed before the procedure to measure the size and number of fibroid tumors. Patients returned to the interventional magnetic resonance imaging and underwent placement of 3 to 5 probes (2-3 mm) under magnetic resonance imaging-directed guidance. Follow-up magnetic resonance imaging determined the size reduction of the lesion, and a clinical evaluation determined the change in symptoms. RESULTS: Nine patients were treated and had substantial reduction in the uterine size (average, 66% volume reduction), and their primary symptoms have either improved or resolved. CONCLUSION: This is the first reported review of interventional magnetic resonance imaging-directed cryotherapy of uterine fibroid tumors. This minimally invasive therapy produced shrinkage of the tumor in 8 of our first 9 patients.

Quantitative analysis of adhesion molecules on cellular constituents of the human uterine microenvironment under the influence of estrogen and progesterone.

The uterus contains all the components of a tertiary lymphoid compartment. We hypothesize that specific leukocyte recruitment to the endometrium during the secretory phase of the menstrual cycle and early pregnancy limits the type of immunocyte that gains access. The present study utilized flow cytometry to define and quantify adhesion molecules possibly used by decidual infiltrating lymphocytes (DIL) as homing receptors, uterine microvascular myometrial endothelial cells (UtMVE-Myo) as addressins, and secretory endometrial stroma cells (STO) as retainment factors. Human umbilical cord vein endothelial cells and peripheral blood lymphocytes were used as control cells for comparison studies. DIL were composed of predominantly lymphocyte function-associated antigen (LFA)-1+, intercellular adhesion molecule (ICAM)-1+, LFA-2+, LFA-3+, gp150,95+, alpha1beta1+, Hermes cell adhesion molecule (H-CAM)+, and neural cell adhesion molecule (N-CAM)+ (CD56(bright)) memory/effector natural killer cells. A significant number of UtMVEC-Myo expressed platelet endothelial cell adhesion molecule (PECAM)-1, a percentage were uniquely LFA-3+, and alpha4 integrin expression was uniquely high. An increased number of STO uniquely expressed alpha3, beta3, and LFA-3, whereas alpha2, alpha4, alphaVbeta3, and H-CAM were significantly increased. Possible unique adhesions of DIL:UtMVEC-Myo included SLe(x):PECAM, vascular cell adhesion molecule-1:alpha4, and LFA-2:LFA-3, whereas DIL:STO included LFA-2:LFA-3 and N-CAM:N-CAM. Unique molecules on DIL may also associate with extracellular matrix (ECM) or complement on UtMVEC-Myo or STO to form gp150,95:fibrinogen/iC3b/C3dg, alpha1beta1:laminin (LM)/collagen (CO), and ICAM-1:fibronectin (FN) interactions. Bridges of ECM may also form between DIL and UtMVEC-Myo adhesion molecules including ICAM-1:FN:ICAM-1 and alpha4beta1:FN:alpha4beta1. DIL:ECM:STO interactions may involve alpha2beta1:CO:alpha2beta1, alpha3beta1:LM/CO/FN:alpha3beta1, alphaVbeta3:VN:alphaVbeta3, and H-CAM:hyaluronate:H-CAM. It is likely that many adhesion molecules play a role in the recruitment and retainment of specialized lymphocytes within the uterine microenvironment. (Mackay et al., 1990).