Endometrial stem/progenitor cells in menstrual blood and peritoneal fluid of women with and without endometriosis.

RESEARCH QUESTION: Are endometrial stem/progenitor cells shed into uterine menstrual blood (UMB) and the peritoneal cavity in women with and without endometriosis during menstruation? DESIGN: Women with (n = 32) and without endometriosis (n = 29) at laparoscopy (total 61), carried out during the menstrual (n = 41) and non-menstrual phase (n = 20) were recruited. The UMB, peritoneal fluid and peripheral blood were analysed by clonogenicity assay and flow cytometry to quantify the concentrations of endometrial clonogenic cells, SUSD2+ mesenchymal stem cells (eMSC) and N-cadherin+ epithelial progenitor cells (eEPC). RESULTS: Clonogenic endometrial cells, eMSC and eEPC were found in most UMB samples at similar concentrations in women with and without endometriosis. In contrast, 62.5% of women with endometriosis and 75.0% without (controls) had clonogenic cells in peritoneal fluid samples during menses. The eMSC were present in the peritoneal fluid of 76.9% of women with endometriosis and 44.4% without, and eEPC were found in the peritoneal fluid of 60.0% of women with and 25.0% without endometriosis during menses. Median clonogenic, eMSC and eEPC concentrations in peritoneal fluid were not significantly different between groups. More clonogenic cells persisted beyond the menstrual phase in the peritoneal fluid of women with endometriosis (menstrual 119/ml [0-1360/ml] versus non-menstrual 8.5/ml [0-387/ml]; P = 0.277) compared with controls (menstrual 76.5/ml [1-1378/ml] versus non-menstrual 0/ml [0-14/ml]; P = 0.0362). No clonogenic endometrial cells were found in peripheral blood. CONCLUSIONS: Clonogenic endometrial cells, SUSD2+ eMSC and N-cadherin+ eEPC are present in UMB and the peritoneal fluid of women with and without endometriosis. Further study of the function of these cells may shed light on the cellular origins of endometriosis.

Cryopreserved oocytes: update on clinical applications and success rates.

IMPORTANCE: Over the past 3 decades, oocyte cryopreservation procedures have improved rapidly. However, there is limited research reviewing the efficacy of different cooling protocols and inadequate data comparing in vitro fertilization (IVF) outcomes from fresh oocytes with cryopreserved oocytes. OBJECTIVE: The present review was performed to investigate advances in oocyte cryopreservation technologies and identify areas for further research, to determine whether results from IVF using cryopreserved oocytes are comparable to IVF using fresh oocytes, and to identify the patient populations requiring access to oocyte cryopreservation. EVIDENCE ACQUISITION: A literature review was conducted. OVID (MEDLINE) and PubMed databases were queried using phrases such as "oocyte or egg" and "cryopreservation," "vitrification," or "slow cooling or slow freezing." A total of 180 studies were selected for review. RESULTS: Current literature suggests that vitrified oocytes produce superior IVF results to slow-frozen oocytes and may yield comparable outcomes to IVF with fresh oocytes in certain patient populations. Patients at risk of infertility due to disease or age-related decline or oocyte donation programs, couples who fail to produce semen when required for IVF, and patients with legal or ethical reasons against embryo cryopreservation may access cryopreserved oocytes. CONCLUSIONS: We suggest that women who comprise the previously mentioned patient populations should be offered oocyte vitrification technology. Further research is required to confirm IVF success across all patient populations and determine the best cryopreservation protocols. RELEVANCE: This review will be relevant to clinicians interested in fertility treatments using cryopreserved oocytes, fertility preservation, oncology and fertility, and immunology and fertility.

The effects of chemotherapy and radiotherapy on fertility in premenopausal women.

UNLABELLED: With the improved survival rate of childhood and young adult cancer patients, the long-term sequelae of the treatments used are increasingly important. In this review, current knowledge of the gonadotoxicity of commonly employed chemotherapeutic agents and radiotherapy regimens is examined. Differences between the effect of "high-risk" and "low-risk" agents are discussed. Tailoring treatment to suit the individual and counseling patients regarding reduced fertility have resulted in the best practice. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completing this CME activity, physicians should be better able to evaluate and use appropriate methods to estimate ovarian reserve, assess the risk of infertility caused by commonly used cytotoxic chemotherapy regimens and radiation, and counsel patients regarding the gonadotoxic effects of cancer treatment.

Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation.

Uterine fibroids are the most common tumours presenting in women. The pathophysiology of fibroids is poorly understood, but disordered angiogenesis and altered smooth muscle cell proliferation are believed to play a role. In this review, current knowledge of both of these processes will be summarized. Differences between 'normal' adjacent myometrium and fibroid tumours within the same uterus are outlined. Exploiting these differences represents one of the best opportunities for the development of medical treatments that target fibroid tissue selectively.

Molecular profiling of human endometrium during the menstrual cycle.

This summary of the findings of investigations of the changing transcriptional profile of human endometrium during the menstrual cycle shows that it is possible to classify the menstrual cycle based on the global gene expression profile, and identifies groups of known and novel genes that may be associated with different biological processes that occur in the endometrium such as implantation and menstruation.

Anatomical evidence for in utero androgen exposure in women with polycystic ovary syndrome.

OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) have masculinized finger length patterns compared to women without PCOS. DESIGN: A case control study. SETTING: University teaching hospital and in vitro fertilization unit. PATIENT(S): Seventy women aged between 18 and 40 years with PCOS were compared to 70 women without PCOS. INTERVENTION(S): Measurement of the second to fourth finger length ratio on the ventral surface of the left and right hand from the basal crease of the digit to the tip was made using Vernier calipers. MAIN OUTCOME MEASURE(S): The second to fourth finger length ratio. RESULT(S): We found a significantly reduced ratio in the right hand of the women with PCOS compared to the controls. The geometric mean right finger length ratio in the PCOS group was 98.3% that of the controls (95% confidence interval, 99.3%-97.3%). CONCLUSION(S): Here we show a subtle difference in the finger length pattern of women with PCOS. This may constitute anatomical evidence of in utero androgen exposure in PCOS.

Bioinformatic analysis of primary endothelial cell gene array data illustrated by the analysis of transcriptome changes in endothelial cells exposed to VEGF-A and PlGF.

We recently published a review in this journal describing the design, hybridisation and basic data processing required to use gene arrays to investigate vascular biology (Evans et al. Angiogenesis 2003; 6: 93-104). Here, we build on this review by describing a set of powerful and robust methods for the analysis and interpretation of gene array data derived from primary vascular cell cultures. First, we describe the evaluation of transcriptome heterogeneity between primary cultures derived from different individuals, and estimation of the false discovery rate introduced by this heterogeneity and by experimental noise. Then, we discuss the appropriate use of Bayesian t-tests, clustering and independent component analysis to mine the data. We illustrate these principles by analysis of a previously unpublished set of gene array data in which human umbilical vein endothelial cells (HUVEC) cultured in either rich or low-serum media were exposed to vascular endothelial growth factor (VEGF)-A165 or placental growth factor (PlGF)-1(131). We have used Affymetrix U95A gene arrays to map the effects of these factors on the HUVEC transcriptome. These experiments followed a paired design and were biologically replicated three times. In addition, one experiment was repeated using serial analysis of gene expression (SAGE). In contrast to some previous studies, we found that VEGF-A and PlGF consistently regulated only small, non-overlapping and culture media-dependant sets of HUVEC transcripts, despite causing significant cell biological changes.

Molecular classification of human endometrial cycle stages by transcriptional profiling.

Endometrium is a dynamic tissue that undergoes cyclic changes each month, under the overall control of estrogen and progesterone. The aims of this study were to investigate the changing global gene expression profile of human endometrium during the menstrual cycle using microarray technology and to determine the correlation between histopathological evaluation and molecular profile of the samples. Standard two-colour cDNA microarrays were performed on the 43 samples against a common reference, using a 10.5 K cDNA glass slide microarray. The results were validated using real-time PCR. Analysis of expression data was carried out using parametric analysis of variance with Benjamini-Hochberg correction. Hierarchical clustering reveals a strong relationship between histopathology and transcriptional profile of the samples. The study identified 1452 genes that showed significant changes in expression (P< or =0.05) across the menstrual cycle, with 425 genes having changes that are at least 2-fold. The data were also independently analysed by a CSIRO algorithm called GeneRaVE that identified a small subset of genes whose expression profiles could be used to classify nearly all the biopsies into their correct cycle stage. We also identified and validated three genes [(natural cytotoxicity triggering receptor (NCR)3, fucosyl transferase (FUT)4 and Fyn-binding protein (FYB)] that had not been shown to have significant cyclic changes in the human endometrium, previously. We have shown for the first time that endometrial cycle stage prediction is possible based on global gene expression profile.

Genomics in obstetrics and gynaecology.

With the Human Genome Project complete, and microarray technology progressing rapidly, the study of whole genomes has become a reality. The emerging field of genomics is full of promise, has become a cornerstone of commercial drug development, and looks certain to make a major contribution to clinical practice in the future. There is an increasing number of genomic studies concerned with obstetric and gynaecological conditions. Despite this, clinicians in their busy practices often lack a basic understanding of genomics and the tools involved in generating genome-based information. In the present review, we aim to provide the clinician with a basic overview of genomics--what it is, what tools it uses, and how it may benefit our patients. The existing published reports on genomic studies in the reproductive field is reviewed.

Migrant fathers and their attitudes to potential male hormonal contraceptives.

The purpose of this study was to assess potential uptake of male hormonal contraception (MHC) in migrant fathers in a post-partum setting, and to compare them to Australian-born fathers. It was a cross-sectional study of a convenience sample from the post-natal ward of a tertiary level obstetric hospital. Seventy-six English-speaking fathers born in South-East Asia or on the Indian subcontinent were surveyed and their responses compared with those provided by 118 Australian-born participants from a previous study. The main outcome measures were acceptability of potential male hormonal contraception on a 5-point scale, and preferred mode of administration. Information on past and future intended contraceptive use, including existing male forms of contraception, was also compared with data collected from the group of Australian-born men. Only 13.6% (95%CI: 5.8-21.4) of migrant fathers would definitely or probably consider trying MHC compared with 47.5% (95%CI: 38.5-56.5) of Australian-born fathers (chi-square, p < 0.001). There were significant differences in desired mode of administration in potential 'triers' from both groups, as well as in attitudes to existing contraception. Two-yearly injection was the most popular method of administration in migrants, with 38.3% of 'triers' listing it as their first choice (compared with 21.4% in published data on Australian-born men; chi-square, p = 0.038). We conclude that migrant groups are less enthusiastic about novel potential MHC. The influence of education on acceptance of this contraceptive possibility needs to be assessed.

Will Australian men use male hormonal contraception? A survey of a postpartum population.

AIM: To survey the attitudes of a population of Australian men to potential use of male hormonal contraception (MHC). DESIGN: Survey of male partners of women who had recently given birth. Men were approached while visiting their female partners on the ward. PARTICIPANTS: 118 out of 148 Australian-born English-speaking men who were approached. SETTING: Postnatal ward of Monash Medical Centre (a public teaching hospital in Melbourne), between October 2000 and April 2001. MAIN OUTCOME MEASURE: Attitudes towards potential use of MHC, rated on a five-point scale. RESULTS: 89/118 men surveyed (75.4%; 95% Cl, 67.7%-83.2%) indicated that they would consider trying MHC if it were available. The three most popular choices for method of administration of MHC were (in descending order) an oral pill, a three-monthly injection, or a two-yearly injection. A statistically significant association was found between acceptability of vasectomy and acceptability of MHC (70.5% of men who indicated they would try MHC [MHC "triers"] found vasectomy acceptable versus 44.5% of MHC "non-triers"; P = 0.011). Triers reported a higher rate of approval of MHC by their female partners than non-triers (79.8% v 13.8%, respectively; P < 0.0001). CONCLUSIONS: MHC appears to be acceptable to a majority of Australian men when surveyed in a postpartum context. Attitudes of men towards existing male contraception, as well as the attitudes of their partners, appear to exert a strong influence on acceptability of MHC.