The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.

OBJECTIVE: To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS). DESIGN: Randomized controlled double-blind trial. SETTING: A tertiary referral center, Hong Kong. PATIENT(S): Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70). INTERVENTION(S): Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months. MAIN OUTCOME MEASURE(S): Menstrual status as well as clinical and biochemical hyperandrogenism. RESULT(S): There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms. CONCLUSION(S): We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).

Hepatitis B infection and outcomes of in vitro fertilization and embryo transfer treatment.

OBJECTIVE: To examine the prevalence of hepatitis B virus (HBV) infection, the associated causes of subfertility, and the outcomes of the first IVF and embryo transfer treatment cycles in these infertile couples. DESIGN: A retrospective cohort study. SETTING: Assisted reproduction technology (ART) unit. PATIENT(S): Two hundred eighty-seven couples undergoing IVF and embryo transfer cycles. INTERVENTION(S): Analysis of data on patients' characteristics, controlled ovarian hyperstimulation (COH), embryology, and pregnancy (PR) and implantation rates of IVF and embryo transfer cycles according to HBV serostatus of the infertile couples, which was routinely screened. MAIN OUTCOME MEASURE(S): The PRs and the implantation rates. RESULT(S): Twenty-nine (10.1%) women were HBV seropositive, whereas 32 (11.1%) of their husbands were HBV seropositive. Concerning the causes of infertility, there was a trend toward more tubal blockage (57.1% vs. 42.2%) in the HBV-infected group. Among the 190 women undergoing their first IVF and embryo transfer cycles, both the ongoing PR or live birth rate and implantation rate in HBV group were significantly higher than the controls (53.3% vs. 24.2% per cycle with embryo transfer; and 43.3% vs. 18.4%, respectively). CONCLUSION(S): Our results demonstrate for the first time significantly higher PRs and implantation rates of IVF and embryo transfer cycles for couples with at least one partner being HBV seropositive. Further studies to elucidate the underlying mechanisms are warranted.

Higher metabolic risk in Chinese women fulfilling the NIH diagnostic criteria for polycystic ovarian syndrome.

Only about 63% of Chinese women with polycystic ovarian syndrome (PCOS) as diagnosed by the 2003 Rotterdam criteria fulfilled the 1990 National Institutes of Health (NIH) diagnostic criteria. Although the NIH criteria are not generally applicable to the Chinese population, women fulfilling the NIH criteria have higher metabolic risk than those who do not and so carry the most clinical significance.

Comprehensive assessment of serum estradiol impact on selected physiologic markers observed during in-vitro fertilization and embryo transfer cycles.

OBJECTIVE: This investigation assessed the effect of serum estradiol levels on outcomes of in-vitro fertilization and embryo transfer (IVF) cycles. MATERIALS AND METHOD: This was a retrospective cohort study of 1123 IVF cycles comparing impact of estradiol (E(2)) levels on follicular development, fertilization, embryo quality, implantation, pregnancy rate, miscarriage rate, and selected obstetric complications. RESULTS: We found high serum E(2) levels to be significantly associated with increased number of mature follicles and mature oocytes retrieved (p<0.01, for both). E(2) levels were also associated with more viable and good-quality embryos (p<0.01). There was no significant impact of E(2) on oocyte maturation, fertilization rate, embryo quality, or overall pregnancy rates. Moreover, high E(2) levels were significantly associated with higher implantation rates and reduced incidence of miscarriage (p<0.05, for both). CONCLUSION: Within the safety range in clinical practice, our data demonstrate a generally positive effect of high serum E(2) on selected IVF parameters.

Mutations of t-complex testis expressed gene 5 transcripts in the testis of sterile t-haplotype mutant mouse.

AIM: To determine the possible roles of the t-complex testis expressed gene 5 (Tctex5) on sperm functions, the full-length sequence of mRNA was studied and compared in the testis between the normal wild-type and the sterile t-haplotype mutant mice. METHODS: We applied rapid amplification of cDNA ends, Northern blot and reverse transcription polymerase chain reaction to analyze the full length of Tctex5 mRNAs isolated from testes of the wild-type and the t-haplotype mice. Reverse transcription polymerase chain reaction was used to semi-quantitatively compare expression of Tctex5 transcripts in the 16 tissues and 9.5 day stage embryos in the wild-type mice. E-translation was applied to estimate the amino acid sequences. RESULTS: One long and one short transcript of Tctex5 mRNA were discovered in mouse testis of wild-type (Tctex5(long-+) and Tctex5(short-+)) and t-haplotype (Tctex5(long-t) and Tctex5(short-t)) mice, respectively. Being enhanced only in the testis, Tctex5(long-t) had 17 point mutations and one 15-bp-deletion in the exon 1 region, comparing with the Tctex5(long-+), whereas the Tctex5(short-t) was similar to the Tctex5(short-+). The short isoforms of Tctex5 mRNAs in the two models encoded exactly the same peptides, but the long isoforms did not. The estimated peptide encoded by Tctex5(long-t) had significant mutations on putative sites of phosphorylation and PP1 binding. CONCLUSION: We established that mutations that occur in the Tctex5 long transcript of the t-haplotype mice are important for normal sperm function, whereas the short transcript of Tctex5 might have a conserved function among different tissues.

Serum vascular endothelial growth factor as a possible indicator of arterial reactivity in postmenopausal women.

OBJECTIVE: To determine whether serum vascular endothelial growth factor (VEGF) concentration is correlated with arterial reactivity in postmenopausal women. METHODS: An observational study was conducted on 24 postmenopausal women who did not receive any hormone therapy in the 6 months preceding the study and had no pre-existing cardiovascular diseases or cardiovascular risk factors. Serum samples were obtained from all participants and analyzed for VEGF concentrations. Arterial reactivity was assessed by the measurement of endothelium-dependent dilatation and endothelium-independent dilatation of the brachial artery, using color duplex Doppler ultrasound. RESULTS: The study population was aged 50.8 years on average, with about 2 years of menopause. Serum VEGF concentration in postmenopausal women was significantly correlated with both endothelium-dependent dilatation (r = -0.66, p < 0.01) and endothelium-independent dilatation (r = -0.65, p < 0.01) of the brachial artery. CONCLUSIONS: Serum VEGF level may be a potential indicator of arterial reactivity in postmenopausal women.

The role of three-dimensional ultrasonography in polycystic ovary syndrome.

The 2003 Rotterdam diagnostic criteria for polycystic ovary syndrome (PCOS) support the objective role of ultrasound in defining the appearance of the PCO, but there are significant limitations of these new guidelines from an ultrasound perspective that must be considered. Three-dimensional (3D) ultrasound provides a new method for the objective quantitative assessment of follicle count, ovarian volume, stromal volume and blood flow within the ovary as a whole. Since the introduction of 3D ultrasonography, there have been increasing publications on PCOS, each addressing different areas and reporting different results. This review critically examines these studies in an attempt to clarify the evidence to date and thereby establish the current role of 3D ultrasonography in PCOS.

Vascular endothelial growth factor plays more than an angiogenic role in the female reproductive system.

Although the most well-known function of vascular endothelial growth factor is its angiogenic activity, it plays more than a simple angiogenic role in the female reproductive system as it is involved in a number of key events in the course of the ovulatory cycle. The modulation of vascular endothelial growth factor expression varies in different reproductive tissues, probably related to its various functions at these different sites.

The effect of exogenous estradiol treatment on the mRNA expression of vascular endothelial growth factor and its receptors in cultured human oviduct mucosal cells.

PURPOSE: To evaluate the responses of cultured oviduct mucosal cells to exogenous estradiol treatment in regulating the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors. METHODS: The mucosal layer of the ampullary regions of the human oviduct was isolated and cultured with (study groups) or without (control group) the addition of exogenous estradiol in five different concentrations. Semiquantitative reverse-transcriptase-polymerase chain reaction was performed on the oviduct mucosal cells before and after the 6-day culture. RESULTS: There were no significant differences in the mRNA expression of VEGF and its receptors, both KDR and flt-1, between the five study groups and the control group. CONCLUSIONS: The mRNA expression of VEGF and its receptors is not altered by exogenous estradiol treatment in cultured oviduct. This helps to explain the mechanism of temporal regulation of VEGF in human oviduct, which reaches the peak level in the peri-ovulatory stage when both the serum estradiol and gonadotropins concentrations are high.

GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.

BACKGROUND: This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF. METHODS: Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation. RESULTS: There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant. CONCLUSION: A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.

Upregulation of mRNA expression of vascular endothelial growth factor and its receptors by exogenous human chorionic gonadotropin in cultured oviduct mucosal cells.

The mucosal cells were isolated from the ampullary regions of 20 human oviducts and cultured with or without hCG in five different concentrations (1-100 ng/mL). As analyzed by the semiquantitative reverse-transcriptase polymerase chain reaction, hCG treatment significantly increased mRNA expression of vascular endothelial growth factor and its receptor flt-1 in the cultured mucosal cells in a dose-dependent manner but had no effect on the expression of another receptor, KDR.

Increased messenger RNA expression of vascular endothelial growth factor and its receptors in the implantation site of the human oviduct with ectopic gestation.

OBJECTIVE: To compare the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1) in the implantation and nonimplantation sites of the human oviduct with ectopic gestation. DESIGN: Prospective observational study. SETTING: University-based Obstetrics and Gynecology Department. PATIENT(S): Ten women undergoing laparoscopic salpingectomy for tubal pregnancy. INTERVENTION(S): The mucosal layer was isolated from the implantation and nonimplantation sites of the oviduct tissue with ectopic gestation. Semiquantitative reverse transcriptase-polymerase chain reaction was performed. MAIN OUTCOME MEASURE(S): The differences in the mRNA expression of VEGF and its receptors between the implantation and nonimplantation sites of the oviduct tissue. RESULT(S): The mRNA expression of VEGF and its receptors, both KDR and flt-1, was significantly higher in the implantation site of the human oviduct with ectopic gestation compared with the nonimplantation site. CONCLUSION(S): The results suggest that VEGF may be the angiogenic factor responsible for the implantation and placentation of an ectopic pregnancy in the oviduct.

Raloxifene therapy in postmenopausal women is associated with a significant reduction in the concentration of serum vascular endothelial growth factor.

OBJECTIVE: To determine whether raloxifene has an effect on serum vascular endothelial growth factor (VEGF) concentration in postmenopausal women. DESIGN: A randomized, placebo-controlled trial. SETTING: University-based obstetrics and gynecology unit. PATIENT(S): Fifty postmenopausal women who did not receive any hormone therapy in the 6 months preceding the study. INTERVENTION(S): The participants were randomly assigned on a one-to-one basis to receive either raloxifene (60 mg daily) or placebo for 36 weeks. MAIN OUTCOME MEASURE(S): Serum VEGF concentrations at baseline and at 12 weeks and 36 weeks after the commencement of intervention. RESULT(S): The serum VEGF concentrations in the raloxifene group were significantly reduced from 247 +/- 16 pg/mL at baseline to 195 +/- 11 pg/mL at 36 weeks after starting raloxifene. The placebo group showed no significant change in the serum VEGF concentrations throughout the intervention period. CONCLUSION(S): Raloxifene therapy in postmenopausal women is associated with a significant reduction in serum VEGF concentration.

In vivo regulation of mRNA expression of vascular endothelial growth factor receptors (KDR and flt-1) in the human oviduct.

OBJECTIVE: To examine the localization of vascular endothelial growth factor receptors (VEGF-R) and the changes in VEGF-R messenger ribonucleic acid (mRNA) expression in various regions of the oviduct from fertile women throughout the ovulatory cycle. DESIGN: Prospective observational study. SETTING: University-based obstetrics and gynecology department. PATIENT(S): Twenty-two women who underwent laparoscopic tubal sterilization or hysterectomy for a benign gynecological condition. INTERVENTION(S): The mucosal layer was isolated from the oviduct tissue. Immunohistochemistry and a semiquantitative reverse-transcriptase-polymerase chain reaction (RT-PCR) was performed. MAIN OUTCOME MEASURE(S): Immunohistochemical localization of VEGF-R proteins in oviduct tissue, and the differences of VEGF-R mRNA expression in the various regions of the oviduct and in the various stages of the ovulatory cycle. RESULT(S): Immunohistochemical study localized VEGF-R, both KDR and flt-1, in the oviduct luminal epithelium, smooth muscle cells as well as blood vessels within the oviduct. Messenger RNA expression of KDR, but not flt-1, was significantly higher in the ampullary and infundibular regions than in the isthmus. Messenger RNA expression of flt-1, but not KDR, varied significantly in the oviduct along the course of an ovulatory cycle, with the highest level in the periovulatory stage. CONCLUSION(S): These results suggest that the two VEGF receptors may have different roles in the oviduct. Our data support a role for KDR in oviduct angiogenesis whereas flt-1 appears to be important in the temporal regulation of oviductal secretion.

Intravenous leiomyomatosis: two cases with different routes of tumor extension.

Intravenous leiomyomatosis is a rare smooth muscle tumor. We report two cases of intravenous leiomyomatosis that grew along different routes of the venous system into the inferior vena cava and the right atrium. The different route of extension makes a difference in the ease of excision of tumor masses. Using MEDLINE together with the references in each publication, we identified all cases of intracardiac leiomyomatosis reported in the English literature in the period between 1980 and 2003 and performed a brief review on this potentially lethal disease entity.

Increased mRNA expression of vascular endothelial growth factor and its receptor (flt-1) in the hydrosalpinx.

BACKGROUND: The adverse effects of hydrosalpinx on the outcomes of IVF have been well documented, but the mechanisms of hydrosalpinx fluid formation remain unclear. This study compares the mRNA expression of vascular endothelial growth factor (VEGF) and its receptors (KDR and flt-1) in the hydrosalpinx with that in the healthy oviduct. METHODS: Oviduct tissue was collected from 10 infertile women with hydrosalpinx and 10 parous women with healthy oviduct. The mRNA expression of VEGF and its receptors in isolated oviduct epithelial cells were analysed using semi-quantitative reverse-transcriptase PCR. RESULTS: mRNA expression of VEGF and its receptor flt-1 in the hydrosalpinx was significantly higher than that in the healthy oviduct, but no significant difference was demonstrated for the KDR receptor. CONCLUSIONS: This study supports the notion that VEGF may play an important role in the hydrosalpinx fluid formation, possibly by promoting vascular and epithelial permeability and therefore serum transudation.

The effect of intra-abdominal pressure on the generation of 8-iso prostaglandin F2alpha during laparoscopy in rabbits.

BACKGROUND: Carbon dioxide pneumoperitoneum induces peritoneal oxidative stress. The aim of this study was to verify the effect of intra-abdominal pressure on oxidative stress in the peritoneum and on post-operative adhesion formation. METHODS: Forty-one rabbits underwent laparoscopic surgery: either gasless, or with CO(2)-pneumoperitoneum at pressures of 5, 10 or 15 mmHg. Serial parietal peritoneal biopsies were taken at various time-points: immediately after reaching the abdominal cavity, 30, 60, 90 and 120 min afterwards, and 15 min after abdominal desufflation. 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)), a marker of oxidative stresss, was assayed by enzyme immunoassay and adhesion formation was scored by second-look laparoscopy on day 14. RESULTS: The gasless group showed no significant changes in 8-iso PGF(2alpha). Conversely, significant changes occurred in CO(2)-pneumoperitoneum in a time- and pressure-dependent manner. Adhesions developed only in the CO(2)-pneumoperitoneum groups, and total adhesion score was correlated with the amount of CO(2) insufflated and intra-abdominal pressure, but not with 8-iso PGF(2alpha), which was correlated with intra-abdominal pressure. CONCLUSION: Intra-abdominal pressure increased 8-iso PGF(2alpha) in the parietal peritoneum in a graded fashion, whilst gasless laparoscopy had no impact. It also influenced the frequency and severity of adhesion formation, but no causal link was found between 8-iso PGF(2alpha) and post-operative adhesion formation.