Search

Objective To evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH. Materials and methods This retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 μg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. The dynamic hormone profiles and embryonic and clinical outcomes of the patients were evaluated. Results We observed significantly lower serum LH levels in the r-FSH + HMG groups during ovarian stimulation. The serum estradiol and progesterone levels were lower in the r-FSH + HMG groups on the trigger day. Nevertheless, there were no significant differences with respect to the number of oocytes retrieved, maturation, fertilization, blastocyst formation rate or ovarian hyperstimulation syndrome (OHSS). The implantation and live birth rates were increased in the r-FSH + HMG groups compared with the r-FSH alone group, with no statistical significance. Conclusions HMG for LH supplementation in the GnRH antagonist protocol for patients with high AMH is not significantly superior to r-FSH alone in terms of ovarian response and pregnancy outcome. Nevertheless, HMG supplementation might be appropriate for women with an initially inadequate response to r-FSH or intracycle LH deficiency.

Objective: Despite the great advance of assisted reproductive technology (ART) in recent decades, many IVF patients failed to achieve a pregnancy even after multiple IVF-ET attempts. These patients are considered to have repeated implantation failure (RIF). While exhausting efforts have been devoted to the improvement of pregnancy rate in RIF patients, it is not clear whether RIF patients have aberrant obstetric or perinatal outcomes after they eventually achieved a pregnancy. Materials and methods: Taking advantage of a relatively large database of IVF-ET cycles at the Chang Gung Memorial Hospital, we compared obstetric and perinatal outcomes of RIF patients who have a successful pregnancy after IVF-ET treatment(s) to those of control IVF-ET patients. Results: Because multiple pregnancies are associated with a high risk of obstetric complications, we restricted the analysis to patients who had singleton pregnancies. Analysis of a total of 596 control and 46 RIF cases showed the rates of almost all obstetric and perinatal outcomes investigated are not different between the two groups. However, the rate of placental abruption in the RIF group (4.35%) appeared to be significantly higher than that of controls (0.50%; OR = 8.99). This difference is still statistically significant after adjustment with the age (adjusted OR = 8.2). Conclusion: While the rates of a spectrum of obstetric and perinatal outcomes are normal in RIF patients, these patients could have an enhanced risk of placental abruption. However, investigations with a large sample size are needed to substantiate this inference. Keywords: RIF, Repeated implantation failure, Placental abruption, IVF, Embryo transfer

Objective: The current study tested the hypothesis that vascular endothelial function, as reflected by the reactive hyperemia index (RHI), and biochemical factors, including VEGF, TNFα, CRP, inhibin A, and inhibin B, were involved in the pathogenesis of ovarian hyperstimulation syndrome (OHSS). Materials and methods: This study was conducted between June 2010 and June 2012, enrolling 15 patients with OHSS and 6 healthy control subjects

Objective: We have recently reported that stress-induced phosphoprotein 1 (STIP1) is over-expressed in endometriosis/adenomyosis tissues. STIP1 may also be involved in immune regulation, thus we attempted to study the association between STIP1 single nucleotide polymorphisms (SNPs) and endometriosis/adenomyosis. Materials and methods: Five STIP1 SNPs (rs7941773, rs2845597, rs4980524, rs2282490, and rs2236647) were selected for genotyping with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in 286 patients with endometriosis/adenomyosis and 288 healthy postmenopausal controls. In vitro studies included luciferase promoter reporter assays and western blot analysis for STIP1 and MMP9 proteins. Results: The frequency of the G allele at rs4980524 was significantly higher in patients with endometriosis/adenomyosis than in control women. The promoter reporter with rs4980524 GG genotype significantly increased luciferase activity than that with TT genotype in endometrial cancer RL95-2 cells, and the primary endometrial stromal cells carrying rs4980524 GG genotype expressed higher protein levels of STIP1 and MMP9 than those carrying the TT one. Conclusion: The G/G allele of STIP1 SNP rs4980524 is associated with the increased expression of STIP1 and MMP9 in endometriosis. Further validation in independent cohorts of endometriosis patients may prove its usefulness as a genetic risk maker for endometriosis/adenomyosis. Keywords: Endometriosis, SNP, STIP1

Objective Although major advances have greatly improved the outcomes of assisted reproductive technology in the last two cascades, there remains significant difficulty in achieving pregnancy for many patients even after repeated attempts of IVF. Interestingly, recent studies have shown that transcutaneous electrical acupoint stimulation (TEAS) can improve the reproductive outcomes of select IVF patients. To determine the utility of TEAS in improving IVF outcomes in patients with a history of implantation failure, we conducted a retrospective study of clinical outcomes of women, who had a prior history of unsuccessful pregnancy outcome after IVF-embryo transfer (IVF-ET), following TEAS treatment. Materials and methods A total of 25 patients, who had failed to conceive after multiple IVF cycles in which good embryos were transferred, received noninvasive low frequency TEAS treatment prior to and during an IVF-ET cycle. The clinical outcomes, including biochemical pregnancy rate, clinical pregnancy rate and implantation rate, were compared to those of prior cycles which received only standard IVF treatment. Results Analysis of reproductive outcomes showed that implantation rate and clinical pregnancy rate increased significantly in IVF cycles that included the TEAS treatment when compared to prior cycles that received only the standard IVF treatment in this cohort of patients. Conclusions This surprising finding indicated that TEAS treatment is a promising technique to improve reproductive outcomes in difficult cases of IVF-ET. Because TEAS treatment is noninvasive and has high reproducibility, and can be applied with limited training, further refinement of this procedure would not only substantiate the beneficial effects of TEAS, but also allow the technique to be more effective and reproducible.

Objective To identify the genetic etiology of recurrent disorders of sex development (DSDs) in a Taiwanese family with 46,XY sex reversal and hypospadias. Design Genetic and functional studies. Setting Academic hospital. Patient(s) A three-generation family consisting of 22 members, with eight cases of 46,XY DSD, of whom four have 46,XY male-to-female sex reversal and four are 46,XY males with hypospadias. Intervention(s) None. Main Outcome Measure(s) Results of exome sequencing and in vitro protein and RNA analyses. Result(s) All patients with DSDs were found to carry heterozygous missense mutations in the doublesex and mab-3-related transcription factor 3 (DMRT3; rs187176004, c.A815C, p.K272T) and 2ʹ,5ʹ-oligoadenylate synthetase 3 (OAS3; rs16942374, c.G2606A, p.R869H) genes. The DMRT3 mutation increased estrogen receptor 1 (ESR1) expression. Upon binding with the OAS3-RNase L complex, wild-type DMRT3 promoted degradation of ESR1 mRNA. However, the DMRT3A815C-OAS3G2606A complex interacted less strongly with ESR1 mRNA and RNase L, ultimately preventing ESR1 mRNA degradation. The interactions between DMRT3, OAS3, and RNase L were confirmed in the patients’ testis. Conclusion(s) Our results indicate that DMRT3 and OAS3 are involved in human DSDs by controlling ESR1 expression.

Objective Benign mature teratoma during pregnancy is common, mostly discovered incidentally by antenatal sonography. However, repeated pregnancy coincident with ovarian mature teratoma is rarely reported. The cases of teratoma with rapid growing characteristics are even more unique. Case report A 17-year-old woman was pregnant at 6 weeks of gestation with a left ovarian teratoma. She underwent artificial abortion followed by surgical removal of the teratoma. However, eleven years after the surgery, a right ovarian teratoma was found incidentally by antepartum sonography at 21 weeks of gestation. The right ovarian teratoma developed uneventfully, with rapid growth during pregnancy. Abdominal delivery at term was accomplished without any complication. Conclusion Younger patients and patients with bilateral or large size dermoid cysts should be followed up closely. Further studies are needed for better understanding of its natural clinical course and the mechanism of progression. The treatment options should be made individually, weighing the risks of torsion, rupture, or obstruction of labor versus the potential for unnecessary surgical risk to mother and fetus.

Objectives: To analyze the relationship between in vitro fertilization (IVF) pregnancy rate and basal serum hormone levels before patients begin an IVF course. Materials and methods: In this retrospective study, we analyzed patients with anti-Müllerian hormone (AMH) data and IVF data from January 2009 to October 2012. Pregnancy rates were calculated by AMH and follicle stimulating hormone quartiles and analyzed using the independent samples t test. Furthermore, patients were divided into three groups by age. The Chi-square test was used to assess the association between the parameters and IVF pregnancy rates. Results: From the 910 IVF treatment courses, 377 (41.4%) clinical pregnancies resulted. The pregnant and nonpregnant groups differed significantly in age and FSH and AMH levels. The pregnancy rate was 53.3% for patients aged 38 years. The pregnancy rate was 53.4% for patients with FSH levels 8.9 mIU/mL. The pregnancy rate was 56.8% for patients with AMH levels >4.0 ng/mL and 20.0% for patients with AMH levels

Integrin-linked kinase (ILK) localizes to focal adhesions, and interacts with the cytoplasmic tail of β subunits of integrins and couples them to the actin cytoskeleton. ILK may act as a kinase and transmit the signals in a phosphatidylinositol 3-kinase-dependent manner, or can act as a scaffold protein to function through cell–matrix interactions, cell signaling, and cytoskeletal organization. Within this pivotal position, ILK mediates many important cellular processes, including survival, proliferation, differentiation, adhesion, migration, contractility, etc. Besides, ILK plays some role in the activation of endothelial progenitor cells and neovascularization, and may also enhance vascular endothelial growth factor expression. Increased ILK activity may promote epithelial-to-mesenchymal transition and induce a transformed, tumorigenic phenotype. Higher expression of ILK was frequently noted in human malignancies. ILK may also be important for mitotic-spindle assembly. Inhibition of ILK causes proliferative defects, induces cell-cycle arrest and apoptosis, and is embryonically lethal. New concepts of gene or cell-based therapy working on the up- or downregulation of ILK have emerged as a valid therapeutic approach for cancer treatment, and also a new hope for vasculogenesis in the ischemic area. The current review will discuss some known mechanisms, and the role of ILK in the modulation of tumorigenesis and reproduction, based on an extensive literature survey.

Introduction The impact of maternal age on euploidy rate and the outcome of PGT-Aisdemonstrated by many studies. But less understanding of the probability of finding at least one euploidy embryoaccordingto maternal age. In this study, weassess patients of different maternal age group in PGT-A cyclesusing aCGH and NGS: 1. Number of biopsy blastocyst per cycle; 2. Numbers of 2PN needed for aeuploidy embryo; 3. Euploidy rate; 4. The proportion of cycles having at least aeuploidy embryo; 5. Livebirth rate through frozen embryo transfer (FET). Materialand Methods We retrospectively analyzed the PGT-A cycles enrolled from 2012 to 2016. To compare the clinical outcomes, the included data were separated into groups based on maternal age at IVF stimulation start. TE biopsy was performed on Day5 to 7 post-retrieval. All biopsied blastocysts were subjected to vitrification immediately. Biopsied TE cells were analyzed using array-CGH and NGS for all 23 chromosomes. Patients transferred euploidy embryo on progesterone Day6 in FET cycles. Results The age groups for analysis were: 42. The cycles having biopsy were88.0%(22/25), 100%(18/18), 88.5%(23/26), 60%(9/15) and 82.3%(14/17). The number of biopsy blastocyst per cycle were 4.9(108/22), 5.8(105/18), 3.9(90/23), 3.2(29/9) and 1.6(23/14) and the number of 2PN needed for aeuploidy embryo were 6.8(218/32), 4.1(158/39), 7(189/27), 7.8(8/62) and 7.1(50/7). Euploidy rates were 29.6% (32/108), 37.1% (39/105), 30.0% (27/90), 27.6% (8/29), and 30.4% (7/23). The proportion of cycles having at least a euploidy embryo were 68.2%(15/22), 83.3%(15/18), 65.2%(15/23), 66.7%(6/9) and 35.7%(5/14). Pregnancy rate per FET were63.6%(7/11), 77.8%(7/9), 53.3%(8/15), 100%(1/1) and 50%(2/4). Live birth rates per FET were 63.6% (7/11), 77.8% (7/9), 46.7% (7/15), 100%(1/1) and 25% (1/4). Conclusions In the course of PGT-A, the clinical outcomes and live birth rate can be predicted according to maternal age. Maternal age increase does not affect the number of 2PN needed for aeuploidy embryo, but it seems that women aged between 35 and 37are more likelyto benefit from PGT- A (the highestopportunity of having at least a euploidy embryo). The results of this research can assist doctors in patient consultations and help patients set realistic expectations.

Adenomyosis was found to have negative impacts on embryo implantation. Leukemia inhibitory factor (LIF), proposed to be a molecular marker for endometrial receptivity, works through the LIF receptor (LIFR) on both the embryo and the endometrium. We aimed to evaluate the endometrial expression of LIF and LIFR and its subsequent signaling in patients with adenomyosis during the window of implantation (WOI). Endometrium was obtained during the WOI from patients with adenomyosis (age

Objective To study the impact of integrin-linked kinase (ILK) in endometrial stromal cells (ESCs) during decidualization. Design Laboratory study with the use of human endometrium. Setting University hospital. Patient(s) Fertile reproductive-age women who had not received hormonal treatment for 3 months before tissue collection. Intervention(s) Endometrium tissue collection, in vitro decidualization of isolated ESCs, and small interfering (si) RNA transfection. Main Outcome Measure(s) Immunohistochemistry, ELISA, Western blot analysis, methylthiazolyl tetrazolium assay, and immunofluorescence staining. Result(s) In vivo expression of ILK is significantly increased in distended-fusiform stromal cells of late secretory endometrium and in cobblestone-shaped decidual cells of early pregnancy. During in vitro decidualization for up to 8 days, confluent cultures of isolated ESCs consistently displayed increased ILK expression and morphologic transformation from fibroblast-like to polygonal cells. Subsequent ILK knockdown by siRNA transfection reversed this transformation, accompanied by decreased phosphorylation of glycogen synthase kinase (GSK) 3β and decreased viable cell numbers. Immunofluorescence staining of the decidualized ESCs demonstrated linkage of increased levels of ILK at the tips of the fan-shaped organization of actin stress fibers located in the submembranous area, which expanded the decidual cells into a typical polygonal appearance. Knock-down of ILK abrogated the polymerization and organization of actin fibers, which reverted the cells to their undecidualized morphology. Conclusion(s) During human endometrial decidualization, ILK is essential for morphologic transformation of ESCs through organization of the actin cytoskeleton; it may also function through subsequent GSK3β signaling, which requires further studies.

To assess the role of diagnostic hysteroscopy in pregnancy outcome in patients starting the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI).A total of 567 infertile women who underwent first IVF treatment were reviewed retrospectively. Two hundred and fifteen (37.9 %) women underwent diagnostic hysteroscopy before the scheduled controlled ovarian hyperstimulation (COH). Two hundred and eighty-four (50.1 %) women only accepted transvaginal ultrasonography (TVU), and 68 (12.0 %) woman did not receive hysteroscopy and TVU before COH. Primary outcome measure was the live birth rate. Secondary outcome measures were the implantation rate, clinical pregnancy rate, and miscarriage rate.There was no difference among three groups with regard to number of oocytes retrieved, fertilization rate, implantation rate, clinical pregnancy rate, miscarriage rate, and live birth rate per cycle. The implantation rate and clinical pregnancy rate were significantly lower in the cycles with endometrial thickness8 mm on human chorionic gonadotropin day (P = 0.001 and 0.018, respectively). Women with greater body mass index (22) were associated with higher incidence of intrauterine lesions (22 of 36, 61.1 %).Diagnostic hysteroscopy prior to COH may not increase the implantation rate and live birth rate for the first IVF/ICSI programs. The efficacy of routinely performing diagnostic hysteroscopy before the first IVF program is needed to re-evaluate.

background: The impact of gonadotrophin-releasing hormone (GnRH) antagonists used in IVF protocols on endometrial tissue remodeling, embryo implantation and the programming of early pregnancy is still unclear. Pregnancy and infant outcomes after treatment with GnRH antagonist for IVF are particular causes of concern. The purpose of this study was to investigate the mechanisms of GnRH antagonist-induced apoptosis of human decidual stromal cells and the effects of GnRH antagonist on the activation of ERK1/2, JNK and GADD45a signaling. methods: Human decidual stromal cells were isolated from decidual tissue. The expression of GnRH-I receptor (GnRH-IR) was examined by immunoblot analysis and immunohistochemistry. The cells were treated with the GnRH antagonist, Cetrorelix. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay was used to examine cell viability. Cleaved caspase-3 and terminal deoxynucleotidyl transferase-mediated dUDP nick-end labeling assay were used as indicators for cell apoptosis. Mitogen-activated protein kinase function was tested for the elucidation of intracellular signalings through the pre-treatment of stromal cells with ERK1/2 (U0126) and JNK (SP600125) inhibitors prior to the Cetrorelix treatment. To characterize the signaling pathway of GnRH antagonist, the endogenous GnRH-IR and GADD45a were knocked down by specific small-interfering RNA (siRNA). results: The GnRH-IR is expressed in human decidual stromal cells. Treatment with GnRH antagonist decreased cell viability, induced apoptosis and increased the phosphorylation of ERK1/2 and JNK. Cells pre-treated with U0126 and SP600125 were rescued from the GnRH antagonist-mediated inhibition of cell growth and did not exhibit GnRH antagonist-induced apoptosis and downstream GADD45a signaling. GnRH antagonist-mediated cell growth inhibition and apoptosis were also abolished by the knockdown of the endogenous GnRH-IR or GADD45a with siRNAs. conclusions: The GnRH antagonist suppresses the growth of decidual stromal cells by inducing apoptosis through the GnRH-IR and through the ERK1/2 and JNK phosphorylation-dependent induction of GADD45a signaling. These results indicate that ERK1/2, JNK and GADD45a are coordinately regulated by the GnRH antagonist through the GnRH-IR to induce apoptosis in human decidual stromal cells, suggesting that the GnRH antagonist may play a role in decidual programming in human pregnancy.

Objective: To evaluate the pregnancy courses and obstetric outcomes in patients conceived after conservative treatment of endometrial cancer. Materials and Methods: Case series and systemic review of pregnancy women after fertility-sparing treatment of endometrial cancer. Patients with early stage endometrial cancer were identified through Tumor Registry in Chang Gung Memorial Hospital between 1990 and 2005 and MEDLINE search. Diagnosed cases were managed by fertility-sparing therapies. Pregnancies followed by assisted reproductive technology and spontaneous or ovulation with intrauterine insemination were designated as Group 1 and Group 2, respectively. Results: Five livebirths in three patients with two sets of twin pregnancy were delivered. Adding 47 women in the MEDLINE search literature, there were 65 deliveries with 77 livebirths. Groups 1 and 2 had 15 and 50 deliveries, respectively. Group 1 had 23 livebirths including four sets of twins and two sets of triplets, whereas 54 livebirths consisted of two sets of twins and one set of triplets were noted in Group 2 (p = 0.003). Seven preterm deliveries were noted in Group 1 and three in Group 2 (p = 0.001). Cesarean rate was 93.3% versus 22.0% (p

Objective To investigate the eutopic endometrial interleukin-18 (IL-18) system including interleukin-18 (IL-18), IL-18 receptor (IL-18R), and IL-18 binding protein (IL-18BP), mRNA, and protein expression in patients with adenomyosis. Design A clinical and molecular study. Setting Clinical and academic research setting in a university medical center. Patient(s) Twenty-eight samples of human eutopic endometria were obtained from surgical specimens of normal cycling women undergoing hysterectomy for uterine adenomyosis (n = 19); the control group (n = 9) was women undergoing hysterectomy for benign reason including uterine fibroids. Intervention(s) Quantitative competitive polymerase chain reaction (QC PCR) and immunohistochemistry studies were performed. Main Outcome Measurement(s) The differences of the IL-18 system mRNA and the ratio of IL-18BP to IL-18 in the eutopic endometrium of uterine adenomyosis and control group were analyzed. Result(s) IL-18 system mRNA and protein expression was demonstrated in the eutopic endometrium of both adenomyosis and control women. Quantitative competitive PCR demonstrated that endometrial IL-18R mRNA and the ratio of IL-18BP to IL-18 were significantly increased in adenomyosis patients in comparison to the control group. Pearson's correlation showed a significant correlation between IL-18 and IL-18R in the eutopic endometrium of women with uterine adenomyosis, but not the control group. Conclusion(s) The expression of the eutopic endometrial IL-18 system and the ratio of antagonist to agonist at the level of the endometrial-myometrial interface (EMI) may possibly be responsible for the pathologic process of adenomyosis.

Objective to understand postpartum weight retention among women of different body sizes at pre-pregnancy, and to explore factors influencing this weight retention. Design a comparative, descriptive study. Pre-pregnancy body mass indices (BMIs) were determined from hospital records. Dependent variables were measured by self-report questionnaires. Setting a 3,900-bed medical centre in northern Taiwan that delivers approximately 4,000 children each year. Participants a systematic sample of 810 women who had delivered children at a medical centre. In total, 602 valid questionnaires were collected. Findings the average pre-pregnancy and six month postpartum BMIs were 21.5 [standard deviation (S.D.)=3.32] and 22.48 (S.D.=3.39), respectively. Overweight (OW) and obesity (OB) increased from 18.27% before pregnancy to 27.57% at six months postpartum. Gestational weight gain (GWG) was 14.36, 14.37, 13.07 and 11.15kg among women in the underweight (UW), normal weight (NW), OW and OB groups, respectively; and six month postpartum weight retention was 3.32, 2.57, 1.67 and −0.29kg. GWG was the most significant predictor of postpartum weight change across groups. Key conclusions women with different body sizes at pre-pregnancy have common and specific risks for postpartum weight retention. Implications for practice individualised interventions should be developed to manage postpartum weight for women of different body sizes. Interventions should establish criteria for GWG and provide strategies to improve body image and modify lifestyle. The overall goal should be to manage postpartum weight gain and to promote women's health.

Summary: Objective: Whole genome amplification (WGA) is a crucial procedure for genomic DNA analysis from limited sources, such as in forensic analysis, embryo biopsy for preimplantation genetic diagnosis, or needle aspiration biopsies. Several strategies for WGA have been developed for either genotyping or microarray-based comparative genome hybridization (array-CGH) during the past decade. Nevertheless, there were few studies in which various WGA methods had been performed side-by-side and results evaluated with multiple methods. Materials and Methods: Ease of performance, qualitative accuracy, and quantitative fidelity of different WGA methods, such as degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR), ligation-mediated PCR (LM-PCR) and strand displacement amplification (SDA), were compared in amplifyinggenomic DNA derived from karyotype-confirmed amniocytes and the cancer cell line SAOS2. Results: Using analysis with microsatellite markers, single nucleotide polymorphism markers, and array-CGH, our results suggested that: (1) genomic DNA amplified from DOP-PCR resulted in false positive and negative results by analysis with array-CGH; (2) SDA is the easiest performance method among the three WGA methods; and (3) amplified DNA products generated by LM-PCR best reflect the original genomic DNA. Conclusion: The amplified DNA products generated by LM-PCR best reflect the original genomic DNA. Key Words: array-CGH, DOP-PCR, LM-PCR, SDA, whole genome amplification

Objective Conventional chromosomal studies or fluorescent in situ hybridization takes days to diagnose fetal aneuploidies during amniocentesis. Here, we evaluated the value of mass spectrometry-based clinical proteomics analysis on amniotic fluid supernatant (AFS) as a rapid detection of fetal aneuploidies. Methods Proteomics profiles generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after fractionating samples with functionalized magnetic beads were used for differentiating 60 normal karyotypic from 20 aneuploid AFS. After the discriminating models were generated using genetic algorithm, we evaluated the clinical efficacy of the models in detecting aneuploidies in two batches (each n = 30) of AFS prior to the release of chromosomal diagnoses. Results Within hours, the two-step proteomics analysis of AFS with the C18 model, followed by the weak cation exchange model, was able to detect aneuploid AFS at 3.3% disease prevalence rate with 100% sensitivity, 72 to 96% specificity, 11 to 50% positive predictive value, and 100% negative predictive value. Conclusion Clinical proteomics analysis of AFS using magnetic beads-based sample preparation and MALDI-TOF-MS can be used as a rapid detection for fetal aneuploidies. With perfect sensitivity and negative predictive value of the two-step proteomics method, it may be used for rapid detection of aneuploid AFS immediately after amniocentesis. Further large-scale examinations are apparently needed to verify the clinical value of this rapid detection. Copyright © 2005 John Wiley & Sons, Ltd.

Objective To investigate the efficacy of the PolScope on imaging the spindle morphology in oocytes at the metaphase II stage before vitrification and after thawing. Design In vitro study. Setting University infertility clinic and academic research laboratory. Intervention(s) Oocytes at the metaphase II stage that were obtained from superovulating mice were vitrified and then thawed. Main outcome measure(s) Morphological features of the spindle in oocytes were evaluated by both the PolScope and immunofluorescent staining. Result(s) Using the PolScope, the morphological features of the spindle of intact thawed oocytes were undetected by 3 hours of thawing in only 25% of cases. Most of the spindle images were recognized during the first hour of observation. Additionally, the statistical analysis of agreement of spindle morphology by both the PolScope and fluorescent staining showed a weighted Kappa value of 0.70, indicating good agreement. Oocytes with good spindle morphology verified by the PolScope before vitrification had a higher survival rate of intact oocytes after thawing compared with those with poor or undetected spindle images. Conclusion(s) The morphological features of the spindle in oocytes evaluated by the PolScope before freezing and after thawing are significantly correlated with those assessed by immunofluorescent staining after fixation. With the assistance of the PolScope, thawed oocytes with good spindle morphology can be verified and selected for further manipulation without fixation and staining.

The study was undertaken to test whether human telomerase reverse transcriptase (hTERT) transcripts in an individual blastomere could be used as an indicator for embryo development.Group A consisted of day 3 normal cleaving embryos at 4- to 8-cell stage, which were surplus and not allocated for uterine transfer. Group B consisted of arrested or fragmented embryos at the same stage, which were considered to be compromised. After blastomere dissociation, RNA purification, reverse transcription, and hTERT PCR amplification, the amplified product was separated by 3% gel electrophoresis.Eighty-six (90.5%) of the 95 intact blastomeres in group A and 78 (70.9%) of the 110 blastomeres in group B demonstrated hTERT mRNA expression. The difference was statistically significant (P0.05, chi-square). Eight (38.1%) of the 21 embryos in group A and 22 (62.9%) of the 35 embryos in group B had at least one blastomere that did not express hTERT mRNA under this procedure. The difference was not significant (P0.05, chi-square).General hTERT mRNA transcripts can be detected in most of the individual blastomeres but cannot be used as an indicator for early embryo development. Further investigations are necessary to elucidate its clinical application.

Purpose : Ovarian tissue banking may be the best strategy to preserve female fertility. But optimal method to obtain viable mature oocytes remains challenging. In order to bypass the long in vitro oocyte growth period, we developed this study to test whether reconstruction of thawed primordial oocytes with enucleated preovulatory germinal vesicle (GV) oocytes could induce dictyate nuclei to undergo chromosomal condensation and meiotic maturation. Methods : Isolated primordial oocytes from thawed mouse ovarian tissue were reconstructed with enucleated GV oocytes. After electrofusion and in vitro maturation, the reconstituted oocytes were assessed for first polar body extrusion, cytoskeleton configuration, and chromosome abnormalities. Results : Primordial oocytes from thawed ovarian tissue showed a high survival rate. Following transfer and electrofusion, they could be fused with enucleated GV oocytes (35.6%, 36/101) and extruded a first polar body (52.8%, 19/36). These mature oocytes showed a normal spindle configuration and chromosome number. Conclusions : We successfully established a mouse cell model to prove that omitting the whole growth and maturation period by transfer of primordial oocytes to developmentally older enucleated oocytes would bypass the long growth period required to the preovulatory stage. Polar body extrusion could also ensue after in vitro growth. This study provided an alternative approach for future investigations in oocyte maturation.

Six hundred thirty-seven Taiwanese Chinese women including 300 patients with endometriosis and 337 controls without endometriosis were enrolled to investigate the association between nonsynonymous single nucleotide polymorphism of the FSH receptor gene and the risk of endometriosis. For the A/G polymorphism of FSH receptor gene (Asn680Ser), a univariate analysis for women with endometriosis demonstrated that both the GG genotype (680Ser/Ser) and GA genotype (680Ser/Asn) were associated with a significantly lower risk of endometriosis.

The purpose of this study was to investigate the possible regulatory roles of insulin-like growth factors (IGF) and IGF binding protein-1 (IGFBP-1) on postmenopausal endometrium in women undergoing hormone replacement therapy (HRT). Endometrial tissues and blood samples were collected from 25 postmenopausal women with abnormal uterine bleeding before and after HRT. As a control, blood and endometrial samples were also obtained at mid-luteal phase (days 18-23 of the menstrual cycle) from 10 women with benign uterine leiomyoma during surgical intervention. Expression of mRNA for IGF-I, IGF-II, type 1-IGF receptor, IGFBP-1, oestrogen receptor (ER) and progesterone receptor (PR) in the endometrium was explored by a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Serum concentrations of IGFBP-1, oestradiol, progesterone, follicle stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) were also determined. In the endometrium obtained from postmenopausal women with abnormal uterine bleeding (before HRT), expression of IGFBP-1 was undetectable, whereas PR expression was abundant. HRT significantly up-regulated expression of IGFBP-1 but down-regulated PR. Moderate expression of IGF-I, IGF-II, type 1-IGF receptor and ER was identified in the postmenopausal endometrium before HRT. HRT significantly down-regulated IGF-I, up-regulated IGF-II, but had no effects on expression of type 1-IGF receptor and ER. In conclusion, up-regulation of IGFBP-1 collaboratively with down-regulation of IGF-I may account for the protective effect of progesterone in HRT on the endometrium.

Granulosa-lutein cell growth differentiation factor-9 (GDF-9), a member of the transforming growth factor beta (TGF-beta) superfamily, is an oocyte-derived factor expressed throughout the development of the maturing follicle and is essential in early follicular development and fertility. Both GDF-9 messenger RNA and protein are detected in granulosa-lutein cells. A statistically significant correlation between GDF-9 expression and the number of dominant follicles on the day human chorionic gonadotropin is administered also is demonstrated. Human granulosa-lutein cell GDF-9 expression may play a role in folliculogenesis dependent on follicle-stimulating hormone in the in vitro fertilization cycle.

The objective of the present study was to investigate the effects of insulin-like growth factor-binding protein-1 (IGFBP-1) on the interaction between mouse embryos and endometrial stromal cells in co-culture systems. To explore quantitatively the changes in expression of IGFBP-1 mRNA from endometrial stromal cells cultured alone or co-cultured with embryos, a combination of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blotting followed by a densitometric analysis was used. In co-culture systems, development of embryos was significantly improved and the production of IGFBP-1 from endometrial stromal cells was stimulated by the embryos. Quantitative analysis showed that expression of IGFBP-1 mRNA in endometrial stromal cells co-cultured with embryos was higher on days 3,5 and 8 (1.6-, 4.5- and 2.3-fold respectively) than in endometrial stromal cells cultured alone. In addition, intensity of PCR products for IGFBP-1 mRNA in endometrial stromal cells co-cultured with embryos was higher on day 5 than on days 3 and 8. However, the expression of IGFBP-1 mRNA in embryos cultured alone was very low. In conclusion, co-culture of embryos with endometrial stromal cells improved the development of embryos and may be associated with the production of IGFBP-1 by the co-cultured endometrial stromal cells. A combination of RT-PCR and Southern blotting followed by a densitometric analysis appeared to be a sufficiently quantitative method to determine changes in IGFBP-1 mRNA values.

Objective To investigate circulating levels of insulin-like growth factor-binding protein 1 (IGFBP-1) and IGFBP-3 in the mother and the fetus in pregnancies complicated by pre-eclampsia, and the relationship between serum levels of IGFBPs and fetal birthweight. Design A prospective study over an 18 month period. Setting A tertiary care academic medical centre. Participants Sixty-six pregnant women with pre-eclampsia (35 cases of mild/moderate pre-eclampsia and 31 cases of severe pre-eclampsia) and 78 nonpra-eclamptic pregnant women of matched gestational weeks and maternal ages. Main outcome measures Serum concentrations of IGFBP-1 and IGFBP-3 at the time of delivery. Results In pre-eclampsia associated with intrauterine growth retardation (IUGR), maternal and cord serum IGFBP-1 levels at the time of delivery were elevated. By contrast, circulating IGFBP-3 levels in both the mother and the fetus were lower in pre-eclampsia with IUGR than in nonpre-eclamptic pregnancy. However, there was no difference in serum IGFBP-1 and IGFBP-3 levels between pre-eclampsia without IUGR and nonpre-eclamptic pregnancy in both the mother and the fetus. Conclusions In pre-eclampsia, elevated concentrations of circulating IGFBP-1 and decreased serum IGFBP-3 levels were observed in both the mother and the fetus. However, these changes may simply reflect low birthweight in pre-eclampsia.

Co-culturing embryos on helper cells can mimic the in-vivo environment, thereby enhancing embryo development in vitro. Insulin-like growth factors (IGF) and their binding proteins (IGFBP) also enhance embryo development. To investigate the kinds of IGFBP produced by various cell monolayers and the effects of IGFBP-3 on mouse embryo co-culture systems, 2-cell ICR mouse embryos were cultured in either human tubal fluid medium alone or in the presence of Vero cells, human oviductal cells or endometrial cells. The helper cells were analysed immunohistochemically to investigate the types of IGFBP produced by various cell monolayers. The concentrations of IGF-I and IGFBP-3 in media obtained from the culture of embryos alone, cells alone or cells plus embryos were determined by radioimmunoassays. On day 7, more blastocysts hatched in the co-culture groups (73% in the Vero cell group, 76% in the endometrial cell group and 74% in the oviductal cell group) than in the control group (43%) (P < 0.0001). The results of immunohistochemistry revealed that (i) all three cell groups produced a lot of IGFBP-1, -2 and -3, but only a little of IGFBP-4 and -5; and (ii) IGFBP-1, -2, and -3 were present in blastocysts in either the presence or absence of helper cells. The IGF-I secreted by cell monolayers or embryos was undetectable (detection limit 0.83 microg/l). The IGFBP-3 concentrations in media obtained from co-cultured embryos and cells were significantly higher than in media without embryos (median values in oviductal cell culture medium, 165 versus 127 microg/l, P = 0.04; median values in endometrial cell culture medium, 277.5 versus 183.5 microg/1, P = 0. 0002; median values in Vero cell culture medium, 219 versus 120 microg/l, P = 0.011). Although IGFBP-3 concentration in the medium that contained embryos alone was undetectable by radioimmunoassay (detection limit 1.1 microg/l), immunohistochemistry demonstrated the presence of IGFBP-3 in the embryos. Co-culture in systems in which there was an increased production of IGFBP-3 led to an improved development of mouse embryos. IGFBP can improve the binding of IGF to cell surface receptors of target tissue, and thus enhance the effect of limited IGF concentrations in promoting embryo development in a co-culture system. We conclude that Vero cells, human endometrial cells and oviductal cells produce IGFBP-1, -2, -3, -4 and -5. IGFBP-3 may play a role in embryotrophic potential by either regulating the action of IGF or directly enhancing embryo development.

The aim of this study was to investigate circulating levels of insulin-like growth factor-binding protein-3 (IGFBP-3) in women with normal pregnancy. A total of 468 pregnant women at various gestational ages and 30 non-pregnant females were recruited in this study. Serum concentration of IGFBP-3 was determined by radioimmunoassay. Maternal serum levels of IGFBP-3 increased as pregnancy progressed. The concentration of IGFBP-3 in pregnancy serum was positively associated with the gestational age. The mean values of circulating IGFBP-3 in the second and third trimesters of pregnancy were higher than those in the first trimester of pregnancy and in non-pregnant females. In addition, there was a highly significant correlation between IGFBP-3 and IGF-I in pregnancy serum. We conclude that, during pregnancy, IGFBP-3 appears to be the principal binding protein for circulating IGF-I and may be involved in the regulation of fetal growth.

Objective To investigate the cyclic changes of serum insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1) and IGFBP-3 levels during ovulatory menstrual cycle. Design A prospective study following a preset protocol. Setting A tertiary-care academic medical center. Participants Thirty young female adults with regular menstrual cycles were recruited (18 with normal luteal phase and 12 with inadequate luteal function confirmed by serum P levels). Main Outcome Measures Serum concentrations of IGF-I, IGFBP-1, and IGFBP-3 from women with regular menstrual cycles were assayed. Circulating E 2 and P levels also were determined to certify the ovulatory cycles. Results In women with normal luteal function, there was a peak of serum IGFBP-1 levels before ovulation concomitant with the preovulatory E 2 peak. The nadir of serum IGFBP-1 levels was in the midluteal phase. Circulating IGFBP-1 elevated rapidly during late luteal phase and reached a peak on the 1st day of menstruation then declined slightly until a preovulatory IGFBP-1 peak occurred. In women with inadequate luteal function (midluteal serum levels of P Conclusions The preovulatory increase in serum IGFBP-1 levels may be of follicular origin and associated with the subsequent luteal function in females with ovulatory cycles. However, the involvement of IGFBP-1 in the process of follicular maturation and luteogenesis, as well as the regulation of luteal function, needs to be explored further.

Background Infertility affects approximately 10–15% of reproductive-age couples. Poor semen quality contributes to about 25% of infertile cases. Resulting from the direct effect on testicular function or hormonal alterations, heavy metals exposure has been related to impaired semen quality. The objective of this study was to assess the level of lead in the seminal plasma in men without occupational exposure to lead, and to determine the relationship between semen quality and lead concentration in the semen. Methods This is a prospective and nonrandomized clinical study conducted in University infertility clinic and academic research laboratory. Three hundred and forty-one male partners of infertile couples undergoing infertility evaluation and management were recruited to the study. Semen samples collected for the analyses of semen quality were also used for the measurement of lead concentrations. Semen samples were evaluated according to the WHO standards. Results All subjects were married and from infertile couples without occupational exposure to lead. There is a significant inverse correlation between the lead concentration in seminal plasma and sperm count. A higher semen lead concentration was correlated with lower sperm count, but not with semen volume, sperm motility or sperm morphology as assessed by simple linear regression. Conclusions We found that semen lead concentration was significantly higher among the patients with lower sperm count. To our knowledge, this is the first study to demonstrate that a high level of lead accumulation in semen may reduce the sperm count contributing to infertility of men without occupational exposure to lead.

Endometriosis is determined by genetic factors, and the prevalence of genetic polymorphisms varies greatly depending on the ethnic group studied. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of 9 genes involved in estrogen biosynthesis and metabolism and the risks of endometriosis. Three hundred patients with endometriosis and 337 non-endometriotic controls were recruited. Thirty four non-synonymous SNPs, which change amino acid residues, were analyzed using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The functions of SNP-resulted amino acid changes were analyzed using multiple web-accessible databases and phosphorylation predicting algorithms. Among the 34 NCBI-listed SNPs, 22 did not exhibit polymorphism in this study of more than 600 Taiwanese Chinese women. However, homozygous and heterozygous mutants of 4 SNPs - rs6165 (genotype GG+GA, 307(Ala/Ala)+307(Ala/Thr)) of FSHR, rs 6166 (genotype GG+GA, 680(Ser/Asn)+680(Ser/Ser)) of FSHR, rs2066479 (genotype AA+AG, 289(Ser/Ser)+289(Ser/Gly)) of HSD17B3 and rs700519 (genotype TT+TC, 264(Cys/Cys)+264(Cys/Arg)) of CYP19, alone or in combination, were significantly associated with decreased risks of endometriosis. Bioinformatics results identified 307(Thr) of FSHR to be a site for O-linked glycosylation, 680(Ser) of FSHR a phosphorylated site by protein kinase B, and 289(Ser) of HSD17B3 a phosphorylated site by protein kinase B or ribosomal protein S6 kinase 1. Results of this study suggest that non-synonymous polymorphisms of FSHR, HSD17B3 and CYP19 genes may modulate the risk of endometriosis in Taiwanese Chinese women. Identification of the endometrosis-preferential non-synonymous SNPs and the conformational changes in those proteins may pave the way for the development of more disease-specific drugs.

Objective To evaluate interrelationships between levels of insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein (IGFBP-I), and ovarian steroids in late preovulatory follicular fluid (FF) after pituitary desensitization with GnRH agonist and controlled ovarian hyperstimulation. Design Follicular fluid and matched serum were collected during the ovum pick-up. Insulin-like growth factor binding protein I, E 2 , P, and androstenedione (A) were measured by means of RIA, whereas T was measured by means of fluoroimmunoassay and IGF-I by means of immunoradiometric assay. Setting University teaching hospital. Participants Fifty-nine patients underwent 62 ovum pick-ups for IVF. Main Outcome Measures Levels of IGF-I, IGFBP-I, E 2 , P 4 (representative of follicular maturity), T, and A in FF and the volume of this fluid were determined. Levels of E 2 to A (representative of aromatase activity) in FF were examined in relation to the volume of FF. Results Levels of FF-IGF-I decreased with increasing volume of FF. This observation is unprecedented. In contrast, FF-P increased with increasing volume of FF. The reverse relationships with FF volume between FF-IGF-I and FF-P may not be causal because no correlation was found between concentrations of FF-IGF-I and FF-P. Our findings are consistent with and complementary to those in previous reports. The follicular fluid E 2 :A ratio, FF-E 2 , FF-A, FF-T, and FF-IGFBP-I were not found to be correlated with volume of FF. Conclusion Decreased levels of FF-IGF-I with unaltered levels of FF-IGFBP-I in larger follicles may favor a shift toward diminished action of IGF-I at the time of immediate preovulation. The physiological significance of this shift remains uncertain as it is not reflected in the levels of steroids in FF.

Background To test whether a site-specific hysteroscopic biopsy-induced injury in the endometrium during the controlled ovarian hyperstimulation cycle improves subsequent embryo implantation in patients with repeated implantation failure, a total of 30 patients who have had good responses to controlled ovulation stimulation but have failed to achieve pregnancy after two or more transfers of good-quality embryos were recruited in this prospective study. Methods A single, site-specific hysteroscopic biopsy-induced injury was generated on the posterior endometrium at midline 10-15 mm from the fundus during the D4-D7 period of the ongoing controlled ovarian hyperstimulation cycle in six patients. Results Patients received endometrial biopsy protocol achieved a pregnancy rate of 100%. By contrast, only 46% of patients with similar clinical characteristics (N = 24) achieved pregnancy without the hysteroscopic biopsy-induced endometrium injury (p < 0.05). Conclusions Our proof-of-concept study demonstrates that a site-specific hysteroscopic endometrium injury performed during the ongoing in vitro fertilization (IVF) cycle, instead of injuries received during prior cycles, significantly improves clinical outcomes in patients with repeated implantation failure.

SummaryGenome-wide association studies (GWAS) use high-throughput genotyping technology to relate hundreds of thousands of genetic markers (genotypes) to clinical conditions and measurable traits (phenotypes). This review is intended to serve as an introduction to GWAS for clinicians, to allow them to better appreciate the value and limitations of GWAS for genotype-disease association studies. The input of clinicians is vital for GWAS, since disease heterogeneity is frequently a confounding factor that can only really be solved by clinicians. For diseases that are difficult to diagnose, clinicians should ensure that the cases do indeed have the disease; for common diseases, clinicians should ensure that the controls are truly disease-free.

Type I GnRH (GnRH-I, GNRH1) and type II GnRH (GnRH-II, GNRH2), each encoded by separate genes, have been identified in humans. The tissue distribution and functional regulation of GnRH-I and GnRH-II clearly differ despite their comparable cDNA and genomic structures. These hormones exert their effects by binding to cell surface transmembrane G protein coupled receptors and stimulating the Gq/11 subfamily of G proteins. The hypothalamus and pituitary are the main origin and target sites of GnRH, but numerous studies have demonstrated that extra-hypothalamic GnRH and extra-pituitary GnRH receptors exist in different reproductive tissues such as the ovary, endometrium, placenta, and endometrial cancer cells. In addition to endocrine regulation, GnRH is also known to act in an autocrine and paracrine manner to suppress cell proliferation and activate apoptosis in the endometrium and endometrial cancer cells through several mechanisms. Both GnRH-I and GnRH-II exhibit regulatory roles in tissue remodelling during embryo implantation and placentation, which suggests that these hormones may have important roles in embryo implantation and early pregnancy. The presence of varied GnRH and GnRH receptor systems demonstrate their different roles in distinct tissues using dissimilar mechanisms. These may result in the generation of new GnRH analogues used for several hormone-related diseases.

Tamoxifen has been reported to be oestrogenic on the lower genital tract. To evaluate its potential positive effect on the endometrium, and consequently early miscarriage and ongoing pregnancy rate, a prospective study was employed in patients for intrauterine insemination who failed to develop an adequate endometrial thickness in a previous ovulatory cycle. Ovarian stimulation was initiated with tamoxifen 40 mg/day from day 3 of the menstrual cycle for 7 days or clomiphene 100 mg/day for 5 days, in combination with 150 IU of human menopausal gonadotrophin on alternate days starting on day 4. Human chorionic gonadotrophin (HCG) was administered when at least one leading follicle was larger than 20 mm. Intrauterine insemination was accomplished 24-36 h after HCG injection and luteal phase supplement was achieved with micronized progesterone 200 mg transvaginally per day. It was found that tamoxifen-treated patients required more stimulation days and used more gonadotrophin, but recruited less follicles larger than 14 mm than clomiphene-treated patients. However, a significantly increased endometrial thickness (P < 0.001) and pregnancy rate (P = 0.015), decreased early miscarriage rate (P = 0.001) and thus improved ongoing pregnancy (P < 0.001) rate were noted in tamoxifen-treated patients. These results suggest that although tamoxifen may not be a first-line treatment in patients with adequate endometrium, it may be a promising alternative for patients with thin endometrium.

Objective To investigate the functional roles of differentially expressed proteins in the amniotic fluid supernatant (AFS) with abnormal karyotypes. Design Basic and clinical research. Setting University hospital. Patient(s) Samples of AFS from 34 fetuses with normal-karyotype, 17 with trisomy 18, and 19 with trisomy 21. Intervention(s) Two-dimensional chromatography followed by mass spectrometry to identify the proteins differentially expressed in AFS of trisomy-18 or trisomy-21 fetuses. Main Outcome Measure(s) Differentially expressed proteins were confirmed with Western blot analysis and ELISA. The roles of biologic networks in the pathophysiology of aneuploidies were analyzed using MetaCore mapping tools. Result(s) Levels of apolipoprotein A1, AP-3μ, and antitrypsin were significantly decreased in trisomy-18 AFS, whereas placental protein-14 was increased. On the other hand, apolipoprotein A1 was decreased in trisomy-21 AFS, but antitrypsin, prealbumin, and transferrin were increased in trisomy 21. Biologic network analyses revealed that the proteins of the trisomy-18 AFS network were involved in immune processes, dysfunction of skin pigmentation, and platelet disorders, whereas those of trisomy 21 were associated with dysfunctional lipid and cholesterol metabolism, processes of metal ion transport, adenosine triphosphate metabolism, and energy-coupled protein transport. Conclusion(s) The combined use of quantitative proteomics and functional network analyses may integrally analyze the pathophysiology of abnormal karyotypes.

Objective The objective of this study was to investigate the association between follicular fluid (FF) levels of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and pregnancy-associated plasma protein-A (PAPP-A), which is a protease for IGFBP-4, and the quality of subsequent embryo development from in vitro fertilized oocytes aspirated from the same follicle. Design Prospective study. Setting University infertility clinic and academic research laboratory. Patient(s) One hundred sixty-two infertile women undergoing controlled ovarian hyperstimulation for IVF and embryo transfer were recruited in a university hospital. Intervention(s) During oocyte retrieval, samples of 225 FFs and matched mature oocytes were collected and studied. Main Outcome Measure(s) Concentrations of FF IGF-I, IGF-II, IGFBP-1, IGFBP-3, IGFBP-4, and PAPP-A were determined using ELISA. Progesterone secretion by cultured granulosa cells (GC) was measured by RIA. Result(s) Levels of IGF-II, IGFBP-3, and IGFBP-4 in FF on the day of oocyte retrieval were significantly correlated with embryo scores on day 3 (72 hours after oocyte retrieval). Levels of IGF-II, IGFBP-3, and IGFBP-4 in FF from follicles in which oocytes developed into day 2 embryos (48 hours after oocyte retrieval; 20 ≥ embryo score ≥ 6) after fertilization were significantly higher than those from follicles in which oocytes were unable to be fertilized and were arrested in embryo development on day 2, whereas the levels of PAPP-A were significantly lower in the former than the latter group. Using multiple regression analysis, we found that high levels of IGFBP-3 and IGFBP-4 combined with low levels of PAPP-A in FF were significantly correlated with successful fertilization and early development into day 2 embryos. In contrast, high FF IGFBP-1 and IGFBP-4 in combination with low FF IGF-I were significantly correlated with a later (day 2–day 3) embryo development. A significant stimulation of P secretion in cultured GCs by the combination of recombinant IGF-II, IGFBP-3, and IGFBP-4 further strengthened these proteins' functional roles in promoting late follicular development. Conclusion(s) High IGF-II, IGFBP-3, IGFBP-4, and low PAPP-A levels in FF at the time of oocyte retrieval suggest better oocyte maturation and early embryo development (within 48 hours after oocyte retrieval), whereas high IGFBP-1, IGFBP-4, and low FF IGF-I levels may favor later embryo development (between 48 and 72 hours after oocyte retrieval).

Objective To investigate the IL-18 system, including IL-18, IL-18 receptor (IL-18R), IL-18 binding protein (IL-18BP), and IL-18 precursor (proIL-18), mRNA and protein expression in human endometrium during the menstrual cycle. Design Controlled study. Setting Clinical and academic research setting in a university medical center. Patient(s) Human endometrium was obtained from surgical specimens of normal cycling women undergoing hysterectomy for benign reasons. Intervention(s) A total of 24 human endometrium samples were obtained at proliferative and secretory phase from surgical specimens of normal cycling women undergoing hysterectomy. Quantitative competitive polymerase chain reaction (QC PCR) and immunohistochemistry were performed. Main Outcome Measure(s) The differences of IL-18 system mRNA and the ratio of antagonist to agonist in both proliferative and secretory phases of endometrium were analyzed. Result(s) Our results showed a complete IL-18 system, including mRNA expression and protein production in both proliferative and secretory phases of the endometrium. The QC PCR demonstrated that both IL-18 and IL-18R decreased and IL-18BP increased mRNA expression in human endometrium in secretory phase compared with proliferative phase. A positive correlation of IL-18 and IL-18R in human endometrium was demonstrated in proliferative phase but not in secretory phase. In addition, there is a significantly higher ratio of IL-18BP to IL-18 mRNA levels in secretory endometrium compared with proliferative phase endometrium ( P Conclusion(s) The expression and ratio of IL-18 antagonist to agonist may be responsible for embryo implantation.

To obtain quantitative data on endometrial volume and subendometrial blood flow by three-dimensional ultrasound clue to endometrial receptivity.A prospective, nonrandomized clinical study.One tertiary center for assisted reproduction.Fifty-four patients aged38 years with normal basal serum FSH level experiencing their first IVF cycle, whose uteri were morphologically normal as confirmed by 3-dimensional (3-D) ultrasound, were studied.Ultrasound evaluation was performed for all patients with 3-D facility by a single operator on the day of hCG administration.Ultrasonographic parameters and conception rates.Subendometrial vascularization flow index (VFI) in predicting the pregnancy rate of IVF was superior to that using vascularization index, flow index, or endometrial volume in the receiver operating characteristics curve analysis. The best prediction rate was achieved by a VFI cutoff value of0.24.The detection of subendometrial blood flow by 3-D power Doppler ultrasound may be a useful ultrasound parameter in the prediction of pregnancy rate of IVF, especially subendometrial VFI.

BACKGROUND: The objective of the present study was to investigate the correlation between inhibin B and estradiol levels in follicular fluid (FF) with the quality of subsequent embryo development from in-vitro fertilized oocytes aspirated from the same follicle. METHODS: A total of 156 infertile women undergoing controlled ovarian stimulation for IVF and embryo transfer was recruited to the present study. Prospectively, 233 FF samples and matched mature oocytes were studied. Concentrations of inhibin B and estradiol were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorometric assay (IFMA) respectively. RESULTS: Inhibin B levels in FF were significantly correlated with embryo scores on days 2 and 3 (48 and 72 h after oocyte retrieval). In contrast, both inhibin B and estradiol levels in FF were inversely related to age. Furthermore, FF inhibin B levels were inversely associated with serum FSH levels on day 3 of the menstrual cycle, which was believed to reflect the ovarian reserve. CONCLUSION: Inhibin B in FF may serve as an effective marker of follicular development and a useful predictor of quality of embryo. In addition, quality of oocyte is age-related and declines as age increases.

Adequate vascular development of the placental bed is essential for normal pregnancy. We assessed serum levels of placenta growth factor, an angiogenic factor, throughout normal pregnancy and determined its association with preeclampsia.Serum samples were collected from (1) 308 healthy pregnant women throughout normal gestation, (2) at delivery from 30 each gestational age-matched patients with normal pregnancy and preeclampsia, and (3) maternal and cord blood samples from normal deliveries with and without labor (n = 37 each). Placenta growth factor levels were determined with an antigen-capture enzyme-linked immunosorbent assay.Maternal placenta growth factor levels during normal pregnancy increased from the first trimester to the late second trimester; they subsequently declined from 30 weeks' gestation to delivery. Significantly less maternal placenta growth factor (P.0001) was found in pregnancies complicated by preeclampsia, and labor significantly lowered placenta growth factor levels in both maternal (P =.0189) and cord serum samples (P.0001).Decreased levels of placenta growth factor during preeclampsia could influence endothelial cell and trophoblast function, thereby contributing to the pathogenesis of the disease.

Despite the expanding role of laparoscopic surgery in many gynaecological fields, some discrepancies still exist regarding the efficacy of laparoscopic myomectomy in treating patients with large symptomatic leiomyoma. In this report, a better operative procedure and the results of treatment are evaluated. Patients (n = 14) presenting with infertility, menorrhagia, pressure symptoms or pelvic mass associated with a large leiomyoma were managed with laparoscopic myomectomy using airlift gasless laparoscopy. Uterine size ranged from 14 to 24 weeks gestational age and the weight of the myoma ranged from 246 to 669 g (mean 454); operative time ranged from 78 to 165 min (mean 104) and blood loss from 90 to 580 ml (mean 201). No major complication occurred during the operation or follow-up. All except one patient were discharged within 72 h of the operation and resumed normal activity within 1 week. When myomectomy is indicated, the airlift gasless laparoscopic approach appears to offer a better alternative to abdominal or pneumoperitoneum laparoscopic surgery in selected cases. Airlift gasless laparoscopy has several advantages: (i) small abdominal incisions and minimal endoscopic equipment are required; (ii) the excised leiomyomata mass can be easily cut into strips and removed through the small abdominal incision; (iii) the uterine defect can be more efficiently repaired using easily performed suture techniques; (iv) high-pressure irrigation and large-volume suction devices can be used without fear of decompressing the pneumoperitoneum; and (v) the potential risk of metabolic and haemodynamic derangements during pneumoperitoneum laparoscopy are obviated. Gasless laparoscopy also has some disadvantages. The exposure obtained with gasless laparoscopy is not as good, under some circumstances, as that achieved by pneumoperitoneum. For patients who are thin, and even those with moderate obesity, the exposure obtained with airlift mechanical suspension is adequate; however, morbidly obese patients with previous abdominal surgery with suspected pelvic adhesions can incur some problems during the operation because of a poor operative field.

Purpose: The purpose of this study was to evaluate the relationship between the total motile sperm count and the success of IUI treatment cycles with postwashed husband spermatozoa in couples with infertility in a large patient population. Patients: When 939 couples underwent 1375 cycles of IUI with varying etiologies of infertility which included male factor, endometriosis, tubal factor, ovulatory dysfunction, uterine factor, cervical factor, and unexplained infertility, the results were 207 pregnancies. Results: The overall pregnancy rate per cycle was 15.1% (207/1375). The total motile sperm count were significantly increased in the pregnant group than the nonpregnant group (38.7×106 versus 28.6 × 106;P

The purposes of this study were to explore whether serum levels of insulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-1 (IGFBP-1) and IGFBP-3 in both maternal and fetal compartments were affected by the stress of labor, and to investigate the relationship between the fetal birthweight and serum levels of insulin, IGF-I and IGFBPs.Blood samples were collected at the time of delivery from 147 parturients with vaginal delivery and 128 cases of Cesarean section (112 cases without labor and 16 cases with arrest of cervical dilatation during the active phase of labor). Serum concentrations of insulin, IGF-I, IGFBP-1 and IGFBP-3 were determined by radioimmunoassays (insulin, IGFBP-1 and IGFBP-3) and immunoradiometric assay (IGF-I).Maternal circulating IGFBP-1 levels in parturients with normal spontaneous delivery (NSD) and in subjects receiving Cesarean section (CS) due to arrest of cervical dilatation during active phase of labor were higher than those undergoing scheduled CS without labor. By contrast, insulin levels in both maternal and umbilical cord serum were higher in parturients with CS without labor than those with NSD. No difference in maternal serum IGFBP-3 levels was observed between NSD and CS at the time of delivery. As for all measurements (insulin, IGF-I, IGFBP-1 and IGFBP-3), serum levels in pregnant women (from both NSD and CS) were strikingly higher than those in the fetus. Serum levels of IGFBP-1 in umbilical cords from both groups of NSD (p0.02) and scheduled CS (p0.01) were inversely correlated with birthweight (BW). By contrast, serum concentration of insulin and IGF-I in umbilical cords from NSD (p0.005 and p0.01; respectively) and scheduled CS (p0.01 and p0.05; respectively) were positively related to BW.From the present results, we conclude that insulin appears to be a regulator for circulating IGFBP-1 during pregnancy. The fetal growth may not be well reflected by maternal serum IGFBP-1 levels, nor by IGFBP-3. By contrast, cord serum IGFBP-1 from CS group without labor may preeminently reflect fetal weight. In additional, serum concentration of insulin and IGF-I in umbilical cord may also be good indicators to reflect the result of neonatal birthweight.

Objective To present a case of cesarean scar pregnancy combined with intrauterine pregnancy after IVF–embryo transfer. Successful embryo reduction was performed and preserved the normal intrauterine gestation. Design Case report. Setting Tertiary referral case center. Patient(s) A woman with cesarean scar pregnancy combined with intrauterine pregnancy after IVF–embryo transfer. Intervention(s) Early diagnosis of heterotopic cesarean scar pregnancy and selective embryo reduction was performed by ultrasound-guided potassium chloride (KCl) directed injection. Main Outcome Measure(s) Successful pregnancy outcome. Result(s) A 38-year-old woman achieve pregnancy by IVF–embryo transfer. Heterotopic cesarean scar pregnancy was diagnosed at 7 weeks gestational age. A transvaginal ultrasound-guided KCl injection was given to terminate the cesarean scar embryo and a healthy infant was delivered 6 months later. Conclusion(s) Heterotopic cesarean scar pregnancy after IVF is extremely rare. Transvaginal intracardiac injection of KCl is a safe and reliable method to terminate the cesarean scar pregnancy. Satisfactory pregnancy outcome should be achieved.