Early Follicular Phase Human Chorionic Gonadotropin Addition May Improve the Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection in Patients With "Unpredictable" Poor Response to Gonadotropin-Releasing Hormone Antagonist Protocol.

Purpose: To compare the effects of early and mid-late follicular phase administration of 150 IU of human chorionic gonadotropin (hCG) on gonadotropin-releasing hormone (GnRH) antagonist protocol in "unpredictable" poor ovarian response (POR) women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Methods: A retrospective single-center cohort study was conducted on 67 patients with "unpredictable" POR in their first IVF/ICSI cycle receiving GnRH antagonist protocol. Patients were treated with a second IVF/ICSI cycle using the same GnRH antagonist protocol with the same starting dose of recombinant follicle-stimulating hormone (rFSH) as the first cycle; a daily dose of 150 IU of hCG was administrated on either stimulation day 1 (Group A, n = 35) or day 6 (Group B, n = 32). The number of oocytes retrieved, number of usable embryos, serum level of estradiol (E2) on day of hCG trigger, and clinical pregnant outcomes were studied. Results: The addition of 150 IU of hCG on either the first day or sixth day of stimulation increases the serum level of E2, luteinizing hormone (LH), and hCG on the day of hCG trigger. Only the use of 150 IU of hCG on the first stimulation day improved the number of oocytes retrieved, mature of oocytes, and usable embryos, but not the addition of hCG on stimulation day 6. Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate showed an increasing trend in patients receiving 150 IU of hCG in the early phase compared with mid-late phase, even thought there was no statistically significant difference. Conclusions: Our study demonstrated that adding 150 IU of hCG in subsequent GnRH antagonist cycle in "unpredictable" poor responders is associated with the improvement of response to stimulation. Furthermore, early follicular phase addition of 150 IU of hCG significantly increased the number of oocytes retrieved and usable embryos than did the mid-late addition of the same dose.

A Rapid Screening Workflow to Identify Potential Combination Therapy for GBM using Patient-Derived Glioma Stem Cells.

The glioma stem cells (GSCs) are a small fraction of cancer cells which play essential roles in tumor initiation, angiogenesis, and drug resistance in glioblastoma (GBM), the most prevalent and devastating primary brain tumor. The presence of GSCs makes the GBM very refractory to most of individual targeted agents, so high-throughput screening methods are required to identify potential effective combination therapeutics. The protocol describes a simple workflow to enable rapid screening for potential combination therapy with synergistic interaction. The general steps of this workflow consist of establishing luciferase-tagged GSCs, preparing matrigel coated plates, combination drug screening, analyzing, and validating the results.

Pregnancy Outcomes of Single/Double Blastocysts and Cleavage Embryo Transfers: a Retrospective Cohort Study of 24,422 Frozen-Thawed Cycles.

This study aims to evaluate the effect of blastocyst- and cleavage-stage embryo transfers with different numbers of transferred embryos on pregnancy outcomes in China. This was a retrospective cohort study that collected 24,422 frozen-thawed embryo transfer (FET) cycles in two affiliated hospitals of Peking University Health Science Center between January 2015 and May 2018. They were divided into four groups: the single cleavage-stage embryo transfer group (C-1) (763 cycles), double cleavage-stage embryo transfer group (C-2) (13,004 cycles), single blastocyst-stage embryo transfer group (B-1) (7913 cycles), and double blastocyst-stage embryo transfer group (B-2) (2046 cycles). Of the four groups, the live birth rate was the lowest in the C-1 group (11.8%) while it was the highest in the B-2 group (33.6%). However, the B-2 group was accompanied with higher risks of miscarriages, maternal complications, twin births, preterm births, and low birth weight. Compared with the C-2 group, the B-1 group had a lower live birth rate (23.0 vs 29.0%; aOR, 0.78; 95% CI, 0.72-0.85), but also had a lower risk for twin births (1.9 vs 23.4%; aOR, 0.06; 95% CI, 0.04-0.09) and preterm births (9.6 vs 16.1%; aOR, 0.51; 95% CI, 0.41-0.65). The probability of live birth in the B-1 group declined from 0.25 at 20-29 years old to 0.08 at > 40 years old, while the probabilities of adverse outcomes went up with maternal age. It can be concluded that single-blastocyst embryo transfer seems to be the best choice for all maternal ages. This group of embryo transfer has significantly reduced adverse neonatal outcomes. Especially, women with younger maternal age in this group appear to prominently benefit from single-blastocyst transfer.

A high-throughput drug combination screen identifies an anti-glioma synergism between TH588 and PI3K inhibitors.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. More than half of GBMs contain mutation(s) of PTEN/PI3K/AKT, making inhibitors targeting the PI3K pathway very attractive for clinical investigation. However, so far, PI3K/AKT/mTOR inhibitors have not achieved satisfactory therapeutic effects in clinical trials of GBM. In this study, we aimed to develop a high-throughput screening method for high-throughput identification of potential targeted agents that synergize with PI3K inhibitors in GBM. METHODS: A Sensitivity Index (SI)-based drug combination screening method was established to evaluate the interactions between BKM120, a pan-PI3K inhibitor, and compounds from a library of 606 target-selective inhibitors. Proliferation, colony and 3D spheroid formation assays, western blotting, comet assay, γ-H2AX staining were used to evaluate the anti-glioma effects of the top-ranked candidates. The drug combination effects were analyzed by the Chou-Talalay method. RESULTS: Six compounds were successfully identified from the drug screen, including three previously reported compounds that cause synergistic antitumor effects with PI3K/mTOR inhibitors. TH588, an putative MTH1 inhibitor exhibited significant synergy with BKM120 in suppressing the proliferation, colony formation and 3D spheroid formation of GBM cells. Further investigation revealed that both DNA damage and apoptosis were markedly enhanced upon combination treatment with TH588 and BKM120. Finally, activation of PI3K or overexpression of AKT compromised the anti-glioma efficacy of TH588. CONCLUSIONS: The screening method developed in this study demonstrated its usefulness in the rapid identification of synergistic drug combinations of PI3K inhibitors and targeted agents.

Endometrium imaging using real-time rotational optical coherence tomography imaging system: A pilot, prospective and ex-vivo study.

This study aimed to evaluate a novel real-time rotational optical coherence tomography (OCT) imaging system (OCTIS) with a fiber-optic probe to look at endometrium and to correlate the OCTIS images with standard histology. OCT could obtain real-time images resembling histological examination. With recent development of customized probes, it allows OCT to be used in the field of gynecology.This is a pilot, prospective, ex-vivo and observational study. Women underwent hysterectomy for various gynecological conditions were recruited and OCTIS images were obtained from endometrium of 15 fresh uterus specimens immediately after hysterectomy. The excised uterus was cut open and OCTIS imaging was obtained. The scanned region of endometrium was excised for histological examination and OCTIS images were precisely compared to corresponding histological images and ultrasound images. Blinded qualitative analysis on OCTIS images was performed by 2 assessors to determine inter-rating reliability on the histopathological diagnosis.Epithelium, glands, cysts, and stroma of endometrium were clearly seen by the OCTIS. Different phases of menstrual cycle of normal endometrium could be differentiated and pathological condition such as hyperplastic and dysplasic endometrium, which corresponded well with histological findings, could be identified. The inter-rater reliability between assessors on overall OCTIS endometrium and neoplastic OCTIS endometrium was moderate (Kendall τb of 0.58) and substantial (Kendall τb of 0.76), respectively.OCTIS can provide real-time, high-resolution and rotational imaging modality to view endometrial structure with high consistency with histological examination and satisfactory agreement between observers. It has a great potential to be developed in the clinical use of endometrial assessment for gynecological applications.

Localization of Mucin 1 in endometrial luminal epithelium and its expression in women with reproductive failure during implantation window.

Pinopode and Mucin 1 (MUC1) have both been proposed as morphological and molecular markers of endometrial receptivity for implantation. However, their spatial relationship in luminal epithelium and its association with reproductive failure are still unclear. This was a prospective cohort study conducted at a university assisted reproductive unit including 9 receptive control women, 18 infertile women, and 22 women with recurrent implantation failure (RIF) and 22 women with recurrent miscarriage (RM). Endometrial tissues were obtained at 7 days after luteinizing hormone surge during implantation window. Luminal epithelium was examined by scanning electron microscopy (SEM). MUC1 localization in luminal epithelium was detected by scanning immunoelectron microscopy (SIM) and compared by modified double immunofluorescence (mIF) staining without antigen retrieval. SEM did not show any significant difference in percentage of secretory cells, any stage of pinopodes, and ciliated cells between control, infertility, RIF and RM groups. SIM identified MUC1 was mainly localized on surface of ciliated cells and at the bottom of cilia, not secretory cells and pinopodes, and its specific localization was validated by mIF staining. MUC1 expression in ciliated cells in control women was significantly higher than those women with reproductive failure, but there was no significant difference between RIF and RM. In conclusion, MUC1 is mainly expressed in ciliated cells, not secretory cells and pinopodes, of the endometrial luminal epithelium during implantation window. The specific expression of MUC1 in the ciliated cells in receptive control women is higher than that of women with reproductive failure during implantation window.

Endometrial Vascularization Characterized by Optical Coherence Tomography and Immunohistochemistry in Women Undergoing In Vitro Fertilization-Embryo Transfer Treatment.

BACKGROUND AND OBJECTIVE: Endometrial angiogenesis is a prerequisite for successful pregnancy. Optical coherence tomography (OCT) is a non-invasive physically optical imaging technique widely used in ophthalmology and cardiology. However, there is no study using OCT to evaluate endometrium. The aim of this study was to use OCT and traditionally histological methods to investigate endometrial vascularization in women undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment and to determine the association with the pregnancy outcome. METHODS: A total of 47 women were included in this study. OCT was used to assess endometrial vascularization by determining the high signal areas precisely on the seventh day after luteinizing hormone surge in non-conception natural cycles. Endometrial biopsies were obtained following OCT and immunohistochemistry was used to determine micro vessel and expression of vascular endothelial growth factor-A (VEGF-A) in the luminal epithelium, glandular epithelium and stroma, separately. Micro vessel counting was performed and the result was expressed as micro vessel density (MVD). A semi-quantitative H-score was used to determine the staining intensity of VEGF-A. RESULTS: In women who successfully conceived after embryo transfer, the proportion of extensive high signal area in the uterine body detected by OCT (80%, 8/10), MVD (median number of micro vessels/mm² of 10, range 4⁻17) and stromal expression of VEGF-A (median H-score of 189, range 72⁻395) were found to be significantly higher than those of women who did not conceive after embryo transfer in the subsequent IVF-ET treatment (OCT: 30%, 3/10; MVD: median number of micro vessels/mm² of 7, range 4⁻10; VEGF-A: median H-score of 125, range 86⁻299, respectively). In addition, a significantly higher stromal expression of VEGF-A (median H-score of 196, range 84⁻395) and MVD (median number of micro vessels/mm2 of 9, range 5⁻16) was found in women with extensive high signal area in uterine body, compared to those with focal or no high signal area (stromal VEGF-A: median H-score of 135, range 92⁻302; MVD: number of micro vessels/mm2 of 6, range 4-11). CONCLUSIONS: Both immunohistochemistry and OCT demonstrated significant difference in vascularization of the peri-implantation endometrium between subjects who did and did not conceive after IVF-ET treatment. Our findings also suggest OCT appears to be a promising non-invasive or minimally invasive alternative to study endometrial vascularity in women with reproductive failure.

Decreased MUC1 in endometrium is an independent receptivity marker in recurrent implantation failure during implantation window.

BACKGROUND: It is postulated that women suffered from recurrent implantation failure (RIF) have different endometrial receptivity compared to those who experienced with idiopathic recurrent miscarriage (RM). In this study, expression of common endometrial markers Leukemia inhibitor factor (LIF), mucin 1 (MUC1) and integrin ß3 were studied and compared. METHODS: Fourteen women with RIF, 25 with RM and 20 fertile controls were recruited for endometrial biopsy during implantation window on day LH +  7. Spatial and temporal expression of MUC1, LIF and Integrin ß3 were compared using semi-quantitative immunohistochemistry. Association of MUC1, LIF and integrin ß3 expression levels with demographic and clinical characteristics were determined. RESULTS: MUC1 expression in both luminal and glandular epithelium in women with RIF were significantly lower than that in women with RM and fertile controls. There were no differences in LIF and Integrin ß3 expression in endometrial epithelium among three groups. Decreased MUC1 expression were not significantly associated with age, BMI, gravidity, parity, cycle length, progesterone level and previous miscarriage. CONCLUSIONS: Deceased expression of MUC1 is an independent marker for endometrial receptivity in RIF women, suggesting MUC1 may contribute to the reproductive failure in RIF women.

The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy-An immunological perspective.

During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy.

Physiological and pathological angiogenesis in endometrium at the time of embryo implantation.

Embryo establishes contact with the endometrium during implantation. Proper endometrial vascular development and maintenance at the time of embryo implantation is crucial for successful pregnancy. Vascular development at the maternal-embryo interface can be regulated by various cell types, of which uterine natural killer (uNK) cells play an important role. Abnormal angiogenesis and uNK cell number/function may lead to reproductive failure, particularly in women with recurrent miscarriage (RM) and women with recurrent implantation failure (RIF) after IVF-ET treatment, which are the important clinical hurdles in reproductive medicine to overcome. In this review, we aim to discuss the current knowledge of physiological angiogenic processes and the pathological angiogenesis at the time of implantation, as well as the possible mechanism and potential treatment.

Prestroke glycemic status is associated with the functional outcome in spontaneous intracerebral hemorrhage.

Admission hyperglycemia is thought to be related to poor neurological function and high mortality in patients with spontaneous intracerebral hemorrhage (sICH). However, it is not known whether prestroke glycemic status affects functional outcome of sICH. The study was aimed to disclose the association between prestroke glycemic status and outcome in patients with sICH. The study included 288 patients with sICH. Prestroke glycemic status was represented by hemoglobin A1c (HbA1c) values measured the next day after admission. Correlations between HbA1c and age, hematoma volume, NIHSS, and mRS were analyzed using Spearman's correlation analysis. Patients were categorized into two groups according to hematoma volume (≤25 mL or >25 mL), mRS values (≤2 or >2), or hematoma location (lobar hematoma or deep hematoma). Logistic regression analyses were used to determine the relative independent risk factors for hematoma volume, hematoma location, and mRS values. In patients with sICH, HbA1c was significantly correlated with hematoma volume, NIHSS, and mRS. High HbA1c levels were independently associated with large hematoma volume, deep ICH, and poor outcome. When patients were stratified by history of diabetes, the predictive effect of HbA1c on outcomes was only observed in patients with diabetes. Admission glucose was also related to hematoma volume, but failed to predict outcome. Although both admission glucose and HbA1c independently predicted hematoma volume in patients with sICH, HbA1c alone could serve as a better predictor of poor outcome in diabetic patients after sICH.

Comparable clinical outcomes and live births after single vitrified-warmed and fresh blastocyst transfer.

Selective single-blastocyst transfer (SBT) in fresh cycles has been effective in reducing multiple pregnancies. However, we do not know whether this successful strategy of fresh transfer cycles is suitable for cryopreserved cycles. The present study was undertaken to evaluate the feasibility and value of SBT in vitrified-warmed cycles. Clinical pregnancy rate (CPR) was similar with vitrified and fresh SBT (46.61% versus 52.15% respectively). Of the pregnant patients, monozygotic twin, miscarriage and ectopic pregnancy rates were similar with vitrified and fresh SBT. For the newborns, no significant difference was observed in live birth, low birthweight, premature delivery and birth defects rates between vitrified and fresh SBT. With respect to the quality of transferred blastocysts (from BB to AA), a similar CPR and miscarriage rate was obtained for both vitrified and fresh SBT when a similar blastocyst cohort graded ≥ 3BB was transferred. The data show that vitrified SBT is an effective means of reducing multiple pregnancy and that comparable clinical outcomes and live births are achieved if single blastocysts graded ≥ 3BB are transferred for both vitrified and fresh SBT. These data should encourage clinics to evaluate their embryo transfer policy and adopt vitrified SBT as everyday practice. Selective single-blastocyst transfer in fresh cycles has been an effective method to reduce the multiple pregnancies. However, due to a lack of adequate studies, we do not know whether this successful strategy in fresh transfer cycles is suitable in cryopreserved cycles. The present study was undertaken to explore the feasibility and value of single-blastocyst transfer in vitrified-warmed cycles. We found that single-blastocyst transfer in vitrified-warmed cycles is an effective means of reducing multiple pregnancy, and comparable clinical outcomes and live births were achieved if single blastocysts graded ≥ 3BB were transferred for both vitrified-warmed and fresh blastocyst transfer. These data should encourage clinics to evaluate their embryo transfer policy and adopt single-blastocyst transfer in cryopreserved cycles as their everyday practice.

Abnormal methylation patterns at the IGF2/H19 imprinting control region in phenotypically normal babies conceived by assisted reproductive technologies.

OBJECTIVE: To evaluate epigenetic risks linked to assisted reproductive technologies (ART) by determining the methylation status of the IGF2/H19 imprinting control region (ICR) in offspring born after ART. STUDY DESIGN: A combined bisulfite restriction analysis (COBRA) and sequencing technique were used to determine the methylation status of the IGF2/H19 ICR in 61 phenotypically normal newborns conceived by ART. Thirty naturally conceived newborns were studied as controls. RESULTS: There was no significant difference in methylation between ART newborns and naturally conceived newborns (46.7 ± 8.2% vs. 48.5 ± 8.7%, p>0.05). Abnormal demethylation patterns of the IGF2/H19 ICR were found in three dizygotic twins conceived by intracytoplasmic sperm injection (ICSI), but all three were phenotypically normal, and their sibling twins exhibited normal methylation patterns. CONCLUSION: We hypothesize that the aberrant methylation patterns probably resulted from imprinting errors of paternal gametes or from in vitro embryo culture. Further investigation to determine whether gene expression can be regulated by other mechanisms in addition to DNA methylation would be beneficial.

Assisted reproductive technologies do not increase risk of abnormal methylation of PEG1/MEST in human early pregnancy loss.

OBJECTIVE: To evaluate the epigenetic risk linked to assisted reproductive technology (ART) by analyzing the methylation patterns of imprinted PEG1 gene in aborted human chorionic villus. DESIGN: Experimental research study. SETTING: Research laboratory. PATIENT(S): Four patients groups were tested: spontaneous abortion after ART (n = 44), multifetal reduction after ART (n = 22), spontaneous abortion of natural pregnancies (n = 45), and induced abortion of natural pregnancies (n = 47). INTERVENTION(S): Methylation patterns of PEG1 in the aborted chorionic villus were determined. MAIN OUTCOME MEASURE(S): The DNA methylation patterns were analyzed using pyrosequencing and bisulfite sequencing polymerase chain reaction. The percentage of methylation was compared in chorionic villus from the four experimental groups. RESULT(S): Regardless of conception method, the PEG1 methylation percentage in chorionic villus from spontaneous abortions was significantly higher than in villus from induced abortions and multifetal reduction. In the spontaneous abortions groups, the percent methylation of PEG1 was similar in the villus derived from ART and from natural pregnancies. The two fertilization methods (IVF and intracytoplasmic sperm injection) did not show significant differences either. However, receiver operating characteristic curve analysis revealed a significant positive correlation between PEG1 methylation percentage and rate of early spontaneous abortions. CONCLUSION(S): As some studies have suggested, imprinting errors of PEG1 may contribute to spontaneous abortion, but ART procedures might not increase the occurrence of aberrant PEG1 methylation patterns.

[In vitro fertilization versus intracytoplasmic sperm injection for primary and secondary infertility using sibling oocytes: clinical analysis of the outcomes].

OBJECTIVE: To evaluate the clinical outcomes of intracytoplasmic sperm injection (ICSI) and conventional in vitro fertilization (IVF) using sibling oocytes for treatment of primary and secondary infertility. METHODS: A total of 149 cycles of IVF and ICSI were conducted between January, 2003 and December, 2008 in our center, including 98 cycles in patients with primary infertility and 51 in those with secondary infertility. According to the embryos derived from ICSI, IVF and their combination, the clinical pregnancy rate, delivery rate and birth defect of the 3 groups were analyzed. RESULTS: The fertilization failure rate of IVF was significantly higher in primary infertility group than in secondary infertility group (10.2% vs 3.9%, P<0.05). No fertilization failure occurred in ICSI group. The fertilization rates and good quality embryo rates in ICSI group were significant higher than those in IVF group, and the abnormal fertilization rate was significantly lower in ICSI group (P<0.05). No significant difference were found in the implantation rates, clinical pregnancy rates, delivery rates or the rates of birth defects of the offsprings between IVF, ICSI and IVF+ICSI groups. CONCLUSION: IVF combined with ICSI may result in increased fertilization rate and avoid total fertilization failure with favorable clinical outcomes in patients with long-term infertility, and ICSI may not increase the birth defects of the offspring in these patients.

[Clinical outcomes and birth defects resulting from intracytoplasmic sperm injection using sperms of different origins and parameters].

OBJECTIVE: To explore the quality of the embryos, clinical outcomes and birth defects resulting from intracytoplasmic sperm injection (ICSI) treatment using sperms of different origins and parameters. METHODS: A total of 980 ICSI-ET (embryo-transfer) cycles were divided into 4 groups, namely normal sperm or mild oligozoospermia group (group A), severe oligozoospermia group (group B), epididymal aspirates group (group C) and testicular biopsies group (group D). The cleavage rate, embryo quality, fertilization rate, clinical pregnancy rate, and rates of birth defects were compared between the groups. RESULTS: The fertilization rate, cleavage rate and good-quality embryo rate were not significantly different among the 4 groups (P>0.05), and the embryo implantation rate and clinical pregnancy rate were significantly higher in group C than in groups A and B (P<0.05). Groups A, B and C showed no significant differences in the rates of birth defects (P>0.05), and no birth defects occurred in group D. CONCLUSIONS: Sperms of different parameters and origins used in ICSI treatment can achieve similar fertilization rate, good-quality embryo rate and delivery rate. The embryo implantation rate and clinical pregnancy rate of epididymal sperm group are higher than those of ejaculated groups, possibly due to the younger age of the patients and a greater number of oocytes retrieved in group C than in groups A and B.

Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study.

OBJECTIVE: To evaluate the combined effect of endometrial thickness and pattern on clinical outcome in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). METHODS: Cycles of IVF/ICSI-ET conducted between January 2003 and December 2008 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded on the day of hCG administration. In the combined analysis, endometrial thickness groups (group 1: equal or <7 mm; group 2: 7-14 mm; group 3: >14 mm) were subdivided into two endometrial patterns (pattern A: triple-line; pattern B: no-triple line). Clinical pregnancy rate (CPR) and early miscarriage rate in different groups were analyzed. RESULTS: A total of 2896 cycles were reviewed. Clinical pregnancy rate (CPR) was 24.4% in group 1-A. There were no second trimester pregnancies in group 1-B. Miscarriage rate in group 2-A was significantly lower compared to group 2-B (P < 0.01), although CPR did not show any significant differences between the groups. A no-triple line endometrial pattern with moderate endometrial thickness (7-14 mm) had a detrimental effect on pregnancy outcome, but not the occurrence of pregnancy. In group 3, there was no difference in CPR and miscarriage rates between the two patterns; adequate endometrial thickness (>14 mm) seemed to mitigate the detrimental impact (high miscarriage rate) of pattern B. CONCLUSION: Combined analysis of endometrial thickness and pattern on the day of hCG administration was a better predictor of the outcome of IVF/ICSI-ET and may be more helpful for patient counseling than the separate analyses.

Aberrant DNA methylation of imprinted H19 gene in human preimplantation embryos.

DNA methylation patterns of the H19 differentially methylated region were successfully determined in 32 of 50 human day 3 embryos produced and discarded after assisted reproductive technology procedures. We found methylation patterns similar to those of somatic cells in 81.3% of embryos and demethylation or hypomethylation patterns in 18.7% of embryos.

[Association of the clinical characteristics and the IVF-ET outcome in infertile women with polycystic ovarian syndrome of different subtypes].

OBJECTIVE: To investigate the association of the clinical characteristics and the outcome of in vitro fertilization and embryo transfer (IVF-ET) in infertile women with polycystic ovarian syndrome (PCOS) of different subtypes. METHODS: A total of 189 infertile women with PCOS undergoing IVF-ET were enrolled in this study. According to Rotterdam PCOS diagnosis criteria, the patients were classified into 3 PCOS subtypes, namely type I with PCO ultrasonography and oligo-ovulation/anovulation and hyperandrogenism (54 women, for whom 58 fresh IVF-ET cycles were performed); type II with PCO ultrasonography and oligo-ovulation/anovulation (117 women with 126 cycles); type III with PCO ultrasonography and hyperandrogenism (18 women with 18 cycles). The number of retrieved oocytes, fertilization rate, implantation rate, clinical pregnancy rate, spontaneous abortion rates and incidence of ovarian hyperstimulation syndrome (OHSS) were compared between the 3 groups. RESULTS: Except for the baseline serum T concentration in the early phase of menstrual cycle, which was significantly higher in groups I and III than in group II, no significant difference was found in the clinical characteristics between the 3 groups (P>0.05). Group I had the highest initial Gn dose, and the oocyte retrieval rates were significantly lower in groups I and III (P<0.05). The patients in group I had lower implantation rate and the clinical, on-going and cumulative pregnancy rates than groups II and III, but the differences were not statistically significant; the embryo early loss rate and spontaneous abortion rate appeared to be higher in groups I and III (P>0.05). Significantly elevated incidence of OHSS were noted in groups I and III (P<0.05). CONCLUSION: The women with different PCOS subtypes according to the Rotterdam criteria all have similar IVF-ET outcomes, and the increased embryo loss rate and spontaneous abortion rate in groups I and III might be associated with excessive androgen that disturbs oocyte and embryo development.