Songying Zhang

A comparison of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of adhesion reformation following hysteroscopic surgery for Asherman syndrome: a cohort study ☆

OBJECTIVE To compare the efficacy of intrauterine balloon, intrauterine contraceptive device and hyaluronic acid gel in the prevention of the adhesion reformation after hysteroscopic adhesiolysis for Ashermans syndrome. STUDY DESIGN Retrospective cohort study of 107 women with Ashermans syndrome who were treated with hysteroscopic division of intrauterine adhesions. After hysteroscopic adhesiolysis, 20 patients had intrauterine balloon inserted, 28 patients had intrauterine contraceptive device (IUD) fitted, 18 patients had hyaluronic acid gel instilled into the uterine cavity, and 41 control subjects did not have any of the three additional treatment measures. A second-look hysteroscopy was performed in all cases, and the effect of hysteroscopic adhesiolysis was scored by the American Fertility Society classification system. RESULTS Both the intrauterine balloon group and the IUD group achieved significantly (P<0.001) greater reduction in the adhesion score than that of the hyaluronic acid gel group and control group. The efficacy of the balloon was greater than that of the IUD (P<0.001). There was no significant difference in results between the hyaluronic acid gel group and the control groups. CONCLUSION The insertion of an intrauterine balloon or intrauterine device is more effective than the use of hyaluronic acid gel in the prevention of intra-uterine adhesion reformation.

CALCIUM-BINDING PROTEIN S100P IS HIGHLY EXPRESSED DURING THE IMPLANTATION WINDOW IN HUMAN ENDOMETRIUM

OBJECTIVE To investigate S100P expression and localization in human endometrium throughout the menstrual cycle. DESIGN Experimental study. SETTING University hospital. PATIENT(S) Eighty-four women. INTERVENTION(S) Complementary DNA (cDNA) microarray analysis was performed on human endometrium from days LH+4, LH+7, and hCG+7. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were used to detect the expression of S100P and of additional S100 family members, S100A4, S100A13, and S100A6. Immunofluorescence was used to detect the localization of S100P protein in LH+7 and LH+4 endometrium. MAIN OUTCOME MEASURE(S) Differential gene expression, levels of S100P messenger RNA (mRNA), and protein expression and immunofluorescent localization of S100P. RESULT(S) A statistical method, based on hierarchical clustering, identified genes whose expression varied at LH+7 compared with LH+4. We found that S100P was the fourth most up-regulated gene at LH+7. The S100P mRNA and protein levels were quite low during the proliferative phase and LH+4, but were elevated significantly at LH+7. The S100P expression at hCG+7 was lower than that at LH+7. However, the expression of S100A4, S100A13, and S100A6 did not vary throughout the menstrual cycle. CONCLUSION(S) S100P was specifically up-regulated during the implantation window. The underlying biological effects of S100P need further exploration.

Recurrent IVF failure is associated with elevated progesterone on the day of hCG administration

OBJECTIVE During in vitro fertilization (IVF) treatment, elevated progesterone on the day of human chorionic gonadotrophin (hCG) administration has been reported to be associated with a reduced chance of live birth. It is not known, however, if the relationship is casual or causal. In the latter situation, one would expect the incidence of elevated progesterone on the day of hCG administration to increase with the number of IVF/embryo transfer (ET) failures. The aim of this study was to investigate if the frequency of elevated progesterone on the day of hCG administration is related to the number of IVF failures. STUDY DESIGN This retrospective, observational, cohort study included a consecutive series of 6673 IVF cycles. Subjects were categorized into one of three groups: Group I, no previous IVF/ET treatment; Group II, one previous IVF/ET treatment failure; or Group III, two or more previous IVF/ET treatment failures. The main outcome measure was the proportion of cycles with elevated progesterone (>6 nmol/l) on the day of hCG administration. RESULTS After adjusting for age, oestradiol level on the day of hCG administration and number of oocytes retrieved, the proportion of women with elevated progesterone on the day of hCG administration remained significantly different between the three groups: Group I, 16.8%; Group II, 31.7%; and Group III, 39.7% (p < 0.001). CONCLUSION Elevated progesterone on the day of hCG administration is more likely in women with recurrent IVF failure. Women with two or more IVF failures are twice as likely to have elevated progesterone on the day of hCG administration as women undergoing their first IVF cycle.

Comparison of progesterone measurement on day of, and day after, HCG administration in IVF–embryo transfer cycles

The aim of this study was to identify whether progesterone measurement on the day after HCG administration has any additional clinical value, over that obtained from progesterone measurement on the day of HCG administration. This was a single-centre, non-interventional retrospective, observational, cohort of a consecutive series of 1457 ovarian stimulation cycles leading to fresh embryo transfer cycles between January 2011 and May 2013. Progesterone was found to rise and increase rapidly by about five-fold over a 24-h period. The result of logistic regression analysis suggests that progesterone measurement around the time of HCG administration is one of the three significant (P <0.001) variables affecting clinical pregnancy rate. The predictive value of progesterone measurement on the day of HCG administration could be improved by having a further measurement 24-h later. If the progesterone levels on both days were normal, the implantation rate was 36%, but if the progesterone level on both days were high, the implantation rate dropped to 22%. Progesterone measurement should be considered on the day of HCG administration and also the day after HCG administration to provide clinically useful information on whether or not embryos should be frozen and transfer deferred to a subsequent cycle.

Differential expression of vascular endothelial growth factor angiogenic factors in different endometrial compartments in women who have an elevated progesterone level before oocyte retrieval, during in vitro fertilization–embryo transfer treatment

OBJECTIVE To investigate the relationship between endometrial expressions of angiogenic factors around the time of embryo implantation and P level before oocyte retrieval during IVF-ET treatment. DESIGN Retrospective study. SETTING University Assisted Reproductive Unit. PATIENT(S) Forty patients were recruited, 20 women with an elevated P level, and 20 women with a normal P level, into cancelled embryo transfer (ET) cycles. INTERVENTION(S) Endometrial biopsy samples were obtained from women who had an elevated or normal P level 7 days after human chorionic gonadotropin administration. The protein expression levels of VEGF-A, VEGF-C, and PLGF were examined using immunohistochemistry. MAIN OUTCOME MEASURE(S) A semiquantitative analysis was performed using histochemical-score analysis of staining intensity in the luminal epithelium, glandular epithelium, and stroma, separately. RESULT(S) Luminal epithelial expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, and PLGF did not significantly differ in women with elevated or normal P levels before oocyte retrieval. Glandular epithelial expression of VEGF-A, VEGF-C, and PLGF was higher in women with elevated P levels, compared with those with normal P levels. A significantly higher stromal expression of VEGF-A and PLGF was found in women with elevated P levels. CONCLUSION(S) A high P level before oocyte retrieval was associated with expression of VEGF angiogenic factors in glandular epithelium and stromal compartment around the time of embryo implantation. Our findings suggest that the lower implantation rates observed in this group of women may relate to decreased endometrial receptivity arising from altered expression of angiogenic factors.

The effect of a high progesterone concentration before oocyte retrieval on the peri-implantation endometrium

In this single-centre, prospective cohort study, the effect of high progesterone level before oocyte retrieval on endometrial morphology and uterine natural killer cell (uKN) count in the peri-implantation period was investigated. A total of 106 women undergoing IVF treatment who did not proceed to fresh embryo transfer were included. Endometrial samples were obtained 7 days after HCG administration. Multiple regression analysis was used to identify factors affecting the results of histological staging and uNK cell count. Progesterone level on the day after HCG administration was the only significant variable associated with the results of histological staging (P = 0.004). Endometrial development in women with high progesterone level was significantly (P < 0.001) more advanced than that of women with normal progesterone; progesterone level on the day of HCG administration was the only significant variable associated with uNK cell count. The median (range) of uNK cell count of 9.6% (2.3-21.6%) in women with high progesterone was significantly (P < 0.001) higher than the median (range) of uNK cell count of 5.7% (1.4-18.7%) in women with normal progesterone. High progesterone level before oocyte retrieval was correlated with advancement in endometrial development as well as increased uNK cell count.

A comparison of the miscarriage rate between women with and without polycystic ovarian syndrome undergoing IVF treatment.

OBJECTIVE To investigate if patients with polycystic ovary syndrome (PCOS) who conceived via IVF treatment had a higher miscarriage rate than non-PCOS subjects after controlling for several important confounding variables relating to pregnancy loss. STUDY DESIGN A retrospective, observational, cohort study including a consecutive series of 564 embryo transfer cycles from PCOS patients and 7494 embryo transfer cycles from non-PCOS patients. Only the first pregnancy arising from IVF treatment was included for subsequent analysis. None of the subjects underwent ovarian diathermy or drilling prior to IVF treatment. Low dose (≤1000mg daily), short term (≤3 weeks) metformin therapy was used in 50 of the 301 PCOS subjects included in the study. RESULTS After controlling for the number of embryo transferred, the type of embryos transferred (fresh or frozen-thawed), and the stage of embryo development at the time of transfer, women with PCOS had a consistently higher biochemical pregnancy rate than women without PCOS (fresh single day 3 embryo transfer, 46.7% (7/15) vs. 14.5% (27/186), respectively, p<0.05; frozen-thawed single day 3 embryo transfer, 25.9% (7/27) vs. 6.1% (11/181), p<0.05; fresh double day 3 embryo transfer, 17.1% (12/70) vs. 7.6% (95/1256), p<0.05; frozen-thawed double day 3 embryo transfer, 7.9% (15/189) vs. 3.4% (66/1968), p<0.05). There was no significant difference in the clinical miscarriage rate between the two groups of subjects. CONCLUSION PCOS patients who conceived following IVF treatment had higher biochemical loss than women without PCOS, but the clinical miscarriage rate was no different between the two groups.

The effect of elevated progesterone levels before oocyte retrieval in women undergoing ovarian stimulation for IVF treatment on the genomic profile of peri-implantation endometrium

To evaluate the effects of high progesterone prior to oocyte retrieval on the genomic profile of peri-implantation endometrium, we conducted this single-center, prospective cohort study. Depending on whether or not the progesterone level on the day of hCG administration and the day after hCG administration were elevated, a total of 20 women undergoing IVF treatment who did not have fresh embryo transfer were included: Group 1 refers to subjects with normal progesterone level on both days; Group 2 refers to subjects with normal progesterone level on the day of hCG administration and high progesterone level on the day after hCG administration; Group 3 refers to subjects with high progesterone level on the day of hCG administration and normal progesterone level on the day after hCG administration; Group 4 refers to subjects with high progesterone level on both days. Five subjects were included in each group. Endometrial samples were obtained 7days after hCG administration. We found that high progesterone level prior to oocyte retrieval predominantly affected components of the NK cell mediated cytotoxicity pathway in the endometrium and that significant differences were only seen when progesterone measurements on both the day of and day after hCG administration were considered together.

Ovarian Fibrosis: A Phenomenon of Concern.

Objective: Ovarian fibrosis is characterized by excessive proliferation of ovarian fibroblasts and deposition of extracellular matrix (ECM) and it is one of the principal reasons for ovarian dysfunction. This review aimed to investigate the pathogenetic mechanism of ovarian fibrosis and to clarify the relationship between ovarian diseases and fibrosis. Data Sources: We searched PubMed for English language articles published up to November 2016. The search terms included ovarian fibrosis OR fibrosis, ovarian chocolate cyst OR ovarian endometrioma, polycystic ovarian syndrome (PCOS), premature ovarian failure, ECM, matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs), transforming growth factor-beta 1 (TGF-&bgr;1), connective tissue growth factor (CTGF), peroxisome proliferator-activated receptor gamma (PPAR-&ggr;), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), and combinations of these terms. Study Selection: Articles were obtained and reviewed to analyze the pathogenic mechanism of ovarian fibrosis and related ovarian diseases. Results: Many cytokines, such as MMPs, TIMPs, TGF-&bgr;1, CTGF, PPAR-&ggr;, VEGF, and ET-1, are involved in ovarian fibrogenesis. Ovarian fibrogenesis is associated with various ovarian diseases, including ovarian chocolate cyst, PCOS, and premature ovarian failure. One finding of particular interest is that fibrogenesis in peripheral tissues around an ovarian chocolate cyst commonly causes ovarian function diminution, and therefore, this medical problem should arouse widespread concern in clinicians worldwide. Conclusions: Patients with ovarian fibrosis are susceptible to infertility and tend to have decreased responses to assisted fertility treatment. Thus, protection of ovarian function should be a priority for women who wish to reproduce when making therapeutic decisions about ovarian fibrosis-related diseases.

S100P regulates trophoblast-like cell proliferation via P38 MAPK pathway.

Abstract S100P was originally isolated from the placenta, and is expressed in very high levels in trophoblast cells, but its role on trophoblast cells proliferation has not yet been studied. In this study, we aimed to investigate the potential role of S100P in human placental development, and the impact of its expression regulation on cellular function as well as molecular mechanisms involved in trophoblast-like cells. We found that the expression of S100P in first trimester placenta was significantly reduced in spontaneous abortion patients with respect to normal pregnant women. Up-regulation of S100P in JAR cells promoted JAR cells proliferation, and increased the expression of phosphorylated P38 (p-P38) mitogen-activated protein kinase (MAPK) and p-ERK MAPK. However, the effects of S100P on JAR cells proliferation were prevented by P38 inhibitor-SB203580, but not by ERK inhibitor-PD98059. These results showed that S100P may have a physiological role in normal pregnant development, and regulate trophoblast-like cell proliferation via modulating the P38 MAPK pathway.