Cong Fang

Premature progesterone rise negatively correlated with live birth rate in IVF cycles with GnRH agonist: an analysis of 2,566 cycles

OBJECTIVEnTo investigate the occurrence of premature progesterone rise (PPR) in GnRH agonist long or short protocol, address the relationship between circulating P levels and live birth rates, and explore the possible mechanism through which PPR affects clinical outcomes and the possible factors related to the occurrence of PPR.nnnDESIGNnRetrospective analysis.nnnSETTINGnReproductive medicine center of a public hospital.nnnPATIENT(S)nA total of 2,566 patients receiving inxa0vitro fertilization/intracytoplasmic sperm injection treatment with GnRH agonist long or short protocol.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nLive birth rates.nnnRESULT(S)nThe corresponding incidence of PPR in long or short protocol was 22.86% (393/1,719) or 27.63% (234/847) with the cutoff value of 1.2 ng/mL or 2.0 ng/mL, respectively, being used to define PPR. Live birth rates decreased under the condition of PPR (40.65% vs. 29.77% in long protocol; 30.18% vs. 23.50% in short protocol). Logistic regression analysis showed that serum P level on the day of hCG administration was a strong predictor of live birth rate in both long and short protocols. Live birth rates in frozen embryo transfer cycles had no significant difference between groups with or without PPR (29.31% vs. 25.35% in long protocol; 24.84% vs. 24.22% in short protocol). Multivariate regression analysis showed that exogenous gonadotropin dose, the duration of stimulation, E(2) and LH levels on the day of hCG administration, the number of oocytes retrieved, and basal FSH level were all involved in PPR.nnnCONCLUSION(S)nIn GnRH agonist cycles, PPR negatively correlated with live birth rate in fresh embryo transfer cycles, although no adverse impact on frozen embryo transfer was observed, implying that PPR may have deleterious effects on endometrial receptivity.

Visualization of meiotic spindle and subsequent embryonic development in in vitro and in vivo matured human oocytes.

PurposeThe aim of this study is to investigate the relationship between spindle location and embryonic development of in vivo and in vitro matured human oocytes.MethodsThe spindles of 134 in vivo matured, 105 in vitro matured oocytes were examined by Polscope at the time of ICSI.ResultsThe spindles were visualized in 83.6 and 77.1% of in vivo and in vitro matured oocytes respectively. The rate of fertilization of in vivo matured oocytes with spindles beneath or adjacent to the first polar body (angle of 0–5°) was significantly higher (93.3%) than all other groups. The proportions of various spindle positions did not differ statistically in in vivo and in vitro matured oocytes.ConclusionsMeiotic spindle location with regard to the first polar body appears to influence fertilization rate.

Frozen-thawed day 5 blastocyst transfer is associated with a lower risk of ectopic pregnancy than day 3 transfer and fresh transfer

OBJECTIVEnTo determine the ectopic pregnancy rate with fresh versus frozen-thawed embryo transfers, and factors associated with ectopic pregnancy in patients undergoing IVF-ET.nnnDESIGNnRetrospective analysis.nnnSETTINGnInstitutional IVF center.nnnPATIENT(S)nA total of 3,183 patients who received 3,340 blastocysts transfers: 1,994 fresh transfers and 1,346 frozen-thawed transfers.nnnINTERVENTION(S)nPatients received fresh day 3 embryos (F-D3 group), fresh day 5 blastocysts (F-D5 group), frozen-thawed day 3 embryos (T-D3 group), or frozen-thawed day 5 or 6 blastocysts (T-D5 and T-D6 groups).nnnMAIN OUTCOME MEASURE(S)nEctopic pregnancy rate.nnnRESULT(S)nThe ectopic pregnant rates were 2.4% in the F-D3 group, 1.7% in F-D5, 1.9% in T-D3, 0.3% in T-D5, and 0.5% in T-D6. The ectopic pregnant rate of the T-D3 group was significantly greater than that of the T-D5 and T-D6 groups (1.9% vs. 0.3% and 0.5%). The ectopic pregnancy rate of the F-D5 group was significantly greater than that of the T-D5 group (1.7% vs. 0.3%).nnnCONCLUSION(S)nFrozen-thawed day 5 blastocyst transfer is associated with a lower ectopic pregnancy rate than frozen-thawed day 3 transfer and fresh transfer in patients undergoing IVF-ET.

Abnormal expression of growth differentiation factor 9 and bone morphogenetic protein 15 in stimulated oocytes during maturation from women with polycystic ovary syndrome

OBJECTIVEnTo investigate the expression pattern of two oocyte-secreted factors-growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BM15)-during oocyte maturation in women with polycystic ovary syndrome (PCOS) and in controls and to evaluate the expression differences in oocytes between the two groups.nnnDESIGNnCase-control study.nnnSETTINGnUniversity-affiliated hospital.nnnPATIENT(S)nTwenty-five oocytes were obtained from 12 patients with PCOS and 82 oocytes from 56 controls.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nThe abundance of GDF9 and BMP15 mRNA in oocytes of the germinal vesicle (GV), metaphase I (MI), and MII stage.nnnRESULT(S)nThe expression of GDF9 and BMP15 mRNA displayed dynamic changes during oocyte maturation in controls after ovarian stimulation, with a decline at the MI stage and an increase to the peak at the MII stage. However, their expression in oocytes from patients with PCOS demonstrated a reduced state without any dynamic change.nnnCONCLUSION(S)nThe results suggest that the expression of GDF9 and BMP15 in oocytes from patients with PCOS cannot reach the normal level even after ovarian stimulation and that the expression pattern is abnormal during oocyte maturation, which may be associated with impaired oocyte quality and developmental competence in PCOS.

Reduced and delayed expression of GDF9 and BMP15 in ovarian tissues from women with polycystic ovary syndrome

PurposeGrowth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) play crucial roles in follicular development and oocyte maturation. This study aimed to investigate and compare the expression of these proteins in ovarian tissues of women with and without polycystic ovary syndrome (PCOS).MethodsOvarian tissues from 28 patients with PCOS and 26 normal ovulatory women were collected, and the expression of GDF9 and BMP15 in oocytes and granulosa cells was evaluated via immunohistochemical staining.ResultsGDF9 and BMP15 were first expressed in primordial follicles at very low levels, and their expression increased gradually with follicular development, reaching the highest levels in Graafian follicles. However, less GDF9 and BMP15 expression was observed in primordial, primary, and secondary follicles in ovarian tissues of PCOS patients compared with levels in the control tissues (Pu2009<u20090.05). In Graafian follicles, GDF9 and BMP15 expression reached comparable levels in the PCOS and control groups (Pu2009>u20090.05).ConclusionsThe expression of GDF9 and BMP15 in ovarian tissues varies among the developmental stages in both oocytes and granulosa cells in human ovarian tissues. The expression of these proteins is reduced and delayed in the early follicular stage in PCOS ovarian tissues, and these differences in expression may be associated with aberrant follicular development in patients with PCOS.

Mechanically expanding the zona pellucida of human frozen thawed embryos: a new method of assisted hatching

OBJECTIVEnTo determine whether a new assisted hatching (AH) method increases the implantation and clinical pregnancy rates of frozen-thawed day-3 (D3) embryos.nnnDESIGNnProspective study.nnnSETTINGnA university hospital in vitro fertilization (IVF) program.nnnPATIENT(S)nPatients who had their first IVF/intracytoplasmic sperm injection (ICSI) cycles between June 1, 2006, and December 31, 2008, with fresh IVF-embryo transfer failures or without fresh embryo transfer.nnnINTERVENTION(S)nThe couples were randomized into thawed embryo transfer after AH versus no AH. In the AH group, the zona pellucida (ZP) of D3 frozen-thawed embryos was expanded by injected hydrostatic pressure after thawing. In the control group, embryos were pierced by ICSI needles without expanding the ZP.nnnMAIN OUTCOME MEASURE(S)nClinical pregnancy and implantation rates.nnnRESULT(S)nThe morphologic features of the blastomeres were carefully monitored and recorded. In the AH group, 244 embryos were thawed, and 178 (73.0%) survived; in the control group, 259 embryos were thawed, and 190 (73.4%) survived. Despite the transfer of a similar number of embryos, the AH group resulted in statistically significantly higher implantation and clinical pregnancy rates compared with the no AH group.nnnCONCLUSION(S)nMechanically expanding the ZP of frozen-thawed D3 embryos with injected hydrostatic pressure after thawing increases the implantation rate compared with control embryos.

Magnolol Inhibits LPS-Induced Inflammatory Response in Uterine Epithelial Cells

Endometritis is an inflammation of the uterine lining that is commonly initiated at parturition. The uterine epithelial cells play an important role in defending against invading pathogens. Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been shown to have anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effect of magnolol in modifying lipopolysaccharide (LPS)-induced signal pathways in mouse uterine epithelial cells. We found that magnolol inhibited TNF-α and IL-6 production in LPS-stimulated mouse uterine epithelial cells. We also found that magnolol inhibited LPS-induced NF-κB activation, IκBα degradation, phosphorylation of ERK, JNK, and P38. Furthermore, magnolol could significantly inhibit the expression of TLR4 stimulating by LPS. These results suggest that magnolol exerts an anti-inflammatory property by downregulating the expression of TLR4 upregulated by LPS, thereby attenuating TLR4-mediated NF-κB and MAPK signaling and the release of pro-inflammatory cytokines. These findings suggest that magnolol may be a therapeutic agent against endometritis.

Day-2 and day-3 sequential transfer improves pregnancy rate in patients with repeated IVF-embryo transfer failure: a retrospective case-control study

The purpose of this study was to evaluate the effect of sequential embryo transfer in patients with repeated IVF failure. A retrospective matched case-control study was conducted and the outcomes of 213 patients with a history of repeated IVF-embryo transfer failure were analysed, of which 33 women underwent sequential embryo transfer on day 2 and day 3 (D2/D3 group), 66 women on day 3 and day 5 (D3/D5 group), 85 women underwent day-3 embryo transfer only (D3 control group) and 29 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction centre of the Sixth Affiliated Hospital of Sun Yat-sen University from August 2010 to December 2011. The results showed that the clinical pregnancy rate of the D2/D3 group was higher than that of the D3 group (48.5% versus 22.4%, P=0.006) while the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (50.9% versus 45.8%). Day-2 and day-3 sequential embryo transfer may improve the clinical outcomes for patients with repeated IVF-embryo transfer failures. The purpose of this study was to evaluate the effect of sequential embryo transfer in patients with repeated IVF failure. A retrospective matched case-control study was conducted and the outcomes of 213 patients with a history of repeated IVF-embryo transfer failure were analysed, of which 33 women underwent sequential embryo transfer on day 2 and day 3 (D2/D3 group), 66 women on day 3 and day 5 (D3/D5 group), 85 women underwent day-3 embryo transfer only (D3 control group) and 29 women underwent day-5 embryo transfer only (D5 control group) in the assisted reproduction centre of the Sixth Affiliated Hospital of Sun Yat-sen University from August 2010 to December 2011. The results showed that the clinical pregnancy rate of the D2/D3 group was higher than that of the D3 group (48.5% versus 22.4%, P=0.006) while the clinical pregnancy rates of the D3/D5 and D5 groups were not significantly different (50.9% versus 45.8%). Day-2 and day-3 sequential embryo transfer may improve the clinical outcomes for patients with repeated IVF-embryo transfer failures.

Inhibitory effects of controlled ovarian stimulation on the expression of GDF9 and BMP15 in oocytes from women with PCOS.

PurposeTo explore the effects of controlled ovarian stimulation (COS) on the expression of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) in oocytes and granulosa cells from patients with or without polycystic ovary syndrome (PCOS).MethodsThis case–control study was conducted in the university affiliated hospital. The study comprised four groups of patients: eighteen PCOS patients with COS (stimulated-PCOS) and twenty-two PCOS patients without COS (unstimulated-PCOS), twenty-nine normal ovulatory women with COS (stimulated-control) and twenty-eight normal ovulatory women without COS (unstimulated-control). The oocytes and granulosa cells were collected and the abundance of GDF9 and BMP15 mRNA in the cells were detected by nested quantitative real-time PCR.ResultsThe abundance of GDF9 and BMP15 mRNA was significantly higher both in oocytes (Pu2009<u20090.01, Pu2009<u20090.001, respectively) and GCs (Pu2009<u20090.01, Pu2009<u20090.05, respectively) from stimulated-control group than in unstimulated-control group. However, there was no significant difference for GDF9 or BMP15 mRNA in oocytes from stimulated-PCOS goup compared with unstimulated-PCOS group (Pu2009>u20090.05, Pu2009>u20090.05, respectively). The abundance of GDF9 mRNA was significantly lower (Pu2009<u20090.01) while the abundance of BMP15 mRNA was significantly higher (Pu2009<u20090.001) in GCs from stimulated-PCOS group than in unstimulated-PCOS group.ConclusionsThe controlled ovarian stimulation can promote the expression of GDF9 and BMP15 both in oocytes and GCs from normal ovulatory women. However, the stimulating effects may be inhibited in oocytes from PCOS patients, which subsequently impair cytoplasm maturation and lead to poor oocyte quality.

Serum estradiol level change after human chorionic gonadotropin administration had no correlation with live birth rate in IVF cycles

OBJECTIVEnTo investigate the correlation between the estradiol (E2) level change after hCG administration and the live birth rate in GnRH agonist long or short protocols, and to explore the possible factors related to E2 dynamics after hCG administration during controlled ovarian hyperstimulation (COH).nnnSTUDY DESIGNnA retrospective analysis was performed on 2868 patients who received IVF/intracytoplasmic sperm injection (ICSI) treatment with GnRH agonist long or short protocol. The patients were divided into three groups according to their serum E2 changes after hCG administration, and the live birth rates were compared among groups. The area under the receiver operating characteristic (ROC) curve was calculated to assess the predictive value of E2 change for the probability of live birth. Logistic regression analysis was also applied to exclude interference from various confounding factors. Finally, multivariate regression analysis was conducted to assess factors related to the E2 change after hCG administration.nnnRESULTSnNo significant difference was observed in live birth rates (4.26%, 36.38% or 30.81% in long protocol (P=0.697); 25.81%, 26.71% or 30.81% in short protocol (P=0.697)) among patients with increasing, plateauing or decreasing E2 responses after hCG administration. The area under the ROC curve for the E2 change in prediction of live birth rate was 0.506 in long protocol, or 0.524 in short protocol. Logistic regression analysis showed that the serum E2 change after hCG administration had no correlation with live birth rate. Multivariate regression analysis showed that the percentage of mature follicles (larger than 14mm) and the duration of stimulation negatively correlated with the E2 change after hCG administration.nnnCONCLUSIONSnIn GnRH agonist cycles, the serum E2 change after hCG administration had no correlation with live birth rate in fresh embryo transfer cycles, and this change negatively correlated with the percentage of mature follicles on the day of hCG administration.