Yijuan Sun

Long-term pituitary downregulation before frozen embryo transfer could improve pregnancy outcomes in women with adenomyosis

Abstract Some studies have shown that long-term gonadotropin-releasing hormone (GnRH) agonist administration before in vitro fertilization/intracytoplasmic sperm in infertile women with endometriosis or adenomyosis significantly increases the chances of pregnancy. We were interested in whether long-term GnRH agonist pretreatment could improve pregnancy outcomes in adenomyosis patients undergoing frozen embryo transfer (FET) after preparation of the endometrium with hormone replacement therapy (HRT). Totally, 339 patients with adenomyosis were included in this retrospective study, 194 received long-term GnRH agonist plus HRT (down-regulation + HRT) and 145 received HRT. There were no differences between the groups in characteristic such as age, body mass index, duration or cause of infertility, serum CA-125 level and basal hormone levels. On the day of progesterone administration, mean endometrial thickness and serum progesterone level were significantly greater in HRT patients. Mean score and number of embryos transferred showed no differences. In down regulation + HRT group, clinical pregnancy, implantation and ongoing pregnancy rates were 51.35%, 32.56% and 48.91%, respectively, significantly higher than that of HRT group (24.83%, 16.07% and 21.38%, respectively). So, we concluded that in FET, long-term GnRH agonist pretreatment significantly improved pregnancy outcomes in patients with adenomyosis.

Associations between insulin resistance, free fatty acids, and oocyte quality in polycystic ovary syndrome during in vitro fertilization.

Context: Both polycystic ovary syndrome (PCOS) and obesity are associated with specific reproductive health complications, including lower oocyte quality and clinical pregnancy rates in assisted conception cycles, which may be a result of metabolism-induced changes in the oocyte through the microenvironment of follicular fluid. Free fatty acids (FFAs) are important biomedical indicators of abnormal lipid metabolism and have pronounced effects on cells, leading to changes in metabolism, cell growth, and differentiation Objective: Our objective was to determine the effect of FFA metabolism in plasma and follicular fluid on oocyte quality in the women with PCOS undergoing in vitro fertilization. Design and Setting: Ninety-three women undergoing in vitro fertilization treatment, including 55 with PCOS and 38 age-matched controls, were recruited. PCOS patients were divided into obese and nonobese subgroups on the basis of their body mass index. Main Outcome Measures: Embryo quality was morphologically assessed, and serum sex hormone and insulin levels were measured. FFAs in plasma and follicular fluid were measured using gas chromatography-mass spectrometry. Results: PCOS was found to be associated with significantly higher LH/FSH, total T, free androgen index (FAI), and lower SHBG levels, independent of obesity(P < .05). Obese women with PCOS had a significantly higher total T level, FAI, fasting insulin, insulin resistance index as determined by homeostasis model assessment for insulin resistance, and lower SHBG levels than the nonobese women with PCOS (P < .05). The embryo fragmentation score was significantly positively correlated with the oleic acid concentration in all PCOS patients (r = 0.22, P = .04, for nonobese patients and r = 0.25, P = .03, for obese patients). Conclusions: Our findings clearly demonstrated that PCOS is associated with significantly higher FAI and insulin resistance levels and decreased plasma SHBG levels, independent of body mass index. Obese PCOS patients had higher palmitoleic acid and oleic acid levels in both the plasma and follicular fluid than did the control subject and nonobese PCOS patients. Our results indicated that developmental competence is associated with oleic and stearic acid concentrations, which may contribute to the poor pregnancy outcomes in patients with PCOS.

Sperm chromatin structure assay results after swim-up are related only to embryo quality but not to fertilization and pregnancy rates following IVF

The aim of this study was to investigate whether the sperm chromatin structure assay (SCSA) results after swim-up are related to fertilization rates, embryo quality and pregnancy rates following in vitro fertilization (IVF). A total of 223 couples undergoing IVF in our hospital from October 2008 to September 2009 were included in this study. Data on the IVF process and sperm chromatin structure assay results were collected. Fertilization rate, embryo quality and IVF success rates of different DNA fragmentation index (DFI) subgroups and high DNA stainability (HDS) subgroups were compared. There were no significant differences in fertilization rate, clinical pregnancy or delivery rates between the DFI and HDS subgroups. However, the group with abnormal DFI had a lower good embryo rate. So, we concluded that the SCSA variables, either DFI or HDS after swim-up preparation, were not valuable in predicting fertilization failure or pregnancy rate, but an abnormal DFI meant a lower good embryo rate following IVF.

Dynamic changes of histone H3 trimethylated at positions K4 and K27 in human oocytes and preimplantation embryos

OBJECTIVE To investigate the distribution patterns of H3K4me3 and H3K27me3 in human oocytes and preimplantation embryos. DESIGN Experimental study. SETTING University reproductive medical center. PATIENT(S) Patients undergoing IVF cycles. INTERVENTION(S) Oocytes and embryos were collected from patients undergoing IVF cycles. MAIN OUTCOME MEASURE(S) The distribution patterns of H3K4me3 and H3K27me3 in oocytes and embryos were analyzed by indirect immunofluorescent staining and scanning confocal microscopy. RESULT(S) H3K4me3 and H3K27me3 signals were detectable at each stage of oocyte and embryonic development. However, only one of the pronuclei showed signal for H3K27me3 in each of the zygotes, whereas H3K4me3 staining was always uniform in all zygotes. The level of H3K4me3 decreased steadily from germinal vesicle to metaphase II stage, obviously increased from zygote stage to four-cell stage, and reached the lowest at eight-cell stage. A sharp increase was then observed at blastocyst stage. The level of H3K27me3 slightly changed from germinal vesicle stage to zygote stage, then decreased steadily and reached the lowest at eight-cell stage, followed by a significant increase at blastocyst stage. CONCLUSION(S) The levels of H3K4me3 and H3K27me3 show dynamic changes during human oocyte maturation and preimplantation embryonic development. Asymmetric distribution of H3K27me3 exists in human zygote pronuclei, whereas H3K4me3 is always uniform in all of the pronuclei.

The effect of human cumulus cells on the maturation and developmental potential of immature oocytes in ICSI cycles

PurposeTo investigate the effect of human cumulus cells on the maturation and developmental potential of immature oocytes in ICSI cycles.MethodsImmature oocytes were randomly divided into two groups: the cumulus-denuded oocyte group (group A) and the cumulus-intact oocyte group (group B). Only oocytes that reached metaphase II (MII) stage after in vitro maturation were used in the ICSI procedure. In vivo mature sibling MII oocytes served as the control group. Maturation rate, fertilization rate, embryo quality and developmental potential were examined.ResultsThere was no significant difference in maturation rate between group A (68.16%) and group B (70.49%; P > 0.05). The total fertilization rate among the three groups was comparable (P > 0.05), while the zygotes with two pronuclei in group A (74.59%) or group B (75.97%) were significantly lower than those in control group (84.29%; P < 0.05). The available embryo rate in group A (11.49%) was markedly lower than that in group B (27.66%; P < 0.05), and both of them were significantly lower than that in control group (62.38%; P < 0.05). The proportion of ≥6-cell embryos in group B (45.74%) was notably higher than in group A (26.44%; P < 0.05), and both were markedly lower than in control group (65.92%; P < 0.05). The proportion of embryos with <10% fragmentation in group A (13.79%) was significantly lower than in group B (29.79%; P < 0.05), and both were notably lower than in control group (42.98%; P < 0.05).ConclusionsThe presence of cumulus cells surrounding the immature oocytes during IVM before ICSI had no influence on nuclear maturation and fertilization, but leads to better subsequent embryonic development. This is perhaps mediated by an improvement in cytoplasmic maturation.

Estrogen level monitoring in artificial frozen-thawed embryo transfer cycles using step-up regime without pituitary suppression: is it necessary?

Background To discuss the meaning of serum oestradiol monitoring in frozen embryo transfer cycle using hormone replacement without pretreatment with gonadotropin hormone (GnRH) agonist. Methods The data from two hundred twelve women undergoing two hundred seventy-four frozen-thawed embryo transfer (FET) cycles was included in this retrospective cohort study. They were detected of serum oestradiol levels and endometrium thicknesses during hormone supplement FET cycles and compared their pregnancy outcomes according to their oestradiol level on progesterone initiation day. Results Patients with different levels of serum oestradiol (percentile 0–25th, 25th–75th and 75th–100th) on progesterone initiation day yielded the endometrium thickness of 9.3 ± 0.12, 8.9 ± 0.07 and 9.1 ± 0.11 mm(P > 0.05) and the pregnancy rate of 32.2%, 38.4% and 36.3% (P > 0.05) respectively. Conclusion The serum estradiol level did not predict pregnancy success in hormone replacement FET cycles, suggesting that oestradiol monitoring in this method of endometrial preparation is unnecessary.

Progesterone levels on oocyte retrieval day can predict the quantity of viable embryos but not pregnancy outcome of intracytoplasmic sperm injection.

The present study aimed to determine whether serum progesterone (P) concentration on the day of oocyte retrieval (OR) affects the quantity of viable embryos and impacts the outcome of intracytoplasmic sperm injection (ICSI). A total of 289 women who underwent ICSI cycles after controlled ovarian hyperstimulation were divided in two groups based on P level (<11.7 and ≥ 11.7 ng/ml) on OR day. Subjects did not differ significantly with respect to age, basal follicle-stimulating hormone levels, body mass index, or estradiol levels on day of administration of human chorionic gonadotropin or OR day. Women with ICSI cycles that had high P levels tended to have more retrieved oocytes, zygotes and embryos than women with lower levels, but the differences did not approach significance. However, the former group with higher P levels did have a significantly greater number of viable embryos (p = 0.003). Finally, the two groups did not show differences in pregnancy outcome in a new ICSI cycle. The study suggests that serum P levels on OR day are related to the quality of viable embryos but not to pregnancy outcome in fresh ICSI cycles.

Blastocyst Formation and Chromosome Statuses of Reconstructed Embryos Derived from Interspecies Somatic Cell Nuclear Transfer iSCNT

Objective To analyze the blastocyst formation and chromosome statuses of reconstructed embryos derived from human-goat interspecies somatic cell nuclear transfer (iSCNT), exploring the development retardant factors. Methods Human specific point probes cep2, cep6, tel2 and 13q14.2, 21q22.13 combining fluorescence in-situ hybridization (FISH) technology were used to test trophectoderm cells of blastocyst and blastomeres of development arrest nuclear transfer (NT) embryos. Results A total of 209 reconstructed embryos were recovered, and the rate of blastocyst formation was 3.8% (8/209). FISH signals showed that chromosomal abnormalities were present in 2 blastocysts (2/8) and 146 development arrest embryos (146/201). Conclusions The rate of blastocyst formation is low, and reconstituted embryos of development arrest showed extensive chromosome abnormalities, suggesting that a chromosomal mechanism may underlie their developmental arrest.

In-vitro Developmental Potential of Single Blastomeres Derived from Day 3 Discarded Human Embryos

Objective To investigate whether isolated blastomeres of discarded human embryos could develop into blastocysts cultured in vitro without zona pellucida. Methods Total discarded 60 embryos, which were not suitable for transplanting or freezing, were collected from 21 patients. Of 60 embryos, 10, 8, 24, 12, and 4 embryos were at 2-, 3-, 4-, 5- and 6-cell stage, respectively. These embryos were split by 0.5% protease combined with mechanical method. The resulting single blastomere was cultured individually, evaluated daily and counted blastocyst development. Pluripotency of inner cell mass (ICM) of the blastocyst was analyzed by the expression of alkaline phosphatase(AKP). Results A total of 229 single blastomeres were isolated from 60 embryos. Defining the day when the embryos were split as the first day (d 1). The majority of the blastomere-derived embryos followed the normal pattern of development with compaction on d 3 and cavitationon d 4 and developed into small blastocysts on d 5. Rates of division, compaction, cavity and expansion of single blastomeres from 4-cell embryos were higher than those in other groups (P Conclusion Some of the blastomeres from discarded human embryo are flexible and able to develop into blastocysts, the potential was related to their donor embryos closely. They seem to follow development pattern of their donor embryos. The blastomere-derived blastocysts have smaller size and fewer cells compared with regular in vitro cultured human embryos. However, AKP expression showed ICM cells with pluripotency. We believe that the value of single blastomere of discarded embryos will be further confirmed in the future.