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"Shi, Juanzi"
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Mutations in TUBB8 and Human Oocyte Meiotic Arrest
2016
Mutations in a tubulin gene caused infertility due to oocyte arrest in about a third of families tested. The investigators found that the mutant tubulins wreak havoc on microtubule assembly in the oocyte.
Successful human reproduction starts when a metaphase II oocyte fuses with a sperm cell to form a fertilized egg. In human oocytes, the meiotic cell cycle begins in the neonatal ovary and pauses at prophase I of meiosis until puberty, when a surge of luteinizing hormone stimulates the resumption of meiosis and ovulation. This leads to progression of the oocyte from metaphase I to metaphase II.
1
–
3
Oocytes arrested in prophase I have an intact nucleus, termed the germinal vesicle, whereas oocytes that have resumed meiosis are characterized by the breakdown of the germinal vesicle. After germinal-vesicle breakdown, metaphase I . . .
Journal Article
High proportion of zygotes with multiple pronuclei increase the embryo multinucleation rate during conventional IVF
2024
The incidence of multiple pronuclei (≥ 3PN) zygotes and blastomere multinucleation was found to be elevated in the presence of increased estradiol (E
2
) levels and a greater number of retrieved oocytes. This implies a potential link between the incidence of multinucleation at the two-cell stage (MN2) and a higher proportion of ≥ 3PN zygotes. We aimed to investigate the effect of high proportion of ≥ 3PN zygotes on MN2 incidence during conventional in vitro fertilization (C-IVF) by using time-lapse monitoring. This study included 1195 patients from January 2020 to December 2022. The patients were categorized into three groups: Group 1 comprised patients with no ≥ 3PN zygotes (
n
= 422), Group 2 included those with 0–25% ≥3PN zygotes (
n
= 617), and Group 3 consisted of patients with more than 25% ≥3PN zygotes (
n
= 156). The MN2 rate, types of MN2 and clinical outcomes were compared among the three groups. Our data indicated that the MN2 rate was significantly lower in groups 1 and 2 compared to group 3 (18.33 versus 25.62%;
p
< 0.001 and 19.45 versus 25.62%;
p
< 0.001). The MN2 embryos exhibited similar rates of high-quality embryos (42.27 versus 43.50 versus 40.67%;
p
= 0.401) and available embryos (84.96 versus 84.04 versus 83.21%;
p
= 0.460) rates among the three groups. There were no significant differences in the proportion of MN2 with different types among the three groups (
p
> 0.05). The embryos displaying binucleated at the two-cell stage in one blastomere (2BI1) and true multinucleated at the two-cell stage in one blastomere (2MULTI1) showed significantly higher blastocyst formation rates compared to embryos exhibiting true multinucleated at the two-cell stage in both blastomeres (2MULTI2) (59.50 versus 45.40%;
p
< 0.001 and 59.40 versus 45.40%;
p
< 0.001). In conclusion, the occurrence of MN2 events might be associated with high proportion of ≥ 3PN zygotes incidence. The types of MN2 had significant reference value when selecting embryos for transfer during the cleavage stage.
Journal Article
Fresh versus Frozen Embryos for Infertility in the Polycystic Ovary Syndrome
2016
In this randomized trial involving infertile women with the polycystic ovary syndrome, frozen-embryo transfer was associated with a higher rate of live birth than was fresh-embryo transfer after the first transfer.
In vitro fertilization (IVF) is widely performed as an infertility treatment and has resulted in the births of more than 5 million infants worldwide.
1
However, there are concerns about the safety of the procedures for women and for their infants.
1
,
2
The ovarian hyperstimulation syndrome (which is caused by ovarian enlargement, an increase in vascular permeability and abdominal ascites, and intravascular hemoconcentration) is a potentially life-threatening complication of ovarian stimulation.
3
Pregnancies conceived by means of IVF are associated with greater risks of maternal and neonatal complications, including preeclampsia, preterm delivery, low birth weight, and congenital anomalies, than are spontaneous pregnancies. . . .
Journal Article
Impact of blastocyst biopsy for preimplantation genetic testing on maternal and neonatal outcomes following single frozen embryo transfer cycles
2025
Background
Up to now, a number of studies have explored the influence of blastocyst biopsy on maternal and neonatal outcomes, and the results have been somewhat inconsistent. Therefore, the aim of this study was to investigate whether blastocyst biopsy is associated with an elevated risk of hypertensive disorders of pregnancy (HDP) and other adverse perinatal outcomes during frozen embryo transfer (FET) cycles in singleton live births resulting from intracytoplasmic sperm injection (ICSI) in women aged ≤ 35 years.
Methods
A total of 1,008 women were involved in this study from January 2020 to June 2022, who underwent ICSI cycles and received single FET, leading to the birth of a live singleton newborn. The study population were categorized into two groups: the preimplantation genetic testing (PGT) group, comprising 269 women whose blastocysts underwent trophectoderm biopsy, and the control group, consisting of 739 women whose blastocysts did not undergo biopsy. The primary outcome assessed in this study was HDP. Additionally, various relevant perinatal outcomes related to both maternal and neonatal health were also evaluated.
Results
In comparison to the control group, notable disparities were observed between the groups in relation to infertility duration, EMT, infertility type, infertility cause and endometrial preparation protocol (
P
< 0.05, for all). The percentage of female gender significantly increased in the PGT group in comparison with the control group (
P
< 0.05). However, the risk of HDP, other maternal and neonatal outcomes exhibited comparable results between the two groups (
P
> 0.05, for all). Moreover, univariate regression analyses further revealed that PGT had no influence on maternal and neonatal outcomes, except for gender (aOR 1.44; 95% CI, 1.03–2.01;
P
= 0.031).
Conclusions
In the short-term perspective, it could be inferred that blastocyst biopsy may not increase the risks associated with HDP or other unfavorable maternal and neonatal outcomes. However, despite the limited sample size, our findings may not be applicable to those aged 35 or over; therefore, larger cohort studies are imperative for the validation of our results.
Journal Article
Maternal age is associated with embryo splitting after single embryo transfer: a retrospective cohort study
2021
PurposeTo determine whether maternal age has an impact on monozygotic twinning (MZT) rates in women undergoing single embryo transfer (SET).MethodsThis is a retrospective cohort study analyzed for the incidence of MZT of all clinical pregnancies after a single embryo transfer was carried out between 2014 and 2018. The effect of different assisted reproductive technology (ART) parameters on the incidence of MZT was evaluated.ResultsThere were a total of 8459 cycles resulting in pregnancy during the study period. Of these pregnancies, 8236 were singletons and 223 were MZT. The preterm birth rate, miscarriage rate, and cesarean section rate were higher in MZT. Birth weight and gestational age at delivery were lower and smaller. In the univariate analysis, the risk of MZT was decreased with frozen embryo transfer (ET). A nonlinear relationship was observed between maternal age and MZT. A negative relationship between maternal age and MZT was observed in the patients’ age ≥ 36 years.ConclusionAdvanced maternal age was associated with a lower rate of MZT. A threshold female age of 36 years existed for lower MZT.
Journal Article
Pretreatment with a GnRH agonist and hormone replacement treatment protocol could not improve live birth rate for PCOS women undergoing frozen-thawed embryo transfer cycles
2021
Background
The ideal protocols of endometrial preparation for polycystic ovary syndrome (PCOS) patients are lacking and need further declaration. Our objective was to compare the clinical outcomes of frozen-thawed embryo transfer (FET) with and without pretreatment gonadotropin-releasing hormone agonist (GnRHa) in PCOS patients.
Methods
In this retrospective cohort study, we used propensity score matching (PSM) to compare the live birth rate between patients who underwent FET with hormone replacement treatment (HRT) and patients with GnRHa pretreatment (GnRHa + HRT). Patients using GnRHa + HRT (
n
= 514) were matched with 514 patients using HRT.
Results
The live birth rate was higher in the GnRHa + HRT group compared with the HRT group with no significant difference (60.12% vs 56.03%,
p
= 0.073). The clinical pregnancy rate (75.29% vs 70.62%), miscarriage rate (14.20% vs 13.81%) and ectopic pregnancy rate (0.39% vs 0.19%) were similar between the two groups. The preterm birth rate in GnRHa + HRT was higher than HRT (20.23% vs 13.04%). No difference was found in live birth between GnRHa +HRT and HRT before adjusting for covariates (crude OR 1.22, 95%CI, 0.99–1.51,
p
= 0.062) and after PSM (OR 1.47, 95%CI, 0.99–2.83,
p
= 0.068). In addition, there is a marginally difference after adjusting for covariates (aOR 1.56, 95%CI, 1.001–2.41,
p
= 0.048), this finding with
p
-value close to 0.05 represent insufficient empirical evidence. Similar results were obtained after propensity score matching in the entire cohort.
Conclusions
GnRHa pretreatment could not improve the live birth rate in women with PCOS.
Journal Article
Sex ratio imbalance following blastocyst transfer is associated with ICSI but not with IVF: an analysis of 14,892 single embryo transfer cycles
2022
Abstract PurposeAssisted reproductive technology (ART) has an impact on secondary sex ratio (SSR), which is seemed to be elevated after blastocyst transfer (BT) but decreased following ICSI procedure. We aim to assess whether the higher SSR associated with BT could be influenced by fertilization method used.MethodsAll consecutive IVF/ICSI cycles (fresh and frozen) involving single embryo transfer (SET) resulting in a live birth between 2015 and 2019 were retrospective analyzed. Logistic regression was used to model the effect on the SSR of maternal and specific ART characteristics.ResultsSix thousand nine hundred twenty-two women were included with the crude SSR of 54.8%. The impact of BT on SSR is influenced by the fertilization method used. After adjustment for potential confounders, the SSR in the ICSI BT group was significantly higher when compared to ICSI cleavage-stage embryo SET (aOR 1.24; 95% CI 1.10–1.40, P < 0.001). However, this effect was not detected among SBT with IVF treatment (aOR 1.04; 95% CI 0.97–1.12, P = 0.260). Assessing blastocyst morphological parameters, high trophectoderm quality was significantly associated with elevated SSR (aOR 1.76, 95% CI 1.34–2.31 [A vs. C], and aOR 1.28, 95% CI 1.14–1.44 [B vs. C]). No significant difference was shown in expansion, inner cell mass, or days of blastocyst formation between male and female blastocysts.ConclusionsThe impact of BT on SSR could be influenced by the fertilization method used. The higher SSR was observed after BT with ICSI procedures but not with IVF. Interpretation of the findings is limited by the potential for selection and confounding bias.
Journal Article
Double trouble? Impact of frozen embryo transfer on the monozygotic twinning rate: a retrospective cohort study from 8459 cycles
2020
PurposeTo compare monozygotic twinning (MZT) rates in patients undergoing fresh embryo transfer (ET) and frozen embryo transfer.MethodsAll clinical pregnancies after single ET carried out in our IVF center between 2014 and 2018 (n = 8459) were retrospectively analyzed for the incidence of MZT. MZT rate was compared in women who underwent fresh ET (n = 3876) and frozen ET (n = 4583).ResultsThere was a total of 120 MZT identified in the fresh ET group (3.10%) and 103 MZT in the frozen ET group (2.25%), which was significant (p = 0.015). In the univariate analysis, the risk of MZT was decreased with frozen embryo transfer (OR 0.72; 95% CI, 0.55–0.94, p = 0.016) and increased with mild stimulation protocol in the fresh cycle (OR 1.90; 95% CI, 1.04–3.45, p = 0.036). Multivariable logistic regression revealed that frozen embryo transfer was associated with a significant decrease risk of MZT (adjusted OR 0.66; 95% CI, 0.46–0.90, p = 0.011).ConclusionsFrozen ET is associated with a lower risk of MZT.
Journal Article
Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure
by
Zhang, Ni
,
Shi, Juanzi
,
Li, Na
in
Abortion, Habitual - pathology
,
Abortion, Habitual - physiopathology
,
Abortion, Habitual - therapy
2022
Background
To determine whether gonadotropin-releasing hormone (GnRH) agonist downregulation combined with hormone replacement therapy (HRT) can improve the reproductive outcomes in frozen–thawed embryo transfer cycles for older patients (aged 36–43 years) with idiopathic recurrent implantation failure (RIF).
Methods
This retrospective cohort study involved 549 older patients undergoing their third cleavage-stage embryo or blastocyst transfer over a 5-year period (January 2015–December 2020) at Northwest Women’s and Children’s Hospital after in vitro fertilization/intracytoplasmic sperm injection cycles. Patients with known endometriosis or adenomyosis were excluded from the study. The patients were divided into three groups according to the endometrial preparation protocol: the natural cycle (NC) group (
n
= 65), the HRT group (
n
= 194), and the GnRH agonist downregulation combined with HRT cycle (GnRH agonist–HRT) group (
n
= 290). The primary outcome was the live birth rate, and the secondary outcomes were the clinical pregnancy, miscarriage, and ongoing pregnancy rates.
Results
The live birth rate in the GnRH agonist–HRT group (36.55%) was higher than that in the HRT group (22.16%) and NC group (16.92%) (
P
< 0.0001). Similarly, a logistic regression model adjusting for potential confounders showed that the live birth rate was higher in the GnRH agonist–HRT group than in the HRT group (odds ratio, 0.594; 95% confidence interval, 0.381–0.926;
P
= 0.021) and NC group (odds ratio, 0.380; 95% confidence interval, 0.181–0.796;
P
= 0.010).
Conclusions
The GnRH agonist–HRT protocol improves the live birth rate in frozen–thawed embryo transfer cycles for patients of advanced reproductive age with RIF. We hypothesize that the GnRH agonist–HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity, leading to an improved live birth rate. These findings are also useful for further investigating the underlying mechanism of the GnRH agonist–HRT protocol in improving the reproductive outcomes for patients of advanced reproductive age with RIF.
Trial registration
This research protocol was approved by the hospital institutional ethics committee (No. 2021002).
Journal Article
Effect of early rescue ICSI in multiple cycles of couples with successful fertilization in the initial cycle of conventional IVF
2025
Background
Total fertilization failure (TFF) or near TFF may lead to cycle cancellation, which is a highly frustrating experience for patients, especially those who have undergone multiple attempts. Early rescue intracytoplasmic sperm injection (R-ICSI) has been shown to yield promising clinical results. In this research, we aimed to investigate whether embryo development and clinical outcomes would be affected in subsequent R-ICSI cycles for couples with successful fertilization in the initial cycle of conventional in vitro fertilization (C-IVF).
Methods
This retrospective cohort study was conducted from January 2014 to December 2023, including 72 couples who demonstrated normal or nearly normal fertilization potential (≥ 40% 2PN rate) in previous C-IVF cycles but subsequently underwent TFF or near TFF in repeated C-IVF cycles. Only the first embryo transfer was analyzed for comparison in each treatment cycle. A comparative analysis was performed between embryo development parameters and clinical outcomes following early R-ICSI versus previous C-IVF.
Results
Our data indicated that couples undergoing their first C-IVF cycle demonstrated a significantly higher early R-ICSI rate compared to those in their second or subsequent treatment cycles (4.00 versus 1.09%;
p
< 0.001 and 4.00 versus 0.68%;
p
< 0.001). For couples undergoing their second cycles, the 2PN rate following early R-ICSI was comparable to that achieved with previous C-IVF (55.42 versus 55.27%;
p
= 0.929). The D3 available embryo rate was significantly higher following early R-ICSI compared to conventional C-IVF (79.34 versus 68.71%;
p
= 0.002). Early R-ICSI demonstrated significantly superior clinical outcomes compared to previous C-IVF, with higher pregnancy (58.06 versus 24.13%;
p
< 0.001), clinical pregnancy (48.39 versus 20.69%;
p
= 0.002), ongoing pregnancy (38.71 versus 8.62%;
p
< 0.001), and live birth rates (38.71 versus 5.17%;
p
< 0.001). For couples undergoing their multiple cycles (≥ 3), early R-ICSI showed significantly lower 2PN (44.44 versus 62.18%;
p
= 0.006) and D3 available embryo (52.27 versus 70.10%;
p
= 0.040) rates compared to previous C-IVF. Early R-ICSI demonstrated no statistically significant differences in clinical outcomes compared to previous C-IVF, including pregnancy (44.44 versus 28.57%;
p
= 0.398), clinical pregnancy (44.44 versus 14.29%;
p
= 0.074), ongoing pregnancy (33.33 versus 9.52%;
p
= 0.109), and live birth (33.33 versus 9.52%;
p
= 0.109) rates.
Conclusion
For patients undergoing two or more IVF treatment cycles, fertilization failure is not a predictor of poor treatment outcomes and early R-ICSI can still lead to a favorable outcome.
Journal Article