The effect of previous induced abortion history on the assisted reproduction outcomes.

PURPOSE: To study whether the history of induced abortion has an effect on the assisted reproduction outcomes in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: 3045 patients who underwent IVF-ET in the Department of Human Reproductive Center of Renmin Hospital from January 2017 to June 2021. They were divided into two groups according to whether there was a history of induced abortion in the past, and the outcomes were compared between the two groups. RESULTS: The clinical pregnancy rate in the group with induced abortion history was lower than that in the group without induced abortion history (63.1% vs 67.1%), but the difference was not statistically significant (P = 0.059). The spontaneous abortion rate in the group with induced abortion history was higher than that in the group without induced abortion history (14.9% vs 11.2%) (P = 0.044). The live birth rate in the group with induced abortion history was lower than that in the group without induced abortion history (52.8% vs 59.0%) (P = 0.006). Stepwise logistic regression analysis showed that endometrial thickness (OR = 0.928, 95% CI = 0.886 ~ 0.972, P = 0.002) and live birth rate (OR = 0.682, 95% CI = 0.495 ~ 0.939, P = 0.019) were negatively correlated with induced abortion history. The rate of spontaneous abortion (OR = 1.452, 95% CI = 1.042 ~ 2.024, P = 0.028) was positively correlated with the history of induced abortion. CONCLUSIONS: The previous history of induced abortion is related to the outcomes of IVF /ICSI-ET, the endometrial thickness on HCG trigger day decreased, the risk of spontaneous abortion increased and the live birth rate decreased in patients with induced abortion history when undergoing IVF/ICSI-ET.

Comparison the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in patients with normal ovarian reserve function.

OBJECTIVE: To compare the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in infertility patients with normal ovarian reserve function undergoing invitro fertilization and embryo transfer. METHODS: A retrospective cohort study was conducted to analyze the clinical data of 2013 cycles of patients with normal ovarian reserve function who underwent invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in the Department of Human Reproductive Center, Renmin Hospital, Hubei University of Medicine from January 2018 and June 2020. The PPOS protocol group included 679 cycles and GnRH-along protocol group included 1334 cycles, the pregnancy outcomes were compared between the two groups. RESULTS: The duration of Gn used and total Gn used dosage in the PPOS protocol group were less than those in the GnRH-along protocol group (Duration of Gn used: 10.05 ± 1.48 vs 11.90 ± 1.85 d, p < 0.001; Total Gn used dosage: 1944.49 ± 533.61 vs 2661.34 ± 987.97 IU, p < 0.001); The LH levels were significantly higher on HCG trigger day in PPOS protocol compared to GnRH-a long protocol (2.8 ± 1 ± 1.07 vs 1.01 ± 0.62 IU/L, p < 0.001), the E2 levels on HCG trigger day in PPOS protocol group was lower than that in the GnRH-a long protocol group (2135.92 ± 1387.00 vs 2417.01 ± 1010.70 pg/mL, p < 0. 001). The number of oocytes retrieved in the PPOS protocol group was lower than that in the GnRH-along protocol group (8.03 ± 2.86 vs 9.47 ± 2.64, p < 0.001). No significant differences were found in pregnancy outcome including clinical pregnancy rate, early miscarriage rate and ectopic pregnancy rate between the two group (p > 0.05); In addition, no severe OHSS occurred in the PPOS protocol group during ovulation induction, while 11 patients of severe ovarian hyperstimulation syndrome (OHSS) occurred in GnRH-a long protocol group (p < 0.001). CONCLUSION: The clinical efficacy of PPOS protocol combining embryo cryopreservation is comparable to that of GnRH-a long protocol in patients with normal ovarian reserve function, and the PPOS protocol is able to reduce the incidence of severe OHSS significantly.

The serum oestradiol/progesterone ratio on the day of OPU + 7, but not the day of OPU + 5, affects the rates of live birth in fresh blastocyst embryo transfer cycles.

BACKGROUND: In an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes. METHODS: This is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E2 and P and the E2/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E2/P ratio tertiles on OPU + 7: the low group (1.3-15.7 pg/ng), middle group (15.7-28.8 pg/ng), and high group (28.8-487.2 pg/ng). The threshold effect of the E2/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve. RESULTS: The level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E2/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E2/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01-1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00-1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00-1.01; P < 0.001), and a nonlinear correlation was observed between the E2/P ratio and LBR on OPU + 7. CONCLUSIONS: A higher E2/P ratio is associated with a higher LBR, but the E2/P ratio should be maintained within a suitable range.

Effect of TSH on oocyte maturation of PCOS patients with normal thyroid function in IVF.

BACKGROUND: The serum TSH level of PCOS patients was higher than that of the general female population. For patients with thyroid dysfunction, the abnormal TSH level is negatively related to the outcomes of assisted reproductive technology, but for PCOS patients with normal thyroid function, the effect of TSH level on outcomes of in vitro fertilization has not been reported. In this study, PCOS patients with normal thyroid function were included in this study to evaluate the effect of TSH on the outcomes of IVF-ET. METHODS: A retrospective cohort study was conducted to analyze the clinical data of 3190 patients who underwent IVF-ET in the Department of Human Reproductive Center of Renmin Hospital Hubei University of Medicine from January 2017 to July 2021, including 594 PCOS patients and 2595 non PCOS patients. The IVF-ET outcomes between the two groups were compared; Multi-factor linear regression analysis was used to analyze the correlation between the related variables and the oocyte maturation of PCOS patients; The ROC curve of the effect of TSH on oocyte maturation in PCOS patients was drawn. The PCOS patients were divided into TSH < 2.98 group (n = 454) and TSH ≥ 2.98 group (n = 141) according to ROC threshold TSH 2.98, and the outcomes were compared. RESULTS: TSH level in PCOS group was significantly higher than that in non-PCOS group (2.42 ± 0.86 vs 2.00 ± 0.89 UU / ml, P < 0.01), and the oocyte maturation rate and 2PN fertilization rate in PCOS group were lower than those in non-PCOS group (90.9% vs 92.4%, P = 0.02) (84.57% vs 86.77%, P = 0.02). There was no significant difference in cleavage rate and high-quality embryo rate between the two groups (P > 0.05); There was no difference in clinical pregnancy rate, abortion rate, ectopic pregnancy rate and live birth rate between the two groups (P > 0.05). Multi-factor linear regression analysis showed that TSH was negatively correlated with oocyte maturation in PCOS patients [ß = -0.124, P = 0.013,95%CI (-0.027 ~ -0.003)]; The oocyte maturation rate in TSH < 2.98 group was significantly higher than that in TSH ≥ 2.98 group (91.7% vs 88.2%, P = 0.001). CONCLUSION: The TSH level of PCOS patients with normal thyroid function is higher than that of normal people, and it is negatively correlated with the oocyte maturation in in-vitro fertilization. The ROC curve showed that when TSH > 2.98uIU/ml, the possibility of immature oocytes was higher (specificity 28.9%, sensitivity 83.0%).

The follicular-phase depot GnRH agonist protocol results in a higher live birth rate without discernible differences in luteal function and child health versus the daily mid-luteal GnRH agonist protocol: a single-centre, retrospective, propensity score matched cohort study.

BACKGROUND: The gonadotropin-releasing hormone agonist (GnRH-a) has been used in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles for a long time. This paper evaluates the efficacy and safety of two commonly used protocols (follicular-phase depot GnRH-a protocol and daily mid-luteal long GnRH-a protocol) in normal responders undergoing IVF/ICSI using propensity score matching (PSM) analysis. METHODS: A total of 6,816 infertile women treated within the period from January 2016 to September 2020 were stratified into cohorts. A total of 2,851 patients received the long-acting group (depot GnRH-a protocol), and 1,193 used the short-acting group (long GnRH-a protocol) after the data-selection process. PSM was utilized for sampling by up to 1:1 nearest neighbour matching to adjust the numerical difference and balance the confounders between groups. The primary outcome was the live birth rate (LBR). Multivariable logistic analysis was used to evaluate the difference between these two protocols in relation to the LBR. RESULT(S): In this study, 1:1 propensity score matching was performed to create a perfect match of 964 patients in each group. After matching, the blastocyst formation rates, oestradiol (E2) value on Day hCG + 9, progesterone (P) value on Day hCG + 9, implantation rates, clinical pregnancy rates, and LBR were more favourable in the depot GnRH-a protocol than in the long GnRH-a protocol (P < 0.05). However, the moderate or severe OHSS rates were higher in the depot group than in the long group (P < 0.001). There were no significant differences in endometrial thickness, luteal support medication, early pregnancy loss rates, mid- and late-term pregnancy loss rates, or foetal malformation rates between the two protocols. CONCLUSION(S): Compared with the daily short-acting GnRH agonist protocol, the follicular-phase depot GnRH-a protocol might improve LBRs in normogonadotropic women without discernible differences in luteal function and child health.

In Vitro Study on the Regulation of Annexin IV and VEGF by hCG in the Human Endometrium.

OBJECTIVE: Whether changes in vascular endothelial growth factor (VEGF) and annexin IV during implantation are regulated through the LH/hCG-R needs further research. To investigate the mechanism of hCG on the expression of annexin IV and VEGF in human endometrial cells. METHODS: Endometrial cells were isolated and identified from human specimens. The proportion of glandular and epithelial cells was analyzed. Annexin IV and VEGF were analyzed by qRT-PCR (mRNA), western blot (proteins), and immunohistochemistry (proteins). Protein location was identified by immunohistochemistry. The cells were cultured with hCG, hCG/PD98059 (a MAPK inhibitor), or no treatment (control). RESULTS: The proportions between the glandular epithelial cells and stromal cells at inoculation and when adding hCG were 25.8 ± 0.2% and 27.8 ± 0.04%, respectively (P > 0.05). LH/hCG-R, annexin IV, and VEGF were found in the cytoplasm of endometrial cells. After 2, 6, 12, and 24 h of hCG treatment, compared with 1 h, VEGF mRNA was increased by 1.25-fold, 3.19-fold, 4.21-fold, and 4.86-fold and annexin IV by 2.23-fold, 3.37-fold, 5.14-fold, and 5.02-fold. Compared with the control group, annexin IV mRNA and protein were increased in the hCG and hCG/PD98059 groups (mRNA/protein: 1.99-fold/1.80-fold and 2.33-fold/1.93-fold, P < 0.05). Compared with the control group, VEGF mRNA and protein were increased in the hCG group (mRNA/protein: 2.30-fold/1.86-fold), but not in the hCG/PD98059 group. CONCLUSION: hCG could upregulate the mRNA and protein expression of annexin IV and VEGF. The upregulation of annexin IV by hCG could not be inhibited by PD98059, but the upregulation of VEGF by hCG could.

Genetic polymorphisms of glutathione S-transferase M1, T1, and P1, and the assessment of oxidative damage in infertile men with varicoceles from northwestern China.

Our objective was to investigate the genetic polymorphisms of the glutathione S-transferase M1, T1, and P1 genes (GSTM1, GSTT1, and GSTP1) and to assess the oxidative damage in infertile men with varicoceles from northwestern China. A total of 65 infertile men with varicoceles and 30 controls were included in the study. Multiplex polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analyses were used to identify the genotypes. Sperm DNA damage was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL). The levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) were measured by high-performance liquid chromatography with electrochemical detection. The activities of malondialdehyde (MDA) and nitric oxide (NO), and the total antioxidant capacity (TAC) were detected by spectroscopic analysis, and sperm characteristics were measured using computer-assisted semen analysis. The frequencies of the GSTM1, GSTT1, and GSTP1 genotypes were not significantly different between the control and patient groups (P > .05). The percentage of TUNEL-positive sperm and the levels of 8-OH-dG, MDA, and NO were higher but the sperm concentration and motility and the TAC were lower in the patients with the GSTM1, GSTT1, and GSTM1/T1 null genotypes than those in the patients with the GSTM1, GSTT1, and GSTM1/T1 present genotypes (P < .05). However, no significant differences were observed between the GSTP1 A/A and A/G+G/G genotypes (P > .05). Our results suggest that the GSTM1 and GSTT1 null genotypes may predispose sperm to increased oxidative damage in infertile men with varicoceles; however, GSTP1 allelic variation was not significantly different between the patient and control groups in this study.