Estradiol (E 2) Reduction Adversely Affect the Embryo Quality and Clinical Outcomes of In Vitro Fertilization and Embryo transfer (IVF-ET).

Objective: The purpose of this study was to explore the influence of decreased serum estradiol (E 2) levels during controlled ovarian hyperstimulation (COH) on in vitro fertilization and embryo transfer (IVF). Methods: The clinical data of 300 IVF-ET cycles with patients were analyzed retrospectively. According to the presence of falling E 2 level during the COH, we divided all subjects into two groups: the E 2 levels fall group (n = 120, group A) and the control group (n = 180, group B). In group A, there were 57 patients with falling E 2 with drug dosage reduction. The other 63 patients experienced the decreased E 2 level spontaneously. The clinical and laboratory variables in the groups were compared. Receiver operator characteristic (ROC) curve analyses were carried out in order to evaluate the predict value of E 2 level on the day of human chorionic gonadotropin (hCG) administration on IVF outcomes. Results: Duration and total dosage of gonadotropin (Gn) used were statistically more in group A than in group B (P < 0.001). The high-quality embryo rate was significantly lower in group A (P = 0.048). Women in group A had lower clinical pregnancy rate (P = 0.029), live birth rate (P < 0.001), ongoing pregnancy rate (P = 0.001), and higher early abortion rates (P = 0.008) than group B. Women with spontaneously falling E 2 group had a higher BMI index than those in the drug dosage reduction group (P = 0.001). More dosage and longer duration of Gn in spontaneously falling E 2 group than in the drug dosage reduction group (P < 0.01). There were no differences in clinical outcomes between the two types of E 2 decreased groups. Results from ROC showed an E 2 level <1987.5 pg/ml on the hCG day might predict early abortion in this study. The sensitivity was 58.4% and the specificity was 78.9%. In addition, an E 2 level >2020 pg/ml on the hCG day might be an index to predict live birth. The sensitivity was 57.0% and the specificity was 61.7%. Conclusions: Reduction of E 2 during COH might adversely affect the clinical pregnancy, early abortion, and ongoing pregnancy of IVF-ET.

Prolonged pituitary downregulation with gonadotropin-releasing hormone agonist improves the live-birth rate: a retrospective cohort study comparing 3 different protocols.

BACKGROUND: The long protocol has been recognized as the gold standard in controlled ovarian hyperstimulation (COH). However, the full dose of gonadotropin-releasing hormone agonist (GnRH-a) under the prolonged protocol has become increasingly popular in China. This study sought to compare pregnancy outcomes among the following 3 groups: a long protocol group, and 2 types of improved prolonged protocol groups. METHODS: A retrospective cohort study was conducted of 550 patients undergoing fresh embryo transfer (ET). Patients were treated either with the improved prolonged protocol in the follicular phase (Group 1; n=288) or the mid-luteal phase (Group 2; n=143), or the long protocol (Group 3; n=119). The clinical and laboratory outcomes of the 3 groups were compared. RESULTS: The general characteristics of the women in the 3 groups were comparable. On the day on which gonadotropin (Gn) was first administered and on the day on which human chorionic gonadotropin (hCG) was administered, the luteinizing hormone (LH) levels of patients in both Groups 1 and 2 were lower than those of patients in Group 3. The number of oocytes retrieved, fertilized, and cleaved, and the number of high-quality embryos in the 3 procedures were similar. However, the number of transferred embryos, the rate of blastocyst progression, and the rate of implantation differed. The clinical pregnancy rates (CPRs)were significantly higher in the prolonged protocol groups (62.5% and 61.5%) than the long protocol group (48.7%). Further, statistically significant differences in the live-birth rates (LBRs) (56.9% vs. 57.3% vs. 42.9%) were observed. However, no differences in early abortion rates were found. CONCLUSIONS: As a result of pituitary downregulation with GnRH-a, the prolonged groups had better CPRs and LBRs than the long protocol group. The prolonged protocol in the mid-luteal phase was equally effective as that in the early follicular phase in fresh in-vitro fertilization (IVF)/intracytoplasmic sperm injection-embryo transfer (ICSI-ET) cycles. High LH levels on the day of hCG may be a predictor of adverse clinical outcomes.

Prednisone combined with letrozole reduced risk of ovarian hyperstimulation syndrome (OHSS) in women undergoing long-term gonadotropin-releasing hormone analog treatment.

BACKGROUND: Ovarian hyperstimulation syndrome (OHSS) is a severe disease that can lead to serious complication. Letrozole has been applied during controlled ovarian hyperstimulation (COH) to reduce the rate of OHSS in women undergoing long-term Gonadotropin-releasing Hormone Analog (GnRHa) treatment for assisted fertility. Prednisone can prevent vasodilatation and increased vascular permeability, which is common during OHSS. However, few studies have evaluated the combined effect of letrozole and prednisone in preventing severe OHSS and is the aim of our retrospective study of patients receiving GnRHa treatment. METHODS: A total of 296 women who accepted autologous in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments were included in this retrospective study. There were three groups: 146 women had letrozole, including letrozole alone (LE group, n=60) and letrozole with prednisone (LE + Pre group, n=86), and 150 women had no treatment (C group). Severe OHSS was diagnosed according to clinical evidence of hydrothorax, severe dyspnea, oliguria/anuria, and intractable nausea/vomiting. RESULTS: The addition of prednisone to letrozole successfully reduced the occurrence rate of severe OHSS than those women administered letrozole alone (55.0% vs. 70.6%, P=0.022). However, the ongoing pregnancy rate was lower in the LE + Pre group than that in the LE-alone group (64.3% vs. 87.0%, P=0.025). Surprisingly, progesterone level on the trigger day (>0.895 ng/mL) is a strong predictor for pregnancy failure with a specificity of 68.3% and sensitivity of 65.7% in the LE-alone group. CONCLUSIONS: Treatment with a combination of letrozole and prednisone may lower the rate of severe OHSS in women with prolonged gonadotropin-releasing hormone agonist protocol during assisted fertility treatment. When the progesterone level on trigger day is over 0.895 ng/mL, letrozole treatment may negatively affect clinical pregnancy.

Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/ß-catenin pathways.

BACKGROUND: Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells. METHODS: The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/ß-catenin signaling pathways were evaluated. RESULTS: We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-ß1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/ß-catenin pathways. CONCLUSIONS: Taken together, ICA could be a potential supplementary agent for cervical cancer treatment.