GnRH antagonist administration on the day of hCG in cases undergoing IVF/ICSI with long agonist protocol is effective in protection of OHSS and does not affect the clinical pregnancy rate nor live birth rate.
Background: Chemical activation is the most frequently used method for artificial oocyte activation (AOA), results in high fertilization rate. Objective: To evaluate the efficiency of oocyte activation with calcium ionophore on fertilization and pregnancy outcomes after intracytoplasmic sperm injection (ICSI) in patients with previous fertilization failure. Design: prospective controlled study Materials and methods: One hundred and eight patients with history of previous fertilization failure undergoing IVF/ICSI treatment with long agonist protocol were randomly divided into two groups: group A (n=54) and group B (n=54) ; a total of 756 metaphase II (MII) oocytes were retrieved . In the oocytes of group A(n=350 oocyte), routine ICSI was applied; while in oocytes in group B (n=406 oocyte) immediately after ICSI, were entered in culture medium supplemented with 5 µΜ calcium ionophore (A23187) for 10 minutes and then washed at least five times with MOPS solution. Main outcome measures: In both groups, the fertilization was evaluated after 16-18 hours. Results: The number of fertilized oocytes and embryos obtained were significantly different between two groups (p=<0.001*). Fertilization rate was significantly higher in group B -where calcium ionophore was applied-compared to group A(control group) (32.2% vs. 9.1%, respectively ,p=0.01*); and Cleavage rate also was significantly higher in group B compared to group A (27.4% vs 12.5% respectively, p=0.028*). Implantation rate was significantly higher in group B than in group A (18.32% vs. 3.12 % respectively, p=0.035*) Pregnancy rate also was significantly higher in group B than in group A (22.2% vs. 1.85% respectively, p=0.042*). Conclusion: Chemical oocyte activation with calcium ionophore resulted in a significant improvement in fertilization, cleavage, implantation and pregnancy rates after ICSI in infertile patients with previous fertilization failure.
OBJECTIVE: Previous studies have identified single nucleotide polymorphisms that impact hormones involved in the hypothalamic-pituitary-ovarian (HPO) axis. However, these genetic variants may present concurrently, the significance of which is not well understood. This study aimed to identify combinations of genetic variants that affect clinically relevant hormones, such as AMH, in ways that singularly occurring variants do not. DESIGN: Retrospective. MATERIALS AND METHODS: AMH levels and genotypes for 18 variants were recorded for 413 women; informed consent was obtained. To investigate joint effects of mutations on AMH, we ran a conditional association analysis as follows. For all pairs of mutations, we conditioned on the first mutation and tested for association on the second. For example, from our original 413 women, 95 women are wildtype (Ser/Ser) for the FSHR p.Ser680Asn mutation. We considered only the subset of 95 wildtype women, and ran association tests between AMH levels and genotype for each of the remaining 17 mutations. We repeated this process 54 times, conditioning on all 3 different genotypes for each of the 18 mutations. To account for multiple testing, we adjusted the p-value using a randomized permutation procedure.RESULTS: We found a few significant genotype combinations associated with AMH levels. For example, we identified the TP53 p.Pro72Arg mutation within the subset of patients that have Ser/Ser for the FSHR p.Ser680Asn mutation. The Ser/Ser/Pro/Pro group has significantly higher AMH levels (mean ¼ 5.88) than the Ser/Ser/Pro/Arg group and the Ser/Ser/Arg/Arg group combined (mean ¼ 2.85). No significant difference in age between the two groups was observed.CONCLUSIONS: The FSHR Ser allele and the TP53 Pro allele are associated with less active forms of their respective proteins. FSHR is responsible for promoting follicle growth and TP53 is associated with cell cycle control, including apoptosis. Individually, these mutations may not sufficiently disrupt folliculogenesis to alter AMH levels, but jointly this threshold may be reached, highlighting the importance of focusing analysis on genotyping combinations. Further investigation of such combinations may clarify the complex biological processes influencing AMH levels, as their significance is not well understood. Ultimately, a greater understanding may help to refine predictions of ovarian response.
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