Improvement of clinical pregnancy and implantation rates of women by different treatment strategies in in vitro fertilization (IVF) cycles

• Main Authors: Hsiu-Hui Chen, 陳秀惠
• Other Authors: 簡麗鳳
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/22364424529893162545

博士 === 國立中興大學 === 生命科學系所 === 105 === In vitro fertilization (IVF) is now an established therapy throughout the world. It has undergone several important improvements. However, there are still some infertile patients, especially women with advance aged or repeated implantation failure, who characterized by poor clinical outcomes. To establish the better cultural environment or technology to improve the clinical outcomes of these patients is the focus of ongoing research. The study including three parts to analyze the different treatment or technique on the clinical outcomes in IVF. The study including three parts to analyze the different treatment strategy on clinical outcomes in advance aged or RIF patients, including (1) the relationship between different age of women in low oxygen cultural system (2) the relationship between peripheral monocytes population and intravenous immunoglobulin (IVIG) treatment outcomes in repeated implantation failure patients (3) the optimal timing of blastocyst vitrification after preimplantation genetic screening (PGS) in IVF patients. The first study was to assess the effect of women age on embryo quality from early cleavage to day 3, and pregnancy potential under a 5% or20% oxygen tension. One hundred seventy-four patients undergoing controlled ovarian stimulation, IVF/intra-cytoplasmic sperm injection (ICSI), and day 3 embryo transfer. Fertilized oocytes were cultured to day 3 stage under a 5% or20% O2 concentration. In younger women (women age <38 years), the early cleavage (2-cell stage) rate in 20% O2 tension was significantly higher (68.3%) than that in 5% O2 (60.1%). However, the rate of day 3 good embryo developed from good early cleavage (79.1%), pregnancy (58.0%) and implantation rates (30.7%) in 5% O2 were significantly higher than those in 20% O2 (66.8%, 40.0% and 18.8%, respectively) for women <38 years of age. In older women (women age ≥38 years), no matter embryo quality or pregnancy rates between 5% and 20% O2 groups were no significant difference. It is suggested that embryos from younger but not older women, cultured in 5% O2 tension, will increase the embryo quality, pregnancy rate and implantation rate. The second study was to evaluate the impact of intravenous immunoglobulin (IVIG) on clinical outcomes of repeated implantation failure (RIF) patients with abnormal levels of peripheral CD56+CD16+NK cells. The percentage of peripheral CD56+CD16+NK NK cells in the early follicular phase on days 2-3 of the menstrual cycle in repeated implantation failure (RIF) patients was used to evaluate the impact of IVIG on ART cycles. A total 283 patients with RIF consisting of at least 3 ART failures and at least 2 high quality embryo transfers were recruited. A logistic regression analysis for the peripheral immunological profile was completed to predict implantation success and compare the implantation and pregnancy rates between groups with <10.6% and ≥10.6% of CD56+CD16+NK cells in the early follicular phase. The logistic regression and receiving operating curve analyses showed that patients with <10.6% of peripheralCD56+CD16+NK cells in the early follicular phase showed a lower pregnancy rate within the RIF group without IVIG. Patients with peripheral CD56+CD16+NK cells <10.6% and without IVIG treatment showed significantly lower implantation and pregnancy rates (12.3% and 30.3%, respectively) when compared with the CD56+CD16+NK cells ≥10.6% group (24.9% and 48.0%, respectively, p<0.05). Furthermore, the patients with CD56+CD16+NK cells <10.6% given IVIG starting before ET had significantly higher implantation, pregnancy and live birth rates (27.5%, 57.4% and 45.6%, respectively) when compared with the non-IVIG group (12.3%, 30.3% and 22.7%, respectively, p<0.05). Our results showed that a low percentage of peripheral CD56+CD16+NK cells (<10.6%) in the early follicular phase is a potential indicator of reduced pregnancy and implantation success rates in RIF patients, and IVIG treatment will likely benefit this patient subgroup. Several studies have shown that overall about 50% of human preimplantation embryos from IVF are chromosomally abnormal. The rate of abnormalities is affected greatly by female age. Chromosomes in eggs from older women have a significantly increased rate of abnormalities. The preimplantation genetic screening (PGS) in blastocyst stage, a stable tool for chromosome analysis, was used on diagnosis of aneuploid embryos and it offers the other choice for selection normal embryos to improve the clinical outcomes in IVF patients. The vitrification is the most tools to use on PGS protocol; however, the optimal of vitrification in biopsied blastocysts is never discussed. The third study was to evaluate what timing of vitrification after trophectoderm (TE) biopsy associated with successful implantation and pregnancy after the embryo transfer of blastocysts subjected to PGS. A total 1329 blastocysts from 223 patients were subjected toper from PGS and frozen embryo transfer (FET) cycles from December 2012 to May 2015. Only the good quality and expanded blastocysts were selected for TE biopsy and the laser assisted hatching was performed on blastocyst stage. After TE biopsy, the re-expansion grades relative to the original blastocoelat time of vitrification were (a) collapsed blastocysts (CB), (b) re-expansion but not full expansion (RE), and (c) full expansion or hatching (FE). The primary outcome measures were the implantation and pregnancy rates per PGS–FET cycle. The time intervals between TE biopsy and vitrification were 0.5–6 h. The implantation (63.7%, 179/281) and clinical pregnancy (74.0%, 128/173) rates in group of RE or FE blastocysts with a ≥3h culture interval were significantly higher than those in group of CB with a <3h culture interval (45.3%, 24/53; 50.0%, 17/34; P = 0.012 and = 0.005, respectively). According to our findings, the optimal vitrification timing enables biopsied blastocysts to reach RE or FE for ≥ 3 h after TE biopsy and provides improved implantation and pregnancy rates after FET. Based on the above results, hypoxic culture of embryo can increase clinical pregnancy and implantation rates in younger women, but hypoxic culture of embryo has no significant effect on older women. On the other hand, treatment of patients with RIF can be based on NK Cells as a diagnostic reference to patients with lower NK cells in patients with IVIG treatment can promote the implantation rate. However, in the PGS, the best time to chill the embryo is 3 or more hours after biopsy. The above three aspects can be used as laboratory or clinical treatment of older or RIF women with increased clinical pregnancy and implantation rates.