Single or Double Elective Embryos Transfer Associated to Preimplantation Genetic Test in in Vitro Fertilization Cycles
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- cumulative pregnancy rate
研究概览
简要总结
In vitro fertilization (IVF) techniques have been improving performance recently and, nowadays, provide a live birth rate of around 25%. The success of IVF techniques is dependent upon maximum efficiency at each stage of treatment, and, at the same time, high success rates with a low risk of complications. Multiple pregnancies are one of the most important adverse event of IVF techniques. In this sense, the use of elective single embryo transfer (SET) has become an option for patients with good prognosis compared to the transfer of multiple embryos, and it is recommended in order to reduce the risk of multiple pregnancies and their consequences. On the other hand, it is known that embryonic quality is a crucial step for the success of IVF techniques and the efficiency of this process is linked to the decrease in the number of embryos to be transferred. Usually, embryo selection is based on morphological and developmental criteria. However, recently, it has been demonstrated that the blastocyst biopsy associated with the chromosomal / genetic screening may be a predictor of the chances of implantation. The investigators group demonstrated the feasibility of performing SET sequentially, promoting satisfactory gestation rates and safety for the mother and baby regarding multiple gestation for patients with good prognosis. Based on these principles, the investigators raised the hypothesis that SET associated with preimplantation genetic diagnosis (PGD) by next-generation sequencing (NGS) for patients with good prognosis can improve the success rates of IVF cycles and, at the same time, avoid multiple pregnancies, as well as maternal-fetal and neonatal risks resulting from this condition. To test this hypothesis, the aim of this study is to compare the results of IVF treatments in patients receiving SET (SET group), SET associated with genetic evaluation by NGS (group NGS + SET), elective transference of two embryos (DET group) and DET associated with genetic evaluation by NGS (NGS + DET). In case of non-pregnancy on the first transfer, there will be subsequent transfers until the remaining embryos are exhausted or the patient reaches the gestation. The primary endpoint will be the cumulative pregnancy rate per treatment cycle and this approach will allow to confirm or not the hypothesis that genetic analysis is effective in improving the embryo selection process and associated with SET will increase clinical gestation rates and decrease rates of multiple gestations and miscarriages.
详细描述
Infertility is an important public health problem, affecting between 8 and 12% of reproductive-age couples, and leading to a high prevalence of childless couples (Bergstrom, 1992; Ombelet and Campo, 2007). The demand for infertility treatment is increasing due to sociocultural factors such as delayed pregnancy, higher incidence of sexually transmitted diseases, obesity rates, and greater acceptance to the available treatments. Recent estimates have shown that more than 1.8 million assisted reproduction treatments (ART) were performed in 2010 and more than 6 million children born were conceived using ART (Dyer et al., 2016).
In vitro fertilization (IVF) techniques have improved performance and currently provide a live embryo transfer rate that is around 25%. However, the success of IVF techniques depends on maximum efficiency in each treatment step, from controlled ovarian stimulation to obtaining adequate numbers of good quality mature eggs, optimal embryo culture conditions, availability of embryos of good quality for transfer and an adequate endometrium for implantation. Changes in clinical and laboratory practices such as the transfer of embryos in the blastocyst stage, improvement of cryopreservation techniques, transfer of thawed embryos after endometrial preparation and single embryo transfer (SET), have been increasingly indicated for patients with good prognosis. At the same time, the use of SET and freezing of all embryos for later transfer of thawed embryos are the major paradigms of ART in recent years (Chambers et al., 2016).
Despite a variation among countries influenced by coverage of health plans, legislation, guides to medical societies, population and culture, in Europe, on average 20% of transfers are single, with up to 69% of cycles in Sweden. In the United States, elective SET is still low, around 10% among women up to 35 years of age (Maheshwari et al., 2011; Practice Committee of the Society for Assisted Reproductive and Practice Committee of the American Society for Reproductive Medicine, 2012). Despite recommendations and increased SET practice, multiple gestation rates in IVF techniques are still high in the overall mean, around 20-25%, as a result of resistance of using SET and maintaining the transfer of multiple embryos with the purpose of obtaining higher gestation rates (Naasan et al., 2012, Kupka et al., 2014, Ishihara et al., 2015). This resistance is due to the idea that transferring more than one embryo may increase the chance of gestation. However, this practice does not take in consideration the increase of maternal and perinatal complications due to multiple pregnancies (Min et al., 2010; Practice Committee of American Society for Reproductive, 2012). In addition, studies have shown that cumulative live birth rates after the transfer of two SET cycles are comparable with a single transfer of two embryos (Pandian et al., 2009; Chambers and Ledger, 2014).
Historically, it is known that among the total number of retrieved oocytes, only a limited amount of them carry the potential to generate full-term gestation. Thus, embryo selection is a crucial step for the success of IVF techniques and the efficiency of this process is related to the decrease in the number of embryos to be transferred, since once it is possible to select embryos with greater implantation potential, the transfer of fewer embryos becomes more feasible and effective. In the routine, the embryonic selection is based on morphological criteria and characteristics of embryo development in order to infer its implantation potential (Ebner et al., 2003).
After controlled ovarian stimulation, approximately 50% of the embryos present chromosomal alterations (Munne et al., 1995). Then, the embryonic genetic evaluation is becoming increasingly used for the selection of euploid embryos for transfer. Blastocyst biopsy associated with chromosomal screening has been shown to be highly predictive of blastocyst developmental potential (Scott et al., 2012), increasing the chances of implantation by selection of euploid blastocysts for transfer in fresh (Scott et al., 2013) and frozen-thawed cycles (Schoolcraft and Katz-Jaffe, 2013).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 37 Years(Adult)
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Couples performing in vitro fertilization cycles using intracytoplasmic sperm injection
- •Performing the first treatment cycle;
- •Body Mass Index (BMI) of 18 to 30 kg / m2;
- •Presence of both ovaries without evidence of significant abnormalities;
- •Absence of any significant pathology of the endometrial cavity, such as polyps, fibroids larger than 4cm and hidrosalpinge;
- •Normal ovarian reserve, determined by antral follicle count> 8 and FSH <12 mIU / mL;
- •Use of fresh ejaculate or cryopreserved partner seminal sample
排除标准
- •Women presenting endometriosis degrees III and IV;
- •Sperm used for fertilization from partner with severe oligozoospermia (<5 million sperm / ml);
- •Women with associated systemic diseases or infectious diseases;
- •Do not have at least two good quality blastocysts on the fifth day of development.
结局指标
主要结局
cumulative pregnancy rate
时间窗: 6 months
percentage of patients who become pregnant after transfer of embryos
次要结局
- multiple pregnancy rate(6 months)
- transfers needed to achieve gestation(6 months)
- cycle cancellation rate(1 month)
- live birth rates(one year)
研究者
Pedro Augusto Araújo Monteleone
Clinical Head of the Reproductive Medicine Center Governador Mario Covas
University of Sao Paulo General Hospital
