Viewing Study NCT03758833



Ignite Creation Date: 2024-05-06 @ 12:25 PM
Last Modification Date: 2024-10-26 @ 12:58 PM
Study NCT ID: NCT03758833
Status: COMPLETED
Last Update Posted: 2024-07-03
First Post: 2018-11-28

Brief Title: eSET or eDET Associated to PGT in IVF
Sponsor: University of Sao Paulo General Hospital
Organization: University of Sao Paulo General Hospital

Study Overview

Official Title: Single or Double Elective Embryos Transfer Associated to Preimplantation Genetic Test in in Vitro Fertilization Cycles
Status: COMPLETED
Status Verified Date: 2024-07
Last Known Status: Recruiting
Delayed Posting: No
If Stopped, Why?: Not Stopped
Has Expanded Access: False
If Expanded Access, NCT#: N/A
Has Expanded Access, NCT# Status: N/A
Acronym: SetDetPgt
Brief Summary: 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
Detailed Description: 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 18 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

In addition preimplantation genetic screening PGS is indication for advanced maternal age Schoolcraft et al 2009 repeated implantation failure Blockeel et al 2008 Rubio et al 2013 repeat miscarriage Shahine and Lathi 2014 and severe male factor Harper and Sengupta 2012 More recently the use of PGS in cases of good prognosis for embryo selection in SET cycles has been proposed for both young and good prognosis patients Yang et al 2012 as well as for those in advanced age Schoolcraft and Katz -Jaffe 2013 with an important increase in the rate of embryo transfer associated with a reduction in the rates of multiple gestation Ubaldi et al 2015

PGD was initially performed by in fluorescent in situ hybridization FISH technology from embryo biopsy on the third day of the development and analysis of one or two blastomeres by evaluating a limited number of chromosomes The evolution of this technology led to the complete analysis of the 24 chromosomes by the comparative genome hybridization CGH platform associated with embryo biopsy in the blastocyst stage and evaluation of a greater number of cells extracted from the trophectoderm This approach is associated with higher rates of clinical gestation improved embryo selection in SET cycles and decreasing multiple gestations in patients with good prognosis Dahdouh et al 2015 More recently the next-generation sequencing NGS platform has been used and validated for embryonic genetic analysis in IVF which is used for whole genome amplification WGA with the advantage of being a technology with potential to improve the embryonic chromosomal diagnosis in terms of robustness automation and ability to detect aneuploidies Fiorentino et al 2014 Wells et al 2014

A recent study developed by the investigators group suggests that patients with good prognosis who perform SET in a fresh cycle and did not become pregnant do not benefit from receiving a second transfer of two embryos since the gestation rates are similar to those of patients who received one embryo in the second transfer with the disadvantage of having a high incidence of multiple pregnancies These results obtained in a retrospective study already indicate the advantages of performing SET in a sequential manner promoting satisfactory gestation rates and safety for the mother and baby with regard to multiple gestation for patients with good prognosis Monteleone et al 2016

Based on these principles the investigators consider that elective single embryo transfer SET associated with preimplantation genetic diagnosis by NGS NGS SET for patients with good prognosis can result in higher success rates of IVF cycles and at the same time decreases multiple pregnancies as well as maternal-fetal and neonatal risks inherited from this condition This protocols is suppose to result in high rates of clinical gestation with less occurrence of abortions and greater overall success of the treatment In order to prove this hypothesis the investigators propose a study that compares the outcomes of IVF treatments in patients receiving the elective transfer of single embryo genetically evaluated by NGS NGS SET and elective transference of two embryos genetically evaluated by NGS NGS DET As a control this study will include embryo transfer groups without preimplantation genetic diagnosis by NGS that is those that are selected for transfer only from morphological criteria as routine being associated also the elective transference of one SET or two embryos DET In case of non-pregnancy in the first cycle of IVF there will be subsequent transfers of one or two embryos respectively for each group until the remaining embryos are exhausted or until the patient reaches the gestation The primary outcome will be the cumulative pregnancy rate per treatment cycle 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 the rates of clinical gestation and decrease the rates of multiple gestations and miscarriages

Study Oversight

Has Oversight DMC: None
Is a FDA Regulated Drug?: False
Is a FDA Regulated Device?: False
Is an Unapproved Device?: None
Is a PPSD?: None
Is a US Export?: None
Is an FDA AA801 Violation?: None