<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03758833</url>
  </required_header>
  <id_info>
    <org_study_id>SET-NGS</org_study_id>
    <nct_id>NCT03758833</nct_id>
  </id_info>
  <brief_title>eSET or eDET Associated to PGT in IVF</brief_title>
  <acronym>SetDetPgt</acronym>
  <official_title>Single or Double Elective Embryos Transfer Associated to Preimplantation Genetic Test in in Vitro Fertilization Cycles</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Sao Paulo General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In vitro fertilization (IVF) techniques have been improving performance recently and,&#xD;
      nowadays, provide a live birth rate of around 25%. The success of IVF techniques is dependent&#xD;
      upon maximum efficiency at each stage of treatment, and, at the same time, high success rates&#xD;
      with a low risk of complications. Multiple pregnancies are one of the most important adverse&#xD;
      event of IVF techniques. In this sense, the use of elective single embryo transfer (SET) has&#xD;
      become an option for patients with good prognosis compared to the transfer of multiple&#xD;
      embryos, and it is recommended in order to reduce the risk of multiple pregnancies and their&#xD;
      consequences. On the other hand, it is known that embryonic quality is a crucial step for the&#xD;
      success of IVF techniques and the efficiency of this process is linked to the decrease in the&#xD;
      number of embryos to be transferred. Usually, embryo selection is based on morphological and&#xD;
      developmental criteria. However, recently, it has been demonstrated that the blastocyst&#xD;
      biopsy associated with the chromosomal / genetic screening may be a predictor of the chances&#xD;
      of implantation. The investigators group demonstrated the feasibility of performing SET&#xD;
      sequentially, promoting satisfactory gestation rates and safety for the mother and baby&#xD;
      regarding multiple gestation for patients with good prognosis. Based on these principles, the&#xD;
      investigators raised the hypothesis that SET associated with preimplantation genetic&#xD;
      diagnosis (PGD) by next-generation sequencing (NGS) for patients with good prognosis can&#xD;
      improve the success rates of IVF cycles and, at the same time, avoid multiple pregnancies, as&#xD;
      well as maternal-fetal and neonatal risks resulting from this condition. To test this&#xD;
      hypothesis, the aim of this study is to compare the results of IVF treatments in patients&#xD;
      receiving SET (SET group), SET associated with genetic evaluation by NGS (group NGS + SET),&#xD;
      elective transference of two embryos (DET group) and DET associated with genetic evaluation&#xD;
      by NGS (NGS + DET). In case of non-pregnancy on the first transfer, there will be subsequent&#xD;
      transfers until the remaining embryos are exhausted or the patient reaches the gestation. The&#xD;
      primary endpoint will be the cumulative pregnancy rate per treatment cycle and this approach&#xD;
      will allow to confirm or not the hypothesis that genetic analysis is effective in improving&#xD;
      the embryo selection process and associated with SET will increase clinical gestation rates&#xD;
      and decrease rates of multiple gestations and miscarriages.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Infertility is an important public health problem, affecting between 8 and 12% of&#xD;
      reproductive-age couples, and leading to a high prevalence of childless couples (Bergstrom,&#xD;
      1992; Ombelet and Campo, 2007). The demand for infertility treatment is increasing due to&#xD;
      sociocultural factors such as delayed pregnancy, higher incidence of sexually transmitted&#xD;
      diseases, obesity rates, and greater acceptance to the available treatments. Recent estimates&#xD;
      have shown that more than 1.8 million assisted reproduction treatments (ART) were performed&#xD;
      in 2010 and more than 6 million children born were conceived using ART (Dyer et al., 2016).&#xD;
&#xD;
      In vitro fertilization (IVF) techniques have improved performance and currently provide a&#xD;
      live embryo transfer rate that is around 25%. However, the success of IVF techniques depends&#xD;
      on maximum efficiency in each treatment step, from controlled ovarian stimulation to&#xD;
      obtaining adequate numbers of good quality mature eggs, optimal embryo culture conditions,&#xD;
      availability of embryos of good quality for transfer and an adequate endometrium for&#xD;
      implantation. Changes in clinical and laboratory practices such as the transfer of embryos in&#xD;
      the blastocyst stage, improvement of cryopreservation techniques, transfer of thawed embryos&#xD;
      after endometrial preparation and single embryo transfer (SET), have been increasingly&#xD;
      indicated for patients with good prognosis. At the same time, the use of SET and freezing of&#xD;
      all embryos for later transfer of thawed embryos are the major paradigms of ART in recent&#xD;
      years (Chambers et al., 2016).&#xD;
&#xD;
      Despite a variation among countries influenced by coverage of health plans, legislation,&#xD;
      guides to medical societies, population and culture, in Europe, on average 20% of transfers&#xD;
      are single, with up to 69% of cycles in Sweden. In the United States, elective SET is still&#xD;
      low, around 10% among women up to 35 years of age (Maheshwari et al., 2011; Practice&#xD;
      Committee of the Society for Assisted Reproductive and Practice Committee of the American&#xD;
      Society for Reproductive Medicine, 2012). Despite recommendations and increased SET practice,&#xD;
      multiple gestation rates in IVF techniques are still high in the overall mean, around 20-25%,&#xD;
      as a result of resistance of using SET and maintaining the transfer of multiple embryos with&#xD;
      the purpose of obtaining higher gestation rates (Naasan et al., 2012, Kupka et al., 2014,&#xD;
      Ishihara et al., 2015). This resistance is due to the idea that transferring more than one&#xD;
      embryo may increase the chance of gestation. However, this practice does not take in&#xD;
      consideration the increase of maternal and perinatal complications due to multiple&#xD;
      pregnancies (Min et al., 2010; Practice Committee of American Society for Reproductive,&#xD;
      2012). In addition, studies have shown that cumulative live birth rates after the transfer of&#xD;
      two SET cycles are comparable with a single transfer of two embryos (Pandian et al., 2009;&#xD;
      Chambers and Ledger, 2014).&#xD;
&#xD;
      Historically, it is known that among the total number of retrieved oocytes, only a limited&#xD;
      amount of them carry the potential to generate full-term gestation. Thus, embryo selection is&#xD;
      a crucial step for the success of IVF techniques and the efficiency of this process is&#xD;
      related to the decrease in the number of embryos to be transferred, since once it is possible&#xD;
      to select embryos with greater implantation potential, the transfer of fewer embryos becomes&#xD;
      more feasible and effective. In the routine, the embryonic selection is based on&#xD;
      morphological criteria and characteristics of embryo development in order to infer its&#xD;
      implantation potential (Ebner et al., 2003).&#xD;
&#xD;
      After controlled ovarian stimulation, approximately 50% of the embryos present chromosomal&#xD;
      alterations (Munne et al., 1995). Then, the embryonic genetic evaluation is becoming&#xD;
      increasingly used for the selection of euploid embryos for transfer. Blastocyst biopsy&#xD;
      associated with chromosomal screening has been shown to be highly predictive of blastocyst&#xD;
      developmental potential (Scott et al., 2012), increasing the chances of implantation by&#xD;
      selection of euploid blastocysts for transfer in fresh (Scott et al., 2013) and frozen-thawed&#xD;
      cycles (Schoolcraft and Katz-Jaffe, 2013).&#xD;
&#xD;
      In addition, preimplantation genetic screening (PGS) is indication for advanced maternal age&#xD;
      (Schoolcraft et al., 2009), repeated implantation failure (Blockeel et al., 2008; Rubio et&#xD;
      al. 2013), repeat miscarriage (Shahine and Lathi, 2014) and severe male factor (Harper and&#xD;
      Sengupta, 2012). More recently, the use of PGS in cases of good prognosis for embryo&#xD;
      selection in SET cycles has been proposed for both young and good prognosis patients (Yang et&#xD;
      al., 2012), as well as for those in advanced age (Schoolcraft and Katz -Jaffe, 2013), with an&#xD;
      important increase in the rate of embryo transfer associated with a reduction in the rates of&#xD;
      multiple gestation (Ubaldi et al., 2015).&#xD;
&#xD;
      PGD was initially performed by in fluorescent in situ hybridization (FISH) technology from&#xD;
      embryo biopsy on the third day of the development and analysis of one or two blastomeres by&#xD;
      evaluating a limited number of chromosomes. The evolution of this technology led to the&#xD;
      complete analysis of the 24 chromosomes by the comparative genome hybridization (CGH)&#xD;
      platform associated with embryo biopsy in the blastocyst stage and evaluation of a greater&#xD;
      number of cells extracted from the trophectoderm. This approach is associated with higher&#xD;
      rates of clinical gestation, improved embryo selection in SET cycles and decreasing multiple&#xD;
      gestations in patients with good prognosis (Dahdouh et al., 2015). More recently, the&#xD;
      next-generation sequencing (NGS) platform has been used and validated for embryonic genetic&#xD;
      analysis in IVF, which is used for whole genome amplification (WGA), with the advantage of&#xD;
      being a technology with potential to improve the embryonic chromosomal diagnosis in terms of&#xD;
      robustness, automation and ability to detect aneuploidies (Fiorentino et al., 2014; Wells et&#xD;
      al., 2014).&#xD;
&#xD;
      A recent study developed by the investigators group suggests that patients with good&#xD;
      prognosis who perform SET in a fresh cycle and did not become pregnant, do not benefit from&#xD;
      receiving a second transfer of two embryos, since the gestation rates are similar to those of&#xD;
      patients who received one embryo in the second transfer, with the disadvantage of having a&#xD;
      high incidence of multiple pregnancies. These results obtained in a retrospective study&#xD;
      already indicate the advantages of performing SET in a sequential manner, promoting&#xD;
      satisfactory gestation rates and safety for the mother and baby with regard to multiple&#xD;
      gestation for patients with good prognosis (Monteleone et al. , 2016).&#xD;
&#xD;
      Based on these principles, the investigators consider that elective single embryo transfer&#xD;
      (SET) associated with preimplantation genetic diagnosis by NGS (NGS + SET) for patients with&#xD;
      good prognosis can result in higher success rates of IVF cycles and at the same time&#xD;
      decreases multiple pregnancies, as well as maternal-fetal and neonatal risks inherited from&#xD;
      this condition. This protocols is suppose to result in high rates of clinical gestation with&#xD;
      less occurrence of abortions and greater overall success of the treatment. In order to prove&#xD;
      this hypothesis, the investigators propose a study that compares the outcomes of IVF&#xD;
      treatments in patients receiving the elective transfer of single embryo genetically evaluated&#xD;
      by NGS (NGS + SET) and elective transference of two embryos genetically evaluated by NGS (NGS&#xD;
      + DET). As a control, this study will include embryo transfer groups without preimplantation&#xD;
      genetic diagnosis by NGS, that is, those that are selected for transfer only from&#xD;
      morphological criteria as routine, being associated also the elective transference of one&#xD;
      (SET) or two embryos (DET). In case of non-pregnancy in the first cycle of IVF, there will be&#xD;
      subsequent transfers of one or two embryos respectively for each group until the remaining&#xD;
      embryos are exhausted or until the patient reaches the gestation. The primary outcome will be&#xD;
      the cumulative pregnancy rate per treatment cycle. This approach will allow to confirm or not&#xD;
      the hypothesis that genetic analysis is effective in improving the embryo selection process&#xD;
      and associated with SET will increase the rates of clinical gestation and decrease the rates&#xD;
      of multiple gestations and miscarriages.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 20, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>cumulative pregnancy rate</measure>
    <time_frame>6 months</time_frame>
    <description>percentage of patients who become pregnant after transfer of embryos</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>cycle cancellation rate</measure>
    <time_frame>1 month</time_frame>
    <description>percentage of cycles cancelled due to all embryos genetic alterated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>multiple pregnancy rate</measure>
    <time_frame>6 months</time_frame>
    <description>percentage of patients who become pregnant of twins</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>live birth rates</measure>
    <time_frame>one year</time_frame>
    <description>percentage of patients who had live birth</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>transfers needed to achieve gestation</measure>
    <time_frame>6 months</time_frame>
    <description>number of embryos transfers needed to achieve gestation</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>in Vitro Fertilization</condition>
  <condition>Single Embryo Transfer</condition>
  <condition>Preimplantation Genetic Diagnosis</condition>
  <condition>Pregnancy</condition>
  <arm_group>
    <arm_group_label>SET</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients receiving the elective single embryo transfer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SET+NGS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients receiving the elective single embryo transfer evaluated genetically by NGS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DET</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>patients receiving the elective double embryo transfer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DET+NGS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients receiving the elective double embryo transfer evaluated genetically by NGS</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>preimplantation genetic test of embryo by new generation sequencing (NGS)</intervention_name>
    <description>This is a genetic test to evaluate 24 chromosomes by the new generation sequencing platform. For that is necessary a embryo biopsy in the blastocyst stage and evaluation of a greater number of cells extracted from the trophectoderm</description>
    <arm_group_label>DET+NGS</arm_group_label>
    <arm_group_label>SET+NGS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Single embryo transfer</intervention_name>
    <description>Transfer of single embryo</description>
    <arm_group_label>SET</arm_group_label>
    <arm_group_label>SET+NGS</arm_group_label>
    <other_name>SET</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Double embryo tranfer</intervention_name>
    <description>Transfer of two embryos</description>
    <arm_group_label>DET</arm_group_label>
    <arm_group_label>DET+NGS</arm_group_label>
    <other_name>DET</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Couples performing in vitro fertilization cycles using intracytoplasmic sperm&#xD;
             injection&#xD;
&#xD;
               -  Performing the first treatment cycle;&#xD;
&#xD;
               -  Body Mass Index (BMI) of 18 to 30 kg / m2;&#xD;
&#xD;
               -  Presence of both ovaries without evidence of significant abnormalities;&#xD;
&#xD;
               -  Absence of any significant pathology of the endometrial cavity, such as polyps,&#xD;
                  fibroids larger than 4cm and hidrosalpinge;&#xD;
&#xD;
               -  Normal ovarian reserve, determined by antral follicle count&gt; 8 and FSH &lt;12 mIU /&#xD;
                  mL;&#xD;
&#xD;
               -  Use of fresh ejaculate or cryopreserved partner seminal sample&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Women presenting endometriosis degrees III and IV;&#xD;
&#xD;
               -  Sperm used for fertilization from partner with severe oligozoospermia (&lt;5 million&#xD;
                  sperm / ml);&#xD;
&#xD;
               -  Women with associated systemic diseases or infectious diseases;&#xD;
&#xD;
               -  Do not have at least two good quality blastocysts on the fifth day of&#xD;
                  development.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>37 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Pedro Monteleone, MD, PhD</last_name>
    <phone>+55 11 98354-9972</phone>
    <email>pedro@monteleone.med.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tatiana Bonetti, PhD</last_name>
    <phone>+55 11 984813107</phone>
    <email>tatibonetti76@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Faculdade de Medicina da Universidade de São Paulo (FMUSP)</name>
      <address>
        <city>Sao Paulo</city>
        <state>SP</state>
        <country>Brazil</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pedro AA Monteleone, PhD</last_name>
      <email>pedro@monteleone.med.br</email>
    </contact>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>May 19, 2022</last_update_submitted>
  <last_update_submitted_qc>May 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo General Hospital</investigator_affiliation>
    <investigator_full_name>Pedro Augusto Araújo Monteleone</investigator_full_name>
    <investigator_title>Clinical Head of the Reproductive Medicine Center Governador Mario Covas</investigator_title>
  </responsible_party>
  <keyword>in vitro fertilization</keyword>
  <keyword>single embryo transfer</keyword>
  <keyword>preimplantation genetic diagnosis</keyword>
  <keyword>clinical pregnancy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03758833
org study id: SET-NGS
nct id: NCT03758833
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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).

      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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: cumulative pregnancy rate
time frame: 6 months
description: percentage of patients who become pregnant after transfer of embryos
measure: cycle cancellation rate
time frame: 1 month
description: percentage of cycles cancelled due to all embryos genetic alterated
measure: multiple pregnancy rate
time frame: 6 months
description: percentage of patients who become pregnant of twins
measure: live birth rates
time frame: one year
description: percentage of patients who had live birth
measure: transfers needed to achieve gestation
time frame: 6 months
description: number of embryos transfers needed to achieve gestation
arm group label: SET
arm group type: Active Comparator
description: patients receiving the elective single embryo transfer
arm group label: SET+NGS
arm group type: Experimental
description: patients receiving the elective single embryo transfer evaluated genetically by NGS
arm group label: DET
arm group type: Active Comparator
description: patients receiving the elective double embryo transfer
arm group label: DET+NGS
arm group type: Experimental
description: patients receiving the elective double embryo transfer evaluated genetically by NGS
intervention type: Diagnostic Test
intervention name: preimplantation genetic test of embryo by new generation sequencing (NGS)
description: This is a genetic test to evaluate 24 chromosomes by the new generation sequencing platform. For that is necessary a embryo biopsy in the blastocyst stage and evaluation of a greater number of cells extracted from the trophectoderm
arm group label: DET+NGS
arm group label: SET+NGS
intervention type: Procedure
intervention name: Single embryo transfer
description: Transfer of single embryo
arm group label: SET
arm group label: SET+NGS
other name: SET
intervention type: Procedure
intervention name: Double embryo tranfer
description: Transfer of two embryos
arm group label: DET
arm group label: DET+NGS
other name: DET
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 37 Years
healthy volunteers: No
last name: Pedro Monteleone, MD, PhD
phone: +55 11 98354-9972
email: pedro@monteleone.med.br
last name: Tatiana Bonetti, PhD
phone: +55 11 984813107
email: tatibonetti76@gmail.com
facility: 
status: Recruiting
contact: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo General Hospital
investigator full name: Pedro Augusto Araújo Monteleone
investigator title: Clinical Head of the Reproductive Medicine Center Governador Mario Covas
mesh term: Disease
sharing ipd: No