<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/NCT03267797</url>
  </required_header>
  <id_info>
    <org_study_id>SCARM-infertility-004</org_study_id>
    <nct_id>NCT03267797</nct_id>
  </id_info>
  <brief_title>hCG-activated PBMC-therapy in RIF Patients</brief_title>
  <official_title>Intrauterine Administration of Autologous hCG-activated Peripheral Blood Mononuclear Cells Improves Pregnancy Outcomes in Patients With Recurrent Implantation Failure; a Double-blind Randomized Control Trial Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SCARM Institute, Tabriz, Iran</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>SCARM Institute, Tabriz, Iran</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>
      Despite the many research done in the field of infertility and in vitro fertilization (IVF),&#xD;
      more than half of the embryos transmitted in the IVF and intracytoplasmic sperm injection&#xD;
      (ICSI) do not implant successfully. Currently, pregnancy failure following at least three&#xD;
      IVF/ET cycle, so that one or two high-quality embryos transmitted in each cycle is defined as&#xD;
      recurrent implantation failure (RIF). Maternal and fetal factors can be a reason for&#xD;
      implantation failure; maternal factors include endometrial receptivity, uterine anatomic&#xD;
      abnormalities, and immunologic factors. Implantation failure with embryonic reasons includes&#xD;
      genetic abnormalities and any factor that affects the implantation and growth of the embryo&#xD;
      within the uterus. In recent years, the involvement of immune-related factors mainly natural&#xD;
      killer cells (NK), dendritic cells (DCs), macrophages (MQ), regulatory T cells (Treg) and&#xD;
      Th-1, in the endometrial differentiation and development and endometrial receptivity, as well&#xD;
      as induction of immunological tolerance to the fetus, have been reported.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      248 women with the history of implantation failure volunteered to receive PBMC-therapy. After&#xD;
      immunologic consultation and doing flow cytometry analysis, 100 women with at least three&#xD;
      IVF/ET failure who had low Th-17/Treg ratio in comparison with healthy control were enrolled&#xD;
      in this study. These 100 patients divided randomly into two groups, 50 patients received PBMC&#xD;
      and 50 patients as the control group received PBS. PBMCs were obtained from patients&#xD;
      themselves five days before embryo transfer (ET) and were cultured with hCG for 48 hours.&#xD;
      Frothy-eight hours later, PBMCs were then administered into the uterine cavity of that&#xD;
      patient from the study group two days before ET. PBS was inseminated into the uterine cavity&#xD;
      of the control group instead of PBMC. The concentration of inflammatory cytokines was&#xD;
      examined in the supernatant of cultured PBMCs 2, 24 and 48 hour after incubation by ELISA.&#xD;
      The pregnancy occurrence was confirmed 12 days after ET through positive pregnancy test&#xD;
      (β-hCG test). The success of implantation and the occurrence of clinical pregnancy were&#xD;
      evaluated by ultrasound through the observation of the number and the location of gestational&#xD;
      sacs at 5-6 weeks and confirming the embryo heart pulsation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 7, 2017</start_date>
  <completion_date type="Actual">July 11, 2019</completion_date>
  <primary_completion_date type="Actual">September 25, 2018</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>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The participants and the person who analyzed the results were blinded in this study. Participants were aware of the study before being randomized and informed consent was obtained from them. It should be noted that the person analyzing the results had no other role in this study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>pregnancy occurrence</measure>
    <time_frame>&quot;12 days after embryo transfer&quot;</time_frame>
    <description>Laboratory tests (beta-hCG test)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>examination of inflammatory cytokines (IL-1B, TNF-a and INF-Y) secretion levels in supernatant</measure>
    <time_frame>&quot;48 hours after culturing&quot;</time_frame>
    <description>ELISA technique</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical pregnancy rate in patients with recurrent implantation failure (RIF)</measure>
    <time_frame>&quot;in 5-6 weeks&quot;</time_frame>
    <description>detection the number and location of gestational sacs by ultrasound</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The live birth rate by patients with recurrent implantation failure (RIF)</measure>
    <time_frame>&quot;After about 9 months of positive βHCG test&quot;</time_frame>
    <description>By gynecologists and obstetricians will monitor</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The miscarriage rate in patients with recurrent implantation failure (RIF)</measure>
    <time_frame>&quot;When ever during the pregnancy period (up to 9 months)&quot;</time_frame>
    <description>By gynecologists and obstetricians will monitor</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Recurrent Implantation Failure</condition>
  <arm_group>
    <arm_group_label>Treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Peripheral blood mononuclear cells (PBMCs) were administered into the uterine cavity of RIF patients in this group.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Phosphate buffer saline (PBS) as placebo was injected into the uterine cavity of RIF patients in this group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Peripheral Blood Monouclear Cell</intervention_name>
    <description>Blood samples (20 mL) were taken from individual patients at the time of ovulation induction. Then PBMC were isolated and cultured (20-30 million cells) 48 hour at the presence of hCG (10IU/ml daily). Afterward,15-20 million PBMCs in 500 microlitres PBS were injected into the uterine cavity two days before embryo transfer (ET) using ET catheter.</description>
    <arm_group_label>Treatment group</arm_group_label>
    <other_name>PBMC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Phosphate Baffer Saline</intervention_name>
    <description>Only 500 microlitres PBS will be injected into the uterine cavity, instead of PBMCs, two days before embryo transfer (ET) using ET catheter.</description>
    <arm_group_label>Control group</arm_group_label>
    <other_name>PBS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        All patients were evaluated in accordance with the following inclusion and exclusion&#xD;
        criteria;&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Having at least three implantation failures following IVF&#xD;
&#xD;
          2. Having primary infertility&#xD;
&#xD;
          3. Age under 45 years old&#xD;
&#xD;
          4. Having regular menstrual cycles&#xD;
&#xD;
          5. BMI under 30&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Having polycystic ovary syndrome&#xD;
&#xD;
          2. The presence of uterine pathology;&#xD;
&#xD;
          3. Poor ovarian reserve&#xD;
&#xD;
          4. Having chromosomal abnormalities&#xD;
&#xD;
          5. Presence of auto anti-bodies such as anti-TPO, anti-TG, ACA, APA, ANA, and anti-dsDNA&#xD;
&#xD;
          6. Presence of mutations involving the coagulation system such as deficiency of factor&#xD;
             XII, Pro C, Pro S&#xD;
&#xD;
          7. Positive HIV, HCV or HBV tests&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mohammad Nouri, Ph.D</last_name>
    <role>Study Chair</role>
    <affiliation>Head of SCARM institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mehdi Yousefi, Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>SCARM institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Valiasr Hospital</name>
      <address>
        <city>Tabriz</city>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <results_reference>
    <citation>Chaouat G, Ledee-Bataille N, Zourbas S, Ostojic S, Dubanchet S, Martal J, Frydman R. Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept. Am J Reprod Immunol. 2003 Sep;50(3):177-86. doi: 10.1034/j.1600-0897.2003.00080.x.</citation>
    <PMID>14629021</PMID>
  </results_reference>
  <results_reference>
    <citation>Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril. 2012 May;97(5):1039-43. doi: 10.1016/j.fertnstert.2012.03.010. Epub 2012 Mar 30.</citation>
    <PMID>22464086</PMID>
  </results_reference>
  <results_reference>
    <citation>Hoozemans DA, Schats R, Lambalk CB, Homburg R, Hompes PG. Human embryo implantation: current knowledge and clinical implications in assisted reproductive technology. Reprod Biomed Online. 2004 Dec;9(6):692-715. doi: 10.1016/s1472-6483(10)61781-6.</citation>
    <PMID>15670421</PMID>
  </results_reference>
  <results_reference>
    <citation>Tomassetti C, Meuleman C, Pexsters A, Mihalyi A, Kyama C, Simsa P, D'Hooghe TM. Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link? Reprod Biomed Online. 2006 Jul;13(1):58-64. doi: 10.1016/s1472-6483(10)62016-0.</citation>
    <PMID>16820110</PMID>
  </results_reference>
  <results_reference>
    <citation>Bulmer JN, Longfellow M, Ritson A. Leukocytes and resident blood cells in endometrium. Ann N Y Acad Sci. 1991;622:57-68. doi: 10.1111/j.1749-6632.1991.tb37850.x. No abstract available.</citation>
    <PMID>2064208</PMID>
  </results_reference>
  <results_reference>
    <citation>Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348-57.</citation>
    <PMID>2419430</PMID>
  </results_reference>
  <results_reference>
    <citation>Chou CH, Chen SU, Shun CT, Tsao PN, Yang YS, Yang JH. Divergent endometrial inflammatory cytokine expression at peri-implantation period and after the stimulation by copper intrauterine device. Sci Rep. 2015 Oct 15;5:15157. doi: 10.1038/srep15157.</citation>
    <PMID>26469146</PMID>
  </results_reference>
  <results_reference>
    <citation>Kosaka K, Fujiwara H, Tatsumi K, Yoshioka S, Higuchi T, Sato Y, Nakayama T, Fujii S. Human peripheral blood mononuclear cells enhance cell-cell interaction between human endometrial epithelial cells and BeWo-cell spheroids. Hum Reprod. 2003 Jan;18(1):19-25. doi: 10.1093/humrep/deg002.</citation>
    <PMID>12525435</PMID>
  </results_reference>
  <results_reference>
    <citation>Ideta A, Sakai S, Nakamura Y, Urakawa M, Hayama K, Tsuchiya K, Fujiwara H, Aoyagi Y. Administration of peripheral blood mononuclear cells into the uterine horn to improve pregnancy rate following bovine embryo transfer. Anim Reprod Sci. 2010 Jan;117(1-2):18-23. doi: 10.1016/j.anireprosci.2009.04.004. Epub 2009 May 3.</citation>
    <PMID>19467808</PMID>
  </results_reference>
  <results_reference>
    <citation>Yu N, Yang J, Guo Y, Fang J, Yin T, Luo J, Li X, Li W, Zhao Q, Zou Y, Xu W. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity in mice with embryonic implantation dysfunction. Am J Reprod Immunol. 2014 Jan;71(1):24-33. doi: 10.1111/aji.12150. Epub 2013 Aug 1.</citation>
    <PMID>23909917</PMID>
  </results_reference>
  <results_reference>
    <citation>Okitsu O, Kiyokawa M, Oda T, Miyake K, Sato Y, Fujiwara H. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol. 2011 Dec;92(1-2):82-7. doi: 10.1016/j.jri.2011.07.001. Epub 2011 Oct 27.</citation>
    <PMID>22035703</PMID>
  </results_reference>
  <results_reference>
    <citation>Nakayama T, Fujiwara H, Maeda M, Inoue T, Yoshioka S, Mori T, Fujii S. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC. Hum Reprod. 2002 Jan;17(1):207-12. doi: 10.1093/humrep/17.1.207.</citation>
    <PMID>11756389</PMID>
  </results_reference>
  <results_reference>
    <citation>Yoshioka S, Fujiwara H, Nakayama T, Kosaka K, Mori T, Fujii S. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod. 2006 Dec;21(12):3290-4. doi: 10.1093/humrep/del312. Epub 2006 Oct 4.</citation>
    <PMID>17021188</PMID>
  </results_reference>
  <results_reference>
    <citation>Al-Azemi M, Raghupathy R, Azizieh F. Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction. Clin Exp Obstet Gynecol. 2017;44(1):98-103.</citation>
    <PMID>29714875</PMID>
  </results_reference>
  <results_reference>
    <citation>Granot I, Gnainsky Y, Dekel N. Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction. 2012 Dec;144(6):661-8. doi: 10.1530/REP-12-0217. Epub 2012 Oct 1.</citation>
    <PMID>23028125</PMID>
  </results_reference>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>August 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 21, 2019</last_update_submitted>
  <last_update_submitted_qc>August 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Recurrent Implantation Failure</keyword>
  <keyword>Peripheral blood mononuclear cell</keyword>
  <keyword>Human chorionic gonadotropin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Recurrence</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/NCT03267797
org study id: SCARM-infertility-004
nct id: NCT03267797
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Despite the many research done in the field of infertility and in vitro fertilization (IVF),
      more than half of the embryos transmitted in the IVF and intracytoplasmic sperm injection
      (ICSI) do not implant successfully. Currently, pregnancy failure following at least three
      IVF/ET cycle, so that one or two high-quality embryos transmitted in each cycle is defined as
      recurrent implantation failure (RIF). Maternal and fetal factors can be a reason for
      implantation failure; maternal factors include endometrial receptivity, uterine anatomic
      abnormalities, and immunologic factors. Implantation failure with embryonic reasons includes
      genetic abnormalities and any factor that affects the implantation and growth of the embryo
      within the uterus. In recent years, the involvement of immune-related factors mainly natural
      killer cells (NK), dendritic cells (DCs), macrophages (MQ), regulatory T cells (Treg) and
      Th-1, in the endometrial differentiation and development and endometrial receptivity, as well
      as induction of immunological tolerance to the fetus, have been reported.
248 women with the history of implantation failure volunteered to receive PBMC-therapy. After
      immunologic consultation and doing flow cytometry analysis, 100 women with at least three
      IVF/ET failure who had low Th-17/Treg ratio in comparison with healthy control were enrolled
      in this study. These 100 patients divided randomly into two groups, 50 patients received PBMC
      and 50 patients as the control group received PBS. PBMCs were obtained from patients
      themselves five days before embryo transfer (ET) and were cultured with hCG for 48 hours.
      Frothy-eight hours later, PBMCs were then administered into the uterine cavity of that
      patient from the study group two days before ET. PBS was inseminated into the uterine cavity
      of the control group instead of PBMC. The concentration of inflammatory cytokines was
      examined in the supernatant of cultured PBMCs 2, 24 and 48 hour after incubation by ELISA.
      The pregnancy occurrence was confirmed 12 days after ET through positive pregnancy test
      (β-hCG test). The success of implantation and the occurrence of clinical pregnancy were
      evaluated by ultrasound through the observation of the number and the location of gestational
      sacs at 5-6 weeks and confirming the embryo heart pulsation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The participants and the person who analyzed the results were blinded in this study. Participants were aware of the study before being randomized and informed consent was obtained from them. It should be noted that the person analyzing the results had no other role in this study.
measure: pregnancy occurrence
time frame: "12 days after embryo transfer"
description: Laboratory tests (beta-hCG test)
measure: examination of inflammatory cytokines (IL-1B, TNF-a and INF-Y) secretion levels in supernatant
time frame: "48 hours after culturing"
description: ELISA technique
measure: Clinical pregnancy rate in patients with recurrent implantation failure (RIF)
time frame: "in 5-6 weeks"
description: detection the number and location of gestational sacs by ultrasound
measure: The live birth rate by patients with recurrent implantation failure (RIF)
time frame: "After about 9 months of positive βHCG test"
description: By gynecologists and obstetricians will monitor
measure: The miscarriage rate in patients with recurrent implantation failure (RIF)
time frame: "When ever during the pregnancy period (up to 9 months)"
description: By gynecologists and obstetricians will monitor
arm group label: Treatment group
arm group type: Experimental
description: Peripheral blood mononuclear cells (PBMCs) were administered into the uterine cavity of RIF patients in this group.
arm group label: Control group
arm group type: Placebo Comparator
description: Phosphate buffer saline (PBS) as placebo was injected into the uterine cavity of RIF patients in this group.
intervention type: Other
intervention name: Peripheral Blood Monouclear Cell
description: Blood samples (20 mL) were taken from individual patients at the time of ovulation induction. Then PBMC were isolated and cultured (20-30 million cells) 48 hour at the presence of hCG (10IU/ml daily). Afterward,15-20 million PBMCs in 500 microlitres PBS were injected into the uterine cavity two days before embryo transfer (ET) using ET catheter.
arm group label: Treatment group
other name: PBMC
intervention type: Other
intervention name: Phosphate Baffer Saline
description: Only 500 microlitres PBS will be injected into the uterine cavity, instead of PBMCs, two days before embryo transfer (ET) using ET catheter.
arm group label: Control group
other name: PBS
criteria: 
gender: Female
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mohammad Nouri, Ph.D
role: Study Chair
affiliation: Head of SCARM institute
last name: Mehdi Yousefi, Ph.D
role: Study Director
affiliation: SCARM institute
facility: 
country: Iran, Islamic Republic of
citation: Chaouat G, Ledee-Bataille N, Zourbas S, Ostojic S, Dubanchet S, Martal J, Frydman R. Cytokines, implantation and early abortion: re-examining the Th1/Th2 paradigm leads to question the single pathway, single therapy concept. Am J Reprod Immunol. 2003 Sep;50(3):177-86. doi: 10.1034/j.1600-0897.2003.00080.x.
PMID: 14629021
citation: Simon A, Laufer N. Repeated implantation failure: clinical approach. Fertil Steril. 2012 May;97(5):1039-43. doi: 10.1016/j.fertnstert.2012.03.010. Epub 2012 Mar 30.
PMID: 22464086
citation: Hoozemans DA, Schats R, Lambalk CB, Homburg R, Hompes PG. Human embryo implantation: current knowledge and clinical implications in assisted reproductive technology. Reprod Biomed Online. 2004 Dec;9(6):692-715. doi: 10.1016/s1472-6483(10)61781-6.
PMID: 15670421
citation: Tomassetti C, Meuleman C, Pexsters A, Mihalyi A, Kyama C, Simsa P, D'Hooghe TM. Endometriosis, recurrent miscarriage and implantation failure: is there an immunological link? Reprod Biomed Online. 2006 Jul;13(1):58-64. doi: 10.1016/s1472-6483(10)62016-0.
PMID: 16820110
citation: Bulmer JN, Longfellow M, Ritson A. Leukocytes and resident blood cells in endometrium. Ann N Y Acad Sci. 1991;622:57-68. doi: 10.1111/j.1749-6632.1991.tb37850.x. No abstract available.
PMID: 2064208
citation: Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348-57.
PMID: 2419430
citation: Chou CH, Chen SU, Shun CT, Tsao PN, Yang YS, Yang JH. Divergent endometrial inflammatory cytokine expression at peri-implantation period and after the stimulation by copper intrauterine device. Sci Rep. 2015 Oct 15;5:15157. doi: 10.1038/srep15157.
PMID: 26469146
citation: Kosaka K, Fujiwara H, Tatsumi K, Yoshioka S, Higuchi T, Sato Y, Nakayama T, Fujii S. Human peripheral blood mononuclear cells enhance cell-cell interaction between human endometrial epithelial cells and BeWo-cell spheroids. Hum Reprod. 2003 Jan;18(1):19-25. doi: 10.1093/humrep/deg002.
PMID: 12525435
citation: Ideta A, Sakai S, Nakamura Y, Urakawa M, Hayama K, Tsuchiya K, Fujiwara H, Aoyagi Y. Administration of peripheral blood mononuclear cells into the uterine horn to improve pregnancy rate following bovine embryo transfer. Anim Reprod Sci. 2010 Jan;117(1-2):18-23. doi: 10.1016/j.anireprosci.2009.04.004. Epub 2009 May 3.
PMID: 19467808
citation: Yu N, Yang J, Guo Y, Fang J, Yin T, Luo J, Li X, Li W, Zhao Q, Zou Y, Xu W. Intrauterine administration of peripheral blood mononuclear cells (PBMCs) improves endometrial receptivity in mice with embryonic implantation dysfunction. Am J Reprod Immunol. 2014 Jan;71(1):24-33. doi: 10.1111/aji.12150. Epub 2013 Aug 1.
PMID: 23909917
citation: Okitsu O, Kiyokawa M, Oda T, Miyake K, Sato Y, Fujiwara H. Intrauterine administration of autologous peripheral blood mononuclear cells increases clinical pregnancy rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure. J Reprod Immunol. 2011 Dec;92(1-2):82-7. doi: 10.1016/j.jri.2011.07.001. Epub 2011 Oct 27.
PMID: 22035703
citation: Nakayama T, Fujiwara H, Maeda M, Inoue T, Yoshioka S, Mori T, Fujii S. Human peripheral blood mononuclear cells (PBMC) in early pregnancy promote embryo invasion in vitro: HCG enhances the effects of PBMC. Hum Reprod. 2002 Jan;17(1):207-12. doi: 10.1093/humrep/17.1.207.
PMID: 11756389
citation: Yoshioka S, Fujiwara H, Nakayama T, Kosaka K, Mori T, Fujii S. Intrauterine administration of autologous peripheral blood mononuclear cells promotes implantation rates in patients with repeated failure of IVF-embryo transfer. Hum Reprod. 2006 Dec;21(12):3290-4. doi: 10.1093/humrep/del312. Epub 2006 Oct 4.
PMID: 17021188
citation: Al-Azemi M, Raghupathy R, Azizieh F. Pro-inflammatory and anti-inflammatory cytokine profiles in fetal growth restriction. Clin Exp Obstet Gynecol. 2017;44(1):98-103.
PMID: 29714875
citation: Granot I, Gnainsky Y, Dekel N. Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction. 2012 Dec;144(6):661-8. doi: 10.1530/REP-12-0217. Epub 2012 Oct 1.
PMID: 23028125
responsible party type: Sponsor
mesh term: Recurrence
sharing ipd: No