<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/NCT03826888</url>
  </required_header>
  <id_info>
    <org_study_id>1807-ABU-055-LM</org_study_id>
    <nct_id>NCT03826888</nct_id>
  </id_info>
  <brief_title>Measurement of Different Anti-Müllerian Hormone Isoforms in Expected Poor Responders</brief_title>
  <official_title>Measurement of Different Anti-Müllerian Hormone Isoforms in Expected Poor Responders: Does it Matter?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ART Fertility Clinics LLC</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ART Fertility Clinics LLC</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>
      This study wants to evaluate significant clinical impact of different AMH isoforms in serum&#xD;
      can be present or absent in expected poor responder participants. The specific AMH isoforms&#xD;
      could therefore be measured in expected poor responder participants in order to obtain a more&#xD;
      realistic clinical picture and therefore be able to give proper information to the&#xD;
      participants and selection of medication dose for ovarian stimulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study has a prospective observational multicentric design and the investigators aim to&#xD;
      investigate the presence of AMH isoforms and the levels of Inhibin B in serum among a&#xD;
      population of participants with low ovarian reserve (AMH blood test below 1.1 ng/ml).&#xD;
      Transvaginal scan for AFC and blood drawn from participants will be obtained on day 2-3 of&#xD;
      menstrual period. The serum will be divided for AMH analysis using different assays: Elecsys&#xD;
      Cobas assay for AMH and AnshLabs AMH isoforms specific assays (picoAMH 24/32 Pro-Mature,&#xD;
      24/37 Midpro-Midpro, 17/15 Mature-Mature and 10/24 Pro-Midpro) and AnshLabs Inhibin B ELISA.&#xD;
&#xD;
      Clinically it is not uncommon to see a discrepancy between the AFC count and the levels of&#xD;
      AMH; this could be potentially explained by the presence of different AMH isoforms not&#xD;
      measured with conventional commercial assays. Also, the evaluation of Inhibin B may be&#xD;
      helpful for ovarian reserve assessment. Quantitation of specific Isoforms of AMH by different&#xD;
      ELISA methods will investigate a possible relationship(s) between specific isoforms of AMH&#xD;
      and poor responders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 25, 2019</start_date>
  <completion_date type="Actual">May 30, 2022</completion_date>
  <primary_completion_date type="Actual">December 23, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Only</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>AMH serum levels</measure>
    <time_frame>1 day</time_frame>
    <description>Differences in AMH serum levels due to the presence of different AMH isoforms when results are compared with AMH measurement in blood performed with Elecsys Cobas AMH assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Inhibin B and ovarian reserve markers</measure>
    <time_frame>1 day</time_frame>
    <description>Correlation between Inhibin B and ovarian reserve markers (AMH serum levels and AFC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AMH serum and AFC</measure>
    <time_frame>1 day</time_frame>
    <description>Correlation between AMH serum levels (measured with different ELISA tests) and AFC.</description>
  </secondary_outcome>
  <enrollment type="Actual">72</enrollment>
  <condition>Anti-Mullerian Hormone Isoforms</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood specimen&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Infertile female undergoing ovarian stimulation&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  pre-treatment AMH recording below 1.1 ng/ml on day 2 or 3 of the menstrual cycle.&#xD;
&#xD;
          -  BMI between 18 and 30 kg/m2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy.&#xD;
&#xD;
          -  Breastfeeding.&#xD;
&#xD;
          -  Intake of oral contraceptive pills or steroids for the last two menstrual cycles.&#xD;
&#xD;
          -  Endometriosis.&#xD;
&#xD;
          -  Previous surgical intervention, which could have an impact on the ovarian reserve,&#xD;
             e.g. ovarian cyst removal, removal of one or both tubes, tubal ligation for&#xD;
             sterilisation&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>IVI Middle East Fertility Clinic</name>
      <address>
        <city>Abu Dhabi</city>
        <zip>60202</zip>
        <country>United Arab Emirates</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Arab Emirates</country>
  </location_countries>
  <reference>
    <citation>McLennan IS, Pankhurst MW. Anti-Mullerian hormone is a gonadal cytokine with two circulating forms and cryptic actions. J Endocrinol. 2015 Sep;226(3):R45-57. doi: 10.1530/JOE-15-0206. Epub 2015 Jul 10.</citation>
    <PMID>26163524</PMID>
  </reference>
  <reference>
    <citation>Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP, et al. Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell. 1986 Jun 6;45(5):685-98. doi: 10.1016/0092-8674(86)90783-x.</citation>
    <PMID>3754790</PMID>
  </reference>
  <reference>
    <citation>Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor defects in persistent Mullerian duct syndrome. Hum Reprod Update. 2005 Jul-Aug;11(4):351-6. doi: 10.1093/humupd/dmi014. Epub 2005 May 5.</citation>
    <PMID>15878900</PMID>
  </reference>
  <reference>
    <citation>Pankhurst MW, McLennan IS. Human blood contains both the uncleaved precursor of anti-Mullerian hormone and a complex of the NH2- and COOH-terminal peptides. Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1241-7. doi: 10.1152/ajpendo.00395.2013. Epub 2013 Sep 17.</citation>
    <PMID>24045871</PMID>
  </reference>
  <reference>
    <citation>Pankhurst MW, Chong YH, McLennan IS. Enzyme-linked immunosorbent assay measurements of antimullerian hormone (AMH) in human blood are a composite of the uncleaved and bioactive cleaved forms of AMH. Fertil Steril. 2014 Mar;101(3):846-50. doi: 10.1016/j.fertnstert.2013.12.009. Epub 2014 Jan 11.</citation>
    <PMID>24424371</PMID>
  </reference>
  <reference>
    <citation>Pankhurst MW, Clark CA, Zarek J, Laskin CA, McLennan IS. Changes in Circulating ProAMH and Total AMH during Healthy Pregnancy and Post-Partum: A Longitudinal Study. PLoS One. 2016 Sep 9;11(9):e0162509. doi: 10.1371/journal.pone.0162509. eCollection 2016.</citation>
    <PMID>27612037</PMID>
  </reference>
  <reference>
    <citation>Robertson DM, Kumar A, Kalra B, Shah S, Pruysers E, Vanden Brink H, Chizen D, Visser JA, Themmen AP, Baerwald A. Detection of serum antimullerian hormone in women approaching menopause using sensitive antimullerian hormone enzyme-linked immunosorbent assays. Menopause. 2014 Dec;21(12):1277-86. doi: 10.1097/GME.0000000000000244.</citation>
    <PMID>24781853</PMID>
  </reference>
  <reference>
    <citation>Robertson DM, Hale GE, Fraser IS, Hughes CL, Burger HG. Changes in serum antimullerian hormone levels across the ovulatory menstrual cycle in late reproductive age. Menopause. 2011 May;18(5):521-4. doi: 10.1097/gme.0b013e3181f8d9e0.</citation>
    <PMID>21178792</PMID>
  </reference>
  <reference>
    <citation>Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P, Godehardt E. Relevance of anti-Mullerian hormone measurement in a routine IVF program. Hum Reprod. 2008 Jun;23(6):1359-65. doi: 10.1093/humrep/den108. Epub 2008 Apr 2.</citation>
    <PMID>18387961</PMID>
  </reference>
  <reference>
    <citation>Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.</citation>
    <PMID>21505041</PMID>
  </reference>
  <reference>
    <citation>Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A. Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One. 2013 Dec 16;8(12):e81629. doi: 10.1371/journal.pone.0081629. eCollection 2013.</citation>
    <PMID>24363812</PMID>
  </reference>
  <reference>
    <citation>Koshy AK, Gudi A, Shah A, Bhide P, Timms P, Homburg R. Pregnancy prognosis in women with anti-Mullerian hormone below the tenth percentile. Gynecol Endocrinol. 2013 Jul;29(7):662-5. doi: 10.3109/09513590.2013.797395.</citation>
    <PMID>23772777</PMID>
  </reference>
  <reference>
    <citation>Seifer DB, Tal O, Wantman E, Edul P, Baker VL. Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimullerian hormone: a multivariate analysis of over 5,000 autologous cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012-2013. Fertil Steril. 2016 Feb;105(2):385-93.e3. doi: 10.1016/j.fertnstert.2015.10.004. Epub 2015 Oct 26.</citation>
    <PMID>26515380</PMID>
  </reference>
  <reference>
    <citation>Broekmans FJ, de Ziegler D, Howles CM, Gougeon A, Trew G, Olivennes F. The antral follicle count: practical recommendations for better standardization. Fertil Steril. 2010 Aug;94(3):1044-51. doi: 10.1016/j.fertnstert.2009.04.040. Epub 2009 Jul 8.</citation>
    <PMID>19589513</PMID>
  </reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 1, 2019</study_first_posted>
  <last_update_submitted>August 4, 2022</last_update_submitted>
  <last_update_submitted_qc>August 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>ART Fertility Clinics LLC</investigator_affiliation>
    <investigator_full_name>Laura Melado</investigator_full_name>
    <investigator_title>IVF Specialist</investigator_title>
  </responsible_party>
  <keyword>IVF</keyword>
  <keyword>AMH isoforms</keyword>
  <keyword>ovarian reserve test</keyword>
  <keyword>poor response</keyword>
  <!-- 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/NCT03826888
org study id: 1807-ABU-055-LM
nct id: NCT03826888
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study wants to evaluate significant clinical impact of different AMH isoforms in serum
      can be present or absent in expected poor responder participants. The specific AMH isoforms
      could therefore be measured in expected poor responder participants in order to obtain a more
      realistic clinical picture and therefore be able to give proper information to the
      participants and selection of medication dose for ovarian stimulation.
The study has a prospective observational multicentric design and the investigators aim to
      investigate the presence of AMH isoforms and the levels of Inhibin B in serum among a
      population of participants with low ovarian reserve (AMH blood test below 1.1 ng/ml).
      Transvaginal scan for AFC and blood drawn from participants will be obtained on day 2-3 of
      menstrual period. The serum will be divided for AMH analysis using different assays: Elecsys
      Cobas assay for AMH and AnshLabs AMH isoforms specific assays (picoAMH 24/32 Pro-Mature,
      24/37 Midpro-Midpro, 17/15 Mature-Mature and 10/24 Pro-Midpro) and AnshLabs Inhibin B ELISA.

      Clinically it is not uncommon to see a discrepancy between the AFC count and the levels of
      AMH; this could be potentially explained by the presence of different AMH isoforms not
      measured with conventional commercial assays. Also, the evaluation of Inhibin B may be
      helpful for ovarian reserve assessment. Quantitation of specific Isoforms of AMH by different
      ELISA methods will investigate a possible relationship(s) between specific isoforms of AMH
      and poor responders.
observational model: Case-Only
time perspective: Prospective
measure: AMH serum levels
time frame: 1 day
description: Differences in AMH serum levels due to the presence of different AMH isoforms when results are compared with AMH measurement in blood performed with Elecsys Cobas AMH assay.
measure: Inhibin B and ovarian reserve markers
time frame: 1 day
description: Correlation between Inhibin B and ovarian reserve markers (AMH serum levels and AFC)
measure: AMH serum and AFC
time frame: 1 day
description: Correlation between AMH serum levels (measured with different ELISA tests) and AFC.
blood specimen
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
gender based: Yes
minimum age: N/A
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Arab Emirates
citation: McLennan IS, Pankhurst MW. Anti-Mullerian hormone is a gonadal cytokine with two circulating forms and cryptic actions. J Endocrinol. 2015 Sep;226(3):R45-57. doi: 10.1530/JOE-15-0206. Epub 2015 Jul 10.
PMID: 26163524
citation: Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP, et al. Isolation of the bovine and human genes for Mullerian inhibiting substance and expression of the human gene in animal cells. Cell. 1986 Jun 6;45(5):685-98. doi: 10.1016/0092-8674(86)90783-x.
PMID: 3754790
citation: Josso N, Belville C, di Clemente N, Picard JY. AMH and AMH receptor defects in persistent Mullerian duct syndrome. Hum Reprod Update. 2005 Jul-Aug;11(4):351-6. doi: 10.1093/humupd/dmi014. Epub 2005 May 5.
PMID: 15878900
citation: Pankhurst MW, McLennan IS. Human blood contains both the uncleaved precursor of anti-Mullerian hormone and a complex of the NH2- and COOH-terminal peptides. Am J Physiol Endocrinol Metab. 2013 Nov 15;305(10):E1241-7. doi: 10.1152/ajpendo.00395.2013. Epub 2013 Sep 17.
PMID: 24045871
citation: Pankhurst MW, Chong YH, McLennan IS. Enzyme-linked immunosorbent assay measurements of antimullerian hormone (AMH) in human blood are a composite of the uncleaved and bioactive cleaved forms of AMH. Fertil Steril. 2014 Mar;101(3):846-50. doi: 10.1016/j.fertnstert.2013.12.009. Epub 2014 Jan 11.
PMID: 24424371
citation: Pankhurst MW, Clark CA, Zarek J, Laskin CA, McLennan IS. Changes in Circulating ProAMH and Total AMH during Healthy Pregnancy and Post-Partum: A Longitudinal Study. PLoS One. 2016 Sep 9;11(9):e0162509. doi: 10.1371/journal.pone.0162509. eCollection 2016.
PMID: 27612037
citation: Robertson DM, Kumar A, Kalra B, Shah S, Pruysers E, Vanden Brink H, Chizen D, Visser JA, Themmen AP, Baerwald A. Detection of serum antimullerian hormone in women approaching menopause using sensitive antimullerian hormone enzyme-linked immunosorbent assays. Menopause. 2014 Dec;21(12):1277-86. doi: 10.1097/GME.0000000000000244.
PMID: 24781853
citation: Robertson DM, Hale GE, Fraser IS, Hughes CL, Burger HG. Changes in serum antimullerian hormone levels across the ovulatory menstrual cycle in late reproductive age. Menopause. 2011 May;18(5):521-4. doi: 10.1097/gme.0b013e3181f8d9e0.
PMID: 21178792
citation: Gnoth C, Schuring AN, Friol K, Tigges J, Mallmann P, Godehardt E. Relevance of anti-Mullerian hormone measurement in a routine IVF program. Hum Reprod. 2008 Jun;23(6):1359-65. doi: 10.1093/humrep/den108. Epub 2008 Apr 2.
PMID: 18387961
citation: Ferraretti AP, La Marca A, Fauser BC, Tarlatzis B, Nargund G, Gianaroli L; ESHRE working group on Poor Ovarian Response Definition. ESHRE consensus on the definition of 'poor response' to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011 Jul;26(7):1616-24. doi: 10.1093/humrep/der092. Epub 2011 Apr 19.
PMID: 21505041
citation: Kedem A, Haas J, Geva LL, Yerushalmi G, Gilboa Y, Kanety H, Hanochi M, Maman E, Hourvitz A. Ongoing pregnancy rates in women with low and extremely low AMH levels. A multivariate analysis of 769 cycles. PLoS One. 2013 Dec 16;8(12):e81629. doi: 10.1371/journal.pone.0081629. eCollection 2013.
PMID: 24363812
citation: Koshy AK, Gudi A, Shah A, Bhide P, Timms P, Homburg R. Pregnancy prognosis in women with anti-Mullerian hormone below the tenth percentile. Gynecol Endocrinol. 2013 Jul;29(7):662-5. doi: 10.3109/09513590.2013.797395.
PMID: 23772777
citation: Seifer DB, Tal O, Wantman E, Edul P, Baker VL. Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimullerian hormone: a multivariate analysis of over 5,000 autologous cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012-2013. Fertil Steril. 2016 Feb;105(2):385-93.e3. doi: 10.1016/j.fertnstert.2015.10.004. Epub 2015 Oct 26.
PMID: 26515380
citation: Broekmans FJ, de Ziegler D, Howles CM, Gougeon A, Trew G, Olivennes F. The antral follicle count: practical recommendations for better standardization. Fertil Steril. 2010 Aug;94(3):1044-51. doi: 10.1016/j.fertnstert.2009.04.040. Epub 2009 Jul 8.
PMID: 19589513
responsible party type: Principal Investigator
investigator affiliation: ART Fertility Clinics LLC
investigator full name: Laura Melado
investigator title: IVF Specialist