xml: <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/NCT06026553</url>
    </required_header>
    <id_info>
      <org_study_id>TORA-IVF-01</org_study_id>
      <nct_id>NCT06026553</nct_id>
    </id_info>
    <brief_title>Assessing Ketorolac (Toradol) at Oocyte Retrieval</brief_title>
    <acronym>Alleviate</acronym>
    <official_title>A Randomized Blinded Placebo Controlled Trial Assessing Ketorolac (Toradol) at Oocyte Retrieval</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Shady Grove Fertility Reproductive Science Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Shady Grove Fertility Reproductive Science Center</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        To determine if a nonsteroidal anti-inflammatory drug (NSAID), Ketorolac (Toradol), can&#xD;
        improve pain control and decrease narcotic use after undergoing egg retrieval.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Postoperative pain control is an essential component to any surgical procedure. Surgery&#xD;
        represents a time during which opioid-naïve patients may be exposed to narcotics, risking&#xD;
        opioid related complications and future opioid-use disorder. Approximately 150,000 oocyte&#xD;
        retrievals are performed per year in the United States, according to the 2017 Assisted&#xD;
        Reproductive Technology National Summary Report. A reduction in exposure to narcotics in this&#xD;
        field has significant public health implications, particularly given that approximately 6% of&#xD;
        new persistent opioid use occurs following minor surgical procedures.&#xD;
  &#xD;
        Ketorolac (Toradol) has been demonstrated to be a safe and efficacious agent to achieve pain&#xD;
        control postoperatively with no significant increase in adverse events.&#xD;
  &#xD;
        The purpose of this prospective randomized blinded placebo controlled trial is to determine&#xD;
        if a nonsteroidal anti-inflammatory drug (NSAID), Ketorolac (Toradol), can improve pain&#xD;
        control and decrease narcotic use after undergoing egg retrieval.&#xD;
  &#xD;
        Approximately 400 women (n=200 in each arm) will be enrolled according to the&#xD;
        inclusion/exclusion criteria among patients of Shady Grove Fertility. Participants will&#xD;
        undergo a standard in vitro fertilization cycle (IVF) followed by egg retrieval (ER).&#xD;
        Participants will be randomized to receive either IV ketorolac or IV placebo at the&#xD;
        conclusion of the egg retrieval, administered by the anesthesia provider. All enrolled&#xD;
        patients will receive standard post-operative pain management. The investigational component&#xD;
        of this study lies in assessing post-operative pain control in the immediate post-operative&#xD;
        period and in the post-operative period after discharge as reflected by pain scores and&#xD;
        narcotic medication usage.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 10, 2022</start_date>
    <completion_date type="Anticipated">January 2025</completion_date>
    <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
    <phase>Phase 1</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>Supportive Care</primary_purpose>
      <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
      <masking_description>Allocation group will not be disclosed to the patient or the physician or the nurse or the outcome assessor. The anesthesia provider administering the IV Ketorolac or Placebo will be unblinded.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Administration of IV narcotic for rescue analgesia during recovery in the post anesthesia care unit (PACU)</measure>
      <time_frame>Oocyte retrieval procedure day</time_frame>
      <description>The primary objective is to evaluate the use of ketorolac as a safe and effective analgesic after transvaginal oocyte retrieval (TVOR) by assessing the number of patients requiring additional analgesia with IV narcotic during recovery in the post anesthesia care unit (PACU).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Dose of narcotic for rescue analgesia during recovery in the PACU</measure>
      <time_frame>Oocyte retrieval procedure day</time_frame>
      <description>Dose of narcotic administered for rescue analgesia during recovery in the PACU</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Type of narcotic for rescue analgesia during recovery in the PACU</measure>
      <time_frame>Oocyte retrieval procedure day</time_frame>
      <description>Type of narcotic administered for rescue analgesia during recovery in the PACU</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intensity of pain at baseline</measure>
      <time_frame>Oocyte retrieval procedure day</time_frame>
      <description>Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): baseline pain score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intensity of pain in PACU</measure>
      <time_frame>Oocyte retrieval procedure day</time_frame>
      <description>Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): PACU pain scores (scored 0-10)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intensity of pain after discharge</measure>
      <time_frame>From oocyte retrieval procedure day up to 1 week post oocyte retrieval</time_frame>
      <description>Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): Home pain scores (scored 0-10)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Home narcotic use</measure>
      <time_frame>From oocyte retrieval procedure day up to 1 week post oocyte retrieval</time_frame>
      <description>Home post-operative narcotic use (recorded as number of pills)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of complications and adverse events</measure>
      <time_frame>From oocyte retrieval procedure day up to 1 week post oocyte retrieval</time_frame>
      <description>Data will be collected on the oocyte retrieval procedure including complications and adverse events in the intra-operative and post-operative periods</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Biochemical pregnancy rate for patients who proceed to a fresh embryo transfer.</measure>
      <time_frame>From date of randomization until ~10 days following embryo transfer</time_frame>
      <description>Biochemical pregnancy is defined as the detection of beta HCG above 5 IU/L</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical pregnancy rate for patients who proceed to a fresh embryo transfer.</measure>
      <time_frame>From date of randomization until 5-8 weeks estimated gestational age</time_frame>
      <description>Clinical pregnancy is defined as the presence of a gestational sac(s)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Implantation rate for patients who proceed to a fresh embryo transfer.</measure>
      <time_frame>From date of randomization until 7-8 weeks estimated gestational age</time_frame>
      <description>Implantation rate is defined as the maximum number of gestational sacs per patient</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Ongoing implantation rate for patients who proceed to a fresh embryo transfer.</measure>
      <time_frame>From date of randomization until 7-8 weeks estimated gestational age</time_frame>
      <description>The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pregnancy loss rate for patients who proceed to a fresh embryo transfer.</measure>
      <time_frame>From date of randomization until pregnancy loss, assessed up to 11 months</time_frame>
      <description>Miscarriage; either biochemical or clinical pregnancy loss. Biochemical pregnancy loss is defined as initial positive beta HCG that did not progress to clinical pregnancy. Clinical pregnancy loss is defined as clinical pregnancy not progressing to live birth. Total pregnancy loss is defined as biochemical and clinical pregnancy loss (initial positive beta HCG that did not progress to live birth).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Live birth rate for patients who proceed to a fresh embryo transfer.</measure>
      <time_frame>From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater, assessed up to 11 months</time_frame>
      <description>Live birth is defined as birth of a liveborn infant at an estimated gestational age of at least 23 weeks or greater.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">400</enrollment>
    <condition>Infertility</condition>
    <condition>Infertility, Female</condition>
    <condition>Oocyte Retrieval</condition>
    <condition>Postoperative Pain</condition>
    <condition>Embryo Transfer</condition>
    <arm_group>
      <arm_group_label>Standard post-operative pain management + Ketorolac (Toradol)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Subject will undergo an IVF cycle with ovarian hyperstimulation and oocyte retrieval. Standard protocols will be used for both study groups and involve administration of gonadotropins to stimulate ovarian follicle growth and regular monitoring with ultrasound and serum estradiol and progesterone levels until follicles reach a desired size. Human Chorionic Gonadotropin (HCG) or leuprolide acetate will be administered to trigger final oocyte maturation prior to oocyte retrieval under anesthesia. On the day of oocyte retrieval, the anesthesia provider will provide syringes of IV ketorolac (30 mg if ≥50 kg or 15 mg if &lt;50 kg per manufacturer dosing) or IV placebo (saline). If assigned to the study arm, IV ketorolac will be administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. Patients will be contacted post-operatively, to access pain scores and record the amount of the prescribed narcotic medications utilized since discharge.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard post-operative pain management + Placebo (saline)</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Subject will undergo an IVF cycle with ovarian hyperstimulation and oocyte retrieval. Standard protocols will be used for both study groups and involve administration of gonadotropins to stimulate ovarian follicle growth and regular monitoring with ultrasound and serum estradiol and progesterone levels until follicles reach a desired size. HCG or leuprolide acetate will be administered to trigger final oocyte maturation prior to oocyte retrieval under anesthesia. On the day of oocyte retrieval, the anesthesia provider will provide syringes of IV ketorolac (30 mg if ≥50 kg or 15 mg if &lt;50 kg per manufacturer dosing) or IV placebo (saline). If assigned to the control arm, IV placebo (saline) will be administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. Patients will be contacted post-operatively, to access pain scores and record the amount of the prescribed narcotic medications utilized since discharge.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ketorolac (Toradol)</intervention_name>
      <description>IV Ketorolac (Toradol) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.</description>
      <arm_group_label>Standard post-operative pain management + Ketorolac (Toradol)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo (saline)</intervention_name>
      <description>IV Placebo (saline) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.</description>
      <arm_group_label>Standard post-operative pain management + Placebo (saline)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Signed informed consent&#xD;
  &#xD;
            2. Females over 18 years of age who are scheduled to undergo oocyte retrieval&#xD;
  &#xD;
            3. Patients must be able to read and understand written English or have an appropriate&#xD;
               certified medical translator available.&#xD;
  &#xD;
            4. Standard eligibility criteria to undergo IVF and embryo transfer at Shady Grove&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Known allergy to ketorolac&#xD;
  &#xD;
            2. Those with known medical conditions precluding them from ketorolac use (active peptic&#xD;
               ulcer disease, recent or history of hemorrhage or perforation, known renal or hepatic&#xD;
               insufficiency, suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis,&#xD;
               bleeding disorders, recent myocardial infarction, or stroke.)&#xD;
  &#xD;
            3. BMI ≥ 40 kg/m2&#xD;
  &#xD;
            4. History of substance abuse&#xD;
  &#xD;
            5. Chronic opioid use&#xD;
  &#xD;
            6. Transabdominal oocyte retrieval&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <gender_based>Yes</gender_based>
      <gender_description>Only female subjects will be recruited for this study as an oocyte retrieval requires ovary(ies) to be present and therefore this is only possible in the biological female sex.</gender_description>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>45 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Kathleen Devine, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shady Grove Fertility Reproductive Science Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tasha Newsome</last_name>
      <phone>(301)545-1289</phone>
      <email>tasha.newsome@sgfertility.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shady Grove Fertility Reproductive Science Center</name>
        <address>
          <city>Rockville</city>
          <state>Maryland</state>
          <zip>20850</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tasha Newsome</last_name>
        <phone>301-545-1289</phone>
        <email>tasha.newsome@sgfertility.com</email>
      </contact>
      <investigator>
        <last_name>Kathleen Devine, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Shady Grove Fertility Reproductive Science Center</name>
        <address>
          <city>Fairfax</city>
          <state>Virginia</state>
          <zip>22031</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tasha Newsome</last_name>
        <phone>301-545-1289</phone>
        <email>tasha.newsome@sgfertility.com</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Waljee JF, Li L, Brummett CM, Englesbe MJ. Iatrogenic Opioid Dependence in the United States: Are Surgeons the Gatekeepers? Ann Surg. 2017 Apr;265(4):728-730. doi: 10.1097/SLA.0000000000001904. No abstract available.</citation>
      <PMID>27429023</PMID>
    </reference>
    <reference>
      <citation>Centers for Disease Control and Prevention. 2017 Assisted Reproductive Technology National Summary Report. US Dept of Health and Human Services; 2021.</citation>
    </reference>
    <reference>
      <citation>Wilson N, Kariisa M, Seth P, Smith H 4th, Davis NL. Drug and Opioid-Involved Overdose Deaths - United States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):290-297. doi: 10.15585/mmwr.mm6911a4.</citation>
      <PMID>32191688</PMID>
    </reference>
    <reference>
      <citation>Kiani Z, Simbar M, Hajian S, Zayeri F. The prevalence of depression symptoms among infertile women: a systematic review and meta-analysis. Fertil Res Pract. 2021 Mar 4;7(1):6. doi: 10.1186/s40738-021-00098-3.</citation>
      <PMID>33663615</PMID>
    </reference>
    <reference>
      <citation>Kato T, Sampei M, Saito K, Morisaki N, Urayama KY. Depressive symptoms, anxiety, and quality of life of Japanese women at initiation of ART treatment. Sci Rep. 2021 Apr 6;11(1):7538. doi: 10.1038/s41598-021-87057-6. Erratum In: Sci Rep. 2021 Nov 17;11(1):22793.</citation>
      <PMID>33824373</PMID>
    </reference>
    <reference>
      <citation>Walter JR. Ketorolac use after oocyte retrieval: doing our part to combat the opioid crisis. F S Rep. 2021 Mar 12;2(2):142-143. doi: 10.1016/j.xfre.2021.03.001. eCollection 2021 Jun. No abstract available.</citation>
      <PMID>34278342</PMID>
    </reference>
    <reference>
      <citation>Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):116S-121S.</citation>
      <PMID>2082307</PMID>
    </reference>
    <reference>
      <citation>Gobble RM, Hoang HLT, Kachniarz B, Orgill DP. Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials. Plast Reconstr Surg. 2014 Mar;133(3):741-755. doi: 10.1097/01.prs.0000438459.60474.b5.</citation>
      <PMID>24572864</PMID>
    </reference>
    <reference>
      <citation>Greer IA. Effects of ketorolac tromethamine on hemostasis. Pharmacotherapy. 1990;10(6 ( Pt 2)):71S-76S.</citation>
      <PMID>2082316</PMID>
    </reference>
    <reference>
      <citation>Maslin B, Lipana L, Roth B, Kodumudi G, Vadivelu N. Safety Considerations in the Use of Ketorolac for Postoperative Pain. Curr Drug Saf. 2017;12(1):67-73. doi: 10.2174/1574886311666160719154420.</citation>
      <PMID>27440142</PMID>
    </reference>
    <reference>
      <citation>Kang J, Chapdelaine P, Laberge PY, Fortier MA. Functional characterization of prostaglandin transporter and terminal prostaglandin synthases during decidualization of human endometrial stromal cells. Hum Reprod. 2006 Mar;21(3):592-9. doi: 10.1093/humrep/dei400. Epub 2005 Dec 8.</citation>
      <PMID>16339169</PMID>
    </reference>
    <reference>
      <citation>Mesen TB, Kacemi-Bourhim L, Marshburn PB, Usadi RS, Matthews M, Norton HJ, Hurst BS. The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval. Fertil Steril. 2013 Sep;100(3):725-8. doi: 10.1016/j.fertnstert.2013.04.048. Epub 2013 May 28.</citation>
      <PMID>23721715</PMID>
    </reference>
    <reference>
      <citation>Seidler EA, Vaughan DA, Leung AQ, Sakkas D, Ryley DA, Penzias AS. Routine ketorolac at oocyte retrieval decreases postoperative narcotic use by more than 50. F S Rep. 2021 Feb 10;2(2):156-160. doi: 10.1016/j.xfre.2021.02.003. eCollection 2021 Jun.</citation>
      <PMID>34278347</PMID>
    </reference>
    <reference>
      <citation>Siristatidis CS, Basios G, Pergialiotis V, Vogiatzi P. Aspirin for in vitro fertilisation. Cochrane Database Syst Rev. 2016 Nov 3;11(11):CD004832. doi: 10.1002/14651858.CD004832.pub4.</citation>
      <PMID>27807847</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 7, 2023</study_first_posted>
    <last_update_submitted>August 30, 2023</last_update_submitted>
    <last_update_submitted_qc>August 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Infertility, Female</keyword>
    <keyword>In Vitro Fertilization</keyword>
    <keyword>IVF</keyword>
    <keyword>Oocyte Retrieval</keyword>
    <keyword>Postoperative Pain Control</keyword>
    <keyword>NSAID</keyword>
    <keyword>Ketorolac</keyword>
    <keyword>Non-Narcotic Analgesia</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Infertility</mesh_term>
      <mesh_term>Infertility, Female</mesh_term>
      <mesh_term>Pain, Postoperative</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ketorolac</mesh_term>
      <mesh_term>Ketorolac Tromethamine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06026553
  org study id: TORA-IVF-01
  nct id: NCT06026553
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  To determine if a nonsteroidal anti-inflammatory drug (NSAID), Ketorolac (Toradol), can
        improve pain control and decrease narcotic use after undergoing egg retrieval.
  Postoperative pain control is an essential component to any surgical procedure. Surgery
        represents a time during which opioid-naïve patients may be exposed to narcotics, risking
        opioid related complications and future opioid-use disorder. Approximately 150,000 oocyte
        retrievals are performed per year in the United States, according to the 2017 Assisted
        Reproductive Technology National Summary Report. A reduction in exposure to narcotics in this
        field has significant public health implications, particularly given that approximately 6% of
        new persistent opioid use occurs following minor surgical procedures.
  
        Ketorolac (Toradol) has been demonstrated to be a safe and efficacious agent to achieve pain
        control postoperatively with no significant increase in adverse events.
  
        The purpose of this prospective randomized blinded placebo controlled trial is to determine
        if a nonsteroidal anti-inflammatory drug (NSAID), Ketorolac (Toradol), can improve pain
        control and decrease narcotic use after undergoing egg retrieval.
  
        Approximately 400 women (n=200 in each arm) will be enrolled according to the
        inclusion/exclusion criteria among patients of Shady Grove Fertility. Participants will
        undergo a standard in vitro fertilization cycle (IVF) followed by egg retrieval (ER).
        Participants will be randomized to receive either IV ketorolac or IV placebo at the
        conclusion of the egg retrieval, administered by the anesthesia provider. All enrolled
        patients will receive standard post-operative pain management. The investigational component
        of this study lies in assessing post-operative pain control in the immediate post-operative
        period and in the post-operative period after discharge as reflected by pain scores and
        narcotic medication usage.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Supportive Care
  masking: Triple (Participant, Care Provider, Outcomes Assessor)
  masking description: Allocation group will not be disclosed to the patient or the physician or the nurse or the outcome assessor. The anesthesia provider administering the IV Ketorolac or Placebo will be unblinded.
  measure: Administration of IV narcotic for rescue analgesia during recovery in the post anesthesia care unit (PACU)
  time frame: Oocyte retrieval procedure day
  description: The primary objective is to evaluate the use of ketorolac as a safe and effective analgesic after transvaginal oocyte retrieval (TVOR) by assessing the number of patients requiring additional analgesia with IV narcotic during recovery in the post anesthesia care unit (PACU).
  measure: Dose of narcotic for rescue analgesia during recovery in the PACU
  time frame: Oocyte retrieval procedure day
  description: Dose of narcotic administered for rescue analgesia during recovery in the PACU
  measure: Type of narcotic for rescue analgesia during recovery in the PACU
  time frame: Oocyte retrieval procedure day
  description: Type of narcotic administered for rescue analgesia during recovery in the PACU
  measure: Intensity of pain at baseline
  time frame: Oocyte retrieval procedure day
  description: Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): baseline pain score
  measure: Intensity of pain in PACU
  time frame: Oocyte retrieval procedure day
  description: Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): PACU pain scores (scored 0-10)
  measure: Intensity of pain after discharge
  time frame: From oocyte retrieval procedure day up to 1 week post oocyte retrieval
  description: Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): Home pain scores (scored 0-10)
  measure: Home narcotic use
  time frame: From oocyte retrieval procedure day up to 1 week post oocyte retrieval
  description: Home post-operative narcotic use (recorded as number of pills)
  measure: Incidence of complications and adverse events
  time frame: From oocyte retrieval procedure day up to 1 week post oocyte retrieval
  description: Data will be collected on the oocyte retrieval procedure including complications and adverse events in the intra-operative and post-operative periods
  measure: Biochemical pregnancy rate for patients who proceed to a fresh embryo transfer.
  time frame: From date of randomization until ~10 days following embryo transfer
  description: Biochemical pregnancy is defined as the detection of beta HCG above 5 IU/L
  measure: Clinical pregnancy rate for patients who proceed to a fresh embryo transfer.
  time frame: From date of randomization until 5-8 weeks estimated gestational age
  description: Clinical pregnancy is defined as the presence of a gestational sac(s)
  measure: Implantation rate for patients who proceed to a fresh embryo transfer.
  time frame: From date of randomization until 7-8 weeks estimated gestational age
  description: Implantation rate is defined as the maximum number of gestational sacs per patient
  measure: Ongoing implantation rate for patients who proceed to a fresh embryo transfer.
  time frame: From date of randomization until 7-8 weeks estimated gestational age
  description: The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred
  measure: Pregnancy loss rate for patients who proceed to a fresh embryo transfer.
  time frame: From date of randomization until pregnancy loss, assessed up to 11 months
  description: Miscarriage; either biochemical or clinical pregnancy loss. Biochemical pregnancy loss is defined as initial positive beta HCG that did not progress to clinical pregnancy. Clinical pregnancy loss is defined as clinical pregnancy not progressing to live birth. Total pregnancy loss is defined as biochemical and clinical pregnancy loss (initial positive beta HCG that did not progress to live birth).
  measure: Live birth rate for patients who proceed to a fresh embryo transfer.
  time frame: From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater, assessed up to 11 months
  description: Live birth is defined as birth of a liveborn infant at an estimated gestational age of at least 23 weeks or greater.
  arm group label: Standard post-operative pain management + Ketorolac (Toradol)
  arm group type: Experimental
  description: Subject will undergo an IVF cycle with ovarian hyperstimulation and oocyte retrieval. Standard protocols will be used for both study groups and involve administration of gonadotropins to stimulate ovarian follicle growth and regular monitoring with ultrasound and serum estradiol and progesterone levels until follicles reach a desired size. Human Chorionic Gonadotropin (HCG) or leuprolide acetate will be administered to trigger final oocyte maturation prior to oocyte retrieval under anesthesia. On the day of oocyte retrieval, the anesthesia provider will provide syringes of IV ketorolac (30 mg if ≥50 kg or 15 mg if <50 kg per manufacturer dosing) or IV placebo (saline). If assigned to the study arm, IV ketorolac will be administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. Patients will be contacted post-operatively, to access pain scores and record the amount of the prescribed narcotic medications utilized since discharge.
  arm group label: Standard post-operative pain management + Placebo (saline)
  arm group type: Placebo Comparator
  description: Subject will undergo an IVF cycle with ovarian hyperstimulation and oocyte retrieval. Standard protocols will be used for both study groups and involve administration of gonadotropins to stimulate ovarian follicle growth and regular monitoring with ultrasound and serum estradiol and progesterone levels until follicles reach a desired size. HCG or leuprolide acetate will be administered to trigger final oocyte maturation prior to oocyte retrieval under anesthesia. On the day of oocyte retrieval, the anesthesia provider will provide syringes of IV ketorolac (30 mg if ≥50 kg or 15 mg if <50 kg per manufacturer dosing) or IV placebo (saline). If assigned to the control arm, IV placebo (saline) will be administered by the anesthesia provider. All enrolled patients will receive standard post-operative pain management. Patients will be contacted post-operatively, to access pain scores and record the amount of the prescribed narcotic medications utilized since discharge.
  intervention type: Drug
  intervention name: Ketorolac (Toradol)
  description: IV Ketorolac (Toradol) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.
  arm group label: Standard post-operative pain management + Ketorolac (Toradol)
  intervention type: Other
  intervention name: Placebo (saline)
  description: IV Placebo (saline) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.
  arm group label: Standard post-operative pain management + Placebo (saline)
  criteria: 
  gender: Female
  gender based: Yes
  gender description: Only female subjects will be recruited for this study as an oocyte retrieval requires ovary(ies) to be present and therefore this is only possible in the biological female sex.
  minimum age: 18 Years
  maximum age: 45 Years
  healthy volunteers: No
  last name: Kathleen Devine, MD
  role: Principal Investigator
  affiliation: Shady Grove Fertility Reproductive Science Center
  last name: Tasha Newsome
  phone: (301)545-1289
  email: tasha.newsome@sgfertility.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  country: United States
  citation: Waljee JF, Li L, Brummett CM, Englesbe MJ. Iatrogenic Opioid Dependence in the United States: Are Surgeons the Gatekeepers? Ann Surg. 2017 Apr;265(4):728-730. doi: 10.1097/SLA.0000000000001904. No abstract available.
  PMID: 27429023
  citation: Centers for Disease Control and Prevention. 2017 Assisted Reproductive Technology National Summary Report. US Dept of Health and Human Services; 2021.
  citation: Wilson N, Kariisa M, Seth P, Smith H 4th, Davis NL. Drug and Opioid-Involved Overdose Deaths - United States, 2017-2018. MMWR Morb Mortal Wkly Rep. 2020 Mar 20;69(11):290-297. doi: 10.15585/mmwr.mm6911a4.
  PMID: 32191688
  citation: Kiani Z, Simbar M, Hajian S, Zayeri F. The prevalence of depression symptoms among infertile women: a systematic review and meta-analysis. Fertil Res Pract. 2021 Mar 4;7(1):6. doi: 10.1186/s40738-021-00098-3.
  PMID: 33663615
  citation: Kato T, Sampei M, Saito K, Morisaki N, Urayama KY. Depressive symptoms, anxiety, and quality of life of Japanese women at initiation of ART treatment. Sci Rep. 2021 Apr 6;11(1):7538. doi: 10.1038/s41598-021-87057-6. Erratum In: Sci Rep. 2021 Nov 17;11(1):22793.
  PMID: 33824373
  citation: Walter JR. Ketorolac use after oocyte retrieval: doing our part to combat the opioid crisis. F S Rep. 2021 Mar 12;2(2):142-143. doi: 10.1016/j.xfre.2021.03.001. eCollection 2021 Jun. No abstract available.
  PMID: 34278342
  citation: Brown CR, Moodie JE, Wild VM, Bynum LJ. Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain. Pharmacotherapy. 1990;10(6 ( Pt 2)):116S-121S.
  PMID: 2082307
  citation: Gobble RM, Hoang HLT, Kachniarz B, Orgill DP. Ketorolac does not increase perioperative bleeding: a meta-analysis of randomized controlled trials. Plast Reconstr Surg. 2014 Mar;133(3):741-755. doi: 10.1097/01.prs.0000438459.60474.b5.
  PMID: 24572864
  citation: Greer IA. Effects of ketorolac tromethamine on hemostasis. Pharmacotherapy. 1990;10(6 ( Pt 2)):71S-76S.
  PMID: 2082316
  citation: Maslin B, Lipana L, Roth B, Kodumudi G, Vadivelu N. Safety Considerations in the Use of Ketorolac for Postoperative Pain. Curr Drug Saf. 2017;12(1):67-73. doi: 10.2174/1574886311666160719154420.
  PMID: 27440142
  citation: Kang J, Chapdelaine P, Laberge PY, Fortier MA. Functional characterization of prostaglandin transporter and terminal prostaglandin synthases during decidualization of human endometrial stromal cells. Hum Reprod. 2006 Mar;21(3):592-9. doi: 10.1093/humrep/dei400. Epub 2005 Dec 8.
  PMID: 16339169
  citation: Mesen TB, Kacemi-Bourhim L, Marshburn PB, Usadi RS, Matthews M, Norton HJ, Hurst BS. The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval. Fertil Steril. 2013 Sep;100(3):725-8. doi: 10.1016/j.fertnstert.2013.04.048. Epub 2013 May 28.
  PMID: 23721715
  citation: Seidler EA, Vaughan DA, Leung AQ, Sakkas D, Ryley DA, Penzias AS. Routine ketorolac at oocyte retrieval decreases postoperative narcotic use by more than 50. F S Rep. 2021 Feb 10;2(2):156-160. doi: 10.1016/j.xfre.2021.02.003. eCollection 2021 Jun.
  PMID: 34278347
  citation: Siristatidis CS, Basios G, Pergialiotis V, Vogiatzi P. Aspirin for in vitro fertilisation. Cochrane Database Syst Rev. 2016 Nov 3;11(11):CD004832. doi: 10.1002/14651858.CD004832.pub4.
  PMID: 27807847
  responsible party type: Sponsor
  mesh term: Infertility
  mesh term: Infertility, Female
  mesh term: Pain, Postoperative
  mesh term: Ketorolac
  mesh term: Ketorolac Tromethamine
  sharing ipd: No