Assessing Ketorolac (Toradol) at Oocyte Retrieval (Alleviate)

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.

Infertility, Female, In Vitro Fertilization, IVF, Oocyte Retrieval, Postoperative Pain Control, NSAID, Ketorolac, Non-Narcotic Analgesia

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.

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.

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.

IV Ketorolac (Toradol) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.

IV Placebo (saline) will be administered at conclusion of oocyte retrieval. All enrolled patients will receive standard post-operative pain management.

Administration of IV narcotic for rescue analgesia during recovery in the post anesthesia care unit (PACU)

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).

Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): PACU pain scores (scored 0-10)

Pain (measured on a scale of 0 (no pain) to 10 (worst pain imaginable)): Home pain scores (scored 0-10)

Data will be collected on the oocyte retrieval procedure including complications and adverse events in the intra-operative and post-operative periods

The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred

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).

Live birth is defined as birth of a liveborn infant at an estimated gestational age of at least 23 weeks or greater.

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

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.

Inclusion Criteria: Signed informed consent Females over 18 years of age who are scheduled to undergo oocyte retrieval Patients must be able to read and understand written English or have an appropriate certified medical translator available. Standard eligibility criteria to undergo IVF and embryo transfer at Shady Grove Exclusion Criteria: Known allergy to ketorolac Those with known medical conditions precluding them from ketorolac use (active peptic ulcer disease, recent or history of hemorrhage or perforation, known renal or hepatic insufficiency, suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, bleeding disorders, recent myocardial infarction, or stroke.) BMI ≥ 40 kg/m2 History of substance abuse Chronic opioid use Transabdominal oocyte retrieval

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