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Ketorolac is a medication often used to relieve pain after surgery. In the past, infertility doctors have been cautious about using ketorolac after egg retrieval for patients planning a fresh embryo transfer (usually done 5 days later). The concern was that ketorolac might increase the risk of bleeding or reduce the chances of the embryo implanting in the uterus. This concern comes from how ketorolac works-it blocks certain chemicals in the body (like prostaglandins and thromboxane) that help with blood clotting and play a role in early pregnancy.
However, a large review of past studies found no real evidence that ketorolac increases bleeding risk. In fact, ketorolac is now routinely used for pain relief in IVF cycles where embryos are frozen and not transferred right away. More recent studies from Boston and Chapel Hill have shown that ketorolac provides better pain control and does not appear to harm IVF outcomes, even when embryos are transferred fresh (within the same cycle).
Despite these encouraging findings, many IVF clinics still avoid using ketorolac during fresh cycles because of the theoretical concerns. That's why we need stronger, higher-quality research.
This study aims to fill that gap by conducting a double-blind randomized controlled trial to find out whether giving ketorolac through an IV after egg retrieval affects important IVF outcomes-especially the chance of implantation and live birth-in patients undergoing fresh embryo transfers. Patients who choose to join the study will randomly be placed into one of two groups. One group will get ketorolac (a pain medicine) after an IVF egg retrieval. The other group will not get ketorolac after egg retrieval. Everything else in their IVF care will stay the same as it normally would.
Primary outcome will be implantation rate following fresh embryo transfers in patients receiving ketorolac (30mg IV) vs no ketorolac for post-retrieval analgesia.
Secondary outcomes will include pain scale, narcotics required, time to discharge, need for evaluation w/in 24 hours for pain/bleeding, clinical pregnancy rates, miscarriage rates, and live birth rates following fresh embryo transfers in patients receiving ketorolac vs no ketorolac for post-retrieval analgesia.
Study Design: double-blind randomized controlled trial Intervention: Ketorolac (30mg intravenous) administration in the immediate post-operative period prior to leaving the procedure room and while patient is still under sedation
Allocation method: 1:1 statistician generated block randomization (blocks of 2, 4, and 6). Patients will be randomized immediately following consent and enrollment.
Materials and Methods: Patients undergoing an IVF autologous cycle at our institution where the female patient is planning on proceeding with a fresh embryo transfer 5 days following ultrasound guided oocyte retrieval will be recruited. Patients may undergo any of our standard controlled ovarian hyperstimulation protocols.
On the day of egg retrieval patients will:
Patients IVF care will otherwise remain the same as planned, including:
Investigators will continue to review and collect data from patients' medical records for up to 45 weeks. This will include demographic and medical information, including, but not limited to:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IV Ketorolac | Experimental | Participants randomized to this arm will receive 30mg IV Ketorolac at the conclusion of their oocyte retrieval. |
|
| No IV Ketorolac | No Intervention | Participants randomized to this arm will not receive IV Ketorolac at the conclusion of their oocyte retrieval. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketorolac 30 mg IV | Drug | We will be evaluating the effect of post-oocyte retrieval ketorolac administration on clinical outcomes in fresh embryo transfer cycles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Implantation Rate | Implantation rate following fresh embryo transfers in patients receiving ketorolac vs no ketorolac for post-retrieval analgesia. We define implantation rate as the proportion of transferred embryos which resulted in fetal heartbeat seen on ultrasound per patient. | From enrollment to the time of confirmation of pregnancy ultrasound at ~6 weeks post-oocyte retrieval (with or without administration of IV Ketorolac) . |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Pregnancy Rate | Clinical pregnancy rate is defined as the proportion of patients who had an embryo transfer which resulted in a pregnancy confirmed by an increasing level of human Chorionic Gonadotropin (hCG) and the presence of a gestational sac detected by ultrasound. | From enrollment to the time of confirmation of pregnancy ultrasound at ~6 weeks post-oocyte retrieval (with or without administration of IV Ketorolac) . |
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Inclusion Criteria:
Exclusion Criteria:
-allergies or medical contraindications to NSAIDs
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jessica Kresowik, MD | Contact | 563-355-2244 | jessica-kresowik@uiowa.edu |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UI Health Care Center for Advanced Reproductive Care | Recruiting | Iowa City | Iowa | 52245 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23721715 | Background | 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. | |
| 24572864 | Background | 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. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Aug 27, 2025 | Sep 5, 2025 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D007246 | Infertility |
| D010149 | Pain, Postoperative |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D020910 | Ketorolac |
| ID | Term |
|---|---|
| D007213 | Indomethacin |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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Participant, investigator, IVF provider, nursing team, and all members involved in assessing outcomes will be blinded. Patient will be under anesthetic influence and be unaware of medication administration. Recovery nurse and surgeon will not be aware or informed of treatment arm.
Anesthesia will be unblinded but will not inform any other members of the medical team whether or not patient received ketorolac.
| Miscarriage Rate | Miscarriage rate is defined as the percentage of patients with miscarriage after a clinical pregnancy. | From date of enrollment through first documented instance of miscarriage up to 40 weeks. |
| Live Birth Rate | Live birth rate is defined as percentage of patients who had a transfer which resulted in a live birth. | From enrollment to the end of pregnancy (~40 weeks) resulting from fresh embryo transfer following the oocyte retrieval in which patient received IV Ketorolac or no IV Ketorolac. |
| Post-operative Pain | In the immediate post-operative period, pain will be assessed per standard practice using the visual analog scale. The visual analog scale is used to assess pain on a scale of 0 to 10 with 0 being no pain and 10 being worst pain. | From enrollment until the time of discharge from oocyte retrieval (~2.5 hours). |
| 27429023 | Background | 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. |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D006571 | Heterocyclic Compounds |