Fresh Embryo Transfer

This prospective observational study will include women undergoing IVF treatment with a GnRH antagonist protocol and fresh embryo transfer at the IVF unit of Shaare Zedek Medical Center. Patients will undergo controlled ovarian stimulation followed by ovulation triggering with hCG, GnRH agonist, or dual trigger according to OHSS risk. After oocyte retrieval and fertilization by IVF/ICSI, embryos will be cultured and transferred. Luteal phase support will consist of either intranasal GnRH agonist (Synarel) or vaginal progesterone. Blood and follicular fluid samples will be collected at predefined time points to assess hormonal, inflammatory, and angiogenic markers, including LH, FSH, estradiol, progesterone, IL-6, IL-8, VEGF, PEDF, and relaxin.

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.

Assisted Reproductive Technologies (ART) aim to increase success rates while minimizing patient risks. For women with high AFC or PCOS, conventional IVF carries a high risk of OHSS (Ho et al., 2019). A modern IVF strategy to prevent this uses a GnRH agonist trigger, requiring a "freeze-all" and subsequent FET (Wong et al., 2017). This reduces OHSS risk but can increase time to pregnancy (Vuong et al., 2021) and treatment burden. IVM is a patient-friendly alternative that eliminates OHSS risk by avoiding high-dose gonadotropins. A 2020 trial by Vuong et al. compared CAPA-IVM-FET to conventional IVF-FET in women with high AFC. IVM yielded a comparable live birth rate (35.2%) versus IVF (43.2%), with a 0% OHSS rate in IVM compared to 0.7% in IVF (Vuong et al., 2020). The optimal transfer method (fresh or frozen) in IVM cycles is debated. A 2021 pilot RCT by Vuong et al. found a freeze-only strategy after CAPA-IVM led to a significantly higher live birth rate (60%) than a fresh transfer (20%) (Vuong et al., 2021), but increased time to pregnancy (194 vs. 150 days) (Vuong et al., 2021). A refined CAPA-IVM protocol, which uses no gonadotropins, allowed for fresh embryo transfer in the same cycle, resulting in a numerically higher ongoing pregnancy rate (43.3% vs. 33.3%) than FET (Vuong et al., 2025). This raises an important question: how does a simplified IVM strategy with fresh transfer compare to the established "safety-net" IVF strategy with FET? These two approaches represent opposing clinical philosophies. No large-scale study has yet compared them in women with PCOS. Therefore, this study is designed to compare the SAIGON protocol (gonadotropin-free CAPA-IVM with fresh ET) against a standard GnRH-antagonist IVF protocol with agonist trigger and subsequent FET.