Progestin primed ovarian stimulation using corifollitropin alfa in PCOS women effectively prevents LH surge and reduces injection burden compared to GnRH antagonist protocol

Utilizing corifollitropin alfa in GnRH antagonist (GnRHant) protocol in conjunction with GnRH agonist trigger/freeze-all strategy (corifollitropin alfa/GnRHant protocol) was reported to have satisfactory outcomes in women with polycystic ovary syndrome (PCOS). Although lessening in gonadotropin injections, GnRHant were still needed. In addition to using corifollitropin alfa, GnRHant was replaced with an oral progestin as in progestin primed ovarian stimulation (PPOS) to further reduce the injection burden in this study. We try to investigate whether this regimen (corifollitropin alfa/PPOS protocol) could effectively reduce GnRHant injections and prevent premature LH surge in PCOS patients undergoing IVF/ICSI cycles. This is a retrospective cohort study recruiting 333 women with PCOS, with body weight between 50 and 70 kg, undergoing first IVF/ICSI cycle between August 2015 and July 2018. We used corifollitropin alfa/GnRHant protocol prior to Jan 2017 (n = 160), then changed to corifollitropin alfa/PPOS protocol (n = 173). All patients received corifollitropin alfa 100 μg on menstruation day 2/3 (S1). Additional rFSH was administered daily from S8. In corifollitropin alfa/GnRHant group, cetrorelix 0.25 mg/day was administered from S5 till the trigger day. In corifollitropin alfa/PPOS group, dydrogesterone 20 mg/day was given from S1 till the trigger day. GnRH agonist was used to trigger maturation of oocyte. All good quality day 5/6 embryos were frozen, and frozen-thawed embryo transfer (FET) was performed on subsequent cycle. A comparison of clinical outcomes was made between the two protocols. The primary endpoint was the incidence of premature LH surge and none of the patients occurred. Dydrogesterone successfully replace GnRHant to block LH surge while an average of 6.8 days of GnRHant injections were needed in the corifollitropin alfa/GnRHant group. No patients suffered from ovarian hyperstimulation syndrome (OHSS). The other clinical outcomes including additional duration/dose of daily gonadotropin administration, number of oocytes retrieved, and fertilization rate were similar between the two groups. The implantation rate, clinical pregnancy rate, and live birth rate in the first FET cycle were also similar between the two groups. In women with PCOS undergoing IVF/ICSI treatment, corifollitropin alfa/PPOS protocol could minimize the injections burden with comparable outcomes to corifollitropin alfa/GnRHant protocol.

P–659 Artificial intelligence (AI) as an assisting tool in generating patient-friendly corifollitropin alfa ovarian stimulation protocol during in vitro fertilization

Study question How machine learning assisted in generating patient-friendly corifollitropin alfa protocol in normal responders? Summary answer In retrospective experiments, our machine learning model integrated physiological measurements of patients and clinical experience to generate a patient-friendly corifollitropin alfa protocol. What is known already Long-acting corifollitropin alfa can simplify the regimen, minimizing injections during the whole cycle. The previous study has described the patient-friendly protocol using corifollitropin alfa without routine pituitary suppression in normal responder can result in non-compromised clinical outcomes. Some studies showed machine learning can help with making clinical decisions and have the ability to learn from physiological measurements. Those methods effectuate certain points throughout short-acting menotropin protocols, however, there are still no robust AI tools for long-acting corifollitropin alfa protocols. Study design, size, duration 1,309 cycles were collected at Stork Fertility Center from November 2016 to October 2019, and 1,221 cycles were available after data cleaning and applying exclusion criteria, which Anti-Mullerian Hormone (AMH) is lower than 2. The data from electronic medical records (EMRs) consisted of age, AMH, body weight, luteinizing hormone (LH), and estradiol (E2) concentrations measured on revisit. Evaluation is performed by one physician who has more than 20 years of experience in IVF. Participants/materials, setting, methods: The protocol generator consisted of 5 parts: doses of Elonva, trigger type, doses of recombinant follicle-stimulating hormone (rFSH), doses of recombinant luteinizing hormone (rLH), and day of oocyte retrieval. The protocol was predicted by age, AMH, and weight firstly, then fine-tuned by LH and E2 after the first revisit. We used the gradient boosting decision tree algorithm to learn the protocol. The dataset was randomly split into 80% for training and 20% for testing. Main results and the role of chance In classification, the model predicted the dose of Elonva achieved an accuracy of 0.913 and an AUC of 0.946, and trigger type got an accuracy of 0.901 and AUC of 0.852 only using features on stimulation day (SD) 1 and gained 0.012 and 0.056 in accuracy and AUC correspondingly after adding features on the first revisit day. In regression, the mean absolute error (MAE) of rFSH dose, rLH dose, and oocytes retrieved day was 156.30 IU, 232.75 IU, and 0.80 days respectively, and after refining, the MAE dropped to 92.37 IU, 100.07 IU, and 0.46 days. The error of predictions in rFSH and rLH was almost equal to half increments of rFSH (150 IU) and one increment rLH (75 IU). This indicated that our model could provide a better prediction of these clinical decisions with one revisit only. Limitations, reasons for caution The present study was a single-center retrospective, and only analyzed the data from normal responders, whose AMH was equal or greater than 2. Though, the recommendations of our system act as references, the physician will make the final decision. Wider implications of the findings: Our result showed the potential of machine learning in generating protocols is promising. Recommendations generated by our model can provide the junior clinical teams to optimize the clinical plans and learn from the experience of experts. We look forward to applying our machine learning model to different protocols. Trial registration number Not applicable

Corifollitropin alfa in different variants of ovarian response in assisted reproductive technology programmes: literature review

This literature review focuses on the use of corifollitropin alfa for ovarian stimulation in assisted reproductive technology (ART) programmes in different groups of patients. Corifollitropin alfa is a gonadotropin drug with prolonged FSH activity. The main difference between corifollitropin alfa and other gonadotropins is the higher level of peak FSH, which leads to the recruitment of more follicles. Another feature is the inability to adjust the gonadotropin dose during the first days of ovarian stimulation. In contrast to traditional indications/contraindications for gonadotropins, the use of cortifollitropin is not recommended in combination with GnRH agonists or in patients with polycystic ovary syndrome.Evidence for the feasibility and efficacy of using corifollitropin alfa in patients with various ovarian response variants in ART programmes has been analysed. Most researchers agree that the use of corifollitropin alfa can be recommended for patients with a presumed poor or normal ovarian response. The use of corifollitropin alfa in patients with a presumed excessive response to ovarian timulation is possible when embryo transfer is not expected: in oocyte donation/oocyte vitrification cycles or in "freeze-all" cycles.A significant advantage of using corifollitropin alfa for oocyte donor patients is the single administration of the drug, which can be done in a medical facility, which reduces the risk of prescription non-compliance.The use of corifollitropin alfa in protocols with GnRH agonists requires further research: firstly, corifollitropin alfa has no LH component and secondly, there is no possibility of ovulation trigger replacement in this protocol if there is a high risk of early ovarian hyperstimulation syndrome.