Speaker: Alberto Vaiarelli

A retrospective analysis was conducted to evaluate the impact of clinical and laboratory strategies on clinical outcomes and IVF success rates. The study, based in Rome, included data from 600 naive couples undergoing intracytoplasmic sperm injection (ICSI) procedures, with up to six ovarian stimulations within three years. The mean age of the population was 38 ± 4 years. The analysis spanned from 2010 to 2020 and aimed to assess cumulative live birth rates, efficiency of treatment, and other outcomes such as the reduction of ovarian hyperstimulation syndrome (OHSS) risk, miscarriage rates, and the prevalence of multiple pregnancies. The study focused on optimizing treatment efficiency by evaluating the time from the first ovarian stimulation to the last IVF procedure. Over the years, strategies were adapted to improve follicle recruitment. This included administering a maximal dose of gonadotropins, averaging 300 units per day. Additionally, LH activity, either recombinant LH or HMG, was increased to enhance follicle recruitment. The findings indicated that the adjustments in treatment protocols contributed to better clinical outcomes, demonstrating the importance of these strategies in IVF success. The analysis provided valuable insights into improving IVF treatment efficacy and patient outcomes. 

In 2010, the agonist protocol was the predominant approach in reproductive cycles. However, by 2020, the antagonist protocol had become the dominant method, used in 80% of cycles. This shift has facilitated the adoption of the agonist trigger, which is now widely used not only to prevent OHSS but also to allow for a second stimulation within the same ovarian cycle. The prevalence of the Duostim protocol, which involves double stimulation in one ovarian cycle, has significantly increased from 5% in 2015 to 30% in 2023. This strategy aims to maximize the number of eggs retrieved, thereby enhancing the potential for more embryos and improving the cumulative live birth rate.

The emphasis on safety has driven the increased use of the agonist trigger. Changes in clinical strategies include the timing of embryo transfers, the increased use of blastocyst transfers, and preimplantation genetic testing for aneuploidy (PGTA). By 2020, 80% of cases involved blastocyst transfers, and 90% of cycles employed a freeze-all strategy to optimize outcomes. The focus on transferring a single high-quality embryo has led to a 99% rate of single embryo transfers.

Embryological advancements have also played a critical role. In approximately 50% of cases, continuous media and time-lapse incubators enhance embryo monitoring and selection. These clinical and embryological strategies have improved cumulative live birth rates across different age groups. The approach aims to maximize ovarian stimulation, increase egg numbers, and reduce the number of embryo transfers by selecting embryos with high implantation potential, thus shortening treatment time. These strategies have improved efficacy, defined as the number of babies born, and efficiency, measured by optimizing clinical outcomes per transfer and reducing the number of embryo transfers needed. Despite these advancements, the miscarriage rate remains around 10% across different age groups. A key performance indicator, the rate of multiple pregnancies, has been successfully reduced to 1% due to the prevalent practice of single embryo transfers, contrasting sharply with Italy's 14% multiple pregnancy rate.

Over the past decade, the implementation and increasing adoption of the antagonist protocol combined with the agonist trigger, freeze-all strategy, blastocyst culture with PGTA, and comprehensive multiple-cycle counselling has been shown to improve IVF outcomes significantly. The next step is anticipated to involve enhancing the multi-cycle approach. From the outset, informing patients that a single cycle may be insufficient is essential. Therefore, planning for two or more embryo transfers and multiple ovarian stimulations is considered a beneficial strategy. This approach aims to reduce the overall time required, decrease dropout rates, and optimize the chances of successful outcomes.

The rationale for continuing with ICSI is primarily due to its integration with the PGTA cycle, which constitutes the majority of cases. Although IVF with the PGTA cycle is feasible, it demands a higher workload. Additionally, the average age of the patient population is 38, prompting a discussion on whether conventional IVF or ICSI is the optimal approach. Under the current protocol, ICSI is performed in all PGTA cycles.

The current strategies can enhance cumulative success by enabling more effective patient stimulation through safe methods like triggering with agonists and employing Freeze-all, which, although not improving egg quality, can improve treatment efficiency. Efficiency here refers to factors such as time, miscarriage rates, and selecting embryos with high implantation potential. The key factor for improving cumulative live birth rates was the number of eggs, which has increased due to more aggressive stimulation protocols. Standardization of lab and clinical procedures was also deemed necessary. While Freeze-all does not directly improve cumulative outcomes, it allows for more patient stimulation regardless of progesterone levels or fresh embryo transfers. Additionally, strategies to minimize patient dropout, such as immediate second stimulations within the same ovarian cycle, were crucial for enhancing cumulative success.

The results of a study indicate a 76% cumulative live birth rate in a population with a mean age above 38, which is high compared to previous studies. The study observed patients over three years, involving up to six ovarian stimulations. It is noted that the cumulative rate varies by age, with a significantly lower rate of 10% for those aged 43-44. The handling of dropout rates is crucial. Only naive patients were included, with an observational period spanning ten years, though only the first three years were considered for the first stimulation. Patients who opted for egg donation were excluded from the study. The study is important as it helps inform patients about the potential success rates of multiple cycles. It emphasizes that persistence and planning multiple ovarian stimulations can lead to high success rates. It provides valuable insights for patients who may lose hope or change their approach after an initial IVF failure, encouraging them to stay committed to achieving success.

The age of the woman is a crucial factor. The multiple-cycle approach is indicated for patients with advanced maternal age. A strong experience with this protocol has been observed in cases of advanced maternal age despite a suboptimal response in the initial cycle. This approach is one of the only strategies available. Improving the quality of oocytes and embryos is, unfortunately, not possible. However, time management and reducing dropout rates are considered important clinical performance indicators. This approach is also utilized in PGTA cycles, where many embryos are necessary to identify a euploid embryo in the advanced maternal age population. 

European Society of Human Reproduction and Embryology, July 7-10, Amsterdam, The Netherlands