Risk Of Ovarian Hyperstimulation Syndrome Research Articles

Enhancing IVF Outcomes with Artificial Intelligence: Current Advances and Future Possibilities

The integration of Artificial Intelligence (AI) into In Vitro Fertilization (IVF) practices has marked a revolutionary shift in reproductive medicine, offering enhanced precision, efficiency, and personalized treatment plans. The rapid advancement of Artificial Intelligence (AI) has led to significant innovations in the field of reproductive medicine, particularly in In Vitro Fertilization (IVF). Traditional IVF procedures, while effective, often face challenges such as variable success rates, high costs, and the emotional burden on patients due to multiple treatment cycles. AI offers a promising solution to these issues by enhancing accuracy, personalization, and efficiency throughout the IVF process. AI algorithms have shown remarkable capabilities in diagnosing infertility by analyzing complex datasets from hormone profiles, genetic testing, and medical imaging, enabling early identification of conditions like polycystic ovary syndrome (PCOS) and endometriosis. Moreover, one of the most promising applications of AI in IVF is embryo grading. However, AI systems have been developed to objectively evaluate embryos based on time-lapse imaging, morphology, and other parameters, improving the selection process. Additionally, AI has been instrumental in optimizing ovarian stimulation protocols by analyzing patient data to determine the appropriate medication dosage, minimizing the risk of ovarian hyperstimulation syndrome (OHSS). This review discusses the current state of AI integration in fertility treatments, successful case studies, and ongoing research to develop more sophisticated AI models. Overall, AI holds immense promise in making IVF more accessible, affordable, and successful for patients worldwide, ushering in a new era of precision medicine in reproductive health.

In vitro maturation of oocytes: what is already known?

Assisted reproductive technologies (ARTs) involve the laboratory manipulation of gametes and embryos to help couples with fertility problems become pregnant. One of these procedures controlled ovarian stimulation uses pharmacological agents to induce ovarian and follicular maturation in vivo. Despite the effectiveness in achieving pregnancy and live births, some patients may have complications due to over-response to gonadotropins and develop ovarian hyperstimulation syndrome (OHSS). In vitro maturation of oocytes (IVM) has emerged as a technique to reduce the risk of OHSS, particularly in women with polycystic ovary syndrome (PCOS), and for fertility preservation in women undergoing oncological treatment. Although there are some limitations, primarily due to oocyte quality, recent advances have improved pregnancy success rates and neonatal and infant outcomes. Different terms have been coined to describe variations of IVM, and the technique has evolved with the introduction of hormones to optimize results. This review we provide a comprehensive overview of IVM and its reproductive outcomes during ARTs.

Impact of Letrozole on Prevention of Early Onset Ovarian Hyperstimulation Syndrome in GnRH Antagonist Protocol: A Randomized Controlled Trial

Abstract Background Ovarian hyperstimulation syndrome (OHSS) is a risk associated with assisted reproductive technology. There is a link between higher incidences of OHSS and higher blood estrogen levels. With its strong, targeted, and reversible inhibition of aromatase and E synthetase, the nonsteroidal aromatase inhibitor letrozole can prevent the conversion of androgens into estrogens. Methods Study populations were divided into two equal groups: Group I: Consisted of 85 women who received controlled ovarian stimulation with a conventional antagonist protocol and letrozole. Group II: Consisted of 85 women who received controlled ovarian stimulation with a conventional GnRH antagonist protocol and a placebo. Results There were statistically significant differences among the groups in terms of Estradiol level on Trigger Day (p = 0.037), Number of oocytes retrieved (p = 0.018). The total days of stimulation and cumulative Gonadotropin dose were significantly lower in the Letrozole group (p = 0.045). There were no significant differences between the groups as regard endometrial thickness at trigger day, number of fertilized oocytes, fertilization rate, embryos transferred per cycle, and fresh embryos transferred, mild and critical early onset OHSS, Cycle cancels, Biochemical pregnancy, and Clinical pregnancy between the two groups (P > 0.05). There was a significant difference as regard moderate and severe early onset OHSS between the two groups (P < 0.05). Conclusion We've concluded that for PCOS patients facing a high risk of OHSS, supplementing the GnRH-ant protocol with LE offers a safer, more effective, cost-efficient, and patient-friendly approach compared to the traditional GnRH-ant protocol. The use of LE alongside conventional protocols might alleviate severe forms of OHSS, even among those at extreme risk, without compromising the potential for implantation, pregnancy, and delivery

Ovarian Hyperstimulation Syndrome (OHSS): A Narrative Review and Legal Implications.

Infertility is a highly meaningful issue with potentially life-changing consequences, and its incidence has been growing worldwide. Assisted reproductive technology (ART) has made giant strides in terms of treating many infertility conditions, despite the risk of developing ovarian hyperstimulation syndrome (OHSS), a potentially life-threatening complication. This narrative review draws upon scientific articles found in the PubMed database. The search spanned the 1990-2024 period. Search strings used included "OHSS" or "ovarian hyperstimulation" and "IVF" and "GnRH" and "hCG"; 1098 results were retrieved and were ultimately narrowed down to 111 suitable sources, i.e., relevant articles dealing with the condition's underlying dynamics, management pathways, and evidence-based criteria and guidelines, crucial both from a clinical perspective and from the standpoint of medicolegal tenability. The following features constitute OHSS risk factors: young age, low body weight, and polycystic ovarian syndrome (PCOS), among others. GnRH antagonist can substantially lower the risk of severe OHSS, compared to the long protocol with a gonadotropin-releasing hormone (GnRH) agonist. However, a mild or moderate form of OHSS is also possible if the antagonist protocol is used, especially when hCG is used for the final maturation of oocytes. For women at risk of OHSS, GnRH agonist trigger and the freeze-all strategy is advisable. OHSS is one of the most frequent complications, with a 30% rate in IVF cycles. Providing effective care for OHSS patients begins with early diagnosis, while also evaluating for comorbidities and complications. In addition to that, we should pay more attention to the psychological component of this complication and of infertility as a whole. Compliance with guidelines and evidence-based best practices is essential for medicolegal tenability.

GnRH agonist-only trigger, compared to dual trigger, reduces oocyte retrieval rate in high responders without affecting cumulative live birth rate.

This study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS). A retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR. We analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p <0.05), while fertilization rates, blastocyst formation rates, and cumulative LBR were comparable. Notably, no OHSS cases had been reported in the GnRH agonist-only group, compared with 7 cases in the dual trigger group. GnRH agonist-only triggers resulted in a lower oocyte retrieval rate compared to dual triggers but did not significantly affect cumulative LBR in high responders. This approach effectively reduces OHSS risk without compromising pregnancy outcomes, making it a preferable option in freeze-all strategies, despite a longer oocyte pick-up duration and a medium cost. GnRH agonist-only trigger, however, may not be suitable for fresh embryo transfers or patients with low serum LH levels on trigger day.

Causal relationship between OHSS and immune cells: A Mendelian randomization study

ObjectiveTo confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. DesignObtaining data, collecting single nucleotide polymorphisms, detecting instrumental variables heterogeneity, assessing causality, and assessing bidirectional causality. SubjectsA two sample Mendelian study to confirm the causal relationship between immune cells and Ovarian Hyperstimulation Syndrome. ExposureImmune cell phenotype (including 22 million SNPs from GWAS on 3757 European individuals). Main outcome measuresInverse variance weighting, one-sample analysis, MR-Egger, weighted median and weighted mode are used to assess the causal relationship between 731 immunophenotypes and Ovarian Hyperstimulation Syndrome. The weighted median and Mendelian Randomization multi-effect residuals and Mendelian Randomization multi-effect residuals and outlier tests are used to assess bidirectional causality between this two. ResultsAfter False Discovery Rate correction, 9 immunophenotypes were found to be significantly associated with the risk of Ovarian Hyperstimulation Syndrome. B cell panel: IgD+ AC (OR, 0.90) 、CD19 on CD24+ CD27+ (OR, 0.86) 、BAFF-R on CD20- CD38 (OR, −1.22); Mature T cell group panel: EM DN (CD4 -CD8-) AC (OR, 1.46); Myeloid cell panel: Mo MDSC AC (OR, 1.13) 、CD45 on CD33br HLA-DR+ (OR, 0.87); Monocyte panel: HLA-DR on monocyte (OR, 0.86) 、CCR2 on CD14+ CD16+ monocyte (OR, 1.15) 、cDC panel: HLA-DR on myeloid DC (OR, 0.89). ConclusionThis study shows the potential link between OHSS and immune cells by genetic means, providing new ideas for future clinical and basic research.

Efficacy analysis of letrozole combined with gonadotropin-releasing hormone antagonists in patients with high risk of ovarian hyperstimulation syndrome undergoing total embryo freezing

Objective: To investigate the clinical efficacy of letrozole combined with gonadotropin-releasing hormone antagonists (GnRH-ant) in patients at high risk of ovarian hyperstimulation syndrome (OHSS) who underwent total embryo freezing after oocyte retrieval. Methods: A retrospective analysis was conducted on 348 female patients who underwent in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) at the Reproductive and Genetic Hospital of the First Affiliated Hospital of Zhengzhou University between January and July 2023. Due to their high risk of OHSS, these patients canceled fresh embryo transfer and opted for total embryo freezing. Based on patients' preferences, those who received GnRH-ant and letrozole after oocyte retrieval were categorized as the intervention group (164 cases), while those who did not receive these medications were categorized as the control group (184 cases). The first luteal phase after oocyte retrieval, OHSS grading, ovarian volume, and estradiol (E2) levels were evaluated in both groups. A multivariate logistic regression model was used to analyze factors related to moderate-to-severe OHSS among patients at high risk of OHSS who underwent total embryo freezing after oocyte retrieval. Results: The age of the intervention and control groups was (29.3±3.8) and (29.4±4.1) years, respectively (P=0.821). The duration of the first luteal phase post-oocyte retrieval was shorter in the intervention group [(7.16±1.39) days] compared to that in the control group [(13.88±2.11) days] (P<0.001). The incidences of mild, moderate, and severe OHSS in the intervention group were 75.0% (123 cases), 23.8% (39 cases), and 1.2% (2 cases), respectively, whereas in the control group they were 12.5% (23 cases), 60.9% (112 cases), and 26.6% (49 cases) (P<0.001). E2 levels on the 2nd and 6th days after oocyte retrieval [M(Q1,Q3)] in the intervention group were 1 520.0 (1 213.8, 1 884.8) and 108.5 (45.6, 218.0) ng/L, respectively, which were statistically significantly lower than those in the control group [1 666.0 (508.8, 1 702.0) ng/L] and [1 761.0 (826.0, 2 546.5) ng/L] (P<0.001). The abdominal cavity effusion in the intervention group [M(Q1,Q3)] were 19.5 (0, 30) and 0 mm, statistically significantly less than those in the control group [46.0 (0, 61.0) mm] and [54.5 (0, 69.5) mm] (P<0.001). On the 6th day after oocyte retrieval, the bilateral ovarian volumes in the intervention group were smaller than those in the control group (P<0.001). Multivariate logistic regression analysis indicated that no combined treatment with letrozole and GnRH-ant was a risk factor of moderate to severe OHSS. The risk of developing moderate to severe OHSS in the control group was 35.312 times higher than that in the intervention group (OR=35.312, 95%CI: 17.488-71.300). Conclusions: The administration of letrozole combined with GnRH-ant post-oocyte retrieval in patients at high risk of OHSS can prevent the occurrence of moderate-to-severe OHSS, shorten the first luteal phase, accelerate the reduction of serum E2 levels, and promote the recovery of ovarian volume and absorption of abdominal fluid.

Can We Harvest More Mature Oocytes by Repeating Gonadotropin-Releasing Hormone Agonist Doses in Polycystic Ovarian Syndrome Patients at Risk of OHSS in Antagonist Cycles? A Randomised Clinical Trial.

There is an ongoing debate about the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for oocyte triggering in polycystic ovarian syndrome (PCOS) patients at risk for ovarian hyperstimulation syndrome (OHSS). In this study, we intend to ascertain whether the use of repeated doses of a GnRH agonist for oocyte triggering in these patients can enhance the outcomes of controlled ovarian stimulation (COS) for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. This randomised clinical trial enrolled 70 PCOS women candidates for IVF/ICSI with the standard antagonist protocol at Royan Institute (Tehran, Iran) from May 2020 to June 2022. Patients at risk of OHSS with oestradiol (E2) levels >3000 pg/ml on the day of trigger were randomly assigned to a control or experimental group. Group A (control group) patients received 0.2 mg triptorelin (Decapeptyl®) for final oocyte maturation. Group B (experimental group) patients received a second dose of 0.1 mg Decapeptyl®12 hours after their first dose, for a total dose of 0.3 mg. IVF/ICSI outcomes were compared between the groups. Ultimately, 35 women from the study group and 33 from the control group completed the treatment cycle. Both groups were comparable in terms of demographic characteristics, baseline hormonal profiles, and PCOS phenotypes. The dosage of gonadotropin, stimulation duration, number of retrieved oocytes, oocyte maturation rate, and oocyte recovery ratio did not significantly differ between the groups. No significant differences were found in terms of the number of blastocyst and cleavage embryos, nor the quality of obtained embryos between the groups. The mild to moderate OHSS rate was significantly lower in the study group (P=0.038). A second dose of GnRH agonist 12 hours after the first dose did not improve the number and maturity of oocytes, or pregnancy outcomes in PCOS patients (registration number: NCT04600986).

P-639 Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes

Abstract Study question Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes Summary answer GnRH-a trigger reduces the incidence and severity of ovarian hyperstimulation syndrome (OHSS) leading to significantly improved clinical outcomes when compared to hCG trigger for FERCs. What is known already Ovulation induction plays a crucial role in the success and safety of ART cycles. hCG is extensively used as an alternative to LH to trigger ovulation. However, high levels of sustained hCG exposure increases the risk of OHSS, a potentially life-threatening complication of ART. To eliminate the risk and incidence of OHSS, GnRH-a can be used to trigger ovulation. Although there are concerns regarding clinical outcomes with fresh transfers following GnRH-a trigger, it elicits a more physiological response compared to hCG. This may lead to improved embryo quality, utilisation, and better clinical outcomes following a freeze-all strategy, reducing patients’ time-to-pregnancy. Study design, size, duration This was a retrospective data analysis of FERC outcomes following fresh IVF or ICSI cycles, involving ovulation induction using either hCG or GnRH-a as a final trigger. The evaluation included results from cycles spanning an eight-year period, from January 2012 to December 2019 at Hammersmith Hospital London. A total of 160 cycles were included in the study, with 76 in the hCG trigger group and 84 in the GnRH-a trigger group. Participants/materials, setting, methods Strict inclusion criteria were employed to render the study groups as comparable as possible and to minimise the effect of independent variables, such as oocyte and sperm factors, on oocyte or embryo developmental competence. Inclusion criteria: women ≤37 years old at the start of treatment, GnRH antagonist stimulation, blastocyst vitrification-warming and transfers only. Statistical significance was calculated using independent t-test and Fisher’s Chi-square exact test. Main results and the role of chance The mean age (±SD) of patients at the time of oocyte retrieval was comparable across groups. The average number of oocytes collected were significantly higher in the GnRH-a group compared to hCG (28.31 vs. 18.07, respectively, P &amp;lt; 0.001). Embryological data (maturation, fertilisation, blastocyst formation, blastocyst utilisation and good quality blastocyst formation rates) were comparable across both groups. OHSS rate was significantly lower in the GnRH-a group (17% vs. 50%. P &amp;lt; 0.0001). The following clinical data were significantly higher (P &amp;lt; 0.05) in the GnRH-a group compared to hCG: implantation rate (56% vs. 36%), clinical pregnancy rate (56% vs. 36%) and live birth rate (42% vs. 27%). Limitations, reasons for caution The biggest limitation of this study is its retrospective nature and the application of various inclusion-exclusion criteria that have resulted in relatively small sample sizes. Additionally, numerous other confounders, e.g. patient body mass index, cause/duration of infertility and stimulation duration, have not been considered in this study. Wider implications of the findings The findings of this study are promising and demonstrate a great potential for benefit in the use of GnRH-a trigger with a freeze-all strategy to minimise the risk of OHSS, diminishing the associated patient morbidity and mortality, reducing healthcare costs, improving clinical outcomes, and reducing the overall time-to-pregnancy for patients. Trial registration number not applicable

P-655 Live birth rate in the fresh cycle associated with number of oocytes in ovarian stimulation with individualised follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to achieve a live birth for women undergoing ovarian stimulation with individualised follitropin delta? Summary answer The live birth rate (LBR) in the fresh cycle was highest in the range of 8-14 oocytes retrieved, peaking at 11 oocytes. What is known already The number of oocytes retrieved following ovarian stimulation for assisted reproductive technologies is regarded a prognostic marker of pregnancy outcome, where high numbers increase chances of live birth but also the risk of complications, especially ovarian hyperstimulation syndrome (OHSS). Thus, an optimum range of oocytes retrieved is essential. Still, there is no consensus regarding this range in fresh cycles. Optimum numbers between 6 and 15 oocytes have been suggested, taking the risk of OHSS into consideration. The individualised dosing algorithm for the recombinant follicle-stimulating hormone follitropin delta has a target range of 8–14 oocytes. Study design, size, duration Individual patient data meta-analysis of 1772 patients from 5 randomised controlled trials using individualised dosing of follitropin delta for ovarian stimulation, with fixed daily dosing based on serum anti-Müllerian hormone (AMH) and body weight. The analysis included patients with ≥1 oocyte retrieved. Outcomes of LBR and OHSS in the fresh stimulation cycle were evaluated in relation to number of oocytes retrieved. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI. Single or double embryo/blastocyst transfer was performed on Day 3/5. All pregnancies were followed until birth. Predicted live birth was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and live birth. Main results and the role of chance The studied population (n = 1772) had a mean age of 32.6 years and median AMH of 17.7 pmol/l. Mean number of oocytes retrieved was 10.4, the LBR was 32.1% and the OHSS rate (any grade and onset) was 6.6%. The LBR steadily increased with the number of oocytes retrieved up to a plateau starting at 8 oocytes, with a LBR above 34% in the range of 8-14 oocytes retrieved, peaking at 34.9% for 11 oocytes. Beyond 14 oocytes, LBR gradually declined. By number of oocytes (grouped), the LBR was 27.8%, 33.6% and 30.9% at 1-7, 8-14 and ≥15 oocytes. In patients with embryo transfer, corresponding rates were 32.8%, 37.2% and 38.7%. In the subgroup analyses, LBR decreased with increasing age (32.7%, 30.7% and 23.4% at &amp;lt; 35, 35-37 and 38-42 years) while it was similar for AMH &amp;lt;15 and ≥15 pmol/l (30.4% and 31.3%, respectively). LBR was highest at 8-14 oocytes in patients &amp;lt;35 years (28.0%, 36.2% and 32.4% at 1-7, 8-14 and ≥15 oocytes), while it was consistently low (&amp;lt;26%) in patients 38-42 years, irrespective of number of oocytes retrieved. The OHSS rate (any grade) increased from 2.1% with 1-7 oocytes, to 5.2% with 8-14 oocytes and 17.0% with ≥15 oocytes. Limitations, reasons for caution A limitation of this study is the small number of patients with &amp;gt;20 oocytes retrieved in the studied population. Wider implications of the findings The current individual patient data meta-analysis suggests an optimum range of 8-14 oocytes retrieved to achieve a live birth in fresh cycles with follitropin delta. Furthermore, the analysis demonstrates a marked increase in OHSS rate from 15 oocytes retrieved. The results support the appropriateness of individualised follitropin delta dosing regimen. Trial registration number NCT01956110, NCT03228680, NCT03296527, NCT03564509, NCT03809429

P-197 Current status and hotspots of in vitro oocyte maturation: a bibliometric study of the past two decades

Abstract Study question What is the current research status and hotspot of in vitro maturation? And how could we improve the efficiency of IVM technique? Summary answer Five hotspots in IVM field were found, including culturing system, supplementation, cooperation in the ovarian follicle, gene expression, and cryopreservation of oocytes. What is known already In vitro maturation (IVM) of oocytes is a promising technique among assisted reproductive technologies. Because ovarian stimulation is minimal or absent in an IVM cycle, IVM technique reduces the risk of ovarian hyperstimulation syndrome (OHSS) and captures the reproductive potential of immature oocytes. However, the developmental competence of IVM oocytes is generally lower than the oocytes matured in vivo. A recent study showed the cumulative live birth rate in IVM is still inferior to standard IVF. The protocol for IVM still needs to be improved in some details. Study design, size, duration The articles and reviews related to IVM in the Web of Science Core Collection (WoSCC) were retrieved on January 16th, 2023. Three bibliometric tools including VOSviewer 1.6.18, CiteSpace 6.1.R6, and Bibliometrix R package 4.1.0 were used to generate network maps and explore frontier knowledge and trends. Participants/materials, setting, methods The data was retrieved and downloaded from WoSCC using the search formula: TS = (“in vitro maturation” OR “IVM”) AND TS = (follic* OR oocyte*) NOT TS=“ivermectin”. The timespan was set from 2003 to 2022. The language was limited to English, and publication types to article or review. VOSviewer detected indicators, including country, institution, journal, and author. CiteSpace analyzed reference co-citation and identified emerging keywords. Bibliometrix explored trending topics in IVM field. Main results and the role of chance A total of 5133 publications about IVM were retrieved from WoSCC, including 4706 articles and 427 reviews. The number of publications in IVM has increased steadily. China and University of Adelaide were the most prolific country and institution in IVM. Theriogenology was the most published and cited journal. Thompson, Jeremy G was the most productive author in the field of IVM, and Eppig, JJ’s papers were cited most. Furthermore, five hotspots were summarized and introduced, including culturing system, supplementation, cooperation in the ovarian follicle, gene expression, and cryopreservation of oocytes. This study comprehensively and visually analyzed the hotspots and frontiers of IVM in the past two decades. In our conclusion, further study could concentrate on: (1) the mechanism of oocytes matured in vivo and in vitro, especially in energy metabolism and intercellular communications; (2) establishment of IVM culture system, including standardized biphasic IVM culturing system and standardized supplementation; (3) the genetic differences between oocytes matured in vivo and in vitro; (4) the mechanism of cryopreservation-inflicted damage and the solution. Limitations, reasons for caution Due to the limitations of the software, the data we used for bibliometric analysis was only retrieved from WoSCC. Also, while bibliometric analysis can help us understand a field visually, it cannot completely replace system retrieval. Wider implications of the findings In this review, we explored and analyzed the field of IVM from 2003 to 2022 comprehensively and visually. Possible trends and hotspots in future were predicted, which may pave the way for future study directions and developments. Trial registration number not applicable

P-129 Transferring blastocysts derived from frozen-thawed cleavage embryos versus frozen-thawed blastocysts: A comparative analysis of pregnancy outcomes

Abstract Study question Is there an enhancement in pregnancy outcomes when cleavage-stage embryos are thawed, cultured for transfer as blastocysts, as opposed to transferring thawed blastocysts? Summary answer The strategy of culturing frozen-thawed cleavage embryos for 2 days and transferring them as blastocysts is not inferior to the transfer of frozen-thawed blastocysts. What is known already Embryo cryopreservation in IVF has many advantages, allowing couples to postpone pregnancy for personal reasons and reducing the risk of ovarian hyperstimulation syndrome. In the past, the common practice involved freezing and transferring cleavage embryos. However, a current trend favors single-embryo transfers at the blastocyst stage, promoting potential self-selection during extended culture. Several studies have raised concerns about potential damage during blastocyst vitrification, prompting investigation into whether cryopreserving cleavage-stage embryos for subsequent culturing to blastocysts yields superior outcomes compared to direct transfer of thawed blastocysts. Study design, size, duration This observational study was conducted at Hung Vuong Hospital from January 2022 to December 2023. We included 509 patients who underwent IVF followed by FET cycles. The D3-5 group (n = 167) comprised embryos that were frozen and thawed at the cleavage stage, subsequently extended two more days of culturing to the blastocyst stage for transfer. The D5 group (n = 342) involved frozen and thawed blastocysts. We excluded donor cycles, surrogacy, and cycles with preimplantation genetics testing. Participants/materials, setting, methods We used vitrification method for embryo cryopreservation. The freezing and thawing process were performed using either Kitazato or Cryotec medium kit, following manufacture’s instruction. Regarding the D3-5 group, thawed cleavage embryos were cultured for two more days until blastulation and transfer. Regarding the D5 group, blastocysts transfer was performed at least 2 hours after warming. The embryo transfer procedure was performed under abdominal ultrasonographical guidance. Pregnancy results were recorded and compared between two groups. Main results and the role of chance Regarding the D3-5 group, a noteworthy proportion of 65.3% cycles were unfortunately cancelled. The primary reason for cycle cancellations was the absence of developed blastocysts for transfer (85.3%). The remaining 14.7% of cancellations were attributed to other reasons. Fertilization rates were comparable between the two groups, with 80.8% in the D3-5 group and 81.5% in the D5 group (p = 0.464). However, the blastulation rate in the D3-5 group (40.1%) was lower than in the D5 group (46.4%), (p = 0.016). Patients in the D5 group demonstrated slightly better pregnancy outcomes compared to the D3-5 group: implantation rate (59.9% versus 51.7%, p = 0.302), clinical pregnancy rate (52.3% versus 44.8%, p = 0.36), ongoing pregnancy rate (37.7% versus 34.5%, p = 0746), live birth rate (33.9% versus 31%, p = 0.78), and miscarriage rate (26.3% versus 20.7%, p = 0.46). However, these differences were not statistical significance. Limitations, reasons for caution This is an observational study, we observed that thawing the cleavage-stage embryos then subsequently culture to the blastocyst stage may lead to the lower blastulation rate or even absence of developed blastocysts for transfer. This approach also increases the workload for embryologists. Wider implications of the findings Culturing frozen-thawed cleavage embryos for 2 days and transferring them as blastocysts increases workload for embryologists and poses a risk of cycle cancellation. We propose that the use of frozen-thawed blastocysts may be a more efficient and patient-friendly option. Trial registration number not applicable

O-059 ART in PCOS

Abstract Polycystic Ovarian Syndrome affects an estimated 8 – 13% of women of reproductive age (WHO). It is the commonest cause of anovulation and infertility. The high AMH, LH, Insulin resistance and hyperandrogenism seen in PCOS women contributes to infertility along with poor oocyte quality and reduced endometrial receptivity. ART procedures are recommended as the third line of treatment after ovulation induction, IUI or ovarian drilling. Prior to IVF, metabolic assessment and lifestyle adjustments with weight management must be done. Adjuvant agents such as metformin melatonin, myoinositol and Vitamin-D have been tried to improve IVF outcomes. Mild stimulation is an option in patients as high risk for ovarian hyperstimulation syndrome (OHSS). Conventional stimulation with low dose FSH, GnRH antagonist down regulation, agonist trigger with freezing of all embryos, significantly reduces risk of OHSS without compromising cumulative live birth rates. Adjustments for stimulation protocols may need to be made for BMI, insulin resistance and AMH. In vitro maturation can be considered in patients with prior severe OHSS, though the results may be inferior. ART in PCOS patients is challenging and even after pregnancy is achieved, there may be a higher risk of adverse obstetric outcomes.

P-605 Effectiveness of follitropin delta in patients with potential poor response: A post hoc analysis from the ESTHER-1 trial

Abstract Study question What is the effectiveness of individualised follitropin delta dosing compared to conventional follitropin alfa dosing in patients with potential poor response undergoing ovarian stimulation? Summary answer Individualised follitropin delta dosing provides a favourable efficacy and safety balance and is as good as follitropin alfa in patients with potential poor ovarian response. What is known already Poor ovarian response to controlled ovarian stimulation constitutes a challenge in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment. The dosing algorithm of follitropin delta incorporates the prediction of ovarian response based on anti-Müllerian hormone (AMH), an accurate marker of ovarian reserve, and body weight, for an individualised dosing. In the general IVF/ICSI population and potential high responders, individualised follitropin delta reduces the risk of ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions for OHSS, with sustained efficacy compared to conventional follitropin alfa. However, the performance of follitropin delta in the subpopulation of patients with potential poor response has not been evaluated. Study design, size, duration Post hoc analysis of 332 patients with potential poor response from the ESTHER-1 trial (determined by AMH level at screening &amp;lt;9 pmol/L). Patients received the maximum daily dose of 12 µg follitropin delta (fixed dosing throughout stimulation) as stipulated by the dosing algorithm for patients with AMH &amp;lt;15 pmol/l, or follitropin alfa at a starting dose of 150 IU, with potential dose adjustments from stimulation day 6 and onwards (maximum daily dose of 450 IU). Participants/materials, setting, methods Participants were women, 18–40 years, undergoing their first IVF/ICSI cycle in a GnRH antagonist protocol, including triggering with human chorionic gonadotrophin, IVF/ICSI insemination, and single or double blastocyst transfer on Day 5. Ultrasound was performed 10–11 weeks after transfer to confirm ongoing pregnancy. All pregnancies were followed until birth. Study outcomes include number of oocytes retrieved and number of good quality blastocysts, ongoing pregnancy and live birth rates, cycle cancellation and OHSS rates. Main results and the role of chance A total of 332 patients (25.0% of the overall ESTHER-1 population) had serum AMH at screening of &amp;lt; 9 pmol/l and were included in the analysis: 168 were treated with follitropin delta and 164 were treated with follitropin alfa. Baseline characteristics were similar between the treatment groups, with a mean age of 34.8 years, a median AMH of 5.7 pmol/l and a mean weight of 64.5 kg. With follitropin delta, the mean daily dose was 12.0 µg and with follitropin alfa 12.4 µg, resulting in mean total doses of 104.6 µg and 112.3 µg, respectively. The mean number of oocytes retrieved was 5.8 ± 3.5 with follitropin delta and 5.5 ± 3.6 with follitropin alfa and the mean number of good-quality blastocysts was 1.2 ± 1.4 with both treatments. The ongoing pregnancy rate was 29.8% with follitropin delta and 29.3% with follitropin alfa and the live birth rates were 29.2% and 28.7%, respectively. Thirteen patients (7.7%) treated with follitropin delta and 14 (8.5%) treated with follitropin alfa had their cycles cancelled due to poor response. One case of OHSS (0.6%) was observed in the follitropin delta group, and 3 cases (1.8%) were observed in the follitropin alfa group. Limitations, reasons for caution The main limitation of the study is its post hoc nature. Furthermore, the study is based on a relatively small number of patients. Wider implications of the findings This subgroup analysis, alongside the normoresponder and the potential hyperresponder subgroup of the ESTHER-1 trial, adds evidence for the effectiveness of follitropin delta across all ovarian reserve subgroups of the infertile population. Trial registration number NCT01956110

O-043 Con

Abstract Dual and/or double trigger improve IVF success - CON The improvement of in vitro fertilization (IVF) outcomes remains a pivotal area of reproductive medicine research, with the dual trigger approach emerging as a significant innovation. This con abstract explores the scientific basis, methodology, and outcomes associated with the dual trigger strategy, juxtaposed with conventional triggering methods in IVF protocols. The dual trigger, incorporating both Gonadotropin-Releasing Hormone Agonist (GnRHa) and Human Chorionic Gonadotropin (hCG), has been posited to improve oocyte maturation, retrieval-, and live birth rates. By scrutinizing recent studies, clinical trials, and meta-analyses, this debate aims to delineate the efficacy, safety, and application scope of this approach. Initial investigations into the dual trigger method have highlighted its potential to ameliorate oocyte quality and maturity, which are crucial determinants of IVF success. The mechanism underlying this improvement involves the simultaneous activation of LH (Luteinizing Hormone) and FSH (Follicle Stimulating Hormone) receptors, enhancing follicular response and oocyte developmental competence. Studies have demonstrated an increase in the number of mature oocytes retrieved, attributed to the more synchronized and comprehensive follicular stimulation afforded by the dual trigger. This augmentation in oocyte quality and quantity directly correlates with enhanced embryo development profiles, and higher implantation and clinical pregnancy rates. Furthermore, the dual trigger method has shown promise in reducing the incidence of Ovarian Hyperstimulation Syndrome (OHSS), a severe complication of IVF treatments. By leveraging the luteolytic effects of GnRHa, this strategy minimizes the risk associated with exogenous hCG administration, thus offering a safer alternative for patients predisposed to OHSS. The application of the dual trigger in specific patient cohorts, such as those with PCOS or poor ovarian responders, has been underlined, indicating its potential for personalized reproductive medicine. However, the implementation of the dual trigger strategy is not without challenges. Variability in patient response necessitates a highly individualized approach, with precise dosing and timing adjustments to optimize outcomes. The existing literature presents a heterogeneity in study designs, populations, and outcome measures, which complicates the direct comparison of dual trigger efficacy against traditional methods. Furthermore, the long-term safety and potential impacts on offspring warrant further investigation, given the recent adoption of this approach. In conclusion, the dual trigger strategy may offer significant benefits in enhancing IVF outcomes. Its potential to improve oocyte maturity and quality could increase the number of retrievable oocytes and reduce the incidence of OHSS. However, it is important to acknowledge that, while the GnRH agonist trigger combined with a freeze-all strategy eliminates the risk of OHSS in women with PCOS, the dual trigger approach followed by fresh embryo transfer does not. Further research is imperative to refine its application, understand its mechanisms fully, and establish comprehensive guidelines for its use. The promise of the dual trigger approach underscores the importance of continuous innovation and evidence-based practices in enhancing the efficacy and safety of IVF treatments.

P-162 Embryo transfer impact: a comprehensive national cohort analysis comparing maternal outcomes across varied embryo stages in fresh and frozen transfers

Abstract Study question What is the ideal choice between fresh and frozen embryos transfer, and should the transfer be done at the cleavage or blastocyst stage? Summary answer This study highlights the clinical pregnancy and live birth superiority of frozen embryo transfer in blastocysts but not in cleavage stage embryos. What is known already Frozen embryo transfer not only improves reproductive outcomes by increasing the chances of live birth and clinical pregnancy but also enhances safety by reducing the risks of OHSS and multiple pregnancies. Due to the consistent findings, there has been a growing discussion in recent years about whether it is advisable to adopt elective frozen embryo transfer as the standard practice. Study design, size, duration In this retrospective cohort study conducted in Taiwan, a comprehensive dataset from the national assisted reproductive technology (ART) database was utilized, covering the period from January 1st, 2013, to December 31st, 2017. The final cohort study encompassed eligible 51762 female participants who had undergone ART and embryo transfer. Pregnancy outcomes and maternal complications during the follow-up were assessed using the population registry dataset from January 1st, 2013, to December 31st, 2018. Participants/materials, setting, methods The study categorizes cases into groups based on whether they underwent fresh or frozen embryo transfers, with additional subgroups based on cleavage stage and blastocyst stage transfers. Exposure variables include clinical pregnancy rate, live birth rate, ovarian hyperstimulation syndrome (OHSS), pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, and preterm premature rupture of membranes (PPROM). Main results and the role of chance For pregnancy outcomes, frozen blastocyst transfers exhibited higher rates of clinical pregnancy (OR 1.33, 95%CI 1.25-1.42) and live births (OR 1.27, 95%CI 1.19-1.36) when compared to fresh blastocyst transfers. However, frozen cleavage stage transfers had lower rates of clinical pregnancy (OR 0.73, 95%CI 0.69-0.77) and live births (OR 0.79, 95%CI 0.74-0.84) compared to fresh cleavage stage transfers. For maternal complications, frozen embryo transfers were associated with reduced risks of OHSS (OR 0.02, 95%CI 0.02-0.03 for blastocyst and OR 0.05, 95%CI 0.03-0.09 for cleavage stage) compared to fresh embryo transfers, but were linked to a higher risk of pregnancy-induced hypertension (OR 1.43, 95%CI 1.19-1.73 for blastocyst and OR 1.23, 95%CI 1.29-1.82 for cleavage stage). No significant differences were observed in the incidence of gestational DM and PPROM among the various transfer groups. Limitations, reasons for caution Our retrospective study design may not offer the same level of rigor as a randomized controlled trial. Furthermore, the reproductive database did not provide detailed information on specific endometrial preparation methods (such as hormone replacement therapy or natural cycle), which could potentially influence implantation outcomes. Wider implications of the findings The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, frozen embryo transfer is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option. Trial registration number KMUHIRB-E(I)-20210222

P-729 Contribution of medical-administrative databases to health monitoring: example of ovarian hyperstimulation syndrome (OHSS)

Abstract Study question Can we monitor post-oocyte retrieval ovarian hyperstimulation syndrome (OHSS) in the French national health data system to complement the French ART vigilance system? Summary answer Medico-administrative databases offer a more comprehensive view of post-oocyte retrieval complications and can be used to detect abnormal increases in frequency and outlier ART centers. What is known already Assisted reproductive technology (ART), widely used in Europe, accounts for about 3% of births in France. The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has established a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. Study design, size, duration The study population was identified from the comprehensive French National Hospital discharge database and included 53,490 women under 46 years old who underwent 65,924 oocyte retrievals in 2022. Women were classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF), fertility preservation (FP), and oocyte donation (OD). Participants/materials, setting, methods Hospital stays for OHSS within two months post-retrieval were analyzed and characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay...). Multivariate analysis was performed to determine the relation between the occurrence of OHSS and women’s characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot was used to compare the OHSS rate per center with the national average. Main results and the role of chance Hospitalized OHSS accounted for 1.1% of retrievals in 2022 (n = 718). The mean age of the women was 31.6 years (SD 4.5). Women with Polycystic Ovary Syndrome (PCOS) accounted for about 4% of the women with OHSS. More than half of OHSS hospital stays lasted less than two days (54%). Of these stays, 2% of women were in intensive care. Multivariate analysis showed a significantly higher OHSS risk in women under 30 and those with PCOS. Other risk factors are currently introduced into the model, such as a history of OHSS or pregnancy. Funnel plot analysis showed that one ART center has an OHSS rate significantly higher than the national average. In the centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. Limitations, reasons for caution Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Moreover, the unavailability of personal or clinical information prevented us from considering certain risk factors. Wider implications of the findings Despite the limits of using medico-administrative databases, this approach provides a better representation of post-ART complications and is a promising way to complement the ART vigilance reporting system. This concept will also be generalized to other complications with regular feedback to professionals. Trial registration number not applicable

Monitoring of controlled ovarian stimulation in IVF

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

Embryo transfer impact: a comprehensive national cohort analysis comparing maternal and neonatal outcomes across varied embryo stages in fresh and frozen transfers.

The utilization of frozen embryo transfer not only enhances reproductive outcomes by elevating the likelihood of live birth and clinical pregnancy but also improves safety by mitigating the risks associated with ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. There has been an increasing debate in recent years regarding the advisability of making elective frozen embryo transfer the standard practice. Our study aims to determine the optimal choice between fresh and frozen embryo transfer, as well as whether the transfer should occur at the cleavage or blastocyst stage. In this retrospective cohort study conducted in Taiwan, data from the national assisted reproductive technology (ART) database spanning from January 1st, 2013, to December 31st, 2017, were analyzed. The study included 51,762 eligible female participants who underwent ART and embryo transfer. Pregnancy outcomes, maternal complications, and singleton neonatal outcomes were evaluated using the National Health Insurance Database from January 1st, 2013, to December 31st, 2018. Cases were categorized into groups based on whether they underwent fresh or frozen embryo transfers, with further subdivision into cleavage stage and blastocyst stage transfers. Exposure variables encompassed clinical pregnancy rate, live birth rate, OHSS, pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, preterm premature rupture of membranes (PPROM), gestational age, newborn body weight, and route of delivery. Frozen blastocyst transfers showed higher rates of clinical pregnancy (CPR) and live births (LBR) compared to fresh blastocyst transfers. Conversely, frozen cleavage stage transfers demonstrated lower rates of clinical pregnancy and live birth compared to fresh cleavage stage transfers. Frozen embryo transfers were associated with reduced risks of OHSS but were linked to a higher risk of pregnancy-induced hypertension compared to fresh embryo transfers. Additionally, frozen embryo transfers were associated with a higher incidence of large for gestational age infants and a lower incidence of small for gestational age infants. The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, FET is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option.

Fertility Preservation and Ovarian Hyperstimulation Syndrome Management in Cancer Care: A Pathophysiological Perspective on Gonadotropin-Releasing Hormone Agonists and Antagonists.

This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted, and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the 'flare-up' effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and the management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.