Triggering Of Final Oocyte Maturation Research Articles

P-703 Is the time interval between triggering final oocyte maturation and oocyte retrieval associated with ART outcomes? A systematic review and meta-analysis

Abstract Study question Is the time interval between triggering final oocyte maturation and oocyte retrieval associated with assisted reproductive technology (ART) outcomes? Summary answer Limited evidence suggests that extending the time interval between triggering final oocyte maturation and oocyte retrieval from 33-36h to 37-41h does not affect ART outcomes. What is known already The time interval between final oocyte maturation and oocyte retrieval varies among IVF centres, although an interval of 33–36 h is the most widely adopted. The use of a prolonged time interval of 37-41h has been suggested to increase the number and competence of oocytes retrieved, their maturation, their ability to be fertilized, their capacity to produce usable embryos and the probability of pregnancy. Considering recently published data, a systematic review is warranted to provide clinicians with updated, evidence-based information regarding the optimal time interval between triggering final oocyte maturation and oocyte retrieval. Study design, size, duration A systematic review and meta-analysis was performed aiming to evaluate the effect of the time interval between triggering final oocyte maturation and oocyte retrieval on ART outcomes. For this purpose, a literature search was carried out until January 2024 in PubMed, MEDLINE and CENTRAL. The primary outcome measure was clinical pregnancy rate, while ovulation before oocyte retrieval, oocytes retrieved, maturation rate, fertilization rate, blastulation rate, implantation rate and miscarriage rate were secondary outcomes. Participants/materials, setting, methods Citation, demographic, methodological and clinical data were extracted from the studies by two independent reviewers. Quality was assessed using the RoB2 Tool by Cochrane. Statistical heterogeneity was assessed by I2. In dichotomous data, estimates were expressed as relative risk (RR) with 95% confidence intervals (CIs), using the fixed or random effects method. In continuous data, differences were pooled across resulting in a weighted mean difference (WMD) with 95% CI. Main results and the role of chance Six eligible RCTs (n = 1081) were identified, published between 1991-2023. In three trials, conventional insemination was used for fertilization, in two trials this was performed by intracytoplasmic sperm injection (ICSI), whereas in one trial either conventional insemination or ICSI were used. The time intervals between triggering final oocyte maturation and oocyte retrieval compared, varied between studies (34.5-36 vs 38.5-40h, 33 vs 41h, 34 vs 38h, 35 vs 37h, 34 vs 39h and 36 vs 38h). Patients were grouped in advance based on these time intervals (short interval group: 33-36h versus long interval group: 37-41h). Ovarian stimulation was performed with GnRH analogues (GnRH antagonists:1 GnRH agonists:5) and gonadotrophins (HMG:4 recombinant FSH:2, while triggering of final oocyte maturation was performed with hCG( recombinant hCG:1 urinary hCG:5). None of the studies was deemed as of low risk of bias. No statistically significant differences were observed between the short nd long interval groups regarding clinical pregnancy rate per randomized patient (RR: 0.83; 95%CI: 0.62-1.11; fixed effects model; heterogeneity: I2:36.4%; five studies, 827 patients). Furthermore, it was not feasible to pool any of the secondary outcome data. This was either because they were not reported, or due to the fact that they were reported inappropriately. Limitations, reasons for caution This meta-analysis included a limited number of RCTs, which were generally of low quality due to methodological limitations and of high risk of bias. Moreover, the total number of patients is still not large enough to draw solid conclusions. Wider implications of the findings Taking into account the limitations of the current meta-analysis, it appears that clinicians may elect a shorter (33–36 h) or a longer (37-41h) interval regarding the timing of oocyte retrieval following triggering final oocyte maturation, without affecting clinical pregnancy rate. Trial registration number PROSPERO: CRD42024501986

O-074 Dual trigger is not superior to GnRH Agonist alone for final oocyte maturation in elective fertility preservation. A Randomized Controlled Trial

Abstract Study question Is Dual trigger for final oocyte maturation associated with a higher number of mature (MII) oocytes compared to GnRH-a trigger alone in elective fertility preservation? Summary answer Adding hCG to GnRH-a for triggering final oocyte maturation does not increase the number of MII oocytes in elective fertility preservation cycles. What is known already Triggering final oocyte maturation represents a key step in ovarian stimulation. In good prognosis patients undergoing oocyte cryopreservation, the current standard approach involves the administration of a single bolus of GnRH-agonist 36 hours before the pick-up. Previous studies have shown a higher number of MII oocytes when Dual Trigger (hCG+ GnRH-a) is performed, compared to recombinant human chorionic gonadotropin (rhCG) alone. Nevertheless, a notable gap exists in the literature, as no studies have investigated the potential additional benefit in final oocyte maturation when dual trigger is compared to GnRH-a alone. Study design, size, duration This is a randomized controlled superiority trial including elective oocyte cryopreservation cycles performed in a University Hospital. A total of 109 women were enrolled in this study between October 2021 to April 2023 with a 1:1 allocation. Eligible patients were ≤40 years old, with an antral follicular count (AFC)<20 and anti-Mullerian hormone (AMH)≤3ng/ml. Patients were randomized to final oocyte maturation triggering with Triptorelin 0,2mg or a dual trigger (Triptorelin 0.2 mg + 250 ug rhCG). Participants/materials, setting, methods Controlled ovarian stimulation was performed using 225-300IU/day of rFSH alfa or beta, or equivalent rFSH delta (15-20μg), tailored to ovarian reserve and BMI. LH surge was suppressed through a progestin-primed ovarian stimulation (PPOS) protocol, with oral administration of micronized progesterone (200mg daily) from the beginning of ovarian stimulation until the trigger day. The primary outcome was the number of MII oocytes. Comparisons are presented as estimated mean difference (EMD) and corresponding 90% confidence interval (CI). Main results and the role of chance Overall, 104 patients were analyzed, 51 in the Dual trigger group and 53 in the control arm (GnRH-a). We found no statistically significant differences in the number of retrieved oocytes comparing Dual Trigger group (8.71 ± 4.90) and GnRH-a group (9.51 ± 5.19). Similarly, the number of MII oocytes demonstrated no significant differences, with 6.86 ± 4.40 in the Dual Trigger group compared to 7.87±4.40 in the GnRH-a group (EMD -1.01 [90%CI: -2.44;0.43]). Exploring the hormonal profile there were no notable variations in estradiol levels (2064.60 ± 890.50 pg/ml vs. 2494.41 ± 1341.05 pg/ml), progesterone levels (7.78 ± 3.88 ng/ml vs. 8.94 ± 5.10 ng/ml), LH (56.28 ± 26.83 IU/L vs. 63.41 ± 32.50 IU/L), and FSH (31.14 ± 7.86 IU/L vs. 31.53 ± 9.89 IU/L) on the day following the trigger. Notably, neither group exhibited any case of Ovarian Hyperstimulation Syndrome (OHSS). Limitations, reasons for caution The sample size was calculated to detect differences on the number of MII oocytes. Therefore, results for secondary outcomes (number of oocytes retrieved and hormonal profile) should be interpreted with caution. Wider implications of the findings Adding hCG to GnRH-a for triggering final oocyte maturation does not confer any additional benefits in elective fertility preservation in term of MII oocytes compared to the administration of GnRH-a alone. Trial registration number NCT04992468

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles

BackgroundThe utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs.MethodsThe stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients’ previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs.ResultsPatients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles.ConclusionCo-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study

BackgroundDiminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin‐releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols.MethodsA total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors.ResultsThere were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted β = 0.538 (0.221–0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031–0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 0.162 (-0.005–0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR.ConclusionsDual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

#287 : A Comparison of hCG Trigger Versus Dual Trigger for Final Oocyte Maturation in Poor Ovarian Responders Undergoing Minimal Stimulation

Background and Aims: Traditionally, hCG has been used for oocyte triggering. However, women with poor ovarian response manifest low oocyte yield and compromised occyte quality. More recently, a combination of hCG and GnRHa (dual trigger) has been shown to improve follcile collection yield and oocyte maturation. The aim of the study is tocompare the result of final oocyte maturation and the embryo formation between two groups of poor ovarian responders undergoing minimal stimulation after triggering by hCG alone versus dual trigger. Method: This randomized control trial was conducted at National Assisted Reproductive Center, National Hospital of Obstetrics and Gynecology. Patients defined as poor ovarian responders according to the Bologna criteria were equally divided into two groups: control (hCG trigger) and investigation (dual trigger) groups. The group received the hCG trigger (6500 IU) and the investigation group received the dual trigger (0.2 mg of Triptorelin plus 6500 IU of hCG). Minimal stimulation IVF protocols consist of 5 days of 100mg clomiphene citrate and small amounts of gonadotropin. Results: One hundred and two patients were included in the study, with 51 women in each treatment group. Dual triggering showed a significant higher number of retrieved oocytes (5.35 ± 3.13 vs 4.35 ± 2.44, P=0.038) and metaphase II oocytes (4.25 ± 3.12 vs 3.35 ± 2.02, P=0.043). Although not reaching statistical significances, increases in the number of fertilized oocytes, embryos, and number of top-quality embryos (TQE) were observed. Conclusion: Dual trigger for final oocyte maturation is associated with better IVF outcome in poor ovarian responders undergoing minimal stimulation. Acknowledgements: The authors are grateful to all physicians, administrative staff at the National Assisted Reproductive Technology Center, National Hospital of Obstetrics and Gynecology, Vietnam for allowing and supporting us to undertake this research.

#100 : Can the Dual Trigger be Effective in Improving Oocyte Maturation and Embryo Quality Compared to the HCG Trigger or the GnRH-a Trigger?

Background and Aims: HCG was the standard trigger of final oocyte maturation in IVF cycles. An alternative trigger with gonadotropin releasing hormone agonist (GnRH-a) was effective in reducing OHSS. But GnRH-a trigger induced increased luteal insufficiency and cycle cancellation. A dual trigger (HCG with GnRH-a) was introduced to reduce OHSS, luteal insufficiency and cycle cancellation. This study was designed to compare the effect of dual trigger on final oocyte maturation n embryo quality with conventional HCG trigger and GnRH-a trigger. Method: We conducted this retrospective cohort study of patients who underwent IVF antagonist cycles from Jan. 2020 to Dec. 2022. Patients undergoing their oocyte retrieval 36 hours after trigger with only HCG 10,000 units, or only leuprolide acetate 40 units, or a dual trigger of HCG 5000 units with leuprolide acetate 40 units. Male factor infertility and oocyte donor cycle were excluded. The main outcomes were retrieved mature oocyte rate and fertilization rate. Secondary outcomes include implantation rate and pregnancy rate. Results: Total 3266 patients were included. Dual trigger was in 2279, GnRH-a in 282 and HCG in 705 cycles. Patients using GnRH-a were younger (33.7± 4.0 years) compared to those receiving dual trigger (37.8±2.3 years) and HCG only (37.2±3.2 years) (p&lt;0.01). Because GnRH-a groups were younger, despite low total gonadotropin dose, the larger number of oocytes were retrieved. Dual trigger resulted in no difference in mature oocyte ratio, compared to HCG trigger and GnRH-a trigger (63.0%, 58.3%, 62.8% p: 0.074). Analysis did not show any statistical differences in fertilization rate between the types of triggering methods. Cycel cancellation due to no oocyte recovered from multiple follicles aspirated was shown only in GnRH-a cycle (6 cases. 2.1%). Conclusion: Compared to HCG trigger and GnRH-a trigger, the dual trigger showed no difference in mature oocyte rate and fertilization rate. To reduce OHSS and cycle cancellations, dual trigger could be considered the standard care in IVF without decreasing oocyte quality.

#314 : Comparison of Dual-Trigger and Human Chorionic Gonadotropin-Only Trigger Among Diminished Ovarian Reserve Who Underwent Intracytoplasmic Sperm Injection: A Retrospective Cohort Study

Background and Aims: Diminished ovarian reserve (DOR) remains one of the greatest challenges for ART treatment. The objective of this study was to compare the laboratory outcomes of dual trigger and human chorionic gonadotropin (HCG) trigger alone in the final oocyte maturation for DOR patients. Methods: In this retrospective study,we evaluated 130 DOR women (dual group, n=75 and HCG group, n=45) underwent intracytoplasmic sperm injection (ICSI) between July 2020 and February 2023 at the Assisted Reproductive Department, Hung Vuong Hospital. DOR was defined as antral follicle count [Formula: see text]5 and serum anti-Müllerian hormone level [Formula: see text]1.2ng/mL. All patients using the GnRH antagonist protocolwith frozen embryo transfer. Baseline characteristics and cycle parameters, as well as IVF outcomes of both groups were compared. Generalized linear model (GLM) with negative binomial distribution for retrieved oocytes outcome and binomial distribution for other outcomes such as maturation rate, fertilization rate, rate of successfully achieving blastocytes and day-3 embryos. Results: Baseline characteristics were similar between the dual trigger group and the HCG group for age (p=0.2), AFC (p=0.44), AMH (p=0.76), BMI (p = 0.12), indication and number of priorARTcycles. The dual-trigger group had a significantly higher number of retrieved oocytes (95% CI 0.125–2.437, p=0.03), metaphase oocyterate (OR = 1.90, 95% CI 1.05–3.43; p=0.033). Fertilized oocyte rate (OR 1.42, 95% CI 2.015–0.795, p=0.967) andday-3 embryos (OR = 1.42, 95% CI 2.70–.73, p=0.294) were comparable in two groups. Conclusions: Our data suggests that dual trigger for final oocyte maturation might improve laboratory outcomes of IVF cycles in DOR patients.

Dual trigger for final oocyte maturation in expected normal responders with a high immature oocyte rate: a randomized controlled trial.

To evaluate whether dual trigger could improve reproductive outcomes in women with low oocyte maturation rates compare to human chorionic gonadotropin (hCG) trigger. This study included expected normal ovarian responders younger than 40 years old whose immature oocyte rate in the previous cycle was more than 50% at the reproductive center from July 2021 to November 2022. A total of 73 patients were enrolled at trigger, including 34 in the hCG trigger group and 39 in the dual trigger group (co-administration of gonadotrophin releasing hormone (GnRH) agonist and hCG, 40 and 34 h prior to oocyte retrieval, respectively). The primary outcome was oocyte maturation rate. There was no significant difference in the number of oocytes retrieved between the two study groups, but the oocyte maturation rate was higher in dual trigger group (84.0% [14.0%] vs. 55.5% [19.8%], p < 0.001). Moreover, there were also higher cumulative pregnancy rate (69.4% vs. 40.0%, p = 0.035) and cumulative live birth rate (66.7% vs. 36.0%, p = 0.022) in dual trigger group. For normal responders with low oocyte maturation rates, the dual trigger may be more effective than the conventional hCG trigger. ClinicalTrials.gov, identifier ChiCTR2100049292.

Follicular flushing increases the number of oocytes retrieved: a randomized controlled trial.

Does follicular flushing increase the number of cumulus-oocyte complexes (COCs) retrieved compared to single aspiration? Follicular flushing significantly increases the number of COCs retrieved compared to single aspiration. On the basis of published meta-analyses, follicular flushing does not seem to increase the number of oocytes retrieved, the probability of clinical pregnancy, or that of live birth and has been associated with an increase in the duration of oocyte retrieval. It should be noted, however, that all the eligible randomized controlled trials (RCTs) in these meta-analyses have randomized patients into either single aspiration or follicular flushing. This study design might not allow the detection of the true effect of follicular flushing. Despite randomization, this might still be obscured, to an extent, by heterogeneity in patients, stimulation characteristics, and differences in the oocyte retrieval procedure. A prospective, single centre, RCT, including 105 patients was performed between July and December 2022. Eligible patients were those undergoing oocyte retrieval for ICSI, aged <43 years, with BMI 18-35 kg/m2. Patients with all types of ovarian response (low-normal-high), as assessed on the day of triggering final oocyte maturation, were included. Random allocation of the ovaries of each patient to either single aspiration or follicular flushing was performed on the day of oocyte retrieval, using a computer-generated randomization list. Patients could enter the study only once. All follicles from ovaries allocated to either follicular flushing or single aspiration, were aspirated by the same 16G double lumen needle, with a constant aspiration pressure of 190 mmHg, resulting in flow rate of 0.42 ml/s. In the ovaries allocated to the follicular flushing group, if a COC was not recovered in the initial aspirate of each follicle, follicular flushing was performed until a COC was retrieved, up to a maximum of five times. The primary outcome measure was the number of COCs retrieved. Secondary outcomes were oocyte recovery rate, oocyte maturation rate, fertilization rate, and rate of good quality embryos on Day 2. Values are expressed as a median (inter-quartile range). Significantly more COCs were retrieved in the follicular flushing as compared to the single aspiration group in all patients [5 (7) vs 2 (3), P < 0.001, respectively], as well as in patients with high [9 (3) vs 5 (4), P < 0.001, respectively], normal [5 (2) vs 2 (3), P < 0.001, respectively] and low [1 (1) vs 1 (1), P < 0.001, respectively] ovarian response. In patients with low ovarian response, no COCs were retrieved in 5.7% of the ovaries in the flushing group vs 42.8% of the ovaries in the single aspiration group (P < 0.001). The oocyte retrieval rate was significantly higher in the follicular flushing vs the single aspiration group, in all patients [88.9% (25.0) vs 45.5% (37.5), P < 0.001, respectively], as well as in patients with high [81.8% (15.9) vs 45.5% (22.2), P < 0.001, respectively], normal [85.7% (28.6) vs 40.0% (30.0), P < 0.001, respectively], and low [100% (0) vs 50.0% (100), P < 0.001, respectively] ovarian response. No significant difference was observed regarding maturation rate [85.2% (30.8) vs 100% (33.3), P = 0.78], fertilization rate [76.4% (50) vs 83.3% (50) P = 0.42], and the proportion of good quality embryos on Day 2 [83.3% (40) vs 100% (50), P = 0.62]. Similarly, no differences in the above variables were observed in patients with different types of ovarian response. Follicular flushing as compared to single aspiration was associated with a significant increase in the duration of oocyte retrieval in all patients [248 s (332) vs 135 s (164), respectively], as well as in patients with high [464 s (225) vs 237 s (89), P < 0.001, respectively], normal [248 s (108) vs 141 s (95), P < 0.001, respectively], and low [64 s (59) vs 48 s (10), P < 0.001, respectively] ovarian response. Although the current study design allows for a more accurate evaluation of the true effect of follicular flushing on the number of COCs retrieved, it does not permit the evaluation of its role on the probability of pregnancy. This is the first RCT to suggest that follicular flushing increases the number of COCs retrieved compared to single aspiration, independently of ovarian response. This implies that follicular flushing plays an important role in the optimization of oocyte retrieval. These results, however, need to be confirmed in future studies, in which an equal flow rate should be used during oocyte retrieval. No external funding was obtained for this study. There are no conflicts of interest to declare. NCT05473455. 15 July 2022. 27 July 2022.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)2.Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)3.Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)4.The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)5.There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III)6.Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2)7.Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2)8.Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations1.The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)2.Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)3.Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C)4.Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B)5.A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C)6.Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E)7.Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C)8.Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A)9.Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B)

Two-dimensional ultrasound results in underestimation of the ovarian follicle size compared to automated three-dimensional imaging in women undergoing IVF.

Traditionally, for the assessment of follicle growth during IVF, two-dimensional (2D) transvaginal ultrasound (US) is used. In the past few years three-dimensional (3D) US has also been introduced. To compare follicular sizes between 2 and 3D ultrasound imaging on the final day of controlled ovarian stimulation. A prospective observational cohort study including 121 women undergoing controlled ovarian stimulation (COS) between January 2017 and July 2018. All women were assessed by transvaginal 2D and 3D ultrasonography to measure ovarian follicle dimensions on the final day of COS. The mean difference in paired comparisons between the 3D and 2D US measurements in 25 women with monofollicular development was + 1.6 ± 2.5mm for the x-dimension and + 1.7 ± 2.4mm for the y-dimension; and in the total number of 1197 paired measurements of follicles the mean difference + 2.1 ± 3.3mm and + 1.8 ± 3.9mm for the x- and y-dimension respectively. In all cases the paired t-test showed that differences were statistically significant (p < 0.01). Further it was conjectured that the 2D underestimation results from the inherent difficulty to precisely place the US probe simultaneously on the perpendicular maximal of the x and y follicle diameters, leading to measurement errors that, by theory, are normally distributed. Running Monte-Carlo simulations based on these measurement errors it was found that both the mean difference and standard deviation are of the same magnitude as the ones found in real measurements, thus proving the conjecture. The utilisation of 3D US results in different measurements of the follicular dimensions, and volumes, when compared to conventional 2D US. The differences in the x- and y-dimensions may affect the outcome of an IVF cycle as they are used to define the day of triggering final oocyte maturation, which is associated with the yield of mature oocytes and the probability of live birth.

P-633 Progesterone elevation on the day of trigger in the presence of low ovarian response signifies abnormal follicular environment and poorer oocyte health

Abstract Study question Is progesterone elevation (PE) in the presence of low number of follicles (unexpected PE) associated with oocyte or embryo quality? Summary answer PE on day of trigger in cycles with ≤4 follicles is associated with significantly reduced fertilisation rates and fewer top-quality blastocysts What is known already The negative effect of PE on pregnancy rates in fresh IVF cycles has been demonstrated by multiple studies and meta-analyses, and most studies support no negative effect on oocyte and embryo quality. However, as it is thought that PE is the product of cumulative secretion of low levels of progesterone from multiple developing follicles, PE in the presence of a low number of follicles (unexpected PE) is considered a different pathophysiological entity. It has been hypothesized, but never proven, that in these cases, PE is the result of follicular dysregulation and that it might indicate poorer follicular and oocyte health. Study design, size, duration This is a multi-centre retrospective analysis of a large cohort (n = 1,393) of IVF/ICSI cycles with a low response to ovarian stimulation (1-4 follicles ≥14mm) performed from January 2018 to April 2022. Only cycles of ovarian stimulation using gonadotrophins and GnRH analogues with a measurement of serum progesterone on the day of triggering final oocyte maturation were included. Natural cycles and cycles involving the administration of clomiphene were excluded. Participants/materials, setting, methods Unexpected PE was defined as serum progesterone levels greater than 4.77 nmol/L (1.5 ng/mL) on day of trigger. The primary outcome was the number of usable blastocysts. Secondary outcomes included the number of oocytes retrieved, two pronuclei (2PN) oocytes, number of top-quality embryos, fertilisation rate and blastocyst formation rate. Generalised estimating equations were used to account for the clustered nature of data. Multivariable regression analysis was performed to control for the effect of multiple confounders. Main results and the role of chance In the univariate regression analysis, the number of oocytes retrieved was not significantly different between cycles with and without PE (mean 2.3 vs. 2.1 respectively; p = 0.550). The number of 2PN oocytes was significantly (p = 0.021) lower in the PE group (mean 0.72, 95%CI 0.31-1.14) compared to the non-PE group (mean 1.21, 95%CI 1.12-1.31). The number of top-quality blastocysts was also significantly (p = 0.003) lower in the PE group (mean 0.03, 95%CI -0.03-0.10) compared to the non-PE group (mean 0.14, 95%CI 0.11-0.17). Fertilisation rates per oocyte retrieved, fertilisation rates per oocyte inseminated and the top-quality blastocyst rate per oocyte retrieved were consistently lower in the PE group at 33.3% (95% CI 19.0-47.6), 26.9% (95% CI 14.8-39.0) and 0.7% (95% CI -0.8-2.1) compared to 58.7% (95% CI 55.8-61.7), 52.3% (95% CI 49.3-55.2) and 5.5% (95% CI 4.3-6.8) in the non-PE group. The negative association of PE with the primary outcome measure of this study was confirmed in the multivariable regression analysis where the number of usable blastocysts was significantly lower in the PE group (adjusted mean 0.14, 95%CI 0.03-0.25) compared to the non-PE group (adjusted mean 0.27, 95%CI 0.23-0.31) after adjusting for confounders. Limitations, reasons for caution This is a retrospective observational study, thus not all confounders may be accounted for. Despite being one of the largest studies conducted in poor responders, the sample size of unexpected PE cycles is relatively small due to its rarity. Therefore, this study may be underpowered to detect smaller effect sizes. Wider implications of the findings This study demonstrates for the first time that unexpected PE on the day of trigger (i.e. in cycles with low ovarian response) is associated with poorer oocyte health as reflected in the reduced fertilisation rates and fewer blastocysts available for transfer. This information can aid in better understanding this phenomenon. Trial registration number Not applicable

P-680 Oocyte maturation triggering protocols in in vitro fertilisation treatment: a systematic review and network meta-analysis

Abstract Study question What is the relative effectiveness and safety of final oocyte maturation trigger protocols in women undergoing in vitro fertilisation (IVF) treatment? Summary answer OHSS rate was lowest with GnRH agonist trigger and no difference in LBR was observed comparing various trigger protocols in normal, high and poor responders. What is known already Oocyte maturation trigger prior to oocyte retrieval is a crucial component of ovarian stimulation(OS). Pituitary suppression is an important component of OS in IVF, involving the use of GnRH analogues. Currently, the GnRH antagonist regimen is predominantly used given its comparable efficacy and lower risk of OHSS compared with GnRH agonist (GnRHa) regimens. Whilst only hCG trigger can be used with GnRH agonist regimens, GnRH antagonist regimen enables use of hCG trigger, GnRH agonist trigger or combinations of both as dual or double trigger. However, there is no consensus on how these trigger protocols compare in their effectiveness and safety. Study design, size, duration The following databases were searched until August 2022: MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov. Randomised controlled trials (RCTs) comparing at least two trigger protocols: hCG trigger, GnRH agonist trigger, dual trigger (hCG and GnRH agonist administered at the same time) and double trigger (GnRH agonist followed by hCG after a time interval) with the antagonist regimen were included. Primary outcome was live birth (LBR) per participant. Secondary outcomes included number of oocytes and OHSS rates. Participants/materials, setting, methods Two reviewers independently screened, selected studies and extracted data. Pairwise and network meta-analyses (NMA) were conducted according to ovarian response groups (normal, high and poor response). Effect estimates were presented as weighted means difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) for continuous and dichotomous outcomes respectively. Quality assessment was performed using GRADE Main results and the role of chance Initial searches identified 4225 studies, of which 54 RCTs involving 5838 women met the inclusion criteria to be included in the analysis. In normal responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.11,95%CI:0.83-1.49;3 studies,430 women,I2=33%,low-certainty evidence, direct comparison(DC)),dual trigger vs hCG(RR:1.14,95%CI:0.99-1.31;4 studies,1007 women,I2=33%,low-certainty evidence, DC),double trigger vs hCG(RR:0.53, 95%CI:0.27-1.06;indirect comparison(IC)),dual vs GnRHa (RR:0.97, 95%CI:0.70-1.34, IC),double vs GnRHa (RR:2.07, 95%CI:0.98-4.38, IC),dual vs double (RR:2.14, 95%CI:1.06-4.32;IC). In high responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.04, 95%CI:0.84-1.29; 3 studies,178 women, I2 = 44%, low-certainty evidence, DC, dual trigger vs hCG (RR:1.82, 95%CI:1.25-2.67; 4 studies,117 women, I2 = 37%, low-certainty evidence, DC), double trigger vs hCG (RR:2.10, 95%CI:1.29-3.43, IC), dual vs GnRHa (RR:0.57, 95%CI:0.37-0.88, IC),double vs GnRHa (RR:0.49,95%CI:0.29-0.88, IC),dual vs double (RR:0.87, 95%CI:0.64-1.18; 1 study,57 women, low-certainty evidence,DC). In poor responders, there may be a difference in LBR when comparing dual trigger to hCG (RR:1.12,95%CI:1.12-2.89 1 study,112 women,low-certainty evidence,DC). OHSS rates were lowest with the use of GnRHa in high responders (RR:0.39,95%CI:0.04-3.78;9 studies;960 women;I2 =43%, low-certainty evidence,DC) and normal responders (RR:0.88, 95%CI:0.78 to 0.99;7 studies; 2246 women; I2=0%, low-certainty evidence,DC). There was no significant difference in number of oocytes or miscarriage risks with the use of any triggers. Limitations, reasons for caution Stratifying results by predicted ovarian response resulted in disconnected networks, limiting our ability to perform NMA for certain groups and outcomes. The certainty of the evidence was limited by high risk of bias. Wider implications of the findings Our results suggest that the use of short GnRH agonist trigger results in reduced OHSS rates in women with predicted normal or high ovarian response. There is no difference in LBR and number of oocytes comparing the different trigger protocols in all response groups (normal, high, poor responders) Trial registration number Not applicable

Introduce an optimal method of ovarian stimulation in the polycystic ovarian syndrome affected: a randomized controlled trial

BackgroundCurrently, optimal method of ovarian stimulation (OS) to in-vitro fertilization (IVF) in the patients with polycystic ovarian syndrome (PCOS) is unknown. The present research aims to study the efficiency of minimal-OS method in treatment of infertile patients with PCOS and also the effect of gonadotropin type (recombinant FSH (r-FSH) vs. urinary Human menopausal gonadotropin (u-HMG)) on treatment cycles with GnRH-antagonist.MethodsIn this randomized controlled trial, a total of 120 eligible patients were randomly allocated into four groups of OS to IVF: minimal-OS with r-FSH, minimal-OS with u-HMG, mild-OS with r-FSH and mild-OS with u-HMG. IVF outcomes of groups were analyzed statically.ResultsThe statistical analysis showed that there were significant differences among groups regarding stimulation duration (p < 0.0001), number of retrieved oocytes (p < 0.0001), number of obtained embryos (p < 0.0001). There were no statistically significant differences in fertilization rate (p = 0.289) and implantation rate (p = 0.757) among our participants. There were also significant differences among these four groups in terms of clinical pregnancy rate (/ET and /cycles) (p < 0.0001, p = 0.021, respectively) and live birth rate/cycles (p < 0.0001). Also cases of freeze all embryos due to prevention of ovarian hyper stimulation syndrome (OHSS) (p = 0.004).ConclusionsOn the basis of present results the minimal-OS with u-HMG may be one of optimal methods of control OS in the patients with PCOS in respect to serum levels of estradiol on the day of triggering final oocyte maturation, total dose of prescribed gonadotropin, the optimal number of oocytes and embryos obtained, rate of clinical pregnancy and the incidence of OHSS risk.Trial registrationNCT, NCT03876145. Registered 15/03/2019. Retrospectively registered, http://www.clinicaltrial.gov/ NCT03876145.

Female BMI and Body Weight Is Not Associated with Oocyte Yield and Maturation in hCG, Agonist or Dual Trigger Cycles: A Large Observational Study including 5000 Cycles.

Triggering final oocyte maturation is a key step of ovarian stimulation. Although previous studies demonstrated a negative association between female BMI and serum hCG levels, little evidence is available regarding the association between oocyte yield and patients' BMI. The scope of the current study was to examine whether the efficiency of the r-hCG and triptorelin to trigger final oocyte maturation may be associated with patients' BMI or weight. This is a retrospective observational study including 5190 ovarian stimulation cycles performed between January 2019 and September 2022 in the Reproductive Medicine Department of Dexeus University Hospital. Cycles were analyzed according to the type of trigger (triptorelin vs. r-hCG vs. dual). The primary outcome measures were oocyte maturation rate (MII/oocytes) and FOI (oocytes/AFC); secondary outcomes were oocyte and MII yield. Multivariable regression analysis, adjusting for confounding factors, demonstrated that BMI was not associated with oocyte maturation rate (OR: 1.00 [95%CI: 0.99; 1.01]), FOI (Beta 0.52 [95%CI: -0.49; 1.54]), number of oocytes (Beta 0.02 [95%CI: -0.08; 0.13]) or MIIs (Beta 0.01 [95%CI: -0.08; 0.10]) retrieved. Similarly, all analyses conducted considering patients' weight failed to reveal any association. Our study demonstrates that, independent of the type of trigger, patients' BMI and weight are not associated with oocyte yield, maturation, or FOI.

Strategies to Improve Outcomes of Ovulation Induction and Assisted Reproductive Technology (ART): The Iraqi Consensus

The ESHRE 2019 Guidelines provide clinicians with valuable evidence-based recommendations to optimize ovarian induction and ovarian stimulation in in vitro fertilization (IVF). However, data from such guidelines are primarily based on randomized controlled trials with highly selected populations that are conducted under very controlled conditions. To complement evidence from clinical guidelines and further improve treatment outcomes, seven Iraqi experts gathered to evaluate opinions on the specific approaches during an IVF cycle in Iraq and developed 15 statements agreed upon: The Iraqi Consensus. A Delphi consensus was conducted to formulate expert opinion on how assisted reproductive technology outcomes could be improved. Step 1 involved the scientific Board, comprising the scientific coordinator, who developed the initial statements and supporting references, which were discussed/amended by seven experts, and refined the final statements and references. Step 2 involved 30 Iraqi experts voted on their level of agreement/disagreement with each statement. Consensus was reached if the proportion of participants agreeing/disagreeing with a statement was &gt;66%. Step 3 data was collected and analyzed then communicated to participating experts. Consensus was achieved for 15 statements with high level of agreement in &gt;85% of statements, tackling follicular development/gonadotropins; pituitary suppression; final oocyte maturation triggering; luteal-phase support. This represents the collective point of view of the experts that took part in the consensus development and are based on local practice. This Delphi consensus provides a real-world clinical perspective from Iraqi experts and complements the international guidelines, and may help to further improve treatment outcomes in Iraq and the region.

Spontaneous dichorionic diamniotic twin pregnancy following a leuprolide acetate trigger and freeze all cycle for OHSS risk: A case report

Introduction: Gonadotropin-releasing hormone (GnRH) agonist triggers are increasingly used in antagonist in vitro fertilization (IVF) cycles to prevent ovarian hyperstimulation syndrome (OHSS) following a robust ovarian response. The luteolytic effects of GnRH agonists inhibit implantation or spontaneous pregnancy, warranting freezing available blastocysts for future transfer after the risk of OHSS subsides. Case Report: A 33-year-old G1P1 with secondary infertility due to polycystic ovarian syndrome underwent IVF with a GnRH antagonist cycle. A leuprolide acetate trigger for final oocyte maturation was prescribed given her risk of OHSS. A spontaneous dichorionic/diamniotic twin pregnancy ensued. Conclusion: This case reinforces the importance of advising abstinence during the stimulation phase of an IVF cycle and that, although rare, the endometrium may allow for spontaneous conception following a leuprolide acetate trigger, which may further potentiate the risk of late OHSS.

Dual trigger and the impact on oocyte quality and embryo development: a Brazilian cohort.

We aimed to analyze controlled ovarian stimulation using GnRH antagonist in association with hCG (dual triggering) versus hCG alone (conventional triggering) for final oocyte maturation triggering in a population of unselected Brazilian women. This was a retrospective observational study of IVF medical records between January 2019 and March 2020. Data from 335 women with infertility were included for study. All patients were divided into hCG trigger (control group; n=178) and dual trigger (n=157). The number of total oocytes and the number of inseminated oocytes were all significantly higher with the dual trigger protocol compared to hCG-only trigger. However, there is no significant difference in patient age, type of infertility, number of in vitro matured oocytes, trigger day, endometrial thickness, AMH concentration, the number of follicles, the number of mature oocytes and the number of fertilized oocytes. Using the dual trigger protocol improved the number of total oocytes retrieved and the number of inseminated oocytes.

A retrospective observational study to see the effect of dual trigger on IVF outcomes in poor ovarian responders

Background: Poor Responders Patients undergoing IVF treatment were given Dual Trigger for final oocyte maturation. Poor responders are the patients in whom, less number of egg were retrieved. Typically, they were with advanced maternal age and poor ovarian reserve (AFC <5-7 follicle or AMH < 1.2ng/ml) or with a history of previous Poor ovarian reserve (<3 oocytes) with Controlled ovarian stimulation. This study aimed to examine the effectiveness of dual trigger for final oocyte maturation in poor responder patients based on Bologna criteria (2011).Methods: A total of 30 IVF cycles of poor responder patients were retrospectively analyzed. The study group (15 patients) was given dual triggers (HCG and GnRH agonist) for final oocyte maturation whereas in control group final oocyte maturation was performed with HCG only. GnRH antagonist Protocol was used in both the groups.Baseline characteristics, number of oocyte retrieved, the number of M-2 and the quality of embryo of both groups were compared.Results: Both the groups were comparable in baseline characteristics. In our study, there was not much difference in number of oocyte retrieved, but there was higher number of M2 and top quality embryo, compared to control group.Conclusion: Dual trigger might be a superior option for final oocyte maturation as compared to hCG trigger alone in terms of IVF cycles outcomes in poor responders and further large scale randomized prospective studies needed to validate our results.

Ovarian hyperstimulation syndrome following the use of GnRH agonist trigger of final oocyte maturation and freeze–all strategy

Rationale: The current literature has a surprising controversy regarding the use of low-dose human chorionic gonadotropin (hCG) for luteal support as an explanation for the development of ovarian hyperstimulation syndrome, and this is because of the gap in the listing of the predisposing factors that put women at an increased risk of ovarian hyperstimulation syndrome. Patient concerns: A case of 25-year-old woman presented with abdominal pain, distention, dyspnea, and nausea with a 6.5 kg increase in weight from baseline. Ultrasonographic examination showed bilaterally enlarged multicystic ovaries after gonadotropin-releasing hormone (GnRH) agonist triggering and cycle segmentation with no hCG rescue administration. Diagnosis: Moderate/severe ovarian hyperstimulation syndrome. Interventions: The woman was admitted to the hospital for medical management of moderate/severe ovarian hyperstimulation syndrome, and pain management was advanced to patient-controlled anesthesia with the start of low molecular weight heparin. On day 2, albumin therapy followed by a furosemide chase was started due to an increase in abdominal girth. On day 1, Cabergoline was maintained, and on day 2 the GnRH antagonist Cetrorelix was started. Outcomes: The woman’s clinical condition improved, and a clinical pregnancy was eventually achieved during the first cryo-warmed blastocyst cycle. Lessons: Ovarian hyperstimulation syndrome can still happen even after the use of GnRH agonist and avoidance of hCG support. Segmentation of in vitro fertilization with complete avoidance of hCG for luteal support remains the best approach.