Triggering Of Oocyte Maturation Research Articles

P-378 Relation between AMH serum levels and recovered mature oocytes in infertile, healthy, and oncological patients

Abstract Study question Does AMH serum levels correlate with the recovered mature oocytes in similar way among infertile, healthy, and oncological patients? Summary answer AMH serum levels correlated well with the number of mature oocytes in infertile, healthy, and oncological patients What is known already AMH is a protein produced by granulosa cells from pre-antral follicles and uses as biomarker of ovarian reserve. The aim of ovarian stimulation in the IVF setting or fertility preservation is obtaining metaphase II oocytes. The value of serum AMH to predict the number of mature oocytes has not been study in a comparative way among infertile patients vs. healthy and oncological population Study design, size, duration Retrospective study of the AMH serum levels and number of recovered mature oocytes in oocyte vitrification cycles from April 2017 to June 2023. We included 78 patients with cancer, 119 healthy patients and 668 infertile patients undergoing oocyte vitrification for fertility preservation or as accumulation of oocytes strategy Participants/materials, setting, methods This single centre study included Infertile patients ≤ 42 with gynaecological pathology (endometriosis, polycystic ovarian syndrome, low ovarian reserve, and/or tubal factor), any type of cancer and healthy women demanding social fertility preservation. We excluded IVF healthy patients (normal patients with exclusively male factor). AMH serum level was measured before ovarian stimulation. We analysed the probability of obtain ≥ 8 mature oocytes considering as normal AMH (1.2 ng/mL). Ethical approval was obtained for this stud Main results and the role of chance IVF patients were older and had higher body mass index than the other two groups. AMH serum level (ng/mL) was similar among groups; in IVF patients (1.88 [1.67-2.09]); oncological patients (2.25 [1.85-2.65]), and healthy women (2.5 [2.2-2.8]). (p= 0.064). Ovarian stimulation was longer and more FSH units were employed in IVF patients. Oestradiol level at the oocyte maturation triggering was lower in oncological patients. The number of MII oocytes was significantly lower in IVF patients (6.1 [5.9-6.4]) compared with oncological and healthy patients (9.2[8.0-10.5]; 9.9 [9.0-10.8], respectively). AMH level correlated well with the number of recovered mature oocytes and similar among groups. The Odds Ratio to recover ≥ 8 mature oocytes considering as normal AMH (1.2 ng/mL) showed a probability 8.3 times higher in healthy patients, but only 0.3 times in IVF patients and 0.5 times in oncological patients. A OR: 9.1 was observed for obtain ≥ 8 mature oocytes between normal vs low AMH. The area under the curve in the ROC curve for AMH was 0.7191 Limitations, reasons for caution This study had limitations in the sample size and differences in ovarian stimulation protocol as oncological patients in hormone-dependent cancer received letrozole while conventional ovarian stimulation with FSH was performed in IVF and healthy patients. IVF patients’ group was heterogeneous in the aetiology of infertility Wider implications of the findings This study remarks the use of AMH in different conditions: infertility, oncological, and healthy status. Although no differences were found in correlation with the number of mature oocytes, the probability to obtain ≥ 8 mature oocytes with normal AMH was higher in healthy women compared with infertile patients Trial registration number 2306-VGO-128-EM

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.

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)&amp;lt;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

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

P-601 Monitoring reproductive hormones during ovarian stimulation: performance and usability of a self-operated at-home urine test

Abstract Study question How effective and user-friendly is a non-invasive, patient-operated urine test (Kinder) in tracking reproductive hormone levels during ovarian stimulation (OS) treatment in an IVF cycle? Summary answer Urinary E1-3G correlates well with blood E2 levels and ovarian follicle development. Patients found it easy and stress-free to perform the urine test at home. What is known already Monitoring blood reproductive hormone levels during OS is a widely accepted practice to ensure the optimal ovarian response to gonadotropin treatment, timing of oocyte maturation triggering and mitigating hyperstimulation risk. However, conventional blood testing is invasive, necessitating patients to travel to clinics for blood sampling, adding to their overall burden. Previous studies have revealed a robust correlation between blood E2 levels, and its corresponding urinary metabolites E1-3G. Kinder is a portable device designed for quantifying urinary E1-3G, allowing patients to conduct tests in the privacy of their homes, and for many obviating the need to travel substantial distances for monitoring. Study design, size, duration This is a prospective, single-cohort, study of Caucasian patients (28-34 years), conducted at Fertility Specialists of Western Australia in Perth, Australia, where patients may travel vast distances for treatment. Twenty-five patients were enrolled from Aug 2022-Aug 2023, and performed home urine tests utilizing the Kinder device in parallel with clinic scheduled blood (ELISA) and ultrasound tests. The primary end point of the study was the correlation between urinary and blood reproductive hormone concentrations (E1-3G). Participants/materials, setting, methods Spearman and Pearson correlation coefficients (CC) and 95% confidence intervals were calculated for E1-3G and E2, and E1-3G/E2 and follicle development (total volume of ovarian follicles by ultrasound). To assess patient acceptability patient-reported outcomes (PRO) were assessed using the State Trait Anxiety Inventory (STAI) questionnaire. Further, patient-reported experiences (PRE) were evaluated through the System Usability Scale (SUS) questionnaire, along with assessing their likelihood to recommend Kinder to their friends or family undergoing IVF treatment. Main results and the role of chance Upon analysing 100 concurrent urine and blood samples from 25 patients, a robust correlation was found between E1-3G and E2 levels (Spearman CC: 0.818, 95% CI: 0.680-0.904; Pearson CC: 0.847, 95% CI: 0.712-0.939). Additionally, we observed a moderate correlation between E1-3G levels and ovarian volume (Spearman CC: 0.701, 95% CI: 0.556-0.805; Pearson CC: 0.670, 95% CI: 0.519-0.781, n = 72), resembled the correlation between E2 levels and ovarian volume (Spearman CC: 0.874, 95% CI: 0.804-0.920; Pearson CC: 0.849, 95% CI: 0.770-0.902, n = 75). PRE: 22 out of 23 patients who completed the survey confirmed that they would definitely, or probably, recommend Kinder. The mean SUS score (91.4) signified an excellent user experience. PRO: Anxiety levels were not affected by use of Kinder (STAI score below threshold of 42.38) in 18/20 patients who completed three STAI surveys (first one before and second one after the initial Kinder test; third one after the third/fourth Kinder test). Although 2/20 patients reported a STAI score of 49 in the final survey, suggesting increased anxiety, both affirmed in the PRE survey that they “will definitely recommend Kinder”, suggesting that the elevated STAI score can be attributed to the overall IVF treatment rather than the use of Kinder itself. Limitations, reasons for caution The sample size is relatively small, necessitating further multi-centre studies with a larger sample size to validate the findings. Wider implications of the findings The results suggest an acceptable interchangeability between at-home urine E1-3G and at-clinic blood E2 monitoring hormone levels during OS treatment. A digital health approach, combining tele-counselling, remote at-home hormone monitoring, and follicle tracking, could reduce patient burden and save many patients the inconvenience of travelling large distances for cycle monitoring. Trial registration number ACTRN12622000488707

In vitro matured oocytes have a higher developmental potential than in vivo matured oocytes after hormonal ovarian stimulation in Callithrix jacchus

BackgroundThe common marmoset, Callithrix jacchus, is an invaluable model in biomedical research. Its use includes genetic engineering applications, which require manipulations of oocytes and production of embryos in vitro. To maximize the recovery of oocytes suitable for embryo production and to fulfil the requirements of the 3R principles to the highest degree possible, optimization of ovarian stimulation protocols is crucial. Here, we compared the efficacy of two hormonal ovarian stimulation approaches: 1) stimulation of follicular growth with hFSH followed by triggering of oocyte maturation with hCG (FSH + hCG) and 2) stimulation with hFSH only (FSH-priming).MethodsIn total, 14 female marmosets were used as oocyte donors in this study. Each animal underwent up to four surgical interventions, with the first three performed as ovum pick-up (OPU) procedures and the last one being an ovariohysterectomy (OvH). In total, 20 experiments were carried out with FSH + hCG stimulation and 18 with FSH-priming. Efficacy of each stimulation protocol was assessed through in vitro maturation (IVM), in vitro fertilization (IVF) and embryo production rates.ResultsEach study group consisted of two subgroups: the in vivo matured oocytes and the oocytes that underwent IVM. Surprisingly, in the absence of hCG triggering some of the oocytes recovered were at the MII stage, moreover, their number was not significantly lower compared to FSH + hCG stimulation (2.8 vs. 3.9, respectively (ns)). While the IVM and IVF rates did not differ between the two stimulation groups, the IVF rates of in vivo matured oocytes were significantly lower compared to in vitro matured ones in both FSH-priming and FSH + hCG groups. In total, 1.7 eight-cell embryos/experiment (OPU) and 2.1 eight-cell embryos/experiment (OvH) were obtained after FSH + hCG stimulation vs. 1.8 eight-cell embryos/experiment (OPU) and 5.0 eight-cell embryos/experiment (OvH) following FSH-priming. These numbers include embryos obtained from both in vivo and in vitro matured oocytes.ConclusionA significantly lower developmental competence of the in vivo matured oocytes renders triggering of the in vivo maturation with hCG as a part of the currently used FSH-stimulation protocol unnecessary. In actual numbers, between 1 and 7 blastocysts were obtained following each FSH-priming. In the absence of further studies, FSH-priming appears superior to FSH + hCG stimulation in the common marmoset under current experimental settings.

In vitro fertilization outcome based on the detailed early luteal phase trajectory of hormones: a prospective cohort study

BackgroundOvarian stimulation and the use of human chorionic gonadotropin (hCG) for triggering oocyte maturation in women undergoing in vitro fertilisation (IVF) introduces several differences in luteal phase hormone levels compared with natural cycles that may negatively impact on endometrial receptivity and pregnancy rates after fresh embryo transfer. Exogenous luteal phase support is given to overcome these issues. The suitability of a pragmatic approach to luteal phase support is not known due to a lack of data on early phase luteal hormone levels and their association with fertility outcomes during IVF with fresh embryo transfer. This study determined early luteal phase profiles of serum progesterone, 17-hydroxyprogesterone and hCG, and associations between hormone levels/hormone level profile after hCG trigger and the live birth rate in women undergoing IVF with fresh embryo transfer.MethodsThis prospective single center, cohort study was conducted in Vietnam from January 2021 to December 2022. Women aged 18–38 years with normal ovarian reserve and undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist protocol were included. Serum hormone levels were determined before trigger, at 12, 24 and 36 h after hCG, and daily from 1 to 6 days after oocyte pick-up. Serum hormone level profiles were classified as lower or upper. The primary outcome was live birth rate based on early luteal phase hormone level profile.ResultsNinety-five women were enrolled. Live birth occurred in 19/69 women (27.5%) with a lower progesterone profile and 13/22 (59.1%) with an upper progesterone profile (risk ratio [RR] 2.15; 95% confidence interval [CI] 1.28–3.60), and in 6/31 (19.4%) versus 26/60 (43.3%) with a lower versus upper serum 17-hydroxyprogesterone profile (RR 2.24; 95% CI 1.03–4.86). Nearly 20% of women had peak progesterone concentration on or before day 3 after oocyte pick-up, and this was associated with significantly lower chances of having a life birth.ConclusionsThese data show the importance of proper corpus luteum function with sufficient progesterone/17-hydroxyprogesterone production for achievement of pregnancy and to maximize the chance of live birth during IVF.Trial RegistrationNCT04693624 (www.clinicaltrials.gov).

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.

Do women with severely diminished ovarian reserve undergoing modified natural-cycle in-vitro fertilization benefit from earlier trigger at smaller follicle size?

To evaluate whether trigger and oocyte collection at a smaller follicle size decreases the risk of premature ovulation while maintaining the reproductive potential of oocytes in women with a severely diminished ovarian reserve undergoing modified natural-cycle in-vitro fertilization. This was a retrospective cohort study including women who had at least one unsuccessful cycle (due to no response) of conventional ovarian stimulation with a high dosage of gonadotropins and subsequently underwent a modified natural cycle with a solitary growing follicle (i.e. only one follicle > 10 mm at the time of trigger). The association between follicle size at trigger and various cycle outcomes was tested using regression analyses. A total of 160 ovarian stimulation cycles from 110 patients were included in the analysis. Oocyte pick-up (OPU) was performed in 153 cycles and 7 cycles were canceled due to premature ovulation. Patients who received their trigger at smaller follicle sizes (≤ 15 mm) had significantly lower rates of premature ovulation and thus higher rates of OPU (98.9% vs 90.8%; odds ratio, 9.56 (95% CI, 1.58-182.9); P = 0.039) compared with those who received their trigger at larger follicle sizes (> 15 mm). On multivariable analysis, smaller follicle sizes at trigger (> 10 to 13 mm, > 13 to 15 mm, > 15 mm to 17 mm) were not associated significantly with a lower rate of cumulus-oocyte complex (COC) retrieval, metaphase-II (MII) oocytes or blastulation when compared to the > 17-mm group. On sensitivity analysis including only the first cycle of each couple, the maturity rate among those with COC retrieval was highest in follicle sizes > 15 to 17 mm (92.3%) and > 13 to 15 mm (91.7%), followed by > 10 to 13 mm (85.7%) and lowest in the > 17-mm group (58.8%). During the study period, five euploid blastocysts developed from 48 fertilized MII oocytes with follicle sizes of 12 mm (n = 3), 14 mm (n = 1) and 16 mm (n = 1) at trigger. Of those, four were transferred and resulted in two live births, both of which developed from follicles with a size at trigger of 12 mm. The ideal follicle size for triggering oocyte maturation may be smaller in women with a severely diminished ovarian reserve managed on a modified natural cycle when compared to conventional cut-offs. The risk of OPU cancellation was significantly higher in women triggered at follicle size > 15 mm and the yield of mature oocytes was not adversely affected in women triggered at follicle size > 13 to 15 mm compared with > 15 to 17 mm. Waiting for follicles to reach sizes > 17mm may be detrimental to achieving optimal outcome. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Neuropeptide expression and action in the reproductive system of the starfish Asterias rubens.

Reproductive processes are regulated by a variety of neuropeptides in vertebrates and invertebrates. In starfish (phylum Echinodermata), relaxin-like gonad-stimulating peptide triggers oocyte maturation and spawning. However, little is known about other neuropeptides as potential regulators of reproduction in starfish. To address this issue, here, we used histology and immunohistochemistry to analyze the reproductive system of the starfish Asterias rubens at four stages of the seasonal reproductive cycle in male and female animals, investigating the expression of eight neuropeptides: the corticotropin-releasing hormone-type neuropeptide ArCRH, the calcitonin-type neuropeptide ArCT, the pedal peptide-type neuropeptides ArPPLN1b and ArPPLN2h, the vasopressin/ocytocin-type neuropeptide asterotocin, the gonadotropin-releasing hormone-type neuropeptide ArGnRH, and the somatostatin/allatostatin-C-type neuropeptides ArSS1 and ArSS2. The expression of five neuropeptides, ArCRH, ArCT, ArPPLN1b, ArPPLN2h, and asterotocin, was detected in the gonoducts and/or gonads. For example, extensive ArPPLN2h expression was revealed in the coelomic epithelial layer of the gonads throughout the seasonal reproductive cycle in both males and females. However, seasonal and/or sexual differences in the patterns of neuropeptide expression were also observed. Informed by these findings, the in vitro pharmacological effects of neuropeptides on gonad preparations from male and female starfish were investigated. This revealed that ArSS1 causes gonadal contraction and that ArPPLN2h causes gonadal relaxation, with both neuropeptides being more effective on ovaries than testes. Collectively, these findings indicate that multiple neuropeptide signaling systems are involved in the regulation of reproductive function in starfish, with some neuropeptides exerting excitatory or inhibitory effects on gonad contractility that may be physiologically relevant when gametes are expelled during spawning.

#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.

Optimising IVF Outcomes

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women, with an overall prevalence of 5% to 15%, and a frequent cause of infertility. Ovulation disorders are the main cause of infertility for the couples. A range of endocrine and metabolic traits are also associated with PCOS and these include obesity, dyslipidemia, insulin resistance, hyperinsulinism and an increased risk of type 2 diabetes mellitus and cardiovascular disease. Studies have found that women with PCOS had a higher live birth rate, clinical pregnancy rate and implantation rate, as well as an increased risk of ovarian hyperstimulation syndrome (OHSS), pregnancy complications including miscarriage, preterm delivery, gestational diabetes mellitus and pregnancy-induced hypertension in their first IVF treatment when compared with non-PCOS controls. During the past three decades, applying IVF for infertility treatment PCOS women has increased significantly, and the landscape of treatment strategies has changed dramatically. GnRH agonist triggering oocyte maturation combined with freeze-all embryos is an effective and commonly used protocol nowadays to achieve good success rate as well as to minimize the risk of OHSS in women with PCOS. Recently, there has been an increasing use of oocyte in-vitro maturation (IVM) for treating infertility in women with PCOS. IVM technique could be considered as an alternative to IVF in centers where it is available. However, strategies to minimize pregnancy complications in women with PCOS remain further studied.

Endocrine profile of the kisspeptin receptor agonist MVT-602 in healthy premenopausal women with and without ovarian stimulation: results from 2 randomized, placebo-controlled clinical tricals

Kisspeptin is an essential regulator of hypothalamic gonadotropin-releasing hormone release and is required for physiological ovulation. Native kisspeptin-54 (KP54) can induce oocyte maturation during in vitro fertilization treatment, including in women at high risk of ovarian hyperstimulation syndrome. MVT-602 is a potent kisspeptin receptor agonist with prospective utility to treat anovulatory disorders by triggering oocyte maturation and ovulation during medically assisted reproduction (MAR). Currently, the endocrine profile of MVT-602 during ovarian stimulation is unreported. ObjectiveTo determine the endocrine profile of MVT-602 in the follicular phase of healthy premenopausal women (Phase-1 trial), and after minimal ovarian stimulation to more closely reflect the endocrine milieu encountered during MAR (Phase-2a trial). DesignTwo randomized, placebo-controlled, parallel group, dose-finding trials. SettingClinical trials unit, Netherlands. ParticipantsHealthy women aged 18-35 years, either without (Phase-1; n=24), or with ovarian stimulation (Phase-2a; n=75). InterventionsPhase-1: Single subcutaneous dose of MVT-602 (0.3, 1.0, or 3.0 μg) or placebo, (n=6 per dose).Phase-2a: Single subcutaneous dose of MVT-602 (0.1, 0.3, 1.0, or 3.0 μg; n=16-17 per dose), triptorelin 0.2 mg (n=5; active comparator), or placebo (n=5). Main Objectives and Outcome MeasuresPhase-1: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones).Phase-2a: Safety/tolerability; pharmacokinetics; pharmacodynamics (LH and other reproductive hormones); time to ovulation assessed by transvaginal ultrasound. ResultsIn both trials, MVT-602 was safe and well-tolerated across the entire dose-range. It was rapidly absorbed and eliminated, with a mean elimination half-life of 1.3-2.2 hours.In the Phase-2a trial, LH concentrations increased dose-dependently; mean maximum change from baseline of 82.4 IU/L at 24.8 hours was observed after administration of 3μg MVT-602 and remained above 15 IU/L for 33 hours. Time to ovulation following drug administration was 3.3-3.9 days (MVT-602), 3.4 days (triptorelin), and 5.5 days (placebo). Ovulation occurred within 5 days of administration in 100% (3 μg), 88% (1μg), 82% (0.3μg), and 75% (0.1μg), of women after MVT-602, 100% after triptorelin, and 60% after placebo. ConclusionsMVT-602 induces LH concentrations of similar amplitude and duration as the physiological mid-cycle LH surge with potential utility for induction of oocyte maturation and ovulation during MAR. Trial RegistrationsEUDRA-CT: 2017-003812-38, 2018-001379-20

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.

Effect of Red Bean Extract (Phaseolus vulgaris L.) on IL-10 Levels in Systemic Lupus Erythematosus Model

Introduction: Systemic Lupus Erythematosus (SLE) is a is a chronic autoimmune inflammatory disease of unknown etiologic. Multiorgan dysfunction in women with SLE causes menstrual irregularities, ovarian failure, follicular atresia, and premature ovarian failure (POF) leading to the cessation of menstruation. Phaseolus vulgaris L. contains isoflavones that can trigger oocyte maturation, stimulate the formation of antral follicles, increase FSH receptor expression and proliferate cell nuclear antigen (PCNA) expression. This study aims to prove the effect of red bean extract (isoflavones) in SLE by and increasing the secretion of anti-inflammatory IL-10 levels. Material and Methods: This study used a true experimental design with a post-test-only controlled group design. The samples used in this study were at least 25 female Balb/c mice. Data on serum IL-10 levels in mice were obtained by measurement using ELISA. The data were statistically analysed using SPSS 16 for Windows software program. The data were tested for normality and homogeneity using parametric non-parametric analysis. Results: The results showed that there was a significant difference in ANA levels with a p-value of 0.000 in each sample. From this test, it was proven that there was a significant increase in IL-10 levels at doses of 75 mg/KgBW (P2) and 100 mg/KgBW (P3) (p-value=0.000) due to the administration of various doses of red bean extract (isoflavones). Conclusion: Red bean extract (isoflavones) had a significant effect in increasing IL-10 levels.

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)

O-295 Dual trigger does not improve reproductive outcomes in advanced maternal age women

Abstract Study question Could dual trigger increase oocyte yield and maturation rate in women of advanced maternal age (≥ 40) undergoing IVF? Summary answer Dual trigger does not result in higher oocyte yield or maturation rates compared to hCG monotrigger What is known already Advanced maternal age is related to poor ovarian response (POR) and remains a major therapeutic challenge in routine IVF practice, because of the association with low live birth rates and high cancellation rates. hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome (by improving oocyte quantity and quality) in normal responders, while evidence in poor responders remains controversial. Study design, size, duration This is a retrospective cohort study including patients attending a private IVF clinic from 1st January 2018 until 1st June 2022. Participants/materials, setting, methods All women who underwent IVF/ICSI in antagonist protocol in our center were included. Patients may have undergone triggering of the final oocyte maturation either with 250mcg of rhCG or 0.2 mg of GnRH agonist. Mature oocytes were inseminated using ICSI. Main results and the role of chance In total, 2242 patients were included, 454 (20.2%) in the rhCG group and 1788 (79.8%) in the dual trigger group. There was no significant difference in female age [41.3 (1.12) vs 41.3 (1.19), p value 0.94]. Total stimulation units and duration were also comparable between groups. The number of oocytes and MII oocytes did not differ significantly between rhCG and dual trigger group [5.8 (4.1) vs 6.3 (4.7) and 4.7 (3.3) vs 4.9 (3.4), p = 0.15 and 0.49, respectively]. Maturation rates were similar 81.7% (22.4) and 79.8% (23.5), p = 0.15, as well as fertilization rates (defined as the number of oocytes fertilized divided by the total number of cumulus-oocyte complexes recruited) [57% (29.7) vs 58.8% (29.4), p value=0.2]. Embryo utilization rates (defined as the total number of embryos transferred and cryopreserved divided by the number of oocytes fertilized) were comparable between the two arms: 69.7% (34.2) vs 70% (33.9), p value =0.22. Multivariate Poisson regression analysis adjusting for relevant confounders (AMH, total stimulation units) showed that the type of triggering strategy (dual trigger vs rhCG) was not associated with either the number of MII oocytes (coefficient 0.2, p value=0.24) or maturation rates (coefficient -1.8, p value 0.12). Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Wider implications of the findings To the best of our knowledge, this is the largest study evaluating dual trigger strategy in advanced maternal age women. Our data demonstrate that dual trigger cannot improve the outcome of low prognosis women and should not be used as a panacea for all IVF patients. Trial registration number NA

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