GnRH Antagonist Cycles Research Articles

A repeated gonadotropin-releasing hormone agonist trigger improves pregnancy outcomes of frozen-thawed embryo transfer in GnRH antagonist cycles: a retrospective propensity-matched score analysis.

To evaluate whether co-treatment of repeated GnRHa triggers with GnRH antagonist protocols can improve the clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) procedures. In this retrospective study, 712 Chinese Han women aged 20-42 undergoing autologous IVF/ICSI-ET with a flexible GnRH antagonist protocol were analyzed. The 735 cycles were split into the single (n = 238) and the repeated (n = 497) GnRHa groups. In the single GnRHa group, 0.2mg of triptorelin was given for oocyte maturation, whereas in the repeated GnRHa group, two doses of 0.2mg were administered 12h apart. PSM design was used for a fair comparison. The main study outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), good-quality embryo rate, and fertilization rate. Multivariate logistic regression analyses were used to identify all potential factors affecting clinical outcomes. Post-PSM, analysis of 159 cycles per group showed the repeated GnRHa group outperforming the single GnRHa group in IVF fertilization rates (71.5% vs. 67.7%, P < 0.05) and good-quality embryo rate (47.1% vs. 43.7%, P < 0.05). Furthermore, the repeated GnRHa group achieved higher CPR (72.6% vs. 53.4%, P < 0.05) and LBR (59.7% vs. 43.8%, P < 0.05) in FET cycles. Multivariate logistic regression indicated a significant negative correlation between the use of a single GnRHa trigger and both clinical pregnancy (OR = 0.382, P < 0.05) and live birth (OR = 0.518, P < 0.05). Our study reported that individuals who received a repeated GnRHa trigger exhibited higher CPR and LBR during FET cycles compared to those who received a single dose GnRHa trigger.

Inter-cycle variability of anti-Müllerian hormone: implications for predicting controlled ovarian stimulation cycle outcomes

BackgroundAnti-Müllerian hormone (AMH) is a widely used marker for estimating ovarian reserve, and it may predict response to ovarian stimulation. While AMH is considered a stable, cycle-independent marker, studies have shown it can exhibit significant fluctuations based on factors like age, reproductive stage, and menstrual cycle phase. The fluctuations in AMH levels can make it challenging to predict individual responses accurately, particularly when the AMH is not measured in the COS cycle. The aim of this study was to assess the inter-cycle variability of serum AMH levels in two consecutive menstrual cycles and their correlation with response to controlled ovarian stimulation outcome in the latter.MethodsIn this single-centre retrospective cohort study, data of normal and low responder patients who underwent intracytoplasmic sperm injection following a GnRH antagonist cycle at a university hospital infertility clinic between January 2022 and December 2023 were reviewed. Serum AMH levels were measured in the early follicular phase of two consecutive menstrual cycles with Elecsys-AMH Roche® system (Roche Diagnostics, Meylan, France). Correlations between AMH levels and controlled ovarian stimulation outcomes, including total oocyte and mature oocyte (MII) counts, were assessed. The study included normal and poor responder women to maintain data integrity.ResultsA total of 79 patients were included in the final analyses. Significant cycle-to-cycle variation in serum AMH levels was observed, with a median variation of 44.3%. Normal responders exhibited a mean change of 0.60 ± 0.46 ng/ml, while poor responders had a mean change of 0.28 ± 0.28 ng/ml. Approximately 20% of patients were reclassified between normal and poor responder categories based on the second AMH measurement. The controlled ovarian stimulation cycle AMH levels showed a stronger correlation with both total oocyte count (r = 0.871, P < 0.001) and MII oocyte count (r = 0.820, P < 0.001) compared to preceding cycle AMH levels.ConclusionAMH levels can exhibit significant variations between consecutive cycles, potentially leading to misclassification of patients. Measuring AMH in the early follicular phase of the COS cycle provides a more accurate prediction of the numbers of total and MII oocytes collected. Consistent and repeated AMH measurements can help clinical decision-making.

Exposure of antral follicles to medroxyprogesterone acetate during stimulation does not cause molecular perturbations in gonadotropin-responsiveness and steroidogenic function of granulosa cells in progestin-primed cycles.

Does medroxyprogesterone acetate (MPA) exposure in progestin-primed ovarian stimulation (PPOS) cycles cause molecular perturbations in the steroidogenic function and gonadotropin responsiveness of the granulosa cells? PPOS cycles are identical to traditional GnRH antagonist cycles not only for clinical IVF characteristics but also for gonadotropin receptor expression, response to gonadotropins, and steroidogenic function at the molecular level. PPOS is increasingly used as an alternative to GnRH antagonists due to the inhibitory effect of progesterone on LH release by reducing GnRH pulsatility at the hypothalamic level. Although a growing body of evidence from clinical studies did not indicate significant differences between PPOS and antagonist protocols for IVF cycle characteristics and obstetrical outcomes, it is still unknown whether exposure of the antral follicle cohort to progesterone or its synthetic derivatives during ovarian stimulation causes any subtle molecular aberrations in terms of steroidogenesis and gonadotropin responsiveness. To address this issue, detailed comparative molecular analyses were conducted in the luteinized mural granulosa cells (GCs) obtained from normal responding IVF patients undergoing PPOS and antagonist cycles. A clinical translational research study was conducted with IVF patients. This study included 55 normal responding IVF patients who underwent ovarian stimulation with either PPOS using MPA (5 mg twice daily) or GnRH antagonist cetrorelix acetate. Recombinant forms of FSH and hCG were used for ovarian stimulation and ovulation triggering, respectively. Luteinized mural GCs obtained during the oocyte retrieval procedure were used for the experiments. Cell culture, quantitative real-time PCR, immunoblotting, confocal time-lapse live cell imaging, and hormone assays were used. Demographic and IVF cycle characteristics of the patients undergoing ovarian stimulation with PPOS and GnRH antagonist were similar, including ovarian response, mature oocyte yield, and fertilization rates. Molecular analyses revealed that the expression of the enzymes involved in sex-steroid synthesis (StAR, SCC, 3β-HSD, 17β-HSD, aromatase) and the uptake/storage/utilization of cholesterol (LDL receptor, Hormone-sensitive lipase, hydroxy-methyl glutaryl Co-enzyme-A reductase, and Sterol O-acyltransferase1) in the GCs of the PPOS cycles were comparable to those of the antagonist cycles. The expression of the receptors for gonadotropins, estrogen, and progesterone hormones was also similar. Basal and hCG-induced increases in 3β-HSD expression and progesterone production and basal and FSH-induced increases in aromatase expression and E2 output of the GCs from PPOS patients did not exhibit any meaningful differences when compared with GCs from antagonist cycles. Furthermore, basal and hCG-induced up-regulation in the LDL receptor expression and cholesterol uptake did not differ between the groups. Confocal imaging also revealed similar patterns of expression for the steroidogenic enzymes and their co-localization with mitochondria. Lastly, the expression of the other important genes regulating cumulus expansion, ovulation, and luteal function [Relaxin, ADAMTS-1, and epidermal growth factor (EGF)-like growth factor amphiregulin] in the GCs of the PPOS and antagonist cycles were similar. N/A. Caution should be exercised when interpreting our data which was derived from normally responding patients whose ovulation was triggered with hCG. It is unclear whether the molecular parameters assessed vary according to infertility etiologies, magnitude of ovarian response, mode of trigger, and any other underlying ovarian pathologies or systemic diseases. MPA was the progestin used for PPOS and whether these findings can be generalized to other progestins is unknown. This study provides reassuring molecular evidence that exposure of antral follicle cohorts to MPA during the follicular growth phase does not have any detrimental effects on steroidogenic, ovulatory, and luteal functions when compared with GnRH antagonist cycles. This study was funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), and equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. N/A.

O-219 Explainable artificial intelligence (XAI) to determine the follicle sizes on trigger day that maximize mature oocyte yield

Abstract Study question Which follicle sizes on trigger day (TD) are key to obtaining mature oocytes, embryos, and blastocysts, thereby enhancing live birth rates? Summary answer Follicles sized 13-18mm are most likely to yield mature oocytes. Live birth rate (LBR) was increased with a greater proportion of follicles in this range. What is known already At the time of oocyte retrieval, follicles that are either too small or too large are less likely to yield mature oocytes. However, there is only limited data examining which follicle sizes on TD administration are optimally sized to yield mature oocytes, nor any data examining whether live birth rates are impacted. Explainable artificial intelligence (XAI) offers a valuable opportunity to leverage clinical data to determine the range of follicle sizes that are most likely to yield mature oocytes and lead to improved downstream outcomes. Study design, size, duration A retrospective study incorporating 19,082 patients undergoing their first IVF/ICSI cycle (2005-2023) across 11 European clinics. Follicle sizes on TD were related to oocyte maturity (14,140 patients), fertilization (17,822 patients), high-quality blastocyst development (17,488 patients), and pregnancy outcomes (12,672 patients). Secondary analyses included stratification by age (&amp;gt;35 years: 4,717 patients; ≤35 years: 5,707), and suppressant protocol (GnRH agonist: n = 5,420 patients; GnRH antagonist: n = 3,982). Participants/materials, setting, methods An ensemble-based XAI model, developed through ‘internal-external validation’, was trained, Bayesian optimized, and independently iteratively tested on hold-out clinic datasets. The model determined follicle sizes contributing most to successful laboratory outcomes by harnessing permutation importance and ‘SHAP’ values. Model performance was evaluated and optimized for mean absolute error (MAE). The top 50% contiguous cohort of influential follicle sizes on TD were identified, and further validated through analysis of follicle sizes on preceding days. Main results and the role of chance XAI analysis revealed that follicles sized 13-18mm on TD were most influential in yielding mature oocytes, especially those sized 15-18mm (MAE: 3.60 ±0.35). Predictive follicle sizes from scans 1-2 days preceding TD administration were consistent with expected mean follicle growth rates. For high-quality blastocysts, follicles sized 14-20mm were contributory, narrowing to 15-18mm in the subset of patients where oocytes had been confirmed to be mature. In hCG-triggered cycles, follicles sized 12-19mm were most likely to yield mature oocytes in GnRH antagonist cycles, whereas follicles sized 14-20mm were most contributory in GnRH agonist cycles. In patients ≤35 years, follicles 13-18mm were most contributory, whereas a wider range of follicles (11-20mm) were contributory in patients &amp;gt;35 years. In line with current practice, having three lead follicles ≥17mm on TD was associated with a median improvement in mature oocyte yield of 10% versus those that did not (p &amp;lt; 0.0001). By comparison, maximizing the proportion of follicles on TD within the optimal size range could better improve mature oocyte yield, for example, by 42% when at least 70% of follicles were sized 15-18mm (p &amp;lt; 0.0001). Likewise, LBR improved as the proportion of follicles sized 13-18mm was increased (&amp;lt;10%: 23.3%; 10-20%: 25.7%; 20-30%: 28.8%; 30-40%: 31.6%). Limitations, reasons for caution These data could help guide when to administer the trigger to optimize clinical outcomes, however prospective assessment of different TD strategies based on the proportion of follicles within the optimal follicle size ranges identified in comparison to current practice based on lead follicle size is required prior to clinical adoption. Wider implications of the findings These findings provide a data-driven approach to personalizing ovarian stimulation in IVF. The findings generated by applying an XAI model could assist clinicians in optimizing TD timing, potentially enhancing clinical outcomes by moving beyond the conventional focus on lead follicle size. Trial registration number not appicable

P-418 What is the optimal midluteal phase circulating progesterone level during a fresh IVF cycle? The answer differs from what one expects in a natural cycle

Abstract Study question Do midluteal phase circulating progesterone (P4) levels relate to the fresh embryo transfer clinical outcome and is rescue P4 useful in such cases? Summary answer Live birth rate (LBR) was significantly lower when P4 levels were below 20ng/ml and did not seem to benefit from rescue intramuscular P4. What is known already Preceding literature on the predictive value of midluteal P4 for LBR has shown conflicting results and frequently included small sample sets and heterogeneous ovarian stimulation protocols. The findings reported ranged from the lack of an association between P4 serum levels and clinical outcome to worse success rates seen either in the groups with the highest or the lowest P4 in midluteal phase. Furthermore, while rescue P4 has been empirically proposed, it has lacked formal assessment thus far. Study design, size, duration In total, 652 patients who underwent a fresh single blastocyst transfer in an IVF cycle in our center between 2014 and 2021 were included in this retrospective cohort study. All were GnRH-antagonist cycles using hCG trigger and luteal support with micronized vaginal progesterone 200mg twice daily. Rescue intramuscular progesterone was systematically administered whenever low midluteal P4 (below 1 standard deviation of the center’s mean) levels were detected. Participants/materials, setting, methods The cycles were subdivided into three groups according to the midluteal P4 levels: &amp;lt;10ng/ml, 10-20ng/ml and &amp;gt;20ng/ml. The primary outcome assessed was LBR, with secondary outcomes including clinical pregnancy (CPR) and pregnancy loss rates. Maternal age and body mass index (BMI), year of treatment, ovarian response, endometrial thickness, cause of infertility and embryo quality were controlled for using multivariable logistic regression. Main results and the role of chance The mean age ± standard deviation of patients was 36.8±3.8 years, while mean weight and BMI were 63.2±11.5kg and 23.3±3.9kg/m2, respectively. LBR in the group with P4&amp;gt;20ng/ml (46.5%) was significantly higher than in the groups with low and intermediate P4 serum levels (23.1% and 28.1%, respectively, p &amp;lt; 0.001). The same was true for CPR (54.5%, 30.8% and 37.9%, respectively, p &amp;lt; 0.001). Conversely, the rate of pregnancy loss in the group with P4&amp;gt;20ng/ml (23.8%) was significantly lower than in the groups with low and intermediate P4 levels (42.6% and 37.5%, respectively, p = 0.018). The multivariable logistic regression confirmed that, after controlling for the confounding variables described above, P4&amp;gt;20ng/ml remained significantly associated with a higher LBR (OR: 2.285; 95% CI: 1.506-3.469) and a lower pregnancy loss rate (OR: 0.488; 95% CI: 0.273-0.873), irrespective of the use of rescue IM P4. Finally, a multivariable linear regression analysis of the patients baseline characteristics suggested that the only parameter predictive of midluteal P4 levels was the female patients’ weight, with an inverse relationship (adjusted regression coefficient: -0,012; 95% CI: -0,016/-0,009). Limitations, reasons for caution As the pituitary suppression, ovulation trigger and luteal support protocols used in the cycles included in the study were homogeneous (in order to maximize the internal validity of the results), this limits the extrapolibility of the results to other stimulation protocols. Furthermore, we caution that this is a retrospective study. Wider implications of the findings The usefulness of both midluteal P4 serum measurements and rescue P4 should continue to be assessed. The reasons behind the need for higher levels of P4 in a fresh cycle, when compared to natural cycles, must also be investigated. Luteal support may require personalization according to female body weight. Trial registration number Not Applicable

Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.

Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. The study was registered at Clinical Trials Gov. (NCT04108039).

Association between serum LH levels on hCG trigger day and live birth rate after fresh embryo transfer with GnRH antagonist regimen in different populations.

To investigate whether serum LH levels on hCG trigger day are associated with live birth rate (LBR) after fresh embryo transfer with GnRH antagonist regimen in different populations. This study was a retrospective study. A total of 3059 fresh embryo transfers were divided into three populations: predicted normal ovarian responders (NOR) (n=2049), patients with PCOS (n=533), and predicted poor ovarian responders (POR) (n=477). Each population was stratified into three groups based on LH levels: < 25th percentile, 25-75th percentile, and > 75th percentile. The primary outcome of the study was LBR, and secondary outcomes included implantation, clinical pregnancy, and early pregnancy loss rates. Univariable and multivariable regression analyses were performed to adjust for potential confounders. In NOR, compared to the reference group (>75th percentile), LBR was significantly lower in the < 25th percentile group (adjusted OR=0.662; 95%CI, 0.508-0.863) and 25-75th percentile group (adjusted OR=0.791; 95%CI, 0.633-0.988). In PCOS patients, LBR decreased significantly in the < 25th percentile group (41.4%) compared to the 25-75th percentile group (53.7%) and > 75th percentile group (56.1%). In addition, the LBR was lower in the < 25th percentile group (33.6%) compared with the 25-75th percentile group (43.4%) and the>75th percentile group (42.0%) in POR, but this was not statistically significant. High serum LH levels are associated with increased LBR after fresh embryo transfer in GnRH antagonist cycles, which may be attributable to higher implantation rate. LH may be a predictor of whether to schedule fresh embryo transfer in IVF cycles for better clinical outcomes.

P-646 The effect of profound LH suppression in GnRH antagonist cycles on IVF/ICSI outcomes-A retrospective study of 400 cycles

Abstract Study question Does low pretrigger LH in GnRH antagonist cycles affect the blastulation rates and cumulative live birth rates? Summary answer Low pretrigger LH in GnRH antagonist cycles does not affect the blastulation rates and cumulative live birth rates in frozen embryo transfer cycles. What is known already • There is conflicting evidence that in GnRH antagonist cycles stimulated with recombinant FSH, low serum LH may effect negatively the pregnancy outcomes in fresh embryo transfer.(Benmachiche et al 2019). • Whether the observed effect of low LH is on the embryo or on the endometrial receptivity is not clear. Study design, size, duration • Retrospective observational single centre study with a study population of 400 undergoing IVF/ICSI in between December 2018- December 2021. • Controlled ovarian stimulation in GnRH Antagonist protocol in unselected population &amp;gt; 21yrs old undergoing IVF/ICSI. • Exclusion Criteria- • Long protocol • Flare protocol • Oocyte cryopreservation cycle • Donor oocyte cycle Participants/materials, setting, methods • Controlled ovarian stimulation is done according to the hospital’s standard operations of practice in flexible antagonist cycle with human menopausal gonadotropins and recombinant/urinary follicle stimulating hormone. • When 3 or more follicles &amp;gt;/=17mm, triggered with GnRH Agonist or dual trigger. • Oocyte pick up scheduled at 35-36hrs following trigger. • Serum LH measured at baseline and at trigger. • Clinical and embryological outcomes are assessed in between low serum LH i.e., &amp;lt;1.5MIU/ML and normal serum LH &amp;gt;/= 1.5 MIU/ML. Main results and the role of chance Demographic variables were comparable between both the arms, except that baseline LH is low in subjects with low pretrigger LH. Mean dose of gonadotropins although not statistically significant, is slightly higher in the low pretrigger LH group. Mean duration of stimulation is higher in low pretrigger LH group and is statistically significant. Mean number of oocytes retrieved, mature oocytes, fertilisation rate, number of blastocysts, day5 and day6 blastocyts, good quality blastocysts and cumulative live birth rates are similar between low pretrigger LH and normal pretrigger LH group. Outcomes between low pretrigger LH and normal pretrigger LH- Mean number of blastocysts- 5.02 +/-3.84 vs 4.72 +/-3.82 (p = 0.44) Mean number of day5 blastocysts- 4 (0-14) vs 3.5(0-20) (p = 0.86) Mean number of day6 blastocysts- 1 (0-8) vs 1 (0-9) (p = 0.4) Mean number of good quality blastocysts- 2(0-19) vs 2 (0-17) (p = 0.68 ) Number of cycles with no blastocysts- 11.1 vs 16.1% (p = 0.35) Cumulative live birth rate 47 vs 48% (p = 0.99) SECONDARY OUTCOMES- Mean dose of gonadotropins- 3282+/- 913 iu vs 3119 vs 926iu (p = 0.07) Mean duration of stimulation- 11.67 +/- 1.87days vs 11.09 +/- 2days (p = 0.01) Mean number of oocytes retrieved-14.98+/- 7.14 vs 13.9+/-7.9 (p = 0.15) Mean number of mature oocytes-11.19+/- 5.64 vs 10.43+/-6.44 (p + 0.21) Mean fertilisation rate-10.7+/- 5.47 vs 9.81+/-6.08 (p = 0.12) Limitations, reasons for caution Retrospective design. Outcomes are assessed in frozen embryo transfer cycles, bur are not compared with fresh embryo transfer cycles. Wider implications of the findings The study provides reassuring data that low serum LH on the day of trigger does not affect the blastulation rates, quality of blastocysts and cumulative live birth rates in frozen embryo transfer cycles. Whether frozen embryo transfer can negate the effect of low pretrigger LH, further studies are needed. Trial registration number Not applicable

P-586 Adding letrozole to gonadotropins during ovarian stimulation for IVF results in a similar cumulative live birth rate at lower costs following a failed IVF cycle

Abstract Study question Following a failed IVF cycle, does adding letrozole for the first 5 days of a repeated cycle have any advantage versus repeating the same protocol? Summary answer Following a failed IVF cycle, letrozole supplementation during ovarian stimulation for IVF results in a similar cumulative live birth rate (CLBR) with 22% less gonadotropins. What is known already Letrozole results in an increase of intraovarian androgen concentration, which augments follicular stimulating hormone (FSH) receptor expression on granulosa cells and follicular responsiveness to exogenous gonadotropins. Letrozole co-treatment with gonadotropins during controlled ovarian stimulation (COH) for IVF has been investigated mainly in poor and normo-responders with conflicting clinical outcomes. This is the first and largest study that investigates the effects of adding letrozole for the first five days of COH for IVF, in GnRH antagonist cycles, to a category of patients who had a prior failed stimulated IVF cycle using the same protocol. Study design, size, duration This is retrospective monocentric study of 426 patients, with a prior failed stimulated IVF cycle using an antagonist protocol, who underwent a second cycle between 2012 and 2017. In those patients, we studied the clinical outcomes of doing a repeated cycle, using the same protocol with the addition of 5mg of letrozole daily in the first 5 days of the cycle (Group A, N = 213) versus doing a repeated similar cycle without letrozole (Group B, N = 213). Participants/materials, setting, methods Groups A and B were matched for age, body mass index, anti-mullerian hormone and infertility diagnosis. Statistical analyses were carried out using student t test, Anova and linear regression models. The primary outcome was the CLBR. Secondary outcomes included the number of mature follicles, the number of mature oocytes (MII), the number of usable embryos, clinical pregnancy rates (CPR), live birth rates (LBR) and the total dose of gonadotropins administered. Main results and the role of chance This is the first study that investigates the effects of co-treatment with letrozole during COH for IVF in the category of patients who had a prior failed IVF cycle. Our results show that patients who received letrozole during COH with gonadotropins, versus gonadotropins alone, had a significantly lower number of MII oocytes (7±4.6 vs 8,2±5.0; P &amp;lt; 0.01). However, despite that, they had a similar number of usable embryos (1.8±1.6 vs 1.9±1.7; P = 0.31), CPR (23.5% vs 28.7%; p = 0.22), LBR per embryo transfer (16.9% vs 22.1%; p = 0.17) and CLBR (27.8% vs 25.3%; p = 0.55). A 22% lower dose of gonadotropins (3468±1389IU vs 4442±1657IU; p &amp;lt; 0.001) was needed to achieve similar pregnancy outcomes in the letrozole group versus the control group, resulting in lower treatment costs. Limitations, reasons for caution The retrospective nature of this study is its main limitation. Wider implications of the findings This study confirms that in women with a prior failed IVF cycle, co-treatment with letrozole results a similar cumulative live birth rate at a significant lower cost. Trial registration number NCT05677828

P-662 Embryo ploidy rates following PPOS or GnRH antagonist protocol. A prospective study with repeated ovarian stimulation

Abstract Study question Is there any difference in embryo ploidy rates following progesterone primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Summary answer Pituitary downregulation with a PPOS protocol with micronized progesterone results in a comparable number of euploid blastocysts with a GnRH antagonist protocol. What is known already Although the GnRH antagonist is consider by most the gold standard protocol for controlling the LH surge during ovarian stimulation for IVF/ICSI, progesterone-primed ovarian stimulation protocols (PPOS) are being increasing used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in equivalent blastocyst euploidy rates as compared with a GnRH antagonist protocol. Study design, size, duration In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive ovarian stimulation (OS) protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Participants/materials, setting, methods Overall, 44 women underwent two OS cycles with identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the 1st cycles was performed with the use of a flexible GnRH antagonist protocol and consecutively, after a washout period of one month, control of LH surge was performed with oral micronized progesterone from stimulation day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (PGT-A). Main results and the role of chance Comparisons between cycles did not reveal differences between the duration of OS neither in the gonadotrophins dose. Hormonal profile on the day of trigger revealed statistically significant differences between cycles in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher Progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. PPOS protocol resulted in a significantly higher number of oocytes (10.27± 5.84 versus 12.68± 8.09), (DBM -2.4 [95% CI -4.1; -0.73]), MIIs (7.34±4.15 versus 9.09± 6.12), (DBM -1.8 [95% CI -3.1; -0.43]), and 2PNs (5.66±3.35 versus 7.14± 4.99), (DBM -1.5 [95% CI -2.6.1; -0.32]) as compared with the GnRH antagonist protocol. Nevertheless, no differences were observed regarding the mean number of blastocysts (2.84±2.12 versus 2.91±2.11), (DBM -0.07 [95% CI -0.67; 0.53]) and the mean number of biopsied blastocysts (2.86±2.15 versus 2.93±2.16), (DBM -0.07 [95% CI -0.70; 0.56]). Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 vs. 1.00 ± 1.12 for the comparison of PPOS vs. GnRh antagonist. Limitations, reasons for caution The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol there was no randomisation, the first cycle was always a GnRH antagonist cycle and the 2nd a PPOS with one month of washout period in between. Wider implications of the findings The current study provides evidence that the PPOS may result in equivalent blastocyst euploidy rates compared with antagonist protocol. This may imply that in case of a freeze-all protocol, clinicians may safely consider PPOS to control the LH surge and patients could benefit from the advantages (cost and oral administration). Trial registration number NCT04108039

P-632 Micronized progesterone is better than GnRH antagonist to prevent LH surge in oocyte donation cycles

Abstract Study question Micronized progesterone or GnRH antagonist: which is better to control the LH surge in the egg donation process? Summary answer Micronized progesterone is better. Is just as effective as GnRH antagonist and offers three additional advantages: cheaper, more convenient, and saves intermediate controls. What is known already GnRH antagonists have been widely considered to prevent LH surge. When fresh embryo transfer is not advised, micronized progesterone has been shown to be an effective alternative with some other very interesting advantages. If efficacy would prove to be similar, there will be three obvious advantages for the preferential use of micronized progesterone over the antagonist protocol: oral or vaginal administration is preferred over subcutaneous injection, cost would be much lower, and progesterone can be used from day one and avoid inconvenient intermediate controls. This would be particularly interesting in egg preservation, preimplantation genetic screening, and oocyte donation programs. Study design, size, duration We retrospectively analyzed our oocyte donation program from 2018 to 2021. All 358 cycles under short cycle protocol were studied. 67 donors were under the Antagonist cycle; age 24,7 years (18 – 32) with normal Body Max Index (22,2 Kg/m2 range 17-29) 291 donors were under the micronized progesterone cycle; age 24,5 years (18-31) with normal Body Max Index (22,3 Kg/m2 range 18-29) Participants/materials, setting, methods 67 donors were under the Antagonist cycle: LH suppression was accomplished by subcutaneous injections of Ganirelix 0.25 mg starting when follicles &amp;gt;14mm or E2 levels &amp;gt;400 pg/ml and continued until GnRH triggering. No patients were cancelled. 291 donors were under the micronized progesterone cycle: endogenous LH suppression was accomplished by vaginal administration of micronized progesterone (200 mg) once a day at bedtime, from stimulation day 1 and continuing until GnRH triggering. Four patients were cancelled. Main results and the role of chance 67 donors were under the GnRH antagonist cycle. 1115 oocytes were retrieved (16,6 range 2-39). All but two donors had egg vitrification: 65 patients, 916 oocytes (14,1 range 1-30) so 82% could be preserved. (916 / 1115). From 67 cycles, 916 vitrified oocytes were obtained (average 13,7). 291 patients were under the micronized progesterone cycle. Four patients were cancelled (no response in two, follicular asynchrony in one and personal reasons in one. No LH surges were observed). From 287 egg collections, 4683 oocytes were retrieved (16,3 range 2-49). All but two patients had vitrification: 285 patients, 3784 oocytes (13,3 range 2-37) so 81% could be preserved. (3784 / 4683). From 291 cycles, 3784 vitrified oocytes were obtained (average 13,2) Both groups were similar: total oocytes recovered per patient (16,3 vs 16,6) egg maturation (81 vs 82%) and global results (13,2 vs 13,7) Micronized progesterone offers three additional advantages: is obviously cheaper than GnRH antagonist. Also, vaginal route is commonly preferred to subcutaneous injections. And allows to offer a more flexible donor program making unnecessary to set some intermediate follicular controls. CONCLUSION: Micronized progesterone offers similar results than GnRH Antagonist with three additional advantages: is cheaper, is more convenient and intermediate controls can be avoided. Limitations, reasons for caution Although they are most likely similar, fertilization and pregnancy rates after both protocols should be deeply analyzed. Wider implications of the findings Micronized progesterone would also be particularly useful in egg preservation cycles and preimplantation genetic screening programs. Trial registration number not applicable

P-598 Analysis of the oocyte yield and Ovarian Sensitivity Index with the use of two gonadotropins (FSHr/FSHu) and two pituitary suppression protocols (PPOS/GnRH-ant)

Abstract Study question Is there a difference, in terms of ovarian yield and sensitivity, comparing a progestin-primed protocols (PPOS) to a GnRH antagonist (GnRH-ant) and using different follitropin? Summary answer PPOS is an effective choice, with both follitropis. Nevertheless, could improve ovarian sensitivity to FSHu increasing the number of oocyte yield without compromising oocyte quality. What is known already The use of new ovarian stimulation protocols, starting during the luteal phase or randomly shows that endogenous progesterone alone is sufficient to block the LH surge and does not compromises oocyte competence and pregnancy outcomes. For these reasons, exogenous progesterone was utilized as an innovative model of pituitary suppression. Most studies have shown the effectiveness of the use of PPOS compared to the GnRH (antagonist or agonist) in IVF cycles. For oocyte donation only three studies were carried out analyzing the effect of PPOS with a recombinant FSH (FSHr) Study design, size, duration It is a retrospective, cohort, paired study. We analyzed egg donation cycles carried out in Next Fertility Valencia from January 2020 to May 2021. In total 93 donors were selected as eligible, each one undergoing both the PPOS and GnRH antagonist cycles for a total of 186 cycles, 54 received FSHr and 39 HP-FSHu. To attempt to eliminate possible bias due to interpersonal differences, every patient was her own control. Participants/materials, setting, methods All donors underwent two controlled ovarian stimulation cycles within 6 months, one using flexible GnRH antagonist (Ganirelix) and the other using medroxyprogesterone acetate (MPA), with FSHr or FSHu monotherapy and a GnRH-agonist triggering. The oocyte yield was analyzed focusing on: the number of oocytes retrieved, mature (MII) oocytes and useful oocytes (mature oocytes without morphological alterations). We also evaluated the Ovarian sensitivity index (OSI) calculating the oocyte number for each 1000 IU of gonadotropin used Main results and the role of chance Total gonadotropin consumption and duration of ovarian stimulation were similar in both models of pituitary suppression regardless the type of FSH. One less control is required with MPA than the GnRH-ant in both FSH groups. There were no premature ovulations in MPA or GnRH antagonist cycles regardless of the gonadotropin used. In the FSHr group no difference was observed in the oocyte yield and OSI between MPA and GnRHa. On the other hand, in the FSHu group a statistically significant improvement in the number of total oocytes retrieved (20,2 ± 8,5 vs 23,8 ± 10,9), total MII (18,0 ± 7,2 vs 21,2 ± 10,4) and OSI (6,4 ± 3,5 vs 7,7 ± 4,6) was observed in favor of the use of MPA. Also, the number of useful MII was higher with MPA (15,7 ± 6,5 vs 18,6 ± 10,4). No significant differences were detected in fertilization and blastocyst rate regardless the type of pituitary suppression and FSH used Limitations, reasons for caution The main limitation lies in the retrospective nature of the study. However, since each patient is her own control (Paired study), it gives an added value Wider implications of the findings The efficacy and efficiency of the MPA does not seem to be affected by the type of gonadotropin used, this further reassures about the possibility of using it with patients in case of fertility preservation cycles, PGT-A/M, "DuoStim" cycles Trial registration number Not applicable

P-657 Elecys anti-Müllerian hormone thresholds for defining ovarian response categories; comparison of published and novel values in 7,988 treatment naïve women

Abstract Study question Test the accuracy of published and novel AMH thresholds in predicting (low, sub-optimal, optimal and high) ovarian response categories in first treatment cycles. Summary answer Published AMH thresholds for poor and excessive ovarian response perform adequately, however, prediction of suboptimal or optimal oocyte yields is difficult reflecting their limited range. What is known already AMH is an established predictor of ovarian response, and can identify women at risk of poor (&amp;lt;4 oocytes) or excessive (&amp;gt;15 oocytes) response. With the development of suboptimal (4 to 9 oocytes) and optimal (10 to 14 oocytes) response categories, a series of AMH ranges for the Roche Elcesys AMH assay has been proposed to predict response for all four categories (AMH &amp;lt;6.4pmol/l, 4.9–11.3 pmol/l, 11.3–20.9 pmol/l, and &amp;gt;14.2 pmol/l). To date there has been no internal or external validation of these single centre derived thresholds, and it is unknown whether they are generalisable to other clinic populations. Study design, size, duration Observational cohort study from 8 UK clinics, incorporating 7,998 women undertaking their first ovarian stimulation cycle for assisted conception or fertility preservation between 2016 and 2022, with a pre-treatment AMH measured using the Roche Elecsys AMH assay. Both GnRH agonist and antagonist cycles were included, with triggering by either recombinant hCG or GnRH agonist once 3 follicles were ³18mm in size with oocyte retrieval performed 36h later. Participants/materials, setting, methods To give equal opportunity to the published and novel thresholds, patients were divided into training (5,330) and testing (2,668) sets. Novel cut-off points for a low, sub-optimal, optimal and high response were derived in the training set. The performance of these novel thresholds and those of published values were then assessed and compared in the testing set by their respective AUC, and precision as defined as the fraction of correct predictions for a certain class. Main results and the role of chance Baseline patient characteristics (mean, SD) were 35.1±4.7 years; BMI 25.5±4.4 kg/m2, with a median AMH 15.2 pmol/l (IQR 8, 26) and a median of 11 (IQR 6,16) oocytes retrieved. These baseline characteristics and outcomes were similar after splitting in the training and testing datasets. Baseline AMH and oocytes collected were moderately correlated (r = 0.54, p &amp;lt; 0.001). 465 (5.8%) cycles were cancelled due to not meeting trigger criteria and classed as poor/low responders. The novel thresholds for low oocyte yield (≤10.05 pmol/l) provided similar performance (AUC 0.70 95%CI 0.66-0.74, sensitivity 0.69, specificity 0.74) to the published thresholds (AUC 0.67, 95%CI 0.62-0.72) in the testing population. Similarly, the novel high (15.9pmol/l) threshold (AUC 0.78, 95%CI 0.75-0.81, sensitivity 0.78, specificity 0.64) exhibited similar performance to the published threshold AUC 0.77, 95%CI 0.74,0.81) in the testing population. Deriving novel thresholds for prediction of 4 categories of response (6.7, 12.9, 18.9pmol) was associated with slightly better precision for low, suboptimal and high categories (p &amp;lt; 0.001), with the fraction of correct predictions for a certain category of response for the novel cut-points; 69.0 % low, 11.7% suboptimal, 14.1% optimal and 78.3% high, as compared to 52.0%, 27.8%, 12.9% and 83.8% respectively for the published values. Limitations, reasons for caution While designing the ovarian stimulation strategies clinicians were aware of the baseline AMH and targeted a perceived optimal response for cumulative live birth (∼15 oocytes), which may have contributed to the performance of both the established and novel AMH thresholds. Wider implications of the findings In a large heterogenous population of women undergoing their first treatment cycle, we confirm the appropriateness of the previously published Elecsys AMH values for prediction of low (&amp;lt;6.4pmol/l) and high (&amp;gt;14.2pmol/l) oocyte yields. Trial registration number N/A

O-132 Comparison of pregnancy rates in antagonist cycles after luteal support with GnRH-agonist versus progesterone – prospective randomized study

Abstract Study question Are pregnancy rates in GnRH-antagonist cycles triggered with hCG and luteal phase support (LPS) with intranasal GnRH-agonist or vaginal progesterone comparable? Summary answer Nasal GnRH-agonist for LPS is associated with higher pregnancy rates compared with standard progesterone support in antagonist-based cycles triggered with hCG What is known already Regardless of its mechanism of action, the use of GnRH-a during the luteal phase in addition to progesterone, either in a single or multiple doses, has become a common practice as a part of ART protocols, based on its association with higher pregnancy and live birth rates . Its use as a sole agent for LPS has not gained the same popularity although studies supporting non-inferiority and even higher live birth rates with GnRH-a as a sole LPS agent have been published. Study design, size, duration A single-center, prospective, randomized study. A total of 150 patients underwent 164 GnRH-antagonist-based IVF cycles triggered with hCG and fresh embryo transfer. The study was conducted between June 9th, 2020, and May 5th, 2022. Participants/materials, setting, methods The study was conducted in the IVF clinic at University-affiliated tertiary medical center. Patients meeting the inclusion criteria who underwent antagonist-based IVF cycles and hCG triggering were enrolled. Computer-based randomization (1:1 ratio) was performed on the day of oocyte pickup (OPU). In both groups LPS was initiated on the evening of the OPU day with either GnRH-agonist nasal spray (Nafareline, nasal spray 200 mcg twice daily)or vaginal micronized progesterone (Utrogestan 300 mg, 3 times daily). Main results and the role of chance A total of 150 patients underwent 164 cycles, 127 cycles of which were included in the study cohort. Of them, 64 (50.4%) and 63 (49.6%) cycles were treated with GnRH-agonist or progesterone respectively as sole luteal phase support. A significantly higher pregnancy rate was found in the GnRH-a group compared with the progesterone group (43.8% versus 25.4% respectively; P = 0.030). After adjustment of several potential confounders such as age, body mass index (BMI), past obstetric history, number of IVF cycles, oocytes retrieved and embryos transferred, GnRH-agonist was still associated with a higher pregnancy rate (odds ratio 3.4, 95% confidence interval 1.4-8.3). Ovarian hyperstimulation syndrome (OHSS) rates were similar between the groups. Significantly higher progesterone levels were measured at β-hCG testing day in the GnRH-a group, both for the cleavage stage embryos (129.1±23.7 nmol/L vs. 97.7±48.9 nmol/L, P = 0.024) and for the blastocysts (127.2±0.1 nmol/L vs. 75.3±49.1 nmol/L, P = 0.034). Limitations, reasons for caution This study is not powered for analysis of clinical pregnancy rates, live birth rates and pregnancy outcomes. Larger studies are needed for research of these outcomes. All patients participating were at low risk for OHSS, therefore the study is underpowered to find significant differences in early or late OHSS.Wider implications of the findings Our findings suggest that intranasal GnRH-agonist administration as a sole luteal support in antagonist-based IVF cycles triggered with hCG results in higher pregnancy rates in comparison with traditional irritating vaginal preparations while not mandating additional support in the first weeks of pregnancy. Trial registration number Clinicaltrials.gov - NCT05484193

Prediction of oocyte maturation rate in the GnRH antagonist flexible IVF protocol using a novel machine learning algorithm – A retrospective study

Oocyte maturation is affected by various patient and cycle parameters and has a key effect on treatment outcome. A prediction model for oocyte maturation rate formulated by using machine learning and neural network algorithms has not yet been described. A retrospective cohort study that included all women aged ≤ 38 years who underwent their first IVF treatment using a flexible GnRH antagonist protocol in a single tertiary hospital between 2010 and 2015. 462 patients met the inclusion criteria. Median maturation rate was approximately 80%. Baseline characteristics and treatment parameters of cycles with high oocyte maturation rate (≥80%, n = 236) were compared to cycles with low oocyte maturation rate (<80%, n = 226). We used an XGBoost algorithm that fits the training data using decision trees and rates factors according to their influence on the prediction. For the machine training phase, 80% of the cohort was randomly selected, while rest of the samples were used to evaluate our model’s accuracy. We demonstrated an accuracy rate of 75% in predicting high oocyte maturation rate in GnRH antagonist cycles. Our model showed an operating characteristic curve with AUC of 0.78 (95% CI 0.73–0.82). The most predictive parameters were peak estradiol level on trigger day, estradiol level on antagonist initiation day, average dose of gonadotropins per day and progesterone level on trigger day. A state-of-the-art machine learning algorithm presented promising ability to predict oocyte maturation rate in the first GnRH antagonist flexible protocol using simple parameters before final trigger for ovulation. A prospective study to evaluate this model is needed.

Impact of pre-treatment in GnRH-antagonist cycles triggered with GnRH agonist on reproductive outcomes.

Pre-treatment (PT) therapies in IVF are known to be used as pre-stimulation modality to improve cycle outcomes. This study aims to assess whether PT in GnRH antagonist cycles triggered with GnRH-agonist impact oocyte maturation response. Data were retrospectively collected for patients who underwent GnRH antagonist cycle with agonist triggering with and without PT. The patients were allocated to groups according to their PT status. The primary outcome evaluated was suboptimal maturation response. Suboptimal maturation to trigger was defined as no oocyte upon retrieval when adequate response was expected. The study population included 196 patients who underwent GnRH antagonist cycle with agonist triggering. The study group included 69 patients who received PT. The control group included 127 patients with no PT. In univariate analysis, the PT group significantly displayed suboptimal response compared to the controls (p = 0.008). All the patients in the study group with suboptimal response (with or without hCG re-triggering) were treated with GnRH-agonist as PT. Basal and pre-trigger LH values were significantly lower in the study group compared to controls (p < 0.001). Multivariate regression analysis revealed that PT with GnRH agonist was a significant predictor for suboptimal response. Pre-treatment, and particularly the use of GnRH-agonist as PT in antagonist cycles triggered with agonist, increases the risk of suboptimal response to GnRH-agonist trigger. This might be explained by prolonged pituitary suppression, which lasts beyond the PT cessation.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve.

It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization (IVF) in high or normal ovarian responders. However, it is not clear whether dual triggering also benefits patients with diminished ovarian reserve (DOR). The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone (GnRH) agonist combined with human chorionic gonadotropin (hCG) for final follicular maturation improves the cumulative live birth rate (CLBR) during the GnRH-antagonist cycle in patients with DOR. This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection (IVF-ICSI) cycles at Peking University People's Hospital from January 1, 2017 through December 31, 2017. Oocyte maturation was triggered by GnRH combined with hCG (n=110) or hCG alone (n=71). Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle. Patients were followed up for 3 years. The dual trigger treatment did not affect CLBR, which is an overall determinant of the success rate of assisted reproductive technology (ART). Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group (90.1% vs. 83.9%, P=0.040). Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR, but did slightly improve fertilization rate, oocyte count, and embryo quality.

Reproductive outcomes of dual trigger with combination GnRH agonist and hCG versus trigger with hCG alone in women undergoing IVF/ICSI cycles: a retrospective cohort study with propensity score matching

BackgroundDespite a large number of studies on the selection of trigger drugs, it remains unclear whether the dual trigger with human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonist, compared to the trigger with hCG alone, can improve the reproductive outcome of patients undergoing assisted reproductive technology. Therefore, this study aimed to compare the laboratory and clinical outcomes of dual trigger versus single trigger.MethodsIn this retrospective cohort study, we evaluated 520 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles between July 2014 and September 2020 at the Reproductive and Genetic Center of Integrative Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All patients underwent IVF/ICSI treatment with fresh embryo transfer using the GnRH antagonist protocol. We used propensity score matching to control for confounding variables and binary logistic regression analysis to determine the correlations between trigger methods and pregnancy outcomes. After propensity score matching, 57 cycles from each group were evaluated and compared for laboratory or clinical outcomes in this retrospective cohort study.ResultsThere was no significant difference in the number of oocytes retrieved, embryos available, top-quality embryos, or the rate of normal fertilization between the dual-trigger and single-trigger protocols, respectively. The incidence of ovarian hyperstimulation syndrome, implantation rate, biochemical pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate, early miscarriage rate, and live birth rate were also similar between the two groups, while the miscarriage rate (37.0% vs. 12.5%, p = 0.045) was higher in the dual-trigger than the single-trigger group. Subsequent binary logistic regression analysis showed that age was a remarkably significant independent predictor of both clinical pregnancy rate (odds ratio = 0.90, 95% confidence interval: 0.84–0.97, p = 0.006) and live birth rate (odds ratio = 0.89, 95% confidence interval: 0.82–0.97, p = 0.005).ConclusionsTherefore, dual-trigger for final oocyte maturation might increase miscarriage rate, but in terms of the laboratory and other pregnancy outcomes such as clinical pregnancy rate, early miscarriage rate or live birth rate, there was no evidence to show that dual trigger was superior to an hCG-trigger alone for patients undergoing GnRH-antagonist cycles with fresh embryo transfer.Trial registrationRetrospectively registered.

Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin improves live birth rates in POSEIDON group 3 and 4 expected poor responders

Objective Aim of this study was to evaluate the effects of dual triggering with gonadotropin releasing hormone agonist and human chorionic gonadotropin (hCG) on outcomes of fresh embryo transfers following gonadotropin antagonist cycles in POSEIDON group 3 and group 4 low prognosis women and to compare the outcomes with hCG-only triggering. Methods This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON group 3 and 4) that underwent fresh embryo transfers following in-vitro fertilization/intracytoplasmic sperm injection cycles with either dual triggering or hCG-only triggering between January 2010 and April 2020. A total of 1068 women that underwent dual triggering and 1931 that underwent hCG-only triggering were included in the study. Results Number of retrieved oocytes, M2 oocytes, oocyte maturation rate, fertilization rate, obtained 2PN embryos, implantation rate, clinical pregnancy rate and live birth delivery rates were found significantly higher in dual-triggering group in comparison to hCG-only group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.02, p < 0.001 respectively). Conclusion Dual trigger with concomitant injections of GnRH agonist and hCG in GnRH antagonist cycles appears to improve IVF outcomes, increase quality of embryos, reduce miscarriage rates and consequently increase live birth delivery rates in POSEIDON groups 3/4 poor responders.

P-664 The effect of LH levels on the day of trigger on the oocyte retrieval and maturation rates in GnRH-antagonist cycles with an agonist trigger

Abstract Study question Are LH levels on day of trigger correlated with the number of oocytes retrieved and oocyte maturation rate in GnRH-antagonist cycles with an agonist trigger? Summary answer Low LH levels on the day of trigger were associated with a lower oocyte retrieval rate yet no correlation with oocyte maturation rates was found. What is known already The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. GnRHa trigger offers important advantages including the prevention of ovarian hyperstimulation syndrome (OHSS) with the elicitation of an endogenous LH and FSH surge. Therefore, we sought to evaluate whether LH levels on the day of the trigger are associated with the efficacy of the trigger in eliciting endogenous LH surge and thereby influencing oocyte retrieval and oocyte maturation rates. Study design, size, duration This retrospective single center study included all GnRH antagonist cycles triggered with GnRHa trigger (Decapeptyl 0.2mg) performed at our IVF unit between July 2013 and December 2020. We studied the association between LH levels on the day of trigger and the number of oocytes retrieved. Additionally, we studied the effect of LH levels on oocyte maturation rates. Participants/materials, setting, methods All GnRH antagonist cycles triggered with GnRHa trigger were included. Data was acquired through individual review of medical records. Linear regression was used to study the correlation between LH levels and oocyte retrieval and maturation rates. Moreover, LH levels on day of trigger were divided ≤1 IU/L and &amp;gt; 1 IU/L to further investigate this correlation. The ratio between Basal LH and LH on day of trigger was investigated as well. Main results and the role of chance There were 211 GnRH antagonist cycles triggered with GnRH agonist trigger during the study period. The mean age of patients in the study group was 30.1±4.8 y/o, mean basal LH levels were - 6.8±3.4 IU/L, mean Basal FSH levels were - 6.7±1.9IU/L and the mean total dose of gonadotropin administered was 1633.4±680.6 Units. The mean E2 levels were 11,444±7018.5 pmol/L and the mean number of oocytes retrieved was 19.8±10.2. A correlation was found between lower LH levels on the day of trigger and the number of oocytes retrieved (p &amp;lt; 0.001). No correlation was found between LH levels on the day of trigger and oocyte maturation rates (p = 0.82). The ratio between Basal LH and LH on day of trigger was not found to be a significant factor influencing either the number of oocytes retrieved or oocyte maturation rate. When dividing the group by LH on day of trigger to below and above 1, a borderline difference was found relating to oocyte retrieval rate between the two groups (p = 0.06). Limitations, reasons for caution The retrospective nature of the study is the main limitation. Patients receiving GnRHa trigger are mainly a selective population of either high responders or patients for fertility preservation stimulated to retrieve many oocytes, therefore findings may not be applicable to normal or poor responders. Wider implications of the findings Low LH levels on day of trigger were found associated with lower oocyte retrieval rates. GnRHa has become an alternative to standard hCG triggering in certain situations. These are preliminary findings of an ongoing study designed to investigate the efficacy of GnRHa trigger according to cycle parameters including LH levels. Trial registration number not applicable