GnRH-ant Protocol Research Articles

Increasing dominant follicular proportion was associated with adverse IVF/ICSI outcomes in low-prognosis women undergoing GnRH antagonist protocol: a retrospective cohort study

PurposeThis study aimed to examine the correlation between different dominant follicle proportions (DFPs) and outcomes of in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) among patients classified under POSEIDON Groups 3 and 4, who underwent gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Additionally, it sought to determine the optimal DFP threshold for trigger timing.MethodsA retrospective analysis was performed on patients classified under POSEIDON Groups 3 (n = 593) and 4 (n = 563) who underwent GnRH-ant protocols for controlled ovarian hyperstimulation (COH) between 2016 and 2022. These patients were categorized into two groups based on their DFPs, defined as the ratio of ≥ 18-mm dominant follicles to ≥ 12-mm follicles on the trigger day (DFP ≤ 40% and DFP ≥ 40%). Statistical analyses, including restricted cubic spline (RCS) and multivariate logistic regression, were employed to assess the relationship between DFP and IVF/ICSI outcomes.ResultsDemographic characteristics of patients were similar across groups. In POSEIDON Groups 3 and 4, DFP > 40 was associated with a significant decrease in the number (No.) of oocytes retrieved, cleaved embryos, and available embryos. Moreover, following the GnRH-ant cycle, the clinical pregnancy and live birth rates in fresh embryo transfer (ET) were notably reduced in the DFP > 40 group compared with the DFP ≤ 40 group, whereas no significant differences were observed in the pregnancy outcomes of the first frozen-thawed embryo transfer (FET) between the groups. In POSEIDON Group 3, the cumulative clinical pregnancy rate (CCPR) and cumulative live birth rate (CLRB) were significantly higher in the DFP ≤ 40 subgroup than in the DFP > 40 subgroup, with a notable decrease in CLRB observed with increasing DFP levels. However, in POSEIDON Group 4, no significant differences in CCPR and CLRB were found between the groups. Logistic regression analysis identified age and the No. of oocytes retrieved as pivotal factors influencing CLRB in Group 4.ConclusionFor patients in POSEIDON Group 3, maintaining a DFP ≤ 40 mm is crucial to achieve optimal laboratory and pregnancy outcomes by avoiding delayed triggering. However, for patients in POSEIDON Group 4, age remains a critical factor influencing CLRB regardless of DFP, although a higher No. of oocytes retrieved and available embryos with DFP ≤ 40 is beneficial.

Effect of LH level on HCG trigger day on clinical outcomes in patients with diminished ovarian reserve undergoing GnRH-antagonist protocol

Research questionDoes luteinizing hormone (LH) levels on human chorionic gonadotropin (HCG) trigger day (LHHCG) affect the clinical outcomes of patients with diminished ovarian reserve (DOR) undergoing gonadotropin-releasing hormone antagonist (GnRH-ant) protocol?MethodsRetrospective analysis fresh embryo transfer cycles of DOR patients who underwent GnRH-ant protocol from August 2019 to June 2023. The participants were divided into different groups according to LHHCG level and age. The clinical data and outcomes were compared between groups.ResultsIn patients with DOR, the HCG positive rate (59.3% versus 39.8%, P = 0.005), embryo implantation rate (34.5% versus 19.7%, P = 0.002), clinical pregnancy rate (49.2% versus 28.4%, P = 0.003), live birth rate (41.5% versus 22.7%, P = 0.005) in LHHCG < 2.58 IU/L group were significantly higher than LHHCG ≥ 2.58 IU/L group. There was no significant correlation between LHHCG level and clinical pregnancy in POSEIDON group 3. In POSEIDON group 4, the HCG positive rate (52.8% versus 27.0%, P = 0.015), embryo implantation rate (29.2% versus 13.3%, P = 0.023), clinical pregnancy rate (45.3% versus 18.9%, P = 0.010) in LHHCG < 3.14 IU/L group were significantly higher than LHHCG ≥ 3.14 IU/L group. Logistic regression analysis indicated that LHHCG level was an independent influencing factor for clinical pregnancy in POSEIDON group 4 patients (OR = 3.831, 95% CI: 1.379–10.643, P < 0.05).ConclusionsLHHCG level is an independent factor affecting pregnancy outcome of fresh embryo transfer in DOR patients undergoing GnRH-ant protocol, especially for advanced-aged women. LHHCG had a high predictive value for POSEIDON group 4 patients, and LHHCG ≥ 3.14 IU/L predicts poor pregnancy outcomes.

P-592 Comparison of the cumulative live birth rate of different doses of rFSH in poor ovarian reserve women undergoing GnRH antagonist ART treatment: a Randomized Controlled Trail

Abstract Study question Does an increased FSH dosage result in higher cumulative live birth rates in advanced age women with poor ovarian reserve treated with IVF or ICSI? Summary answer In poor ovarian reserve women, FSH dose of 300 IU/day does not improve cumulative live birth rates as compared to 150 IU/day. What is known already Natural fecundity and pregnancy rate following ART decrease dramatically in women aged 35 years and above. An open-label multicenter RCT described no difference in the cumulative live birth rate between the increased FSH dose (225/450 IU/day) and standard dose (150 IU/day) in women with a predicted poor ovarian response. Nevertheless, it is still unclear whether advanced age women with poor ovarian reserve who are undergoing IVF/ICSI benefit from a higher gonadotrophin dose. Therefore, we aimed to assess whether rFSH 300 IU/day compared to 150 IU/day in advanced age women with poor ovarian reserve resulted in higher cumulative live birth rates. Study design, size, duration A single center prospective randomized controlled trail that included first in vitro fertilization cycle with a GnRH-ant protocol and subsequent fresh and frozen-thawed cycles from April 2019 to December 2022. The study group included 104 women that received rFSH 150 IU/day and 99 women received rFSH 300 IU/day in antagonist protocol. Participants/materials, setting, methods Women for their first stimulation cycle, aged 35 to 42 years with antral follicle count（AFC）≤ 5 or anti-mullerian hormone （AMH） ≤ 1.2 ng/ml were randomized. Study group and control group respectively received 300 IU and 150 IU rFSH from menstrual cycle day 2 or 3 till the day of trigger. The primary outcome was cumulative live birth rate per woman per stimulation over a 2-year period to account for the first live birth. Main results and the role of chance This study included 203 women with the GnRH antagonist protocol. Of them, 99 patients were in 300 IU/day rFSH group, and 104 patients were in 150 IU/day rFSH group, respectively. The two groups were comparable for all baseline characteristics. The cumulative live birth rate for increased rFSH dosing (300 IU) versus standard dosing (150 IU) was 13.13% (13/99) versus 25% (26/104) per stimulation cycle. (P = 0.049). There were no differences in cumulative pregnancy rates 27.27% (27/99) vs 35.58% (37/104) per stimulation cycle. (P = 0.262). The cumulative live birth rate and cumulative pregnancy rates per transfer cycle in 300 IU/day rFSH group vs 150 IU/day rFSH group presented no statistical difference. No significant difference was found in secondary outcomes including time to live birth, number of MII oocytes, number of transferable embryos, implantation rate, multiple pregnancy rate, ectopic pregnancy rate and miscarriage rate between the two groups. Limitations, reasons for caution As this study is open-label, potential selective cancelling of cycles in women could have influenced the cumulative results. Also, this study practiced in a single-center and specific patient population, the results may not be generalizable to a broader population. Wider implications of the findings In women 35 years or older with poor ovarian reserve, improving rFSH dosage to 300IU in GnRH-ant protocol did not improve cumulative live birth rate. rFSH 150IU/day may be recommended at the start of COS to achieve live birth outcomes while decrease costs. Trial registration number ’not applicable

Effect of body mass index on progesterone level on trigger day in gonadotropin-releasing hormone antagonist cycles

Objective To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles. Methods This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group (n = 230):18.5 kg/m2≤BMI < 24 kg/m2; overweight group (n = 122): 24 kg/m2≤BMI < 28 kg/m2; Obesity group (n = 60): BMI ≥ 28 kg/m2. Variables with p < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol. Results After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p < .05). Conclusion The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.

Dydrogesterone-primed ovarian stimulation versus gnrh antagonist protocol in in-vitro fertilization for poor responders: A pilot study

PPOS (Progestin-Primed Ovarian Stimulation) has shown efficacy in preventing early luteinization and improving outcomes in infertile women. However, data among those with poor ovarian response (POR) are limited. This study aimed to evaluate the effect of PPOS protocol on the chance of success throughout the IVF process in patients with POR (POSEIDON group III &amp; IV) undergoing IVF/ICSI in Vietnam. This was a randomized controlled trial involving 120 infertile women with POR. PPOS or GnRH-ant protocol was randomly applied to the participants of either group (n = 60 in each group). The primary outcome measures the chances of achieving oocyte maturation and retrieval, fertilization, and embryo formation. The effect of PPOS compared to GnRH-ant protocol was estimated as marginal risk-ratio (RR) from binomial regression analysis. We found that the chance of success in achieving MII oocytes, fertilization, and high-quality D3 and D5 embryos were equivalent between the two protocols; (RR (95% CI) were 0.97 (0.88-1.07), 1.00 (0.89-1.14), 1.04 (0.96-1.14), 1.14 (0.74-1.73), respectively). In conclusion, PPOS protocol using DYG slightly improves the IVF funnel in women with POR undergoing IVF/ICSI; however, these differences were not significant. Therefore, we concluded that the efficacy of the PPOS protocol is equivalent to that of the GnRH-ant stimulation protocol. Clinical Trial Registration Number: NCT06191809. Method: A randomized controlled trial involving 120 infertile women with POR was conducted. PPOS or GnRH-ant protocol were randomly applied to the participants of either group (n = 60 in each group). The primary outcome measures the chances of achieving oocyte maturation and retrieval, fertilization, and embryo formation. The effect of PPOS compared to GnRH-ant protocol was estimated as marginal risk-ratio (RR) from binomial regression analysis. Results: The chance of success in achieving MII oocytes, fertilization, and high-quality D3 and D5 embryos were equivalent between the two protocols (RR (95% CI) were 0.97 (0.88-1.07), 1.00 (0.89-1.14), 1.04 (0.96-1.14), 1.14 (0.74-1.73), respectively). Conclusion: PPOS protocol using DYG slightly improves the IVF funnel in women with POR undergoing IVF/ICSI; however, these differences were not significant. Therefore, we concluded that the efficacy of the PPOS protocol is equivalent to that of the GnRH-ant stimulation protocol.

The comparision among euploidy of preimplantation blastocysts in different controlled ovary stimulation (COH) protocols.

To compare differences in euploidy rates for blastocysts in preimplantation genetic testing for aneuploidy (PGT-A) cycles after gonadotropin-releasing hormone agonist (GnRH-a) long and short protocols, GnRH-antagonist (GnRH-ant) protocol, progestin-primed ovarian stimulation and mild stimulation protocols, and other ovary stimulation protocols. This was a retrospective cohort study from the Assisted Reproductive Medicine Department of Shanghai First Maternity and Infant Hospital. A total of 1657 PGT-A cycles with intracytoplasmic sperm injection after different controlled ovary hyperstimulation protocols were analyzed, and a total of 3154 embryos were biopsied. Differences in euploidy rate per embryo biopsied, embryo euploidy rate per oocyte retrieved and cycle cancellation rate were compared. For the PGT-A cycles, the euploidy rate per embryo biopsied was lower in the GnRH-ant protocol than in the GnRH-a long protocol (53.26 vs. 58.68%, respectively). Multiple linear regression showed that the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied (β = -0.079, p = 0.011). The euploidy rate per embryo biopsied was not affected by total gonadotropin dosage, duration of stimulation and number of oocytes retrieved. The embryo euploidy rate per oocyte retrieved was similar in all protocols and was negatively correlated with the total number of oocytes retrieved (β = -0.003, p = 0.003). Compared with the GnRH-a long protocol, the GnRH-ant protocol was associated with a lower euploidy rate per embryo biopsied. The total gonadotropin dosage, duration of stimulation and number of oocytes retrieved did not appear to significantly influence euploidy rates.

Comparison of the pregnancy outcomes of progestin-primed vs. antagonist ovarian stimulation in patients with poor ovarian response: a retrospective study

Objectives Progestin-primed ovarian stimulation (PPOS) is an efficient controlled ovarian stimulation (COS) method. The study explored the pregnancy outcomes between PPOS and antagonist ovarian stimulation protocol (GnRH-ant) in infertile patients with poor ovarian response (POR). Methods This retrospective study included patients with POR who underwent COS at the Reproductive Medical Center of Shanxi Maternal and Child Health Hospital from January 2021 to April 2022. The cycles were grouped as the GnRH-ant group and the PPOS group. The primary outcome was the clinical pregnancy rate; the secondary outcomes included the biochemical pregnancy abortion rate and live birth rate. Results Frozen embryo transfer was used in all cycles in this study. The cycles were divided into the GnRH-ant (n = 236 cycles) and PPOS (n = 273 cycles) groups. Age, BMI, type of infertility, infertility duration, FSH, LH, PRL, E2, T, P, and the number of cycles in the hospital were similar between the two groups (all p > 0.05). No statistically significant differences were observed in the clinical pregnancy rate (primary outcome, 32.71% vs. 43.90%, p = 0.082), total Gn dose, total Gn days, ART mode (IVF or ICSI), AFC, MII follicles, 2PN embryos, fertility, cycle cancelation rate, biochemical pregnancy rate, abortion rate, or live birth rate between the two groups (all p > 0.05). The PPOS group exhibited a higher rate of high-quality embryos than the GnRH-ant group (50.12% vs. 42.90%, p = 0.045). Conclusions The PPOS protocol was comparable to the GnRH-ant protocol regarding induction parameters and cycle cancelation, biochemical pregnancy, clinical pregnancy, and abortion rates but might be associated with a higher proportion of high-quality embryos.

Optimal timing of GnRH antagonist initiation in IVF-ET: a retrospective cohort study on advanced maternal age women.

Several studies have compared the effects of fixed and flexible gonadotropin releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization and embryo transfer (IVF-ET). However, which GnRH-ant initiation strategy is better remains controversial. Moreover, no studies have assessed the optimal timing of GnRH-ant initiation in women of advanced maternal age (AMA). In this retrospective cohort study, a total of 472 infertile women aged ≥ 35 years old undergoing their first IVF cycle from August 2015 to September 2021 at a tertiary academic medical center were recruited, of whom 136 followed fixed GnRH-ant protocol and 336 followed flexible GnRH-ant protocol. The primary outcomes measured were the cumulative live birth rate (CLBR) per IVF cycle and the time to live birth (TTLB) from the date of oocyte retrieval. Cox proportional models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) of CLBR regarding GnRH-ant timing. No significant difference in CLBR was found between the fixed and flexible GnRH-ant groups (27.9% vs 20.5%, p=0.105). The TTLB was also comparable between groups (10.56 vs 10.30 months, p=0.782). The Kaplan-Meier analysis for CLBR also showed comparable results between groups (P=0.351, HR=0.83; 95%CI: 0.56-1.23). After establishing a multiple Cox proportional hazard model, the fixed GnRH-ant group still had comparable CLBR with the flexible GnRH-ant group (HR=0.85; 95%CI: 0.53-1.38; P=0.518). Subgroup and sensitivity analyses also demonstrated similar results. GnRH-ant protocols can be tailored to the needs of AMA women, and timing of GnRH-ant initiation can be adjusted flexibly.

Correlation between controlled ovarian stimulation protocols and euploid blastocyst rate in pre-implantation genetic testing for aneuploidy cycles

BackgroundSeveral studies have explored which COS protocol yields a higher blastocyst euploidy rate, but findings have been inconsistent. The present study aimed to explore whether controlled ovarian stimulation (COS) protocols was associated with euploid blastocyst rate in pre-implantation genetic testing for aneuploidy (PGT-A) cycles.MethodsThe study was a retrospective study where data were obtained from three reproductive medicine centers. The study included PGT-A cycles with the GnRH-a, GnRH-ant, or PPOS protocols, and the data on patient demographics, protocols, and embryonic outcomes were collected for the PGT-A cycles performed between January 2019 and August 2022.ResultsThis study included 457 PGT-A cycles from three reproductive medicine centers, with 152, 126, and 179 cycles performed using the PPOS, GnRH-a, and GnRH-ant protocols, respectively. The baseline characteristics of the three groups show no significant differences were observed in female BMI, infertility type, and infertility duration among the PPOS, GnRH-a, and GnRH-ant protocol groups. The study found no significant association between Gn dosage, Gn duration, and blastocyst euploidy. The mean number of euploidy blastocysts in PPOS protocol was significantly lower than that of GnRH-a protocol and GnRH-ant protocol (0.75 ± 0.92 vs. 1.79 ± 1.78 vs. 1.80 ± 1.67). The euploidy rate per biopsy blastocyst (48.4% vs. 49.1% vs. 33.1%), per oocyte retrieved (15.0% vs. 14.7% vs. 10.5%), and per MII oocyte (17.7% vs. 16.4% vs. 11.7%) were significantly higher in the cycles using the GnRH-ant and GnRH-a protocols than that of PPOS protocol group. Regression analyses indicated that, compared with the PPOS protocol, the GnRH-ant protocol was positively associated with the euploid blastocyst rate and the mean number of euploid blastocysts, whereas the GnRH-a protocol showed no such relationship.Limitations and reasons for cautionThe main limitation of this study was the retrospective design. Although this study also used other tests to account for confounding factors and reduce potential bias, multiple tests have its own weaknesses.ConclusionsGnRH-ant protocol was the most effective for PGT-A cycles. The findings emphasize the need for personalized treatment strategies, considering patient demographics, and optimizing COS protocols to enhance the chances of successful outcomes in ART procedures.

#390 : Why Our Clinical Pregnancy Rates Have Improved Over the Past Two Years: Exploring Key Points of Gonadotropin-Releasing Hormone Antagonist Protocol in Fresh Embryo Transfer Cycles

Background and Aims: GnRH-ant protocol is effective in preventing a surge of pituitary luteinising hormone during controlled ovarian stimulation. In recent years, GnRH-ant protocol has been optimised to improve in vitro fertilisation outcomes. However, firstly, the success rate of frozen embryo transfer is consistently better than that of fresh embryo transfer and secondly, the success rate of GnRH-ant protocol on fresh embryo transfer is lower than that of the long protocol. This study aims to draw out a comparison of before and after data from our own centre to find the reasons for the gradual maturation of GnRH-ant protocol on fresh embryo transfer. Our study proposed to investigate the determinants affecting fresh embryo transfer in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols. Method: We reviewed 2464 fresh embryo transfer cycles for IVF/ICSI-ET assisted reproduction techniques performed at our centre from 1 January 2015 to 31 December 2019. The exclusion criteria were as follows: endometriosis grade III to IV (American Fertility Society classification of endometriosis); adenomyosis; severe male oligospermia or obstructive azoospermia. Firstly, we compared the single-cycle clinical pregnancy rates between 2015 to 2017 and 2018 to 2019. Next, we performed a multifactorial regression analysis to understand what changes our centre had made between the five years in terms of years. Finally, data from 2015 to 2019 were grouped as a whole and then subjected to understand exactly where the differences in clinical pregnancy rates were affecting the GnRH-ant protocol for fresh embryo transfer. Results: A total of 1,388 cycles were included from 2015 to 2017, with a clinical pregnancy rate of 51.42% (688/1388). 1,076 cycles were included from 2018 to 2019, with a clinical pregnancy rate of 57.43% (618/1076). 2018 to 2019 compared to 2015 to 2017 for first-time IVF/ICSI. There was a 6.01% increase in clinical pregnancy rate for women who had assisted conception and performed GnRH-ant protocol with fresh embryo transfer. The results of the univariate analysis conducted suggested that the factors influencing the classification of clinical pregnancy included female basal E2 base, LH base, FSH base, P base, female Gn initiation date E2 start, LH start, FSH start, P start, Gn initiation volume and number of Gn days, antagonist addition date E2 add, LH add, FSH add, P add, plate machine day E2 trigger, LH trigger, P trigger, plate machine day number of different follicles in the meridian follicles 10-14 mm, follicles 14-16 mm, follicles 16-18 mm, follicles 18mm or more. Multifactorial regression analysis after correction suggested that age, BMI, endometrial thickness on the day of transfer, number of embryos transferred and progesterone level on HCG Day were independent influencing factors for successful pregnancy with antagonist regimen and fresh embryo transfer. Conclusion: Age, BMI, endometrial thickness on the day of transfer, number of embryos transferred and progesterone levels on HCG Day were independent influences.

Non-inferiority of progestin-primed ovarian stimulation versus GnRH antagonist protocol: A propensity score-weighted analysis

PurposeTo evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation. MethodsIn this retrospective cohort study, we included 804 patients who were treated between January 1st, 2022, and July 1st, 2023. Outcomes of ovarian stimulation were compared between the PPOS (n = 206) and GnRH-ant (n = 598). The primary outcome was the number of good cleavage embryos. ResultsBaseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher than in patients with GnRH-ant (4,420 vs 3,830 pg/ml, respectively) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The number of oocytes, MII oocytes, cleavage and blastocyst embryos were comparable between the two protocols. After the first transfer of embryos, the clinical pregnancy rate and implantation rate were higher in the PPOS group, while the pregnancy rate and ongoing pregnancy were not significantly different. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation. ConclusionsThe PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol, with notable distinctions in clinical pregnancy and implantation rate. The serum LH concentration during ovarian stimulation using PPOS was well-controlled.

GnRH antagonist protocol versus progestin-primed ovarian stimulation in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

The aim of this meta-analysis was comparing the efficacy of GnRH antagonist (GnRH-ant) protocol and progestin-primed ovarian stimulation (PPOS) in polycystic ovarian syndrome (PCOS) women. A search was conducted from PubMed, Embase, The Cochrane library, Web of Science, and Scopus databases to collect clinical papers regarding GnRH-ant protocol and PPOS protocol from inception to September 2023. Subsequently, the retrieved documents were screened, and the content of the documents that conformed to the requirements was extracted. Moreover, statistical meta-analyses were conducted using the RevMan 5.4 software. Furthermore, with the use of a star-based system and the Cochrane handbook, the methodological quality of the covered papers was evaluated on the Ottawa-Newcastle scale. A total of eight papers were covered in the meta-analysis, with 2156 PCOS women enrolled (i.e., 1085 patients in the GnRH-ant protocol group and 1071 patients in the PPOS group). As indicated by the meta-analysis results, the PPOS group was correlated with a lower risk of ovarian hyperstimulation syndrome (OHSS) (SMD = 9.24, [95% CI: (2.50, 34.21)], P = 0.0009), more gonadotropin (Gn) dose (SMD = - 0.34, [95% CI: (- 0.56, - 0.13)], P = 0.002) compared with GnRH-ant group. No statistical difference was identified on the oocytes condition and pregnancy outcomes. As revealed by the data of this study, the progesterone protocol is comparable with the GnRH-ant protocol in oocytes condition and clinical outcomes. The progestin-primed ovarian stimulation could serve as an alternative for polycystic ovarian syndrome women who have failed in GnRH antagonist protocol. The above-described conclusions should be verified by more high-quality papers due to the limitation of the number and quality of included papers. PROSPERO registration: CRD42023411284.

LH on GnRH-ant day to basal LH affects the IVF/ICSI outcome of PCOS women undergoing GnRH-antagonist protocol.

The aim of this study was to investigate the influence of ratio of serum luteinizing hormone (LH) on gonadotropin-releasing hormone antagonist (GnRH-ant) day to basal LH (hLH/bLH) on in-vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) outcome in polycystic ovary syndrome (PCOS) women who received GnRH-ant protocol for controlled ovarian hyperstimulation (COH). This retrospective study was conducted in women with PCOS (n = 1116) who underwent the GnRH-ant protocol for COH between 2015 and 2022 and were stratified as group A (hLH/bLH < 1, n = 489) and group B (hLH/bLH ≥ 1, n = 627) according to the variation of serum LH. The outcomes of COH and the first frozen embryo transfer (FET) cycle were compared between group A, B and the linear relationship between hLH/bLH ratio and IVF/ICSI outcomes were studied by multivariate linear regression analysis and restricted cubic spline (RCS) models. There were significant differences in baseline characteristics and outcomes between group A and B. Group A had higher levels of bLH, AMH, estradiol (E2) on GnRH-ant start day and lower levels of LH on GnRH-ant start day. Group B has better ovulation induction outcomes: more retrieved oocytes, normally fertilized oocytes (2PN), cleavage embryos, available embryos and high-quality blastocysts. Multivariate linear regression analysis found no statistically significant connection between hLH/bLH and clinical outcomes. RCS models showed hLH/bLH had nonlinear association with outcomes, including number of oocytes retrieved, 2PN, available embryos, incidence of OHSS, chemical pregnancy, clinical pregnancy, abortion and live birth. hLH/bLH ratio could be a more forward-looking indicator of clinical outcome in women with PCOS undergoing GnRH-ant protocols than LH on trigger day and the ratio of LH level on trigger day to basal LH. hLH/bLH = 1 may be the best condition for higher live birth rate and lower OHSS rate.

The effect of luteinizing hormone changes in GnRH antagonist protocol on the outcome of controlled ovarian hyperstimulation and embryo transfer

BackgroudTo investigate the effect of Luteinizing hormone (LH) level changes on the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer (ET) in gonadotropin-releasing hormone antagonist (GnRH-ant) protocol.MethodsA total of 721 patients undergoing GnRH-ant protocol COH for the first IVF/ICSI cycles were retrospectively analyzed. COH process were divided into 2 stages, before (stage 1) and after (stage 2) the GnRH-ant initiation, and each with 5 groups basing on LH levels: LH decreased more than 50% (groups A1, A2), decreased 25-50% (groups B1, B2), change less than 25% (groups C1, C2), increased 25-50% (groups D1, D2), and increased more than 50% (groups E1, E2).ResultsThere were no significant differences among groups of stage1 regarding COH and ET outcomes. For stage 2, the more obvious the decrease of LH level, the more the number of oocytes retrieved, mature oocytes, fertilized oocytes, embryos cleavaged and the numbers of embryo available (P < 0.05), but without significant differences regarding ET outcomes. We also found the freeze-all rate in Group A2 was higher (P < 0.001).ConclusionLH level changes before GnRH-ant addition were not related to COH and ET outcomes. LH level changes after the addition of GnRH-ant were related to the outcome of COH, and no significant differences were found relating to ET outcomes.

Effectiveness of oestrogen pretreatment in patients with expected poor ovarian response (POSEIDON groups 3 and 4) undergoing GnRH antagonist protocol: study protocol for a randomised controlled trial

IntroductionWomen characterised by diminished ovarian reserve are considered to have poor ovarian response (POR) according to Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria. Patients in this population often have...

Dose Nomogram of Individualization of the Initial Follicle-Stimulating Hormone Dosage for Patients with Polycystic Ovary Syndrome Undergoing IVF/ICSI with the GnRH-Ant Protocol: A Retrospective Cohort Study.

For high responders with polycystic ovary syndrome (PCOS), there is no clear recommendation for the initial follicle-stimulating hormone (FSH) dosage to ensure an optimal number of retrieved oocytes and avoid ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine the ideal initial FSH dosage of in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) using the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol to obtain the optimal number of retrieved oocytes and minimize the risk of OHSS. The data of 1898 patients with PCOS aged 20-40years from January 2017 to December 2020 were retrospectively analyzed to explore the factors related to the number of retrieved oocytes. Statistically significant variables were used to construct a dose nomogram and it was then validated using an independent cohort of patients with PCOS from January 2021 to December 2021. Multivariate analyses demonstrated that body mass index (BMI) was the most significant factor to predict the number of retrieved oocytes compared to body weight (BW) and body surface area (BSA). Among patients with PCOS aged 20-40years undergoing their first IVF cycles with the GnRH-ant protocol, age was not a significant predictor of the initial FSH dosage. We developed a nomogram based on BMI, basal FSH, basal luteinizing hormone (bLH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) to calculate the ideal initial FSH dosage for patients with PCOS undergoing IVF/ICSI using the GnRH-ant protocol. In addition, low BMI and high bLH and AMH levels and AFC appear to be risk factors for OHSS. We clearly demonstrated that the initial FSH dosage for patients with PCOS undergoing IVF/ICSI with the GnRH-ant protocol may be calculated on the basis of the woman's BMI and ovarian reserve markers. The nomogram will help guide clinicians in the selection of the most appropriate initial FSH dose in the future.

P-611 Progestin-Primed Ovarian Stimulation is a non-inferior alternative to the GnRH Antagonist Protocol in patients undergoing ovarian stimulation: a propensity score weighting analysis

Abstract Study question To evaluate the effectiveness of the progestin-primed ovarian stimulation (PPOS) protocol versus the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol in ovarian stimulation. Summary answer The PPOS protocol with dydrogesterone provided similar embryo outcomes to the GnRH-ant protocol. The serum LH concentration during ovarian stimulation using PPOS was well-controlled. What is known already Since Yanping Kuang's proposal PPOS in 2015, several studies on the effectiveness of this treatment regimen have been published. Although it has been suggested that outcomes of the PPOS regimen were comparable to those of GnRH-ant regimen, the findings were limited due to differences in study design, patient characteristics, dosage and type of progestins. While medroxyprogesterone acetate is often used in PPOS studies, dydrogesterone has seen far less popularity. Additionally, dydrogesterone is a relatively weak LH inhibitor compared to MPA, leading to concern about the increased incidence of unexpected LH surge Study design, size, duration We conducted a retrospective study among women who underwent In Vitro Fertilization at the Assisted Reproduction Center, Tam Anh General Hospital, Vietnam from January 1st, 2022 to October 10th, 2022. Participants/materials, setting, methods We included 804 patients who underwent ovarian stimulation, among which 208 used the PPOS protocol with dydrogesterone (30 mg dydrogesteron per day from the beginning of stimulation until the trigger-day) and 598 women used the GnRH-ant protocol (cetrorelix 0.25 daily, from day 6 of ovarian stimulation until the trigger-day). In addition to unadjusted analysis, we used propensity score weighting to account for confounding that might possibly remain. Main results and the role of chance Baseline characteristics were comparable in both groups. In both unadjusted and adjusted analysis, the mean number of good cleavage embryos in PPOS (6.33) was non-inferior to GnRH-ant (6.44; unadjusted ratio of two means 1.02, 95%CI 0.92, 1.13). The trigger-day estradiol level in patients with PPOS was higher (4,420 vs 3,830 pmol/L in GnRH-ant) despite similar total follicle stimulating hormone dose and fewer days of ovarian stimulation. The overall number of oocytes retrieved, the number of MII oocytes, the number of cleavage embryos, the number of blastocysts, and the number of good blastocysts were comparable between the two protocols. None of the PPOS patients had an unexpected LH surge, and serum LH levels decreased slightly during ovarian stimulation. Limitations, reasons for caution Due to the nature of the retrospective study design, we did not record the progesterone level on the trigger-day in the PPOS regimen; therefore, identifying LH surge based on LH and progesterone levels is not feasible. Furthermore, we did not study the outcomes of embryo transfer. Wider implications of the findings These results supported the use of PPOS with dydrogesterone as a cheap and effective alternative for clinicians in clinical practice. In patients with an indication for freeze-all embryo, the PPOS protocol could be recommended. Trial registration number Not Applicable

P-119 Relation of graphical follicle models to the cumulative live birth rate in GnRH-antagonist stimulation treatment cycles

Abstract Study question Is it possible to create a model that combines follicle number and size to help physicians visualize the trigger requirements to predict oocyte utilization? Summary answer Findings support graphical follicle model as an innovative, simple, and practiced parameter for predicting clinical results in ovary stimulation treatment and facilitating personalized protocol adjustment. What is known already Previous studies have observed the number and size of follicles are two independent indicators of whether the oocyte is adequate and mature and are used to predict the trigger time in routine clinical practice. However, due to individualized differences, it currently relies mainly on physician experience. Study design, size, duration This retrospective study included 8405 patients started their first in vitro fertilization cycle with a GnRH-ant protocol including fresh and subsequent frozen-thawed cycles during 2016–2020. Participants/materials, setting, methods We classified follicles recorded on the HCG day by size. We then produced graphical models, and classified into Inverted-trapezoid (large follicles in dominant proportion), Polygon (moderate follicles in dominant proportion), Trapezoid (small follicles in dominant proportion), Rectangle (equivalent proportions of the three size categories). The Cochran–Mantel–Haenszel and Generalized Linear Model(GLM) were used to evaluate the difference among models in relation to maturity, fertilization, and number of viable embryos, as well as cumulative live birth rate. Main results and the role of chance In GLM analysis, after adjusting the confounders, there are differences between models of CLBR. The CLBR of the different models was higher in the Polygon and Inverted-trapezoid model than Trapezoid and Rectangle model (42.75%, 39.56%, vs. 37.38%, 28.57%, respectively; all P&amp;lt;0.05). For oocytes derived from very large follicles ( &amp;gt; 20 mm), the CLBR was lower than that of patients with ≤ 20 mm follicles [26.10% vs. 42.10%, OR = 1.74 (95% confidence interval 1.52–2.00), P&amp;lt;0.01] in Inverted-trapezoid model, but there was no difference between models. And the risk of ovarian hyperstimulation syndrome (OHSS) rate of patients with ≤ 20 mm follicles was lower than that of patients with &amp;gt; 20 mm follicles [8.64% vs. 17.89%, OR = 0.57 (95%CI: 0.49−0.65), P&amp;lt;0.01] in Inverted-trapezoid model. Patients who received an adjusted Gn dose(whether Decreased or Increased-dose protocol) showed no difference in CLBR among models (Polygon vs Inverted-trapezoid vs Trapezoid vs Rectangle model: 47.07% vs. 49.21% vs. 47.69% vs. 42.42%, P &amp;gt; 0.05); but when patients continued with the same starting dose in Fixed-dose protocol, the CLBR of the Polygon model was higher than that of other models (40.43% vs. 34.32, 31.13% vs. 26.46%, respectively; all P value &amp;lt;0.05). Limitations, reasons for caution This study is retrospective. Due to analysis of real-world data, the follicular corresponding outcome following measurement was not obtained. Besides, the majority of patients received 2 cleavage stage embryos transfer, this approach may impact the external validity of follicle model. Wider implications of the findings The follicle models can demonstrate ovarian response of patients. It is better for patients to reach the Inverted-trapezoid model with dominate follicles &amp;gt; 18 mm and &amp;lt;20 mm. Adjusting the protocol is critical to the outcome. But how to improve follicle models by regulating stimulation remains to be further studied. Trial registration number not applicable

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

BackgroundAlthough numerous studies have investigated the potential correlation between follicular fluid (FF) steroid concentrations and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes, few have accounted for the effect of controlled ovarian hyperstimulation regimes on FF steroid concentrations. ObjectiveTo comprehensively compare follicular steroid concentrations between women stimulated with gonadotropin-releasing hormone agonist (GnRHa) and antagonist (GnRHant) protocols and to explore the associations between FF steroid concentrations and IVF/ICSI outcomes. MethodsA total of 295 infertile women undergoing IVF/ICSI from January 2018 to May 2020 were enrolled. Eighty-four and 211 women received GnRHa and GnRHant protocols, respectively. Seventeen steroids in FF were quantified by liquid chromatography tandem mass spectrometry (LC–MS/MS), and the correlation of follicular steroids with clinical pregnancy was explored. ResultsFollicular steroid concentrations were similar between the GnRHa and GnRHant groups. Follicular cortisone levels were adversely associated with clinical pregnancy in fresh embryo transfers. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.639 (95% confidence interval = 0.527–0.751, p = 0.025) for predicting non-pregnancy, with an optimal cutoff value of 15.81 ng/mL (sensitivity = 33.3%, specificity = 94.1%). Women with FF cortisone concentrations ≥15.81 ng/mL were fifty times less likely to achieve clinical pregnancy in fresh embryo transfers than those with FF cortisone levels below this threshold (adjusted OR = 0.019, 95% confidence interval = 0.002–0.207, p = 0.001) after adjusting for age, body mass index, baseline serum progesterone levels, serum levels of luteinizing hormone, estradiol and progesterone on human chorionic gonadotropin day, ovarian stimulation protocols, and the number of transferred embryos. ConclusionsThere was no significant difference in intrafollicular steroid levels between GnRHa and GnRHant protocols, and intrafollicular cortisone level ≥15.81 ng/mL was found to be a strong negative predictor of clinical pregnancy in fresh embryo transfers with high specificity.

Nomogram for Predicting Live Birth after the First Fresh Embryo Transfer in Patients with PCOS Undergoing IVF/ICSI Treatment with the GnRH-Ant Protocol.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. A better understanding of factors associated with pregnancy outcomes and successful prediction of live birth after IVF/ICSI are important to guide clinical practice. This was a retrospective cohort study investigating live birth after the first fresh embryo transfer using the GnRH-ant protocol in patients with PCOS between 2017 and 2021 at the Reproductive Center of Peking University Third Hospital. A total of 1018 patients with PCOS were qualified for inclusion in this study. BMI, AMH level, initial FSH dosage, serum LH and progesterone levels on the hCG trigger day, and endometrial thickness were all independent predictors of live birth. However, age and infertility duration were not significant predictors. We developed a prediction model based on these variables. The predictive ability of the model was demonstrated well, with areas under the curve of 0.711 (95% CI, 0.672-0.751) and 0.713 (95% CI, 0.650-0.776) in the training cohort and validation cohort, respectively. Additionally, the calibration plot showed good agreement between the prediction and the observation (p = 0.270). The novel nomogram could be helpful for clinicians and patients in clinical decision-making and outcome evaluation.