Gonadotropin-releasing Hormone Antagonist Cycles Research Articles

Is there a preferred time interval between gonadotropin-releasing hormone (GnRH) agonist trigger and oocyte retrieval in GnRH antagonist cycles? A retrospective cohort of planned fertility preservation cycles.

The ideal time frame between gonadotropin-releasing hormone (GnRH) agonist (GnRHa) trigger administration and oocyte retrieval in GnRH antagonist cycles has not been well studied. Our goal was to evaluate the effect of this time interval on oocyte yield and oocyte maturation rate in GnRH antagonist cycles designated for non-medical ("planned") oocyte cryopreservation. We conducted a retrospective cohort study including patients who underwent elective fertility preservation, using the GnRH antagonist protocol and exclusively triggered by GnRH-agonist. We focused on the effect of the trigger-to-retrieval time interval on oocyte yield and maturation rate, while also incorporating age, body mass index (BMI), anti-Müllerian hormone (AMH) levels, basal Follicle-Stimulating Hormone (FSH) levels, as well as the type and dosage of gonadotropin FSH medication. 438 cycles were included. Trigger-to-retrieval time interval ranged from 32.03 to 39.92h. The mean oocyte yield showed no statistically significant difference when comparing retrievals < 36h (n = 240, 11.86 ± 8.6) to those triggered at ≥ 36h (n = 198, 12.24 ± 7.73) (P = 0.6). Upon dividing the cohort into four-time quartiles, no significant differences in the number of retrieved oocytes were observed (P = 0.54). Multivariate regression analysis failed to reveal any significant associations between the interval and the aforementioned variables. The GnRHa trigger to oocyte retrieval interval range in our cohort did not significantly affect oocyte yield and maturation rate.

Age and dual trigger were found to be significant predictors of live birth in POSEIDON group 3 and 4 women treated with the GnRH antagonist protocol: a retrospective cohort study.

Despite recent advancements in assisted reproductive technology (ART), the effective management of patients with poor ovarian response (POR) remains a formidable challenge. While various treatment strategies and predictors of live births have been documented to provide guidance to fertility specialists in managing poor responders, research efforts have predominantly encompassed all POSEIDON groups. In this study, our objective was to analyze the factors correlated with live births (LB) within a subset of the POSEIDON groups, with a particular focus on POSEIDON groups 3 and 4. Charts of 406 patients belonging to POSEIDON groups 3 and 4 who underwent ART treatment at a university-affiliated infertility clinic following a gonadotropin-releasing hormone (GnRH) antagonist cycle between January 2016 and December 2021 were analyzed. Clinically significant factors associated with live births were incorporated into a logistic regression model for multivariate analysis to ascertain independent predictors of LB. Additionally, a receiver operating characteristic (ROC) curve analysis was conducted to establish the optimal cut-off values. Live births were achieved in 48 cycles (8.7%). Female age (OR, 0.930; 95% CI: 0.874-0.991; p < 0.024), baseline serum luteinizing hormone (LH) levels (OR, 0.854; 95% CI: 0.741-0.984; p < 0.029), and dual triggers (OR, 4.004; 95% CI: 1.290-12.426; p < 0.016) were identified as independent factors associated with LB following multivariate logistic regression analysis. The optimal age cut-off was determined to be 33 years, with a sensitivity of 70.8% and specificity of 75%. Younger age, lower baseline serum LH levels, and dual-trigger administration appear to enhance the likelihood of live birth in POSEIDON groups 3 and 4 following treatments with the GnRH antagonist protocol.

Oral medroxyprogesterone acetate for the use of ovulation suppression in in vitro fertilization: a cohort trial

To broadly assess the efficacy of medroxyprogesterone acetate (MPA) for ovulatory suppression during in vitro stimulation (IVF) when compared to gonadotropin releasing hormone (GnRH) antagonist cycles DESIGN: Cohort Trial SETTING: A single academic-affiliated private fertility practice SUBJECTS: Patients of all diagnoses aged 18-44 years undergoing autologous IVF for fertility treatment between 2020-2023 EXPOSURE: Comparison of MPA vs. antagonist IVF stimulation cycles MAIN OUTCOME MEASURES: Rates of premature ovulation, oocyte and embryo yield, embryo quality, pregnancy rates, and logistical benefits RESULTS: Prospective data was collected on 418 patients who underwent MPA-protocol ovarian stimulation (MPA group) which was compared to 419 historical control GnRH antagonist cycles (control group). Age was similar between groups (35.6 +/- 4.6 vs. 35.7 +/- 4.8 years; p = 0.75). There were no cases of premature ovulation in the MPA group compared to a total of five cases in the control group (0% vs. 1.2%; RR 0.09, 95% CI 0.01-1.66). No differences were seen between number of oocytes retrieved (14.3 +/- 10.2 vs. 14.3 +/- 9.7; p = 0.83), blastocysts (4.9 +/- 4.6 vs. 5.0 +/- 4.6; p = 0.89), or euploid blastocysts (2.4 +/- 2.6 vs. 2.2 +/- 2.4; p = 0.18) in the MPA vs. control group respectively. Clinical pregnancy rate was similar between groups (70.4% vs. 64.2%; RR 0.92, 95% CI 0.72 - 1.18). There was no difference in length of IVF stimulation or dose of stimulation medications. Patients in the MPA group saved an average of $491 +/- $119 on medications, had an average of one less monitoring visit (4.4 +/- 0.9 vs. 5.6 +/- 1.1; p < 0.01), and 5.0 +/- 1.2 less injections per cycle. When adjusting for age and ovarian reserve, protocol group (MPA vs. control) did not influence having an embryo available for transfer (76.6% vs. 73.4%; adjusted RR 1.05, 95% CI 0.94 - 1.14). For ovulatory suppression during IVF cycles, MPA was effective at preventing ovulation while demonstrating similar cycle and reproductive outcomes, with the additional benefits of patient cost savings, increased convenience with decreased number of visits, and fewer injections.

Retrospective Analysis of Fresh Single Blastocyst Transfer versus Two Cleavage-Stage Fresh Day-3 Embryo Transfer with High-Quality Embryos during Gonadotropin-Releasing Hormone Antagonist Cycles in High Responders

Retrospective Analysis of Fresh Single Blastocyst Transfer versus Two Cleavage-Stage Fresh Day-3 Embryo Transfer with High-Quality Embryos during Gonadotropin-Releasing Hormone Antagonist Cycles in High Responders

Adjuvant letrozole administration in gonadotropin releasing hormone antagonist cycles do not affect ploidy status of embryos

ObjectiveTo evaluate the effects of adjuvant letrozole administration on euploid embryo rates in gonadotropin releasing hormone (GnRH) antagonist cycles. MethodsThis retrospective study was conducted by analyzing data of patients that underwent GnRH antagonist cycles with intra-cytoplasmic sperm injection (ICSI) and pre-implantation genetic testing for aneuploidy between 2013 and 2021. Study included a total of 713 patients which 84 of them were received adjuvant letrozole and 629 patients underwent ovulation induction without any adjuvant therapy. ResultsIn patients with letrozole administration, total dose of consumed gonadotropins were significantly lower (2166.80 ± 738.82 IU vs. 2541.96 ± 755.76 IU; p < 0.001, respectively), and duration of stimulation was slightly longer (9.80 ± 1.23 days vs. 9.53 ± 1.38 days; p = 0.037) in comparison to patients without letrozole administration. Overall euploidy rates were found similar among letrozole group and control group (28.02 % ± 31.08 % vs. 23.02 % ± 30.87 %; p = 0.109). Similar rate of euploidy remained even after stratification of patients in accordance with female age. There was no significant difference in terms of live birth rates between letrozole administered group and control group (66.7 % vs 62.2 %, respectively). ConclusionCo-treatment with 5 mg/day letrozole for 5 days does not appear to affect euploidy rates of obtained embryos in GnRH antagonist cycles with ICSI.

Gonadotropin Versus Gonadotropin/Letrozole Protocol in Previously Failed Antagonist Cycles in Patients with Low Prognosis

Objective: Letrozole is an aromatase inhibitor which has been used for ovulation induction. Our aim is to evaluate the effectiveness of adding letrozole to gonadotropins in the early follicular phase of gonadotropin-releasing hormone antagonist (GnRH-a) protocol in patients with poor ovarian response who had failed in the preceding GnRH-a cycle.&#x0D; Materials and Method: Ninety-eight patients with poor ovarian response who had previously failed GnRH-a cycle were included. Patients (n; 58) who were treated with letrozole plus gonadotropins (LzGA) were compared with patients (n; 40) who received gonadotropins (GT). The number of total oocytes retrieved, the number of MII oocytes and fertilized oocytes, fertilization and implantation ratios, the rate of cycle cancellation as well as clinical pregnancy and live birth rates&#x0D; Results: The LzGA group had a significantly shorter duration of GnRH-a stimulation and higher progesterone level at trigger day (p=0.005, p=0.049 respectively). Although letrozole administration demonstrated lower estradiol levels at trigger day and the total dose of gonadotropins used were lower in LzGA group, this was statistically non-significant (p=0.13, p=0.13 respectively).&#x0D; Conclusion: Adding letrozole to gonadotropins in GnRH-a protocol in patients with poor prognosis did not improve pregnancy outcomes. But it seems to decrease IVF costs by reducing the GnRH-antagonist and gonadotropin dosage.

Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles?

Research questionDoes the trigger to oocyte retrieval interval (TORI) affect oocyte maturation rates differently in progestin-primed ovarian stimulation (PPOS) and gonadotrophin-releasing hormone (GnRH) antagonist cycles? DesignThis was a retrospective cohort study. The interaction between the stimulation protocol and TORI was assessed in a linear mixed effects multivariable regression analysis with oocyte maturation rate as the dependent variable, and stimulation protocol (GnRH antagonist or PPOS), age (continuous), gonadotrophin type (FSH or human menopausal gonadotrophin), trigger (human chorionic gonadotrophin [HCG] or GnRH agonist), TORI (continuous) and days of stimulation (continuous) as the independent variables. Oocyte maturation rate was defined as number of metaphase II oocytes/number of cumulus–oocyte complexes retrieved. The maturation rate was calculated per cycle and treated as a continuous variable. ResultsA total of 473 GnRH antagonist and 205 PPOS cycles (121 conventional PPOS and 84 flexible PPOS) were analysed. The median (quartiles) female age was 36 (32–40) years. Of these cycles, 493 were triggered with HCG and 185 with a GnRH agonist. The TORI ranged between 33.6 and 39.1 h, with a median (quartiles) of 36.2 (36–36.4) hours. Maturation rates were similar between fixed PPOS, flexible PPOS and antagonist cycles (median 80%, 75% and 75%, respectively, P = 0.15). There was no significant interaction between the stimulation protocols and TORI for oocyte maturation. ConclusionsPPOS cycles do not seem to require a longer TORI than GnRH antagonist cycles.

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

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

Effects of letrozole co-treatment on the cumulative live-birth rate among normal responders in gonadotropin-releasing hormone antagonist cycles.

Studies have shown that letrozole cotreatment can improve clinical outcomes in high and poor responders in GnRH-antagonist protocol. However, whether letrozole is also beneficial to normal responders is not known. To investigate the clinical value of letrozole cotreatment during ovarian stimulation in vitro fertilization for normal ovarian reserve patients who were treated with the GnRH antagonist protocol, we conducted a retrospective study that based data from 1 January to 31 December 2017 for all IVF-ICSI GnRH-antagonist protocols. A total of 252 women who aged <40 years, FSH <10 IU/L on day 3 and antral follicle counting (AFC) >6 were included in the analysis (96 in the letrozole group and 156 in the no-letrozole group). The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen-thawed embryos) among both groups. The initial gonadotropin (Gn) dosage and total Gn dosage were significantly lower and the number of days of Gn treatment was significantly fewer in the letrozole group than the non-letrozole group (p < 0.05). There were also significant between-group differences in luteinizing hormone, estradiol, and progesterone concentrations; and the number of metaphase II oocytes on the day of human chorionic gonadotropin treatment (p < 0.05). There was a significant difference in the implantation rate between the two groups that the letrozole group higher than the non-letrozole group (39.79 vs. 27.96%, p = 0.006), but there was no significant difference in the cumulative live-birth rate. The combination of letrozole with a GnRH antagonist may have no effect on the clinical pregnancy rate or cumulative live-birth rate in patients with a normal ovarian reserve. However, letrozole may increase the rate of embryo implantation and may reduce the requirement for exogenous gonadotrophins and, consequently, the cost of an IVF treatment cycle. In addition, the decreased estradiol level in the ovarian simulation by letrozole supports letrozole can be a safe solution for fertility preservation in estrogen-related cancer patients.

Prediction of ovarian response using the automated Elecsys anti-Müllerian hormone assay in gonadotrophin-releasing hormone antagonist cycles

Research questionWhat is the capability of serum anti-Müllerian hormone (AMH) measured using the automated Elecsys® AMH immunoassay to (Roche Diagnostics International Ltd) determine ovarian response after fertility treatment? DesignSingle-centre, retrospective, observational, cohort study including women undergoing ovarian stimulation. Serum AMH concentrations were determined using the Elecsys AMH immunoassay based on one blood sample drawn 6 months or less before treatment. Stimulation was conducted in accordance with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Patients were divided into four ovarian response categories based on their oocyte yield: low (0–3), suboptimal (4–9), optimal (10–15) and high (>15). Areas under the curve were calculated for each ovarian response group. ResultsOverall, 1248 patients were enrolled. The AMH concentration had a strong positive correlation with oocyte yield (Spearman's rho = 0.74, P < 0.001). Areas under the curve (95% CI) for AMH predicting ovarian response were 0.85 (0.83 to 0.88) for low and 0.89 (0.87 to 0.91) for high response. Optimal serum AMH cut-offs for predicting a low and high response using the Elecsys AMH immunoassay were 6.4 pmol/l (0.89 ng/ml) and 14.2 pmol/l (1.99 ng/ml), respectively. Multivariable regression analysis showed that 47% (R2 = 0.470) of variation in ovarian response could be attributed to AMH alone, increasing to 50.9% (R2 = 0.509) with the addition of age, body weight, and total dose of gonadotrophin. ConclusionOvarian response and oocyte yield after stimulation in a GnRH antagonist cycle can be predicted with high accuracy using a single determination of serum AMH before ovarian stimulation.

The LH endocrine profile in gonadotropin-releasing hormone analogue cycles

Research question: What does the evolution of serum luteinizing hormone (LH) levels look like throughout the follicular phase of cycles in which gonadotrophins and gonadotropin-releasing hormone (GnRH) analogues in the context of ovarian stimulation for assisted reproduction technologies (ART) were used? Design: This was a retrospective, observational cohort study in a tertiary infertility clinic. 1303 patients aged between 18 and 43 years of age were included with a total of 2200 cycles for ART, using GnRH-analogues for pituitary down-regulation stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH). Follicular evolution of LH during ovarian stimulation in different treatment protocols was modeled as repeated measures. Results: LH evolution showed a significant decrease in antagonist/hMG cycles of 0.17 IU/L per day (95% CI [-0.20, −0.12]) and 0.26 IU/L per day in rec-FSH cycles (95% CI [-0.29, −0.22]). This decrease was significantly stronger in rec-FSH cycles than in hMG cycles (estimated difference of 0.09 IU/L per day, 95% CI [0.04, 0.15]). Short agonist/hMG cycles showed a significant increase in LH of 0.04 IU/L per day (95% CI [0.01, 0.08]), while the increase of 0.01 IU/L per day in cycles with rec-FSH was not significant (95% CI [-0.08, 0.10]). Conclusion: Follicular evolution of LH during controlled ovarian stimulation differs between different GnRH analogue cycles. A statistically significant decrease in LH was shown in GnRH antagonist cycles being more pronounced with rec-FSH compared to hMG. This decrease in LH in antagonist cycles and the potential impact on estradiol levels and follicle growth needs further examination.

Effect of serum progesterone levels on hCG trigger day on pregnancy outcomes in GnRH antagonist cycles.

ObjectiveThe present study analyzed the effect of hCG trigger day progesterone (P) levels on the live birth rate (LBR) in the gonadotropin-releasing hormone (GnRH) antagonist protocol.Materials and methodsThis study was a single-center retrospective study. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles performed from January 2017 to December 2020 were included in the analysis. This study included people with a normal ovarian response to fresh embryo transfer of GnRH antagonist protocols. All cycles were divided into 2 groups by P level on the day of human chorionic gonadotropin (hCG) trigger, P<1.0 ng/ml and P≥1.0 ng/ml. The primary outcome measure was LBR.ResultA total of 867 cycles with P<1.0 ng/ml and 362 cycles with P≥1.0 ng/ml were included in the analysis. The clinical pregnancy rate (CPR) was higher in the P<1.0 ng/ml group than the P≥1.0 ng/ml group (44.9% vs. 37.6%, P=0.02). The early spontaneous abortion rate was comparable between the groups (14.4% vs. 14.7%, P=0.93). For live birth, the rate for the P<1.0 ng/ml group was 35.3%, which was significantly higher than the 29.0% in the P≥1.0 ng/ml group (P=0.03). After binary logistic regression analysis, the P level on the hCG trigger day (adjusted odds ratio=0.74, 95% CI=0.55-0.99, P=0.04) was an independent risk factor for LBR. For the P level on the hCG trigger day, the LBR was lower in the P≥1.0 ng/ml group compared to the P<1.0 ng/ml group.ConclusionFor normal ovarian response patients using the GnRH antagonist protocol, serum P≥1.0 ng/ml on the hCG trigger day resulted in a lower LBR than the P<1.0 ng/ml group. When P≥1.0 ng/ml, whole embryo freezing may be considered.

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.

Recombinant LH supplementation improves cumulative live birth rates in the GnRH antagonist protocol: a multicenter retrospective study using a propensity score-matching analysis

BackgroundLuteinizing hormone (LH) is critical in follicle growth and oocyte maturation. However, the value of recombinant LH (r-LH) supplementation to recombinant follicle stimulating hormone (r-FSH) during controlled ovarian stimulation in the gonadotrophin releasing hormone (GnRH) antagonist regimen is controversial.MethodsThis multicenter retrospective cohort study recruited 899 GnRH antagonist cycles stimulated with r-LH and r-FSH in 3 reproductive centers and matched them to 2652 r-FSH stimulating cycles using propensity score matching (PSM) for potential confounders in a 1:3 ratio. The primary outcome was the cumulative live birth rate (CLBR) per complete cycle.ResultsThe baseline characteristics were comparable in the r-FSH/r-LH and r-FSH groups after PSM. The r-FSH/r-LH group achieved a higher CLBR than the r-FSH group (66.95% vs. 61.16%, p = 0.006). R-LH supplementation also resulted in a higher 2-pronuclear embryo rate, usable embryo rate, and live birth rate in both fresh embryo transfer cycles and frozen-thawed embryo transfer (FET) cycles. No significant differences were found in the rate of moderate and severe ovarian hyperstimulation syndrome (OHSS), or cycle cancellation rate in the prevention of OHSS.ConclusionsR-LH supplementation to r-FSH in the GnRH antagonist protocol was significantly associated with a higher CLBR and live birth rate in fresh and FET cycles, and improved embryo quality without increasing the OHSS rate and cycle cancellation rate.

Effects of letrozole co-treatment on outcomes of gonadotropin-releasing hormone antagonist cycles in POSEIDON groups 3 and 4 expected poor responders.

To evaluate the effects of adjuvant letrozole administration on outcomes of gonadotropin-releasing hormone (GnRH) antagonist cycles with intra-cytoplasmic sperm injection in POSEIDON groups 3 and 4 expected poor responder women. This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON groups 3 and 4) that underwent GnRH antagonist cycles with intra-cytoplasmic sperm injection between 2010 and 2020. A total of 488 patients with letrozole co-administration and 2564 patients without any adjuvant treatment that underwent GnRH antagonist cycles within the selected period of time were included in the study. Implantation rates, clinical pregnancy rates and live birth delivery rates were significantly higher in letrozole administered patients in comparison to controls among POSEIDON group 3 women (0.39 ± 0.46 vs 0.27 ± 0.40, p = 0.01; 46.1% vs 33%, p = 0.014; 42.7% vs 31.5%, p = 0.034, respectively). Mean total doses of gonadotropins required per cycle were significantly lower in letrozole administered patients among both POSEIDON groups 3 and 4 women (2864.65 ± 878.47IU vs 3757.27 ± 1088.89IU, p < 0.001; 3286.06 ± 770.16IU vs 3666.48 ± 959.66IU, p < 0.001, respectively). Adjuvant letrozole co-administration in intra-cytoplasmic sperm injection cycles following GnRH antagonist protocol appears to improve implantation, clinical pregnancy and live birth delivery rates in women with POSEIDON group 3 expected poor ovarian response.

P-569 Reduction of gonadotropin-dosage towards the end of ovarian stimulation for IVF/ICSI improves ART-outcome in a subgroup of patients

Abstract Study question To identify in an unselected patient population those patients, who would benefit from a gonadotropin stepdown towards the end of ovarian stimulation in IVF/ICSI-treatment Summary answer Reduction of gonadotropin-dosage during ovarian stimulation for IVF/ICSI is beneficial in FSH-stimulated patients, aged 26-30 years, and in HMG-stimulated patients, aged 36-40 years of age What is known already Ovarian stimulation with gonadotropins for multi-follicular growth is a crucial part of IVF/ICSI-treatment. Intensive administration of gonadotropins might lead to progesterone elevation (PE) in the late follicular phase, impacting negatively the endometrial receptivity and possibly the embryo quality. During follicular growth, the number of FSH- and LH-receptors shift from predominantly FSH-receptors in the early to predominantly LH-receptors in the late follicular phase, reducing susceptibility of the follicle towards systemic FSH-levels. In a good prognosis population, it was shown that lower systemic FSH-levels on the trigger-day lead to significantly lower progesterone levels without reducing the number of retrieved/mature oocytes. Study design, size, duration Retrospective analysis of 1276 ovarian stimulation cycles, performed as GnRH (Gonadotropin-Releasing-Hormone)-antagonist protocol in an unselected patient population, between January 2018 and December 2020 at ART Fertility Clinic, Abu Dhabi, UAE. Ovarian stimulation cycles were split according to the stimulation medication used (either only recombinant FSH (rFSH) or only human menopausal gonadotropin (HP-HMG)) and whether stimulation-dosage was reduced (reduction group, RG) during the stimulation course or not (non-RG). Furthermore, patients were stratified into age-groups. Participants/materials, setting, methods Couples with primary / secondary infertility and an indication for ovarian stimulation for IVF/ICSI were included, independent of their age or ovarian reserve parameters. Only GnRH antagonist cycles, with either rFSH or HP-HMG as sole medication for ovarian stimulation and available data on Antral Follicle Count (AFC), gonadotropin-dosage at stimulation-start and -end, oocyte yield (number of retrieved / mature) and hormonal parameters of estradiol, progesterone and FSH were included. Main results and the role of chance A total of 1276 ovarian stimulation cycles were included, 495 (38.79%) with rFSH and 781 (61.21%) with HP-HMG as stimulation medication. In the FSH-group, 295 patients reduced (reduction-group=RG) and 200 did not reduce (=non-RG) FSH-dosage during stimulation. In all age-categories (&amp;lt;25; 26-≤30; 31-≤35; 36-≤40; 41-45years), FSH-end-dosage was significantly lower in the RGs compared to the non-RGs (p &amp;lt; 0.001, respectively). Despite not significantly different patient characteristics (AFC, BMI (Body Mass Index), mean age, FSH-starting dosage), in patients aged 26-≤30years, a significantly higher number of oocytes (retrieved/mature) were obtained in the RG (16.0±7.1 vs 20.4±8.3;p&amp;lt;0.001 / 12.6±6.5 vs 15.8±7.0;p=0.004, respectively) without an increase in progesterone-levels (1.0±1.3 vs 0.9±0.6ng/ml;p=0.95). The HP-HMG group was composed of 437 patients in the RG and 344 patients in the non-RG-group. In all age-categories (&amp;lt;25; 26-≤30; 31-≤35; 36-≤40; 41-52years), HP-HMG-end-dosage was significantly lower in the RGs (p &amp;lt; 0.001, respectively). The age-group 36-≤40 showed no significant differences in AFC, BMI, age and HP-HMG-starting-dosage, and still, a significantly higher number of oocytes (retrieved/mature) were obtained in the RG-group (7.2±5.61 vs 9.8±6.13;p&amp;lt;0.001 / 5.7±4.7 vs 7.8±5.0;p&amp;lt;0.001, respectively). The progesterone-levels on trigger day in the nRG-group was 0.5±0.3ng/ml and 0.6±0.4ng/ml in the RG group, which is significantly different (p &amp;lt; 0.001), however, clinically insignificant. Limitations, reasons for caution The retrospective design is a limitation to this study as well as the exclusion of ovarian stimulation cycles, which were cancelled and no oocyte pick-up procedure was performed. Furthermore, in some age-categories, patients in RG and non-RG were different regarding their basic characteristics. Wider implications of the findings This analysis demonstrates, that in specific patient populations, gonadotropin-dosage can be reduced without impacting the oocyte yield and preventing progesterone-elevation despite higher oocyte yield. Furthermore, reduction of gonadotropins towards the end of the follicular phase results in a more physiologic course of the gonadotropin-levels during ovarian stimulation. Trial registration number not applicable

P-657 Administration of an extra Gonadotropin dose on trigger day in patients undergoing elective egg freezing

Abstract Study question Does an extra Gonadotropin (GT) dose on trigger day during a gonadotropin-releasing hormone (GnRH) antagonist cycle for oocyte cryopreservation result in improved cycle outcomes? Summary answer An extra GT dose on trigger day in patients undergoing elective egg freezing is not associated with increased oocyte yield. What is known already The most common controlled ovarian hyperstimulation (COHS) protocol used in elective oocyte cryopreservation cycles is a GnRH antagonist protocol with a GnRH agonist trigger. There is no consensus about the timing of the final gonadotropin dose administration. Some physicians add an extra GT dose during the ovulation trigger day and others advise to receive the last GT dose the day before. The yield of this extra GT dose was not previously evaluated. Study design, size, duration A retrospective cohort study, consisting of cycles of elective oocyte cryopreservation at Hadassah Medical Center from 1.2017 through 5.2021. Patients were divided into 2 groups- women who received their last GT dose a day before the GnRH agonist trigger, and women who received the last GT on the trigger day. Background and gynecologic characteristics, as well as COHS cycle parameters, were compared. The primary outcome was the average number of mature oocytes in each group. Participants/materials, setting, methods Women 30-41 years who were admitted for elective oocyte cryopreservation. Women who were referred due to medical reasons or cycles with a protocol other than GnRH antagonist were excluded. Ovarian stimulation with GT began on the 3rd day of the cycle, and five days later, a GnRH antagonist was added. When more than two mature follicles were demonstrated, a GnRH agonist trigger was administrated and approximately 36 hours later, the oocyte aspiration procedure was performed Main results and the role of chance During the study period, 448 elective egg freezing cycles were performed, 151 cycles with an extra dose on the trigger day and 297 cycles without an extra GT dose. The groups did not differ in their background characteristics, age, BMI, GT used, and the number of induction days. However, the extra GT group had significantly higher day 3 follicular stimulating hormone (FSH), lower anti-Mullerian hormone (AMH), and lower maximal Estradiol (E2) levels. The extra GT dose group had a significantly lower mean number of mature oocytes (11.1±7.1 vs. 6.4±4.5, p &amp;lt; 0.001). To adjust for the maximal E2 parameter, that differed between the groups, an additional analysis was performed, dividing the two groups into subgroups of cycles with maximal E2 above and below 10,000 pmol\l. Interestingly, even in cycles with maximal E2 above 10,000 pmol\l, the extra dose group had poorer results (10.3±4.3 vs. 12.7±7.2, p &amp;lt; 0.001). This difference was also noted in cycles with E2 below 10,000 pmol\l (5.4±4.0 vs 8.7±6.1 mature oocytes, p = 0.011). Additionally, a multiple regression model for the prediction of several oocytes retrieved showed that the extra GT dose parameter was not associated with increased oocytes number. Limitations, reasons for caution The retrospective design of this study and the differences in cycle characteristics between patients that did or did not receive an extra GT dose on trigger day make it prone to selection bias. Wider implications of the findings Our study shows that administration of an extra GT dose on trigger day in oocyte cryopreservation cycles does not yields more mature oocytes. However, wider prospective studies are needed to thoroughly investigate the implications of this treatment’s effect on cycle outcomes. Trial registration number Not applicable

Effects of growth hormone co-treatment on in vitro fertilization outcomes in women with expected normal ovarian response

Objective:This study aimed to evaluate the effects of adjuvant growth hormone (GH) therapy on in vitro fertilization outcomes in women with infertility with expected normal ovarian response who underwent gonadotropin-releasing hormone (GnRH) antagonist protocol with dual triggering.Materials and Methods:Records of women who underwent GnRH antagonist cycles with dual triggering in a single tertiary center between 2017 and 2020 were retrospectively analyzed. A total of 1054 women with expected normal ovarian response were evaluated, of which 131 were found to receive GH co-treatment (study group). Moreover, 950 women did not receive any adjuvant therapy (control group). Their cycle outcomes were compared.Results:The number of retrieved oocytes, oocyte maturation rates, quality of embryos, miscarriage rates, and multiple pregnancy rates were comparable among women who underwent GnRH antagonist cycles with and without GH co-treatment. The number of obtained 2PN embryos (5.68±2.46 vs 5.06±2.5; p=0.003), fertilization rates (0.84±0.16 vs 0.76±0.18; p<0.001), implantation rates (0.34 vs 0.25; p=0.006), clinical pregnancy rates (50.4% vs 38%; p=0.008), and live birth delivery rates (41.8% vs 32.2%; p=0.007) were significantly higher in women who received GH co-treatment.Conclusion:GH co-treatment significantly increased the clinical pregnancy rates and live birth delivery rates in women with infertility and expected normal ovarian response who underwent GnRH antagonist protocol with dual triggering for oocyte maturation, which was possibly due to the increasing endometrial receptivity or improving oocyte quality.

Adding Low Dose hCG to rFSH in GnRH Antagonist ICSI Cycles: A Randomized Controlled Trial

Inhibition of luteinizing hormone (LH) by gonadotropin releasing hormone (GnRH) antagonist may lead to suboptimal response during ovarian stimulation. In addition, several studies suggest that low level of LH is associated with lowered fertilization and implantation rate and increased early pregnancy loss rate. The aim of this study is to study the effect of adding low dose human chorionic gonadotropin (hCG - 200 IU), as an LH supplement, to recombinant follicle stimulating hormone (rFSH) in a GnRH antagonist cycles in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment. Sixty-three infertile women undergoing IVF were randomly divided into two groups. One group was stimulated with the conventional stimulation protocol (rFSH alone), while the second group received 200 IU hCG in addition to rFSH in the late follicular phase (hCG + rFSH). Both groups' results including pregnancy rate, total dose of rFSH required, duration of stimulation, endometrial thickness, oocytes and embryos characteristic, serum hormone levels (Testosterone, Estradiol, Progesterone, and LH) and level of epidermal growth factor (EGF) were compared. The results show that pregnancy rate among the group of women who received the low dose hCG was higher than those who did not receive hCG. However, this difference did not reach statistical significance. Furthermore, other cycle outcomes and hormonal values were comparable between the two stimulation protocols.

Early Follicular Phase Human Chorionic Gonadotropin Addition May Improve the Outcomes of In Vitro Fertilization/Intracytoplasmic Sperm Injection in Patients With "Unpredictable" Poor Response to Gonadotropin-Releasing Hormone Antagonist Protocol.

PurposeTo compare the effects of early and mid-late follicular phase administration of 150 IU of human chorionic gonadotropin (hCG) on gonadotropin-releasing hormone (GnRH) antagonist protocol in “unpredictable” poor ovarian response (POR) women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.MethodsA retrospective single-center cohort study was conducted on 67 patients with “unpredictable” POR in their first IVF/ICSI cycle receiving GnRH antagonist protocol. Patients were treated with a second IVF/ICSI cycle using the same GnRH antagonist protocol with the same starting dose of recombinant follicle-stimulating hormone (rFSH) as the first cycle; a daily dose of 150 IU of hCG was administrated on either stimulation day 1 (Group A, n = 35) or day 6 (Group B, n = 32). The number of oocytes retrieved, number of usable embryos, serum level of estradiol (E2) on day of hCG trigger, and clinical pregnant outcomes were studied.ResultsThe addition of 150 IU of hCG on either the first day or sixth day of stimulation increases the serum level of E2, luteinizing hormone (LH), and hCG on the day of hCG trigger. Only the use of 150 IU of hCG on the first stimulation day improved the number of oocytes retrieved, mature of oocytes, and usable embryos, but not the addition of hCG on stimulation day 6. Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate showed an increasing trend in patients receiving 150 IU of hCG in the early phase compared with mid-late phase, even thought there was no statistically significant difference.ConclusionsOur study demonstrated that adding 150 IU of hCG in subsequent GnRH antagonist cycle in “unpredictable” poor responders is associated with the improvement of response to stimulation. Furthermore, early follicular phase addition of 150 IU of hCG significantly increased the number of oocytes retrieved and usable embryos than did the mid-late addition of the same dose.