Day Of hCG Trigger Research Articles

Effect of Progesterone Levels on the Day of hCG Trigger on Quality of Embryos in ICSI Cycles

This study aimed to identify whether there is a correlation between the concentration of Progesterone and the number of Mature Oocytes (MII) and between the concentration of progesterone and the number of Fertilized Oocytes 2PN, in addition to identify the Categories of the progesterone concentration range which may negatively affect the embryo quality and fertilization rate.

The impact of anti-Müllerian hormone on endometrial thickness in gonadotropin stimulation/intrauterine insemination cycles: is there an effect on pregnancy outcomes?

To study the association, if any, between anti-Müllerian hormone (AMH) and pre-ovulatory endometrial thickness (ET) in gonadotropin/intrauterine insemination (IUI) cycles. This retrospective cohort study included a total of 964 patients undergoing 1926 gonadotropin/IUI cycles at an academic fertility center. Primary outcome measure was the association between serum AMH and measured ET on the day of and the day before human chorionic gonadotropin hormone (hCG) ovulation trigger. The effect of a model combining AMH and ET on early pregnancy outcomes was a secondary measure. In 52.8% of cycles, ET was last assessed and recorded on the day of hCG administration, while in the remaining 47.2% on the day prior to trigger. In unadjusted regression models, AMH was weakly correlated with ET on hCG trigger day [bAMH (95%CI) = 0.032 (- 0.008, 0.070), p = 0.015]. When adjusting for potential confounders, the positive correlation became significant [0.051 (0.006, 0.102), p = 0.047]. Similar findings were observed when assessing the correlation between AMH and ET on the day prior to hCG trigger. ET was non-significantly associated with the odds of clinical pregnancy, when adjusting for potential confounders, except for when restricting the analysis to couples with idiopathic infertility [OR (95%CI), p-value: 0.787 (0.623, 0.993), 0.044]. Our findings support an effect of serum AMH on endometrial development in gonadotropin induced cycles, even when adjusting for the diagnosis of PCOS. ET was not associated with the odds of achieving a clinical pregnancy, except for couples with idiopathic infertility.

Eight weeks of androgen priming by daily low-dose hCG injections before ICSI treatment in women with low ovarian reserve.

Does 8 weeks of continuous low-dose hCG administration increase the proportion of antral follicles that reach the preovulatory state during ovarian stimulation (OS) in women with low ovarian reserve? The proportion of antral follicles (2-10 mm) that reached the preovulatory state did not increase. The administration of androgens prior to OS might upregulate FSH receptor (FSHR) expression on granulosa cells, making follicles more responsive to exogenous FSH stimulation during OS. LH and hCG stimulate the local follicular androgen synthesis in theca cells and may be used as an endogenous androgen priming method. Exogenous priming by testosterone and dehydroepiandrosterone (DHEA) have been shown to increase the number of retrieved oocytes and live birth rate but the studies are small, and their use is associated with side effects. A prospective, paired, non-blinded single-center study including 20 women serving as their own controls conducted between January 2021 and July 2021 at The University Hospital Copenhagen Rigshospitalet, Denmark. Participants underwent two identical consecutive IVF/ICSI treatments, a Control cycle and a Study cycle, separated by ∼8 weeks (two menstrual cycles) of daily injections of 260 IU recombinant hCG (rhCG). A freeze-all strategy was applied in the Control cycle. Both IVF/ICSI cycles were performed in a fixed GnRH antagonist protocol using a daily dose of 300 IU recombinant FSH (rFSH) and GnRH antagonist 0.25 mg from stimulation days 5-6. Follicular output rate, defined as the number of follicles >16 mm on hCG trigger day divided by the antral follicle count (2-10 mm) at baseline, did not increase after 8 weeks of hCG priming (P = 0.8). The mean number of oocytes retrieved was significantly higher after the hCG priming being 4.7 (2.8) vs 3.2 (1.7) in the Study and Control cycle, respectively (P = 0.01). The duration of stimulation was longer in the Study versus the Control cycle (P = 0.05), despite the use of identical hCG trigger criterion and similar diameters of the three biggest follicles on hCG trigger day in the two cycles (P = 0.9). The sample size was small, and the number of oocytes retrieved was not the primary endpoint. Larger studies are needed to confirm this finding. Long-term, low-dose rhCG administration may increase the number of oocytes retrieved during IVF/ICSI in women with low ovarian reserve, but more research is needed before firm conclusions can be drawn. This study was funded by an unrestricted grant from Gedeon Richter. A.P. reports personal consulting fees from PregLem SA, Novo Nordisk A/S, Ferring Pharmaceuticals A/S, Gedeon Richter Nordics AB, Cryos International, and Merck A/S outside the submitted work and payment or honoraria for lectures from Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, Merck A/S, and Theramex and Organon & Co. Grants to the institution have been provided by Gedeon Richter Nordics AB, Ferring Pharmaceuticals A/S, and Merck A/S and receipt of equipment by the institution from Gedeon Richter Nordics AB is reported. The remaining authors have no conflicts of interest to declare. ClinicalTrials.gov Identifier: NCT04643925.

The effect of previous induced abortion history on the assistedreproduction outcomes.

To study whether the history of induced abortion has an effect on the assistedreproduction outcomes in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). 3045 patients who underwent IVF-ET in the Department of Human Reproductive Center of Renmin Hospital from January 2017 to June 2021. They were divided into two groups according to whether there was a history of induced abortion in the past, and the outcomes were compared between the two groups. The clinical pregnancy rate in the group with induced abortion history was lower than that in the group without induced abortion history (63.1% vs 67.1%), but the difference was not statistically significant (P = 0.059). The spontaneous abortion rate in the group with induced abortion history was higher than that in the group without induced abortion history (14.9% vs 11.2%) (P = 0.044). The live birth rate in the group with induced abortion history was lower than that in the group without induced abortion history (52.8% vs 59.0%) (P = 0.006). Stepwise logistic regression analysis showed that endometrial thickness (OR = 0.928, 95% CI = 0.886 ~ 0.972, P = 0.002) and live birth rate (OR = 0.682, 95% CI = 0.495 ~ 0.939, P = 0.019) were negatively correlated with induced abortion history. The rate of spontaneous abortion (OR = 1.452, 95% CI = 1.042 ~ 2.024, P = 0.028) was positively correlated with the history of induced abortion. The previous history of induced abortion is related to the outcomes of IVF /ICSI-ET, the endometrial thickness on HCG trigger day decreased, the risk of spontaneous abortion increased and the live birth rate decreased in patients with induced abortion history when undergoing IVF/ICSI-ET.

Premature timing of progesterone luteal phase support initiation did not negatively impact live birth rates in modified natural frozen thawed embryo transfer cycles

Study questionIn a modified natural cycle frozen-thawed embryo transfer (mNC-FET), does the premature timing of progesterone luteal phase support (LPS) initiation 24 h following human chorionic gonadotropin (hCG) trigger impact live birth? Summary answerPremature LPS initiation did not negatively affect the live birth rate (LBR) in mNC-FET cycles compared with conventional LPS initiation 48 h after hCG triggering. What is known alreadyDuring natural cycle FET, human chorionic gonadotropin is routinely used to mimic endogenous luteinizing hormone (LH) surge to induce ovulation, which allows more flexibility in embryo transfer scheduling, thus relieving the burden of multiple visits by patients and laboratory workloads, which is also known as mNC-FET. Moreover, recent data demonstrates that ovulatory women undergoing natural cycle FETs have a lower risk of maternal and fetal complications due to the essential role of the corpus luteum in implantation, placentation and pregnancy maintenance. While several studies have confirmed the positive effects of LPS in mNC-FETs, the timing of progesterone LPS initiation is still unclear, as compared with fresh cycles where robust research has been conducted. To the best of our knowledge, no clinical studies comparing different beginning days in mNC-FET cycles have been published. Study design, size, durationThis retrospective cohort study involved 756 mNC-FET cycles performed at a university-affiliated reproductive center between January 2019 and August 2021. The primary outcome measured was the LBR. Participants/materials, setting, methodsOvulatory women ≤42 years of age who were referred for their autologous mNC-FET cycles were included in the study. According to the timing of progesterone LPS initiation following the hCG trigger, patients were assigned into two categories: premature LPS group (progesterone initiation 24 h after hCG trigger, n = 182) versus conventional LPS group (progesterone initiation 48 h after hCG trigger, n = 574). Multivariate logistic regression analysis was used to control for confounding variables. Main results and the role of chanceThere were no differences in background characteristics between the two study groups, except for the proportion of assisted hatching (53.8% in premature LPS group versus 42.3% in conventional LPS group, p = 0.007). In the premature LPS group, 56 of 182 patients (30.8%) had a live birth, compared to 179 of 574 patients (31.2%) in the conventional LPS group, with no significant difference observed between groups (adjusted odds ratio [aOR] 0.98, 95% confidence interval [CI] 0.67–1.43, p = 0.913). In addition, there was no significant difference between the two groups in other secondary outcomes. A sensitivity analysis for LBR according to the serum LH and progesterone levels on hCG trigger day also confirmed the aforementioned findings. Limitations, reasons for cautionIn this study, retrospective analysis was conducted in a single center and was therefore prone to bias. Additionally, we did not anticipate monitoring the patient's follicle rupture and ovulation after hCG triggering. Future prospective clinical trials remain necessary to confirm our results. Wider implications of the findingsWhile exogenous progesterone LPS was added 24 h after hCG triggering, embryo-endometrium synchrony would not be adversely affected so long as sufficient time was allowed for endometrial exposure to exogenous progesterone. Our data support promising clinical outcomes following this event. As a result of our findings, clinicians and patients will be able to make better informed decisions. Study funding/competing interest(s)No specific funding was available for this study. The authors have no personal conflicting interests to declare. Trial registration numberN/A.

Controlled ovarian hyperstimulation parameters are not associated with de novo chromosomal abnormality rates and clinical pregnancy outcomes in preimplantation genetic testing.

This study aimed to determine whether controlled ovarian hyperstimulation (COH) parameters influence the incidence of de novo chromosomal abnormalities (> 4 Mb) in blastocysts and, thus, clinical pregnancy outcomes in preimplantation genetic testing (PGT). Couples who underwent preimplantation genetic testing for structural chromosome rearrangements (PGT-SR) and monogenic disorders (PGT-M) were included in this study. The relationships of maternal age, paternal age, stimulation protocol, exogenous gonadotropin dosage, duration of stimulation, number of oocytes retrieved and estradiol (E2) levels on human chorionic gonadotropin (hCG) trigger day with the incidence of de novo chromosomal abnormalities were assessed. Blastocysts were biopsied, and nuclear DNA was sequenced using next-generation sequencing (NGS). Clinical pregnancy outcomes after single euploid blastocyst transfers under different COH parameters were assessed. A total of 1,710 and 190 blastocysts were biopsied for PGT-SR and PGT-M, respectively. The rate of de novo chromosomal abnormalities was found to increase with maternal age (p< 0.001) and paternal age (p = 0.019) in the PGT-SR group. No significant differences in the incidence of de novo chromosomal abnormalities were seen for different maternal or paternal age groups between the PGT-SR and PGT-M groups (p > 0.05). Stratification analysis by gonadotropin dosage, stimulation protocol, duration of stimulation, number of retrieved oocytes and E2 levels on hCG trigger day revealed that de novo chromosomal abnormalities and clinical pregnancy outcomes were not correlated with COH parameters after adjusting for various confounding factors. The rate of de novo chromosomal abnormalities was found to increase with maternal or paternal age. COH parameters were found to not influence the incidence of de novo chromosomal abnormalities or clinical pregnancy outcomes.

Serum Progesterone Levels on the Day of Human Chorionic Gonadotrophin Trigger, and its effects on the Outcome of In Vitro Fertilization, and Embryo Transfer: A Two-Center Study

Abstract Introduction: Gonadotrophin-releasing hormone analogs were expected to make preovulatory progesterone (P4) elevation rare during in vitro fertilization (IVF) cycles, but despite its widespread use, subtle rise in P4 levels on the day of ovulation trigger has a documented prevalence of 5%–38%. The effect of preovulatory progesterone levels on IVF outcomes is still controversial and published data from West Africa is sparse. Materials and Methods: This was a prospective observational study of 107 women who underwent IVF in both Garki and Nisa hospitals in Abuja, Nigeria. A serum sample was obtained from participants on the day of human chorionic gonadotrophin administration for a single determination of progesterone level. Oocytes retrieved, biochemical pregnancy, and clinical pregnancy were the primary outcomes. Results: The mean P4 on human chorionic gonadotrophin (hCG) trigger day was 2.07 ± 0.24 ng/mL and 48 (44.9%) had P4 &gt; 1.5 ng/mL. There was no relationship between P4, and the number of oocytes retrieved but implantation, biochemical pregnancy, and clinical pregnancy were significantly diminished when P4 &gt;1.5 and &lt;1 ng/mL: biochemical pregnancy (27.3% vs. 61.5% vs. 14.6%, χ2 = 17.896; P &lt; 0.0001), clinical pregnancy (24.2% vs. 50.0% vs. 14.6%, χ2 = 11.041; P = 0.004). Conclusion: Pregnancy rates are diminished when P4 on hCG trigger day is elevated.

Thin endometrial lining: is it more prevalent in patients utilizing preimplantation genetic testing for monogenic disease (PGT-M) and related to prior hormonal contraceptive use?

Is a thin endometrial lining before ovulation triggering more prevalent in patients utilizing preimplantation genetic testing for monogenic disease (PGT-M) compared to the regular IVF/ICSI population and is this associated with prior hormonal contraceptive use? Thin (<8 mm) endometrial lining is more prevalent in PGT-M patients compared to the regular IVF/ICSI population and is associated with both longer prior hormonal contraceptive use and a shorter cessation interval of hormonal contraceptives before IVF/ICSI treatment. Thin endometrial lining has been associated with lower pregnancy rates in IVF/ICSI cycles and increased chances of miscarriage and low birth weight. Endometrial thinning and atrophy occur during hormonal contraceptive use. Patients utilizing PGT-M typically use hormonal contraceptives up until treatment to avoid the risk of conception of a genetically affected child. Whether this could negatively affect endometrial thickness achieved during subsequent IVF/ICSI cycles is not known. A retrospective case control study was performed, including all PGT-M patients attending the University Medical Centre Groningen (cases), between 2009 and 2018. The control group consisted of two non-PGT IVF/ICSI patients for each PGT-M patient, matched for age and treatment period. First cycles of 122 PGT-M patients and 240 controls were included. Cessation interval of hormonal contraceptives was categorized as late cessation (cessation <1 year prior to treatment) or early cessation (>1 year prior to treatment). Endometrial thickness was routinely measured on the day of hCG triggering or 1 day prior. The prevalence of an endometrial lining <8 mm was compared between PGT-M patients and controls. Hormonal contraceptive use (both duration and cessation interval) was compared between both groups. Univariable and multivariable regression analyses were performed to identify risk factors for thin endometrial lining. In addition, cycle and pregnancy outcomes were compared within control/PGT-M groups between patients with endometrial lining > or <8 mm. Thin endometrial lining on the day of hCG triggering was found significantly more often in the PGT-M group, compared to controls: 32% vs 11% (mean difference 21.0%, 95% CI: 11.7, 30.3%). As expected, more patients in the PGT-M group ceased their hormonal contraception late (<1 year): 64% vs 2% in the control group (mean difference 61.9%, 95% CI: 53.0, 70.8%). Average duration of hormonal contraceptive use was 10.6 years in the PGT-M group vs 9.3 years in controls (mean difference 1.3 years, 95% CI: 0.2, 2.3 years). Multivariable logistic regression analysis identified late cessation (OR: 6.0, 95% CI: 1.9-19.2) and duration of prior hormonal contraceptive use (OR per year increase 1.1, 95% CI: 1.0-1.2) as significant independent risk factors for a thin endometrial lining. In relation to outcome, we found a statistically significant increase in miscarriage rate in PGT-M patients with an endometrial lining <8 mm compared to those with an endometrial lining >8 mm (20.0% vs 1.7%, mean difference 18.3%, 95% CI: 2.3, 34.3%). A trend towards lower birth weight and gestation- and gender-adjusted birth weight (z-score) was also found in this group. No statistically significant differences were detected in pregnancy rate, live birth rate, or incidence of preterm delivery or SGA. Within the control group, no statistically significant differences were found in outcomes between patients with an endometrial lining <8 compared to an endometrial lining >8 mm. The study is retrospective. Various types of hormonal contraceptives were reported which possibly exert different effects on the endometrial lining. In relation to pregnancy outcome measures, numbers were very limited; therefore, no firm conclusions should be drawn. This study provides further insight into the role of prior hormonal contraceptive use as a possible contributor to the occurrence of thin endometrial lining during ART treatment. Future studies should provide more information on its clinical relevance, to determine whether PGT-M patients can be reassured, or should be counselled to stop hormonal contraceptive use and change to an alternative contraceptive method prior to PGT treatment. No specific funding was used and no conflicts of interests are declared. N/A.

The Effect of Human Growth Hormone on Endometrial Growth in Controlled Ovarian Hyperstimulation Cycles.

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient's cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls. Primary outcome was absolute growth in endometrial thickness from pre-stimulation start to day of hCG trigger. Mixed-model regression analysis controlled for patient correlation over repeat cycles and potential confounders. 80 patients were included. Mean age was 39.7 years; mean BMI was 23.8 kg/m2. Majority of patients were nulliparous, non-smoking, and White or Asian. Most common diagnosis was diminished ovarian reserve. Endometrial growth was compared between 159 COH cycles with hGH and 80 COH control cycles; mean increase was 4.5 mm and 3.9 mm, respectively-an unadjusted difference of 0.6 mm (95% CI: 0.2-1.1, p = 0.01). After adjusting for demographic/clinical factors, hGH was associated with 0.9 mm greater endometrial growth (0.4-1.4, p &lt; 0.01). Absolute increase in endometrial thickness was higher in COH cycles that included hGH. Further prospective studies in embryo transfer cycles are needed.

Adverse impact of elevated serum progesterone and luteinizing hormone levels on the hCG trigger day on clinical pregnancy outcomes of modified natural frozen-thawed embryo transfer cycles.

The relationship between serum progesterone (P) and luteinizing hormone (LH) levels on the human chorionic gonadotropin (hCG) trigger day and the clinical pregnancy outcomes in modified natural frozen-thawed embryo transfer (mNC-FET) cycles are controversial. This was a retrospective study of 788 mNC-FET cycles. A smooth fitting curve and threshold effect analysis was performed to identify the effect of serum P and LH levels measured on the hCG day on the clinical pregnancy rate (CPR) and live birth rate (LBR) of mNC-FET cycles. The CPR and LBR decreased significantly when the LH level on the hCG day was greater than or equal to 32 IU/L. Further subgroup analysis showed that the CPR decreased significantly when the P level on the hCG day was equal to or greater than 1 ng/mL. When the P level was lower (< 1 ng/mL), the patients with an LH level greater than or equal to 32 IU/L had reduced CPR and LBR in mNC-FET cycles. Applying the hCG trigger on a day with a higher P level (≥ 1 ng/mL) leads to a decreased CPR and LBR. hCG administration with a higher LH level (≥ 32 IU/L) also leads to a decreased CPR and LBR in mNC-FET cycles when the P level is less than 1 ng/mL.

E2 level > 2950 pg/ml on hCG trigger day is an independent predictor for birthweight loss of full-term singletons born after fresh embryo transfers in non-PCOS patients

BackgroundPrevious studies have demonstrated that the supraphysiological E2 level is negatively correlated with birthweight. However, the cut-off value of E2 level that significantly affects birthweight is unknown, and there is no definite conclusion regarding this level. Our study aimed to explore the threshold of the effect of E2 levels on birthweight.DesignA retrospective cohort study of 1846 samples was performed. All patients ≤42-years-old underwent autologous IVF cycles between August 1st, 2016 and April 30th, 2020. We categorized our data into four groups according to the E2 level: Group 1: ≤2000 pg/mL; Group 2: 2001–3000 pg/mL; Group 3: 3001–4000 pg/mL; and Group 4: > 4000 pg/mL.ResultsThe results of the multivariate regression analyses showed that when the E2 level was 3001–4000 pg/mL (adjusted β: − 89.64, 95% [CI]: − 180.29 to − 6.01; P = 0.0336) and greater than 4000 pg/mL (adjusted β: − 138.10, 95% [CI]: − 272.87 to − 10.33; P = 0.0181), weight loss was significant. Furthermore, the odds of full-term SGA were 1.40 times higher with E2 levels of 3001–4000 pg/mL (adjusted OR: 1.40, 95% [CI]: 1.090 to 3.18; P = 0.0256) and 2.55 times higher with E2 > 4000 pg/mL (adjusted OR: 2.55, 95% [CI]: 1.84 to 3.86; P = 0.0063) compared to the reference group. It can also be seen from the adjusted curves and the threshold effects that when the E2 level > 2950 pg/mL and > 3121 pg/mL, the incidence of SGA increased and the birthweight decreased, respectively.ConclusionsOur data suggest that E2 levels > 2950 pg/mL is an independent predictor for greater odds of full-term SGA singletons born after fresh embryo transfer.

Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle

To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis. Impact Statement What is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction. What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG. What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.

Estimation of follicular growth—widely used, seldom studied

We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient’s age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1–4 days before trigger, does not affect pregnancy rates.

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.

Inter-Cycle Variation in Endometrial Thickness in Fresh Embryo Transfer Cycles: Predictors and Association with Pregnancy Outcome

Background: The use of intracytoplasmic sperm injection (ICSI) has increased substantially worldwide, primarily in couples with non-male factor infertility. We recently published the results of a large randomised controlled trial (RCT) comparing ICSI and IVF showing no significant improvement of ICSI over IVF in couples with normal semen concentration and motility. Here, we assess the cost-effectiveness of ICSI in these couples, with additional attention for subgroups. Aim: To evaluate the inter-cycle variation in endometrial combined thickness (ECT) in fresh embryo transfer cycles Method: This was a retrospective cohort study in a single university affiliated fertility clinic in Chengu, China. We studied women undergoing IVF/ ICSI treatment in a fresh stimulated cycle, and measured endometrial combined thickness on the day of HCG trigger in consecutive stimulated IVF/ICSI cycles. Inter-cycle variation in ECT was the main outcome measure. Secondary outcomes were the relationship between ECT and treatment outcomes clinical pregnancy, live birth and miscarriage. Results: The mean ECT in consecutive fresh stimulated cycles was 10.28 ⊠ 2.15mm in cycle 1 (n=7038), 9.93 ⊠ 2.11mm in cycle 2 (n=1287), 9.49 ⊠ 2.22mm in cycle 3 (n=148) and 8.63 ⊠ 1.82mm in cycle 4 (n=17) (p [Formula: see text]0.01.). An incremental increase in the clinical pregnancy rate was demonstrated for each additional millimetre in ECT up to a threshold level of 12-15mm. There was no evidence of systematic bias on the visual assessment of the Bland Altman plot in women undergoing 2 consecutive cycles of treatment (mean bias 0.46, (95% limits of agreement -5.62 to 5.65)). Multivariate predictors of ECT were the number of previous treatment cycles, secondary infertility, infertility diagnoses of anovulation, endometriosis, male factor or unexplained infertility and the number of follicles greater than 14mm on the day of HCG trigger. There was a small, significant interaction between female age and ECT on the outcome clinical pregnancy. Conclusion: There is a slight decrease in mean ECT in women undergoing consecutive stimulated IVF/ICSI cycles which is potentially explained by the increased occurrence of pregnancy with thicker ECT. Each millimetre increase in late follicular ECT increases the odds ratio of clinical pregnancy to a threshold level of 12-15mm.

P-583 PCOS patients got better IVF/ICSI outcomes with “higher” progesterone level on hCG day: a retrospective study of Ten years data

Abstract Study question We aimed to investigate whether serum Progesterone (P) on the day of hCG trigger can be used as a biomarker to predict the IVF/ICSI outcomes in PCOS patients. Summary answer PCOS patients got better IVF/ICSI outcomes with “higher” progesterone level (2.7-5.9mmol/L). What is known already There were several studies suggesting serum Progesterone (P) on the day of hCG trigger can be used as a biomarker to predict IVF outcomes, and to decide fresh cycle embryo transfer or frozen all. But there was few study focus on PCOS patients. Study design, size, duration This is a single-center retrospective cohort study in PCOS women undergoing the first transfer of an IVF cycle between January 1st 2010 and December 31th 2019. There were 141,539 oocyte retrieval cycles during the study period, and 97,189 cycles were their first IVF cycle. PCOS was diagnosed according to the Rotterdam criteria. Among them, 3,146 cycles full filled the inclusion and exclusion criteria, and all with two embryos transferred on Day 3. Participants/materials, setting, methods We compared the live birth rate of fresh embryo transfer, stratified for serum P level. We looked for interaction between serum P level and live birth rate of fresh cycles. The serum P level within normal range (&amp;lt; 6nmol/L) on the day of hCG trigger day was divided into 4 quartiles. The four quartiles were defined as ≤ 1.35 nmol/L (Q1), &amp;gt;1.35-1.93 nmol/L (Q2), &amp;gt;1.93-2.7 nmol/L (Q3), &amp;gt;2.7 nmol/L (Q4). Main results and the role of chance The baseline characteristics with no different between groups, except BMI. The patients in Q4 group with lowest BMI, significantly higher number of oocytes retrieved and live birth rate (P &amp;lt; 0.05) . The Logistic regression analysis of the relative factors on live birth rate including BMI, basal LH and number of oocytes retrieved [P = 0.003, 0.030, 0.037 respectively, 95%CI (1.022, 1.111), (1.004, 1.076), (1.002, 1.082)]. Limitations, reasons for caution Due to the retrospective nature of this study, a well-designed and matched large sample prospective study is needed. The definition of elevated P level and the method of hormonal assessments were different between studies, this limiting the comprehensive analysis of researches and the further verification of existing results. Wider implications of the findings PCOS patients who with normal range P level on hCG day, got better IVF/ICSI outcomes with “higher” progesterone level (2.7-5.9mmol/L). Weight control is important for PCOS patients accepting IVF treatment. Trial registration number NOT APPLICABLE

P-675 Determining endogenous progesterone levels on the day of HCG triggering in modified natural cycles before frozen-thawed blastocyst transfer. Results and influence on clinical pregnancy rates

Abstract Study question Is the endogenous progesterone level (EPL) on the day of hCG administration associated with pregnancy outcomes in modified natural cycles before embryo transfer? Summary answer The present analysis suggested the negative effect of EPL on clinical pregnancy when progesterone was above 1,1 ng/ml on the day of HCG triggering. What is known already Endogenous progesterone levels (EPL) experience an abrupt increase following the ovulatory LH surge. It is described that this change in basal EPL contributes to modulating the endometrial receptivity in preparation for embryo implantation. Several authors reported a negative impact on the pregnancy of high serum EPL on the day of HCG. These studies revealed accelerated endometrial changes and a subsequent decoupling of the implantation window. These observations involved only patients who underwent ovarian stimulation before the embryo transfer. However, studies based on EPL in modified natural cycles before blastocyst transfer are very limited. Study design, size, duration The present non-interventional pilot cohort study aimed to determine the EPL in patients undergoing an endometrium preparation for frozen-thawed embryo transfer in non-stimulated cycles, and its association with clinical pregnancy rates. A total of 46 participants were included in this analysis. To reduce variability, the mean EPL was calculated excluding 2 outlier values in our dataset. The cut-off value of EPL was established using the Youden-index, and the T-student was used for further statistical comparisons. Participants/materials, setting, methods Patients following our IVF program, who underwent frozen-thawed embryo transfer during the period of study. Our data includes cycles with own and with donated oocytes. The total oocyte average age was 33,5±6,7. All transfers were performed at blastocyst stage. Main results and the role of chance The overall clinical pregnancy rate per embryo transfer was 70,5% (31/44), with an implantation rate of 66,7% (32/48). The mean number of transferred embryos was 1,09, with a single embryo transfer rate of 90,9%. The total mean of EPL was 0,31±0,26 [IC95% 0,23-0,39], with patients who achieved a clinical pregnancy (0,30±0,21; n = 31) showing significantly lower EPL (p-value=0,04) than the non-pregnant participants (0,41±0,40; n = 10). Three out of 44 patients had a biochemical pregnancy, with a mean EPL of 0,12±0,01. EPL cut-off value was establish at 1,1 ng/ml. The evaluation of the total dataset (n = 46 patients, including 2 outliers) showed that 8,7 % of a total of these cases had an EPL above the threshold of 1,1 ng/ml. The clinical pregnancy rate in this subgroup of patients was 25,0%. Limitations, reasons for caution This study includes a limited number of cases. Further analysis is required to confirm the present results and to allow data stratification for additional inter-group comparisons. Wider implications of the findings Evaluating EPL may contribute to improving the clinical outcome in natural modified cycles. We observed that EPL is expected to be lower in non-stimulated than in stimulated cycles, compared to previously published studies. These observations highlight the importance to manage treatment-related EPL thresholds, in particular, to establish transfer decision-making policies. Trial registration number n/a

P-382 Decrease of serum estradiol prior to human chorionic gonadotrophin administration have an impact on live birth in IVF/ICSI cycles

Abstract Study question Whether decrease of serum estradiol prior to human chorionic gonadotrophin administration have an impact on live birth in IVF/ICSI cycles? Summary answer The E2 change before the day of hCG administration had significant correlation with live birth. The live birth rate decreased with decreasing serum E2 level. What is known already The objective of this study was to assess the effects of a decrease of estradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration on in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) outcomes, including cycles with long, antagonist and micro stimulus protocols. Study design, size, duration In this retrospective cohort study, 1303 patients who received IVF/ICSI non-donor treatment were identified. Patients were divided into two groups according to live birth and the characteristics of IVF/ICSI cycles were compared between groups, including baseline infertility parameters, ovarian stimulation characteristics and embryo laboratory manipulation parameters. Participants/materials, setting, methods In this retrospective cohort study, 1303 patients who received IVF/ICSI non-donor treatment were identified. Patients were divided into two groups according to live birth and the characteristics of IVF/ICSI cycles were compared between groups, including baseline infertility parameters, ovarian stimulation characteristics and embryo laboratory manipulation parameters. The multivariate logistic regression model was performed to adjust potential confounders and assess correlation between E2 dynamics before hCG administration and live birth. Main results and the role of chance Our results revealed that patients without live birth had higher age (32.13 ± 4.33 vs. 30.21 ± 3.71, P &amp;lt; 0.001) and pervious miscarriages (0.57 ± 0.95 vs. 0.46 ± 0.83, P = 0.0295), while had lower number of oocytes retrieved (8.95 ± 4.69 vs. 12.36 ± 5.54, P &amp;lt; 0.001), day of hCG E2 (8269.53 ± 4104.22 vs. 9580.71 ± 3534.11, P &amp;lt; 0.001) and endometrium thickness (10.37 ± 3.66 vs. 11.50 ± 3.40, P &amp;lt; 0.001) compared with patients with live birth. Additionally, the multivariate logistic regression analysis displayed significant impact of serum E2 change on the live birth, and the achievement of live birth [OR (95%CI) 0.81 (0.71, 0.92), P = 0.001] decreased with the decreasing level of serum E2 before hCG trigger day. Estradiol stratification analyses displayed the OR and 95% CI for the association between △E2 and live birth among patients with different levels of estradiol decline (&amp;lt;25%, 25%–50%, 50%–75%, &amp;gt;75%). Compared with the &amp;lt;25% decline and 25%–50% decline groups, the ORs of 50%–75% and &amp;gt;75% decline groups were 1.66 (95% CI: 1.12-2.45, P = 0.012) and 2.00 (95% CI: 1.39-2.89, P &amp;lt; 0.001), respectively, after adjusting potential confounders. Limitations, reasons for caution There was concealment of randomization and blinding of outcome assessments reducing the risk of selection and measurement bias. Wider implications of the findings In summary, the E2 change before the day of hCG administration had significant correlation with live birth, and the live birth decreased with the decreasing level of serum E2 before hCG trigger day. The patients with a greater decline in the E2 level more likely to had poor clinical outcomes. Trial registration number Chi CTR1900026088

P-679 Comparison of hormone replacement treatment (HRT) and true-natural cycle (t-NC) protocols for endometrial priming: An analysis of 1,815 warmed blastocyst transfer cycles

Abstract Study question Does the ongoing pregnancy rate (OPR) of HRT with or without GnRH-agonist suppression and t-NC protocols differ in patients undergoing warmed blastocyst transfer? Summary answer HRT, with or without GnRH-agonist suppression, and t-NC protocols are associated with comparable OPRs in patients undergoing warmed blastocyst transfer. What is known already Despite the worldwide increase in frozen embryo transfer cycles, the most optimal protocol for priming of the endometrium is debated. Although HRT offers flexibility, recent evidence points tot-NC being superior to HRT regarding safety, i.e., maternal, obstetric, and neonatal outcomes.However, there are still conflicting data regarding pre-clinical losses and reproductive outcomes when comparing the two protocols. Study design, size, duration In this longitudinal prospective study, 1,815 consecutive patients undergoing 1,815 warmed blastocyst transfer cycles at the Anatolia IVF Centre, Ankara, between 2015-2021, were included. HRT with pituitary suppression was the protocol of choice during 2015- 2017, whereas HRT without suppression and t-NC were more commonly employed during the latter part of the period. Participants/materials, setting, methods All patients with an available day-5/6 vitrified blastocyst(s) were included. Each patient was included only once. The three protocols were t-NC and HRT - with or without suppression. The prerequisites for t-NC was being a local patient with regular menstrual cycles. For t-NC, neither human chorionic gonadotropin (hCG) nor luteal phase support was administered. The primary outcome measure was OPR, defined as pregnancy &amp;gt;12 weeks of gestation. Main results and the role of chance Of the 1,815 cycles,124 were t-NC, 477 were HRT with suppression, and 1,214 were HRT without suppression. For the stimulated cycles leading to FET, no difference was seen among the three groups regarding female age, body mass index, duration of infertility, number of previous embryo transfer attempts, ovarian stimulation protocol, estradiol levels on the day of hCG trigger, number of oocytes retrieved, number of preimplantation genetic testing-aneuploidy, freeze-all cycles and number of embryos transferred. The positive pregnancy test rates of the HRT protocol with or without suppression were higher when compared with that of t-NC (63.7%, 66.6%, and 58.1%,respectively; p = 0.05). The respective figure for clinical pregnancy rates were 56.6%, 60.8% and 55.6% (p = 0.07). However, the pre-clinical (biochemical) loss rates (11.9%, 10.9%, and 4.9%, respectively; p = 0.05), as well as the miscarriage rates (11.9%, 10.9%, and 4.9%, respectively; p = 0.04), were higher in the HRT groups with or without suppression compared to those of t-NC. The OPRs of t-NC, HRT with or without suppression were comparable (53.2%, 45.1%, and 49.0%, respectively; p = 0.73). The protocol for endometrial priming was not an independent predictor of ongoing pregnancy at logistic regression analysis when potential confounders were used as covariates (OR = 0.998; 95%CI 0.669-1.490, p = 0.99). Limitations, reasons for caution The longitudinal study design and the lack of obstetric and perinatal outcome data are limitations. Wider implications of the findings Compared with t-NC, the HRT protocol with/without suppression is associated with higher positive pregnancy test rates albeit increased pre-clinical and clinical loss rates, resulting incomparable OPRs. When compared with t-NC, the HRT protocol could be associated with enhanced endometrial receptivity at the expense of decreased selectivity. Trial registration number not applicable

P-626 Eight weeks of androgen priming by low dose hCG before IVF/ICSI in women with low ovarian reserve

Abstract Study question Does eight weeks of low dose hCG priming improve the outcome of ovarian stimulation for IVF/ICSI in women with low ovarian reserve. Summary answer Significantly more oocytes were retrieved following eight weeks of low dose hCG priming, when compared to an identical IVF/ICSI treatment immediately before the priming period. What is known already Administration of androgens prior to ovarian stimulation for IVF might upregulate the FSH receptor level on granulosa cells making the follicles more responsive to exogenous FSH. LH and hCG stimulate the follicular androgen synthesis, acting through LH receptors on the theca cells, enabling their use as an intra-ovarian androgen priming method. Exogenous testosterone and DHEA priming have been shown to increase the number of retrieved oocytes and the live birth rate, but systemic androgen administration is associated with side effects. Long term ‘intra-ovarian’ priming with hCG without systemic effects in women with low ovarian reserve has not previously been investigated. Study design, size, duration A prospective, paired, non-blinded study including 20 women serving as their own controls conducted between January 2021 and July 2021 at The University Hospital Copenhagen Rigshospitalet, Denmark. Participants underwent two identical consecutive IVF/ICSI treatments, a Control cycle including elective freezing of all blastocysts and a Study cycle with fresh blastocyst transfer. The Control and Study cycle were separated by approximately eight weeks (two menstrual cycles) of androgen priming by daily injections of 260 IE hCG. Participants/materials, setting, methods Inclusion criteria were age 18-40 years, regular menstrual cycle 23-35 days and AMH &amp;lt;6.29 pmol/L. Control and Study IVF/ICSI cycles were performed in a fixed GnRH-antagonist protocol using a daily dose of 300 IU rFSH and GnRH antagonist 0.25 mg from stimulation day 5-6. Primary endpoint was the follicular output rate defined as the pre-ovulatory follicle count (&amp;gt;16 mm) on hCG trigger day divided by the antral follicle count (2-10 mm) on cycle day 2-3. Main results and the role of chance 20 women with a mean (SD) age of 36.8 (3.2) years and an AMH level of 3.7 (1.5) pmol/L were included and completed the study. The number of oocytes retrieved was significantly higher in the Study compared to Control Cycle: 4.7 (2.8) vs. 3.2 (1.7), (P = 0.007), and the number of blastocysts was 1.2 (1.6) vs. 0.6 (0.7) in the Study compared to Control cycle, (P = 0.11). The follicular output rate was 0.4 (0.4) in the Study cycle initiated immediately after eight weeks of hCG priming, which was similar to the follicular output rate of 0.38 (0.2) in the Control cycle performed just before initiating the priming period (P = 0.81). The number of follicles above 10 mm on trigger day was 7.3 (5.0) in the Study and 5.3 (2.9) in the Control cycle (P = 0.018). Although the duration of stimulation seemed longer in the Study compared to Control cycle, 10.1 (1.5) and 8.9 (2.7) days respectively (P = 0.05), the same trigger criterion was defined and used in the two cycles confirmed by a similar mean diameter of the two biggest follicles on trigger day: 18.5 (1.1) vs. 18.3 (1.1) mm in the Study and Control cycle, respectively (P = 0.91). Limitations, reasons for caution The sample size calculation was based on the follicular output rate, and the study was not powered to look at oocyte retrieval rates. Bigger studies are needed to confirm this finding. Wider implications of the findings Although no increase in the follicular output rate was demonstrated, significantly more oocytes were retrieved after eight weeks of hCG priming, which is an important finding in a population of women with low ovarian reserve. Benefits of long term low dose hCG priming must be confirmed in a larger study. Trial registration number NCT04643925