Reproductive outcomes of dual trigger therapy with GnRH agonist and hCG versus hCG trigger in women with diminished ovarian reserve: a retrospective study.

BACKGROUND: Diminished ovarian reserve (DOR) is one of the obstacles affecting the reproductive outcomes of patients receiving assisted reproductive therapy. The purpose of this study was to investigate whether dual trigger, including gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG), can improve pregnancy outcomes in patients with DOR undergoing in vitro fertilization (IVF) cycles using mild stimulation protocols. METHODS: A total of 734 patients with DOR were included in this retrospective study. Patients were divided into a recombinant hCG trigger group and a dual trigger group (hCG combined with GnRHa) according to the different trigger drugs used. The main outcome measures included the number of oocytes retrieved, the fertilization rate, the number of transferable embryos, the implantation rate, the clinical pregnancy rate, the miscarriage rate, the live birth rate (LBR), and the cumulative live birth rate (CLBR). Generalized linear model and logistic regression analyses were performed for confounding factors. RESULTS: There were 337 cycles with a single hCG trigger and 397 cycles with dual trigger. The dual trigger group demonstrated significantly higher numbers of retrieved oocytes [3.60 vs. 2.39, adjusted ß = 0.538 (0.221-0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted ß = 0.277 (0.031-0.523)] and transferable embryos [1.22 vs. 0.95, adjusted ß = 0.162 (-0.005-0.329)] than did the hCG trigger group, whereas no significant difference in the fertilization rate was observed between the two groups. Moreover, the embryo transfer cancellation rate (35.5% vs. 43.9%) was obviously lower in the dual trigger group. Among the fresh embryo transfer cycles, the implantation rate, clinical pregnancy rate, miscarriage rate and live birth rate were similar between the two groups. After controlling for potential confounding variables, the trigger method was identified as an independent factor affecting the number of oocytes retrieved but had no significant impact on the CLBR. CONCLUSIONS: Dual triggering of final oocyte maturation with hCG combined with GnRHa can significantly increase the number of oocytes retrieved in patients with DOR but has no improvement effect on the implantation rate, clinical pregnancy rate or LBR of fresh cycles or on the CLBR.

The Implications of Double Human Chorionic Gonadotropin (hCG) Trigger on a Pseudo-Empty Follicle Syndrome Patient Seeking Infertility Treatment Through Assisted Reproductive Technology (ART).

In the field of assisted reproductive technology (ART), empty follicle syndrome (EFS) is a known condition in which no oocytes are found despite adequate follicular development, which leads to a troublesome situation for patients seeking infertility treatment. In this case study, an EFS patient seeking treatment for infertility at an in vitro fertilization (IVF) clinic was examined to determine the effects of employing a double human chorionic gonadotropin (hCG) trigger. The final oocyte maturation and retrieval are induced by using the double hCG trigger, which includes giving two doses of hCG. In this particular patient, the study looks at the results of follicular development, oocyte retrieval, fertilization rates, embryo quality, and pregnancy rates. The conclusion provides information on how well the double hCG trigger affects treatment outcomes for EFS patients. According to the results of this case study, the two-stage hCG trigger procedure is suggested to enhance the results of oocyte retrieval in the uncategorized EFS patient. In all cycles after the procedural change, the double trigger's application led to effective oocyte maturation and retrieval. The study also showed that the double hCG trigger procedure had no negative consequences on patient safety or ovarian response. There were also no signs of ovarian hyperstimulation syndrome (OHSS) or any other problems. Due to the higher likelihood of oocyte retrieval, the patient also reported better emotional health and less anxiety during subsequent treatment cycles. The positive result of this case study demonstrates the potential advantages of a double hCG trigger procedure in pseudo-EFS patients receiving IVF treatment. When handling EFS cases, this modified strategy may be used as a potential answer by infertility clinics. The effectiveness and safety of the double hCG trigger procedure still need to be confirmed by doing randomized controlled trials on larger populations in order to validate the result.

Comparison between hCG and GnRH Agonist for Ovulation Trigger in GnRH Antagonist In-Vitro Fertilization Cycles in a Tertiary Hospital in Malaysia: An observational study.

OBJECTIVE: hCG is commonly used as an ovulation trigger in IVF. Its usage is associated with OHSS. GnRH agonist is an alternative to hCG and is associated with reduced incidence of OHSS. This study compared the cycle outcomes of GnRH agonists with hCG as an ovulation trigger in IVF cycles. METHODS: The medical notes of 209 IVF cycles receiving GnRH agonist and hCG as ovulation trigger over 18 months were reviewed in this retrospective study. The number and quality of mature oocytes, the number and quality of embryos, pregnancy rates, and outcomes were compared using Independent T-test or One-way ANOVA for normal distribution. The Mann-Whitney test or Kruskal-Wallis test was used for not normally distributed. p<0.05 was considered statistically significant. RESULTS: The cycle outcomes of 107 GnRH agonist-trigger and 102 hCG-trigger were compared. The MII oocytes retrieved and 2PN count was significantly higher in the GnRH agonist trigger group (p<0.001). Clinical pregnancy rate and ongoing pregnancy were higher in the GnRH agonist trigger group but were not statistically significant. The GnRH agonist trigger group was associated with low OHSS than the hCG trigger group (n=2(1.9%) and n=12(11.8%) respectively, p=0.004). CONCLUSION: GnRH agonist trigger is an option as a final maturation trigger in high-responder women undergoing IVF or ICSI cycles.

Effect of Elevated Progesterone Levels on hCG Trigger Day on Clinical Pregnancy Outcome in Short-Acting GnRHa Downregulated Cycles.

Background: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear. Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis. Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day. Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.

Effects of reduced follicle-stimulating hormone dosage before human chorionic gonadotropin trigger on in vitro fertilization outcomes.

OBJECTIVE: To determine whether a reduced dose of follicle-stimulating hormone (FSH) before human chorionic gonadotropin (hCG) trigger during ovarian stimulation can affect in vitro fertilization (IVF) outcomes. METHODS: This study included 347 patients with a normal ovarian response who received a reduced dose of FSH before hCG trigger for 2-3 days (Group A) and 671 patients who did not receive a reduced dose (Group B) from a university-affiliated IVF center between January 2021 and December 2022. The primary endpoint was estrogen (E2) and progesterone (P) levels on the day of hCG trigger, fresh embryo transfer cycles, laboratory outcomes, and clinical outcomes between the two groups. RESULTS: On the day of hCG trigger, Group A had significantly lower E2 and P levels than those in Group B (3454.95 ± 1708.14 pg/mL versus 3798.70 ± 1774.26 pg/mL, p = 0.003; and 1.23 ± 0.53 ng/mL versus 1.37 ± 0.59 ng/mL, p < 0.001, respectively). The proportion of patients with P levels ≥ 1.5 ng/mL was 22.48% in Group A compared to 34.58% in Group B (p < 0.001), while the proportion of patients with E2 ≥ 5000 pg/mL was 15.27% in Group A compared to 25.93% in Group B (p < 0.001). The fresh embryo-transfer cycle rate in Group A was higher than that in group B (54.47% and 32.64%, respectively; p < 0.001). Despite the reduction in FSH dosage, there were no significant differences between groups regarding the number of oocytes retrieved, total number of mature oocytes, normal fertilization rate, cleavage rate, Day 3 top-quality rate, implantation rate, pregnancy rate per cycle, and early pregnancy loss rate. CONCLUSION: While a reduced dose of FSH prior to hCG trigger during ovarian stimulation did not significantly affect IVF outcomes, it was associated with lower E2 and P levels, resulting in fewer cycles with E2 ≥ 5000 pg/mL and P ≥ 1.5 ng/mL on the day of the hCG trigger.

The thicker the endometrium, the better the neonatal outcomes?

STUDY QUESTION: Is endometrial thickness (EMT) on the hCG trigger day related to the neonatal outcome of a single birth after fresh embryo transfer (ET)? SUMMARY ANSWER: An EMT ≤7.8 mm was an independent predictor for greater odds of preterm delivery (PTD) of singletons born after fresh ET. WHAT IS KNOWN ALREADY: There may be a positive association between live birth rates and EMT after fresh ET. It is still unknown whether a similar association is seen for the neonatal outcomes of singletons in fresh cycles. STUDY DESIGN SIZE DURATION: This retrospective study involved singleton live births in women undergoing autologous IVF cycles during the period from 1 October 2016 to 31 July 2021. PARTICIPANTS/MATERIALS SETTING METHODS: A total of 2010 women who fulfilled the inclusion criteria were included. A multivariable regression analysis was performed to detect the relationship between EMT and neonatal outcomes after controlling for potential confounders. Smooth curve fitting and threshold effect analysis were used to evaluate the accurate cutoff value of EMT. MAIN RESULTS AND THE ROLE OF CHANCE: The results of the multivariate regression analyses showed that the odds of PTD were reduced by 45% with an EMT of 9.00-9.90 mm (adjusted odds ratio (OR): 0.55, 95% CI: 0.13 to 0.98; P = 0.0451), reduced by 58% with an EMT of 10.00-10.90 mm (adjusted OR: 0.42, 95% CI: 0.06 to 0.87; P = 0.0211) and reduced by 75% with an EMT >11 mm (adjusted OR: 0.25, 95% CI: 0.04 to 0.66; P = 0.0034), compared to the group with an EMT of 6.00-8.90 mm. It could also be seen from the adjusted smooth curves that the odds of PTD decreased and gestational age (GA) increased with increasing EMT. Combined with the analysis of threshold effects, the results indicated that when the EMT was ≤7.6 mm, the incidence of PTD decreased as the EMT gradually increased (adjusted OR: 0.47, 95% CI: 0.03 to 0.99; P = 0.0107), and when the EMT was ≤7.8 mm, the GA increased (adjusted ß: 1.94, 95% CI: 1.26 to 2.63; P < 0.0001) as the EMT gradually increased. LIMITATIONS REASONS FOR CAUTION: The main limitation of our study is its retrospective design. Although we found a significant decrease in PTD as the EMT increased, in terms of GA, the magnitude of the differences was modest, which may limit the clinical relevance of the findings. WIDER IMPLICATIONS OF THE FINDINGS: Our data provide new insight into the relationship between EMT and neonatal outcomes by indicating that a thin endometrium of ≤7.8 mm is associated with an increased odds of PTD of singletons after fresh ET. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Natural Science Foundation of China (grant no. 82071717). There are no conflicts of interest.

Serum progesterone on the day of human chorionic gonadotropin (hCG) trigger as a predictor of in-vitro fertilization (IVF) outcome - a retrospective analysis of seven years.

OBJECTIVE: To investigate the relationship between progesterone (P4) levels on the day of hCG trigger and IVF outcomes. METHODS: This is a retrospective analysis of IVF cycles from January-2013 to December-2019 from a single center. Women (21-39 years) submitted to IVF treatment for various infertility factors were included, while donor oocyte cycles and cancelled cycles were excluded from the study. The primary outcome measure was live birth rate. RESULTS: A total of 2149 cycles were analyzed. Of these, 223 (10.38%) were in the low P4 group (<0.5 ng/ml), 1163 (54.12%) in the normal P4 group (0.5-1.5 ng/ml), and 763 (35.50%) in the high P4 group (>1.5ng/ml). The groups were comparable with respect to age, factor of infertility and baseline AMH. The antagonist protocol was significantly more prescribed to the high P4 group (p<0.001). Live birth rates were 14.4%, 21.6%, and 21% (p<0.001), respectively, in three groups. Univariate analysis found that total cetrotide dose, total number of retrieved and fertilized oocytes, total number of embryos formed, transferred, and vitrified, and P4 on the day of hCG (p<0.001) were statistically significant after adjusting for age and BMI. In multivariate logistic regression after adjusting for age and BMI, only high P4 (aOR:0.60; p<0.001), total cetrotide dose (aOR: 0.82; p<0.001), and total utilizable embryos (aOR:1.11; p=0.029) were statistically significant. CONCLUSIONS: Having an elevated serum progesterone level on the day of hCG trigger was associated with lower pregnancy rates, but this is still not a robust marker to predict live births. More good quality evidence is needed.

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 StatementWhat 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.

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.

BACKGROUND: Previous 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. DESIGN: A 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. RESULTS: The results of the multivariate regression analyses showed that when the E2 level was 3001-4000 pg/mL (adjusted ß: - 89.64, 95% [CI]: - 180.29 to - 6.01; P = 0.0336) and greater than 4000 pg/mL (adjusted ß: - 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. CONCLUSIONS: Our 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.

Comparison of an HCG-only trigger versus dual trigger for final oocyte maturation in a progestin-primed ovarian stimulation protocol.

RESEARCH QUESTION: Is there any difference in clinical outcomes between a human chorionic gonadotrophin (HCG)-only trigger and a dual trigger combining gonadotrophin-releasing hormone agonist (GnRHa) and HCG in a progestin-primed ovarian stimulation (PPOS) protocol? DESIGN: This retrospective cohort study included women younger than 40 years old with a normal ovarian reserve who underwent IVF/intracytoplasmic sperm injection treatment with a PPOS protocol. Participants were allocated to two groups according to the triggering medicines. The clinical outcomes were compared, with cumulative live birth rate (CLBR) being the primary outcome. RESULTS: In total, 1066 women were included, 565 in the HCG-only group and 501 in the dual trigger group. Demographic parameters were comparable between the groups. Fewer oocytes were retrieved in the HCG-only trigger group (dual trigger 12.56 ± 7.12 versus HCG-only trigger 11.62 ± 6.02, P = 0.020). No significant difference was observed in the numbers of two-pronuclear embryos (7.12 ± 4.90 versus 6.76 ± 4.45, P = 0.208) and high-quality embryos (4.01 ± 3.70 versus 3.96 ± 3.32, P = 0.815). The CLBR after one complete cycle was also similar (40.72% versus 43.72%, P = 0.354). Multivariate logistic analysis confirmed that the trigger method had no association with CLBR (odds ratio [OR] 0.763, 95% confidence interval [CI] 0.578-1.005, P = 0.055) in the PPOS-treated patients. CONCLUSIONS: Compared with the HCG-only trigger group, comparable embryological and clinical outcomes were achieved, although more oocytes were retrieved in the dual trigger group. This suggests that there may be no extra benefit from dual triggering, and that it should not be recommended for routine use in the general population undergoing PPOS protocols.

Effect of the co-administration of HCG and GnRH agonist (dual trigger) versus standard HCG trigger on morphokinetic embryo parameters.

RESEARCH QUESTION: Does dual trigger (the co-administration of triptorelin 0.2 mg and recombinant human chorionic gonadotrophin (HCG) [Decapeptyl 0.2 mg + Ovitrelle 250 µg]) versus standard recombinant HCG (Ovitrelle 250 µg) affect embryo quality and morphokinetic parameters? DESIGN: Morphokinetic parameters and embryo quality of embryos derived from the first gonadotrophin-releasing hormone (GnRH) antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles triggered by dual trigger or standard HCG trigger in women ≤42 years. Outcome measures included time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second cycle (s2), duration of the second cycle (cc2) and known implantation data (KID) scoring for embryo quality. Multivariate linear and logistic regression analyses were performed for confounding factors. RESULTS: A total of 4859 embryos were analysed: 1803 embryos from 267 cycles in the dual trigger group and 3056 embryos from 463 cycles in the HCG trigger group. The groups were similar in patient and treatment characteristics apart from a higher maternal body mass index and lower maturation rate in the dual trigger group. Time to second polar body extrusion was shorter in the dual trigger group. Cleavage timings from zygote to an 8-cell embryo did not differ between the two groups. There was a higher percentage of embryos with an optimal cc2 duration in the HCG group. In multivariate logistic regression models, the trigger type was not a significant factor for cell cycle division parameters. CONCLUSIONS: Overall, there was no significant difference in the morphokinetic parameters or quality of embryos evaluated using a time-lapse monitoring system between embryos derived following dual trigger compared with HCG.

Adverse impact of elevated progesterone levels on human chorionic gonadotropin trigger day on blastocyst transfer outcomes in gonadotropin-releasing hormone agonist cycles.

OBJECTIVE: Dose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles? STUDY DESIGN: This was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred. RESULTS: When the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer. CONCLUSION: An increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles.

Is there an optimal timing interval between hCG trigger and oocyte vitrification?

OBJECTIVE: Oocyte vitrification has been developed as a promising alternative to slow freezing; however, the clinical outcome is highly operator dependent. From the past study, we know the timing of cryoprotectant exposure and understand that the intervals between the application of liquid nitrogen and thawing solution are crucial factors in the vitrification process. However, the optimal time intervals between hCG trigger and oocyte vitrification and equilibration remain unknown. This study aimed to evaluate the optimal intervals before and during modified vitrification. MATERIALS AND METHODS: This retrospective study included 66 patients undergoing vitrified-thawed oocyte cycles from June 2018 to May 2019. Oocyte in vitro maturation (IVM) is defined as the maturation in vitro of an immature oocyte collected using a standard pick up procedure. Oocytes were grouped into the following intervals: (1) human chorionic gonadotropin (hCG) trigger to oocyte vitrification (<38 h; 38-39 h; >39 h; IVM) (2) oocyte equilibration time (<10 min; 10-12 min; 12-15 min). The vitrification and warming procedures were performed following the steps as shown in the Cryotec method. RESULTS: A total of 390 mature oocytes were vitrified with the Cryotec method. The survival rates were not significantly different among the various intervals after the hCG trigger (97.59%; 95.54%; 100%); however, there was a trend of decreased survival rate in IVM group (66.67%). The oocyte survival rates were not significantly different among the various times of oocyte equilibration (96.77%; 97.33%; 95.42%). CONCLUSIONS: This was the first study to demonstrate no correlation between oocyte survival rate and the time intervals between hCG trigger and oocyte vitrification. Nor did the oocyte survival rate correlate with the various equilibration times during vitrification, as long as the oocyte was mature. In the future, large, prospective, randomized controlled studies will be required to confirm the clinical outcomes.

Dual Trigger with hCG Plus GnRHa for Final Oocyte Maturation in PGT-A Cycles Results in Similar Euploidy Rates when Compared to hCG-Only Trigger.

Factors that may have an effect on euploidy rate of blastocysts have been investigated thoroughly in the literature. We aimed to assess whether dual trigger alters the ploidy chance of a blastocyst in preimplantation genetic screening for aneuploidy (PGT-A) cycles. This retrospective cohort study was conducted in a total of 385 PGT-A cycles at a single tertiary center for various indications. Final oocyte maturation was triggered using human chorionic gonadotropin (hCG) or the combination of hCG and gonadotropin-releasing hormone agonists (GnRHa) (dual trigger). Participants were divided based on triggering method and all demographic and clinical characteristics of the patients were compared. Final oocyte maturation was triggered in 143 cycles with hCG (37.1%), and in 242 cycles with dual trigger (62.9%). The duration of stimulation was shorter in the dual trigger arm compared to the hCG trigger group (10.0 ± 1.6 vs. 9.4 ± 1.4 days, p ≤ .001). Euploidy rates per blastocyst tested were 23.4% and 26.1% respectively for hCG and dual trigger groups without significance. Similar rates of euploidy were noted, even after age stratification. There was no significant difference between the groups regarding positive pregnancy result and ongoing pregnancy rates (p = .779 vs. p = .188). Although dual triggering, compared to hCG triggering, does not provide an additional superiority on blastocyst euploidy rate, further studies in women with different infertility etiology are needed to specifically evaluate the impact of triggering method on ploidy rates.

Increasing dominant follicular proportion negatively associated with good clinical outcomes in normal ovarian responders using the depot GnRH agonist protocol: a large-sample retrospective analysis.

BACKGROUND: Currently, there is no universal criteria for the trigger time of controlled ovarian hyperstimulation (COH), especially with the emerging depot GnRH agonist protocol. It is challenging to explore an indicator that is representative of target follicle cohort development as an alternative to the conventional approach of determining the trigger time based on a few leading follicles. METHODS: This was a large-sample retrospective analysis. Between January 2016 and January 2020, 1,925 young normal ovarian responders who underwent their first in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycle using the depot GnRH agonist protocol were included. They were divided into three groups based on the dominant follicular proportion (DFP, defined as the ratio of ≥ 18 mm dominant follicles/ ≥ 14 mm large follicles on the human chorionic gonadotropin (HCG) day; Group A: < 30%; Group B: 30%-60%; and Group C: ≥ 60%). The binary logistic regression and multivariate linear regression were used to assess whether the DFP was associated with clinical pregnancy, the number of frozen blastocysts, the blastocyst formation rate, and the low number of frozen blastocysts. RESULTS: The logistic regression analysis showed that compared with Group A, the odds ratio (OR) for clinical pregnancy was 1.345 in Group B (P = 0.023), and there was no statistical difference between Group C and Group A (P = 0.216). The multivariate linear regression analysis showed that DFP was negatively associated with the number of frozen blastocysts (ß ± SE: Group B vs. Group A = - 0.319 ± 0.115, P = 0.006; Group C vs. Group A = - 0.432 ± 0.154, P = 0.005) as well as the blastocyst formation rate (ß ± SE: Group B vs. Group A = - 0.035 ± 0.016, P = 0.031; Group C vs. Group A = - 0.039 ± 0.021, P = 0.067). Furthermore, the OR for the low number of frozen blastocysts was 1.312 in Group B (P = 0.039) and 1.417 in Group C (P = 0.041) compared to Group A. CONCLUSIONS: For young normal ovarian responders using the depot GnRH agonist protocol, increasing DFP might reduce the developmental potential of oocytes and reduce the number of available blastocysts, and this might result in a lower cumulative pregnancy rate. However, further confirmation using strict prospective randomised controlled studies is required.

Double HCG trigger improves recovery of oocytes in women with a paucifollicular response to ovarian stimulation: A pilot study.

OBJECTIVE: To examine whether adding a second HCG trigger, 12.5 h after the first (36.5 h before ovarian puncture), can facilitate recovery of oocytes in women with a paucifollicular response to ovarian stimulation. METHODS: A total of 85 women aged 35-42 years, with a paucifollicular response to ovarian stimulation and who had experienced a total failure of oocyte recovery after the standard HCG ovulation trigger 36.5 h before ovarian puncture, were subsequently treated by the same protocol but with the addition of a second HCG trigger 12.5 h later. The recovered oocytes were inseminated by intracytoplasmic sperm injection (ICSI) and all available embryos were transferred 3 days later. RESULTS: The double trigger enabled recovery of cumulus oophorus cells from most of the follicles in the women who experienced failure of total recovery of oocytes after a single trigger. Fifteen patients became pregnant, and no signs of ovarian hyperstimulation syndrome were observed. Nine women delivered a healthy child. CONCLUSION: In women aged 35-42 years with a paucifollicular response to ovarian stimulation, a double HCG trigger appears to improve the rate of oocyte recovery. The conclusion of this pilot study needs to be confirmed by larger prospective trials.

Time, time, time: see what governs the luteal phase endocrinology.

Two modes of ovulation trigger are used in IVF: hCG, acting on ovarian LH receptors, and GnRH agonist, eliciting pituitary LH and FSH surges. These two modes are evaluated herein, focusing on how they serve specific time-sensitive events crucial for achieving embryo implantation and pregnancy. hCG trigger is associated with significant timing deviation from physiology. Peak progesterone is not synchronized with implantation window; progesterone level does not rise continuously to a mid-luteal peak, but rather drops from a too early peak. The luteal phase endocrinology post GnRH agonist trigger is characterized by a quick and irreversible luteolysis. Therefore, freeze all strategy is advised, if there is a risk of ovarian hyperstimulation syndrome. If fresh transfer is desired, numerous approaches for luteal phase support have been suggested. However, a thorough understanding of time-sensitive events suggests that a single 1,500 IU hCG dose, administered 48 h post oocyte retrieval, is all that is needed to fully support the luteal phase and secure best chances of achieving pregnancy.

HCG trigger versus GnRH agonist trigger in PCOS patients undergoing IVF cycles: frozen embryo transfer outcomes.

OBJECTIVE: The use of Gonadotrophin releasing hormone agonist (GnRHa), with freeze-all strategy followed by frozen embryo transfer (FET) has been found to eliminate the risk of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovarian syndrome (PCOS) undergoing IVF cycles. However, physicians still hesitate to routinely use GnRHa as a trigger, replacing human chorionic gonadotrophin (hCG), for concerns of compromised cycle outcome. We aimed to evaluate outcomes following the transfer of embryos in FET cycles obtained from GnRHa trigger in comparison with hCG trigger in PCOS patients of Asian origin. METHODS: Prospective observational cohort study. 210 PCOS patients undergoing IVF in an antagonist protocol who were randomized in the previous study (to evaluate if GnRHa trigger is a better alternative than hCG in PCOS patients to prevent OHSS; Group A: GnRHa trigger (n=92)] and Group B: hCG trigger (n=101)], were followed up in FET cycles to assess the outcomes. RESULTS: The odds of cumulative live birth rate per stimulation cycle favors GnRHa trigger against the hCG trigger [OR=2.15; (CI 1.2-3.83); p=0.008]. A significantly higher number of mature oocytes (19.1±11.7 versus 14.1±4.3; p<0.001) and blastocysts (4.2±1.63 versus 3.26±1.22; p<0.001) were available in the GnRHa group as compared to the hCG group. CONCLUSION: The cumulative live birth rate was better following transfer of frozen-thawed embryos generated from GnRHa-triggered cycles compared to hCG trigger. Hence, in PCOS undergoing IVF, as a good practice point, hCG trigger should be replaced by a GnRHa trigger with vitrification of all embryos followed by FET.

The Association Between Elevated Progesterone Level on Day of hCG Trigger and Live Birth Rates in ART Cycles: A Single Centre Observational Study.

BACKGROUND: The advent of ovarian stimulation within an in vitro fertilization (IVF) cycle has resulted in modifying the physiology of stimulated cycles and has helped optimize pregnancy outcomes. In this regard, the importance of progesterone (P4) elevation at time of human chorionic gonadotrophin (hCG) administration within an IVF cycle has been studied over several decades. Our study aimed to evaluate the association of P4 levels at time of hCG trigger with live birth rate (LBR), clinical pregnancy rate (CPR) and miscarriage rate (MR) in fresh IVF or IVF-ICSI cycles. METHODS: This was a retrospective cohort study (n=170) involving patients attending the Centre for Reproductive and Genetic Health (CRGH) in London. The study cohort consisted of women undergoing controlled ovarian stimulation using GnRH antagonist or GnRH agonist protocols. Univariate and multiple logistic regression analyses were used to evaluate the association of clinical outcomes. Differences were considered statistically significant if p≤0.05. RESULTS: As serum progesterone increased, a decrease in LBR was observed. Following multivariate logistical analyses, LBR significantly decreased with P4 thresholds of 4.0 ng/ml (OR 0.42, 95% CI:0.17-1.0) and 4.5 ng/ml (OR 0.35, 95% CI:0.12-0.96). CONCLUSION: P4 levels are important in specific groups and the findings were statistically significant with a P4 threshold value between 4.0-4.5 ng/ml. Therefore, it seems logical to selectively measure serum P4 levels for patients who have ovarian dysfunction or an ovulatory cycles and accordingly prepare the individualized management packages for such patients.

Shortcomings of an unphysiological triggering of oocyte maturation using human chorionic gonadotropin.

Final maturation of follicles has, in connection with ovarian stimulation and infertility treatment, traditionally been achieved by the administration of a human chorionic gonadotropin (hCG) bolus trigger of 5,000 to 10,000 IU. This trigger serves two purposes: induce oocyte maturation; and serve as luteal phase support owing to its long half-life. It now appears that the hCG bolus trigger is unable to support both these two purposes optimally. In particular, after an hCG trigger, the early luteal phase is hormonally abnormal and different from conditions observed in the natural menstrual cycle: the timing of the initiation of hCG and progesterone rise is much faster after an hCG trigger than in a natural menstrual cycle; the maximal concentrations of hCG and progesterone considerably exceed those naturally observed; and the timing of the peak progesterone concentration after an hCG trigger is advanced several days compared with the natural cycle. Furthermore, the hCG trigger without any follicle-stimulating hormone activity may induce oocyte maturation less efficiently than the combined luteinizing hormone and follicle-stimulating hormone surge normally seen. Collectively, the endometrium is likely to be advanced after an hCG trigger, and the implantation potential is probably not optimal. The precise effect on pregnancy rates after the different progressions of hCG and progesterone concentrations during the early luteal phase has not yet been determined, but more individualized methods using more physiological approaches are likely to improve reproductive outcomes.