Human Chorionic Gonadotropin Trigger Research Articles

Does hCG-trigger in the mild stimulation protocol for endometrial preparation have any effect on pregnancy outcome in frozen-thawed embryo transfer?

BackgroundRecent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles.MethodsIn the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles.ResultsDemographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41–3.86, P-value = 0.001).ConclusionPregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field.

GnRH antagonist protocol with hCG triggering ameliorates fertilization defect caused by failure of cumulus cell pentraxin-3 expression in unilateral endometriomas.

The aim of the study was to determine the expression pattern of long pentraxin 3 (PTX3) mRNA in cumulus cells (CCs) isolated from metaphase II oocytes of women with unilateral endometrioma undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone antagonist (GnRHa) protocol. A total of 60 CC samples, 30 from the affected ovary and 30 from the contralateral ovary, were collected from 12 patients with unilateral endometrioma who underwent flexible GnRHa protocol with recombinant human chorionic gonadotropin (rhCG) trigger. Thirty CC samples collected from the left ovary of 12 women with male factor infertility were used as external controls. Long PTX3 mRNA expression in each group was analyzed by real-time polymerase chain reaction (RT-PCR). Relative gene expression (fold-change) was calculated according to the 2-ΔΔCt equation. Fertilization rates after intracytoplasmic sperm injection (ICSI) were recorded for each group. CC-PTX3 mRNA expression in the unilateral endometrioma group was significantly lower than the mRNA expression of the disease-free ovary (0.90±0.01 vs. 0.25±0.02, p<0.01). CC-PTX3 mRNA expression of MII oocytes of the disease-free ovary was found to be similar to the control group (1.02±0.03 vs. 0.90±0.01, p=0.107). A significant 3.6-fold downregulation was observed in the CC-PTX3 mRNA expression of the endometrioma group compared to the CC-PTX3 mRNA expression in the contralateral ovary. CC-PTX3 mRNA expression in the endometrioma group was downregulated 4.08-fold compared to the CC-PTX3 mRNA expression of the control group (1.02±0.03 vs. 0.25±0.02, p<0.001). The cumulus morphologies of the endometrioma group with low CC-PTX3 expression and the groups with normal CC-PTX3 levels were similar. Fertilization rates of the endometrioma group were similar to the contralateral ovary and control groups. Unilateral endometrioma reduces CC-PTX3 expression but does not affect disease-free ovaries. The GnRHa protocol improved the fertilization rates, suggesting that failed CC-PTX3 expression is an in vivo pathology.

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

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

Using progesterone to follicular index ratio is better correlated with intracytoplasmic sperm injection outcome than using serum progesterone level alone.

to investigate the possibility of using the ratio of serum progesterone level to the number of follicles, according to ovarian response in the day of human chorionic gonadotrophin trigger, as a predictor of cycle outcome. A prospective intervensional study was conducted at Kamal Al-Samarai Hospital for Infertility Treatment and IVF during the period from December 2020 to September 2021. Ninety infertile women underwent intracytoplasmic sperm injection (ICSI) cycles using antagonist protocol. Moreover, once the patient reached triggering criteria, meticulous recording of follicular index together with serum estrogen level and serum progesterone level are measured. Fresh embryo transfer of cleavage stage embryo is done once serum progesterone level was less than 1.5 ng/mL. A follow-up to confirm pregnancy rate and cycle outcome was done. The study showed a positive pregnancy rate of 28.9%. The relationship between progesterone follicular index (Prog/FI) ratio and (ICSI) outcome was highly significant with a p value of 0.001. Additionally, an inverse relationship, as the ratio was lower the pregnancy rate was improved, was documented. The receiver operating characteristic (ROC) curve for progesterone follicular index ratio was 0.711 with a cut off value of 0.0354 ng/mL in addition to a sensitivity of 65.6 and a specificity of 65.4. The serum progesterone level is an independent factor for the prediction of intracytoplasmic sperm injection (ICSI) outcome, whereas the progesterone follicular index ratio can be used as a potential marker for predicting ICSI outcome in fresh embryo transfer.

O-206 Natural, modified natural or artificial endometrial preparation strategies for frozen embryo transfer in ovulatory women (MONART): a randomized controlled trial

Abstract Study question Are live birth rates after natural (NC), modified natural (mNC) endometrial preparation superior to artificial cycle (AC) strategies for ovulatory women undergoing frozen embryo transfer? Summary answer Live birth rates were comparable between NC, mNC, and AC. However, NC and mNC resulted in a significantly higher cycle cancellation rate. What is known already The number of frozen embryo transfer (FET) cycles has increased dramatically. In ovulatory women undergoing FET, three common strategies can be used for endometrial preparation: NC, mNC (NC + human chorionic gonadotropin trigger), and AC protocols. Previous studies comparing the effectiveness of these strategies had several drawbacks, including small sample size, lack of consistency between studies in the assessment and reporting of outcomes, and the retrospective origin, which introduced potential biases. Therefore, there is a lack of consensus on the optimal endometrial preparation protocol for FET. Study design, size, duration This single-center, open-label, randomized controlled trial was conducted at IVFMD, My Duc Hospital in Ho Chi Minh City, Vietnam. From March 2021 to March 2022, a total number of 1,428 participants were randomized (476 per group). The primary outcome of the study was live birth after one FET. Secondary outcomes were fertility outcomes, early pregnancy complications, obstetrical outcomes, perinatal and neonatal complications, and endometrial preparation cycle cancellation rates. Participants/materials, setting, methods Eligible participants were ovulatory women aged 18–45 with FET treatment, underwent no more than three IVF/intracytoplasmic sperm injection-FET cycles, had no more than two day-3 or one blastocyst transferred. Women with menopause/anovulation, contraindications for hormonal administration, uterine abnormalities who underwent in-vitro maturation, pre-implantation genetic testing, oocyte donation cycles were excluded. The FET strategies included FET after the first endometrial preparation cycles with AC, mNC, or NC, as per randomization, and the second with AC. Main results and the role of chance A total of 4,779 participants were screened, of whom 1,428 eligible individuals (476 per group) were randomized after written informed consent. The live birth rate after one FET was 36.6% (174/476) in the natural cycle strategy group, 33.4% (159/476) in the modified natural cycle strategy group, and 34.0% (162/476) in the artificial cycle strategy group (relative risk [95% confidence interval] for natural versus artificial cycle strategy: 1.07 [0.87–1.33] and for modified natural versus artificial cycle strategy: 0.98 [0.79–1.22]). Maternal and neonatal outcomes were comparable between groups, in particular,hypertensive disorders in pregnancy. For both natural and modified cycle groups, 20.08% (99/476) of the first FET cycles were canceled before subsequent successful ET versus none in the artificial cycle group. Limitations, reasons for caution Due to the nature of the intervention, blinding was not possible. The study was conducted in ovulatory women in a single center in Vietnam, which may limit the generalisability of the findings. Wider implications of the findings Live birth rates and obstetric/neonatal outcomes after the natural cycle, modified natural cycle, or artificial cycle strategies for ovulatory women undergoing FET are comparable, with higher cancellation rates in both the natural cycle and the modified natural cycle groups. Trial registration number NCT04804020

Levothyroxine may not adequately prepare hypothyroid women for controlled ovarian hyperstimulation

BackgroundThyroid axis dysregulation during controlled ovarian hyperstimulation (COH) is more pronounced in hypothyroid‐treated women. Whether or not this leads to compromised thyroid hormone levels within the ovarian follicular fluid is not known.AimsTo determine whether ovarian follicular thyroid hormone levels are compromised in adequately replaced hypothyroid women undergoing controlled ovarian hyperstimulation (COH), and/or influence cycle/pregnancy outcomes.Materials and MethodsProspective cohort study involving 46 euthyroid (anti‐thyroid peroxidase antibody negative) and 16 levothyroxine‐replaced women with baseline thyroid‐stimulating hormone (TSH) &lt;2.5 mIU/L attending their first COH cycle. Follicular fluid TSH, free triiodothyronine (T3) and free thyroxine (T4) were recorded at oocyte pick‐up. Serum levels were measured at: (i) baseline; (ii) human chorionic gonadotropin trigger day; and (iii) cycle conclusion. The number of mature oocytes retrieved, fertilisation, early pregnancy loss and live birth rates were compared.ResultsMedian serum TSH levels were similar at baseline (1.76 vs 1.24 mIU/L, P = 0.053), but free T3 levels were lower (4.5 vs 4.8 pmol/L, P = 0.029) in levothyroxine‐replaced compared to euthyroid women, with serum TSH levels increasing across ovarian stimulation (P = 0.006) into pregnancy testing (P = 0.030). Follicular fluid free T3 levels were lower in levothyroxine‐replaced women (median 4.3 vs 4.6 pmol/L, P = 0.032). Fertilisation rates were lower (52% vs 71%, P = 0.043) in women requiring levothyroxine replacement, but numbers of mature oocytes retrieved, early pregnancy loss and live births did not differ.ConclusionAdequately replaced hypothyroid women achieve lower ovarian follicular fluid free T3 levels and poorer fertilisation rates compared to euthyroid women undergoing COH. Optimising T3 levels may be pivotal in improving COH outcomes in hypothyroid women.

Menstrual abnormalities effects on clinical features and in vitro fertilization pregnancy outcomes in women with polycystic ovarian syndrome

The diagnostic criteria and phenotypes in polycystic ovary syndrome are heterogeneous. Currently, it is unclear how to assess a patient's prognosis based on the onset time of menstruation disturbance. Evidence on this topic is scarce and has mainly focused on menstrual patterns. This study aimed to assess the association between the onset time of menstrual disturbance and clinical features and in vitro fertilization pregnancy outcomes in patients with polycystic ovary syndrome. Our study was a secondary analysis of data collected as part of a randomized controlled trial conducted to compare live birth rates between fresh embryo transfer and frozen embryo transfer in 1508 individuals with polycystic ovary syndrome. Here, 1500 participants were classified into 2 groups according to the onset time of menstrual disturbance: immediately after menarche (early group) and after at least 1 year of regular menstruation (late group). We compared the prepregnancy clinical features, variables of ovarian stimulation, pregnancy outcomes after the initial cycle of embryo transfer, and perinatal and neonatal complications in the 2 groups. Compared with the late group, the early group had more antral follicles (32.00 [range, 27.25-39.50] vs 28.00 [range, 24.00-36.00]; P<.001), an elevated level of antimüllerian hormone (7.02 ng/mL [range, 3.60-11.47] vs 5.66 ng/mL [range, 3.65-8.92]; P=.024), a higher level of baseline luteinizing hormone (10.01±5.93 vs 8.51±5.53 IU/l; P<.001) and luteinizing hormone-to-follicle-stimulating hormone ratio (1.51 [range, 1.00-2.32] vs 1.45 [range, 0.92-2.13]; P<.001), lower levels of fasting glucose (5.47 mmol/L [range, 5.11-5.73] vs 5.50 mmol/L [range, 5.17-5.76]; P<.001), and insulin at 2 hours after 75-g oral glucose tolerance test (56.85 µU/mL [range, 34.63-94.54] vs 59.82 µU/mL [range, 33.56-94.67]; P=.027), a higher level of high-density lipoprotein (1.26 mmol/L [range, 1.04-1.37] vs 1.21 mmol/L [range, 1.07-1.45]; P=.006). During in vitro fertilization, the early group had a higher level of peak estradiol (4596.50 pg/mL [range, 2639.25-6321.00] vs 3954.00 pg/mL [range, 2378.75-6113.50]; P=.013), and luteinizing hormone (2.52 IU/L [range, 1.40-4.21] vs 1.93 IU/L [range, 0.91-3.32]; P=.010) on the day of human chorionic gonadotropin trigger. There was no statistically significant difference observed in the number of oocytes and embryos, the rates of pregnancy and live birth, and the risks of obstetrical and neonatal between the 2 groups. An early onset of menstrual disturbance in patients with polycystic ovary syndrome may be associated with slightly more severe reproductive features and slightly milder metabolic features. Nonetheless, the outcomes of in vitro fertilization and the initial cycle of embryo transfer were comparable between the 2 groups.

Analysis of use of different rFSHs during IVF/ICSI-assisted conception in elderly population and effect of double trigger on clinical outcomes

Objective To compare the number of oocytes retrieved and clinical outcomes of ovulation induction in an older population treated with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) (IVF/ICSI) using different rFSH options and the effectiveness of antagonist treatment to induce ovulation using gonadotropin-releasing hormone agonists (GnRH-a) in combination with an human chorionic gonadotropin (HCG) trigger. Methods A total of 132 fresh cycles were selected for this study, which were treated with IVF/ICSI in our hospital from March 2022 to December 2022. Observations were made according to different subgroups and the effects of different triggering methods on the number of oocytes obtained, embryo quality, and clinical outcomes. Results The initial gonadotropin (Gn) dose, the number of oocytes, and the number of MII oocytes were higher in group A than in group B (p < .05), and the clinical pregnancy rate was 29.41% in group A. Group B had a clinical pregnancy rate of 27.5%. The double-trigger group was superior to the HCG-trigger group in terms of the number of 2PN, the number of viable embryos, and the number of high-quality embryos (p < .05). The use of a double-trigger regimen (OR = 0.667, 95%CI (0.375, 1.706), p = .024) was a protective factor for the clinical pregnancy rate, whereas AFC (OR = 0.925, 95%CI (0.867, 0.986), p = .017) was an independent factor for the clinical pregnancy rate. Conclusions The use of a dual-trigger regimen of GnRH-a in combination with HCG using an appropriate antagonist improves pregnancy outcomes in fresh embryo transfer cycles in older patients.

Estradiol Decline Before hCG Administration in COH Has a Negative Effect on IVF Outcomes in Patients Without OC Pretreatment.

Together with ultrasound measurement of follicle size, serum estradiol (E2) provides guidance for controlled ovarian hyperstimulation (COH). However, during the COH process, some patients experience decreased serum E2 level, especially before human chorionic gonadotropin (hCG) trigger. In order to elucidate the effect of E2 reduction as well as the role of oral contraceptive pretreatment, a retrospective study was performed in our center from 2013 to 2019. In total, 333 patients who experienced an E2 decrease prior to hCG administration were recruited as E2 decline group, while 333 patients with continuously E2 increase during COH were considered as control group. Based on pretreatment strategy, the two groups were further categorized into oral contraceptive (OC) and non-OC sub-groups, and IVF and clinical outcomes were compared between paired groups. Number of dominant follicles on hCG day and normally fertilized zygotes were significantly decreased in E2 decline group, and the significantly reduced live birth rate in E2 decline group indicated the close relationship between E2 decline and clinical outcomes. To analyse further, we found that in patients without OC pretreatment, the pregnancy rate and live birth rate of E2 decline group (n = 141) were significantly lower than control group (n = 136) (56.3% versus 68.0%, 50.8% versus 63.5%, respectively). However, for patients with OC pretreatment, no difference was detected between two groups, suggesting a potential effect of OC pretreatment on clinical outcomes. E2 decline prior to hCG-triggering day adversely affects IVF and clinical outcomes in patients without OC pretreatment, especially fertilization rate and live birth rate.

Human Chorionic Gonadotropin Trigger Day Progesterone to Oocyte Ratio Predicts Pregnancy Outcomes of In Vitro Fertilization Cycles: A Retrospective Cohort Study and Literature Review

Human Chorionic Gonadotropin Trigger Day Progesterone to Oocyte Ratio Predicts Pregnancy Outcomes of In Vitro Fertilization Cycles: A Retrospective Cohort Study and Literature Review

#369 : A Case of Luteal Phase Deficiency (LPD) and Polycystic Ovarian Syndrome (PCOS). When Routine is not Enough

Background and Aims: Luteal phase deficiency (LPD) is a consequence of the inability of the corpus luteum (CL) to produce an adequate level of progesterone. This manifests clinically as a short menstrual cycle and infertility. Abnormal follicular development and inadequate steroidogenesis in lutein cells of the CL have been implicated in CL dysfunction and LPD. LPD and PCOS are independent disorders sharing a common pathophysiology. The aim of this case report is to highlight the importance of additional luteal phase support for patients with PCOS. Case report: A 34-year-old Indian lady with anovulation secondary to PCOS failed to get pregnant after 7 years of marriage. Her menses were irregular, and she had hirsutism. She was also overweight. (BMI 26.4 kg/m2) Her hormonal profile showed a reversal of the FSH/LH ratio of 2:1, and serum progesterone was low. (&lt;1.6 IU/L). A transvaginal scan showed a classic pearl string sign, which was typical for patients with PCOS. She underwent laparoscopic dye insufflation and ovarian drilling, during which four puncture points were made on each ovary at 4 watts for 4 seconds. Later, she underwent a round of timed sexual intercourse and intrauterine insemination. (IUI) Dydrogesterone (10 mg, 8 hourly) was started for luteal phase support as per unit protocol. However, she complained of per vaginal spotting starting on day 7 after human chorionic gonadotropin (hcg) trigger, and both times, treatment was unsuccessful. Then, she had another round of ovarian stimulation with clomiphene citrate 50 mg daily and had IUI. She was given micronized progesterone 100 mg 12 hours a day in addition to the dydrogesterone. The urine pregnancy test was positive, and she is having a healthy, on-going pregnancy. Conclusion: Patients with PCOS may suffer from a defective luteal phase. Hence, it is important to supplement PCOS patients with additional support during the luteal phase, as this can lead to a successful pregnancy.

#314 : Comparison of Dual-Trigger and Human Chorionic Gonadotropin-Only Trigger Among Diminished Ovarian Reserve Who Underwent Intracytoplasmic Sperm Injection: A Retrospective Cohort Study

Background and Aims: Diminished ovarian reserve (DOR) remains one of the greatest challenges for ART treatment. The objective of this study was to compare the laboratory outcomes of dual trigger and human chorionic gonadotropin (HCG) trigger alone in the final oocyte maturation for DOR patients. Methods: In this retrospective study,we evaluated 130 DOR women (dual group, n=75 and HCG group, n=45) underwent intracytoplasmic sperm injection (ICSI) between July 2020 and February 2023 at the Assisted Reproductive Department, Hung Vuong Hospital. DOR was defined as antral follicle count [Formula: see text]5 and serum anti-Müllerian hormone level [Formula: see text]1.2ng/mL. All patients using the GnRH antagonist protocolwith frozen embryo transfer. Baseline characteristics and cycle parameters, as well as IVF outcomes of both groups were compared. Generalized linear model (GLM) with negative binomial distribution for retrieved oocytes outcome and binomial distribution for other outcomes such as maturation rate, fertilization rate, rate of successfully achieving blastocytes and day-3 embryos. Results: Baseline characteristics were similar between the dual trigger group and the HCG group for age (p=0.2), AFC (p=0.44), AMH (p=0.76), BMI (p = 0.12), indication and number of priorARTcycles. The dual-trigger group had a significantly higher number of retrieved oocytes (95% CI 0.125–2.437, p=0.03), metaphase oocyterate (OR = 1.90, 95% CI 1.05–3.43; p=0.033). Fertilized oocyte rate (OR 1.42, 95% CI 2.015–0.795, p=0.967) andday-3 embryos (OR = 1.42, 95% CI 2.70–.73, p=0.294) were comparable in two groups. Conclusions: Our data suggests that dual trigger for final oocyte maturation might improve laboratory outcomes of IVF cycles in DOR patients.

Optimizing FSH Concentration Modulation in the Short-Acting GnRH-a Long Protocol for IVF/ICSI: A Retrospective Study.

Exogenous gonadotropin (Gn) is given to regulate follicle-stimulating hormone (FSH) levels to achieve optimal ovarian response in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The objective of this study was to analyze the optimal degree of change in FSH blood concentration with ovarian responsiveness in a short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol for IVF/ICSI. This retrospective study was conducted at Changzhou Maternity and Child Health Hospital's Reproductive Center from May 2017 to May 2023. A total of 794 ovarian stimulation cycles for IVF/ICSI using the short-acting GnRH-a long protocol was included. Ovarian responsiveness was assessed based on the number of follicles > 14mm on human chorionic gonadotropin (HCG) trigger day, refine-follicular output rate (Refine-FORT) and good quality embryos. Delta 1 referred to the change in FSH level between days 6-8 of gonadotropin usage and baseline FSH, while Delta 2 referred to the change in FSH level between HCG trigger day and days 6-8 of gonadotropin usage. Simple and multiple linear regression analysis were performed to adjust for confounding factors. The number of follicles > 14mm on HCG trigger day was found to be the most suitable indicator for evaluating ovarian responsiveness compared to the number of follicles > 16mm and the number of retrieved oocytes. When Delta 1 ranged from 1.94 to 3.37, the number of follicles > 14mm on HCG trigger day was the highest. When Delta 1 ranged from 3.37 to 5.90, the Refine-FORT was the highest. However, when Delta 1 exceeded 5.90, the number of follicles > 14mm on HCG trigger day, Refine-FORT and good quality embryo all significantly decreased. On the other hand, when Delta 2 was ≤ - 1.58, the number of follicles > 14mm on HCG trigger day and the Refine-FORT were both the highest. This study identifies optimal Delta 1 and Delta 2 ranges for effective ovarian responsiveness in a short-acting GnRH-a long protocol for IVF/ICSI and introduces the novel measure of the number of follicles > 14mm on HCG trigger day. The optimal range for Delta 1 was 1.94 to 3.37, and Delta 2 should be < - 1.58 for achieving a higher number and quality of oocytes.

Dual trigger for final oocyte maturation in expected normal responders with a high immature oocyte rate: a randomized controlled trial.

To evaluate whether dual trigger could improve reproductive outcomes in women with low oocyte maturation rates compare to human chorionic gonadotropin (hCG) trigger. This study included expected normal ovarian responders younger than 40 years old whose immature oocyte rate in the previous cycle was more than 50% at the reproductive center from July 2021 to November 2022. A total of 73 patients were enrolled at trigger, including 34 in the hCG trigger group and 39 in the dual trigger group (co-administration of gonadotrophin releasing hormone (GnRH) agonist and hCG, 40 and 34 h prior to oocyte retrieval, respectively). The primary outcome was oocyte maturation rate. There was no significant difference in the number of oocytes retrieved between the two study groups, but the oocyte maturation rate was higher in dual trigger group (84.0% [14.0%] vs. 55.5% [19.8%], p < 0.001). Moreover, there were also higher cumulative pregnancy rate (69.4% vs. 40.0%, p = 0.035) and cumulative live birth rate (66.7% vs. 36.0%, p = 0.022) in dual trigger group. For normal responders with low oocyte maturation rates, the dual trigger may be more effective than the conventional hCG trigger. ClinicalTrials.gov, identifier ChiCTR2100049292.

Predictors for persistent endometrial cavity fluid from fresh to subsequent frozen embryo transfer

Introduction: During the process of assisted reproductive technology, clinicians are always faced with the problem of endometrial cavity fluid (ECF) interfering with pregnancy outcomes, especially those patients with ECF. The aim of this study was to identify which characteristics of those patients with ECF during the preparation of fresh embryo transfer would predict their recurrent ECF when they were to undergo this cycle of frozen embryo transfer due to cancellation of fresh embryo transfer or failure to obtain a live birth after fresh embryo transfer. Methods: We collected relevant clinical information of those patients receiving assisted reproduction therapy at Reproductive Hospital affiliated with Shandong University between January 2014 and December 2020, including those patients who developed ECF before fresh embryo transfer and canceled fresh embryo transfer for different reasons or did not obtain pregnancy after transfer. Patients were divided into persistent and transient ECF groups according to whether they still had ECF before the current cycle of frozen embryo transfer. We compared relevant data that may influence the persistence of ECF and performed logistic regression analysis to examine whether these variables were associated with the persistence of ECF. Results: The proportion of continued existence of ECF was 14.13% (276/1953). The variables related to the persistence of ECF were as follows: polycystic ovarian syndrome status, previous hysteroscopic adhesiolysis history, history of cesarean section, controlled ovarian hyperstimulation protocol, and endometrial thickness on human chorionic gonadotropin trigger day. Conclusions: It is recommended to inform those patients who present with a thin endometrium on human chorionic gonadotropin trigger day, the diagnosis of polycystic ovarian syndrome, a history of hysteroscopic adhesiolysis, cesarean section history, or were treated with gonadotropin-releasing hormone antagonist protocol that the ECF is less likely to resolve spontaneously, and early intervention based on the corresponding high-risk factors should be recommended.

Clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection cycles.

This study investigated the clinical and laboratory factors associated with the presence of dysmorphic oocytes in intracytoplasmic sperm injection (ICSI) cycles. The study involved 200 ICSI cycles, performed from 2020 to 2021, that yielded at least one mature oocyte. Clinical characteristics and ovarian stimulation methods were compared between 68 cycles with at least one dysmorphic oocyte (the dysmorphic group) and 132 cycles with normal-form oocytes only (the non-dysmorphic group). Dysmorphic oocytes were characterized by dark cytoplasm, cytoplasmic granularity, cytoplasmic vacuoles, refractile bodies in the cytoplasm, smooth endoplasmic reticulum in the cytoplasm, an oval shape, an abnormal zona pellucida, a large perivitelline space, debris in the perivitelline space, or an abnormal polar body. The ages of the women, indications for in vitro fertilization, serum anti-Müllerian hormone levels, and rates of current ovarian endometrioma were similar between the dysmorphic and non-dysmorphic groups. In both groups, the three ovarian stimulation regimens, two types of pituitary suppression, and total gonadotropin dose were employed similarly. However, the dual-trigger method was used more frequently in the dysmorphic group (67.6% vs. 50%, p=0.024). The dysmorphic group contained significantly more immature oocytes and exhibited significantly lower oocyte maturity (50% vs. 66.7%, p=0.001) than the non-dysmorphic cycles. Within the dysmorphic group, significantly lower oocyte maturity was found in the cycles using a dual-trigger, but not in those with a human chorionic gonadotropin trigger. ICSI cycles with dysmorphic oocytes are closely associated with reduced oocyte maturity. This association was observed exclusively in dual-trigger cycles.

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

ObjectiveTo 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.MethodsThis 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.ResultsOn 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.ConclusionWhile 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.

Comparison between Agonist Trigger with HCG Luteal Phase Supplementation vs HCG Trigger with Progesterone Luteal Phase Supplementation in Antagonist Controlled Hyperstimulation Cycle Regarding Clinical Pregnancy Rate

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the comparison between conventional HCG trigger and progesterone luteal phase support vs Agnosit trigger and HCG microsdose luteal phase support as regards to pregnancy rate. Methods 100 patients were recruited for this trial Cases with Polycyctic ovaries were excluded from the study. The study was approved by Ethical committee of Ain Shams university. Patients received Gonal-F (Merck Serono S.p.A., Via delle Magnolie 15, I70026 Modugno (Bari), Italy.) in a dose ranginging between 150-300 IU for stimulation and the dose was adjusted according to response starting day 6. Premature LH surge was prevented with 0.25 mg of a GnRH antagonist (Cetrotide; Merck international) starting on day 6, when two or more follicles reach a size of 18–20 mm, patients were randamized into 2 groups of 50 each. Trigger of ovulation was done by a single dose of 0.2 mg triptorelin (Decapeptyl®ferring pharmaceutical company, Germany) and luteal phase support with daily 125 IU HCG injections in Group 1. Group 2 received A single dose of HCG 10000 IU was given followed by progesterone supplementation with 100mg IM progesterone (Prontogest® IBSA Swisserland). 2 Embryo were transferred and an ultrasound at 4 weeks after embryo transfer for cases with positive pregnancy test. As regards to clinical pregnancy group 1 had 28 of the 50 (56%) Positive clinical pregnancy while control was 26 of the 50 (52%), the difference was not statistically significant (P &amp;gt; 0.68). No cases of moderate or severe ovarian hyperstimulation were observed during the study. To conclude, Agonist trigger combined with microdose HCG had a comparable pregnancy rate resulst to HCG trigger and conventional progesterone support for luteal support without increasing the risk of ovarian hyper stimulation.

Dual trigger improves the pregnancy rate in fresh in vitro fertilization (IVF) cycles compared with the human chorionic gonadotropin (hCG) trigger: a systematic review and meta-analysis of randomized trials.

The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles. A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR). We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]). The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity. After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.

The effect of gonadotrophin-releasing hormone agonist versus human chorionic gonadotrophin trigger on pregnancy and neonatal outcomes in Letrozole-HMG IUI cycles

BackgroundGnRHa and hCG are both used for oocyte maturation and ovulation triggering. However, GnRHa have a shorter half-life than hCG, which leads to luteal phase deficiency. Letrozole (LE) has been found to improve the luteal function. Thus, the choice of triggering strategy can be different in intrauterine insemination (IUI) cycles using LE and human menopausal gonadotropin (HMG). The aim of this study was to compare the pregnancy and neonatal outcomes of patients triggered with GnRHa versus hCG versus dual trigger in LE-IUI cycles.MethodsThis retrospective cohort study included 6,075 LE-HMG IUI cycles between January 2010 and May 2021 at a tertiary-care academic medical center in China. All cycles were divided into three groups according to different trigger strategies as hCG trigger group, GnRHa trigger group and dual trigger group. The primary outcome was clinical pregnancy rate. Logistic regression analysis was performed to explore other risk factors for clinical pregnancy rate.ResultsNo significant difference was observed in clinical pregnancy rate between hCG, GnRHa and dual trigger cycles in LE-HMG IUI cycles (P = 0.964). The miscarriage rate was significantly lower in the GnRHa trigger group, and higher in the dual trigger group, compared with the hCG group (P = 0.045). Logistic analysis confirmed that triggering strategy was associated with miscarriage (aOR:0.427, 95%CI: 0.183–0.996, P = 0.049; aOR:0.298, 95%CI: 0.128–0.693, P = 0.005). No significant differences were observed regarding neonatal outcomes between the three groups.ConclusionsOur findings suggested that both GnRHa and dual trigger can be used to trigger ovulation in LE-HMG IUI cycles, but dual trigger must be used with caution.