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IntroductionThis study compared, in high responders undergoing IVF treatment, GnRH agonist-only trigger and dual trigger on oocyte retrieval rate and cumulative live birth rate (LBR). The aim was to determine if the GnRH agonist-only triggers had provided outcomes comparable to dual trigger, while minimizing the risk of ovarian hyperstimulation syndrome (OHSS).Materials and methodsA retrospective, matched case-control study was conducted at Taichung Veterans General Hospital, Taiwan, including women who underwent IVF/ICSI between January 1, 2014, and December 31, 2022. Inclusion criteria were: GnRH antagonist protocol and estrogen level >3,000 pg/ml on trigger day. Exclusion criteria were: immune/metabolic diseases, donated oocytes, and mixed stimulation cycles. Propensity score matching was applied to balance age, AMH level, and oocyte number between the GnRH agonist-only and dual trigger groups. Outcomes were analyzed for patients who had complete treatment cycles, focusing on oocyte retrieval rate and cumulative LBR.ResultsWe analyzed 116 cycles in the agonist-only group, and 232 cycles in the dual trigger group. No inter-group difference was found in their age, BMI, and AMH levels. The dual trigger group had a higher oocyte retrieval rate (93% vs. 80%; p

Abstract 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 β = 0.538 (0.221–0.855)], fertilized oocytes [2.55 vs. 1.94, adjusted β = 0.277 (0.031–0.523)] and transferable embryos [1.22 vs. 0.95, adjusted β = 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.

Aim: to assess the effects of a dual trigger by gonadotrophin-releasing hormone (GnRH) agonist and low-dose human chorionic gonadotropin (hCG) on in vitro fertilization (IVF) outcomes in women with normal ovarian response.Materials and Methods. This case-control analysis comprised 118 patients who responded normally to ovarian stimulation with a GnRH antagonist protocol at Hue Center for Reproductive Endocrinology and Infertility, Vietnam, between January 2018 and October 2019. Recruitment was achieved through case-control matching: a case (with Dual trigger – group A) was paired with control (with hCG trigger – group B) in a 1:1 ratio. The primary markers of success were the retrieval of oocytes and embryological data, the pregnancy rate, and the incidence of ovarian hyperstimulation syndrome (OHSS).Results. 59 patients in group A and 59 women in group B were recruited. Two groups had comparable patient characteristics and ovarian reserve. The initial dose, total dose, duration of gonadotropin administration, and peak of estradiol level were not statistically different across groups. The number of recovered oocytes (10.3 ± 4.2 vs. 10.0 ± 3.3; p = 0.663), mature oocytes (8.6 ± 3.7 vs.8.1 ± 2.8; p = 0.346), and high-quality embryos (56.2 ± 28.9 vs. 59.8 ± 35.9; p = 0.555) was equivalent. Fertilization, clinical pregnancy, and live birth rates were comparable between the dual trigger and hCG groups. In neither group were any occurrences of OHSS seen.Conclusion. Dual trigger may substitute hCG for final oocyte maturation and fresh embryo transfer in patients with normal responses to GnRH antagonist protocol-induced ovarian stimulation without compromising IVF outcomes.

ObjectiveTo evaluate whether dual trigger could improve reproductive outcomes in women with low oocyte maturation rates compare to human chorionic gonadotropin (hCG) trigger.MethodsThis 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.ResultsThere 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

BackgroundRisk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone.MethodsWe retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle.ResultsFollowing confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035–47.274). Group 1 (b = −12.72; 95% CI −20.9 to −4.55) and BMI (b = −0.25; 95% CI −0.5 to −0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS.ConclusionsThe maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.

Abstract Background Despite a large number of studies on the selection of trigger drugs, it remains unclear whether the dual trigger with human chorionic gonadotropin (hCG) and gonadotropin-releasing hormone (GnRH) agonist, compared to the trigger with hCG alone, can improve the reproductive outcome of patients undergoing assisted reproductive technology. Therefore, this study aimed to compare the laboratory and clinical outcomes of dual trigger versus single trigger. Methods In this retrospective cohort study, we evaluated 520 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles between July 2014 and September 2020 at the Reproductive and Genetic Center of Integrative Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine. All patients underwent IVF/ICSI treatment with fresh embryo transfer using the GnRH antagonist protocol. We used propensity score matching to control for confounding variables and binary logistic regression analysis to determine the correlations between trigger methods and pregnancy outcomes. After propensity score matching, 57 cycles from each group were evaluated and compared for laboratory or clinical outcomes in this retrospective cohort study. Results There was no significant difference in the number of oocytes retrieved, embryos available, top-quality embryos, or the rate of normal fertilization between the dual-trigger and single-trigger protocols, respectively. The incidence of ovarian hyperstimulation syndrome, implantation rate, biochemical pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate, early miscarriage rate, and live birth rate were also similar between the two groups, while the miscarriage rate (37.0% vs. 12.5%, p = 0.045) was higher in the dual-trigger than the single-trigger group. Subsequent binary logistic regression analysis showed that age was a remarkably significant independent predictor of both clinical pregnancy rate (odds ratio = 0.90, 95% confidence interval: 0.84–0.97, p = 0.006) and live birth rate (odds ratio = 0.89, 95% confidence interval: 0.82–0.97, p = 0.005). Conclusions Therefore, dual-trigger for final oocyte maturation might increase miscarriage rate, but in terms of the laboratory and other pregnancy outcomes such as clinical pregnancy rate, early miscarriage rate or live birth rate, there was no evidence to show that dual trigger was superior to an hCG-trigger alone for patients undergoing GnRH-antagonist cycles with fresh embryo transfer. Trial registration Retrospectively registered.

Objective Dual trigger is used to induce final oocyte maturation during the process of controlled ovarian hyperstimulation, yet yielding controversial results. Also, there are yet no data regarding the effect of the dosage of the dual trigger on clinical outcomes. Based on the Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) criteria, this study aimed to determine the clinical difference of a single bolus versus two boluses of gonadotropin-releasing hormone agonist (GnRHa) in POSEIDON group IV patients using dual trigger. Methods We screened a total of 1,256 patients who underwent in vitro fertilization (IVF) cycles who met the POSEIDON group IV criteria. Six hundred and twenty-nine patients received one bolus of GnRHa, and 627 patients were given two boluses. All patients received the same dose of recombinant human chorionic gonadotropin during the dual trigger cycle. Results Metaphase II oocyte retrieval rate, fertilization rate and clinical pregnancy rate did not differ between the two groups. However, a lower percentage of at least one top-quality embryo transfer (34.3% vs. 26.0%, P=0.001) in the two bolus-GnRHa group was noted. Conclusion A double bolus of GnRHa did not show superior clinical results compared to a single bolus of GnRHa in the dual trigger IVF cycle. Therefore, GnRHa doses for use should be decided based on individual clinical situations considering cost-effectiveness and patient compliance, but further investigation will be needed.

Objective The objective of this study was to evaluate the effectiveness of dual trigger, which is a combination of gonadotropin-releasing agonist (GnRH-a) and recombinant human chorionic gonadotropin (hCG) in the final oocyte maturation, in the outcome of intrauterine insemination (IUI). Methods This retrospective observational study was conducted from January 2016 to October 2018 and involved 639 IUI cycles at the Halim Fertility Center, Indonesia. Controlled ovarian stimulation was performed during IUI cycles. The ovulation triggers were divided into two groups: group I received a combination of GnRH-a and recombinant hCG as a dual trigger, and group II received only recombinant hCG as a single trigger. The baseline characteristics, cycle parameters, and IUI outcomes of both groups were compared. Results Our study included a total of 639 IUI cycles, 334 were in the dual trigger group and 305 in the single trigger group. The clinical pregnancy rates were significantly higher in the dual trigger group than in the single trigger group (P

Beginning in October 2020 and ending in April 2021, researchers from Al-Nahrain University's High Institute for Infertility Diagnosis and Assisted Reproductive Technologies compared the success rates of two different methods of diagnosing and treating infertility. The major purpose of the research was to assess the impact of a combined trigger (follicle-stimulating hormone [FSH] and human chorionic gonadotropin [hCG]) on endometrial receptivity (endometrial thickness, endometrial pattern, sub-endometrial blood flow). A total of 100 females took part in the study. All patients gave their informed written consent, and the study was approved by the Al-Nahrain University Ethics Committee. Procedure Time To confirm ovulation, measure and analyze the endometrial pattern, and examine the sub-endometrial blood flow, a vaginal ultrasound was done 36 to 48 hours following trigger ovulation. All four hormones (FSH, LH, Progesterone, and E2) were tested in the blood at the same time to determine whether a couple was fertile, a complete medical history, and physical examination whereas performed on each member of the pair. An ultrasound vaginal probe was used to do the transvaginal examination. Patients were placed in the dorsal lithotomy position with an empty bladder for early follicular US (CD 2-3) to assess the number of antral follicles, measure endometrial thickness, and rule out ovarian cysts or other pathology. A second ultrasound was performed during the middle of the cycle (CD9-14) to determine whether a mature follicle had been found. A multiplanar image of the uterus was acquired after an ultrasound scan was swept across the mid-sagittal plane. Endometrial thickness in the median longitudinal plane of the uterus was calculated as the largest distance from one basal endometrial interface via the endometrial canal to the opposite endometrial-myometrial interface of the anterior-posterior uterine wall. A statistically significant difference was found between Group A's average E2 concentration of 69.62 pg/mL and Groups B and C's concentrations of 53.32 and 36.65 pg/mL. (P 0.001). In group C, there was a statistically significant difference in E2 levels on the day of the trigger and the day of the IUI (P = 0.036). On the day of IUI compared to the day of trigger, no statistically significant differences were seen between the study groups for any of the other hormonal indicators (P > 0.05). There were no significant differences (P > 0.05) in any of the baseline clinical measures between the research groups. All clinical indicators were comparable across groups (P > 0.05). There were no statistically significant differences (P > 0.05) between the research groups on any other clinical indicators. When comparing groups, A, B, and C on the decline in RI between the trigger and IUI days, group A significantly outperformed the others (P = 0.003). There was no statistically significant difference (P > 0.05) in any of the other clinical parameters between the IUI and trigger groups on the day of IUI.

Background: This study compared outcomes of the standard 6000 IU human chorionic gonadotropin (hCG) triggerwith a dual trigger comprised of 6000 IU hCG and 1 mg leuprolide acetate for final oocyte maturation in an intracytoplasmic sperm injection (ICSI) cycle. By convention, ICSI was performed in most cases at the clinic.Materials and Methods: In this retrospective study, a total of 50 women were included in each arm. Participantswere matched for age, indication and number of prior assisted reproduction technology (ART) cycles. Women at riskfor ovarian hyperstimulation syndrome (OHSS) were excluded. A flexible gonadotropin releasing hormone (GnRH)antagonist protocol was used and final oocyte maturation was triggered when two leading follicles were >17 mm.Distribution of variables was evaluated visually with histograms. Continuous variables were defined by mean (standarddeviation) or median (25th-75th percentile) depending on distribution characteristics. Categorical variables weredefined by numbers and percentages. Continuous variables were compared between the groups with the t test orMann-Whitney U test as appropriate. Categorical variables were compared by the chi-square test and its derivativesas appropriate. A two-sided P

The major limitations associated with gonadotropin-releasing hormone agonist (GnRHa) triggering are inferior clinical outcomes in fresh embryo transfer cycles caused by luteal phase insufficiency following the GnRHa triggering. We included 153 high-risk patients in this study. In group I, the patients received gonadotropin-releasing hormone agonist (GnRHa) trigger + 1,500 IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day; in group II, the patients had a dual trigger (GnRHa + 1,500 IU hCG); and in group III (control), 10,000 IU hCG trigger was prescribed for the final oocyte maturation. The levels of LH, estradiol, and progesterone were evaluated in serum on the stimulation starting day, day 6 of stimulation, on the day of the trigger administration, OPU day, days 3 and 5 post-OPU, and day 14 post-ET, as well as in follicular fluid. Progesterone concentration was significantly lower in group I on OPU+5 compared to the hCG group (I vs. III, р = 0.0065). Progesterone levels were significantly lower in group II in serum on OPU+5 compared to groups I and III (I vs. II, р = 0.0068; II vs. III, р = 1.76 × 108). The progesterone levels were significantly higher in follicular fluid in group III compared to the study groups (I vs. III, р = 0.002; II vs. III, p = 0.009). However, no significant differences in clinical outcomes were found between the groups. Then, we divided all women into pregnant and non-pregnant groups and found that estradiol (p = 0.00009) and progesterone (p = 0.000036) on the day of the pregnancy test were significantly higher in the pregnant women group. Also, progesterone on OPU day was significantly higher in the non-pregnant group (p = 0.033). Two cases of moderate ovarian hyperstimulation syndrome (OHSS) late-onset occurred in group I (3.5%, 2/56), no case of moderate/severe OHSS late-onset in group II, and three cases of moderate late-onset in group III (5.7%, 3/53). The low-dose hCG supplementation improves the luteal phase insufficiency after GnRHa triggering, which is confirmed by the comparable pregnancy rates in fresh transfer cycles between the groups. However, low-dose hCG carries a similar risk of OHSS as the full dose of hCG in high-responder patients.

Abstract Background Traditionally, final follicular maturation is triggered by a single bolus of human chorionic gonadotropin (hCG). This acts as a surrogate to the naturally occurring luteinizing hormone (LH) surge to induce luteinization of the granulosa cells, resumption of meiosis and final oocyte maturation. More recently, a bolus of gonadotropin-releasing hormone (GnRH) agonist in combination with hCG (dual trigger) has been suggested as an alternative regimen to achieve final follicular maturation. Methods This study was a systematic review and meta-analysis of randomized trials evaluating the effect of dual trigger versus hCG trigger for follicular maturation on pregnancy outcomes in women undergoing in vitro fertilization (IVF). The primary outcome was the live birth rate (LBR) per started cycle. Results A total of 1048 participants were included in the analysis, with 519 in the dual trigger group and 529 in the hCG trigger group. Dual trigger treatment was associated with a significantly higher LBR per started cycle compared with the hCG trigger treatment (risk ratio (RR) = 1.37 [1.07, 1.76], I2 = 0%, moderate evidence). There was a trend towards an increase in both ongoing pregnancy rate (RR = 1.34 [0.96, 1.89], I2 = 0%, low evidence) and implantation rate (RR = 1.31 [0.90, 1.91], I2 = 76%, low evidence) with dual trigger treatment compared with hCG trigger treatment. Dual trigger treatment was associated with a significant increase in clinical pregnancy rate (RR = 1.29 [1.10, 1.52], I2 = 13%, low evidence), number of oocytes collected (mean difference (MD) = 1.52 [0.59, 2.46), I2 = 53%, low evidence), number of mature oocytes collected (MD = 1.01 [0.43, 1.58], I2 = 18%, low evidence), number of fertilized oocytes (MD = 0.73 [0.16, 1.30], I2 = 7%, low evidence) and significantly more usable embryos (MD = 0.90 [0.42, 1.38], I2 = 0%, low evidence). Conclusion Dual trigger treatment with GnRH agonist and HCG is associated with an increased live birth rate compared with conventional hCG trigger. Trial registration CRD42020204452 .

IntroductionThe choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate.Methods and AnalysisWe propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: recombinant hCG (6500 IU) will be injected only 36 hours before OPU for final oocyte maturation (hCG-only trigger); co-administration of GnRH-a and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (Dual trigger). The primary outcome is metaphase-II (MII) oocytes rate. Secondary outcomes are number of oocytes retrieved, fertilization rate, top-quality embryos rate, blastula formation rate, embryo implantation rate, clinical pregnancy rate, miscarriage rate, live birth rate, cumulative pregnancy/live birth rates, and ovarian hyperstimulation syndrome (OHSS) rate.Ethics and DisseminationThe reproductive ethics committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine certified this study (Identifier: SDUTCM/2021.7.26) as ethical. All individuals will sign written informed consent. All data and biological samples will be protected according to law. The results of this study will be disseminated in a peer-reviewed scientific journal.Clinical Trial Registration[chictr.gov.cn], identifier [ChiCTR2100049292].

Abstract Purpose To determine the optimal maturation method to increase the yield of mature oocytes, especially for cancer patients with fewer chances of fertility preservation (FP) before gonadotoxic therapy. Methods A total of 373 cycles in 293 patients undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin‐releasing hormone (GnRH) antagonist protocol were enrolled. The control group (n = 225) received 250 µg of recombinant human chorionic gonadotropin (rhCG) while the study group (n = 148) received 250 µg of rhCG and 0.2 mg of triptorelin for triggering. Subgroup analyses were performed for stimulation cycles with diminished ovarian reserve (DOR; anti‐Müllerian hormone (AMH) levels

Study QuestionDoes dual trigger in freeze-all in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles improve the cumulative live-birth outcome compared with human chorionic gonadotropin (hCG) trigger?Summary AnswerDual trigger for final follicular maturation improves the cumulative pregnancy and live-birth rates compared with hCG trigger in freeze-all IVF/ICSI cycles.What Is Known AlreadyDual trigger could increase the numbers of oocytes and mature oocytes and improve pregnancy rates.Study Design, Size, DurationThis retrospective cohort analysis included data from 4438 freeze-all IVF/ICSI cycles between January 2012 and December 2017.Participants/Materials, Setting, MethodsWomen aged 20−49 years who underwent ovarian stimulation and oocyte retrieval for autologous IVF/ICSI with a freeze-all policy in our centre were enrolled. Data on number of oocytes retrieved, number of mature oocytes, clinical pregnancy rate, live-birth rate, cumulative pregnancy rate, and cumulative live-birth rate (CLBR) were assessed and compared between patients who underwent a dual trigger and hCG trigger. Multivariate logistic regression was performed to identify and adjust for factors known to independently affect the CLBR.Main Results and the Role of ChanceA total of 4438 IVF/ICSI cycles were analyzed, including 1445 cycles with single hCG trigger and 2993 cycles with dual trigger. The cumulative biochemical pregnancy rate (60.8% vs. 68.1%, P

“Dual triggering” for final oocyte maturation using a combination of a gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) can improve clinical outcomes in high responders during in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) GnRH-antagonist cycles. However, whether this dual trigger is also beneficial to normal responders is not known. We retrospectively analyzed the data generated from 469 normal responders from 1 January to 31 December 2017. The final oocyte maturation was undertaken with a dual trigger with a GnRHa combined with hCG (n = 270) or hCG alone (n = 199). Patients were followed up for 3 years. The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen–thawed embryos) among both groups. Women in the dual-trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear (2PN) embryos (8.37 vs. 7.67) and a higher number of embryos available (4.45 vs. 4.03). However, the cumulative live-birth rate and the all-inclusive success rate for assisted reproductive technology was similar between the two groups (54.07 vs. 59.30%). We showed that a dual trigger was not superior to a hCG-alone trigger for normal responders in GnRH-antagonist cycles in terms of the cumulative live-birth rate.

Abstract Background Diminished ovarian reserve (DOR) remains one of the greatest obstacles affecting the chance of a successful live birth after fertility treatment. The present study was set to investigate whether using a “dual trigger” consisted of human chorionic gonadotropin (hCG) plus gonadotropin releasing hormone agonist (GnRH-a) for final oocyte maturation could improve the IVF cycle outcomes for patients with diminished ovarian reserve. Methods A total of 427 completed GnRH-antagonist downregulated IVF cycles with fresh embryo transfer (ET) were included in this retrospective analysis. DOR was defined as antral follicle count ≤5 and serum anti-Müllerian hormone level ≤ 1.1 ng/mL. The control group (n = 130) used a 6500 IU of recombinant hCG for trigger, and the study group (n = 297) used 0.2 mg of triptorelin plus 6500 IU of recombinant hCG for trigger. Results The dual-trigger group had significantly higher oocyte fertilization rate (73.1% vs. 58.6%), clinical pregnancy rate (33.0% vs. 20.7%) and live birth rate (26.9% vs. 14.5%) when compared to the hCG trigger group. In addition, the abortion rate (17.4% vs. 37.0%) and embryo transfer cancellation rate (6.1% vs. 15.4%) were both significantly lower in the dual trigger group. The primary outcome measure was the live birth rate per oocyte retrieval cycle. Secondary outcome measures were embryo transfer cancellation rate, clinical pregnancy rate, implantation rate, chemical pregnancy rate and abortion rate per oocyte retrieval cycle. Conclusions Dual triggering the final oocyte maturation with GnRH-a and standard dose of hCG can significantly improve the live birth rate, clinical pregnancy rate, and fertilization rate in women with diminished ovarian reserve undergoing GnRH antagonist down-regulated IVF-ICSI cycles.

Abstract Background Ovarian hyperstimulation syndrome remains a serious complication during in vitro fertilization cycles if high dose human chorionic gonadotropin (hCG) is used to trigger ovulation in high responder patients. Though much of this risk is mitigated with trigger using gonadotropin releasing-hormone (GnRH) agonist alone, it may result in lower birth rates. GnRH-agonist trigger and adjuvant low dose hCG has been proposed to improve birth rates, but timing of this hCG support to corpus luteum function has never been fully described. In this randomized, prospective trial, we explore differences in live birth rates and incidence of ovarian hyperstimulation syndrome (OHSS) in high-responder patients undergoing in vitro fertilization (IVF) receiving low dose hCG at the time of GnRH-agonist (dual trigger) or hCG adjuvant at the time of oocyte retrieval. Does the timing of hCG support make a difference? Results Thirty-four subjects high-responder patients were randomized to receive low-dose hCG at the time of GnRH-agonist trigger (Group 1) and 37 received low-dose hCG at the time of oocyte retrieval (Group 2). There were no differences in the baseline characteristics and outcome of ovarian stimulation between the two groups. There were no differences in the live birth rates between Group 1 and Group 2 by intention-to-treat (14/34, 41.2% versus 21/37, 56.8%, p = 0.19) or per-protocol (14/26, 53.8% versus 19/31, 61.3%, p = 0.57) analyses. There was a slightly higher incidence of OHSS in Group 2 compared to Group 1 although the difference was not statistically significant (3/31, 9.7% versus 1/26, 3.8%). All the cases of OHSS in Group 2 were moderate while the one case of OHSS in Group 1 was mild. Conclusions For high responder patients receiving GnRH-agonist trigger, low dose hCG supplementation allowed high pregnancy rates after fresh embryo transfer, regardless of whether it was given at the time of trigger or at oocyte retrieval. Dual trigger may be preferable to reduce the risk of OHSS.

Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of controlled ovarian stimulation. The use of gonadotropin releasing hormone (GnRH) agonist for the trigger of oocyte maturation is effective in the prevention of OHSS although it may result in a lower pregnancy rate. The use of adjuvant low dose human chorionic gonadotropin (hCG) at the time of trigger or at the time of oocyte retrieval may improve pregnancy rates. The goal of this dual trigger study is to evaluate the safety and efficacy of the use of low dose hCG administered at the time of GnRH agonist trigger or 35 h later as well as the potential impact on pregnancy rates. The population will consist of 82 women undergoing IVF treatment who are at risk of developing OHSS. This study will be a single center prospective randomized double-blind placebo controlled trial. The randomization schedule will be administered by the Investigational Drug Services of the University. After controlled ovarian stimulation, induction of oocyte maturation will be achieved using a GnRH agonist and patients will be randomized to receive either low dose hCG 1000 IU at the time of trigger and placebo at oocyte retrieval (Study group) or placebo at the time of trigger and hCG 1500 IU at the time of oocyte retrieval (Control group). The main outcomes will be live birth rates and incidence of OHSS. Two ancillary studies will include a quality of life survey and serum assessment of independent corpus luteum function.

Background: Prior studies have shown that patients with a >10% estradiol (E2) rise after trigger had more oocytes retrieved than plateauing or decreasing E2 responders. However, multiple follicles develop at different stages of maturation during controlled ovarian stimulation (COS) and may exhibit different responses to trigger. The association between the magnitude of E2 increase and oocyte retrieval outcomes is still unclear.Methods: This was a retrospective cohort study of 2,898 women undergoing their first COS cycles with normal response from January 2014 to December 2017 at a tertiary-care academic medical center. Patients were categorized into five groups according to the percentage increase in E2 levels before and after dual trigger: 0.05).Conclusions: A higher E2 rise after dual trigger is independently associated with a lower oocyte and mature oocyte yield in normal responders. Further studies are needed to explore the efficacy of individualized time interval from trigger to oocyte retrieval based on the magnitude of E2 increase after trigger.

BACKGROUND: Mature oocytes are prerequisite for achieving the process of in vitro fertilization. Human chorionic gonadotropin (hCG) is the standard trigger used for stimulating ovulation but is associated with ovarian hyperstimulation syndrome (OHSS). Gonadotropin-releasing hormone agonist trigger achieves oocyte maturation and lowers the incidence of OHSS, but it has limitations of higher pregnancy loss rate and miscarriage rates. Coadministration of both hormones is found to improve the pregnancy rates and the number of mature oocytes retrieved. We aimed to assess if the dual trigger is better than the conventional hCG in triggering oocyte maturation. METHODOLOGY: The study included 76 female patients aged 24–43 years who were randomly divided into two groups with 38 patients in each arm. The study included patients with antimullerian hormone (AMH) 4 ng/ml and AFC/ovary >12 to avoid OHSS risk with hCG trigger. RESULTS: The study showed statistically insignificant differences between dual group versus hCG group in terms of the number of oocytes retrieved (10.0 ± 5.6 vs. 8.7 ± 5.0; P = 0.2816), the number of mature oocytes recovered (8.4 ± 5.0 vs. 7.2 ± 4.0; P = 0.2588), fertilization rate (5.9 ± 4.2 vs. 5.6 ± 3.3; P = 0.7390), and the number of usable embryos on day 3 (4.0 ± 3.0 vs. 4.0 ± 2.4; P = 0.8991). CONCLUSION: The dual trigger is equivalent to hCG in triggering oocyte maturation.

Empty follicle syndrome (EFS) is an uncommon, but the frustrating complication of assisted reproductive technology with failure to obtain oocytes after an adequate ovarian response to stimulation. Most of the reported cases of EFS are drug-related problems which are actually avoidable and do not represent any potential pathology and that the risk of genuine EFS (GEFS) is much smaller than was once thought. Our case is thefirst report of a pregnancy obtained after management of GEFS with dual trigger in a gonadotropin-releasing hormone (GnRH) antagonist cycle. In this report, we present a patient who underwent two oocyte retrievals, in which no oocytes were obtained. In the third in-vitrofertilization cycle, a dual trigger with the combination of GnRH agonist and human chorionic gonadotropin yielded 11 oocytes, which led to the transfer of 2 blastocysts resulting in a live birth. Changing the treatment protocol with dual trigger brought about a successful outcome.