hCG For Final Oocyte Maturation Research Articles

The efficacy of GnRH agonist trigger followed by hCG add-back in normal responders for fresh embryo transfer: a case-control analysis from Vietnam

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.

O-295 Dual trigger does not improve reproductive outcomes in advanced maternal age women

Abstract Study question Could dual trigger increase oocyte yield and maturation rate in women of advanced maternal age (≥ 40) undergoing IVF? Summary answer Dual trigger does not result in higher oocyte yield or maturation rates compared to hCG monotrigger What is known already Advanced maternal age is related to poor ovarian response (POR) and remains a major therapeutic challenge in routine IVF practice, because of the association with low live birth rates and high cancellation rates. hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome (by improving oocyte quantity and quality) in normal responders, while evidence in poor responders remains controversial. Study design, size, duration This is a retrospective cohort study including patients attending a private IVF clinic from 1st January 2018 until 1st June 2022. Participants/materials, setting, methods All women who underwent IVF/ICSI in antagonist protocol in our center were included. Patients may have undergone triggering of the final oocyte maturation either with 250mcg of rhCG or 0.2 mg of GnRH agonist. Mature oocytes were inseminated using ICSI. Main results and the role of chance In total, 2242 patients were included, 454 (20.2%) in the rhCG group and 1788 (79.8%) in the dual trigger group. There was no significant difference in female age [41.3 (1.12) vs 41.3 (1.19), p value 0.94]. Total stimulation units and duration were also comparable between groups. The number of oocytes and MII oocytes did not differ significantly between rhCG and dual trigger group [5.8 (4.1) vs 6.3 (4.7) and 4.7 (3.3) vs 4.9 (3.4), p = 0.15 and 0.49, respectively]. Maturation rates were similar 81.7% (22.4) and 79.8% (23.5), p = 0.15, as well as fertilization rates (defined as the number of oocytes fertilized divided by the total number of cumulus-oocyte complexes recruited) [57% (29.7) vs 58.8% (29.4), p value=0.2]. Embryo utilization rates (defined as the total number of embryos transferred and cryopreserved divided by the number of oocytes fertilized) were comparable between the two arms: 69.7% (34.2) vs 70% (33.9), p value =0.22. Multivariate Poisson regression analysis adjusting for relevant confounders (AMH, total stimulation units) showed that the type of triggering strategy (dual trigger vs rhCG) was not associated with either the number of MII oocytes (coefficient 0.2, p value=0.24) or maturation rates (coefficient -1.8, p value 0.12). Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Wider implications of the findings To the best of our knowledge, this is the largest study evaluating dual trigger strategy in advanced maternal age women. Our data demonstrate that dual trigger cannot improve the outcome of low prognosis women and should not be used as a panacea for all IVF patients. Trial registration number NA

P-676 Comparison of hCG triggering versus hCG in combination with a GnRH agonist: a prospective randomized controlled trial

Abstract Study question Does co-administration of GnRH agonist and Human chorionic gonadotropin(dual trigger) in PGT cycles improve the number of usable blastocysts per patient compared to hCG alone? Summary answer Using the dual trigger has no effect on the number of usable blastocysts undergoing the GnRH-ant protocol for PGT compared to triggering with hCG alone. What is known already HCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates. Study design, size, duration A prospective, randomized, open-label controlled clinical trial (ChiCTR-ICR-2000031342), enrolled patients attending our university affiliated Infertility and IVF center (the Reproductive and Genetic Hospital of CITIC-Xiangya, China) between August 2020 and June 2021. This sample size achieves with a power of 80%, at a significance level(α) of 0.05. A sample size of 160 patients, 80 randomized to each group, was chosen to allow for those 10% dropped out. Participants/materials, setting, methods The inclusion criteria for participating were: women age 20–35years, AMH≥1.2ng/ml and /or AFC ≥5, Couples with PGT-SR preimplantation genetic testing for chromosomal structural rearrangements (patients with abnormal chromosomal structure only in male or female), undergoing one of their first PGT cycle attempts. Patients fulfilled the criteria on the trigger day were randomly assigned to receive hCG or the dual trigger for final oocyte maturation. The primary outcome was the number of usable blastocysts per patient. Main results and the role of chance 160 patients were included in the study. The age (29.1 years versus 29.4 years), BMI (22.1 kg/m2 versus 21.9 kg/m2) and the AMH (5.3 ng/ml versus 5.3 ng/ml) were comparable between the two groups. Based on PP analysis, there were no statistical difference in the number of eggs retrieved (17.1 versus 15.9), the MII oocytes (13.3 versus 12.5), the number of usable blastocysts per patient (5.0 versus 4.6) and top-quality blastocysts per patient (3.4 versus 3.2) between the two groups. Limitations, reasons for caution None Wider implications of the findings The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely. Trial registration number ChiCTR-ICR-2000031342

P-707 RCT of Dual-Triger (GnRH-Agonist & hCG) versus hCG-Trigger alone for Normal Responders in IVF-ICSI Cycles

Abstract Study question Does Dual Triger with GnRH-Agonist with hCG in IVF-ICSI cycles in normal responders improve oocyte quality and pregnancy outcome compared to Triger with hCG alone? Summary answer Yes, Dual Triger with GnRH-Agonist with hCG in IVF-ICSI cycles in normal responders improve oocyte quality and pregnancy outcome compared to Triger with hCG alone. What is known already Dual-Triggering for final oocyte maturation combining GnRH-Agonist with hCG can improve clinical outcomes in high responders during IVF–ICSI cycles. . However, there is insufficient evidence regarding the impact of a Dual-Trigger on the reproductive outcome in normal responders. Some studies reported a significantly improved ongoing pregnancy rate and live-birth rate in fresh-embryo-transfer cycles for a dual-trigger group compared with the hCG-trigger group in normal responders . By contrast, several studies have demonstrated that dual trigger of oocyte maturation was not associated with a change in the live-birth rate in FET cycles for normal ovarian responders . Study design, size, duration RCT of 214 patients of IVF-ICSI Cycles between 2016 - 2020 were included in the study .The inclusion criteria in the study were: Age < 40 years, AMH >1 ng/ml, AFC : 07-20 and FSH <10 IU/l. The exclusion criteria were Poor-Ovarian-Reserve (Low-AMH <1 ng/ml) and patients at high-risk of developing OHSS (High-AMH >07 or AFC >20). Recombinant-FSH dose was adjusted according to E2 levels and follicular monitoring along with a flexible GnRH-Antagonist-Protocol. Participants/materials, setting, methods RCT of 214 patients of IVF-ICSI Cycles between 2016-2020 were included in the study and were divided in two groups. Administration of the GnRH-antagonist was initiated based on a flexible protocol and final oocyte-maturation was triggered either by hCG alone (contol group) or by combining GnRH-Agonist with hCG (2000 IU) (study group).Data on number of oocytes retrieved, number of mature (MII) oocytes, embryos and blastocysts and clinical pregnancy rate were assessed and compared. Main results and the role of chance The Implantation-Rate (16% versus 33%) and the Clinical-Pregnancy-Rate per patient (18% versus 38%) were significantly higher in the Dual Triger of GnRH-Agonist with hCG study group, compaired to contol group of Triger with hCG alone. Dual-trigger approach appears superior to an hCG trigger alone with regard to the number of top-quality embryos produced. Final oocyte maturation is the key step in ART cycles and Human-Chorionic-Gonadotropin (hCG) alone has been used for final oocyte maturation for many years and has been demonstrated to promote an increased pregnancy rate. However, the administration of hCG for final oocyte maturation results in supraphysiologic steroid levels in the luteal phase due to its long half-life and is consequently associated with an increased risk of OHSS. The hCG trigger may have negative impacts on endometrial receptivity and embryo quality . The GnRH-Agonist trigger benefits the induction of both an FSH and an LH surge and the possibility of retrieving more mature MII oocytes than is expected with an hCG trigger . Drawback of a GnRHa trigger was LH depletion and the withdrawal of LH support of the corpus luteum , however this problem has been overcome with intensive luteal phase support (LPS) and luteal-phase hCG administration . Limitations, reasons for caution The present study did not include a third arm of patients who were triggered with GnRH-Agonist alone. If we had added the third arm, we would have been able to test whether it was the administration of GnRH-Agonist or the co-administration of GnRH-Agonist and hCG that improved the outcome . Wider implications of the findings We conclude that using the dual trigger for final follicular maturation in normal responder increases the number of good quality mature MII oocytes and top-quality blastocysts compared to triggering with hCG alone. The increase in the number of good quality blastocysts improved the outcome of the IVF-CSI cycle in normal responders. Trial registration number not applicable

Evolution of serum progesterone levels in the very early luteal phase of stimulated IVF/ICSI cycles post hCG trigger: a proof of concept study.

Studies have suggested that controlled ovarian hyperstimulation adversely affects endometrial receptivity due to advanced endometrial maturation. This adverse effect is mainly attributed to supraphysiological levels of both estrogen and progesterone identified in stimulated cycles. There is a paucity of published data investigating the very early luteal steroid profile following hCG trigger. This prospective, observational study was undertaken to determine the increase in serum progesterone levels after human chorionic gonadotrophin (hCG) trigger in stimulated IVF/ICSI cycles. This proof-of-concept study included 11 patients requiring ovarian stimulation for IVF/ICSI and who planned to avail of pre-implantation genetic screening with embryo vitrification of their biopsied embryos at blastocyst stage. For each study participant, five additional blood samples were drawn at the following specific times in the stimulation cycle, on the morning (10.00-12.00) of the assigned day to induce final oocyte maturation with hCG trigger, immediately prior to administration of hCG for final oocyte maturation, 1h, 2h, and 36h post hCG trigger. A prediction model, the Gompertz curve, was used to determine serum progesterone levels at intervals between the 2h post hCG trigger sample and the day of oocyte retrieval. Statistically significant increases in serum progesterone levels were identified following hCG administration as early as 1h following trigger (P4 0.57ng/ml, p < 0.05), 2h following trigger (P4 0.88ng/ml, p < 0.001) and on the day of oocyte retrieval (P4 9.68ng/ml, p < 0.001). According to our prediction model, the Gompertz curve, the projected serum progesterone level at 4h post trigger would have achieved a level of 1.45ng/ml, 8h post trigger of 3.04ng/ml, and 12h post trigger of 4.8ng/ml. The very early and significant increases in serum progesterone following hCG trigger are clearly demonstrated in this study. The endometrium is undoubtedly exposed to rapidly increasing serum progesterone levels post hCG trigger that would not be identified until much later in natural menstrual cycles. This study is registered with clinicaltrials.gov under the identifier NCT04417569.

DUAL TRIGGER IMPACT ON REPRODUCTIVE OUTCOMES OF GNRH ANTAGONIST CYCLES FOR IVF: A SYSTEMATIC REVIEW AND META-ANALYSIS

Human chorionic gonadotrophin (hCG) represents the gold standard trigger of final oocyte maturation in controlled ovarian stimulation cycles. An alternative trigger with gonadotrophin-releasing hormone agonist (GnRH-a) has been demonstrated to be effective in GnRH antagonist (GnRH-ant) cycles, inducing a more physiologic LH and FSH surge, but enhancing lutheal insufficiency and poorer pregnancy outcomes. Some authors suggest that a dual trigger using GnRH-a combined with hCG could be the best choice, although it remains controversial. The aim of this meta-analysis is to assess the efficacy of dual trigger compared to hCG trigger for final oocyte maturation in GnRH-ant cycles, and its impact on IVF reproductive outcomes. A systematic review and meta-analysis of randomized control trials (RCT) and observational studies comparing clinical outcomes of patients underwent IVF cycles after dual trigger with hCG plus GnRH-a versus hCG alone were performed. PubMed, Embase, The Cochrane Library, and Web of Science databases were searched for relevant studies. The main outcome measure was clinical pregnancy rate. Secondary outcomes included number of retrieved, mature, and fertilized oocytes, as well as top-quality embryos. Sub-analysis considering normo-responder or poor-responder patients separately was conducted. 10 RCTs and 16 observational studies were included. Dual trigger was associated to significantly higher clinical pregnancy rates per cycle than hCG trigger (normal responders [NR] odds ratio [OR] 1.84, 95% confidence interval [95CI] 1.36-2.48; poor responders [PR] OR 2.62, 95CI 1.52-4.53). Also, the dual trigger group presented higher number of retrieved oocytes (NR MD 1.32, 95CI 0.89-1.76; PR MD 0.38, 95 IC 0.16-0.60), mature oocytes (NR difference in means [MD] 1.32, 95CI 0.93-1.71; patients with prior high rate of immature oocytes MD 2.95, 95CI 2.16-3.73), fertilized oocytes (NR MD 1.13, 95CI 0.55-1.71; patients with prior high rate of immature oocytes MD 2.45, 95CI 1.42-3.49), and top-quality embryos (NR MD 0.7, 95CI 0.38-1.02; PR MD 0.7, 95CI 0.5-0.9; patients with prior high rate of immature oocytes MD 1.36, 95CI 0.05-2.67). Dual trigger with GnRH-a and hCG for final oocyte maturation seems to be superior to hCG in patients with normal and poor response to ovarian stimulation. Compared to hCG alone, dual trigger also improves fertilization rates and clinical pregnancy rates, although this outcomes need to be cautiously considered due to the moderate quality of the evidence.

GnRH agonist and hCG (dual trigger) versus hCG trigger for final follicular maturation: a double-blinded, randomized controlled study.

Does co-administration of GnRH agonist and Human chorionic gonadotropin (hCG; dual trigger) in IVF cycles improve the number of mature oocytes and pregnancy outcome compared to hCG alone? Using the dual trigger for final follicular maturation increases the number of oocytes, mature oocytes and number of blastocysts (total and top-quality) compared to triggering with hCG alone. hCG is used at the end of controlled ovarian hyperstimulation as a surrogate LH surge to induce final oocyte maturation. Recently, based on retrospective studies, the co-administration of GnRH agonist and hCG for final oocyte maturation (dual trigger) has been suggested to improve IVF outcome and pregnancy rates. A single center, randomized controlled, double-blinded clinical trial between May 2016 and June 2018 analyzed by intention to treat (ITT). One hundred and fifty-five normal responder patients were randomized either to receive hCG or dual trigger for final oocyte maturation. Data on patients age, BMI, AMH, number of oocytes retrieved, number of metaphase 2 (MII) oocytes, zygotes and blastocysts, clinical pregnancy rate and live birth rate were assessed and compared between the dual trigger group and the hCG group. We performed a planned interim analysis after the recruitment of 50% of the patients. Based on the totality of outcomes at the interim analysis we decided to discontinue further recruitment. One hundred and fifty-five patients were included in the study. The age (36 years versus 35.3 years P = NS), BMI (24 kg/m2 versus 23.7 kg/m2) and the AMH (20.1 pmol/l versus 22.4 pmol/l) were comparable between the two groups. Based on ITT analysis, the number of eggs retrieved (11.1 versus 13.4, P = 0.002), the MII oocytes (8.6 versus 10.3, P = 0.009), total number of blastocysts (2.9 versus 3.9, P = 0.01) and top-quality blastocysts transferred (44.7% versus 64.9%; P = 0.003) were significantly higher in the dual trigger group compared to the hCG group. The clinical pregnancy rate (24.3% versus 46.1%, OR 2.65 (1.43-1.93), P = 0.009) and the live birth rate per transfer (22% versus 36.2%, OR= 1.98 (1.05-3.75), P = 0.03) were significantly higher in the dual trigger group compared to the hCG group. None. The enhanced response observed with the dual trigger might lead to better IVF outcomes were it used more widely. The study was funded by TRIO Fertility. There are no conflicts of interest to declare. ClinicalTrials.gov identifier: NCT02703584. March 2016. May 2016.

Does ‘Dual Trigger’ Increase Oocyte Maturation Rate?

The aim of this study was to evaluate the oocyte maturation rate when GnRH-a and hCG (dual trigger) are co-administered, compared to the standard hCG trigger within the same patient. Included in the study were GnRH antagonist ICSI cycles performed in 137 patients who had a standard hCG trigger cycle and a dual trigger cycle between 1/1/2013 and 31/12/2017. The mean patient age (35.9 ± 5.6 and 35.2 ± 5.9; <0.001), FSH dose (4140 ± 2065 and 3585 ± 1858; <0.01), number of retrieved oocytes (10.3 ± 6.2 and 8.9 ± 6.1; 0.011) were higher in the dual trigger group compared to the hCG trigger group, oocyte maturation rate was identical. Maturation rate following dual trigger was significantly higher among 34 patients who had a maturation rate of <70% following hCG triggering and among 16 patients with a maturation rate <50% rate following hCG trigger (54% vs. 74%, p < .001 and 44% vs. 73%, p = .006; respectively). In conclusion, co-administration of GnRH agonist and hCG for final oocyte maturation substantially increased the oocyte maturation rate in patients with low oocyte maturation rate in their hCG triggered cycle, but not in an unselected population of patients.IMPACT STATEMENTWhat is already known on this subject? The co-administration of GnRH agonist and hCG for final oocyte maturation prior to oocyte retrieval may improve IVF outcome in patients with a high proportion of immature oocytes. The few studies on dual trigger in patients with a high proportion of immature oocytes or in normal responders have shown conflicting results.What do the results of this study add? We found that co-administration of GnRH agonist and hCG for final oocyte maturation substantially increased the oocyte maturation rate in patients with low oocyte maturation rate in their hCG triggered cycle, but not in an unselected population of patients.What are the implications of these findings for clinical practice and/or further research? The results of this study implicate that in selected population with low oocyte maturation rate, there is an advantage in using dual trigger. However, larger prospective trials are warranted to better assess oocyte response in dual trigger.

Dual triggering of final oocyte maturation in poor ovarian responders: a prospective randomized controlled trial

Women with POR (Bologna criteria) manifest a very low follicular response to controlled ovarian stimulation irrespective of the stimulation protocol utilized. Dual triggering of oocyte maturation was shown to improve follicle collection yield and oocyte maturation in women with predicted normal ovarian response. These benefits have been attributed to the GnRHa-induced FSH surge believed to promote oocyte nuclear maturation and cumulus expansion. The aim of the study is to show whether the co-administration of a GnRH agonist and hCG for final oocyte maturation improve oocyte collection and maturation rates in women with poor ovarian response (POR) compared with hCG alone. This is an ongoing prospective randomized controlled trial seeking to randomize 140 women with POR undergoing IVF/ICSI treatment into receiving a dual trigger for final oocyte maturation compared with conventional hCG, between May 2018 and December 2019. Women with POR (Bologna criteria) were randomized to receive either a combination of 0.3 mg Triptorelin subcutaneously (Decapeptyl; Ipsen Beaufour; Denmark) and 10,000 IU hCG subcutaneously (Choriomon; IPSA Pharmaceuticals; Switzerland) or 10,000 IU hCG alone. Primary outcomes were oocyte collection and maturation rates. Secondary outcomes were clinical and ongoing pregnancy rates. Chi Square analysis was utilized for categorical data and student t test for continuous variables. A p <0.05 was considered for statistical significance. Sixty-eight patients have been recruited to this point with a cycle cancelation of 7.35% (5/68). A total of 63 patients were randomly allocated to the dual trigger (n=28) and hCG alone (n=35) groups. Baseline demographic and stimulation characteristics were comparable between the two groups. The total number of oocytes (4 vs. 4.2; p=0.65), number of mature oocytes (3.1 vs. 3.2; p=0.81), and number of 2PN zygotes (2.6 vs. 2.2; p=0.32) were not significantly different between the dual trigger and hCG alone groups. The oocyte collection (62.5% vs. 64.6%; p=0.75) and oocyte maturation rates (77.5% vs. 76.2%; p=0.82) were also comparable. Per embryo transfer, the clinical pregnancy rate (15.2 vs. 12.6; p=0.96) and ongoing pregnancy rate (13.8 vs. 12.6; p=0.63) showed no statistical differences. There was no significant increase in oocyte collection or maturation rates following dual triggering of final oocyte maturation compared with hCG alone in women with POR. POR (Bologna criteria) represents a subgroup of women with a very poor pregnancy prognosis and also a very challenging fertility management. Although the preliminary findings of this trial do not seem to hold promises in favor of an improved outcome with dual triggering of oocyte maturation in this subgroup of women, conclusive evidence are expected only following completion of the recruitment period.

Pregnancy predictors in the fresh cycle using dual trigger protocol

Dual trigger protocol using a combination of GnRH agonist and hCG for final oocyte maturation has been shown to minimize ovarian hyperstimulation syndrome (OHSS) risk without compromising fresh embryo transfer outcomes. Therefore, we sought to determine if any cycle characteristics were associated with predictive of pregnancy outcomes in fresh cycles that utilized this protocol for in-vitro fertilization.

Dual trigger vs. HCG for final oocyte maturation. a prospective randomized controlled, double blinded study: preliminary results

Dual trigger vs. HCG for final oocyte maturation. a prospective randomized controlled, double blinded study: preliminary results

Outcomes Comparison of In-Vitro Fertilization (IVF) between GnRH Agonist Trigger and hCG for Final Oocyte Maturation

&lt;p&gt;&lt;strong&gt;Introduction:&lt;/strong&gt; For decades, human chorionic gonadotropin (hCG) has been used for final oocyte maturation. It is proven to have highest life birth rate, comparing to gonadotropin releasing hormone (GnRH) agonist, but unfortunately it can increases the risk of developing ovarian hyper stimulation syndrome (OHSS). There is an ongoing debate over the optimal agent that can trigger final oocyte maturation in antagonist protocol, leading to higher IVF success rate without increasing the risk of OHSS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective:&lt;/strong&gt; To compare IVF outcomes in patient using GnRH agonist trigger and hCG for final oocyte maturation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;A retrospective review of in vitro fertilization patient at Daya Medika Clinic and Yasmin Clinic.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Result: &lt;/strong&gt;76 women were analyzed consist of 38 women using GnRH agonist and 38 women using hCG. We found no significant differences on biochemical pregnancy rate (24.00% and 20.51%) between two group, but there were significant differences on fertilization rate (67.72% and 61.32%), cleavage rate (95.04% and 88.92%) and blastocyst rate (13.90% and 7.38%). There was one patient developed OHSS in hCG group&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;GnRH agonists can be considered for use as a trigger final oocyte maturation in the antagonist protocol because some IVF outcomes data showed that GnRH agonists triggering were better than hCG without increasing the risk of OHSS&lt;/p&gt;

Dual trigger for final oocyte maturation improves the oocyte retrieval rate of suboptimal responders to gonadotropin-releasing hormone agonist

To identify the risk factors for suboptimal response to GnRH agonist (GnRH-a) trigger and evaluate the effect of hCG on the outcome of patients with suboptimal response to GnRH-a. A retrospective data analysis. A tertiary-care academic medical center. A total of 8,092 women undergoing 8,970 IVF/intracytoplasmic sperm injection (ICSI) treatment cycles. All women underwent hMG + medroxyprogesterone acetate (MPA)/P treatment cycles during IVF/ICSI, which were triggered using a GnRH-a alone or in combination with hCG (1,000, 2,000, or 5,000 IU). Viable embryos were cryopreserved for later transfer. The rates of oocyte retrieval, mature oocytes, fertilization, and the number of oocytes retrieved, mature oocytes, and embryos frozen. In total, 2.71% (243/8,970) of patients exhibited a suboptimal response to GnRH-a. The suboptimal responders (LH ≤15 mIU/mL) had a significantly lower oocyte retrieval rate (48.16% vs. 68.26%), fewer mature oocytes (4.10 vs. 8.29), and fewer frozen embryos (2.32 vs. 3.54) than the appropriate responders. Basal LH levels served as the single most valuable marker for differentiating suboptimal responders with the areas under the receiver operating curve of 0.805. Administering dual trigger (GnRH-a and hCG 1,000, 2,000, 5,000 IU) significantly increased oocyte retrieval rates (60.04% vs. 48.16%; 68.13% vs. 48.16%; and 65.76% vs. 48.16%, respectively) in patients with a suboptimal response. Basal LH level was useful predictor of the suboptimal response to GnRH-a trigger. Administrating dual trigger including 1,000 IU hCG for final oocyte maturation could improve the oocytes retrieval rate of GnRH-a suboptimal responder.

Revisiting ovarian hyper stimulation syndrome: Towards OHSS free clinic.

A rapid development and application of assisted reproductive technologies (ARTs) and ovulation-induction drugs may lead to ovarian hyper stimulation syndrome (OHSS). Young age, low body mass index (BMI), polycystic ovarian syndrome (PCOS), previous OHSS, high follicle count, and elevated serum estradiol (E2) are the certain factors that predispose women to OHSS. Many strategies have been used to reduce or avoid OHSS. Use of human chorionic gonadotropin (hCG) increases ovarian vascular permeability and is responsible for activating the vascular endothelial growth factors (VEGF) pathway and thus the entire cascade, leading to symptomatic OHSS. Gonadotropin-releasing hormone (GnRH) agonists are used as a replacement for hCG for final oocyte maturation in antagonist cycles. Reducing or eliminating the use of hCG and use of GnRH agonist triggered GnRH antagonist cycles and cryopreservation of oocytes or embryos is the most promising approach in making OHSS free clinic a reality.

Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low proportion of mature oocytes

Objective: Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation – 40 and 34 h prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved.Patients and methods: We compared the stimulation characteristics of 12 IVF cycles, which include the cycle with the double trigger to the same patients' previous IVF attempt, triggered with hCG-only.Results: Patients who received the double trigger (study group) had a significantly higher number of mature oocytes – MII (6.5 versus 3.6 p < 0.008), number of embryos transferred (2.4 versus 1.1 p < 0.03), a significantly higher proportions of MII oocytes per number of oocytes retrieved (69.7% versus 47.1% p < 0.03) and a higher number of top quality embryos (3.1 versus 1 p < 0.02), as compared to their previous control cycles (hCG-only trigger). Six pregnancies were recorded in the study group and none in the control group.Conclusions: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) improves IVF outcome in patients with high proportion of immature oocytes.

Co-administration of GnRH-agonist and hCG, for final oocyte maturation (double trigger), in patients with low rate of mature oocytes

Human chorionic gonadotropin (hCG) is usually used at the end of controlled ovarian hyperstimulation (COH), as a surrogate LH surge, to induce final oocyte maturation and resumption of meiosis. Recently, the co-administration of GnRH agonist and hCG for final oocyte maturation - 40 and 34 hours prior to OPU, respectively (double trigger) was suggested to improve IVF outcome in patient with genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger might improve the proportions of metaphase-II (MII) oocytes in patients with low proportion of mature oocytes (<66%) per number oocytes retrieved.

Co-administration of GnRH-agonist and hCG for final oocyte maturation (double trigger) in patients with low number of oocytes retrieved per number of preovulatory follicles--a preliminary report.

BackgroundRecently, the co-administration of GnRH agonist and hCG for final oocyte maturation- 40 and 34 hours prior to OPU, respectively (double trigger) was suggested as the treatment of genuine empty follicle syndrome. In the present study, we aim to evaluate whether the double trigger improves the number of oocytes retrieved in patients with low (<50%) number of oocytes retrieved per number of preovulatory follicles.MethodsIn this proof of concept cohort historical study, we compared the stimulation characteristics of 8 IVF cycles, which include the double trigger to the patients’ previous IVF attempt, triggered with hCG-only.ResultsPatients who received the double trigger (study group) had a significantly higher number of oocytes retrieved, number of 2PN, number of embryos transferred and significantly higher proportions of the number of oocytes retrieved to the number of follicles >10 mm and >14 mm in diameter on day of hCG administration, with a tendency toward a higher number of TQE, as compared to their previous cycles (hCG-only trigger). Three ongoing clinical pregnancies were recorded in the study group and none in the hCG-only trigger group.ConclusionsCo-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (double trigger), is suggested as a valuable new tool in the armamentarium for treating patients with low/poor oocytes yield despite an apparently normal follicular development and E2 levels and in the presence of optimal hCG levels on the day of OPU.

Effect of low dose hCG support on GnRH-agonist triggered IVF/ICSI cycles

To assess the reproductive outcome (pregnancy rate and OHSS rate) in high responders after triggering final oocyte maturation with a combination of GnRH-agonist and hCG (500 to 1,000 IU) as compared with those triggered with GnRH-agonist alone and those treated with long protocol. Controlled interventional study. In high responders, three groups of ovulation induction cycles were allocated as below: (30 cycles for each group) 1. GnRH-antagonist protocol, triggered with a combination of GnRH-agonist and hCG (500 to 1,000 IU, depending on the peak Estradiol level) for final oocyte maturation 2. GnRH-antagonist protocol, triggered with GnRH-agonist alone for final oocyte maturation. 3. Long protocol (triggered with 10,000 IU hCG for final oocyte maturation) The clinical pregnancy rate and the rate of ovarian hyperstimulation syndrome (OHSS) were compared among the three groups. No significant differences were seen regarding positive hCG/ET rate, clinical pregnancy rate, and rate of early pregnancy loss between group 1 (GnRH-agonist and hCG dual trigger) and group 3 (long protocol). A tendency of lower pregnancy rate was noted in group 2 (GnRH-agonist trigger alone). There was no OHSS in group 1 (GnRH-agonist and hCG dual trigger) and group 2 (GnRH-agonist trigger alone). For higher responders, dual trigger with a combination of GnRH-agonist and hCG is safe considering the complication of OHSS, and as effective as conventional long protocol regarding the pregnancy outcome.

New algorithm for OHSS prevention

Ovarian hyperstimulation syndrome (OHSS) still remains a life-threatening complication of in vitro fertilization treatment (IVF), keeping patients and especially those, who previously experienced OHSS, from attempting infertility treatment and childbearing. The recent implementation of four new modalities: the GnRH antagonist protocol, GnRH agonist (GnRHa) triggering of ovulation, blastocyst transfer and embryo/oocyte vitrification, renders feasible the elimination of OHSS in connection with ovarian hyperstimulation for IVF treatment. The proposed current algorithm is based on the number of follicles developed after ovarian stimulation, setting a cut-off level at the development of 18 or more follicles. Further, fulfilling this criterion, the algorithm is based on four decision-making points: the final day of patient work-up, the day of triggering final oocyte maturation, day-1 post oocyte pick-up (OPU) and day-5 post OPU.If the physician decides to administer hCG for final oocyte maturation regardless the type of analogue used, he has the option on day-1 to either freeze all embryos or to proceed to day-5. On this day, based on the clinical condition of the patient, a decision should be made to either transfer a single blastocyst or to vitrify all blastocysts available. However, this strategy will not guarantee an OHSS free luteal phase especially if a pregnancy occurs. If the physician decides to trigger ovulation with GnRHa, feasible only with the antagonist protocol, embryos can be cultured until day-5. On this day a transfer can be performed with no risk of OHSS and spare blastocysts may be vitrified. Alternatively, on day-1 or day-2 post OPU, all embryos could be frozen.Hopefully, in a near future, GnRHa triggering and vitrification of oocytes will become everyday practice. Only the combined use of a GnRH antagonist protocol with GnRHa triggering and subsequent single blastocyst transfer or embryo/oocyte freezing will completely abolish the risk of OHSS after ovarian hyperstimulation.

What is the optimal moment for IUI in natural cycles? Human chorionic gonadotropin or luteinizing monitoring? Preliminary results of a randomized study

OBJECTIVE: We recently reported the superiority of the natural cycle to a natural cycle controlled by the administration of hCG for planning the frozen-thawed ET, demonstrating a probable negative impact of exogenous hCG on endometrial receptivity (Fatemi et al., 2010).Based on the above findings we conducted the first prospective study that assesses whether there is a difference in pregnancy rate after IUI in a natural cycle with spontaneous LH /progesterone rise compared to natural cycles controlled by hCG for final oocyte maturation and ovulation.