Protocol In Poor Responders Research Articles

Expression of concern: “The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial” [Eur. J. Obstet. Gynecol. Reprod. Biol. 228 (2018) 161–165, ISSN 0301-2115, https://doi.org/10.1016/j.ejogrb.2018.06.035

Expression of concern: “The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial” [Eur. J. Obstet. Gynecol. Reprod. Biol. 228 (2018) 161–165, ISSN 0301-2115, https://doi.org/10.1016/j.ejogrb.2018.06.035

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in poor responders: Risk of premature LH surge and outcome of oocyte retrieval

PurposeFor poor ovarian responders (PORs), gonadotropin-releasing hormone (GnRH) antagonist was commonly used for prevention of premature LH surge during controlled ovarian stimulation (COS) over the past two decades. The application of progestin-primed ovarian stimulation (PPOS) recently increased, but the role of PPOS for PORs was uncertain. We aimed to analyze the incidence of premature luteinizing hormone (LH) surge and the outcome of oocyte retrieval among PPOS and GnRH antagonist protocol for PORs. MethodsThis was a single-center retrospective study, which enrolled the PORs (defined by the Bologna criteria) undergoing COS with PPOS or flexible GnRH antagonist protocol during January 2018 to December 2021. We compared the incidence of premature LH surge (LH > 10 mIU/mL) and the outcome of oocyte retrieval between the PPOS group and the GnRH antagonist group. ResultsA total of 314 women were recruited, with 54 in the PPOS group and 260 in the GnRH antagonist group. The PPOS group had lower incidence of premature LH surges compared with the GnRH antagonist protocol group (5.6% vs 16.9%, P value 0.035). There was no significant difference between the two groups regarding the number of oocytes retrieved (3.4 vs 3.8, P value 0.066) and oocyte retrieval rates (88.9% vs 88.0%, P value 0.711). ConclusionCompared with PPOS, GnRH antagonist protocol had higher risk of premature LH surges for PORs but may not affect pregnancy rates. PPOS is suitable for oocyte or embryo cryopreservation, but should not totally replace GnRH antagonist protocol for patients undergoing in vitro fertilization (IVF).

O-071 In progestin primed double stimulation protocol: Is luteal phase stimulation more effective than follicular phase stimulation in poor responders? A randomized controlled study

Abstract Study question Is follicular phase or luteal phase stimulation more effective in progestin primed double stimulation protocol in poor responders? Summary answer The luteal phase stimulation was more effective than follicular phase stimulation in the progestin primed dual stimulation protocol in poor responders. What is known already Poor ovarian responders involve 9–24% of patients undergoing in vitro fertilization (IVF), with the management of these patients posing an everyday practical challenge. Owing to the follicular waves theory, two or three waves of folliculogenesis were detected during the interovulatory interval, two consecutive ovarian stimulation protocols could be initiated in the follicular phase and the subsequent luteal phase. This is an effective way to increase the number of oocytes and embryos obtained over a relative short period of time. Furthermore, there is increasing evidence that progestins can be a reliable method of preventing premature LH surge during ovarian stimulation. Study design, size, duration This was a randomized controlled study performed at the Infertility and Assisted Reproduction Unit of ElShatby Maternity Hospital, Alexandria University and Madinah Fertility Centre. The study was conducted on 90 infertile women with poor ovarian response as defined by the Bologna criteria. 7 patients were excluded due to protocol violation, loss to follow-up and patient withdrawal. The study commenced in September 2020 and was finalized in September 2021. Participants/materials, setting, methods Group 1 45 patients were given the progestin primed double stimulation protocol. Dydrogesterone was started from the first day of the ovulation induction till the end of luteal phase stimulation. Embryo transfer was scheduled in a subsequent cycle. Group 2 45 patients were given the flexible GnRh antagonist protocol in 2 cycles. The best blastocyst from either cycle was transferred in the second cycle. Main results and the role of chance When comparing the follicular and luteal phases, the M2 oocytes number retrieved in the luteal phase was statistically significantly higher than the follicular phase, with the median number of 4 oocytes against a median number of 2 oocytes (P value 0.001). The fertilization rate was significantly higher in the M2 oocytes of the luteal phase stimulation (P value 0.04). The resultant embryos from the luteal stimulation phase were statistically significantly higher than the follicular phase, with the median number of 3 embryos against a median number of 1 embryo (P value <0.001). However, we found that the days of controlled ovarian hyperstimulation were statistically significant higher in stimulation of the luteal phase with the median of 12 days against the 10 days seen in follicular phase stimulation (P value 0.002). Consequently, the total dosage of gonadotropins was statistically significant higher in the luteal phase with a P value of 0.007. After Subgroup analysis, Poseidon Group 4 patients demonstrated that a significantly higher number of oocytes were retrieved after the progestin primed double stimulation than after two waves of flexible GnRh antagonist stimulation (median of 12 oocytes against a median of 10 oocytes with P value 0.01). Limitations, reasons for caution Firstly, preimplantation genetic testing was not performed to detect euploid embryos which could be vital when comparing both the phases and the protocols. Secondly, despite the importance of the live birth rate as an outcome measure, we did not enroll this measure. Wider implications of the findings In the light of our findings, we recommend the usage of progestin primed dual stimulation protocol in poor responder patients. Additionally, we call for multicentric randomized controlled research to verify this protocol as a first-line treatment protocol in poor responder patients. Trial registration number ClinicalTrials.gov ID: NCT04537078

Early administration of gonadotropin-releasing hormone antagonist versus flexible antagonist ovarian stimulation protocol in poor responders: a randomized clinical trial

BackgroundDetermining the initiation day of antagonist administration is an important and challenging issue and different results have been reported in the previous studies. The present study was designed to compare the controlled ovarian hyperstimulation (COH) cycles outcomes of early-onset gonadotropin-releasing hormone antagonist (GnRH-ant) protocol with conventional flexible GnRH-ant protocol in patients with poor ovarian response (POR) diagnosis. This randomized clinical trial was performed on infertile women who were diagnosed as poor responders in in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles at Arash Women’s Hospital affiliated to Tehran University of Medical Sciences. POR was defined according to the Bologna criteria and the eligible women were randomly allocated into an experimental (early-onset GnRH-ant) and control (conventional flexible GnRH-ant) groups. The women in the experimental group received recombinant gonadotropins (150–225 IU) and GnRH-ant (0.25 mg) simultaneously on the second day of the cycle. In the control group, the starting and the dose of gonadotropins were similar but daily administration of GnRH-ant was initiated when the leading follicle diameter was ≥ 13 mm. The COH outcomes were compared between groups (n=58 in each group).ResultsThe analysis showed that the two groups did not have statistically significant differences in terms of the ovarian stimulation duration and the total dose of used gonadotropins. The total number of metaphase II (MII) oocytes in the experimental group was significantly higher than that of in control group (P = 0.04). Moreover, clinical and ongoing pregnancy rates per embryo transfer (ET) in the experimental group were significantly higher than those in the control group (P = 0.02 and P = 0.03, respectively); however, the implantation and miscarriage rates were similar between groups.ConclusionsThe early-onset GnRH-ant protocol can improve the number of retrieved and MII oocytes and probably the pregnancy outcomes after fresh embryo transfer in POR patients. However, larger randomized clinical trials are required to compare the pregnancy outcomes after this approach with other COH protocols with considering cost-effectiveness issue.Trial registrationIRCT20110731007165N9.The name of the registry: Ladan Kashani.The date of trial registration: 8.02.2020.

STUDY OF THE EFFECT OF ADDING LETROZOLE TO GONADOTROPIN-RELEASING HORMONE ANTAGONIST PROTOCOL IN POOR RESPONDERS UNDERGOING INTRACYTOPLASMIC SPERM INJECTION

Background: Poor responders constitute a less fortunate group of patients attending any IVF/ICSI clinic. Identifying these patients helps in choosing the most appropriate stimulation protocol.Aim:This is a randomized controlled prospective study that aimed to study the effect of adding letrozole to GnRH antagonist protocol in poor responders undergoing ICSI.Materials and Methods: This study was carried out on a sample of 70 infertile couple, thirty five patients in each group, five cases were canceled in group I (letrozole/antagonist group), while six patients in group II (antagonist group) canceled the cycle. In group I, letrozole 5mg was given from day 2 cycle for 5 days. Initial dose of HMG 300 I.U from day three cycle, then the dose was modulated according to response in both groups and ICSI was done. The women were followed to detect the occurrence of pregnancy by measuring serum B-hCG 14 day after embryo transfer and clinical pregnancy was followed up at 6th week of gestation.Results: The dose of HMG was significantly lower in group I than in group II, while there were no significant statistical differences in the duration of stimulation, number of oocytes retrieved, fertilization rate, implantation rate, cycle cancelation rate, and clinical pregnancy rate with adding letrozole to GnRH antagonist cycles in women with POR.Conclusion: Letrozole is recommended to be added to ICSI stimulation protocols in poor responders. Although it didn't affect the pregnancy rate, letrozole decreases the dose and the cost of ICSI cycles.

Efficacy of growth hormone supplementation with ultrashort GnRH antagonist in IVF/ICSI for poor responders; randomized controlled trial

ObjectivesTo compare the ICSI-ET outcomes in poor responders who underwent ovarian stimulation by the ultrashort GnRH antagonist protocol with or without adjuvant GH injection. Material and methodsThis randomized controlled study was conducted at Al-Azhar University from December-2018 to June-2019 upon 156 participants. All patients received the same preparations. After randomization, in the study group, women have received GH 4 IU/day subcutaneous injection from the second day of the cycle stopped one day before ovum pickup. While in the control group, women have received subcutaneous saline in the same dosing as in the study group. After intervention, all procedures were the same in both groups. The main outcome measure was the clinical pregnancy rate. Statistical analysis was based on the intention-to-treat population. ResultsBoth groups were comparable with regard their baseline characteristics (p-values > 0.05). Ovulation characteristics were comparable (p-values > 0.05). The level of E2 is significantly (p-value = 0.003) higher in the GH group. The oocyte retrieved number was significantly (p-value < 0.001) higher in the GH group 4.94 ± 1.77 than in the control group 3.74 ± 1.82. The mean number of MII oocytes was significantly (p-value < 0.001) higher in the GH group 3.3 ± 1.36 than in the control group 2.29 ± 1.24. Fertilization characteristics, implantation rate, pregnancy rate were comparable (p-values > 0.05). ConclusionDespite the fact that this study showed no significant increase in the clinical and chemical pregnancy rates by the addition of GH to the ultrashort antagonist protocol in poor responders, the number of retrieved oocytes was significantly higher in the GH group. Clinical trial registrationClinicalTrials.gov Identifier: NCT03759301.

Letrozole as co-treatment agent in ovarian stimulation antagonist protocol in poor responders: A double-blind randomized clinical trial.

BackgroundOvarian stimulation (OS) for poor ovarian response (POR) patients is still a major challenge in assisted reproductive techniques. Aromatase inhibitors as co-treatment in antagonist protocol are suggested to these patients, but there are controversial reports.ObjectiveTo evaluate the effectiveness Letrozole (LZ) as adjuvant treatment in gonadotropin-releasing hormone (GnRH)-antagonist protocol in POR patients undergoing in vitro fertilization/ intracytoplasmic sperm injection cycles.Materials and MethodsThis double-blind randomized clinical trial was conducted in Arash women's hospital. One hundred sixty infertile women with POR based on Bologna criteria were allocated into two groups randomly: LZ + GnRH-antagonist (LA) and placebo + GnRH-antagonist (PA) groups. In the experimental group, the patients received 5 mg LZ on the first five days of OS with 150 IU of recombinant human follicle-stimulating hormone (rFSH) and 150 IUof human menopausal gonadotropin (HMG). The cycle outcomes were compared between groups.ResultsThe total number of retrieved oocytes and the metaphase II oocytes in LA-treated group were significantly higher than those in the control group (p = 0.008, p = 0.002). The dosage of hMG used and the duration of OS and antagonist administration in LZ-treated group were significantly lower than those of the control group. The number of patients with no oocyte, in the control group, was higher than the LZ-treated group, and the clinical pregnancy rate in LA-treated group (25%) was higher than the control group (18%); however, the differences were not significant statistically.ConclusionAdding 5 mg of LZ to rFSH/hMG antagonist protocol may improve the in vitro fertilization/intracytoplasmic sperm injectioncycle outcome in POR patients.

The different impact of stimulation duration on oocyte maturation and pregnancy outcome in fresh cycles with GnRH antagonist protocol in poor responders and normal responders

ObjectiveTo study the impact of stimulation duration on intracytoplasmic sperm injection (ICSI) - embryo transfer (ET) outcome in poor and normal responders during controlled ovarian stimulation using gonadotropin-releasing hormone (GnRH) antagonist protocol. Materials and methodsThis is a retrospective cohort study. There were 1481 women undergoing ICSI-ET cycles. Women with ovum pick-up number ≤3 were defined as poor responders (n = 235), and those with a number ≥4 were normal responders (n = 1246). ResultsThe mean stimulation duration was shorter in poor responders with pregnancy group as compared with normal responders with pregnancy group (7.8 ± 2.2 vs. 9.2 ± 1.6 days, p < 0.01). Poor responders with a shortest stimulation duration (≤6 days) appeared a higher live birth rate (≤6 days: 33.3%, 7–8 days: 20.0%, 9–10 days: 15.9%, and ≥11 days: 11.1%, p = 0.18). Normal responders with a shortest stimulation duration (≤6 days) appeared a lowest live birth rate (≤6 days: 28.6%, 7–8 days: 35.8%, 9–10 days: 33.6%, and ≥11 days: 29.3%, p = 0.61). Oocyte maturation rate was significantly lower at stimulation durations ≤6 days group (≤6 days: 67%, 7–8 days: 80%, 9–10 days: 85%, and ≥11 days: 87%, p = 0.02) in normal responders. ConclusionIn ICSI-ET cycles, stimulation duration appears to have different impact on oocyte maturation, clinical pregnancy rates and live birth rates in both poor and normal responders.

Addition of Growth Hormone to the Stimulation Protocol in Poor Responders - An Option for Increasing Pregnancy Rates in Failed IVF Cycles - A Short Communication

Addition of Growth Hormone to the Stimulation Protocol in Poor Responders - An Option for Increasing Pregnancy Rates in Failed IVF Cycles - A Short Communication

Does the \u201cdelayed start\u201d protocol with gonadotropin-releasing hormone antagonist improve the pregnancy outcome in Bologna poor responders? a randomized clinical trial

BackgroundRecently, a novel approach with delaying the start of controlled ovarian stimulation along with gonadotropin-releasing hormone (GnRH) antagonist pretreatment for 7 days after estrogen priming for further suppression of endogenous follicle stimulating hormone (FSH) during the early follicular phase, resulting in more FSH-responsive follicles and thus improving synchronous follicular development was introduced. Two clinical trials have examined this strategy and reported controversial results. This study aimed to compare the effect of delayed-start GnRH antagonist protocol and standard GnRH antagonist in patients with poor ovarian response (POR) undergoing in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI).MethodsThis randomized clinical trial was conducted at infertility department of Royan Institute from January 2017 to June 2018. Poor ovarian response was defined according to the Bologna criteria. The eligible women were randomly allocated into an experimental and control groups. In experimental group, patients received delayed-start GnRH antagonist protocol with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin and in control group, patients treated with estrogen priming antagonist protocol. IVF/ICSI outcomes were compared between groups.ResultsAmong all the 250 patients examined 156 women were eligible for study and finally 120 patients were allocated to intervention (n = 60) and control (n = 60) groups. Demographic characteristics and hormonal profiles of the patients did not differ between groups. The statistical analysis showed that there were significant differences between groups regarding the total dose of used gonadotropins (P < 0.001), stimulation duration (P < 0.001), number of retrieved oocytes (P = 0.01) and top quality embryo (P < 0.001) and also cancellation (P = 0.002) and fertilization rates (P = 0.002).ConclusionOn the basis of present results the delayed-start protocol in poor responders can improve the fertilization rate and quality of embryos and reduce the cycle cancellation but have no significant effect on clinical pregnancy rate; however, larger randomized clinical trials are required to compare it with other protocols.Trial registrationNCT, NCT03134690. Registered 1 May 2017 - Retrospectively registered, http://www.clinicaltrial.gov/ NCT03134690.

The addition of growth hormone adjuvant therapy to the long down regulation protocol in poor responders undergoing in vitro fertilization: Randomized control trial

Objectiveto detect the impact of growth hormone (GH) co-treatment to the long down regulation protocol, on the outcomes of IVF/ICSI cycles in poor responders. Study Designthis parallel open label randomized control trial was conducted in a university hospital. It included 240 females satisfying the bologna criteria for poor responders. The enrolled females were randomized into 2 groups: A (long/GH) receiving GH adjuvant therapy to the long protocol and group B (control) receiving the long protocol alone. The main outcome measure was the live birth rate (fresh, frozen and cumulative). ResultsGH supplementation improved the number of collected oocytes (5.4 ± 1.7 vs. 4.3 ± 2.1), MII oocytes (4.1 ± 2.1 vs. 2.1 ± 1.4), fertilized oocytes (4.0 ± 2.2 vs. 2.0 ± 1.2), transferred embryos (2.4 ± 0.9 vs. 1.6 ± 1.1) and cryopreserved (0.5 ± 0.7 vs. 0.2 ± 0.5). There was no significant difference in the live birth rate whether fresh (17.5% vs. 14.1%) or cumulative (18.3% vs. 14.7%). ConclusionsFurther studies are needed to know the true impact of adding GH to the induction protocols in poor responders, as there was no difference in the live birth rates between the study groups, indicating a lack of trend toward benefit from GH supplementation in poor responders.Clinical Trial Registration: NCT02338206.

Pregnancy outcome in delayed start antagonist versus microdose flare GnRH agonist protocol in poor responders undergoing IVF/ICSI: An RCT

Over the years, many article on different aspects of pathogenesis and management of poor ovarian responders have been published but there is no clear guideline for treating themyet. This study was designated to compare the effectiveness of a delayed start protocol with gonadotropin-releasing hormone (GnRH) antagonist and microdose flare-up GnRH agonist protocol in poor ovarian responders. This randomized clinical trial consisted of 100 poor ovarian responder women in assisted reproductive technologies cycles. They were divided randomly in delayed-start antagonist protocol (with estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation) and microdose flare-up GnRH agonist protocol. The main outcome was clinical pregnancy rate and second outcome was the number of retrieved oocytes, mature oocytes, 2PN number, fertilization rate, and implantation rate. Fertilization rate, clinical pregnancy rate, and ongoing pregnancy rates were not significantly different between the two studied protocols. Number of retrieved oocytes (5.10±3.41 vs. 3.08±2.51) with p=0.002, mature oocytes (4.32±2.69 vs. 2.34±1.80) with p=0.003, number of 2PN (3.94±1.80 vs. 2.20±1.01) with p=0.001 and implantation rate (19.40% vs. 10.30%) with p=0.022 were significantly higher in delayed antagonist group. The delayed-start protocol can improve ovarian response in poor responders by stimulating and synchronizing follicle development.

Outcomes of poor responders following growth hormone co-treatment with IVF/ICSI mild stimulation protocol: a retrospective cohort study.

No research has studied the effect of GH co-treatment in mild stimulation protocol for poor responders. We therefore conducted this retrospective analysis to assess the outcome of IVF/ICSI cycles after the adjunct GH use to the mild stimulation protocol in poor responders. 132 poor responders who received mild stimulation protocol at Reproductive Medicine Center of Changzheng Hospital from January 2014 to December 2016 were included in this study. Good-quality embryo rate, clinical pregnancy rate, and live birth rate were compared between the GH group (n=61) and control group (n=71). IVF good-quality embryo rate (68.1 versus 51.5%; P=0.008*) and ICSI good-quality embryo rate (53.9 versus 36.7%; P=0.045*) was significantly higher in the GH group. Though the clinical outcomes did not reach a statistically significant difference between the two groups due to the limited sample size, there was a trend of higher rate in GH group in the aspect of clinical pregnancy rate (52.4 versus 47.1%; P=0.609) and live birth rate (35.7 versus 27.5%; P=0.392). The results suggested that the adjuvant GH treatment in mild stimulation protocol for poor responders could significantly improve good-quality embryo rate, and might therefore improve the clinical outcomes.

Efficacy of luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist priming protocol in poor responders undergoing in vitro fertilization.

ObjectivesWe investigated whether luteal estrogen administration and an early follicular Gonadotropin-releasing hormone antagonist (E/G-ant) priming protocol improves clinical outcomes in poor responders to controlled ovarian stimulation for in vitro fertilization (IVF)-embryo transfer, and identified underlying mechanisms.MethodsThis restrospective study consisted of 65 poor responders who underwent the E/G-ant priming protocol. Sixty-four other poor responders undergoing conventional protocols without pretreatment were included as the control group. Clinical outcomes were compared between 2 groups.ResultsThe E/G-ant priming protocol group exhibited improvements over the control group in terms of the number of retrieved oocytes (3.58±2.24 vs. 1.70±1.45; P=0.000), mature oocytes (2.68±2.11 vs. 1.65±1.23; P=0.000), fertilized oocytes (2.25±1.74 vs. 1.32±1.26; P=0.001), good embryos (1.62±0.91 vs. 1.14±0.90, P=0.021). Day 3 follicle-stimulating hormone (FSH; 8.40±4.84 vs. 16.39±13.56; P=0.000) and pre-ovulation progesterone levels (0.67 vs. 1.28 ng/mL; P=0.016) were significantly higher in the control group than in the E/G-ant priming group. The overall rate of positive human chorionic gonadotropin tests was higher in the E/G-ant priming group than in the control group (32.3% vs.16.1%; P=0.039). Also, clinical pregnancy rate (26.2% vs. 12.5%; P=0.048) and the rate of live births (23.1% vs. 7.1%; P=0.023) were significantly higher in the E/G-ant priming group than in the control group.ConclusionThe E/G-ant priming protocol would lead to promising results in poor responders to IVF by suppressing endogenous FSH and by preventing premature luteinization.

Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

Background:Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART). Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards.Objective:The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF) outcomes.Materials and Methods:This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30), delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30) treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results:Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups.Conclusion:There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

A comparison of microdose flare versus antagonist protocol in poor responders chosen according to the Bologna criteria

Background: Uncertainty exists in deciding the optimal stimulation protocol in poor responders undergoing in-vitro fertilization (IVF). Our study aims to compare microdose flare and antagonist protocols in the management of patients considered to be poor responders, chosen according to Bologna criteria. Materials and Methods: In a prospective observational study, 66 poor responders as per the Bologna criteria were recruited to undergo IVF-ICSI cycles using either microdose flare protocol (Group I; n = 28) or the flexible antagonist (Group II; n = 38). Pregnancy rate per cycle was taken as the primary outcome. Total days of stimulation, total dose of gonadotropins, estradiol (E2) and progesterone levels on the day of human chorionic gonadotropin (hCG) trigger, cycle cancellation rate, total oocytes retrieved, total Metaphase II (MII) oocytes, number of embryos formed, number of Grade I embryos, fertilization and cleavage failure, total number of cycles that did not reach embryo transfer were taken as secondary outcome measures. Results: There was no significant difference in the pregnancy rates between the two groups. The microdose flare group (Group I) had higher levels of E2 on the day of hCG trigger (P = 0.03) and more number of MII oocytes (P = 0.04). Conclusion: Patients stimulated with the microdose flare protocol had significantly more E2 levels with the recovery of more MII oocytes, but this did not transform to higher pregnancy rates. A large multicentered randomized trial would be required to draw definite conclusion to achieve significant difference between the cycle cancellation and pregnancy rates between these two protocols for poor responders.

A comparison among different methods of letrozole combined with gonadotropin in an antagonist protocol and high-dose gonadotropin ovarian stimulation antagonist protocol in poor ovarian responders undergoing in vitro fertilization.

This study aimed at comparing the effects of different methods of letrozole combined with gonadotropin (Gn) and high-dose Gn ovarian stimulation in antagonist protocol. Retrospectively reviewed 220 poor responders from August 2012 to July 2014 at Peking University Third Hospital Reproductive Medical Center. Patients were divided into Group 1 (LZ 5mg for 5days sequentially overlapping with Gn cycles; n=60), group 2 (LZ 7.5mg for 3days sequentially with Gn cycles; n=60), and group 3 (high-dose Gn cycles; n=100). We compared the basic status of patients and clinical outcomes of the three groups. Basic characteristics of patients were comparable among groups. Group 1 had significantly higher LH levels on day 7 and hCG than Group 2 and 3 (P<0.05). Group 1 had significantly higher early LH elevation rate (>20IU/L) on the hCG day than Groups 2 and 3 (11.7 vs. 6.7 and 2.0%; P<0.05). The amount of Gn used in LZ groups was significantly lower than Group 3 (P<0.01). However, the clinical pregnancy rate and live birth rate were comparable among groups. In conclusion, the LZ/antagonist protocol is a cost-effective and patient friendly protocol, LZ 5mg for 5days sequentially overlapping with Gn protocol has comparable pregnancy outcomes, and LZ 7.5mg for 3days sequentially with the Gn protocol even has better clinical outcomes when compared with the standard GnRH antagonist protocol in poor responders. LZ 7.5mg for 3days sequentially with the Gn protocol appeared to have resulted in fewer improper LH surges and better outcomes than LZ 5mg for 5days sequentially overlapping with Gn in antagonist protocol.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF.

Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). Conclusion. The combination protocol does not provide additional efficacy.

Comparison of long GnRH agonist versus GnRH antagonist protocol in poor responders.

Objective:To compare long GnRH agonist with GnRH antagonist protocol in poor responders.Materials and Methods:Medical charts of 531 poor responder women undergoing in-vitro fertilization (IVF) cycle at Zeynep Kamil Maternity and Children’s Hospital, IVF Center were retrospectively analysed. Those who received at least 300 IU/daily gonadotropin and had ≤3 oocytes retrieved were enrolled in the study. Poor responders were categorized into two groups as those who received long GnRH agonist or GnRH antagonist regimen.Results:Treatment duration and total gonadotropin dosage were significantly higher in women undergoing the long GnRH agonist regimen compared with the GnRH antagonist regimen (p<0.001 for both). Although the number of total and mature oocytes retrieved was similar between the groups, good quality embryos were found to be higher in the GnRH antagonist regimen. The day of embryo transfer and number of transferred embryos were similar in the groups. No statistically significant differences were detected in pregnancy (10.5% vs 14.1%), clinical pregnancy (7.7% vs 10.6%) and early pregnancy loss rates (27.2% vs 35%) between the groups.Conclusion:GnRH antagonist regimen may be preferable to long GnRH regimen as it could decrease the cost and treatment duration in poor responders.

Comparison between Micro-Dose GnRH Agonist and GnRH Antagonist Protocol in Poor Responders Undergoing Intracytoplasmic Sperm Injection with Embryo Transfer

Objective: To compare the effect of the multiple-dose GnRH antagonist protocol with the microdose GnRH agonist flare-up (MF) protocol in poor ovarian responders for ICSI. Design: Retrospective, Clinical study. Setting:IVF center. Patient(s): Two hundred eighty-six poor responder patients undergoing ICSI-embryo transfer cycle. Intervention(s): one hundred Forty four patients (144 cycles) included in group 1 (microdose GnRH-a flare-up protocol) and one hundred fourty two patients (42 cycles) included in group 2 (multiple dose GnRH antagonist protocol). Main Outcome Measure(s): Serum E2 levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate, pregnancy rate (PR) and live birth rate (LR). Results: Total gonadotropin dose used was significantly lower (2730235,45 vs 3189317,81; P<0.05), duration of stimulation was significantly longer and E2 level was significantly higher in group 1. The mean number of oocytes retrived, mature oocytes retrived, embryos transferred and the rate of at least one top-quality embryo transferred was similar in the two groups. The implantation rate was significantly higher in the microdose flare-up group than in the multiple-dose antagonist group (18.79% vs 8.28%; P<.001). Clinical pregnancy and live birth rates were similar in the two groups. Conclusion(s): We achieved comparable pregnancy and live birth rates in poor responders with the use of either GnRH antagonist or flare protocol. However, a significantly higher gonadotropin dose used and lower implantation rate in the antagonist group tips the balance in favor of the flare-up protocol.