Ultrashort gonadotropin-releasing hormone agonist combined with flexible multidose gonadotropin-releasing hormone antagonist for poor responders in in vitro fertilization/embryo transfer programs

Orvieto, Raoul; Kruchkovich, Jenny; Rabinson, Jacob; Zohav, Efraim; Anteby, Eyal Y.; Meltcer, Simion

doi:10.1016/j.fertnstert.2007.06.022

Cited by 41 publications

(26 citation statements)

References 20 publications

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“…In this study, the authors compared the use of the ultrashort GnRH-agonist combined with the flexible GnRH-antagonist in 21 poor responder patients with the patient's previous cycle. They found a significantly greater number of follicles larger than 14 mm, a higher number of oocytes retrieved and embryos transferred, and a reasonable clinical pregnancy rate (14.3%) [9]. In a follow up manuscript, the same authors reported that the use of the ultrashort flare GnRH-agonist combined with flexible multidose GnRH-antagonist for patients with repeated IVF failures again showed improvement when compared to the patient's previous cycle [8].…”

Section: Discussionmentioning

confidence: 95%

“…The concept of using a short-term microdose GnRH agonist followed by a GnRH antagonist during stimulation has recently been presented as an additional alternative protocol for poor responders [3,4,8,9]. This protocol combines the benefit of the initial stimulatory effect of the agonist flare on endogenous FSH, with the LH suppression provided by the antagonist.…”

Section: Discussionmentioning

confidence: 99%

“…This protocol combines the benefit of the initial stimulatory effect of the agonist flare on endogenous FSH, with the LH suppression provided by the antagonist. In 2008, Orvieto et al [9] published a study assessing poor responder patients with repeated IVF failures and poor embryo quality. In this study, the authors compared the use of the ultrashort GnRH-agonist combined with the flexible GnRH-antagonist in 21 poor responder patients with the patient's previous cycle.…”

Section: Discussionmentioning

confidence: 99%

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Ultrashort Flare GnRH Agonist with GnRH Antagonist (MDA/Ant) Protocol Compared with Clomiphene Citrate/ Gonadotropins (CC/GND) for Poor Responder Patients

Sueldo¹

2016

JFIV Reprod Med Genet

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Background: The ultrashort flare GnRH agonist/ GnRH antagonist protocol (MDA/Ant) has recently been advocated as a useful option for poor ovarian response (POR). POR patients with repeated IVF failures were offered stimulation with MDA/Ant (Group 1) or clomiphene citrate/gonadotropins (CC/Gnd; Group 2).Objective: The aim of this study was to compare Group 1 versus Group 2 in a POR population, from January 1st, 2010 until October 1st, 2014. Design: Retrospective Cohort Analysis.Methods: A total of 116 IVF cycles were included in the study. Group 1 received 21 days of oral contraceptives (OCP's), and were then treated with leuprolide acetate 40 mcg twice a day for the first 3 days, followed by high dose gonadotropins with a flexible start Gonadotropin Releasing Hormone (GnRH) antagonist. Group 2 received CC 100mg x 5 days, and on CC day 4 rec-FSH 600 IU was added.Results: No differences were found in age, body mass index (BMI), day 3 follicle stimulating hormone (FSH), or previous number of failed cycles. There were no differences noted in clinical pregnancy rate or live birth rate. Group 2 required a significantly lower amount of total gonadotropins, but Group 1 had a significantly lower rate of cycle cancellation. Conclusions:Although a higher dose of gonadotropins was required, the significantly lower cancellation rate when compared with Group 2 suggests that the MDA/Ant regimen may be a useful alternative protocol for poor responder patients. In Group 1 (n=69), patients took OCPs for approximately 21 days (range 15-25 days). Three days after the last pill, patients began taking microdose leuprolide acetate 40 mcg twice a day (BID) for 3 days. The next day, patients stopped the microdose leuprolide administration, and started recombinant follicle stimulating hormone (FSH) (rec-FSH; Follistim, Organon Pharmaceuticals, West Orange, NJ; or Gonal-F, Serono Pharmaceuticals, Rockland, MA) with or without the addition of human menopausal gonadotropins (hMG) (Menopur, Ferring Pharmaceuticals, Tarrytown, NY) for a total gonadotropin dose of 450-600 IU/day, at physician discretion. The gonadotropin regimen was maintained daily and adjusted individually according to serum estradiol (E2) concentrations and ovarian response as noted by ultrasound. When follicles reached ≥14 mm in mean diameter and/or E2 ≥350 pg/ml, patients started ganirelix acetate (Ganirelix; Organon Pharmaceuticals, West Orange, NJ) 0.25 mg subcutaneous (SC) daily. When at least 2 leading follicles reached ≥17 mm in diameter, human chorionic gonadotropin (hCG) 5,000-10,000 IU was administered, and oocyte retrieval was performed 35 hr later.Stimulation in Group 2 (n=47) started on the second day of menses with CC 100 mg PO daily x 5 days. On the fourth day of CC, patients started rec-FSH with or without the addition of hMG for a total gonadotropin dose of 450-600 IU/day. Individual adjustments in dose were made in the same fashion as mentioned above. When follicles reached ≥14 mm in mean diameter and/or E2 ≥350 pg/ml, patients started ganirelix...

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ultrashort Flare GnRH Agonist with GnRH Antagonist (MDA/Ant) Protocol Compared with Clomiphene Citrate/ Gonadotropins (CC/GND) for Poor Responder Patients

Sueldo¹

2016

JFIV Reprod Med Genet

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“…In addition, the impact of these protocols on endometrial receptivity also remains controversial (15,16). As a result, neither of these protocols has been effective in improving ART outcomes in this subgroup of patients (7,17,18). The idea of the combination of the microdose GnRH-a flare-up and GnRH antagonist protocol to minimize these detrimental effects and to combine the beneficial effects of these two stimulation protocols for poor responders was first presented by Berger et al as a novel protocol -the "Agonist-Antagonist Protocol (AAP)" (19).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare-up protocol in poor responders: a preliminary study

Berker

Duvan

Kaya

et al. 2010

Fertility and Sterility

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Objective: To determine the potential effect of the ultrashort gonadotropin-releasing hormone (GnRH) agonist/GnRH antagonist protocol versus the microdose GnRH agonist protocol in poor responders undergoing intracytoplasmic sperm injection (ICSI). Material and Methods:The patients in the Agonist-Antagonist Group (n=41) were administered the ultrashort GnRH-agonist/ antagonist protocol, while the patients in the Microdose Group (n=41) were stimulated according to the microdose flare-up protocol. The mean number of mature oocytes retrieved was the primary outcome measure. Fertilization rate, implantation rate per embryo and clinical pregnancy rates were secondary outcome measures. Results:There was no differenc between the mean number of mature oocytes retrieved in the two groups. There were also no statistical differences between the two groups in terms of peak serum E 2 level, canceled cycles, endometrial thickness on hCG day, number of 2 pronucleus and number of embryos transferred. However, the total gonadotropin consumption and duration of stimulation were significantly higher with the Agonist-Antagonist Group compared with the Microdose Group. The implantation and clinical pregnancy rates were similar between the two groups. Conclusion:Despite the high dose of gonadotropin consumption and longer duration of stimulation with the ultrashort GnRH agonist/ antagonist protocol, it seems that the Agonist-Antagonist Protocol is not inferior to the microdose protocol in poor responders undergoing ICSI. (J Turkish-German Gynecol Assoc 2010; 11: 187-93) Key words: Poor responder, mature oocytes, Agonist-Antagonist protocol, microdose flare-up protocol Received: 11 August, 2010 Accepted: 19 November, 2010 Amaç: ICSI uygulanan zayıf over cevaplı hastalarda ultra kısa GnRH agonist/GnRH antagonist protokolünün mikrodoz GnRH agonist protokolüne karşı potansiyel etkisini belirlemek. Gereç ve Yöntemler:Mikrodoz grubundaki (n=41) hastalar mikrodoz flare up protokolüne uygun olarak stimüle edilirken AgonistAntagonist grubundaki (n=41) hastalara da ultra kısa GnRH-agonist/ antagonist protokolü uygulandı. Bu çalışmanın primer sonuç değeri toplanan ortalama matür oosit sayısı iken, fertilizasyon oranı, embryo başına implantasyon oranı ve klinik gebelik oranı da sekonder sonuç değerleriydi. Bulgular:İki grup arasındaki toplanan ortalama matür oosit sayıla-rı arasında fark yoktu. Serum E 2 düzeyleri, iptal edilen sikluslar, hCG günü endometrial kalınlığı, 2 pronukleus sayıları ve transfer edilen embryo sayılarında da iki grup arasında istatistiksel farklılıklar yoktu. Bununla birlikte Agonist-Antagonist grubunda total gonadotropin tüketimi ve stimülasyon süresi Mikrodoz grubuyla karşılaştırıldığında belirgin olarak daha yüksekti. İki grup arasındaki implantasyon ve klinik gebelik oranları ise birbirine benzerdi. Sonuç: Abstract ÖzetOriginal Investigation 187

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“…In an attempt to distinguish the optimal approach by means of stimulation protocol for these patients, the combined ultrashort GnRH agonist/GnRH antagonist (ultrashort GnRH-ag/GnRH-ant) protocol has been reported to result in a significantly higher number of follicles with a higher yield of oocytes retrieved and embryos transferred, as well as a reasonable clinical pregnancy rate in patients with previous failed IVF attempts and poor embryo quality (8). The rationale of employing this protocol for POR lies within the separate benefits that the accompanying adjuncts, prior to ovarian stimulation, may offer: Firstly, estradiol pretreatment prevents corpus luteum formation and the ensuing hormonal stimulation.…”

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confidence: 99%

Estradiol Pretreatment in an Ultrashort GnRH Combined with a GnRH Antagonist Protocol in A Cohort of Poor Responders Undergoing IVF/ICSI: A Case-control Study

Siristatidis

Salamalekis

Vogiatzi

et al. 2016

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Abstract. Aim: To provide results of the use of estradiol pretreatment in a combination of an ultrashort gonadotropinreleasing hormone (GnRH) agonist and antagonist protocol, in an attempt to improve the clinical outcomes in "poor responders", according to the Bologna criteria, undergoing in vitro fertilization (IVF (0/20 vs. 3/20, p=0.231) as also in the respective number of clinical pregnancies (2/20 vs. 5/20, p=0.407) and cancellations (10/20 vs. 6/20, p=0.197) Several approaches in assisted reproduction technology (ART) require a higher yield of oocytes, in order to typically present with a greater number of embryos for each couple increasing their chances for a successful embryo transfer and a positive outcome, in terms of pregnancy. On this basis, controlled ovarian hyperstimulation (COH) has been considered a routine approach in ART as it leads to a higher number of oocytes and embryos to transfer and, potentially, select from. However, advanced age of the female partner and the anticipated hormonal variations may lead to a reduced ovarian reserve and, thus, a weakened response to ovarian stimulation, minimizing the chances of retrieving the anticipated number of oocytes.Poor ovarian response (POR) characterizes a significant proportion of ART patients and poses a serious challenge in assisted reproduction, due to the lowered response following external stimulation, the high cancellation rates observed in these cycles and the increased incidence of implantation failure that accompanies them as found to occur in 9-24% of these cycles (1). Ferraretti et al. have presented the Bologna criteria, according to which a poor responder in an ART cycle is identified in order to adjust the approach parameters to the degree of obtaining the best possible outcome for the subfertile women/couples. According to these criteria, poor responders are identified by (i) advanced maternal age or any other risk factors for POR; (ii) a previous POR and (iii) an abnormal ovarian reserve test (2).

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Ultrashort gonadotropin-releasing hormone agonist combined with flexible multidose gonadotropin-releasing hormone antagonist for poor responders in in vitro fertilization/embryo transfer programs

Cited by 41 publications

References 20 publications

Ultrashort Flare GnRH Agonist with GnRH Antagonist (MDA/Ant) Protocol Compared with Clomiphene Citrate/ Gonadotropins (CC/GND) for Poor Responder Patients

Ultrashort Flare GnRH Agonist with GnRH Antagonist (MDA/Ant) Protocol Compared with Clomiphene Citrate/ Gonadotropins (CC/GND) for Poor Responder Patients

Comparison of the ultrashort gonadotropin-releasing hormone agonist-antagonist protocol with microdose flare-up protocol in poor responders: a preliminary study

Estradiol Pretreatment in an Ultrashort GnRH Combined with a GnRH Antagonist Protocol in A Cohort of Poor Responders Undergoing IVF/ICSI: A Case-control Study

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