Serum luteinizing hormone level on the third day after ovarian stimulation in GnRH agonist short protocol is predictive of outcome in poor responders but not in normal responders

Objectives: To identify whether prognostic value of LH measurement in normal responders (NR) is different from poor responders (POR).

Methods: A retrospective, single-center study was conducted among patients who underwent ovarian stimulation with short protocol, with 300 NR and 101 POR, according to Bologna Consensus criteria. LH was measured on 3rd and 5th day after stimulation and HCG administration day.

Results: There was significant difference in the clinical pregnancy rate per cycle initiated among those with LH level on the third day after stimulation (a) below the 25 centile (b) between the 25 and 75 centile and (c) above the 75 centile in women with POR (7.7%, 15.1% vs. 36.4%, p?=?0.02) but not in NR. There was significant correlation between LH ranks and clinical pregnancy rate in POR (p?=?0.02) but not in NR. Factors associated with clinical pregnancy rate in POR were age and LH on the third of stimulation, while factors in NR were age, AFC and FSH.

Conclusion: LH level on the 3rd day of stimulation was predictive of clinical pregnancy in POR but not in NR.     

Comparison of different stimulation protocols efficacy in poor responders undergoing IVF: A retrospective study

Purpose: To compare the efficacy of different stimulation protocols on pregnancy outcomes in poor responders undergoing in vitro fertilization (IVF). Materials and methods: This was a retrospective study to compare the efficacy of four different protocols including gonadotropin-releasing hormone (GnRH) agonist (long, short and miniflare) and GnRH antagonist on pregnancy outcomes in poor responders. This investigation was performed on 566 poor respond patients who were candidates for IVF. Main outcome measures included the total number of oocytes and mature oocytes retrieved, pregnancy rates, implantation and overall cancellation rates which were compared between four mentioned groups. Results: Number of follicles >18?mm on hCG day were significantly higher in GnRH-a long versus GnRH antagonist, GnRH-a short and GnRH-a miniflare protocols. The mean number of oocytes and mature oocytes retrieved were significantly higher in GnRH-a long versus miniflare (4.7?±?3.05 versus 3.26?±?2.9 and 3.69?±?3.1 versus 2.65?±?2.2, respectively). There were no significant differences in implantation, pregnancy and overall cancellation rates between four groups. Conclusion: The present study suggests that the application of four different protocols in poor respond patients seem to have similar efficacy in improving clinical outcomes such as implantation, pregnancy rates and cancellation rate even though GnRH-a long protocol yielded more retrieved oocytes and mature oocytes compared to GnRH-a miniflare protocol.     

Effectiveness of Low Dose of Gonadotropin Releasing Hormone Agonist on Hormonal Flare-Up

Purpose: The hormonal response (flare-up) followingadministration of a standard dose (100 g) or a low dose(25 g) of gonadotropin releasing hormone agonist(GnRH-a) (Triptorelin) was compared in patients prior to an in vitrofertilization (IVF) cycle and during the early follicular phaseof a short-term IVF protocol. Methods: The gonadotroph (FSH, LH) and steroid [estradiol(E₂) and progesterone (P)] flare-up was studied on twoconsecutive cycles in 30 normo-ovulatory women. Patientswere randomized to receive either 25 or 100 g of triptorelinfor three days at the beginning of the first cycle. Then doseswere switched according to a crossing over design in thesecond cycle. Results: No significant difference in the magnitude of FSHand E₂ release could be observed following administrationof the two doses of agonist whereas maximal plasma LHlevel was significantly reduced after injection of 25 g oftriptorelin. Conclusions: As compared to a standard dose, using a lowdose of GnRH-a induces an hormonal flare-up which seemsadequate for an optimal follicular recruitment.     

A controlled trial of natural cycle versus microdose gonadotropin-releasing hormone analog flare cycles in poor responders undergoing in vitro fertilization

OBJECTIVE: To determine the efficacy of natural-cycle IVF compared with controlled ovarian hyperstimulation in poor responders. DESIGN: Randomized, controlled study. SETTING: Private center for assisted reproduction. PATIENT(S): One hundred twenty-nine women who were poor responders in a previous IVF cycle. INTERVENTION(S): Fifty-nine women underwent 114 attempts of natural-cycle IVF, and 70 women underwent 101 attempts of IVF with controlled ovarian hyperstimulation with microdose GnRH analog flare. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, pregnancy rate (PR) per cycle, PR per transfer, and implantation rate. RESULT(S): The poor responders treated with natural-cycle IVF and those treated with micro-GnRH analog flare showed similar PRs per cycle and per transfer. The women treated with natural-cycle IVF showed a statistically significant higher implantation rate (14.9%) compared with controls (5.5%). When subdivided into three groups according to age (or=36-39 years, >or=40 years), younger patients had a better PR than the other two groups. CONCLUSION(S): In poor responders, natural-cycle IVF is at least as effective as controlled ovarian hyperstimulation, especially in younger patients, with a better implantation rate.     

GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial

Objective

To compare the efficacy of the long GnRH agonist and the fixed GnRH antagonist protocols in IVF poor responders.

Study design

This was a randomized controlled trial performed in the Iakentro IVF centre, Thessaloniki, from January 2007 to December 2011, concerning women characterised as poor responders after having 0–4 oocytes retrieved at a previous IVF cycle. They were assigned at random, using sealed envelopes, to either a long GnRH agonist protocol (group I) or a GnRH antagonist protocol (group II).

Results

Overall 364 women fulfilled the inclusion criteria and were allocated to the two groups: finally 330 participated in our trial. Of these, 162 were treated with the long GnRH agonist protocol (group I), and 168 with the fixed GnRH antagonist protocol (group II). Numbers of embryos transferred and implantation rates were similar between the two groups (P = NS). The overall cancellation rate was higher in the antagonist group compared to the agonist group, but the difference was not significant (22.15% vs. 15.2%, P = NS). Although clinical pregnancy rates per transfer cycle were not different between the two groups (42.3% vs. 33.1%, P = NS), the clinical pregnancy rate per cycle initiated was significantly higher in the agonist compared to the antagonist group (35.8% vs. 25.6%, P = 0.03).

Conclusions

Although long GnRH agonist and fixed GnRH antagonist protocols seem to have comparable pregnancy rates per transfer in poor responders undergoing IVF, the higher cancellation rate observed in the antagonist group suggests the long GnRH agonist protocol as the first choice for ovarian stimulation in these patients.     

Efficiency of follicle-stimulating hormone, commenced in the luteal phase, for overcoming a poor response in assisted reproduction

Aim:  The efficacy of commencement of recombinant follicle-stimulating hormone (recFSH) during the luteal phase in the long-protocol gonadotropin-releasing hormone (GnRH) agonist regimen in poor responders was compared with the conventional protocol in a prospective, randomized, controlled study.
Methods:  Forty-two women who responded poorly to previous conventional controlled ovarian hyperstimulation were included in the study. Recombinant FSH (150 IU) was started simultaneously with the GnRH agonist long protocol in the study group. The control group was started recFSH on Day 2 of menstruation in the long-protocol GnRH agonist regimen. The number of metaphase (M) II oocytes, the number of embryos transferred, and the pregnancy rate were analyzed as main outcome measures.
Results:  Patients in the study group had a higher number of MII oocytes compared with the control group (6.8 vs 3.2, respectively; P  < 0.005), received a higher number of embryos (2.7 vs 1.2, respectively; P  < 0.05), and had higher pregnancy rates (38% vs 15%, respectively; P  < 0.005).
Conclusions:  Commencement of recFSH during the luteal phase simultaneously with the long-protocol GnRH agonist regiment in poor responder women produces better results compared with the conventional long-protocol GnRH agonist plus high-dose recFSH regimen.     

Agonist "flare-up" versus antagonist in the management of poor responders undergoing in vitro fertilization treatment

OBJECTIVE: To compare the agonist flare-up and antagonist protocols in the management of poor responders to the standard long down-regulation protocol. DESIGN: Retrospective comparative study. SETTING: Assisted conception center. PATIENT(S): One hundred thirty-four patients undergoing IVF/ intracytoplasmic sperm injection (ICSI) treatment, who responded poorly to the standard long down-regulation protocol in their first treatment cycle. In the second cycle, 77 received short flare-up agonist and 57 received antagonist protocol. We analyzed the outcome of the second cycle. INTERVENTION(S): Peak serum E(2) was assayed on the day of hCG administration. MAIN OUTCOME MEASURE(S): Cycle cancellation rate due to poor ovarian response. RESULT(S): There was no cycle cancellation in the flare-up protocol and 7% cancellation rate in the antagonist protocol due to lack of response. A significantly higher number of patients had embryo transfer in the flare-up protocol. There was no difference in pregnancy rate (PR) between the two groups. CONCLUSION(S): Both the flare-up and the antagonist protocols significantly improved the ovarian response of known poor responders. However, a significantly higher cycle cancellation rate and less patients having embryo transfer in the antagonist group tips the balance in favor of the flare-up protocol.     

A randomized prospective study on the effect of short and long Buserelin treatment in women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response

Fifty four women with repeated unsuccessful in vitro fertilization (IVF) cycles due to inadequate ovarian response to stimulation with human menopausal gonadotropins (hMG) participated in this study. They were randomized to receive either gonadotropin releasing hormone agonist (GNRHa), Buserelin, prior to and during induction of ovulation by hMG (Group I—long protocol), or GnRHa starting on the first day of the cycle together with induction of ovulation by hMG (Group II—short protocol). Mean follicular phase serum luteinizing hormone (LH) and progesterone (P) levels were significantly lower in Group I than in Group II (P<0.01). Cancellation rate was significantly lower in Group I than in Group II (P<0.01). The long GNRHa protocol resulted in statistically significant lower cancellation rates, more oocytes per pickup (OPU), more embryos trans-ferred per patient, and a higher pregnancy rate. Significantly more hMG ampoules and more treatments days were required in the long GNRHa protocol. Our data demonstrate that the use of GNRHa prior to and during ovarian stimulation with hMG offers a very good alternative for patients with repetitive unsuccessful IVF cycles due to inadequate response.     

A comparison of treatment results of the different treatment protocols in patients with poor ovarian response

To compare the effect of the different protocols in patients receiving in vitro fertilization treatment due to poor ovarian response. Seventy-seven of the patients included in the study were treated with gonadotropin (450?IU) + GnRH antagonist (group 1), 84 of the patients were treated with gonadotropin (450 IU) + microdose GnRH analog (group 2), and 53 of the patients were treated with clomiphene citrate (100 mg/day) + gonadotropin (300?IU) + GnRH antagonist (Group 3). In assessing total gonadotropin dosage, patients in Group 3 detected significantly less gonadotropin as compared to the other two groups (p?相似文献   

GnRH拮抗剂配伍HMG方案对卵巢低反应患者IVF—ET治疗结局分析

目的探讨促性腺激素释放激素拮抗剂（GnRH拮抗剂）配伍HMG方案对卵巢低反应患者控制性超排卵的效果，及其对体外受精-胚胎移植结局的影响。方法研究对象为前次IVF—ET治疗失败，证明是卵巢低反应，要求再次IVF—ET治疗的患者，随机分为2组，实验组使用GnRH拮抗剂＋HMG方案，共21个周期，对照组使用GnRH激动剂短方案，共23个周期。将两组患者的年龄、基础FSH水平、Gn使用天数和剂量、hCG日血清E2水平、获卵数、受精率、临床妊娠率、胚胎种植率等进行比较。结果两组患者不孕年限、与前次IVF—ET间隔时间、周期取消率、Gn使用天数、HCG日E2水平、获卵数、受精方式、受精率，胚胎移植数等比较差异均无显著性（P〉0．05）。拮抗剂组与激动剂组的平均年龄分别为：（37．7±3．3）岁和（35．9±4．1）岁；平均基础FSH分别为：（14．21±6．76）μ／L和（10．04±4．60）μ／L。平均Gn使用量：拮抗剂组为（32．3±17．8）支，激动剂组为（39．8±12．2）支。拮抗剂组与激动剂组的临床妊娠和胚胎种植率分别为（42．1％vs10．5％）和（25．7％vs5．0％），两组患者的年龄、基础FSH、平均Gn用量、临床妊娠率、胚胎种植率等比较差异均有显著性（P〈0．05）。结论GnRH拮抗剂与HMG配伍，对卵巢低反应的患者是一种有效的超排卵治疗方案，可以提高IVF—ET的临床妊娠率和胚胎种植率，并且费用低廉。     

Management of the poor responder: the role of GnRH agonists and antagonists

Purpose Evaluate the relative benefit of various doses and regimens of GnRH agonists (GnRHa) and antagonists (GnRHant) in the management of the poor responder. Methods Review of English language publications with an emphasis on prospective randomized trials where available. Results The lack of a uniformly applied definition of the poor responder and dearth of prospective randomized trials make data analysis difficult. Traditional GnRHa flare and long luteal phase protocols do not appear to be beneficial. Reduction of GnRHa doses, “stop” protocols, and microdose GnRHa flare regimes all appear to enhance outcomes, although the relative benefit of one approach over another has not been conclusively demonstrated. GnRHant does improve outcomes in this patient population, although, in general, pregnancy rates appear to be lower in comparison to microdose GnRHa flare regimes. Conclusions There is no one controlled ovarian hyperstimulation (COH) protocol which is best suited for all poor responders. Low dose GnRHa regimes appear to be most advantageous. Prediction of compromised response prior to cycle initiation by a thorough assessment of ovarian reserve as well as a careful review of past response should allow for selection of an appropriate COH protocol for each individual patient. Capsule GnRH antagonists and low dose GnRH agonists have been employed with varying degrees of success in the management of the poor responder.     

超长方案降调节后LH添加时机对子宫内膜异位症患者IVF-ET的影响

目的:探讨在子宫内膜异位症(EMs)合并不孕患者体外受精-胚胎移植(IVF-ET)超促排卵过程中,经超长方案长效GnRH-a降调节后添加LH的合适时机。方法:回顾分析2010年1月至2012年4月在我中心行IVF-ET助孕的118例不孕合并EMs患者,共123个周期。所有周期均采用超长方案,根据添加LH时卵泡的直径分为3组:10～14mm(A组),14～16mm(B组)及≥16mm(C组),比较3组患者的卵巢反应性及IVF妊娠结局。结果:A组的P水平(0.72±0.63)显著低于B组(1.08±0.72)和C组(1.11±0.71)。A组的优质胚胎率和妊娠率分别为75.81%和55.00%,显著高于B、C组;A组获卵数(7.42±4.86)显著低于C组(11.34±5.71)(P<0.05)。结论:EMs合并不孕患者经超长方案长效GnRH-a降调节后,尽早添加外源性LH,可有效降低孕酮水平,提高优质胚胎率和妊娠率。     

Effects of luteal estradiol pre-treatment on the outcome of IVF in poor ovarian responders

Background: In view of the discrepancies about the luteal estradiol treatment before stimulation protocols having some potential advantages compared with the standard protocols in poor ovarian responders undergoing IVF, a meta-analysis of the published data was performed to compare the efficacy of the luteal estradiol pre-treatment protocols in IVF poor response patients. Methods: We searched for all published articles. The searches yielded 32 articles, from which seven studies met the inclusion criteria. We performed this meta-analysis involving 450 IVF patients in luteal estradiol pre-treatment protocol group and 606 patients in standard protocol group. Results: The luteal estradiol protocol resulted in a significantly higher duration of stimulation compared with the standard protocol. In addition, the number of oocytes retrieved and mature oocytes retrieved were significantly higher in the luteal estradiol protocols than those in the standard protocols. The cycle cancellation rate (CCR) in the luteal estradiol protocols was lower than the standard protocols. Moreover, no significant difference was found in the clinical pregnancy rate (CPR). Conclusions: The addition of the estradiol in the luteal phase preceding IVF in poor responders improved IVF cycle outcomes, including increasing the number of oocytes retrieved and mature oocytes retrieved and decreasing the CCR.     

Elevated level of plasma vascular endothelial growth factor after gonadotropin-releasing hormone agonist treatment for leiomyomata

Objective. Uterine leiomyomata are the most common gynecological benign tumor and greatly affect reproductive health and well-being. The pathophysiology and epidemiology of fibroids are poorly understood. Gonadotropin-releasing hormone agonist (GnRH-a) pretreatment is one of the unfavourable factors for leiomyomata treatment with uterine artery embolisation (UAE). In this study, we investigated the plasma level of vascular endothelial growth factor (VEGF) in uterine leiomyoma patients with or without GnRH-a pretreatment.

Study design. Thirty-two women who underwent UAE for symptomatic uterine leiomyoma were analysed. The plasma level of VEGF was studied before UAE.

Results. The level of plasma VEGF was significantly higher in the GnRH-a pretreated group compared with the non-treated group.

Conclusion. A compensative reaction for vasculature after GnRH-a treatment is speculated. Higher level of VEGF in GnRH-a pretreatment group could be one of the unfavourable factors for the treatment of uterine leiomyomata by UAE.     

Relationship between follicular fluid hormone levels,embryo quality,and maternal age during<Emphasis Type="Italic">in vitro</Emphasis> fertilization after the short or long protocol with a gonadotropin releasing hormone agonist

Purpose  To examine the relationship between embryo quality and follicular fluid hormonal level in short and long protocol gonadotrophin releasing hormone agonist treatment cycles. Methods  A total of 90 patients had non-polycystic ovary syndrome (non-PCOS) and 10 had PCOS. A total of 100 subjects underwentin vitro fertilization (IVF). Thirty-six subjects underwent conventional IVF and 64 subjects underwent intra-cytoplasmic sperm injection (ICSI). The dominant follicles were initially retrieved and a hormonal assay was done. A total of 32 patients underwent a short protocol and 66 patients were treated with the long protocol. Estradiol (E₂), progester-one (P₄), total testosterone (TIE) and androstenedione (ASG) levels in follicular fluid (FF) were compared in the two treatment groups (short and long protocol), in regard to maternal age and oocyte/embryo quality. Results  The retrieval FF volume was not significantly different between the PCOS and non-PCOS patients; however, P₄ was significantly lower with PCOS (P < 0.01). Analysis of four different hormone levels was not significantly different between the short and long protocol groups. No significant relationship was found between four hormone levels in regard to oocyte morphology and embryo quality. The levels of P₄ of younger women was significantly lower than that of older women; furthermore, a significantly higher TTE and ASG were found in the younger women. Progesterone was found to statistically significantly increase with FF volume. Conclusion  Follicular fluid P₄ from the younger group was significantly lower, and TTE and ASG was significantly higher when compared to the older group. Analysis of four different hormone levels revealed no significant difference between the short and long protocol groups. No significant relationship was found between four hormone levels, oocyte morphology, and embryo quality.