Mini-dose long gonadotropin-releasing hormone (GnRH) agonist versus agonist flare stimulation protocol for in vitro fertilization poor responders

ObjectivesTo compare 2 stimulation protocols, mini-dose long gonadotropin releasing hormone (GnRH) agonist versus agonist flare for in vitro fertilization poor responders.DesignProspective comparative nonrandomized clinical trial.SettingDr. Samir Abasss IVF center, Jeddah, Kingdom of Saudi Arabia from april 2012 to December 2012 on 50 women undergoing IVF/ICSI fulfilling the criteria of poor responders.Material and methodsPatients were allocated into 2 groups, group 1 (n = 25) received mini-dose long agonist and group 2 (n = 25) received agonist flare protocol.Main outcomeNumber of oocytes retrieved (primary outcome), duration of stimulation (days), peak E2 level on the day of hCG injection, number of fertilized oocytes, number of transferred embryos and pregnancy rate/cycle.ResultsBoth groups were comparable regarding age, body mass index and duration of infertility (years). The difference in basal FSH and duration of stimulation (days) does not reach statistical significance (p value 0.833 and 0.373 respectively). There was a high statistical difference between both groups regarding peak E2 on day of hCG injection, number of oocytes retrieved, number of fertilized oocytes, number of transferred embryos; which is higher in the mini-dose agonist group (p value 0.00).Pregnancy rate/cycle was higher in the mini-dose agonist group (9/25 vs. 6/25) however this difference does not reach statistical significance (p value 0.355) which may be attributed to small sample size or advanced maternal age.ConclusionMini-dose long GnRHa stimulation protocol appears to be more beneficial for poor responders than GnRHa agonist flare.     

Prospective evaluation of two stimulation protocols for low responders who were undergoing in vitro fertilization-embryo transfer

OBJECTIVE: To compare two stimulation protocols designed for low responders undergoing IVF. DESIGN: Randomized, prospective study. SETTING: University hospital IVF unit. PATIENT(S): Sixty low responders who were recruited on the basis of results in previous cycles. INTERVENTION(S): Modified flare protocol in which a high dose of GnRH agonist was administered for the first 4 days, followed by a standard agonist dose, or a modified long protocol in which a standard agonist dose was used until pituitary down-regulation, after which the agonist dose was halved during stimulation. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved. RESULT(S): Twenty-nine cycles were performed with the modified flare protocol and 31 were performed with the modified long protocol. Significantly more oocytes were obtained with the modified long protocol than the modified flare protocol (4.42 +/- 2.6 vs. 3.07 +/- 2.15). The number and quality of embryos available for transfer was similar in both groups. One clinical pregnancy (3.4%) was achieved with the modified flare protocol, and 7 pregnancies (22.5%) were achieved using the modified long protocol. CONCLUSION(S): These preliminary results substantiate the poor prognosis and outcome for low responders undergoing IVF. A modified long "mini-dose" protocol appears to be superior to a modified mega-dose flare protocol in terms of oocyte yield and cycle outcome.     

Cessation of Low-Dose Gonadotropin Releasing Hormone Agonist Therapy Followed by High-Dose Gonadotropin Stimulation Yields a Favorable Ovarian Response in Poor Responders

Purpose: This study is a prospective nonrandomized study to determine the effect of a new protocol of controlled ovarian hyperstimulation (COH) using low doses and a half-period of gonadotropin releasing hormone agonist (GnRHa) followed by high doses of gonadotropin in patients who were supposed to be poor responders to standard long protocols of GnRHa administration. Methods: From Dec 1996 to Nov 1998, 50 patients who were classified as poor responders were scheduled for 52 cycles of a modified controlled ovarian hyperstimulation protocol. They were categorized into 3 groups: a group of poor responders to COH in the previous IVF or IUI cycles, a group with elevated Day 3 FSH levels, and a group over the age of 40 years. All patients received GnRH agonist from the midluteal phase of the previous cycle to the onset of menstruation in the next cycle. Then high doses of gonadotropins (HMG/FSH) were given. The patients then had standard courses of in vitro fertilization and embryo transfer (IVF-ET) or transfallopian embryo transfer (TET). Results: Six of the 52 cycles of the modified protocols were cancelled because of poor ovarian response. One premature ovulation was noted before ovum retrieval was performed. In the other 45 cycles, an average of 6.3 mature oocytes were retrieved. The total pregnancy rate and implantation rate were 20.5 and 11.5%, respectively. Conclusions: The low dose and half duration of GnRHa therapy lessened the suppression of the response of the ovaries to COH compared with the regular long protocol of GnRHa down regulation therapy. This resulted in a low cancellation rate (11.8%), a favorable embryo implantation rate (11.5%), and an acceptable clinical pregnancy rate (20.5%).     

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.     

3种控制性促排卵方案治疗卵巢反应不良效果的比较

目的:探讨3种控制性促排卵方案治疗卵巢反应不良年轻患者的效果。方法:回顾分析2009年6月至2011年7月在中山大学附属第一医院生殖中心行辅助生育治疗、年龄30～40岁、出现2次及以上卵巢反应不良周期患者的所有周期共240个,选取其中标准GnRH激动剂长、短及拮抗剂方案共220个周期。在220个周期中GnRH激动剂长方案86个周期为长方案组、短方案83个周期为短方案组、拮抗剂方案51个周期为拮抗剂方案组。比较3组病例的临床资料、实验室资料和妊娠结局,评估不同促排卵方案治疗卵巢反应不良的结果。结果:短方案组基础FSH高于长方案组(P=0.039),但Gn总量少于长方案组(P=0.000),两组胚胎质量及妊娠结局的差异无统计学意义。短方案组基础FSH与拮抗剂方案组的差异无统计学意义,虽然Gn使用量高于拮抗剂方案组(P=0.000),但获卵数亦高于拮抗剂方案组(P=0.001),且周期取消率低于拮抗剂方案组(P=0.013)。3组其他临床资料(年龄、不孕年限等)、受精数、受精率、可利用胚胎率、胚胎种植率及妊娠结局等差异均无统计学意义(P>0.05)。比较添加生长激素对长、短方案获卵数的影响,差异无统计学意义(P>0.05)。结论:GnRHa短方案用于小于40岁的卵巢反应不良患者的促排卵效果较优。     

A novel strategy of using corifollitropin alfa in the ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol in unselected patients: A patient-friendly alternative

ObjectiveTo compare the outcomes of in vitro fertilization (IVF) and fresh embryo transfer (ET) using corifollitropin alfa in ultrashort gonadotropin-releasing hormone agonist (GnRHa) protocol and GnRH antagonist protocol.Materials and methodsA total of 245 unselected patients undergoing IVF/fresh ET were enrolled between January 1 and December 31, 2017, including 135 treated with ultrashort GnRHa protocol and 110 treated with antagonist protocol. The primary outcomes were number of total injections and outpatient department (OPD) visits before ovulation triggering. The secondary outcomes were the duration of stimulation, dosage of additional gonadotropin for ovarian hyperstimulation, rates of pregnancy, clinical pregnancy, live birth, ovarian response, and ovarian hyperstimulation syndrome (OHSS) rate.ResultsPatients treated with ultrashort GnRHa required less additional gonadotropin, fewer total injections, but had better ovarian responses, including more oocytes retrieved, more metaphase II oocytes, and more blastocysts than those treated with antagonist did. A premature LH surge occurred only in six patients treated with antagonist protocol. The rates of pregnancy (37.0% vs. 43.6%), clinical pregnancy (25.2% vs. 34.6%), and live birth (19.3% vs. 30.0%) did not differ significantly between the two groups. The OHSS rate was similar in the two groups.ConclusionIn unselected patients using corifollitropin alfa, the ultrashort GnRHa protocol needed lower dose of additional gonadotropin and fewer injections but produced similar pregnancy outcomes than antagonist protocol did, suggesting that the ultrashort GnRHa protocol could be an alternative.     

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.     

Comparison of Clinical Outcome and Costs with CC + Gonadotropins and GnRHa + Gonadotropins During IVF/ICSI Cycles

OBJECTIVE: To compare clinical outcome and costs of CC + gonadotropins with GnRHa + gonadotropins during IVF/ICSI cycles. MATERIALS AND METHODS: Clinical outcome and expenses of 382 CC + gonadotropin and 964 GnRHa + gonadotropin cycles were compared. Medication costs were calculated on the basis of the mean number of ampoules and the proportion of various gonadotropins. Costs per clinical pregnancy were calculated on the basis of expenses and clinical pregnancy rates. RESULTS: Women in the CC + gonadotropin group were younger, and had fewer follicles, oocytes, embryos, and embryos transferred. Clinical pregnancy rates were higher in the GnRHa group (35.9 % vs 26.2%, p < 0.001). More ampoules of gonadotropins were used in the GnRHa group (24.0 +/- 0.3 vs 20.0 +/- 0.5, p < 0.001). Medication costs per cycle were higher in the GnRHa group (US dollars 357 vs 248). Expenses per pregnancy however were lower in the GnRHa group (USdollars 4197 vs 5335 with IVF; USdollars 5590 vs 7244 with ICSI). When different age subgroups with similar baseline characteristics and stimulation parameters were compared, pregnancy rates were significantly higher in the GnRHa groups. Medication cost per cycle was higher in the GnRHa subgroups, and the expense per pregnancy was lower with GnRHa protocol. CONCLUSIONS: Cost per cycle is higher with GnRHa + gonadotropin. However, because of the better performance of the GnRHa + gonadotropin stimulation, the cumulative costs are reduced by the time a clinical pregnancy is achieved.     

Luteal start of exogenous FSH in poor responder women

Purpose To compare the effectiveness of using recFSH commenced in the luteal phase with a long GnRH agonist protocol or in the early follicular phase with a short GnRH agonist protocol, in infertile women designated as poor responders undergoing treatment with assisted reproduction in a prospective, randomized, controlled study. Materials and methods Forty-two couples undergoing an ICSI cycle of whom female partner diagnosed as poor responder were included in the study. Recombinant FSH was given daily from day 21 of the previous cycle upon initiation of GnRH agonist in the study group. Control group was given FSH on day 2 in a short protocol GnRH agonist regimen. The number of metaphase 2 oocytes was analysed as the main outcome measure; pregnancy rate and clinical pregnancy rate were secondary outcome measures. Results Patients in the study group had significantly higher number of metaphase 2 oocytes. Although not statistically significantly patients in the study group had higher pregnancy/clinical pregnancy rates, as well. Conclusion This preliminary study shows that luteal start of recFSH simultaneously with long protocol GnRH agonist in poor responder women produced better results comparing to short protocol GnRH agonist plus high dose FSH regimen. Capsule: Luteal administration of recFSH along with GnRHa in poor responder women in an ART cycle increases metaphase 2 oocyte number significantly comparing to GnRHa flare-up protocol     

Comparison of mild and microdose GnRH agonist flare protocols on IVF outcome in poor responders

Purpose  

To compare the IVF outcome of clomiphene citrate/gonadotropin/antagonist (mild protocol) and microdose GnRH agonist flare protocols for poor responders undergoing in vitro fertilization.     

A simplified universal approach to COH protocol for IVF: ultrashort flare GnRH-agonist/GnRH-antagonist protocol with tailored mode and timing of final follicular maturation

Recently, several new promising modifications have been introduced to clinical practice that may simplify and optimize IVF outcome. In the present opinion paper we present a simplified approach to controlled ovarian hyperstimulation protocol (COH), which combines the benefits of the ultrashort flare GnRH agonist/GnRH antagonist protocol and the personalized tailored mode and timing of ovulation triggering, aiming to improve IVF outcome while eliminating of severe OHSS.In patients at risk to develop severe ovarian hyperstimulation syndrome (OHSS), GnRH agonist (GnRHa) trigger if offered for final follicular maturation. While in those achieving ≥20 oocytes, the freeze all policy with the subsequent frozen-thawed embryo transfers (ET) is recommended, in those where less than 20 oocytes are retrieved, patients are re-evaluated 3 days after oocyte retrieval (day of ET) for signs of early moderate OHSS. If no early signs of OHSS developed, one embryo was transferred, and the patients are instructed to inject 1500 IU of HCG. In cases where signs of early moderate OHSS appear, the freeze all policy is recommended.In Patients not at risk to develop severe OHSS- three different modes of concomitant administration of both GnRHa and a standard bolus of hCG (5000–10,000 units) prior to oocyte retrieval were suggested. Standard hCG dose concomitant with GnRHa (dual trigger), 35–37 h before oocyte retrieval is offered to normal responders patients, resulting in improved oocyte/embryo quality and IVF outcome. GnRHa 40 h and standard hCG added 34 h prior to oocyte retrieval (double trigger), respectively are offered to patients demonstrating abnormal final follicular maturation despite normal response to COH. The double trigger results in significantly higher number of oocytes retrieved, 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, higher number of MII oocytes and proportion of MII oocytes per number of oocytes retrieved, with the consequent significantly increased number of top-quality embryos, as compared to the hCG-only trigger cycles. Standard hCG dose concomitant with GnRHa (dual trigger), 34 h before oocyte retrieval should be offered to poor responders patients, aiming to overcome premature luteinization, while achieving high yield of mature oocytes.Further studies are required to support this new concept prior to its implementation as a universal COH protocol to IVF practice.     

GnRH agonist trigger with intensive luteal phase support vs. human chorionic gonadotropin trigger in high responders: an observational study reporting pregnancy outcomes and incidence of ovarian hyperstimulation syndrome

A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had?≥18 follicles?≥11mm or serum oestradiol?>18,000pmol/l on the day of trigger. Patients had a single or double embryo transfer at cleavage or blastocyst stage. Logistic regression was used to adjust for differences between the groups. An intention-to-treat analysis of all cycles was performed. No statistically significant differences were observed in terms of positive pregnancy test, clinical pregnancy rate and live birth rate. Only one patient (0.3%) was hospitalized with severe OHSS in the GnRHa group, compared to 26 patients (13%) in the hCG group. In conclusion, GnRHa trigger is associated with similar pregnancy rates with hCG trigger and a significant reduction in hospitalization for severe OHSS after an intention to treat analysis was performed.     

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.     

Pituitary suppression regimens in poor responders undergoing IVF treatment: a systematic review and meta-analysis

Many randomized trials have evaluated the use of various pituitary suppression regimens to improve outcome of poor responders undergoing IVF treatment. A systematic review was conducted of the trials of gonadotrophin-releasing hormone (GnRH) agonist long regimen, GnRH agonist short regimen, GnRH antagonist regimen, as well as other pituitary suppression regimens in poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. The search included MEDLINE, EMBASE, Cochrane Library, National Research Register and ISI proceedings, and all randomized controlled trials comparing the various pituitary suppression regimens in poor responders were included. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The main outcome measures were number of oocytes retrieved, cycles cancelled before oocyte retrieval and pregnancy rates. A total of 680 women considered as poor responders undergoing IVF/ICSI treatment were included in nine randomized controlled trials. The quality of these studies was variable: for example, only three of the studies had clear evidence of allocation concealment. Meta-analyses of the results of the studies did not show a consistent benefit for any one pituitary suppression regimen over the other regimens in improving outcome measures. Currently available evidence does not favour any one pituitary suppression regimen for women with poor ovarian response undergoing IVF/ICSI treatment.     

Minimal ovarian hyperstimulation for in vitro fertilization using sequential clomiphene citrate and gonadotropin with or without the addition of a gonadotropin-releasing hormone antagonist

OBJECTIVE: To compare the results of a minimal-stimulation protocol with those of a standard protocol used for IVF. DESIGN: Retrospective, controlled study. SETTING: University center. PATIENT(S): Fifty-five patients undergoing IVF using a minimal-stimulation protocol with or without adjuvant therapy with a GnRH antagonist. A control group consisted of age- and diagnosis-matched patients undergoing a standard long GnRH agonist (GnRH-a)-gonadotropin stimulation during the same time period. INTERVENTION(S): Clomiphene citrate and gonadotropins, with or without the GnRH antagonist ganirelix. MAIN OUTCOME MEASURE(S): Oocytes recovered and pregnancy rates. RESULT(S): The number of oocytes retrieved was significantly lower for the minimal-stimulation regimen compared with the case of the long GnRH-a protocol (4.8 +/- 2.6 vs. 16.2 +/- 7.5, respectively). The clinical pregnancy rate per transfer, however, was not significantly different between the two regimens (37% vs. 41%, minimal stimulation vs. long GnRH-a protocol, respectively). The addition of ganirelix resulted in at least the same pregnancy outcome as compared with the case of cycles without the antagonist. CONCLUSION(S): Minimal stimulation using clomiphene citrate followed by gonadotropin for IVF results in pregnancy rates equal to the standard long GnRH-a-gonadotropin protocol. The addition of ganirelix resulted in at least similar results with the advantage of eliminating the occurrence of a premature endogenous LH surge.     

Value of suppression with a gonadotropin-releasing hormone agonist prior to gonadotropin stimulation for in vitro fertilization

This study examined the use of gonadotropin-releasing hormone agonist (GnRHa) suppression before gonadotropin stimulation in 26 patients with failed prior in vitro fertilization (IVF) attempts and variable basal serum gonadotropin levels. Leuprolide, 1 mg subcutaneously per day, was administered from the midluteal phase of the cycle before IVF treatment. Concomitantly, stimulation was initiated on cycle day 3 with human menopausal gonadotropin (hMG) and follicle stimulating hormone (FSH). Based on their prior IVF attempts and serum gonadotropin levels on cycle day 3, 9 patients were high responders with elevated mean basal luteinizing hormone (LH)/FSH, 8 were low responders with elevated mean basal FSH/LH, 7 were intermediate responders with normal mean basal FSH/LH and a history of premature LH surge, and 2 had elevated (perimenopausal) mean FSH and LH. Leuprolide was discontinued on the day of human chorionic gonadotropin (hCG) administration. Prior IVF attempts in the same patients with the same protocol, but without GnRHa suppression, were used as controls. The mean number of ampules of hMG and FSH was significantly higher in leuprolide cycles than in controls. The mean day of hCG administration was also higher for leuprolide cycles than for controls. The mean LH and progesterone levels on the day of hCG were significantly lower in leuprolide cycles. The mean number of preovulatory oocytes aspirated and transferred was higher in leuprolide cycles. Cancellation and pregnancy rates were improved in leuprolide cycles. It is concluded that prior GnRHa suppression is beneficial for follicular recruitment for IVF. More patients with variable basal serum gonadotropin levels need to be studied before definite recommendations are made.     

GnRH Antagonist Improved Blastocyst Quality and Pregnancy Outcome After Multiple Failures of IVF/ICSI–ET with a GnRH Agonist Protocol

BACKGROUND: To determine the efficacy of a gonadotrophin-releasing hormone (GnRH) antagonist, cetrorelix, in improving the quality of embryos and pregnancy outcome, we performed a study in patients with a history of multiple failures of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles with a GnRH agonist (GnRHa) long protocol. METHODS: Forty women with no live births after conventional IVF or ICSI embryo transfer (ET) and subsequent blastocyst transfer (BT) with a GnRHa long protocol entered this study. The treatment protocol consisted of a daily dose of clomiphene citrate 100 mg for 5 days and gonadotrophin injections daily from cycle day 4 onward. Cetrorelix, 0.25 mg/day, was started when the leading follicle reached 14 mm. Induction of ovulation was triggered with human chorionic gonadotrophin (HCG) (N = 36) or GnRHa (N = 4). It was possible to perform BT in 38 patients. RESULTS: Comparison of the results with the results for BT with the previous GnRHa protocol showed no significant differences in number of oocytes retrieved or the zygote- and blastocyst-development rate. With the cetrorelix protocol, however, number of patients whose embryos had developed to at least one expanded blastocyst on day 5 was significantly higher than with the GnRHa protocol (25 vs. 9) (p < 0.001), and 16 of the women became pregnant (42.1%), with 7 delivering 9 infants, 4 ending in abortion (25%), and 5 in progressing. CONCLUSIONS: The use of a GnRH antagonist in controlled ovarian hyperstimulation improves the outcome of pregnancy of patients with a history of multiple failure of IVF/ICSI-ET in a GnRHa protocol, most likely due to improvement of the quality of the blastocysts generated.     

Modified Natural Cycle Using GnRH Antagonist Can Be an Optional Treatment in Poor Responders Undergoing IVF

Purpose: To investigate the efficacy of gonadotrophin-releasing hormone (GnRH) antagonist supplementation during natural cycles in poor responders undergoing IVF-ET treatment.Methods: We retrospectively evaluated 540 cycles of 433 suitable patients who were divided by treatment protocol into modified natural, antagonist, and long agonist groups. There were 52 modified natural cycles with GnRH antagonist supplementation, 200 stimulated cycles with GnRH antagonist, and 288 long GnRH agonist cycles. Cycle characteristics and treatment outcomes were compared between the groups.Results: The mean number of oocytes retrieved in the modified natural group was significantly lower than in the stimulated antagonist and long agonist groups (1.4± 0.5 vs. 2.3± 1.1 and 2.5± 1.1, respectively, p < 0.05). The respective implantation and pregnancy rates were 10% and 14.3%, 6.75% and 10.2%, and 7.4% and 10.6%. Cycle outcome and cycle properties were similar.Conclusions: Modified natural IVF cycle with GnRH antagonist supplementation is a feasible alternative to ovarian stimulation protocols in poor responders.     

Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization-embryo transfer.

AIM: The combination of gonadotropin-releasing hormone (GnRH) antagonist and gonadotropin represents a valid alternative to the classical protocol with GnRH agonist for ovulation induction in patients with polycystic ovary syndrome (PCOS). The use of metformin is of benefit to women with PCOS. The aim of the present study was to compare the stimulation characteristics and in vitro fertilization (IVF)-embryo transfer (ET) outcomes of the standard short GnRH antagonist protocol for ovarian stimulation with or without metformin. MATERIALS AND METHODS:We recruited 40 PCOS patients. The population studied was divided into two groups (A and B). Group A was pretreated for 2 months with metformin 1.5 g/day (Glucophage(R); Merck Pharm), and then stimulated with recombinant follicle-stimulating hormone (rFSH) 150 UI/day (Gonal F(R) 75 UI; Serono). GnRH antagonist, cetrorelix acetate 0.25 mg/day (Cetrotide(R); Serono), was started when the leading follicle reached 14 mm diameter on ultrasound scan. Group B was treated only with rFSH 150 UI/day and GnRH antagonist 0.25 mg/day when the leading follicle was >or=14 mm in diameter. RESULTS: In group A we found a statistically significant (p < 0.05) decrease in the number of ampoules of rFSH (A vs. B: 18+/-6 vs. 24+/-8) and estradiol levels (A vs. B: 2400+/-600 vs. 3370+/-900 pg/ml) (all values mean+/-standard deviation). Group A had significantly fewer cancelled cycles (A vs. B: 1 vs. 3; p < 0.05). The incidence of ovarian hyperstimulation syndrome was 5% in group A and 15% in group B (p < 0.05). In patients treated with metformin, the total number of follicles on the day of human chorionic gonadotropin treatment (23+/-1.2 vs. 33+/-2.6) was decreased with no change in the number of follicles >or=14 mm in diameter (A vs. B: 18+/-1.2 vs. 19+/-1.7). However, the mean number of mature oocytes (A vs. B: 8.4+/-1.5 vs. 5.0+/-1.5) was increased with metformin treatment (p < 0.05). No difference was found in the number of cleaved embryos (A vs. B: 2.5+/-0.5 vs. 2.2+/-0.3). CONCLUSIONS: The use of metformin with GnRH antagonist improves the outcome of ovarian stimulation in IVF-ET cycles in PCOS patients.     

促性腺激素释放激素激动剂超短方案在超促排卵中的应用

目的：探讨促性腺激素释放激素激动剂（ＧｎＲＨ－ａ）超短方案在促排卵中的作用。方法：以采用克罗米芬联合人绒毛膜促性腺激素（ＣＣ／ｈＣＧ组，５０个周期、３１例），及克罗米芬联合人绝经期促性腺激素、绒毛膜促性腺激素（ＣＣ／ｈＭＧ／ｈＣＧ组，１６个周期、１６例）方案者为对照，对比ＧｎＲＨ－ａ超短方案联合人绝经期促性腺激素、绒毛膜促性腺激素方案者（ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ组，１５个周期、１５例）ｈＣＧ注射日激素水平、优势卵泡个数、子宫内膜厚度、宫颈评分及妊娠率。ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ组全部来自采用ＣＣ助孕失败或采用ＣＣ／ｈＭＧ／ｈＣＧ方案显示卵巢反应性差的患者。结果：ＣＣ／ｈＭＧ／ｈＣＧ组有３例（１８．８％）发生过早黄素化。ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ组ｈＣＧ注射日血清黄体生成素（ＬＨ）水平明显低于对照组，其优势卵泡个数、子宫内膜厚度及宫颈评分都明显高于对照组，差异均具有显著性（Ｐ＜０．０５）。３组周期妊娠率相近。结论：ＧｎＲＨ－ａ超短方案／ｈＭＧ／ｈＣＧ方案为一种较好的促超排卵方案，对ＣＣ助孕失败及ＣＣ／ｈＭＧ／ｈＣＧ方案卵巢反应性差的患者仍有较好的效果。