GnRH-antagonist Multiple-dose Protocol Research Articles

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept

Aim: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase. Patients and Methods: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle. Results: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%). Conclusions: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients’ subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Stop GnRH-Agonist Combined With Multiple-Dose GnRH-Antagonist Protocol for Patients With "Genuine" Poor Response Undergoing Controlled Ovarian Hyperstimulation for IVF.

Objective: To examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may improve conventional IVF/intracytoplasmic sperm injection (ICSI) cycle in poor ovarian response (POR) patients.Design: Cohort historical, proof of concept study.Setting: Tertiary, University affiliated Medical Center.Patient(s): Thirty POR patients, defined according to the Bologna criteria, who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist controlled ovarian hyperstimulation (COH) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle, were included. For the purposes of this study, we eliminated a bias in this selection by including only “genuine” poor responder patients, defined as those who yielded up to 3 oocytes following COH with a minimal gonadotropin daily dose of 300 IU.Main Outcome Measure(s): Number of oocytes retrieved, number of top-quality embryos, COH variables.Result(s): The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly higher numbers of follicles >13 mm on the day of hCG administration, higher numbers of oocytes retrieved, and top-quality embryos (TQE) with an acceptable clinical pregnancy rate (16.6%). Moreover, as expected, patients undergoing the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol required significantly higher doses and a longer duration of gonadotropins stimulation.Conclusion(s): The combined Stop GnRH-ag/GnRH-ant COH protocol is a valuable tool in the armamentarium for treating “genuine” poor ovarian responders. Further, large prospective studies are needed to elucidate its role in POR and to characterize the appropriate patients subgroup (before initiating ovarian stimulation) that may benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol for patients with IVF failures due to poor embryo quality-A proof of concept

Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol for patients with IVF failures due to poor embryo quality-A proof of concept

The role of Letrozole (LE) in controlled ovarian stimulation (COS) in patients at high risk to develop ovarian hyper stimulation syndrome (OHSS). A prospective randomized controlled pilot study

BackgroundRecently, it has been shown that PCOS patients with extremely high anti-Mullerian hormone (AMH) level are more likely to experience OHSS during IVF, compared to PCOS patients with lower AMH level. While recent data questioned the effect of Letrozole (LE) on the occurrence of OHSS in non-PCOS patients, it role in PCOS patients with very high AMH level was never investigated in a prospective manners. Hence, our main objective was to evaluate the clinical outcome of PCOS patients at very high risk for OHSS undergoing two different COS protocols (with or without LE). MethodsA prospective randomized controlled study (RCT) of 51 patients with specifically high levels of AMH undergoing one of two COS protocols. The control group (group A) consisted of 24 PCOS women who received low-dose gonadotropins using the multiple-dose GnRH-antagonist protocol, GnRH agonist-triggered and “freeze all”. The study group (group B) consisted of 24 women with PCOS who received the same protocol combined with LE. High risk criteria for OHSS were: PCOS patients with low BMI, young age, and extremely high level of serum AMH (inclusion criteria for AMH > 50 pmol/L). ResultsCumulative live birth rates per retrieval were similar in both groups. While no single case of severe OHSS was observed in, in the study group (group B), the rate of moderate and mild OHSS was 5 times lower compared to the control group (P < 0.05). ConclusionIn PCOS patients with extremely high AMH levels the LE co-administration to GnRH-Ant protocols results in reduced incidence of OHSS than conventional GnRH-Ant protocols. LE co-administration may prove to be highly effective in preventing OHSS, even in the women who are at high risk to these dangerous complications.

Should corifollitropin alfa be offered to patients with “genuine” poor response to controlled ovarian hyperstimulation?

Objective: To examine whether poor ovarian response (POR) patients during conventional IVF/ intracytoplasmic sperm injection (ICSI) cycle, may benefit from multiple-dose GnRH-antagonist protocol with 150 mg of corifollitropin alfa via a cohort historical study. at a Tertiary, University affiliated Medical Center. Materials and Methods: Eighteen POR patients, defined according to the Bologna criteria, who underwent a subsequent 150 mg corifollitropin alfa cycle, within three months of the previous failed conventional IVF/ICSI cycle were included. The elimination of bias in this selection, for the purposes of this study, was achieved by including only a subgroup of “genuine” poor responder patients, those who yielded up to three oocytes following COH with a minimal gonadotropin daily dose of 300 IU. One hundred fifty mg corifollitropin alfa, administered on day 2-3 of the menstrual cycle, followed highly purified human menotropin (HP-hMG) or rFSH + rLH from stimulation day 5-6, within a flexible multiple-dose GnRH-antagonist COH cycle. Pregnancy rate, number of oocytes retrieved, number of embryos transferred, and COH variables were assessed. Results: The corifollitropin alfa COH protocol provided a non-significant one more oocyte, with no pregnancies. Considering the equivalence of 150 mg corifollitropin alfa to 2,100 IU of FSH, offering corifollitropin has no cost-effective advantages. Discussion: The corifollitropin alfa COH is of no benefit for “genuine” POR and alternative strategies, such as increasing the daily FSH dose or proceeding to egg-donation, should be seriously considered for this population.

Performance of prognostic modelling of high and low ovarian response to ovarian stimulation for IVF.

What is the performance of previously established regression models in predicting low and high ovarian response to 150 μg corifollitropin alfa/GnRH-antagonist ovarian stimulation in an independent dataset? The outcome of ovarian stimulation with 150 μg corifollitropin alfa in a fixed, multiple dose GnRH-antagonist protocol can be validly predicted using logistic regression models with AMH being of paramount importance. Predictors of ovarian response have been identified in FSH/GnRH agonist protocols as well as ovarian stimulation with corifollitropin alfa/GnRH-antagonist. Multivariable response models have been established already, however, external validation of model performance has so far been lacking. Data from a prospective, multi-centre (n = 5), multi-national, investigator-initiated, observational cohort study were analysed. Infertile women (n = 211), body weight >60 kg, were undergoing ovarian stimulation with 150 μg corifollitropin alfa in a GnRH-antagonist multiple dose protocol for transvaginal oocyte retrieval for IVF. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle Day 2 or 3 of spontaneous menstruation before ovarian stimulation. Main outcomes were low (<6 oocytes) and high (>18 oocytes) ovarian response. Firstly, previously established prediction models for low ovarian response (LOR) and high ovarian response (HOR) were tested using the original parameters. Secondly, re-estimated parameters generated from the present data were tested on the established models. Thirdly, for the development of new predictive models of both LOR and HOR, several logistic regression models were estimated. Resulting prediction models were compared by means of the area under the receiver operating characteristic curve (AUC) and bias-corrected Akaike's Information Criterion (AICc) to identify the most reasonable model for each scenario. The previously established prediction models for low and high response performed remarkably well on this dataset (low response AUC 0.8879 (95% CI: 0.8185-0.9573) and high response AUC 0.8909 (95% CI: 0.8251-0.9568)). A newly developed simplified model for LOR with log-transformed AMH values and only age as another covariate showed an AUC of 0.8920 (95% CI: 0.8237-0.9603) with the lowest AICc of all models compared. For predicting HOR, we suggest a simplified model using AMH, FSH and AFC (AUC of 0.8976, 95% CI: 0.8206-0.9746). All analyses were done on data from women with a body weight >60 kg. The newly developed simplified models may suffer from overfitting and need to be tested in further independent data sets. Patient selection for ovarian stimulation with corifollitropin alfa should utilize established response prediction models. The clinical impact of this needs to be evaluated in future studies. The study was funded by university funds. M.O.S., T.L. and I.R.K. have nothing to declare. G.G. has received personal fees and non-financial support from MSD, Ferring, Merck-Serono, Finox, TEVA, IBSA, Glycotope, Abbott, Marckryl Pharma, VitroLife, NMC Healthcare, ReprodWissen, ZIVA and BioSilu. Not applicable.

Ovarian response to 150 µg corifollitropin alfa in a GnRH-antagonist multiple-dose protocol: a prospective cohort study

The incidence of low (<6 oocytes) and high (>18 oocytes) ovarian response to 150 µg corifollitropin alfa in relation to anti-Müllerian hormone (AMH) and other biomarkers was studied in a multi-centre (n = 5), multi-national, prospective, investigator-initiated, observational cohort study. Infertile women (n = 212), body weight >60 kg, underwent controlled ovarian stimulation in a gonadotrophin-releasing hormone-antagonist multiple-dose protocol. Demographic, sonographic and endocrine parameters were prospectively assessed on cycle day 2 or 3 of a spontaneous menstruation before the administration of 150 µg corifollitropin alfa. Serum AMH showed the best correlation with the number of oocytes obtained among all predictor variables. In receiver-operating characteristic analysis, AMH at a threshold of 0.91 ng/ml showed a sensitivity of 82.4%, specificity of 82.4%, positive predictive value 52.9%and negative predictive value 95.1% for predicting low response (area under the curve [AUC], 95% CI; P-value: 0.853, 0.769–0.936; <0.0001). For predicting high response, the optimal threshold for AMH was 2.58 ng/ml, relating to a sensitivity of 80.0%, specificity 82.1%, positive predictive value 42.5% and negative predictive value 96.1% (AUC, 95% CI; P-value: 0.871, 0.787–0.955; <0.0001). In conclusion, patients with serum AMH concentrations between approximately 0.9 and 2.6 ng/ml were unlikely to show extremes of response.

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.

The comparison of the effect on IVF results of metformin and insulin used during IVF cycles of infertile women with overt diabetes

To compare the effect of metformin and insulin on controlled ovarian stimulation (COS) and IVF results in infertile women with type 2 diabetes undergoing IVF/intracytoplasmic sperm injection (ICSI). Retrospective cohort study. A total of 52 consecutive IVF/ICSI cycles were included in 35 women with preexisting type 2 diabetes who were treated with either the metformin (metformin group, 29 cycles) or the insulin (insulin group, 23 cycles) for glycemic control. IVF/ICSI cycles in which a GnRH antagonist multiple dose protocol (MDP) is used for COS was included in this study. There were no significant differences in patient's characteristics between metformin and insulin groups. There were also no differences in total dose and days of recombinant human FSH (rhFSH) administered, and numbers of retrieved oocytes, mature oocytes, fertilized oocytes, and embryos transferred between the two groups. However, the number of grade 1 or 2 embryos was significantly higher in metformin group of 3.9 ± 2.9 compared with 2.2 ± 2.3 in insulin group (P = .025). Follicular fluid (FF) TNF-a and IL-6 concentrations at oocyte retrieval were significantly lower in metformin group than in insulin group (P = .030, P = .009). There were no differences in the clinical pregnancy rate, embryo implantation rate, miscarriage rate and multiple pregnancy rate between the two groups. The use of metformin for glycemic control is more effective in reducing FF TNF-a and IL-6 levels in COS cycles and improving embryo quality compared with insulin treatment in infertile women with type 2 diabetes undergoing IVF/ICSI.

Corifollitropin alfa versus daily recombinant FSH treatment for controlled ovarian stimulation in poor responders

To compare the effect of long-acting recombinant FSH (rFSH), corifollitropin alfa with daily rFSH administered during 1st 7days of controlled ovarian stimulation (COS) using GnRH antagonist multiple dose protocol (MDP) in poor responders undergoing IVF/intracytoplasmic sperm injection (ICSI).

Luteal estradiol supplementation in gonadotropin-releasing hormone antagonist cycles for infertile patientsin vitrofertilization

ObjectiveTo evaluate the effect of the addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles for infertile patients undergoing IVF/ICSI.MethodsOne hundred and ten infertile patients, aged 28 to 39 years, were recruited for this prospective randomized study. They were randomly assigned to receive vaginal progesterone gel (Crinone) along with 4 mg estradiol valerate (group 1, n=55) or only Crinone (group 2, n=55) for luteal support. A GnRH antagonist multiple dose protocol using recombinant human FSH was used for controlled ovarian stimulation (COS) in all of the subjects. The COS results and pregnancy outcomes of the two groups were compared.ResultsGroup 1 and 2 were comparable with respect to the patient characteristics. The COS and IVF results were also comparable between the two groups. There were no differences in the clinical pregnancy rate (PR) and multiple PR between the two groups. However, the embryo implantation rate were significantly higher in group 1 than that in group 2 (22.2% vs. 13.3%, p=0.035). The incidence of luteal vaginal bleeding (LVB) was significantly lower in group 1 (7.4% vs. 27.8%, p=0.010).ConclusionThe addition of estradiol to luteal progesterone supplementation in GnRH antagonist cycles reduces the incidence of LVB and increases the embryo implantation rate in infertile patients undergoing IVF/ICSI.

Follicular fluid concentrations of IGF-I, IGF-II, IGFBP-3, VEGF, AMH, and inhibin-B in women undergoing controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist

To compare follicular fluid concentrations of IGF-I, IGF-II, IGFBP-3, inhibin-B, VEGF, and AMH in women undergoing controlled ovarian hyperstimulation with a long-luteal GnRH agonist protocol or multiple-dose GnRH antagonist protocol. A total of 80 cycles were included; long-luteal GnRH agonist group (n=40) and multiple dose GnRH antagonist group (n=40). All follicular fluid samples were obtained from mature follicles during oocyte retrieval. IGF-I and IGFBP-3 concentrations were measured by immunoradiometric assay. IGF-II, VEGF, AMH, and inhibin-B concentrations were measured by enzyme-linked immunosorbent assay. There were no significant differences in the concentrations of the studied follicular fluid markers, cycle parameters, and treatment outcomes between GnRH agonist and GnRH antagonist protocols. The long-luteal GnRH agonist protocol and multiple-dose GnRH antagonist protocol seem to have similar effects on the follicular microenvironment in women undergoing controlled ovarian hyperstimulation.

Effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase compared with GnRH agonist long protocol in non-obese and obese patients with polycystic ovary syndrome undergoing IVF/ICSI

ObjectiveTo evaluate the effectiveness of GnRH antagonist multiple dose protocol applied during early and late follicular phase (MDP-EL) in comparison with standard GnRH agonist luteal long protocol (LP) in each non-obese and obese polycystic ovary syndrome (PCOS) women undergoing IVF.MethodsTwo hundred eleven infertile women with PCOS were recruited and randomized to undergo either GnRH antagonist MDP-EL (antagonist group) or standard GnRH agonist luteal LP (agonist group). IVF cycle outcomes were compared between the two groups.ResultsTotal dose and days of recombinant human follicle stimulating hormone (rhFSH) administered were significantly fewer in the antagonist group than in the agonist group. Incidence of severe ovarian hyperstimulation syndrome was significantly lower in the antagonist group. However, IVF and pregnancy outcomes were similar in the two groups. When all subjects were divided into non-obese and obese subgroups, in non-obese PCOS subgroup, IVF and pregnancy outcomes were comparable in the antagonist and agonist groups but total dose and days of rhFSH were also significantly fewer in the antagonist group. Similar findings were also observed in obese PCOS subgroup.ConclusionGnRH antagonist MDP-EL is at least as effective as GnRH agonist LP and may be a more patient-friendly alternative in controlled ovarian stimulation for PCOS patients undergoing IVF, independent of body mass index.

GnRH antagonist multiple dose protocol with oral contraceptive pill pretreatment in poor responders undergoing IVF/ICSI

ObjectiveTo investigate the effectiveness of GnRH antagonist multiple-dose protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment and GnRH agonist low-dose long protocol (LP).MethodsA total of 120 poor responders were randomized into three groups according to controlled ovarian stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1), GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low-dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were pretreated with OCP for 21days in the cycle preceding COS, and ovarian stimulation using recombinant human FSH (rhFSH) was started 5 days after discontinuation of OCP.ResultsThere were no differences in patients' characteristics among three groups. Total dose and days of rhFSH used for COS were significantly higher in group 3 than in group 1 or 2. The numbers of mature oocytes, fertilized oocytes and grade I, II embryos were significantly lower in group 2 than in group 1 or 3. There were no significant differences in the clinical pregnancy rate and implantation rate among three groups.ConclusionGnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH agonist low-dose LP in poor responders and can benefit the poor responders by reducing the amount and duration of FSH required for follicular maturation.

The effect of transdermal testosterone gel pretreatment on controlled ovarian stimulation and IVF outcome in low responders

To investigate the effectiveness of treatment with transdermal testosterone gel (TTG) before controlled ovarian stimulation (COS) using GnRH antagonist multiple-dose protocol (MDP) in low responders undergoing IVF/intracytoplasmic sperm injection (ICSI). Prospective randomized controlled trial. University-affiliated infertility clinic. A total of 110 low responders, who were defined as patients who failed to produce ≤ 3 follicles with a mean diameter of ≥ 16 mm with the result that ≤ 3 oocytes were retrieved despite the use of a high gonadotropin dose (>2,500 IU) in a previous failed IVF/ICSI cycle. Patients were randomized into TTG pretreatment group or control group. For TTG pretreatment group, 12.5 mg TTG were applied daily for 21 days in the cycle preceding COS for IVF. COS results and IVF outcome. There were no differences in patients' characteristics between the two groups. Total dose and days of rhFSH used were significantly fewer in the TTG pretreatment group than in the control group. The numbers of oocytes retrieved, mature oocytes, fertilized oocytes, and good-quality embryos were significantly higher in the TTG pretreatment group. Embryo implantation rate and clinical pregnancy rate per cycle initiated also were significantly higher in the women pretreated with TTG. No patient reported adverse effects attributed to TTG use. TTG pretreatment might be beneficial in improving both response to COS and IVF outcome in low responders undergoing IVF/ICSI.

Somatostatin analogue cotreatment is effective on ovarian response to controlled ovarian stimulation in nonobese patients with polycystic ovary syndrome, but not in obese women

OBJECTIVE: To investigate the effects of somatostatin analogue, octreotide, given concurrently with recombinant human follicle stimulating hormone (rhFSH) on ovarian response to controlled ovarian stimulation (COS) according to body mass index (BMI) in infertile patients with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate (CC). DESIGN: Prospective, randomized controlled trial. MATERIALS AND METHODS: COS was performed using GnRH antagonist multiple-dose protocol in early and late follicular phase (MDP-EL) for all patients. Patients were randomly allocated either to octreotide or control groups in each nonobese (BMI < 23)(n=80) and obese (BMI ≥ 23)(n=64) PCOS groups. For octreitide groups, 100 micrograms of octreotide were administered daily concomitantly with rhFSH from the starting day of COS up to the day of human chorionic gonadotropin (HCG) injection. RESULTS: Two cycles in the control group of nonobese patients and one cycle in the control group of obese patients were abandoned because of excessive follicular development. In nonobese patients, the number of follicles ≥ 14mm, serum estradiol and IGF-1 levels on the day of hCG injection, and the number of retrieved oocytes were lower in octreotide group (P<0.001, P<0.001, P=0.005, P=0.002, respectively). However, in obese patients, there were no differences in COS results except rhFSH dose used between octreotide and control groups. In nonobese patients, the incidence of severe ovarian hyperstimulation syndrome (OHSS) was lower in octreotide group, with 15% (6/40) compared with 0% in control group (P=0.026). There were no differences in the clinical pregnancy rate and miscarriage rate between octreotide and control groups in both nonobese and obese groups. CONCLUSION: Octreotide supplementation to rhFSH in COS cycles is beneficial in reducing the excessive follicular development and the incidence of severe OHSS without a deleterious effect on pregnancy outcome in nonobese PCOS patients, but this treatment does not work in obese PCOS patients.

Impact of GnRH analogues on oocyte/embryo quality and embryo development in in vitro fertilization/intracytoplasmic sperm injection cycles: a case control study

BackgroundDespite the clinical outcomes of ovarian stimulation with either GnRH-agonist or GnRH-antagonist analogues for in vitro fertilization (IVF) being well analysed, the effect of analogues on oocyte/embryo quality and embryo development is still not known in detail. The aim of this case-control study was to compare the efficacy of a multiple-dose GnRH antagonist protocol with that of the GnRH agonist long protocol with a view to oocyte and embryo quality, embryo development and IVF treatment outcome.MethodsBetween October 2001 and December 2008, 100 patients were stimulated with human menopausal gonadotrophin (HMG) and GnRH antagonist in their first treatment cycle for IVF or intracytoplasmic sperm injection (ICSI). One hundred combined GnRH agonist + HMG (long protocol) cycles were matched to the GnRH antagonist + HMG cycles by age, BMI, baseline FSH levels and by cause of infertility. We determined the number and quality of retrieved oocytes, the rate of early-cleavage embryos, the morphology and development of embryos, as well as clinical pregnancy rates. Statistical analysis was performed using Wilcoxon's matched pairs rank sum test and McNemar's chi-square test. P < 0.05 was considered statistically significant.ResultsThe rate of cytoplasmic abnormalities in retrieved oocytes was significantly higher with the use of GnRH antagonist than in GnRH agonist cycles (62.1% vs. 49.9%; P < 0.01). We observed lower rate of zygotes showing normal pronuclear morphology (49.3% vs. 58.0%; P < 0.01), and higher cell-number of preembryos on day 2 after fertilization (4.28 vs. 4.03; P < 0.01) with the use of GnRH antagonist analogues. The rate of mature oocytes, rate of presence of multinucleated blastomers, amount of fragmentation in embryos and rate of early-cleaved embryos was similar in the two groups. Clinical pregnancy rate per embryo transfer was lower in the antagonist group than in the agonist group (30.8% vs. 40.4%) although this difference did not reach statistical significance (P = 0.17).ConclusionAntagonist seemed to influence favourably some parameters of early embryo development dynamics, while other morphological parameters seemed not to be altered according to GnRH analogue used for ovarian stimulation in IVF cycles.

Co-transfer of fresh and collected cryopreserved embryos (COFACCE) obtained in minimal stimulation cycles for low responders

OBJECTIVE: To investigate the effectiveness of co-transfer of fresh and collected cryopreserved embryos obtained in minimal stimulation cycles for low responders. DESIGN: Retrospective cohort study. MATERIALS AND METHODS: We analyzed a total of 12 infertile women with a low response cycle to controlled ovarian stimulation(COS) in a previous cycle, who underwent co-transfer of fresh and collected cryopreserved embryos (COFACCE). All patients received COS using minimal stimulation with rhFSH and GnRH antagonist in all IVF cycles. Retrieved oocytes were inseminated and 2 pronucleate zygotes were cryopreserved and collected. When fresh oocytes were retrieved and fertilized in the next cycle after three cryopreserved embryos were collected, COFACCE was performed. As a nonrandomized control group, we selected 12 patients who underwent the standard GnRH antagonist multiple-dose protocol (MDP) at the same time, matched according to age and ovarian response to COS in a previous cycle. In both groups, only one completed cycle per patient was analyzed. RESULTS: For COFACCE cycles, oocyte retrieval was successfully performed in 45 cycles out of 53 initiated cycles(84.9%). The mean number of initiated cycles required for one COFACCE cycle was 4.4±0.7. Total dose and days of rhFSH used per initiated cycle were 397.6±138.4 IU and 2.8±0.9 days. Cumulative total dose of rhFSH used per completed cycle were significantly lower in COFACCE group than in control group (P=0.0001). The mean numbers of grade I/II embryos and embryos transferred per completed cycle were significantly higher in COFACCE group (P=0.0001, P=0.004, respectively). The clinical pregnancy rate was higher in COFACCE group, with 41.7% (5/12) per COFACCE cycle compared with 16.7% (2/12) per ET cycle in control group, but statistical significance was not found. CONCLUSIONS: COFACCE trial can be a cost-effective and patient-friendly alternative for low responders and therefore, it can be considered as the last chance before egg donation.

Comparison of GnRH antagonist protocol with or without oral contraceptive pill pretreatment and GnRH agonist low-dose long protocol in low responders undergoing IVF/intracytoplasmic sperm injection

This prospective randomized study was performed to compare the efficacy of GnRH antagonist multiple-dose protocol (MDP) with or without oral contraceptive pill (OCP) pretreatment and GnRH agonist low-dose long protocol (LP) in 82 patients undergoing IVF/intracytoplasmic sperm injection (ICSI). GnRH antagonist MDP with OCP pretreatment was at least as effective as GnRH agonist low-dose LP in low responders, and can benefit the low responders by reducing the amount of FSH and the number of days of stimulation required for follicular maturation.

Microdose gonadotropin-releasing hormone agonist flare-up protocol versus multiple dose gonadotropin-releasing hormone antagonist protocol in poor responders undergoing intracytoplasmic sperm injection–embryo transfer cycle

To compare the efficacy of microdose GnRH agonist (GnRH-a) flare-up and multiple dose GnRH antagonist protocols in patients who have a poor response to a long luteal GnRH-a protocol. Prospective, randomized, clinical study. University hospital. Forty-two poor responder patients undergoing intracytoplasmic sperm injection (ICSI)-embryo transfer cycle. Twenty-one patients received microdose leuprolide acetate (LA) (50 microg twice daily) starting on the second day of withdrawal bleeding. The other 21 patients received 0.25 mg of cetrorelix daily when the leading follicle reached 14 mm in diameter. Serum E(2) levels, number of growing follicles and mature oocytes, embryo quality, dose of gonadotropin used, cancellation, fertilization, implantation rate and pregnancy rate (PR). The mean serum E(2) concentration on the day of hCG administration was significantly higher in the microdose GnRH-a group than in the GnRH antagonist group (1,904 vs. 1,362 pg/mL). The clinical PRs per started cycle of microdose GnRH-a and GnRH antagonist groups were 14.2% and 9.5%, respectively. There were no statistically significant differences in the other ovulation induction characteristics, fertilization and implantation rates. Microdose GnRH-a flare-up protocol and multiple dose GnRH antagonist protocol seem to have similar efficacy in improving treatment outcomes of poor responder patients.