Dose Of GnRH Antagonist Research Articles

P–685 Luteinization after final oocyte maturation induction is not compromised in women that receive double dose of Gonadotrophin-releasing hormone antagonists during controlled ovarian hyperstimulation

Abstract Study question Does the use of double dose of GnRH antagonists during COH in women with risk of premature LH surge alter luteinization after final oocyte maturation induction? Summary answer The use of double dose of GnRH antagonist in women with risk of premature luteinizing hormone surge dosent affect luteinization after final oocyte maturation induction. What is known already GnRH antagonists are used to prevent a premature LH surge during controlled ovarian hyperstimulation. The antagonists directly inhibit gonadotrophin release within several hours through competitive binding to pituitary GnRH receptors, producing a rapid suppression of LH and FSH, with no initial flare effect. In women with diminished ovarian reserve (DOR) it is not uncommon that premature luteinization cannot be completely prevented using a daily dose GnRH antagonist. To date, no study has evaluated the effects of using a daily double dose of GnRH antagonists to prevent a premature LH surge and its effect on luteinization after final oocyte maturation induction. Study design, size, duration This monocentric retrospective analysis evaluated the effect on luteinization after final oocyte maturation induction in twenty women during COH who received a daily double dose of GnRH antagonists (Cetrotide 0.25 mg/mL, Merck) from January 2020 to December 2020. Participants/materials, setting, methods Women with severe DOR and history of premature luteinization during COH received a double dose of GnRH antagonist when the leading follicle reached 12–14 mm (am and pm). When two follicles reached ≥18 mm in diameter, final oocyte maturation was induced with dual trigger using Leuprolide acetate and hCG. Progesterone, estradiol, bHCG, and LH levels were measured the day after final oocyte maturation induction to assure adequate luteinization. Main results and the role of chance In total twenty women were included in the analysis. Mean age 36.8± 4.2, AMH 0.65± 0.32 ng/ml, baseline antral follicle count 4± 2.3, serum hormone levels the day of ovulation induction trigger: progesterone 0.89± 0.34 ng/ml, LH 1.6± 2.1 ng/ml, estradiol 1235 ± 1420 pg/ml. Post-surge serum hormone levels average reached adequate levels: estradiol 1645 ± 1116 pg/ml, progesterone 20.4 ±2.2 ng/ml, LH 62.66± 10.5 IU/ml and, bHCG 247±115 IU/ml. A total of 76 oocytes were retrieved (3.8± 0.8 oocytes per patient), 63.1% (48/76) MII, 22% (17/76) MI, 14% (11/76) GV. Limitations, reasons for caution The retrospective nature of the study, small sample size, and potential variability in the study center’s laboratory protocol(s) compared to other reproductive treatment centers may limit the external validity of our findings. Wider implications of the findings: The daily use of double dose of GnRH antagonists during COH offers the possibility of preventing a premature LH surge in women with DOR with high risk of early ovulation, without compromising luteinization after final oocyte maturation induction. Trial registration number NA

Discovery of a Lead Brain-Penetrating Gonadotropin-Releasing Hormone Receptor Antagonist with Saturable Binding in Brain.

We report the synthesis, radiosynthesis and biological characterisation of two gonadotropin‐releasing hormone receptor (GnRH−R) antagonists with nanomolar binding affinity. A small library of GnRH−R antagonists was synthesised in 20–67 % overall yield with the aim of identifying a high‐affinity antagonist capable of crossing the blood–brain barrier. Binding affinity to rat GnRH−R was determined by autoradiography in competitive‐binding studies against [125I]buserelin, and inhibition constants were calculated by using the Cheng–Prusoff equation. The radioligands were obtained in 46–79 % radiochemical yield and >95 % purity and with a molar activity of 19–38 MBq/nmol by direct nucleophilic radiofluorination. Positron emission tomography imaging in rat under baseline conditions in comparison to pretreatment with a receptor‐saturating dose of GnRH antagonist revealed saturable uptake (0.1 %ID/mL) into the brain.

Comparing the Implications of IVF-Induced Pregnancy by Two Regimens with a Flexible Dose of GnRH Antagonist and a Half Fixed Dose of GnRH Antagonist

Introduction: In an IVF cycle after ovulation stimulation, the goal is to prevent LH surge and wasting follicles. The use of GnRH antagonists to achieve this goal has been considered by infertility specialists in recent years. Two fixed or flexible drug regimens have been tested. The aim of this study was to compare the implications of induced pregnancy by two regimens with a flexible dose of GnRH antagonist and a half fixed dose of GnRH antagonist that was evaluated for the first time. Materials and Methods: This randomized double-blinded controlled trial was conducted on 140 patients referring to the infertility department of Shariati Hospital between June 2017 and June 2018 who were candidates for IVF. Patients who were candidates for cyclic therapy with GnRH antagonists were randomly assigned (with a randomized table of numbers) to either the fixed dose group with a half dose of the GnRH antagonist (Group A, n = 70) or the flexible GnRH antagonist dose (Group B, n = 70). Results: There was also difference in the numbers of IVF or IUI cycles across the two groups. The mean degree of the sperm motility and sperm morphology percentages were similar in the spouses of women in the two groups. With regard to the outcome of IVF, no difference was revealed in the mean number of mature follicles, number of retrieved oocytes, and number of transferred embryos (Table 3). The successful clinical pregnancy rate in the groups A and B was 20.0% and 18.6% respectively with no difference (p = 0.830). The successful clinical pregnancy rate in the groups A and B was 20.0% and 18.6% respectively with no difference (p = 0.830). Based on the multivariable logistic regression analysis, the fixed dose regimen with half dose of GnRH antagonist or GnRH flexible dose antagonist dose did not affect the IVF success. The final determinants of the success of IVF were the percentage of sperm morphology (OR = 1.237, P = 0.015) and BMI of the patients (OR = 0.836, P = 0.019). Conclusion: Both GnRH antagonist regimens with flexible doses and the GnRH antagonist with a half fixed dose have similar effects on the outcome of IVF. Among the factors predicting the success rate of IVF, the role of reducing the morphology of sperm and obesity is very prominent.

Diminished ovarian reserve predisposes to premature luteinizing hormone surges in gonadotropin-releasing hormone antagonist cycles in In vitro fertilization

Context/Background:A premature luteinizing hormone (LH) surge, in in vitro fertilization (IVF) cycles with gonadotropin-releasing hormone (GnRH)-antagonist downregulation, leads to cycle cancellation. Currently, risk factors for the development of premature LH surge remain unknown.Objective:The aim of the study was to determine the incidence and identify the contributing factors for premature LH surge in IVF cycles with GnRH antagonist suppression.Design:This was a retrospective cohort study.Setting:IVF-embryo transfer program at a fertility and research center.Materials and Methods:The study included all patients undergoing IVF from December 1, 2014, to November 30, 2018, in whom GnRH-antagonist (cetrorelix 0.25 mg/d) flexible protocol was used. The primary outcome measure was the identification of premature LH surges (documented by a 2.5-fold increase in LH from the baseline above a threshold of 17 mIU/mL) with or without a decrease in E2 and appearance of free fluid on ultrasound.Results:Premature LH surges occurred in 15 (2.16%) of 692 patients undergoing IVF with GnRH-antagonist suppression. Patients with premature surges had significantly lower ovarian reserve as compared to the controls (as seen from their higher age group, higher day 2 follicle-stimulating hormone (FSH), lower antral follicle counts, and lower anti-Müllerian hormone).Conclusions:Premature LH surge in a GnRH-antagonist cycle can lead to cycle cancellation and disappointment. Although this is a rare event, the incidence is higher in patients with diminished ovarian reserve. Further studies are needed to determine if giving the human chorionic gonadotropin trigger a day earlier or giving higher doses of GnRH-antagonist can benefit such cases.

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.

GnRH antagonist administered twice the day before hCG trigger combined with a step-down protocol may prevent OHSS in IVF/ICSI antagonist cycles at risk for OHSS without affecting the reproductive outcomes: a prospective randomized control trial.

The purpose this study is to investigate whether a double antagonist dose (0.25mg/12h) administered the day before hCG trigger is effective in preventing ovarian hyperstimulation syndrome (OHSS) in GnRH antagonist IVF/intracytoplasmic sperm injection (ICSI) cycles at risk for OHSS. This is a prospective randomized control study, conducted from November 2012 to January 2016. A total of 194 patients undergoing a IVF/ICSI GnRH antagonist cycle that were at risk of OHSS and chose to proceed with embryo transfer and avoid cycle cancellation or embryo cryopreservation were allocated into two groups. The inclusion criteria consisted of a rapid rise of oestradiol ≥3500pg/ml combined with ≥18 follicles >11mm in diameter without any mature follicle >16mm, in any day of stimulation. Overall, 97 patients (intervention group A) received a double dose of GnRH antagonist (0.25mg/12h) the day before hCG while 97 patients (control group B) did not. Recombinant FSH administration was tapered to 100IU/24h the day of the allocation in both groups. Incidence of early-onset moderate/severe OHSS was significantly lower in intervention group A compared to control group B (0 vs 12.37%, P<0.001). Clinical pregnancy rate per cycle (50.52 vs 42.27%, P=0.249) was not significantly different between the two groups. Oestradiol (3263.471±1271.53 vs 5233±1425.17, P<0.001), progesterone (0.93±0.12 vs 1.29±0.14, P<0.001) and luteinizing hormone (1.42±0.31 vs 1.91±0.33, P<0.001) were significantly lower in group A the day of the hCG triggering. The administration of a rescue double GnRH antagonist dose the day before hCG trigger may represent a safe alternative preventive strategy for early OHSS without affecting the reproductive outcomes. ISRCTN02750360.

Clinical experience with an ovarian stimulation protocol for intrauterine insemination adopting a gonadotropin releasing hormone antagonist at low dose

Studies testing the effectiveness of GnRH antagonists in controlled ovarian stimulation (COS) for intrauterine insemination (IUI) have provided controversial results. The present study was undertaken to evaluate, whether the use of a half of the conventional dose of the GnRH antagonist cetrorelix can be effective in increasing the successful rate of IUI cycles. Patients started COS with human menopausal gonadotropin (hMG) on day three of the menstrual cycle. Cetrorelix was started when at least one follicle of ≥14 mm, was detected at the ultrasound scan, according to the flexible multiple daily dose protocol, and continued until the trigger day with recombinant hCG. Patients adopting GnRH antagonist at low dose had a pregnancy rate (21.7%) that was significantly higher (p < 0.05) in comparison to women receiving hMG only (8.7%). These results suggest that adding a reduced dose of GnRH antagonist to the COS for IUI cycles significantly improves the outcome of the procedure.

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.

Cessation of gonadotropin-releasing hormone antagonist on triggering day in flexible multiple-dose protocol: A randomized controlled study

ObjectiveTo investigate outcomes of stimulated IVF cycles in which GnRH antagonist was omitted on the ovulation triggering day.MethodsA total of 86 women who underwent controlled ovarian hyperstimulation with recombinant FSH and GnRH antagonist flexible multiple-dose protocols were recruited and prospectively randomized into the conventional group (group A) or cessation group (group B). The GnRH antagonist, 0.25 mg/day of cetrorelix, was started when the leading follicle reached 14 mm in diameter and was continuously administered until the hCG triggering day (group A, 43 cycles) or until the day before hCG administration (group B, 43 cycles). The maturity of oocytes, fertilization rate, embryo quality, and implantation and clinical pregnancy rates were evaluated.ResultsThe duration of ovarian stimulation, total dose of gonadotropins, serum estradiol levels on hCG administration day, and number of oocytes retrieved were not significantly different between the two groups. The total dose of GnRH antagonist was significantly lower in group B than group A (2.5±0.9 vs. 3.2±0.8 ampoules, p<0.05). There was no premature luteinization in any of the subjects. The proportion of mature oocytes and fertilization rate were not significantly different in group B than group A (70.7% vs. 66.7%; 71.1% vs. 66.4%, respectively). There were no significant differences in the implantation or clinical pregnancy rates.ConclusionOur prospective randomized study suggested that cessation of GnRH antagonist on the hCG administration day during a flexible multiple-dose protocol could reduce the total dose of GnRH antagonist without compromising its effects on pregnancy rates.

Serum anti-Müllerian hormone and basal serum FSH as predictors of poor ovarian response in assisted conception cycles

The aim of the study was to correlate serum AMH and serum FSH levels with ovarian response to stimulation in IVF–ICSI cycles. This was a prospective observational study conducted in a private assisted conception unit. One hundred and two patients were selected on their first IVF cycle. Basal serum FSH and serum AMH were measured one month before the stimulation cycle. A fixed dose GnRH antagonist protocol was used in all cycles transferring a maximum of three day-3 cleavage stage embryos. We defined poor ovarian response as retrieval of fewer than four mature oocytes in cycles requiring ⩾ 3000 IU of gonadotropins for stimulation or cycle cancellation due to poor response. The correlation between different parameters was expressed as a Spearman’s correlation coefficient. The clinical value of AMH and FSH as predictors of poor ovarian response as well as predictors of pregnancy was evaluated by constructing relevant receiver operator characteristics curves (ROC curves). Of these 102 cycles, 28 fitted our definition of poor response while the remaining 74 cycles all produced an adequate response to stimulation. There was a statistically significant difference between the adequate responders group and poor responders group regarding their mean age (31.5 versus 39.6, p < 0.001), the mean value of AMH (2.84 ng/ml versus 0.9 ng/ml, p < 0.0001) as well as the mean value of basal FSH (7.6 IU/ml versus 9.7 IU/ml, p < 0.0001). Serum AMH level had a positive correlation while serum FSH had a negative correlation with the number of oocytes collected while only serum AMH had a significant positive correlation with the occurrence of pregnancy. ROC curve analysis of our results showed that serum AMH with an optimal cut-off value of 1.2 ng/ml is a reliable predictor of poor ovarian response with an area under the ROC curve of 90.4%. Serum basal FSH with an optimal cut-off value of 8.9 IU/ml was of lower value than AMH as a predictor of poor ovarian response with an area under the ROC curve of 81.9%. However, neither serum AMH nor basal serum FSH was found to able to reliably predict the occurrence of pregnancy with an area under the ROC curve of 59.4% and 58.6% respectively. Our results show that serum AMH level is more reliable than basal serum FSH as a predictor of poor ovarian response to stimulation with a cut-off value of 1.2 ng/ml shown to predict poor ovarian response with a sensitivity of 91.7%.

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.

Does the addition of clomiphene citrate or letrazole to gonadotropin treatment enhance the oocyte yield in poor responders undergoing IVF?

To evaluate the effect of adjunctive letrazole or clomiphene in IVF stimulation protocols. A retrospective analysis of high dose GnRH antagonist IVF cycles (450-600 IU of gonadotropins) that have met poor responder criteria. Selected consecutive cycles in same patients differed solely in presence or absence of adjunctive clomiphene or letrazole. Supplementation with clomiphene citrate in poor responders showed significant improvements (p < 0.05) in estradiol levels (1506 vs. 1044 pg/ml), number of dominant follicles (5.6 vs. 3.9), oocytes retrieved (5.2 vs. 3.4) and number of transferred embryos (1.7 vs. 1.1). It significantly improved biochemical pregnancy rates (18.1% vs. 5.9%) while reducing cycle cancellations (11.7% vs. 32.6%). Letrozole supplementation showed similar effects. Both Clomiphene and Letrazole performed similarly and showed significant effects. However, despite increasing oocyte yield and embryo transfer rates, the overall clinical and live birth rate in this population remained low and showed no measurable increase.

Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter ‘extended pilot study’

To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when < or = 5 follicles developed in a preceding cycle following a long agonist protocol with the use of > 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5 before expected start of menstruation and continued for 4-7 days. On cycle day 2-3 a starting dose of rFSH (300-400 IU/day) was given. At a leading follicle diameter of 14 mm, ganirelix administration was resumed until final oocyte maturation was induced with 10,000 IU hCG. GnRH antagonist only marginally affected the intercycle FSH rise; basal levels of FSH remained similar to those seen after 4 days of antagonist administration. The protocol effectively induced low LH levels and luteolysis, but daily administration of 350 IU rFSH (median) for 11 days only led to the collection of 3 oocytes in 49 oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release may improve the stimulation results in poor responders.

Double GnRH-antagonist dose before HCG administration may prevent OHSS in oocyte-donor cycles: a pilot study

This pilot study evaluated the possibility of preventing early ovarian hyperstimulation syndrome (OHSS) by increasing the daily dose of gonadotrophin-releasing hormone (GnRH) antagonist administration (to twice a day) in oocyte-donor cycles stimulated with the antagonist protocol. The study included 72 oocyte donors who underwent ovarian stimulation using the GnRH antagonist protocol and might have had their cycle cancelled because of ovarian hyper-response. All women were donors presenting a rapid rise of oestradiol > or = 3000 pg/ml early in the stimulation period with more than 15 follicles of < or = 15 mm in diameter. By decreasing the rFSH dose to 75 IU a day with an additional daily dose of GnRH antagonist (0.25 mg twice a day), the oestradiol concentrations were lowered or reached a plateau before human chorionic gonadotrophin was given. A marked decrease in oestradiol concentrations and ovarian volume was observed on the day of oocyte retrieval and 3 days post retrieval. None of the donors needed coasting, were cancelled or developed OHSS. In over-responding oocyte donors, by increasing the usual GnRH-antagonist dose to twice a day during ovarian stimulation, the oestradiol rise can be blocked while a minimal follicular stimulation may continue without the risk of developing OHSS or affecting the outcome.

Affordable ART for developing countries: a cost benefit comparison of low dose stimulation versus high dose GnRH antagonist protocol

Low dose stimulation (LS) is emerging as an alternative regime in assisted reproductive technology (ART). This study aimed to compare the cost-effectiveness of LS to the high dose GnRH antagonist (Atg) regime. An observational prospective study conducted at an academic infertility unit from January to June 2007. Outcome measures included the numbers of follicles, oocytes and embryos, morphological quality of oocytes and embryos, clinical pregnancy (PR) and complication rate. Ninety five first attempt ICSI cycles consisting of 54 LS and 41 Atg were analyzed. Subjects in both groups had comparable sociodemographics and reproductive characteristics. LS generated significantly fewer follicles, total oocytes, mature oocytes (all p < 0.0005) and immature oocytes (p = 0.009) than Atg but the number of excellent quality oocytes was similar. Significantly fewer embryos were available in LS although the proportion of usable embryos was higher, 83.2% vs. 67.0% for Atg. Mean embryos per transfer was 2.0 +/- 1.1 vs. 2.6 +/- 1.0 (p = 0.02) for a clinical PR per transfer of 43.2% vs. 50.0% for LS and Atg respectively. LS regime had a shorter gonadotrophin administration period with resultant COH cost one third of the Atg protocol (both, p < 0.0005). The cost per live birth per started cycle worked out to be USD 13,200 and 24,900 for LS and Atg respectively. Furthermore, LS had fewer incidences of OHSS compared to the Atg regime, 3.7% vs. 12.2%. LS cost benefits included lower amounts of gonadotrophin used and fewer injections. It is a viable alternative regime in producing comparable clinical PR at lower cost and less complication in ART.

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.

Comparison of multiple dose GnRH antagonist and minidose long agonist protocols in poor responders undergoing in vitro fertilization: a randomized controlled trial

To investigate the efficacy of gonadotropin releasing hormone antagonist (GnRH) in poor responders undergoing in vitro fertilization. Ninety-six patients with poor ovarian response in previous treatment cycles were prospectively randomized into two groups. Forty-four patients were stimulated with GnRH antagonist multidose protocol and 45 patients received a standard long agonist protocol. Ovarian response was evaluated by transvaginal ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes were statistically compared between groups. There was significantly reduced duration of stimulation and consumption of gonadotrophins in the antagonist group when compared to the agonist group. The estradiol concentrations on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes retrieved, and the number of embryos transferred were similar for both groups. In the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the agonist group, ten (22.2%) clinical pregnancies were achieved but the difference was not statistically significant. The present study was not powered to detect clinically relevant differences between two protocols in outcomes such as pregnancy rate, with confidence.

Patient Friendly IVF — A Gonadotropin Stimulation Protocol of 10-Injections Total

Background: Currently, the majority of mixed-medication stimulation protocols for IVF gonadotropin therapy necessitate 2–4 daily injections for the patient. The addition of needle anxiety to the already stressful IVF therapy may potentially have a negative impact on outcome. The current proposal puts forward a stimulation protocol that utilizes a single gonadotropin injection per day, with a single depot dose GnRH antagonist for down-regulation, for a total of 9–11 injections for the entire cycle.

Long-term suppression of reproductive function by a single dose of gonadotropin-releasing hormone antagonists in a sheep model

To determine the effect of single long-acting doses of GnRH antagonists on reproductive function in a sheep model. Observational, model study. University-affiliated research unit. Nine intact mature Merino sheep in experiment 1 and 12 mature Merino-crossed ewes with the ovary autotransplanted to the neck in experiment 2. Synchronization of estrous cycle either with intravaginal progestins or prostaglandin F2alpha analogues and treatment with a single dose of GnRH antagonist; evaluation of reproductive activity, plasma sampling, and ovarian ultrasonography. Determination of estrus behavior; plasma concentrations of P, FSH, LH, and inhibin A; and number and size of ovarian follicles. In both experiments, the concentrations of FSH and LH were suppressed when compared with those in control ewes. In experiment 1, the ovulatory cycles were suppressed for > or = 55 days in treated sheep. In experiment 2, there were no follicles sized > or = 5 mm in treated ewes for 50 days. The suppression of the development of large follicles for > or = 30 days after a single injection of a long-acting GnRH antagonist provides a novel convenient method of pretreatment before COS.

P-15: Early substitution of low dose GnRH antagonist improves ART outcomes in normal responders who have failed a standard, long GnRH agonist protocol

P-15: Early substitution of low dose GnRH antagonist improves ART outcomes in normal responders who have failed a standard, long GnRH agonist protocol