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

BACKGROUND. This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF. METHODS. Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation. RESULTS. There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant. CONCLUSION. A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.     

GnRH agonist as luteal phase support in assisted reproduction technique cycles: results of a pilot study

BACKGROUND: The aim of the study was to investigate whether intranasal (IN) administration of a GnRH agonist could provide luteal support in IVF/ICSI patients. METHODS: Controlled ovarian hyperstimulation (COH) was performed using hMG/FSH and a GnRH antagonist. Patients were then randomly allocated to either 10,000 IU hCG, followed by vaginal administration of micronized progesterone (3x 200 mg/day) (group A), or 200 microg IN buserelin followed by either 100 microg every 2 days (group B), or 100 microg every day (group C), or 100 microg twice a day (group D), or 100 microg three times a day (group E). Luteal support was continued for 15 days. RESULTS: Twenty-three patients were randomized. Groups B and C were discontinued prematurely in view of the short luteal phase. The luteal phase was significantly shorter in groups B, C and D, whereas group E was comparable with group A, 13.5 and 13.0 days, respectively. In the mid-luteal phase, median progesterone levels were significantly lower in groups B, C and D, whereas group E was comparable with group A, 68.9 and 98.0 ng/ml, respectively. Estradiol (E2) was significantly reduced in groups B and D but sustained in group E. In the hCG group, LH levels were undetectable (<0.1 IU/l), whereas LH was detectable and significantly higher in groups C, D and E. Two pregnancies were obtained in the hCG group (two of five), one ectopic and one ongoing. Three pregnancies were obtained in group E, one miscarriage and two ongoing twin pregnancies (three of five). CONCLUSION: IN administration of buserelin may be effective in triggering follicular maturation and providing luteal phase support in patients undergoing assisted reproduction techniques (ART).     

GnRH agonist versus GnRH antagonist in oocyte donation cycles: a prospective randomized study

BACKGROUND: The specific role of LH in folliculogenesis and oocyte maturation is unclear. GnRH antagonists, when administered in the late follicular phase, induce a sharp decrease in serum LH which may be detrimental for IVF outcome. This study was performed to evaluate whether the replacement of GnRH agonist (triptorelin) by a GnRH antagonist (ganirelix; NV Organon) in oocyte donation cycles has any impact on pregnancy and implantation rates. METHODS: A total of 148 donor IVF cycles was randomly assigned to use either a GnRH antagonist daily administered from the 8th day of stimulation (group I) or a GnRH agonist long protocol (group II) for the ovarian stimulation of their donors. The primary endpoints were the pregnancy and the implantation rates. RESULTS: The clinical pregnancy rate per transfer (39.72%, 29/73 versus 41.33%, 31/75) based on transvaginal scan findings at 7 weeks of gestation, the implantation rate (23.9 versus 25.4%) and the first trimester abortion rate (10.34 versus 12.90%) were similar in the two groups. CONCLUSION: In oocyte donation cycles the replacement of GnRH agonist by a GnRH antagonist appears to have no impact on the pregnancy and implantation rates when its administration starts on day 8 of stimulation.     

GnRH antagonist in assisted reproduction: a Cochrane review

BACKGROUND: In the present systematic review, we wished to compare the efficacy of gonadotrophin-releasing hormone (GnRH) antagonist and GnRH agonist administration for controlled ovarian hyperstimulation in assisted conception. METHODS: Five randomized controlled trials fulfilled the inclusion criteria. In four studies, the multiple low-dose (0.25 mg) antagonist regimen was applied and, in one study, the single high-dose (3 mg) antagonist regimen was investigated. In all trials, reference treatment included a long protocol of GnRH agonist (buserelin, leuprorelin or triptorelin) starting in the mid-luteal phase of the preceding cycle. RESULTS: In comparison with the long protocol of GnRH agonist, the overall odds ratio for the prevention of premature LH surges was 1.76 [95% confidence interval (CI) 0.75-4.16], which was not statistically significant. There were significantly fewer clinical pregnancies in those treated with GnRH antagonists (OR 0.79; 95% CI 0.63-0.99). There was no statistically significant reduction in incidence of severe ovarian hyperstimulation syndrome between the two regimens (relative risk 0.51; OR 0.79; 95% CI 0.22-1.18). CONCLUSIONS: We concluded that the fixed GnRH antagonist protocol is a short and simple protocol with good clinical outcome, but the lower pregnancy rate compared with the GnRH agonist long protocol and the non-significant difference between both protocols regarding prevention of premature LH surge and prevention of severe ovarian hyperstimulation syndrome necessitates counselling subfertile couples before recommending change from GnRH agonist to antagonist. The clinical outcome may be further improved by developing more flexible antagonist regimens, taking into account individual patient characteristics.     

Timing luteal phase support in GnRH agonist down-regulated IVF/embryo transfer cycles

BACKGROUND: The aim of this study was to compare the effect of three different times of onset of luteal phase support on ongoing pregnancy rate in infertile patients undergoing treatment with GnRH down-regulated IVF and embryo transfer (IVF/ET). MATERIALS AND METHODS: All consecutive eligible patients planned to undergo their first IVF treatment cycle were randomly allocated to receive vaginal progesterone as luteal support at three different time points, that is, after HCG administration for final oocyte maturation (HCG group), at the day of oocyte retrieval (OR group) or at the day of ET (ET group). The primary endpoint of this study was ongoing pregnancy rate. RESULTS: A total of 385 women were randomized, 130 were allocated to the HCG group, 128 to the OR group and 127 to the ET group. An ongoing pregnancy rate of 20.8% was found in the HCG group versus 22.7 and 23.6% in the OR group and ET group, respectively. The mean number and quality of the retrieved oocytes and the transferred embryos did not differ. CONCLUSION: Based on this data, an 18% difference in ongoing pregnancy rate between the three different times of onset of luteal phase support in GnRH agonist down-regulated IVF/ET cycles can be refuted. Smaller clinically meaningful differences may be present.     

Ovarian response and pregnancy outcome related to mid-follicular LH levels in women undergoing assisted reproduction with GnRH agonist down-regulation and recombinant FSH stimulation

BACKGROUND: The effect of LH levels on stimulation day 8 on ovarian response and pregnancy outcome were evaluated in women receiving pituitary down-regulation with GnRH agonists (0.8 mg Suprefact) s.c. daily until pituitary down-regulation and 0.4 mg/day during ovarian stimulation) and ovarian stimulation with recombinant FSH. METHODS: Blood samples were prospectively collected from a total of 207 normal women undergoing assisted reproduction and analysed retrospectively. Based on LH levels on stimulation day 8 patients were divided into four groups: <0.5, 0.51-1.0, 1.01-1.5, >1.51 IU/l. RESULTS: Estradiol levels on day 8 and estradiol per oocyte retrieved showed a highly significant correlation with LH concentrations on day 8. The total consumption of exogenous FSH and duration of gonadotrophin stimulation was inversely related to LH levels on day 8 (P < 0.002). The frequencies of fertilization and clinical pregnancies were superior in the two middle groups. Only 12% of the patients showed LH levels <0.5 IU/l, which, however, may be explained by the particular mode and doses of GnRH agonist used. CONCLUSIONS: Circulating levels of LH on day 8 have a significant impact on ovarian response and pregnancy outcome. LH should neither be too high nor too low. The mode of administration and the dose of the GnRH agonist used may determine the number of women who experience LH levels below 0.5 IU/l.     

Ovarian cyst formation following GnRH agonist administration in IVF cycles: incidence and impact

BACKGROUND: The formation of functional ovarian cysts has been recognized as one of the side effects of GnRH agonist administration. The formation of cysts during IVF treatment may be of no clinical significance or may negatively influence its outcome. The objective of this study was to determine the incidence of ovarian cyst formation following GnRH agonist administration and to examine their effect on IVF outcome. METHODS: A prospective study of 1317 IVF patients who developed one or more functional ovarian cysts of >or=15 mm following GnRH agonist treatment was performed. Transvaginal ultrasonographic-guided cyst aspiration was carried out in 76 randomly allocated patients out of 122 patients who were found to have functional ovarian cysts before starting ovarian stimulation with gonadotropins. RESULTS: The incidence of follicular cyst formation was 9.3%. Cyst cycles in comparison with non-cyst cycles had significantly elevated day 3 basal FSH (mean+/-SD of 8.3+/-3.2 versus 5.3+/-2.6 mIU/ml, P<0.05) and required more ampoules of gonadotropins (46.3+/-16.5 versus 35+/-14.6, P<0.01). Furthermore, they showed a statistically significant decrease in the quality and number of oocytes retrieved, fertilization rate, number and quality of embryos, implantation and pregnancy rates, with a significant increase in cancellation and abortion rates. Patients with bilateral cysts had a significantly lower number of oocytes and embryos retrieved, with a lower proportion of metaphase II oocytes. They also had a higher proportion of poor quality embryos. Cyst aspiration was not associated with a significant difference in the above parameters. CONCLUSIONS: The incidence of cyst formation during GnRH agonist treatment is lower than previously reported. In such cases, the quality of oocytes and embryos were significantly compromised, with a significant increase in the cycle cancellation rate and a decrease in the implantation and pregnancy rates. Neither conservative management nor cyst aspiration improved the IVF outcome.     

GnRH agonist protocol administration in the luteal phase in ICSI-ET cycles stimulated with the long GnRH agonist protocol: a randomized, controlled double blind study

BACKGROUND: GnRH agonist administration in the luteal phase was reported to beneficially affect the clinical outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This double blind, randomized, placebo controlled trial evaluates whether a single dose GnRH agonist administered 6 days after ICSI increases ongoing pregnancy rates following ET in cycles stimulated with the long GnRH agonist protocol. METHODS: Five hundred and seventy women undergoing ET following controlled ovarian stimulation with a long GnRH agonist protocol were included. In addition to routine luteal phase support with progesterone, women were randomized to receive a single 0.1 mg dose of triptorelin or placebo 6 days after ICSI. Randomization was done on the day of ET according to a computer generated randomization table. Ongoing pregnancy rate beyond 20th week of gestation was the primary outcome measure. The trial was powered to detect a 12% absolute increase from an assumed 38% ongoing pregnancy rate in the placebo group, with an alpha error level of 0.05 and a beta error level of 0.2. RESULTS: There were 89 (31.2%) ongoing pregnancies in the GnRH agonist group, and 84 (29.5%) in the control group (absolute difference +1.7%, 95% confidence interval -5.8% to +9.2%). Implantation, clinical pregnancy and multiple pregnancy rates were likewise similar in the GnRH agonist and placebo groups. CONCLUSIONS: Single 0.1 mg triptorelin administration 6 days after ICSI following ovarian stimulation with the long GnRH agonist protocol does not seem to result in an increase >or=12% in ongoing pregnancy rates.     

Beneficial effect of luteal-phase GnRH agonist administration on embryo implantation after ICSI in both GnRH agonist- and antagonist-treated ovarian stimulation cycles

BACKGROUND: GnRH agonist was recently suggested as a novel luteal-phase support that may act at different levels, including the pituitary gonadotrophs, the endometrium and the embryo itself. This prospective randomized study evaluates the effect of GnRH agonist administered in the luteal phase on ICSI outcomes in both GnRH agonist- and GnRH antagonist-treated ovarian stimulation protocols. METHODS: Six hundred women about to undergo ovarian stimulation for ICSI (300 using a long GnRH agonist protocol and 300 using a GnRH antagonist protocol) were enrolled in this study. Patients treated with each of these two protocols were randomly assigned to receive a single injection of GnRH agonist or placebo 6 days after ICSI. Implantation and live birth rates were the primary outcomes. RESULTS: Administration of 0.1 mg of GnRH agonist triptorelin on day 6 after ICSI led to a significant improvement of implantation and live birth rates after ICSI as compared with placebo. In GnRH antagonist-treated ovarian stimulation cycles, luteal-phase GnRH agonist also increased ongoing pregnancy rate. Moreover, luteal-phase GnRH agonist administration increased luteal-phase serum HCG, estradiol and progesterone concentrations in both ovarian stimulation regimens. CONCLUSIONS: Luteal-phase GnRH agonist administration enhances ICSI clinical outcomes after GnRH agonist- and GnRH antagonist-treated ovarian stimulation cycles, possibly by a combination of effects on the embryo and the corpus luteum.     

Endocrinology: Prospective randomized study of clomiphene citrate and gonadotrophins versus goserelin and gonadotrophins for follicular stimulation in assisted reproduction

We performed a prospective randomized study of goserelin, along-acting gonadotrophin-releasing hormone agonist (GnRHa)and human menopausal gonadotrophin (HMG) versus clomiphene citrateand HMG for follicular stimulation in assisted reproductionto investigate whether the use of this GnRHa provides a clearadvantage in terms of pregnancy per treatment cycle in unselectedpatients, who entered a first trial of assisted reproduction.From a retrospective analysis comparing the two stimulationprotocols, a relative increase of the pregnancy rate per cycleof 50% was anticipated. To detect this difference with a powerof 90%, 300 patients had to be included. The main prognosticfactors affecting the outcome of assisted reproduction wereequally divided among the two groups by a minimization procedure.The pregnancy rates per cycle were significantly better in thegoserelin/HMG group than in the clomiphene citrate/HMG group,both for all procedures of assisted reproduction combined (36.8versus 24.5%; P < 0.02) and for the main procedure of in-vitrofertilization (IVF) (37.0 versus 23.5%; P < 0.02). Differencesin pregnancy rates per oocyte retrieval and per embryo transferwere less pronounced (37.8 versus 30.8%; P = 0.40 and 44.4 versus36.8%; not significant). On the other hand, stimulation withgoserelin/HMG was associated with a higher number of ampoulesof HMG (44.9 versus 9.9; P < 0.0001), a longer duration ofstimulation (11.2 versus 8.7 days; P < 0.0001) and an incidenceof ovarian stimulation of 4.5% (7/154) versus 0% in the clomiphenecitrate/HMG group. Goserelin was well tolerated and proved tobe very reliable as an adjunct of follicular stimulation inassisted reproduction. The main determinants of the higher efficacyof goserelin/HMG in assisted reproduction were the virtual absenceof cancellation of the cycle and the increased number of oocytes.     

The effect of GnRH analogues for pituitary suppression on ovarian response in repeated ovarian stimulation cycles

Introduction

Ovarian stimulation is employed in assisted reproduction techniques in order to obtain as many oocytes as possible. The early rise in oestradiol levels may lead to the premature end of the respective cycle. In order to avoid such an effect, pituitary suppression has been employed. The aim of this study was to evaluate whether maintenance or replacement of the type of GnRH analogue (i.e., agonist or antagonist) employed for pituitary suppression in the consecutive intracytoplasmic sperm injection (ICSI) cycle would negatively influence oocyte quality and ICSI outcome.

Material and methods

A retrospective observational study was conducted including 181 women with primary infertility. Patients were divided into four different groups according to the GnRH analogue used for pituitary suppression in the first and consecutive cycle.

Results

When a GnRH agonist was employed for pituitary suppression in the first cycle, the consecutive cycle showed comparable outcomes when performed with either a GnRH agonist or a GnRH antagonist. When the first cycle was performed with a GnRH antagonist, the use of the GnRH agonist in the successive cycle led to an increased number of oocytes retrieved (7.5% vs. 10.3%, p = 0.032) and the production of a higher number of embryos (4.5% vs. 6.3%, p = 0.036).

Conclusions

When the first cycle is carried out with a GnRH antagonist, the use of a GnRH agonist in the successive cycle would lead to increased numbers of oocytes collected and embryos produced.     

Comparison of the GnRH agonist and antagonist protocol on the same patients in assisted reproduction during controlled ovarian stimulation cycles

Despite the fact that both gonadotropin-releasing hormone (GnRH) agonist and antagonist protocol are effective in suppressing the incidence of premature luteinizing hormone (LH) surges through reversibly blocking the secretion of pituitary gonadotropins, the exact impact of these two distinctive protocols on the clinical setting of patients for in vitro fertilization and embryo transfer (IVF-ET) treatment, however, remained controversial. We thus in the present report conducted a retrospective study to compare the impact of GnRH agonist and antagonist protocol on the same patients during controlled ovarian stimulation cycles. A total of 81 patients undergoing 105 agonist and 88 antagonist protocol were analyzed. We failed to detect a significant difference between two protocols for the difference in duration of ovarian stimulation, number of recombinant FSH (Gonal-F) ampoules used, number of oocytes retrieved, serum levels for estradiol (E2) and progestone (P), thickness of endometrium, and the zygote- and blastocyst-development rate. It is seemly that high quality embryo rate was higher in the antagonist protocol, but the data did not reach a statistical significance. Nevertheless, Implantation rate and clinical pregnancy rate were significantly higher in the antagonist protocol (10.64% and 30.26%, respectively) than that of the agonist protocol (5.26% and 15.82%, respectively). Our data also suggest that the GnRH antagonist protocol is likely to have the advantage for improving the outcome of pregnancy in those patients with a history of multiple failures for the IVF-ET treatment.     

Prospective randomized study of D-Trp6-LHRH versus buserelin in long desensitization protocols for medically assisted conception cycles

In a prospective, controlled, randomized study where two differentagonists were used, we compared three different long desensitizationprotocols for induction of multiple follicular growth in medicallyassisted conception cycles. In protocol A, 30 patients wereinjected with buserelin twice a day for 15 days prior to ovarianstimulation until human chorionic gonadotrophin (HCG) administration.In protocol B, 30 patients were injected with a single doseof long acting Triptorelin (3.75mg) 15 days before the ovarianstimulation onset. In protocol C, 30 patients were injectedwith the long acting Triptorelin 4 weeks before ovarian stimulationfollowed by daily administration of 0.1 mg of the same agonistuntil HCG injection. There was no difference in the ovarianresponse to exogenous gonadotrophin stimulation, except forthe presence of premature luteinization in two patients in groupB. A significantly higher number of mature oocytes was collectedfrom patients with protocol A; however, the fertilization andcleavage rate demonstrated no significant difference among thethree groups of patients. The ongoing pregnancy rate and theimplanation rate per treatment cycle were very similar in thethree study groups. When the convenience, cost and side-effectsfor the patient are being considered, protocol B should be selectedas the first choice when the agonist is utilized for the purposeof inducing pituitary desensitization before and during ovarianstimulation.     

Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: preliminary report: short communication

A new treatment option for patients undergoing ovarian stimulation is the gonadotrophin-releasing hormone (GnRH) antagonist protocol, with the possibility to trigger a mid-cycle LH surge using a single bolus of GnRH agonist, reducing the risk of developing ovarian hyperstimulation syndrome (OHSS) in high responders and the chance of cycle cancellation. This report describes the use of 0.2 mg triptorelin (Decapeptyl) to trigger ovulation in eight patients who underwent controlled ovarian hyperstimulation with recombinant FSH (rFSH, Puregon) and concomitant treatment with the GnRH antagonist ganirelix (Orgalutran) for the prevention of premature LH surges. All patients were considered to have an increased risk for developing OHSS (at least 20 follicles > or =11 mm and/or serum oestradiol at least 3000 pg/ml). On the day of triggering the LH surge, the mean number of follicles > or =11 mm was 25.1 +/- 4.5 and the median serum oestradiol concentration was 3675 (range 2980-7670) pg/ml. After GnRH agonist injection, endogenous serum LH and FSH surges were observed with median peak values of 219 and 19 IU/l respectively, measured 4 h after injection. The mean number of oocytes obtained was 23.4 +/- 15.4, of which 83% were mature (metaphase II). None of the patients developed any signs or symptoms of OHSS. So far, four clinical pregnancies have been achieved from the embryos obtained during these cycles, including the first birth following this approach. It is concluded that GnRH agonist effectively triggers an endogenous LH surge for final oocyte maturation after ganirelix treatment in stimulated cycles. Our preliminary results suggest that this regimen may prove effective in triggering ovulation and could be said to prevent OHSS in high responders. The efficacy and safety of such new treatment regimen needs to be established in comparative randomized studies.     

Recombinant human LH supplementation during GnRH antagonist administration in IVF/ICSI cycles: a prospective randomized study

BACKGROUND: When administered in the late follicular phase to prevent an LH surge, GnRH antagonists induce a sharp decrease in serum LH levels that may be detrimental for assisted reproductive technology cycle outcome. Therefore, a prospective study was designed to assess the effects of recombinant human (r)LH supplementation during GnRH antagonist (cetrorelix) administration. METHODS: The protocol consisted of cycle programming with oral contraceptive pill, ovarian stimulation with rFSH and flexible administration of a single dose of cetrorelix (3 mg). A total of 218 patients from three IVF centres were randomized (by sealed envelopes or according to woman's birth date) to receive (n = 114) or not (n = 104) a daily injection of rLH 75 IU from GnRH antagonist initiation to hCG injection. RESULTS: The only significant difference was a higher serum peak E2 level in patients treated with rLH (1476 +/- 787 versus 1012 +/- 659 pg/ml, P < 0.001) whereas the numbers of oocytes and embryos as well as the delivery rate (25.2 versus 24%) and the implantation rate per embryo (19.1 versus 17.4%) were similar in both groups. CONCLUSIONS: These results show that in an unselected group of patients, there is no evident benefit to supplement GnRH antagonist-treated cycles with rLH.     

Soft versus firm embryo transfer catheters for assisted reproduction: a systematic review and meta-analysis

BACKGROUND: The true impact of the embryo transfer catheter choice on an IVF programme has not been fully examined. We therefore decided to systematically review the evidence provided in the literature so that we may evaluate a single variable in relation to a successful transfer, the firmness of the embryo transfer catheter. METHODS: An extensive computerized search was conducted for all relevant articles published as full text, or abstracts, and critically appraised. In addition, a hand search was undertaken to locate any further trials. RESULTS: A total of 23 randomized controlled trials (RCT) evaluating the types of embryo transfer catheters were identified. Only ten of these trials, including 4141 embryo transfers, compared soft versus firm embryo catheters. Pooling of the results demonstrated a statistically significantly increased chance of clinical pregnancy following embryo transfer using the soft (643/2109) versus firm (488/2032) catheters [P = 0.01; odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.08-1.79]. When only the truly RCT were analysed, the results were again still in favour of using the soft embryo transfer catheters [soft (432/1403) versus firm (330/1402)], but with a greater significance (P < 0.00001; OR = 1.49, 95% CI = 1.26-1.77). CONCLUSION: Using soft embryo transfer catheters for embryo transfer results in a significantly higher pregnancy rate as compared to firm catheters.     

GnRH agonist as novel luteal support: results of a randomized, parallel group, feasibility study using intranasal administration of buserelin

BACKGROUND: The study objective was to investigate whether repeated intranasal administration of a GnRH agonist could provide convenient and safe luteal support. METHODS: Twenty-four patients with unexplained infertility were enrolled. All patients were treated with an aromatase inhibitor. When ovulation trigger criteria were met, patients were randomly allocated to either 5000 IU hCG (group A), or 200 microg intranasal buserelin followed by 100 microg every 3 days (group B), 100 microg every 2 days (group C), or 100 microg every day (group D), up to day 14 of the luteal phase. All patients underwent intrauterine insemination. RESULTS: Follicular development was similar in all groups with 1.1 +/- 0.3 follicles > or = 16 mm, 229.4 +/- 95.2 pg/ml estradiol (E2) and 0.8 +/- 0.5 ng/ml progesterone (mean+/-SD). The luteal phase duration (median; 95% confidence interval) was 15 (14.1, 15.0), 14 (12.5, 15.5), 15 (11.8, 18.2) and 15 (14.4, 15.6) days in groups A, B, C and D respectively. From luteal phase day 7 onwards, progesterone levels tended to be higher in group D compared with A. On day 14 of the luteal phase, progesterone levels were 3.0 (0.8, 5.2), 1.7 (-0.5, 3.9), 3.9 (-0.7, 8.5) and 7.7 (3.4, 11.9) ng/ml in groups A, B, C and D respectively (P = 0.045). No pregnancy was recorded in group A, but there was one biochemical pregnancy in group B, one biochemical and one singleton clinical pregnancy in group C, and two singleton clinical pregnancies in group D. CONCLUSION: Intranasal administration of buserelin could be effective to provide luteal support. This treatment was associated with a good pregnancy rate (5/18, 28%).     

Continuous versus cyclic use of combined oral contraceptives for contraception: systematic Cochrane review of randomized controlled trials

BACKGROUND: With the recent US Food and Drug Administration approval of a combination oral contraceptive that causes a withdrawal bleed every 3 months instead of monthly, avoidance of menstruation through extended or continuous administration (>28 days of active pills) of combined oral contraceptives may become more commonplace for reasons of personal preference rather than limited to treatment of menstrual-associated medical disorders. METHODS: The review aimed to compare contraceptive efficacy, compliance, continuation, satisfaction, bleeding profiles, and menstrual symptoms of combined oral contraceptives with continuous dosing (>28 days of active pills) versus traditional cyclic dosing (21 days of active pills and 7 days of placebo). We searched five computerized databases as well as reference lists of relevant articles for randomized controlled trials (RCT) using continuous or extended combined oral contraceptives for contraception. Two reviewers independently extracted data from eligible articles. RESULTS: Six RCT met inclusion criteria and were of good quality. Contraceptive efficacy and compliance were similar between groups. Discontinuation overall, and for bleeding problems, was not uniformly higher in either group. When studied, participants reported high satisfaction with both dosing regimens. Five out of the six studies found that bleeding patterns were either equivalent or improved with continuous-dosing regimens. The continuous-dosing group had greater improvement of menstrual-associated symptoms (headaches, genital irritation, tiredness, bloating, and menstrual pain). CONCLUSIONS: The variations in pill type and time-interval for continuous dosing make direct comparisons between regimens unfeasible. To allow for comparisons, future studies should choose a previously researched pill and dosing regimen. More attention needs to be directed towards participant satisfaction and menstruation-associated symptoms.     

GnRH agonist (buserelin) or hCG for ovulation induction in GnRH antagonist IVF/ICSI cycles: a prospective randomized study

BACKGROUND: We aimed to determine the efficacy of ovarian hyperstimulation protocols employing a GnRH antagonist to prevent a premature LH rise allowing final oocyte maturation and ovulation to be induced by a single bolus of either a GnRH agonist or hCG. METHODS: A total of 122 normogonadotrophic patients following a flexible antagonist protocol was stimulated with recombinant human FSH and prospectively randomized (sealed envelopes) to ovulation induction with a single bolus of either 0.5 mg buserelin s.c. (n = 55) or 10,000 IU of hCG (n = 67). A maximum of two embryos was transferred. Luteal support consisted of micronized progesterone vaginally, 90 mg a day, and estradiol, 4 mg a day per os. RESULTS: Ovulation was induced with GnRH agonist in 55 patients and hCG in 67 patients. Significantly more metaphase II (MII) oocytes were retrieved in the GnRH agonist group (P < 0.02). Significantly higher levels of LH and FSH (P < 0.001) and significantly lower levels of progesterone and estradiol (P < 0.001) were seen in the GnRH agonist group during the luteal phase. The implantation rate, 33/97 versus 3/89 (P < 0.001), clinical pregnancy rate, 36 versus 6% (P = 0.002), and rate of early pregnancy loss, 4% versus 79% (P = 0.005), were significantly in favour of hCG. CONCLUSIONS: Ovulation induction with a GnRH agonist resulted in significantly more MII oocytes. However, a significantly lower implantation rate and clinical pregnancy rate in addition to a significantly higher rate of early pregnancy loss was seen in the GnRH agonist group, most probably due to a luteal phase deficiency.     

Comparison of follicular fluid IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A concentrations and their ratios between GnRH agonist and GnRH antagonist protocols for controlled ovarian stimulation in IVF-embryo transfer patients

BACKGROUND: Insulin-like growth factors (IGF) and their binding proteins (IGFBP) play a major role in the autocrine and paracrine regulation of folliculogenesis. This is the first study that has compared follicular fluid (FF) IGF-I, IGF-II, IGFBP-3, IGFBP-4 and pregnancy-associated plasma protein (PAPP)-A concentrations, and their ratios, to investigate whether there was any difference in the intrafollicular microenvironment between the GnRH agonist (GnRHa) and antagonist (GnRHant) protocols for controlled ovarian stimulation (COS). METHODS: A total of 68 IVF cycles were included in this study; two groups were studied: GnRHa long protocol group (n = 36) and the flexible GnRHant multiple-dose protocol group (n = 32). FF was obtained from dominant follicles during oocyte retrieval and stored at -70 degrees C until assayed. IGF-I, IGF-II and IGFBP-3 concentrations were measured by radioimmunoassay and IGFBP-4 and PAPP-A by enzyme-linked immunosorbent assay. RESULTS: The duration of COS was significantly longer, and total dose of gonadotrophins used, serum estradiol (E(2)) levels on hCG day and the number of oocytes retrieved were significantly higher in the GnRHa long protocol group. The concentrations of FF IGF-II and IGFBP-4 were significantly higher, and the ratio of IGF-I/IGFBP-4 was significantly lower in the GnRHa long protocol group. Serum E(2) levels per mature follicle were not different between the two groups. CONCLUSIONS: Our data may indicate a difference of intrafollicular microenvironment between cycles using GnRHa long protocols and those using GnRHant protocols. However, the difference in microenvironment does not appear to result in a difference in clinical outcome.