Comparison between a GnRH antagonist and a GnRH agonist flare-up protocol in oocyte donors: a randomized clinical trial

BACKGROUND: Little information is available on the outcome of controlled ovarian hyperstimulation (COH) using GnRH antagonist in oocyte donation cycles especially in comparison with the short GnRH agonist protocol. This study was aimed at comparing the two stimulation protocols in oocyte donation (OD) cycles. METHODS: A total of 113 donors randomly received COH using either GnRH antagonist or GnRH agonist. The primary endpoint was the mean number of mature oocytes retrieved per started donor cycle. Secondary endpoints were the mean number of cumulus-oocyte-complexes (COCs) retrieved, the mean proportion of mature oocytes, pregnancy and implantation rates in recipients. RESULTS: Oocytes were distributed to 166 recipients. The mean number (+/- SD) of COC (11.6 +/- 5.8 versus 12.1 +/- 6.7), mature oocytes (8.4 +/- 4.4 versus 8.9 +/- 5.3) and the proportion of mature oocytes (70.8 versus 75.7%) retrieved per started donor cycle were similar in the antagonist and agonist groups, respectively. The implantation rate (26.1 versus 30.1%), clinical (40.2 versus 45.6%) and ongoing pregnancy rate per recipient cycle (32.2 versus 37.9%) were comparable in antagonist and agonist protocols, respectively. CONCLUSIONS: Similar mean number of mature oocytes and comparable pregnancy rates are achieved after OD in which donors received COH using GnRH antagonist or short GnRH agonist protocols.     

GnRH antagonists followed by a decline in serum estradiol results in adverse outcomes in donor oocyte cycles

BACKGROUND: The aim of this retrospective study was to assess clinical outcomes using GnRH antagonists in oocyte donation cycles. METHODS: Between July 2000 and June 2001, 40 recipient cycles generated from donor oocytes were evaluated. Controlled ovarian hyperstimulation (COH) was started on cycle day 2 using recombinant gonadotrophins (225 IU daily). GnRH antagonist was started on cycle day 6 of COH. All recipients were synchronized to donors using GnRH agonist followed by estrogen and progesterone supplementation. Main outcome measures were days of stimulation (DOS), number of ampoules used, peak serum estradiol, number of oocytes, fertilization rate, embryo score, clinical on-going pregnancy rate and implantation rate. RESULTS: Thirty-seven donor cycles (93%) underwent oocyte retrieval, resulting in 36 embryo transfers. Fourteen cycles (35%) had decreased serum estradiol after initiation of GnRH antagonist. No differences were seen in numbers of FSH ampoules, DOS, peak serum estradiol, number of retrieved oocytes, fertilization rate and embryo quality. However, clinical pregnancy rate per initiated cycle [14% (2/14) versus 54% (14/26)], ongoing pregnancy rate per initiated cycle [7% (1/14) versus 46% (12/26)] and implantation rate (4 versus 24%) were all significantly less (P <0.05) following a decrease in serum estradiol after initiation of GnRH antagonist. No clinical predictor, including donor age, basal day 2 FSH or estradiol, ovarian morphology or serum estradiol prior to GnRH antagonist, was predictive of a decline in serum estradiol following GnRH antagonist. CONCLUSION: These data demonstrate an adverse effect on clinical outcome in cycles, resulting in a decline in serum estradiol after GnRH antagonist administration. This effect was unpredictable and provided a simplified protocol for oocyte donation cycles; nonetheless, further study is needed to clarify the adverse effects of GnRH antagonists in oocyte donation cycles.     

Profound LH suppression after GnRH antagonist administration is associated with a significantly higher ongoing pregnancy rate in IVF

BACKGROUND: The significance of suppressed LH levels in GnRH antagonist cycles for IVF outcome is currently unknown. The purpose of this study was to evaluate prospectively the association between LH levels and ongoing pregnancy achievement after GnRH antagonist initiation in IVF cycles. METHODS: Ovarian stimulation with a fixed dose of 200 IU recombinant FSH and daily GnRH antagonist (ganirelix) 0.25 mg from day 6 of stimulation was initiated in 116 women. Patients were not pretreated with an oral contraceptive. Induction of final oocyte maturation was performed with HCG 10,000 IU as soon as three follicles of > or =17 mm were present in ultrasound, and was followed by oocyte pick-up, conventional IVF or ICSI, and embryo transfer. The luteal phase was supplemented with vaginal progesterone. RESULTS: A significant decrease of both ongoing pregnancy rate and implantation rate was present across groups of patients with increasing LH levels. The highest implantation rate and ongoing pregnancy rate was present in those patients with LH levels on day 8 of stimulation < or =0.5 IU/l. CONCLUSIONS: Profound suppression of LH on day 8 of stimulation is associated with a significantly higher chance of achieving an ongoing pregnancy. More studies are necessary to evaluate this phenomenon further.     

Embryo implantation and GnRH antagonists: embryo implantation: the Rubicon for GnRH antagonists

When gonadotrophin-releasing hormone (GnRH) was discovered, the agonist and antagonist of GnRH were developed to control the release of FSH and LH by the gonadotrophs. More than 10 years of research were needed to develop a GnRH antagonist free of histamine release. Recent studies have shown that these GnRH antagonists are effective in preventing a rise in LH during ovarian stimulation in IVF. However, a decrease in ongoing pregnancies seems to suggest that implantation rates per transferred embryo are reduced in GnRH antagonist-stimulated cycles. In my opinion, these data highlight an area less well known to clinicians: the role of the GnRH antagonist at the cellular level in extrapituitary tissues. There are sufficient data in the literature suggesting that GnRH antagonist is an inhibitor of the cell cycle by decreasing the synthesis of growth factors. Given that, for folliculogenesis, blastomere formation and endometrium development, mitosis is everything; the interaction between the GnRH antagonist and the GnRH receptor (present in all these cells and tissues) may compromise the mitotic programme of these cells. This is the Rubicon for the GnRH antagonist: to demonstrate irrevocably that, at the minimal doses necessary to suppress LH release, it does not affect processes such as implantation, embryo development and folliculogenesis.     

A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists

BACKGROUND: Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed. METHODS: 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. RESULTS: No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). CONCLUSIONS: Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.     

Addition of GnRH antagonist in cycles of poor responders undergoing IVF

Concern about the use of gonadotrophin-releasing hormone (GnRH) agonists in ovarian stimulation of poor responder IVF patients has arisen from the claim that GnRH agonists might have a direct deleterious effect through their receptors on the ovary. In this study, we compared two ovarian stimulation protocols in which no GnRH agonists were used. In all, 40 patients with a poor response in previous treatment cycles were included. They were divided into two groups: group I (n = 20) received ovarian stimulation for 20 cycles, without the addition of either GnRH agonist or antagonist; while group II (n = 20) patients received ovarian stimulation for 20 cycles, including the administration of a GnRH antagonist (Cetrorelix, 0.25 mg daily) during the late follicular phase. There was no statistically significant difference between the groups for mean age, duration of infertility, baseline FSH concentration, cancellation rate, number of ampoules of gonadotrophin used, number of mature oocytes retrieved, oestradiol concentrations on the day of injection of human chorionic gonadotrophin (HCG), fertilization rate and number of embryos transferred. The clinical pregnancy and implantation rates in group II appeared higher than in group I, but were not significantly different (20 and 13.33% compared with 6.25 and 3.44% respectively). The addition of GnRH antagonists to ovarian stimulation protocols might be a new hope for poor responder IVF patients, but this report is preliminary and further controlled randomized prospective studies with larger sample sizes are required.     

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.     

GnRH antagonists in ovarian stimulation for IVF

The present review describes, on the basis of the currently available evidence, the consensus reached by a group of experts on the use of gonadotropin-releasing hormone (GnRH) antagonists in ovarian stimulation for IVF. The single or multiple low-dose administration of GnRH antagonist during the late-follicular phase effectively prevents a premature rise in serum luteinizing hormone (LH) levels in most women. Although controversy remains, most comparative studies suggest a slight, not significant reduction in the probability of pregnancy after IVF using GnRH antagonist versus GnRH agonist co-treatment. Published meta-analyses suggest that this slight difference in pregnancy rates is not attributed to chance. Further studies applying varying treatment regimens and outcome measures are required. Data are not in favour of a need to modify the starting dose of gonadotropins. Data are not in favour of increasing gonadotropin dose at GnRH antagonist initiation. The addition of LH from the initiation of ovarian stimulation or from GnRH antagonist administration does not appear to be necessary. Replacement of human chorionic gonadotropin (HCG) by GnRH agonist for triggering final oocyte maturation is associated with a lower probability of pregnancy. The optimal timing for HCG administration needs to be explored further. GnRH antagonist initiation on day 6 of stimulation appears to be superior to flexible initiation by a follicle of 14-16 mm, although earlier GnRH antagonist administration is worth further evaluation. Luteal phase supplementation in GnRH antagonist protocols remains mandatory in IVF. Effects of GnRH antagonist co-treatment on the incidence of ovarian hyperstimulation syndrome remains uncertain, although a trend is present in favour of the GnRH antagonists. The role of GnRH antagonists in ovarian stimulation for IVF appears to be promising, although many questions regarding preferred dose regimens and effects on clinical outcomes remain.     

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.     

Are GnRH antagonists comparable to agonists for use in IVF?

We believe that appropriate comparison of optimal GnRH agonist and antagonist regimens has not been performed yet. Currently available meta-analyses included all comparative studies between GnRH agonists and antagonists performed so far, including less than optimal GnRH antagonist regimens. After critical appraisal of the various studied GnRH antagonist regimens in terms of follicular development and IVF outcome, we postulate that early suppression of endogenous FSH results in optimal follicular development. Additionally, stable and early suppression of LH and progesterone levels during the entire period of stimulation may be an advantage for implantation and pregnancy outcome. In this respect, single dose and particularly flexible protocols seem to be less advantageous. Early FSH and LH suppression can be achieved by early GnRH antagonist administration (stimulation day 1) or by oral contraceptive (OC) pretreatment. More studies comparing long GnRH agonist protocols with 'long' GnRH antagonist protocols, with enough power to identify differences in pregnancy rates, are required before appropriate comparison can be made.     

Enhancement of embryo developmental potential by a single administration of GnRH agonist at the time of implantation

BACKGROUND: Several reports have shown that inadvertent administration of a GnRH agonist in the luteal phase does not compromise pregnancy. Moreover, some studies suggested that, unexpectedly, the embryo developmental potential is improved in these conditions. This prospective controlled study was designed to test this hypothesis. METHODS: In an oocyte donation programme, oocytes from each donor (n = 138) were shared by two recipients, one of whom was given a single dose of a GnRH agonist (0.1 mg triptorelin) 6 days after ICSI, and the other received placebo at the same time. RESULTS: Oocyte recipients treated with GnRH agonist 6 days after ICSI had higher implantation (36.9 versus 25.1%), twin pregnancy (16.7 versus 3.6%), twin delivery (13.8 versus 2.2%) and birth (31.1 versus 21.5%) rates and similar miscarriage and abortion rates as compared with the placebo group. CONCLUSIONS: GnRH agonist administration at the time of implantation enhances embryo developmental potential, probably by a direct effect on the embryo.     

Timed oocyte collection in an assisted conception programme using GnRH analogue

Three-hundred-and-twenty-five patients on an assisted conception programme underwent 378 cycles of oocyte retrieval (OPU) following ovarian stimulation using a GnRH analogue and human menopausal gonadotrophins (HMG), a regimen which allows programmed cycles and delayed oocyte retrieval. Eighteen cycles were excluded (failed OPU in three and failure of fertilization in 15). In 360 cycles, patients completed their treatment with either in-vitro fertilization/embryo transfer (IVF/ET) (116) or gamete intra-Fallopian transfer (GIFT) (244), of which 241 took place at the normal time and 119 were delayed for 24 h or more to avoid weekend operating. The overall pregnancy rate per OPU was 29.5%, with the IVF group being 24.1% and the GIFT group being 32.8%. In the group of patients in whom OPU was delayed, the pregnancy rate was significantly higher in each sub-group than in the corresponding non-delayed sub-group (overall, 37.0 versus 25.7%; IVF/ET, 38.5 versus 16.9%; GIFT, 36.3 versus 31.1%). There was a significantly higher number of oocytes collected, gametes/embryos transferred in the group whose OPU had been delayed. In patients receiving GnRH analogue and HMG for ovarian stimulation, delaying oocyte retrieval is not harmful, may result in an improved outcome and allows OPU to be performed on routine operating lists. This facility, together with the improved pregnancy rates associated with this protocol of ovarian stimulation should improve the cost-effectiveness of assisted conception programmes.     

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 (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.     

Minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and concomitant substitution with recombinant FSH: a pilot study

BACKGROUND: The use of the natural cycle for IVF offers the advantage of a patient-friendly and low-risk protocol. Its effectiveness is limited, but may be improved by using a GnRH antagonist to prevent untimely LH surges. METHODS: In this pilot study, minimal stimulation IVF with late follicular phase administration of the GnRH antagonist cetrorelix and simultaneous substitution with recombinant FSH was applied for a maximum of three cycles per patient. Main outcome measures were pregnancy rates per started cycle and cumulative pregnancy rates after three cycles. RESULTS: A total of 50 patients completed 119 cycles (2.4 per patient). Fifty-two embryo transfers resulted in 17 ongoing pregnancies [14.3% per started cycle; 32.7% per embryo transfer; 95% confidence interval (CI) 7.9-20.7% and 19.7-45.7%, respectively]. One dizygotic twin pregnancy occurred after transfer of two embryos, the other pregnancies were singletons. The cumulative ongoing pregnancy rate after three cycles was 34% (95% CI 20.6-47.4%). Live birth rate was 32% per patient (95% CI 18.8-45.2%). CONCLUSIONS: Pregnancy rates after IVF with minimal, late follicular phase stimulation are encouraging. Considering the low-risk and patient-friendly nature of this protocol, it may be a feasible alternative to IVF with ovarian hyperstimulation.     

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.     

Menstruation-free interval and ongoing pregnancy in IVF using GnRH antagonists

BACKGROUND: The purpose of this study was to evaluate prospectively the association between the achievement of ongoing pregnancy and the time interval from the end of menstruation until the administration of HCG (menstruation-free interval) in patients treated by IVF. METHODS: A fixed dose of 200 IU of recombinant FSH (rFSH) was started in 90 patients on day 2 of the menstrual cycle and daily GnRH antagonist was initiated on day 6 of stimulation. Triggering of final oocyte maturation was performed with 10,000 IU of HCG as soon as three follicles of > or =17 mm were present at ultrasound. RESULTS: Single embryo transfer was performed in 64.6% of the patients who reached embryo transfer (53/82). Ongoing pregnancy rate per embryo transfer was 18.3% (95% CI 11.4-28.0%). The menstruation-free interval significantly predicted the probability of ongoing pregnancy in a logistic regression analysis, controlling for female age and LH on day 1 of stimulation (odds ratio for the menstruation-free interval: 0.70; 95% CI: 0.54-0.92). CONCLUSION: The longer the interval from the end of menstruation until the administration of HCG, the lower the probability of ongoing pregnancy in patients stimulated with recombinant FSH and GnRH antagonist for IVF.     

GnRH拮抗剂与GnRH激动剂短方案IVF-ET结局的比较

目的比较GnRH antagonist与GnR Hagonist短方案的IVF-ET结局。方法2006年8月至2007年8月GnR Hantagonist治疗组54人和GnR Hagonist短方案对照组132人,记录促性腺激素的用量及其用药天数、hCG日子宫内膜厚度和激素水平、获卵数、受精率、卵裂率、优胚率、妊娠率和OHSS发生率等指标。结果两组促性腺激素的用量及其用药天数、获卵数、受精率、卵裂率、着床率和妊娠率相比较均无显著差异（P〉0.05）。GnR Hantagonist组在hCG日激素水平低,与对照组比较其差异有统计学意义。结论行GnR Hantagonist方案IVF-ET助孕治疗与传统的GnR Hagonist短方案比较,其hCG日雌激素水平下降可能是OHSS发生率显著下降的主要因素;但卵泡的发育、卵母细胞的受精率、卵裂率及妊娠率和着床率均不受影响。GnR Hantagonist的使用为IVF-ET助孕药物提供了一种新的选择。     

Use of microdose GnRH agonist protocol in women with low ovarian volumes undergoing IVF

Ovarian volume measurements have been recently shown to be predictive of response to ovarian stimulation. Women with small ovarian volumes, i.e. <3 cm(3), have a higher incidence of cycle cancellation, together with a lower peak oestradiol concentration, lower number of retrieved oocytes, and lower pregnancy rates, compared with women with larger ovarian volumes. We prospectively investigated whether a higher dose, microdose flare gonadotrophin-releasing hormone (GnRH) agonist protocol, can improve IVF outcome in women with a small ovarian volume. Only the first IVF cycle was reviewed. In total, 109 women aged <40 years undergoing 109 cycles were prospectively evaluated. Women with an ovarian volume of < or =3 cm(3) noted on the day of luteal GnRH agonist administration had their stimulation regimen changed to a more aggressive microdose flare GnRH agonist protocol. In all, 30 women (27.5%) with an ovarian volume of <3 cm(3), and 79 women (72.5%) with an ovarian volume of >3 cm(3) were compared. Women with an ovarian volume of <3 cm(3) had a significantly higher incidence of unexplained infertility as their presenting aetiology, compared with women with a larger ovarian volume (33 and 8.6%, P = 0.0036). There was a significant negative correlation between age and ovarian volume, and between day 3 FSH concentration and ovarian volume. We also report a significant positive correlation between body mass index and ovarian volume. There was also a significant positive correlation between ovarian volume and the number of oocytes retrieved. Despite a trend towards higher day 3 FSH concentrations, a significantly longer duration of stimulation, higher gonadotrophin requirements, and lower oocyte yield, the implantation and pregnancy rates were comparable between the two groups. Women with a small ovarian volume noted at baseline ultrasound can have comparable implantation and pregnancy rates to those with larger ovarian volumes with the use of a higher dose gonadotrophin, microdose GnRH agonist stimulation.