Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women

Messinis, Ioannis E.; Vanakara, Polyxeni; Zavos, Apostolos; Verikouki, C.; Georgoulias, Panagiotis; Dafopoulos, Konstantinos

doi:10.1016/j.fertnstert.2009.12.055

Cited by 30 publications

(24 citation statements)

References 16 publications

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“…While a daily dose of 0.25 mg ganirelix has been demonstrated to be an effective dose to prevent premature LH rises during multiple follicular development in in vitro fertilization cycles, there is some evidence that a GnRH antagonist is less effective in blocking the positive feedback effect of estradiol in women with mild or nonstimulated ovaries [23,24]; this is in agreement with the lower ovarian response of women with an LH rise during ganirelix treatment in the current retrospective analysis. The cause of these LH rises remains to be elucidated but it has been suggested that a reduced production of gonadotropin surge-attenuating factor may be involved, which is hypersecreted in the case of induced multiple follicular development [23].…”

Section: Discussionsupporting

confidence: 86%

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Clinical impact of LH rises prior to and during ganirelix treatment started on day 5 or on day 6 of ovarian stimulation

Frattarelli¹,

Hillensjø

Broekmans

et al. 2013

Reprod Biol Endocrinol

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BackgroundWe sought to evaluate the incidence and clinical impact of luteinizing hormone (LH) rises prior to and during gonadotropin-releasing hormone (GnRH) antagonist treatment started on day 5 or 6 of ovarian stimulation with recombinant follicle-stimulating hormone (rFSH).MethodsPooled data from three trials with the GnRH antagonist ganirelix started on day 5 (n = 961) and from five trials with ganirelix started on day 6 (n = 1135) of ovarian stimulation with rFSH were retrospectively analyzed.ResultsThe incidence of LH rises (LH ≥ 10.0 IU/L) prior to ganirelix treatment was 2.3% and 6.6% on ganirelix start days 5 and 6, respectively (P < 0.01). During ganirelix treatment this incidence was 1.2% and 2.3%, respectively (P = 0.06). Women with LH rise on day 5 or 6 had a higher ovarian response with more oocytes recovered, mean ± SD, 12.9 ± 8.5 versus no LH rise, 10.2 ± 6.4 (P < 0.01). In women with and without LH rise prior to ganirelix treatment the ongoing pregnancy rates were similar (26.0% vs 29.9%; odds ratio [OR], 0.89; 95% confidence interval [CI], 0.55-1.44). Women with LH rise during ganirelix treatment had a lower ovarian response with 7.5 ± 6.7 oocytes recovered versus no LH rise, 10.2 ± 6.4 (P = 0.02) and a tendancy for a lower chance of ongoing pregnancy (16.7% vs 29.9%; OR, 0.52; 95% CI, 0.21-1.26).ConclusionsThe incidence of early and late LH rises was low but may be further reduced by initiating ganirelix on stimulation day 5 rather than on day 6. In contrast to women with an early LH rise, women with a late LH rise may have a reduced chance of ongoing pregnancy.

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Section: Discussionsupporting

confidence: 86%

“…The cause of these LH rises remains to be elucidated but it has been suggested that a reduced production of gonadotropin surge-attenuating factor may be involved, which is hypersecreted in the case of induced multiple follicular development [23]. …”

Section: Discussionmentioning

confidence: 99%

Clinical impact of LH rises prior to and during ganirelix treatment started on day 5 or on day 6 of ovarian stimulation

Frattarelli¹,

Hillensjø

Broekmans

et al. 2013

Reprod Biol Endocrinol

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“…A premature luteinizing hormone rise is commonly seen in the GnRH antagonist simulation protocol, especially before the GnRH antagonist is administered, owing to a lack of inhibition. The underlying mechanisms are poorly identified, but could be related to a positive feedback loop between high estradiol concentrations and the pituitary gland during ovulation stimulation .…”

Section: Discussionmentioning

confidence: 99%

The effect of premature luteinizing hormone increases among high ovarian responders undergoing a gonadotropin‐releasing hormone antagonist ovarian stimulation protocol

Geng

Lai

Yang

et al. 2018

Intl J Gynecology & Obste

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“…In such cycles, the endogenous LH surge is either blocked or markedly attenuated because of the overproduction of the gonadotropin surge attenuating factor (GnSAF) 36,39 . When a GnRH antagonist is used, premature LH peaks occur on several occasions due to the inability of these drugs to block the positive feedback effect of estradiol 43,44 . It is likely that the action of GnSAF facilitates the action of the GnRH antagonist, converting thus a premature LH surge into an abortive surge.…”

Section: Multiple Follicular Developmentmentioning

confidence: 99%

The role of gonadotropins in the follicular phase

Messinis¹,

Messini²,

Dafopoulos³

2010

Annals of the New York Academy of Sciences

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Folliculogenesis in humans is a lengthy process that involves several regulators. Pituitary gonadotropins play crucial roles in the late stages, particularly in the last 15 days of follicle maturation. During the intercycle rise of follicle-stimulating hormone (FSH), selection of the dominant follicle takes place. This is a complex process that also involves locally produced substances. At the same time, luteinizing hormone (LH) stimulates the synthesis of androgens, which serve as the substrate for the production of estrogens. During the second half of the follicular phase, the follicle becomes dependent on LH. Induction of multiple follicular development by exogenous FSH results in a marked suppression of endogenous LH. For normal follicle maturation, both an LH threshold and an LH ceiling have been considered. In the context of an in vitro fertilization program, application of protocols for ovarian stimulation that will prevent the marked suppression of endogenous LH secretion might provide a better approach to treatment optimization.

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Failure of the GnRH antagonist ganirelix to block the positive feedback effect of exogenous estrogen in normal women

Cited by 30 publications

References 16 publications

Clinical impact of LH rises prior to and during ganirelix treatment started on day 5 or on day 6 of ovarian stimulation

Clinical impact of LH rises prior to and during ganirelix treatment started on day 5 or on day 6 of ovarian stimulation

The effect of premature luteinizing hormone increases among high ovarian responders undergoing a gonadotropin‐releasing hormone antagonist ovarian stimulation protocol

The role of gonadotropins in the follicular phase

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