GnRH antagonist rescue in high responders at risk for OHSS results in excellent assisted reproduction outcomes

Walter Reed National Military Medical Center, Washington, DC, United States
Reproductive biomedicine online (Impact Factor: 3.02). 05/2012; 25(3):284-91. DOI: 10.1016/j.rbmo.2012.05.004
Source: PubMed


Gonadotrophin-releasing hormone (GnRH) antagonist rescue is performed by replacing a GnRH agonist with a GnRH antagonist in patients with rapidly rising serum oestradiol who are at risk of ovarian hyperstimulation syndrome (OHSS) during stimulation. It results in a rapid reduction in serum oestradiol, allowing for the avoidance of cycle cancellation and the continuation of exogenous gonadotrophin administration. A total of 387 patients who underwent GnRH antagonist rescue for ovarian hyperresponse were compared with 271 patients who did not receive GnRH antagonist rescue and had oestradiol concentrations >4000 pg/ml on the day of human chorionic gonadotrophin (HCG) administration. GnRH antagonist rescue decreased the mean oestradiol concentration by 35% on the first day of use. There was no difference in oocyte maturity (82% versus 83%) or fertilization rate (69% versus 67%) between the antagonist rescue and comparison groups, respectively. The percentage of high-grade embryos on day 3 and the blastocyst development rate were also similar between groups. The live-birth rate was 41.9% in the antagonist rescue group and 36.9% in the comparison group. GnRH antagonist rescue enabled cycle completion with high live-birth rates in patients at risk for OHSS. GnRH antagonist was associated with high oocyte quality, blastocyst development and pregnancy. RBM Online (c) 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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    • "On the other hand, GnRH antagonist treatment has been utilized as the primary intervention for patients undergoing ovarian stimulation who have rapidly rising estradiol concentrations and are at risk for OHSS. GnRH antagonist prevents OHSS by decreasing serum estradiol concentrations, achieving excellent outcomes, while there is no adverse impact on cycles [20]. Moreover, a OHSS rat model revealed that treatment with both a GnRHanta and a GnRHa resulted in significant reductions in serum estradiol and peritoneal vascular permeability, as well as decreased ovarian expression of VEGF, and its two receptors and GnRHanta are more potent than GnRHa in preventing early OHSS through down-regulation of the expression of VEGF and its receptors in hyperstimulated ovaries [21]. "
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    ABSTRACT: Objective To investigate the effects of V1A receptor antagonist through inhibition of vasopressin-induced VEGF secretion in an experimental model. Study design : Thirty rats were randomly divided into five groups. Four groups were given 10 IU pregnant mare serum gonadotropin/day (sc) at 8:00–8:30 am on days 22-25 of life. They were administered 30 IU hCG at 8:00–8:30 am on day 26 of life. On days 26 and 27 of life at 8:00 am and 4:00 pm, (ip) per animal, 50 mcg/kg/day GnRH antagonist in the GnRH antagonist group, 0.3 mg relcovaptan in the high dose relcovaptan group, and 0.15 mg relcovaptan in the low dose relcovaptan group were administered. The control group was given the same dosage of 0.9% saline solution (ip) on days 22-26 day of life. The main outcomes were weight gain, ovarian weights, peritoneal fluid VEGF values, corpus luteum count, and atretic follicle count. Results Weight gain was highest in the OHSS group; it was almost twice as much in the OHSS group than it was in the control group. Ovarian weights were significantly lower in all treatment groups (p = 0.03). There was no statistically significant difference in ovarian weights between the GnRH antagonist and relcovaptan groups (p = 0.176). The evaluation of peritoneal fluid VEGF-A levels revealed statistically significant differences between levels in the treatment groups and in the OHSS group (p = 0.005). Atretic follicle count in the OHSS group was significantly lower (p = 0.048). In all treatment groups, CL counts were prominently lower than they were in the OHSS group (p = 0.002). Conclusion Relcovaptan may be a novel strategy for decreasing risk of OHSS by inhibition of vasopressin-induced VEGF secretion through V1A receptor antagonist.
    European journal of obstetrics, gynecology, and reproductive biology 01/2013; 174(1). DOI:10.1016/j.ejogrb.2013.12.001 · 1.70 Impact Factor
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    Fertility and sterility 01/2013; 99(6). DOI:10.1016/j.fertnstert.2012.12.053 · 4.59 Impact Factor
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    ABSTRACT: Objective To evaluate cumulus cell (CC) expression profile modulation after different stimulation protocols. Design CCs transcriptome variations were evaluated by microarray in patients undergoing different treatments for ovarian stimulation, namely, r-hLH + r-hFSH and hp-hMG, compared with a control group treated with r-hFSH. Setting Healthy patients undergoing assisted reproduction protocols. Patient(s) Sixteen healthy women with regular cycles and tubal disease or unexplained infertility. Intervention(s) Four patients received hp-hMG, four received r-hFSH + r-hLH, and eight received r-hFSH daily. Aspiration of the oocytes was performed 36 hours after hCG administration. Only samples derived from cumulus-oocyte complexes containing mature oocytes showing polar body were processed. Main Outcome Measure(s) Comparison of genes differentially expressed in both treatment groups with the use of a hierarchic clustering analysis. Result(s) Data clustering analysis allowed detection of four clusters containing genes differentially expressed in both treatment groups compared with control. Functional analysis of the affected transcripts revealed genes involved in oocyte development and maturation. Conclusion(s) r-hLH and hCG, though acting on the same receptor, produce a differential activation of intracellular pathways. It can be hypothesized that this effect depends on their different structures and specific binding affinity for the receptor.
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