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• W2034898048 abstract "The use of aromatase inhibitors (AIs) in IVF patients remains controversial. AIs can be considered for ovulation induction for IVF in women who are normal and poor responders, are at risk of ovarian hyperstimulation syndrome or thrombosis, who have endometriosis, and/or are undergoing fertility preservation procedures as a result of estrogen-dependent cancers, primarily breast and endometrial cancers. Although the biologic plausibility of the capacity of AIs in IVF patients is promising, results should be interpreted with caution, because the efficacy of AIs needs to be proven in randomized trials. The use of aromatase inhibitors (AIs) in IVF patients remains controversial. AIs can be considered for ovulation induction for IVF in women who are normal and poor responders, are at risk of ovarian hyperstimulation syndrome or thrombosis, who have endometriosis, and/or are undergoing fertility preservation procedures as a result of estrogen-dependent cancers, primarily breast and endometrial cancers. Although the biologic plausibility of the capacity of AIs in IVF patients is promising, results should be interpreted with caution, because the efficacy of AIs needs to be proven in randomized trials. Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/garcia-velascoj-aromatase-inhibitors-ivf/ Discuss: You can discuss this article with its authors and with other ASRM members at http://fertstertforum.com/garcia-velascoj-aromatase-inhibitors-ivf/ The use of aromatase inhibitors (AIs) as an adjuvant treatment in IVF has been assessed in the past decade (1Requena A. Herrero J. Landeras J. Navarro E. Neyro J.L. Salvador C. et al.Use of letrozole in assisted reproduction: a systematic review and meta-analysis.Hum Reprod Update. 2008; 14: 571-582Crossref PubMed Scopus (121) Google Scholar, 2Bosdou J. Venetis C. Kolibinakis E. Toulis K. Goulis D. Zepiridis L. et al.The use of androgen-modulating agents in poor responders undergoing in vitro fertilization: a systematic review and meta-analsysis.Hum Reprod Update. 2012; 18: 127-145Crossref PubMed Scopus (102) Google Scholar, 3Papanikolau E. Polyzos N. Humaidan P. Pados G. Bosch E. Tournaye H. et al.Aromatase inhibitors in stimulated IVF cycles.Reprod Biol Endocrinol. 2011; 9: 85-88Crossref PubMed Scopus (33) Google Scholar, 4Lee V. Ledger W. Aromatase inhibitors for ovulation induction and ovarian stimulation.Clin Endocrinol (Oxf). 2011; 74: 537-546Crossref PubMed Scopus (22) Google Scholar). AIs can be considered for ovulation induction for IVF in normal and poor responders, women at risk of ovarian hyperstimulation syndrome (OHSS) or thrombosis, who have endometriosis, and/or who are undergoing fertility preservation procedures as a result of estrogen-dependant cancers, primarily breast and endometrial cancers. Studies are heterogeneous, and the evidence is scarce, mainly owing to unfounded safety fears or the risk of teratogenesis, which has limited the generation of well designed studies based on preliminary retrospective series or pilot trials. AI use for IVF in hormone-dependent cancers and the risk for teratogenicity will not be discussed here, because they are addressed elsewhere in this section of Views and Reviews. AIs inhibit aromatization of androgens to estrogens, mainly in the ovarian granulosa cells, inducing a reduction in circulating estrogen levels, which has several implications for IVF:Pituitary escape from estrogen feedback, leading to elevated gonadotropins and improved follicular recruitmentA transient accumulation of these intraovarian androgens, creating an androgenic microenvironment in the maturing follicle that may enhance follicular sensitivity to FSH with a relatively short duration, because letrozole has a short has life (∼45 h). This may be of interest in poor responders, because it has been shown that along with ovarian aging a significant androgen reduction is observed, and androgen pretreatment may improve ovarian performance and follicle development.A strong reduction in the secretion of estrogens from the granulosa cells. The reduction of circulating steroid levels is an attractive option to minimize the risk of thrombosis in hyperestrogenic states and/or the risk of complications if OHSS develops, as well as to provide additional safety in women who have hormone-dependent cancers undergoing controlled ovarian hyperstimulation (COH) for fertility preservation.Inhibition of aromatase could potentially improve endometrial receptivity, particularly in patients with endometriosis in whom aromatase is aberrantly expressed. According to basic and clinical studies, there are three different areas in which the use of aromatase inhibitors may prove beneficial for IVF patients: improving cycle outcome in low-responder patients, reducing the risk of OHSS, and reducing the risk that high estrogen levels can pose to women with a high response to COH. The rationale for using AIs in poor responders to COH is based on their capacity to transiently accumulate androgens in the ovarian micromilieu, which may increase ovarian sensitivity to FSH, because it is known that androgens play a crucial role in early follicular development and granulosa cell proliferation (5Hillier S. De Zwart F. Evidence that granulosa cell aromatase induction/activation by follicle-stimulating hormone is an androgen receptor-regulated process in-vitro.Endocrinology. 1981; 4: 1303-1305Crossref Scopus (123) Google Scholar, 6Weil S. Vendola K. Zhou J. Adesanya O. Wang J. Okafor J. et al.Androgen receptor gene expression in the primate ovary: cellular localization, regulation and functional correlations.J Clin Endocrinol Metab. 1998; 7: 2479-2485Crossref Scopus (246) Google Scholar, 7Garcia-Velasco J.A. Rodriguez S. Agudo D. Pacheco A. Schneider J. Pellicer A. FSH receptor in vitro modulation by testosterone and hCG in human luteinized granulosa cells.Eur J Obstet Gynecol Reprod Biol. ePub ahead of print, September 7, 2012; (doi:10.1016/j.ejogrb.2012.08.020)PubMed Google Scholar). Both of the third-generation AIs, anastrazole and letrozole, which are highly potent reversible inhibitors, have been used as adjuvant treatments in an attempt to create a hyperandrogenic intraovarian state in women who previously had a poor response to COH. The biologic plausibility of the theory of androgenization is attractive, but is it clinically relevant? We evaluated the impact of letrozole as an adjuvant treatment in 147 women with a previous IVF cycle cancelled due to low response (8Garcia-Velasco J.A. Moreno L. Pacheco A. Guillen A. Duque L. Requena A. et al.The aromatase inhibitor letrozole increases the concentration of intraovarian androgens and improves in vitro fertilization outcome in low responder patients: a pilot study.Fertil Steril. 2005; 84: 82-87Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar). Letrozole (2.5 mg) was administered to 71 patients during the first 5 days of the stimulation, whereas the control subjects received a similar dose of FSH/hMG. Interestingly, letrozole-treated patients showed significantly higher levels of follicular fluid T and A (80.3 pg/mL vs. 43.8 pg/mL and 57.9 mg/mL vs. 37.4 mg/mL, respectively). Clinically speaking, patients who received letrozole had a higher number of oocytes retrieved (6.1 vs. 4.3) and a higher implantation rate (25% vs. 9.4%). This initial observation could not be confirmed in a proper randomized trial, because around the same time the manufacturer of letrozole, based on an inadequately designed study (9Biljan M. Hemmings R. Brassard N. The outcome of 150 babies following the treatment with letrozole or letrozole and gonadotropins.Fertil Steril. 2005; 84: S95Abstract Full Text Full Text PDF Google Scholar), suggested not using AIs in assisted reproduction. Reassuring data from later publications could not completely resolve this issue (10Tulandi T. Martin J. Al-Fadhi R. Kabli N. Forman R. Hitkari J. et al.Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate.Fertil Steril. 2006; 85: 1761-1765Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar). However, additional publications became available. The concept that AIs could contribute to the follicular response was validated in normal responders, both with letrozole (11Verpoest W. Kolibianakis E. Papanikolau E. Smitz J. van Steirteghem A. Devroey P. Aromatase inhibitors in ovarian stimulation for IVF/ICSI: a pilot study.Reprod Biomed Online. 2006; 13: 166-172Abstract Full Text PDF PubMed Scopus (55) Google Scholar) and anastrazole (12Lossl K. Andersen C.Y. Loft A. Freiesleben N. Bangsboll S. Andersen A.N. Short-term androgen priming by use of aromatase inhibitor and hCG before controlled ovarian stimulation for IVF. A randomized controlled trial.Hum Reprod. 2008; 23: 1820-1829Crossref PubMed Scopus (38) Google Scholar), even though embryo quality in this particular population was not improved. A large, prospective trial compared the impact of letrozole co-treatment in past or potential poor responders with a microdose GnRH agonist flare protocol, finding similar results in stimulation parameters and a higher pregnancy rate with the microflare protocol (13Schoolcraft W. Surrey E. Minjarez D. Stevens J. Gardner D. Management of poor responders: can outcomes be improved with a novel gonadotropin-releasing hormone antagonist/letrozole protocol?.Fertil Steril. 2008; 89: 151-156Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar). In this study, the definition of poor responders in the patients may not have been exactly the same as in other studies, as patients had a mean number of 9 antral follicles and produced between 12 and 13 oocytes. Although other potential confounders could have contributed to the different results such as different protocols, doses, or even GnRH analogues a larger sample size would have been necessary to verify these findings. Nevertheless, further trials suggested that letrozole co-treatment could be an effective protocol that could be used in poor ovarian responders, reducing cancellations and costs, although live birth rates remained low (14Yarali H. Esinler I. Polat M. Bozdag G. Tiras B. Antagonist/letrozole protocol in poor ovarian responders for intracytoplasmic sperm injection: a comparative study with the microdose flare-up protocol.Fertil Steril. 2009; 92: 231-235Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 15Ozmen B. Sonmezer M. Atabekoglu C. Olmus H. Use of aromatase inhibitors in poor-responder patients receiving GnRH antagonist protocols.Reprod Biomed Online. 2009; 19: 478-485Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 16Jovanovic V. Kort D. Guarnaccia M. Sauer M. Lobo R. Does the addition of clomiphene citrate or letrozole to gonadotropin treatment enhance the oocyte yield in poor responders undergoing IVF?.J Assist Reprod Genet. 2011; 28: 1067-1072Crossref PubMed Scopus (20) Google Scholar, 17Lee V. Chan C. Ng E. Yeung W. Ho P. Sequential use of letrozole and gonadotrophin in women with poor ovarian reserve: a randomized controlled trial.Reprod Biomed Online. 2011; 23: 380-388Abstract Full Text Full Text PDF PubMed Scopus (32) Google Scholar, 18Goswami S. Das T. Chattopadhyay R. Sawhney V. Kumar J. Chaudhury K. et al.A randomized, single blinded controlled trial of letrozole as a low cost IVF protocol in women with poor ovarian response: a preliminary report.Hum Reprod. 2004; 19: 2031-2035Crossref PubMed Scopus (146) Google Scholar). It is obvious that today the most effective way to avoid OHSS is the use of agonist triggering rather than hCG in women under the antagonist protocol, because the corpora lutea have a short life after agonist triggering. However, thousands of cycles are still being performed worldwide under the long agonist protocol (19Tur-Kaspa I, Fauser B. The use of TnRH agonist in IVF protocols. Available at: http://www.ivf-worldwide.com/survey/survey-the-use-of-gnrh-agonist-in-ivf-protocols-results.html. Accessed September 1, 2012.Google Scholar), where agonist triggering is not an option. Thus, reducing the production of high amounts of E2 by the granulosa cells may help to minimize the risk of developing OHSS as well as the risk of thrombosis. The effect of letrozole has been investigated as an option to inhibit E2 production and modulate LH levels during the luteal phase. Fatemi et al. (20Fatemi H. Popovic-Todorovic B. Donoso P. Papanikolau E. Smitz J. Devroey P. Luteal phase oestradiol suppression by letrozole: a pilot study in oocyte donors.Reprod Biomed Online. 2008; 17: 307-311Abstract Full Text PDF PubMed Scopus (16) Google Scholar) investigated this concept in a pilot study that included three oocyte donors who were given letrozole (5 mg) and three others who received placebo. Serum E2 concentrations on days 4, 7, and 10 after hCG administration for final oocyte maturation were significantly lower compared with placebo. However, no differences were observed in progesterone and LH profiles during the same period. Garcia-Velasco et al. (21Garcia-Velasco J.A. Quea G. Piró M. Mayoral M. Ruiz M. Toribio M. et al.Letrozole administration during the luteal phase after ovarian stimulation impacts corpus luteum function: a randomized, placebo-controlled trial.Fertil Steril. 2009; 92: 222-225Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar) performed a randomized trial to explore the same concept. Thirty volunteers were randomized to receive letrozole (2.5 mg) or placebo after hCG triggering. As expected, serum E2 concentrations dropped dramatically in those receiving AIs (279 pg/mL vs. 1,589 pg/mL) on day 4 after hCG, and similarly on days 7 and 10. Although P did not change, LH serum concentrations were lower in the control group on days 7 and 10 after hCG, when serum E2 was higher. The quick reduction in serum E2 levels allowed a faster recovery of the LH concentrations, an interesting concept not only for egg donors who are undergoing embryo transfer, but also for patients undergoing COH for fertility preservation and women at risk of OHSS who freeze all their embryos or who cancel hCG administration to reduce the potential risk that high E2 levels pose. In both studies (20Fatemi H. Popovic-Todorovic B. Donoso P. Papanikolau E. Smitz J. Devroey P. Luteal phase oestradiol suppression by letrozole: a pilot study in oocyte donors.Reprod Biomed Online. 2008; 17: 307-311Abstract Full Text PDF PubMed Scopus (16) Google Scholar, 21Garcia-Velasco J.A. Quea G. Piró M. Mayoral M. Ruiz M. Toribio M. et al.Letrozole administration during the luteal phase after ovarian stimulation impacts corpus luteum function: a randomized, placebo-controlled trial.Fertil Steril. 2009; 92: 222-225Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar), VEGF levels or any other vascular permeability factors were not studied. We should bear in mind that E2 reduction does not necessarily mean that the risk of severe OHSS is lessened, so extrapolating lower E2 levels to a lower risk of OHSS is not necessarily true. However, this reduction in E2 levels contributes to reduced risk of thrombosis. Another potential benefit of AIs for patients undergoing IVF might be to inhibit aromatase, the key enzyme in the biosynthesis of E2, not only in the granulosa cells but also “in situ” in endometriotic tissue and the eutopic endometrium of women with endometriosis, because aromatase is expressed in these tissues (22Casper R.F. Mitwally M. Aromatase inhibitors for ovulation induction.J Clin Endocrinol Metab. 2006; 91: 760-771Crossref PubMed Scopus (204) Google Scholar). A pilot study was recently published to study the concept of dual suppression. A 3-month GnRH agonist course combined with anastrazole (1 mg daily) was used in infertile women with endometriomas undergoing IVF (23Lossl K. Loft A. Freiesleben N. Bangsboll S. Andersen C.Y. Pedersen A. et al.Combined down-regulation by aromatase inhibitor and GnRH-agonist in IVF patients with endometriomas—a pilot study.Eur J Obstet Gynecol Reprod Biol. 2009; 144: 48-53Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar). A significant reduction in endometrioma volume (29%) and serum CA-125 concentration (61%) was observed. Although the pregnancy rate was 45%, a high pregnancy loss was noted; the live birth rate was 15%, which may be due to poor embryo quality, as in other endometriosis patients (24Ruiz-Florez F. Garcia-Velasco J.A. Is there a benefit for surgery in endometriomas-associated infertility?.Curr Opin Obstet Gynecol. 2012; 24: 136-140Crossref PubMed Scopus (40) Google Scholar). No further validation of this concept has been made available. In line with this concept, women with endometriosis show aberrant endometrial aromatase expression, which is associated with poor reproductive outcomes (25Brosens J. Verhoeven H. Campo R. Gianaroli L. Gordts S. Hazekamp J. et al.High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome.Hum Reprod. 2004; 19: 352-356Crossref PubMed Scopus (87) Google Scholar). Long-term GnRH agonist therapy has been assayed in an attempt to improve IVF outcome in these women (26Surrey E. Silverberg K. Surrey M. Schoolcraft W. Effect of prolonged gonadotropin-releasing hormone agonist therapy on the outcome of in vitro fertilization–embryo transfer in patients with endometriosis.Fertil Steril. 2002; 78: 699-704Abstract Full Text Full Text PDF PubMed Scopus (187) Google Scholar, 27Salam H. Garcia-Velasco J.A. Dias S. Arici A. Long-term pituitary down-regulation before in vitro fertilization (IVF) for women with endometriosis.Cochrane Database Syst Rev. 2006; : CD004635PubMed Google Scholar), because it suppresses endometrial aromatase expression (28Ishikara H. Kitawaki J. Kado N. Koshiba H. Fushiki S. Honjo H. Gonadotropin-releasing hormone agonist and danazol normalize aromatase cyctochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas.Fertil Steril. 2003; 79: 735-742Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar). Because AIs are capable of suppressing the P450 aromatase enzyme in situ, they might hypothetically improve endometrial receptivity. Very recently, Miller et al. (29Miller P. Parnell B. Bushnell G. Tallman N. Forstein D. Lee Higdon III, H. et al.Endometrial receptivity defects during IVF cycles with and without letrozole.Hum Reprod. 2012; 27: 881-888Crossref PubMed Scopus (87) Google Scholar) examined the effect of letrozole on infertile women with endometriosis undergoing IVF who lacked normal integrin expression, a marker of endometrial receptivity. They confirmed that the use of aromatase inhibitors might improve the IVF success rates in a subset of women with endometriosis and implantation failure. The use of AIs in IVF patients is still controversial. However, the biologic plausibility of their capacity to improve follicular recruitment by escaping from estrogen feedback, to transiently increase androgen concentrations to improve follicle development, inhibit aromatase to potentially improve endometrial receptivity, or decrease estrogen levels and consequently the risk of thrombosis is promising. Even if the available evidence seems favorable, the results should still be interpreted with caution, because the efficacy should be proven in randomized trials. For this purpose, and based on available safety data (10Tulandi T. Martin J. Al-Fadhi R. Kabli N. Forman R. Hitkari J. et al.Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate.Fertil Steril. 2006; 85: 1761-1765Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar), a reassuring statement from medical societies and/or the pharmaceutical industry would be needed. Still, further research is needed on FSH receptor modulation during ovarian stimulation, dose-finding studies should be performed, the impact on endometrial receptivity in women with and without endometriosis should be further analyzed, and the ideal timing for coadjuvant treatment needs to be defined." @default.
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• W2034898048 cites W2081565312 @default.
• W2034898048 cites W2096067447 @default.
• W2034898048 cites W2096723253 @default.
• W2034898048 cites W2100241837 @default.
• W2034898048 cites W2105251513 @default.
• W2034898048 cites W2110983321 @default.
• W2034898048 cites W2115337926 @default.
• W2034898048 cites W2116648077 @default.
• W2034898048 cites W2125629974 @default.
• W2034898048 cites W2126004175 @default.
• W2034898048 cites W2132173246 @default.
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