Clinical relevance of genetic variants of gonadotrophins and their receptors in controlled ovarian stimulation: a systematic review and meta-analysis

被引:101
作者
Alviggi, Carlo [1 ,2 ]
Conforti, Alessandro [1 ]
Santi, Daniele [3 ,4 ]
Esteves, Sandro C. [5 ,6 ]
Andersen, Claus Yding [7 ]
Humaidan, Peter [8 ,9 ]
Chiodini, Paolo [10 ]
De Placido, Giuseppe [1 ]
Simoni, Manuela [3 ,4 ]
机构
[1] Univ Naples Federico II, Dept Neurosci Reprod Sci & Odontostomatol, I-80131 Naples, Italy
[2] CNR, Ist Endocrinol & Oncol Sperimental, I-80131 Naples, Italy
[3] Univ Modena & Reggio Emilia, Dept Biomed Metab & Neural Sci, Unit Endocrinol, I-41126 Modena, Italy
[4] Azienda Osped Univ Modena, I-41126 Modena, Italy
[5] Univ Estadual Campinas, UNICAMP, Androfert Androl & Human Reprod Clin, BR-13075460 Campinas, SP, Brazil
[6] Univ Estadual Campinas, UNICAMP, Dept Surg, Div Urol, BR-13075460 Campinas, SP, Brazil
[7] Univ Hosp Copenhagen, Fac Hlth & Med Sci, Lab Reprod Biol, DK-2100 Copenhagen, Denmark
[8] Skive Reg Hosp, Fertil Clin, Skive, Denmark
[9] Aarhus Univ, Fac Hlth, DK-7800 Aarhus, Denmark
[10] Univ Campania Luigi Vanvitelli, Med Stat Unit, I-80138 Naples, Italy
关键词
assisted reproduction; ovarian stimulation; polymorphisms; FSH; gonadotrophins; LH; pharmacogenomics; SINGLE-NUCLEOTIDE POLYMORPHISMS; HORMONE RECEPTOR; FSH RECEPTOR; SER680ASN POLYMORPHISM; PHARMACOGENETIC APPROACH; PROMOTER POLYMORPHISM; LUTEINIZING-HORMONE; STEROID-PRODUCTION; SERUM FSH; ASSOCIATION;
D O I
10.1093/humupd/dmy019
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
BACKGROUND: Genotype has been implicated in the outcome of ovarian stimulation. The analysis of patient-specific genotypes might lead to an individualized pharmacogenomic approach to controlled ovarian stimulation (COS). However, the validity of such an approach remains to be established. OBJECTIVE AND RATIONALE: To define the impact of specific genotype profiles of follicle-stimulating hormone, luteinizing hormone and their receptors (FSHR, LHR and LHCGR) on ovarian stimulation outcome. Specifically, our aim was to identify polymorphisms that could be useful in clinical practice, and those that need further clinical investigation. SEARCH METHODS: A systematic review followed by a meta-analysis was performed according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines without time restriction. We searched the PubMed/MEDLINE, Cochrane Library, SCOPUS and EMBASE databases to identify all relevant studies published before January 2017. Only clinical trials published as full-text articles in peer-reviewed journals were included. The primary outcome was the number of oocytes retrieved. OUTCOMES: Fifty-seven studies were assessed for eligibility, 33 of which were included in the qualitative and quantitative analyses. Data were independently extracted using quality indicators. COS outcomes related to seven polymorphisms (FSHR [rs6165], FSHR [rs6166], FSHR [rs1394205], LHB [rs1800447], LHB [rs1056917], LHCGR [rs2293275] and LHCGR [rs13405728]) were evaluated. More oocytes were retrieved from FSHR (rs6165) AA homozygotes (five studies, 677 patients, weighted mean difference [WMD]: 1.85, 95% CI: 0.85-2.85, P < 0.001; I-2 = 0%) than from GG homozygotes and AG heterozygotes (four studies, 630 patients, WMD: 1.62, 95% CI: 0.28-2.95, P = 0.020; I-2 = 56%). Moreover, stimulation duration was shorter in FSHR (rs6165) AA homozygotes than in AG carriers (three studies, 588 patients, WMD -0.48, 95% CI: -0.87 to -0.10, P = 0.010, I-2 = 44%). A higher number of oocytes (21 studies, 2632 patients WMD: 0.84, 95% CI: 0.19 to 1.49, P = 0.01, I-2 = 76%) and metaphase II oocytes (five studies, 608 patients, WMD: 1.03, 95% CI: 0.01-2.05, P = 0.050, I-2 = 0%) was observed in AA than in GG homozygote carriers. FSH consumption was significantly lower in FSHR (rs1394205) GG homozygotes (three studies, 411 patients, WMD: -1294.61 IU, 95% CI: -593.08 to -1996.14 IU, P = 0.0003, I-2 = 99%) and AG heterozygotes (three studies, 367 patients, WMD: -1014.36 IU, 95% CI: -364.11 to -1664.61 IU, P = 0.002, I-2 = 99%) than in AA homozygotes. WIDER IMPLICATIONS: These results support the clinical relevance of specific genotype profiles on reproductive outcome. Further studies are required to determine their application in a pharmacogenomic approach to ovarian stimulation.
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收藏
页码:599 / 614
页数:16
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