IVI-RMA Lisboa, 1-9ª, Av. Infante Dom Henrique 333 H, Lisbon, Portugal.
Dexeus Fertility, Dexeus University Hospital, 08028, Barcelona, Spain.
Reprod Sci. 2024 Nov;31(11):3560-3568. doi: 10.1007/s43032-024-01700-x. Epub 2024 Sep 25.
To analyze whether combinations of polymorphisms within FSHR gene influence ovarian response (OR) to stimulation. A multicenter prospective cohort study was conducted from 11/2016-06/2019 in Europe and Asia including predicted normo-responders under 38y. Patients underwent ovarian stimulation using fixed-dose 150 IU rFSH in a GnRH antagonist protocol. FSHR variants rs6165, rs6166 and rs1394205 were genotyped and combined in diplotypes. OR was compared following multivariable regression. rs6165/rs6166 genotype AG/AG exhibited more hypo-response (33.1% vs. 24%,adjOR 1.77 [95%CI 1.08-2.90]) and lower Follicle to Oocyte Index (FOI) compared with other diplotypes (EMD -11.72 [95%CI -20.89;-2.55]). Genotype GG/AA showed less hypo-response (19.1% vs. 31%, adjOR 0.48 [95%CI 0.24-0.96]), while AA/AA had higher FOI (EMD 20.04 [95%CI 4.51;35.56]). Concerning rs6165/rs1394205, less oocytes (EMD -1.99 [95%CI -3.57;-0.42]) and lower FOI (EMD -12.07 [95%CI -23.09;-1.05]) were retrieved with genotype AG/AG and higher FORT with genotype AA/AG (EMD 17.88 [95%CI 3.77;31.98]). Regarding rs6166/rs1394205, less hypo-response (16.3% vs. 29.5%,adjOR 0.42 [95%CI 0.19-0.97]), more oocytes (EMD 3.45 [95%CI 1.57;5.34]) and higher FOI (EMD 17.57 [95%CI 4.41;30.73) were found with genotype AA/GG. Genotype AA/AG presented higher FORT (EMD 13.47 [95%CI 2.51,24.42]), while more hypo-response (56.3% vs. 26.4%,adjOR 6.30 [95%CI 1.88;21.08]) and lower FOI (EMD -23.51 [95%CI -45.04;-1.97]) was reported with AG/AA. In accordance with our previous studies, FSHR polymorphisms have a statistically significant impact on OR, both individually and in association. However, only rs6166/rs1394205 genotype AA/GG seems to have a clinically significant effect, with a decrease in the prevalence of hypo-response, higher oocyte yield and increase in FOI.
为了分析 FSHR 基因内的多态性组合是否会影响卵巢反应（OR）对刺激的反应。在欧洲和亚洲进行了一项多中心前瞻性队列研究，纳入了预计在 38 岁以下的预测正常反应者。患者在 GnRH 拮抗剂方案中接受固定剂量 150IU rFSH 的卵巢刺激。对 FSHR 变体 rs6165、rs6166 和 rs1394205 进行了基因分型，并组合成单体型。采用多变量回归比较 OR。与其他单体型相比，rs6165/rs6166 基因型 AG/AG 表现出更多的低反应（33.1% vs. 24%，adjOR 1.77[95%CI 1.08-2.90]）和更低的卵泡卵母细胞指数（FOI）（EMD-11.72[95%CI-20.89；-2.55]）。基因型 GG/AA 表现出较少的低反应（19.1% vs. 31%，adjOR 0.48[95%CI 0.24-0.96]），而 AA/AA 具有更高的 FOI（EMD 20.04[95%CI 4.51；35.56]）。关于 rs6165/rs1394205，基因型 AG/AG 获得较少的卵母细胞（EMD-1.99[95%CI-3.57；-0.42]）和更低的 FOI（EMD-12.07[95%CI-23.09；-1.05]），而基因型 AA/AG 具有更高的 FORT（EMD 17.88[95%CI 3.77；31.98]）。关于 rs6166/rs1394205，基因型 AA/GG 发现较少的低反应（16.3% vs. 29.5%，adjOR 0.42[95%CI 0.19-0.97]），更多的卵母细胞（EMD 3.45[95%CI 1.57；5.34]）和更高的 FOI（EMD 17.57[95%CI 4.41；30.73]）。基因型 AA/AG 表现出更高的 FORT（EMD 13.47[95%CI 2.51，24.42]），而基因型 AG/AA 表现出更多的低反应（56.3% vs. 26.4%，adjOR 6.30[95%CI 1.88；21.08]）和更低的 FOI（EMD-23.51[95%CI-45.04；-1.97]）。与我们之前的研究一致，FSHR 多态性对 OR 具有统计学意义的影响，无论是单独还是联合。然而，只有 rs6166/rs1394205 基因型 AA/GG 似乎具有临床意义，低反应的发生率降低，卵母细胞产量增加，FOI 增加。
