Clinica Pronatus Centro de Reprodução Humana, Belém, Pará, Brazil.
Programa de Pós Graduação de Ciências Médicas da Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
JBRA Assist Reprod. 2021 Jul 21;25(3):439-446. doi: 10.5935/1518-0557.20210004.
This paper aimed to assess the correlation between LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15 polymorphisms, which are related to follicular development, and decreased ovarian response in women undergoing controlled ovarian hyperstimulation (COH) for IVF.
This age-matched case-control study included three or four controls per woman undergoing COH. Controls were women with normal ovarian response (NOR) and cases were women with poor ovarian response (POR) in oocyte retrieval (three or fewer oocytes). DNA was extracted from peripheral blood and potential associations with gene polymorphisms related to follicular development (LH, LHR, GDF9, FSHR, AMH, AMHR2, and BMP15) were analyzed.
Sixty-six patients were included, 52 in the NOR and 14 in the POR group. Two GDF9 polymorphisms were associated with follicular response after COH, one associated with POR - the presence of a mutant polymorphism in heterozygosis and homozygosis of the GDF9 398-39 (C to G) [23% NOR versus 68% POR (OR 4.01, CI 1.52-10.6, p=0.005)] - and another associated with protective response - the presence of normal homozygosis of GDF9 (C447T) [19.2% NOR versus 50% POR (OR 0.34, IC 0.14-0.84, p=0.019)]. No additional associations were found between the other analyzed polymorphisms and POR.
This study found that GDF9 appears to play an important role in follicular development, whereas polymorphisms in its DNA chain may negatively affect ovarian reserve, such as 398-39 (C to G), or positively, as seen in C447T.
本研究旨在评估与卵泡发育相关的 LH、LHR、GDF9、FSHR、AMH、AMHR2 和 BMP15 多态性与接受 IVF 控制性卵巢过度刺激（COH）的女性卵巢反应下降之间的相关性。
本病例对照研究按照年龄匹配，纳入每例 COH 女性 3 至 4 名对照。对照组为卵巢反应正常（NOR）的女性，病例组为取卵时卵巢反应不良（POR）的女性（取卵时获卵数为 3 枚或更少）。从外周血中提取 DNA，并分析与卵泡发育相关的基因多态性（LH、LHR、GDF9、FSHR、AMH、AMHR2 和 BMP15）与潜在关联。
共纳入 66 例患者，NOR 组 52 例，POR 组 14 例。有 2 个 GDF9 多态性与 COH 后卵泡反应相关，其中一个与 POR 相关 - 杂合和纯合 GDF9 398-39（C 到 G）存在突变多态性[23%NOR 组与 68%POR 组（OR4.01，CI1.52-10.6，p=0.005)]-另一个与保护性反应相关- GDF9 正常纯合性[19.2%NOR 组与 50%POR 组（OR0.34，CI0.14-0.84，p=0.019）]。在其他分析的多态性与 POR 之间未发现其他关联。
本研究发现 GDF9 似乎在卵泡发育中起重要作用，而其 DNA 链的多态性可能会对卵巢储备产生负面影响，如 398-39（C 到 G），或者像 C447T 一样产生正面影响。
