Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Department of Obstetrics and Gynaecology, Section Reproductive Medicine, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Department of Obstetrics & Gynaecology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Hum Reprod. 2015 May;30(5):1102-9. doi: 10.1093/humrep/dev034. Epub 2015 Mar 8.
Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)?
BA concentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid (UDCA) derivatives were associated with development of top quality embryos on Day 3 after fertilization.
Granulosa cells are capable of synthesizing BA, but a potential correlation with oocyte and embryo quality as well as information on the presence and role of BA subspecies in follicular fluid have yet to be investigated.
STUDY DESIGN, SIZE, DURATION: Between January 2001 and June 2004, follicular fluid and serum samples were collected from 303 patients treated in a single academic centre that was involved in a multicentre cohort study on the effectiveness of MNC-IVF.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Material from patients who underwent a first cycle of MNC-IVF was used. Serum was not stored from all patients, and the available material comprised 156 follicular fluid and 116 matching serum samples. Total BA and BA subspecies were measured in follicular fluid and in matching serum by enzymatic fluorimetric assay and liquid chromatography-mass spectrometry, respectively. The association of BA in follicular fluid with oocyte and embryo quality parameters, such as fertilization rate and cell number, presence of multinucleated blastomeres and percentage of fragmentation on Day 3, was analysed.
Embryos with eight cells on Day 3 after oocyte retrieval were more likely to originate from follicles with a higher level of UDCA derivatives than those with fewer than eight cells (P < 0.05). Furthermore, follicular fluid levels of chenodeoxycholic derivatives were higher and deoxycholic derivatives were lower in the group of embryos with fragmentation compared with those without (each P < 0.05). Levels of total BA were 2-fold higher in follicular fluid compared with serum (P < 0.001), but had no predictive value for oocyte and embryo quality.
LIMITATIONS, REASONS FOR CAUTION: Only samples originating from first cycle MNC-IVF were used, which resulted in 14 samples only from women with an ongoing pregnancy, therefore further prospective studies are required to confirm the association of UDCA with IVF pregnancy outcomes. The inter-cycle variability of BA levels in follicular fluid within individuals has yet to be investigated. We checked for macroscopic signs of contamination of follicular fluid by blood but the possibility that small traces of blood were present within the follicular fluid remains. Finally, although BA are considered stable when stored at -20°C, there was a time lag of 10 years between the collection and analysis of follicular fluid and serum samples.
The favourable relation between UDCA derivatives in follicular fluid and good embryo development and quality deserves further prospective research, with live birth rates as the end-point.
STUDY FUNDING/COMPETING INTERESTS: This work was supported by a grant from the Netherlands Organisation for Scientific Research (VIDI Grant 917-56-358 to U.J.F.T.). No competing interests are reported.
胆汁酸（BA）及其各自的亚种是否存在于人类卵泡液（FF）中，它们与改良自然周期体外受精（MNC-IVF）中的胚胎质量有关吗？
卵泡液中的 BA 浓度比血清高 2 倍，熊去氧胆酸（UDCA）衍生物与受精后第 3 天发育为优质胚胎有关。
颗粒细胞能够合成 BA，但卵母细胞和胚胎质量的潜在相关性，以及 BA 亚种在卵泡液中的存在和作用的信息，尚未被研究。
研究设计、大小和持续时间：2001 年 1 月至 2004 年 6 月期间，从参与 MNC-IVF 有效性多中心队列研究的单个学术中心接受治疗的 303 名患者中采集了卵泡液和血清样本。
参与者/材料、设置、方法：使用接受首次 MNC-IVF 周期的患者的材料。并非所有患者的血清都未储存，可用的材料包括 156 份卵泡液和 116 份匹配的血清样本。通过酶荧光测定法和液相色谱-质谱法分别测量卵泡液和匹配血清中的总 BA 和 BA 亚种。分析卵泡液中 BA 与卵母细胞和胚胎质量参数（如受精率和细胞数、多核胚泡的存在和第 3 天的碎片百分比）之间的关系。
与少于 8 个细胞的胚胎相比，取卵后第 3 天有 8 个细胞的胚胎更有可能来自于 UDCA 衍生物水平较高的卵泡（P<0.05）。此外，与无碎片的胚胎相比，有碎片的胚胎的胆酸衍生物水平更高，脱氧胆酸衍生物水平更低（各 P<0.05）。卵泡液中的总 BA 水平比血清高 2 倍（P<0.001），但对卵母细胞和胚胎质量没有预测价值。
局限性、谨慎的原因：仅使用来自 MNC-IVF 首次周期的样本，这导致只有 14 个样本来自正在妊娠的女性，因此需要进一步的前瞻性研究来证实 UDCA 与 IVF 妊娠结局的关系。个体内卵泡液中 BA 水平的周期间变异性尚未被研究。我们检查了卵泡液中是否有血液的宏观污染迹象，但仍有可能存在小量的血液痕迹。最后，尽管 BA 在 -20°C 下储存时被认为是稳定的，但卵泡液和血清样本的采集和分析之间存在 10 年的时间滞后。
卵泡液中 UDCA 衍生物与良好的胚胎发育和质量之间的有利关系值得进一步的前瞻性研究，以活产率为终点。
研究资金/竞争利益：这项工作得到了荷兰科学研究组织（VIDI 资助 917-56-358 给 U.J.F.T.）的支持。没有报告竞争利益。
