van de Vijver Arne, Drakopoulos Panagiotis, Van Landuyt Lisbet, Vaiarelli Alberto, Blockeel Christophe, Santos-Ribeiro Samuel, Tournaye Herman, Polyzos Nikolaos P
Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium Department of Clinical Medicine, Faculty of Health, University of Aarhus, Aarhus, Denmark
Hum Reprod. 2016 Aug;31(8):1749-54. doi: 10.1093/humrep/dew107. Epub 2016 May 11.
What is the effect of vitamin D deficiency on the pregnancy rates following frozen embryo transfer (FET)?.
Vitamin D deficiency does not affect pregnancy rates in FET cycles.
Although there is evidence that the potential impact of vitamin D deficiency on reproductive outcome may be mediated through a detrimental effect on oocyte or embryo quality, the rationale of our design was based on evidence derived from basic science, suggesting that vitamin D may have a key role in endometrial receptivity and implantation. Only few retrospective clinical studies have been published to date with conflicting results.
STUDY DESIGN, SIZE, DURATION: This study is the first prospective observational cohort study from the Centre for Reproductive Medicine at the University Hospital of Brussels. The duration of the study was 1 year.
PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 280 consecutive patients, who had at least one blastocyst frozen and were planned for a FET, were enrolled in the study following detailed information and signing of a written informed consent. Serum analysis of 25-OH vitamin D was measured on the day of embryo transfer, and the impact of vitamin deficiency was investigated on reproductive outcomes.
Among all patients, 45.3% (n = 127) had vitamin D deficiency (<20 ng/ml), and 54.6% (n = 153) had vitamin D levels ≥20 ng/ml. Positive human chorionic gonadotrophin rates were similar among patients with vitamin D deficiency and women with total serum 25-OH vitamin D levels ≥20 ng/ml (40.9 versus 48.3%, P = 0.2). Similarly, no difference was found in clinical pregnancy rates in women with vitamin D deficiency [32.2% (41/127)] compared with those with higher vitamin D levels [37.9% (58/153)]; P = 0.3. When analyzing the results according to different thresholds, as proposed by the Endocrine Society, clinical pregnancy rates were comparable between vitamin D deficient (<20 ng/ml), vitamin D insufficient (20-30 ng/ml) and vitamin D replete women (≥30 ng/ml) [32.3% (41/127) versus 39.5% (36/91) versus 35.5% (22/62), respectively, P = 0.54]. Multivariate logistic regression analysis showed that vitamin D status is not related to pregnancy outcome.
LIMITATIONS, REASONS FOR CAUTION: Ethnicity in relation to vitamin D status was not assessed, given that the vast majority of patients included in our study were Caucasian, whereas we did only assess 25-OH vitamin D levels and not bioavailable vitamin D. Furthermore, although we failed to find a difference between vitamin D deficient women and women with vitamin D levels ≥20 ng/ml, we need to underscore that our study was powered to detect a difference of 15% in clinical pregnancy rates.
Vitamin D deficiency does not significantly impair pregnancy rates among infertile women undergoing frozen-thawed cycles. The measurement of vitamin D levels in this population should not be routinely recommended.
STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared.
维生素D缺乏对冻融胚胎移植(FET)后的妊娠率有何影响?
维生素D缺乏不影响FET周期的妊娠率。
尽管有证据表明维生素D缺乏对生殖结局的潜在影响可能通过对卵母细胞或胚胎质量的有害作用来介导,但我们设计的理论依据是基于基础科学得出的证据,表明维生素D可能在子宫内膜容受性和着床中起关键作用。迄今为止,仅有少数回顾性临床研究发表,结果相互矛盾。
研究设计、规模、持续时间:本研究是布鲁塞尔大学医院生殖医学中心开展的第一项前瞻性观察队列研究。研究持续时间为1年。
参与者/材料、环境、方法:共有280例连续患者入组本研究,这些患者至少有一个囊胚被冷冻且计划进行FET,在获取详细信息并签署书面知情同意书后纳入。在胚胎移植当天测定血清25-羟基维生素D水平,并研究维生素缺乏对生殖结局的影响。
在所有患者中,45.3%(n = 127)存在维生素D缺乏(<20 ng/ml),54.6%(n = 153)的维生素D水平≥20 ng/ml。维生素D缺乏患者和血清总25-羟基维生素D水平≥20 ng/ml的女性中,人绒毛膜促性腺激素阳性率相似(40.9%对48.3%,P = 0.2)。同样,维生素D缺乏女性的临床妊娠率[32.2%(41/127)]与维生素D水平较高的女性[37.9%(58/153)]相比无差异;P = 0.3。根据内分泌学会提出的不同阈值分析结果时,维生素D缺乏(<20 ng/ml)、维生素D不足(20 - 30 ng/ml)和维生素D充足的女性(≥30 ng/ml)的临床妊娠率相当[分别为32.3%(41/127)、39.5%(36/91)和35.5%(22/62),P = 0.54]。多因素逻辑回归分析表明,维生素D状态与妊娠结局无关。
局限性、谨慎理由:鉴于本研究纳入的绝大多数患者为白种人,未评估与维生素D状态相关的种族因素,而且我们仅测定了25-羟基维生素D水平,而非生物可利用的维生素D。此外,尽管我们未发现维生素D缺乏女性与维生素D水平≥20 ng/ml的女性之间存在差异,但我们需要强调,我们的研究有能力检测出临床妊娠率15%的差异。
维生素D缺乏不会显著损害接受冻融周期的不孕女性的妊娠率。不建议对该人群常规检测维生素D水平。
研究资金/利益冲突:本研究未使用外部资金。未声明存在利益冲突。