Hvidman Helene W, Bang Anne Kirstine, Priskorn Lærke, Scheike Thomas, Birch Petersen Kathrine, Nordkap Loa, Loft Anne, Pinborg Anja, Tabor Ann, Jørgensen Niels, Nyboe Andersen Anders
The Fertility Clinic, Copenhagen University Hospital, Rigshospitalet, Copenhagen O, DK-2100, Denmark.
Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen K, DK-2100, Denmark; International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), University of Copenhagen, Denmark.
Eur J Obstet Gynecol Reprod Biol. 2017 Oct;217:44-52. doi: 10.1016/j.ejogrb.2017.08.015. Epub 2017 Aug 14.
To investigate the association between anti-Müllerian hormone (AMH), a well-established marker of the ovarian reserve, and time-to-pregnancy (TTP) in natural conceptions, and to assess changes in serum-AMH in early pregnancy.
A cross sectional study comprising 279 women aged 21-42 years with a natural conception recruited during 2012-2014. AMH was measured in gestational week 10-19. AMH z-scores (z-AMH) adjusted for gestational week at blood sampling were categorised in the 1st, 2nd-4th (reference), and 5th quintile. Data were analysed by discrete-time survival-analysis and results presented as odds ratios (OR), 95% confidence interval (CI); OR <1 indicating a longer TTP and OR >1 indicating a shorter TTP.
The median AMH-level was 23.0 (range:<3.0;144.0)pmol/l, and serum-AMH decreased by 7.5% (95% CI:-12.0%;-2.8%) per gestational week. Mean±SD female age was 30.9±3.6years. The median TTP was 2 (range: 1-32) months. After adjustment for possible confounders including total sperm count, TTP was unrelated to female age (aOR:1.0, 95% CI:0.9;1.0) and continuous z-AMH (aOR:0.8, 95% CI:0.7;1.0), but women in the low z-AMH group had a shorter TTP than the reference group (aOR:1.7, 95% CI:1.1;2.7). TTP was prolonged in preconception oral contraceptive (OC) users (aOR:0.7, 95% CI:0.5;1.0, p=0.04). Compared with women having used OC <2 years, TTP was significantly longer in women having used OC for 2-12 years (aOR:0.5, 95% CI:0.2;1.0, p=0.048) and >12 years (aOR:0.4, 95% CI:0.2;0.9, p=0.022) after age-adjustment.
TTP was unrelated with z-AMH when modelled as a continuous covariate. Unexpectedly, TTP was shorter in the low z-AMH group. Natural conception was observed in women with a wide range of AMH-levels including women with undetectable serum-AMH. A continuous decrease in serum-AMH was observed during first and second trimester. Preconception OC-use was identified as an independent predictor of a prolonged TTP, and the duration of OC-use appeared to influence the delay in conception. Although this is presently one of the largest studies investigating the association between AMH and fecundability in fertile women, the study has some limitation including a relatively low participation rate and a risk of selection bias in addition to AMH assessment in pregnancy and a retrospective collection of TTP and OC-use associated with a risk of recall bias. These limitations may explain the unexpected finding of a shorter TTP in the low z-AMH group.
研究抗苗勒管激素(AMH)这一公认的卵巢储备标志物与自然受孕时的受孕时间(TTP)之间的关联,并评估早孕期血清AMH的变化。
一项横断面研究,纳入了2012年至2014年期间招募的279名年龄在21 - 42岁之间自然受孕的女性。在妊娠第10 - 19周测量AMH。根据采血时的孕周调整后的AMH z评分(z - AMH)被分为第1、第2 - 4(参照)和第5五分位数。通过离散时间生存分析进行数据分析,结果以比值比(OR)、95%置信区间(CI)表示;OR <1表示TTP较长,OR >1表示TTP较短。
AMH水平中位数为23.0(范围:<3.0;144.0)pmol/l,血清AMH每孕周下降7.5%(95% CI:-12.0%;-2.8%)。女性平均年龄±标准差为30.9±3.6岁。TTP中位数为2(范围:1 - 32)个月。在调整包括总精子数在内的可能混杂因素后,TTP与女性年龄(调整后OR:1.0,95% CI:0.9;1.0)和连续的z - AMH(调整后OR:0.8,95% CI:0.7;1.0)无关,但低z - AMH组女性的TTP比参照组短(调整后OR:1.7,95% CI:1.1;2.7)。受孕前使用口服避孕药(OC)的女性TTP延长(调整后OR:0.7,95% CI:0.5;1.0,p = 0.04)。与使用OC <2年的女性相比,年龄调整后,使用OC 2 - 12年的女性TTP显著更长(调整后OR:0.5,95% CI:0.2;1.0,p = 0.048),使用OC >12年的女性TTP更长(调整后OR:0.4,95% CI:0.2;0.9,p = 0.022)。
将z - AMH作为连续协变量建模时,TTP与之无关。出乎意料的是,低z - AMH组的TTP较短。在包括血清AMH检测不到的女性在内的广泛AMH水平范围内的女性中都观察到了自然受孕。在孕早期和孕中期观察到血清AMH持续下降。受孕前使用OC被确定为TTP延长的独立预测因素,且使用OC的持续时间似乎会影响受孕延迟。尽管这目前是研究AMH与可育女性生育力之间关联的最大规模研究之一,但该研究存在一些局限性,包括参与率相对较低、存在选择偏倚风险,此外还有孕期AMH评估以及TTP和OC使用情况的回顾性收集存在回忆偏倚风险。这些局限性可能解释了低z - AMH组TTP较短这一意外发现。