妊娠早期hCG升高缓慢与胎盘发育异常有关吗？

OBJECTIVE

摘要

Serum hCG levels are measured in early gestation to help ascertain pregnancy viability. It has been postulated that hCG trends could reflect early placentation and thereby correlate with adverse obstetric outcomes. Slope of hCG rise was previously shown to be different between pregnancies following fresh versus frozen embryo transfers (ET). We hypothesize that pregnancies with slower hCG rise in early gestation could be associated with an increased risk for subsequent abnormal placentation.

妊娠早期测定血清hCG水平以确定是否怀孕。hCG变化趋势能够反映早期胎盘发育情况并且与多种妊娠结局有关。已发现，hCG上升的斜率在鲜胚及冻胚移植后的妊娠中是不同的。我们假设妊娠早期hCG升高缓慢可能与随后胎盘发育异常的高风险有关。

MATERIALS AND METHODS

材料及方法

Participants in this prospective observational study were derived from the Developmental Epidemiological Study of Children born through Reproductive Technologies (DESCRT) cohort in the San Francisco Bay Area, California. In this analysis, all patients had underlying infertility and conceived via assisted reproductive technology. Pregnancies with multiple gestations (n=17) and those that resulted in miscarriage (n=41) were excluded. Two serum hCG levels were documented for each pregnancy episode in weeks 4-5 of gestation. The hCG slope was calculated as the difference of the natural log-transformed hCG values divided by the number of days between the two hCG measurements. The 2-day hCG rise (%) was also calculated for each pregnancy episode. The hCG slope and 2-day percentage rise were compared between pregnancies from fresh and frozen ETs using the Mann-Whitney test. Abnormal placentation was defined as the presence of placenta previa, placenta accreta, placental abruption, and/or abnormal cord insertion. Logistic regression was used to assess for an association between hCG slope and abnormal placentation, adjusted for age, body mass index (BMI), and type of ET. Analyses were performed at the .05 level using Stata v17.0.

在这次前瞻性观察研究中，参与者来自加利福尼亚旧金山港湾地区通过生殖技术出生的儿童发展流行病学研究队列。在此次研究中，所有患者均患有潜在的不孕症并且通过辅助生殖技术怀孕。多胎妊娠（n=17）及流产（n=41）的情况被排除在外。记录下每次妊娠4～5周两种血清hCG的水平。hCG斜率计算为自然对数变换后的hCG值除以两次hCG测量之间的天数。还计算了每个妊娠周期的隔日hCG上升百分比。隔日hCG上升值也同样计算出来。使用Mann-Whitney方法比较鲜胚与冻胚移植中hCG上升的斜率及隔日升高的百分率。胎盘发育异常是指胎盘前置、胎盘植入、胎盘早剥以及/或胎盘脐带附着异常。用逻辑回归的方法调整了年龄、体重指数以及移植方式后，评估hCG斜率与胎盘发育异常之间的关系。使用Stata v17.0软件进行了在0.05水平上的分析。

RESULTS

结果

A total of 457 pregnancy episodes were included in this analysis: 113 (24.7%) resulted from fresh ET and 344 (75.3%) from frozen ET. The mean (SD) age was 38.6 (4.3) years old, and the mean (SD) BMI was 24.3 (4.1) in this cohort. The mean (SD) hCG slope was 0.44 (0.09) for the cohort, and was higher in pregnancies that resulted from frozen ET [0.45 (0.09)] compared to fresh ET [0.42 (0.09)] (p<0.01). The mean (SD) 2-day hCG rise (%) was 179.4 (103.7) for the cohort; 2-day hCG rise following frozen ET was 187.3 (110.3) compared to 155.3 (75.8) following fresh ET (p<0.01). Logistic regression analysis adjusted for age, BMI, and type of ET showed no significant association between hCG slope and subsequent development of abnormal placentation (OR 0.97, 95% CI: 0.03-32.80, p=0.99).

本分析包括457个妊娠周期：113个（24.7%）来自新鲜胚胎移植，344个（75.3%）来自冷冻胚胎移植。该队列中的平均（标准差）年龄为38.6（4.3）岁，平均（标准差）BMI为24.3（4.1）。该队列的平均（标准差）hCG斜率为0.44（0.09），冷冻胚胎移植所导致的妊娠的hCG斜率[0.45（0.09）]高于新鲜胚胎移植[0.42（0.09）]（p<0.01）。该队列的隔日hCG上升百分比为179.4（103.7）；冷冻胚胎移植后的隔日hCG上升百分比为187.3（110.3），而新鲜胚胎移植后的为155.3（75.8）（p<0.01）。考虑年龄、BMI和胚胎移植类型的Logistic回归分析显示hCG斜率与异常胎盘发育之间没有显著关联（OR 0.97，95% CI: 0.03-32.80，p=0.99）。

CONCLUSIONS

结论

Pregnancies that resulted from fresh ET had slower hCG rise compared to those from frozen ET. A lower hCG slope was not associated with increased odds of subsequent abnormal placentation.

鲜胚胎移植治疗后妊娠的hCG上升速度较冷冻胚胎移植较慢。较低的hCG斜率并不增加随后异常胎盘发育的概率。

IMPACT STATEMENT

影响陈述

Trend of hCG rise in early gestation differs between pregnancies following fresh versus frozen embryo transfer, suggesting a difference in early uterine environment between these two treatment types. Further studies are needed to identify early biomarkers for subsequent abnormal placentation.

早期妊娠时hCG的上升趋势在鲜胚移植与冻胚移植中是不同的，这提示两种移植方式的早期宫内环境是有区别的。我们需要做深入的研究来确定随后胎盘发育异常的生物标志物。

文章来源：

A SLOWER HUMAN CHORIONIC GONADOTROPIN (HCG) RISE IN EARLY PREGNANCY WAS NOT ASSOCIATED WITH THE DEVELOPMENT OF ABNORMAL PLACENTATION IN PATIENTS WHO CONCEIVED USING ASSISTED REPRODUCTIVE TECHNOLOGY Durgana, Chantal et al.Fertility and Sterility, Volume 120, Issue 4, e287