Ma Shujuan, Zheng Yixiang, Fang Mingli, Xiong Yiquan, Hu Liang, Liu Yvonne, Gong Fei, Krämer Bernhard K, Lin Ge, Hocher Berthold
Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, Hunan, China.
Key Laboratory of Reproductive and Stem Cell Engineering, Central South University, Changsha, Hunan, China.
Hum Reprod. 2025 Jun 1;40(6):1173-1182. doi: 10.1093/humrep/deaf055.
Does COVID-19 vaccination affect the risk of pregnancy-induced hypertension (PIH) in women undergoing ARTs, and does this risk differ based on vaccine type (inactivated vs recombinant) and timing relative to embryo transfer?
Women who received inactivated COVID-19 vaccines before undergoing ART had a significantly increased risk of developing PIH, particularly when vaccinated with two or more doses or when embryo transfer occurred within 1 month of vaccination.
COVID-19 vaccination during pregnancy reduces the risk of severe COVID-19 illness with no significant safety concerns for the mother or fetus. PIH is a common complication in ART pregnancies, particularly in older women and those with higher BMI, but the effects of different COVID-19 vaccine types on PIH risk in ART pregnancies remain unclear.
STUDY DESIGN, SIZE, DURATION: A retrospective cohort study analyzing 3911 women undergoing ART after receiving COVID-19 vaccines. The study period spanned from 1 December 2020 to 30 September 2022.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were categorized based on COVID-19 vaccination status, vaccine type (inactivated vs recombinant), and the timing of vaccination relative to embryo transfer. The primary outcome was the development of PIH. Multivariate robust Poisson regression was used to assess the association between vaccination and PIH, while subgroup analyses explored the risk across variables like age, BMI, and embryo transfer type.
Women vaccinated with an inactivated COVID-19 vaccine prior to embryo transfer had a significantly higher incidence of PIH compared to unvaccinated counterparts (relative risk [RR] = 1.45; 95% CI 1.10-1.92; P = 0.009). In contrast, recombinant vaccines did not show a significant association with increased PIH risk (RR = 1.19; 95% CI 0.69-2.05; P = 0.537). The risk was particularly pronounced among women receiving two or more doses of the inactivated vaccines and those who had embryo transfers within 1 month of vaccination. Subgroup analyses showed elevated PIH risk in women aged ≥30 years old, those with BMI ≥22 kg/m2, individuals with secondary infertility, and those undergoing cleavage-stage or fresh embryo transfers.
LIMITATIONS, REASONS FOR CAUTION: The study's retrospective design limits causal inference. The sample is from a single ethnic background, and familial hypertension history was not available, potentially introducing residual confounding.
The study suggests that the type and timing of COVID-19 vaccination may influence PIH risk in ART pregnancies. These findings underscore the need for careful consideration of vaccination type and timing in ART protocols and highlight the importance of further prospective studies to validate these results before influencing clinical decision-making.
STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Hunan High-Level Talent Aggregation Project [2022RC4007]; the National Natural Science Foundation of China [72004148]; the Hunan Provincial Enterprise Joint Fund [2024JJ9093]; the Hunan Provincial Grant for Innovative Province Construction [2019SK4012]; the Deutschlandstipendium of the Charite; the non-restricted research grant of Boehringer Ingelheim Ltd.; and the Research Grant of CITIC-Xiangya [YNXM-202304, 202217]. The authors report no conflicts of interest.
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新冠病毒疫苗接种是否会影响接受辅助生殖技术（ART）的女性发生妊娠期高血压（PIH）的风险，且这种风险是否因疫苗类型（灭活疫苗与重组疫苗）以及相对于胚胎移植的时间不同而有所差异？
在接受ART之前接种灭活新冠病毒疫苗的女性发生PIH的风险显著增加，尤其是接种两剂或更多剂疫苗时，或在接种疫苗后1个月内进行胚胎移植时。
孕期接种新冠病毒疫苗可降低患重症新冠病毒疾病的风险，对母亲或胎儿无明显安全问题。PIH是ART妊娠中的常见并发症，尤其在年龄较大和体重指数较高的女性中，但不同类型的新冠病毒疫苗对ART妊娠中PIH风险的影响尚不清楚。
研究设计、规模、持续时间：一项回顾性队列研究，分析了3911名接种新冠病毒疫苗后接受ART的女性。研究期间为2020年12月1日至2022年9月30日。
参与者/材料、环境、方法：根据新冠病毒疫苗接种状况、疫苗类型（灭活疫苗与重组疫苗）以及相对于胚胎移植的接种时间对参与者进行分类。主要结局是发生PIH。采用多变量稳健泊松回归评估疫苗接种与PIH之间的关联，同时进行亚组分析以探讨年龄、体重指数和胚胎移植类型等变量的风险情况。
与未接种疫苗的女性相比，在胚胎移植前接种灭活新冠病毒疫苗的女性PIH发病率显著更高（相对风险[RR]=1.45；95%置信区间1.10 - 1.92；P = 0.009）。相比之下，重组疫苗与PIH风险增加无显著关联（RR = 1.19；95%置信区间0.69 - 2.05；P = 0.537）。在接受两剂或更多剂灭活疫苗的女性以及在接种疫苗后1个月内进行胚胎移植的女性中，这种风险尤为明显。亚组分析显示，年龄≥30岁的女性、体重指数≥22 kg/m²的女性、继发性不孕的个体以及接受卵裂期或新鲜胚胎移植的女性PIH风险升高。
局限性、谨慎原因：该研究的回顾性设计限制了因果推断。样本来自单一民族背景，且无法获取家族高血压病史，可能存在残余混杂因素。
该研究表明，新冠病毒疫苗接种的类型和时间可能会影响ART妊娠中的PIH风险。这些发现强调了在ART方案中需要仔细考虑疫苗接种类型和时间，并突出了在影响临床决策之前进行进一步前瞻性研究以验证这些结果的重要性。
研究资金/利益冲突：本研究得到湖南省高层次人才聚集项目[2022RC4007]、国家自然科学基金[72004148]、湖南省企业联合基金[2024JJ9093]、湖南省创新型省份建设专项[2019SK4012]、Charite的德国奖学金、勃林格殷格翰有限公司的无限制研究资助以及中信湘雅研究资助[YNXM - 202304, 202217]的支持。作者声明无利益冲突。
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