Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
JAMA Psychiatry. 2022 Feb 1;79(2):133-142. doi: 10.1001/jamapsychiatry.2021.3647.
Individuals conceived with assisted reproductive techniques (ARTs) could be at elevated risk of psychiatric disorders owing to potential adverse effects of the procedures themselves, or because such traits or their risk factors may be more common in couples with infertility.
To investigate the risk of psychiatric disorders in adolescents and young adults conceived with ARTs and to evaluate the role of treatment-related parental characteristics.
DESIGN, SETTING, AND PARTICIPANTS: This prospective follow-up of a nationwide birth cohort used linkage of Swedish population registers with coverage through 2018. All children born in Sweden from January 1, 1994, to December 31, 2006, were included in the analysis. Follow-up was completed on December 31, 2018, when participants were 12 to 25 years of age, and data was analyzed from March 17, 2020, to September 10, 2021.
In vitro fertilization with or without intracytoplasmic sperm injection and transfer of fresh or frozen-thawed embryos.
Clinical diagnoses of mood disorder, including major depression, anxiety, obsessive-compulsive disorder (OCD), or suicidal behavior, were identified from hospital records and outpatient specialist care. Suicide was additionally identified from death certificates. Antidepressant use was identified from dispensations of prescribed medications.
A total of 1 221 812 children (48.6% female, 51.4% male) born between 1994 and 2006 were followed up to a median age of 18 (IQR, 15-21) years. Among these participants, 31 565 (2.6%) were conceived with ART. Compared with all others, adolescents conceived with ART had an elevated risk of OCD (hazard ratio [HR], 1.35 [95% CI, 1.20-1.51]), but the association was attenuated and no longer statistically significant after adjustment for parental characteristics (adjusted HR [aHR], 1.10 [95% CI, 0.98-1.24]) and was no longer present when restricted to individuals born to couples with known infertility (aHR, 1.02 [95% CI, 0.89-1.17]). Adolescents conceived with ARTs were not at elevated risk of depression or suicidal behavior compared with other adolescents (irrespective of parental infertility). Type of fertilization (standard in vitro fertilization or intracytoplasmic sperm injection) had no association with outcomes. Compared with non-ART-conceived children of couples with infertility, fresh, but not frozen, embryo transfer was associated with a lower risk of mood disorders (aHR, 0.90 [95% CI, 0.83-0.97]), making frozen embryo transfer appear less advantageous when directly contrasted with fresh embryo transfer.
These findings suggest that adolescents conceived with ARTs around the millennium are not at risk of poor psychiatric health compared with the general population, except for an elevated risk of OCD that may be explained by differences in parental characteristics.
由于程序本身的潜在不良影响，或者由于不孕夫妇的这些特征或其风险因素可能更为常见，因此通过辅助生殖技术（ART）受孕的个体可能面临更高的精神障碍风险。
调查通过辅助生殖技术受孕的青少年和年轻人患精神障碍的风险，并评估与治疗相关的父母特征的作用。
设计、环境和参与者：这是一项全国性出生队列的前瞻性随访研究，利用瑞典人口登记处的链接进行分析，覆盖范围截至 2018 年。所有于 1994 年 1 月 1 日至 2006 年 12 月 31 日期间在瑞典出生的儿童均纳入分析。2018 年 12 月 31 日完成随访，此时参与者年龄为 12 至 25 岁，数据分析于 2020 年 3 月 17 日至 2021 年 9 月 10 日进行。
体外受精（包括或不包括胞浆内精子注射）和新鲜或冷冻解冻胚胎的移植。
通过医院记录和专科门诊专家护理来识别心境障碍的临床诊断，包括重度抑郁症、焦虑症、强迫症（OCD）或自杀行为。通过死亡证明来识别自杀。通过处方药物的配药来识别抗抑郁药物的使用情况。
共有 1221812 名（48.6%女性，51.4%男性）于 1994 年至 2006 年期间出生的儿童接受了中位年龄为 18 岁（IQR，15-21）年的随访。其中，31565 名（2.6%）是通过辅助生殖技术受孕的。与其他所有人相比，通过辅助生殖技术受孕的青少年患 OCD 的风险更高（风险比[HR]，1.35[95%CI，1.20-1.51]），但在调整父母特征后，这种关联减弱且不再具有统计学意义（调整后的 HR[aHR]，1.10[95%CI，0.98-1.24]），并且当限制为已知不孕夫妇所生的个体时，这种关联不再存在（aHR，1.02[95%CI，0.89-1.17]）。与其他青少年相比，通过辅助生殖技术受孕的青少年在抑郁或自杀行为方面没有更高的风险（无论父母是否存在不孕不育）。受精类型（标准体外受精或胞浆内精子注射）与结果无关。与不孕夫妇非辅助生殖受孕的儿童相比，新鲜而非冷冻胚胎移植与较低的情绪障碍风险相关（aHR，0.90[95%CI，0.83-0.97]），这表明与新鲜胚胎移植相比，冷冻胚胎移植似乎没有优势。
这些发现表明，与一般人群相比，在千禧年左右通过辅助生殖技术受孕的青少年在精神健康方面没有风险，除了 OCD 风险升高，这可能与父母特征的差异有关。
