羟氯喹治疗复发性妊娠失败:来自法国前瞻性多中心登记处的数据。

IF 6 1区 医学 Q1 OBSTETRICS & GYNECOLOGY
Amandine Dernoncourt, Kaies Hedhli, Noémie Abisror, Meryam Cheloufi, Jonathan Cohen, Kamila Kolanska, Chloé McAvoy, Lise Selleret, Eric Ballot, Emmanuelle Mathieu d'Argent, Nathalie Chabbert Buffet, Olivier Fain, Gilles Kayem, Arsène Mekinian
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引用次数: 0

摘要

研究问题:有复发性妊娠失败(RPL)病史的妇女在接触羟氯喹(HCQ)后妊娠的结果如何?在我们对妊娠早期接触过 HCQ 的有 RPL 史的妇女的妊娠队列中,我们发现决定这些妊娠成功与否的唯一因素是先前流产的次数:已知:母体免疫系统失调是导致 RPL 的原因之一。HCQ具有免疫调节和血管保护的双重作用,是治疗原因不明的RPL的潜在方法:FALCO(Facteurs de récidive précoce des fausses couches)登记处是一个正在进行中的法国多中心不孕不育登记处,成立于2017年,包括从多家大学医院招募的有自发性RPL病史(至少三次早期流产(≤妊娠12周(WG)))的女性(年龄在18至49岁之间):纳入FALCO登记处登记的、接触过HCQ的自然妊娠(受孕前或怀孕初期)。不包括同时接触肿瘤坏死因子抑制剂、白细胞介素-1和-2抑制剂、静脉注射免疫球蛋白和/或静脉注射血脂的孕妇。允许同时接受低剂量阿司匹林(LDA)、低分子量肝素(LMWH)、黄体酮和/或泼尼松治疗。所有患者都接受了建议的 RPL 检查评估。怀孕的患者按照法国的建议接受了产科治疗,并接受了前瞻性随访。主要终点是妊娠超过 12 个月,次要终点是活产:主要结果和偶然性的作用:评估了 74 名女性中 100 例接触 HCQ 的妊娠。据报告,78 例(78%)妊娠同时暴露于泼尼松,56 例(56%)妊娠同时暴露于 LDA,41 例(41%)妊娠同时暴露于 LMWH。62例(62%)妊娠在12周内结束,另外38例(38%)在12周后继续妊娠。发生额外早期自然流产的风险随先前流产次数的增加而增加,但与年龄无关。在妊娠持续时间≤12 WG 和持续时间超过 12 WG 的妊娠中,在 RPL 调查中发现的异常情况和接触其他药物的情况分布相似。至少有一种自身抗体(Ab)阳性(即抗核抗体滴度≥1:160,常规和/或非常规抗磷脂抗体≥1阳性,和/或抗甲状腺抗体≥1阳性)且卵巢储备功能未减退的孕妇(18/51,35.3%)的妊娠进展超过12WG的发生率并不比无此类自身抗体的孕妇(18/45,40.0%)高(P = 0.63)。多变量分析表明,在调整年龄和受孕前使用 HCQ 的时间后,既往流产次数≤4 次是唯一能显著预测妊娠 > 12 WG 的因素(调整后的比值比 (OR) = 3.13 [1.31-7.83],P = 0.01):我们的研究存在局限性,包括缺乏对照组、部分患者的 RPL 诊断程序数据不完整、无法获得子宫内膜活检结果以及有关父亲年龄和行为因素的信息。因此,无法考虑所有潜在的混杂因素:有RPL病史的妇女在孕早期接触HCQ似乎并不能防止再次流产,这表明HCQ对母体免疫系统相关机制的影响有限:试验注册号:clinicaltrial.gov NCT05557201。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.

Study question: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?

Summary answer: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.

What is known already: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.

Study design, size, duration: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.

Participants/materials, setting, methods: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.

Main results and the role of chance: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).

Limitations, reasons for caution: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.

Wider implications of the findings: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.

Study funding/competing interest(s): The research received no specific funding, and the authors declare no competing interests.

Trial registration number: clinicaltrial.gov NCT05557201.

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来源期刊
Human reproduction
Human reproduction 医学-妇产科学
CiteScore
10.90
自引率
6.60%
发文量
1369
审稿时长
1 months
期刊介绍: Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues. Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.
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