Rhesus testing and anti-D prophylaxis in RhD-negative women undergoing first-trimester abortion—Systematic review and opinion
by Kristina Gemzell-Danielsson, Sharon Cameron, Teresa Bombas, Mirella Parachini, Marek Lubusky, Aubert Agostini, Sandra Kroeze, Mary Favier, Myriam Chebbah, Varlet Alice-Anaïs, Linda Verhagen, Christian Fiala
International Journal of Gynecology & Obstetrics: Early View
First published: 29 July 2025
Abstract
Background
The introduction of immunoglobulin G (IgG) anti-D prophylaxis for Rhesus D (RhD)-negative women has substantially reduced the incidence of RhD alloimmunization and hemolytic disease of the fetus and newborn in Europe by 85%, transforming fetal health outcomes. However, there is little evidence for the need of giving IgG anti-D prophylaxis to RhD-negative women in first-trimester abortions.
Objectives
To analyze the international and national evidence-based guidelines on Rh testing and anti-D prophylaxis in first-trimester abortion, along with current literature both supporting and opposing this practice, to facilitate informed decision making in clinical practice.
Search Strategy
A systematic search was conducted in Pubmed/MEDLINE, EMBASE, Cochrane Library, Google Scholar, and Gry literature for publications from January 1, 2003 to January 17, 2024.
Selection Criteria
Guidelines, reviews, meta-analyses, observational and qualitative studies, randomized trials, real-world data, and cohort studies that addressed the use of IgG anti-D prophylaxis in first-trimester abortions were included.
Data Collection and Analysis
Identified studies were screened and assessed independently by two authors. A standardized extraction grid was used to extract information from the selected articles.
Main Results
Guidelines published from 2022 onwards, such as those from the World Health Organization, recommend against anti-D for women undergoing first-trimester abortion. In contrast, most older guidelines recommend RhD testing and the administration of IgG anti-D prophylaxis in abortions even before 12 weeks of amenorrhea, although exact gestational age thresholds vary widely. These discrepancies in the management of RhD-negative women undergoing first-trimester abortion are caused by different interpretations of the available evidence, IgG anti-D availability, cultural and social influences, as well as legal and regulatory considerations.
Conclusions
This review highlights the need for evidence-based, harmonized guidelines on IgG anti-D prophylaxis in first-trimester abortions. It is crucial for healthcare providers to stay informed on the latest recommendations and engage in shared decision-making with women undergoing first-trimester abortion.
Introduction
First-trimester abortion is a common and safe procedure to terminate a pregnancy performed through two methods, medical (administration of mifepristone followed by misoprostol) or surgical (vacuum aspiration). In most European countries, more than 90% of abortions are performed before 13 weeks of amenorrhea and over two-thirds of abortions are carried out before 9 weeks of amenorrhea. First-trimester abortion is considered a low-risk procedure, with a complication rate of less than 2% when performed by trained healthcare providers.
Prevalence of the Rhesus (Rh)-negative blood type varies significantly across the globe. It is most frequent among those of European and North American ancestry, where 15%–17% of people have the RhD-negative phenotype. In comparison, the occurrence is lower in Africa and India, ranging from 3% to 8%, and exceedingly rare in Asia, with only 0.1%–0.3% of the population being Rh-negative. Determination of RhD status and the administration of immunoglobulin G (IgG) anti-D prophylaxis to RhD-negative women undergoing first-trimester abortion, continues to be a subject of discussion and evolving practice within the field of reproductive health care. Historically, the clinical practice has been to routinely test for RhD status and administer IgG anti-D to all non-sensitized RhD-negative women, regardless of their pregnancy term. In most cases, a full dose of IgG anti-D is given, 250–300 μg (1250–1500 IU), which is sufficient to neutralize 30 mL of fetal blood in the women’s blood circulation. This practice was deduced from the Rh alloimmunization risk caused by the feto-maternal transfusion of RhD-positive red blood cells (RBCs) during delivery, sensitizing the mother’s immune system. This RhD alloimmunization can lead to life-threatening complications for the fetus in subsequent pregnancies, such as hemolytic disease of the RhD-positive newborn, and was therefore considered an important risk to mitigate.
However, in early pregnancy there are few if any fetal RBCs present with a questionable antigenic capacity. It is inherently difficult to study the potential impact of a small volume of fetal RBCs on the woman’s immune system. Consequently, the evidence about the need of anti-D prophylaxis in first-trimester abortion has been very limited and inconsistent. Recent guidelines questioned routine RhD testing and IgG anti-D administration for first-trimester abortions, citing the low risk of RhD sensitization due to minimal fetal RBCs, along with potential drawbacks like increased costs, delays in care, and barriers to abortion access. The negative impact of Rh testing is particularly significant in medical abortion as it becomes an increasingly self-managed procedure. Blood typing and the administration of IgG are the only invasive interventions in an otherwise entirely oral treatment. Additionally, the introduction of medical abortion has led to a significant decrease in average gestational age at which abortions are performed in most countries. Consequently, the balance between benefits and potential risks of this practice had to be re-evaluated; also keeping in mind that the IgG are of human origin, derived from blood donors who were sensitized. As evidence evolves, it is crucial that healthcare providers stay informed on the latest recommendations and make accurate decisions based on reliable data, to ensure that the management of RhD status and anti-D prophylaxis balance benefits and potential risks for each woman undergoing first-trimester abortion.
This review brings together and critically analyzes the existing guidelines on Rh testing and anti-D prophylaxis in the context of first-trimester abortion, alongside current literature supporting or opposing this practice to enable an informed decision-making in clinical practice….
The analysis of RhD practices reveals a lack of evidence-based data resulting in a significant variability in recommendations and approaches among the different countries. Notably, concerning RhD screening, while the latest international (WHO 2022), Australian and Italian (Italian Superior Institute of Health recommendations on medical abortion) recommendations on abortion advise that it is not mandatory for women undergoing first-trimester abortion, many recent guidelines recommend it during first-trimester abortion….
The recommended gestational age above which IgG anti-D should be given to women who had an abortion is even more heterogeneous. Indeed, many European countries’ recommendations were written before 2022 and recommend anti-D prophylaxis for RhD-negative women undergoing first-trimester abortion, in particular Austria (>6 weeks of amenorrhea), the Netherlands (>7 weeks of amenorrhea), Germany (<9 weeks of amenorrhea), and Ireland (>10 weeks of amenorrhea). Conversely, international guidelines and some national guidelines (from WHO, National Abortion Federation [NAF], the USA, and the UK, Royal College of Obstetricians and Gynecologists [RCOG] published in 2022 or after, suggest anti-D prophylaxis for RhD-negative women after 12 or more weeks of amenorrhea….
The heterogeneity in guidelines and practices regarding anti-D prophylaxis in first-trimester abortion is mainly due to the lack of evidence….
Additionally, the latest WHO guidelines recommend against anti-D prophylaxis for both medical and surgical abortions below 12 weeks of amenorrhea….
Conclusions
Guidelines issued after 2022 generally do not recommend routine anti-D prophylaxis for first-trimester abortion (<12 weeks of amenorrhea), regardless of the method, mainly because of a lack of evidence supporting the effectiveness of IgG anti-D administration in early abortion. The discrepancies among evidence-based guidelines and the nuanced underlying considerations, underscore the importance of rigorous evidence appraisal, contextual awareness, and patient-centered decision making when deciding on RhD-typing and IgG anti-D prophylaxis in early abortion care. Prioritizing patient safety, accessibility, and cost-effectiveness in protocol management is essential. Standardizing protocols globally while accommodating local contexts and individual patient needs is paramount. Continuous research and collaboration are essential to establish evidence-based guidelines and address current practice gaps. Hence, ongoing discussions and collaboration among healthcare providers and policy makers are crucial to ensure that anti-D prophylaxis during first-trimester abortion aligns with patient-centered principles and advances in medical knowledge….
[Editor’s Note: This is a very long, very detailed, very complicated research report, especially for those of us who are not clinicians. I have tried to limit the text here mainly to include clear findings and the recommendations shared/supported by the authors because they are in line with WHO guidance, because they believe that is the best route to follow, while at the same time recommending the need for further research. I hope that in spite of not yet wanting to be definitive, their main conclusion to date is clear – that is, that with first trimester abortion, guidelines issued after 2022 generally do not recommend routine anti-D testing or prophylaxis, while leaving the door open as further research is carried out.]