Abstract
Clinical lecture by Dr. Phil Boyle (57:58). Reviews RCOG Green Top Guidelines on recurrent miscarriage (2023 revision), contrasts with RRM/NeoFertility approach, and presents a detailed case report. Covers: evidence grading for thrombophilia testing, progesterone support (stronger evidence than aspirin/heparin per RCOG), IVF does not help with recurrent miscarriage (RCOG evidence), surgery referral after balanced cycles, DHEA for low androgens, LDN, thyroid, natural killer cells, 15 contributing factors. Key teaching: miscarriage risk 30% after 3 losses, 40% after 4, 50% after 5. Also covers the 80% live birth success rate for couples with recurrent miscarriage at NeoFertility.
Related research
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Evaluation and treatment of recurrent pregnancy loss: a committee opinion
Practice Committee of the American Society for Reproductive Medicine, 2012 · Fertil Steril
The majority of miscarriages are sporadic and most result from genetic causes that are greatly influenced by maternal age. Recurrent pregnancy loss (RPL) is defined by two or more failed clinical pregnancies, and up to 50% of cases of RPL will not have a clearly defined etiology.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
Recurrent pregnancy loss: a committee opinion
Practice Committee of the American Society for Reproductive Medicine, 2026 · Fertility and Sterility
Current strategies for the assessment and treatment of recurrent pregnancy loss are discussed. This replaces the previous document, titled, "Evaluation and treatment of recurrent pregnancy loss: a committee opinion," last published in 2012.
Guidelines by Clinical Area · Fertility and Infertility Guidelines
ESHRE good practice recommendations on recurrent implantation failure
Cimadomo D et al., 2023 · Human Reproduction Open · Free full text on PubMed Central
Abstract How should recurrent implantation failure (RIF) in patients undergoing ART be defined and managed? This is the first ESHRE good practice recommendations paper providing a definition for RIF together with recommendations on how to investigate causes and contributing factors, and how to improve the chances of a pregnancy. RIF is a challenge in the ART clinic, with a multitude of investigations and interventions offered and applied in clinical practice, often without biological rationale or with unequivocal evidence of benefit. STUDY DESIGN, SIZE, This document was developed according to a predefined methodology for ESHRE good practice recommendations. Recommendations are supported by data from the literature, if available, and the results of a previously published survey on clinical practice in RIF and the expertise of the working group. A literature search was performed in PubMed and Cochrane focussing on ‘recurrent reproductive failure’, ‘recurrent implantation failure’, and ‘repeated implantation failure’. PARTICIPANTS/MATERIALS, SETTING, The ESHRE Working Group on Recurrent Implantation Failure included eight members representing the ESHRE Special Interest Groups for Implantation and Early Pregnancy, Reproductive Endocrinology, and Embryology, with an independent chair and an expert in statistics. The recommendations for clinical practice were formulated based on the expert opinion of the working group, while taking into consideration the published data and results of the survey on uptake in clinical practice. The draft document was then open to ESHRE members for online peer review and was revised in light of the comments received. MAIN The working group recommends considering RIF as a secondary phenomenon of ART, as it can only be observed in patients undergoing IVF, and that the following description of RIF be adopted: ‘RIF describes the scenario in which the transfer of embryos considered to be viable has failed to result in a positive pregnancy test sufficiently often in a specific patient to warrant consideration of further investigations and/or interventions'. It was agreed that the recommended threshold for the cumulative predicted chance of implantation to identify RIF for the purposes of initiating further investigation is 60%. When a couple have not had a successful implantation by a certain number of embryo transfers and the cumulative predicted chance of implantation associated with that number is greater than 60%, then they should be counselled on further investigation and/or treatment options. This term defines clinical RIF for which further actions should be considered. Nineteen recommendations were formulated on investigations when RIF is suspected, and 13 on interventions. Recommendations were colour-coded based on whether the investigations/interventions were recommended (green), to be considered (orange), or not recommended, i.e. not to be offered routinely (red). LIMITATIONS, While awaiting the results of further studies and trials, the ESHRE Working Group on Recurrent Implantation Failure recommends identifying RIF based on the chance of successful implantation for the individual patient or couple and to restrict investigations and treatments to those supported by a clear rationale and data indicating their likely benefit. This article provides not only good practice advice but also highlights the investigations and interventions that need further research. This research, when well-conducted, will be key to making progress in the clinical management of RIF. STUDY FUNDING/COMPETING INTEREST(S) The meetings and technical support for this project were funded by ESHRE. N.M. declared consulting fees from ArtPRED (The Netherlands) and Freya Biosciences (Denmark); Honoraria for lectures from Gedeon Richter, Merck, Abbott, and IBSA; being co-founder of Verso Biosense. He is Co-Chief Editor of Reproductive Biomedicine Online (RBMO). D.C. declared being an Associate Editor of Human Reproduction Update, and declared honoraria for lectures from Merck, Organon, IBSA, and Fairtility; support for attending meetings from Cooper Surgical, Fujifilm Irvine Scientific. G.G. declared that he or his institution received financial or non-financial support for re
Anti-Infective and Anti-Inflammatory Agents · Immune Modulating Agents
Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant
Empson M et al., 2005 · The Cochrane database of systematic reviews · Free full text on PubMed Central
A range of treatments have been proposed to improve pregnancy outcome in recurrent pregnancy loss associated with antiphospholipid antibody (APL). Small studies have not resolved uncertainty about benefits and risks. To examine outcomes of all treatments given to maintain pregnancy in women with prior miscarriage and APL. We searched the Pregnancy and Childbirth Group's Trials Register (30 May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1988 to June 2003), Lupus (volume one to eight, 1991 to 1999) and conference proceedings from the International Symposium on APL up to 1999. Randomised or quasi-randomised, controlled trials of interventions in pregnant women with a history of pregnancy loss and APL. Two review authors independently assessed quality and extracted data for studies up to December 1999. One review author performed this for studies after 1999. Thirteen studies were found (849 participants). The quality was not high; 50% had clear evidence of allocation concealment. Participant characteristics varied between trials. Unfractionated heparin combined with aspirin (two trials; n = 140) significantly reduced pregnancy loss compared to aspirin alone (relative risk (RR) 0.46, 95% confidence interval (CI) 0.29 to 0.71). Low molecular weight heparin (LMWH) combined with aspirin compared to aspirin (one trial; n = 98) did not significantly reduce pregnancy loss (RR 0.78, 95% CI 0.39 to 1.57). There was no advantage in high-dose, over low-dose, unfractionated heparin (one trial; n = 50). Three trials of aspirin alone (n = 135) showed no significant reduction in pregnancy loss (RR 1.05, 95% CI 0.66 to 1.68). Prednisone and aspirin (three trials; n = 286) resulted in a significant increase in prematurity when compared to placebo, aspirin, and heparin combined with aspirin, and an increase in gestational diabetes, but no significant benefit. Intravenous immunoglobulin +/- unfractionated heparin and aspirin (two trials; n = 58) was associated with an increased risk of pregnancy loss or premature birth when compared to unfractionated heparin or LMWH combined with aspirin (RR 2.51, 95% CI 1.27 to 4.95). When compared to prednisone and aspirin, intravenous immunoglobulin (one trial; n = 82) was not significantly different in outcomes. AUTHORS' Combined unfractionated heparin and aspirin may reduce pregnancy loss by 54%. Large, randomised controlled trials with adequate allocation concealment are needed to explore potential differences between unfractionated heparin and LMWH.
Boyle et al. 2025, Boyle 2025