Abstract
Study question
To which extent do the current international guidelines and recommendations concerning recurrent pregnancy loss (RPL) differ?
Summary answer
All guidelines apply definitions for RPL, however few diagnostic and therapeutic options are described. Diagnostics should be based on best evidence and current scientific knowledge.
What is known already
Established risk factors for RPL include anatomical, genetic, endocrine, hemostatic and immune alterations. The European Society of Reproduction and Embryology (ESHRE), American Society of Reproductive Medicine (ASRM), German/Austrian/Swiss Society of Obstetrics and Gynecology (DGGG/OEGGG/SGGG) and the Royal College of Obstetricians and Gynecologists (RCOG) published guidelines concerning diagnostic and therapeutic options in RPL. Due to the different guideline processes and date of publication actuality as well as complexity differ widely.
Study design, size, duration
We compared the guidelines of the ESHRE, ASRM, DGGG/OEGGG/SGGG and RCOG with regard to definition, diagnostic and therapeutic aspects. The guidelines were published between 2011 and 2018. Structured guideline processes with regular (complete) updates are only provided by the DGGG/OEGGG/SGGG.
Participants/materials, setting, methods
After thorough literature research (Pubmed, Embase) all existing guidelines and recommendations were analysed and compared considering the current state of knowledge. The RCOG recommendations from 2011 were updated in 2014 and 2017, the ARSM expert letter was last updated in 2012. The ESHRE guideline was published in 2017. The first version of the DGGG/OEGGG/SGGG guideline was published 2006, updated in 2013 and upgraded to a higher evidence-level in 2018 and is currently under review.
Main results and the role of chance
All guidelines agree that a diagnostic work-up is indicated after at least two clinical pregnancies and should exclude anatomical malformations, an antiphospholipid syndrome and thyroid dysfunction. Furthermore, lifestyle modifications are recommended by all. The general evaluation of an inherited thrombophilia is not recommended by any guideline. Exclusion of other risk factors like parental chromosomal disorders, a polycystic ovary syndrome or insulin resistance are only included in some guidelines, partly due to a lack of diagnostic criteria (luteal phase insufficiency) or due to the different year of publication of the recommendations (e.g. chronic endometritis). All guidelines recommend treating APLS by administering low-dose aspirin (75–100mg daily) in combination with unfractionated/low-molecular-weight heparin. With regard to uterine malformations whether or not a septum should be dissected is still a matter of debate: ESHRE and RCOG consider evidence insufficient, while DGGG/OEGGG/SGGG and ASRM recommend a surgical intervention. In case of chronic endometritis, the DGGG/OEGGG/SGGG recommends antibiotic therapy e.g. with doxycycline (200 mg daily for 14 days).
Limitations, reasons for caution
Different health economic as well as consensus aspects in the process of guideline development have a significant influence on the individual guidelines and recommendations.
Wider implications of the findings: Since personalized diagnostic and therapeutic strategies in RPL patients are required, physicians have to decide when to follow the guideline and when to expand diagnostics and therapy. Therefore, the knowledge of the weaknesses of each guideline and its developmental process is helpful for treating RPL couples.
Trial registration number
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Subclinical chronic endometritis and test of cure rates in a recurrent pregnancy loss cohort
