Recurrent Spontaneous Miscarriage: a Comparison of International Guidelines

Abstract

While roughly 30% of all women experience a spontaneous miscarriage in their lifetime, the incidence of recurrent (habitual) spontaneous miscarriage is 1 – 3% depending on the employed definition. The established risk factors include endocrine, anatomical, infection-related, genetic, haemostasis-related and immunological factors. Diagnosis is made more difficult by the sometimes diverging recommendations of the respective international specialist societies. The present study is therefore intended to provide a comparison of existing international guidelines and recommendations. The guidelines of the ESHRE, ASRM, the DGGG/OEGGG/SGGG and the recommendations of the RCOG were analysed. It was shown that investigation is indicated after 2 clinical pregnancies and the diagnosis should be made using a standardised timetable that includes the most frequent causes of spontaneous miscarriage. The guidelines concur that anatomical malformations, antiphospholipid syndrome and thyroid dysfunction should be excluded. Moreover, the guidelines recommend carrying out pre-conception chromosomal analysis of both partners (or of the aborted material). Other risk factors have not been included in the recommendations by all specialist societies, on the one hand because of a lack of diagnostic criteria (luteal phase insufficiency) and on the other hand because of the different age of the guidelines (chronic endometritis). In addition, various economic and consensus aspects in producing the guidelines influence the individual recommendations. An understanding of the underlying decision-making process should lead in practice to the best individual diagnosis and resulting treatment being offered to each couple.

Prevalence and associated factors of recurrent pregnancy loss in Nigeria according to different national and international criteria (ASRM/ESHRE vs. WHO/RCOG)

“…The established risk factors of RPL include endocrine, anatomical, infection-related, genetic, hemostasis-related and immunological factors ( 9 ). In a previous study by Youssef et al, aimed at determining whether the distribution of RPL-associated factors was different in women with two vs. three or more pregnancy losses, no associated factor was found in 71.5% of couples with RPL and these did not differ statistically between women with two vs. three or more pregnancy losses ( 10 ).…”

Integrated analysis of lncRNA and mRNA expression profiles in patients with unexplained recurrent spontaneous abortion

“…Various mechanisms protect the fetus from the mother's immune system. So far, research on the immunological aspects of RSA mainly focuses on antiphospholipid syndrome (APLS), autoantibodies, cytokines, HLA polymorphisms, and HLA expression on trophoblasts as well as natural killer cells in peripheral blood and in the endometrium 5 . Although not accurately quantified, it is believed that a significant proportion of URSA is related to immune etiologies 6,7 and that abortion may occur due to the continuous disorder of several immune pathways 8 .…”

“…So far, research on the immunological aspects of RSA mainly focuses on antiphospholipid syndrome (APLS), autoantibodies, cytokines, HLA polymorphisms, and HLA expression on trophoblasts as well as natural killer cells in peripheral blood and in the endometrium. 5 Although not accurately quantified, it is believed that a significant proportion of URSA is related to immune etiologies 6,7 and that abortion may occur due to the continuous disorder of several immune pathways. 8 Recently, several genes (IFNG, IL10, KIR2DS2, KIR2DS3, KIR2DS4, MBL, and TNF), that are associated with overactive immune and inflammatory responses, have been reported to be associated with the RSA pathogenesis.…”

Effect of thyroid function on assisted reproduction outcomes in euthyroid infertile women: A single center retrospective data analysis and a systematic review and meta-analysis

“…TSH at serum concentrations above reference values (0.5–4.5 mIU/L) has been associated with adverse reproductive and pregnancy outcomes, including infertility, miscarriages, prematurity, and congenital defects, even when FT4 is within values ( 2 , 4 , 5 ). International guidelines on recurrent miscarriage uniformly recommend that TSH levels should be <2.5 mIU/L in women with this diagnosis and hypothyroidism ( 6 ). Nevertheless, the effect of TSH variations within the reference values on reproductive outcomes is still unclear in patients without the aforementioned diagnoses.…”

“…TSH and FT4 are used as the main parameters to evaluate thyroid function, taking into account that both undergo changes during pregnancy, and therefore their concentrations must have been well established before the gestational period ( 7 , 8 ). Accumulating evidence suggests that for patients with subclinical hypothyroidism undergoing assisted reproductive techniques, the ideal serum TSH value is <2.5 mIU/L, which can be obtained by treatment with levothyroxine (LT4) if necessary ( 6 , 9 ). However, the use of LT4 in patients negative for thyroid antibodies and with TSH within the normal range is controversial, even if TSH value >2.5 mIU/L ( 9 ).…”