Refresh our knowledge on RPL (Recurrent pregnancy loss)
Recurrent pregnancy loss is disheartening to
the couple and to the treating clinician. There has been a wide range of
research from aetiology to management of recurrent pregnancy loss. It is one of
the most debated topic among clinicians and academics. The ideal management is unanswered. This
review is aimed to produce an evidence-based guidance on clinical management of
recurrent miscarriage. The review is structured to be clinically relevant. We
have searched electronic databases (PubMed and Embase) using different key
words. We have combined the searches and arranged them with the hierarchy of
evidences. We have critically appraised the evidence to produce a concise
answer for clinical practice. We have graded the evidence from level I to V on
which these recommendations are based.
KEYWORDS:
Aspirin;
antiphospholipid syndrome; immunotherapy; low molecular weight heparin;
recurrent miscarriage; recurrent pregnancy loss; unexplained
PMID:
Early recurrent
miscarriage: Evaluation and management
OBJECTIVE:
To establish recommendations for early recurrent miscarriages
(≥3 miscarriages before 14weeks of amenorrhea).
MATERIALS AND METHODS:
Literature review, establishing levels of evidence and
recommendations for grades of clinical practice.
RESULTS:
Women evaluation includes the search for a diabetes (grade A),
an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A),
a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia
(grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade
C), and a couple chromosome analysis (grade A). For unexplained early recurrent
miscarriages, treatment includes folic acid and progesterone supplementation,
and a reinsurance policy in the first quarter (grade C). It is recommended to
prescribe the combination of aspirin and low-molecular-weight heparin when APS
(grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of
hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine
if hyperprolactinemia (grade B), a substitution for vitamin deficiency or
hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and
treating an uterine acquired abnormality (grade C).
CONCLUSION:
These recommendations should improve the management of couples
faced with early recurrent miscarriages.
Early recurrent miscarriage: Evaluation and
management].
[Article in French]
Gallot V1, Nedellec S2, Capmas P3, Legendre G4,
Lejeune-Saada V5, Subtil D6, Nizard J7, Levêque J8, Deffieux X2, Hervé B9,
Vialard F9.
Author information
Abstract
OBJECTIVE:
To establish recommendations for early
recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea).
MATERIALS AND METHODS:
Literature review, establishing levels of
evidence and recommendations for grades of clinical practice.
RESULTS:
Women evaluation includes the search for a
diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid
dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and
a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered
ovarian reserve (grade C), and a couple chromosome analysis (grade A). For
unexplained early recurrent miscarriages, treatment includes folic acid and
progesterone supplementation, and a reinsurance policy in the first quarter
(grade C). It is recommended to prescribe the combination of aspirin and
low-molecular-weight heparin when APS (grade A), glycemic control in diabetes
(grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of
thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a
substitution for vitamin deficiency or hyperhomocysteinemia (grade C),
sectionning a uterine septum (grade C) and treating an uterine acquired
abnormality (grade C).
CONCLUSION:
These recommendations should improve the
management of couples faced with early recurrent miscarriages.
Current concepts and new trends
in the diagnosis and management of recurrent miscarriage
Pregnancy is a proinflammatory and hypercoagulable state.
Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is
a rather rare condition with an estimated incidence of 1% to 3%. However,
despite years of investigation, the etiology is not established in up to 50% of
cases. A multidisciplinary approach in the evaluation of miscarriage is
essential to understand the cause and risk of recurrence. Although genetic
factors are the major cause of spontaneous miscarriages, their relationship
with recurrent miscarriage is less frequent. Recently, many kinds of genetic
polymorphisms have also been found to be associated. Endocrine disorders such
as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism
are linked with recurrent miscarriage. The relationship between recurrent
miscarriage and subclinical thyroid disorders and thyroid autoimmunity is
disputed, especially in early miscarriages. Uterine malformations should be
considered as a cause of recurrent miscarriage. Although autoimmune-based
recurrent miscarriage has been described, mainly antiphospholipid antibodies,
the role of alloimmune mechanisms remains poorly understood. The influence of
congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid
antibody-related recurrent miscarriage, and some endocrinologic disorders, have
a specific and effective treatment. Still, the effectiveness of some common
treatments needs to be demonstrated.
Association of parental
methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in couples
with unexplained recurrent pregnancy loss
Abstract
OBJECTIVE:
The aim of this study was to identify the association of
parental MTHFR C677T gene polymorphism in couples with and without RPL history.
RESULTS:
During the study, 21.4% (15/70) of Ala222Val polymorphism was
observed among RPL couples while no polymorphism was seen among normal, healthy
couples. Our study did not find any association between MTHFR C677T
polymorphism and gender (p > 0.05), gestational period (p > 0.05),
geographical region (p > 0.05) and menstrual history (p > 0.05). However,
significant association was seen between MTHFR C677T polymorphism and number of
losses (p < 0.05), concluding that the risk of the polymorphism increased
with the increase in number of losses. Significant variation in the MTHFR C677T
genotype with number of losses among RPL couples were seen but not with other
study variables.
EIF5A1 promotes trophoblast
migration and invasion via ARAF-mediated activation of the integrin/ERK
signaling pathway.
Trophoblast
dysfunction is one mechanism implicated in the etiology of recurrent
miscarriage (RM). Regulation of trophoblast function, however, is complex and
the mechanisms contributing to dysregulation remain to be elucidated. Herein,
we found EIF5A1 expression levels to be significantly decreased in
cytotrophoblasts in RM villous tissues compared with healthy controls. Using
the HTR-8/SVneo cell line as a model system, we found that overexpression of EIF5A1
promotes trophoblast proliferation, migration and invasion in vitro. Knockdown
of EIF5A1 or inhibiting its hypusination with N1-guanyl-1,7-diaminoheptane
(GC7) suppresses these activities. Similarly, mutating EIF5A1 to EIF5A1K50A to
prevent hypusination abolishes its effects on proliferation, migration and
invasion. Furthermore, upregulation of EIF5A1 increases the outgrowth of
trophoblasts in a villous explant culture model, whereas knockdown has the
opposite effect. Suppression of EIF5A1 hypusination also inhibits the outgrowth
of trophoblasts in explants. Mechanistically, ARAF mediates the regulation of
trophoblast migration and invasion by EIF5A1. Hypusinated EIF5A1 regulates the
integrin/ERK signaling pathway via controlling the translation of ARAF. ARAF
level is also downregulated in trophoblasts of RM villous tissues and
expression of ARAF is positively correlated with EIF5A1. Together, our results
suggest that EIF5A1 may be a regulator of trophoblast function at the
maternal-fetal interface and low levels of EIF5A1 and ARAF may be associated
with RM.
A national survey on public
perceptions of miscarriage
Author information
1
Program for Early and Recurrent Pregnancy Loss (PEARL), Department
of Obstetrics & Gynecology and Women's Health, Albert Einstein College of
Medicine, the Department of Obstetrics & Gynecology and Women's Health,
Mount Sinai Medical Center, the Department of Obstetrics and Gynecology,
Montefiore Medical Center, and the Department of Obstetrics & Gynecology,
New York University Langone Medical Center, New York, New York; the Department
of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's
Hospital and Harvard Medical School, and the Department of Epidemiology,
Harvard School of Public Health, Boston, Massachusetts; and the University of
Sydney Medical School, Sydney, Australia.
Abstract
OBJECTIVE:
To assess attitudes and perceptions of U.S.
survey respondents regarding prevalence, causes, and emotional effects of
miscarriage.
METHODS:
We used a questionnaire consisting of 33
questions administered in January of 2013 to men and women aged 18-69 years
across the United States.
RESULTS:
Participants from 49 states completed the
questionnaire: 45% male and 55% female (N=1,084). Fifteen percent reported they
or their partner experienced at least one miscarriage. Fifty-five percent of
respondents believed that miscarriage occurred in 5% or less of all
pregnancies. Commonly believed causes of miscarriage included a stressful event
(76%), lifting a heavy object (64%), previous use of an intrauterine device
(28%), or oral contraceptives (22%). Of those who had a miscarriage, 37% felt
they had lost a child, 47% felt guilty, 41% reported feeling that they had done
something wrong, 41% felt alone, and 28% felt ashamed. Nineteen percent fewer
people felt they had done something wrong when a cause for the miscarriage was
found. Seventy-eight percent of all participants reported wanting to know the
cause of their miscarriage, even if no intervention could have prevented it
from occurring. Disclosures of miscarriages by public figures assuaged feelings
of isolation for 28% of respondents. Level of education and gender had a
significant effect on perceptions and understanding of miscarriage.
CONCLUSION:
Respondents to our survey erroneously
believed that miscarriage is a rare complication of pregnancy, with the
majority believing that it occurred in 5% or less of all pregnancies. There
were also widespread misconceptions about causes of miscarriage. Those who had
experienced a miscarriage frequently felt guilty, isolated, and alone.
Identifying a potential cause of the miscarriage may have an effect on
patients' psychological and emotional responses.
LEVEL OF EVIDENCE:
II.
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