- •Contents
- •Contributors
- •Foreword
- •Preface
- •1. Epidemiology of recurrent pregnancy loss
- •2. Signaling between embryo and mother in early pregnancy: Basis for development of tolerance
- •3. Genetics of spontaneous abortions
- •3e. Should CVS or amniocentesis be performed in RPL without screening?
- •4. Does the maternal immune system regulate the embryo’s response to teratogens?
- •6. Endocrinology of pregnancy loss
- •7. Antiphospholipid syndrome – pathophysiology
- •8. Diagnosis of aPL-associated abortions
- •10. Defects in coagulation factors leading to recurrent pregnancy loss
- •11. Uterine anomalies and recurrent pregnancy loss
- •12. Immunobiology of recurrent miscarriage
- •13. Infections and recurrent pregnancy loss
- •16. Obstetric outcomes after recurrent pregnancy loss
- •17. Coping with recurrent pregnancy loss: Psychological mechanisms
- •19. Investigation protocol for recurrent pregnancy loss
- •20. A patient’s perspective
- •Index
Index
N.B. Page numbers in italic denote figures and tables.
abnormal liveborns, chromosomal |
anticoagulant–procoagulant balance 128 |
APS see antiphospholipid syndrome |
anomalies in 23 |
anticoagulants 272 |
arachidonic acid 110 |
inversions 31–2 |
physiological 130 |
arcuate uterus 148–9, 148 |
translocations 30 |
see also specific agents |
ascertainment bias 259–60 |
trisomies 28 |
anticytokine effect 110–11 |
aspirin |
abnormal ovarian reserve 83 |
antinuclear antibodies (ANA) 167 |
for APS 119, 121, 122, 235, 272 |
abortion |
antipaternal antibodies 174 |
in labor/postpartum 123 |
definition 1 |
antiphospholipid (aPL) |
for thrombophilia/pregnancy loss 133, 141 |
see also miscarriage; spontaneous abortion |
and hCG secretion 111 |
autoantibodies 9 |
acardiac conjoined twins 73 |
heterogeneity 116–17 |
autoimmune abortions 165–8 |
adhesiolysis, hysteroscopic 156 |
immunoglobulin isotypes 116 |
aPL-antibody-associated 166–7 |
afibrinogenemia 129 |
testing for |
not aPL-antibody-associated 167–8 |
age |
assays 115 |
workup 165 |
controlling for, in studies 258 |
time of testing 117 |
autosomal monosomy 24 |
and RPL 3–4 |
titers 116 |
autosomal trisomy 24–5, 24 |
age-related factors 4, 7–8 |
types of aPL 115–16 |
β2-glyprotein 1 (β2GP1) 107, 108 |
PGD for 46–7 |
antiphospholipid (aPL) antibodies 9, 115–18 |
|
and trisomies 25, 26 |
characterization 166–7 |
antibodies 108 |
alloimmune abortions 168–75 |
formation 166 |
autoantibodies 108–9 |
immunopathology 172, 174 |
during pregnancy 167 |
bacterial identification 203–4 |
natural killer (NK) cells 174 |
and prognosis 274–5 |
bacterial vaginosis (BV) 195–201, 272 |
Th1 response-inducing factors 172 |
in RPL 127 |
antibiotics 197, 199, 200, 204 |
immunotherapy, preventative 175 |
types tested for 117 |
and prevalence 197 |
workup 174–5 |
antiphospholipid-associated abortions 115–18 |
and previous premature labor 197–8 |
alloimmune testing 272 |
antiphospholipid co-factor 107 |
when BV is incidental finding 198–9 |
alloimmunization, obstetric complications |
antiphospholipid syndrome (APS) 9 |
definition 195 |
after 236 |
chromosomal abnormalities 35 |
miscarriage 199–201 |
American Academy of Pediatrics on |
clinical associations 119 |
early 199–200 |
withdrawing intensive care 225 |
etiology 107–9 |
late 200 |
American College of Obstetricians and |
evaluation 272 |
therapy, effect of 200–1 |
Gynecologists (ACOG) |
experimental 108 |
organisms associated 195 |
on APS management 123 |
and Helicobacter pylori 204 |
premature delivery 196–9 |
on karyotyping 41 |
immunization 107 |
BCL-2 protein 62 |
on RPL management 269, 270–1, 272 |
management 119–25 |
bicornuate uterus 148, 148, 150–1, 151, 161 |
amniocentesis 55–7 |
consensus guidelines 119 |
bicornuate bicollis 150 |
amnion rupture sequence defects 73–4 |
glucocorticoids 121 |
bicornuate unicollis 150 |
amniotic bands 72, 73–4, 76 |
heparin 119–21, 122 |
biochemical pregnancies, definition of 269–70 |
amoxycillin 202 |
hydroxychloroquine 121–2 |
biofilms 204 |
anencephaly 68, 71 |
intravenous immunoglobulin 122 |
bleeding diatheses 127–30 |
aneuploidy |
labor/postpartum 123 |
blinding (masking) 259–60 |
and developmental defects 75 |
pregnancy monitoring 123 |
|
incidence/prevalence 45 |
of ‘probable APS’ 122 |
Canadian Paediatric Society on withdrawing |
recurrent see recurrent aneuploidy |
of refractory APS 122–3 |
intensive care 225 |
serum markers 55 |
mechanisms of reproductive failure |
cardiolipin antibodies (aCL) 115–16 |
ultrasound markers 55–6 |
anticytokine effect 110–11 |
caspases 62–3 |
aneuploidy screening (PGD-AS) |
arachidonic acid/prostacyclin 110 |
causes of RPL 185–8 |
diagnostic 50–1 |
placental cell apoptosis 111 |
cervical cerclage 149, 156, 160–1, 207, 211–16 |
observational studies 50 |
thrombosis 109–10 |
clinical value 212–14 |
therapeutic 49–50 |
outcomes 235–6 |
complications 214 |
anger 246 |
pathophysiology 107–13 |
emergency 215–16 |
annexin V 109–10 |
treatment 235–6 |
patient selection 215 |
antibiotics |
antithyroid antibodies (ATA) 81–2, 167–8 |
techniques 211–12 |
and bacterial vaginosis 197, 199, 200, 204 |
anxiety 243–4 |
timing of placement 214–16 |
and mycoplasmas 201 |
coping activities 248 |
cervical incompetence/insufficiency 160–1 |
and premature delivery 196 |
apolipoprotein H 107 |
cervical competence continuum model |
previous 197–8 |
apoptosis 62 |
207–8 |
and unexplained pregnancy loss 202–3 |
in fetal tolerance 170 |
cervical length 210, 213–14 |
see also specific agents |
placental cell 111 |
definition 207 |
285
INDEX
cervical incompetence/insufficiency |
decidual immune cells 173 |
endocrine factors in RPL (Continued) |
(Continued) |
decision-making process in extreme |
elevated follicle-secreting hormone 84 |
diagnosis 207–11 |
prematurity 226–7 |
frequency 79 |
differential 210–11 |
denial 246 |
hyperprolactinemia 80 |
pathophysiology 207–8 |
depression 243, 244, 246 |
inhibins 79, 84–5 |
Cervical Incompetence Prevention |
DES see diethylstilbestrol |
insulin resistance 83 |
Randomized Cerclage Trial |
developmental defects |
polycystic ovary syndrome (PCOS) 83 |
(CIPRACT) 160, 215 |
etiology 74–5 |
thyroid abnormalities 80–2 |
cervical length and insufficiency |
see also fetal structural malformations |
see also luteal phase defect |
210, 213–14 |
developmental gene abnormalities 32–3 |
endometriosis 150 |
cesarean section after RPL 232 |
developmental toxins 62–3 |
endothelial cells in APS 109–10 |
Chlamydia trachomatis antibodies |
susceptibility to 59 |
enoxaparin 133–4, 139 |
194–5 |
diabetes, gestational |
prophylaxis 140, 141, 144 |
chlamydial infections 194–5, 202 |
odds ratio in RPL 233 |
for thrombophilia 236 |
chorangiopagus parasiticus (CAPP) 73 |
after RPL 233 |
epidemiology 1–13 |
chorionic villus sampling (CVS) |
diabetes-induced teratogenicity 60 |
clinical associations 6, 10 |
errors in 40 |
diabetes mellitus 82–3 |
familial aggregation 5–6, 6, 9–10 |
and screening 55–7 |
didelphys uterus 148, 148, 149–50, 149, 150 |
lifestyle factors 6–7, 10 |
in transcervical embryoscopy |
dietary supplements 272 |
maternal age 3–4, 7–8 |
69, 69 |
diethylstilbestrol (DES) 151, 162 |
number of previous miscarriages 2–3, 3, 7 |
chromosomal abnormalities 7, 39–40 |
diethylstilbestrol (DES)-exposed uterus |
occurrence 1–2, 7 |
developmental genes 32–3 |
148, 151, 161 |
partner specificity 6, 10 |
frequency 23–4, 35–8 |
disability rates of ELBW infants 222, |
relevant factors 1–7 |
parental 37, 37, 39, 40 |
222, 223, 224, 224 |
research/management 7–10 |
and PGD 46 |
double trisomy 24, 25–6 |
subgroups of RPL 4–5, 8–9 |
prognosis 274 |
chromosomes 25 |
equivalence trials 264 |
in preimplantation embryos 23 |
Down syndrome 55–7 |
erythromycin 200, 202 |
prognosis 40, 274 |
detection rate 56, 57 |
estrogen and thrombosis 135 |
recurrent aneuploidy 27–9 |
doxycycline 200, 202 |
ethical dilemmas |
and RPL subgroup 8 |
duplication anomalies 73 |
extreme prematurity 224–8 |
spectrum 24–7 |
dysfibrinogenemia 129 |
withdrawing intensive care 225–6 |
structural 29–32, 56 |
|
withholding intensive care 224–5 |
frequency 70 |
early missed abortions 74–5 |
European Society of Human Reproduction |
and PGD 51–2 |
early pregnancy factor (EPF) 19 |
and Embryology (ESHRE) |
cleft lip 72, 72 |
early pregnancy recognition 15 |
PGD Consortium Data Collection 51 |
and teratogens 60, 62, 63–4 |
early RPL 5 |
on RPL management 269, 271, 272 |
clindamycin 197, 198, 200, 202 |
hCG therapy 99 |
Special Interest Group for Early Pregnancy |
clinical associations 6, 10 |
Edwards syndrome 55 |
(SIGEP) 156, 255 |
coagulation factor defects 127–37 |
ELBW (extreme low birthweight) infants |
exencephaly 68, 71 |
cytokine imbalances 134 |
see prematurity, extreme |
extreme low birthweight (ELBW) infants see |
factor XIII deficiency 127–9 |
embryo–maternal signaling 15–22 |
prematurity, extreme |
fibrinogen deficiency 129–30 |
genomic elements 17 |
|
hormones 135 |
hypothesis 15 |
facial dysplasia 71 |
microparticles 134–5 |
onset 16–17 |
factor II (FII) G20210A 127, 128, 130, 143 |
thrombophilias 130–4 |
uniqueness of signal 17 |
factor V Leiden (FVL) 127, 128, 130, 143 |
cognitive restructuring 248–9 |
universal tolerance biomarker 18–20 |
and thromboprophylaxis 144 |
comparative genomic hybridization |
embryonic growth disorganization |
factor XIII (FXIII) deficiency 127–9 |
(CGH) 40, 41 |
70, 74, 77 |
FXIII replacement 128–9 |
conjoined twinning 73 |
embryoscopy, transcervical |
mechanism of action 128 |
control, loss of 247 |
complementing ultrasound 76 |
familial aggregation 5–6, 6, 9–10 |
coping mechanisms 243–53 |
fetal structural malformations 67–78 |
fertilization process and signaling 16–17 |
cognitive restructuring 248–9 |
in spontaneous/missed abortions 67 |
fetal anomalies |
corpus luteum |
triploid embryo 69 |
and IVIG 238 |
deficiency see luteal phase defect |
uterine abnormalities diagnosed 68 |
obstetric outcomes after RPL 232–3 |
rescue 15, 16 |
technique |
and paternal leukocyte immunization |
CVS see chorionic villus sampling |
chorionic villus sampling (CVS) 69, 69 |
237, 237 |
cyclophosphamide 59–60, 62 |
embryo evaluation 68–9 |
see also chromosomal abnormalities; fetal |
cytokines 134, 238 |
endovaginal sonography 68 |
structural malformations |
in alloimmune abortions 169–70 |
gestational sac localization and entry 68 |
fetal structural malformations 67–78 |
anticytokine effect in APS 110–11 |
hysteroscope insertion 67 |
common defects 70–4 |
in embryo tolerance 18, 89, 94 |
tissue sampling 69 |
amnion rupture sequence 73–4 |
imbalances 134, 238 |
uterine cavity exploration 67–8 |
duplication anomalies 73 |
and obstetric complications 238–9 |
uterine evacuation 69 |
head 70–2 |
in teratogen susceptibility 63 |
encephaloceles 71 |
limbs 72–3 |
therapeutic 183 |
endocrine factors in RPL 79–87 |
trunk 72 |
cytomegalovirus 193–4 |
diabetes mellitus 82–3 |
umbilical cord 73 |
286
|
|
INDEX |
fetal structural malformations (Continued) |
human chorionic gonadotropin (hCG) |
incidence |
cytogenetic findings 75 |
supplementation 99, 272 |
aneuploidy 45 |
and diabetes 83 |
arguments against 101–5 |
RPL 1–2 |
embryonic growth disorganization 70, 74, 77 |
arguments for 97–100 |
‘individualized prognostic strategy’ 225 |
embryoscopy technique, transcervical 67–70 |
in early pregnancy 102–4 |
indoleamine 2,3-deoxygenase (IDO) 170 |
etiology in early missed abortions 74–5 |
following ovulation induction 102 |
infections |
karyotype and morphology 74, 75, 76 |
recurrent miscarriage 102–4 |
and APS 107–9 |
morphological/cytogenetic evaluation, |
oligomenorrhea 102, 102, 103–4 |
detection 203–4 |
clinical significance of 76–7 |
placebo effect 103, 103 |
future developments 203–4 |
fetal tolerance see tolerance of embryo |
trials/meta-analyses 103 |
and RPL 193–206 |
fetomaternal immunoreactivity 59–66 |
threatened miscarriage 102 |
infertility |
and embryonic development 59 |
human leukocyte antigen (HLA) 9, 10 |
coping 245 |
mechanisms |
in embryo–maternal signaling 15, 19 |
patient’s perspective 281–2, 284 |
embryo apoptosis regulation 62–3 |
HLA-C 171 |
inhibins 79, 84–5 |
at fetomaternal interface 63–4 |
HLA-G 19, 170–1 |
insulin resistance 83 |
and teratologic susceptibility 59–62 |
in immune response initiation 174 |
intensive care |
fibrinogen deficiency 127, 129–30 |
hydrosalpinx 161 |
withdrawing 225–6 |
fibroids 152 |
hydroxychloroquine 121–2 |
withholding 224–5 |
embolization 160 |
hyperinsulinemia 83 |
interleukin IL-3 110–11 |
financial loss 247 |
hyperprolactinemia 80 |
International Histocompatability |
fluorescence in situ hybridization, |
hypertension, pregnancy-induced 233–4, 233 |
Workshops 168 |
multiplex (M-FISH) 41 |
hyperthyroidism 80–1 |
interpregnancy conception interval |
follicle-secreting hormone (FSH), elevated 84 |
hypofibrinogenemia 129 |
264–5 |
|
hypothyroidism 81 |
interventions see therapy |
Gardnerella vaginalis 196, 198 |
hysterosalpingography (HSG) 152, |
intrauterine adhesions (synechiae) 152 |
gastroschisis 72 |
154–5, 160 |
intrauterine growth restriction (IUGR) |
gavage feeding, withdrawal of 227–8 |
advantages/disadvantages 155 |
and APS 235 |
genetic counseling 28 |
in cervical incompetence 208 |
and IVIG 237, 238 |
genetics |
hysteroscopy, diagnostic 154 |
odds ratio in RPL 234 |
chromosomal abnormalities 7 |
advantages/disadvantages 155 |
and paternal leukocyte immunization |
factor XIII deficiency 129 |
|
237, 237 |
familial aggregation 5–6 |
immune response |
after RPL 234 |
single gene mutations 143–4 |
avoidance by fetus 89 |
intravenous immunoglobulin (IVIG) |
spontaneous abortions 23–34 |
see also embryo–maternal signaling; |
122, 123, 182, 276 |
Th1-triggered abortion 174 |
fetomaternal immunoreactivity |
for alloimmune abortion 175 |
glucocorticoids 121 |
cytokine/hormone network 169–70 |
for APS 235–6 |
glucose challenge test 272 |
facilitation reaction 168–9 |
arguments against 191 |
Graves disease 81 |
fetal tolerance, mechanisms enhancing 170 |
arguments for 185–8 |
grief/grieving process 244, 245–6 |
natural killer (NK) cells 171 |
indications 186 |
stages 246 |
in normal pregnancy 168–71 |
mechanisms of action 186 |
teaching couples 248 |
recognition of embryo 16–17 |
mode of action 239 |
growth factors in teratogen susceptibility |
and teratogen susceptibility 60 |
outcome classification 187 |
63–4 |
Th2-type response 169 |
patient selection 185–6 |
guilt 243, 244, 246 |
immune system and teratogens 59–66 |
rationale 189–90 |
|
immunization |
success rates 186–7 |
hCG see human chorionic gonadotropin |
alloimmune abortion 175 |
inversions, chromosomal 31–2 |
head defects 70–2 |
antiphospholipid syndrome 107 |
abnormal liveborns 31–2 |
healing 246 |
see also paternal leukocyte immunization |
subsequent losses 32 |
heat shock-induced teratogenicity 60 |
immunobiology of RPL 165–77 |
investigation protocol for RPL 269–80 |
Hegar test 208 |
immunoglobulin, intravenous (IVIG) see |
case presentations 277–9 |
Helicobacter pylori 107, 203, 204 |
intravenous immunoglobulin |
inclusion criteria 269–70 |
heparin |
immunological factors and RPL subgroup 8–9 |
prognosis |
for APS 235, 272 |
immunological mechanisms 185 |
good 273–4 |
for fibrinogen deficiency 130 |
abortion 173 |
medium 274–5 |
mode of action 134, 239 |
normal pregnancy 173 |
poor 275–6 |
trophoblast, effects on 134 |
immunological paradox of pregnancy 168 |
subsequent 271–3 |
see also low-molecular-weight heparin; |
immunomodulation and progesterone 93–4 |
specific forms of RPL 276–7 |
unfractionated heparin for APS |
immunoreactivity, fetomaternal see |
loss of live embryos 276–7 |
hereditary thrombophilias see thrombophilias, |
fetomaternal immunoreactivity |
mixed pattern of pregnancy loss 277 |
hereditary |
immunostimulation, maternal 59, 60, 61 |
recurrent second-trimester fetal |
heritability 6 |
simplified model 64 |
death 276 |
herpes simplex virus 194 |
immunotherapy 276 |
standard protocols 270–1 |
hormones and thrombosis 135 |
arguments against 189–92 |
isolation 246 |
human chorionic gonadotropin (hCG) |
efficacy 190–1 |
IVIG see intravenous immunoglobulin |
79, 85, 101 |
‘immunotrophic’ theory 169 |
|
in pregnancy maintenance 101 |
imperforate hymen 148 |
Jones metroplasty 161 |
287
INDEX
karyotype
and fetal malformation morphology
75, 76
and prognosis 269 in RPL 27, 28–9
karyotyping fetal 272
arguments against 39–43 arguments for 35–8 consensus 41–2
in early abortion 76
outcome of subsequent pregnancy 35–6, 36
techniques 35, 40 parental 37, 40, 272
laparoscopy, diagnostic 154 advantages/disadvantages 155
late RPL 5, 8
lifestyle factors 6–7, 10, 272 limb defects 72–3 listeriosis 193
liveborns, abnormal, chromosomal anomalies in 23
inversions 31–2 translocations 30 trisomies 28
low-molecular-weight heparin for APS 119–21, 122, 235
guidelines 120–1
in labor/postpartum 123 mechanism of action 120 monitoring 121
risks 121 complications 139 dosage 140
for fibrinogen deficiency 130 indications 139
mechanism of action 134, 141 mode of action 239 monitoring 141
in pregnancy 139 for RPL 143
for thrombophilia/pregnancy loss 140–1, 236
luteal phase defect 79–80, 97 causes 79
diagnosis 79–80 investigation 272
and progesterone supplementation 90, 93 treatments 80, 98
problems with trials 98–9 luteinizing hormone (LH) 83
magnetic resonance imaging (MRI) 154 advantages/disadvantages 155, 155
male partner, controlling for, in studies 258 masking (blinding) 259–60
maternal age PGD/PGS for 46–7
recurrent aneuploidy 28 RPL 3–4, 4, 7–8
McDonald cerclage technique 211, 215 medicolegal perspective on extreme
prematurity 226 metformin 83
methodological issues in therapy assessment 255–68
ascertainment bias 259–60 baseline risk of miscarriage 257–8 blinding (masking) 259–60 clinical heterogeneity 256–7 co-intervention 260–1
control event rate 257–8 difference in outcome, detecting
261–2
exclusion of implantation failures 256–7 female age, controlling for 258
group allocation concealment 259 historical controls 262 intention-to-treat analysis 262–3 intervention groups, ensuring similarity
between 258–9
karyotypic analysis of abortus 266 male partner, controlling for 258 null hypothesis testing 263–5 onset of treatment 265 population 256
post-randomization exclusions 262–3 randomization 258–9
recurrent miscarriage, definition of 256 research question 258
sample size estimation 261–2 selection bias 258, 259 treatment bias 260–1, 265–6 treatment effect 262, 265
estimation accuracy 266 magnitude 257
metronidazole 197, 198, 203 metroplasty
abdominal 156, 158, 161 hysteroscopic 156, 157–8, 162 septum-sparing 159 Strassman 156–7, 161 Tompkins, modified 158
microcephaly 69, 71 microparticles 134–5 midtrimester loss
cerclage, role of 207–17 and viability 219–30
miscarriage definitions 1, 270
patient’s perspective 281, 284 missed abortions
early 74–5
transcervical embryoscopy 67–70 monosomy, autosomal 24 monosomy X 24, 26–7
frequency 24, 70 mosaic trisomy 24 mosaicism 26, 32
and CVS 40 and PGD-AS 50
Mullerian duct defects 147–52 classification 147–8, 148 development 147–8
multiplex fluorescence in situ hybridization (M-FISH) 41
mycoplasmas 201–2 myomas 151, 159–60 myomectomy
hysteroscopic 156, 159
myomectomy (Continued) laparoscopic 159 laparoscopy-assisted (LAM) 159–60
natural killer (NK) cells 9
in alloimmune abortions 174 and embryo tolerance 18 inhibition by PIBF 89
and IVIG 175, 186, 190
in maintenance of pregnancy 171
in paternal leukocyte immunization 182 neonatal death, definition of 220
neural tube defects 71–2 non-inferiority trials 264
nuclear antigens, antibodies to 167 number of previous miscarriages 2–3, 3, 7
and prognoses 272–3, 273
obstetric outcomes after RPL 231–41 diabetes mellitus 233
fetal anomalies 232–3
incidence of complications 231–5 intrauterine growth restriction (IUGR) 234 perinatal mortality 234–5 pregnancy-induced hypertension 233–4 preterm labor 234
statistical analyses 231 study method 231 vaginal bleeding 232
oligomenorrhea
hCG therapy 99, 99, 102, 103–4 clinical trials 102–3, 102
omphalocele 72
ovarian reserve, abnormal 83
p53 protein 62 palliative care
extreme prematurity 227–8 gavage feeding 227–8 hospice concepts 228
prolonged terminal weaning 227 partial moles 26
partner specificity 6, 10 Patau syndrome 55
paternal leukocyte immunization 175, 276 arguments against 190–1
arguments for 179–84
‘blocking antibody theory’ 183, 189 expected chance of live birth 181 meta-analyses 179–80, 180
mode of action 239
obstetric outcomes after 237, 237 rationale 189
patient’s perspective 281–4 peer relationships 247 perinatal deaths
contribution of extreme prematurity 219–20
in Victoria 220
and IVIG 237, 238 odds ratio in RPL 235
and paternal leukocyte immunization 237, 237
after RPL 234–5
peripheral blood NK cell testing 190 PGD see pregestational diagnosis
288
INDEX
phosphatidylethanolamine (aPE) |
prematurity (Continued) |
recurrent pregnancy loss (RPL) |
antibodies 115, 116 |
survival rates of ELBW infants 221, 221, |
associated complications 232 |
phospholipids 166 |
222–4, 222, 224 |
causes 185 |
PIBF see progesterone-induced blocking factor |
withdrawing intensive care 225–6 |
classification 4–5, 8–9 |
placebo effect 260 |
withholding intensive care 224–5 |
definition 1 |
placebo surgery 260 |
and mycoplasmas 201 |
early 67 |
placenta |
preterm labor |
specific forms 276–7 |
in embryo– maternal signaling 15 |
and IVIG 238 |
therapeutic alternatives 49–51 |
infarcts/thrombosis 130–1 |
odds ratio in RPL 234 |
unexplained 49–51 |
placental apoptosis 134 |
and paternal leukocyte immunization 237, |
repeat fetal aneuploidy see recurrent |
placental cell apoptosis 111 |
237 |
aneuploidy |
plasmapheresis 123 |
after RPL 234 |
repeated implantation failure (RIF) 257 |
platelet-activating factor (PAF) 15, 18–19 |
prevalence |
reproductive autoimmune failure |
polar body analysis 25 |
aneuploidy 45 |
syndrome (RAFS) 165 |
polycystic ovary syndrome (PCOS) 10, 83 |
RPL 1, 2, 7 |
reproductive autoimmune syndrome (RAS) 165 |
polydactyly 72–3 |
primary RPL 4, 5, 8, 8, 9, 256 |
associated autoantibodies/immune |
polypectomy, hysteroscopic 156, 157 |
procoagulant–anticoagulant balance 128 |
disorders 168 |
polyploidy 24, 26 |
progesterone |
clinical/laboratory findings 166 |
and developmental defects 75 |
deficiency spectrum 90 |
resuscitation of ELBW infants 224–5 |
frequency 70 |
and immunomodulation 93–4 |
and gestational age 224 |
polyps 151–2 |
in pregnancy maintenance 79 |
Robertsonian translocations 30 |
polysomy of sex chromosomes 24, 27 |
and pregnancy outcome 90–1 |
and PGD 51 |
prednisone 121 |
and thrombosis 135 |
Royal College of Obstetricians and |
preeclampsia |
progesterone-induced blocking factor |
Gynecologists (RCOG) |
and APS 235 |
(PIBF) 89 |
on karyotyping 38, 41, 76 |
and IVIG 238, 238 |
progesterone receptors 89 |
on RPL management 269, 270, 272 |
and paternal leukocyte immunization |
progesterone supplementation 80, 97, |
Royal College of Pediatrics and Child Health |
237, 237 |
98, 272 |
on resuscitation of ELBW infants 225 |
pregestational diagnosis (PGD) |
arguments against 93–6 |
Royal College of Pathologists (RCPath) on |
aneuploidy screening (PGD-AS) |
clinical data 94–5 |
karyotyping 41 |
diagnostic 50–1 |
scientific basis 93–4 |
RPL see recurrent pregnancy loss |
observational studies 50 |
arguments for 89–92 |
rubella 194 |
therapeutic 49–50 |
and donor oocytes 89 |
|
arguments against 49–53 |
prognostic factors 272–3 |
secondary RPL 4–5, 5, 8, 8, 9, 256 |
arguments for 45–8 |
prolactin 80, 81 |
selection bias 258, 259 |
indications 46 |
prolonged terminal weaning 227 |
selective resuscitation see intensive care, |
and maternal age 47 |
prostacyclin 110 |
withholding |
parental chromosomal abnormalities 46 |
protein C 109 |
self-esteem 246–7 |
patient selection 45–6 |
psychological reactions to RPL 243–5 |
semiallogenic graft, conceptus as 168 |
for recurrent aneuploidy 46 |
affected domains of life 246–7 |
septate uterus 148, 153, 157–60, 157 |
pregestational screening (PGS) 37, 41 |
grieving process 245–6 |
septoplasty 157–9, 272 |
chromosomes sought 35, 37, 46 |
male partner 247–8 |
sex chromasome polysomy 24, 27 |
and maternal age 47 |
physician 248 |
frequency 24 |
in recurrent aneuploidy 36, 37 |
psychoneuroimmunology 250–1 |
sexual life 247 |
for recurrent aneuploidy 46 |
stress 249–50 |
sham operation 260 |
pregnancy |
support for couples 248–9 |
Shirodkar cerclage technique 211 |
immune response in 168–71 |
psychological coping mechanisms 243–53 |
signaling 15–22 |
immunological mechanisms 173 |
cognitive restructuring 248–9 |
corpus luteum, rescue of 16 |
immunological paradox of 168 |
psychoneuroimmunology 250–1 |
see also embryo–maternal signaling |
preimplantation embryos |
|
smoking 10 |
chromosomal abnormalities in 23 |
2,3-quinoxalinedimethanol-1,4-dioxide 59 |
social support 244 |
frequency of losses 23 |
|
sonohysterography 153–4 |
preimplantation factor (PIF) 15 |
randomization 258–9 |
advantages/disadvantages 155–6, 155 |
synthetic 18 |
reciprocal translocations 30 |
Special Interest Group for Early |
as universal tolerance biomarker 19–20 |
and PGD 51 |
Pregnancy (SIGEP) 156, 255 |
prematurity |
recurrent aneuploidy 27–9 |
spina bifida 72 |
and bacterial vaginosis 196–9, 200 |
and clinical management 29 |
split-hand/-foot malformation 73 |
and DES exposure 151, 162 |
and karyotyping 36, 37 |
spontaneous abortion |
extreme |
and maternal age 28 |
definition 39 |
decision-making process 226–7 |
and number of losses 28, 29 |
early 76–7 |
disability rates of ELBW infants 222, 222, |
PGD for 46 |
genetics 23–34 |
223, 224, 224 |
prevalence 27–8 |
transcervical embryoscopy 67–70 |
ethical dilemmas 224–8 |
recurrent miscarriage, definitions of 1, 256 |
steroids 121, 123, 272 |
medicolegal perspective 226 |
Recurrent Miscarriage Immunotherapy |
stillbirth, definition 219–20 |
palliative care 227–8 |
Trialists Group (RMITG) meta-analyses |
stress 249–50 |
and perinatal mortality 219–20 |
179, 181, 182, 232 |
animal models 250 |
289
INDEX
stress (Continued) marital 247
and psychoneuroimmunology 250–1 subseptate uterus 148
support for couples 244–5, 248–9 support groups 244, 248 supportive care 49, 250
survival rates of ELBW infants 221, 221, 222–4, 222, 224
syndactyly 73, 73 syphilis 195
T-shaped uterus 151
‘tender loving care’ 156, 182, 271, 272, 273 teratogens
embryo’s responses 59–66 regulating apoptosis in embryo 62–3
tertiary RPL 4, 256 tetracycline 202 tetraploidy 24, 26 therapy
estrogen 98
evidence-based evaluation 255–68 human chorionic gonadotropin 98 progesterone 98
study criteria for RPL treatments 94 for unexplained RPL 49–51
see also specific agents
thrombophilias, hereditary 130–4, 185, 272 autoimmune see antiphospholipid syndrome cohort studies 133
fetal 135
and fetal loss 139 early 131–2, 143 late 132–3
hereditary 127 outcomes 236 prevalence
first-trimester losses 131–2
late obstetric complications 132–3 and prognosis 275 thromboprophylaxis
arguments against 143–5 arguments for 139–42
treatment 133–4 thrombophilic risk factors 139 thromboprophylaxis
arguments against 143–5 arguments for 139–42 clinical studies 144–5 pregnancy outcomes 144
thrombosis
in APS 109–10
in fibrinogen replacement 130 hormones and 135
in placenta 130–1
thyroid abnormalities 80–2, 272 thyroid-stimulating hormone 81 tissue factor 109
tolerance of embryo 16–20 mechanisms enhancing 170
Tompkins metroplasty, modified 158 Topper and Farquharson cerclage technique
211–12
TORCH infections 193–4 testing for 272
torsion of umbilical cord 73 toxoplasmosis 194
transforming growth factor β (TGF-β) 63, 64 translocations, chromosomal 29–31
abnormal liveborns 30 frequency 29–30
and PGD 51, 52 subsequent losses 30–1
transvaginal sonography (TVS) 152 cervical incompetence 210 didelphys uterus 149, 150
septate uterus 157, 158
see also ultrasound, three-dimensional transverse limb reduction defect 73 treatment see therapy
treatment bias 260–1, 265–6 treatment effect 262, 265
estimation accuracy 266 magnitude 257
triploidy 24, 26
and spina bifida 72 trisomies
autosomal 24–5, 24 double 24, 25–6
chromosomes 25 and encephaloceles 72 frequency 24, 70
and maternal age 25, 26 mosaic 24
in recurrent aneuploidy 27 trunk defects 72
tuberculosis 193
tumor necrosis factor α (TNF-α) 63, 64
ultrasound advantages/disadvantages 154, 155
in cervical incompetence 208–10, 209, 210 markers for aneuploidy 55–6 three-dimensional 152–3
advantages/disadvantages 155 bicornuate uterus 151 didelphys uterus 150
septate uterus 153, 158
with sonohysterography 154 unicornuate uterus 149
umbilical cord defects 73 unfractionated heparin for APS 119–21
guidelines 120–1
in labor/postpartum 123 mechanism of action 120 monitoring 121
risks 121
unicornuate uterus 148, 148, 149, 149 universal tolerance biomarker 18–20
Ureaplasma urealyticum 195, 196, 198, 200, 201, 202
ureteroplacental arteries, thrombosis of 131 uterine agenesis/hypoplasia 148, 148 uterine anomalies 68, 147–64
imaging 152–5
diagnostic hysterography 154, 155 diagnostic laparoscopy 154, 155 hysterosalpingography (HSG) 152, 155 magnetic resonance imaging (MRI) 154, 155 method choice 154–5, 155 sonohysterography 153–4, 155
uterine anomalies (Continued) three-dimensional ultrasound 152–3, 155 transvaginal sonography (TVS) 152, 155
incidence 147
Müllerian duct defects 147–52 arcuate uterus 148–9, 148 bicornuate uterus 148, 148, 150–1,
151, 161 classification 147–8, 148 development 147–8
didelphys uterus 148, 148, 149–50,
149, 150 imperforate hymen 148
intrauterine adhesions (synechiae) 152 myomas 151, 159–60
polyps 151–2
septate uterus 148, 153, 157–60, 157 subseptate uterus 148
T-shaped uterus 151
unicornuate uterus 148, 148, 149, 149 uterine agenesis/hypoplasia 148, 148
and prognosis 275 reproductive outcomes 147 treatment 155–62
abdominal metroplasty 156, 158, 161 cervical cerclage 149, 156, 160–1 hysteroscopic adhesiolysis 156 hysteroscopic metroplasty 156, 157–8, 162 hysteroscopic myomectomy 156, 159 hysteroscopic polypectomy 156, 157 hysteroscopic septoplasty 157–9 laparoscopic myomectomy 159 laparoscopic salpingectomy 161 laparoscopy-assisted myomectomy
159–60
septum-sparing metroplasty 159 Strassman metroplasty 161
uterine cavity exploration 67–8, 272 flora 196, 196
uterine integrity investigations 152–5 uterine septum resection see septoplasty uterus didelphys see didelphys uterus
vaginal bleeding and IVIG 237, 238
and paternal leukocyte immunization 237, 237
after RPL 232 vaginal flora 195–7, 196 viability
in extreme prematurity 220–4 and midtrimester loss 219–30 outcome
and gestational age 222–3 and place of birth 220 recent improvements 221 and transfer in utero 221
prematurity and RPL risk 221–2 Victorian Infant Collaborative Study
(VICS) 220–3
vs other regional studies 223–4 Victorian Infant Collaborative Study
(VICS) 220–3
Whipple’s disease 203
290