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