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 IMMUNOLOGY OF RECURRENT
PREGNANCY LOSS AND IMPLANTATION
FAILURE
This page intentionally left blank
 Reproductive Immunology

IMMUNOLOGY OF
RECURRENT
PREGNANCY LOSS
AND
IMPLANTATION
FAILURE
VOLUME 3
Edited by

JOANNE KWAK-KIM, MD, MPH

Agnes D. Lattimer MD, Professor, Director, Reproductive Medicine and Immunology, Obstetrics and Gynecology,
Clinical Sciences Department, Chicago Medical School, Rosalind Franklin University of Medicine and Science,
Vernon Hills, IL, USA

Series Editor

GIL MOR
John M. Malone Jr., MD, Endowed Chair, Scientific Director, C.S. Mott Center for Human Growth and Development,
Wayne State University School of Medicine, Detroit MI, USA
Academic Press is an imprint of Elsevier
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our
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Typeset by MPS Limited, Chennai, India

 Contents

List of contributors xv 4.4 Natural killer cell education (maternal KIR/

About the editor xix maternal HLA-C combinations) and
pregnancy risks 16
5 Evaluation 17
I 6 Reproductive outcome 19
7 Treatment 19
Introduction 7.1 Corticosteroid treatment 19
1. Clinical reproductive immunology: a 7.2 Intravenous immunoglobulin G
window to understanding reproduction and treatment 20
immunology 3 7.3 Other treatments 20
8 Summary and recommendations 21
JOANNE KWAK-KIM
References 22
References 5

II 3. T helper cell pathology and recurrent

Recurrent pregnancy losses pregnancy losses; Th1/Th2, Treg/Th17, and
other T cell responses 27
2. Natural killer (NK) cell pathology and JOON CHEOL PARK, JAE WON HAN AND SUNG KI LEE
reproductive failure: NK cell level, NK cell
cytotoxicity, and KIR/HLA-C 9 1 The immunologic perspective of recurrent
SVETLANA DAMBAEVA, THANH LUU, LUJAIN ALSUBKI
pregnancy loss 27
AND JOANNE KWAK-KIM 2 Definition and prevalence of recurrent pregnancy
loss 27
1 Introduction 9 3 Prevalence 28
2 Natural killer cells—definition 10 4 Immune regulations in normal pregnancy and
2.1 Natural killer cells receptors 10 recurrent pregnancy loss 28
2.2 Natural killer cell cytokines 11 4.1 T cells during a menstrual cycle 28
2.3 Natural killer cell subsets 12 4.2 T cells in human pregnancy 29
2.4 Natural killer cells education and 4.3 Three immunologic stages during a
licensing 13 pregnancy 29
3 Natural killer cell-related pathologies 13 4.4 Paternal and fetal antigen-specific tolerance
4 Natural killer cells in reproduction 15 during a pregnancy 31
4.1 Uterine natural killer cells 15 4.5 Underlying immunopathology that impairs
4.2 Peripheral blood natural killer cells 15 reproduction 31
4.3 Maternal killer immunoglobulin-like receptor/ 5 Diagnostic approaches 39
placental HLA-C combinations and 5.1 Laboratory technique 39
pregnancy risks 15 5.2 Candidates for evaluation 40

v
vi Contents

6 Treatment and reproductive outcome 40 2.2 Differentiation and development of mast

6.1 Corticosteroids 40 cells 72
6.2 Intravenous immunoglobulins 43 2.3 Mast cell activation 73
6.3 Tacrolimus 44 2.4 Types of mast cells 73
6.4 Other immunosuppressants 45 2.5 Mast cell granules 74
6.5 Tumor necrosis factor inhibitors 45 3 Role of mast cells in reproductive system 74
6.6 Vitamin D 46 3.1 Male reproductive tract 74
7 Summary and recommendations 46 3.2 Female reproductive system 75
References 47 4 Mast cell-related immunopathology in
reproduction 77
4. B cell pathology and recurrent 4.1 Male infertility 77
pregnancy loss 55 4.2 Endometriosis 78
RUTH MARIAN GUZMAN-GENUINO AND 4.3 Recurrent pregnancy loss 81
KERRILYN R. DIENER 4.4 Mast cells and in vitro fertilization
failures 83
1 Introduction 55 4.5 Mast cell activation disease 83
2 B cell function during pregnancy 56 5 Summary and Recommendation 87
2.1 Humoral immunity 56 References 88
2.2 Asymmetric antibodies and
autoantibodies 56 6. Role of human leukocyte antigen in
2.3 B cell lymphocytopenia 57 the pathogenesis of recurrent
2.4 Regulatory B cells 58 pregnancy loss 93
3 Immunopathologies related to reproduction 59 CHIARA TERSIGNI AND NICOLETTA DI SIMONE
3.1 B cell immune dysregulation in pregnancy 59
3.2 Antiphospholipid syndrome 59 1 Introduction 93
3.3 Suboptimal implantation 61 2 Recurrent pregnancy loss and human leukocyte
antigen studies 93
3.4 Intrauterine growth restriction 61
3 Human leukocyte antigen class I and II
3.5 Preeclampsia 62
molecules 94
3.6 Preterm birth 62
3.1 Expression of human leukocyte antigen class I
4 Recurrent pregnancy loss 63
and II molecules in the human
5 Diagnosis 63
placenta 95
6 Treatments 64
3.2 Abnormal expression of human leukocyte
6.1 Lymphocyte immunotherapy 65
antigen molecules in RPL 98
6.2 Intravenous immunoglobulin therapy 65 4 Evaluation of human leukocyte antigen antigens
6.3 B cell-targeting therapies 65 in assisted reproduction 99
7 Summary and recommendations 66 5 Treatment 99
References 66 6 Conclusions 99
7 Summary and recommendations 100
5. Mast cell pathology and reproductive References 100
failures 71
MARIA SOCORRO L. AGCAOILI-DE JESUS, LARA THERESA
7. Stress-induced immune deviations and
C. ALENTAJAN-ALETA, CHERIE C. OCAMPO-CERVANTES, reproductive failure 103
JENIFER R. OTADOY-AGUSTIN AND JOANNE KWAK-KIM
RONJA WÖHRLE, PETRA CLARA ARCK AND
KRISTIN THIELE
1 Introduction 71
2 Mast cells biology 71 1 Immune-endocrine adaptations during normally
2.1 Origin of mast cells 72 progressing pregnancies 103
 Contents vii
1.1 Distinct immunological features of maternal 3 Prevalence 138
immune adaptation to pregnancy 105 4 Underlying immunopathologies related to
2 Maternal stress perception 106 reproduction 138
2.1 Stressors 106 4.1 Inhibition of sperm transport by antisperm
2.2 The strength of stress 106 antibodies at the level of cervical
2.3 The severity of a stressor 107 mucus 138
3 The prevalence of stress 107 4.2 Inhibition of sperm transport by antisperm
4 Neuro-endocrine-immune imbalances and antibodies from uterine cavity to Fallopian
pregnancy 108 tubes 139
5 How to assess stress perception? 111 4.3 Inhibition of sperm egg interaction by
6 How to treat high-stress perception? 111 antisperm antibodies 139
7 Consequences of maternal stress on reproductive 4.4 Impairment of early embryo development by
outcome 112 antisperm antibodies 140
8 Summary and recommendations 113 4.5 Antisperm antibodies and recurrent
References 113 pregnancy loss 141
4.6 Reports showing a positive association
8. Antiphospholipid syndrome and between antisperm antibodies and recurrent
recurrent pregnancy losses 121 pregnancy loss 141
ERRA ROBERTA, TRESPIDI LAURA, OSSOLA WALLY AND 4.7 Reports showing a negative association
MERONI PIER LUIGI between antisperm antibodies and recurrent
pregnancy loss 143
1 Introduction 121 4.8 Pregnancy outcome in infertile women with
1.1 Definition 121 sperm-immobilizing antibodies 143
1.2 Prevalence 122 5 Evaluation 145
1.3 Underlying immunopathology 123 5.1 Test for antisperm antibodies 145
2 Evaluations 125 5.2 Application of computer-aided sperm analysis
2.1 Diagnosis 125 for the detection of sperm-immobilizing
2.2 When should we look for aPL? 126 antibodies 145
2.3 Antiphospholipid antibodies as a risk 6 Treatment 146
factor 127 6.1 Treatment modalities 146
3 Clinical practice management 128 6.2 Strategy for the treatment of infertile women
3.1 Risk stratification 128 with sperm-immobilizing antibodies 146
3.2 Treatment 128 7 Reproductive outcomes 147
4 Monitoring 130 8 Summary and recommendations 148
5 Delivery and puerperium 131 References 148
6 Fetal and neonatal outcome 131
7 aPL and infertility 131
8 Summary and recommendations 132 10. Antithyroid antibodies and
References 132
reproductive function 153
ELENA BORODINA, ALEXANDER M. GZGZYAN,
9. Antisperm antibodies and reproductive LYAILYA KH. DZHEMLIKHANOVA, DARIKO A. NIAURI
failure 137 AND YEHUDA SHOENFELD
HIROAKI SHIBAHARA, YUEKUN CHEN, AYANO YAMAYA,
YU WAKIMOTO, ATSUSHI FUKUI AND AKIKO HASEGAWA 1 Introduction 153
2 Definition of autoimmune thyroiditis 153
1 Introduction 137 3 Prevalence 154
2 Definition 138 4 Underlying immunopathology 154
viii Contents

4.1 Antithyroid antibodies as an 7.3 Preconceptional counseling 173

epiphenomenon 154 7.4 Prenatal care in the subsequent
4.2 Antithyroid antibodies as a reason for the pregnancy 173
compromised function of the thyroid 8 Summary and recommendations 174
gland 154 References 174
4.3 Mechanisms by which antithyroid antibodies
can cause reproductive failures 155
5 Evaluation 159 12. Infectious and noninfectious
6 Treatment 159
7 Reproductive outcomes 160
endometritis and recurrent
8 Summary and recommendation 160 pregnancy loss 177
References 161 FUMINORI KIMURA, AINA MORIMUNE, AKIKO
NAKAMURA, JUN KITAZAWA, TETSURO HANADA AND
TAKASHI MURAKAMI

11. Fetal/neonatal alloimmune-mediated 1 Introduction 177

thrombocytopenia and recurrent 2 Definition 177
pregnancy loss 165 2.1 Infectious endometritis 178
2.2 Noninfectious (immune) endometritis 184
SI WON LEE, TIFFANY ALEXIS CLINTON AND
SUN KWON KIM 3 Summary and recommendations 188
References 188
1 Introduction 165
2 Definition 165
3 Prevalence 167 13. Thrombophilic pathologies in
4 Underlying immunopathology related to recurrent pregnancy losses 193
reproduction 167
AE RA HAN AND SUNG KI LEE
4.1 Maternal allosensitization by fetal human
platelet antigen 167 1 Introduction 193
4.2 Thrombosis and cellular immune 2 Thrombophilia 194
activation 168 2.1 Inherited thrombophilia 194
5 Evaluation 168 2.2 Acquired thrombophilia 194
5.1 Diagnostic criteria 168 2.3 Prevalence of inherited thrombophilia 195
5.2 Clinical features 169 3 Physiologic hypercoagulability in pregnancy 195
5.3 Testing modalities 169 4 Inherited thrombophilia and recurrent pregnancy
5.4 Screening and diagnosis 170 loss 196
6 Treatment 171 5 Evaluation 196
6.1 Medications 171 5.1 Who needs to be tested? 196
6.2 Timing and mode of delivery 171 5.2 Which tests should be done? 197
6.3 Intrapartum and postpartum 5.3 What criteria can be applied? 197
management 172 6 Treatment of inherited thrombophilia 197
6.4 Possible side effects: risks and 6.1 Anticoagulants 198
monitoring 172 6.2 Management of inherited thrombophilia in
7 Reproductive outcomes 173 recurrent pregnancy loss women 198
7.1 Postpartum management and 7 Reproductive outcomes 199
evaluation 173 8 Summary and recommendations 200
7.2 Future reproductive options 173 References 200
 Contents ix
14. Rheumatic diseases and reproductive 8 Summary and recommendations 215
outcomes 205 References 215
BROOKE MILLS AND BONNIE L. BERMAS

1 Rheumatic conditions and pregnancy

III
outcome 205 Repeated implantation failures
2 Rheumatoid arthritis 206
15. The role of reproductive immunology
2.1 Definition and prevalence 206
2.2 Underlying immune mechanism contributing
in recurrent pregnancy loss and repeated
to reproductive outcomes in rheumatoid implantation failure 223
arthritis 206 JENNY S. GEORGE, ROISIN MORTIMER AND
RAYMOND M. ANCHAN
2.3 Evaluation 206
2.4 Treatment 207 1 Introduction 223
2.5 Reproductive outcomes 207 2 Definitions and terminology 224
3 Systemic lupus erythematosus 208 3 Prevalence 224
3.1 Definition and prevalence 208 4 Underlying immunopathology related to
3.2 Underlying immune mechanisms contributing reproduction 225
to reproductive outcomes in systemic lupus 5 Evaluation 226
erythematosus 208 5.1 Cytogenetic abnormalities 227
3.3 Evaluation 208 5.2 Anatomic anomalies 227
3.4 Treatment during pregnancy 208 5.3 Antiphospholipid antibody syndrome 227
3.5 Reproductive outcome 209 5.4 Hormonal disturbances 227
4 Systemic sclerosis 209 5.5 Thrombophilias 228
4.1 Definition and prevalence 209 6 Treatment 228
4.2 Underlying immune mechanism contributing 6.1 Treatment of recurrent pregnancy loss 228
to reproductive outcomes in systemic 6.2 Treatment of recurrent implantation
Sclerosis 209 failure 229
4.3 Evaluation 210 6.3 Uterine interventions 229
4.4 Treatment modalities 210 6.4 Laboratory and procedural technologies and
4.5 Reproductive outcomes 210 interventions 231
5 Antiphospholipid antibody syndrome 211 6.5 Immunomodulatory therapies 232
5.1 Definition and prevalence 211 6.6 Endometrial therapies 234
5.2 Underlying immunopathology related to 6.7 Combination therapy 234
reproduction 211 7 Reproductive outcomes 235
5.3 Evaluation 211 7.1 Recurrent pregnancy loss 235
5.4 Treatment of antiphospholipid antibody 7.2 Recurrent implantation failure 235
syndrome during pregnancy 212 8 Summary and recommendations 235
5.5 Reproductive outcomes 213 References 236
6 Neonatal lupus 213
6.1 Definition and prevalence 213 16. The embryo in reproductive failure:
6.2 Underlying immune mechanisms related to immunological view 241
reproductive outcome 214
TIA BRODEUR AND NAVID ESFANDIARI
6.3 Evaluation 214
6.4 Treatment modalities 214 1 Introduction 241
6.5 Reproductive outcomes 214 2 Embryo-derived signals influencing the local
7 Conclusion 215 immune environment 242
x Contents

2.1 Human chorionic gonadotropin 242 3.1 Peripheral blood natural killer cell
2.2 Early pregnancy factor 243 cytotoxicities and proportions 261
2.3 Platelet-activating factor 243 3.2 Endometrial and decidual natural killer cell
3 Embryo-endometrial dialogue 243 cytotoxicities and proportions 262
3.1 Inflammatory cytokines 243 3.3 Natural killer cell activating and inhibitory
3.2 Prostaglandins 244 receptors 262
3.3 Leukemia inhibitory factor 244 3.4 Natural killer cell-producing cytokines 263
4 Recurrent implantation failure 244 4 Candidates for evaluation 263
4.1 Definition 245 5 Treatment 264
4.2 Prevalence 245 5.1 Anticoagulants (aspirin and heparin) 264
4.3 Evaluation 245 5.2 Corticosteroids 264
5 Improving implantation rate 249 5.3 Immunoglobulins 265
5.1 Embryo selection 249 5.4 Fat emulsion infusion therapy 266
5.2 Embryo morphokinetics 249 5.5 Hydroxychloroquine 266
5.3 Metabolomics and metabolite concentrations 5.6 Tumor necrosis factor inhibitors 267
in embryos culture media 249 5.7 Vitamin D 267
5.4 Embryo culture conditions 250 6 Summary and recommendations 267
5.5 Sequential embryo transfer 250 References 269
5.6 Assisted hatching 250
5.7 Therapies to improve sperm aneuploidy 251
18. Helper T cell pathology and repeated
6 Immunomodulation 251 implantation failures 273
6.1 Granulocyte colony-stimulating factor 251 KOJI NAKAGAWA, KEIJI KURODA AND
RIKIKAZU SUGIYAMA
6.2 Platelet-rich plasma 252
6.3 Granulocyte colony-stimulating factor and 1 The role of helper T cells in reproductive
platelet-rich plasma 252 medicine 273
6.4 Intralipid 252 2 Th cell immunopathology and repeated
6.5 Human leukocyte antigen 253 implantation failure 275
6.6 Intrauterine human chorionic 3 Prevalence 275
gonadotropin 253 4 The theoretical understanding for the application
6.7 Endometrial injury (“scratching”) 254 of immunomodulation therapy in recurrent
7 Summary and recommendations 254 implantation failure 276
References 254 5 Evaluation 277
6 Immunomodulation treatments targeting T helper
cell pathology 278
17. Natural killer cell pathology and 6.1 Glucocorticoids 278
repeated implantation failures 259 6.2 Tacrolimus 280
ATSUSHI FUKUI, AYANO YAMAYA, SHINICHIRO SAEKI, 7 Reproductive outcome 282
RYU TAKEYAMA, TORU KATO, YU WAKIMOTO AND 8 Summary and recommendations 282
HIROAKI SHIBAHARA
References 283
1 Introduction 259
1.1 Repeated implantation failure 259 19. B-cell pathology and repeated
1.2 Prevalence of repeated implantation implantation failures 287
failure 260 SHIHUA BAO, MENGYANG DU AND XIAO WANG
2 Natural killer cell and pregnancy 260
3 Underlying immunopathologies related to 1 Introduction 287
reproduction 261 2 B-cell immunopathology and reproduction 288
 Contents xi
2.1 B-cell subsets 288 21. Thrombophilia, antiphospholipid
2.2 Antibody-producing B cells in antibodies, and anticoagulation in
pregnancy 289 recurrent implantation failure 317
2.3 Nonprecipitating asymmetric antibodies 289
MARCELO BORGES CAVALCANTE AND
2.4 Autoantibodies 290 RICARDO BARINI
2.5 Breg cells in pregnancy 290
3 Dysregulation of B cells in women with repeated 1 Introduction 317
implantation failure 292 2 Definition of thrombophilia 318
4 Clinical translational perspectives of B-cell 2.1 Acquired thrombophilia 318
immunopathology 293 2.2 Inherited thrombophilias 319
4.1 Prednisone 293 3 Prevalence 322
4.2 Hydroxychloroquine 293 3.1 Antiphospholipid antibodies 322
4.3 Intravenous immunoglobulin 294 3.2 Inherited thrombophilia 323
4.4 Rituximab 294 4 Underlying immunopathologies related to
4.5 Breg-based therapy 295 reproduction 323
5 Summary and recommendations 295 5 Diagnosis 324
References 296 5.1 Antiphospholipid syndrome 324
5.2 Inherited thrombophilia 325
6 Treatment 326
20. Endometrial pathology and repeated 7 Summary and recommendations 327
implantation failures 303 References 328
MAUD LANSIAUX, VIRGINIE VAUCORET AND
NATHALIE LÉDÉE
IV
1 Introduction 303 Dysregulated neuroimmune-
2 Endometrial pathologies 304
2.1 Anatomical disturbances 304 endocrine network in reproductive
2.2 Displaced window of implantation 305 failures
3 Endometrial immunopathology 306
22. The ovarian immune pathology and
3.1 How to detect endometrial immune
pathology? 306
reproductive failures 333
LI WU, XUHUI FANG, YANSHI WANG AND
3.2 The UtimPro test 307
JOANNE KWAK-KIM
3.3 UtimPro test outcomes 307
3.4 Incidence of abnormal UtimPro test 308 1 Introduction 333
4 Immune treatments for women with abnormal 2 Ovarian immunology 334
immune profile 308 3 Ovarian autoimmunity 335
4.1 The personalization and its rationale 308 3.1 Autoimmune lymphocytic oophoritis 335
4.2 Glucocorticoids 308 3.2 Molecular and cellular targets for ovarian
4.3 Intralipids 309 autoimmunity 335
4.4 Luteal human chorionic gonadotropin 4 Primary ovarian insufficiency 337
supplementation 310 4.1 Definition 337
4.5 Low molecular weight heparin 310 4.2 Clinical manifestation 338
4.6 Scratching 310 4.3 The histopathological types of primary
4.7 Supplementation in progesterone 311 ovarian insufficiency 338
5 Key points 311 4.4 The etiologies of primary ovarian
References 312 insufficiency 338
xii Contents

5 Diseases associated with ovarian 4.3 Chronic inflammation and the

autoimmunity 339 endometrium 361
5.1 Polycystic ovary syndrome 339 4.4 Chronic inflammation and the placenta 362
5.2 Ovarian endometriosis 340 5 Conclusion 362
5.3 Recurrent pregnancy losses 341 6 Summary and Recommendations 363
5.4 Unexplained infertility 341 References 364
6 Diagnosis of primary ovarian insufficiency 342
6.1 Diagnostic approaches 343 24. Metabolic control of immune
6.2 Diagnosis of autoimmune oophoritis 343 responses in women with recurrent
7 Treatment for autoimmune primary ovarian
insufficiency 344
pregnancy loss and recurrent implantation
7.1 Women with a desire for reproduction 344 failure 379
7.2 Women without a desire for YIQIU WEI, SONGCHEN CAI, JINLI DING, YONG ZENG,
TAILANG YIN AND LIANGHUI DIAO
reproduction 345
8 Reproductive outcomes 345 1 Introduction 379
9 Summary and recommendations 345 2 Definition and prevalence 380
References 346
2.1 Antiphospholipid syndrome in recurrent
pregnancy loss and recurrent implantation
failure 381
23. Polycystic ovarian syndrome and 2.2 Insulin resistance and polycystic ovary
reproductive failure 351 syndrome in recurrent pregnancy loss and
JOSEPH DUERO AND RESHEF TAL recurrent implantation failure 381
2.3 Autoimmune thyroid disease in recurrent
1 Introduction 351 pregnancy loss and recurrent implantation
2 Hyperandrogenism and reproductive failure in failure 381
polycystic ovarian syndrome 353 2.4 Hyperprolactinemia in recurrent pregnancy
2.1 Causes of hyperandrogenism 353 loss and recurrent implantation
2.2 Hyperandrogenism and ovaries 354 failure 381
2.3 Hyperandrogenism and the 2.5 Other immunological and metabolic factors in
endometrium 355 recurrent pregnancy loss and recurrent
2.4 Hyperandrogenism and the placenta 356 implantation failure 382
3 Insulin resistance and reproductive failure in 3 Underlying immunometabolic pathologies related
polycystic ovarian syndrome 356 to recurrent pregnancy loss and recurrent
3.1 Molecular basis for insulin resistance 357 implantation failure 382
3.2 Insulin resistance and obesity 357 3.1 Antiphospholipid syndrome 382
3.3 Insulin resistance and the ovaries 358 3.2 Insulin resistance 383
3.4 Insulin resistance and the 3.3 Autoimmune thyroid disease 384
endometrium 358 3.4 Other immune factors 385
3.5 Insulin resistance and the placenta 358 4 Evaluation 385
4 Chronic inflammation and reproductive failures in 5 Treatment and reproductive outcomes 386
polycystic ovarian syndrome 359 5.1 Treatment of antiphospholipid
4.1 Mechanisms of inflammation in polycystic syndrome 386
ovarian syndrome and interplay with 5.2 Treatment of insulin resistance and polycystic
insulin resistance and ovary syndrome 389
hyperandrogenism 359 5.3 Treatment of autoimmune thyroid
4.2 Chronic inflammation and ovaries 360 disease 390
 Contents xiii
6 Summary and recommendations 390 26. Laboratory approaches for reproductive
Fundings 390 failure: immunological biomarkers for
References 390
reproductive failures 403
KATHARINE WOLF, KENNETH BEAMAN, SVETLANA
DAMBAEVA AND ALICE GILMAN-SACHS
25. Endometriosis and reproductive
1 Genomic evaluation 403
failures 395 1.1 Human leukocyte antigen-C and natural
GENTARO IZUMI, KAORI KOGA AND YUTAKA OSUGA killer cells 403
1 Introduction 395 1.2 Prevalence of abnormal genomic test 404
2 Local decidual measurements 405
2 Mechanism of endometriosis-related reproductive
failure 396 2.1 Endometrial immune profile testing 405
3 Immune aspect of endometriosis-related pregnancy 2.2 Endometrial decidualization score 407
failure 396 3 Peripheral blood cell analysis 408
3.1 Chronic endometritis 396 3.1 T helper (Th) 1/Th2 cell ratio 408
3.2 Cytokines 397 3.2 Natural killer cell levels and
3.3 Immune cell and surveillance against cytotoxicities 408
retrograde menstruation 397 4 Autoantibodies in recurrent pregnancy loss 409
4 Treatment options 397 4.1 Antiphospholipid antibodies 409
4.1 Hormonal treatment 397 4.2 Anti nuclear antibodies (ANA) 410
4.2 Hysterosalpingography 398 4.3 Other autoantibodies 411
4.3 Immune therapy 398 5 Endocrine workup 411
4.4 Laparoscopic surgery 398 6 Other assays 411
7 Summary and recommendations 411
4.5 In vitro fertilization protocol
References 412
options 399
Further reading 413
4.6 Fresh versus frozen embryo transfer 399
5 Summary and recommendations 400
References 400 Index 415
This page intentionally left blank
 List of contributors

Maria Socorro L. Agcaoili-De Jesus Division Bonnie L. Bermas Division of Rheumatic

of Allergy and Immunology, Department of Diseases, University of Texas Southwestern
Medicine, University of the Philippines Medical Center, Dallas, TX, United States
College of Medicine, Philippine General Elena Borodina Department of Obstetrics,
Hospital, Manila, Philippines Gynecology and Reproductive Sciences, Saint
Lara Theresa C. Alentajan-Aleta Division of Petersburg State University, Saint Petersburg,
Allergy and Immunology, Department of Russia; Laboratory of the Mosaic of
Medicine, University of the Philippines Autoimmunity, Saint Petersburg State
College of Medicine, Philippine General University, Saint Petersburg, Russia
Hospital, Manila, Philippines Tia Brodeur Division of Reproductive
Lujain Alsubki Reproductive Medicine and Endocrinology and Infertility, Department of
Immunology, Obstetrics and Gynecology, Obstetrics and Gynecology and Reproductive
Clinical Sciences Department, Chicago Sciences, Larner College of Medicine at the
Medical School, Rosalind Franklin University University of Vermont, Burlington, VT,
of Medicine and Science, Vernon Hills, IL, United States
United States Songchen Cai Shenzhen Key Laboratory for
Raymond M. Anchan Center for Infertility Reproductive Immunology of Peri-
and Reproductive Surgery, Brigham and implantation, Shenzhen Zhongshan Institute
Women’s Hospital, Harvard Medical School, for Reproduction and Genetics, Shenzhen
Boston, MA, United States Zhongshan Urology Hospital, Shenzhen, P.R.
Petra Clara Arck Division of Experimental China
Feto-Maternal Medicine, Department of Marcelo Borges Cavalcante Postgraduate
Obstetrics and Fetal Medicine, University Program in Medical Sciences, Universidade
Medical Center Hamburg-Eppendorf, de Fortaleza (UNIFOR), Fortaleza, Ceará,
Hamburg, Germany Brazil; CONCEPTUS – Reproductive
Shihua Bao Department of Reproductive Medicine, Fortaleza, Ceará, Brazil
Immunology, Shanghai First Maternity and Yuekun Chen Department of Obstetrics and
Infant Hospital, Tongji University School of Gynecology, School of Medicine, Hyogo
Medicine, Shanghai, P.R. China Medical University, Nishinomiya, Hyogo, Japan
Ricardo Barini Department of Obstetrics and Tiffany Alexis Clinton Department of
Gynecology, Campinas University Obstetrics and Gynecology, Henry Ford
(UNICAMP), Campinas, São Paulo, Brazil Health System, Detroit, MI, United States
Kenneth Beaman Clinical Immunology Svetlana Dambaeva Clinical Immunology
Laboratory, Faculty of Microbiology and Laboratory, Faculty of Microbiology and
Immunology, Center for Cancer Biology, Immunology, Center for Cancer Biology,
Infection and Immunology, The Chicago Infection and Immunology, The Chicago
Medical School, Rosalind Franklin University Medical School, Rosalind Franklin University
of Medicine and Science, Chicago, IL, United of Medicine and Science, Chicago, IL, United
States States

xv
xvi List of contributors

Nicoletta Di Simone Department of Atsushi Fukui Department of Obstetrics and

Biomedical Sciences, Humanitas University, Gynecology, School of Medicine, Hyogo
Pieve Emanuele, Milan, Italy; IRCCS Medical University, Nishinomiya, Hyogo,
Humanitas Research Hospital, Rozzano, Japan; Fukushima Medical Center for Child
Milan, Italy and Woman, Fukushima Medical University,
Fukushima, Japan
Lianghui Diao Shenzhen Key Laboratory for
Reproductive Immunology of Peri-implantation, Jenny S. George Center for Infertility and
Shenzhen Zhongshan Institute for Reproduction Reproductive Surgery, Brigham and
and Genetics, Shenzhen Zhongshan Urology Women’s Hospital, Harvard Medical School,
Hospital, Shenzhen, P.R. China Boston, MA, United States
Kerrilyn R. Diener Clinical and Health Alice Gilman-Sachs Clinical Immunology
Sciences Unit, University of South Australia, Laboratory, Faculty of Microbiology and
Adelaide, SA, Australia; Robinson Research Immunology, Center for Cancer Biology,
Institute and Adelaide Medical School, The Infection and Immunology, The Chicago
University of Adelaide, Adelaide, SA, Medical School, Rosalind Franklin University
Australia of Medicine and Science, Chicago, IL, United
States
Jinli Ding Reproductive Medicine Center,
Renmin Hospital of Wuhan University, Ruth Marian Guzman-Genuino Clinical and
Wuhan, Hubei, P.R. China Health Sciences Unit, University of South
Australia, Adelaide, SA, Australia
Mengyang Du Department of Reproductive
Alexander M. Gzgzyan Department of
Immunology, Shanghai First Maternity and
Obstetrics, Gynecology and Reproductive
Infant Hospital, Tongji University School of
Sciences, Saint Petersburg State University,
Medicine, Shanghai, P.R. China
Saint Petersburg, Russia; FSBSI “The
Joseph Duero Department of Obstetrics, Research Institute of Obstetrics, Gynecology
Gynecology and Reproductive Sciences, Yale and Reproductology named after D.O. Ott,”
School of Medicine, New Haven, CT, United Saint Petersburg, Russia
States
Ae Ra Han Cha University, Fertility Center,
Lyailya Kh. Dzhemlikhanova Department of Daegu, Republic of Korea
Obstetrics, Gynecology and Reproductive
Jae Won Han Department of Obstetrics and
Sciences, Saint Petersburg State University,
Gynecology, Konyang University College of
Saint Petersburg, Russia; FSBSI “The
Medicine, Daejeon, Republic of Korea
Research Institute of Obstetrics, Gynecology
and Reproductology named after D.O. Ott,” Tetsuro Hanada Deparment of Obstetrics and
Saint Petersburg, Russia Gynecology, Shiga University of Medical
Science, Otsu, Shiga, Japan
Navid Esfandiari Division of Reproductive
Endocrinology and Infertility, Department of Akiko Hasegawa Department of Obstetrics
Obstetrics and Gynecology and Reproductive and Gynecology, School of Medicine, Hyogo
Sciences, Larner College of Medicine at the Medical University, Nishinomiya, Hyogo,
University of Vermont, Burlington, VT, Japan
United States Gentaro Izumi Department of Obstetrics and
Xuhui Fang Reproductive Medicine Center, Gynecology, Graduate School of Medicine,
Department of Obstetrics and Gynecology, The University of Tokyo, Tokyo, Japan
The First Affiliated Hospital of USTC, Toru Kato Department of Obstetrics and
Division of Life Sciences and Medicine, Gynecology, School of Medicine, Hyogo
University of Science and Technology of Medical University, Nishinomiya, Hyogo,
China, Hefei, Anhui, P.R. China Japan
 List of contributors xvii
Sun Kwon Kim Department of Obstetrics and Medical School, Rosalind Franklin University
Gynecology, Division of Maternal-Fetal of Medicine and Science, Vernon Hills, IL,
Medicine, Henry Ford Health System, United States
Detroit, MI, United States Brooke Mills Division of Rheumatic Diseases,
Fuminori Kimura Department of Obstetrics University of Texas Southwestern Medical
and Gynecology, Nara Medical University, Center, Dallas, TX, United States
Kashihara, Nara, Japan Aina Morimune Deparment of Obstetrics and
Jun Kitazawa Deparment of Obstetrics and Gynecology, Shiga University of Medical
Gynecology, Shiga University of Medical Science, Otsu, Shiga, Japan
Science, Otsu, Shiga, Japan Roisin Mortimer Center for Infertility and
Kaori Koga Department of Obstetrics and Reproductive Surgery, Brigham and
Gynecology, Graduate School of Medicine, Women’s Hospital, Harvard Medical School,
The University of Tokyo, Tokyo, Japan Boston, MA, United States
Keiji Kuroda Division Manager of Takashi Murakami Deparment of Obstetrics
Implantation Research and Endoscopy, and Gynecology, Shiga University of Medical
Center for Reproductive Medicine and Science, Otsu, Shiga, Japan
Implantation Research, Sugiyama Clinic Koji Nakagawa Director, Center for
Shinjuku, Tokyo, Japan Reproductive Medicine and Implantation
Joanne Kwak-Kim Reproductive Medicine Research, Sugiyama Clinic Shinjuku, Tokyo,
and Immunology, Obstetrics and Japan
Gynecology, Clinical Sciences Department, Akiko Nakamura Deparment of Obstetrics
Chicago Medical School, Rosalind Franklin and Gynecology, Shiga University of Medical
University of Medicine and Science, Vernon Science, Otsu, Shiga, Japan
Hills, IL, United States Dariko A. Niauri Department of Obstetrics,
Maud Lansiaux Hôpital des Bluets, Centre de Gynecology and Reproductive Sciences, Saint
PMA, Paris, France Petersburg State University, Saint Petersburg,
Russia; Laboratory of the Mosaic of
Trespidi Laura Department of Obstetrics and
Autoimmunity, Saint Petersburg State
Gynaecology, Fondazione Ca Granda,
University, Saint Petersburg, Russia; FSBSI
Ospedale Maggiore Policlinico, Milan, Italy
“The Research Institute of Obstetrics,
Nathalie Lédée Hôpital des Bluets, Centre de Gynecology and Reproductology named after
PMA, Paris, France; MatriceLab D.O. Ott,” Saint Petersburg, Russia
Innove, Pépinière Paris- Santé- Cochin, Paris,
Cherie C. Ocampo-Cervantes Division of
France
Allergy and Immunology, Department of
Si won Lee Department of Obstetrics and Medicine, University of the Philippines
Gynecology, Mount Sinai Medical Center, College of Medicine, Philippine General
Miami Beach, FL, United States Hospital, Manila, Philippines
Sung Ki Lee Department of Obstetrics and Yutaka Osuga Department of Obstetrics
Gynecology, Konyang University College of and Gynecology, Graduate School of
Medicine, Daejeon, Republic of Korea Medicine, The University of Tokyo, Tokyo,
Meroni Pier Luigi Istituto Auxologico Italiano, Japan
IRCCS, Immunorheumatology Research Jenifer R. Otadoy-Agustin Division of Allergy
Laboratory, Milan, Italy and Immunology, Department of Medicine,
Thanh Luu Reproductive Medicine and University of the Philippines College of
Immunology, Obstetrics and Gynecology, Medicine, Philippine General Hospital,
Clinical Sciences Department, Chicago Manila, Philippines
xviii List of contributors

Joon Cheol Park Department of Obstetrics and Ossola Wally Department of Obstetrics and
Gynecology, Keimyung University School of Gynaecology, Fondazione Ca Granda,
Medicine, Daegu, Republic of Korea Ospedale Maggiore Policlinico, Milan, Italy
Erra Roberta Department of Obstetrics and Xiao Wang Department of Reproductive
Gynaecology, Fondazione Ca Granda, Immunology, Shanghai First Maternity and
Ospedale Maggiore Policlinico, Milan, Italy Infant Hospital, Tongji University School of
Shinichiro Saeki Department of Obstetrics Medicine, Shanghai, P.R. China
and Gynecology, School of Medicine, Hyogo Yanshi Wang Reproductive Medicine Center,
Medical University, Nishinomiya, Hyogo, Department of Obstetrics and Gynecology,
Japan The First Affiliated Hospital of USTC,
Hiroaki Shibahara Department of Obstetrics Division of Life Sciences and Medicine,
and Gynecology, School of Medicine, Hyogo University of Science and Technology of
Medical University, Nishinomiya, Hyogo, China, Hefei, Anhui, P.R. China
Japan Yiqiu Wei Reproductive Medicine Center,
Yehuda Shoenfeld Laboratory of the Mosaic Renmin Hospital of Wuhan University,
of Autoimmunity, Saint Petersburg State Wuhan, Hubei, P.R. China
University, Saint Petersburg, Russia; Ariel Ronja Wöhrle Division of Experimental Feto-
University, Ariel, Israel; Zabludowicz Center Maternal Medicine, Department of Obstetrics
for Autoimmune Diseases; Sheba Medical and Fetal Medicine, University Medical Center
Center, Tel-Aviv, Israel Hamburg-Eppendorf, Hamburg, Germany
Rikikazu Sugiyama CEO, Center for
Katharine Wolf Clinical Immunology
Reproductive Medicine and Implantation
Laboratory, Faculty of Microbiology and
Research, Sugiyama Clinic Shinjuku, Tokyo,
Immunology, Center for Cancer Biology,
Japan
Infection and Immunology, The Chicago
Ryu Takeyama Department of Obstetrics and Medical School, Rosalind Franklin University
Gynecology, School of Medicine, Hyogo of Medicine and Science, Chicago, IL, United
Medical University, Nishinomiya, Hyogo, States
Japan
Li Wu Reproductive Medicine Center,
Reshef Tal Department of Obstetrics, Department of Obstetrics and Gynecology,
Gynecology and Reproductive Sciences, Yale The First Affiliated Hospital of USTC,
School of Medicine, New Haven, CT, United Division of Life Sciences and Medicine,
States University of Science and Technology of
Chiara Tersigni Fondazione Policlinico China, Hefei, Anhui, P.R. China
Universitario A. Gemelli IRCCS, Dipartimento Ayano Yamaya Department of Obstetrics and
di Scienze della Salute della Donna e del Gynecology, School of Medicine, Hyogo
Bambino e di Sanità Pubblica, Rome, Italy Medical University, Nishinomiya, Hyogo,
Kristin Thiele Division of Experimental Feto- Japan
Maternal Medicine, Department of Obstetrics Tailang Yin Reproductive Medicine Center,
and Fetal Medicine, University Medical Center Renmin Hospital of Wuhan University,
Hamburg-Eppendorf, Hamburg, Germany Wuhan, Hubei, P.R. China
Virginie Vaucoret Hôpital des Bluets, Centre Yong Zeng Shenzhen Key Laboratory for
de PMA, Paris, France Reproductive Immunology of Peri-
Yu Wakimoto Department of Obstetrics and implantation, Shenzhen Zhongshan Institute
Gynecology, School of Medicine, Hyogo for Reproduction and Genetics, Shenzhen
Medical University, Nishinomiya, Hyogo, Zhongshan Urology Hospital, Shenzhen, P.R.
Japan China
 About the editor

done, which applies basic science techni-

ques to clinical problems, is cutting edge.
She has over 160 publications in peer-
reviewed articles and books. She edited
two special volumes, “Topics in Clinical
Reproductive Immunology” and “The
Clinical Reproductive Immunology,” pub-
lished in the American Journal of
Reproductive Immunology. In addition, she is
the editor of two books, “Endometrial gene
expression; an emerging paradigm for
Dr. Joanne Kwak-Kim, MD, MS, MPH, is reproductive disorder” and “Reproductive
the Agnes D. Lattimer MD Professor, immunology: recurrent pregnancy losses
Obstetrics and Gynecology, Clinical and repeated implantation failures.”
Sciences Department, and Center for Dr. Kwak-Kim is the editor-in-chief of
Cancer Cell Biology, Immunology and the Journal of Reproductive Immunology, an
Infection, Chicago Medical School, associate editor of the American Journal of
Rosalind Franklin University of Medicine Reproductive Immunology, and an editorial
and Science, and the Director of board member of many peer-reviewed sci-
Reproductive Medicine and Immunology, entific journals. She is a sought-after lec-
Rosalind Franklin University Health Clinic. turer and has reviewed numerous national
She also served as an Assistant Chair, and international scientific studies. In addi-
Department of Obstetrics and Gynecology, tion, she has provided external scientific
Chicago Medical School, and the Medical advisory services to scientific institutions
Director, Rosalind Franklin University worldwide.
Health System. She has mentored and continues to men-
Dr. Kwak-Kim has spent the last three tor medical students, residents, PhD stu-
decades serving as a clinician, a researcher, dents, and postdoctoral fellows. As a
and an educator. Her keen interest lies in mentor of trainees, she is an outspoken
reproductive immunology, particularly advocate of reproductive medicine and
recurrent pregnancy loss and repeated immunology specialties. When asked, what
implantation failures, which have been the a reproductive immunologist needs to suc-
focus of her research. Her work in natural ceed, she recommends a creative mind, a
killer cells and Th1/Th2 immune responses listener’s ear, and a compassionate heart—
in women with recurrent pregnancy losses attributes that have served Dr. Kwak-Kim
and repeated implantation failure is distin- well in her over 30 years of exemplary
guished. The research work that she has service.

xix
Another random document with
no related content on Scribd:
 When his mother had gained control of herself once more, she sat down
by the side of the bed, and, taking his hand, she held it clasped passionately
in hers, while she sat looking at him, without once speaking. For some
reason, he could not look at her, perhaps because in the intensity of her
emotion she was asking from him a response which he could not give. He
was ashamed, but it was impossible to pretend. Instead of any longer
seeming almost a part of her, he was detached now in a strange, definite
fashion. In his weakness, it seemed to him that he was seeing her for the
first time and he was ashamed and sorry for her. He knew that before long
she, too, would understand that there was a difference, that in some way
their relationship had been broken forever. The old Philip was dead, and the
new one suddenly pitied her from a great distance, as he pitied Naomi. It
was as if the weakness gave him a clairvoyance, a second sight, which
illuminated all the confusion of mind that had preceded the long night.
Lying there, with his eyes closed, her passionate cry, “Philip, my boy!”
burned itself into his brain. He was, he knew, unworthy of that consuming
love she had for him.
After a long time he heard her asking, “Philip, are you awake?”
“Yes, Ma.” But he did not open his eyes.
“I have some good news that will delight you.”
What could it be? Perhaps she had arranged his return to Megambo. She
would think that was good news.
“It’s about Naomi. You’re a father now, Philip ... twice a father, Philip.
You’ve two children. They were twins.”
The knot of perplexity which had been tormenting his brain suddenly
cleared away. Of course! That was what he couldn’t remember about
Naomi. She had been going to have a baby, and now she had had two. Still
he did not open his eyes. It was more impossible now than ever. He did not
answer her, and presently Emma asked, “You heard what I said, Philip?”
“Yes, Ma.”
“You’re glad, aren’t you?”
He answered her weakly, “Of course ... why, of course, I’m glad.”
Again there was a long silence. He was ashamed again, because he had
been forced to lie, ashamed because he wasn’t proud, and happy. His
mother sat there trying to raise his spirits, and each thing she said only
drove them lower. In that curious clarity of mind which seemed to possess
his soul, he knew with a kind of horror that he had wanted to waken alone,
free, in a new country, where he would never again see Naomi, or his
mother, or the lace curtains, or the familiar, worn rocking-chair. That, he
saw now, was why he had wanted to die. And now he was back again, tied
to them more closely than ever.
At last he said in a low voice, “It was like Naomi, wasn’t it ... to have
twins?”
“What do you mean?”
He hesitated a moment, and then said, “I don’t know ... I’m tired ... I
don’t know.”
Again a silence. Deep inside him something kept urging him to break
through all this web which seemed to be closing tighter and tighter around
him. The last thought he could remember before slipping into the nightmare
returned to him now, and, without knowing why, he uttered it, “There won’t
be any more children.”
“Why?” asked Emma. “What are you trying to say?”
“Because I don’t mean to live with Naomi ever again. It’s a wicked thing
that I’ve done.”
She began to stroke his forehead, continuing for a long time before she
spoke. She was having suddenly to face things—things which she had
always known, and pretended not to know. At last she said, “Why is it a
wicked thing to live with your lawful wife?”
The world began to whiz dizzily about his head. Odd flashes of light
passed before his closed eyes. It seemed to him that he must speak the truth,
if he were ever to open them again without shame.
“Because she’s not really my wife ... she’s just like any woman, any
stranger ... I never loved her at all. I can’t go on ... living like that. Can’t
you see how wicked it is?”
Emma was caught in her own web, by the very holy principles she
upheld—that it was wrong to marry some one you did not love. It was this
same thing which disturbed her peace of mind about Moses Slade.
“You loved her once, Philip, or you wouldn’t have married her.”
“No, I didn’t know anything then, Ma.” The color of pain entered his
voice. “Can’t you see, Ma? I wasn’t alive then. I never loved her, and now
it’s worse than that.”
The stroking of his forehead suddenly ceased. “I don’t know what you’re
talking about, Philip.... We’d better not go on now. You’re tired and ill.
Everything will be different when you are well again.”
For a second time there came to him a blinding flash of revelation. He
saw that she had always been like that: she had always pushed things aside
to let them work themselves out. An awful doubt dawned upon him that she
was not always right, that sometimes she had made a muddle of everything.
A feeling of dizziness swept over him.
“But it will break her heart, Philip,” she was saying. “She worships
you.... It will break her heart.”
Through a giddy haze he managed to say, “No ... I’m so tired.... Let’s not
talk any more.” He felt the nightmare stealing back again, and presently he
was for some strange reason back at Megambo, sitting under the acacia-
tree, and through the hot air came the sound of voices singing, in a minor
key:
 “Go down to the water, little monkey,
To the life of lives, the beginning of all things.”

He thought wildly, “I’ve got to get free. I must run.... I must run.”
Emma, holding his hand, felt the fever slipping back. She heard him
saying, “Go down to the water, little monkey,” which clearly made no
sense, and suddenly she sprang up and called Miss Bull, the nurse.
“It’s odd,” said Miss Bull, white and frightened, “when he was so much
better. Did anything happen to upset him?”
“No,” said Emma. “Nothing. We barely talked at all.”
The nurse sent Essie for the doctor, reproaching herself all the while for
having allowed Emma to stay so long a time by the bed. But it was almost
impossible to refuse when a woman like Mrs. Downes said, “Surely seeing
his mother won’t upset him. Why, Miss Bull, we’ve always been wonderful
companions—my boy and I. He never had a father, you see. I was both
mother and father to him.” Miss Bull knew what a gallant fight she’d made,
for every one in the Town knew it. A widow, left alone, to bring up her boy.
You couldn’t be cruel enough to stop her from seeing her own son.
When the doctor came and left again, shaking his head, Emma was
frightened, but her fright disappeared once more as the fever receded again
toward morning, and when at last she fell asleep, she was thinking, “He
doesn’t belong to her, after all. He’s never belonged to her. He’s still my
Philip.” There was in the knowledge a sense of passionate triumph and joy,
which wiped out all else—her doubts about Moses Slade, her worry over
Philip’s future, even the sudden, cold terror that gripped her as she felt the
fever stealing back into his thin, transparent hand. He didn’t belong to
Naomi. Why, he almost hated her. He was still her boy.... And she had
defeated Naomi.
In the darkness the tears dampened the pillow. God had not, after all,
forsaken her.
 PART THREE

THE STABLE

1
At the back of the great Shane house there clustered a little group of
buildings arranged in plantation style. There were a laundry, a kennel, an
office and a stable with a double row of box-stalls. The whole was
overgrown with dying vines and was connected with the big white-trimmed
brick house by a sort of gallery, roofed but open on the sides. The buildings
were empty now, since the old woman had taken to her canopied bed, save
for the pair of fat old horses who never went out any more and now stood
fat and sleek, groomed carefully each day by the old negro who acted as
groom and general factotum. One daughter had given up her life to the poor
and the other to the great world and no one cared any longer if the hinges
rusted on the stable doors and the great wrought-iron gates sagged at the
entrance to the park. Ghosts haunted the place—the ghost of the wicked old
John Shane who had built the Castle, the ghosts of all the great who had
stayed at the Castle in the glamorous days before the coming of the black
Mills. Old Julia Shane lay dying, aloof, proud, rich and scornful. Nobody
cared....
When the strike came the whole park fell into a state of siege, walled in
on the one side by the Mills and on the other by the filthy houses of the
steelworkers. The warfare raged just outside its borders. Sometimes in the
night a shot sounded in the darkness. But neither side invaded the territory:
it remained in some mysterious way neutral and sacred, as if the lingering
spirit of the old woman who lay dying in the smoke-blackened house held
the world at bay. The doctor came twice daily, making his way bravely
through the black district of the strike; once each day, the old nigger
Hennery went timorously across the Halstead Street bridge to fetch food.
Irene Shane and sometimes Hattie Tolliver, a cousin who came to “take
hold,” went in and out. Otherwise the place lay deserted and in solitude,
waiting.
Early in December, when the first blackened snow lay among the dead
trees of the park, Irene Shane and Mary Conyngham visited the stables. It
was the first time Irene had gone there since she was a young girl and kept a
pony called Istar. To Mary Conyngham it was a strange place never before
visited. They were accompanied by the old nigger Hennery.
Above the stalls of the fat horses there was a room once occupied by a
coachman, which now lay empty save for a table, two or three chairs, an
iron stove and a bed. At each end of the room there was a big window partly
covered by the vines that overran the whole building. It was here that the
two women and the old negro came.
Irene, dressed in her shabby gray clothes, opened the door of the
harness-closet, looked inside, and then regarded the room with a sweeping
glance. “This ought to serve, very well,” she said.
Mary was pleased. “It’s perfect, I should think.”
“Put those newspapers in the stove, Hennery, and light them,” said Irene.
“He can’t work here unless there’s some means of heat.”
The papers went up in a burst of flame. The stove worked perfectly.
The two women looked at each other. “Will you tell him, then?” asked
Mary.
“Yes ... Krylenko will tell him. I don’t know him at all.”
Suddenly Mary kissed the older woman on the cheek. It was an odd,
grotesque gesture, which failed of all response. It was like kissing a piece of
marble to kiss a woman like Irene Shane.
“Thank you, Irene,” she said.
Irene ignored the speech, and turned to the old negro. “Clean the room
out, Hennery. There’s a Mr. Downes coming here to paint now and then.”
“What? Pitchers?” asked Hennery.
“Yes, pictures. He’s to come and go as he likes. You needn’t worry about
him.”
They left him raising clouds of dust with a worn stable-broom. It did not
strike him that there was anything extraordinary in the arrangement. He had
come to Shane’s Castle a buck nigger of eighteen, when John Shane was a
bachelor. He was sixty-five now. Anything, he knew, might happen at
Shane’s Castle. Life there possessed a sort of subterranean excitement.
As he swept he kept thinking that Miss Lily was already on her way
home from Paris, coming to see her Mammy die. She hadn’t been home in
seven years. When Miss Lily came home, everything was changed. All the
excitement seemed to rise above the surface, and all life changed and
became a tingling, splendiferous affair. Even the presence of death in the
Castle couldn’t dampen the effect of Miss Lily.

2
With that first fall of snow the fever began to lose a little its hold upon
the twice-stricken community. As it waned the new terror came to take its
place—a terror that, like the fever, rose out of the black of the Flats.
Bristling barriers of ugly barbed-wire sprang up overnight and for days
each train brought in criminals shipped from the slums of a dozen cities to
protect the sheds and furnaces. In the beginning it was neither the strikers,
nor the men who owned the Mills, but the Town itself which suffered.
Business in the shops bordering the diseased area fell off; but, far worse
than that, there began to occur one after another, with terrifying regularity, a
whole series of crimes. Houses were broken into, a woman was attacked at
twilight in the raw, new park, two fat business men were held up and
beaten, and the Farmers’ and Industrial Bank, the institution of the corrupt
Judge Weissman, was robbed and then quickly failed under mysterious
circumstance. It was the gunmen brought in to make war on the strikers
who committed the crimes, but it was the strikers who were accused. Save
for Philip and Mary Conyngham, and perhaps McTavish, they had no
friends on the Hills. The Shanes could not be counted, since they stood
apart in an isolation of their own. A panic-stricken community began to
imagine innumerable horrors. The newspapers wrote editorials predicting
anarchy and dissolution. They talked of the “sacred rights of property” and
used clouds of similar high-sounding phrases. Moses Slade, seeing perhaps
a chance to harvest new crops of votes by “standing by his community in
such a crisis,” returned to head a sort of vigilance committee whose purpose
was to fasten all crime upon the strikers.
By this heroic act he soon rose high in the esteem of Emma, so high
indeed that it seemed to wipe out all her doubts concerning her marriage. It
was an action of which she approved with all her spirit. She herself went
about talking of “dirty foreigners” and the need of making laws to exclude
them from a nation favored by God, until Moses took her aside and advised
her not to talk in such a vein, because the very strength of the Mills
depended on new hordes of cheap labor. If they throttled immigration, labor
would rule. Didn’t she understand a simple thing like that?
She understood. Moses Slade seemed to her a paragon. “Why,” she told
Philip, “he understands all the laws of economics.”
Philip, restless and convalescent, listened to her in silence. He even met
the Honorable Moses Slade, who eyed him suspiciously as a cat and asked
about his future plans.
“I haven’t any,” said Philip. “I don’t know what I mean to do,” and so
put Moses Slade once more upon a bed of pins and needles concerning
Emma’s qualifications as a bride.
The omnipresence of the Congressman’s name in Emma’s conversation
had begun to alarm Philip. He saw presently that she meant to tell him
something, and after a time he came to guess what it was. He saw that she
was breaking a way through his prejudices and her own; and in that odd
sense of detachment born of the fever he faced the idea with disgust. It was
not only that he disliked Mr. Slade; it seemed to him that there was
something disgraceful in the idea of his mother marrying again after so
many years. It was in a strange way a disloyalty to himself. Moses Slade
was a new ally in the forces against him. The idea came to torment him for
hours at a time, when he was not pondering what was to be done about
Naomi, how he could escape from her without hurting her too deeply.
The two women, Naomi and his mother, hovered over him with the
solicitude of two women for a man whom they had snatched from death. In
these first days when he came downstairs to sit in the parlor there was
always one of them with him. Naomi left him only long enough to nurse the
twins. She was, as Mabelle observed, very fortunate, as she was able to feed
them both, and there were not many women, Mabelle remarked with a
personal pride, who could say the same. And under Mabelle’s guidance
Naomi adopted the same methods: the moment the twins set up a wail they
were fed into a state of coma. Mabelle had great pride in them, as if she had
played in some way a part in their very creation. She was always in the
house now, for Emma’s request and Elmer’s commands were of no avail
against her instinct for human companionship. With the twins crying and
little Jimmy running about, the house seemed overrun with children. And
little Jimmy had turned into what Mabelle described as “a whiner.”
“I don’t know what to do about him,” she said. Her method was to cuff
him over the head, thus changing the whine instantly into a deafening
squall.
Naomi used her own convalescence as an excuse for clinging to the
soiled flowered kimono and the green mob-cap.
It was a state of affairs which could not long endure and the climax arose
on the afternoon when Emma, returning unexpectedly, found a scene which
filled her with horror. In his chair by the window sat Philip, looking white
and sick. Behind him on the sofa Naomi in wrapper and mob-cap fed the
twins. Little Jimmy sat on the floor pulling photographs out of the album at
the back of the family Bible. Draping the backs of the mahogany chairs
hung white objects that were unmistakably diapers. Two of the objects were
even hung to dry upon the very frame of Jason Downes’ enlarged
photograph!
For a moment Emma simply stood in the doorway in a state of paralysis.
At the sight of her Naomi sat up defiantly and Mabelle smiled blandly.
Philip, wearily, did not even turn to witness the picture. And then, quickly,
like a bird of prey, Emma swooped upon the diapers, gathering them up in a
neat roll. Then she turned on Naomi.
“It’s the last time I want this to happen in my house.” She seized the
family Bible from Jimmy, who began to squall, setting off the twins like
matches brought too close to a fire. “I won’t have it looking like a bawdy-
house,” she cried. “With you sitting here all day in a wrapper, like a chippy
waiting for trade.” Words that she would have denied knowing came to her
lips in a stream.
This time Naomi did not weep. She sprang up from the sofa as if to
attack Emma. “Take care what you say! Take care what you say! You old
hypocrite!”
Emma turned suddenly to Philip. “You hear what she called me!”
And Naomi, like an echo, cried, “You heard what filthy names she called
me.”
Mabelle, terrified, rolled her cowlike eyes, and tried to stifle Jimmy’s
screams. Philip did not even turn. He felt suddenly sick.
 Naomi was saying, “If I hadn’t all the work to do.... If I had the right
kind of husband—”
Emma interrupted. “I took care of my child and did all the work as well.
I never complained or made excuses.”
“You didn’t have twins.... Sometimes my back fairly breaks. Oh, if I had
the right kind of husband, I wouldn’t be in your dreary old house!”
Emma turned again, “Philip ... Philip....”
But Philip was gone. She saw him, hatless and without an overcoat,
running through the snow that had begun to come down slowly and softly
as a white eiderdown.

3
He only stopped running when he grew so weak that he could no longer
make an effort. He had gone, without knowing why, in the direction of the
Mills, and presently he found himself, with a savage pain just beneath his
heart, sitting on the steps of McTavish’s undertaking parlors. It was almost
dark, and the air was cold and still; he felt it creeping about him as the heat
went out of his body. He knew that if he caught cold he would die and
suddenly he wanted to live, horribly. It was as if that sickening scene had in
some way released him from the bondage of the two women. They seemed
all at once to belong to another world in which he played no rôle, a world
strange and horrible and fantastic. Even the twins did not seem to be his
children, but creatures born somehow of the two women and all they stood
for in his tired mind. They were two squalling tomato-colored infants in
whom he could take no interest—a judgment sent by fate as a punishment
for his own weakness and indecision. He grew bitter for the first time and
out of the bitterness there was born a new strength.
Sitting there in the softly falling snow, he resolved to go his own way.
He couldn’t desert Naomi and his children, but he could tell her that he was
through with her once and for all. And he saw suddenly the whole sickening
depth of the tangle—that it was her fault no more than his, that she had
suffered as much as himself, that perhaps in the end she would suffer more,
because (he knew it with a kind of disgust) she loved him with all her soul
and body.
 Beating his arms against his body, he rose and turned the handle of the
door. McTavish was inside, alone, sitting by the stove. At the sound of the
handle turning, he looked up and grinned.
“Hello, Philip,” he said, and then quickly, “What the hell are you doing
out without a coat or hat?”
Philip grinned, and the very grin hurt his face, as if it had been frozen by
the cold. “I came out in a hurry ... I wanted to borrow a coat and hat off
you.”
McTavish rose and stretched his great arms, yawning, watching Philip all
the while. “Driven out?” he asked at last, with a sharp look.
“Yes,” said Philip quietly. “Driven out.” He knew suddenly that
McTavish understood. He remembered all at once what he had said, “I
knew your Ma before you were born. You can’t tell me anything about her.”
“Here,” suddenly the undertaker was pouring whisky. “Here, drink this.
I’ll get you a coat.”
He disappeared into that portion of the establishment where the dead
were kept, and returned in a moment bearing a coat and hat. The curious,
pungent odor of the place clung to him.
“Here,” he said. “It’s all I’ve got. You couldn’t wear my clothes. You’d
be drowned in them.” He laid the coat and hat on a chair by the stove.
“These ought to about fit you. They belonged to Jim Baxter, who got
bumped off at the grade-crossing while comin’ home drunk last week. His
wife has never come for ’em. I guess he won’t need a coat where he is
now.” He sat down and took Philip’s wrist, feeling the flow of blood. “Feel
better now? Your heart seems all right.”
“I’ve always been strong as an ox.”
“It ain’t the same after you’ve had a fever.”
They sat in silence for a moment and then McTavish asked, “You don’t
mind wearin’ a dead man’s clothes?”
“No,” said Philip. “No.” Anything was better than going back to the
slate-colored house.
“When you’re in my business, you get over squeamish feelings like that.
Dead men and live ones are all the same, except you know the dead ones
are mebbe missing a lot of fun.”
 “No ... I don’t mind, Mr. McTavish.” Philip looked up suddenly.
“There’s one thing you could do for me. You could send word around to the
house that I’m not coming home to-night.”
A grin lighted up the big face. “Sure I will.... I’ll take the word myself.”
After a pause, “Where will you go?”
“I don’t know ... somewhere.” He rose and put on Jim Baxter’s coat and
hat. “I’m going down to the Flats now.”
“Your friends have been raising hell down there.”
“Yes ... that’s why I want to go down there now.... They’ll think I’m
dead.”
“No ... they won’t think that. That Dago friend ... Krylenko ... is that his
name? He’s been asking for you, and Mary Watts ... Mary Conyngham she
is now, she’s been asking, too ... almost every day.”
He must have seen the sudden light come into Philip’s eye, for he said
suddenly, turning to the window, “There’s a good girl ... a brave one, too.”
“Yes,” said Philip.
“She’s the kind of a wife a man ought to have. There aren’t many like
her.”
“No.”
There was a long silence and McTavish said, “They can’t win down
there ... everything’s against ’em. It’ll be over in two months and a lot of
’em never be able to get work within ten miles of a mill ever again.”
Philip said nothing. He thrust his hands deep into the pockets of Jim
Baxter’s coat.
“They tried it too soon. They weren’t strong enough. They’ll win some
day, but the time isn’t yet.”
Philip looked at him sharply. “I’m on their side. I know what it’s like
down there. Nobody else knows, except Irene Shane and Mary
Conyngham.”
“Does your Ma know it?” asked McTavish, with a grin.
“She must know it. She pretends not to.”
“And the Reverend Castor?”
“No ... I suppose he doesn’t.”
 Philip thanked him abruptly, and went out of the door. When he had
gone, McTavish poked up the fire, and sat staring into it. “I’m a regular old
woman in some ways,” he thought, “trying to meddle in people’s affairs.
But it needs a whole army to cope with Em.”

4
Outside, the world of the Flats lay spread out before him no longer alive
with flame and clamor, but still now and cold and dead beneath the softly
falling snow. There was no glow of fire; no wheel turned. Only the
locomotives shrieked and puffed backward and forward over the shining
rails. The streets were alive with people: they stood in little groups in the
snow. On the bridge a little knot of them surrounded a speaker unknown to
him, who harangued them in three tongues, urging them not to lose faith. At
Hennessey’s corner the lights cast a glow over the fallen snow—it was
really white now that there was no longer any soot—and the tinny piano
sent forth its showers of brassy notes into air that was no longer filled with
the pounding of gigantic hammers. And the saloon was filled to the doors.
Now and then a drunken Pole or Croat fell through the doors into the street.
He saw what McTavish meant. They weren’t strong enough yet. They were
so weak that Hennessey alone could defeat them: his banging cash register
could swallow up their strength. He was a better friend of the Mill owners
than all the men brought in to break the strike.
As he followed the path that lay among the garbage heaps by the side of
the oily brook, it occurred to him that it was odd how strong he felt on this
first sally from the house. He was strong, and suddenly so content that he
forgot even the scene from which he had fled, running like a madman. It
was as if he gained strength from treading the very soil of the Flats, as if it
came to him from the contact of all these human creatures battling for
existence. And among them he was lost, alone as he had been on those rare
happy hours at Megambo when he had gone off into the jungle at the peril
of his life. The snow fell all about him, silently, into the oil-muffled brook.
Crossing a vacant lot where the rubbish lay hidden beneath a carpet of
snow, he came at last to the familiar doorway which he had not seen since
the night six months before when he stood hidden in its shadow listening to
the voice of Mary Conyngham. Feeling his way along the dark passageway,
smelling of coal-gas and cabbage, he came at last to Krylenko’s door. He
knocked and the familiar voice called out something in Russian.
Pushing open the door, he saw Krylenko sitting on the edge of his iron
bed with his head in his hands. There was no light in the room, but only the
reflection of a rubbish fire some one had built in the yard outside the house.
For a moment Philip stood leaning against the door, and when Krylenko did
not raise his head, he said, “It’s me ... Philip Downes.”
When he saw Krylenko’s face, he knew that the strike was lost. Even in
the reflected firelight, he seemed years older. He was thin, with deep lines
on either side of his mouth.
“Oh, it’s you, Feeleep.... I thought it was the old woman.”
He rose and put a match to the gas and then peered closely into Philip’s
face, with the look of a man waking from a deep sleep.
“It’s you.... Sit down.”
Philip knew the room well. It was small and square, with no furniture
save a bed, two pine chairs and a washstand. Above the bed there was a
shelf made by Krylenko himself to hold the dangerous books that Irene
Shane and her mother had given him ... John Stuart Mill and Karl Marx and
a single volume of Nietzsche.
“And how do you feel ... huh?” asked Krylenko, seating himself once
more on the bed.
“All right. Look at me.”
“Kind-a skinny.”
“You, too.”
“Yeah! Look at me!” Krylenko said bitterly. “Look at me.... A bum! A
failure! No job! Nothing.”
“It’s not as bad as that.”
“It will be.” He looked up. “Did yuh pass Hennessey’s place?”
“Yes.”
“Well, you see what it is ... trying to make a lot of pigs fight. All they
want is to quit work and get drunk. That’s all it means to them.”
“It’s not over yet.”
“It will be ... I’m gonna fight it to the end. They’re startin’ to operate the
B chain to-night ... a lot of niggers from the South that ain’t organized.” He
got up and went over to the window, standing with his back to Philip. “We
can make trouble for another month or two and then I’m finished, and me ...
I’m out of a job for good ... down ... on the blacklist. You know what that
means.”
It was an eloquent back, big, brawny and squared with defiance, despite
all the tone of despair in his voice. The rumpled, yellow hair fairly bristled
with vitality and battle. Philip thought, “He’s not done yet. He’s going on.
He’s got something to believe in ... to fight for. For him it’s only begun.
He’s got a giant to fight ... and I’m fighting only two women.”
Suddenly Krylenko turned. “Look,” he said. “Look,” pointing out of the
window. “That’s what they’re up to now. They’ve bought up all the loose
houses and they’re turning the strikers out in the snow ... on a night like
this, God damn ’em. Look!”
Philip looked. Across the street in the falling snow lay a pitiful heap of
odds and ends of some Slovak household ... pots, kettles, battered chairs,
blankets, a mattress or two. A woman and four small children, none of them
more than six, stood drearily watching.
“And it’s a hell of a thing to do.... A free country, hell! It belongs to a lot
of crooked rich men.” Suddenly, he thrust his big fist through the pane of
glass and the tinkling fragments fell into the snow in the yard. “We’re
finished this time ... but we’ve only begun!” He laughed. “The windows
don’t matter. They bought this house, too. A lot of niggers are movin’ in to-
morrow.”
The blood was running from his cut knuckles and he bound them round
silently with a red cotton handkerchief. Presently, he said, “You’re looking
for your paints and pictures.... They ain’t here.... Mrs. Conyngham took ’em
away.”
“Mrs. Conyngham!”
“Yeah.... She came and got ’em herself. She’s fixed up a place for you up
at Shane’s Castle ... in the stable. I was to tell you and I forgot. She did it
when she heard about the Mills buyin’ up this row of houses. It’s in the
stable and you’re to go up there whenever you want. There’s a stove and
everything.”
He spoke in agitation, as though the paints, the pictures, were nothing
compared to his own troubles. A little thing, of no use! Suddenly he turned,
“And you, what are you goin’ to do?”
 “When?”
“Now you’re finished, too. They’ve done with you, too. You’re one of
’em. Don’t forget that.”
Yes, that was a thing he hadn’t thought of. There must be people in the
Town who hated him the way they hated the Shanes, and perhaps Mary
Conyngham ... as renegades, traitors. And while he waited there in the
squalid room, watching Krylenko sitting with his head buried in his hands,
there came to him for the first time a curious, intoxicating sense of
satisfaction in being one of that odd little band—Krylenko, the saintly
Irene, the dying old woman in Shane’s Castle, and Mary Conyngham. The
wind had begun to rise, and with it little gusts of snow swirled in through
the broken window. He thought suddenly, “We are the leaven in the lump.”
He was not quite certain what he meant by that; he only knew that the lump
was concerned vaguely with that mass of materialism and religion which
made the character of the Town ... a religion tamed and shopworn and
subdued to commercial needs, a faith worn down to the level of
convenience. Groping, it seemed to him that he was beginning to emerge at
last, to be born as a soul, an individual.
“I mean to paint,” he said suddenly.
“That won’t feed you ... and your children.”
“No ... I’ll manage somehow.” Nothing seemed impossible ... nothing in
the world ... if he could only shake himself free. He thought, without any
reason, “Krylenko is no more one of the mill workers than I am. If he were
really one of them, he would be drunk now in Hennessey’s place. There is
something which sets him apart.... He isn’t one of them either. He’s as
unhappy as I am.”
Looking up, he asked suddenly, “And what about Giulia? Are you going
to marry her?”
Without raising his hand, Krylenko answered, “No ... that’s finished
now. If we’d won, it would have been all right. But now ... it’s no good ...
I’ll be nothing but a tramp and bum.”
He spoke in a strange, dead voice, as if he were saying, “It’s a snowy
night,” as if something had died in him.
“No ...” he repeated. “That’s all finished. But you ... you’ve got
everything before you ... and that girl ... Mrs. Conyngham....” He looked up
suddenly, “She has faith in you ... that’s something.” He looked at the great,
nickeled watch he carried. “I’ve gotta go now. I’ve got to see about putting
up tents for all of ’em who’ve been thrown out of their houses. It’s a hell of
a night to live in a tent.” Rising, he took up his black felt hat. “What are you
going to do?”
Philip wakened suddenly out of a haze of thought. “Me! I want to stay
here to-night.”
“Here in this room?”
“Yes.”
“All right.... Turn in there.” He pointed to the rickety iron bed. “I’ll be
out most of the night, gettin’ coal and blankets. See you later.”
When he had gone, Philip felt suddenly ill again, and hopelessly weary.
He lay down on the bed wrapped in Jim Baxter’s overcoat, and in a moment
fell asleep.
At two, when Krylenko finally returned, there was a little drift of snow
by the broken window. Going over to the bed, he stood for a time looking
down at Philip, and then, with a great gentleness, he lifted him, and,
drawing out the blanket, laid it over him, carefully tucking in the edge to
keep out the cold. When he had finished, he lay down, keeping well over to
the edge in order not to disturb Philip. It was all done with the tenderness of
a strong man fostering the weak, of a great, clumsy father protecting a little
boy.

5
In the morning Philip awakened to find Krylenko already gone. It was
still snowing as he went out into the empty street and made his way toward
the shed where there was always hot coffee for the strikers and their
families. He stood there among them, drinking his coffee and feeling the old
sense of satisfaction of being in a world stripped bare to those things which
lay at the foundations of life. This was solid, with a rawness that bit into the
soul. He took out a pencil and on a bit of newspaper began to sketch
fragments of the scene about him—a Croat woman who was feeding coffee
to her three small children out of a clumsy teacup, a gigantic, bearded
Slovak and his wizened, tubercular wife, a baby wrapped in the ragged
remains of a pair of overalls, a thin, white, shivering girl, with the face of a
Madonna. They were simply sketches, reduced to the very skeletons of
drawing, yet they were in a way eloquent and moving. He felt
intoxicatingly sure of his hand, and he saw all at once that they were the
best things he had ever done. Set down on the face of columns of printing,
they caught the cold misery and the dumb bravery of these puzzled,
wretched people, suffering silently in the midst of a hostile, foreign country.
Looking at the sketches, he saw that by some ironic chance he had chosen
to draw directly upon an editorial condemning them. He began to read. The
fragment was torn, and so had no beginning. “ ...sacred rights of property
must be protected against the attacks of men little better than brutes who
have come, infected with poison of socialism and anarchy, to undermine the
institutions of a great, free and glorious nation favored by God. These
wretches must be treated as they deserve, without consideration, as beasts
bent upon tearing down our most sacred institutions and destroying our
God-given prosperity.”
It was signed in bold black type with the name MOSES SLADE. He was
quite safe in his attack, thought Philip: foreign-born mill workers had no
votes.
A hand touched Philip’s shoulder and a voice said, “Give me that.” It
was Krylenko. “I can use it,” he said. “I know just where it belongs.”
He gave it to Krylenko without a word.
From the steaming coffee-shed he made his way through a street filled
with people and bordered with pitiful little heaps of shabby household
goods like that which he had seen from Krylenko’s window the night
before. He passed Hennessey’s place and, crossing the railroad tracks, came
within the area of the Mills. It was silent here. Even the trolleys had ceased
to run since one car had had its windows shattered. Beyond this he came to
the great iron fence that shut in the park of Shane’s Castle. At the gates he
turned in, following the drive that ran between rows of dead and dying
Norway spruce up to the house that crowned the hill. It was silent in the
park and the falling snow half veiled the distant gables and odd Gothic
windows of the big house. Among the dead trees it occurred to him that
there was a peace here which did not exist elsewhere in the whole Town. It
was an enchanted place where a battered old woman, whom he had seen but
once or twice, lay dying.
Following the drive, he passed the wrought-iron portico and the little
cast-iron Eros who held a ring in his outstretched hand and served as a
hitching-post. The towering cedars that gave the place a name—Cypress
Hill—which all the world had long ago forgotten, loomed black and
melancholy against the sky. And, turning the corner, he came suddenly
within sight of the stables.
Before the door an old negro swept away the falling snow with a worn
and stubby broom. He did not hear the approach of Philip, for he was deaf
and the snow muffled the sound of footsteps. It was only when Philip said
“Good-morning” that he turned his head and, grinning, said, “You must be
Mr. Downes.”
“Yes.”
“The room’s all ready for you.”
The old man, muttering to himself, led the way. At the top of the stairs,
he said, “If I’d knowed you was a-comin’ I’d a-had a fire.”
The place was all swept and in order and in one corner stood all the
things which Mary Conyngham had carried there from Krylenko’s room.
The sight of them touched him with emotion, as if something of Mary
herself clung to them. He wanted to see her more than he wanted anything
in the world. He stood looking out of the window while the old nigger
waited, watching him. He was sure that in some way she could wipe out the
sickening memory of that awful scene. The window gave out over the Mills,
which lay spread out, cold and desolate and silent, save for the distant K
section, where smoke had begun to drift from the chimneys. He would paint
the scene from this window, in all its dreary bleakness—in grays and whites
and cold blues, with the faintest tinge of pink. It was like a hell in which the
fires had suddenly burned to cold ashes. No, he must see Mary. He had to
see her. He couldn’t go on like this. It wasn’t possible for any human
creature to be thirsty for so long—thirsty for peace and honesty and
understanding.
He began to see himself in the mawkish light of one who suffered and
was put upon, and what had been impossible before began in the light of
self-pity to seem possible.
He had (he knew) to go back to the slate-colored house. Turning, he said
to the old nigger, “I’m coming back,” and then halting, he asked, “How’s
Mrs. Shane?”
“She ain’t no better, sir. She’s dying, and nothin’ kin save her.” Suddenly
the black face lighted up. “But Miss Lily’s come back. She came back last
night.”
“Yes?”
“You don’t know Miss Lily, mebbe.”
“No.... I’ve seen her years ago riding through the Town.”
“Then you don’t know what she’s like.... The old Missie can die now
that Miss Lily’s come home. She jus’ couldn’t die without seein’ Miss Lily.”
Philip scarcely heard him. He was thinking about his own troubles, and
Lily Shane was a creature who belonged to another world whose borders
would never touch his own. Even as a boy, looking after her as she rode in
the mulberry victoria up Park Avenue, it never occurred to him that he
would ever come nearer to her. There was something magnificent about her
that set her apart from all the others in the Town. And there was always the
wicked glamour that enveloped one who, it was whispered, had had a child
out of wedlock and then declined to marry its father.
How could Lily Shane ever touch the world of Uncle Elmer and Naomi
and Emma and Mabelle? No, she did not exist for him. She was like one of
the actresses he had followed furtively along Main Street as a boy, because
a mysterious, worldly glamour clung to those ladies who appeared in town
one night and disappeared the next into the great world. No creature could
have been more remote than these coryphées from the slate-colored house
and the prayer-meetings of the Reverend Castor.

6
It was the Reverend Castor himself who greeted Philip on the doorstep
when he reached home at last. Philip would have avoided him, but the
clergyman was coming down the path as he turned into it and so there was
no escape.
He greeted Philip with a smile, saying, “Well, it’s good to see you about
again, my boy. We had a bad time over you ... thought you weren’t going to
make the grade.”
Philip grinned. “I’m not so easy to be rid of.” He felt a sudden refreshing
sense of superiority over the preacher, strange in all his experience. It was
simply that he had no longer any awe of him as a man of God.
The Reverend Castor coughed and answered, “Oh! My dear boy. We
didn’t want to be rid of you. That’s the last thing....” He protested nervously
and added, “I just dropped in for a moment to see how your wife was doing
... and the twins. You ought to be proud, my boy, of two such fine babies ...
two. Most people are thankful for one.”
“I would have been, too.”
“You don’t mean you aren’t delighted with what God has sent you?”
“No ... of course not ... I was only making a joke.” It hardly seemed
honest, Philip thought, to give God the credit for the twins.
“I suppose we’ll be having Mrs. Downes back with us in the choir
soon.... Since Mrs. Timpkins has moved to Indianapolis I’ve asked your
wife to be the leader and the librarian of the music.”
“Yes ... she ought to be back soon. She seems strong again.”
There was an awkward silence, and the Reverend Castor’s kindly blue
eyes turned suddenly aside. He started to speak and then halted abruptly and
seized Philip’s hand a second time. “Well, good-by. I must be off.”
He was gone quickly, and for a moment Philip stood looking after him,
puzzled by his strange, nervous manner. He was sorry for this poor man,
whom he had always disliked. It was a sorrow he could not explain, save
that his life must be a hell with a wife like his, and all the women of the
parish on his neck. He did his duty, the Reverend Castor. He never shirked.
It was good of him to call on Naomi. She would like such attention from the
head of her church. It would bring back to her, Philip thought, some of the
old glory and importance that had waned steadily since the night they had
got down from the train, shivering, and fearful of what lay before them.
And she would be pleased at being asked to lead the choir and take care
of the music. It was odd what little things brought happiness to her. She had
need of the little things, for he meant to hurt her. He was certain now that it
was the only way out. It would be easier for her to face the truth.
He found her sitting in the parlor where the Reverend Castor had left her.
She was dressed for the first time since the twins were born, and she had
been crying. As he entered, she came over to him and, putting her arms
about his neck, pressed her head against Jim Baxter’s overcoat, and said,
“I’m ashamed, Philip ... I want to die. I couldn’t help it yesterday. It’s the
way I feel! I feel so tired.”
The whole action disturbed him horribly. She had never done such a
thing before; she had never done more than kiss him chastely. He freed
himself and, still holding her hands, said, “I understand. It’s all over now
and I understand.”
She began to cry again helplessly, pitifully. “You’ll forgive me? You’ll
forgive me?”
“There’s nothing to forgive. I understand it.” He pushed her gently into a
chair, and sat down beside her, silently, wondering how he could bring
himself to say what he had to say.
“It’s because I’m so unhappy, Philip.... I’ve been unhappy ever since we
left Megambo ... ever since that Englishwoman stopped there. I wish to God
we’d never seen her.”
“Let’s not think about her. She had nothing to do with it.”
“And it’s so awful in this dreary house. I’m nothing here, Philip.... I’m
less than a hired girl. Your Ma hates me....” He tried to speak, but she cried
out passionately, “I can’t go on living here ... I can’t ... I can’t.”
As he sat there, all his horror of scenes, of that wretched scene in the
same room the evening before, swept over him. It was like a physical
sickness rising into his throat and choking him. He was confused, too, with
a sense of impotent rage.
“And after you ran away she told Mabelle she was never to enter the
house again.... Now I haven’t any one.”
No, she hadn’t any one, but she didn’t know yet how alone she really
was.
“Naomi,” he said quietly. “Naomi ... listen to me ... try to control
yourself.”
“Yes.... Yes.... I’m trying to.” Her pale, homely face was even paler with
weeping. Her eyes were swollen beneath the transparent lashes and her nose
was red.
“Naomi ... would you like to have a house of your own?”
“Oh, Philip ... yes.”
“I don’t mean a whole house, but a place to live ... two or three rooms
where you’d be away from my mother.”
“Yes ... yes. I’d do better. I’d take care of things ... if I had a chance in
my own place. Oh, Philip—if you’d only be kind to me.”
 He stroked her hand suddenly, but it was only because he pitied her. “I
try to be kind, Naomi.”
“You’ve been so hard to me ... just like a stone—ever since we left
Megambo. Oh, I knew it ... I knew even when....” She broke off suddenly,
without finishing. Philip looked away, sick with misery. He pitied her, but
he could not love her. She went on and on. “Out there I had something to
live for ... I had my work. I loved it. It was the only life I’d ever known. It
was everything. And here ... there’s nothing. I don’t know how to live here.”
“There are the children,” he said in a quiet voice.
“Yes ... but that’s not what I mean. It’s my soul I’m thinking of. It’s
rotting away here....”
“Mine was rotting at Megambo.” She did not answer him, and he said,
“There’s church work to do, and now Reverend Castor wants you to lead
the choir.”
“But it’s not the same, and they’re all jealous of me ... all those women
... jealous because I’m more important because I’ve been a missionary, and
jealous because Reverend Castor shows me favors. Oh, I know. I don’t
belong here, and they don’t want me here. Oh, I don’t know what’s to
become of me!”
There was a long silence, in which they sat there, dumbly trying to find
some way out of the hopeless muddle, trying to patch together something
which was now in tatters, if it had ever existed at all. Philip’s thin jaw was
set in that hard, stubborn line that made even his mother afraid.
“Naomi,” he said presently, “I’ll get you a place to live. It won’t be
much, for I haven’t much money, but you’ll be free ... to do what you
please. Only ... only, Naomi ... I ... I....” Suddenly, his head fell forward, and
he buried his face in his hands. In a voice that was hardly audible he said, “I
don’t want to live with you any longer. It’s ... it’s all over.”
For a long time there was no sound in the room, save the ticking of the
great onyx clock beneath the picture of Jason Downes. Naomi didn’t even
sob; but presently she said, in a voice like the voice of a deaf person,
“Philip, you mean you’re going to leave me?”
“No,” he said slowly. “No ... it’s not that exactly. I shan’t leave you. I’ll
come and see you every day and the children—only I won’t sleep in the
house. I’m going to sleep where I work.”
 In the same dead voice she asked, “You’re not going back to the Mills?”
“No, I’m not going back to the Mills ... they wouldn’t have me now. I’m
going to paint....”
“Pictures?”
“Yes ... pictures. That’s what I’ve always wanted to do and now ... now,
nothing can stop me.” There was in his voice a sudden cold rasp, as of steel,
which must have terrified her. He thought, “I’ve got to do it, if I’m to live.
I’ve got to do it.”
She said, “But you could have a good congregation. You could preach.”
“No, that’s the last thing I could do. I’m through with all that.”
“Oh, my God! Oh, my God!”
He raised his head, and saw that she was biting her handkerchief.
“Naomi,” he said. “Naomi,” and the sound of her name seemed to
precipitate a sudden climax. She fell on her knees and beat them with her
fists.
“You won’t do that, Philip. You can’t ... you can’t leave me for
everybody to mock at. Say that you won’t ... I was wrong in the beginning,
but now I’ll do anything. I’ll lie down and let you walk over my body!”
“Naomi,” he said. “Please! For God’s sake!”
“Oh, don’t you see! It’s different now ... I love you. Don’t you see that
makes it different?”
“It can’t make it different, Naomi. I can’t pretend what isn’t true ... it’s a
thing a man can’t do.”
Suddenly she stopped sobbing and looked up at him, her face all white
and contorted. “You can’t say that! You can’t mean it! It isn’t true!”
“It’s true, Naomi. I can’t help myself. I wish to God I could!”
“And you didn’t love me ... even ... even then?”
He made a heroic effort. “No ... not even then.”
She flung herself on the floor, pressing her face against the carpet,
moaning and moaning. Kneeling down, he picked her up bodily and laid her
on the sofa. Bending over her—
“Naomi ... listen to me. It’s not my fault. It’s not yours. It’s all a muddle.
Nobody’s to blame.”
 Then she sat up suddenly. “Yes, there is. It’s your mother who’s to
blame. She made me marry you. It all began with that. I didn’t want to ... I
didn’t want to marry any one, but I wanted to have a mission of my own.
She did it. She’s to blame, and now she hates me. She thinks I’ve stolen you
from her.”
She buried her face in the cushions and lay sobbing. After a time, Philip
said, “Naomi ... listen to me. You didn’t steal me from her.”
“Who did then?” said Naomi’s muffled voice.
“I don’t know. It just happened. I suppose it’s one of the things that
happen in life. I’ve grown up now. I’ve grown up since we went to
Megambo. That’s all. I know my own mind now.”
“Oh, you’re hard, Philip ... harder than flint.” She sat up slowly. “I’ll do
anything for you. You can wipe your feet on me. I can’t let you go now ... I
can’t ... I can’t!” She began suddenly to laugh. “I’ll do anything! I’ll prove
to you I can keep house as well as your mother. I’ll show you how I can
care for the children. They’re your children, too. I’ll learn to cook ... I’ll do
anything!”
He did not answer her. He simply sat staring out of the window like an
image carven of stone. And he was saying to himself all the while, “I can’t
yield. I daren’t do it. I can’t—not now.” And all the while he felt a kind of
disgust for the nakedness of this love of Naomi’s. It was a shameful thing.
And during all their life together he had thought her incapable of such love.
She kept moaning and saying, over and over again, “I’ve got nothing
now. I’m all alone ... I’ve got nothing now.”
He rose, and laid a hand on her shoulder. “I’m going now, Naomi. I’m
not going to the restaurant. I’ll come back this afternoon. It’ll be all right.
We’ll work it out somehow.”
She looked up at him. “You’ve changed your mind?”
“No, I don’t mean that. No, it’s better this way.”
“I’ll show you, Philip, what a good wife I can be.”
He picked up his hat, Jim Baxter’s hat, and suddenly he thought, “The
old Philip is dead—as dead as Jim Baxter. I’ve dared to do it.”
Aloud he said, “Let’s not talk any more now. I’ll be back in an hour or
two when you feel better.”
 Then he went away, and outside the house, among the lilacs, he was
suddenly sick.

7
He found a tiny flat of three rooms over a drugstore halfway up the hill
from the railway station. It had been occupied by the family of a salesman
who traveled for a house which manufactured false teeth. He had been
promoted to a western territory where, with the great boom in the silver
mines, the market for gold teeth had risen enormously.
He was a little fat man, with enormous black mustaches, all aglow with
his promotion. “It’s the best gold tooth territory in America,” he told Philip.
The apartment rented for thirty dollars a month. The bubbling salesman
would leave the furniture behind for two hundred and fifty dollars. Philip
could move in the day after to-morrow.
He left the place, his whole body warmed by the satisfaction of having
acted, of having done something definite. But the thing was not settled yet,
because his mother still remained to be told.
He found her in the kitchen of the restaurant, superintending the
preparation of mince-meat according to a recipe of her own which
eliminated all intoxicating liquors. Standing over the negress who did the
work, she was the essence of vigor and authority, her face crimsoned by the
heat of the place, her hair all in disorder.
“Ma,” he said to her. “I have something I want to discuss with you.”
After bidding the negress wait until she returned, she followed him
quickly, surprised and troubled by the look in his eye and the set of his jaw.
The talk took place at the table behind the screen where Moses Slade came
every day to eat.
“It’s about Naomi, Ma ... I’ve taken some rooms for her to live in. She
won’t trouble you any longer. We’ll move out on Tuesday.”
She looked at him for a moment in astonishment. “But, Philip,” she said,
“you ought to have consulted me. You mustn’t do that. We can’t even think
of it.”
“The rent is paid. I’ve bought furniture.”
“Where did you get the money?”
 “I used what Grandpa left me.”
“I thought you’d pledged the interest on that to the mission.”
“I’ve taken it back. I took it back before I was sick.”
She didn’t say anything for a long while. She saw suddenly that he was
changed, more hardened even than she had feared. He didn’t even come to
her any longer for advice. He had shut her out altogether. At last she said,
“But, Philip, what will people think—when I’ve a house big enough for you
all?”
“I don’t care any longer what people think. I can’t go through any more
scenes like yesterday. Besides, a man has a right to his own house.”
“But, Philip ... my house is your house. I’ve worked all these years and
sacrificed.... Oh, you don’t know what it’s meant sometimes. I wouldn’t
even let Uncle Elmer help me—so that you’d have the house for your own.
It wasn’t for myself.... I could have got along somehow.”
He looked away from her at the mustard-pot in the center of the table.
“You know that you can’t get on with Naomi—and she hates living in your
house.”
“I can try ... we can both try. If only she’d take a little interest and not
make the place into a pigstye.”
“You know she won’t change.”
“Philip, I’ll do anything.... I’ll put up with Naomi ... I won’t say a word,
only don’t leave me now after all the years when I’m an old woman.”
She saw the stubborn jaw set in a hard line. The sight of it stirred a
sudden, turbulent emotion: it was his father’s jaw over again, terrifying in
its identity. What had she done to deserve such treatment from these two
men to whom she had given up all her life without once a thought of
herself? She had worked for them, sacrificed....
Philip was saying, “It won’t make any difference. Even if you and
Naomi never spoke to each other. You’d be hating each other all the time.
Don’t you see? That’s what I can’t stand.”
She reached over and touched his hand. “Philip ... once you used to
come to me with everything, and now ... now you treat me like a stranger ...
me, your own mother. Why don’t you come to me? I want to share your life,
to be a part of it. It’s all I live for. You’re all I’ve got.”
 He felt her trying to capture him once more. What she said was true ...
you couldn’t deny it. She had given her whole life to him. Every word she
spoke hurt him.
“I don’t know, Ma. Nothing has happened except maybe that I’m grown
up now. I’m a man. I’ve got to decide things for myself.”
It was that hard, brutal jaw which she couldn’t overcome. It had thwarted
her always. With Jason, when his jaw was set thus, it was as if his heart had
turned to stone.
“Where did you go last night?”
He told her, and the answer frightened her. In the Flats, in a Dago’s
boarding-house, her son had passed a night.
“Where did that coat come from?”
“It belonged to Jim Baxter, who was killed at the grade-crossing last
week. I borrowed it from McTavish.”
“So you’ve been seeing him.”
“Yes, he told you I wouldn’t come home, didn’t he?”
“Yes,” she said, with a sudden flash of anger. “Yes ... he told me. I wish
you wouldn’t see so much of him, Philip. He’s a wicked man.”
He made no response to this sudden, feeble sally of the old authority. He
had, she discovered with awe, that old trick of his father’s—of not
answering in an argument unless he had something to say. It was an unfair
method, because it always kept the argument upon the level of reason,
excluding all the force of the emotions.
“And I’m not coming home any more to sleep, Ma. That’s all finished.”
He must have seen the look of fear in her eyes. It was that look he had
seen there whenever, for a moment, she seemed to lose control of that solid
world she had built up.
“But, Philip ... it’s your house ... your own home. You’ve never had any
other.” He said nothing, and she asked, “Where are you going to sleep?”
Slowly, and then carefully, so that it would hurt her as little as possible,
he told her about the stable at Shane’s Castle, and his plan of painting. She
listened, half believing that she could not be in her right mind, that what she
heard was only part of a nightmare. She kept interrupting him, saying, “But,
Philip, you never told me ... I didn’t know,” and when he had finished, she
said abruptly, “That wasn’t the plan I had for you, Philip; I’ve been talking
with Reverend Castor and he thinks we could arrange to get you a good
congregation.”
“No ... that’s all finished. It’s no use even talking of it.”
She went on, ignoring him. “And if that didn’t please you, I thought ...
well, you could take the restaurant because, well ...” she looked away from
him, “you see, I’m thinking of getting married.”
She saw his face grow red with anger. “Not to that humbug, Moses
Slade!”
“Yes, Philip. But it’s wrong of you to call him a humbug. He’s a
distinguished man, a good man, who stands for the best in the community.”
“He’s a hypocrite and a humbug!”
An uncontrollable rage took possession of him. It was impossible that he
was to have Moses Slade, the humbug who had written that editorial about
the strike, for a stepfather. No, it was outlandish, too impossible, that a good
woman like his mother should be taken in by that lecherous old rip.
“Philip,” she was saying. “You don’t understand. I’ve been alone always
... except for you—ever since your father died. It would be a good marriage,
a distinguished marriage, and I wouldn’t be alone in my old age.”
“You couldn’t marry him. You couldn’t marry a fat old man like that.”
He fancied that he saw her wince. “It isn’t a question of love, Philip, at
our age. It’s companionship. I’m very fond of him, and he’s been thoughtful
—so thoughtful all the time you were sick.”
“It’s disgusting!”
It was odd, what had happened—that he found himself for the first time
in his life taking a high hand with his mother. It was an intoxicating
sensation.
“If I give him up, I’ll be giving up a great opportunity for good. As a
Congressman’s wife, there’s no end to the things I could accomplish....” She
began to cry. “But I’ll give him up ... I’ll give him up if you won’t turn your
back on your poor mother. I’d do anything for you, Philip. You’re all I’ve
got, and I hoped for so much—to see you one of the great men of the
church, a Christian leader, fighting on the side of God.”
“It’s no good, Ma. I won’t go back to that.”
One of the waitresses appeared suddenly from behind the screen. “Mrs.
Downes ...” she began.
 “Go away! Go away! I’ll talk to you later.”
The girl disappeared.
“And that isn’t all, Ma. I’m not going to live with Naomi any more. I’m
through with that. I meant what I said when I was sick.”
“Philip—listen to me, Philip!”
“No ... I’ll come to see her and the children. But I’m through.”
“What will people think? What will they say?”
“You can tell them I’ve got a night job.... Nobody’ll know, except Aunt
Mabelle, where Naomi is going to live. Nobody will see me come or go. It’s
in Front Street.”
“Front Street! Why, that’s on the edge of the Flats! You can’t do that!”
He looked at her for a long time in despairing silence. “My God, Ma!
Can’t you see? Can’t you understand? From now on, I’m going to stand on
my own. I’m going to work things out. I’ve got to get out of this mess....
I’ve got to.”
He rose abruptly, and put on his hat.
“Philip,” she asked, drying her eyes, “where are you going now?”
“I’m going to buy blankets for myself.”
“Philip, listen to me. For God’s sake, listen! Don’t ruin everything. I’ve a
right to something. I’m your mother. Doesn’t that mean anything?”
He turned for a moment hesitating, and then quickly said, “Ma, don’t
talk like that, it isn’t fair.”
Without another word, he put on his hat and hurried out of the restaurant.
Once outside, the cold air cleared his head, and he was thankful that he
had been hard as a stone. Again he was sorry for Emma in a vague,
inexplicable fashion; she could never understand what it was that made him
hard. She couldn’t see why he had to behave thus.
“I wish to God,” he thought bitterly, “that I’d had a mother who wasn’t a
fine woman. Life would have been so much easier. And I can’t hurt her ... I
can’t. I love her.”
And suddenly he saw that in all their talk together nothing had really
been settled. Nothing had been changed or decided.