Section 1: PhySiology 1 1. Anatomy of the Male and Female Reproductive System 3 Mir Jaffar, BV Srinivas
Male Reproductive System 3; Female Reproductive System 9
2. Oogenesis and Folliculogenesis 15 Mandeep Kaur, PM Gopinath
Primordial Germ Cells 15; Oocyte Formation 16; Postnatal Oogenesis 16; Primordial Follicle Formation 16; Formation of Primary and Secondary Follicles 17; Initial Recruitment 17; Preantral Follicle Development 17; Formation and Role of Gap Junctions 18; Antral Follicle Development 18; Rescue from Atresia or Cyclic Recruitment 19; Role of 2-Cell 2-Gonadotropin Concept in Follicle Selection 19; Selection of a Dominant Follicle 20; Preovulatory Follicle and LH Surge 20; Role of Inhibin and Activin in Folliculogenesis 20; Other Growth Factors 20; Prevention of Premature Luteinization 21; Ovulation 21; Follicular Stimulating Hormone Surge 21; Fall in Estradiol Levels and Shutdown of LH Surge 22; Luteal Phase 22; Luteal Follicular Transition 22
3. Regulation of Menstrual Cycle 26 Arveen Vohra, Nameeta Mokashi Bhalerao, Kamini A Rao
Reproductive Neuroendocrinology 26 The Hypothalamo-Hypophyseal Portal Circulation 27; Hormones in Female Reproduction 28;
Hypothalamic-Pituitary-Ovarian Axis 32; Ovarian Feedback on the Hypothalamus and Pituitary 32
Physiology of Menstrual Cycle 34 Ovarian Cycle 34; Follicular Phase 34; Ovulation 39; Luteal Phase 41; The Luteal-Follicular
Transition 41; Uterine Endometrial Cycle 42; Proliferative or Follicular Phase 43; Secretory or Luteal Phase 43; Implantation Phase 44; Menstrual Phase or Phase of Endometrial Breakdown 44
4. Sperm Production and Migration 50 Manishi Mittal, Kamini A Rao
Primordial Germ Cells 50; Gonadogenesis 50; The Seminiferous Tubules 50; Spermatogenesis 50; Spermiation 53; Epididymal Maturation 53; Endocrine Control 54; Genetic Control 55; Nitric Oxide 55; Blood-testis Barrier 56; Effect of Temperature 57; Seminal Plasma 57; Ejaculation 57; Sperm Migration through the Female Genital Tract 57
5. Ultrastructure of Human Gametes, Fertilization and Embryos in Assisted Reproduction: A Personal Survey 60
A Henry Sathananthan
Review of Early Literature 61; Methodology 61; The Male Gamete 61; The Female Gamete 64; Fertilization 69; Preimplantation Development 74; Abnormal Gametes and Embryos 74
6. Endometrial Receptivity 82 Deepika K
Window of Implantation 82; The Endometrial Cycle—Towards Uterine Receptivity 83; Assessment of Endometrial Receptivity 84; Impact of Ovarian Stimulation on Endometrial Receptivity 92; Endometriomics 94
Contents
Volume 1 Infertility
xx Volume—2 IVF and Laboratory Aspects of Andrology
7. Implantation 106 Deepika K
Preimplantation Embryo Devel opment and Genomic Activation 106; Hatching of the Blastocyst 107; Morphological Steps of Implantation 107; Endocrine Control of Implantation 113; Embryo Maternal Signaling: How the Embryo Dialogues with the Mother to Accomplish Implantation? 114; Immune Acceptance of Pregnancy 116; Summary of Embryo Implantation 119
Section 2: RePRoductive endocRinology 125 8. Hyperprolactinemia and Thyroid Disorders 127 Arati R Rao
Hyperprolactinemia 127 Prolactin: The Hormone 127; Hyperprolactinemia 128
Thyroid Disorders in Infertility 132 Hyperthyroidism 132; Hypothyroidism 134
9. Hirsutism 138 Pramila Kalra
Pathophysiology of Hirsutism 139; Etiology of Hirsutism 140; Investigations 143; Treatment 144
10. Fertility Management in Primary and Secondary Amenorrhea 148 Sathya Balasubramanyam
Primary Amenorrhea 149; Secondary Amenorrhea 152
11. Luteal Phase Defect 155 Sankalp Singh, Swati Singh, CM Ashraf
Pathophysiological Basis of Luteal Phase Abnormality 155; Etiological Factors Linked to Presence of Luteal Phase Defect 156; Assessment of Luteal Phase Defect 159; Treatment of Luteal Phase Defect 160
12. Anovulatory Infertility 165 Abha Majumdar, Mangal Nisha Sharma
World Health Organization Classification of Anovulation 165; WHO Class 1 165; WHO Class 2 167; WHO Class 3 176
Section 3: Male infeRtility 183 13. Etiology and Pathophysiology of Male Infertility 185 PA Baiju
Primary Testicular Disease 185; Scrotal Hyperpyrexia 188; Obesity 188; Gonadotoxic Drugs and Radiation 188; Genetics of Primary Testicular Disease 188; Aging 190; Obstructive Lesions of Male Genital Tract 192; Systemic Diseases 193
14. Clinical and Endocrinological Evaluation of the Infertile Male 196 Usha Sriram
Evaluation of the Infertile Male 196; Main Etiologies of Male Infertility 196; Clinical Evaluation 196; Medications 197; Physical Examination 197; Endocrine Assessment 198; A Stepwise Approach to Male Infertility 199
15. Microbiology of Semen and Male Genital Tract Infections 200 Sachin Narvekar
Diagnosis of Male Genital Tract Infections 200; Specific Bacterial Infections 201; Viruses 204; Leukocytospermia 206
Contents xxi
16. Sexual Dysfunctions in Male Infertility 212 SS Vassan
Biological Basis of Male Sexual Response 212; Pelvic Floor Muscles and Sphincters during Erection and Ejaculation 213; Nonconsummation of Marriage 213; Protocol for Urinary Alkalization 216; Vibratory Stimulation 217; Erectile dysfunction 220
17. Cytogenetics and Molecular Genetics of Male Infertility 227 Jayarama S Kadandale, Swathi Shetty, Pooja S Kulshreshtha
Cytogenetic Abnormalities 227; Genetics of Y Chromosome-Derived Infertility 232; Genetic Testing 236; Genetic Counseling 237
18. Role of Ultrasound in Male Infertility 239 Kuldeep Jain, Bharti Jain
Etiological Distribution 239; Scrotal Ultrasonography 240; Transrectal Ultrasonography and Male Infertility 244
19. Varicocelectomy in Infertile Male 247 Saad Alshahrani, Alaa Hamada, Ashok Agarwal
Diagnosis of Varicocele 247; Grades of Varicocele 248; Origin of Varicocele 248; Varicocele and Male Infertility 248; Pathophysiology of Varicocele 249; Is It Progressive Disease? 250; Management of Varicocele 250; Treatment Modalities 251; Complications 255; Varicocele Repair Outcomes 256
20. Medical Management of Male Infertility 262 N Pandiyan, D Ramesh Raja
Physiology of Spermatogenesis 262; Principles of Medical Management of Male Infertility 263; Empirical Therapy 265
21. Evaluation and Treatment of Azoospermia 266 Rajashekaran, R Jayaganesh, Pankaj Kalotia
Initial Diagnosis of Azoospermia 266; Classification of Azoospermia 266; Initial Evaluation of the Azoospermic Patient 267; Genetic Testing in Patients with Azoospermia 269; Treatment Options for Obstructive Azoospermia 270; Role of Varicocele Repair in Patients with Nonobstructive Azoospermia 272; Recommendation for the Evaluation of Azoospermia 272
22. Sperm Retrieval Techniques for Assisted Reproductive Technologies 275 Srinivas BV, Mir Jaffar
Indications for Surgical Sperm Retrieval 275; Sources of Sperm Retrieval 276; Epididymal Sperm Retrieval Techniques 276; Testicular Sperm Retrieval Techniques 278; Future Trends 281
Section 4: geneRal oveRview 283 23. Patient Selection and Management 285 BN Chakravarty
Identification of Cause (s) and Categorization of Infertile Couples 285; Counseling 289; Management Protocols 290; Overview of Assisted Reproductive Technology—Current Scenario and Future Thoughts 299
24. Immunology in Infertility 310 Kamala Selvaraj, Priya Selvaraj
Etiology 310; Immune System of Our Body 312; ASAB and IVF Outcome 312; Diagnosis 312; Clinical Effects of Antisperm Antibodies 313; Treatment for Antisperm Antibody 316
xxii Volume—2 IVF and Laboratory Aspects of Andrology
25. Environment and Infertility 320 Abha Majumdar, Neeti Tiwari
Mechanism of Action 320; Environment and Infertility 320
26. Declining Fertility 330 Arati R Rao
Section 5: feMale factoR infeRtility 333 27. Evaluation of Infertile Female Patients 335 Sandhya Krishnan, Kamini A Rao
Indications for Initial Evaluation 335; Steps for Evaluation 336; Diagnostic Evaluation 336; Ovulatory Function 336; Ovarian Reserve 337; Uterine Abnormality 338; Tubal Patency 339; Peritoneal Factors 340
28. Uterine and Cervical Factors in Infertility 342 Arati R Rao
The Role of the Cervix in Reproduction 342; Etiology of the Cervical Factor 343; Investigation of the Cervical Factor 343; Cervical Mucus Scoring 343; Postcoital Test 344; Treatment of Cervical Factor 347
The Role of the Uterus in Reproduction 348 Intrauterine Adhesions 348; Leiomyoma 348; Endometrial Polyps 348; Adenomyosis 349;
Congenital Uterine Anomalies 349; Tuberculosis 351; New Biomarkers 351; Investigation of the Uterine Factor 351
29. Tubal Factor of Infertility and Assisted Reproduction 358 Sadhana Desai, Partha Guha Roy
Evaluation of Tubal Factor 358; Assisted Reproductive Technologies versus Tubal Surgery 359; Tubal Infertility and Factors Affecting the ART Result 360; Conventional IVF versus ICSI for Couples with Tubal Factor of Infertility and Normozoospermia 362
30. Evaluation of Fallopian Tube Infertility 365 Sarita Suresh, Pankaj Kalotia, Kamini A Rao
Embryologic Development 365; Anatomy 365; Physiology 366; Pathology and Causes of Tubal Obstruction 367; Fallopian Tube and Infertility 367; Investigations of Tubal Infertility 367; Tubal Tuberculosis: Features on Hysterosalpingography 369
31. Infections and Infertility 386 Pankaj Desai
General Aspects of Infections and Infertility 386; Specific Infections: Pelvic Tuberculosis and Infertility 387; Specific Infections: Chlamydia 392; Specific Infections: Gonorrhea 394; Specific Infections: Mycoplasma 395; Nonspecific Pelvic Infection 396
32. Genital Tuberculosis and Infertility 399 Sonia Malik, Vandana Bhatia
Incidence of Genital Tuberculosis 399; Pathophysiology 399; Genital Tuberculosis and Infertility 399; Active Tuberculosis 400; Latent Tuberculosis 400; Restoring Fertility in Tuberculosis 401; Dilemmas in Management 402
33. Transvaginal Ultrasound and Doppler in Infertility 404 Sonal Panchal, CB Nagori
Diagnosis of Abnormalities Causing Subfertility 404; Cycle Assessment 422
Contents xxiii
34. Endoscopy in Infertility 435 Nutan Jain, Tania G Singh, Vandana Jain, Anubha Arora
Laparoscopy in Infertility 435 Laparoscopic Surgery on Uterus 435; Laparoscopic Tubal Surgery 437; Endometriosis 443;
Laparoscopic Ovarian Surgery 445
Hysteroscopy in Infertility 448 Role in In Vitro Fertilization 448; Submucous Fibroids 449; Hysteroscopic Tubal Cannulation for
Proximal Tubal Block 451; Hysteroscopy for Metroplasty 453; Intrauterine Adhesions (Asherman’s Syndrome) 456
35. Assessment of Ovarian Reserve 459 Nameeta Mokashi Bhalerao, Kamini A Rao
Variability of Reproductive Aging 459; Ovarian Reserve 459; Diagnostic or Screening Test 460; Clinical Markers 460; Endocrine Markers 461; Endocrine Dynamic Tests 463; Ultrasonographic Markers 464; Clinical Implications of Ovarian Reserve Tests in ART Practice 464
36. Endometriosis in Infertility 469 Rakesh Sinha, Shweta Raje, Gayatri Rao
Localization and Appearance of Endometriosis 469; Diagnosis and Staging 471; Treatment 472; Management of Ovarian Endometrioma before IVF 476; Stage of Endometriosis and Surgery Outcome 477; Endometriosis and Infertility: Guidelines by the Practice Committee of American Society of Reproductive Medicine 2012 477
37. Interventional and Surgical Management of Fibroids with Infertility 480 Ritika Arora, Mala Arora
How Fibroids Cause Infertility 480; Should All Myomas be Treated in Women Seeking Fertility?; 480 Nonmedical Management of Uterine Fibroids 480; Steps of Laparoscopic Myomectomy 483
38. Reconstructive Surgeries Enhancing Fertility 494 Amr H Wahba, Ahmed Hussein, Osama Shawki
Reconstruction of Distorted Pelvic Anatomy 494; Reconstruction of Blocked Fallopian Tubes 496; Reconstruction of Distorted Uterine Cavity 497
39. Obesity in Infertility Practice 505 Nivedita Shetty
Defining Obesity 505; Obesity and Reproductive Health 506
40. Unexplained Infertility 514 Pratap Kumar
Chances of Conception and Age 514; Testing for Unexplained Infertility 514; Embryo Development and Genetics Control 515; Uterine Receptivity and Unexplained Infertility 515; Molecular Control of the Implantation Window 515; Treatment 516
41. Fertility Preservation in Female Patients 519 Bina Vasan
Balancing Cancer and Fertility 519; Assisted Reproduction and Fertility Preservation 519; Breast Cancer 520; Cancer of the Cervix 520; Endometrial Cancer 520; Childhood Cancers 521; Lymphomas 521; Autoimmune Diseases 521; Benign Ovarian Diseases 521; Effect of Cancer Treatment on Female Fertility 522; Established Methods for Fertility Preservation 522; Obstacles to Fertility Preservation 524; Ethical Dilemmas 524
xxiv Volume—2 IVF and Laboratory Aspects of Andrology
Section 6: ovulation induction 527 42. Drugs for Controlled Ovarian Stimulation 529 Rishma Dhillon Pai, Hrishikesh Pai, Nandan Roongta
The Drugs 529; Adjuncts for Ovarian Stimulation 535
43. Superovulation Strategies in Assisted Conception 538 Duru Shah, Shefali Bansal
Gonadotropin Preparations 538; Recombinant Gonadotropins 539; Long-acting Gonadotropins 539; Protocols for Stimulation with Gonadotropins 539; Premature Luteinizing Hormone Surge 540; Gonadotropin-releasing Hormone Agonists 540; Gonadotropin-Releasing Hormone Antagonists 543; Comparison of Gonadotropin-Releasing Hormone Agonist versus Antagonist Protocols 545; Clinical Applications of Ovarian Stimulation Protocols 545; World Health Organization Classification for Anovulation 547; Luteal Phase Support in Controlled Ovarian Stimulation 549; Assessment of Ovarian Reserve 549
44. Agonists in Reproductive Medicine 552 CV Kannaki Uthraraj
Gonadotropin-releasing Hormone: The Molecule and Mechanism of Action 552; Preparations 553; Dosage 553; Side Effects 553; Agonist in Controlled Ovarian Hyperstimulation: Suppression of Luteinizing Hormone 554; Comparative Studies of Agonist and Antagonist Protocols 556; Choice of Agonist Protocols According to the Response Profile 556; Results of the IVF Survey of the Use of Agonist Protocols 558; Agonist as a Trigger 558; Agonist in the Treatment of Endometriosis 558; Agonist and Fibroid Management 559; Agonists in Precocious Puberty 559; Agonists for Gonadal Protection During Chemotherapy 559
45. GnRH Antagonists 562 Divya Sardana, Kamini A Rao
Structure 562; Mechanism of Action 562; Dosage 563; Antagonist Protocols 563; Pharmacodynamics and Pharmacokinetics 564; Evidence-Based Practice 565; Oral Contraceptive Pill Preprogramming 566; Increasing the Dose of Gonadotropins with Antagonist 566; Special Subgroups 566; Alternative GnRH-Antagonist Protocols 567; Other uses of Antagonists 568
46. Monitoring of Ovulation Induction 573 Nandita Palshetkar, Hrishikesh Pai, Nandan Roongta, Rohan Palshetkar
Monitoring the Ovulation Induction Cycle 573; Extent of Monitoring 573; Home Monitoring 574; Clinical Monitoring 575; Minimal Monitoring 579; Prevention of Ovarian Hyperstimulation Syndrome 580
47. Ovulation Triggers and the Role of Gonadotropin-releasing Hormone Agonist Trigger in Assisted Reproduction 582 Korula George, Mohan Kamath
48. Individualized Ovarian Stimulation 586 Priya Bhave Chittawar
Why Individualization of Ovarian Stimulation is Required in In Vitro Fertilization Cycles? 586; How to Individualize Ovarian Stimulation? 587; Using the Ovarian Reserve Tests in Combination to Form Predictive Models 588
49. Mild Approaches in Assisted Reproduction 594 Mohan Kamath, Korula George
Types of Milder Protocols 594; Embryo Quality/Endometrial Receptivity 597; Future Trends 597
Contents xxv
50. Role of LH in Ovarian Stimulation 599 GAA Ramaraju, Mamata Deendayal, Devika Gunasheela, R Gutgutia, Geeta Haripriya, Mirudubhashini, Nayana Patel, Ameet Patki
Role of Luteinizing Hormone in Physiology: The Physiological Hormonal Interplay 600; Pharmacogenomics and Ovarian Stimulation 601
51. Progesterone in Ovarian Stimulation 607 Harpreet Kaur, Kamini A Rao
Source of Progesterone 608; Profiles During Ovarian Stimulation 608; Clinical Implications of High Progesterone During Ovarian Stimulation 608; Proposals for Prevention of Premature Progesterone Rise 609
52. Understanding the Prognostic Factors and Optimizing In Vitro Fertilization Outcome 611 Nivedita Shetty
Prior to Controlled Ovarian Stimulation 611; During Controlled Ovarian Stimulation 616; During Oocyte Retrieval 616; After Oocyte Retrieval 617
53. Luteal Phase Support 622 Umesh N Jindal, Swati Verma
Luteal Phase Deficiency 623; Luteal Phase Support 624; Onset and Discontinuation of Luteal Phase Support 626
Section 7: aRtificial inSeMination 629 54. Intrauterine Insemination 631 Natachandra Chimote, Nishad Chimote, Bindu Mehta
Utilization of Intrauterine Insemination 631; Indications for Intrauterine Insemination Treatment 631; Intrauterine Insemination Procedures and Insemination Methods 633; Types of Intrauterine Insemination Catheters 634; Timing of Insemination 634; Outcome of Intrauterine Insemination Cycles 634; Intrauterine Insemination in Cycles Stimulated with Clomiphene 635; Ovarian Stimulation with Gonadotropins 635; Intrauterine Insemination in Follicle Stimulating Hormone-Stimulated Cycles 636; Conditions Affecting the Prognosis 637; The Premature Luteinizing Hormone Surge in Intrauterine Insemination Cycles 638; Luteal Phase Support: Is it Necessary in Stimulated Intrauterine Insemination Cycles? 638; Luteal Phase after Ovarian Stimulation 638; Clinical Decisions about Intrauterine Insemination and In Vitro Fertilization 639; The Background Prognosis 639; Treatment Plan 639; Counseling Couples 640; Prevention of Multiple Pregnancy 640; Cost-effectiveness 640
55. Optimizing Success in Intrauterine Insemination 645 Sheila Balakrishnan
Indications 645; Factors Optimizing Success 646
Section 8: aSSiSted RePRoductive technologieS 651 56. Anesthesia and In Vitro Fertilization 653 Divya Sardana, Ravikumar, Kamini A Rao
Types of Anesthesia 653
57. Oocyte Retrieval 658 Rajesh Chaudhary, Kamini A Rao
Historical Review 658; Mode of Oocyte Retrieval 658; Planning Oocyte Retrieval 659; Anesthesia to Conscious Sedation/Analgesia 660; Preparation 660; Transvaginal Oocyte Retrieval
xxvi Volume—2 IVF and Laboratory Aspects of Andrology
Procedure 661; Oocyte Retrieval in Special Situations 665; Complications 667; Troubleshooting 667; Learning Curve 668
58. Embryo Transfer 672 Gautam N Allahbadia, Akanksha Allahbadia, Rubina Merchant, Goral N Gandhi
Clinical Discussion 673; Recent Advances 678
Section 9: dileMMaS in aSSiSted RePRoductive technologieS 683 59. Role of Adjuvant Therapy in In Vitro Fertilization 685 Chandrika Kulkarni, Kamini A Rao
Adjuvants for Ovarian Stimulation in Poor Responders 685; Adjuvants for Hyper-responders 688; Others 689; Adjuvants for Improving Endometrial Receptivity 690
60. Altering Management Strategies in Women with a Poor Response to Ovarian Stimulation 697 Late Mehroo D Hansotia, Jaydeep D Tank
Predicting a Poor Response 698; Altering Strategies for Poor Responders 699; Alternative Strategies 701
61. Recurrent Implantation Failure 704 Madhuri Patil
Etiology 704
62. Empty Follicle Syndrome 724 K Jayakrishnan
Classification 724; Incidence 724; Underlying Mechanism 724; Prognosis 726; Management Options 726
63. Elective Single Embryo Transfer 730 Gautam Khastgir
Risks of Multiple Pregnancies for Children 730; Risks of Multiple Pregnancies for Mother 731; Outcome of Elective Single Embryo Transfer 731; Criteria for Elective Single Embryo Transfer 733; Embryo Quality for Elective Single Embryo Transfer 734; Improved Outcome Even in Singletons with eSET 735; Health Economic Aspects of Single Embryo Transfer 736
64. Role of Aneuploidy Screening in Preimplantation Embryos 741 Howard Carp, B Feldman
Target and Timing of Pregestational Screening 741; Techniques 742; Pitfalls 743; Results of Pregestational Screening 743; Authors’ Recommendations 744
65. Epigenetics, Imprinting Errors and IVF 746 Padma Rekha Jirge
Epigenetics and Genomic Imprinting 746; Imprinting Disorders and ART 747
Section 10: coMPlicationS of aSSiSted RePRoductive techniqueS 751 66. Ovarian Hyperstimulation Syndrome: Clinical Aspects 753 Joseph G Schenker, Yoel Shufaro
Classification of Ovarian Hyperstimulation Syndrome 753; Complications 754; Incidence 755; Risk Factors 755; Pathogenesis of Ovarian Hyperstimulation Syndrome 755; Human Chorionic Gonadotropin 757; Treatment 757; Prevention 758
67. Ectopic Pregnancy 761 PG Paul, Harneet Kaur, Dimple K, Gaurav Chopade
Epidemiology and Risk Factors 761; Diagnosis 761; Management Options 762; Laparoscopic Surgery 763; Salpingostomy 763; Segmental Excision 766; Salpingectomy 766; Old Ectopic 766; Nontubal Ectopic Pregnancy 767; Reproductive Outcome 767
Contents xxvii
68. Iatrogenic Multiple Pregnancy and Assisted Reproductive Technologies 770 Veronica Irene Yuel
Incidence 770; Risks Associated with Multiple Pregnancies 770; Strategies to Reduce the Risk of Multiple Pregnancies During Assisted Reproductive Technologies 772
69. Fetal Reduction 776 Revathi S Rajan, Kamini A Rao
Background 776; Medicolegal Issues and Psychological Impact 776; Procedure 777; Methods 777; Prerequisites 777; Technique 778; Other Methods 779; Potassium Chloride 779; Complications 779; Failed Reduction 779; Selective Reduction 779; Studies on Fetal Reduction 779
70. Oncogenic Risk Related to Assisted Reproductive Technology 782 Manish Banker, Pravin Patel, Varsha Chauhan, Aarti Gupte, Hetal Benani, Dipesh Sorathia
Possible Mechanisms for Oncogenicity 782; Assisted Reproductive Technology and Maternal Oncogenic Risk 782
Section 11: thiRd PaRty RePRoduction 789 71. Oocyte and Embryo Donation 791 Ameet Patki, Alok Sharma
Indications for Donor Oocyte 791; Evaluation of Oocyte Recipients 792; Evaluation of the Partner of the Oocyte Recipient 792; Selection of the Donor 792; Pretreatment Evaluation of Endometrial Receptivity 794; Results of Donor Oocyte Programs 795; Legal Implications of Donor Oocyte Program 795; Embryo Donation 795; Ethical and Social Implications 796; Recent Advances 796
72. Oocyte Sharing Program 798 Devika Gunasheela, Jyothi Patil, Ashwini S
History of Egg Sharing in United Kingdom 798; Indications for Oocyte Donation 799; Sources of Oocyte Donors 800; Egg Sharing 800; Evaluation of the Oocyte Recipient 800; Evaluation of the Partner of the Oocyte Recipient 801; Selection and Screening of the Donor 801; Payment to the Donor 802; Counseling 802; Protocol for the Donor and Recipient 802; Outcomes 804; Ethical and Moral Issues 804
73. Surrogacy 807 Jaideep Malhotra, Narendra Malhotra, Nayna Patel, Parul Arora, Neharika Malhotra Bora
Indications for Treatment by Surrogacy 808; Patient Selection 808; Selection of the Surrogate 808; Screening of the Surrogate 808; Counseling 810; Cycle Management 810; Replacement in a Controlled Cycle 810; Surrogacy and Law 810; Ethical Issues 811; Suggestions 811
74. Challenges Faced in Setting-up of a Surrogate House within the ICMR Guidelines 819 Nayna Patel
Advantages of Having a Surrogate House 819; Assisted Reproductive Technologies 2008 Guidelines 819
75. Adoption 821 Jaideep Malhotra, Narendra Malhotra, Parul Arora, Keshav Malhotra
Adoption Types 822; Who can Adopt? 822; Adoption Issues 823
Section 12: MiScellaneouS 825 76. Batch In Vitro Fertilization: Practical Considerations 827 Ashadeep Chandrareddy, Baiju Ahmed Kutty, Seema Pandey
Batch In Vitro Fertilization 827; Different Types of Settings where Batching is Done 827; Preparation for a Batch 828; Batch 828; Advantages of Batching 830; Disadvantages of Batching 830; Strategies to Optimize Outcome in Batch IVF 831
xxviii Volume—2 IVF and Laboratory Aspects of Andrology
77. Alternatives to Assisted Reproductive Technology 834 Nalini Mahajan
Alternatives to Intrauterine Insemination 834; Alternatives to In Vitro Fertilization 834; Indications 834; Treatment Protocol 834; Alternatives to Intrauterine Insemination 835; Alternatives to In Vitro Fertilization 837
78. Endometrial Preparation in Frozen-thawed Embryo Transfer 841 Shivani Singh, Shalu Gupta, Nalini Mahajan
Advantages of FET 841; Main Indications of Freezing the Embryos in ART Cycle 841; Natural Cycle FET 842; Modified Natural Cycle FET 842; Stimulated FET Cycles 843; Hormone Replacement Cycle FET 843; Ovarian Downregulation with GnRH Analogs with Hormone Replacement Cycle FET 844; Programming of FET Cycles in Terms of Thawing and Transfer 844; Adjuvant Therapy for Improving Endometrial Receptivity in FET 845
Section 13: outcoMe following aSSiSted RePRoductive technologieS 849 79. Obstetric Outcome Following Assisted Reproductive Technology 851 Sunita Tandulwadkar, Bhavana Mittal, Vineeta Kharb, Nirzari Mangeshikar
Comparison of Pregnancy Outcome in Fertile versus Subfertile Women 851; Comparison of the Pregnancy Outcomes of Subfertile Women after Infertility Treatment and in Naturally Conceived Pregnancies 851; Comparison of Pregnancy Outcome in Fertile Women versus ART Pregnancies in Subfertile Women 852; Comparison of Pregnancy Outcome in Natural Conception in Subfertile Women/Use of Ovulation Induction (with or without Intrauterine Insemination), and Use of In Vitro Fertilization 853
80. Outcome of Children Born through Assisted Reproductive Technology 855 Mandeep Kaur, Kamini A Rao
Hurdles before Livebirth 855; Assisted Reproductive Technology Couples 856; Congenital Abnormality 856; Multiple Pregnancies 857; Outcome in Singleton Pregnancies 858; Neonatal and Childhood Development 858; Psychological Concerns 859
Section 14: gRief counSeling 863 81. Counseling in Infertility and with Assisted Reproductive Technologies 865 Prathap Tharyan
Infertility is a Global Problem 865; Infertility, and Its Treatment, is Associated with Considerable Distress 865; Counseling in Infertility and ART 866
Section 15: ethical and legal iSSueS 873 82. The Ethical, Legal and Social Issues of Modern Assisted Reproductive Technology Treatment 875 Jayam Kannan, RK Sharma, Robert Fischer
Reporting Regulations 875; Financial Aspect for ART Treatment 875; Preimplantation Genetic Testing 876; Fertility Preservation 876; Gamete Donation 876; Embryo Donation 877; Surrogacy and Gestational Carriers 877; Possible Deleterious Effects of ART 877; The Ethicolegal Scenario of Infertility Treatment in India 878
Section 16: futuRe clinical aPPlicationS 883 83. Endometrial Stem Cells and Reproduction 885 Satish Patki, Ujjwala Patki
Stem Cells in the Endometrium 885; Components of the Endometrium and their Originating Stem Cell Types 886; Role of the Endometrial Stem Cells in the Establishment of the Pregnancy 886; Local Injury to the Endometrium and the Stem Cell-mediated Improvement in the Implantation Process 887; The Endometrial Stem Cell Culture “In Vitro” 888; Endometrial Reconstruction with the Stem Cells 888; Stem Cells and Pathogenesis of Endometriosis 888
Contents xxix
Volume 2 IVF and Laboratory Aspects of Andrology
Section 17: andRology 893 84. Semen Analysis in 21st Century Medicine: A Paradigm Shift 895 Vasan SS
The American Urological Association (AUA) Best Practice Policy and the American Society for Reproductive Medicine (ASRM) Practice Committee Report 895; The Probabilistic Nature of Human Fertility 895; Semen Analysis 895; WHO Fifth Manual: Was there a Need for a Shift in Approach of Assessment? 896; Differences in Assessment between 4th Edition as Compared to the 5th Edition of WHO Manual 899; Historical Aspects on Attempts to Define Lowest Levels of Semen Parameters Usually not Associated with Infertility 903
85. Sperm Chromatin Assessment 906 Priya Kannan
Clinical Significance 906; Causes of Sperm DNA Damage 907; Assays for Detection of Sperm DNA Integrity 907
86. Ejaculatory Failure 911 Rupin Shah
Pathophysiology 911; Clinical Classification 911; Sperm Retrieval Techniques 912
87. Sperm Preparation in Assisted Conception: Laboratory Techniques 915 Natachandra Chimote, Nishad Chimote, Bindu Mehta
Semen Collection 916; Semen Analysis 916; Medium for Sperm Preparation 916; Selecting Sperm Preparation Techniques 917; Alternative Methods 921
88. Semen Banking 924 Natachandra Chimote, Nishad Chimote, Bindu Mehta
Techniques for Cryopreservation 925; Effect of Cryopreservation on DNA of Sperm 928; Reproductive Outcome with Cryopreserved Semen 928; ICMR Guidelines for Semen Banks 929
Section 18: eMbRyology 935 89. History of In Vitro Fertilization 937 Neelima Gupta
History of In Vitro Fertilization: The Milestones 938; The Future 953
90. In Vitro Fertilization and Embryo Transfer 959 Haifa Honeneih, Kannamannadiar Jayaprakasan, Alex C Varghese
IVF Laboratory and Culture Systems 959; Oocyte Retrieval 960; Fertilization 962; Embryo Transfer 971
91. Intracytoplasmic Sperm Injection 973 Alex C Varghese, Giles Palmer
Indications for ICSI 973; Location of ICSI Set-up 973; Choice of Microtools 974; Microinjection 974; Intracytoplasmic Sperm Injection: Procedure and Equipment 974; Intracytoplasmic Morphologically Selected Sperm Injection 980; Automation of ICSI 982
92. Analysis of Fertilization 985 Nandita Palshetkar, Hrishikesh Pai, Nandan Roongta
The Physiology of Fertilization 985; Fertilization in Assisted Reproductive Technology 986; Noninvasive Evaluation of the Zygote 987; Abnormal Fertilization 988; Assessment Techniques 990
xxx Volume—2 IVF and Laboratory Aspects of Andrology
93. Morphological Assessment of Oocyte and Embryo 992 Vijay Mangoli, Ranjana Mangoli
Oocyte 992; Zygote 997; Early Cleavage 998; Cleavage Stage Embryos 998
94. Blastocyst Culture and Transfer 1003 Rajvi H Mehta
Why Culture Embryos to the Blastocyst Stage In Vitro? 1003; Morphological Evaluation of Blastocysts 1004; Factors Influencing Blastocyst Development 1005; Advantages and Applications of Blastocyst Culture 1006; Limitations of Blastocyst Transfer 1006; Obstetric and Perinatal Outcomes 1007
95. Advantages and Disadvantages of Embryo Transfer on Day 2, Day 3 and Blastocyst Stage 1010 Vijay Mangoli, Ranjana Mangoli
Embryogenesis 1010; Is Blastocyst Stage Transfer Advantageous? 1012
96. Embryo Transfer Techniques 1016 Hrishikesh Pai, Nandita Palshetkar, Rishma Dhillon Pai, Nandan Roongta
Pre-embryo Transfer 1016; Procedure of Embryo Transfer 1019; Embryo Transfer Procedure 1023; Embryo Transfer: Troubleshooting 1025; Preventing an Ectopic Following Embryo Transfer 1027; Variations of Embryo Transfer Technique 1027
97. Cryopreservation of Oocytes and Embryos by Slow Freezing Method 1031 Varsha Samson Roy
Historical Aspects 1031; Need for Oocyte Cryopreservation 1032; Advantages of Embryo Freezing 1032; Cryobiological Principles of Slow Freezing 1032; Selection of Embryos for Freezing 1033; Role of Assisted Hatching in Frozen Embryos 1033; General Rules for Freezing and Thawing 1034; Slow Cooling of Human Oocytes 1034; Safety of Oocyte and Embryo Freezing 1037
98. Oocyte Vitrification 1039 Varsha Samson Roy
Medical Indications of Oocyte Freezing 1039; Cryobiology—Vitrification 1040; Cryoprotectants 1040; Cryotools 1040; With or Without Cumulus Cells 1041; Temperature at Vitrification 1041; Oocyte Cryopreservation-induced Stress 1041; Disease Transmission Issues 1042; Protocols for Oocyte Vitrification 1042; Protocol for Oocyte Warming 1043
99. Vitrification 1046 Gaurav Majumdar
Principle of Vitrification 1046; Various Factors Determine Ultimate Survival 1047; Vitrification: Closed Systems 1049
Section 19: advanceS in aSSiSted RePRoductive technologieS 1053 100. Assisted Hatching 1055 Gaurav Majumdar
Causes for Impaired Hatching 1055; Plausible Mechanisms 1056; Pitfalls of Assisted Hatching 1056; Selection for Embryo Hatching 1056; Overview of Techniques 1057; Medical Management 1059
101. Embryo Biopsy for Preimplantation Genetic Diagnosis 1061 Shailaja Gada Saxena, Prabhat Ranjan
Evolution of Embryo Biopsy 1061; Steps Involved in Embryo Biopsy 1061; Timing of Embryo Biopsy 1063; Postbiopsy Embryo Development 1065; Role of Cryopreservation 1065
Contents xxxi
102. In Vitro Maturation of Oocytes: A Practical Approach 1068 Varsha Samson Roy
Oocyte Maturation In Vivo 1068; Advantages and Indications for IVM 1069; Clinical Aspects of IVM 1069; Role of hCG in IVM 1070; IVM Aspiration 1070; Oocyte Identification 1070; IVM Culture 1071; Assessment of Oocyte Maturity 1071; Fertilization of IVM Oocytes 1072; Embryo Development 1072; Protein Synthesis 1072; Pregnancy Rates with IVM 1072; Safety of IVM 1073
103. Ovarian Tissue Cryopreservation 1076 Balaji Prasath, Amr Kader, Sujatha R, Alex C Varghese
Cryobiology of Ovarian Tissue 1076; Ovarian Tissue Cryopreservation in Humans 1077; How to Obtain Ovarian Tissue? 1078; Vitrification 1080; Modified Slow Freezing 1085; Sites of Transplantation 1086; Additional Approaches with Ovarian Tissue Cryopreservation 1087; Ethical Concerns in Ovarian Tissue Cryopreservation 1087
104. Time-lapse Video for Assessing the Embryos 1092 Vineet Mishra
How Time-lapse Monitoring Helps? 1092; Time-lapse Technologies in IVF Laboratories 1092; Features of Time-lapse Monitoring 1093; Embryo Selection Parameters 1093; Documented Morphological Selection Criteria 1093; Safety Studies Conducted with the Time-lapse Video 1094; Limitations of Time-lapse Systems and Early Morphokinetic Markers 1094; Images of Embryos Cultured in Embryoscope 1094
105. Polarization Microscopy and Its Clinical Applications 1097 Deepika K, Dileep Kumar R
Principle 1097; Device 1097; Spindle Imaging 1098; Zona Imaging 1102; Sperm Selection 1104
106. OMICS 1108 Jyoti Bali, Hrishikesh Pai
Metabolomics 1109; Analytical Technologies 1110; The Embryonic Proteome 1113; The Embryonic Secretome 1114; Genomics 1114
107. IMSI and Its Clinical Significance 1118 VM Thomas, R Ramya
IMSI Procedure 1118; Microscope Equipment 1119; MSOME Criteria for IMSI 1120; Clinical Significance of IMSI 1120; IMSI for All 1121; IMSI and Severe Male Factor Infertility 1121; IMSI and Sperm DNA Fragmentation 1121; IMSI and Routine Semen Analysis 1122; IMSI and Prolonged Sperm Manipulation 1122
108. Microfluidics in Assisted Reproductive Technology 1124 Viloria Tamara, Ana Cobo, Josep Lluís Romero, Marcos Meseguer, María José de los Santos
Manufacturing Microfluidic Devices 1125; Sperm Isolation 1125; Oocytes Denudation 1126; In Vitro Fertilization 1126; Embryo Culture 1128; Integrated Platforms 1130; Microfluidics for Automated Vitrification 1132
Section 20: ethical and legal iSSueS 1135 109. Certification and Accreditation: Relevance to an IVF Center 1137 Achala Mohan
Certification 1137; Accreditation 1138
110. Accreditation of an Assisted Reproductive Technology Laboratory 1142 Rajvi H Mehta
Introduction and Background 1142; Need for Accreditation 1142; National and International Guidelines on Assisted Reproductive Technology 1142; Validation of whether the Guidelines are
xxxii Volume—2 IVF and Laboratory Aspects of Andrology
Followed or Not 1143; Accreditation as an Indicator of Quality Assurance 1143; International Principles of Accreditation 1143; International Standards Organization 1144; Quality Assurance in Assisted Reproductive Technology 1144; Documentation for Quality Assurance and Certification 1144
Section 21: laboRatoRy ManageMent 1147 111. Setting-up an ART Laboratory 1149 Madhuri Patil
Layout and Components of an ART Laboratory 1149; Construction and Selection of Building Material 1150; “Burning in” of the Completed ART Laboratory before Use 1151; Essential Equipment for the ART Laboratory 1151; Newer Equipment 1156; Consumables Required for the ART Laboratory 1160; Important Facts 1163; Equipment Required for Clinical Procedures 1164; Personnel and Experience 1164; Maintenance and Discipline in ART Laboratory 1165; Quality Control and Assurance 1167; Quality Control Procedures 1167
112. Quality Control of In Vitro Fertilization Laboratory 1169 Ratna Chattopadhyay, BN Chakravarty
Markers of Quality of an IVF Laboratory 1169; Minimum Physical Requirements for an ART Clinic 1170; Essential Equipment and Their Maintenance 1172; Record Keeping and Documentation 1175; Essential Qualifications of the ART Team 1175; Training and Upgrading of Knowledge of the ART Team Members 1176; Maintenance of “Code of Practice” 1176; Future Thoughts regarding Improvement of Outcome or Quality of the Laboratory 1176
113. Embryo Culture Systems 1178 Goral N Gandhi, Gautam N Allahbadia, Sakina Kagalwala, Monali Madne, Ramya Ramani, Varsha Chipkar
Culture Media 1178; Media Systems 1180; Culture Conditions 1181; Media Storage and Equilibration 1182; Incubators 1182; Air Purification Unit 1182; Quality Control 1183
114. Micromanipulators 1186 Mir Jaffar, Theodore Jones, Dileep Kumar R, Kamini A Rao
Micromanipulators 1186; Microinjectors 1191
115. Troubleshooting in Assisted Reproductive Technology 1194 Priya Selvaraj, Kamala Selvaraj
Reporting Success 1194; Contributory Parameters 1195; Clinical Parameters 1195; Laboratory Parameters 1198; Ideal Laboratory Working Conditions 1198; Culture Parameters: Checklist 1201; Ten Tips for Good ART Practices 1202; Optimizing Embryo Transfer Technique 1203; Target for Success 1203
Index 1205
1. Oocyte Cumulus Complex Evaluation 1 Kamini A Rao, Divyashree PS
Mature Oocyte Corona Cumulus 2; Approximately Mature Oocyte Corona Cumulus 2; Immature Oocyte Corona Cumulus 3; Postmature Oocyte Corona Cumulus 3; Atretic Oocyte Corona Cumulus 4
2. Oocyte Nuclear Maturity Evaluation 5 Divyashree PS, Kamini A Rao, Anu Kottur
Metaphase II 6; Metaphase I 6; Germinal Vesicle Oocyte (40x) 7; Germinal Vesicle Oocyte (20x) 7; Oocytes in Different Stages of Maturation 8
3. Oocyte Dysmorphisms 9 Divyashree PS, Bezar Ghan VV, Kamini A Rao
Granular Cytoplasm 10; Vacuoles 11; Smooth Endoplasmic Reticulum Cluster 13; Refractile Bodies 14; Polar Body 15; Perivitelline Space 18; Zona Pellucida 20
4. The Sperm 25 Anitha S Kumari K, Dileep Kumar R, Hemanth Kumar MA
Sperm Count and Motility 26; Sperm Morphology 27; Sperm Viability 28; Sperm Viability by Hypo-osmotic Swelling Test 29; DNA Fragmentation Index 30
5. Normal Embryo Development 31 Bezar Ghan VV, Divyashree PS, Kamini A Rao
Pronuclear Stage 32; Syngamy 32; Two-cell Stage 33; Four-cell Stage 33; Eight-cell Stage 34; Compaction 34; Early Blastocysts 35; Expanded Blastocysts 35; Hatching Blastocysts 36; Hatched Blastocysts 36
6. Embryo Scoring 37 Bezar Ghan VV, Divyashree PS, Anitha S Kumari K
Symmetrical Pronuclei 37; Nonsymmetrical Pronuclei 39; Abnormal Pronuclei 40; Two-cell Grade 1 Embryos 42; Two-cell Grade 2 Embryos 43; Four-cell Grade 1 Embryos 44; Four-cell Grade 2 Embryos 45; Four-cell Grade 3 Embryos 46; Eight-cell Grade 1 Embryos 47; Eight-cell Grade 2 Embryos 48; Eight-cell Grade 3 Embryos 49; Grade 1, Day 4 Embryos 50; Grade 2, Day 4 Embryos 51; Grade 3, Day 4 Embryos 52; Early Blastocyst 54; Blastocyst 57; Expanded Blastocyst 58; Hatching Blastocysts 61; Hatched Blastocysts 62
7. In Vitro Fertilization/Intracytoplasmic Sperm Injection 64 Bezar Ghan VV, Divyashree PS
Oocyte Insemination in IVF 64; Intracytoplasmic Sperm Injection 65
8. Advanced Techniques 74 Anitha S Kumari K, Bezar Ghan VV, Divyashree PS, Dileep Kumar R, Anu Kottur, Kamini A Rao
Physiological Intracytoplasmic Sperm Injection 74 Anitha S Kumari K, Bezar Ghan VV, Divyashree PS
Picsi Dish 74
Contents
Volume 3 Atlas of Human Embryology
xvi Volume—3 Atlas of Human Embryology
Intracytoplasmic Morphologically Selected Sperm Injection 76 Bezar Ghan VV, Dileep Kumar R, Anitha S Kumari K , Divyashree PS
Poloscopy 77 Divyashree PS, Bezar Ghan VV, Anu Kottur
Time-lapse Imaging 80 Divyashree PS, Anitha S Kumari K, Bezar Ghan VV Laser-assisted Hatching 83 Bezar Ghan VV, Divyashree PS, Kamini A Rao
9. Cryopreservation 86 Bezar Ghan VV, Anitha S Kumari K, Divyashree PS
Cryopreservation of Oocytes 86; Cryopreservation of Embryos 94; Blastocyst Cryopreservation 104; Blastocyst Warming 107
10. Assisted Reproductive Technology Lab Setting 112 Divyashree PS, Hemanth Kumar MA, Dileep Kumar R
Essential Equipment of ART Lab 112; Laminar Flow Cabinets 113; Incubators 114; Essential Equipment for Clinical Procedures 121
Index 133