Nova IVI Textbook of Infertility and Assisted Reproductive Technology Sulbha Arora, Manish Banker, Sneha Sathe, Ritu Hinduja, Richa Jagtap
INDEX
Page numbers followed by f refer to figure, fc refer to flowchart, and t refer to table.
A
Abdominal pain 618
mild 276
moderate 276
severe 277
symptomatic relief of 276
Abortion 752
counseling 753
late spontaneous 653
recurrent spontaneous 63
repeated 49
risk of 223
spontaneous 708, 733
Acanthosis nigricans 239, 296
Acetaldehyde 226, 549
Acid 326
fast bacilli, microscopic examination of 620
phosphatase 76
Tyrode's solution 571
Acne 252, 253
Acquired immunodeficiency syndrome 617
Acrosome reaction 195, 447, 482
test 199
Adenomas 311
Adenomyoma 100, 100t, 612
cystic 612
endocervical 612
focal 607f
Adenomyomectomy, partial 612
Adenomyosis 605, 607, 609612, 614, 650, 652, 653f, 656
alternative therapy for 611
complete excision of 612
cyst of 653f
cystic 612
diagnosis of 611
influence of 656
management of 611
pathognomonic signs of 611
T-shape secondary 653f
typical signs of 610
Adenomyotic
foci, adenomyotic 612
structures, cystic 612
tissue, inadequate excision of 612
uteri, myocytes of 609
Adhesiolysis, hysteroscopic 96
Adhesion syndrome 650
Adipocytes, abdominal 290
Adiponectin gene 243
Adipose
cells 259
tissue dysfunction 247
Adiposity 610
Adjuvant androgens, randomized controlled trial of 347
Adjuvant therapy 286, 345
targeting glucose metabolism 354
Adnexa 699
Adnexal masses 23, 621
Adnexal torsion 433
Adnexal tumescence, unilateral 646
Adoption 756758
causes of 762
sounds 757
Adrenal androgen-secreting tumors 252
Adrenal glands 246
Adrenocorticotropic hormone secretion 131
Adrenogenital syndrome 131
Agenesis 643
Agglutination, type of 444
Air fluid method 509f
Air quality 731
Albumin 278, 457
Albuterol 279
Alcohol consumption 256
Alkylating agent 415, 743, 745
Allergic reaction 214
Allis tissue forceps 203
Alpha receptor 583
Amenorrhea 48, 311, 312, 314, 634
hyperandrogenic 176
hypogonadotropic 176
hypothalamic 176, 180
American Association of Clinical Endocrinologists 293
American Fertility Society 641f, 642, 643
Classification 643t, 644f, 654f
American Heart Association 293
American Society for Reproductive Medicine 73, 144, 237, 263, 275, 296, 305, 306, 308, 347, 370, 557, 576, 638, 664, 676, 679
Medicine Guidelines 773
American Society of Clinical Oncology 347, 746
American Thyroid Association 303, 305, 306, 308
American Urological Association 72, 144, 155
Amino acid 327, 489, 491
essential 495f
nonessential 495f
serine 326
Amitriptyline 311
Amniocentesis, use of 740
Amphiregulin 380
Anaphylactic reactions, occurrence of 214
Anastrozole 175, 321
dose of 321
Androgen 132, 239
addition of 347
aromatization of 379, 390
binding protein 3
biosynthesis 246
desensitize hypothalamus, concentrations of 247
excess 246, 296
signs of 23
Society 238, 289
levels, estimation of 239
precursor dehydroepiandrosterone 379
receptor gene 244
supplements 28
synthesis, dysregulation of 246
Androgenization 389
Andrology laboratory 548, 550, 556
future of 84
Androstenedione 303f, 369, 379
conversion of 263
Anejaculation 52, 53, 139
iatrogenic 200
on-demand 125
total 125
Aneuploid 706
chromosome, detection of 716
conceptions 708
embryos 718
sperm, incidence of 718
Aneuploidy 502
prevalence of 719
rate 353
studies 544
Angiogenesis 608
Anogenital distance 154
Anorgasmic anejaculation 125127
etiology 126
Anovulation 262
Anovulatory disorders 185
Anovulatory infertility
causes of 266
management of 266, 271
Antagonist protocol 334, 340
Antegrade ejaculation, failure of 52, 53
Antegrade propulsion 126
failure of 126
Anthracycline antibiotics 663
Antibiotics 257, 493
Antibodies
polyclonal 328
tests for 81
Anticardiolipin antibodies 689
Anti-Chlamydia trachomatis antibodies 678
Anticoagulants 701
Antidepressants 53
tricyclic 311
Antiestrogen 132, 323
clomiphene citrate 256
Antiglobulin reaction, mixed 81
Antihypertensive drugs 21
Antimetabolite 663, 744
cancer drug gemcitabine 663
Anti-Müllerian hormone 3, 37, 95, 210, 253, 271, 344, 383, 405, 417, 594, 639, 663, 679, 687
levels 424
low 337
ovarian markers like 663
Antinuclear antibodies 15, 698
Antioxidant 132, 133, 257, 259, 491
defense capacity, natural 122
properties 122t
therapy 122
oral 122t
Antiphospholipid
antibody 678
prevalence of 699
screening of 689
syndrome 14, 15t, 688, 691
Antiprostaglandin 134
Antipsychotics 311
Antiretroviral agents 777
Antiseptic solution 203
Antisperm 678
antibody 15, 73, 82, 139, 215, 677
assay 81
formation of 444
tests for 73, 82
Antithrombin deficiency 689, 714
Antithrombotic agents 691
Antithyroid peroxidase antibody 699
Antral follicle 6, 291, 663
count 37, 104, 337, 344, 383, 403, 405, 417, 424, 663, 679
evaluation of 351
single cohort of 416
small 352
Antrum 6
formation requires 324
Anuria, severe 277
APLA syndrome 15
Apoptosis
remarkable degree of 611
typical of 198
Apoptotic sperms 199
Appendicitis 274, 631, 634
Arcuate uterus 646
incidence of 645
ultrasound of 642f
Aromatase inhibitors 132, 174, 189, 263, 320, 322, 389, 390, 611, 666, 680
advantages of 320
adverse effects 175
dosage 175
extended letrozole therapy 175
letrozole step-up protocol 175
use of 664
Aromatic amines 139
Aromatization 6, 7fc
Array comparative genomic hybridization 528
Arterial blood gas measurements 279
Arteries 371
Arthritis, gonococcal 636
Artificial endometrial preparation 398
Artificial insemination 207, 223, 744
applicable 772
catheter 204, 651
consent for 221, 222, 771
Artificial orifice 524
Artificial reproductive techniques 55, 195
Ascites 275, 618
decreases, removal of 277
drainage of 277
ultrasound evidence of 276
Ascitic fluid 618
tapping 618
Asebir classification 502t
Asherman's syndrome 47, 48, 51, 105, 618, 624, 699
Asparagine, group of 326
Aspermia 80, 116, 443
Aspirin 347, 412, 695
low dose 701
Assisted hatching 570, 571, 573, 764
methods 571
role of 570
timing 573
Assisted reproductive technology 36, 57, 58, 72, 86, 89, 99, 120, 130, 134, 144, 147, 181, 212, 219, 220, 258, 276, 283, 304, 306, 334, 359, 370, 371, 403, 408, 420, 439, 456, 489, 511, 515, 552f, 561, 570, 624, 626, 650, 664, 571, 672, 763, 770, 771, 773, 776, 783
application of 283
clinics 220
culture media 491
design of 548
field of 770
regulation 764
results 472, 473, 474
safety in 776
services 225
success of 338
treatment 751
Asthenoteratozoospermia 80, 446
Asthenozoospermia 71, 80, 115, 117, 130, 134, 138, 167, 198, 201, 446
Atraumatic grasper 268f
Atretic follicles, amount of 562
Atrophy 71
Autografting cryopreserved-thawed ovarian cortical tissue 665
Autoimmune disease chemotherapy, severe 743
Autoimmune disorders 14, 15
Automatic pipettes 228f, 550
Autonomy
legal recognition of 780
principle of 776
Autosomal dominant inherited disorder 667
Autosomal homolog 713
Autosomes 706
Azoospermia 47, 52, 54, 55, 71, 80, 116, 117, 139, 146, 152, 154, 161, 167, 208, 446, 708, 713
classification of 153t
clinical diagnosis of 155t
diagnosis of 152
epidemiology 152
etiological classification 152
evaluation of 152, 153
factor 712, 712f
regions 156
management of 152, 156
nonobstructive 139, 146, 152, 208, 709
nonobstructive 152t
obstructive 47, 52, 139, 160, 163, 208
operative procedures for 160
physical examination 154
reconstructive surgery 160
surgical management of 157, 160
treatment of 156
Azoospermic population 156
B
Bacillus calmette-guérin 621
Balance low pregnancy rates 778
Basal body temperature 32
method 209
monitoring 33
Basal glucose 293
Basal hormonal levels 54t
Basalis layer 10
Baseball suturing, second layer of 94f
Basement lamina 6
Benchtop centrifuge 226
Benzene 154, 226, 549
Best stimulation protocol 403
Beta-thalassemia 209
Bevacizumab 744
Bicornuate 644
bicollis 644
unicollis 644
uterus 642f, 644, 646, 655f, 699
incidence of 644
surgical correction for 646
Bilateral distal isthmic obstruction 621
Biochemical analysis 618
Biological cell functions 257
Biopsy
embryos, method for cryopreservation of 532
of testis, tru-cut needle 162
procedures 526
types of 531t
Biosimilar product, treatment using 330
Birth control pill 345
Birth defects 733
rates of 733
Birth weight
high 739
low 397, 398, 579, 696, 735
Bladder
endometriosis 598f
neck
closure 126
dysfunction 443
surgery 200
neurologic impairment of 597
psoas hitch 601
resection, segmental 601
Blastocoelic fluid 720
Blastocyst 395, 526, 572, 573, 671, 773
artificial collapse of 521
cavitating 506, 506f
collapse, duration of 536
development, effect of 521t
early 506f, 521
expansion, duration of 536
for transfer globally 500
formation 537t
rate 538
morphology 545
percentage of optimal 539
resultant 495
scoring 504
stage 517
transfer 511
trophectoderm 524
vitrification, result of 520
Blastomere, 501, 531
biopsy 528, 529f
technical aspects of 528
compaction of 500
number of 501
remain totipotent 529
shape of 502
size of 502
small 503
Bleeding 404
intermenstrual 584
Bleomycin 744
Bloating, abdominal 276
Blood 32
borne malignancies 418
count, complete 278
flow, compromising 277
natural killer, peripheral 671
pressure 23, 293, 294t
diastolic 293, 294
tests, routine 621
Blunt biopsy needle 573
Body adiposity, upper 291
Body mass index 23, 132, 189, 243, 257, 262, 290, 293, 297, 338, 403
normal 267
Bollywood-styled adoptions, temptation of 758
Bone marrow transplant 743
Bovine pituitary 562
Bovine serum albumin 215
Brain 246
Breast
cancer 295, 415, 743, 747
combination 743, 744
examination 23
secretions 23
Bromocriptine 313, 314
Bronchiectasis 20, 153
Brucellosis 52, 621
Buffer, types of 231
Bulbocavernosus muscle 127
Bulbourethral glands 3
Buserelin 336, 340
Busulfan 415, 562, 743, 744
Butyrophenones 311
C
Cabergoline 176, 313, 314
therapy 313
Calcium 76, 529
and mitogen-activated protein kinases 378
channel blockers 154, 311
gluconate 279
ionophore 123
Calpain-10 gene 244
Cancer 780
and fertility 415
and quality of life 664
colorectal 742
diagnosis of 742
drug therapy 742
gynecological 662, 666
therapy 415
treatment of 742
types of 781
Candidate Gene Association Studies 243
Capacitation 729
Cara steering committee, member of 762
Carbohydrate 294t, 491
moieties 377
N-acetylgalactosamine 326
Carbon dioxide 196, 494, 549
Carboplatin 744
Carcinoma, embryonal 662
Cardiovascular disease 253, 289, 289f, 292, 297
risk of 256
Carmustine 744
Carnitine 133
Carnoy fixative 530
Carotenoids 133
Carotid intima-media thickness 294
Caspase activation 198
Catheter
bulb, distended cavity postdeflation of 43f
choice of 204
problems of 214
types of 169, 509
Catholic christians 732
Catsperm function 123
Cavities, abdominal 274
Cefotetan 635
Ceftriaxone 635
Ceiling effect 384
Cell
apoptosis of 742
cumulus 478
dehydration 460f
disruption of 742
division 502, 503f
electrophoresis assay 121
embryo 505f
free nuclear deoxyribonucleic acid, presence of 720
mass
quality of inner 534
total 8
number 501, 529
pre-equilibration of 457
removal 531
volume regulation 491
Cellular atoms, ionization of 742
Centers for Disease Control and Prevention 27, 635, 693
Central Adoption Resource Authority 758
Central nervous system 21
Centrifuges 549
Centromere 707
Cervical
abnormality 23
anomaly 644
aplasia, unilateral 644
atrophy 48
canal 214, 643f
cancer 47, 48, 665, 742
early stage 665
conization 678
discharge 634
factor infertility 168
incidence of 168
mild 186
fibroid 48, 49
hostility 220
insufficiency 699
intraepithelial neoplasia, treatment of 699
level 320
lymph node enlargement 619
mucus penetration test 449
stenosis 47, 205
congenital 48
surgeries 23
trauma 699
Cervicitis, chronic 48, 678
Cervix 32, 47, 100, 214, 618, 678
after surgery, stenosis of 188
anatomical distortion of 47
anatomy of 508
conization of 48
hypertrophied 48
Cetrorelix 336
Cetuximab 744
Chemical toxins 22
Chemotherapeutic Drugs Act 662
Chemotherapy 71, 415, 662, 743, 743t, 745
alkylating agent 743, 744
platinum-based 663
types of 663, 663t
Chest
examination 23
wall lesions 311
X-ray 621
Chlamydia 52, 131
trachomatis 131, 632, 696
antibodies 185
Chlamydial infection 635
Chlorambucil 743, 744
Chlorhexidine 651
Chlorine 76
Chlormethine 744
Chlorpromazine 311
Cholecystitis 634
Cholesterol
high-density 293
total 291
Choriocarcinoma 662
Choriogonadotropin
alpha 181
receptor 359
Chorionic basal plate 735
Chorionic deciduitis, incidence of 735
Chorionic gonadotropin 325, 329
Chromatin decondensation test, nuclear 700
Chromatography radioimmunoassays 239
Chromopertubation 87f
laparoscopic 208
Chromosomal abnormalities, sex 708, 709
Chromosomal aneuploidy 677, 719
detection of 716, 720
Chromosomal translocations 708
Chromosomally abnormal embryos, higher percentages of 718
Chromosome 718
abnormalities 709
aneuploidies 716
derivative 707
heteromorphisms 709
inversions 707
screening 671
comprehensive 397
sex 706, 718
translocation 707
trisomies of 705
Chronology 527, 529, 530
Cimetidine 20, 28, 53, 154, 311
Circumference, abdominal 277, 293
Cirrhosis 311
Cisplatin 744
impact 663
Citric acid 76
Cleavage stage 526
embryo 501, 511, 572, 573, 773
biopsy methods 526t
Clindamycin 635
Clomiphene 192, 211, 263, 271, 322, 680
citrate 95, 168, 173, 174, 189, 209, 262, 266, 283, 319, 320, 322, 373, 421, 422f, 423f, 430f, 683
challenge test 37
efficacy of 189
regimens of 173
treatment, failure of 174
Cloning 770
Coelomic epithelium 662
Cogwheel appearance 626
Coital and deposition problem 47, 53
Coital frequency 23
and timing 22
Colchicine 154
Collin's knife 647f, 648f
Colon cancer 747
Color Doppler ultrasound classification 144
Colorectal resection 602
Colposcopy 48
Colpotomy 636
Comet assay 82, 83
Complex tissue culture media 490
Computer assisted semen analysis 73, 84
Conservative surgery 89
Continuous suturing, first layer of 94f
Contraception, previous methods of 23
Contraceptive pills 406
Controlled ovarian
hyperstimulation 111, 180, 192, 319, 322, 415, 576
aim of 189
stimulation 169, 329, 361, 377, 395, 418, 520, 679
cycles of 188
Conventional cytogenetic methods 711
Conventional staining method 620
Cook soft-pass artificial insemination catheter 204
Copper 134
Core pluripotency network, member of 561
Corifollitropin alpha 329, 345, 346, 406
Corpora lutea 359
Corpus luteum 8, 302f, 368
observation of 33
rescue of 335
survival 380
Cortical tissue cryopreservation 747
Corticosteroids 176
Cotrimoxazole 131
Counselling, types of 218
Coxsackievirus 696
Craniopharyngioma 311
C-reactive protein 292, 294
Creatinine 420
Cremasteric veins 144
Cross-border reproductive care 763, 764, 768
advantages of 765
disadvantages of 766
incidence of 763
Cryopreservation 221, 338, 556, 764
costs 399
methods 460t, 516
programs 521
protocol 201
role of 515
techniques for 457, 518
Cryoprotectants 456, 457
concentration of 355, 515
Cryostorage units 548
Cryosurgery 48
Cryotanks 550
Cryotop system 521
Cryotransfers 517
Cryptorchidism 28
Cryptozoospermia 80, 116, 117, 198, 446
Crystalloids 278
Cul-de-sac masses 23
Culture media, components of 214
Cusco's bivalve vaginal speculum 203
Cushing syndrome 28
Cut-off reference values 78
Cycle segmentation, policy of 355
Cyclic adenosine monophosphate 134, 324
Cyclophosphamide 415, 562, 663, 743, 744
Cyproterone 154
Cyst
adenomyotic 612
aspiration 592
laparoscopic 592
development 404
formation 337
intramyometrial 610
laterality of 595
wall
ablation of 592
bulging of 91f
enucleation of 91f
Cystectomy, laparoscopic 592, 595
Cystic fibrosis 14, 52, 209, 678
gene mutation 13, 14
transmembrane 14
conductance regulator 52, 73
Cytocompatible scaffolds, use of 564
Cytokine 57, 583
expression of 380
secretion 62
Cytomegalovirus 696
Cytoplasmic
anomalies 504
droplets 446
inclusions, membrane-bound 479
pitting 504
ring 504
transfer 764
Cytoreductive surgery 611, 612
Cytosine arabinoside 744
Cytotoxic drugs 22
depress sperm density 20
D
Dactinomycin 744
Danazol 611
D-chiro-inositol 258, 321
De novo deoxyribonucleic acid 561
Decellularized human testicular tissue 564
Deep endometriosis, impact of 599
Dehydration, effective 280
Dehydroepiandrosterone 239, 256f, 347, 389391
levels, high 176
sulphate 256f
levels of 321
Dehydrogenase, hydroxysteroid 379
Delhi Artificial Insemination (Human) Act 772
Delivery rate, cumulative 517f
Density gradient 197, 201
advantages of 197
centrifugation 186
disadvantages of 197
technique 197f
Deoxyadenosine 138
Deoxynucleotidyl transferase 121
mediated deoxyuridine triphosphate 474
terminal 121
Deoxyribonucleic acid 121, 129f, 198, 200, 447, 459, 461, 469, 677
cryopreservation on 460
damage 460t
direct tests 448
indirect tests 449
origin of 121
fragmentation 123
index test 448
integrity, techniques based on 474
nuclear 544
technology 330
Depression 218
Dexamethasone 176, 319, 321, 347
Dextrans 457
Diabetes 26, 28, 53
gestational 296, 740
mellitus 22, 53, 200, 286, 289f, 291, 292t, 293, 297
Diabetic neuropathy 200
Diathermy 267
Dichlorodihydrofluorescein 122
Dichlorodiphenyltrichloroethane 139
Didelphys 644, 646
Diethylcarbamazine 131
Diethylstilbestrol 20, 641f, 643
Diffuse immunohistochemical expression 666
Digestive endometriosis 600f
Dihydroethidium 122
Dihydrotestosterone 155
Dimeric glycoprotein 360
Dimethyl sulfoxide 457
Diploid cells 706
Discordant mosaicism rates 716
Distal fenestration 629
Diuretics 278
Diverticulitis 634
Dizygotic gestations 574
Dizziness 277
Dominant follicle 417
selection of 7
Domperidone 311
Donor gametes 770, 773, 774
screening of 776
use of 774
Donor insemination 135
legal and ethical concerns of 219
option of 208
Donor oocyte 672
cycles 737
Donor semen 200
samples 465
Donor sperm 771
cryopreserved 733
insemination 207209
mandatory quarantine of 207
sample, placement of 207
use of 223
Donors
anonymity of 764
duties of 223
information of 774
rights of 223
selection, rules for 222
Dopamine 310
agonist 133, 313, 314t
receptor blockers 311
synthesis inhibitors 311
Douglas cul-de-sacs 650
Down's syndrome 706
Doxorubicin 663, 743, 744
Drug-resistant tuberculosis, diagnosis of 621
Dubin grading system 144
Ductal system 52
Dye exclusion assays 447
Dyschezia 597
severe 597
Dysfunctional uterine bleeding 266
Dysgerminoma 662
Dyslipidemia 240, 246, 296
Dysmenorrhea 48, 320, 591, 597, 611, 618, 638
Dyspareunia 591, 597, 634, 638
Dyspnea 277
Dysuria 584, 597
E
Earle's balanced salt solution 489
Ecosystem 762
Ectopic endometrial glands, presence of 605
Ectopic pregnancy 215, 223, 274, 634
development of 646
rate 330
Edwards’ syndrome 706
Efficient embryo cryopreservation program 521
Egg donation 764
program 403
Egg donor 396
program 403
treatment 736
Egg yolk citrate 457
Ehlers-Danlos syndrome 699
Eicosanoids 8
Ejaculation 21
failure, managing 125
premature 53
problems 167, 220
retrograde 52, 53, 126, 127, 134, 200
unexpected failure of 125
Ejaculatory disorders 52, 53
Ejaculatory duct 3, 710
obstruction 52, 161
traditionally transurethral resection of 52
transurethral resection of 161
Ejaculatory dysfunction 28, 47, 52, 153, 169, 188
Ejaculatory failure 169
Elective single embryo transfer 397
Electric charge, techniques based on 475
Electrocardiogram 278
Electrocoagulation, laparoscopic 612
Electroejaculation 126, 127, 169, 200
Electrolytes 275, 278
imbalance 277
Electron microscopy, scanning 60
Electrophoresis separation 475
Electroporation 138
Electrosurgical incision, consists of 647
Embracement, feeling of 750
Embryo 221, 395, 398, 411, 417, 503f, 505f, 664, 672, 687, 781
accurate selection of 500
adoption 738
biopsy and tubing 524
chemical 525
laser 525
mechanical 525
cryopreservation of 745, 782
cryopreserved 356
numbers of 393
culture 489
media, evolution of 489
cytokinesis 544
deposition 509
development, technology for 534
donation 732, 738, 753
freezing of 355, 747
grouping and oil overlay 494
implantation 480, 539, 584
rate 484
in vitro 494
kinetics 544t
loading 509, 509f
manipulation 731
mosaicism, potential impact of 716
per dish 535
ploidy 544
quality 362, 480, 481t
safety of 531
selection 500, 508, 778, 780
stage 395
storage of 745, 770, 773
to transfer, number of 510
toxins, mask potential 489
transfer 60, 345, 400, 410, 500, 507, 508, 519, 570, 578, 672, 689, 690
cycles, natural frozen-thawed 191
day of 752
ease of 508
personalized 64
procedure, pregnancies per 578
single 510, 534, 673, 778
transferred, numbers of 393
use of 220
vitrification 285, 287, 520, 563, 577
Embryology 112
Embryonic
defects 677
like stem cells, small 563
mosaicism, presence of 716
trophectodermal cells 570
Embryoscope 544
system 487f
Empirical therapy 131
Empty sella syndrome 311
Encephalopathy diseases, transmissible spongiform 327
Endocervical
canal 214
infection, presence of 631
polyps 214
uterus 214
Endocrine
control 326
dynamic tests 36, 37
environmental 247
evaluation 53, 54
factors 693
Society 305, 306
static markers 36
Endocrinological disorders, different types of 262t
Endocrinopathy, signs of 154
Endodermal sinus tumor 662
Endogenous gonadotropin 319
secretion 177
Endometria 656
Endometrial advancement 363, 370
Endometrial biopsy 33, 66, 296, 369, 666, 678, 689
utility of 679
Endometrial cancer 47, 48, 295, 662, 666
majority of 662
Endometrial carcinoma 175
conservative management of 666
Endometrial cavity 50f, 184, 187, 214, 583, 612
Endometrial damage 618
Endometrial disease, absence of 624
Endometrial echogenicity 102f
Endometrial embryo interaction 687
Endometrial factor 671
personalization of 690
Endometrial function 609
Endometrial histology 620
Endometrial hyperplasia, risk of 266
Endometrial implant
ablation of 90f
with scissors, excision of 89f
Endometrial inflammation 584
Endometrial level 320
Endometrial lining 189
ciliary movement of 631
Endometrial maturation 369, 370
premature acceleration of 353
Endometrial microbiome 66
Endometrial midline 103f
Endometrial myometrial interface 100
Endometrial polypectomy 690
Endometrial polyps 51, 96, 96f, 214, 240, 341, 687, 699
Endometrial preparation 11, 530, 735
Endometrial receptivity 181, 353, 363, 368, 577, 689, 690
analysis 690
array 11, 61, 64t, 65t
diagnosis of 58
Endometrial steroid receptors 369
Endometrial thickness 180, 190, 341, 369, 412, 577
assessment 180
measurement of 101f
trilaminar 180
Endometrial transcriptomics 63
Endometrial transformation, secretory 371
Endometrioid carcinoma, standard treatment for 666
Endometrioma 90, 591595, 781
bilateral 90f, 595
diagnosis of 591
impact of 593
management of 592
number of 595
rupture of 593
size of 595
surgical treatment for 595
unilateral 594
Endometriosis 47, 48, 51, 86, 89, 92f, 168, 179, 185, 591, 650, 651, 781
advanced 773
colorectal 599
deep 599, 601, 602, 650
infiltrating 92
early stage 192
features of 591
intraperitoneal 599
mild 89, 361, 423f, 426, 89, 593
minimal 89, 322
to mild 167
moderate 90
presentation of 591
progression of 593
severe 90, 179, 602
signs of 679
symptoms of 679
Endometriotic
cyst
nature of 595
ruptured 634
lesions, extensive laparoscopic excision of 599
nodules, location of 597
tissue 611
Endometritis
chronic 66, 687
combination of 631
Endometrium 10, 32, 33, 57, 100, 105, 107, 340, 368, 369, 411, 609, 689
advanced 353
after secretory phase, fate of 10, 11fc
evolution of 58f
functional capacity of 735
insensitivity of 735
layers of 10
myometrium
interphase 652
junction 652
nonreceptive 687
non-stimulated 398
preparation 368
method of 398
secretory transformation of 368
to progesterone, preovulatory exposure of 371
transcervical resection of 612
Endometroid 662
Endomyometrial resection 612
Endoplasmic reticulum
mitochondria 478
smooth 479, 500
Endosalpingitis 632
Endoscopy, role of 86, 622
Endothelial cells 10
Endothelial dysfunction markers 292
Endothelial like growth factors 379
Enoxaparin sodium 279
Enzyme-linked immunosorbent assay 73
Eosin-Nigrosin stain 81
Eperm morphology, evolution of 445
Epiblastic cells, potential of 560
Epidermal growth factor 327, 380
Epididymal sperm aspiration, microsurgical 135, 161
Epididymis 3, 21, 154, 441, 710
enlarged adherent 131
portions of 710
Epididymitis 28, 52, 618
Epididymo-orchitis, chronic 131
Epileptic seizures 311
Epiregulin 380
Epirubicin 743
Epithelial cell adhesion molecule 564
Epithelial ovarian cancer, subtypes of 662
Erectile dysfunction 28, 52, 53, 167
Erlotinib 744
Erythrocyte sedimentation rate 635
Erythromycin 28, 131
Escherichia coli 131, 632
Estradiol 37, 191, 213, 324, 362, 368
addition of 346
concentrations 369
level 177, 326, 370
premature feedback of 213
serum levels, determination of 191
valerate pretreatment 404
Estrogen 57, 310, 390
administration 410, 411t
assays 34
receptor
alpha 583
modulator, selective 585, 611
reduced 369
sensitive cancers 665
start and stop 410
transformed into 389
Estrone-3 glucuronide 34
Ethambutol 623
Ethics Committee Opinion of American Society for Reproductive Medicine 735
Ethylbenzene 154
Ethylenediaminetetraacetic acid 459f, 492
Euploid blastocyst 545
transfer 716
Euploid embryo 364, 544, 688
high percentage of 688
European Academy of Andrology 714
European Group for Study of Insulin Resistance 293
European Recombinant Human Luteinizing Hormone 381
European Society for Gynaecological Endoscopy 643, 644t, 645f, 654f
European Society for Human Reproduction and Embryology 190, 237, 296, 396, 643, 644t, 645f, 764
classification 654f
Guidelines 225, 548
Multicentre Trial 682
European Thyroid Association 305, 306, 308
Euthyroid status 208
Exercise, types of 257
Exogenous follicle-stimulating hormone 576
ovarian reserve test 37
Exogenous gonadotropins, effect of 346
Exosalpingitis 632
Extracellular calcium 138
F
Fallopian tubes 40, 104, 170, 184, 469, 618
normal 111
Fast track and standard treatment trial 682, 683
Fasting
glycemia, impaired 297
insulin, levels of 244
Fat and obesity associated gene 243
Fatty acids 286, 290
Female genital tuberculosis, prevalence of 617
Female gonads 5
Female infertility 179
mechanical causes in 47
Female pronuclei, formation of 483
Female reproductive system 5
Female sterilization 87
Ferriman-Gallwey scoring 238f
Fertile couples, normal 129
Fertility 59, 116, 609, 662
genetic of 705
history 19
natural 598
preservation 415, 518, 576, 664, 737, 742, 743, 747, 780
prognosis 262
related failures 120
sparing options 665
specialists 359
treatment 736, 776
unexplained 423f
Fertilization 6, 9, 480, 577, 712, 782
and embryology Act 774
and pregnancy rates 136
assessment 483, 500
failure of 136
initial stages 480
microassisted 135, 137
process 136, 138, 682
rates 302f, 594
Fetal
cells 671
growth restriction 671
hypoxia 246
loss 715, 743
late nonrecurrent 714
malpositions 653
Fetotoxicity 175
Fetus, neurodevelopment of 696
Fever, low grade 618
Fibrillin-3 gene 244
Fibroblast 8
growth factor receptor 3 564
Fibroids 4750, 100, 100f, 100t, 106t, 583, 699
current management of 584
degenerated 634
intracavitary 587
intramural 584
large 49
types of 584
ultrasound images of 50
Fibromas 187
Filled-by-mass technology 329
Final oocyte maturation 360, 372, 406
Fine needle aspiration cytology 635
First polar body 480, 524
First uterine pass 371
Fistulae, presence of 624
Fluid 100, 278
Fluorescence in situ hybridization 396, 527, 530, 531, 544, 716
Fluorescent staining 620
Fluorochrome-auramine-rhodamine staining 620
Fluorouracil 743, 744
Fluoxetine 311
Folate 133
Foley's catheter 105
Folic acid 286
Follicle
amount of 359
aspiration of 213
development 170, 324
monitor 191
interaction disrupts granulosa cells 324
luteinized unruptured 108
maturation, steps of 377
retrieval 530
size 187
syndrome, Empty 361
Follicle-stimulating hormone 3, 36, 72, 104, 131, 155, 173, 256f, 261, 262, 267, 302, 303f, 319, 324, 325f, 326f, 327, 328, 334, 339, 346, 359, 377, 404, 408, 410, 421, 422f, 424, 433f, 562, 570, 576, 578, 594
biosimilar 330
dose of 339, 417
injections plus intracervical insemination 190
levels 188, 208
mid-follicular 369
long-acting 329
priming, role of 577
receptor 383
recombinant 330, 338, 353
secretion 745
stimulated follicle 325
Follicular
androgenization 389
physiological basis 389
characteristics assessment 108
development 104
diameter increases 369
maturation, promoting 379
ovarian stimulation, late 417
phase 6, 170
early 13
late 13
rupture, incidence of 181
Folliculogenesis 577
defective 677
Follitropin
alpha 328, 330, 380
beta 328
Formaldehyde 226, 549
Fragile X mental retardation
gene mutation 13, 14
protein 14
Fragmentation 501, 503, 529
level of 469
Free androgen index 239
Freeze
oocytes 657
thaw 364
Freezing 201
Fresh embryo 395
transfer 399
cycles 397
Frozen
blastocyst transfer cycles 396
embryo transfer 359, 373, 398, 398t, 408
cycles 373, 397, 412
indications for 399
natural cycle 408
stimulated cycle 410
successful 408
pelvis 634
sample containers 553
semen sample, use of 744
thaw sperm preparation 200
thawed oocytes, fertilization rates of 395
Fructose 76
reflects secretory function 447
Full blastocyst 506, 506f
Fundal adenomyoma 609f, 610f
Fungal dermatitis, chronic scrotal 131
Furosemide 279
G
Galactorrhea 23, 311, 312, 314
isolated 312
Gametes
and embryos, storage and handling of 220, 222
cryopreservation of 780
development of 561
donation, guidelines for 774t
fate of 770, 773
intrafallopian transfer 136
processing of 221
sharing of 774
use of 220
Gametogenesis 32, 709
Ganirelix 181, 336
Garcia-velasco paper 390
Gas cylinders, quality of 730
Gene
disorders, single 526
expression 58f, 62
Genetic 243
abnormalities 677
alterations 154
analysis 155
counseling 778
defects 687
inherited 714
disorder 208
evaluation 55
information 733
locus, single 245
screening 395, 399, 527, 530, 531
rise in 396
tests 53, 73
provisions for 221
Genital
atrophy 611
examination 23, 154
infections 121
tract infection 131
tuberculosis 617, 618, 618t, 624, 747
Genome-wide Association Study 243, 244
Genomic hybridization, techniques of comparative 353
Gentamicin 28, 214
Germ cell 3, 662
deoxyribonucleic acid damage 133
number of 562
primary 4
specific RNA-binding proteins 713
tumor 662
mixed 662
Germ warfare 770
Germinal vesicle 576, 578
number of 259
repeated retrieval of 577
Germline mutations 667
Gestational age 397, 398
small for 398
Glands 10
accessory 441
proliferation index in 369
Glandular structure, accessory 3
Glucocorticoids 246, 347, 700
Glucose 76, 279, 291, 294
6-phosphate dehydrogenase 129f
concentration 244
fasting 296
inhibiting hepatic production of 286
intolerance 201, 253
metabolism 259
disturbances 291
tolerance
impaired 240, 289f, 292t
perform oral 296
test 296, 297
Glutathione peroxidase 449
Glycemic control, poor 28
Glycerophosphocholine 76
Glycine 457
Glycoprotein 327, 378f
hormone 377
receptor 378
Glycosylation 377
degree 360
N-linked 378f
patterns 330
single site of 377
Golgi-derived vesicles 478
Gonadal toxins 22
Gonadotoxic
effect of chemotherapy, minimizing 665
factors, elimination of 139
hormone assays 32
Gonadotropin 13, 32, 95, 133, 167, 168, 176, 177, 179, 190, 209, 211, 246, 263, 283, 284, 302f, 303f, 319, 320, 322, 324, 325, 330, 334, 351, 380t, 680, 681, 683
abnormalities 247
amount of 406
analogue stimulating test 37
appropriate dosage of 338
biosimilar 330
choice of 176
combination of 345
concentrations 369
contents, standardization of 328
conventional 322
dose of 190, 213, 322, 336, 339342, 345, 351, 353, 354, 416, 417
exogenous 271, 383, 520
extracts, use of 325
high doses of 344, 345
history of 325
improved delivery of 347
induced cycle 180
injections 335
insufficiency 329
low dose of 213, 353
mid-cycle surge of 359, 360
natural midcycle surge of 362
preparation 329, 340, 342, 380
development of 326f
principal 324
quantification of 328
receptors 173
reduction in dose of 341
regimens 176, 339
conventional regimen 176
low dose 176, 345
step-down regimen 176
releasing hormone 12, 106, 133, 173, 283, 303f, 304, 345, 403, 404, 408, 415, 424, 592
agonist 272, 283, 334, 335f, 336, 337, 360, 369, 372, 403, 406, 411, 433f, 585, 601, 611, 656
analog 179, 180, 340, 345, 354, 359, 433f
antagonist 12, 191, 213, 336, 336f, 337, 346, 353, 370, 404, 433f, 664, 735
pulses 13t
receptors in pituitary 396
release of 319
trigger 372
type of 377
requirement 336
secretion 311, 390
starting dose of 337
stimulation 209, 383
structure 325
substance 325
system, two-cell two 7, 7fc
therapy 176, 208, 324, 681
triggers, surge of 360
types of 209, 284, 327, 331, 339
use of 176
Gonorrhea 52
Granular cytoplasm 479
Granularity, severe central 480
Granules, cortical 478
Granulocyte
colony stimulating factor 412, 701
investigating role of 701
peroxidase-positive 445
Granulosa
and theca cells, present in 389
cell 8, 275, 324, 352, 368, 377379, 562
apoptosis cascade in 361
aromatase activity 310
development 347
luteinized 9fc, 347
nonmitotic 663
luteinization of 324, 360
stromal cell tumors 662
theca cells, luteinizing 360
Growth factors 492
beta pathway, transforming 363
upregulation of 380
Growth hormone 389, 393
addition of 346
Guanine 711
Guilt 218
feeling of 219
Gynandroblastoma 662
Gynecological cancers, effect of 662
Gynecomastia 28, 29, 312
Gyperthyroidism 303f
H
Haemophilus influenzae 632
Haloperidol 311
Hashimoto's thyroiditis 696
Hatched blastocyst 507f
Hatching cleavage stage embryos 573
Head defects 78, 446
Headache 312, 404, 611
Health issues, perinatal 578
Heart 246
disease, coronary 29, 257, 294
Heat 22
Heating blocks 550
Heating devices 550
Heating surfaces 550
Hematocrit 420
Hematogenous dissemination, result of 631
Hematometra 48
Hematospermia 80, 446
Hemi uterus 644
Hemizona 449
Hemoconcentration 275, 277
Hemocytometry 444
Hemoglobin 296
Hemorrhage 215, 274, 275
antepartum 398
intra-abdominal 274
Hemospermia 80, 446
Heparin 191, 695, 701
unfractionated 695
Hepatic triglycerides, levels of 291
Hepatitis B 26, 75
infection 209
virus 456
surface antigen 167
Hepatitis C 186
infection 209
virus 167, 215
transmission 186
Herceptin 663
Hereditary thrombophilia 689
anticoagulant therapy 691
risk factors 714t
Hernia, history of 71
Herpes simplex virus 696
Hiller-cell immunoglobulin-like receptors 698
Hipoprotein, high-density 291, 297
Hirsutism 23, 238, 252, 253, 291
mild 238f
moderate 238f
severe 238f
Histones, acetylation of 713
Homeostasis model assessment 291, 296
Homocysteine levels 715
Homozygotes 714
Hormonal
agents 132
analysis 155
assays 34
fluctuations 261
milieu 267
phenomenon 247
status 155t
Hormone
profile 411
replacement
cycle 410, 411
frozen embryo transfer cycle 410, 411
therapy 737
treatment cycle 410f
tests 72
Human alpha thalassemia, diagnosis of 720
Human blastocysts, produce 490
Human body, instrumentalization of 781
Human cadaveric testes 564
Human chorionic gonadotropin 181, 208, 213, 263, 274, 285, 324, 326f, 327, 329, 335f, 336f, 359, 360, 368, 371, 377, 396, 408, 417, 420, 576, 578
injection 169, 179, 205
molecules 378f
priming, role of 577
trigger 363
use of 352
Human dignity 781
Human embryo 12, 489
culture media 490
in vitro 489
Human endometrium 57
Human Fertilization and Embryology Authority in United Kingdom 772
Human functional gametes, source of 560
Human germ cell formation 565
Human gonadotropins, structural complexity of 328
Human granulosa cells, luteinized 380
Human immunodeficiency virus 26, 75, 167, 186, 456, 617, 770, 776
testing for 635
transmission 770, 773
Human in vitro fertilization, analysis of 493fc
Human leukocyte antigen 526, 689
C 698
field of 776
G 698
killer immunoglobulin-like receptor 15
typing of embryos 779
Human menopausal gonadotropin 176, 209, 264, 284, 325, 327, 330, 331, 339, 380, 390, 408, 410, 683
highly purified 345, 380
preparations 327
stimulated cycles 369
Human menotropin in antagonist protocol 390
Human neuroendocrine regulation 360
Human oocytes, in vitro maturation of 579f
Human ovarian follicular development 324
Human reproduction 75, 112
basics of 3
Human semen, components of 441
Human spermatozoa 81f, 456, 461f
abnormal forms of 79f
Human tubal fluid 489
Human uterus 638
Hybridization, comparative genomic 396
Hydrocele surgery 71
Hydrocelectomy 20
Hydrosalpinges 688
mild 628f
removal of 690
Hydrosalpinx 41f, 42f, 89, 104f, 340, 341, 621, 626, 627, 633, 651
aspiration of 629
beads-on-string sign of 627f
cogwheel appearance of 627f
follicularis 626
methods 626
pathognomonic of 626
pathophysiology of 627
results 626
simplex 626
surgical intervention for 627, 628f
types of 626
ultrasound features of 626
waist sign of 627f
Hydroureter, ureterolysis of left 92f
Hydroxyethyl 457
Hydroxylase 379
Hyperandrogenemia 238, 239, 247
Hyperandrogenism 237, 238, 240, 243, 246, 251, 252, 256, 262, 291, 352
Hypercholesterolemia 295
Hyperechogenic striations, presence of 652
Hyperferritinemia 292
Hyperglycemia 292
Hyperhomocysteinemia 292, 700, 715
Hyperinsulinemia 244, 247, 261, 262, 290, 352, 354
inhibits 247
Hyperinsulinism, secondary 289
Hyperkalemia 275, 277, 279, 352
Hyperlipidemia 29, 262
Hyperpigmentation 28
Hyperplasia 687
congenital adrenal 28, 252, 321, 390
Hyperplastic capsule 266
Hyperprolactinemia 304, 305, 310, 311, 314, 314t, 697
causes of 310, 311, 311t
clinical manifestations 311
evaluation for 313fc
laboratory evaluation 312
medication-induced 311
mild degrees of 311
physiologic causes of 310
prevalence of 304
signs of 313
symptoms of 312t
treatment for 312, 313, 313fc, 314
Hyperspermia 443
Hyperstimulation 211
chances of 209
syndrome 213
Hypertension 209, 296, 399, 400, 740
arterial 292
gestational 735
prevalence of 295
Hyperthecosis 252
Hyperthyroidism 28, 302, 308, 696
Hypertonic solution 515
Hypertriglyceridemia 292, 295
Hypoalbuminemia 285, 352
Hypoestrogenemia 396
Hypoestrogenism 404
Hypogonadism
hypergonadotropic 54, 155
hypogonadotropic 54, 176, 180, 208, 312, 381
Hyponatremia 275, 277, 352
Hypo-osmotic solution 81f
Hypo-osmotic swelling 81
test 447, 448, 700
Hypoplasia 53, 643
Hypospermia 443
Hypotension 277
postural 313
Hypothalamic infundibular nucleus 360
Hypothalamic-pituitary
adrenal axis 246
ovarian axis function 268
stalk section 311
Hypothyroidism 26, 28, 302, 302f, 305, 308, 696
prevalence of 303, 303f
primary 311
subclinical 302, 304
Hypovolemia, intravascular 275
Hysterogram
postoperative 648f
preoperative 648f
Hysterolaparoscopy 641
Hysterosalpingo-contrast sonography 699
procedure 43, 43f
Hysterosalpingogram 621, 626, 626f, 678
Hysterosalpingography 41, 42, 42f, 111, 208, 321, 631, 638
normal 41f
Hysterosalpingosonography 688, 690
Hysteroscopic evaluation 48
Hysteroscopic septectomy, effectiveness of 646
Hysteroscopic techniques 612
Hysteroscopy 51, 221, 584, 611, 646, 651, 658f, 688, 690, 699
operative 612
post excision 610f
Hysterosonography 651
I
Ifosfamide 415, 744
Ileitis, regional 631
Imatinib 744
Immotile sperms, percentage of 200
Immune cells 671
Immunoglobulin 695
intravenous 700
Implantation
failure
recurrent 62, 671, 687, 690fc
repeated 52t, 396
rate 519, 578
recurrent failure of 689
window of 57, 58f, 368
In situ hybridization assay 120
In vitro fertilization 40, 58, 88, 111, 115, 119, 125, 131, 135, 146, 161, 167, 221, 256, 257, 264, 283, 302f, 305, 306, 334, 345, 351, 404, 408, 415, 417f, 420, 472, 489, 570, 576, 593, 599, 600, 650, 664, 671, 679, 681, 683, 688, 711, 732, 744, 770, 771, 777
benefits of 600
classical 534
color Doppler in 108
conventional 136, 576
cycles
monitoring 340
stimulation protocols in 334
inception of 500
laboratory 727
troubleshooting in 727
multifollicular development for 431
natural cycles 347
program, troubleshooting in 727
treatment 181, 319
In vitro insemination 136
In vitro maturation 576, 578t, 579
In vitro spermatogenesis 564
In vitro techniques 239
Indian Council for Medical Research 220, 231, 238, 557
Indomethacin 134
Induced pluripotent stem cell 560, 561
Infections 52
Infertility 1, 19, 4749, 86, 129, 143, 239, 252, 266, 291, 302, 304, 310, 314, 583, 602, 605, 618, 676, 708, 763
baseline scan in 99
causes of 47, 130, 239, 308
counseling 750, 751
couple of 130
cytogenetic aspects of 705
duration of 22, 23, 130, 168
emotional impacts of 750
evaluation, standard 110
genetic aspects of 710
idiopathic 143
immunologic 131
incidence of 743
investigation, standard 168
management 594
psychosocial consequences of 218
mechanical causes of 47
mild male factor 167, 192
periods of 170
preoccupation with 218
prevalence of
primary 302
unexplained 676
shorter duration of 267
treatment 125, 167, 170
unexplained 110, 167, 168, 220, 361, 426, 430f, 431f, 676, 679, 682t
Inflammation
acute 678
adjacent foci of 631
low grade 352
Inguinal hernias, repair of 20, 28
Injection system 552
Inner cell mass 105f, 506, 507f, 572
Inositol 76, 286
triphosphate 378
Inseminate
regurgitation of 205
volume of 205, 211
Insemination 167
double 210
pre-ovulation 205
heavy conventional 137
number of 169
posthumous 770, 772
artificial 223
single 210
timing of 179, 181, 187, 205, 210
tips and tricks 203
wrong 770, 772
Insulin 279, 291, 294
gene 244
like growth factor 391
local synthesis of 346
production of 268
receptor
gene 244
substrate 1 244
resistance 239, 244, 246, 247, 252, 261, 262, 286, 289291, 293, 320, 321, 352, 354
diagnosis of 296t
levels of 262
sensitivity check index, quantitative 296
sensitizing drugs 258, 283
role of 256
signaling genes 244
Intensive care unit 280
Interferon-gamma release assay 621
Internal spermatic veins 144
International Consensus Classification Criteria for Antiphospholipid Syndrome 695, 695t
International Federation of Fertility Societies 223
International Federation of Gynecology and Obstetrics 584
International Societies on Screening and Treatment of Thyroid Disorders in Infertility 304
Interstitial salpingitis, chronic 633
Intestines 618
Intracellular calcium, elevation of 138
Intracervical insemination 207
Intracervical orifice 214
Intracytoplasmic sperm
injection 4, 73, 111, 119, 120, 130, 131, 138, 146, 160, 167, 195, 207, 221, 359, 392, 464f, 466f, 474, 500, 519, 527, 528, 535, 536f, 540, 561, 593, 664, 677, 681, 683, 689, 711, 733, 745, 764, 771, 779
advantages of 161
cycles 266
disadvantages of 161
embryo transfer 345
pipettes 463
treatment 186, 370
insemination 744
microinjection 483
Intrafallopian transfer procedures 136
Intrafollicular melatonin concentrations 244
Intralipid therapy 701
Intraluminal
folds, normal 44f
spread of infection, preventing 633
transfer 371
Intramuscular gonadotropins, use of 176
Intramyometrial cysts, presence of 610
Intrauterine
adhesions 96, 96f, 699
removal of 690
contraceptive device 631
growth restriction 246, 701, 743
infection 170
insemination 40, 99, 111, 118, 125, 130, 134, 165, 167, 169, 170, 173, 179, 184, 186, 188, 189, 195, 203, 207, 209, 212, 220, 222, 223, 322, 341, 361, 373, 472, 593, 677, 681, 683, 733, 771
advantages of 189
catheters 556
clinical use of 184
combination of 361
complications of 170, 212
cycles, number of 192
donor 220, 222, 223
indications for 167, 185, 220
laboratory, designing 225
medicolegal aspects of 220
outcome, factor influencing 170
posthumous 223
pregnancy complications after 215
psychosocial aspects in 218
requirements for 184
sperm preparation for 169
stimulation protocols for 173
super ovulation during 319
techniques of 203
ultrasound guided 191
malformations, acquired 699
pathologies 650, 655
Iodine deficiency, endemic 696
Iron 134
Isoform 326
profile 326, 328, 330
Isoniazid 617, 623
Italian Society for Haemostasis and Thrombosis 715
K
Kallmann's syndrome 153, 180
Kaplan-Meier
curve 517f
plotting 519f
Kartagener syndrome 28
Karyotype
abnormal 715
analysis 708
Kayexalate 279
Ketoconazole 28, 154
Killer-cell immunoglobulin-like receptors 671
Kisspeptin, role of 361
Klinefelter disease 28
Klinefelter syndrome 28, 154, 156, 705, 706
L
Labotect artificial insemination catheter 204
Lactate dehydrogenase 94
Lactobacillus 66
dominant microbiota 66
Laminar air flow
hoods 226, 553
types of 554f
Laparoscopic adenomyomectomy, robot-assisted 613
Laparoscopic monopolar needle ovarian drilling technique 268
Laparoscopic ovarian
drilling 95, 266, 267, 268f, 269f, 271, 320
complications 270
indication for 267
port placement for 268f
multi-needle intervention 267
surgery 256, 266
suspension 744
Laparoscopic salpingectomy, rules for 628
Laparoscopic techniques 612, 656
Laparoscopy 44, 221, 627, 656, 690, 699
treatment 111
use of 185
Laptop 453
L-arginine 412
Laser
assisted hatching 572
treatment 270
types of 270
Layering technique, scheme of 451f
Leiomyoma 48, 50, 610
Leprosy 621
Lesion, adenomyotic 612
Letrozole 174, 175, 177, 189, 263, 389, 390, 421, 680
dose 390
in ovulation induction 390
in premenopausal women 391
protocols 346
supplementation 346
teratogenic effect of 321, 391
Leukemia 415
inhibitory factor 560
Leukocyte 8, 62, 80
count, low 275
subtypes, multiple 469
Leukocytosis 275, 277, 352
Leukocytospermia 80, 131, 446
Leukospermia 80, 446
Leuprolide 340
Leuprorelin 336
Levaquin 635
Levonorgestrel-releasing intrauterine device 611, 666
Levothyroxine 305
Leydig cell 3
damage 742
Libido, absence of 21
Linear probe assay 621
Lipid 62
metabolisms 294t
peroxidation 122, 129f
protein complexes 458
Lipoprotein
cholesterol
high-density 240, 294
low density 291, 294
low density 7, 240, 297
Liquid chromatography 253
Liquid nitrogen 515
storage containers 553
tank 230f
Listeria monocytogenes 696
Lithium 28
Lithotomy position 203, 210
Live birth
rate 518, 521t, 673
cumulative 517f, 519, 519f
reported after fertility preservation 518t
Liver
enzymes 278, 352
elevated 277
function tests 133, 275
abnormal 277
toxicity 175
Lomustine 744
Low birth weight 398, 579
preventing 25
Low molecular weight heparin 435
Low proliferation index 369
Luminol 449
Luteal phase 6, 8, 368
after ovulation trigger 363
defect 108
prevalence of 370
deficiency 180
endometrium 104
late 13
pretreatment in 403
rescue 356
steroid level 359
support 169, 191, 210, 364, 370373
duration of 372
symptoms 363
Luteinisation
premature 180, 213
requirement for 213
time of 360
Luteinizing hormone 3, 36, 72, 95, 111, 181, 187, 256f, 261, 302f, 303f, 319, 324, 326, 326f, 327, 359, 377, 378, 378f, 379, 380t, 384, 416, 478
activity 329, 380
binds 378
disadvantages of 409
exogenous 576
hypersecretion of 267
influence of 368
levels 208
suppressed 384
metabolic function of 378
monitoring 408
occurrence of premature 353
onset of 179
physiological function of 378
prevent premature 334, 345
promotes 377
role of 331, 377, 379
structure and function of 377
supplementation 381
surge 60
Luteolysis 369
Lutropin alpha 380
Lyase activity 379
Lycopene 122
Lymph node
dissection, retroperitoneal 127, 200
malignancy 747
Lymphocyte immunization therapy 700
Lymphomas 415
Lymphovascular space invasion 665
absence of 666
Lynch syndrome 667
M
Macroadenomas 314
Macromolecules 492
Macrophages 445
Macroprolactinomas 311
Magnesium 134
Magnetic resonance imaging 49, 50, 51f, 95, 584, 610
Magnetic-activated cell sorting 196, 200, 451, 471
advantages of 200
and apoptosis 471
assembly of 199
disadvantages of 200
principle of 199f
technique 471, 472
Makler chamber 444
grid 77, 78f
Male factor
infertility 137, 167, 168
severe 120
mild-to-moderate 361
Male fertility, evaluation of 75
Male gamete 475
integrity of 195
Male infertility 53, 120, 123, 155, 179, 423f, 426, 711, 712t
best practice policy committee 147
causes of 143
diagnosis of 441
mechanical
causes in 51
factors in 52t
mild 168
practical management of 113
treatment of 134
Male reproductive
system 3
tract 445
Male seminogram reference values 118t
Male subfertility 167, 168
diagnosis of 120
Malformation 646
rate, congenital 330
Malignancy, type of 518
Mammalian cells 456
Mammalian fertilization 448
Mammalian preimplantation embryos 491
Manganese 134, 154
Marital discord 218
Marriage, consummation of 223, 770
Maryland grasper 268f
Mass
abdominal 618
spectrometry 239
Master cell bank 328
Masturbation anejaculation 126
Maternal age, advanced 693, 716
Maternal androgen, elevation of 246
Maternal-fetal
interface 671
tolerance process 671
Maturation, part of 478
Mayer-Rokitansky-Kuster-Hauser syndrome 645
Mechlorethamine 744
Medicolegal issues 770, 773
Medroxyprogesterone acetate 405, 666
Megestrol acetate 666
Meiosis, completion of 9
Meiotic progression, kinetics of 578f
Melanoma, malignant 742
Melphalan 743, 744
Membranes, preterm premature rupture of 698
Menarche, early 583
Meningioma 311
Menopause, prevention of 745
Menotropin 327, 380
Menses, spontaneous 417f
Menstrual
abnormality 49
age 36
bleeding 597, 611
cycle 62, 253
charting 32, 33
diagnosis of 59
luteal phase of 368, 664
normal 261
diarrhea 597
disorders, incidence of 291
disturbance 251, 303, 308, 311, 312f
dysfunction 239
dysuria, severe 597
history 22, 23
irregularities 240, 304, 312
phase 10
Menstruation, physiology of 6
Mercaptopurine 744
Meseguer's algorithm, validation of 541
Mesodermic epiblast phenotype expressing 561
Mesothelium 662
Metabolic derangements, complete 239
Metabolic disturbances, presence of 352
Metabolic features, management of 258
Metabolic syndrome 239, 240, 283, 289, 289f, 292, 293t
Metformin 175, 253, 258, 286, 321, 354
consisted of 321
contraindication 175
dose 175
lower cost of 321
mechanism 175
side effects 175
Methadone 154
Methotrexate 154, 663, 743, 744
Methylenetetrahydrofolate reductase 715
gene 715
mutation 689
Metoclopramide 311
Metronidazole 635
Metroplasty 646
difficulty of 646
hysteroscopic 95, 646, 699
Microadenomas 311, 314
Microalbuminuria 292
Microarray comparative genomic hybridization 690
Microdeletions 565
prevalence of 712
types of 712
Microdroplets 463
technique 464f
Microfluidic sperm sorting, techniques based on 475
Microgradients, techniques based on 475
Microinjection, midtime of 535
Micromanipulation technique 137
different 571
Micropipettes 226
Microscopes, types of 553f
Migration 12
Miscarriage 638, 696, 752
higher risk of 735
incidence of 287
rate 578
recurrent 13, 716
first-trimester 698
Mitochondria 460
Mitochondrial membrane 198
Mitogenic action 324
Mitotic nonluteinized granulose cells 663
Mock transfer 508
Molecular studies 711
Molecular test 620
Monoamine oxidase inhibitors 28
Monoclonal antibodies 744
Monofollicular growth 360, 421
Monogenetic diseases, case of 526
Monogenic disease 719
transmission of 719
Monopolar electrode 90f
Monopolar polycystic ovarian drilling needle 268
Monosomy X 705
Monozygotic twinning 573
Morphokinetic parameters 545
Morphological assessment 500
Mortality, perinatal 398
Morula stage 504
Mosaic Klinefelter condition 139
Motile sperm 138, 146
count, total 201
number of 161
organelle morphology examination 472
Motile spermatozoa 471
normal 169
Motility 76, 443
low 81
nonprogressive 77, 115
progressive 53, 77, 80
rapid 115, 444
total 53
Mouse bioassay 495
Mouse embryo assay 493, 495
Mouse embryonic stem cells, use of 560
Mouse oocytes 563
Mouse vasa homolog 563
Müllerian abnormalities 653, 657
Müllerian anomalies 640
Müllerian development 640fc
Müllerian duct 40, 639, 643, 710
abnormalities, classifications of 653
anomalies 638
complete development of 639
Müllerian fusion, incomplete 638
Müllerian malformation 650, 654
Multifetal gestation 738
Multifollicular development 359, 369, 421
chances of 320
Multifollicular recruitment, maximal 339
Multinucleation 501
absence of 542
Multiple dose protocols 336
Multiple follicle development, induction of 405
Multiple organ system failure 275
Multivitamin combinations 134
Mumps orchitis, postpubertal 28
Mycobacteria growth indicator tube 620
Mycobacterial staining 620
Mycobacterium
bovis 617
tuberculosis 52, 617
Mycoplasma 52, 328, 696
genitalium 632
Myocardial infarction 294
Myoinositol 286
restores ovulation 259
Myoma 48, 93, 588fc, 650, 651, 655, 656, 688
enucleation of 94f
intracavitary 587
intramural 587, 656
presence of 651
Myomectomy 584, 690
abdominal 588
hysteroscopic 587
laparoscopic 93, 587, 588
result of hysteroscopic 656
Myometrial architecture 609
Myometrial tissue 743
Myometrium 50f, 93f
central 644
heterogeneous 100
normal anatomy 606
physiology 606
N
N-acetyl-cysteine 134
Nafarelin 336
National Assisted Reproductive Technology 266
National Cholesterol Education Program 292
National Institute for Health and Care Excellence guidelines 73, 168
National Institute of Child Health and Human Development 237, 263
National Tuberculosis Control Programme, revised 617
Natural and stimulated cycles 368
Natural cycle
frozen embryo transfer
drawbacks of 409
modified 409
modified 409
practical challenges in 408
Natural killer cells 697
Nausea 274, 276, 279
Neck and midpiece defects 446
Necrozoospermia 80, 116118, 446
Needle aspiration biopsy of testis 162
Neisseria gonorrhoeae 632
Neodymium-doped yttrium aluminum garnet 268
Neofolliculogenesis 562, 563
Neomycin 28
Neonatal intensive care unit 398
Neosalpingostomy 628, 628f
Neubauer 226, 556
chamber 77
Neuroendocrine control 4fc, 12fc
Neuroendocrinology 12
Neurogenic
anejaculation 127, 128
failure 127
orgasmic anejaculation 127
Neurologic
impotence 134
symptoms 313
Neuropeptide 678
Neutrophil 8, 445
Next-generation sequencing 716
Nicotinamide adenine dinucleotide phosphate 129f
Nitroblue tetrazolium, amount of 449
Nitrofurantoin 20, 28, 154
Nitrogen tanks 553
N-methyl-D-aspartate 61
Nonapoptotic spermatozoa, selection of 122
Nondominant follicles 577
deselection of 379
Nonexcisional techniques 612
Nonfunctioning pituitary 311
Noninvasive preimplantation genetic testing 719
Noninvasive technique 720
Non-lactobacillus bacteria 66
Nonmotile organisms, spread of 631
Non-natural changes 395
Nonpermeating cryoprotectants 457t
Nonpolyposis colorectal cancer syndrome, hereditary 667
Nonsteroidal anti-inflammatory
agents 426
drugs 22
Nontoxic 231, 232
Nontubal infertility 136
Nontubercular mycobacteria 621
Normogonadotropic normoestrogenic 213
Normogonadotropic women 377
prognosis 384
Normo-ovulatory patients 370
Normoresponders, protocols for 334
Normozoospermia 80, 446
Novy cornual cannulation set, modified 86
Nuclear hypertrophy 609
Nucleation 503
Nucleic acid amplification test, cartridge-based 620
Nucleolar precursor bodies 483, 500, 500f, 502
Nucleotide polymorphism, single 243
Nulliparity 667
Nutritional supplements 132, 134
O
Obesity 26, 28, 29, 32, 240, 246, 291, 296, 667
Obstetric problems 215
Ocular motility disturbances 312
Office hysteroscopy 45
Office polypectomy 656
Ofloxacin 635
Oligo-anovulation 238
chronic 251
Oligoasthenoteratozoospermia 71, 80, 130, 446
management of 129
severe 200
treatment in 130
Oligoasthenozoospermia 80, 138, 446
sever 139
Oligomenorrhea 239, 311, 312, 314
Oligoozoospermia, mild 167
Oligosaccharides 326
Oligospermia 707
presence of 134
severe 52, 55, 153
Oligospermic infertility, techniques in 136
Oligoteratozoospermia 80, 446
Oligozoospermia 80, 115, 117, 129, 146, 446, 708, 713
new concept of 117
severe 201
Oligozoospermic semen 197
Oliguria 275, 277
severe 277
Omental adhesions 622
Omentum 618
Oncofertility 415
prevention of 780
Oocyte 285, 287, 395, 398, 417, 479, 480, 482, 563, 572, 745, 770
accumulation of 395
and embryo
quality 352
vitrification 515
autologous 735
chimerism, presence of 562
chromosomes 526
cluster 480
complex
cumulus 478
mature cumulus 478
consumed, total number of 517f
control fresh 517
count, optimal 362
cryopreservation 415, 664, 745, 781
mature 577
reliability of 515
superovulation 664
cryopreserve 516, 518, 781
donor 737
cytoplasm 448
denudation 530
determine number of 356
donated vitrified 516t
donation 732, 734, 735, 737, 738, 753
advent of 602
cycle 672
indication for 673
intergenerational 736
methods of 737
donor of 405, 771, 782
dysmorphism
distribution of 481t
type of 481t
elongated 479
fertilizable period of 179
freezing of 355, 746
fresh 517
in vitro maturation of 286
like cells, spontaneous formation of 563
maturation 351, 354, 356t, 359, 406, 424
induction of 354
role for 360
stage of 478
meiotic division of 526
membrane 482
normal 399, 480
number of 341, 383, 680
mature 594
retrieved 393
obtained 403
of outbred mice 490
penetration test, zona-free hamster 449
phenotype 480
phenotypic characteristics, assessment of 479
pickup 369
quality 108, 259, 578, 594
recovery 415
retrieval 363, 370, 372, 404, 418, 577
retrieved, number of 345
slow-freezed 395
storage 745
transport 8
use of cryopreserved 737
using vitrification of 518
vitrification 516, 518, 518t, 737, 747
cofacce 347
vitrified 517
with abnormal polar bodies 479
with large perivitelline space 479
with multiple abnormalities 479
with vacuoles 479
Oogenesis 5, 5fc
Oogonia 5
Oolemma 527
Oophorus, cumulus 6, 105f
Ooplasma 478
Open system device 516
Oral contraceptive 283
combined 404
pills 283, 345
Oral ovulogens
use of 322
with gonadotropins, combination of 322
Orchiectomy 20
Orchiopexy 20
Orchitis 71
Organogenesis 639
Orgasmic anejaculation 125, 126
Orthodox christians 732
Orthostatic hypotension 275
Osmolality 443
Osteoporosis 312
Ovarian androgen production, excessive 261
Ovarian biomarkers 344, 383
Ovarian biopsy 36, 38
Ovarian blood flow 38
Ovarian bursal cavity 562
Ovarian cancer 618, 662, 665
epithelial 662
types of 662
Ovarian cell dedifferentiation process 563
Ovarian cortex autotransplantation 781
Ovarian cyst 274
Ovarian drilling, techniques of 268
Ovarian dysfunction 237
syndrome of 237
Ovarian endometrioma 591, 599
impact of 593, 594
Ovarian endometriosis, effects of 591
Ovarian failure 270
iatrogenic 736
predicting age of 663f
premature 47, 270, 663
Ovarian follicle, development of 32
Ovarian follicular vascularity 36
Ovarian fragments 562
Ovarian function, preservation of 744
Ovarian hyperstimulation syndrome, severe 337
Ovarian hyperstimulation 212, 271
cycles, multifollicular 182
prevent 340
random-start controlled 664
syndrome 106, 169, 181, 211, 213, 223, 258, 266, 274, 285, 351, 352, 372, 381, 395, 396, 399, 403, 418, 420, 421, 422f, 423f, 516, 576, 680, 781
classification of 275, 420f
high risk of 359
implementation of 396
incidence of 329, 423f, 424t, 664
management of 425, 425f
mild 276
moderate 276
prevention of 384, 395, 424
risk of 239, 283, 370
severe 276, 425f
Ovarian insufficiency, premature 14
Ovarian malignancy 747
Ovarian morphology 269
abnormal 261
Ovarian pathologies 105
Ovarian reserve 36, 415, 595
tests 36, 110
Ovarian response 344, 347
poor 344, 383
strategies in high 356t
treatments in low 389
Ovarian responsiveness 594
Ovarian rupture 275
Ovarian size 277
Ovarian stem cells 561
Ovarian steroidogenesis 331
Ovarian stimulation 173, 208, 283, 284, 337, 340, 403, 404, 416, 418
cancer on 415
complications of 212
management 420
prevention 420
conventional methods of 416
drugs 403
during intrauterine insemination 322
effective 341
goal of 420
gonadotropin for 403
history of 274
oral agents for 173
progestin primed 405
protocols 353, 415
in cancer patients 416
in fertility preservation 415
regimens 405
used for 322, 339
Ovarian stroma 662
Ovarian suppressor agents 745
Ovarian surface
epithelium 563
laparoscopic electrocautery of 269
Ovarian tissue 663, 745
autotransplantation of 665
cryopreservation 577, 665
normal 271
storage 746
Ovarian torsion 215
Ovarian transposition 744
laparoscopic lateral 744f
Ovarian triggering, drugs for 403
Ovarian tumor 634
Ovarian volume 38, 252, 663
Ovary 104, 107, 618, 743
bilateral 99
reconstruction of right 91f
Ovulation 6, 8, 32
assessment of 110
causes of 8
confirmation of 105
enhancement of 421, 426
evaluation of 678
induction 168, 173, 180, 261, 262, 406, 421, 426, 680
citrate for 258
cycles 361
history of 320, 321
oral drugs for 319
predictor kits 34
process of 677
stimulation 108
time of 179
trigger 359, 361363
in ovulation induction cycles 361
Ovulatory cascade 360
Ovulatory cycle, natural 360
Ovulatory disorders 47, 262
Ovulatory dysfunction 168, 239, 361, 677
mechanism of 302
Ovulatory follicle
collapse of 33
selection of 213
Ovulatory function, assessing 32
Ovulatory hormone replacement therapy cycle 411
Ovulatory infertility, causes of 261
Ovulatory menstrual cycle, endometrial changes during 10
Ovulogens, oral 167, 319, 322
Ovum
donation programs 516
from fallopian tubes 33
pick-up, day of 752
Oxaliplatin 744
Oxidation-reduction potential, measurement of 82
Oxidative stress 82, 122, 678
analysis, clinical application of 122
Oxygen
concentration 493
percentage of 549
P
Pain
abdominal 634
radiation of 597
relief 276
Pap smears, abnormal 23
Paracentesis 277, 279
Paracentric inversions 708
Paracrine
changes 353
factor 379
mechanisms, presence of 583
Para-mesonephric origin 638
Paraovarian cyst 634
Partial thromboplastin time, activated 278
Patau's syndrome 707
Pellet 450
Pelvic
abscess 631
drainage of 636
adhesions 47, 51, 651
endometriosis 634
examination 619
extraovarian endometriosis 597600
infection 47, 274
inflammatory disease 23, 40, 86, 631, 632, 636
acute 632, 634
chronic 618, 633, 634
clinical manifestations of 633
etiology of 632
five stages of 632t
lymphadenectomy 665
pain 49
chronic 591, 618
peritonitis 631
radiation therapy 415
surgery 28
tenderness 23
ultrasound 275
three-dimensional 698
Penicillin 214
Penile lesions 29
Penile vibratory stimulation 169
Pentoxifylline 134, 138
Percutaneous epididymal sperm aspiration 52, 135, 158f, 161, 456
Percutaneous testicular sperm aspiration 158f
Perfusion scans 279
Pergolide 314
Pergonal treatment 325
Pericentric inversions 708
Periconception 25
Perifollicular blood flow 108f
Perifollicular vascularity 187
Perihepatitis 631
Periovarian adhesions 270
Periovulatory anejaculation 125
Perisplenitis 631
Peritoneal carcinomatosis 622
Peritoneal signs 277
Peritoneal tuberculosis 622
Peritoneal tubo-ovarian pathology 651
Peritonitis 632
Peritubal adhesions 677
Perivitelline space 526
Peroxidase staining 445
Peroxisome proliferator-activated receptors 243
Persistent anxiety 218
Personalizing protocol 337
Personnel management 231, 557
pH test paper 556
Phenothiazines 28, 311
Phenylephrine 127
Phenylketonuria 26
Phenytoin 154
Phosphatidylserine 198
externalization of 123
Phosphocholine 76
Phylogenetic discrepancies 564
Piezo pulses 526
Piezo-mediated devices 525, 526
Piperazine ethanesulfonic acid 492
Pituitary
desensitization 403, 404
disease 311
gland 310
glycoprotein
hormone 377
independent of 324
secretion 131, 310
tumor, secreting 54
Placebo-controlled trials 132
Placenta
abruption 715
favor entry, removal of 631
previa 398, 601, 739, 740
Placental abruption 398, 739
Placenta-mediated diseases 715
Plasma membrane 122, 462
translocation 198
Plastic enlargement 646
Plurimetabolic syndrome 292
Pluripotency-associated markers 563
Pluripotency-related transcription factor, role of 561
Plus doxorubicin 743
Polar body 483, 500f, 531, 536f, 540
biopsy 526, 527f
technical aspects of 527
placement 500
structure 500
Polycystic morphology 239
Polycystic ovarian syndrome 95, 168, 237239, 243, 246, 247, 251, 253, 256, 259, 261, 266, 267, 283, 289, 319, 421, 422, 422f, 424, 427f429f, 576, 667, 697
development of 247
diagnosis of 238, 251
pathophysiology 246
patients 338
surgical management of 266
Polycystic ovary 32, 237239, 243, 251, 253, 256, 261, 262, 268, 321, 390, 576
diagnosis of 251
morphology 239
pathogenesis 243t
presence of 351
syndrome 213, 238, 262, 283, 294, 297, 315
diagnosis of 262
management of 251, 253
prevalence of 237
Society 296
symptomatology of 237
Polyembryoma 662
Polyethylene glycols 457
Polymerase chain reaction 186, 215, 524, 528, 530, 544, 620, 718
Polymorphonuclear leukocytes 445
Polynuclear leukocytes 445
Polypectomy, hysteroscopic 96
Polypeptide hormone secreted 310
Polypoid adenomyomas 612
Polyps 47, 48, 105, 106t, 652, 652f, 655, 656
Polyuria 584
Poor fertility, history of 22
Positive predictive value 537
Postcoital cervical mucus 168
Postcoital test 168
Postejaculatory urine analysis 54
Postembryo transfer 510, 752
Postfertilization zona 570
Postmenopausal bleeding 584
Postmiscarriages counseling 753
Postmyomectomy intrauterine adhesions, formation of 656
Postpubertal testis 743
Post-vasectomy, idiopathic 130
Potassium 76
citrate 127
Potential contamination, risk of 492
Pouch of Douglas 42, 105, 633
obliteration of 92f
Povidone iodine 651
Practice Committee of American Society for Reproductive Medicine 678
Preantral follicle 6, 324, 663
Pre-conception and Pre-natal Diagnostic Techniques Act 223
Predictive negative value 293
Prednisolone 700
oral 131
role of 701
Pre-eclampsia
higher risk of 736
incidence of 215
increased risk of 734
Pregnancy 609, 666, 782
after uterine-sparing surgery 613
chances of 682
complications, increased risk of 736
establishment of 33
history 23
likelihood of 372
loss 693, 715
early 360
recurrent 396, 688, 693, 700, 709, 709f, 717
lower ongoing 396
multiple 169, 209, 213, 239, 285, 426, 428f, 430f, 431, 776, 778
high 212
high frequency of 738
incidence of 427f429f, 431f434f
prevention 777
number of 395
predictive of 412
rate 170, 283, 500, 678, 688, 712
clinical 573
cumulative 519
lower 728
similar ongoing 398
spontaneous 143
risk of multiple 212, 271
spontaneous 132, 168, 680
subsequent spontaneous 146
termination of 631
test 634
Pregnanediol-3α-glucuronide 35
Pregnant mare's serum gonadotropin 326f
Pregnenolone 379
metabolism 379
Preimplantation development 572
Preimplantation embryo 137, 495f
Preimplantation embryonic development 570
Preimplantation genetic
diagnosis 13, 120, 396, 524, 544, 545, 548, 572, 764, 776, 778
application of 779
screening 524, 531, 532, 544, 572, 700, 738, 740
testing 689, 690, 709, 715, 718, 764
for aneuploidy 716
for monogenic diseases 718
Premature luteinization, incidence of 192
Premeiotic germ cells, development of 712
Prenatal diagnosis 709, 778
Preovulatory follicle 7, 105, 324, 378
seven 213
Prepubertal ovary 663
Prepubertal testis 743
Pressure, intra-abdominal 277
Preterm birth 398, 696, 701, 735
terms of 397
Primordial follicle 6, 745
growth of 324
Primordial germ cell 560, 561
Procarbazine 744
Progesterone 57, 123, 303f, 360, 362, 368, 371, 379, 583, 701
administration 371
assay 35
role of 411
biosynthesis 368
concentration of 170, 369
higher 369
elevated 399, 400
in natural cycles, role of luteal phase 409
influence of 369
intramuscular 371
levels 370, 395
drop 340
micronization of 371
micronized 405
natural 371
micronized 191
oral 371
presence of elevated 370
receptor 583, 666
membrane component 61
modulator, selective 585, 611
stop 412
vaginal administration of 371
Proinflammatory cytokine 678
Prolactin 13, 54, 155, 305, 310
control 310
hypersecretion 310
levels 307, 310
secreting adenomas 311
secreting pituitary adenomas 311
Prolactinoma 133, 311, 313
masses, size of 313
Proliferative phase 10
Proliferator-activated receptor gamma 259
Pronuclear morphology 500
Pronuclear scoring 483
Pronucleus 500f, 502
Prophylactic doses 279
Prostaglandin 8, 57
rich prostatic secretions 186
synthesis of 8
Prostate 3
gland 4
transurethral resection of 28
Prostatitis 28
Protein 60
C 689
deficiency 714
isoforms, large complex 330
S 689
Prothrombin 714
mutation 689
time 278
Prothrombotic mutations 715
Pseudocyesis 311
Pseudoephedrine 127
Pseudopolicystic endocrine 389
Pseudo-unicornuate uterus 622
Psychological counseling 219
Puberty, onset of 5
Pulmonary tuberculosis, signs of 619
Pulsatile manner 310
Pulse oximetry 278
Pyometra 48
Pyosalpinx
chronic 633
result of 626
Pyospermia 80, 445, 446
Pyrazinamide 623
Q
Quality assurance 493
Quality control 232, 493, 495
participation in internal 559
tested for 231
Quality laboratory performance 232
Quality management system 557, 558
Quinagolide 314
R
Radiation 71
therapy, postoperative 314
Radioactive iodine therapy 696
Radiofrequency energy 629
Radiotherapy 663, 742, 743t
Raffinose 457
Raman spectroscopy 474
Randomized controlled trial 89, 271, 392, 421
Reactive oxygen species 73, 82, 129f, 445
testing, assessment of 449
etiology of 129f
Recent Spanish Study, aim of 734
Receptor activation 378
Receptor expression 62
Recombinant follicle stimulating hormone 284, 328, 344, 390, 392
Recombinant gonadotropin, effectiveness of 330
Recombinant human
chorionic gonadotropin 360
follicle-stimulating hormone 380
luteinizing hormone 380
Recombinant luteinizing hormone, addition of 346
Rectal function 597
Rectal stenosis 597
Rectovaginal endometriosis 599
Rectum cancer 747
Refractile and necrotic bodies 479
Refractory antiphospholipid syndrome 696
Refrigerator 226
Reiter's syndrome 636
Renal disease 296
Renal failure 280
chronic 311
Reproduction 3
medically-assisted 782
multifactorial disorder of 679
third-party 732
Reproductive disorders 289f
Reproductive endocrinology 416
Reproductive technologies 469
Reproductive tissues 780
Reproductive tract 32
Resistance syndrome 292
Respiratory disease, upper 22
Respiratory distress syndrome
acute 276, 420
adult 275
Resveratrol 257
treatment 258
Retinoic acid 564
Retrieve sperm 162
Retroperitoneal surgery 28
Rhesus antigens 209
Ribonucleic acid 61, 563, 712
messenger 710
paternal messenger 469
ranges exhibited abnormal 544
Rifampicin 617, 623
Risperidone 311
Rituximab 663
Rmbryo transfer, double 510, 672, 778
Robertsonian translocations 707
Rollerball endometrial ablation 612
Roots identification 728, 729
Rosiglitazone 319
Rotterdam consensus criteria 251
Rotterdam's phenotypes 238t
Rubella 26, 696
S
Sactosalpinx 626
Sadness 218
Safe technique 395
Salicylic acid 191
Saline infusion
sonography 42
sonohysterography 50, 50f
Salpingectomy
group 688
laparoscopic 628
Salpingitis 631
acute 632
history of 631
isthmic nodosa 86
appearance of 622
Salpingography, selective 44
Salpingo-oophorectomy, bilateral 666
Salpingo-ovariolysis 88
laparoscopic 88
Salt solutions, simple 490
Sarcoidosis 311
Sarcomas 415
Scar 650
tissue 610
Schistosomiasis 631
Sclerosis, multiple 28, 53, 200
Scrotal surgery 28
Sdenomyosis 609
Seager electroejaculator 127
Secretory endometrial maturation, advanced 369
Secretory phase 10
Seizure disorders 26
Selenium 122, 133, 134
supplementation 134
Semen 4, 771
alterations 779
analysis 53, 72, 75, 84, 110, 154, 441, 442
abnormal 54
limitation of 78
performing 442
reference values 53t
routine 76
characteristics 443t
collection 186
room 125, 221
composition of 76t
condition, suboptimal 129
cryopreservation 462
effect of 459
microscopic evaluation of 443
parameters 53, 115
pH, normal 443
physical examination of 442
preparation 169
purpose of 195
techniques 470
processing 220
laboratory 221
quality 122, 446t
sample
analysis 441t
analysis, chamber for 228f
classification of 78
collection 442
cryopreservation of 456
diagnostic classification of 80t
freezing of 462
handling 442
volume 76
Seminal abnormalities, persistent 148
Seminal classification 116
Seminal duct 152
Seminal ductal
dysfunction 152
obstruction 152
Seminal fluid 186
Seminal plasma 195, 214
analysis of 447
biochemical analysis of 447
devoid of 220
Seminal vesicles 3, 4, 447
Seminiferous
epithelium 564
tubule 155
biopsy technique, single 162
Septal incision, hysteroscopic 647f, 648f
Septal resorption 639
Septate uterus 642f, 644
hysterogram of 641f
incidence of 645
magnetic resonance imaging of 643f
transverse section of 642f
Septic abortion 634
Septic thrombophlebitis 633
Septoplasty 658f
Septum 105, 655f
resection 690
Serological microfluorescence test 635
Serological tests 621
Seromuscular sutures 88f
Serosa
maximal residual 612
muscular layer 612
Serotonin
receptor inhibitors, selective 28, 311
reuptake inhibitors 311
Sertoli cell 3
functions 155
only syndrome 712
Sertoli-Leydig cell tumors 662
Serum
anti-müllerian hormone 352
creatinine 275, 277, 278
estradiol 341
level 341, 351
evaluation of 352
luteinizing hormone 155, 237
progesterone
concentrations 369
increase, value of 369
prolactin 305, 311, 320, 321
concentrations 311
levels 312, 312f, 313
normalizing 133
thyroid-stimulating hormone 304f
Sex chromosomes, karyotype for 718
Sex cord stromal tumors 662
Sex hormone 308
binding globulin 189, 239, 244, 256, 256f, 262, 290, 303f
Sex selection 223, 774, 779
for nonmedical reasons 779
Sex steroids 22
Sex-linked diseases 139
Sexual abstinence
periods of 155
reduction of 122
Sexual dysfunction 23, 54, 167, 312
refractory 134
Sexual history 20, 22, 72
Sexually acquired reactive arthritis 636
Sexually transmitted
diseases 23, 26, 28, 71, 209, 631, 747
history of 20
infections 22, 26, 232
Sialic acid 326, 377
amount of 326
Sialic residues 326
Sialylation 377
Sickle cell disease 209
Sigmoid colon 633
Sildenafil 412
Silico methods 720
Sim's speculum 210
Simplex optimized media 490
Simultaneous insemination 517
Simvastatin 257, 259
Single dominant follicle, development of 369
Sinopulmonary infection, chronic 52
Sinusitis 153
Situational anejaculation 125, 127
Six o’ clock suture 88f
Small intestine, loops of 633
Social freezing 395
Society for Reproductive Endocrinology and Infertility 390
Society of Human Reproduction and Embryology 344
Sodium 76
bicarbonate 127, 279
Solomon 294
Somatic stem cells, characteristics of 583
Sonographic evaluation 73
Sonohysterogram 104f
nomenclature 104f
Sonohysterography 106t
Sonosalpingography 42
Speculum, sterilized 214
Sperm 163, 221, 482, 672, 770, 771, 773
abnormalities, mild 179
acrosome intactness test 448
aneuploidy 700
apoptosis 123
early steps of 198
banking 743
bioassay 495
by cryopreservation, storage of 456
capacitation 9, 227f
role in 447
test 449
cells, mature 123
chromatin
decondensation assay 121
dispersion 82, 83, 474
integrated assay 82
stability assay 121
structure assay 82, 83, 461, 474
collection 186
concentration 53, 76, 185, 444
and motility, methodology for 77
low 144
modification of 136
count 80
chamber 226, 556
low 81, 129, 130
total 80
cryopreservation 201, 465f
techniques of 456
deoxyribonucleic acid
damage, types of 121
fragmentation tests 121, 121t
fragmentation, application of 121
integrity testing 73
postmeiotic 713
testing, benefits of 82
testing, limitation of 82
donation 732, 733, 753
donor of 771
dysfunction 133
fertilization, defective 677
for insemination, number of 135
fraction of 135
free fluids 82
freeze-drying 459f
function tests 73, 81, 447
injection
physiological intracytoplasmic 473
post-intracytoplasmic 729
technique, physiological intracytoplasmic 474
maturation and transport 4
microscopic structure of 4
migration of compromised 475
mitochondrial activity index test 449
morphology 445
abnormal 81
motility 80, 122, 198, 460
new categories of 117
rate 185
multiple defects 447f
nonphysiological concentration of 205
normal 79f
number, total 53
oxidative status 122
parameters of concentration 120
penetration assay 449
physiology of 195
preparation 441, 450, 480, 482
techniques 195
techniques, conventional 471
processing 186, 227f
quality 133
retrieval
in men 163
methods of 163
operative 163
posthumous 223
procedures 161
technique 135, 157, 157t
techniques, nonmicrosurgical 158f
selection 474
in human female 470f
perform 472
techniques 469, 474
 conventional, advantages 470
 conventional, disadvantages 470
structure of 75f
surgical extraction of 771
swelling, grades of 448f
transport disorders 51
use of cryopreserved 781
viability test 448f
vitality 118
test 81, 81f
vitalizers 132
wash, simple 169
washing 196
Spermatid nuclei injection, round 139
Spermatogenesis 3, 4fc, 121, 144, 563, 564, 713, 743
abnormal 54, 718
failure 208
induction of 133
loss of 713
normal 54
plasticity of 563
restoration of 563
restore 564
Spermatogenic arrest 20
Spermatogonia 713
signaling 713
Spermatogonial stem cell 561, 563
Spermatozoa 81, 115, 122, 138, 443, 445, 445f, 456, 459, 460, 464, 464f, 469471, 473f, 474, 475, 718
abnormal 130
agglutination of 444
aggregation of 444
ejaculated 134, 449
fertilization rates of 130
immotile 195
lyophilization of 459
mature 471
normal functional 470
numbers of 469
progressive mobile 232
quality of 210
single 471
small number of 152
staining of 81f
Spermatozoon 444, 482
interaction of 482
Spinal abnormalities, congenital 53
Spinal cord
injury 28, 52, 53, 200
lesions 311
Spinal level of lesion 127
Spinal trauma 200
Spindle cell cancer 747
Spindle transfer 732
Spirit burners 226, 229f, 556
Spironolactone 20, 53, 154
Sponge holding forceps 203
Stabilize cells 456
Stalk section 311
Statin-induced beneficial effects 257
Statistical analysis 559
Steatosis, hepatic 292
Steelman-Pohley in vivo assay 328
Stein-Leventhal syndrome 256
Stem cells 560
pluripotent 560
use of 224
Stereomicroscopes 552
Sterile gloves 214
Sterile procedures in laboratory 214
Sterility 59, 328
Steroid 32
hormones 243
levels of 246
substances releases 360
production of ovary 368
Steroidogenesis 9fc
abnormal 247
central regulator of 378
process 389
Steroidogenic acute regulatory protein 379
Steroid
from androgens 362
regulated genes 244
Stimulates follicular development 421
Stimulating gonadotropins, use of 189
Stimulation 167, 680
cycles, previous 403
exogenous 269
protocol, minimal 340
Strassman metroplasty operation 699
Strassman procedure 646
Stratum basalis 11
Stratum compactum 11
Stratum spongiosum 11
Straws 462
Streptococcus faecalis 131
Streptomycin 214, 623
Stroke 294
Stroma 369
progesterone in 369
Stromal cells 10
Stromal echogenicity 239
Stromal volume 188
Subcutaneous goserelin 611
Subendometrial blood flow, detection of 187
Subfertility 49, 676
workup of 618
Submucosal fibroids 587, 699
Submucosal myomas 687
Submucous
fibroid 50f, 105, 584
myoma
ESGE classification of 49t
presentation of 49
myomas 214, 587
Subserous
fundal fibroid 51f
myomas 587
Subzonal injection 138
Sucrose 457
Suction irrigation cannula 268f
Sulfamethoxazole 131
Sulfasalazine 20, 154
Sulfonated 326
Sulfonation 377
Sulfonic group 377
Supraphysiological hormonal levels 369
Supraphysiological levels 339, 361
Surgery
benefits of 598, 599
excisional 599
hysteroscopic 655
previous 22, 47
Surrogacy 223, 732, 739, 781
agreement for 771
conventional 739
Swim-up technique 196, 196f, 450f
Syncope 277
Synthetic progesterone derivates 371
Systemic arterial hypertension 246
Systemic blood circulation 155
Systemic lupus erythematosus 14
Systemic medical illness 22
Systolic blood pressure 294
T
Tachycardia 275
Tachypnea 275, 277
Tail defects 446
principal 78
Tamm-Horsfall glycoprotein 327
Tamoxifen 173, 319, 321, 323, 663, 666
citrate 132, 175
Tandem repeats-alu elements, number of 562
Taxanes 663, 744
Taxonomic units, operational 66
Tay-Sachs disease 209
Telescope 268f
Temperature fluctuations 494
Tenaculum 205
Tenderness, abdominal 23
Tense ascites 277
Teratoma 662
Teratozoospermia 80, 115, 117, 130, 139, 201, 446
rate, irrespective of 185
Test tube racks 226, 556
Testicular biopsy 53, 54
Testicular cancer 28f
setting of 28
Testicular consistency 154
Testicular detorsion 20
Testicular dysfunction 152
Testicular failure 155
complete 54
primary 71
Testicular malignancy 71
Testicular sperm
aspiration 162, 456, 472, 465
extraction 135, 146, 158f
microdissection 163
Testicular swelling 71
Testicular tissue cryopreservation 781
Testicular torsion 28
Testis 743
Testosterone 155, 189, 239, 245, 390, 562
deficiency 154
exogenous 28
gel 347
application of 391
in low response 392t
levels 320, 321
patches 347
total 239, 291
Tetracycline 28, 154
Tetraploid 709
Thalassemia 208
Thaw embryo transfer 409f, 410f
cycle 408t
protocols for 408
stimulation cycle for 410f
Thawing method 201
Theca cell 246, 324, 368, 378, 379
compartment 369
luteinization 368
Theca externa cells 6
Theca interna cells 6
Therapeutic anticoagulation 279
Therapeutic counseling 219
Therapeutic testicular mapping 162
Thermometers 226
Thiazolidinediones 259, 319, 321
Thioridazine 154
Thoracic duct 279
Thoracocentesis 279
Three O’ clock suture, tying of 88f
Threonine 326
Thromboembolic complications 434
prevention of 279
Thromboembolism 275, 276, 279, 280, 689
risk of 279
Thrombomodulin 293
Thrombophilia 687, 688, 690, 694
acquired 689, 693
hereditary 691
inherited 715
Thrombophilic defect 714
Thymine 711
Thyroid
autoimmunity 697
disease 23, 308
disorder 302, 696
distribution of 304t
dysfunction 302
management of 303
mechanism of 302f
enlargement 23
evaluation, interpreting results of 305t
function 303
hormone 13, 307, 308
measurement of 305
peroxidase antibodies 302, 305307
stimulating hormone 377
Thyroidectomy 696
Thyroiditis, chronic autoimmune 696
Thyroid-stimulating hormone 13, 72, 302, 302f, 305, 678
levels 307f
Thyrotropin-releasing hormone 305, 310
Thyroxine 305
therapy 308
treatment 303
benefits of 303
Tilly's group hypothesized 562
Tissues, engrafted 564
Tocopherol 412
Toluene 154
Torsion 274
Toxoplasma gondii 696
Trachelectomy, radical 665
Transabdominal sonography 239
Transabdominal ultrasonography 610
Transabdominal ultrasound 252
Transdermal testosterone 389, 391
pretreatment 392
side effects of 393
use of 393
Transferred media, viscosity of 508
Transferrin 327
Transfundal metroplasty 646
Transgenerational transmission 779
Transgenic green fluorescent protein 562
Translesional vascularity 610
Transmembrane
conductance regulator 156
protein 482
Transrectal ultrasound, basis of 161
Transscrotal ultrasonography 54
Transvaginal examination 41f
Transvaginal sonography 42, 89, 99, 104, 642
technical aspects of 99
Transvaginal ultrasonography 610
Transvaginal ultrasound 35, 190, 221
scanning 181
Trastuzumab 744
Trauma 28
Trendelenburg position 205
Trichomonas 52
Trigger
timing of 179
type of 370
Triggering agents 360
Triglycerides 294
Trimethoprim 131
Triphenylethylene derivative 321
Triploid 709
embryos, high incidence of 718
Triptorelin 336, 340, 406
Triradiate tubular cavity 648
Trisomy 700
Trophectoderm 507, 507f, 531, 534, 572
biopsy 530, 531f
technical aspects of 530
cell
analysis 531
protruding 573
Trophoblast
cells 671
extravillous 671
Tubal abnormalities 47, 87
Tubal anastomosis, laparoscopic 88
Tubal blockage 47
bilateral 47
Tubal cannulation 86f
hysteroscopic 86
Tubal catheterization 44
Tubal disease 89, 179
Tubal dysfunction 677
Tubal evaluation 40
Tubal factor 47
Tubal infertility 136
Tubal ligation, proximal 629
Tubal occlusion
hysteroscopic proximal 629
proximal 86
superimposed 632
Tubal patency 208
assessment of 678
evaluation of 105
Tubal perfusion, selective 45
Tubal surgeries 86
Tubal wall appears 633
Tubercular salpingitis 632
Tuberculin sensitivity test 621
Tuberculosis 52
extrapulmonary 617, 622
Tuberculous intrathoracic lymphadenopathy 622
Tubes
evaluation of 40
place sample 228f
Tubo-ovarian
abscess 631
ruptured 632
lesions 622
diagnosis of 622
mass 633
Tumor 311
necrosis factor 11
alpha 678, 698
binding protein 327
Tunel assay 82, 83
Turner's syndrome 705, 737
Twin pregnancy 215, 735, 778
Twisted ovarian cyst 634
Tygerberg's strict criteria 117
Typhoid fever 621
Typhus 621
Tyrode's acid 531
Tyrosine kinase 244
inhibitors 744
U
Ulipristal acetate 656
Ultrasonography 204
Ultrasound 37, 49, 53, 54, 59, 252
guidance 508
use of 508
imaging, abdominal 214
role of 621
three-dimensional 690
Undescended testes 71
Unicornuate 105
uterus 645, 646
Ureaplasma 52, 131, 696
urealyticum 131
Ureteral reimplantation 601
Ureteral stenosis 601
Urethra 3
Urinary alkalizer 127
Urinary assay 34
of pregnanediol 35
Urinary derived gonadotropins 340
Urinary follicle-stimulating hormone 328, 339
Urinary gonadotropins 330, 405
Urinary incontinence 307, 307f
Urinary luteinizing hormone 678
Urine 32
derived gonadotropins, proteins in 214
of postmenopausal women 325
output 278
pregnancy test 210
Urofollitropin 328
Urogenital examination 21
Urogenital history 20
Urokinase 327
Uropean Society of Human Reproduction and Embryology 528
Uterine abnormalities, congenital 653, 687
Uterine anatomy, abnormal 687
Uterine anomalies 698, 699
congenital 638, 640t, 641f, 642645, 698
Uterine artery 107
embolization 613
waveform 107f
Uterine bleeding, abnormal 296
Uterine causes 47
Uterine cavity 49, 399, 400, 584
division of 643f
evaluation 105
hysteroscopy of 66
Uterine contractions 508
Uterine diseases 781
Uterine factor 47
Uterine fibroids 634
classification of 49
FIGO classification of 584f
Uterine fluid 508
Uterine immune system 671
Uterine malformations 644
Uterine morcellation 588
Uterine muscle, relaxation of 368
Uterine natural killer 671
Uterine pathology 208
Uterine perfusion 107
Uterine problems 677
Uterine procedure 48
Uterine retroversion 610
Uterine rupture 656
risk of 614
spontaneous 613
Uterine septum 95, 95f
Uterine size 23
Uterine sparing surgery
conservative 614
types of 612
Uterine synechiae 657, 687, 688
Uterine vascular damage 743
Uterine walls, posterior 648
Uterosacral ligaments 92f
Uterovaginal lymph vessels 371
Uterus 50, 92f, 99, 100, 104, 167, 203, 618, 771
absence of 645, 782
after vasopressin injection, blanching of 90f
anatomy of 508
assessment of 110
cavity of 631
congenital absence of 710
didelphic 699
didelphys 644
distortion of 49
dysmorphic 641f, 643f, 644
functionality of 782
metroplasty of T-shape 659f
subseptate 646, 647f
surgical removal of 47
T-shape 622, 655f
V
Vagina 32, 33, 618, 643f
congenital absence of 710
tuberculosis of 618
Vaginal agenesis 645
Vaginal anomaly 644
Vaginal cul-de-sac, anterior 650
Vaginal cytology 33
Vaginal discharge 23, 634
Vaginal douching 631
Vaginal factor 47
Vaginal nodule, excision of 93f
Vaginal progesterone 356, 371
supplementation 412
Vaginal supplementation 412
Vaginismus 47, 48, 167, 188
primary 48
secondary 48
Vaginosis, bacterial 631
Valproic acid 154
Valsalva maneuver 144
Valves, malfunction of 144
Vapor nitrogen 230f
Varicella 26
Varicocele 28, 29, 143145, 148
associated infertility 147
bilateral 145
repair 143, 146148
subclinical 145
surgery 143
diagnosis and classification 144
pathophysiology 144
Varicocelectomy 20, 143
Vas deferens 3, 28, 710
absence of 710
congenital bilateral absence of 52, 156, 208, 710
infections causing obstruction of 52
Vascular endothelial growth factor 8, 258, 268, 277, 396
Vasectomy 52
Vasoactive intestinal peptide act 310
Vasoepididymal anastomosis 160
disadvantages of 161
Vasoepididymostomy 157
Vasovasal anastomosis 161
Vasovasostomy 157
Veins 371
Venn diagram 771f
Venous thromboembolism 714
risk of 715
Ventilation 279
Verapamil 311
Veress needle 268f
Vermin proofing, steps for 221
Viability test 447
Vibrator therapy 127
Vinblastine 744
Vinca alkaloids 744
Vincristine 744
Viral contamination 328
Viscosity measures 443
Visual
acuity, reduced 312
changes 311
disturbances 312
field defects 312
Vitamin 258, 491, 492
A 134
B complex 258
C 122, 133, 134
D deficiency 699
E 122, 133, 134
Vitrification 395, 519, 532, 720
technique 355, 521
use of 356
Vitrous state 395
Volatile organic compounds
minimizing 549
presence of 730
Volvox globator spheres 464
Vomiting 274, 276, 279
Vulva 618
tuberculosis of 618
W
Waist circumference 293
Waist-hip ratio 290
Wallace artificial insemination catheter 204
Warmth oocyte embryo transfer cycles 373
Wash technique, simple 198f
Weight gain, rapid 275
Weight loss 286
White blood cell 420
Whole-genome analysis 243
Wolffian ducts 639, 710
Working cell banks, source of 328
World Health Organization 57, 176, 184, 209, 262, 292, 441, 446t, 693, 763
X
X chromosome 156, 565, 583, 706
X syndrome, triple 706
Xylene 154
Y
Y chromosome 565
microdeletion 710714
test 13, 14
Young's syndrome 52, 153
Z
Zica virus 399, 400
Ziehl-Neelsen staining 620
Zinc 122, 133
Zona binding 9
Zona digestion
controlled 572
enzymatic 572
mechanical 572
partial 137, 572
Zona drilling 531
Zona glycoprotein 138
Zona pellucida 6, 137, 464f, 478, 479, 482, 500, 524, 570
binding test 449
breaching of 524
empty 462
morphology 481t
phenotype 482
Zona reaction 9
Zygote 483, 500f, 501, 503f
classification 501f
formation 9
from gamete to 478
×
Chapter Notes

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1Investigating Infertility
  1. Basics of Human Reproduction: As we Understand it Now
  2. Role of History Taking and Clinical Examination in an Infertile Couple
  3. Preconceptional Evaluation of a Couple
  4. Assessing Ovulatory Function and Ovarian Reserve
  5. Tubal Evaluation: An Eternal Dilemma
  6. Mechanical Issues in Fertility: How to Evaluate?
  7. How to Assess the Receptivity of the Human Endometrium
  8. Assessment of the Male
  9. Role of Semen Analysis in Understanding Fertility Potential
  10. Role of Endoscopy in Infertility
  11. Ultrasound and Color Doppler in Fertility
  12. When to Stop Investigating and Start Treating?2

Basics of Human Reproduction: As we Understand it NowCHAPTER 1

Azadeh Patel,
Jayesh Patel,
Manish Banker
 
INTRODUCTION
Reproduction as we understand happens when a sperm fertilizes the ovum to form a zygote which would further develop into an embryo, fetus, and deliver as a child in future. But the process of development and maturation of the gametes and fertilization is very complex. Understanding of biology of gametes and human reproduction has led to evolution of technologies and techniques to help the infertile couples, over the years. The techniques used, try to mimic the natural way of conception. Thus, it is very important to understand the anatomy of the reproductive tract and physiology of the conception to evaluate the cause of infertility and to provide proper necessary treatment.
The union of sperm and egg is one of the essentials of reproduction; however, the remote site of occurrence of this event and microscopic dynamic nature, made it difficult to study for many years. Greater understanding of sperm and egg development and union provides major benefits of the clinical application of the assisted reproductive technologies. This chapter includes understanding of gametogenesis, sperm and egg transport, fertilization, implantation with associated genetics and immunology.
 
HISTORY
In 1677, Anton van Leeuwenhoek of Delft, Holland, by Galileo's microscope described the “little animals of the sperm.” After 198 years, Wilhelm August Oscar Hertwig, in Germany, demonstrated the union of sperm and egg, fertilization, in the sea urchin. In 1951, Min Chueh Chang and Colin Russell Austin made discovery of sperms spending some time in the female reproductive tract before acquiring ability to fertilize the egg was made in rat and rabbit respectively.1,2
 
MALE REPRODUCTIVE SYSTEM
Male reproductive system consists of scrotum and testes within it, epididymis, vas deferens, ejaculatory duct, urethra, penis and accessory glandular structure (SVs: seminal vesicles, bulbourethral glands, and prostate).
The testes contain two anatomical units:
  1. A network of seminiferous tubules comprised of:
    • Sertoli cells: They contain follicle-stimulating hormone (FSH) receptors, and synthesize inhibin B, anti-Müllerian hormone (AMH) and androgen-binding protein.
    • Germ cells: This develops into sperm by spermatogenesis.
  2. An interstitium containing Leydig cells that produce androgens (testosterone mainly) and peritubular myoid cells. Luteinizing hormone (LH) receptors are found on Leydig cells (Flowchart 1).
Tight junctions between the Sertoli cells separate the tissue into two functional compartments (basal and adluminal), which are distinct structure and have limited permeability for diffusion of macromolecules between them. The basal compartment consists of the outer layers of the seminiferous tubules containing the spermatogonia. The adluminal compartment contains the inner portion of the seminiferous tubules, including primary spermatocytes and more advanced stages of spermatogenesis.
 
Spermatogenesis (Flowchart 2)
The male gamete is called as spermatozoa or sperm. Spermatogenesis/spermiogenesis is a complex, multistep process involving the proliferation and differentiation of spermatogonia into mature sperm, taking place in testes.4
zoom view
Flowchart 1: Neuroendocrine control male.
zoom view
Flowchart 2: Spermatogenesis.
After the primary germ cells (PGCs) reaches the testes in the intrauterine life, they divide into Type A1 spermatogonia, which has ovoid nucleus with chromatin and nuclear membrane. They are found near the basement membrane and are sperm stem cells. They are capable to divide into Type A2 spermatogonia or self-renewal into Type A1 spermatogonia. Type A2 spermatogonia forms Type A3 spermatogonia and successively Type A4 spermatogonia. All these have capacity of self-renewal. If Type A4 spermatogonia do not undergo self-renewal, it can undergo either cell death by apoptosis or differentiates into intermediate spermatogonium stage with the onset of puberty. Those who enter the process of spermatogenesis divide mitotically into Type B spermatogonia. From this, they divide mitotically to form Primary spermatocyte, which each undergo first meiotic division to form a pair of Secondary spermatocytes, which complete the second division of meiosis. The haploid cells thus formed are called spermatids. With the division from Type A1 spermatogonium to spermatid, the cells move farther from the basement membrane toward the lumen. The spermatids located at the border of the lumen, loose their cytoplasmic connection and become sperm.3 The seminiferous tubules empty into the network of tubules called as rete testes, through which sperm move to the epididymis.
Optimal spermatogenesis requires temperatures lower than body temperature, hence mammalian testis are located outside the body cavity.
Microscopic structure of sperm consists of:
  • Head: Containing nucleus and acrosome
  • Mid-piece: Containing mitochondria
  • Tail: Containing axial filament and end piece.
 
Sperm Maturation and Transport
Sperm formation takes approximately 65 days from the spermatocyte stage,3 and the transport of sperm through the epididymis to the ejaculatory ducts requires about 14 days. Maturation of sperm begins during their passage through the epididymis, as evidenced by enhancement of motility, but the final maturation (or capacitation) of sperm take place in the female genital tract after ejaculation. In epididymis, the sperm acquire surface glycoprotein (beta-defensin 126) that protects the sperm while they travel through the cervical mucus. The caudal epididymis stores sperm and make them available for ejaculation, thus providing repetitive fertile ejaculations. Adequate testosterone levels in circulation and maintenance of normal scrotal temperature is required for optimal sperm-function preservation and storage.4 During ejaculation epididymal content is mixed with secretion from the prostate gland and seminal vesicle (SV).5
Otherwise the epididymis is believed to play only the storage role, as the sperm obtained by testicular biopsy is directly injected into an oocyte in intracytoplasmic sperm injection (ICSI), and is very successful in achieving fertilization and pregnancy.6
Semen forms a gel almost immediately following ejaculation but then liquefies in 20–30 minutes by prostatic enzymes. The alkaline pH of semen provides temporary protection for the sperm from the acidic environment of the vagina, but most sperm left in the vagina are immobilized within 2 hours. The most motile and fortunate sperms gain entrance into cervical mucus and then enter into the uterus. This entry is rapid, and sperm have been found in mucus 5within 90 seconds of ejaculation.7 Contractions of the female reproductive tract occur during coitus and male forces (the flagellar activity of the sperm) are responsible for successful transport. The sperm swim and migrate through pores in the cervical mucus that are smaller than the sperm head; therefore, the sperm must actively push their way through the mucus. Those sperm incapable in motility are held at the level of cervical mucus.
 
FEMALE REPRODUCTIVE SYSTEM
  • It comprises of two ovaries (female gonads) on each side of the body, two fallopian tubes, uterus, cervix and the vagina. Vagina is the female copulating organ and the sperms are deposited in the vagina after ejaculation.
  • The function of the ovaries is to cyclically produce ovum for fertilization and of steroidogenesis by secreting cyclical estrogen and progesterone.
 
Oogenesis (Flowchart 3)
  • Embryologically ovaries appear as early as 5th intrauterine week, and the PGCs start dividing by mitosis as early as 6–8th intrauterine week, reaching to 6–7 million oogonias by 16–20th intrauterine week. This represents the maximum ovarian capacity for the germ cells, mitosis does not occur after that.
  • With the commencement of meiosis I by 7–8th intrauterine week the oogonia get arrested at the diplotene stage of prophase and they are now called as primary oocytes. The oogonia not undergoing meiosis are degenerated by apoptosis. So at the time of birth ovaries are left with only 2 million, and then 300,000 primary oocytes till puberty, out of which approximately only 400 will ovulate in reproductive years.
  • Onset of puberty is marked by activation of HPO axis, and a cohort of oocytes is recruited by nonhormonal followed by hormonal selection for development and maturation by ovarian cycle every month. The oocyte of the dominant follicle undergoes resumption and completion of meiosis I with the onset of LH surge and the first polar body (containing 23X chromosomes and small amount of oocyte cytoplasm, in the perivitelline space) is released; now it is called as secondary oocyte. Just before the ovulation, it gets arrested at metaphase stage of second meiotic division, which is completed after sperm penetration.
  • Thus, the ovum available for fertilization has 23X, and the rest 23 (X or Y) chromosomes come from sperm after fertilization.
    zoom view
    Flowchart 3: Oogenesis.
    6The second polar body containing 23X chromosomes from the oocyte with cytoplasm is released in the perivitelline space. Nowadays polar body biopsy from the metaphase II ovum, for patients undergoing IVF is possible to detect chromosomal abnormality of the ovum in case of high maternal age.8
  • There is continuous loss of the oogonias and the oocytes by apoptosis from the intrauterine life to 45–50 years after birth. When the ovarian reserve gets exhausted it leads to menopause. The amount of the ovarian reserve can be measured by a marker AMH that is secreted by the preantral and small antral follicles in the ovarian cycle.9 It suggests the number of the primordial follicles recruited from the primary pool of ovary. It is believed to be constant marker throughout the cycle.10
 
Physiology of Menstruation
The studies and ideas, over the past few decades have made a scientific progress in understanding the nature of the normal menstrual cycle and role of higher center and gonadal hormones in it. The normal cycle can be divided into:
  • Follicular phase
  • Ovulation
  • Luteal phase.
 
Follicular Phase
This phase occurs over a period of 10–14 days, featuring action of hormones and local autocrine-paracrine peptides, leading to growth of the cohort of primordial follicles containing the follicle destined to ovulate through various stages of development.
The primordial follicle:
  • The primordial follicle is resting stage of follicle containing oocyte, arrested in the diplotene stage of prophase of meiosis I, surrounded by single layer of spindled-shaped granulosa cells.
  • The recruitment is nonhormonal and the selection of a cohort probably depends on residual pool of primordial follicles.
  • Onset of follicular maturation is marked by increase in the oocyte size, change in the granulosa cells from spindle to cuboidal, formation of small gap junctions in between granulosa cells and oocyte which acts as pathway for exchange of nutrition, metabolite and signal interchange.
  • Oocyte depends on the glycolysis end product, pyruvate for energy source from granulosa cells.11
  • Activin and BMP are promoters and inhibin and AMH are inhibitors of primordial follicular development and growth.12
The preantral follicle:
  • With the increasing follicular growth, the oocyte enlarges and is surrounded by a membrane called as zona pellucida, and the granulosa cells undergo multilayer proliferation and the theca cells form the surrounding stroma.
  • Once the granulosa cells become 3–6 layered, they are separated from the stromal cells by basement lamina. The stromal cells close to the basement lamina are called as theca interna cells, and those in the outer region are called as theca externa cells.
  • This growth of follicle is gonadotropin dependent.
  • Follicle-stimulating hormone receptor number rise quickly till 1,500 receptors per granulosa cells in the preantral stage.13
  • Role of androgens, in early follicular development is very complex. In low androgen concentration, by FSH stimulation, androgens are converted to estrogen by the process of aromatization, but higher concentration stimulates the 5α-reductase activity that reduces androgen to more potent 5 α -androgens. These further inhibits conversion to estrogen and also inhibits FSH- induced LH receptors formation1416 (Flowchart 4).
The antral follicle:
  • Under synergistic influence of estradiol and FSH, there is increase in follicular fluid in the intracellular spaces of the granulosa cells, eventually coalescing to form a cavity, called as antrum, and the follicle is now called as antral follicle.
  • The granulosa cells surrounding the oocyte are now called as cumulus oophorus.
  • The antrum is rich in hormones mainly estrogen, growth factors and cytokines, and provides environment and nutrition for development and maturation of oocyte.
  • The follicle with greatest rate of granulosa cells proliferation; produce highest estradiol concentration acquires dominance amongst them and is believed to yield a healthy oocyte.
  • In contrary, those follicles with least estrogenic concentrations and higher androgenic levels, inhibits granulosa cell proliferation and undergo atresia and degeneration of oocyte.
  • In case of premature LH rise, leads to excess androgen production that favors degeneration.
  • The synthesis of the steroid hormones in a follicle, is explained by two-cell, two-gonadotropin system.7
zoom view
Flowchart 4: Aromatization.
Two-cell, two-gonadotropin system (Flowchart 5):
  • In preantral and antral follicles, the FSH receptors are located only on granulosa cells, and LH receptors on the theca interstitial cells located in the theca interna cells.
  • The LH acts on the theca cells and facilitates conversion of low-density lipoprotein (LDL) cholesterol to androgens and these androgens are transported to granulosa cells and acts as a substrate to get converted into estrogens under the influence of FSH. This conversion depends upon follicular sensitivity to FSH, brought about by the action of FSH and estrogen.
  • Thus, in the final stages of follicular maturation, LH is important for increasing amount of androgens, which are the substrate for estrogen production and promoting growth of the dominant follicle, with the regression of the smaller ones.
Selection of the dominant follicle:
  • With the increasing concentration of estrogen, it exerts a negative feedback on the HPO axis and withdraws the release of FSH. This leads to regression of the all follicles by apoptosis, except the dominant follicle.
  • The dominant follicle is selected by 5–7th day of the cycle and escapes the suppression, because of previous higher sensitivity and longer exposure to FSH. It has its own estrogen production and continues to grow.
  • Also, the vascularity of theca cells of the dominant follicle increases as compared to others, thus delivering more gonadotropins to it than other.
  • FSH now changes its action of estrogen production and starts up-regulation of LH receptors on granulosa cells. Once stimulated, LH can form its own receptors on FSH primed granulosa cells.17,18
  • With the decreasing concentration of FSH, and mid-follicular estrogen rise, exerts a positive feedback on HPO axis and influences LH release. LH levels rises steadily over the late follicular phase, stimulating more androgen production in the theca cells.
zoom view
Flowchart 5: Two-cell two-gonadotropin theory.
The preovulatory follicle:
  • The granulosa cells of the preovulatory follicle enlarge and acquire lipid inclusions and the theca cells becomes vacuolated and vascular.
  • The oocyte now proceeds with meiosis I.
  • Estrogen rises slowly at first, and then rapidly, marking its peak 24–36 hours prior to the ovulation. Peak estradiol level stimulates the onset of LH surge.
  • In preovulatory follicle, LH inhibits further growth of the follicle and promotes luteinization of the granulosa cells that results in progesterone production19 and stimulates progesterone receptor expression on the granulosa cells, unlike traditionally believed it to be expressed mediated by estrogen.208
  • The rising midcycle 17α hydroxy progesterone causes positive feedback on pituitary and leads to midcycle FSH surge and peak.
  • Under the influence of rising LH, there is midcycle increase in local and peripheral androgens which increase follicular atresia in the ovary and increases libido systemically.
 
Ovulation
  • The process in which mature oocyte along with its cumulus cells (COC) are expelled out of the ovary into the peritoneal cavity is called as ovulation.
  • Ovulation occurs:
    • 10–12 hours after LH peak
    • 34–36 hours of the onset of LH surge
    • 24–36 hours after peak estradiol levels
  • A threshold of LH concentration should be maintained for 14–27 hours for full maturation of the oocyte to occur.21 LH surge lasts for 48–50 hours.22
  • Causes of ovulation:
    • FSH surge causes conversion of plasminogen to more potent plasmin that causes activation of collagenase, which causes disruption of the follicular wall. This results in movement of the follicle, destined to ovulate to come to the surface of the ovary. Proteolytic digestion of the follicular apex is called as stigma.
    • Synthesis of prostaglandins and other eicosanoids: They are produced under the influence of LH. LH along with prostaglandin E (PGE2) leads to cumulus expansion and resumption of meiosis. PGE2 causes contraction of the smooth muscle cells and expels the COC.
    • Stretching factor: Passive stretching causes flattening of the surface by necrobiosis and rise in the intrafollicular pressure more than 10–15 mm Hg causes ovulation.
  • Thus, the oocyte (arrested in metaphase stage of second meiotic division with a polar body) along with its cumulus cells and some follicular fluid ovulates, but the meiosis is completed only after fertilization by the sperm (marked by formation of the second polar body).
  • The time that elapses from a primary follicle to ovulation is approximately 85 days.23
Oocyte transport:
  • Oocyte transport begins from the ovulation and ends when the morula stage of the embryo reaches the uterine cavity.
  • It reaches the ampulla of the fallopian tube within 15–20 minutes of ovulation.
  • The tubal transport is toward the uterus and is dependent on the flow of the secretory fluids by the ciliary movement and the tubal smooth muscle contraction.
  • Interaction and the sperm penetration take place in the ampullary region of the fallopian tube.
 
Luteal Phase
Luteal phase starts after ovulation and ends with the onset of menstruation. It corresponds to the secretory phase of the endometrial cycle and lasts for 14 days. It is divided into early and late luteal phase.
  • Before ovulation, the granulosa cells starts to increase in size and assume a vacuolated appearance with deposition of yellow pigment, lutein, thus called as luteinization, and the follicle is called as corpus luteum after ovulation.
  • Corpus luteum is made up of luteal cells, endothelial cells (constitutes 35% of total cell mass), leucocytes (mainly neutrophils), and fibroblasts.
  • Angiogenesis is the hallmark of the luteal phase, after the cessation of the LH surge; the capillaries penetrate reaching till the central cavity and filling it with blood. It is mediated by vascular endothelial growth factor (VEGF) and angiopoietins produced by the luteinized granulosa cells.2426 The corpus luteum has one of the highest blood flow per unit mass in the body.
  • Luteinizing hormone mediates steroidogenesis in the luteal phase from LDL cholesterol. LH regulates LDL-receptor binding, internalization and postreceptor processing, in the luteinized granulosa cells during the early luteal phase in response to midcycle LH surge. This leads to production of progesterone and estrogen both (Flowchart 6).
  • Progesterone rises to peak after 8 days of ovulation. Under the action of LH, inhibin B of the follicular phase changes to inhibin A that contributes to suppression of FSH in luteal phase and thus prevention of new follicular growth.
  • There is a short wave of follicular recruitment, mostly due to midcycle FSH surge, but there is no follicular growth because of luteal phase FSH suppression.
  • The corpus luteum rapidly declines after 9–11 days of ovulation due to luteolytic action of estrogen, prostaglandin F (PGF2α) produced in the luteal phase, nitric oxide, endothelin and other factors.
  • Late luteal phase is marked by rapidly declining levels of estradiol and progesterone as an effect of luteolysis.
  • In early pregnancy, hCG rescues the corpus luteum and sustains pregnancy till fetoplacental circulation is established by the end of first trimester.9
zoom view
Flowchart 6: Steroidogenesis in luteinized granulosa cell.
Luteal follicular transit: This is time extending from the onset of late luteal phase, marking rapidly declining levels of progesterone and estradiol to the selection of the dominant follicle for the next cycle. It is marked by menstruation.
  • The demise of the corpus luteum results in nadir of progesterone, estrogen and inhibin A. Thus, this removes the suppression of the release of FSH secretion from the pituitary.
  • Also the decrease in the estradiol and progesterone removes the negative feedback mechanism on the hypothalamus and pituitary, favoring increase in the frequency of gonadotropin-releasing hormone (GnRH) and gonadotropin release.
  • This leads to release of FSH and recruitment of new follicular cohort of primordial follicles and again the dominant follicle is selected for next cycle.
 
FERTILIZATION
Mammalian fertilization comprises of sperm migration through the female reproductive tract and sperm-egg interaction in the ampullary portion of the fallopian tube.
It is completed in five stages:
  1. Sperm capacitation
  2. Zona binding
  3. Acrosomal reaction
  4. Zona reaction (Cortical reaction)
  5. Completion of meiosis and zygote formation.
 
Sperm Capacitation
  • The sperms ejaculated in the vagina, do not have ability to fertilize unless they undergo a process called capacitation.
  • Capacitation is the process of cellular changes occurring in the female reproductive tract after ejaculation by which sperm become competent to fertilize an ovum, by releasing surface cholesterol and other glycoproteins acquired from epididymis.
  • The sperms then enter the fallopian tube and wait for the ovum at the isthmic region.
  • After ovulation, when the ovum is in vicinity it attracts the sperms by chemotactic factors and the capacitated sperms acquire hypermobility to help them gain velocity to enter ZP.
 
Zona Binding
  • Sperm penetrate the matrix of the cumulus oophorus, which is rich in proteins and carbohydrates such as hyaluronan, an unsulfated glycosaminoglycans, this is called as sperm-cumulus interaction.
  • Sperm bind to the ZP for about a minute and then penetrate it rapidly, mediated by acrosin, a trypsin-like proteinase that is bound to the inner acrosomal membrane of the sperm.2729
 
Acrosomal Reaction
  • The acrosome is a Golgi-derived exocytotic organelle that covers the tip of the sperm head.
  • Acrosomal reaction is the acrosomal exocytosis that releases the acrosomal enzymes necessary for zona penetration and fertilization.
  • It happens only in the capacitated sperm bound to ZP. This process is mediated by influx of calcium ions and efflux of hydrogen ions.
  • After penetration of the ZP, sperm immediately meet and fuse with the oocyte plasma membrane.
 
Zona Reaction (Cortical Reaction)
The hardening of ZP after one sperm penetration to avoid entry of another sperm is called zona reaction. The hardening of the extracellular layer is by cross-linking of structural proteins, and inactivation of ligands for sperm receptors.30
 
Completion of Meiosis and Zygote Formation
  • Fusion of the sperm and oocyte causes metabolic activation of the oocyte.
  • The meiosis of the oocyte is completed about 3 hours of sperm insemination, marked by the release of second polar body containing haploid (23X) number of chromosomes.
  • The addition of haploid chromosomes from the sperm restores the diploid number of the fertilized egg.10
 
UTERUS, ENDOMETRIUM, AND IMPLANTATION
The uterus is an important female reproductive organ, which holds feto-placental unit during pregnancy. Endometrium is the dynamic inner mucosal lining of the uterus, which responds to the hormonal changes of ovarian cycle and sheds cyclically as well as provides favorable physiological environment for embryo implantation, thus it is considered essential for reproduction.
 
Layers of Endometrium
  • Functionalis layer (upper two-thirds): Consists of epithelial cells and glands. Its main purpose is to provide receptive environment for embryo (blastocyst) implantation.
  • Basalis layer (lower one-third): Consists of endometrial stem cells and basal cells, to regenerate functional endometrium following menstrual loss.31
 
Endometrial Changes during an Ovulatory Menstrual Cycle
Cyclical sequence of changes is essential to prepare receptive endometrium approximately every month for implantation, failing which the endometrium breaks down and sheds in the form of menses.
These changes occur in three main phases:
  1. The menstrual phase
  2. The proliferative phase
  3. The secretory phase.
 
Menstrual Phase
  • It is a transitional phase marked by exfoliation of endometrium till onset of endometrial proliferative phase of the next cycle.
  • In histology, epithelial reparative changes along with remnants of menstrual shedding are seen.
  • The epithelial repair is fast; by day 4 of the cycle, more than two-thirds of the cavity is covered with new epithelium.32 By day 5–6, the entire cavity is re-epithelialized and stromal growth begins.
  • Ultrasound findings: The endometrium is relatively indistinct during menses with menstrual blood collection seen sometimes and then becomes a thin hyperechoic line after cessation of menses.
 
Proliferative Phase
  • It coincides with ovarian follicular phase and increased estrogen secretion by growing follicles. This estrogen is responsible for reconstruction, growth, and proliferation of the endometrium. Estrogen also induces progesterone receptors on endometrium.
  • In histology, all of the tissue components (glands, stromal cells, and endothelial cells) demonstrate proliferation, which peaks on days 8–10 of the cycle, reflecting rising estradiol levels in the circulation and maximal estrogen receptor concentration in the endometrium.33,34 Depending on the advancement of these histological changes, this phase is divided into early and late proliferative phase.
  • Ultrasound findings: Endometrium becomes thicker, grows from approximately 1 mm to 7–10 mm and develops in “triple line” pattern.
 
Secretory Phase
  • It is associated with the luteal phase of ovarian cycle after ovulation and it is a constant phase of 14 days; the endometrium now demonstrates a combined effect of estrogen and progesterone activity.
  • Endometrial height is fixed now at its preovulatory extent (approximately 7–10 mm) despite continuous availability of estrogen.
  • Progesterone secreted by corpus luteal cells is responsible for cessation of proliferative changes and it induces secretory changes in endometrial glands.
  • The first histologic sign that ovulation has occurred is the appearance of subnuclear intracytoplasmic glycogen vacuoles in the glandular epithelium on cycle day 17–18.
  • The glands acquire tortuosity and creates “cork-screw pattern” while spiral vessels become more coiled.
  • The peak secretory changes are seen approximately 7 days after LH surge and it generally coincide with blastocyst implantation.
  • Ultrasound findings: Endometrium loses its “triple line” image and becomes more uniformly hyperechoic.
 
Fate of Endometrium after Secretory Phase (Flowchart 7)
  • In the absence of fertilization and implantation, corpus luteum regresses which causes hormonal support withdrawal.
  • Estrogen and mainly progesterone withdrawal is responsible for various events which leads to endometrial breakdown and shedding.
  • Endometrial tissue breakdown also involves a family of enzymes, matrix metalloproteinase, that degrade components (including collagens, gelatins, fibronectin, and laminin) of the extracellular matrix and basement membrane.35,3611
zoom view
Flowchart 7: Fate of endometrium after secretory phase.Source: Modified from Fritz MA, Leon Speroff L. Clinical Gynecologic Endocrinology and Infertility, 8th edition. Lippincott William and Wilkins; 2010. p. 134.
  • Matrix metalloproteinase is activated under influence of increasing VEGF concentration (in response to progesterone withdrawal), which causes vasoconstriction and hypoxia in the endometrial layers to be shed.
  • Also tumor necrosis factor (TNFα)-inhibits endometrial proliferation and induces apoptosis.
  • Vasoconstriction and myometrial contractions associated with the menstrual events are believed to be significantly mediated by prostaglandins (PGF2α and PGE2).
  • The basalis endometrium remains as it is during menses, and repair takes place from this layer.
 
Endometrial Preparation for Implantation
From the 7th to 13th day postovulation, with thickness of 7–10 mm, the endometrium is differentiated into three distinct zones, which after implantation forms the decidua of the pregnancy:
  1. Stratum basalis (less than one-fourth of the tissue) is the unchanged basalis fed by its straight vessels and surrounded by indifferent spindle-shaped stroma.
  2. Stratum spongiosum (mid-portion, approximately 50% of the total) is lace-like, composed of loose edematous stroma with tightly coiled spiral vessels and glands.
  3. Stratum compactum (superficial one-fourth) containing all the components but tightly compacted.
    • The change from proliferative to secretory endometrium and preparing it for the arriving blastocyst is a very well synchronized process.
    • This process involves temporary expression of many biochemical and molecular events in the endometrium for a time being called implantation window.
    • The endometrial receptivity array consists of a customized array containing 238 differentially expressed genes in endometrial samples that are within the window of implantation regardless of their histologic appearance, is a recent diagnostic tool to predict receptive behavior of endometrium to blastocyst.37
 
Implantation
Implantation is defined as the process by which an embryo attaches to the endometrial lining and penetrates first the epithelium and then the circulatory system of the mother to form the placenta.
  • Implantation begins with the loss of the ZP (hatching) about 2–3 days after, morula enters the uterine cavity.38 Thus, implantation occurs 5–7 days after fertilization (at the 32–256 cells-blastocyst stage).
  • Successful implantation requires invasion of healthy and genetically normal blastocyst and secretory receptive endometrium simultaneously. But there are various hormonal and immunological factors affecting implantation.
Implantation takes place in three stages:
  1. Apposition
  2. Adhesion
  3. Invasion (and placentation).
Apposition and adhesion:
  • Apposition begins at blastocyst stage as development of inner cell mass and trophectoderm are essential for initiating implantation.
  • A prerequisite step for apposition to endometrial lining is hatching of blastocyst from ZP which occurs in vitro by contraction and expansion of blastocyst while in vivo by the presence of lytic enzymes in uterine fluid dissolve ZP.
  • The polar trophoblast cells besides the inner cell mass are primarily involved in adhesion with endometrial epithelial cells.
  • Various cytokines (CSF-1, LIF, and IL-1) and adhesion molecules (including integrins, selectins, and trophinin) play their role in the process of adhesion by increasing capillary permeability near implanting blastocyst and providing extracellular matrix support.
Invasion and placentation:
  • Trophoblastic (called extravillous trophoblastic cells) invasion begins after the second week of ovulation and is completed after 10th or 11th day.12
  • The purpose of invasion (migration) is to remodel uterine vasculature by replacing maternal endothelium and converting high resistance, low flow vasculature in to high flow, low resistance vascular system in order to provide high blood flow interchange system between mother and fetus.
  • Deep endometrial stromal invasion by human embryo is called interstitial implantation.
  • The early embryo secretes a variety of enzymes (e.g. collagenase and plasminogen activators), that are important for digesting the intercellular matrix that holds the epithelial cells together.
  • By invading endometrial stromal cells and basement membrane, blastocyst then erodes the endothelium of maternal capillaries to make sinusoidal sacs lined with endovascular trophoblast, thus providing connection with maternal blood.
  • Further invasion is limited by various inflammatory cytokines secreted from the infiltrated lymphocytes in the endometrial cells and immunological factors like endometrial NK cells.
The first hormonal evidence of implantation (the appearance of hCG) occurs on 8, 9, or 10 days after ovulation; the earliest was 6 days and the latest 12 days.39
 
NEUROENDOCRINOLOGY
The HPO axis (Flowchart 8) plays a very important role by interplay of hormones. The direction signals sent by hypothalamus, and the operating signals given by anterior pituitary causes production of steroid hormones and ovulation. Depending upon, the amount of the hormone production, the lower centers send the positive or negative feedback signals in order to produce or reduce the signal for its hormone production respectively. This axis can be disturbed by various factors including increase in prolactin and TSH levels.
There are three types of feedback mechanisms:
  1. Long feedback mechanism: From the ovary to pituitary and hypothalamus depending upon steroid hormone production.
  2. Short feedback mechanism: From pituitary to hypothalamus depending upon gonadotropin secretion.
  3. Ultrashort feedback mechanism: From pituitary or hypothalamus for their autoregulation.
 
Neurohormone/Gonadotropin-releasing Hormone
zoom view
Flowchart 8: Neuroendocrine control in female.
  • It is a decapeptyl hormone, released from the arcuate nucleus of the hypothalamus into the portal circulation of anterior pituitary, secretion of which stimulates the release of gonadotropins (FSH and LH) from the anterior pituitary.
  • It is released in pulsatile manner (also called as LH pulse), and changes its amplitude and frequency depending upon the cycle day and requirement of the gonadotropin (Table 1).
  • Lower GnRH pulse frequencies and less amplitude favor FSH secretion, higher GnRH pulse frequency with higher amplitude favors LH secretion. Functions of GnRH on anterior pituitary:
    1. It causes synthesis and storage of gonadotropins.
    2. Activation: Movement of the gonadotropins from the storage site to the pool for direct secretion; a self-priming action.
    3. Direct secretion of gonadotropins.
  • Also, GnRH stimulates synthesis of activin, inhibin and follistatin. Activin enhances GnRH response on pituitary by forming its receptors on pituitary.40,41 Inhibin and follistatin suppresses the activity of activin.42
  • Catecholaminergic system has direct effect on release of GnRH. Norepinephrine stimulates the release while dopaminergic pathway inhibits the release of GnRH.
  • GnRH antagonist injections are now available by multiple amino acid substitution. They suppress gonadotropin secretion immediately by blocking the receptor site of GnRH on pituitary and thus making it unavailable for it. Nowadays, this is widely used as short protocol for COH in cases of patients undergoing IVF, in precocious puberty, endometriosis and prostate cancer. They degrade rapidly if given oral.
  • GnRH agonists are also widely used in COH by long protocol, for down regulation before starting IVF cycle and for treatment of endometriosis.13
Table 1   Gonadotropin-releasing hormone (GnRH) pulses.
Phase time
GnRH pulse amplitude
GnRH pulse frequency
Early follicular phase
6.5 IU/L
90 minutes
Mid-follicular phase
5.0 IU/L
-
Late follicular phase
7.2 IU/L
60–70 minutes
Early luteal phase
15.0 IU/L
100 minutes
Mid-luteal phase
12.2 IU/L
-
Late luteal phase
8.0 IU/L
200 minutes
Source: Clinical Gynecologic Endocrinology and Infertility, 8th edn. Lippincott Williams & Wilkins; 2011
 
Gonadotropin (FSH and LH)
  • They are water-soluble glycoproteins of higher molecular weight.
  • They are secreted by the beta cells of the anterior pituitary.
  • They have two subunits α and β. The amino acid composition of α subunit of FSH, LH, and hCG is the same; they differ in their β-subunits.
  • We have already understood the functions of FSH and LH in ovarian cycle.
  • Injectable gonadotropins are widely used for COH in treatment of infertility.
 
Prolactin
  • It is a polypeptide.
  • Its use in reproductive physiology is not clearly understood.
  • It is secreted by the alpha cells of anterior pituitary.
  • Its secretion remains under chronic inhibition by the dopaminergic pathway.
  • But if the prolactin levels increases in the blood, it stimulates hypothalamic-dopaminergic pathways, thus suppressing prolactin secretion but also GnRH secretion.
  • That results into hypogonadotrophic hypogonadism.
  • Mild hyperprolactinemia (20–50 ng/mL) causes poor preovulatory follicular growth and thus short luteal phase.43,44 Moderate hyperprolactinemia (50–100 ng/mL) causes anovulation, oligomenorrhea, or amenorrhea. Severe hyperprolactinemia (> 100 ng/mL) causes hypogonadism and estrogen deficiency and related consequences.45,46
 
Thyroid Hormone
  • Thyroid stimulating hormone (TSH) is released from the beta cells of the anterior pituitary.
  • Higher TSH causes disturbed folliculogenesis and defective spermatogenesis and embryogenesis. Hypothyroidism can affect fertility due to anovulatory cycles, luteal phase defects, hyperprolactinemia, and sex hormone imbalance.47
We have already studied about estrogen and progesterone in ovarian cycle in this chapter.
 
GENETICS IN REPRODUCTION
Genetic abnormality is often one of the causes of infertility, failure of infertility treatment, miscarriage, congenital abnormalities in child and some of the comorbidity. Genetics contributes to reproduction by influencing varieties of physiological process including gametogenesis, quality of gametes and hormonal homeostasis.
Reproduction genetic is a branch which deals with the relationship between genotype and reproduction. It includes studying the transmission of the genetic material and its epigenetic modification from one generation to next and also the effects of abnormalities in the genetic material on reproduction.
 
Genetic Tests of Infertile Couple
Availability of genetic tests from basic to advance to diagnose any genetic abnormalities in infertile couples/patients helps selecting further treatment plans like ICSI with preimplantation genetic diagnosis (PGD) or donor gametes/zygote. Basic genetic evaluation includes:
  • Karyotyping
    • In infertile female
    • In infertile male
    • In recurrent implantation failure
    • In recurrent miscarriage
  • Cystic fibrosis gene mutation
  • Fragile-X mental retardation gene mutation
  • Y-chromosome microdeletion test.
 
Karyotyping
Karyotyping in infertile female:
  • The prevalence of chromosomal abnormalities in women with regular ovulation, as reflected by a regular menstrual cycle, is reported to be 0.58%.48
  • Chromosomal abnormalities are higher in women with primary amenorrhea, premature ovarian failure and in cases of recurrent miscarriage (RM).14
  • Women carrying extra X-chromosomes are at risk of reduced ovarian reserve and premature ovarian insufficiency (POI).
  • Assessment of ovarian reserve is essential whenever numerical chromosomal translocations are involved.
  • Women lacking an X-chromosome (Turner syndrome, 45XO) are known to be infertile with streak ovaries.
Karyotyping in infertile male:
  • Chromosomal abnormalities account for approximately 5% of causes of infertility in males, and the prevalence increases to 15% in the population of azoospermic males.49
  • Aneuploidy is the most common abnormality seen in infertile male, specifically of sex chromosome.
  • Klinefelter's syndrome (nonmosaic, 47, XXY; and mosaic, 47, XXY/46, XY), is the most common chromosomal abnormality caused by aneuploidy with 5% prevalence in severe oligospermic men and 10% in azoospermic men.50 The syndrome causes arrest of spermatogenesis at primary spermatocyte level. The affected men are sterile but sperm can be seen in the ejaculate of some men with nonmosaic pattern.
  • Chromosomal translocation is another source of aneuploidy. Robertsonian translocations are more common in oligozoospermic and azoospermic men, with rates of 1.6% and 0.09%, respectively.51,52 Carriers of Robertsonian translocations may exhibit a normal phenotype but could be infertile because of a lack of gamete production.
Karyotyping in recurrent implantation failure:
In couples presenting with RIF the prevalence of chromosomal abnormalities on karyotyping is 2.11%, more specifically 2.73% in women with RIF compared to 1.89% in male partners of women suffering from RIF.53
Karyotyping in recurrent miscarriage:
The prevalence of structural balanced chromosomal translocation in either partner of a couple experiencing RM increases according to the number of miscarriages; 2.2% after one miscarriage; 4.8% after two miscarriages; and 5.2% after three miscarriages.54 However, the frequency of numerical chromosomal abnormalities in miscarriages with advancing age is also high.
 
Y-chromosome Microdeletion Test
  • Y-chromosome microdeletions, in the AZF region, have been observed in between 3% and 15% of men with severe oligozoospermia and non-obstructive azoospermia.55
  • Proper genetic counseling should be done, as this can be transmitted to the male offspring.
 
Cystic Fibrosis Gene Mutation
  • Cystic fibrosis is the most common autosomal recessive condition in northern Europeans with a carrier rate of 1 in 25 Caucasians.
  • Cystic fibrosis transmembrane regulator gene mutations are associated with reproductive tract abnormalities such as congenital absence of the vas deferens and congenital epididymal obstruction.5658
  • In contrast to patients with AZF deletions, these patients typically have normal spermatogenesis with normal testicular size and consistency, normal FSH, absence of the vas deferens, and/or an indurated epididymis.
  • However, there has been no study to date showing that these genetic conditions are mutually exclusive. Therefore, the possibility exists that a single patient can genetically demonstrate both conditions.
 
Fragile X Mental Retardation 1 Gene Mutation
Fragile X syndrome has a prevalence of 1 in 4,000 males and 1 in 6,000 females and is the most common cause of mental retardation in men.59 This syndrome is caused by mutation in fragile X mental retardation 1 (FMR-1) gene, which codes for fragile X mental retardation protein (FMRP), it might be associated with poor ovarian response during ovarian stimulation.
Couples with high maternal age or with RM and RIF can be offered IVF/ICSI with PGS. This involves taking a biopsy of a single blastomere from day 3 embryo or trophectoderm biopsy from a blastocyst and checking for any aneuploidy.60,61 In this case there is a choice of transferring only euploid embryo. In case of couples with single gene disorders, IVF/ICSI along with PGD can be offered, which tests the single cell biopsied from the embryo for that specific genetic abnormality. The embryo, which is free from the disorder, can be transferred.62
 
IMMUNOLOGY IN REPRODUCTION
  • Autoimmunity influence reproduction by:
    • Affecting the reproductive life and fertility of both sexes, and
    • Affecting implantation of the embryo by either failure of implantation or rejection of implantation resulting in abortion.
  • Autoimmune disorders involve an immune response directed against a specific part of host or self, like systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLA) syndrome.
  • Alloimmune disorders involve an abnormal maternal immune response, to fetal or placental antigens, e.g. 15maternal cytotoxic antibodies, absent maternal blocking antibodies, and disturbance of NK cell function and distribution.
  • Mechanisms involved in autoimmune disorders:
    • Direct action of antibodies (antiphospholipid, antithyroid, antinuclear antibodies) without any clinical disorder.
    • By affecting process of spermatogenesis, oogenesis, implantation and pregnancy loss.
    • By causing vasculitis, impairing the blood circulation.
The major immunological disorders affecting fertility are:
  • Antisperm antibodies (ASAs)
  • APLA
  • Human leukocyte antigen-killer cell immunoglobulin- like receptor (HLA-KIR)
Antisperm antibody: The presence of ASAs in serum and in the secretions of the reproductive system is seen in some infertile patients. Its role, however, in reproduction remains debatable as many authors have revealed ASA in a relatively high percentage of both infertile as well as fertile couples. Thus, ASA test is not an essential workup in the evaluation of infertile patients.
The role of ASAs is in various mechanisms have been proposed affecting male fertility: sperm agglutination and impaired cervical mucus penetration, complement-mediated sperm injury through the female genital tract, and interference with gametes interaction.63
Various tests for qualitative detection (like agglutination tests, MAR, complement-mediated sperm immobilization or cytotoxicity assays, anti-human antibody-coated immunobeads, IFA and immunogold assay) and for quantitative detection (like ELISA, radiolabeled antiglobulin assays, radioisotopes and enzymes are quantitative probes and FCM) and tests for identification of specific bond (like immunoblotting and affinity chromatography) have been evolved but have so far not been used in the routine laboratory investigation of the subfertile couple.
APLA syndrome or APS: APS is a systemic autoimmune inflammatory thrombotic disorder, characterized by the presence of antiphospholipid (aPL) antibodies in the serum of the patient and associated with an array of obstetric complication with or without vascular thromboembolic events.
The diagnostic criteria for APS are mentioned in Table 2.64
Antiphospholipid antibodies are directed against various phospholipid-binding proteins. The most important of these proteins is β-2 glycoprotein but some less frequent targets include prothrombin, thrombin, tPA, annexin-2, etc.
The exact mechanism through which these antibodies mediate the prothrombotic state is not clear but proposed mechanisms of action include:
  • Activation of cellular elements (platelets, endothelial cells, and monocytes)
  • Inhibition of the fibrinolytic system
  • Activation of the coagulation cascade, and
  • Activation of the complement system.
Anticoagulation and antiplatelet medications have been the mainstay of the treatment of this disease.
Human leucocyte antigens-killer immunoglobulin-like receptor: Blastocyst adheres and implants into the decidualized endometrial cell lining. HLA-KIR is an antigen antibody interaction, which if favorable results into successful correct implantation and placentation and if incorrect results into implantation failure or incorrect placentation leading to abortion, or pregnancy complications like preeclampsia, prematurity, etc.
HLA system is the locus of genes, which encodes for the proteins on the surface of the cells associated with the regulation of the immune system. EVT cells of the blastocyst express a large repertoire of class I HLA-C and nonclassical HLA-G and HLA-E antigens, whereas the class I antigens HLA-A and HLA-B and class II antigens are absent.65,66
Table 2   Diagnostic criteria for antiphospholipid syndrome (APS)64 (the updated international preliminary classification criteria for APS).
Clinical criteria
Laboratory criteria
Vascular thrombosis (arterial/venous/microvascular)
One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue or organ
Lupus anticoagulant present in plasma on two or more occasions at least 12 weeks apart, detected according to the guidelines of the International Society on Thrombosis and Hemostasis
Obstetric morbidity
One or more premature birth of normal neonate before 34 weeks of gestation
Anticardiolipin antibody (IgG and/or IgM iso-type), in serum or plasma, present in medium or high titers on two or more occasions at least 12 weeks apart, measured by a standardized ELISA
One or more unexplained death of a normal fetus at or beyond 10 weeks of gestation
Three or more unexplained spontaneous abortions before 10 weeks’ gestation
Anti-β2 glycoprotein I antibody (IgG and/or IgM isotype) in serum or plasma, present on two occasions at least 12 weeks apart, measured by a standardized ELISA
16HLA-C genotypes are the main one and could be HLA-C1 or HLA-C2.67 Of the two, C2 is a stronger ligand than C1. HLA genes are inherited one from mother and one from father in each cell. So, EVT cell would express HLA C1C1, HLA C1C2, or HLA C2C2. HLA C1C1 is the most compatible, where as HLA C2C2 is the least.
Uterine NK cells express receptor KIR for ligand HLA of the EVT cells. The maternal KIR genotype could be haplotype AA (no activating KIRs), AB, or BB (1–10 activating KIRs).67
Interaction and compatibility between KIR and its HLA (ligand) facilitates migration followed by invasion of EVTs into maternal vasculature. Thus, maternal immune system is not going to reject the semiallogenic fetus. The recognition of HLA-C expressing trophoblasts by maternal KIR positive NK cells during pregnancy is important for successful placentation.6871
Noncompatibility of expression of genotypes of HLA and KIR results in failure of trophoblastic invasion which might be correlated with an increased risk of RM, preeclampsia and fetal growth retardation.70,71
 
CONCLUSION
It is essential to understand reproductive biology, physiology and reproductive endocrinology to help in making differential diagnosis from various causes of infertility in evaluation of both the partners. Reproductive Genetics and immunology play a very important role in case of understanding reason for failure of infertility treatment, and thus helps to provide a treatment suitable to the conditions.
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