Textbook of assisted reproductive techniques volume 2 clinical perspectives

Textbook of Assisted Reproductive Techniques Established as the definitive reference for the IVF clinic, this Sixth Edition has been extensively revised, with the addition of several important new contributions on clinical topics, including the use of digitalization and precision medicine in the IVF clinic, the environment and reproduction, the use of gonadotropin-releasing hormone agonists and the efficiency of IVF, controlled ovarian stimulation for freeze-all cycles, immunology in ART, home monitoring of ART cycles, luteal-phase support in ART, the POSEIDON stratification of “low prognosis” patients in ART, controlled ovarian stimulation for low-responder patients, adjuvants for poor responders, innovative therapies in diminished ovarian reserve and primary ovarian insufficiency patients, and fertility options for transgender and nonbinary individuals As previously, methods, protocols, and techniques of choice are presented by IVF pioneers and eminent international ­experts David K Gardner, AM, FAA, DPhil, is the Scientific Director of Melbourne IVF, Melbourne, and a Distinguished Professor in the School of BioSciences at the University of Melbourne, Australia Ariel Weissman, MD, is a Senior Physician at the IVF Unit, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon, and a full Professor of Obstetrics and Gynecology at the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Colin M Howles, PhD, FRSM, is based at Aries Consulting SARL, Geneva, Switzerland, and is an Honorary Fellow, University of ­Edinburgh, UK Zeev Shoham, MD, is a Professor at the Hebrew University, Jerusalem, Israel, a consultant in IVF, and co-founder of IVF-Worldwide This volume is available on its own (ISBN 9781032214801) or as part of the two-volume set (ISBN 9781032245348) Taylor & Francis Taylor & Francis Group http://taylorandfrancis.com Textbook of Assisted Reproductive Techniques Volume 2: Clinical Perspectives Sixth Edition Edited by David K Gardner AM, FAA, DPhil Scientific Director, Melbourne IVF, Melbourne, and Distinguished Professor, School of BioSciences, University of Melbourne, Australia Ariel Weissman MD Senior Physician, IVF Unit, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Holon Professor of Obstetrics and Gynecology, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Colin M Howles PhD, FRSM Aries Consulting SARL, Geneva, Switzerland and Honorary Fellow, University of Edinburgh, Edinburgh, UK Zeev Shoham MD Professor, The Hebrew University Consultant in IVF and Co-founder of IVF-Worldwide, Jerusalem, Israel Sixth edition published 2024 by CRC Press 6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742 and by CRC Press Park Square, Milton Park, Abingdon, Oxon, OX14 4RN CRC Press is an imprint of Taylor & Francis Group, LLC © 2024 selection and editorial matter, David K Gardner, Ariel Weissman, Colin M Howles, and Zeev Shoham; individual chapters, the contributors This book contains information obtained from authentic and highly regarded sources While all reasonable efforts have been made to publish reliable data and information, neither the author[s] nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made The publishers wish to make clear that any views or opinions expressed in this book by individual editors, authors or contributors are personal to them and not necessarily reflect the views/opinions of the publishers The information or guidance contained in this book is intended for use by medical, scientific or health-care professionals and is provided strictly as a supplement to the medical or other professional’s own judgement, their knowledge of the patient’s medical history, relevant manufacturer’s instructions and the appropriate best practice guidelines Because of the rapid advances in medical science, any information or advice on dosages, procedures or diagnoses should be independently 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reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers For permission to photocopy or use material electronically from this work, access www.copyright.com or contact the Copyright Clearance Center, Inc (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400 For works that are not available on CCC please contact mpkbookspermissions@tandf.co.uk Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for identification and explanation without intent to infringe ISBN: 9781032214764 (Vol hardback) ISBN: 9781032214788 (Vol paperback) ISBN: 9781003268598 (Vol eBook) ISBN: 9781032214801 (Vol hardback) ISBN: 9781032214856 (Vol paperback) ISBN: 9781003268611 (Vol eBook) ISBN: 9781032761695 (Vol Indian edition) ISBN: 9781032761701 (Vol Indian edition) ISBN: 9781032245348 (Two-volume set/Hardback) ISBN: 9781032558578 (Two-volume set/Paperback) ISBN: 9781032752877 (Indian edition, two-volume set/Hardback) DOI: 10.1201/9781003268611 Typeset in Warnock Pro by KnowledgeWorks Global Ltd CONTENTS Preface ix Contributors xi 32 Quality Management in Reproductive Medicine 351 Michael Alper 33 The Use of Digitalization and Precision Medicine in the IVF Clinic 360 Fleur Cattrall 34 Lifestyle, Periconception, and Fertility 366 Jessica A Grieger, Lisa J Moran, Sarah A Robertson, Rui Wang, and Robert J Norman 35 Human Reproduction Across the Life Course and the Total Environment 376 Leah Martin, Yu Zhang, Irene Souter, and Carmen Messerlian 36 Indications for In Vitro Fertilization Treatment .395 Julie Labrosse and Michaёl Grynberg 37 Initial Investigation of the Infertile Couple 400 Ranit Hizkiyahu, William Buckett, and Togas Tulandi 38 Prognostic Testing for Ovarian Reserve 409 Simone L Broer, Charlotte HE Weimar, Bart CJM Fauser, and Frank J Broekmans 39 Drugs Used for Ovarian Stimulation: Clomiphene Citrate, Aromatase Inhibitors, Metformin, Gonadotropin-Releasing Hormone Analogues, and Gonadotropins 419 Colin M Howles and Zeev Shoham 40 The Role of Follicle-Stimulating Hormone and Luteinizing Hormone in Ovarian Stimulation: Current Concepts 443 Ernesto Bosch, Elena Labarta, and Elkin Muñoz 41 Endocrine Characteristics of Assisted Reproductive Technology Cycles 450 Bulent Urman, Baris Ata, and Hakan Yarali 42 The Use of Gonadotropin-Releasing Hormone Agonists and the Efficiency of In Vitro Fertilization 463 Pasquale Patrizio, Sanaz Ghazal, Judith AF Huirne, and Roel Schats 43 Gonadotropin-Releasing Hormone Antagonists in Ovarian Stimulation for In Vitro Fertilization 472 Efstratios M Kolibianakis, Pinelopi G Ioannidou, Julia K Bosdou, Georg Griesinger, and Basil C Tarlatzis 44 GnRH Agonist Triggering 480 Katherine Koniares, Leah Kaye, Claudio Benadiva, and Lawrence Engmann 45 Segmentation of In Vitro Fertilization Cycles 494 Ana Raquel Neves and Nikolaos P Polyzos 46 Controlled Ovarian Stimulation for Freeze-All Cycles 502 Yossi Mizrachi and Ariel Weissman 47 Immunology in ART 515 Isabel Cuadrado-Torroglosa, Diana Alecsandru, and Juan A Garcia-Velasco 48 Monitoring of Stimulated Cycles in Assisted Reproduction 534 Martina Capuzzo and Antonio La Marca 49 Home Monitoring of ART Cycles 539 Wenjing Zheng, Jan Gerris, Eline Dancet, and Thomas D’Hooghe v vi Contents 50 Oocyte Collection 547 Andrew Murray and Gab Kovacs 51 Luteal Phase Support in Assisted Reproduction Techniques .555 Cristina Rodríguez-Varela and Elena Labarta 52 Treatment Strategies in Assisted Reproduction for the Poor-Responder Patient 561 Ariel Weissman and Colin M Howles 53 The Poseidon Stratification of “Low-Prognosis Patients in ART”: Management Strategies and Outcomes 591 Sandro C Esteves, Hakan Yarali, Peter Humaidan, and Carlo Alviggi 54 Controlled Ovarian Stimulation for Low-Responder Patients .613 Alberto Vaiarelli, Danilo Cimadomo, Cecilia Rucci, Pasquale Petrone, Carlotta Scarafia, Laura Rienzi, and Filippo Maria Ubaldi 55 Adjuvants for Poor Responders 622 Christos A Venetis 56 Innovative Therapies in Diminished Ovarian Reserve (DOR) and Primary Ovarian Insufficiency (POI) Patients 636 Francesc Fabregues, Janisse Ferreri, and Marta Mendez 57 Repeated Implantation Failure 647 David Reichman, Hey-Joo Kang, and Zev Rosenwaks 58 Ultrasonography in Assisted Reproduction 659 Laurel Stadtmauer, Jayapriya Jayakumaran, David Cohen, and Ilan Tur-Kaspa 59 Sperm Recovery Techniques: Clinical Aspects and Laboratory Processing 677 Herman Tournaye, Neelke De Munck, Patricio Donoso Pozo, and Francisco Osorio Martini 60 Embryo Transfer Technique 696 Leah Roberts and Jason Franasiak 61 Cycle Regimes for Frozen-Thawed Embryo Transfer 701 Jane Reavey and Tim Child 62 IVF Anaesthesia 706 Alexander Ioscovich, Yair Binyamin, and Daniel Shatalin 63 Endometriosis and ART 714 Jamie Merkison, Marisa Berger, Christian Huang, Aaron Rosen, and Alan DeCherney 64 Polycystic Ovary Syndrome and Assisted Reproduction 725 Adam H Balen 65 Fertility Preservation Strategies 734 Claus Yding Andersen and Stine Gry Kristensen 66 Uterus Transplantation: In Transition from Experimental to Clinical Procedure 746 Mats Brännström, Ghada Hussein, Ali Khatibi, and Pernilla Dahm-Kähler 67 Viral Disease and ART 756 Carole Gilling-Smith 68 Fertility Options for Transgender and Nonbinary Individuals 770 Amanda R Schwartz and Molly B Moravek 69 Ovarian Hyperstimulation Syndrome .783 Federica Di Guardo and Christophe Blockeel Contents vii 70 Bleeding, Severe Pelvic Infection, and Ectopic Pregnancy 794 Raoul Orvieto 71 Egg and Embryo Donation 802 Mark V Sauer and Haley G Genovese 72 Gestational Surrogacy 813 Hadas Ganer Herman, Arieh Raziel 73 Patient Support in the Assisted Reproduction Technology Programme 819 Sharon N Covington and Laura S Covington 74 The Relationship between Stress and In Vitro Fertilization Outcome .829 Alice D Domar 75 Risk and Safety Management in Assisted Reproduction Technology 834 Paul Pirtea, Dominique de Ziegler, Sean Soketang, Chloe Tran, and Jean-Marc Ayoubi Index 841 Taylor & Francis Taylor & Francis Group http://taylorandfrancis.com PREFACE The first edition of the Textbook of Assisted Reproductive Techniques was published in 2001 As the textbook now enters its sixth edition, some 45 years since the birth of Louise Brown, the world’s first test tube baby in the United Kingdom, it is remarkable to reflect upon the changes in assisted human conception that have been documented in each successive edition of the textbook Over the past 20 years, we have witnessed the widespread implementation of single blastocyst transfer, and the ability to undertake trophectoderm biopsy and genetic analysis now using next-generation sequencing to accurately determine chromosomal copy number, and to provide precise genetic diagnosis for patients as needed This shift in practice of transferring only one high-quality embryo has brought us closer to the mantra of “one embryo, one baby.” Cryopreservation, historically performed using slow-rate controlled freezing, has now been superseded by vitrification for both oocytes and embryos, with oocyte cryopreservation becoming a realistic treatment for fertility preservation, especially for oncology patients and younger women wishing to preserve their fertility Improvements in laboratory culture techniques and incubation devices, including time-lapse imaging, have also contributed to the adoption of single-embryo transfers without reducing the chance of a live birth Excitingly, more technologies are now available for sperm assessment, and the knowledge underpinning in vitro maturation has facilitated the development of potential new approaches for IVF As for ovarian stimulation protocols, there has been, over the past 20 years of this textbook series, a major shift in practice The clinical acceptance of the GnRH antagonist protocol, first registered in 1999, took more than 10 years to be widely adopted With the possibility of using a GnRH agonist to trigger follicular maturation, the protocol has become the preferred choice, facilitating the concept of an “OHSS-free clinic.” A plethora of new pharmaceutical FSH agents have been introduced into practice that have resulted in increased patient convenience and drug delivery precision (due to use of pen devices) rather than increased live birth rates This is a further reflection of the complexity of the overall IVF treatment process—in particular, the pivotal role that the embryology laboratory continues to play in improving cycle success Sadly, however, over the duration of this textbook’s life span, we have lost several authors—all dear friends and colleagues— whom we miss and to whom we are grateful for their enormous contributions to our field during their lifetimes: • • • • • • • • • • Marinko Biljan, Quebec Isaac Blickstein, Rehovot Jean Cohen, Paris Howard W Jones Jr, Norfolk Michelle Lane, Adelaide Ragaa Mansour, Egypt Queenie V Neri, New York Lynette Scott, Boston Carl Wood, Melbourne Yury Velinsky, Chicago Finally, we lost one of the pioneering fathers of this field, Bob Edwards, a giant in our field on whose shoulders we have all been fortunate to stand David K Gardner, Ariel Weissman, Colin M Howles, and Zeev Shoham ix Risk and Safety Management in Assisted Reproduction Technology night Recognizing the importance of this safety measure highlights how and particularly when patients have to be made aware of it The best time for reminding patients of this measure is on the day of ovulation triggering, early enough for action to be taken and not too long before the retrieval day so as to incur the risk of the recommendation being forgotten Awareness of the patient workload (Figure 75.4) is therefore a crucial safety step that is as important as the workload of the medical team In the defence deployed against haemorrhage risks, the spouse is a key element in the whole safety link Misinformation or information provided at an erroneous time deprives the patient of a key safety feature if, ultimately, the spouse is not with the patient during that first night Safety of the whole process indeed includes the presence of the spouse for intervening—returning to the hospital—if need be We see therefore that proper safety operation of outpatient procedures such as ART implies mastering the workload pattern—What? How much/many? When?—of both the medical team and patients Each may encounter their limit with an excess workload—the safety ceiling However, this will likely happen at distinct times in the ART process for patients and the medical team Contrary to what prevails in aviation—passengers might as well be sandbags—patients need to be included as active partners in the workload analysis of an ART operation and therefore in the whole of safety management Education conceived as “safety inside” Safety and, in particular, a safety culture cannot be force-fed to people who have long been managing their work operations individually with limited concerns for outside inputs into safety management The perfect vector for inoculating a safety culture in medical operation is education [3], which can dispense new knowledge items laced with related pertinent safety issues This is what we identify as education conceived as “safety inside,” by analogy to a certain microprocessor found “inside” computers of all kinds and makes Conclusion Safety management is a science that has taken medicine by storm under the impetus of insurance companies and hospital administration ART, a highly repetitive by-procedure operation, is no exception The nature of ART as generally conducted in healthy individuals should be an example of ultimate safety achievement 839 References de Ziegler D, Gambone JC, Meldrum DR, et al Risk and safety management in infertility and assisted reproductive technology (ART): From the doctor’s office to the ART procedure Fertil Steril 2013;100:1509–17 Meldrum DR, de Ziegler D Introduction: Risk and safety management in infertility and assisted reproductive technology Fertil Steril 2013;100:1497–8 de Ziegler D, de Ziegler N, Sean S, et al Training in reproductive endocrinology and infertility and assisted reproductive technologies: Options and worldwide needs Fertil Steril 2015;104: 16–23 Boothman RC, Imhoff SJ, Campbell DA Jr Nurturing a culture of patient safety and achieving lower malpractice risk through disclosure: Lessons learned and future directions Front Health Serv Manage 2012;28:13–28 Schenker JG, Ezra Y Complications of assisted reproductive techniques Fertil Steril 1994;61:411–22 Nardelli AA, Stafinski T, Motan T, et al Assisted reproductive technologies (ARTs): Evaluation of evidence to support public policy development Reprod Health 2014;11:76 Guo J, Meng F, Ma N, et al Meta-analysis of safety of the coadministration of statin with fenofibrate in patients with combined hyperlipidemia Am J Cardiol 2012;110:1296–301 Schulman S, Spencer FA Antithrombotic drugs in coronary artery disease: Risk benefit ratio and bleeding J Thromb Haemost 2010;8:641–50 Villette C, Bourret A, Santulli P, et al Risks of tubo-ovarian abscess in cases of endometrioma and assisted reproductive technologies are both under- and overreported Fertil Steril 2016;106:410–5 10 Messini CI, Daponte A, Anifandis G, et al Standards of care in infertility in Europe Eur J Obstet Gynecol Reprod Biol 2016;207:205–10 11 Nelson SM Venous thrombosis during assisted reproduction: Novel risk reduction strategies Thromb Res 2013;131(Suppl 1): S1–3 12 Streuli I, Fraisse T, Ibecheole V, et al Intermediate and premutation FMR1 alleles in women with occult primary ovarian insufficiency Fertil Steril 2009;92:464–70 13 Harper J, Geraedts J, Borry P, et al Current issues in medically assisted reproduction and genetics in Europe: Research, clinical practice, ethics, legal issues and policy Hum Reprod 2014;29: 1603–9 14 Denham CR, Sullenberger CB 3rd, Quaid DW, et al An NTSB for health care: Learning from innovation: Debate and innovate or capitulate J Patient Saf 2012;8:3–14 15 Skinner H Bad medicine: Resilience Br J Gen Pract 2017;67:13 INDEX Note: Locators in italics represent figures and bold indicate tables in the text A AACEP protocol, 581–582 Absolute uterine factor infertility (AUFI), 746 ACA, see Affordable Care Act ACOG, see American College of Obstetricians and Gynecologists Acquired immunodeficiency syndrome (AIDS), 756, 757 ACR, see American College of Radiology Acupuncture, 696, 709 Adalimumab, 517 Adenomyoma, 665 Adenomyosis, 530, 650, 665 Adjuvants for poor responders androgens, 623 antioxidants, 630–631 challenges and interpreting literature, 622 dehydroepiandrosterone, 626–628 growth hormone, 628–629 ovarian stimulation for ART, strategies to treat, 623, 623 testosterone, 623–626 therapeutic challenge, 622 Adjuvants or add-ons, 623 Advanced maternal age (AMA), 396, 397, 613, 614, 616–618, 804 Aerosol-generating procedures (AGPs), 764 AFC, see Antral follicle count Affordable Care Act (ACA), 772 Age-related fertility decline, 416 AGPs, see Aerosol-generating procedures AI, see Artificial intelligence AIDS, see Acquired immunodeficiency syndrome Airmanship, 837 AIUM, see American Institute of Ultrasound in Medicine Alfentanil, 708 Alkylating agents, 734 AMA, see Advanced maternal age American Academy of Child and Adolescent Psychiatry, 770 American College of Obstetricians and Gynecologists (ACOG), 663 American College of Radiology (ACR), 664 American Institute of Ultrasound in Medicine (AIUM), 663 American Society of Anesthesiologists (ASA), 706; see also Anesthesia American Society of Reproductive Medicine (ASRM), 396, 496, 539, 542, 725, 758, 771, 774, 784, 785 AMH, see Anti-Mullerian hormone Anaesthesia, 697 Analgesics, 697 ANAs, see Antinuclear antibodies Anastrozole, 421, 422, 684; see also Aromatase inhibitors Androgenization, 403; see also Female infertility Androgen receptor (AR), 457, 626 Androgens, 378 COS for low-responder patients, 618–619 in folliculogenesis, 623 steroidogenesis of, 626 Androstenedione, 725 Anejaculation, 678 Ang-2, see Angiopoietin-2 Angiopoietin-2 (Ang-2), 481 Anovulatory infertility, 419, 725 Anti-Müllerian hormone (AMH), 401, 409, 539, 591, 725, 729, 783, 803; see also Female infertility; Ovarian reserve biomarkers Anti-ovarian antibodies (AOAs), 528 Antibiotics, 697 Antigen-presenting cells (APCs), 515, 516 Antinuclear antibodies (ANAs), 527–528 Antioxidants CoQ10, 630 L-arginine, 631 melatonin, 630–631 physiological basis of intervention, 630 poor responders, 631 Antiphospholipid syndrome (APS), 524, 527, 527 Antral follicle count (AFC), 450, 534, 539, 591, 783; see also Female infertility; Ovarian reserve biomarkers 3D, 660 Anxiolysis, see Minimal sedation AOAs, see Anti-ovarian antibodies APCs, see Antigen-presenting cells APS, see Antiphospholipid syndrome AR, see Androgen receptor Aromatase, 421 Aromatase inhibitors, 421; see also Ovarian stimulation anastrozole, 421 drugs available, 421–422 generations of, 421 letrozole, 421 pharmacokinetics, 421 side effects, 421 ART, see Assisted reproductive technology Artificial intelligence (AI), 360; see also Digital IVF clinic based algorithms, 361, 364 black box nature, 361 emergence of, 360 4th industrial revolution, 360 ASA, see American Society of Anesthesiologists; Antisperm autoantibodies Asherman’s syndrome, see Intrauterine adhesions Aspermia, 403; see also Male infertility Aspirin or metformin, 787 ASRM, see American Society of Reproductive Medicine Assisted reproduction technology (ART), 352, 380, 419, 504; see also Endometriosis; Risks in ART; Safety management system home monitoring of, see Home monitoring of ART cycles hormonal assessment, 534–535 imaging, 659 immunology in, see Immunology in ART immunomodulator studies in, 524, 525–526 to inculcate safety culture, 839 laboratory guidelines, 352 low-prognosis patients, POSEIDON group, 594–597, 595 LPS in, see Luteal phase support pre-stimulation assessment, 534 quality control and assurance, 836–837 strategies in, 561, 582 ultrasound, 534, 535 workload pattern, 838 Assisted reproduction technology cycles, 450 androgens, 457–458 early progesterone levels, 452, 454 flare effect, 451 follicle rupture prevention, 451 follicular phaseprogesterone, 453 FSH window, 450, 451 GnRH agonist injections, 451 gonadotropin-dependent recruitment, 450 hCG and progesterone levels, 455 late follicular-phase progesterone elevation, 452, 454 LH ceiling, 451 luteal phase following ovarian stimulation, 455–457 multi-follicular growth induction, 450 negative feedback mechanisms, 450 ovarian stimulation, 450, 458 random start ovarian stimulation, 458 role of LH, 451–452 triggering oocyte maturation, 454–455 Asthenospermia, 404 Atresia, 561 Audits, 356 Autoimmunity anti-ovarian antibodies, 528 antinuclear antibodies, 527–528 antiphospholipid syndrome, 524, 527, 527 celiac disease, 529 diabetes-associated autoantibodies, 529 latent autoimmune diabetes in adults, 528 oral glucose tolerance test, 529 thyroid peroxidase antibodies, 528 Azoospermia, 404, 678 B BA, see Buserelin acetate Basal body temperature (BBT), 400–401 BBT, see Basal body temperature BFRs, see Brominated flame retardants Bicornuate uterus, 746–747 Bioinformatics, 360 841 Index 842 Bleeding, 794 intraperitoneal or retroperitoneal, 794–795 management, 794 vaginal, 794 Blood (platelet-rich plasma), 636 BMDSCs, see Bone marrow-derived SCs BMI, see Body mass index BMP, see Bone morphogenic protein BMT, see Bone marrow transplantation Body mass index (BMI), 360, 362, 400, 423, 431, 432, 456, 507, 563, 577, 579, 594, 596, 600, 614, 618, 728, 778, 783, 830 Bologna criteria, 401 Bone marrow-derived SCs (BMDSCs), 640 Bone marrow transplantation (BMT), 734, 735 Bone morphogenic protein (BMP), 640 British Medical Association (BMA), 813 Brominated flame retardants (BFRs), 376, 378 Buserelin acetate (BA), 565 C Cabergoline, 730 Caesarean section (CS); see also Ultrasonography scar niche, 667–668 Cappuccino effect, 548, 550; see also Oocyte collection CBAVD, see Congenital bilateral absence of the vas deferens CBT, see Cognitive behavioural therapy CC, see Clomiphene citrate CD, see Celiac disease CDC, see Centers for Disease Control and Prevention Ceiling effect, 577, 578 Celiac disease (CD), 529 Centers for Disease Control and Prevention (CDC), 410, 495, 561, 661, 762, 763, 802 Central nervous system (CNS), 707, 796 CF, see Cystic fibrosis Chatbot, 363 Chemicals, 378–379; see also Reproductive health long-lived chemicals, 378–379, 380 short-lived chemicals, 378, 379 Chemotherapy drugs, 734 Chinese hamster ovary (CHO), 427 Chlamydia trachomatis, 395, 400, 529 Chlorotrianisene, 419 CHO, see Chinese hamster ovary Chorionic gonadotropin, 426; see also Gonadotropin CI, see Confidence interval Cigarette smoke, 376, 377 CLBR, see Cumulative live birth rate ClearPlan® fertility monitoring system, 541–542 Clinical pregnancy rate (CPR), 495, 701 Clomiphene citrate (CC); see also Ovarian stimulation action mechanism, 419 anovulatory infertility, 419–420 chlorotrianisene, 419 drug description, 419 indications and contraindications, 419–420 side effects and safety, 420 structure, 419 treatment, 420 CMV, see Cytomegalovirus CNS, see Central nervous system Coenzyme Q10 (CoQ10), 630 clinical evidence, 630 physiological basis of intervention, 630 Cognitive behavioural therapy (CBT), 831, 832 Commissioning couple, 813; see also Gestational surrogacy Confidence interval (CI), 420, 475, 475, 574, 594, 595, 601, 602, 680, 715, 727, 730 Congenital bilateral absence of vas deferens (CBAVD), 403–405, 677, 687–689 Congenital unilateral agenesis of vas deferens (CUAVD), 405 Conscious sedation, see Moderate sedation; Monitored anesthesia care CONSORT (Consolidated Standards of Reporting Trials), 608 Continuous-long protocol, 466 Contraceptive pill (CP), 446 Controlled ovarian stimulation (COS), 419 drawbacks of large cohort of follicles, 503 DuoStim, 504 evidence-based medicine, 509 for freeze-all cycles, see Freeze-all cycles GnRH agonist vs antagonist, 505 indications for cycle segmentation, 503 for low-responder patients, see Poor ovarian response luteal phase and random start stimulation, 504 practical and medical considerations, 503 pre-treatment interventions, 503 preferred timing of initiating, 504 progesterone-primed ovarian stimulation, 505–506 summary of recommendations, 509 Corpus luteum, 452 Cortisol and IVF outcome, 831 COS, see Controlled ovarian stimulation Covid-19 (SARS-CoV-2); see also Viral disease digital health systems, 542 and infertility patients, 832 outbreak of, 763–764 patient support as, 821 positive pregnancies, 530 in pregnancy, 764, 821 SARS-CoV-2, 763–764 vaccination, 370 CP, see Contraceptive pill CPR, see Clinical pregnancy rate CRL, see Crown–rump length Cross-border surrogacy, 816; see also Gestational surrogacy Crown-rump length (CRL), 671 Cryopreservation, 788 Cryptozoospermia, 404 CUAVD, see Congenital unilateral agenesis of vas deferens Cumulative live birth rate (CLBR), 494, 495, 497, 502 Cumulative live birth rate per intention to treat (CLBR per ITT), 613 Cycle segmentation, see Elective frozen embryo transfer Cystic fibrosis (CF), 403, 405, 689, 709 Cytomegalovirus (CMV), 529–530 D DAA, see Diabetes-associated autoantibodies Danish Fertility Preservation Program, 736; see also Fertility preservation Deceased donor (DD) UTx; see also Uterus transplantation cases, 750, 751 hysterectomy (open surgery technique), 747 reports, 750 Deep sedation, 706 Deep veno-thromboembolism (DVT), 834–835 DEHP, see Di(2-ethylhexyl) phthalate exposure Dehydroepiandrosterone (DHEA), 626–628 clinical evidence, 627 physiological basis of intervention, 626–627 synthesis and critical appraisal of evidence, 627, 628 DeHydroEpiAndrosterone-Sulfate (DHEA-S), 401 Delivery rooms (DRs), 837 Deming cycle (the “Plan–Do–Check–Act” cycle), 352 Dermoid cysts, 661 DET, see Double embryo transfer DHEA, see Dehydroepiandrosterone DHEA-S, see DeHydro EpiAndrosterone-Sulfate Diabetes-associated autoantibodies (DAA), 529 Diagnostic and Statistical Manual of Mental Disorders (DSM-V), 770 Dichloro-diphenyl-trichloroethane (DDT), 381 Digital fingerprint or digitome, 360 Digital health systems, 542 Digital Imaging and Communications in Medicine (DICOM), 361 Digital IVF clinic AI-based algorithms, 360, 361, 364 big data, 364 electrochemical sensors, 363 enhanced clinician experience, 361 governance and legislation, 363–364 key performance indicators, 362 mobile health apps, 363 optimize clinic workflow, 361 patient-centred solutions, 362–363 precision medicine, 360, 362 predictive analytics and decision support tools, 360–361 real-time laboratory data, 363 smartphone communication, 362, 363 transition to digitalization, 361–362 use of blockchain, 363–364 wearables, 363 Diminished ovarian reserve (DOR) patients, 575 conventional and drug-free IVA, 637–638, 638, 638 mitochondrial therapies, 641–643 platelet-rich plasma, 639–640 stem-cell-based therapy, 640–641 in vitro activation (IVA), 636–639 Index DIVF, see Donor IVF DINCH metabolites, 386 Di(2-ethylhexyl) phthalate (DEHP) exposure, 381 DNA integrity, 404 DNA sequencing technology, 360 Donation of egg and embryo, 802 clinical and obstetric outcomes, 808–809 cycle synchronization, 808 embryo donation, 809–810 endometrial stimulation, 806–808 future directions, 810 genetic screening form, 807 indications for, 802–804, 803 live birth delivery, 803 non-iatrogenic POI, 802 oocyte donor recruitment, 804–805 oocyte donor screening, 805–806 recipient screening, 804 Turner syndrome, 802 Donor IVF (DIVF), 809; see also Donation of egg and embryo Dopamine-receptor agonist treatment, 787–788 Doppler flow, 668 DOR, see Diminished ovarian reserve patients Double/Dual stimulation (DuoStim), 494, 502, 504, 614 Double embryo transfer (DET), 522 Drilling, see Laparoscopic ovarian diathermy DRs, see Delivery rooms DSM-V, see Diagnostic and Statistical Manual of Mental Disorders DUAL-T, see Dual Trigger for Elective Fertility Preservation Dual Trigger for Elective Fertility Preservation (DUAL-T), 495 Duchenne muscular dystrophy, 542 DuoStim framework of, 617 luteal phase stimulation, 617 novel strategy to manage poor responders, 616–617 in single ovarian cycle, 614, 615 Dydrogesterone (DYG), 503 E E2, see Estradiol Ectopic pregnancy corneal, 671 Educational events, 357 EEJ, see Electroejaculation EFQM, see Excellence Model of the European Foundation for Quality Management “E-freeze” study, 730 EFS, see Empty follicle syndrome E-waste, see Electronic-recycling waste Early cessation protocol, 466 EARTH cohort, 385 EDCs, see Endocrine disrupting chemicals EFI, see Endometriosis Fertility Index EGF, see Epidermal growth factor Elective frozen embryo transfer, 502 Elective single embryo transfer (eSET), 701 Electroejaculation (EEJ), 678, 679; see also Sperm recovery techniques protocol, 686–687 843 Electronic medical record (EMR), 360 Electronic-recycling waste (E-waste), 376 Electronic witnessing systems, 362 Elevated serum progesterone, 475 EMA, see European Medicines Agency Embryo incubation techniques, 653 manipulation, 720 Embryo cryopreservation, 776 Embryo-endometrium desynchrony late follicular-phase progesterone rise, 496 non-conventional protocols of ovarian stimulation, 496 ovarian response category, 496–497 pre-implantation genetic testing, 496 slowly growing embryos, 495–496 Embryo transfer (ET) technique, 422, 555, 564 complications, 794 fresh cycles, 496 post-transfer techniques, 698 pre-transfer techniques, 696–697 transfer techniques, 697–698 US-guided procedures, 659 Empty follicle syndrome (EFS), 482 EMR, see Electronic medical record EMT, see Endometrial thickness Endocrine disrupting chemicals (EDCs), 370, 376; see also Reproductive health adverse reproductive health outcomes, 378, 379 in biological systems and transgenerational inheritance, 381 dietary exposures to, 377–378 dysfunction of immune system and metabolic diseases, 382–383 effects on reproductive system, 383 environmental exposures to, 376, 377 epigenetic modifications and oncogenesis, 381–382 examples of, 378 long-lived, 380 mechanisms of action, 381, 383 metabolization of, 376 natural ligand, 382 personal care products, 377 short-lived, 378, 379 Endocrine Society, 774 Endocrinology manipulation, 575–582; see also Assisted reproduction technology AACEP protocol, 581 follicle-stimulating hormone, 576 FSH role, 575–577 inherent biological mechanisms, 575 luteal-phase manipulations, 580–582 OCP pretreatment, 580 Endometrial receptivity, 536–537 Endometrial receptivity array (ERA), 650 Endometrial scratch, 652, 696; see also Tubal pathology Endometrial thickness (EMT), 535, 668 Endometrioma, 661 Endometriosis, 396, 714–721; see also Assisted reproduction technology and ART, 715–716 COS and oocyte retrieval, 716–718 embryo manipulation, 720 fertilization and early embryo development, 718 future directions, 720–721 immune dysfunction in, 714 implantation, pregnancy, and loss, 718–720 and infertility, 714–715 in vitro fertilization–ET outcome comparison, 717 meta-analysis, 719 ovulation induction and insemination, 715 surgery and ART, 720 Endometriosis Fertility Index (EFI), 396 Endotoxin-releasing bacteria, 795–796 Environmental exposures, 383–387, 384; see also Reproductive health and ART outcomes, 385 clinical interventions, 386 to common pollutants, 383, 384 current interventions and successful strategies, 387 fertility and fecundability, 383–384 importance of male participation, 386–387 pregnancy and birth outcomes, 385–386 and semen quality, 385 to short-lived or non-persistent chemicals, 384 Environmental Protection Agency (EPA), 378, 449 EPA, see Environmental Protection Agency Epidermal growth factor (EGF), 639 Eponymous cysts, 726 ERA, see Endometrial receptivity array ERs, see Estrogen receptors Escherichia coli, 529 eSET, see Elective single embryo transfer ESHRE, see European Society of Human Reproduction and Embryology ESP, see Extended sperm preparation Estradiol (E2), 67, 443, 463, 536, 539, 563, 660 precursors, 579 Estrogen receptors (ERs), 419 ET, see Embryo transfer technique EUP, see Extrauterine pregnancy European Medicines Agency (EMA), 428 European Society of Human Reproduction and Embryology (ESHRE), 352, 539, 542, 562, 622, 629, 725, 758, 774, 816 European Union Agency for Fundamental Rights Survey, 771 EU Tissue Directive, 352 EVT, see Extravillous trophoblast Excellence Model of the European Foundation for Quality Management (EFQM), 352–353 Exposome; see also Reproductive health built and natural environments, 376–377 contributing to disease, 376 cultural, social, and individual environments, 377–378 and routes of exposure, 376 Extended sperm preparation (ESP), 678; see also Sperm recovery techniques Extrauterine pregnancy (EUP), 796–798 after ART, 796–797 diagnosis and treatment, 798 heterotopic pregnancy following ART, 798 risk factors, 797–798 Extravillous trophoblast (EVT), 516 Index 844 F Face2Gene, 361 Facial recognition, 361 FAI, see Free androgen index FDA, see U.S Food and Drug Administration Female immune response, 367 Female infertility, 400; see also Infertility anti-Mullerian hormone, 401 antral follicle count, 401 day-3 serum FSH and E2, 401 diagnostic evaluation, 400 fallopian tube pathology, 402 history, 400 hormonal tests, 401 hysterosalpingo-contrast sonography, 402 hysterosalpingography, 402 laparoscopy, 402–403 lifestyle modification, 400 ovarian reserve, 401 ovulatory function, 400–401 physical examination, 400 preconception care, 400 uterine abnormalities, 402 Female reproductive aging, 409; see also Ovarian reserve test age related decline, 409 age-related subfertility and ovarian reserve, 409 fertility decline, 409 ovarian follicle decline, 410 ovarian reserve prediction, 409 on singleton live birth rates, 410 variability of, 409, 410 Fentanyl, 708 Fertility, 366; see also Periconception diet, 369 environmental pollutants, 370 factors affecting, 368 occupational factors, 370 pre-pregnancy preparation, 370–371 prescription drugs, 370 recreational drugs, 369–370 sexually transmitted diseases, 370 smoking, 369 societal importance, 366 stress, 370 treatment, 431 vaccinations, 370 weight, exercise, and nutrition, 368 workup, 400 Fertility preservation, 734, 774 alkylating agents, 734 candidates for fertility-preserving methods, 734–735 chemotherapy and radiotherapy effects, 734, 741–742 chemotherapy drugs, 734 Danish protocol, 736–737 Dobbelt sealing and storage of cryotubes, 738 female, 735–736, 736 fertility restoration, 742 frozen–thawed human ovarian cortex, 738 future aspects, 742 hormonal suppression, 735 instruments used for ovarian cortex preparation, 737 longevity of grafts, 741 male, 741 malignant cell risk, 741 measures of, 735 oocyte or embryo cryopreservation, 735 options for transfeminine people, 776, 777 options for transmasculine people, 774 orthotopic and heterotopic transplantation, 739 outcomes with pubertal suppression, 779 ovarian tissue cryopreservation, 736, 737, 739 pregnancy and live birth rate, 740–741 restoration of ovarian activity, 739–740, 740 risk assessment, 735 slow freezing vs vitrification, 737–738 subfertility, 741 thawing procedure, 739 transplantation of cryopreserved ovarian tissue, 740 transportation of cryopreserved ovarian tissue, 738–739 xenotransplantation of human ovarian tissue, 737, 738 Fertility Quality of Life (FertiQoL), 821 FertiQoL, see Fertility Quality of Life FET cycles, see Frozen embryo transfer (FET) cycles Fetal growth restriction (FGR), 522 Fetal hyperandrogenism, 726 FGF, see Fibroblast growth factor FGR, see Fetal growth restriction Fibroblast growth factor (FGF), 639 Fine-needle aspiration (FNA), 681; see also Sperm recovery techniques of testis for sperm retrieval protocol, 687 FISH, see Fluorescent in situ hybridization 5G internet, 360 Flare effect, 451, 452 Flare-up effect, 432, 567, 568, 616 Fluorescent in situ hybridization (FISH), 648 FNA, see Fine-needle aspiration FOI, see Follicle-to-oocyte index Follicle-to-oocyte index (FOI), 600–601, 603, 604 Follicular-phase progesterone rise (FPPR), 540 Follicular stimulating hormone (FSH), 401, 443, 494, 528, 539, 576, 617, 623; see also Endocrinology manipulation; Ovarian stimulation follicular fluid hormonal determinations, 445 hypogonadotropic patients, 443–444 physiological background, 443 pregnancy per cycle, 446 receptor polymorphism, 576 serum hormone concentrations, 444 window, 450, 451 Folliculogenesis, 635–636, 637 classical theory, 614 continuous recruitment, 614 multiple waves, 614 Food and Drug Administration (FDA), 643 Foxo3 gene, 636 FPPR, see Follicular-phase progesterone rise Free androgen index (FAI), 368 Freeze-all cycles, 494 advantages of, 502 combination of gonadotropins, 504–505 consequences of LFPE, 508–509 consequences of sustained supraphysiologic oestradiol levels, 508 COS, see Controlled ovarian stimulation criteria for ovulation triggering, 507–508 dose of gonadotropins during COS, 505 indications for cycle segmentation, 503 optimal number of oocytes retrieved, 494, 502–503 ovarian stimulation, see Ovarian stimulation, freeze-all cycles preferred ovulatory trigger, 506–507 preferred regimen for pituitary suppression, 505 Freeze-thaw cycle, 685 Fresh IVF cycles deficiency in, 555 luteal phase monitoring in, 558, 558–559 progesterone behaviour during, 556, 557, 558 progesterone sources in, 556 Frozen embryo transfer (FET) cycles, 494, 496, 502, 697, 701 endometrial thickness and quality in, 702–703 hormone preparations in, 702 hormone-replacement cycles, 701–702 maternal and perinatal outcomes of, 703 natural, 701 protocols, 701–702 quality of embryo at time of freezing, 703 refreezing of thawed embryos, 703 stage of embryo at time of freezing, 703 stimulation regimes, 702 zona pellucida breaching, 703 FSH, see Follicular stimulating hormone FSH–Cterminal peptide (FSH–CTP), 429 FSH–CTP, see FSH–Cterminal peptide Full surrogacy, see Gestational surrogacy G GA, see General anesthesia Gamete intrafallopian transfer (GIFT), 708 GC, see Granulosa cell GDM, see Gestational diabetes mellitus Gelport®, 750 Gender dysphoria, 772, 776 Gender identity, 770, 771; see also Transgender and nonbinary individuals General anaesthesia (GA), 708–709; see also IVF anaesthesia Genetic couple, 813, 816; see also Gestational surrogacy Germ cell aplasia, 677 Gestational diabetes mellitus (GDM), 727 Gestational sac (GS), 671 Gestational surrogacy, 813, 817 Asherman’s syndrome, 814 assessment and counselling of intended parents, 814–815 choice of treatment protocol, 815 compensation, 816 cross-border surrogacy, 816 gestational carrier assessment, 815 in treatment and neonatal care aspects, 816 Index long-term post-treatment aspects, 816 Mayer–Rokitansky–Küster–Hauser syndrome, 814 patient selection for treatment, 814–815 religious attitudes, 816 results, 815–816 Genome-wide association studies (GWAS), 726 Gestational carrier, 813, 816 Gestational diabetes (GD), 753 GH, see Growth hormone GIFT, see Gamete intrafallopian transfer Global PCOS Alliance, 725 Gloves worn, 697 Glycodelin, 727 GM-CSF, see Granulocyte-macrophage colony-stimulating factor GnRH, see Gonadotropin releasing hormone GnRHa, see Gonadotropin releasing hormone agonists Gonadotropin, 424–426; see also Ovarian stimulation chorionic, 426 corifollitropin-α, 429–430 -dependent recruitment, 450 developments in infertility treatment, 426 follitropin-α, 428–429 follitropin-δ, 429 follitropin-ε, 429 GONAL-f, 428 human chorionic, 424–426 human menopausal, 426 pharmacokinetics of serum β-hCG, 425 production of hMG, 427 purification of urinary FSH and HP-FSH, 427 quantifying and standardizing, 427 recombinant human, 427–428 safety profile of, 430 substance, 426 Gonadotropin releasing hormone (GnRH), 419, 432, 494, 624, 752; see also Ovarian stimulation agonist vs antagonist, 505 analogues, 432, 433 antagonist protocols, 539, 787 structure of, 433, 434 Gonadotropin-releasing hormone agonists (GnRHas), 432, 463, 465–466, 494, 495, 564 action mechanism, 432 administration route, 465 advantages and disadvantages of, 464 amino acid sequence and substitution of, 464 biosynthesis, 432–433 clinical applications, 465 efficiency of IVF, 468 flare-up effect, 567 GnRHa stop protocols, 565–567 hormone levels for FSH, LH, and E2, 464 hypogonadotropic hypogonadism, 465 injections, 451 long GnRH agonist protocol, 564– 565 micro-dose flare GnRH agonist protocol, 568 micro-dose flare GnRHa regimens, 569 optimal dose, 466 optimal scheme, 466–467 845 short GnRH agonist protocol, 568 short GnRHa regimens, 567–568 side effects, 433 stimulation regimens, 569 structural modifications, 463, 464 structure of analogs, 433 teratogenic effects, 434 in treatment of poor responders, 564 Gonadotropin-releasing hormone agonist trigger, 480, 488 adjuvant hCG at time of oocyte retrieval, 485 adjuvant hCG two days following oocyte retrieval, 485 adjuvant low-dose HCG, 484–485 administration, 481–482 advantages, 488 breast cancer patients, 488 controversies on, 480 cycle segmentation, 486 dual trigger with HCG, 484–485 follicular fluid and granulosa/luteal cells, 481 freeze-all for PGT cycles, 487–488 indications, 480, 480 intensive luteal support, 484 luteal coasting, 485–486 luteal GnRHa, 485 luteal-phase steroid profile, 483 luteal-phase support protocols, 486 luteinizing hormone surge, 481 to modify luteal phase and pregnancy rates, 483 natural vs GnRHa-induced mid-cycle surge, 480 OHSS incidence, 487 oocyte donation cycles, 488 oocyte yield after, 482–483 ovarian hyperstimulation syndrome, 487 protocols to improve conception rates, 486–487 recombinant LH, 485 safety of GnRHa use, 488 standard luteal support, 484 trials demonstrating effect of, 482 use in clinical situations, 488 very low HCG dose, 485 Gonadotropin-releasing hormone antagonists (GnRH-ants), 434, 472, 566; see also Endocrinology manipulation; Natural cycle action mechanism, 434 administration, 472–473 advantages of, 435 alternative approaches and treatment protocols, 573 assessment of ovarian response to stimulation, 562–564 atresia, 561 cycle characteristics of randomized controlled trials, 572 cycle initiation, 473–474 delayed start GnRH antagonist protocol, 474 elevated serum progesterone, 475 endocrine associations in, 475 FSH dose at antagonist initiation, 475 FSH starting dose, 474 GnRH agonists vs., 472 Gonadotrophin stimulation, 474–475 high-dose gonadotropins, 564, 582 LH addition to FSH, 475 long acting FSH, 475 long GnRHa protocol, 582 luteal support in, 476 micro-dose flare GnRHa protocol, 582 oocyte accumulation and embryo banking, 582 oocyte yield per AMH quintile, 563 ovarian stimulation using, 476 practical considerations, 582 prospective studies, 571–573 protocol, 570, 582 recombinant LH addition to recombinant FSH, 475 retrospective studies, 570–571 safety and tolerability studies, 434–435 strategies, 582 structure formulation of native, 434 synthesis of, 434 terminology, 562 third-generation, 516 in treatment of poor responders, 569–573 triggering of oocyte maturation, 475–476 GONAL-f FbM, 428 Good Research for Comparative Effectiveness (GRACE), 608 Granulocyte-macrophage colony-stimulating factor (GM-CSF), 516 Granulosa cell (GC), 561 Growth hormone (GH) clinical evidence, 628–629 human GH, 628–629, 629 physiological basis of intervention, 628 synthesis and critical appraisal of evidence, 629, 629 GS, see Gestational sac GWAS, see Genome-wide association studies H HAART, see Highly active antiretroviral therapy Haemorrhage, 834 Hazards, 834; see also Safety management system Hair cortisol concentration level (HCC), 830–831 HBV, see Hepatitis B virus HCC, see Hair cortisol concentration level HCG, see Human chorionic gonadotropin HCV, see Hepatitis C virus HDV, see Hepatitis D virus Healthy People 2030, 770 HEFA, see Human Embryology and Fertilization Act Hemoclips®, 748 Hepatitis B virus (HBV), 756, 761–762; see also Viral disease ART outcome, 762 Hepatitis C virus (HCV), 756, 761–762; see also Viral disease ART outcome, 762 Hepatitis D virus (HDV), 761; see also Viral disease Heterotopic pregnancy, 671 Index 846 HFEA, see Human Fertilization and Embryology Authority HGH, see Human growth hormone HH, see Hypogonadotropic hypogonadism Highly active antiretroviral therapy, 756–757 Highly purified (HP), 426 High performance liquid chromatography (HPLC), 419 Hippo pathway, 636, 637 Hippo signalling, 636 HIV, see Human immunodeficiency virus HIV Prevention Trials Network 052 study (HPTN 052), 757 HLA, see Human leukocyte antigen HMG, see Human menopausal gonadotropin Home monitoring of ART cycles; see also Assisted reproductive technology digital health systems and tele-counselling, 542 hypothetical home-monitoring set-up, 543 remote ovarian cycle monitoring with tele-counselling, 540–541 remote salivary hormone testing, 542 remote urinary hormone testing, 541–542 SOET system (remote self-operated ultrasound), 541 traditional clinic-based ovarian cycle monitoring, 539–540 of transvaginal ultrasound, 540 Homing phenomenon, 640 Horizontal communication, 357 Hormonal tests, 401; see also Female infertility HOS, see Hypo-osmotic swelling test HP, see Highly purified HPLC, see High performance liquid chromatography HRP, see Human Reproduction HSA, see Human serum albumin HSG, see Hysterosalpingography HTLV-1 and-2, see Human T-lymphocyte virus and Human chorionic gonadotropin (hCG), 494, 504, 535, 701, 783 Human Embryology and Fertilization Act (HEFA), 816 Human Fertilization and Embryology Authority (HFEA), 518, 822 Human GH (hGH), 569, 628–629, 629 Human immunodeficiency virus (HIV), 756; see also Viral disease for ART, 757 assisted reproduction, 758 concordant couples, 759–760 discordant couples, 757–758 effect on eggs and other female fertility factors, 760 effect on fertility and ART outcome, 760–761, 761 effect on sperm, 760 ethical considerations, 761 highly active antiretroviral therapy, 756–757 HIV-1 and HIV-2, 756 IUI, IVF, and ICSI outcome, 760–761 mother-to-child transmission (MTCT) risk, 759 positive serodiscordant women, 759 serodiscordant men and sperm washing, 758–759 sexual transmission risk, 757 third-party assisted reproduction (surrogacy), 760 vertical transmission risk, 761 Human leukocyte antigen (HLA), 515 Human menopausal gonadotropin (hMG), 425, 504, 628, 752; see also Gonadotropin Human Reproduction (HRP), 366 Human serum albumin (HSA), 736 Human T-lymphocyte virus and (HTLV-1 and- 2), 762; see also Viral disease Huntington’s disease, 709, 710 HyCoSy, see Hysterosalpingo-contrast sonography HyFoSy, see Hysterosalpingo-foam sonography Hyperinsulinemia, 729 Hypogonadotropic hypogonadism (HH), 419, 443, 465, 677 Hypo-osmotic swelling (HOS) test, 404 Hypoplastic uterus, 747 Hypovolemic hyponatremia, 783 Hysterosalpingo-contrast sonography (HyCoSy), 395, 402; see also Ultrasonography Hysterosalpingo-foam sonography (HyFoSy), 395 Hysterosalpingography (HSG), 395, 402 Hysteroscopic metroplasty, 402 Hysteroscopy, 402 Hysterosonography, 402 I ICSI, see Intracytoplasmic sperm injection ICUs, see Intensive care units IFFS, see International Federation of Fertility Societies IGF, see Insulin like growth factor IGF-I, see Insulin-like growth factor I ILs, see Interleukins Immunology in ART; see also Assisted reproductive technology autoimmunity, 524–529 immune inhibition at maternal–fetal interface, 516 immunomodulatory therapies, 517–518 inflammation and immune balances, 516–517 inflammatory states, 515–516 local immunological imbalances, 530 local infections and pregnancy, 529–530 macrophages, 515 natural killer cells, 515, 518–524 T cells, 515 trophoblastic invasion, 522, 522 use of corticosteroids, 524 IMPRINT (Improving the Reporting of Clinical Trials of Infertility Treatments), 608 IMSI, see Intracytoplasmic morphologically selected sperm injection Individual patient data meta-analysis (IPD-MA), 411 Infertility, 400, 405, 826; see also Female infertility; Male infertility; Uterus transplantation assessment of couple, 400 -associated medical conditions, 400 counseling, 821 fertility workup, 400 treatment, 419 Insulin like growth factor (IGF), 452 Insulin-like growth factor I (IGFI), 623, 639 Intended parents, 813; see also Gestational surrogacy Intensive care units (ICUs), 837 International Federation of Fertility Societies (IFFS), 813 International Organization for Standardization (ISO), 351–352; see also Quality management criteria of, 352 ISO 9001, 351–352 quality manual, 355 International Society for Mild Approaches in Assisted Reproduction (ISMAAR), 573 Intracavitary abnormalities, 664 Intracytoplasmic morphologically selected sperm injection (IMSI), 649 Insulin-like growth factors and (IGF-1 and IGF-2), 623, 639, 726 Interferon-γ, 516 Interleukins (ILs), 516 International Committee for Monitoring Assisted Reproductive Technologies (ICMART), 592 International Society of Uterus Transplantation (ISUTx), 753 Internet of things (IoT), 360, 361 Intracytoplasmic sperm injection (ICSI), 362, 396, 517 Intrauterine adhesions (IUAs), 663, 666, 746 Intrauterine insemination (IUI), 385, 395–397, 467, 715, 758 Intravenous hypnotics, 708 Intravenous injection of immunoglobulin G (IVIG), 517–518 In vitro activation (IVA), 636–639; see also Diminished ovarian reserve patients conventional and drug-free, 637–638, 638, 638 In vitro fertilization (IVF) treatment advanced maternal age, 397 endometriosis, 396 non-severe male infertility, 396 polycystic ovary syndrome (PCOS), 396 tubal infertility, 395–396 unexplained infertility, 396–397 In vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), 591, 758, 829 In vitro maturation (IVM) of immature oocytes, 788 of oocytes for women with PCOS, 730 IoT, see Internet of things IPD, see Individual patient data IPD-MA, see Individual patient data meta-analysis ISMAAR, see International Society for Mild Approaches in Assisted Reproduction ISO, see International Organization for Standardization IUA, see Intrauterine adhesions Index IUI, see Intrauterine insemination IVA, see In vitro activation IVF, see In vitro fertilization IVF anaesthesia alternative and non-pharmacological pain management, 709 anaesthesia for PGT, 709–710 complications of sedation, 707 drugs used in sedation, 707–708 fertilization and embryo culture in laboratory, 706 general anaesthesia, 708–709 neuraxial anaesthesia, 708 ovarian stimulation and monitoring, 706 pain control during TUGOR, 706–707 PCB and POB techniques, 709 pregnancy rate, 706 sedation, 706 transfer of embryos to uterus, 706 IVM, see In vitro maturation K Karyotype analysis, 405 Ketamine, 707–708 Key performance indicators (KPIs), 362 Killer-cell immunoglobulin-like receptors (KIR), 521, 521–523 Killer cell lectin-like receptors (KLRs) family, 523 Kisspeptin, 729 Kisspeptinneurokinin-B-dynorphin (KNDy), 729 Klinefelter’s syndrome (KS), 405 KLRs, see Killer cell lectin-like receptors family KNDy, see Kisspeptinneurokinin-B-dynorphin Know your risk, 835; see also Risks in ART KPIs, see Key performance indicators KS, see Klinefelter’s syndrome L Laparoscopy, 402–403 L-arginine clinical evidence, 631 physiological basis of intervention, 631 Laboratory information systems (LIMS), 361 LADA, see Latent autoimmune diabetes in adults Laparoscopic ovarian diathermy (LOD), 730 Late follicular phase progesterone elevation (LFPE) driving forces for, 454 during ovarian stimulation for IVF, 452, 453 on reproductive outcome, 454 serum progesterone levels, 454 Latent autoimmune diabetes in adults (LADA), 528, 531 LBR, see Live birth rate LD hysterectomy; see also Live donors UTx; Uterus transplantation open surgery technique, 747–748 robotics technique, 748–749 Lessons from aviation, 837 by-procedure operation vs resilience, 837–838 847 checklists, 837–838 medicalship, 837 medicine and aviation, 838–839 Letrozole, 421, 788; see also Aromatase inhibitors Letrozole/antagonist (LA), 581 Leukemia inhibitory factor (LIF), 651 Leukocyte immunoglobulin-like receptors B (LILRB), 516 Leuprolide acetate (LA), 565 Levothyroxine, 528 LFPE, see Late follicular phase progesterone elevation LH, see Luteinizing hormone LH ceiling, 451 LIF, see Leukemia inhibitory factor Life course epidemiology; see also Reproductive health exposure to EDCs, 379–380 integrated model, 380, 380 and paternal contribution, 380–381 prenatal window, 381 Lifestyle assessment and management, 371 society-wide approach to achieve lifestyle changes, 371 LILRB, see Leukocyte immunoglobulin-like receptors B LIMS, see Laboratory information systems Live birth rate (LBR), 494, 502, 592, 701, 729 Live donors (LD) UTx; see also Uterus transplantation complications in, 750 reports, 750 LMWH, see Low molecular weight heparin LOD, see Laparoscopic ovarian diathermy Long GnRHa protocol, 582 Low molecular weight heparin (LMWH), 651 Low responder (LR), 582 androgens, 618–619 customization of hormonal stimulation, 614–615 DuoStim, 616–617 LH activity, 618 management of poor prognosis patients, 615–616 mild ovarian stimulation, 617 modified natural cycle, 617–618 new theories of folliculogenesis, 614 number of oocytes retrieved and age, 613 oestradiol priming in luteal phase, 618 from ovarian physiology to multiple follicle growth, 613–614 ovarian reserve, 613 protocols, advantages and disadvantages, 614 LPS, see Luteal phase support LR, see Low responder Luteal phase stimulation cycle, 496 Luteal phase support (LPS), 789; see also Assisted reproductive technology deficiency in fresh IVF cycles, 555 luteal phase monitoring in fresh IVF cycles, 558, 558–559 progesterone behaviour during fresh IVF cycles, 556, 557, 558 progesterone sources in fresh IVF cycles, 556 Luteinizing hormone (LH), 401, 443, 494, 539, 577–580, 725, 783; see also Endocrinology manipulation; Gonadotropinreleasing hormone agonist trigger; Ovarian stimulation advanced reproductive age women, 445–446 basic physiological background, 443 ceiling, 451 ceiling effect, 577 COS for low-responder patients, 618 hypogonadotropic patients, 443–444 normogonadotropic patients, 445 ongoing pregnancy per started cycle, 446 OS for IVF, 444–447 patients with high levels of, 446–447 poor responders, 446 serum hormone concentrations, 444 supplementation, 578 surge, 481 therapeutic window concept, 577 use in OS for IVF, 444–447 Lymphocyte immunotherapy (LIT), 523 M MAC, see Monitored anesthesia care Machine learning, 360 Magnetic resonance-guided focused ultrasound (MRgFUS), 664; see also Ultrasonography Magnetic resonance imaging (MRI), 402, 650 Male infertility, 403; see also Infertility aspermia, 403 causes of, 400 DNA integrity, 404 endocrine tests, 405 evaluation of infertile couple, 406 genetic testing, 405 history, 403 laboratory investigations, 403–405 NOA and severe oligozoospermia, 405 non-sperm cells, 404 obstructive azoospermia, 405 physical examination, 403 semen analysis, 403–405 sperm DNA fragmentation, 404 sperm motility, 404 sperm vitality, 404 ultrasound, 404–405 Marfan syndrome, 709 Massage, 696 Master cell bank (MCB), 427 Maternal–fetal tolerance, 518 Maternal reproductive disorders, 368 Mayer–Rokitansky–Küster–Hauser syndrome (MRKHs), 746, 749, 814; see also Gestational surrogacy MCB, see Master cell bank Medicalship, 837 Medroxyprogesterone acetate (MPA), 503, 573 Melatonin clinical evidence, 631 general ART population, 631 physiological basis of intervention, 630–631 poor responders, 631 Index 848 Menopause, 409, 416 Mental health issues, 825 MESA, see Microsurgical epididymal sperm aspiration Metaphase II ( MII) oocyte, 599–600, 601 Metformin, 422; see also Ovarian stimulation pharmacokinetics, 424 side effects and safety, 424 Microsurgical epididymal sperm aspiration (MESA), 681; see also Sperm recovery techniques protocol, 688 Micro-TESE (mTESE), 683; see also Sperm recovery techniques Midazolam, 707 Mild ovarian stimulation, 474, 617 Mind/body interventions, 831, 832 Minimal sedation (anxiolysis or twilight sleep), 706 Minnesota Multiphasic Personality Inventory-2 (MMPI-2), 822 Mitochondrial DNA (mtDNA), 810 Mitochondrial therapies, 636, 641–643 background and physiological bases of technique, 641, 643–644 human studies, 643 replacement techniques, 643 MMPI-2, see Minnesota Multiphasic Personality Inventory-2 MNC, see Modified natural cycle Moderate sedation (conscious sedation), 706 Modified natural cycle (MNC), 573–575, 617–618, 701 Monitored anaesthesia care (MAC) infusion, 707 Monitoring of ovarian stimulation assessment during, 535–537 endometrial thickness, 535 hormonal assessment, 534–535, 535 oestradiol, 536 pre-stimulation assessment, 534 progesterone, 536 serum oestradiol and endometrial receptivity, 536 serum progesterone and endometrial receptivity, 536–537 ultrasound, 534, 535 Monkeypox (MPXV), 756, 764–765; see also Viral disease DNA, 764–765 outbreak of, 764 MPA, see Medroxyprogesterone acetate MPXV, see Monkeypox MRgFUS, see Magnetic resonance-guided focused ultrasound MRI, see Magnetic resonance imaging MSCs, see SCs of mesenchymal origin mtDNA, see Mitochondrial DNA mTESE, see Micro-TESE Multi-organ donor, see Deceased donor UTx Multiple testicular sampling, 683; see also Sperm recovery techniques MURCS (Malformations Urinary Cardiac and Skeletal), 814 Mycoplasma, 529 Myotonic dystrophy, 709, 710 N NAT, see Nucleic acid test Natural cycle (NC), 563 modified, 573–575 terminology, 573–574 Natural killer (NK) cells; see also Immunology in ART immunomodulator studies in ART, 524, 525–526 local infections and pregnancy, 529–530 peripheral blood, see Peripheral blood natural killer cells roles in placentation and immunological compatibility, 518 uterine, see Uterine natural killer cells NC, see Natural cycle Negative feedback mechanisms, 450 Negative predictive values (NPVs), 664 Neuraxial anaesthesia, 708; see also IVF anaesthesia NGFs, see Non-growing follicles NOA, see Non-obstructive azoospermia Non-growing follicles (NGFs), 561 Non-obstructive azoospermia (NOA), 404, 405, 677; see also Male infertility Non-progressive motility (NP motility), 404 Non-severe male infertility, 396 Non-sperm cells, 404 Nonsteroidal anti-inflammatory drugs (NSAIDs), 786 Norethisterone, 503 No-scar technique, 681; see also Sperm recovery techniques NP motility, see Non-progressive motility NPVs, see Negative predictive values NSAIDs, see Nonsteroidal anti-inflammatory drugs Nucleic acid test (NAT), 756, 763 O OA, see Obstructive azoospermia Obstructive azoospermia (OA), 404, 405, 677; see also Male infertility OC, see Oral contraceptive OCP, see Oral contraceptive pill OD, see Oocyte donation cycles Odds ratio (OR), 420 OECD, see Organization for Economic Cooperation and Development Oestradiol, 534–535, 536, 772 Oestrogen, 378 steroidogenesis of, 626 OGTT, see Oral glucose tolerance test OHSS, see Ovarian hyperstimulation syndrome Oligospermia, 404 Oocyte collection, 547, 549–550 anesthesia/analgesia, 547 avoiding turbulent flow, 550 cappuccino effect, 548 checklist, 551 cleansing/sterilizing vagina, 547–548 clinical competence assessment, 552 complications, 551–553 Cullen’s sign, 552 curetting follicle, 550 damage within follicle, 549 diameter to volume ratios of follicles, 548 equipment, 548 failure, 552 follicle and needle volumes, 548 guidance, 552–553 history, 547 oocyte damage, 549 pre-treatment of pathology, 552 rapid, 549 suction, 548 technique, 549–551 temperature control, 550 troubleshooting, 552 ureteric obstruction, 552 vacuum application, 548–549 vertebral osteomyelitis, 552 Oocyte donation (OD) cycles, 502, 508 Oocyte pickup (OPU), 794 Oocytes retrieval, 659 Oogonia stem cells (OSCs), 640 Open testicular biopsy under local anesthesia protocol, 688; see also Sperm recovery techniques Operating rooms (ORs), 837 Opioids, 707 OPU, see Oocyte pickup OR, see Odds ratio Oral contraceptive (OC), 838 Oral contraceptive pill (OCP), 473, 503 Oral glucose tolerance test (OGTT), 529 Organizational chart, 354 Organization for Economic Cooperation and Development (OECD), 351 ORs, see Operating rooms ORTs, see Ovarian reserve tests OS, see Ovarian stimulation OSCs, see Oogonia stem cells Ovarian hyperstimulation syndrome (OHSS), 422, 447, 494, 534, 536–537, 539, 540, 613, 622, 729–730 agonist trigger for final oocyte maturation, 787 albumin and calcium administration, 788 aspirin or metformin, 787 classification of, 785, 785 clinical features and diagnosis, 784 co-adjuvant treatments, 787 conditions requiring patient admission to hospital, 786 cryopreservation, 788 demographic factors, 783 dopamine-receptor agonist treatment, 787–788 human chorionic gonadotropin, 783 hyperstimulated ovaries, 784 increased severity signs, 786–787 initial assessment, 784 IVM of immature oocytes, 788 letrozole, 788 luteal phase support, 789 ovarian reserve markers, 783 ovarian stimulation parameters, 783–784 pathophysiology, 783 patient management, 786 primary prevention, 787 risk factors, 783 secondary prevention, 787 Index symptoms of, 784 tertiary prevention, 787–788 unusual cases of, 784 use of GnRH antagonist protocol, 787 vasopressin-induced VEGF secretion blockade, 787 withholding gonadotropins, 787 Ovarian reserve, 409 Ovarian reserve evaluation, 401; see also Female infertility Ovarian reserve test (ORT), 409, 416, 417, 562; see also Female reproductive aging age and follicle reserve, 411 age-related fertility decline, 416 ART treatment outcome prediction, 411 clinical value of, 411 excessive-response prediction, 412 fecundity prediction, 414 menopause prediction, 414, 416 nomograms, 415 physiological background to, 409–410 poor-response prediction, 411–412 predicted probability of live birth, 413 pregnancy prediction, 412–413 reproductive lifespan prediction, 414 reproductive lifespan prediction in specific situations, 416 ROC curves, 412, 413 study characteristics, 416 tailoring treatment in ART practice, 413 and valuation, 410–411 Ovarian sensitivity index, 505 Ovarian stimulation (OS); see also Aromatase inhibitors; Clomiphene citrate; Gonadotropin; Gonadotropin-releasing hormone; Luteinizing hormone; Metformin adjunctive therapies, 431–432 advanced reproductive age women, 445–446 assessment during, 535–537 controlled, see Controlled ovarian stimulation defined, 534 drugs used for, 419 final oocyte maturation triggering, 494–495 freeze-all cycles, 494 gonadotropin-releasing hormone, 432 gonadotropins safety profile, 430 individualization of, 431 for IVF, use of LH, 444–447 luteal phase following, 455–457 monitoring of, see Monitoring of ovarian stimulation non-conventional protocols of, 496 normogonadotropic patients, 445 optimal number of oocytes retrieved, 494 optimizing outcomes of, 430 patients with high levels of LH, 446–447 pituitary suppression, 494 poor responders, 446 r-hFSH vs hMG, 430–431 two-cell–two-gonadotropin model, 431 unconventional, 458 Ovarian teratomas, see Dermoid cysts Ovarian tests, 401; see also Female infertility Ovulation induction (OI), 419 849 Oxford Nanopore sequencing platform, 360 Oxytocin antagonist, 696–697 P PACU, see Post-anaesthesia care unit Paracervical block (PCB) technique, 709; see also IVF anaesthesia Patient-centered approach, 819, 826; see also Support services in ART clinic administration, 825 diversity factors in ART, 821 future direction, 826 gender differences and ART stress, 820 infertility counseling, 821 information and education, 824 methods, 821–822 patient support service provider, 821–822 psycho-education and implications counselling, 822 psychological screening and preparation, 822–823 result of pandemic, 821 results, 825–826 situations as guidelines, 823 strategies for ART patient support, 826 stress and ART, 819–820 stress during ART cycles, 820–821 supportive counselling, 823–824 technology and digital intervention, 824–825 therapeutic counselling, 823 PbNK, see Peripheral blood natural killer cells PBS, see Phosphate-buffered saline PCO, see Polycystic ovary PCOS, see Polycystic ovary syndrome PCR, see Polymerase chain reaction assays PEDF, see Pigment epithelium-derived factor Pelvic inflammatory disease (PID), 795–796 curative, 796 effect on IVF–ET outcome, 795–796 endotoxemia, 795–796 local inflammatory reaction, 796 mechanisms underlying pelvic infection, 795 role of prophylactic antibiotics in IVF–ET, 796 temperature elevation, 796 treatment, 796 Penile vibratory stimulation (PVS), 678; see also Sperm recovery techniques protocol, 687 Percutaneous epididymal sperm aspiration (PESA), 681; see also Sperm recovery techniques protocol, 687–688 Per fluorinated chemicals (PFCs), 378 Periconception, 366, 371; see also Fertility adaptation to adverse influences, 367 care, 366–368 female immune response, 367 goals of periconception health, 366 periconception events, 368 stages of reproductive development, 366 Peripartum emergency hysterectomy, 746 Peripheral blood natural killer (pbNK) cells; see also Natural killer cells uNK cells vs, 518–519 Personality Assessment Inventory (PAI), 822 PESA, see Percutaneous epididymal sperm aspiration PFCs, see Per fluorinated chemicals pFSH, see Purified FSH PGD, see Pre-implantation genetic diagnosis PGT, see Pre-implantation genetic testing PGT-M, see Preimplantation genetic testing for monogenic disorders Phosphate-buffered saline (PBS), 736 PID, see Pelvic inflammatory disease Pigment epithelium-derived factor (PEDF), 481 PIH, see Pregnancy induced hypertension Placenta previa (PP), 753 Platelet activation method, 639 Platelet-rich plasma (PRP) background and physiological bases of technique, 639 human studies, 639, 640 limitations and challenges, 639–640 ovarian activation via secretome, 641 results, 639 POB, see Pre-ovarian block technique POC, see Point of care devices POF, see Premature ovarian failure POI, see Premature ovarian insufficiency Point of care (POC) devices, 541 Polycystic ovaries (PCO), 725 Polycystic ovary syndrome (PCOS), 396 aetiology and pathophysiology, 725–726 biochemistry within, 727 definition, 725 fetal hyperandrogenism, 726 hyperinsulinemia, 729 insulin resistance and metformin of IVF for women, 728–729 metabolic health and obesity in, 727–728 ovarian hyperstimulation syndrome, 729–730 pre-ovulatory trigger, 729 prevalence and spectrum of, 725–728 reproductive health in, 726–727 superovulation strategies of IVF for women, 728–729 in vitro maturation of oocytes for women, 730 Polymerase chain reaction assays (PCR), 756 Poor ovarian response (POR), 411, 562, 615, 636; see also Low responder Poor responders, 561 POR, see Poor ovarian response POSEIDON group AFC and AMH, 594–596 case study and practical considerations, 607, 607, 608 classification, 622 clinical trials, 608, 610 clinical validation, 593–594, 597 criteria and rationale, 591–593 cumulative delivery in, 596, 598, 599 follicle-to-oocyte index, 600–601, 603, 604 goal of, 609 of low-prognosis patients in ART, 594–597, 595 management strategies and outcomes, 601, 603 metric of success and ART calculator, 597, 599–600, 600, 601, 602 Index 850 MII oocyte, 599–600, 601 reporting trials, 608, 609 in routine clinical practice, 594 treatment rationale, strategies, and outcomes, 603–604, 605, 606, 607 POSORT (POSEIDON Statement Of Reporting Trials), 608, 609 Post-anaesthesia care unit (PACU), 708 Postmenopausal osteoporosis, 434 Post-transfer techniques, 698; see also Embryo transfer technique intercourse, 698 supine rest after transfer, 698 PP, see Placenta previa PPOS, see Progesterone-primed ovarian stimulation PR, see Progesterone receptors Prader orchidometer, 403 Pre-eclampsia (PE), 753 Pre-exposure prophylaxis (PrEP), 757, 758 Pregnancy induced hypertension (PIH), 809 Pre-implantation genetic diagnosis (PGD), 706, 709 Pre-implantation genetic testing (PGT), 494, 496 anaesthesia for, 709–710 Pre-implantation genetic testing for aneuploidy (PGT-A), 502, 613 Premature ovarian insufficiency (POI), 802; see also Donation of egg and embryo Pre-ovarian block (POB) technique, 709; see also IVF anaesthesia PrEP, see Pre-exposure prophylaxis Pre-transfer techniques, 696–697; see also Embryo transfer technique acupuncture, 696 analgesics and anaesthesia, 697 antibiotics, 697 endometrial scratch, 696 gloves worn, 697 massage, 696 oxytocin antagonist, 696–697 transcutaneous electrical acupoint stimulation, 696 Precision medicine, 360, 362; see also Digital IVF clinic Preimplantation genetic testing for monogenic disorders (PGT-M), 502 Premature luteinization, 540 Premature ovarian failure (POF), 636 Premature ovarian insufficiency (POI), 416, 528 PrEP, see Pre-exposure prophylaxis Preterm labour (PTL), 753 Primary ovarian insufficiency (POI), 636, 734 conventional and drug-free IVA, 637–638, 638, 638 mitochondrial therapies, 641–643 platelet-rich plasma, 639–640 PRP technique, 639 stem-cell-based therapy, 640–641 in vitro activation, 636–639 Primary recruitment, 450 PR motility, see Progressive motility Progesterone, 519, 535, 536, 539 elevated serum, 475 Progesterone-primed ovarian stimulation (PPOS), 494, 505–506 Progesterone receptors (PR), 519 Progestin primed ovarian stimulation (PPOS), 451 Progressive motility (PR motility), 404 Proinflammatory markers, 650 Pronuclear stage transfer (PROST), 709 Propofol, 707, 708 PROST, see Pronuclear stage transfer PRP, see Platelet-rich plasma PTEN gene, 636 Pubertal suppression, 779 Purified FSH (pFSH), 427; see also Gonadotropin PVS, see Penile vibratory stimulation Q QMSs, see Quality management systems Quality control (QC) parameters, 362 Quality management systems (QMSs), 351–358 audits and reviews, 356 criteria of ISO standard, 352 Denning cycle, 352 different, 351 documentation in, 353–355 document control, 356 educational events, 357 elements of, 351 employee training, 357 EU tissue and cells directive, 358 EU Tissue Directive, 352 excellence model of European foundation, 352–353 guidelines for ART laboratories, 352 hierarchic ranks, 357 incidents and complaints, 356–357 ISO 9001 standards, 351–352 management and employee interactions, 357–358 management of processes, 353–356 management’s responsibility, 353 organizational chart, 354 quality policy, 353 staff management, 357 total, 352–353 Quality policies, 353 R Radio frequency electromagnetic radiation (RF-EMR), 378 Radio frequency electromagnetic waves (RF-EMW), 378 Radio frequency identification (RFID) tags, 362 Radiotherapy, 746 Randomized controlled trial (RCT), 397, 421, 503, 622, 625–626, 696 Random start, 494, 502, 504, 614 Random start ovarian stimulation, 421 Rapid freezing (RF) protocol, 685 Rapid oocyte recovery technique, 550; see also Oocyte collection RCT, see Randomized controlled trial RDS, see Respiratory distress syndrome Recombinant FSH (rFSH), 427; see also Gonadotropin physicochemical consistency of, 428 Recombinant LH (rLH), 444, 504 Recreational drugs, 369–370 Recurrent miscarriage (RM), 517 Recurrent pregnancy loss (RPL), 516 REI, see Reproductive endocrinology and infertility Relative risk (RR), 420 Remifentanil, 707 Remote ovarian cycle monitoring, 540–541 Remote salivary hormone testing, 542 Remote self-operated ultrasound, see SOET system Remote urinary hormone testing, 541–542 Repeated implantation failure (RIF), 647; see also Tubal pathology blastocyst culture, 647–648 embryo genetics, 648 parental genetics, 647 sperm genetics, 649 tubal pathology, 651 uterine pathology, 649–651 Reproductive health, 366 chemicals, 378–379 and environmental exposures, 383–387, 384 exposome, 376–378 hormone structures, 378 integrated model, 380, 380 life course perspective, 379–381, 387 mechanisms of action, 381–383 outcomes and associated toxicants, 383–387 and windows of vulnerability, 379–381 RESOLVE, 824 Respiratory distress syndrome (RDS), 753 Revised American Society of Reproductive Medicine (rASRM) score, 396 RF, see Rapid freeze RF-EMR, see Radio frequency electromagnetic radiation RF-EMW, see Radio frequency electromagnetic waves RFID, see Radio frequency identification tags rFSH, see Recombinant FSH RIF, see Repeated implantation failure Risks, 834 Risks in ART, 834–836; see also Safety management system functional, 836 haemorrhage, 834 in mountain climbing example, 835 operational, 835 personal, 836 types of, 836 rLH, see Recombinant LH Robotics technique, 361, 748–749 Rotterdam criteria, 725 RPL, see Recurrent pregnancy loss RR, see Relative risk S SA, see Semen analysis Safety culture, 839 Index Safety management system (SMS), 834, 839; see also Risks in ART in ART, 835 hazards and risks, 834 hazards in ART, 834 know your risk, 835 mountain climbing example, 835 risks in ART, 834–835 Saline hysterography (SHG), 650 Salvador–Warts–Hippo (SWH) pathway, 636 SART, see Society for Assisted Reproductive Technology SCSA, see Sperm chromatin structure assay SCs of mesenchymal origin (MSCs), 640–641 SD, see Standard deviation Secondary or cyclic, gonadotropin dependent recruitment, 450 Sedation, 706 deep sedation, 706 minimal sedation (anxiolysis or twilight sleep), 706 moderate sedation (conscious sedation), 706 Segmentation in IVF cycles ART success rates, United States, 495 avoidance of embryo–endometrium desynchrony, 495–497 cryopreservation of oocytes or embryos, 495 maternal and perinatal risks, 497 ovarian stimulation in freeze-all cycles, 494 risk of OHSS, 495 SE-HPLC, see Size-exclusion HPLC Self-operated endovaginal telemonitoring (SOET), 541, 541, 542 Semen analysis (SA) asthenospermia, 404 clinical evaluation, 403 identification of non-sperm cells, 404 interpreting, 403 low semen volume, 404 oligospermia and azoospermia, 404 parameters, 403 pH of the semen, 404 reference values of, 404 sperm vitality, 404 teratospermia, 404 Semi-volatile organic chemicals (SVOCs), 376 Serum oestradiol, 536 Serum progesterone, 536–537 SET, see Single embryo transfer Sex hormone binding globulin (SHBG), 624 Sexually transmitted diseases (STDs), 758 SF, see Slow freezing protocol SHBG, see Sex hormone binding globulin SHG, see Saline hysterography Single embryo transfer (SET), 592; see also Embryo transfer technique Size-exclusion HPLC (SE-HPLC), 427 Slow freezing (SF) protocol, 685, 690 SlowflowHD, 668, 668 SMS, see Safety management system Society for Assisted Reproductive Technology (SART), 796 SOET, see Self-operated endovaginal telemonitoring SOPs, see Standard operating procedures Spermatogonial stem cell (SSC), 741 851 Sperm chromatin structure assay (SCSA), 404 Sperm cryopreservation, 776 Sperm recovery rate (SRR), 683; see also Sperm recovery techniques Sperm recovery techniques, 677 anejaculation, 678 azoospermia, 677, 678 cryopreservation and thawing of testicular sperm, 685–686, 690 electroejaculation, 678–679, 686–687 epididymal or testicular, 678 epididymal sperm aspiration, 681 fine-needle aspiration, 681 FNA of testis for, 687 germ cell aplasia, 677 MESA protocol, 688 microscope-guided testicular sperm extraction, 683 multiple testicular sampling, 683 non-obstructive azoospermia, 682 no-scar technique, 681 obstructive azoospermia, 680 open testicular biopsy, 689 penile vibratory stimulation, 678 percutaneous epididymal sperm aspiration, 681 PESA protocol, 687–688 retrieving spermatozoa, 679–684 surgical sperm recovery, 677–678 testicular, 684, 686 testicular biopsy l, 689 testicular spermatozoa, 677 testicular sperm in lab, 684–685 Sperm vitality, 404 Spermatogenesis, 726 SRR, see Sperm recovery rate SSC, see Spermatogonial stem cell Standard deviation (SD), 430 Standard operating procedures (SOPs), 354, 836 Staphylococcus spp, 529 STDs, see Sexually transmitted diseases Stem cell (SC) niche, 636, 640 Streptococcus spp, 529 Stress and IVF outcome CBT or mind/body techniques, 832 conflicting results, 830 contradictory findings, 831 Covid-19 pandemic and infertility patients, 832 emotional burden of infertility, 832 empathic communication strategies, 832 encourage patients, 831–832 impact of distress, 829–832 inconclusive physiological data, 831 innovative approach, 831–832 meta-analyses, 830 no relationship, 830 physiological support for relationship, 830–831 positive relationship, 829–830 psychological impact of infertility, 829 psychological interventions and pregnancy rates, 831 treatment termination, 831 STROBE (Strengthening the Reporting of Observational Studies in Epidemiology), 608 Subfertility, 741; see also Fertility preservation Substance gonadotropin, 426; see also Gonadotropin Support services in ART, 821–822; see also Patient-centered approach clinic administration, 825 counseling, 823–824 information on, 824 SVOCs, see Semi-volatile organic chemicals SWOT analysis, 616 T TESE, see Testicular sperm extraction TAI, see Thyroid autoimmunity Tanner stage 2, 779 TEAS, see Transcutaneous electrical acupoint stimulation Tele-counselling, 542 remote ovarian cycle monitoring with, 540–541 Telehealth, 360 Teratospermia, 404 Testicular aspiration, 684; see also Sperm recovery techniques Testicular biopsy, 689; see also Sperm recovery techniques Testicular sperm; see also Sperm recovery techniques sampling by TESE, 682 Testicular spermatozoa, 677 Testicular sperm cryopreservation techniques, 685–686; see also Sperm recovery techniques rapid freezing, 685 slow freezing, 685, 690 ultra-rapid freezing, 685 Testicular sperm extraction (TESE), 679; see also Sperm recovery techniques; Testicular sperm Testosterone (T), 725 clinical evidence, 624–625 physiological basis of intervention, 623–624 synthesis and critical appraisal of evidence, 625, 625–626 TGNB, see Transgender and nonbinary individuals T helper, 516 Third-party reproduction, 813; see also Gestational surrogacy 3D antral follicular count, 660 Three-dimensional (3D) US, 402 “Three-parent baby” technique, 643 Thrifty genotype, 726 Thrombophilia, 651 Thyroid autoimmunity (TAI), 528 Thyroid peroxidase (TPO) antibodies, 528 Thyroid stimulating hormone (TSH), 401, 528 Time to pregnancy (TTP), 384 TOA, see Tubo-ovarian abscess Toll Like Receptor (TLR4), 529 Total intravenous anaesthesia (TIVA) technique, 708 Total Quality Management (TQM), 352–353; see also Quality management TPO, see Thyroid peroxidase antibodies TQM, see Total Quality Management Index 852 Traditional Chinese medicine, 709 Traditional clinic-based ovarian cycle monitoring, 539–540 patient perspective on, 540 Transcutaneous electrical acupoint stimulation (TEAS), 696 Transferase-mediated dUTP nick-end labeling assay (TUNEL assay), 404 Transfer techniques, 697–698; see also Embryo transfer technique placement of catheter, 698 removing mucus, 698 retained embryo, 698 three-dimensional ultrasound guidance, 697 time interval before withdrawal, 698 time of loading, 697 transvaginal ultrasound guidance, 697 type of catheter, 697–698 ultrasound guidance, 697 Transforming growth factor-ß (TGF-ß), 517, 639 Transgender and nonbinary individuals (TGNB) additional considerations for youth, 779 ART outcomes for individuals, 777–779 barriers to care, 771–772 discrimination of, 771 embryo cryopreservation, 776 feminizing hormones and reproductive potential, 773–774 fertility preservation options, 774, 776, 777 gender-affirming treatments, 772–773 gender identity, 770, 771 oocyte and embryo cryopreservation, 774–775 ovarian tissue cryopreservation, 775–776 parenting, 770–771 pubertal suppression, 779 reproductive options for, 776–777, 778 sperm cryopreservation, 776 testicular tissue cryopreservation, 776 testosterone and reproductive potential, 773 Transvaginal ultrasonography (TVUS), 401, 535 Transvaginal ultrasound-guided oocyte retrieval (TUGOR), 706 pain control during, 706–707 T regulators (Tregs), 516, 518 TSH, see Thyroid stimulating hormone T-shaped uterus, 402, 747 TTP, see Time to pregnancy TTTS, see Twin–twin transfusion syndrome Tubal infertility, 395–396; see also IVF treatment Chlamydia trachomatis, 395 future trials, 395–396 tubal surgery, 395 Tubal pathology, 651; see also Repeated implantation failure assisted hatching, 651–652 co-culture, 652–653 endometrial scratch, 652 techniques, 651–653 thrombophilia, 651 Tubo-ovarian abscess (TOA), 835 TUGOR, see Transvaginal ultrasound-guided oocyte retrieval Tumour necrosis factor (TNF) a, 516, 517 TVUS, see Transvaginal ultrasonography Twilight sleep, see Minimal sedation Two-cell–two-gonadotropin model, 431 U UAE, see Uterine artery embolization Ubiquinol, see Coenzyme Q10 (CoQ10) u-hCG, see Urinary hCG Ultra-rapid freezing (URF) protocol, 685 Ultrasonography, 659, 672 acquired uterine abnormalities, 664–666 adenomyoma, 665 adenomyosis, 665 ART complications and outcome, 670–671 caesarean section scar niche, 667–668 congenital uterine anomalies, 666–667 dermoid cysts, 661 Doppler and 3D ultrasound, 668, 669 fallopian tube patency, 668–669 fallopian tube ultrasound, 668–669 heterotopic pregnancy, 671 hydrosalpinges and ART outcome, 670 intracavitary abnormalities, 664 intrauterine adhesions, 666 OHSS, 670–671 ovarian cysts, 660–661 ovarian reserve, 659–660 ovary ultrasound, 661 polycystic ovary ultrasound, 661 pregnancy ultrasound, 671 SonoAVC, 662 3D AFC, 660 US-guided IVF, 670 uterine polyp sonogram, 663 uterus endometrial thickness and ART, 663 voxel count, 662 Ultrasound (US), 400, 659; see also Ovarian reserve biomarkers; Ultrasonography UN, see United Nations UNDP, see United Nations Development Programme UNFPA, see United Nations Population Fund Unexplained infertility, 396–397 Unicornuate uterus, 667, 747 United Nations (UN), 366 United Nations Development Programme (UNDP), 366 United Nations Population Fund (UNFPA), 366 UNK, see Uterine natural killer cells Ureaplasma, 529 URF, see Ultra-rapid freezing protocol Urinary hCG (u-hCG), 425; see also Gonadotropin US, see Ultrasound U.S Food and Drug Administration (FDA), 669, 806 Uterine artery embolization (UAE), 665 Uterine natural killer (uNK) cells; see also Natural killer cells in angiogenesis and EVT invasion, 520–521 cells functions and secretions with gestational age, 521 context of pregnancy, 520–521 controlling trophoblastic invasion, 520 endometrial homeostasis, 520 KIR/HLA-C combinations, 521, 521–523 maternal–fetal interactions, 521, 521–523, 522 origin of, 519–520 remodelling of spiral arteries, 520 throughout menstrual cycle, 519 vs peripheral blood natural killer cells, 518–519 Uterus transplantation (UTx) complications in live donors, 750 complications in recipients, 750–751 deceased donor hysterectomy, 747 deceased donor reports, 750 efficacy of IVF and obstetrical outcomes, 751 embryo transfer in, 752–753 IVF treatment after, 752 IVF treatment before, 751–752 live donor hysterectomy, 747–749 live donor reports, 750 obstetrical and neonatal outcome, 753 open surgery technique, 749 plausible uterus transplantation patients, 746–747 reported pregnancies with live births, 754 reproductive outcome, 753 results, 750–751 robotics technique, 749–750 support and sponsorship, 753 types of, 747–750 UTx, see Uterus transplantation V Varicocele, 403 Vascular endothelial growth factor (VEGF), 481, 506, 639, 729, 783 Vasopressin-induced VEGF secretion blockade, 787 VEGF, see Vascular endothelial growth factor Veno-thrombo embolism (VTE), 836 Vero cells, 652 Vertical communication, 357 Viral disease, 756; see also Human immunodeficiency virus ART outcomes, 760 Covid-19 pandemic, 763–764 HBV and HCV, 762 HTLV-1 and-2, 762 laboratory protocols for viral positive patients, 765 Monkeypox, 756, 764–765 viral screening, 765 Zika, 756, 762–763, 763 Virtual organ computer-aided analysis (VOCAL), 668 VOCs, see Volatile organic compounds Volatile organic compounds (VOCs), 376 VTE, see Veno-thrombo embolism Index 853 W X Z WCBs, see Working cell banks WHO, see World Health Organization Withholding gonadotropins, 787 Working cell banks (WCBs), 427 World Health Organization (WHO), 351, 539, 542, 677, 757 World Professional Association for Transgender Health (WPATH), 774 X-linked Duchenne muscular dystrophy, 710 ZIFT, see Zygote intrafallopian transfer Zika virus (ZIKV), 756, 762–763, 763; see also Viral disease nucleic acid testing, 763 RNA, 762–763 ZIKV, see Zika virus Zygote intrafallopian transfer (ZIFT), 708 ZyMot, 649 Y YAP, see Yes associated protein Yeast, 529 Yes associated protein (YAP), 636