MANAGEMENT OF INFERTILITY : a practical approach

Front Cover MANAGEMENT OF INFERTILITY MANAGEMENT OF INFERTILITY Copyright Contents Contributors Preface 1 - History and epidemiology of human fertility Fertility in the ancient world Fertility in the post-Renaissance era Fertility in modern times The hypothalamic-pituitary-ovarian axis The gonadotrophins Gonadal steroids Immuno-assays and the female hormonal interplay Other milestones in the history of fertility The IVF revolution Further developments in assisted reproduction The story of ICSI Embryo selection, fertility preservation, and the future Epidemiology of human fertility Normal fertility patterns and the definition of infertility Prevalence of infertility Seeking infertility treatment Factors affecting the success of infertility treatment Burden of infertility Access to infertility services References 2 - Setting up an ART unit: planning, design, and organization Planning Location Reachability Communication Design and building Required surface Design Waiting room Examination room Semen pick area Semen laboratory IVF laboratory Storage areas Controlled accesses Emergency access Materials and implants Materials Floors Resilient coatings Materials for thermal and acoustic insulation False ceiling Paints Plants Installations Light Power and UPS Gas station Liquid nitrogen and cryoroom Air quality LAN network PMA and home automation Ergonomics and flows Workflows Ergonomics Examples about ergonomics in an embryology laboratory Responsibility and organization Staff and experience Stafff requirements Organization chart European model [39] Staff and management Laboratory director Laboratory supervisors Clinical embryologists American model (ASRM) [40] Personal Doctors Nurses Laboratory Auxiliary personnel Training and specialized experience Study director Medical director Doctor performing egg retrieval and embryo transfers Nurses Director of the embryology laboratory Embryology laboratory technician References 3 - Building the assisted reproduction laboratory Introduction Purposes of the lab Location Laboratory Andrology laboratory Liquid nitrogen containers storage room Gas cylinders central and management General material storage The building structure Air flow Furniture Equipment Safety Personal experience Concluding remarks References 4 - Workup of female infertility Introduction Classification of infertility interview Approaching the interview First interview Anamnestic interview Physical examination Exams required Ovarian reserve test (ORT) Serum hormone assessment Ultrasound assessment Ovulation and luteal phase support Coagulation profile assessment Genetic profile assessment Serologic assessment Sonohysterosalpingography 3D transvaginal ultrasound Hysteroscopy PAP test or HPV-DNA test Breast ultrasound or radiography Timing of exams Secondary interview Follow-up interview Conclusion References 5 - Work-up of male infertility Epidemiology Etiology and risk factors Diagnostic work-up Patient's history Infertility history Medical history Lifestyle factors Surgical history Family history Sexual history Physical examination Semen analysis Measurement of sperm DNA fragmentation index Hormonal evaluation Genetic testing Chromosomal abnormalities Autosomal abnormalities Cystic fibrosis gene mutations Y microdeletions Measurement of oxidative stress Imaging Scrotal ultrasound Transrectal US Other Summary References 6 - Prothrombotic gene polymorphisms and adverse reproductive outcomes in assisted reproductive technology Physiology of coagulation Coagulation factors' gene mutations Activated protein C resistance (factor V Leiden mutation) Antithrombin deficiency Protein C and protein S deficiency Prothrombin G20210A mutation Hyperhomocysteinemia Plasminogen activator inhibitor type 1 Elevated factor VIII Blood coagulation in pregnancy Prothrombotic hereditary coagulopathies and recurrent pregnancy loss ART procedures in current practice Prothrombotic gene polymorphisms and adverse reproductive outcomes in ART Preconceptional and prenatal diagnostic approach Possible management options Conclusions References 7 - Endocrinological causes of female infertility Introduction Anovulation Ovarian aging Ovarian reserve Primary ovarian insufficiency Polycystic ovary syndrome Hypothalamic-pituitary axis pathology Hyperprolactinemia Hyper- and hypoandrogenism Therapeutical intervention Estrogen antagonists Gonadotropins treatments Preventing complications Ovarian hyperstimulation syndrome Multiple gestations Final considerations References 8 - Management of tubal factor Tubal infertility Etiology Tubal lesions Proximal Distal Congenital lesions What are the subtle tubal lesions? Diagnosis Therapeutic options Tubal flushing Tubal surgery General principles Surgery of pelvic adhesions Proximal pathology Distal pathology Subtle tubal lesions Conclusion References 9 - Cervical and uterine congenital anomalies Introduction Embryology: the origin of anomalies Pathogenesis Etiology Prevalence Other associated anomalies Clinical presentation Classification Diagnosis 2D ultrasound Hysterosalpingography Hysteroscopy 3D ultrasound Magnetic resonance Uterine abnormalities Septate uterus Diagnosis Clinical relevance Surgical treatment Results after hysteroscopic metroplasty Complete septa with double cervix Unicornuate uterus Diagnosis Clinical importance Associated anomalies Surgical repair Results after hysteroscopic metroplasty Dysmorphic uterus Diagnosis Clinical importance Surgical repair Results after hysteroscopic metroplasty Bicornate uterus Clinical importance Diagnosis Surgical repair Results after surgery Robert's uterus Diagnosis Clinical importance Surgical repair Control after hysteroscopic surgery Recommendations and conclusions References 10 - Uterine fibroids and infertility Introduction and definition Uterine fibroids and infertility Pathophysiology Uterine myometrial peristalsis Diagnosis Management Recommendation Conclusion References 11 - Endometriosis and infertility Pathophysiology Potential mechanisms for endometriosis-related infertility Management of endometriosis-associated infertility Fertility preservation in women with endometriosis References 12 - Endocrinological causes of male infertility Introduction Hormonal actions on spermatogenesis Hormonal regulations of spermatogenesis Endocrine conditions associated with male infertility Male hypogonadism Hyperprolactinemia Thyroid disorders Obesity Exogenous administration of testosterone and anabolic steroid Evaluation of an infertile man from an endocrinological point of view Therapies GnRH Gonadotropin Antiestrogens Aromatase inhibitors The protocol of hormonal treatment of infertile men References 13 - Sperm DNA fragmentation: impact on ART outcome Introduction Measuring SDF within the context of ART The impact of SDF on IUI The impact of SDF on IVF and ICSI Impact of SDF on fertilization Impact of SDF on clinical pregnancy Impact of SDF on embryogenesis Impact of SDF on miscarriage and live birth rate Approaches to reduce SDF in ART Varicocele treatment Treatment of male genital tract infections Addressing lifestyle and exposure risk factors Antioxidant therapy Frequent ejaculation Sperm selection techniques and use of ART Future directions Summary of key points References 14 - Male accessory gland infection: diagnosis and treatment Definition and classification Impact on fertility: explanatory mechanisms Diagnosis Microbiological testing Ultrasound Therapeutic strategies Antibiotics Antiinflammatory drugs Fibrinolytics Antioxidants Conclusion References 15 - Hormonal and nonhormonal treatment of male infertility Etiology of male infertility Pathophysiology of spermatogenesis Principles of management Hypothalamo-pituitary disease Testicular failure Idiopathic male infertility Empirical hormonal therapy GnRH analogs Gonadotropins Androgens Aromatase inhibitors Selective estrogen receptor modulators Empirical non-hormonal therapy Antioxidants Antibiotics Lifestyle modification Obesity and weight loss Diet and exercise Alcohol Smoking Caffeine Recreational drugs Stress References 16 - Surgical management of male infertility and sperm retrieval Surgical management of conditions related to male infertility Varicocele Introduction Radiological techniques: retrograde sclerotherapy or embolization Radiological techniques: anterograde sclerotherapy or embolization Surgical techniques: retroperitoneal approach Surgical techniques: laparoscopic approach Surgical techniques: inguinal and subinguinal approach Summary about varicocele treatment Retractile testis in adulthood Ejaculatory ducts obstruction Transurethral resection Vasovasostomy and vasoepididymostomy Sperm retrieval in azoospermic men Sperm retrieval in obstructive azoospermia Sperm retrieval in nonobstructive azoospermia References 17 - How to choose the appropriate ART technique and counseling about reproductive outcomes References Further reading 18 - Preparing the couple for ART: necessary and unnecessary diagnostic tests Introduction Tests to be performed by both partners Blood group with Rh factor Blood glucose Kidney and liver function Viral screening: HIV, HBV, and HCV Human papillomavirus (HPV) screening Hemoglobin electrophoresis Karyotype Cystic fibrosis mutations Tests to be performed by the woman Preconception counseling Thrombophilia screening Cervico-vaginal swab FSH, LH, and estradiol Clomiphene citrate challenge test AMH Progesterone TSH and TPOAb Pelvic ultrasound examination Hysterosalpingography and hysterosonosalpingography Chlamydia antibody test (CAT) Hysteroscopy Laparoscopy Tests to be performed by the man Semen analysis Microbiological assessment FSH, LH, testosterone, prolactin Scrotal ultrasonography Transrectal ultrasonography Y chromosome microdeletion analysis Sperm DNA fragmentation tests Tests for antisperm antibodies Diagnostic testicular biopsy References 19 - Ovulation induction protocols Introduction Indications Cervical indications Sperm etiology Unexplained etiology Ejaculation disorders Immunological etiology Pre-IUI tests Performing intrauterine insemination Ovarian stimulation Spontaneous cycle Antiestrogens Clomiphene citrate Aromatase inhibitors Gonadotropins Semen preparation IUI procedure How many IUIs do we need to achieve? Prognostic factors of IUI Etiologies and prognostic factors Rank of the attempt and prognostic factors Age and duration of infertility Characteristics of stimulation Number of motile sperm inseminated (NMSI) Sperm morphology Conclusion Bibliography 20 - Ovarian stimulation protocols Introduction Conventional protocols GnRH agonist protocols GnRH antagonist protocols Comparison of GnRH-a and GnRH-ant protocols Gonadotropins Novel protocols References 21 - Oocyte retrieval Introduction Setting and equipment Preparation of the patient for oocyte retrieval On the day of oocyte retrieval Technique Anesthesia during oocyte retrieval Oocyte recovery After the oocyte retrieval Complications References 22 - Oocyte quality evaluation and cryopreservation Human oocyte quality evaluation General aspects Oocyte quality assessment by morphology under light microscopy Evaluation of maturity Morphologic parameters of oocyte quality Cumulus-oocyte complex morphology Cytoplasm and polar body morphology Meiotic spindle evaluation Oocyte quality assessment by polarized light microscopy Oocyte quality assessment by follicular fluid dynamics Follicular fluid hormones Growth factors of the transforming growth factor-beta (TGF-beta) superfamily in follicular fluid Insulin-like growth factors in follicular fluid Reactive oxygen species in follicular fluid Metabolomics of follicular fluid Oocyte quality assessment by molecular approaches Oocyte quality assessment by AI Metaphase II (MII) oocyte dysmorphisms Cytoplasmic abnormalities Extracytoplasmic abnormalities Factors affecting oocyte quality Endometriosis Age Polycystic ovary syndrome Oocyte cryopreservation The current technologies for oocyte cryopreservation The recommendations for clinical applications of OC as fertility preservation The clinical outcomes of oocyte cryopreservation The risks of oocyte cryopreservation Conclusion References 23 - Ovarian hyperstimulation syndrome Introduction Definition Epidemiology Risk factors Classifications Timing of presentation Severity of presentation Pathophysiology Clinical presentation Clinical assessment History Physical examination Laboratory and imaging tests Prevention Identification of risk factors Potential strategies or intervention before ovarian stimulation Avoid gonadotropin for ovulation induction in non-IVF cycles Oral contraceptive (OC), progestogen or estrogen Natural IVF cycles Gonadotropin starting dose for IVF cycles Personalization Mild ovarian stimulation Choice of the gonadotropin for high-risk patients Regimens of ovarian stimulation Drug co-administrations CC or letrozole Metformin FSH dose decrease Coasting Strategies for controlling LH surge GnRH analogs Use of progestin-primed ovarian stimulation Ovulation triggering strategies for high-risk patients hCG LH GnRH agonist Kisspeptin Elective cryopreservation Cancellation cycle Elective single embryo transfer (eSET) In vitro maturation (IVM) of oocytes Other treatments or procedures Intensification of monitoring and surveillance Dopaminergic agonists (cabergoline, quinagolide) Aspirin Corticosteroids (methylprednisolone) Calcium infusion Ketoconazole Diosmin Luteal GnRH antagonist administration Volume expanders Luteal phase support Treatment Outpatients Inpatients Conclusions References 24 - Sperm quality evaluation and cryopreservation Sperm quality evaluation Sample collection Reference ranges Semen analysis Basic assessments Ejaculate volume Macroscopic assessment Microscopic assessment Extended assessments Sperm DNA fragmentation Genetic and genomic tests Testing for antibody coating of spermatozoa Assessment of accessory gland function (biochemical assays) Advanced assessments Quantification of reactive oxygen species Computer-aided sperm analysis Sperm preparation and selection Routine techniques Advanced techniques Cryopreservation of spermatozoa Sample collection Cryopreservation techniques Indications Fertility preservation Cancer treatment Gender reassignment With assisted reproductive techniques Autologous use Heterologous use Risks Challenges Future References 25 - In vitro fertilization and embryo culture in time-lapse imaging Introducing time-lapse devices Embryo selection using time lapse Patient perspectives and feedback Anticipating the future Summary References 26 - Intracytoplasmic sperm injection Background Indications Male factor Non-male factor Popularity Results Ejaculated spermatozoa Surgically retrieved spermatozoa ICSI for difficult cases Extreme male factor Elevated DNA fragmentation Persistent fertilization failure Considerations and future perspective References 27 - Embryo transfer Introduction Learning curves Biofluidic dynamics of embryo transfer The role of the catheter and loading embryos Preparation of the uterus for transfer Mock transfer and transvaginal ultrasound for the measurement of the endometrial cavity length and position Is the ultrasound support effective? Placement of embryos in the uterine cavity Conclusions References Further reading 28 - Luteal phase support Introduction Physiology of the luteal phase Pharmacodynamics and types of presentation of progesterone Routes of administration Oral progesterone Intramuscular progesterone Vaginal progesterone Subcutaneous progesterone Transdermal progesterone LPS in assisted reproductive treatments Intrauterine insemination In vitro fertilization Progesterone's dosages and routes Personalized luteal phase The onset of progesterone supplementation Ending of LPS LPS and egg donation/frozen-thawed embryo transfer (FET) cycles Use of estradiol in LPS Use of hCG in LPS Use of LH in LPS Use of GnRH agonists in LPS Disorders of endometrial receptivity and Personalized Embryo Transfer Conclusions References 29 - Preimplantation genetic testing Principle and history of preimplantation genetic testing Principle The first steps of clinical preimplantation genetic testing Worldwide applications of PGT and the first questions on its efficacy Protocol of PGT ICSI and embryo culture Embryo biopsy Molecular analysis Embryo vitrification/warming and embryo transfer Genetic counseling Quality and risk assessment Results and efficacy of PGT Efficacy of embryo culture, embryo biopsy, and consequences on clinical outcomes Database results Results and efficacy of PGT-M Results and efficacy of PGT-SR Results and efficacy of PGT-A to indications Whole chromosome mosaicisms and segmental chromosomal abnormalities Chromosomal concordance between inner cell mass and trophectoderm cells Noninvasive PGT Conclusions and the future of PGT Acknowledgments References 30 - Embryo quality evaluation and cryopreservation Embryo quality evaluation Cryopreservation References 31 - Frozen embryo transfer Introduction Background How to prepare the endometrium for FET Natural cycle and modified natural cycle Hormone replacement treatment Maternal and obstetric outcomes of FET Conclusions References 32 - Egg and sperm donation Introduction Indications for egg donation Indications for sperm donation Legal aspects Organizing a gamete donation program Phenotype matching Genetic matching Donors Selection of donors Donor age Treatment protocol for the donor Synchronous donation Synchronization with the recipient Ovarian stimulation for the donor and trigger Donor pick-up Asynchronous donation Complications Recipients Recipient selection Recipient's age Synchronization with the donor Endometrial preparation and growth Endometrial preparation for embryo reception Type and route of progesterone to be used Start day Post-transfer treatment Exclusive or shared donor and number of eggs per recipient Treatment complications in the recipient Complications for the mother Complications in the newborn Results Egg bank References 33 - Recurrent miscarriage Introduction Definition Epidemiology Etiologies Genetic causes Parental chromosomal anomalies Embryonic aneuploidy Parental karyotyping and products of conception cytogenetic analysis Sperm DNA fragmentation Uterine factors Uterine structural anomalies Congenital uterine anomalies Acquired uterine abnormalities Chronic endometritis Immunologic factors Autoimmune disorders: antiphospholipid syndrome Uterine immune system and immunotherapy Endocrine disorders Thyroid disorders Diabetes Hyperprolactinemia Polycystic ovary syndrome Vitamin D deficiency Luteal phase deficiency Inherited thrombophilia Evaluation for recurrent miscarriage Conclusion References 34 - Repeated implantation failure Introduction Definitions Causes Diagnostic work-up General Hysteroscopy Immune profile biomarkers Investigation of chromosomal abnormalities Molecular assays Metabolomics Reaching a robust conclusion Interventions Endometrial injury Antibiotics Human chorionic gonadotropin Immunotherapy Intravenous immunoglobulin Granulocyte colony-stimulating factor Tacrolimus and sirolimus Other immunomodulatory agents Conclusion on immunotherapy Atosiban Low molecular weight heparin Freeze-all policy Growth hormone Gonadotropin-releasing hormone Assisted hatching Combined strategies Other treatment options Conclusion References 35 - Gestational carrier Introduction Indications for surrogacy Selection process and criteria of gestational carrier Counseling and legal requirements Synchronization of cycle Obstetric care of surrogate Risks associated with surrogacy Ethical, religious, and financial concerns about the surrogacy procedure Psychological impact with surrogacy Conclusion References 36 - Female and male fertility preservation in oncology Introduction Multidisciplinary fertility sparing team Counseling and psychological support Eligibility for fertility sparing Cancer treatments that affect female fertility Treatment for breast cancer Treatment for Hodgkin lymphoma Ovarian and uterine exposure to radiotherapy Cancer treatments that affect male fertility Chemotherapy side effects Radiation therapy side effects Surgery effects Techniques for fertility preservation of female patients Oocyte and embryo cryopreservation Cryopreservation of ovarian tissue GnRH agonists Fertility-sparing surgery in gynecological cancers Conservative treatment for cervical cancer Conservative treatment for ovarian neoplasms Ovarian borderline tumors Invasive epithelial ovarian cancer Conservative treatment for endometrial hyperplasia and cancer Techniques for fertility preservation in males Semen cryopreservation Gonadic suppression Cryopreservation of testicular tissue Techniques for fertility preservation in pediatric patients Pregnancy after fertility preservation in cancer survivors References 37 - Psychological impact of infertility and ART procedures Introduction The psychosocial impact of infertility Coping and adjustment and the couple unit Psychosocial impact during treatment Ending fertility treatment Recommendations for clinicians Research limitations Conclusion References 38 - Risk, safety, and outcome monitoring in the IVF clinic Introduction Monitoring of risk, safety, and outcome in ovarian stimulation Monitoring of risk, safety, and outcome in oocyte retrieval Monitoring of risk, safety, and outcome for semen collection and preparation Monitoring of risk, safety, and outcome in laboratory In vitro fertilization Intracytoplasmatic sperm injection Embryo culture Preimplantation genetic/diagnostic test Cryopreservation Embryo transfer Other outcomes Monitoring of risk, safety, and outcome for the entire IVF process Efficacy outcomes Safety outcomes Long-term outcomes for progeny and women Progeny Oncological risk References 39 - Regulation, data management, informed consent, and legal issues for ART Introduction ART regulation ART regulation in European countries The role of religion Cross-border reproductive care Quality and data management Informed consent References 40 - Impact of COVID-19 on ART (Assisted Reproductive Technologies) Introduction SARS-CoV-2 and reproductive system Some questions in the practice of ART The impact of COVID-19 on ART care in Europe and the United States The impact of vaccine for couples who want a pregnancy or for responsible parenting The COVID-19 Pfizer and Moderna vaccine The COVID-19 AstraZeneca and Johnson vaccine References Index A B C D E F G H I J K L M N O P Q R S T U V W Y Back Cover Management Of Infertility: A Practical Approach Offers An Accurate And Complete Reference For The Management Of Infertility And A Robust Step-by-step Guide For Assisted Reproduction Technologies (arts), Including How To Plan, Design And Organize The Clinical Setting And Laboratory. It Also Provides An Evidence-based, Complete And Practical Description Of The Available Methods For Diagnosis And Management Of Male And Female Infertility. This Book Is Designed To Help Researchers, Students, And Clinicians Worldwide To Gain A Complete Knowledge About Both Basic And Advanced Knowledge For The Diagnosis And Management Of Infertility And Related Disorders. Provides Step-by-step Description About How To Design, Plan And Organize An Assisted Reproductive Technology (art) Unit And Laboratory Deeply Discusses Both Male And Female Factor Infertility, Providing A Complete Guide For The Diagnosis And Treatment Of The Different Causes Of Infertility Addresses All The Techniques Of Assisted Reproduction And In Vitro Fertilization, Discussing Their Use In Different Clinical Settings