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Infertility Management
Sushma Deshmukh
1: INTRODUCTION
CHAPTER 1:
Doctor We Want a Child
Divide the Patients in Four Categories
CHAPTER 2:
Initial Work-up and Diagnosis
Physical Examination of the Couple
Female
Male
Counseling
Transvaginal Sonography
Laboratory Investigations
Specific Hormonal Investigations
Hysterosalpingography
Baseline Ovulation Study
Laparoscopy and Hysteroscopy
Diagnosis and Management
Anovulatory
Tubal
Tubal Block
Endometriosis
Mild to Minimal
Moderate and Severe Endometriosis
Male Factor
Medical Management
Surgical
ART Support
Unexplained Infertility
Luteal Phase Defect
ART
Indications
There are Variety of Techniques
Others are:
Other Variants are:
Conclusion
2: IMPORTANT ASSETS
CHAPTER 3:
Transvaginal Sonography in Infertility
Ultrasound Assessment of the Male Partner
Transrectal Ultrasonography
Assessment of the Female Reproductive Tract
Vaginal and Cervical Factor Infertility Evaluation
Uterine Factor Assessment and Evaluation
The Uterus
Endometriosis
Fibroids
Congenital Anomalies
Sonohysterography
Endometriosis of the Uterus (Adenomyosis)
Evaluation of Endometrial Growth
Smith's Grading
Endometrial Thickness and Menstrual Cycle
Color Doppler
Tubal Evaluation
Sonosalpingography
Ovarian Evaluation by Ultrasound
Ovarian Study
Follicular Development
Prediction of Ovulation
Confirming Ovulation
Ovary in Anovulatory Cycles
Endometrium
Early Proliferative Phase
Late Proliferative Phase
Luteal Phase
Endometrial Motion
Role of Transvaginal Color Doppler in Infertility
Study of Menstrual Cycle by Color Doppler
Changes in the Ovary
The Phases are as Follows
Doppler Assessment of Uterine and Ovarian Flow in Infertility and IVF
Role of Transvaginal Color Doppler in Other Conditions Associated with Infertility
Luteinized Unruptured Follicle
Luteal Phase Defect
Fibroid
Endometriosis
Tubal Causes
Polycystic Ovarian Disease
Uterine Factor
Color Doppler and its Contribution towards in Vitro Fertilization
Avoidance of Ovarian Hyperstimulation Syndrome
Optimal Conditions for Embryo Transfer
Ultrasound Guided Assisted Reproduction Techniques
Historical Review
Conclusion
CHAPTER 4:
Semen Analysis
Important Concerns
Semen Collection
Sample Collection in a Case of Retrograde Ejaculation
Semen Examination
Volume
Viscosity
Liquefaction
Color/Appearance/Odor
pH
Fructose Estimation
Microscopic Examination
Sperm Concentration
Manual/Conventional Techniques
Automated Method
Sperm Motility
Sperm Morphology
Head Defects
Neck/Mid-piece Defect
Tail Defects
Viability
Hypo-osmotic Swelling Test
Antisperm Antibody
Semen Culture
WHO Criteria of Normal Semen
Sperm Processing
Conclusion
CHAPTER 5:
Graphical Evaluation of Fallopian Tube and Uterus
Hysterosalpingography
Indications
Infertility
Recurrent Abortion
To Monitor the Effects of Tubal Surgery
Contraindications
Procedure
Precautions
Difficulties
Complications
Interpretation of HSG
Normal HSG (Fig. 5.1)
Abnormal Hysterosalpingogram
Cervix
Uterine Cavity
Fallopian Tube
Therapeutic Effects of HSG
Predictive Value of HSG
Conclusion
Hydrohysterosonography
Sonosalpingography
SION Procedure
Hysterosalpingo Contrast Sonography (HyCoSy)
Radionuclide HSG
Selective Salpingography
HSG Guided Procedure
Advantages of the Graphical Study
CHAPTER 6:
Fallopian Tube Recanalization
Introduction
Historical Review
Tubal Anatomy
Intramural Segment
Interstitial Portion
Pretubal Bulge
Isthmus
Normal Tubal Physiology
Pathophysiology
Indications for Tubal Recanalization
Hysterosalpingography
Laparoscopy
Tubal Recanalization
Cannulation Routes
Hysteroscopic Recanalization
Technique
Our Experience
Our Recommendations
Complications and Contraindications
Conclusion
CHAPTER 7:
Expanding Scope Through Endoscopy Part I
Introduction
Endoscopy in Infertility
Laparoscopy and Hysteroscopy
Diagnostic
Therapeutic (Operative Endoscopy)
Laparoscopy
Endometriosis
Polycystic Ovarian Syndrome
Effects
Complications
Tubal Surgery
Fibroids
Operative Hysteroscopy
Fertility Enhancing Surgeries
Conclusion
CHAPTER 8:
Expanding Scope Through Endoscopy Part II
Laparoscopy (Diagnostic)
Laparoscopy (Operative)
Laparoscopic Management of Adnexal Masses
Laparoscopic Detorsion of Adnexae
Laparoscopic Salpingectomy of Hydrosalpinx
Laparoscopic Tubal Surgery
Laparoscopic Myomectomy
Myomectomy
Operative Technique—Principles
Debates and Controversies
Obstetrics Quality of Laparoscopic Myomectomy Scars
Recurrence after Laparoscopic Myomectomy
Postmyomectomy Adhesions Laparoscopic Versus Laparotomy
Adjuncts to the Laparoscopic Approach for Secure Suture Repair of Myoma Defects
Conclusion
Complications of Laparoscopic Surgery
Urinary Tract Complications
Electrosurgical Complications
Features of Puncture and Electrical Injuries of the Bowel
Puncture Injuries
Electrical Injuries
Laparoscopic Robot-assisted Surgery
Telepresence Surgery
Our Experience
Hysteroscopic Surgery
Conclusion
3: TRACKLING WITH ANOVULATION
CHAPTER 9:
Anovulation: Is it Easy to Manage?
Central Causes
Hypothalamus (Flow chart 9.1)
Pituitary
Abnormal Feedback
Disturbances in FSH and LH cause anovulation
Metabolic
Local Ovarian Conditions
Endometriosis
PCOS
Infectious Process
General
Obesity
Evaluating and Managing Anovulation
Normal Thyroid and Prolactin Levels
In ovulatory cycle
Patient can have Withdrawal Bleeding, then do Baseline LH and FSH
Patients having Regular Menstrual Cycle
Conclusion
CHAPTER 10:
Polycystic Ovarian Syndrome
Introduction
History and Current Concepts
Pathophysiology and Etiology
Ovary
Hypothalamus
Insulin Resistance and Hyperinsulinemia
Hyperinsulinemia
Hyperthecosis
Hyperprolactinemia in PCOS
Leptin
Genetics of the PCOS
Confirming the Diagnosis
History and Symptoms
Clinical Examination
Biochemical Tests
Ultrasound and Imaging
Endometrium in PCOS
Approach to the Case
Baseline Parameters
Baseline Ovulation Study
Classification of the Patient
Management
Weight Reduction and Exercise
Medical Treatment
Clomiphene Citrate
How to Use?
Response of Polycystic Ovarian Syndrome Patient to Clomiphene Citrate
Aromatase Inhibitors (AI)
Gonadotropins
How to start with gonadotropins?
Complications of Stimulation
Insulin Sensitizers (Table 10.1)
Metformin
Troglitazone
Rosiglitazone
Pioglitazone
D-Chiro-inositol
Other Preparations
Surgical Treatment
Mechanism of Action
Treatment of Hirsutism
Drugs used
In Nutshell
CHAPTER 11:
Ovulation Induction
Introduction
Physiology of Gonadotropin Secretion
Gonadotropin Independent Follicular Recruitment
Gonadotropin Dependent Follicular Development
Follicle-stimulating Hormone Window (Number of Days the FSH Levels are above Threshold)
Follicular Selection
Follicular Dominance
Oocyte in the Dominant Follicle
Normal Ovulation and Endometrial Response
Abnormal Cycles
Indications for Ovulation Induction
Prerequisites before Ovulation Induction
Drugs Used for Ovulation Induction
Ovulation Inducing Agents are Clomiphene Citrate
Mechanism of Action of Clomiphene Citrate
How to Use?
Dose of Clomiphene Citrate
How to Monitor?
Results of Clomiphene Citrate
Complications
Word of Caution
Predictors of Response to CC
Adjuvant Therapies
Clomiphene Citrate Resistant Polycystic Ovarian Syndrome
Conclusion
Tamoxifen Citrate
Letrozole
Mechanism of Action
Advantages
Doses and Protocols
Important Aspects of A-I
Gonadotropins
Historical Review
Two Cell, Two Gonadotropin Theory
Role of Native FSH and LH
Principles of Gonadotropin Therapy
Indications for Gonadotropin Therapy
Gonadotropin Preparations (Table 11.2)
Different Dose Regimes
How to Use?
GnRH Analogs/GnRH Antagonist
Principle of Action
GnRH Agonist
GnRH Antagonist
Preparations
Different Sonological and Lab Situations
Conclusion
Special Conditions
Polycystic Ovarian Syndrome
Hyperprolactinemia
Hyperprolactinemia and its Effects
Diagnosis
Problems with Hyperprolactinemia
Clinical Situation and Treatment
Drugs Used
Galactorrhea
Hyperprolactinemia without prolactinoma different drugs are used
Prolactinoma
Microadenoma
Macroadenoma
Hypogonadotropic Hypogonadism
Two Types
Management
Poor Responders
Management
Conclusion
Monitoring of Ovulation Induction in Stimulated Cycles
Current Trends
Why to Hyperstimulate and Why to Monitor?
How to Monitor?
Ultrasound Monitoring
Study of Endometrium
Ovulation Trigger
Ovulation to be Confirmed by
Hormonal Monitoring
Traditional Methods
Conclusion
Complications of Ovulation Induction
Ovarian Hyperstimulation Syndrome
Classification
Mild
Moderate
Severe
Critical OHSS
Risk Factors for OHSS
Prevention of OHSS
Treatment
Monitoring of Group 1-2
Monitoring Moderate and Severe OHSS
Conclusion
Multiple Pregnancy
Ovarian Malignancy
Conclusion
CHAPTER 12:
Newer Drugs in Infertility
Introduction
For Induction/Stimulation
Enclomiphene
Anastrozole
Pharmacodynamics
Advantages and Safety
Conclusion
Modulators/Regulators
Myo-inositol
What is Myo-inositol?
How it improves insulin's action?
Effects of Myo-inositol
Improvement of Ovarian Reserve: Dehydroepiandrosterone
Rediscovery of DHEA
How does DHEA works?
How DHEA affect OR?
Results of Various Studies
Conclusion
CHAPTER 13:
Thyroid and Hyperprolactinemia in Infertility
Thyroid Disease and Infertility
Hypothyroidism
Effect of Hypothyroidism on Female Fertility
Management
Thyrotoxicosis
Screening of Baby
Role of Antimicrosomal Antibody Evaluation
Evaluation in Male
Hyperprolactinemia and Infertility
Physiology
Causes of Hyperprolactinemia
Physiological
Drugs
Neurogenic
Pituitary Lesions
Hypothalamic Lesions
Endocrine Disorders
Medical Illness
Ectopic Prolactin Production
Diagnosis
Presentation of the Patient
Treatment (Flow chart 13.1)
Medical Therapy
4: SOME SPECIAL CONDITIONS
CHAPTER 14:
Endometriosis and Infertility
Theories of Disease Development
Prevalence
Prevalence Studies of Subfertility
Diagnosis
Laparoscopic Appearance of Endometriosis
Symptoms and Staging
Endometriosis and Infertility
Surgical Treatment of Early-stage Endometriosis on Fertility
Surgical Treatment of Advanced-stage Endometriosis
Medical Treatment of Endometriosis
Current Therapies
Future Therapies
Endometriosis and Assisted Reproduction
Intrauterine Insemination and Endometriosis
In Vitro Fertilization and Endometriosis
Endometriomas and Infertility
Summary—Key Points
CHAPTER 15:
Luteal Phase Defect in Infertility
Corpus Luteum of Early Pregnancy
Etiology of Luteal Phase Defect
Pathophysiologic Mechanisms
Luteal Support
Progesterone and Progestogens
Natural Progesterone
Micronized Progesterone
Mechanism of Action
Routes of Administration
Intramuscular Natural Progesterone
Pharmacokinetics of Natural Progesterone
Absorption
Vaginal Route
Oral Route
Intramuscular Route
Distribution
Metabolism
Excretion
Dose of Natural Progesterone
First Uterine Pass Effect
Addition of Estradiol to Natural Progesterone
Stimulation of Luteal Functions by Human Chorionic Gonadotropin
Safety
Allylestrenol
17 alpha hydroxyprogesterone caproate
Safety
Luteal Support and IVF
Conclusion
CHAPTER 16:
Controversies and Luteal Phase Defect
Definition
Incidence
Role of Progesterone in a Normal Luteal Phase of Menstrual Cycle
Pathophysiology
Diagnosis of LPD
Clinical
Laboratory Studies
Serum P
Urinary LH
Imaging Studies
Endometrial Biopsy
LPD due to Ovulation Induction Drugs
Clomiphene Citrate
HMG
Bromocriptine
GnRH Therapy (Flow chart 16.1)
Treatment
Dydrogesterone in ART Cycles
Duphastan
Conclusion
CHAPTER 17:
Unexplained Infertility
Incidence
Requirement of Diagnosis
Probable Causes
Male Factors
Female Factors
Important Concerns
Implantation Markers
Treatment
Treatment Plan
Treatment Options
Ovulation Induction
Clomiphene Citrate
Letrozole
Gonadotropins
Ovulation Induction with IUI
Treatment Plan
In vitro Fertilization and ICSI
Conclusion
CHAPTER 18:
Pelvic Inflammatory Disease and Infertility
Introduction
Definition
Etiology
High-risk Factors
Microbiological Etiology
How to Diagnose?
Clinical
Laboratory Diagnosis
Diagnosis by Other Specific Tests
Management
Outpatient Regimen A
Outpatient Regimen B
Parenteral Therapy
Indications
Parenteral Regimen A
Parenteral Regimen B
After Parenteral Regimen A
After Parenteral Regimen B
CHAPTER 19:
Fibroids and Infertility
Etiology and Risk Factors
Important Concerns
How Fibroids Cause Infertility?
When to Start the Treatment?
Strategy
Treatment Options
Surgical
Myomectomy
Medical Therapy
Controversies
Conclusion
CHAPTER 20:
Cervical Factors and Infertility
Functions of Cervix
Two Types of Endocervical Cells
Nonciliated Secretory Cells
Two types of cervical mucus
Ciliated Cells
Cervical Mucus Proteins
Etiology of Cervical Factor Infertility
Evaluation of Cervical Factors
Lab Evaluation
Treatment of Cervical Factor
Conclusion
5: MALE INFERTILITY
CHAPTER 21:
General Evaluation
History for Evaluation of the Infertile Male
Sexual History
Past History
Physical Examination
General Examination
Genital Examination
Basic Laboratory Evaluation
Semen Analysis
Hormonal Evaluation
Clinical Diagnosis Based on Hormonal Status
Classification of Male Infertility on the Basis of Initial Evaluation
Conclusion
CHAPTER 22:
Problems of Male and its Treatment
Classification of Male Infertility on the Basis of Initial Evaluation
Absent or Low Volume Ejaculate
Azoospermia
Oligoasthenospermia
Normal but Infertile
Idiopathic Infertility
Empirical Therapy for Idiopathic Male Infertility
Conclusion
6: IUI AND IVF WHEN AND WHY?
CHAPTER 23:
Let us Learn about IUI
Definition
Rationale
Indications of IUI
Unexplained Infertility
Cervical Factor
Male Factor
Severe Male Factor Infertility
Ejaculatory Failure
Psychological Conditions
Endometriosis
Immunological
Routine Patient Work-up
For Husband
Optional tests
For Wife
Ovarian Stimulation and Ovulation Induction
Ovulatory Patients
Ovarian Induction in Anovulatory Patients
Clomiphene Citrate Therapy
Outcomes
Technical Factors
Characteristic of an Ideal Cannula
Cannulas Available
Semenology and Sperm Preparation
Semen Collection
Sperm Preparation
Direct Swim-up
Pellet and Swim-up
Density Gradient
Isocare-one Step
Factors Influencing Pregnancy Rates with IUI
General Factors
Female Age
Male Age
Number of IUI Cycle
Number of Insemination Per Cycle
Controlled Ovarian Stimulation
Concomitant use of GnRH Agonists with Superovulation and IUI
Pure FSH versus FSH Combination in IUI
Laboratory Factors
Conclusion
CHAPTER 24:
ART and Various Options
Types of ART
Selection of the Patient for IVF-ET
ART Lab Set-up
OPD
ART Lab-Embryology Lab
Location
List of Instruments
Semen Collection Room
Power Back-up
ART Team
Economics
Basic Steps in IVF
Journey from Mother to Lab
Ovarian Stimulation
Ovum Pick-up
Equipment
Procedure
Precautions
Journey from Laboratory to Mother
Intracytoplasmic Sperm Injection
ICSI requirements
Embryo Transfer
Equipment
Procedure
Important Concerns
Other ART Options
Oocyte Donation
Indications
Donor
Success
Embryo Donation
Surrogate Mother
Cryopreservation
Cryopreservation can be
Preimplantation Genetic Diagnosis
Assisted Hatching
Method of Assisted Hatching
Blastocyst Culture
Advantages
Conclusion
7: IMPORTANT PRACTICAL HINTS
CHAPTER 25:
Important Practical Hints
Start Evaluation with the Couple Oriented Approach
Go Step-by-Step
Approach to the Diagnosis with Minimal Investigations
Treatment Plan Should be Given to the Couple and to be Applied from Next Cycle
Ultrasound, Laparoscopy and Hysteroscopy
Consideration of the Patient with Age, Anxiety for the Baby
Various Clinical Situations
Conclusion
INDEX
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