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Infertility and Assisted Reproduction
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Book description

Assisted reproductive technology (ART) is available to two-thirds of the world's population, and world-class experts, representing research from 18 different countries, have contributed to this groundbreaking textbook, detailing the techniques and philosophies behind medical procedures of infertility and assisted reproduction. This is one of the most rapidly changing and hotly debated fields in medicine. Different countries have different restrictions on the research techniques that can be applied to this field, and, therefore, experts from around the world bring varied and unique authorities to different subjects in reproductive technology. Encompassing the latest research into the physiology of reproduction, infertility evaluation and treatment, and assisted reproduction, it concludes with perspectives on the ethical dilemmas faced by clinicians and professionals. This book will be the definitive resource for those working in the areas of reproductive medicine world wide.

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'The future [of medicine] is always difficult, but the authors have made a nice summary of the latest trends and certainly good suggestions to where we are presently moving toward.'

Source: Acta Obstetricia et Gynecologica Scandinavica

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Contents


Page 1 of 3


  • 1 - Folliculogenesis: From Preantral Follicles to Corpus Luteum Regression
    pp 3-9
  • View abstract

    Summary

    This chapter reports a variety of factors involved in the different stages of follicular development. Elucidation of the mechanisms that regulate follicular development may lead to the prevention of female reproductive disorders or other pathological conditions and to the development of new culture methods for oocytes for in vitro fertilization. Follicle-stimulating hormone (FSH) is considered to be the fundamental driver of folliculogenesis. Gonadotropins are even used in controlled ovarian stimulation (COS), which is an important component of assisted reproduction technology (ART). The main hormone product of the Corpus Luteum (CL) is progesterone, which induces the necessary endometrial modifications required for the acquisition of a receptive state, an anticipation of embryo implantation. If pregnancy does occur, regression must be inhibited since the CL is the main source of steroidogenesis, supporting the establishment and maintenance of a successful pregnancy.
  • 2 - Mechanisms of Follicular Development: The Role of Gonadotrophins
    pp 10-24
  • View abstract

    Summary

    Folliculogenesis in women is a dynamic and uninterrupted process from fetal life until menopause. During follicle growth, the oocyte undergoes functional changes in order to become fertilizable at ovulation. However, various factors derived from the oocyte seem to play a crucial role for preantral follicle development. The growth of large antral follicles is depended on gonadotrophins. These hormones are obligatory for follicle maturation during the follicular phase of the cycle. Although follicle stimulating hormone (FSH) is important for follicle growth, steroidogenesis in the early follicular phase is the result of the cooperation of FSH and luteinizing hormone (LH) in the context of the two-cell two-gonadotrophin theory. The dual action of LH might have a potential application in IVF programs to control the number of follicles that develop during the exogenous administration of FSH, particularly in patients prone to excessive response of the ovaries, such as in polycystic ovary syndrome.
  • 3 - Human Follicle Culture In Vitro
    pp 25-37
  • View abstract

    Summary

    This chapter focuses on human follicle culture and briefly describes follicle culture in some of the animal models that were inspiring for progress in humans. Several culture media used to grow human follicles in vitro have been supplemented with the growth factors to assess their potential physiological significance in regulating the earliest stages of follicular development in human. The ovarian cortical tissue is mainly populated with primordial follicles. In vitro follicle culture involved the use of isolated early-stage follicles. There are two approaches to the isolation of follicles: mechanical (microdissection) and enzymatic (use of enzyme). Basically, three major approaches in follicle culture techniques can be distinguished: culture of ovarian cortical tissue (humans and larger animals), culture of entire ovaries (rodents), and culture of isolated follicles (humans, larger animals, and rodents). Several histomorphometric methods are used to investigate follicular development in vitro.
  • 4 - Endometrial Receptivity
    pp 38-45
  • View abstract

    Summary

    Endometrial receptivity to embryo implantation has been an enduring bottleneck of the reproductive system in humans. The advent of in vitro fertilization (IVF) opened the possibility to revert to donated oocytes for cases of infertility linked to premature ovarian failure (POF). For being effective, however, donor egg IVF required that the endometrium was rendered receptive with the sole use of the exogenous hormones E2 and progesterone. It is likely that part of the benefit of luteal support with exogenous progesterone is mediated by an effect on the myometrium. The luteal phase is characterized by a state of uterine quiescence that is brought by progesterone secreted by the corpus luteum after ovulation. The impact of uterine contractility on IVF outcome stresses the role of precautions that need to accompany ET in an attempt to minimize the impact the measures themselves have on uterine contractions (UC).
  • 5 - Molecular Mechanisms of Implantation
    pp 46-52
  • View abstract

    Summary

    This chapter summarizes the information concerning the systems implicated in the regulation of implantation and endometrial receptivity in humans. If focuses on the chemokine system and the comparison of two similar processes, human implantation and leukocyte transendothelial migration. The chapter presents new strategies based on array technology that aim to clarify the fragmented information existing in the field. Clues about the relevance of the chemokines in the process of implantation come from the chemokine interferon inducible protein 10 kDa (IP-10). IP-10 has been involved in the regulation of blastocyst migration, apposition, and initial adhesion in ruminants. The ultimate goal of DNA microarrays technology is to establish a standard for recording and reporting microarray-based gene expression data, which will in turn facilitate the establishment of databases and public repositories and enable the development of data analysis tools.
  • 6 - Evaluation of the Infertile Female
    pp 55-69
  • View abstract

    Summary

    Female fertility begins to decline many years before menopause, despite continued regular ovulatory cycles. Decreased fecundity with increasing female age has long been recognized in demographic and epidemiological studies. Traditionally, the evaluation of the infertile female consists of: (i) ovulation assessment (ovulatory factors), (ii) evaluation of the uterine morphology (ovulation assessment) and tubal patency (tubal factors), (iii) assessment of the presence of pelvic pathology (by laparoscopy) (peritoneal factors), and (iv) postcoital test (cervical factors). Hysterosalpingography (HSG), laparoscopy are widely used in assessing infertility. Chlamydia antibody testing is a screening method for assessing tubal infertility. HSG, sonohysterography, hystero-salpingo contrast sonography (HyCoSy), magnetic resonance imaging (MRI) and hysteroscopy are used in assessment of uterine factors related to infertility. Currently, the best method to monitor ovulation is transvaginal ultrasound, which can be used to demonstrate the growth of a dominant follicle and provide presumptive evidence of ovulation and leutinization.
  • 7 - Fertiloscopy
    pp 70-75
  • View abstract

    Summary

    Fertiloscopy is performed as an ambulatory technique. There are five steps in this procedure: hydropelviscopy, dye test, salpingoscopy, microsalpingoscopy, and hysteroscopy. One of the prerequisite of operative fertiloscopy was to be as effective as the same procedure practiced during laparoscopy. Compared to laparoscopy, fertiloscopy has also some advantages like the facility to perform salpingoscopy and microsalpingoscopy. Fertiloscopy was first designed to avoid diagnostic laparoscopy. Operative possibilities were developed later. The complication rate is low, almost always avoidable if contraindications are strictly respected. Endometriosis may also be treated by operative fertiloscopy, when minimal or moderate. If the lesions are extensive or severe, then laparoscopy has to be the preferred option. Some techniques like fertiloscopic ovarian drilling in polycystic ovarian syndrome (PCOS) patients have already demonstrated its interest in the pregnancy rate obtained without the risks of ovarian hyperstimulation syndrome (OHSS).
  • 8 - Microlaparoscopy
    pp 76-81
  • View abstract

    Summary

    Microlaparoscopy offers the advantage of carrying out many diagnostic and operative gynecologic procedures in a rapid, minimally invasive approach. Proper patient selection is very important for the success of the procedure. Microlaparoscopy could be performed either with general anesthesia or with local anesthesia under conscious sedation, which is a state of depressed consciousness allowing communication with the patient during the procedure. An umbilical incision is made (a local anesthetic block is done first in a case of conscious sedation) through which the interlocking trocar with the Verres needle is introduced to the abdomen. Most of the patients can leave the office within one hour of the procedure. Microlaparoscopy is currently used for infertility assessment, surgical management of endometriosis, lysis of pelvic adhesions, ovarian drilling, gamete intrafallopian transfer, tubal embryo transfer, hydrosalpinx removal before in vitro fertilization (IVF), and management of ectopic and heterotopic pregnancy.
  • 9 - Pediatric and Adolescent Gynecologic Laparoscopy
    pp 82-90
  • View abstract

    Summary

    This chapter focuses on the use of laparoscopy in treatment and diagnosis of patients with pelvic pain, adnexal masses, and pelvic inflammatory disease (PID). A discussion of incidental appendectomy in these patients will also be presented. The decision to perform incidental appendectomy is based on the premise that the appendix is a vestigial, functionless organ, with the potential only to contribute to pathological change. PID can have devastating consequences to adolescent females. With the advent of in vitro fertilization, surgeons should attempt to perform the most conservative surgery that is safely possible, in order to maintain the option of future childbearing. Diagnosis of endometriosis should not be delayed in adolescents. A delay may not only postpone symptomatic relief but also worsen the patient's future fertility and allow the disease to progress. Laparoscopy, as it applies to the pediatric and adolescent population, is a relative newcomer to the field.
  • 10 - Laparoscopic Tubal Anastomosis
    pp 91-98
  • View abstract

    Summary

    The success rate of tubal anastomosis, measured as the rate of intrauterine gestations after surgery, is generally quite high, especially if there is an appropriate patient selection and evaluation prior to surgery. Laparoscopic technique of tubal anastomosis was developed in 1998 after many years of performing minilaparotomy and traditional microsurgery in several hundred cases. A specially designed, malleable, tubal cannulator is introduced through the cervix and guided to the proximity of the tubal ostia under laparoscopic control. The stent facilitates the performance of the laparoscopic tubal anastomosis tremendously. The laparoscopic approach is essentially identical to that of the open-abdomen technique except for the use of specialized instrumentation to facilitate its performance via laparoscopy. A proper preoperative evaluation of the ovarian reserve and male factor are important determinants as to whether the patient will be best served by having a laparoscopic tubal anastomosis or in vitro fertilization.
  • 11 - Tubal Microsurgery versus Assisted Reproduction
    pp 99-106
  • View abstract

    Summary

    Both patency and normal anatomy of the fallopian tube are essential for reproduction. There are many pathological conditions that affect the fallopian tube and consequently affect human reproduction. During the past 28 years, the introduction of in vitro fertilization helped many infertile couples to achieve successes, despite tubal pathology. Salpingitis isthmica nodosa is now believed to be a proliferative process of the endosalpinx into the myosalpinx, leading to hypertropic process and fibrosis in the wall of the fallopian tube and the isthmus. Tubal sterilization is performed for women who have a disease that contraindicates pregnancy. The fallopian tube could be affected with endometriosis directly or indirectly. Surgical management of endometriosis of the fallopian tube follows the same principles of dealing with endometriosis of the pelvic cavity, and this could be accomplished by the use of CO2 laser or harmonic scalpel or microcautery.
  • 12 - The Future of Operative Laparoscopy for Infertility
    pp 107-114
  • View abstract

    Summary

    Laparoscopy allows for the comprehensive evaluation of the pelvis and uterus including confirmation of tubal patency and evaluation of tubo-ovarian relationships. Laparoscopy represents an effective alternative to artificial reproductive technology (ART) for women with tubal disease/hydrosalpinx, leiomyoma, endometriosis, and/or unexplained infertility. Diagnostic laparoscopy combined with operative endoscopic procedures allow prompt and complete identification of all contributory factors, helping the physician to institute appropriate therapy, and will help ensure higher conception rates over shorter intervals. In the recent era of evidence-based medicine, it is recommended that a multicentric prospective randomized study is needed to prove the efficacy of laparoscopic evaluation in predicting the fertility outcome in patients experiencing infertility. Careful selection of patients based on clinical history as well as physical examination and non-invasive laboratory techniques will identify those patients most likely to benefit from endoscopic examination for their infertility evaluation.
  • 13 - Operative Hysteroscopy for Uterine Septum
    pp 115-131
  • View abstract

    Summary

    This chapter presents a comprehensive review of the reproductive problems that could be associated with uterine septum. The classification of uterine anomalies divides the uterine septum into complete (septate) or partial (subseptate) groups, according to whether the septum approaches the internal os or not, respectively. Although surgery (hysteroscopy, alone or with laparoscopy) constitutes the gold standard for the diagnosis of uterine septum, various imaging tools including hysterosalpingography (HSG), ultrasonography, and magnetic resonance imaging (MRI) have great value in the diagnosis with high level of accuracy. The hysteroscopic approach for surgical resection of uterine septum is a safe and effective approach. While generally it is an operator preference whether to utilize ablative energy, for example, electrical diathermy or laser, or to utilize sharp scissors without energy, the outcome of treatment is comparable as regards complication and reproductive performance after surgery.
  • 14 - Laser in Subfertility
    pp 132-136
  • View abstract

    Summary

    This chapter gives a brief description of the physical principles and the applications of the most commonly used lasers in subfertility surgery. The most common application of laser in subfertility surgery is endometriosis. The role of extensive surgery to treat deeply infiltrating endometriosis is debatable with the exception of endometriomas where excision seems to be superior to ablation regarding spontaneous pregnancy rate. The Nd:YAG laser has been used successfully to treat intrauterine adhesions with encouraging reproductive outcomes. The Nd:YAG laser has been widely used for hysteroscopic myomectomies as one- or two-stage procedure. Interstitial myolysis using a bare optic fiber of KTP, YAG, or diode laser has been reported as resolving symptoms and leaving a uterus capable of child bearing. The KTP or the Nd: YAG is the laser of choice for uterine septums, and the CO2 laser is used for vaginal septums.
  • 15 - Ultrasonography of the Endometrium for Infertility
    pp 137-142
  • View abstract

    Summary

    Ultrasound (US) measurement of the endometrium is now an indispensable part of ovulation induction monitoring and assisted reproductive technologies (ART). This chapter describes the use of US in the evaluation of infertility and monitoring ovulation induction for ART and for relations or artificial insemination. It discusses the critical US values for ovulation induction (OI) and in vitro fertilization (IVF). Endometrial Pattern, endometrial thickness, and endometrial waves are evaluated. On statistical analysis, biochemical pregnancies were significantly related to endometrial thickness and pattern and were unrelated to maternal age or number of previous spontaneous abortions. For optimal pregnancy and birth results, endometrial thickness should be 9 mm or thicker on, at the time of spontaneous luteinizing hormone (LH) surge, or when human chorionic gonadotropin (hCG) is administered, OI cycles for relations or intrauterine insemination (IUI) and when hCG is administered in IVF cycles.
  • 16 - Ultrasonography of the Cervix
    pp 143-151
  • View abstract

    Summary

    With the advancement of ultrasound (US) technology with introduction of 3D technology as well, detailed examination of the uterine cervix, anatomy, and accurate measurements have become possible. Benign gynecologic conditions seen by US in non-pregnant state include nabothian cysts, cervical polyps, fibroids and Mullerian anomalies. The importance of transvaginal US in diagnosing placenta previa lies also in the ability by transvaginal US to determine exact distance of placental edge from internal os, which will consequently determine mode of delivery. US is the main diagnostic tool for cervical pregnancy. Doppler is a very important tool as well, due to its difficult diagnosis, it should be differentiated from the cervical stage of spontaneous abortion and nabothian cyst and cervical choriocarcinoma. The risks of cervical pregnancy are mainly severe hemorrhage, necessitating hysterectomy in many situations, and it usually occurs in nulliparous or low-parity women, adding to the dilemma of management.
  • 17 - Transrectal Ultrasonography in Male Infertility
    pp 152-156
  • View abstract

    Summary

    Transrectal ultrasound (TRUS) evaluates the distal components of the ejaculatory duct system including the ampullae of the vas deferens, the seminal vesicles, ejaculatory ducts, and the prostate. Patients with complete distal ejaculatory obstruction and partial distal obstruction are ideal candidates for TRUS evaluation. The examination can be performed with the patient in the lithotomy, knee-chest, or lateral decubitus position. Lateral decubitus position is the preferred position as this provides easy access for the operator and less discomfort for the patient. On TRUS examination, the seminal vesicles appear as hypoechoic areas with fine septations. Anteroposterior diameter up to 15 mm is considered normal. Importantly, TRUS can reveal the anatomical relationship between ejaculatory channels and calcifications. It can also detect proximal dilatation of the ejaculatory tract, which indirectly implies the presence of a distal obstruction. TRUS can also be used for therapeutic aspiration and reduction in the size of obstructive cysts.
  • 18 - The Basic Semen Analysis: Interpretation and Clinical Application
    pp 157-160
  • View abstract

    Summary

    This chapter establishes fertility/subfertility thresholds for sperm concentration, motility, progressive motility, and sperm morphology using Tygerber strict criteria. It seems as if the sperm morphology threshold of 0-4 percent normal forms indicates a higher risk group for subfertility and fits the in vitro fertilization (IVF) and intrauterine insemination (IUI) data calculated previously. A concentration of below fifteen million per ml and percent motility below 30 percent also reflect parameters in the subfertile range. Swim-up and sperm functional tests must be encouraged to assist clinicians in the day-to-day handling of male factor infertility and be of immense help to make a good decision on a specific male problem. It is estimated that intracytoplasmic sperm injection (ICSI) should be indicated when male infertility is properly diagnosed based upon a state-of the- art extended evaluation of the male partner and also in cases with previous failed fertilization.
  • 19 - Evaluation of Sperm Damage: Beyond the WHO Criteria
    pp 161-177
  • View abstract

    Summary

    This chapter reviews the clinical significance of sperm chromatin abnormalities, oxidative stress (OS), apoptosis, and microwave hazards for male gametes highlighting the laboratory methods available to assess these aspects of sperm structure and function. DNA fragmentation is particularly frequent in the ejaculates of subfertile men. Assays for detection of sperm nuclear DNA damage can be divided into three groups: sperm chromatin structural probes, tests for direct assessment of sperm DNA fragmentation, and sperm nuclear matrix assays. To accurately quantify OS, levels of reactive oxygen species (ROS) and antioxidants should be measured in fresh samples. Direct methods such as pulse radiolysis and electron-spin resonance spectroscopy have been useful for other systems of the body. Magnetic-activated cell sorting (MACS) using annexin V-conjugated super paramagnetic microbeads can effectively separate non-apoptotic spermatozoa from those with deteriorated plasma membranes based on the externalization of Phosphatidylserine (PS).
  • 20 - Male Factor Infertility: State of the ART
    pp 178-186
  • View abstract

    Summary

    Rational treatment of the infertile male requires a correct and complete etiological diagnosis. Varicocele develops during puberty, and it is the most common cause of male infertility with prevalence varying between 30 and 60 percent. Thermography, endovascular treatment, and transcatheter embolization are treatment options for varicocele patients. Male accessory gland infection (MAGI) may result from infestation by sexually transmitted pathogens. The prevalence of immunological infertility is related to that of the diseases initiating the antibody formation, but it is no more than 5 percent in our population. Idiopathic sperm deficiency probably results from the combination of unfavorable external and lifestyle factors which includes conditions like idiopathic oligozoospermia, asthenozoospermia, or teratozoospermia. Intrauterine insemination (IUI) is an effective mode of treatment but if IUI remains unsuccessful after a maximum of four cycles, intracytoplasmic sperm injection (ICSI) should be recommended.
  • 21 - Diagnosis and Treatment of Male Ejaculatory Dysfunction
    pp 187-192
  • View abstract

    Summary

    Encompassing a broad spectrum of conditions, ejaculatory dysfunction (EjD) includes premature ejaculation (PE), anejaculation(AE), and retrograde ejaculation (RE). This chapter discusses the incidence rate, diagnosis methods and treatment options available for treating EjD. Behavioral/psychological treatments, topical anesthetic agents, serotonin reuptake inhibitors (SSRIS) and phosphodiesterase (PDE)-5 inhibitors are the treatment options available for PE. Penile vibratory stimulation, electroejaculation, and surgical sperm extraction from the epididymis or testes are all successful methods for obtaining sperm for later use with ART in AE where the success rates of other methods are low. Common causes of RE can be categorized as anatomic, neurogenic, pharmacological, or idiopathic in origin. Anticholinergics, alpha-adrenergic agonists, or similar combinations may be used to modulate bladder neck activity but are not as effective as imipramine, which should be considered the first-line therapeutic agent for RE.
  • 22 - Ovulation Induction
    pp 193-201
  • View abstract

    Summary

    Efforts to improve treatment outcome of ovulation induction are increasingly focused on patient characteristics instead of treatment characteristics. Fertility treatment for hypogonadotropic anovulation may consist of a pulsatile gonadotropin-releasing hormone (GnRH) pump or direct stimulation of the ovaries with exogenous gonadotropins (FSH and LH). Although the classical treatment sequence for normogonadotropic anovulation (WHO2) is clomiphene citrate followed by FSH, a number of new interventions are proven to be useful for these patients. Patients presenting with oligo- or amenorrhea due to hyperprolactinemia may be effectively treated with dopamine agonists. Antiestrogens are first-line treatment options in normogonadotropic anovulation. The major complication of ovulation induction is development of multiple follicles resulting in increased chances of multiple pregnancy and ovarian hyperstimulation syndrome (OHSS). New compounds or strategies such as insulin sensitizers, aromatase inhibitors, and laparoscopic ovarian electrocautery (LEO) should be compared to traditional compounds in patient subgroups with various characteristics.

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