Kononenko, I. B.
Snegovoi, A. V.
Kovalenko, E. I.
Manzyuk, L. V.
Selchuk, V. Yu.
Importance of evaluation of ovarian function in women with breast cancer when using endocrinotherapy.
This user-friendly, practical guide provides an excellent introduction to good clinical practice in the investigation and treatment of infertility, using the very latest assisted reproductive technologies. There are chapters on clinical assessment of the male and the female, followed by detailed chapters on the full range of clinical procedures that can be put in place to help overcome infertility. In addition, other chapters deal with IVF, GIFT and ZIFT and clinical aspects of PGD, which has an increasingly important role these days. Guidance is given on how to set up and run a successful IVF unit based on the experience of the authors, and for the benefit of those new to the field or responsible for developing an IVF service for their patients. With its clinical focus, this will undoubtedly become an essential introduction to assisted reproduction for doctors, embryologists, and nurses.
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Public awareness of the scientific progress made in the field of assisted conception has led to an increased number of people seeking treatment. The first consultation between an infertile couple and the clinician specializing in infertility is a crucial starting point for collecting the medical history, clinical examination and the evaluation of the appropriateness of a range of investigations to establish the cause of infertility, following which a strategy for treatment can be planned. When the full history has been taken, a clinical examination must be performed. The ovulation is confirmed by measuring progesterone in the mid-luteal phase. Clinical history and assessment of basal follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin can be sufficient for the diagnosis of the majority of causes of anovulation. The evaluation of tubal patency and the uterine cavity is of crucial importance in the preliminary assessment of infertile women.
This chapter deals firstly with the anatomy and physiology of male reproduction, and then gives an account of the aetiology and management of male factor infertility. The male reproductive system consists of the penis, testes, ejaculatory ducts and accessory sex glands. The testis produces the majority (6-7 mg/day) of testosterone, although a small amount is also produced by the adrenal glands. Spermatogenesis and synthesis of testosterone are under control of the anterior pituitary gland. Prior to investigating the infertile male, the clinician must ensure that the female partner has been thoroughly evaluated. The World Health Organization has defined the minimal semen parameters for fertility. These parameters are volume, pH, sperm concentration, total sperm number, motility and morphology. The surgical causes of male infertility include varicocele and cryptorchidism. The infertile male should be managed in a tertiary centre where appropriate facilities exist for microsurgery, assisted conception techniques and cryostorage of sperm.
This chapter discusses sperm analysis by macroscopic inspection and microscopic examination. Spermatozoa are not the only cellular constituents of human semen. Every human semen sample is contaminated with leukocytes. The conventional semen profile consists of an analysis of sperm count, motility and morphology in the unfractionated ejaculate. The introduction of computer-aided sperm analysis (CASA) systems has allowed detailed quantitative analysis of sperm motility to be undertaken that are characterized by high precision. Cervical mucus is undoubtedly one of the most severe barriers that spermatozoa have to traverse on their route to the site of fertilization in vivo. The ability of acrosome-reacted human spermatozoa to fuse with the vitelline membrane of the oocyte can be assessed by the hamster oocyte penetraton assay. Male infertility differs from female infertility because it is fundamentally not an endocrine condition. Most infertile men are normogonadotrophic and possess normal androgen levels.
In the UK, strict adherence to guidelines laid down by the Human Fertilisation and Embryology Authority (HFEA) has made the recruitment of sperm donors an arduous task. In donor insemination, the protection of the recipient and potential offspring from sexually transmitted and other inheritable disorders is paramount. When compared with embryos, the cryopreservation of sperm is usually relatively crude. Density gradient centrifugation (DGC) is almost universally accepted as the superior sperm preparation method for assisted reproductive techniques, donor insemination being no exception. Donor insemination provides an excellent research model. Several authors have used the system to examine the influence of semen parameters and sperm function testing on success rates. Donor insemination also provides an excellent tool to examine other factors governing success, for example, timing of inseminations and subtle female factors as the male gametes are of reasonably standardized quality.
The treatment options that face a couple prior to in vitro fertilisation (IVF) depend upon the cause of their infertility. To clarify the definition of male factor subfertility to produce a pragmatic approach to treatment, Van Voorhis published a study that correlates the effect of the total motile sperm count with the outcome of assisted reproduction. A diagnosis of unexplained infertility cannot be made without a laparoscopy to exclude the presence of pelvic adhesions or endometriosis. There is evidence that in couples with otherwise unexplained infertility, the fecundity of women with minimal and mild endometriosis is improved by laparoscopic ablation of the endometriotic deposits. The commonest cause of anovulatory infertility is polycystic ovarian syndrome (PCOS). Unexplained infertility is reported to occur in up to 60% of couples. The simplest, least invasive and cheapest regime for superovulation and intrauterine insemination (IUI) is the use of clomiphene citrate.
The primary aim of an in vitro fertilisation (IVF) treatment cycle is the creation of two 'good quality' pre-embryos for transfer, with a secondary aim of additional embryos for cryopreservation. The use of gonadotrophin releasing hormone (GnRH) agonists with gonadotrophins has resulted in greater ease of planning the superovulation stimulation. The move towards pituitary desensitization with a GnRH agonist has become almost universal in assisted conception clinics. The GnRH agonist is commenced in either the mid-luteal or follicular phase of the cycle and continued through to the day of human chorionic gonadotrophins (HCG). Modifications of the GnRH decapeptide have enabled the development of competitive inhibitors of gonadotrophin secretion. Clinical evidence followed in therapeutic trials for IVF suggests that recombinant-follicle stimulating hormone (FSH) yields more oocytes and embryos. Particular consideration needs to be given to superovulation when polycystic ovaries are present.
Tim J. Child, Women's Centre, John Radcliffe Hospital, Oxford, UK,
Imran R. Pirwany, McGill Reproductive Centre, Royal Victoria Hospital, Montreal, Quebec, Canada,
Seang Lin Tan, McGill Reproductive Centre, Royal Victoria Hospital, Montreal, Quebec, Canada
When an appropriate follicular response to gonadotrophin stimulation has been achieved, the patient receives a subcutaneous injection of 5000 or 10000 iu of human chorionic gonadotrophin (HCG) to commence the final stage of oocyte maturation. Many women require more than one in vitro fertilisation (IVF) cycle and oocyte retrieval can be a painful procedure. Therefore, adequate sedation and analgesia is important for oocyte retrieval. The vacuum pressure for follicular aspiration should be less than 150 mmHg, since at pressures above this the rate of oocyte injury increases. Randomized controlled trials demonstrate that follicular flushing after aspiration does not significantly increase the number of oocytes retrieved or the pregnancy rate. During oocyte retrieval the aspiration needle should avoid endometriomas. This chapter discusses risks of oocyte retrieval, immature oocyte recovery and embryo transfer with embryo transfer procedures applicable in special circumstances.
Ovarian hyperstimulation syndrome (OHSS) is characterized by ovarian enlargement and a shift of fluid from the intravascular to the extravascular space. OHSS is classified into mild OHSS, moderate OHSS, and severe OHSS. Vascular endothelial growth factor is a powerful mediator of vessel permeability. Angiogenin may play a role in neovascularization leading to the development of OHSS. The different complications of OHSS are vascular complications, liver dysfunction, renal complications, respiratory complications, and gastrointestinal complications. Current management of OHSS relies on the prediction and active prevention. Any patient undergoing ovarian stimulation is at risk of OHSS but it appears to be more frequent in younger women (aged less than 35 years) and women with polycystic ovarian syndrome (PCOS). This chapter discusses oestradiol monitoring of ovulation, ultrasonographic monitoring of OHSS, and prevention and treatment of OHS that includes basic treatment and surgical treatment.
The different forms of early pregnancy loss (EPL) are: threatened miscarriage, inevitable miscarriage, missed miscarriage and recurrent miscarriage. Gestational trophoblastic disease (GTD) is a term commonly applied to a spectrum of interrelated diseases originating from the placental trophoblast. The main categories of GTD are complete hydatidiform mole, partial hydatidiform mole and choriocarcinoma. Studies have described the outcome of assisted reproductive technology (ART) pregnancies following prenatal diagnosis but there appear to be no cytogenetic data regarding pregnancy loss before 11 weeks of gestation. Molar pregnancies may be complete (diploid and androgenetic usually arising from fertilization by a haploid sperm which doubles its chromosomes and takes over the ovum) or partial (triploid and predominantly genetically male). Progesterone and human chorionic gonadotrophin (HCG) have been used in the diagnosis, management and treatment of abnormal early pregnancy. This chapter discusses management of multiple gestation pregnancy (MGP) after ART, and multifetal pregnancy reduction (MFPR).
To women traditionally considered irreversibly sterile due to ovarian failure, oocyte donation and exogenous steroid replacement offers the prospect of achieving a successful pregnancy. Women requiring oocyte donation comprise two main groups: women with primary or secondary ovarian failure, and women with normal menstrual cycles. There will always be an imbalance between supply of and demand for donated oocytes due to ethical considerations. Women of ethnic origin groups must be screened for haemoglobin electrophoresis, sickle cell and Tay-Sachs disease. Adequate and sustained steroid hormone secretion by the corpus luteum of the ovulatory cycle is required for establishing and maintaining pregnancy in humans for the first seven to nine weeks. This chapter discusses oestrogen replacement, progesterone replacement, replacement protocols, oocyte donation in menstrually cyclic recipients, and implantation window. As average life expectancy and quality of life increase, pregnancy from oocyte donation to post-menopausal women becomes more possible.
The major indications for treatment by in vitro fertilization (IVF)-surrogacy are congenital absence of the uterus and previous hysterectomy for haemorrhage or malignancies. The genetic couple is seen in consultation so that a full history can be taken and a full examination carried out. A surrogate host may be a relative of the genetic couple or a close friend. Counselling and appropriate legal advice is essential to all parties of a surrogacy arrangement. Usually, the genetic mother undergoes an (IVF) cycle with a standard follicular stimulation regimen and oocyte collection. After the process of examination, counselling and Ethics Committee approval, the surrogate host is reviewed and her treatment cycle arranged. To date, relatively few reports of large series of IVF-surrogacy treatments have been published. The major complications arising out of treatment by IVF-surrogacy have involved legal issues, the custody of the resulting child being the main example.
Couples referred for preimplantation genetic diagnosis (PGD) are known to be at genetic risk due to an affected family member or the birth of an affected child. PGD involves three stages: IVF, embryo biopsy and single cell diagnosis. Polymerase chain reaction (PCR) is used for the diagnosis of single gene defects such as cystic fibrosis, screening of specific diagnosis of X-linked diseases and the triplet repeats disorders such as myotonic dystrophy. For PGD patients, especially those carrying fragile X syndrome, a test of ovarian reserve is recommended. The embryo biopsies discussed in this chapter are: polar body biopsy, cleavage stage biopsy, blastocyst biopsy. The chapter lists out single gene disorders for which successful PGD protocols have been reported. Fluorescent in situ hybridization (FISH) determines the number of copies of a particular chromosome or region of a chromosome when it is difficult or impossible to obtain good quality metaphase preparations.
Fibroids are a frequent finding in women with infertility. Gonadotrophin releasing hormone agonists (GnRH-agonist) will cause both uterine and fibroid shrinkage and a reduction or elimination of menstrual flow. Uterine artery embolization offers an alternative method of treatment that allows conservation of the uterus. Under local anaesthesia and sedation, an 18-gauge needle can deliver heat to a fibroid with localized ablation of a fibroid. Hysteroscopic myomectomy may be considered for women with submucous fibroids less than 3 cm. Uterine septum is the most common congenital abnormality of the female reproductive tract with an incidence of 2-3% in the general population. This chapter discusses hydrosalpinx, endometriosis and ovulation induction, endometriosis and intrauterine insemination, endometriosis and in vitro fertilization, and management of ovarian cyst. It also explains elevated follicle stimulating hormone (FSH), thin endometrium, assisted reproductive techniques, and embryo transfer.
Gamete intrafallopian transfer (GIFT) involves a direct transfer of human gametes, sperm and oocytes into the fallopian tubes. Zygote intra-fallopian transfer (ZIFT) involves the transfer of embryos at the pronucleus stage into the fallopian tubes. In in vitro fertilization (IVF), the four- to eight-cell embryo is transferred 48-72 hours after oocyte collection and thus reaches the uterine cavity some two to three days earlier than would occur in a natural cycle. Centres offer comprehensive assisted conception, including IVF, GIFT and ZIFT. IVF-embryo transfer has become acceptable, with improvements in vaginal ultrasound, oocyte retrieval techniques and ambulant care with local sedation and analgesia. In women aged above 40 years, a flexible number of oocytes transferred during GIFT maximizes the chance of achieving singleton pregnancy. ZIFT is indicated for couples who have had repeatedly failed IVF cycles. GIFT/ZIFT is considered for patients who have cervical stenosis or in utero exposure to diethylstilbestrol.
Counselling is undertaken by psychological therapists to enable people to identify the source of their distress, to explore ways of coping more effectively, to implement change, and the tolerance of change, in their lives. The three types of counselling specified in the Human Fertilisation and Embryology (HFEA) code of practice are implication counselling, support counselling and therapeutic counselling. The offer of the opportunity to use a counselling service should be clearly endorsed by all clinic staff as an integral part of client care. Counselling takes place when there is a 'therapeutic alliance' between the counsellor and the client. The assisted reproductive technology (ART) unit is the last stop for many men and women in their quest for a child. Constantly dealing with heightened emotions can take its toll and working with distressed clients for whom failure may be more likely than success is bound to cause stress and anxiety.
Many of the nurses are expanding their role to meet the changing needs of assisted conception treatment, but it is important that nursing in this field continues to develop within guidelines for safe clinical practice. The factors influencing the role of the nurse in assisted reproduction are: size of clinic, services offered, previous experience, staffing levels, and geographical factors. The role of the nurse in assisted conception is really that of treatment program coordinator and as such the nurse plays an important role within a multidisciplinary team. Nurses working in assisted conception must clearly understand the emotional aspects of infertility. The nurse has a comprehensive role to play by using his/her interpersonal and counselling skills, but it is essential that the nurse understands his/her limitations and when it is appropriate to refer to a professional counsellor. High expectations from professionals and patients can lead to additional pressure on nurses.
In setting up a new in vitro fertilization (IVF) unit it is necessary to convince others that there is an economical need for one to be established. The two methods for procedure costing for the IVF unit are top-down approach and bottom-up approach. The calculation of likely activity is based on a number of factors that include market research, existing waiting lists, referral base, currently available service in the area and their activity. Assisted conception services fall into three categories: wholly private and independent; state funded units; and part academic-part patient funded units. This chapter describes the clinical and laboratory set-up requirements including quality control, laboratory set-up, entry restriction, air-filtration, laboratory lighting, safety and security, and generator back-up for an IVF unit. The IVF chamber is a controlled environmental chamber which is mobile and is specifically designed to maintain ideal temperature and pH during the handling of gametes and embryos.
The ideal information technology solution is a totally integrated system, encompassing all areas of the daily clinical and administrative work routine. The ideal software integrates all aspects of the processing of information. Where patients are registered through a central hospital system, interaction with existing hospital systems is sometimes appropriate, and seamless interfacing between the clinic software and the hospital system should be achieved. This chapter describes a scenario that gives an overview of the possible application of information technology in an assisted conception unit. It lists the advantages of a computerized system over a paper-based system. Due to the lack of commercially available software in the past, a number of clinics have resorted to creating their own software package. Taking an integrated approach to the installation and implementation of the computer system ensures that maximum advantage is gained.
Fertility is markedly compromised several years before the menopause, suggesting that factors other than complete depletion of the follicular store play a role in the loss of oocyte competency in ageing women. The reduced reproductive potential of older women is related to the functional and structural qualities of the oocytes. Older women are more likely to be affected by a number of pathologies that can reduce their fertility potential. Increasing maternal age is also associated with an increase in ovulatory dysfunction. Reduction in uterine receptivity as a possible contributing factor to the decline in fertility with age has been difficult to ascertain. Fibroids that distort the uterine cavity can reduce the chances of successful implantation. This chapter discusses various assisted reproductive technologies, namely, in vitro fertilization (IVF)/gamete intrafallopian transfer (GIFT), ovarian stimulation for IVF/GIFT, donor insemination, oocyte donation, assisted embryo hatching, blastocyst transfer and preimplantation genetic diagnosis (PGD) of aneuploidies.
This chapter discusses the issues in gamete donation including payment or compensation to donors, and anonymity and secrecy in gamete donation. The interests of children and parents seem to coincide as several studies have already shown that children conceived by 'assisted reproduction' fare very well in the measured personal and social criteria. The two main ethical principles of preimplantation genetic diagnosis (PGD) are: increasing the welfare of the future child by avoiding a known potential harm; and enabling the autonomy of the potential parents to choose a technique with which they feel more comfortable. PGD/human leukocyte antigen (HLA) typing is a recent development in PGD and concerns an existing child affected by a terminal disease whose parents request HLA typing of embryos for replacement. PGD is not the only method for sex selection but is more reliable than the more innocuous sperm sorting.