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The aim of treatment with a gonadotropin-releasing hormone (GnRH) agonist is elimination of the luteinizing hormone (LH) surge and fluctuating LH concentrations, which compromise outcome in cycles of ovarian stimulation for in-vitro fertilization (IVF). This chapter addresses the characteristics of the standard long-course protocol. It is most common to initiate treatment in the luteal phase to minimize the consequences of the flare effect seen in the first few days of treatment with a GnRH agonist. The down-regulation effect of agonists can be established and maintained by multiple applications of nasal spray, single daily injection, or depo formulations lasting variable lengths of time. When the patient is down-regulated at the start of follicle stimulating hormone (FSH) treatment, subsequent follicular growth and recruitment is dictated by two elements: the ovarian reserve, which dictates the number of follicles available for recruitment, and the profile of circulating FSH concentrations.
This chapter reviews the available literature on the clinical assessment of the endometrium. It focuses on the tools available to diagnose and treat both infertility and pregnancy loss. Infertility and recurrent pregnancy loss are often attributable to implantation failure. The mechanism of implantation varies widely between species, reflecting the evolving conflicts between maternal and embryonic interests. Serum progesterone measurements are a mainstay of hormonal assessment to document ovulation and appear to correlate well with endometrial biopsy results. Doppler flow studies are non-invasive ultrasound methods used to evaluate the blood flow to the uterus and endometrium. Causes of repeat in-vitro fertilization (IVF) failure that are related to endometrial receptivity defects have recently been reviewed. Cost and side effects of treatments will be reduced as clinical assessment of the endometrium yields more information about the causes of infertility or pregnancy loss.
Uterine natural killer cells exert their function by production of high levels of cytokines such as granulocyte-macrophage colony stimulating factor (GM-CSF), colony stimulating factor-1 (CSF-1) and interleukin-2 (IL-2). Recurrent miscarriage (RM) is a stressful condition for both patients and clinicians. As uterine natural killer (uNK) cells share many similar properties with peripheral blood NK cells, their population in the blood has been reported to be associated with RM. Steroids are used as anti-inflammatory agents to try to improve success of implantation, as aside from the immunology of pregnancy, there could be other inflammatory processes in the practice of in-vitro fertilization (IVF) such as stimulation from the intrauterine catheter during embryo transfer. As with RM, immunomodulation therapies have been tried to suppress NK cell activity. A recent meta-analysis of three trials shows that IvIg treatment significantly increases the live-birth rate in patients who fail IVF.
The cervix is the cylindrical portion of the uterus which enters the vagina and lies at right angles to it. It is well documented in the literature that pregnancy following assisted reproductive technologies (ART) has a higher risk of adverse outcomes. A meta-analysis comparing in-vitro fertilization (IVF) with spontaneous conceptions showed that IVF singleton pregnancies had significantly higher odds of perinatal mortality. Cervical funneling is described as dilatation of the internal os so that the cervical canal changes in shape, with bulging of the bag of membranes through the dilated cervix into the cervical canal. Vasa previa is diagnosed by transvaginal or transabdominal ultrasound, and with Doppler flow studies. Cervical pregnancy is a rare ectopic pregnancy defined as implantation of the gestational sac in the endocervix. Due to its difficult diagnosis, cervical pregnancy should be differentiated from the cervical stage of spontaneous abortion, nabothian cyst, and cervical choriocarcinoma.
Three-dimensional (3D) ultrasound technologies are beneficial in some applications of obstetrics and gynecology and may aid in the evaluation of abnormal ovaries. Although the diagnostic criteria of polycystic ovary syndrome (PCOS) do not include 3D imaging, Allemand performed a study establishing the diagnostic threshold for 3D Ultrasonography of PCOS. The administration of gonadotropins for both insemination cycles as well as in-vitro fertilization cycles relies upon the use of serial real-time ultrasound examinations. In clinical practice, TV ultrasound monitoring during controlled ovarian hyperstimulation (COH) is performed to improve safety and precise monitoring of ovarian response to gonadotropin stimulation. PCOS patients have an increased number of preantral follicles; hence, close monitoring for ovarian hyperstimulation syndrome (OHSS) is essential. 3D ultrasound is a new imaging modality that improves the sensitivity and specificity of ultrasound. Recent advances in 3D ultrasound have the potential to better our understanding of follicular development, ovulation, and uterine receptivity.
When clomiphene citrate (CC) is used for ovulation induction, endometrial thickness is often decreased compared with spontaneous cycles during and immediately following the days CC is taken, because of its antiestrogen effect. A triple-line pattern on the day of human chorionic gonadotropin (hCG) administration has been reported to be necessary for implantation in controlled ovarian hyperstimulation (COH) cycles, where human menopausal gonadotropin (hMG) or follicle stimulating hormone (FSH) is administered. A triple-line endometrial pattern on the day of hCG administration in in-vitro fertilization (IVF) cycles is related to serum estradiol level, the number of mature oocytes, and the number of top-quality embryos and is unrelated to serum progesterone levels. Preclinical miscarriage, also referred to as biochemical pregnancy, in which quantitative hCG levels initially indicate pregnancy but decrease before a gestational sac can be seen on ultrasound, and clinical miscarriage of embryos with karyotype is the result of inadequate endometrial development.
During the preclinical development of in-vitro fertilization (IVF) in the human, oocytes were frequently obtained at laparotomies for various indications and the time for the operative procedure was generally not scheduled close to ovulation. The ovaries could now easily be scanned without using the full-bladder technique, and transvaginal ultrasound-guided oocyte retrieval (TVOR) could generally be performed with only use of some sedative in combination with local anesthesia. In order to increase the oocyte recovery rate it was found that Teflon tubing between needle and sampling tube was optimal. Today there are various sampling sets commercially available, including needle, tubing, and sampling tubes. The different complications of TVOR are bleeding and infection. In conclusion, available data regarding possible adverse effects of ultrasonography on oocytes have been interpreted to indicate that the technique, in this respect, is as safe as laparoscopy.
Reproductive endocrinologists use the concept of fecundability in addition to discussing pregnancy rates. Fecundability is a valuable clinical and scientific concept, as it creates the framework for the quantitative analysis of fertility potential. The factor affecting prognosis is the age of the female partner. An important part of the basic infertility evaluation is assessment of fallopian tube patency. A hysterosalpingogram (HSG) is the frequently utilized modality for tubal assessment. Patients who are prepared to enter into in-vitro fertilization (IVF) treatment are encouraged to undergo salpingectomy because of very low pregnancy rates after neosalpingostomy, high rate of recurrent occlusion, risk of ectopic pregnancy, and decreased success rates after IVF when hydrosalpinx is present. Ovarian reserve testing should be offered routinely to women over 35, as well as to those with unexplained infertility to respond to conventional infertility treatment, and to those contemplating assisted reproductive technologies (ART) therapy.
This chapter summarizes normal immune function and its relationship to immunologic infertility. The normal immune system identifies and destroys antigen within the body. The humoral immune system is suited to the destruction of whole, extracellular antigens, including most bacteria, larger parasites, and viruses. Antispermatogenic autoantigens induce autoimmunity to the germinal epithelium, resulting in a specific decline in sperm production due to germ cell destruction. Tail-directed sperm antibodies are more likely to impair motility and cause agglutination, sperm head-directed antibodies may preferentially affect zona binding and fertilization, as suggested by immobilization and penetration assays. Corticosteroids prevent the chemotaxis of inflammatory cells, impede cytokine release, decrease antibody production, and even weaken antigen-antibody association. Intrauterine insemination (IUI) is suited for treatment of infertility when there is evidence of cervical mucus problem, whether it is due to antibodies or not, as demonstrated by the inability of sperm to penetrate the cervical mucus.
Many couples whose infertility treatment requires in-vitro fertilization (IVF) also need intracytoplasmic sperm injection (ICSI) as a part of the procedure. In many respects ICSI has revolutionized infertility treatment as a whole. Both research data and clinical experience have shown that providing a sperm sample during this crucial stage of IVF/ICSI treatment could increase performance anxiety for both fertile and infertile men. The successful use of assisted reproductive technologies over the past 25 years or more has brought with it procedures that allow couples who cannot conceive using their own gametes the alternative of achieving pregnancy through the use of donated oocytes, donated sperm, and even donated embryos. The psychological evaluation is also intended to rule out gross psychopathology and depression, potential substance abuse, as well as a history of current or past family violence or abuse. Marital stability is also assessed within the context of the consultation.
In-vitro fertilization (IVF) has rapidly become a treatment for male factor infertility. Mature oocytes are inseminated in a Petri dish and examined 18 hours later for morphologic proof of fertilization. Gamete intrafallopian transfer (GIFT) is designated for women who have at least one functioning fallopian tube. Micromanipulation procedures progressed because of discouraging results with IVF for the male-factor patient. Although application of acid solutions or enzymes, and mechanical opening of the human zona pellucida have been developed, only partial zona dissection (PZD) has been successful in humans. One of the most significant risks associated with ART is the ovarian hyperstimulation syndrome (OHSS). Preimplantation genetic screening (PGS) for aneuploidies has been performed in patients with advanced maternal age, unexplained recurrent miscarriage, recurrent implantation failure, nonobstructive and obstructive azoospermia (NOA and OA), and severe sperm morphology anomalies.
This chapter discusses current methodology and the advantages and limitations of blastocyst biopsy. The first phase of blastocyst biopsy involves making a hole in the zona pellucida (ZP). The dissection of the ZP may be performed mechanically, by the application of acid Tyrodes solution, or through the use of laser technology. The cryopreservation of biopsied embryos continues to be one of the weak points of preimplantation genetic diagnosis (PGD). The results published by most groups show that embryos with an opening in the ZP are more sensitive to the freezing process, which is reflected in reduced survival and developmental rates among frozen-thawed biopsied embryos. Vitrification as an alternative to classical freezing techniques is adopted as part of numerous in-vitro fertilization (IVF) programs due to its simplicity and, above all, the excellent results obtained not only in oocytes but also in early embryos and blastocysts.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication of ovulation induction, which may cause serious impact on the patient's health, with 0.1-2 percent of the patients developing severe forms of the syndrome. Many substances involved in the regulation of vascular permeability (VP) have been implicated in causing OHSS. The use of low doses of dopamine may be useful in severe OHSS patients. The OHSS primary prevention is to reduce its incidence, being the most important step to identify patients at risk that will undergo in-vitro fertilization (IVF) treatment, using a softer stimulation protocol and giving these patients special attention and close monitoring than usual with frequent ultrasound and serum estradiol levels. Until recently, OHSS treatment was reduced to the management of its complications. New data as the vascular endothelial growth factor (VEGF) system studies are providing new insights for prevention and treatment of OHSS.
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