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.

Human semen is ejaculated into the anterior vagina and, within minutes, spermatozoa enter the cervix by traversing the cervical mucus. Human sperm capacitation is initiated when the male gamete traverses the cervical mucus, with the removal of inhibitory factors from the seminal plasma. Studies performed in several mammalian species have shown that sperm cells that have completed capacitation first bind to the zona pellucida (ZP) and undergo acrosomal exocytosis (AE). Acrosome-reacted spermatozoa penetrate the ZP, reach the perivitelline space, and bind and fuse to the egg plasma membrane. Sperm-ZP binding involves the interaction of ZP components with sperm surface proteins of capacitated cells, known as primary binding. The evaluation of the subfertile male should include a basic semen analysis, followed by bioassays aimed at assessing sperm functional competence. Many of the molecular mechanisms underlying mammalian sperm capacitation, AE, and fusion with the egg modulate somatic cell functions.

Clomiphene revolutionized the management of infertility in 1967 when it was approved for treatment of anovulation due to polycystic ovaries (PCO). The pharmacokinetics and pharmacodynamics of clomiphene explain its characteristic actions. After ovulation induction with clomiphene, serum progesterone and estradiol serum levels are increased during the luteal phase of the cycle in a direct dose-response relationship. Ultrasound of the ovaries should always be performed before initiating clomiphene treatment for the first time to rule out preexisting ovarian neoplasm, endometriomas, and persistent corpus luteum cysts to evaluate the number and size of antral follicles. Progesterone is used to confirm ovulation to determine if the dose of clomiphene is sufficient. Pregnancy rates may be increased in clomiphene cycles by increasing the number of follicles that develop, by improving endometrial conditions and cervical mucus, and by intrauterine insemination (IUI) when numbers of sperm on a postcoital test are low or absent.

This chapter describes the technique of embryo transfer (ET) to evaluate the various modifications proposed in order to maximize the chances of pregnancy, and discusses the different approaches available for managing difficult ETs. Before embarking on an ET, the following factors should be considered: embryo selection, choice of the catheter, performing a trial (mock or dummy) ET, ET medium, ultrasound, flushing the cervical mucus before performing ET. Randomized trials have shown that ultrasound guidance and the use of soft catheters as opposed to firm catheters are associated with higher pregnancy rates. They have also shown that the presence of air in the catheter, its immediate removal, bed rest after ET, sexual intercourse, and the administration of aspirin after ET do not affect the results. Routine use of antibiotics, uterine relaxants, and medication to increase uterine blood flow await further evaluation.

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.