In atresia of large, growing follicles, the degeneration of the mature oocyte is delayed and appears to occur secondary to degenerative changes in the follicular wall (Plate 93, page 874). This delay indicates that once the oocyte has achieved its maturity and competence, it is no longer sensitive to the same stimuli that initiate the atresia in granulosa cells. The follicular changes include the following sequential events:  Initiation of apoptosis within the granulosa cells, indicated by cessation of mitosis and expression of endonucleases and other hydrolytic enzymes within the granulosa cells  Invasion of the granulosa layer by neutrophils and macrophages  Invasion of the granulosa layer by strands of vascularized connective tissue  Sloughing of the granulosa cells into the antrum of the follicle  Hypertrophy of the theca interna cells  Collapse of the follicle as degeneration continues Invasion of connective tissue into the cavity of the follicle
Recent studies indicate that several gene products regulate the process of follicular atresia. One of these products is the
There are several indications for in vitro fertilization (IVF), but the primary one is infertility as a result of surgically un-correctable damage to, or absence of, the uterine tubes. To induce multiple follicle development and maturation, women selected for an IVF procedure undergo controlled hyper-stimulation of the ovaries. Hyperstimulation is achieved by different hormonal therapies using human menopausal go-nadotropins and clomiphene citrate (Serophene), with or without FSH. Mature preovulatory oocytes are collected from the Graafian follicles by either laparoscopic or ultrasound-guided percutaneous aspiration or transvaginal aspiration. Before insemination, the oocytes are preincubated in a specialized medium with serum complements for a time determined by their stage of maturity. The collected semen is placed in a special medium. The oocytes are then added to the medium containing the col-lected semen for fertilization. Twelve to 16 hours later, the oocytes are examined with the differential interference con-trast microscope to determine the presence of female and male pronuclei, the indication of successful fertilization (Fig. F23.2.1a). At this stage, the fertilized oocyte may be frozen for future IVF transfers. Generally, 80% of mature oocytes cultured in vitro are fertilized. At this point, the embryo is transferred to a special growth medium for 24 to 48 hours, where it is allowed to grow to the stage of four to six cells (Fig. F23.2.1b). Several embryos are then trans-ferred into the uterus via the vagina and cervical canal on the third or fourth day after the initial aspiration of the oocyte. Before embryo transfer, the uterus has been pre-pared to receive the embryo by administration of appropri-ate hormones. Embryos are therefore placed into a hormonally prepared uterus under conditions equivalent to those in normal implantation (see page 852). Intensive pro-gesterone treatment is usually begun just after the transfer to mimic the function of the corpus luteum of pregnancy. In recent years, existing treatment protocols have been optimized to such an extent that success rates of pregnancy and delivery with IVF programs have reached greater than 30% per embryo transfer. Further improvements in preg-nancy rates may be achieved by the introduction of new drugs, such as recombinant FSH or gonadotropin-releasing hormone (GnRH) antagonists that provide individualized hormonal treatment. Additionally, the occurrence of multiple pregnancies, which is the main complication of IVF, may be limited by reducing the number of transferred embryos.