Ovarian stimulation protocols vary tremendously and have evolved from fairly simplistic administration of exogenous hormones derived from urinary sources to quite sophisticated blends of gonadotrophin-releasing hormone (GnRH) analogs, recombinant follicle-stimulating hormone (FSH), luteinizing hormone (LH), and other compounds. The common denominator in all ovarian stimulation protocols is that ultrasonography is used to determine their effects on the ovaries of each patient. All the protocols have been designed to override the physiologic mechanism of selection of a single dominant follicle, obviate atresia in the cohort of follicles recruited into the follicular wave, and foster and sustain the development of many follicles to an imminently pre-ovulatory state so that properly matured oocytes may be retrieved for IVF. Ultrasonography is essential in determining the numbers and fates of individual follicles stimulated by exogenous gonadotrophins. Toward this end, the follicular response of each woman to the stimulation protocol and the number of oocytes desired and clinical assessment of the risk of ovarian hyperstimulation will dictate increasing or decreasing daily doses of gonadotrophins. It is important to note that the expected linear relationship between circulating estradiol concentrations and follicular diameter may not exist during ovulation induction. Similarly, we understand that all follicles probably do not contribute equally to the concentrations in the systemic circulation.
In all the ART ovarian stimulation protocols, regardless of their technical complexity, the timing for human chorionic gonadotrophin (hCG) or recombinant LH administration is critical to establish a time for oocyte retrieval which will yield the highest quality of oocytes in the proper stage of development with the highest probability of fertilization. Although transabdominal ultrasonography has been used, transvaginal ultrasonography (TVUS) is the best means that we have to follow the course of follicular growth and development (1,2). With TVUS, we have a rapid, non-invasive, and highly visual approach to following the fates of individual follicles and cohorts of follicles. When we combine our knowledge of natural ovarian physiology with concomitant assessment of circulating estradiol concentrations and oocyte development, we may predict the optimal timing for induction of the final stages of folliculogenesis and oogenesis and oocyte retrieval (3-5). The relationships between follicle size and oocyte maturity remain not particularly well elucidated; however, the oocyte maturity certainly plays a role in the ability of the resulting embryos to develop to the blastocyst stage (6-8).
hCG is usually administered to trigger the final phases of follicular maturation when the largest follicle first attains a predetermined diameter (e.g., 18-20 mm). The time of hCG administrations varies in many programs based upon the individual clinician's feel for the stimulation cycle and laboratory logistics. Most commonly, 5000 or 10,000 IU hCG is administered. Oocyte retrieval for IVF is then typically scheduled for 30-34 hr thereafter. Many programs use only ultrasonographic monitoring to determine the course of ovarian stimulation and it has been demonstrated that including estradiol monitoring during the stimulation protocol seldom changed the timing of hCG administration and did not affect pregnancy rates or the risks of ovarian hyperstimulation syndrome (OHSS) (9).
The characteristics and appropriate sizes of follicles which produce mature oocytes ready for fertilization remain the subject of much controversy and research. Although we know that mature oocytes yield the highest fertilization rates (Fig. 1), through recent developments in the embryo laboratory, we know that in vitro maturation and fertilization are quite viable ideas in ART practice (10,11). The role of ultrasonography in vitro maturation (VM)-IVF protocols will very definitely revolve around the optimal timing of oocyte retrieval for optimal fertilization and cleavage rates (1114). Ovulation has been reported from follicles as small as 14mm and oocytes collected from small follicles may indeed fertilize. In a recent study, oocytes from follicles less than 10 mm in diameter and in vitro maturation were used to increase the number of transferable embryos (15). Through research in animal models, we know that there appears to be a correlation between computer-assisted ultrasound image attributes of follicles and the ability of the oocyte to fertilize; however, similar studies in humans have apparently not yet been completed (16).
Examination of growth rates for individual follicles may be a useful characteristic with which to predict the number of follicles which may develop during ovarian stimulation protocols. This information is equally important when assessing the risks of ovarian hyperstimulation. In the past, follicular growth rates during induced cycles were observed to be faster than those of natural cycles (17). However, a mathematical equation developed to equate follicular growth rate to follicular age was used to conclude that the growth rates of individual follicles in spontaneous cycles were similar to those recruited by human menopausal gonadotrophin therapy (18). Reduced growth rates of follicles in cycles where a pregnancy was established led to the conclusion that growth rate was a more useful characteristic for prediction of ovulation than follicular diameter (19). Follow-up work does not appear to have been done. It will be logistically challenging to combine daily detailed ultrasound measurements of individually mapped follicles with per follicle outcomes from the embryo laboratory and final pregnancy outcomes. However, the rationale that follicular growth rates may be more accurate in predicting the actual maturity of the ova is intriguing. Recent detailed studies on follicular growth have shown that follicles grow at approximately 1.5 mm per day regardless of whether they developed during natural menstrual cycles, oral contraceptive cycles, or during ovarian stimulation (20,21). These data fit well with a new mathematical model developed to predict the ovarian response to superstimulation protocols and based upon daily data on follicular growth rates (22,23). It is evident that new imaging-based studies are required.
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A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.