In 2010, Robert Edwards received the Nobel Prize for Physiology or Medicine, 32 years after the first “test tube baby” was delivered in the United Kingdom in 1978 by his obstetrical colleague Patrick Steptoe (1). Since this time the number of babies born as a result of artificial reproductive techniques has been exponential; the US Centers for Disease Control (CDC) estimates that assisted reproductive technology (ART) now accounts for slightly more than 1% of total US births (2) and 12% of women of childbearing age in the United States have used an infertility clinic.

There are many definitions for assisted reproductive techniques or technologies. The CDC was required to define ART by the Fertility Clinic Success Rate and Certification Act of 1992 and defined ART to include “all fertility treatments in which both the egg and sperm are handled.” In general, it involves surgically removing eggs from a woman’s ovaries, combining them with sperm in a laboratory and returning them to the woman’s body or donating them to another woman (2). It does not include techniques where only the sperm is handled, that is, intrauterine or artificial insemination, or when the woman only uses drugs to stimulate egg production without intending to have the eggs removed, or techniques such as timed intercourse. The term in vitro fertilization (IVF) is commonly used but actually refers to only one technique of ART—the various techniques are described later in the chapter. ART is further categorized by whether the procedure uses the woman’s own eggs (non-donor) or eggs from another woman (donor) and whether the embryos used were newly fertilized (fresh) or, previously fertilized, frozen, and then thawed (frozen).

In the year 2007, there were 142,435 ART cycles performed at 430 clinics in the United States, resulting in 43,412 live births and 57,569 infants (56% singleton and 26% multiple infant births). Sixteen percent of these cycles used frozen embryos, the percentage of live births from frozen embryos is usually smaller than from fresh embryos (29.9% vs. 35.9%) because some embryos do not survive the freezing process; however, it is important to understand that transfer of frozen embryos are less expensive and invasive than fresh embryo transfers as the woman does not need to undergo ovarian stimulation therapy and oocyte retrieval (2) (Figs. 48-1, 48-2).

Reasons for using ART are varied. In 2007, infertility diagnoses for woman using fresh oocytes or embryos included male factors such as low sperm count or function representing 18.5% of cases, followed by diminished ovarian reserve in 10.3%, tubal factors in 9%, ovulatory dysfunction in 6.6%, and endometriosis in 4.7% of cases (2) (Fig. 48-3). Ethnic background does not seem to affect pregnancy outcomes or the type of ART, except that African Americans are more likely to have a tubal factor causing infertility than Caucasian women (3).

Delayed childbearing is occurring with increasing frequency and maternal age is the most important factor determining ART outcome (2). Advancing maternal age is associated with a decreased response to ovarian stimulation, lower retrieved oocyte numbers, and lower rates of fertilization and embryo cleavage (4). Increasing numbers of older women are presenting to ART clinics with infertility primarily due to reduced ovarian reserve; in 2007, 61% of women using ART were over the age of 35 years, and 20% were over the age of 41 years, making the average age for all women using ART being 36 years (Fig. 48-4). The vast majority of women younger than 35 years of age used their own eggs (96%), whereas 75% of women older than 44 years of age used donor eggs. Forty percent of cycles amongst women younger than 35 years of age resulted in live births compared to 5% in women aged 43 to 44 years, and 2% among women older than 44 years (2) (Fig. 48-5). In addition to these fertility considerations, the aging mother with potential comorbidities may present greater challenges for care by the anesthesiologist.

The human ovary normally produces one dominant follicle on every menstrual cycle, which has one mature egg inside it. Most forms of ART involve producing multiple eggs by artificially stimulating the ovary to produce multiple follicles (5). The ART cycle begins with downregulation of the pituitary gland and ovaries using a gonadotrophin-releasing hormone (GnRH) agonist or antagonist given subcutaneously for approximately 2 weeks, the intent of which is to shut down the ovaries and prevent the development of the single dominant follicle. After 2 weeks, the ovaries are then stimulated, by either a mixture of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or FSH alone; these drugs are given subcutaneously or intramuscularly for about 10 days. Follicular maturation is monitored every 2 to 3 days by ultrasound and blood tests. When there are approximately four to eight follicles human chorionic gonadotrophin (hCG) is given.
hCG acts as a surrogate for the normal mid-cycle surge of LH that causes resumption of meiosis within the oocytes and preparation for fertilization. Ovulation predictably occurs 36 to 40 hours after hCG administration and retrieval is timed within this period (typically 32 to 34 hours following hCG). Delayed retrieval is inadvisable as spontaneous ovulation may occur leading to reduced numbers of mature oocytes or, more seriously, can lead to ovarian hyperstimulation syndrome (OHSS). The oocytes can be retrieved laparoscopically, but presently are more commonly retrieved by transvaginal oocyte retrieval (TVOR), which involves insertion of a specialized transvaginal ultrasound probe with an attached needle into the vagina (Fig. 48-6). The needle is then inserted through the fornix of the vagina into a follicle under ultrasound guidance, and the follicular contents are aspirated. The contents are then washed and examined under a microscope by an embryologist to look for oocytes; typically five to fifteen oocytes are collected during a single procedure. The next steps depend on the particular technique of ART.