The confluence of two clinical specialties: genetics and assisted reproductive technologies.(Advanced Practice)

The latter half of the 20th century was a highly proliferative phase in the advancement of knowledge, technology, and clinical application for the fields of human genetics and reproduction. Scientists and clinicians spent many decades prior to the 1950s researching and documenting the incidence and clinical characteristics associated with a genetic disorder, and the human and environmental factors that affected the fecundity rate of women (the ability to conceive, typically expressed as a percent of documented conceptions per menstrual cycle). This knowledge was used to counsel and direct the care of individuals and couples who desired the addition of a child to their family unit. Unfortunately, the information available to clinicians was limited and specific genetic disorders or causes of infertility frequently were not well understood.

The identification and visualization of the structure of DNA in 1952, and the ability to retrieve and fertilize an oocyte (egg) outside the human body in 1978, forever changed the scope of reproductive options available to two very different groups of individuals: (a) those with or at risk for transmission of a genetic disorder, and (b) those experiencing the inability to conceive or give birth to a biologic child (Fasouliotis & Schenker, 1999; Watson & Crick, 1953). By the 1990s, the significant advances in these two clinical specialties intersected. This confluence of knowledge, technology, and clinical application created additional opportunities and alternatives that have simultaneously benefited both groups of individuals seeking to have a healthy child.

Assisted Reproductive Technologies

The first attempts to fertilize mammalian ova began in 1878. One century later and after 15 years of intensive research, Doctors Robert Edwards and Patrick Steptoe successfully accomplished the birth of a healthy child conceived through the process of in vitro fertilization (IVF) and embryo transfer (ET) (Fasouliotis & Schenker, 1999). With this achievement, assisted reproductive technologies (ART) rapidly advanced and provided a range of "high-tech" reproductive alternatives based upon the core technology of IVF (see Table 1). These procedures joined the basic reproductive options of hormonal stimulation, artificial insemination, and surgical repair of reproductive system anomalies to provide a broader scope of choice for individuals or couples experiencing infertility. More than 6.1 million people, or 10% of reproductive-age individuals, are estimated to have experienced involuntary infertility in the year 2002 (America Society for Reproductive Medicine [ASRM], 2003). Basic infertility services may be used to treat the greatest majority (85% to 90%) of infertile males and females, but the remaining 10% to 15% require ART (ASRM, 2003).

Initially, IVF-ET cycles were performed in conjunction with the natural hormonal stimulation of the ovary. The single mature oocyte was retrieved by needle aspiration of the fluid from the follicle (ovarian structure that contains the developing oocyte and nutrient-filled fluid), using laparoscopic visualization to perform the procedure. Timing of the oocyte retrieval in a natural cycle was not precise. The IVF procedure frequently did not result in the successful identification of a mature oocyte. Throughout the 1980s, advances in pharmacologic stimulation of both ovaries to produce multiple mature oocytes, and the refinement of ultrasound-guided needle aspiration of follicles in lieu of laparoscopy, favorably changed the probability that one or more mature oocytes would be retrieved from a woman in a single menstrual cycle.

Until 1991, adoption and artificial insemination with donor sperm were the only reproductive options available to males diagnosed with severe oligospermia or azoospermia (respectively, reduced number or absence of sperm in an ejaculate). ART further advanced with the development and success of intracytoplasmic sperm injection (ICSI) (Palermo, Joris, Devroey, & Van Steirteghem, 1992) and later, fine needle aspiration (FNA) of sperm from the testes (ASRM, 1999). With this technology, a single sperm may be injected directly into the cytoplasm of an oocyte, eliminating the need for the spermatozoa to travel to and penetrate the zona pellucida (outer layer) of the oocyte. That single sperm for the procedure of ICSI may also be obtained from either a semen ejaculate or testicular aspirate. In the same manner that IVF eliminated the need for the oocyte to travel from the ovary down the fallopian tube (site of fertilization) to the uterus (site of embryo implantation), FNA negated the need for spermatozoa to move from the testes through the vas deferens and exit the urethra by the process of ejaculation.

Experience with and refinement of these technologies continue to increase the likelihood that an infertile woman, man, or couple is able to conceive and give birth to a child through the various technologies now available (see Table 2). Every year, ART clinics report programmatic statistics for each individual center using the template established by the Society for Assisted Technology and the Centers for Disease Control in accordance with the Fertility Clinic Success Rate and Certification Act (FCSRCA, Public Law 102-493, October 24, 1992) (Wright, Schieve, Reynolds, & Jeng, 2003). To date, 850,000 ART cycles have been initiated in the United States alone. This has resulted in the birth of over 210,000 children conceived through the process of IVF (ASRM, 2002; Toner, 2002) (see Table 3).

Advances in Genetics…