Human Fertility

Assisted human reproduction technologies (ARTs) have flourished in the mid- to late-twentieth century. Greater understanding of human biology and reproduction has led to technological developments to assist individuals or couples experiencing infertility due to a wide range of indications. The field has evolved from a combination of technological advances (such as laparoscopy and transvaginal ultrasonography) together with pharmaceutical developments (notably purified extracts of human menopausal gonadotropic hormones) and theoretical knowledge and practical techniques taken from gynecology, genetics, urology, and associated medical specialties. However, the origins of many current ART techniques can be traced to early practices in animal husbandry.
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Humans have used some less technological methods to promote their reproduction without the involvement of medical professionals, notably artificial insemination by donor (AID) or by husband/partner (AIH). The introduction of semen or concentrated specimens of spermatozoa (sperm) into a woman’s reproductive tract by noncoital means can be successfully performed with instruments as simple as a turkey baster. However in recent years, fears about donor health status, risk of infection (HIV and otherwise), and legal issues (such as establishing paternity) have caused most AI to be performed in medical clinics under a physician’s supervision. Some doctors avoided paternity issues by mixing sperm from several donors including the male partner, but recent advances in genetic technologies allowing paternity testing using DNA have resulted in clarification in many jurisdictions of the legal standing of children born from AI (though issues remain for instance with custody and adoption of AID children born to lesbian couples). AI is sometimes coupled with use of gonadotrophic hormones to stimulate ovulation at the time of insemination to maximize the chances of fertilization occurring, although these drugs are associated with some risks to the women to whom they are given.

In vitro fertilization and transcervical embryo transfer (IVF-ET) had its first successful birth in 1978, in the clinic of Patrick Steptoe and Robert Edwards, who drew on embryological studies done for over 20 years in mice, rabbits, and other animals. The procedure involved laparoscopic aspiration of an oocyte (egg cell or more generally ‘‘egg’’) during a natural cycle (thus circumventing damaged fallopian tubes), followed by IVF using ejaculated sperm and transfer of the cleaving embryo into the woman’s uterus. More generally in IVF-ET, eggs are harvested and mixed in Petri dishes either with donor sperm (AID), or with sperm from the male partner (AIH, if primary male infertility is not thought to be at issue), typically using the healthiest sperm to facilitate fertilization. Eggs may be obtained from the female or donated by another woman (e.g., in cases of premature ovarian failure, genetic abnormalities, or reduced egg production due to advanced maternal age). Most women undergo controlled ovarian hyperstimulation (as described above) prior to aspiration of eggs to increase the number of eggs that are viable. Surrogacy (the establishment of pregnancy in another woman who either donates an egg to combine with the male partner’s sperm or carries a fetus produced through combination of the couple’s own gametes) has occurred in cases where the female partner in a couple wishing to have a genetically-related child cannot carry a pregnancy (e.g., due to lack of uterus for congenital reasons or following hysterectomy), but the practice has been curtailed in recent years due to legal restrictions following custody disputes between surrogates and couples.

The number of fertilized embryos created and transferred differs according to anticipated success, typically related to the putative cause of infertility in the couple as well as the clinic’s experience. But in recent years, improved methods have created higher success rates both in terms of creation of viable embryos as well as implantation of the embryo posttransfer (the latter had been and remains the major technological barrier to successful pregnancies via IVF). The result has been multiple gestations (often resulting in subsequent ‘‘selective reduction’’; that is, termination of one or more fetuses to avoid the increased risks associated with multiple births), as well as emerging social, ethical, and legal issues associated with the status and disposition of supernumerary embryos. Consequently, many clinics have adopted more conservative approaches to the number of embryos created and transferred at any one time, and there is legislation or guidelines in some places to limit the number of embryos that can be transferred during one IVF cycle. Supernumerary embryos can be cryopreserved (typically at the four- to eight-cell stage) for later IVF cycles, donation to other infertile couples, or under certain circumstances for research. By the mid-1980s, techniques for cryopreservation were sufficiently developed to allow successful pregnancies using ET with frozen embryos, which permitted women to avoid multiple cycles of ovarian stimulation. More recently, IVF-ET has been combined with preimplantation genetic diagnosis (PGD) techniques to allow testing of embryos for genetic diseases (the technique was originally developed as an alternative to prenatal diagnosis for fertile couples with known genetic risks) and chromosomal abnormalities to allow selection and transfer only of unaffected embryos.
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A number of additional ARTs have been developed in the last 20 years. Gametic intrafallopian transfer (GIFT), which involves placement of eggs (which have been removed from the follicles) together with sperm directly into the oviducts for fertilization, was first described in 1985, and is used with women with fallopian tube problems. This technique quickly became very popular because it did not require sophisticated IVF culture systems and could be done in clinics with less ART expertise and without a full IVF laboratory, and because it produced better results than IVF, perhaps because fertilization occurs in a natural environment (greater success rates are also due to patient selection, as was later recognized). Zygote intrafallopian transfer (ZIFT) involves transfer of the zygote (a fertilized egg that has not yet divided) into the oviduct after IVF, but is less frequently used. Intracytoplasmic sperm injection (ICSI) is a popular micromanipulation technique used to enhance fertilization rates, particularly for men with a reduced sperm count or with impaired sperm motility, banked sperm (obtained prior to chemotherapy or radiation), or sperm obtained through electroejaculation (e.g., in those with spinal cord injuries or recently after death, the latter being ethically and legally problematic). Pregnancy can be achieved with only a single spermatozoon injected directly into the cytoplasm of the oocyte. The technique also can be combined with those allowing separation of male and female sperm to avoid birth of children of a particular sex (for reasons of sex selection, which is considered ethically controversial by many, or avoidance of sex-linked diseases).