Robert Edwards and Patrick Steptoe made a significant contribution to the treatment of infertility in 1978, with the successful birth of Louise Brown after in vitro fertilization (IVF). Twenty-two years later, the Centers for Disease Control and Prevention (CDC) reported that IVF resulted in 25,228 live births in the United States. The success of IVF has been estimated to be one live birth in every five IVF cycles. While the use of sperm donation and intrauterine insemination (IUI) with either partner or donated sperm has been available for many years, it is advances in assisted reproductive technologies (ART) that have revolutionized the care and management of couples dealing with infertility.
There are a number of different technologies available including IVF, intracytoplasmic sperm injection (ICSI), preimplantation genetic diagnosis (PGD), and third party reproduction (donor egg, donor sperm, surrogacy).
Invitro fertilization is a procedure that involves removing eggs from a woman’s ovaries and fertilizing them outside her body in a glass dish. The embryos that are produced are then transferred into the woman’s uterus through the cervix. The first step is to treat the woman with hormones to produce multiple eggs. Most women produce at least 4-6 eggs capable of being fertilized, but some may produce as many as 20-30 eggs. The eggs are removed and placed in a sterile dish along with sperm. Fertilization and early cell division takes place in the dish and can be seen under the microscope. Once the fertilized eggs have divided into 6- to 8-cell-stage embryos, they are returned to the uterus and are expected to implant in the uterus and continue with a normal pregnancy. The success of IVF has been estimated to be one live birth in every five IVF cycles. Two variations of IVF are gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT). GIFT uses the same initial procedure, but instead of waiting for fertilization to take place in the dish, the eggs and sperm are placed directly into the fallopian tubes using a laparo-scope through small incisions in the abdomen. ZIFT involves placing the egg that was fertilized (zygote) in the dish directly into the fallopian tubes instead of the uterus.
Intracytoplamic sperm injection was developed by researchers in Brussels in 1992 and involves the direct microinjection of a single sperm into the cytoplasm of a single egg (oocyte). This technique was developed to help males who are infertile due to very low sperm count or very limited numbers of healthy sperm. This procedure has been reported to dramatically increase fertilization rate by 50-80%, with a successful pregnancy rate of about 20-30% for couples with male infertility. Since the first reports of successful pregnancies after ICSI, there has been an effort to assess the genetic risks that may be associated with this technique as ICSI bypasses the natural mechanisms of sperm selection during reproduction. While there have been some reports of the occurrence of birth defects in children conceived after ICSI, the incidence of a congenital malformation is estimated to be 2.5-3%, which is similar to that of the general population. Also, some causes of male infertility can be genetic and passed on, so male offsprings might have reproductive problems as adults.
Preimplantation genetic diagnosis is a relatively new technique developed 10 years ago that combines advances in molecular genetics and assisted reproductive technologies. Preimplantation genetic diagnosis is a technology that can be used during IVF to test for genetic disorders in the embryo, prior to being transferred back into the uterus. Once the embryos are obtained, they are placed under a microscope and a single cell is removed from each embryo with a glass needle (pipette). That cell can then be tested for the presence of the genetic disorder the couple was at risk for. Embryos that are unaffected—do not have the genetic disorder—can then be transferred into the uterus. For example, Tay-Sachs disease, Duchenne muscular dystrophy, Down syndrome, and cystic fibrosis are a few of the genetic disorders that have been successfully bypassed by using Preimplantation genetic diagnosis. Preimplantation genetic diagnosis was developed for couples for whom pregnancy termination after conventional prenatal diagnosis was not an option. The risks of Preimplantation genetic diagnosis are similar to those of IVF, namely, multiple fetal pregnancies. Preliminary studies show no risk for spontaneous abortions or birth defects; however, the data from long-term follow-up of children conceived after Preimplantation genetic diagnosis have yet to be collected.
Third-party reproduction refers to using donated gametes (eggs or sperm), donated embryos, or a donated uterus (surrogacy or a gestational carrier) by a third person (the donor) to an infertile couple (the recipient). There are genetic issues involved with donated eggs, sperm, and embryos in particular. Gamete donors undergo genetic screening according to guidelines established by the American Society for Reproductive Medicine (ASRM) in 1997. In addition, some programs offer donated embryos from couples who have gotten pregnant following IVF and no longer need the other remaining fertilized eggs. Donor eggs are often recommended when a woman has a uterus but her ovaries do not produce healthy eggs, or ovaries were previously removed due to cancer or infection. Using IVF techniques, the egg donor is given hormone medication to stimulate ovulation and then the eggs are retrieved. These are then mixed with the infertile woman’s partner’s sperm or donated sperm and the resulting embryo is transferred back into the recipient. Donor sperm is used when the male is infertile. The sperm can be injected directly into the uterus (IUI) and conception occurs naturally or can be mixed in the laboratory with eggs to create embryos. When using donated sperm, it is recommended that it be frozen for several months to rule out the presence of infectious diseases such as HIV. Surrogacy (having another woman carry the pregnancy) is considered when a woman does not have a uterus because of a previous hysterectomy or was born without a uterus. In this case, either the couple’s eggs and sperm or donor eggs and sperm can be used. Using the same IVF techniques, the embryo is transferred into the surrogate mother.
While all of these assisted reproductive technologies have provided many new options for infertile couples, the achievement of a pregnancy using assisted reproductive technologies can have physical, emotional, and social consequences. One adverse consequence of IVF is an increased rate in multiple fetal pregnancies. These can be potentially harmful for both mother and fetus due to higher rates of cesarean sections, prematurity, low birthweight, infant death, and disability. According to the CDC, the multiple-infant birth rate after assisted reproductive technologies was 38% in 1998, compared to only 3% in the general population. Moreover, despite advances in assisted reproductive technologies, IVF still remains relatively unsuccessful. Only about 22% of assisted reproductive technologies cycles performed in the United States in 2000 in all aged women resulted in a live birth. Women who are under the age of 35 have the highest success rates and women over the age of 40 have lower success rates. Finally, assisted reproductive technologies is expensive. Costs vary depending on the center and what is done. Costs can range from a few thousand dollars per cycle to $10,000 per cycle.
See Also: Menstrual cycle disorders, Miscarriage, Pregnancy
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