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Assisted Reproductive Technologies

Assisted reproductive technologies consist of procedures pertaining to the handling of oocytes and embryos outside of the body, with gametes or concepti replaced into the body to establish pregnancy. The most commonly used procedure is in vitro fertilization (IVF), which involves extraction of oocytes, fertilization in the laboratory, and transfer of embryos through the cervix into the uterine cavity.

In Vitro Fertilization–Embryo Transfer

Infertility due to abnormal fallopian tubes or endometriosis, idiopathic infertility, male infertility, and immunologic infertility all respond well to IVF. Women who have failed to conceive with donor insemination or ovulation induction are also excellent candidates. Rough guidelines as to when ART may be considered are after 2 years of unexplained infertility, 1 year after treatment of a particular defect, or after at least 1 year of donor insemination or ovulation induction. These may be modified, depending on factors such as age, presence of severe defects, or multiple infertility factors assisted reproductive technologies, infertility, infertilty, invitro fertilization, in vitro, in betro, bitro, fertilisation


Levels of FSH and estradiol can be used to identify women with abnormal ovarian function and a reduced prognosis. When the FSH level exceeds 25 mIU/mL on day 3 of menses, successful birth is

is similarly low, although this finding has less significance in younger patients. Age alone predicts prognosis, with successful birth occurring in about one third as many women more than 40 years of age

Many programs test the fertilizing capacity of sperm using zona-free hamster eggs. Some males may fail to fertilize with routine methods of sperm preparation, whereas alternative methods may enhance sperm penetration. Routine use of sperm enhancement (eg, with Test-Yolk buffer) also may be considered. Testing for antisperm antibodies is essential if the patient's own serum is to be used in the culture medium, but it is

Ovarian Stimulation and Monitoring

Most IVF cycles are conducted with ovarian stimulation because the pregnancy rate increases with the number of embryos transferred. A meta-analysis of randomized trials has shown a twofold odds ratio for

Both transvaginal ultrasonography and serum estradiol are used to determine when hCG should be injected to initiate resumption of meiosis. With the natural cycle, serum or urinary LH levels must be monitored either to ensure that the LH surge has not begun or to time retrieval according to the onset of the LH surge. The ultrasonographic appearance and thickness of the endometrium have been found to be prognostic for successful pregnancy; a sonolucent superficial layer and a thickness of more than 8-9 mm are ideal.

Oocyte Retrieval

The follicle aspiration is scheduled for 34-36 hours after hCG injection. With administration of GnRH agonist and human menopausal gonadotropin, this can be extended to as late as 38 hours with minimal risk of ovulation. Prophylactic antibiotics are commonly given. Retrieval is almost always performed by


Usually, 50,000-500,000 sperm are added to each oocyte, depending on sperm parameters, after a period of 2-8 hours of preincubation to allow further oocyte maturation. The oocytes are stripped of their surrounding cells and examined 12-20 hours after insemination. Visualization of two pronuclei confirms normal

Embryo Culture and Quality Control

A variety of media has been used with success for embryo culture. Electrolyte concentrations are often adjusted to simulate the levels in a normal human fallopian tube. Serum from the patient, umbilical cord blood, or designated donors most often have been added to media to provide protein and growth factors.

Embryo Transfer

Embryos are most often replaced 2 or 3 days after oocyte retrieval. Embryos are graded, and those chosen for transfer are loaded in a minute volume of medium into a transfer catheter. The catheter tip is advanced

Luteal-Phase Supplementation

With GnRH agonist and human menopausal gonadotropin cycles, it is necessary to support the luteal phase with hCG or progesterone. The latter is probably as effective and carries less risk of ovarian hyperstimulation. Progesterone supplementation is generally continued until 10 days to 2 weeks of gestation.

Early Pregnancy

Pregnancy is diagnosed by rising levels of hCG. Clinical pregnancy is confirmed by the presence of a gestational sac. It is inappropriate for a program to count biochemical pregnancies (rising hCG only) in their "pregnancy" rate. Because about 5% of clinical pregnancies are ectopic, a careful transvaginal ultrasonogram should be done at 4 and 6 weeks after transfer. Cornual pregnancies can occur and are easily visualized. Cervical pregnancies also can occur. A tubal pregnancy usually can be detected, but the patient Complications

There has been a very low incidence of pelvic infection after follicle aspiration. This incidence can be further minimized by using prophylactic antibiotics and preparing the vagina with povidone-iodine. Ovarian hyperstimulation occurs in about 0.2% of stimulated cycles; it is more common in anovulatory women. Multiple pregnancy occurs in approximately 33% of pregnancies. It is more common in programs with higher Cryopreserved Embryos

There is no known limit on duration of embryo storage. Women who are successful with the fresh embryos are likely to be successful with frozen embryos from the same cycle. About two thirds of embryos survive the

Pregnancy Outcome

There is a minor trend toward preterm labor in singleton pregnancies. The rate of spontaneous abortion is slightly increased (from 10% to about 20%). The rate of congenital anomalies has not been increased. In one report, the rate of abnormalities was lower after embryo freezing.

Micromanipulation of Oocytes and Embryos

Rapid progress in micromanipulation has resulted in dramatic improvements in success rates with ART. In addition, the development of new techniques to treat specific abnormalities (eg, relative azoospermia, genetic disorders) has been pioneered. These techniques involve microsurgical procedures performed on oocytes

Assisted Hatching

The zona pellucida was believed to be a potential hindrance to implantation. Theories suggest that during the passage through the fallopian tube there is a thinning or shedding, or both, of the zona pellucida. If this does not occur, morphologically normal embryos do not implant. Uterine embryo transfer is believed to minimize, but not completely eliminate, the amount of time the embryo is exposed to the tubal environment. It has been theorized that techniques that weaken the zona might enhance implantation. Indeed, studies evaluating embryonic implantation after mechanical or chemical weakening of the zona have demonstrated an


Concern about the safety of these techniques exists despite very little evidence of problems among the thousands of babies whose births have been possible because of them. Genetic studies of resulting offspring have failed to reveal an increased incidence of abnormalities. However, the concern exists that

Preimplantation Genetic Diagnosis

The ability to exclude before the initiation of pregnancy those embryos obtained in vitro that have diagnosed genetic deficiencies offers an attractive means to prevent in-heritable genetic disease. The benefits include the elimination of the risks associated with chorionic villus sampling or amniocentesis, as well

Use of Donor Gametes

The fertilization rate is entirely normal with frozen donor sperm. The pregnancy rate with donated oocytes is generally 1.5- to 2-fold higher than with routine IVF because donors are generally young or fertile or both. Both known and anonymous oocyte donors are used. This has allowed women who have failed multiple IVF

Choosing an In Vitro Fertilization Program

Success rates are generally reported as clinical pregnancies and deliveries per retrieval. These rates are available through the American Society for Reproductive Medicine on an annual basis for individual programs. For 1994, the average delivery rate per retrieval was 21.2%. Rates are separated for women older than age 39 years and for couples with abnormal sperm count or motility (Table 10). The women under age 40 and

Embryo or Gamete Replacement

Embryo replacement can be performed transcervically or transfimbrially 2 or 3 days after oocyte insemination. Ga-mete replacement also can be in the form of GIFT. The number of embryos or gametes replaced should be contingent on the

Care of the Donor After Embryo Transfer

Ovarian hyperstimulation syndrome is a potential risk that must not be overlooked. Donors at risk include those with a maximal estradiol level

Care of the Recipient After Embryo Transfer

The recipient should be maintained on exogenous estrogen and progesterone replacement until pregnancy is confirmed; this replacement therapy

Other Procedures

Peritoneal oocyte and sperm transfer is a procedure in which 1) the oocytes are retrieved and 2) the oocytes and sperm are placed into the pelvic cavity by ultrasound guidance. Direct intraperitoneal insemination is a procedure in which sperm are


When a woman who desires children has no uterus or cannot carry a child for health reasons, the use of surrogates raises issues of possible exploitation and the propriety of paying for such services. In some instances mothers or sisters have volunteered to carry children. Such cases raise fewer problems in general