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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.
Tests
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 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.
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.
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.
Insemination
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 freezing.