Assisted reproductive techniques (ARTs) involve manipulation of sperm and ova or embryos in vitro with the goal of producing a pregnancy.
ARTs may result in multifetal pregnancy, but risk is much less than that with controlled ovarian stimulation. If risk of genetic defects is high, the embryo can often be tested for defects before transfer and implantation (preimplantation genetic testing).
In vitro fertilization (IVF)
IVF can be used to treat infertility due to oligospermia, sperm antibodies, tubal dysfunction, or endometriosis as well as unexplained infertility.
The procedure typically involves the following:
- Controlled ovarian stimulation: Clomiphene plus gonadotropins or gonadotropins alone can be used. A gonadotropin-releasing hormone (GnRH) agonist or antagonist is often given to prevent premature ovulation. After sufficient follicular growth, human chorionic gonadotropin (hCG) is given to trigger final follicular maturation and ovulation. Alternatively, a GnRH agonist can be used to trigger ovulation in women at high risk of ovarian hyperstimulation syndrome.
- Oocyte retrieval: About 34 hours after hCG is given, oocytes are retrieved by direct needle puncture of the follicle, usually transvaginally with ultrasound guidance or less commonly laparoscopically. At some centers, natural cycle IVF (in which a single oocyte is retrieved) is offered as an alternative; pregnancy rates with this technique are lower than those with retrieval of multiple oocytes, but costs are lower and success rates are increasing.
- Fertilization: The oocytes are inseminated in vitro. The semen sample is typically washed several times with tissue culture medium and is concentrated for motile sperm, which are then added to the medium containing the oocytes. At this point, intracytoplasmic sperm injection—injection of a single sperm into each oocyte—may be done, particularly if spermatogenesis is abnormal in the male partner.
- Embryo culture: After sperm are added, the oocytes are cultured for about 2 to 5 days.
- Embryo transfer: Only 1 or a few of the resulting embryos are transferred to the uterine cavity, minimizing the chance of a multifetal pregnancy, the greatest risk of IVF. The number of embryos transferred is determined by the woman’s age and likelihood of response to IVF. Some or all embryos (especially if women are at high risk of ovarian hyperstimulation syndrome) may be frozen in liquid nitrogen for transfer in a subsequent cycle. There is an increasing tendency to place only one embryo at each transfer and to freeze the remaining embryos for use in subsequent cycles if pregnancy does not result.
Birth defects may be slightly more common after IVF, but experts are uncertain whether the increased risk is due to IVF or to factors contributing to infertility; infertility itself increases risk of birth defects. Still, as of early 2018, the overwhelming majority of the > 7 million children born after IVF have no birth defects. Worldwide, an estimated 200,000 babies are born after IVF every year.
Preimplantation genetic testing can be done using cells from the polar body of an oocyte or cells from an embryo (either a blastomere from a 3-day-old embryo or trophectoderm cells from a 5- or 6-day-old embryo). Testing may involve preimplantation genetic screening to rule out aneuploidy and/or preimplantation genetic diagnosis to check for specific serious hereditary disorders. If test results are delayed, the blastocyst can be frozen and transferred in a later cycle after the results are known.
Preliminary data for 2018 indicate that in the US, the cumulative chances of taking home a live baby for each oocyte retrieval (counting all transfers of the patient's own embryos—both fresh and frozen-thawed) was 47.6% for women < 35 (10.4% were twins; 0.02% were triplets or more) and 10.4% for women aged 41 to 42.
Use of donor oocytes is usually recommended for women > 42.
Gamete intrafallopian tube transfer (GIFT)
GIFT is an alternative to IVF but is rarely used because success rates for IVF have increased.
GIFT is used most often when women have one of the following:
- Unexplained infertility
- Normal tubal function plus endometriosis
Multiple oocytes and sperm are obtained as for IVF but are transferred—transvaginally with ultrasound guidance or laparoscopically—to the distal fallopian tubes, where fertilization occurs.
Live birth rates per cycle are about 25 to 35%.
Intracytoplasmic sperm injection (ICSI)
This technique is useful when
- Other techniques are unsuccessful or are likely to be so.
- A severe sperm disorder is present.
Oocytes are obtained as for IVF. A single sperm is injected into each oocyte to avoid fertilization by abnormal sperm. The embryo is then cultured and transferred as for IVF.
In 2014, over two thirds of all ART cycles in the US involved intracytoplasmic sperm injection. There is no benefit to using intracytoplasmic sperm injection in couples with low oocyte yield or advanced maternal age. If a couple's infertility involves the woman, > 30 of these procedures must be done to make one additional pregnancy likely. Thus, the additional costs and risks of intracytoplasmic sperm injection must be considered when deciding whether to use it.
Risk of birth defects may be increased after intracytoplasmic sperm injection, possibly because of the following:
- The procedure itself can damage the sperm, egg, or embryo.
- Sperm from men who have mutations of the Y chromosome may be used. Most reported birth defects involve the male reproductive tract.
Other techniques are sometimes used. They include the following:
- A combination of IVF and GIFT
- Zygote intrafallopian tube transfer (rarely used)
- Use of donor oocytes or embryos
- Transfer of frozen embryos to a surrogate mother
Some of these techniques raise moral and ethical issues (eg, rightful parentage in surrogate motherhood, selective reduction of the number of implanted embryos if multifetal pregnancy results).
For postmenopausal women who are > 50 years and have an older male partner, use of IVF is controversial.
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