Assisted reproductive technology

Assisted reproductive technology includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization, intracytoplasmic sperm injection, and cryopreservation of gametes and embryos, and the use of fertility medication. When used to address infertility, ART may also be referred to as fertility treatment. ART primarily belongs to the field of reproductive endocrinology and infertility Some forms of ART may be used about fertile couples for genetic purposes. ART may also be used in surrogacy arrangements, although not all surrogacy arrangements involve ART.
The existence of sterility will not always require ART to be the first option to consider, as there are occasions when its cause is a mild disorder that can be solved with more conventional treatments or with behaviors based on promoting health and reproductive habits.

Procedures

General

With ART, the process of sexual intercourse is bypassed and fertilization of the oocytes occurs in the laboratory environment
In the US, the Centers for Disease Control and Prevention defines ART to include "all fertility treatments in which both eggs and sperm are handled. In general, ART procedures involve surgically removing eggs from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman." According to CDC, "they do not include treatments in which only sperm are handled or procedures in which a woman takes medicine only to stimulate egg production without the intention of having eggs retrieved."
In Europe, ART also excludes artificial insemination and includes only procedures where oocytes are handled.
The World Health Organization, also defines ART this way.

Ovulation induction

is usually used in the sense of stimulation of the development of ovarian follicles by fertility medication to reverse anovulation or oligoovulation. These medications are given by injection for 8 to 14 days. A health care provider closely monitors the development of the eggs using transvaginal ultrasound and blood tests to assess follicle growth and estrogen production by the ovaries. When follicles have reached an adequate size and the eggs are mature enough, an injection of the hormone hCG initiates the ovulation process. Egg retrieval should occur 36 hours before ovulation.

In vitro fertilization

is the technique of letting fertilization of the male and female gametes occur outside the female body.
Techniques usually used in in vitro fertilization include:

Transvaginal ovum retrieval is the process whereby a small needle is inserted through the back of the vagina and guided via ultrasound into the ovarian follicles to collect the fluid that contains the eggs.
Embryo transfer is the step in the process whereby one or several embryos are placed into the uterus of the female with the intent to establish a pregnancy.

Less commonly used techniques in in vitro fertilization are:

Assisted zona hatching is performed shortly before the embryo is transferred to the uterus. A small opening is made in the outer layer surrounding the egg in order to help the embryo hatch out and aid in the implantation process of the growing embryo.
Intracytoplasmic sperm injection is beneficial in the case of male factor infertility where sperm counts are very low or failed fertilization occurred with previous IVF attempt. The ICSI procedure involves a single sperm carefully injected into the center of an egg using a microneedle. With ICSI, only one sperm per egg is needed. Without ICSI, you need between 50,000 and 100,000. This method is also sometimes employed when donor sperm is used.
Autologous endometrial coculture is a possible treatment for patients who have failed previous IVF attempts or who have poor embryo quality. The patient's fertilized eggs are placed on top of a layer of cells from the patient's own uterine lining, creating a more natural environment for embryo development.
In zygote intrafallopian transfer, egg cells are removed from the woman's ovaries and fertilized in the laboratory; the resulting zygote is then placed into the fallopian tube.
Cytoplasmic transfer is the technique in which the contents of a fertile egg from a donor are injected into the infertile egg of the patient along with the sperm.
Egg donors are resources for women with no eggs due to surgery, chemotherapy, or genetic causes; or with poor egg quality, previously unsuccessful IVF cycles or advanced maternal age. In the egg donor process, eggs are retrieved from a donor's ovaries, fertilized in the laboratory with the sperm from the recipient's partner, and the resulting healthy embryos are returned to the recipient's uterus.
Sperm donation may provide the source for the sperm used in IVF procedures where the male partner produces no sperm or has an inheritable disease, or where the woman being treated has no male partner.
Preimplantation genetic diagnosis involves the use of genetic screening mechanisms such as fluorescent in-situ hybridization or comparative genomic hybridization to help identify genetically abnormal embryos and improve healthy outcomes.
Embryo splitting can be used for twinning to increase the number of available embryos.
Pre-implantation genetic diagnosis

A pre-implantation genetic diagnosis procedure may be conducted on embryos prior to implantation, and sometimes even of oocytes prior to fertilization. PGD is considered in a similar fashion to prenatal diagnosis. PGD is an adjunct to ART procedures, and requires in vitro fertilization to obtain oocytes or embryos for evaluation. Embryos are generally obtained through blastomere or blastocyst biopsy. The latter technique has proved to be less deleterious for the embryo, therefore it is advisable to perform the biopsy around day 5 or 6 of development. Sex selection is the attempt to control the sex of offspring to achieve a desired sex in case of X chromosome linked diseases. It can be accomplished in several ways, both pre- and post-implantation of an embryo, as well as at birth. Pre-implantation techniques include PGD, but also sperm sorting.

Others

Other assisted reproduction techniques include:

Mitochondrial replacement therapy is the replacement of mitochondria in one or more cells to prevent or ameliorate disease. MRT originated as a special form of IVF in which some or all of the future baby's mitochondrial DNA comes from a third party. This technique is used in cases when mothers carry genes for mitochondrial diseases. The therapy is approved for use in the United Kingdom.
In gamete intrafallopian transfer, a mixture of sperm and eggs is placed directly into a woman's fallopian tubes using laparoscopy following a transvaginal ovum retrieval.
Reproductive surgery, treating e.g. fallopian tube obstruction and vas deferens obstruction, or reversing a vasectomy by a reverse vasectomy. In surgical sperm retrieval, the reproductive urologist obtains sperm from the vas deferens, epididymis or directly from the testis in a short outpatient procedure.
By cryopreservation, eggs, sperm and reproductive tissue can be preserved for later IVF.
Risks

The majority of IVF-conceived infants do not have birth defects.
However, some studies have suggested that assisted reproductive technology is associated with an increased risk of birth defects.
Artificial reproductive technology is becoming more available. Early studies suggest that there could be an increased risk for medical complications with both the mother and baby. Some of these include low birth weight, placental insufficiency, chromosomal disorders, preterm deliveries, gestational diabetes, and pre-eclampsia.
In the largest U.S. study, which used data from a statewide registry of birth defects,
6.2% of IVF-conceived children had major defects, as compared with 4.4% of naturally conceived children matched for maternal age and other factors. ART carries with it a risk for heterotopic pregnancy.
The main risks are:

Genetic disorders
Low birth weight. In IVF and ICSI, a risk factor is the decreased expression of proteins in energy metabolism; Ferritin light chain and ATP5A1.
Preterm birth. Low birth weight and preterm birth are strongly associated with many health problems, such as visual impairment and cerebral palsy. Children born after IVF are roughly twice as likely to have cerebral palsy.

Sperm donation is an exception, with a birth defect rate of almost a fifth compared to the general population. It may be explained by that sperm banks accept only people with high sperm count.
Germ cells of the mouse normally have a frequency of spontaneous point mutations that is 5 to 10-fold lower than that in somatic cells from the same individual. This low frequency in the germline leads to embryos that have a low frequency of point mutations in the next generation. No significant differences were observed in the frequency or spectrum of mutations between naturally conceived fetuses and assisted-conception fetuses. This suggests that with respect to the maintenance of genetic integrity assisted conception is safe.
Current data indicate little or no increased risk for postpartum depression among women who use ART.
Socio-ethical considerations of advanced parental age:
The increasing use of ART by older individuals, facilitated by techniques such as elective oocyte cryopreservation, raises significant socio-ethical questions. While often framed as a tool for enhancing reproductive autonomy by allowing individuals to delay childbearing for personal or professional reasons, this practice is subject to ethical debate. Proponents argue it empowers women by providing greater biological control. However, critics warn it may medicalize a social problem—the difficulty of balancing career and family—and create pressure for women to use this technology. Furthermore, it presents a potential ethical challenge regarding the welfare of the future child, as some studies suggest that children of significantly older parents may face unique psychosocial challenges, including a higher probability of losing parents at a younger age. This has sparked complex debates in clinical ethics about the balance between reproductive rights and the potential interests of the child.
Study results indicate that ART can affect both women and men's sexual health negatively.
Usage of assisted reproductive technology including ovarian stimulation and in vitro fertilization have been associated with an increased overall risk of childhood cancer in the offspring, which may be caused by the same original disease or condition that caused the infertility or subfertility in the mother or father.
That said, In a landmark paper by Jacques Balayla et al. it was determined that infants born after ART have similar neurodevelopment than infants born after natural conception.
ART may also pose risks to the mother. A large US database study compared pregnancy outcomes among 106,000 assisted conception pregnancies with 34 million natural conception pregnancies. It found that assisted conception pregnancies were associated with an increased risk of cardiovascular diseases, including acute kidney injury and arrhythmia. Assisted conception pregnancies were also associated with a higher risk of caesarean delivery and premature birth.
In theory, ART can solve almost all reproductive problems, except for severe pathology or the absence of a uterus, using specific gamete or embryo donation techniques. However, this does not mean that all women can be treated with assisted reproductive techniques, or that all women who are treated will achieve pregnancy.