Artificial insemination

Artificial insemination (AI) is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment for humans, and is common practice in animal breeding, including dairy cattle (see Frozen bovine semen) and pigs.

Artificial insemination may employ assisted reproductive technology, sperm donation and animal husbandry techniques. Artificial insemination techniques available include intracervical insemination and intrauterine insemination. The beneficiaries of artificial insemination are women who desire to give birth to their own child who may be single, women who are in a lesbian relationship or women who are in a heterosexual relationship but with a male partner who is infertile or who has a physical impairment which prevents full intercourse from taking place. Intracervical insemination (ICI) is the easiest and most common insemination technique and can be used in the home for self-insemination without medical practitioner assistance. Compared with natural insemination (i.e., insemination by sexual intercourse), artificial insemination can be more expensive and more invasive, and may require professional assistance.

Some countries have laws which restrict and regulate who can donate sperm and who is able to receive artificial insemination, and the consequences of such insemination. Some women who live in a jurisdiction which does not permit artificial insemination in the circumstance in which she finds herself may travel to another jurisdiction which permits it.

History
The first reported case of artificial insemination by donor occurred in 1884: Dr. William H. Pancoast, a professor in Philadelphia, took sperm from his "best looking" student to inseminate an anesthetized woman. The woman was not informed about the procedure, unlike her infertile husband. The case was reported 25 years later in a medical journal. The sperm bank was developed in Iowa starting in the 1920s in research conducted by University of Iowa medical school researchers Jerome Sherman and Raymond Bunge.

In the 1980s, direct intraperitoneal insemination (DIPI) was occasionally used, where doctors injected sperm into the lower abdomen through a surgical hole or incision, with the intention of letting them find the oocyte at the ovary or after entering the genital tract through the ostium of the fallopian tube.

General
The sperm used in artificial insemination may be provided by either the woman's husband or partner (partner sperm) or by a known or anonymous sperm donor (see sperm donation (donor sperm)).

If the procedure is successful, the woman will conceive and carry a baby to term in the normal manner. A pregnancy resulting from artificial insemination is no different from a pregnancy achieved by sexual intercourse. In all cases, the woman is the biological mother of any child produced by AI, and the male whose sperm is used is the biological father.

There are multiple methods used to obtain the semen necessary for artificial insemination. Some methods require only men, while others require a combination of a male and female. Those that require only men to obtain semen are masturbation or the aspiration of sperm by means of a puncture of the testicle and epididymus. Methods of collecting semen that involve a combination of a male and female include interrupted intercourse, intercourse with a 'collection condom', or the post-coital aspiration of the semen from the vagina.

There are a number of reasons why a woman with a male partner would use artificial insemination to achieve pregnancy. For example, a woman's immune system may be rejecting her partner's sperm as invading molecules. Women who have issues with the cervix – such as cervical scarring, cervical blockage from endometriosis, or thick cervical mucus – may also benefit from artificial insemination, since the sperm must pass through the cervix to result in fertilization.

In the case of heterosexual couples who are finding it difficult to conceive, before artificial insemination is turned to as the solution, doctors will require an examination of both the male and female involved in order to remove any and all physical hindrances that are preventing them from naturally achieving a pregnancy. The couple is also given a fertility test to determine the motility, number, and viability of the male's sperm and the success of the female's ovulation. From these tests, the doctor may or may not recommend a form of artificial insemination.

Preparations
Timing is critical, as the window and opportunity for fertilization is little more than twelve hours from the release of the ovum. To increase the chance of success, the woman's menstrual cycle is closely observed, often using ovulation kits, ultrasounds or blood tests, such as basal body temperature tests over, noting the color and texture of the vaginal mucus, and the softness of the nose of her cervix. To improve the success rate of AI, drugs to create a stimulated cycle may be used, but the use of such drugs also results in an increased chance of a multiple birth.

Sperm can be provided fresh or washed. The washing of sperm increases the chances of fertilization. Pre- and post-concentration of motile sperm is counted. Sperm from a sperm bank will be frozen and quarantined for a period, and the donor will be tested before and after production of the sample to ensure that he does not carry a transmissible disease. For fresh shipping, a semen extender is used.

If sperm is provided by a private donor, either directly or through a sperm agency, it is usually supplied fresh, not frozen, and it will not be quarantined. Donor sperm provided in this way may be given directly to the recipient woman or her partner, or it may be transported in specially insulated containers. Some donors have their own freezing apparatus to freeze and store their sperm.

Techniques
Semen used is used either fresh, raw, or frozen. Where donor sperm is supplied by a sperm bank, it will always be quarantined and frozen, and will need to be thawed before use. When an ovum is released, semen is introduced into the woman's vagina, uterus or cervix, depending on the method being used.

Sperm is occasionally inserted twice within a 'treatment cycle'.

Intracervical insemination
Intracervical insemination (ICI) is painless and is the easiest and most common insemination technique. It closely replicates the ejaculation of semen by the penis into the vagina during intercourse.

ICI involves the introduction of unwashed or raw semen into the vagina at the entrance to the cervix, usually by means of a needleless syringe.

It is the simplest type of artificial insemination, and unwashed or raw semen is normally used, but semen supplied by a donor through a sperm bank which has been prepared for IUI use may also be used. The procedure is commonly used in home, self-insemination and practitioner insemination procedures, and for insemination where semen is provided by private donors.

In order to perform an ICI insemination, air must be expelled from a needle-less syringe which is then filled with semen which has been allowed to liquify. Any further enclosed air must be removed by gently pressing the plunger forward. The woman lies on her back and the syringe is then inserted into the vagina. Care is optimal when inserting the syringe, so that the tip is as close to the entrance to the cervix as possible. A vaginal speculum may be used for this purpose. The plunger is then slowly pushed forward and the semen in the syringe is gently emptied deep into the vagina. It is important that the syringe is emptied slowly for best results. The syringe may be left in place for several minutes before removal. The woman can bring herself to orgasm so that the cervix 'dips down' into the pool of semen, again replicating closely vaginal intercourse, and this may improve the success rate. The woman is advised to lie still for about half-an-hour to improve the success rate.

One insemination during a cycle is usually sufficient. Additional inseminations may not improve the chances of a pregnancy.

Ordinary sexual lubricants should not be used in the process, but special fertility or 'sperm-friendly' lubricants can be used for increased ease and comfort.

When performed at home without the presence of a professional, aiming the sperm in the vagina at the neck of the cervix may be more difficult to achieve and the effect may be to 'flood' the vagina with semen, rather than to target it specifically at the entrance to the cervix. This procedure is therefore sometimes referred to as intravaginal insemination (IVI). Sperm supplied by a sperm bank will be frozen and must be allowed to thaw before insemination. The sealed end of the straw itself must be cut off and the open end of the straw is usually fixed straight on to the tip of the syringe, allowing the contents to be drawn into the syringe. Sperm from more than one straw can generally be used in the same syringe. Where fresh semen is used, this must be allowed to liquefy before inserting it into the syringe, or alternatively, the syringe may be back-loaded.

A conception cap, which is a form of conception device, may be inserted into the vagina following insemination and may be left in place for several hours. Using this method, a woman may go about her usual activities while the cervical cap holds the semen in the vagina close to the entrance to the cervix. Advocates of this method claim that it increases the chances of conception. One advantage with the conception device is that fresh, non-liquefied semen may be used. The partner or donor may ejaculate straight into the cap and this can be immediately inserted into the vagina. Other methods may be used to insert semen into the vagina notably involving different uses of a conception cap. This may, for example, be inserted filled with sperm which does not have to be liquefied. The male may therefore ejaculate straight into the cap. Alternatively, a specially designed conception cap with a tube attached may be inserted empty into the vagina after which liquefied semen is poured into the tube. These methods are designed to ensure that donor or partner semen is inseminated as close as possible to the cervix and that it is kept in place there to increase the chances of conception.

Intrauterine insemination
Intrauterine insemination (IUI) involves injection of washed sperm into the uterus with a catheter. If unwashed semen is used, it may elicit uterine cramping, expelling the semen and causing pain, due to content of prostaglandins. (Prostaglandins are also the compounds responsible for causing the myometrium to contract and expel the menses from the uterus, during menstruation.) Resting on the table for fifteen minutes after an IUI is optimal for the woman to increase the pregnancy rate.

Unlike ICI, intrauterine insemination normally requires a medical practitioner to perform the procedure. A female under 30 years of age has optimal chances with IUI; for the man, a TMS of more than 5 million per ml is optimal. In practice, donor sperm will satisfy these criteria. A promising cycle is one that offers two follicles measuring more than 16 mm, and estrogen of more than 500 pg/mL on the day of hCG administration. A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates. However, GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles according to a randomized controlled trial.

IUI is a more efficient method of artificial insemination than ICI and, because of its generally higher success rate, is usually the insemination procedure of choice for single women and lesbians using donor semen in a fertility centre and who are less likely to have fertility issues of their own. Enabling the sperm to be inserted directly into the womb will produce a better chance of conceiving.

It is also a method used by couples using donor sperm in a fertility centre.

IUI can be used in conjunction with controlled ovarian hyperstimulation (COH). Still, advanced maternal age causes decreased success rates; women aged 38–39 years appear to have reasonable success during the first two cycles of ovarian hyperstimulation and IUI. However, for women aged over 40 years, there appears to be no benefit after a single cycle of COH/IUI. Medical experts therefore recommend considering in vitro fertilization after one failed COH/IUI cycle for women aged over 40 years.

A double intrauterine insemination theoretically increases pregnancy rates by decreasing the risk of missing the fertile window during ovulation. However, a randomized trial of insemination after ovarian hyperstimulation found no difference in live birth rate between single and double intrauterine insemination.

Intrauterine tuboperitoneal insemination
Intrauterine tuboperitoneal insemination (IUTPI) involves injection of washed sperm into both the uterus and fallopian tubes. The cervix is then clamped to prevent leakage to the vagina, best achieved with a specially designed double nut bivalve (DNB) speculum. The sperm is mixed to create a volume of 10 ml, sufficient to fill the uterine cavity, pass through the interstitial part of the tubes and the ampulla, finally reaching the peritoneal cavity and the Pouch of Douglas where it would be mixed with the peritoneal and follicular fluid. IUTPI can be useful in unexplained infertility, mild or moderate male infertility, and mild or moderate endometriosis. In non-tubal sub fertility, fallopian tube sperm perfusion may be the preferred technique over intrauterine insemination.

Intratubal insemination
Intratubal insemination (ITI) involves injection of washed sperm into the fallopian tube, although this procedure is no longer generally regarded as having any beneficial effect compared with IUI. ITI however, should not be confused with gamete intrafallopian transfer, where both eggs and sperm are mixed outside the woman's body and then immediately inserted into the fallopian tube where fertilization takes place.

Pregnancy rate


The pregnancy or success rates for artificial insemination are 10 to 15% per menstrual cycle using ICI, and 15–20% per cycle for IUI. In IUI, about 60 to 70% have achieved pregnancy after 6 cycles.

However, these pregnancy rates may be very misleading, since many factors, including the age and health of the recipient, have to be included to give a meaningful answer, e.g. definition of success and calculation of the total population. For couples with unexplained infertility, unstimulated IUI is no more effective than natural means of conception.

The pregnancy rate also depends on the total sperm count, or, more specifically, the total motile sperm count (TMSC), used in a cycle. The success rate increases with increasing TMSC, but only up to a certain count, when other factors become limiting to success. The summed pregnancy rate of two cycles using a TMSC of 5 million (may be a TSC of ~10 million on graph) in each cycle is substantially higher than one single cycle using a TMSC of 10 million. However, although more cost-efficient, using a lower TMSC also increases the average time taken to achieve pregnancy. Women whose age is becoming a major factor in fertility may not want to spend that extra time.

Samples per child
The number of samples (ejaculates) required to give rise to a child varies substantially from person to person, as well as from clinic to clinic. However, the following equations generalize the main factors involved:

For intracervical insemination:
 * $$N = \frac{V_s \times c \times r_s}{n_r} $$

The pregnancy rate increases with increasing number of motile sperm used, but only up to a certain degree, when other factors become limiting instead.
 * N is how many children a single sample can give rise to.
 * Vs is the volume of a sample (ejaculate), usually between 1.0 mL and 6.5 mL
 * c is the concentration of motile sperm in a sample after freezing and thawing, approximately 5–20 million per ml but varies substantially
 * rs is the pregnancy rate per cycle, between 10% to 35%
 * nr is the total motile sperm count recommended for vaginal insemination (VI) or intra-cervical insemination (ICI), approximately 20 million pr. ml.



With these numbers, one sample would on average help giving rise to 0.1–0.6 children, that is, it actually takes on average 2–5 samples to make a child.

For intrauterine insemination, a centrifugation fraction (fc) may be added to the equation:
 * fc is the fraction of the volume that remains after centrifugation of the sample, which may be about half (0.5) to a third (0.33).


 * $$N = \frac{V_s \times f_c \times c \times r_s}{n_r} $$

On the other hand, only 5 million motile sperm may be needed per cycle with IUI (nr=5 million)

Thus, only 1–3 samples may be needed for a child if used for IUI.

Social implications
One of the key issues arising from the rise of dependency on assisted reproductive technology (ARTs) is the pressure placed on couples to conceive; 'where children are highly desired, parenthood is culturally mandatory, and childlessness socially unacceptable'.

The medicalization of infertility creates a framework in which individuals are encouraged to think of infertility quite negatively. In many cultures donor insemination is religiously and culturally prohibited, often meaning that less accessible "high tech" and expensive ARTs, like IVF, are the only solution.

An over-reliance on reproductive technologies in dealing with infertility prevents many – especially, for example, in the "infertility belt" of central and southern Africa – from dealing with many of the key causes of infertility treatable by artificial insemination techniques; namely preventable infections, dietary and lifestyle influences.

If good records are not kept, the offspring when grown up risk accidental incest.

Morality in Christianity
An Anglican writer says that, "To achieve union but not children by means of contraceptives and to achieve children but not union by means of artificial insemination are both equally wrong." Heterosexual intercourse is viewed by the Catholic Church as an act meant to be experienced only by married couples; it is viewed as a physical representation of the spiritual unity of marriage between a husband and wife. According to the Catechism of the Catholic Church, artificial insemination "dissociates the sexual act from the procreative act. The act which brings the child into existence is no longer an act by two persons giving themselves to one another, but one that 'entrusts the life and identity of the embryo into the power of doctors and biologists and establishes the domination of technology over the origin and destiny of the human person. Such a relationship of domination is, in itself, contrary to the dignity and equality that must be common to parents and children'".

Legal restrictions
Some countries restrict artificial insemination in a variety of ways. For example, some countries do not permit AI for single women, and some Muslim countries do not permit the use of donor sperm. As of May 2013, the following European countries permit medically assisted AI for single women:
 * 🇦🇲 Armenia
 * 🇧🇾 Belarus
 * 🇧🇪 Belgium
 * 🇧🇬 Bulgaria
 * 🇨🇾 Cyprus
 * 🇩🇰 Denmark
 * 🇪🇪 Estonia
 * 🇫🇮 Finland
 * 🇩🇪 Germany
 * 🇬🇷 Greece
 * 🇭🇺 Hungary
 * 🇮🇸 Iceland
 * 🇮🇪 Ireland
 * 🇱🇻 Latvia
 * 🇲🇰 Macedonia
 * 🇲🇩 Moldova
 * 🇲🇪 Montenegro
 * 🇳🇱 Netherlands
 * 🇷🇴 Romania
 * 🇷🇺 Russia
 * 🇪🇸 Spain
 * 🇺🇦 Ukraine
 * United Kingdom

In animals


AI is useful for pets, livestock, endangered species, and animals in zoos or marine parks difficult to transport.

Reasons and techniques
It may be used for many reasons, including to allow a male to inseminate a much larger number of females, to allow use of genetic material from males separated by distance or time, to overcome physical breeding difficulties, to control the paternity of offspring, to synchronise births, to avoid injury incurred during natural mating, and to avoid the need to keep a male at all (such as for small numbers of females or in species whose fertile males may be difficult to manage).

Semen is collected, extended, then cooled or frozen. It can be used on site or shipped to the female's location. If frozen, the small plastic tube holding the semen is referred to as a straw. To allow the sperm to remain viable during the time before and after it is frozen, the semen is mixed with a solution containing glycerol or other cryoprotectants. An extender is a solution that allows the semen from a donor to impregnate more females by making insemination possible with fewer sperm. Antibiotics, such as streptomycin, are sometimes added to the sperm to control some bacterial venereal diseases. Before the actual insemination, estrus may be induced through the use of progestogen and another hormone (usually PMSG or Prostaglandin F2α).

History
The first viviparous to be artificially fertilized was a dog. The experiment was conducted with success by the Italian Lazzaro Spallanzani in 1780. Another pioneer was the Russian Ilya Ivanov since 1899. In 1935 Suffolk sheep diluted semen was sent from Cambridge by plane to Krakow, Poland, and international research joint (Prawochenki from Poland, Milovanoff from USSR, Hammond from Cambridge, Walton from Scotland, and Thomasset from Uruguay).

Modern artificial insemination was pioneered by John O. Almquist of the Pennsylvania State University. His improvement of breeding efficiency by the use of antibiotics (first proven with penicillin in 1946) to control bacterial growth, decreasing embrionic mortality and increase fertility, and various new techniques for processing, freezing and thawing of frozen semen significantly enhanced the practical utilization of AI in the livestock industry, and earned him the 1981 Wolf Foundation Prize in Agriculture. Many techniques developed by him have since been applied to other species, including that of the human male.

Species
Artificial insemination is used in many non-human animals, including sheep, horses, cattle, pigs, dogs, pedigree animals generally, zoo animals, turkeys and even honeybees.

Artificial insemination of farm animals is very common in today's agriculture industry in the developed world, especially for breeding dairy cattle (75% of all inseminations). Swine are also bred using this method (up to 85% of all inseminations). It provides an economical means for a livestock breeder to improve their herds utilizing males having very desirable traits.

Although common with cattle and swine, AI is not as widely practised in the breeding of horses. A small number of equine associations in North America accept only horses that have been conceived by "natural cover" or "natural service" – the actual physical mating of a mare to a stallion – the Jockey Club being the most notable of these, as no AI is allowed in Thoroughbred breeding. Other registries such as the AQHA and warmblood registries allow registration of foals created through AI, and the process is widely used allowing the breeding of mares to stallions not resident at the same facility – or even in the same country – through the use of transported frozen or cooled semen.

In modern species conservation, semen collection and artificial insemination is used also in birds. In 2013 scientist of the Justus-Liebig-University of Giessen, Germany, from the working group of Michael Lierz, Clinic for birds, reptiles, amphibians and fish, developed a novel technique for semen collection and artificial insemination in parrots producing the world's first macaw by assisted reproduction.