Artificial insemination

"IUI" redirects here. For other uses, see IUI (disambiguation).

Artificial insemination
Schematic illustration of artificial insemination
ICD-9-CM	69.92
MeSH	D007315

Artificial insemination (AI) is the deliberate introduction of semen into a female's vagina or oviduct for the purpose of achieving a pregnancy through fertilisation by means other than copulation. It is the medical alternative to sexual intercourse, or natural insemination.

Artificial insemination is a fertility treatment for humans, and is a common practice in the breeding of dairy cattle (see the main article frozen bovine semen) and pigs, and is also used in other animal breeding. Artificial insemination may employ assisted reproductive technology, donated sperm, and/or animal husbandry techniques.

In humans

Artificial insemination is a means whereby a woman can achieve pregnancy not involving sexual intercourse.

There are a number of reasons why a woman would choose artificial means 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 an impotent male, donor sperm may be used. A sperm donor may also be used when two women wish to have a biological child, or by a single woman who does not have a male partner, when she does not want a male partner, or when a male partner's physical limitation impedes his ability to impregnate her by natural means, ie. by sexual intercourse.

Preparations

A woman needing artificial insemination to achieve pregnancy can obtain sperm from her male partner or from a sperm donor, for example, the woman's partner produces too few motile sperm, or if he carries a genetic disorder, or if the woman has no male partner. Sperm is usually obtained through masturbation or the use of an electrical stimulator, although a special condom, known as a collection condom, may be used to collect the semen during intercourse.

Sperm provided by a sperm bank will be produced by a donor attending at the sperm bank's premises in order to ascertain the donor's identity on every occasion. The donor masturbates to provide an ejaculate in a small container. The contents of the container are usually extended with chemicals in order to provide a number of vials for insemination. The sperm is frozen and quarantined for a period of usually six months and the is donor re-tested prior to the sperm being used for artificial insemination.

A woman's menstrual cycle is closely observed, by tracking basal body temperature and changes in vaginal mucus, or using ovulation kits, ultrasounds or blood tests.

When using intrauterine insemination (IUI), the sperm must have been “washed” in a laboratory and concentrated in Hams F10 media without L-glutamine, warmed to 37C. The process of “washing” the sperm increases the chances of fertilization and removes any mucus and non-motile sperm in the semen. Pre and post concentration of motile sperm is counted.

Sperm from a sperm bank will be frozen and quarantined for a particular period and the donor will be tested before and after production of the sample to ensure that he does not carry a transmissible disease. Sperm samples donated in this way are commonly produced through masturbation by the sperm donor at the sperm bank. A chemical known as a cryoprotectant is added to the sperm to aid the freezing and thawing process. Further chemicals may be added which separate the most active sperm in the sample as well as extending or diluting the sample so that vials for a number of inseminations are produced. 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. Private donor sperm is usually produced through masturbation, but some donors use a collection condom to obtain the sperm when having sexual intercourse with their own partners.

Procedure

When an ovum is released, semen is introduced into the woman's vagina or uterus. The semen may be fresh or it may be frozen semen which has been thawed. Where donor sperm is supplied by a sperm bank, it will always be quarantined and frozen and will need to be thawed before use.

For vaginal artificial insemination, semen is usually placed in the vagina using a needleless syringe. A longer tube, called a tom cat, may be attached to the end of the syringe to facilitate deposit of the semen deeper into the vagina. The woman is generally advised to lie still for a half hour or so after the insemination to prevent seepage and to allow fertilization to take place.

A more efficient method of artificial insemination is to insert semen directly into the woman's uterus. Where this method is employed it is important that only 'washed' semen be used and this is inserted into the uterus by means of a catheter. Sperm banks and fertility clinics usually offer 'washed' semen for this purpose, but if partner sperm is used it must also be 'washed' by a medical practitioner to eliminate the risk of cramping.

Semen is occasionally inserted twice within a 'treatment cycle'. A double intrauterine insemination has been theorized to increase 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.

An alternative method to the use of a needleless syringe or a catheter involves the placing of partner or donor sperm in the woman's vagina using a specially designed cervical cap, a conception device or conception cap. This holds the semen in place near to the entrance to the cervix for a period of time, usually for several hours, to allow fertilization to take place. Using this method, a woman may go about her usual activities while the cervical cap holds the semen in the vagina. One advantage with the conception device is that fresh, non-liquified semen may be used.

If the procedure is successful, the woman will conceive and carry to term a baby. The baby will be the woman's biological child, and the biological child of the man whose sperm was used to inseminate her, whether he is the woman's partner or a donor. A pregnancy resulting from artificial insemination will be no different from a pregnancy achieved by sexual intercourse. However, there may be a slight increased likelihood of multiple births if drugs are used by the woman for a 'stimulated' cycle.

Donor variations

Either sperm provided by the woman's husband or partner (artificial insemination by husband) or sperm provided by a known or anonymous sperm donor (artificial insemination by donor) can be used.

Techniques

Intracervical insemination

Intracervical insemination (ICI) is the easiest and most popular insemination technique. The process closely replicates natural insemination, with fresh semen being directly deposited on to the neck of the cervix by the penis during vaginal intercourse. When the male ejaculates, sperm deposited this way will quickly swim into the cervix and toward the fallopian tubes where an ovum recently released by the ovary(s) hopefully awaits fertilization. It is the simplest method of artificial insemination and "unwashed" or raw semen is normally used. It is commonly used in home, self-insemination and practitioner insemination procedures, and for inseminations where semen is provided by private donors.

ICI involves insemination with raw fresh or frozen semen (which has been thawed) and which has been provided by the woman's partner or by a sperm donor into the cervix usually by injecting it with a needleless 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. After the syringe has been filled with semen, it should be raised a little bit and any air bubbles removed by gently pressing the plunger forward before inserting the syringe into the vagina.

The syringe should be inserted carefully so that the tip is as close to the entrance to the cervix as possible. The woman should be comfortable at all times. A vaginal speculum may be used to hold open the vagina so that the cervix may be observed and the syringe inserted more accurately through the open speculum. The plunger is then pushed forward and the semen in the syringe is emptied into the vagina. The syringe (and speculum if used) may be left in place for several minutes and the woman is advised to lie still for about half-an-hour to increase the chances of conception.

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 in order to hold the semen close to the entrance to the cervix.

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.

Timing is critical as the window and opportunity for fertilization is little more than 12 hours from the release of the ovum. For each woman who goes through this process be it AI (artificial insemination) or NI (natural insemination), to increase chances for success an understanding of her rhythm or natural cycle is very important. Home ovulation tests are now available. Doing and understanding Basal Temperature Tests over several cycles with is a slight dip and quick rise at the time of ovulation. She should note the color and texture of her vaginal mucous discharge. At the time of ovulation the protective cervical plug is released giving the vaginal discharge a stringy texture with an egg white color. A woman may also be able check the softness of the nose of her cervix by inserting two fingers. It should be considerably softer and more pliable than normal.

When performed at home without the presence of a professional this procedure is sometimes referred to as intravaginal insemination (IVI).

Intrauterine insemination

Washed sperm, spermatozoa that have been removed from most other components of the seminal fluids, can be injected directly into a woman's uterus in a process called intrauterine insemination (IUI). If the semen is not washed 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.) The woman should rest on the table for 15 minutes after an IUI to optimize the pregnancy rate.

Unlike intracervical insemination, intrauterine insemination must normally be performed by a medical practitioner.

To have optimal chances with IUI, the female should be under 30 years of age, and the man should have a TMS of more than 5 million per ml. 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.

It can be used in conjunction with ovarian hyperstimulation. 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 ≥40 years, there appears to be no benefit after a single cycle of COH/IUI. It is therefore recommended to consider in vitro fertilization after one failed COH/IUI cycle for women aged ≥40 years.

Intrauterine tuboperitoneal insemination

Intrauterine tuboperitoneal insemination (IUTPI) is insemination where both the uterus and fallopian tubes are filled with insemination fluid. The cervix is clamped to prevent leakage to the vagina, best achieved with the specially designed Double Nut Bivalve (DNB) speculum. The sperm is mixed to create a volume of 10 ml, sufficient enough 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

IUI can furthermore be combined with intratubal insemination (ITI), 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

Success rates, or pregnancy rates for artificial insemination 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.

Approximate pregnancy rate as a function of total sperm count (may be twice as large as total motile sperm count). Values are for intrauterine insemination. (Old data, rates are likely higher today)

Generally, it is 10 to 15% per menstrual cycle using ICI, and and 15–20% per cycle for IUI. In IUI, about 60 to 70% have achieved pregnancy after 6 cycles.

As seen on the graph, the pregnancy rate also depends on the total sperm count, or, more specifically, the total motile sperm count (TMSC), used in a cycle. It 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 before getting pregnant. Women whose age is becoming a major factor in fertility may not want to spend that extra time.

Samples per child

How many samples (ejaculates) that are required 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:

$N={\frac {V_{s}\times c\times r_{s}}{n_{r}}}$

• N is how many children a single sample can give rise to.
• V_s 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
• r_s is the pregnancy rate per cycle, between 10% to 35%
• n_r is the total motile sperm count recommended for vaginal insemination (VI) or intra-cervical insemination (ICI), approximately 20 million pr. ml.

The pregnancy rate increases with increasing number of motile sperm used, but only up to a certain degree, when other factors become limiting instead.

Derivation of the equation (click at right to view)

In the simplest form, the equation reads:

$N={\frac {n_{s}}{n_{c}}}\times r_{s}$

N is how many children a single sample can give rise to

n_s is the number of vials produced per sample

n_c is the number of vials used in a cycle

r_s is the pregnancy rate per cycle

n_s can be further split into:

$n_{s}={\frac {V_{s}}{V_{v}}}$

n_s is the number of vials produced per sample

V_s is the volume of a sample

V_v is the volume of the vials used

n_c may be split into:

$n_{c}={\frac {n_{r}}{n_{s}}}$

n_c is the number of vials used in a cycle

n_r is the number of motile sperm recommended for use in a cycle

n_s is the number of motile sperm in a vial

n_s may be split into:

$n_{s}=V_{v}\times c$

n_s is the number of motile sperm in a vial

V_v is the volume of the vials used

c is the concentration of motile sperm in a sample

Thus, the factors can be presented as follows:

$N={\frac {V_{s}\times c\times r_{s}}{n_{r}}}\times {\frac {V_{v}}{V_{v}}}$

N is how many children a single sample can help giving rise to

V_s is the volume of a sample

c is the concentration of motile sperm in a sample

r_s is the pregnancy rate per cycle

n_r is the number of motile sperm recommended for use in a cycles

V_v is the volume of the vials used (its value doesn't affect N and may be eliminated. In short, the smaller the vials, the more vials are used)

Approximate live birth rate (r_s) among infertile couples as a function of total motile sperm count (n_r). Values are for intrauterine insemination.

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 (IUI), a centrifugation fraction (f_c) may be added to the equation:

f_c 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 (n_r=5 million)

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

History

The first reported case of artificial insemination by donor occurred in 1884: a Philadelphia professor of medicine 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.

Social implications

One of the key global issues resulting 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, especially those with large Muslim populations, 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.

Artificial insemination in livestock and pets

A breeding mount with built-in artificial vagina used in semen collection from horses for use in artificial insemination

Pioneering AI begun in Russia in 1899 by Ivanoff. In 1935 Suffolk sheep diluted semen was sent from Cambridge by plane to Krakoiv Poland, in and international research joint (Prawochenki from Poland, Milovanoff from URSS, Hammond from Cambridge, Walton from Scotland, and Thomasset from Uruguay). Artificial insemination is used in many non-human animals, including sheep, horses, cattle, pigs, dogs, pedigree animals generally, zoo animals, turkeys and even honeybees. 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).

IA tools brought from the USSR by Dr. Ing. Luis Thomasset in 1935 to work at Cambridge Laboratories and South America.

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).

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 Prof. Dr. 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 (Lierz et al., 2013).

Modern Artificial Insemination was pioneered by Dr. 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 fertiilty, 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.

See also

• Accidental incest
• Conception device
• Donor conceived people
• Ejaculation
• Embryo transfer
• Ex-situ conservation
• Frozen zoo
• Intracytoplasmic sperm injection
• Semen extender
• Sperm bank
• Sperm donation
• Sperm sorting
• Surrogacy
• Wildlife

References

• Hammond, John, et al., The Artificial Insemination of Cattle (Cambridge, Heffer, 1947, 61pp)

External links

• Detailed description of the different fertility treatment options available
• A history of artificial insemination
• What are the Ethical Considerations for Sperm Donation?
• United States state court rules sperm donor is not liable for children
• UK Sperm Donors Lose Anonymity
• AI technique in the equine
• IntraUterine TuboPeritoneal Insemination (IUTPI)
• The Hastings Center's Bioethics Briefing Book entry on assisted reproduction
• Annales de Gembloux L´Organisation Scientifique de l Índustrie Animale en URSS, Artificial Insemination in the URSS, by Luis Thomasset, 1936
• More Information on Intrauterine Insemination