Artificial insemination

"IUI" redirects here. For other uses, see IUI (disambiguation).
Artificial insemination
Intervention
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 fertilization by means other than sexual intercourse. It is the medical alternative to sexual intercourse, or natural insemination, and is a fertility treatment for humans, a common practice in the breeding of dairy cattle (see Frozen bovine semen) and pigs, and is also used in other animal breeding.

Artificial insemination may employ assisted reproductive technology, donated sperm, or animal husbandry techniques.

In humans

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

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.[1] 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, i.e. by sexual intercourse.

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.

Preparations

A woman needing artificial insemination to achieve pregnancy can obtain sperm from her male partner or from a sperm donor; she may need a sperm donor if her partner produces too few motile sperm, if he carries a genetic disorder, or if she has no male partner. Sperm is usually obtained through male masturbation or by the use of an electrical stimulator, although a special condom, known as a collection condom, may be used to collect the semen during sexual 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 donor is 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), it is required that the sperm be "washed" in a laboratory and concentrated in Hams F10 media without L-glutamine, warmed to 37C.[2] This is because 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 extend or dilute 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, there is a need for a medical practitioner to wash it 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.[3]

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.

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. 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, enclosed air is removed by gently pressing the plunger forward before inserting the syringe 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. Ensuring that the woman is comfortable is often a priority. 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 twelve hours from the release of the ovum. For each woman who goes through this process, be it AI (artificial insemination) or (natural insemination), to increase chances for success, an understanding of her rhythm or natural cycle is important, often with the aid of ovulation tests such as basal temperature tests over, noting the color and texture of the vaginal mucous,and the softness of the nose of her cervix.

When performed at home without the presence of a professional this procedure is sometimes referred to as intravaginal insemination (IVI).[4]

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.) Resting on the table for fifteen minutes after an IUI is optimal for the woman to increase the pregnancy rate.[5]

Unlike intracervical insemination, intrauterine insemination normally requires a medical practitioner to perform the procedure. A female under thirty years of age has optimal chances with IUI; for the man, a TMS of more than 5 million per ml is optimal.[6] 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.[6] A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates.[7] However, GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles according to a randomized controlled trial.[8]

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.[9] Medical experts therefore recommend considering in vitro fertilization after one failed COH/IUI cycle for women aged ≥40 years.[9]

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.[10] In non-tubal sub fertility, fallopian tube sperm perfusion may be the preferred technique over intrauterine insemination.[11]

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.[12] 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.[13] For couples with unexplained infertility, unstimulated IUI is no more effective than natural means of conception.[14][15]

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)[citation needed]

Generally, it is 10 to 15% per menstrual cycle using ICI, and[16] and 15–20% per cycle for IUI.[16][unreliable source?] In IUI, about 60 to 70% have achieved pregnancy after 6 cycles.[17]

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:

$N = \frac{V_s \times c \times r_s}{n_r}$
• 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[18]
• 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% [16][19]
• nr is the total motile sperm count recommended for vaginal insemination (VI) or intra-cervical insemination (ICI), approximately 20 million pr. ml.[20]

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

Approximate live birth rate (rs) among infertile couples as a function of total motile sperm count (nr). Values are for intrauterine insemination.[citation needed]

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 (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)[19]

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.[21] 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.[22]

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.[23][24]

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'.[25] 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.[25]

Artificial insemination in livestock and pets

A man performing artificial insemination of a cow.
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 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.[26] 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 (Lierz et al., 2013).[27]

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 [28] 1981 Wolf Foundation Prize in Agriculture. Many techniques developed by him have since been applied to other species, including that of the human male.

Notes

1. ^ ref name="The International Federation of Gynecology and Obstetrics (FIGO)" group="International Federation of Gynecology and Obstetrics">Robinson, Sarah (2010-06-24). "Professor". International Federation of Gynecology and Obstetrics. Retrieved 2012-12-27.
2. ^ Adams, Robert, M.D."invitro fertilization technique", Monterey, CA, 1988
3. ^ Bagis T, Haydardedeoglu B, Kilicdag EB, Cok T, Simsek E, Parlakgumus AH (May 2010). "Single versus double intrauterine insemination in multi-follicular ovarian hyperstimulation cycles: a randomized trial". Hum Reprod 25 (7): 1684–90. doi:10.1093/humrep/deq112. PMID 20457669.
4. ^ European Sperm Bank USA
5. ^ Laurie Barclay. "Immobilization May Improve Pregnancy Rate After Intrauterine Insemination". Medscape Medical News. Retrieved October 31, 2009.
6. ^ a b Merviel P, Heraud MH, Grenier N, Lourdel E, Sanguinet P, Copin H (November 2008). "Predictive factors for pregnancy after intrauterine insemination (IUI): An analysis of 1038 cycles and a review of the literature". Fertil. Steril. 93 (1): 79–88. doi:10.1016/j.fertnstert.2008.09.058. PMID 18996517.
7. ^ Marshburn PB, Alanis M, Matthews ML, et al. (September 2009). "A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates". Fertil. Steril. 93 (1): 286–8. doi:10.1016/j.fertnstert.2009.07.972. PMID 19732887.
8. ^ Bellver J, Labarta E, Bosch E, et al. (June 2009). "GnRH agonist administration at the time of implantation does not improve pregnancy outcome in intrauterine insemination cycles: a randomized controlled trial". Fertil. Steril. 94 (3): 1065–71. doi:10.1016/j.fertnstert.2009.04.044. PMID 19501354.
9. ^ a b Harris, I.; Missmer, S.; Hornstein, M. (2010). "Poor success of gonadotropin-induced controlled ovarian hyperstimulation and intrauterine insemination for older women". Fertility and Sterility 94 (1): 144–148. doi:10.1016/j.fertnstert.2009.02.040. PMID 19394605. edit
10. ^ Leonidas Mamas, M.D.,Ph.D (March 2006). "Comparison of fallopian tube sperm perfusion and intrauterine tuboperitoneal insemination:a prospective randomized study". Fertility and Sterility Journal 85 (3): 735–740. doi:10.1016/j.fertnstert.2005.08.025. PMID 16500346.
11. ^ G S Shekhawat, MD (2012). "Intrauterine insemination versus Fallopian tube sperm perfusion in non-tubal infertility". Internet Medical Journal.
12. ^ Hurd WW, Randolph JF, Ansbacher R, Menge AC, Ohl DA, Brown AN (February 1993). "Comparison of intracervical, intrauterine, and intratubal techniques for donor insemination". Fertil. Steril. 59 (2): 339–42. PMID 8425628.
13. ^ IVF.com
14. ^ Fertility treatments 'no benefit'. BBC News, 7 August 2008
15. ^ Bhattacharya S, Harrild K, Mollison J, et al. (2008). "Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial". BMJ 337: a716. doi:10.1136/bmj.a716. PMC 2505091. PMID 18687718.
16. ^ a b c Utrecht CS News Subject: Infertility FAQ (part 4/4)
17. ^ Intrauterine insemination. Information notes from the fertility clinic at Aarhus University Hospital, Skejby. By PhD Ulrik Kesmodel et al.
18. ^ Essig, Maria G.; Edited by Susan Van Houten and Tracy Landauer, Reviewed by Martin Gabica and Avery L. Seifert (2007-02-20). "Semen Analysis". Healthwise. WebMD. Retrieved 2007-08-05.
19. ^ a b Cryos International – What is the expected pregnancy rate (PR) using your donor semen?
20. ^ Cryos International – How much sperm should I order?
21. ^ "Letter to the Editor: Artificial Impregnation". The Medical World: 163–164. April 1909. (cited in Gregoire, A. and Mayer, R. (1964). "The impregnators". Fertility and Sterility (16): 130–134.)
22. ^ Kara W. Swanson, “The Birth of the Sperm Bank,” Annals of Iowa, 71 (Summer 2012), 241–76.
23. ^ Oral Sex, a Knife Fight and Then Sperm Still Impregnated Girl. Account of a Girl Impregnated After Oral Sex Shows Sperms' Incredible Survivability By LAUREN COX. abcNEWS/Health Feb. 3, 2010
24. ^ Cimino, C.; Guastella, G.; Comparetto, G.; Gullo, D.; Perino, A.; Benigno, M.; Barba, G.; Cittadini, E. (1988). "Direct intraperitoneal insemination (DIPI) for the treatment of refractory infertility unrelated to female organic pelvic disease". Acta Europaea fertilitatis 19 (2): 61–68. PMID 3223194.
25. ^ a b Marcia C. Inhorn (2003). "Global infertility and the globalization of new reproductive technologies: Illustrations from Egypt". Social Science and Medicine 56: 1837–1851.
26. ^ The Jockey Club has never allowed artificial insemination.
27. ^ http://www.nature.com/srep/2013/130625/srep02066/full/srep02066.html
28. ^ 1981 Wolf Foundation Prize in Agriculture

References

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