INTRODUCTION — Artificial insemination refers to the introduction of semen into the vagina, uterus, or oviduct by a means other than sexual intercourse. When the procedure is performed using sperm from a man other than the patient's partner, it is termed therapeutic donor insemination (TDI) [1-3].

Therapeutic donor insemination (TDI) has been in use longer than any other artificial reproductive technique for treatment for male infertility. In 1987, over 170,000 women in the United States were treated for infertility using donor insemination, and in 1990, it was estimated that TDI produced 11,400 to 23,400 pregnancies annually [4].

INDICATIONS — Historically, TDI was primarily a treatment of male factor infertility. However, the indications for TDI have expanded such that it has become an alternative approach to fertility for some women [5]. The procedure can be considered in:

●Couples in whom one or both partners are carriers of a heritable disease

●Couples who are serodiscordant for sexually transmissible viral infections

●Couples who fail to achieve fertilization with in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)

●Women without a male partner

●Couples who are incompatible for red cell antigens (eg, D, Kell) associated with hemolytic disease of the newborn and with a history of a severely affected infant

Male partner infertility — When the male partner has azoospermia, severe oligospermia, or other severe semen abnormalities resulting in infertility, the main treatment options are: (1) adoption, (2) TDI, (3) ICSI, and (4) remaining childless. Many couples choose to have ICSI with or without testicular biopsy as the initial approach to treatment of infertility due to severe semen abnormalities [6]. However, the high cost of ICSI forces other couples to undergo TDI for financial reasons. (See "Intracytoplasmic sperm injection".)

Heritable disease — The potential for heritable disease in offspring should be considered in couples in whom either or both partners are affected by the disease or when asymptomatic carrier couples have an affected child. Depending upon the genetics of the disorder, such couples may opt for TDI from a noncarrier or phenotypically normal donor. Preimplantation genetic diagnosis with selection of unaffected blastocytes for implantation and prenatal genetic amniocentesis/chorionic villous biopsy with termination of an affected fetus are other options. These options are only useful when laboratory studies can identify the responsible gene or detect a diagnostic marker. (See "Preimplantation genetic testing".)

Serodiscordance for viral infection — Men who have sexually transmissible viral infections, such as hepatitis C and HIV, and a seronegative partner risk infecting the uninfected partner with their semen [7]. One option for these couples is TDI from an uninfected donor. In one survey of serodiscordant couples, 48 percent of respondents stated they would prefer TDI to timed unprotected intercourse [8].

Failed ART — TDI can be successful in infertile couples after failure of different testicular sperm retrieval procedures (ie, testicular sperm extraction, microsurgical epididymal sperm aspiration) or after fertilization failure by IVF or ICSI. In one study, as an example, 19 couples at the Oregon Health and Science University who failed 32 ICSI cycles chose to pursue TDI [9]. A total of 61 TDI cycles were completed and 16 of the 19 couples conceived within seven cycles of donor insemination. The pregnancy rate per cycle was 28 percent, and an average of 3.2 inseminations were required to achieve a pregnancy.

Absence of a male partner — A report by the Ethics Committee of the American Society for Reproductive Medicine (ASRM) affirmed the right of single, gay, and lesbian persons to have access to fertility services [10]. TDI is commonly used to achieve pregnancy in women without a male partner, such as single women and lesbian couples. In 1979, physicians reported that only 9.5 percent of TDIs were performed on females without male partners; however, by 1990 that number increased to 35 percent [11,12]. In addition, a survey of assisted reproductive technology clinics revealed that 74 to 79 percent of clinics offered services to single or lesbian women [13]. The number of single or lesbian women who perform self-inseminations is unknown.

CONTRAINDICATIONS — Women with subfertility due to tubal factors, uterine malformations, active pelvic infection, or uncorrected anovulation are not good candidates for donor insemination.

GUIDELINES — Although TDI has been an established medical practice since the early twentieth century, little surveillance or regulation was placed on the practice until 1979, when a landmark survey of TDI practices in the United States was published [11]. The study showed that physicians usually selected the donors, and that most physicians used medical students or hospital residents, while 10 percent used donors from military academies, husbands of patients in their practice, or friends. Screening was often limited and consisted primarily of the physician asking if the donor had any family or personal history of genetic diseases. Only 29 percent of physicians screened donors with biochemical tests other than blood type, and these tests were primarily for communicable diseases. In addition, 50 percent of respondents rejected donors who had a history of a sexually transmitted disease or drug use; 50 to 70 percent attempted to match donors with the recipient's husband in hair color, skin color, eye color, and/or height, while 8 percent did not attempt any donor matching; and nearly one third used multiple donors within a single cycle. Most physicians limited the use of a donor to six pregnancies, while 10 percent used each donor for nine or more pregnancies, and 88 percent had no specific policy regarding the maximum use of a donor. Only one-third kept permanent records regarding donors and children from donor cycles on record.

Since this study, the field of sperm donation has been revolutionized with increased regulation regarding selection criteria and screening for sexually transmitted diseases and genetic disorders. In the United States, the ASRM 2013 Guidelines for Gamete and Embryo Donation provide the most recent detailed recommendations for evaluation of potential sperm, oocyte, and embryo donors, incorporating current information about optimal screening and testing for sexually transmitted infections (including HIV), genetic diseases, and psychological assessments [5]. The document includes information from the US Centers for Disease Control and Prevention, the US Food and Drug Administration, and the American Association of Tissue Banks. In 2014, the Ethics Committee of the ASRM published a report on the interests, obligations, and rights of the [egg or sperm] donor in gamete donation [14]. A synopsis of these guidelines, and additional information, are described below. Federal regulations for gamete and embryo donation in the United States are available online:

●www.fda.gov/BiologicsBloodVaccines/default.htm

Donor requirements — It is clear that for ethical reasons, no individual associated with a facility performing the TDI, including the physician, can serve as a donor in that practice.

Donors should be of legal age (≥18 years old) but ideally younger than age 40 years; however, many sperm banks limit the age of their donors to under 35 years. The upper age limit is meant to limit the possibility of aneuploidy related to paternal age, although the data are conflicting. While one study of over 2100 donor insemination cycles reported increasing male age negatively impacted pregnancy rates [15], a larger study of nearly 39,000 women who underwent TDI reported no differences in the live birth or miscarriage rates with increasing age of the donor [16]. (See "Effect of advanced paternal age on fertility and pregnancy".)

A psychological assessment by a mental health professional should be performed on all donors. The emotional, psychological, and social aspects of sperm donation are addressed as part of this evaluation. Donors are also required to complete questionnaires regarding their attitudes or concerns about transmission of information to or future contact with biological progeny. (See 'Legal and ethical concerns' below.)

Donors are limited to producing 25 births in a population of 800,000 people to minimize the risk of inadvertent consanguinity; however, specific guidelines and limitations vary among countries due to differences in population size and cultural and psychosocial influences [17]. In France, anonymous donor insemination was estimated to be responsible for 0.46 percent of consanguineous births and 0.01 percent of recessive diseases [18]. In fact, consanguineous unions between descendants of anonymous sperm donors were four times less numerous than those between descendants with false paternities.

Donors should also be informed of their responsibility to update their records with future changes in their health status.

Donors are advised to abstain from ejaculation for 48 to 72 hours prior to producing a specimen [19], and the specimen must be evaluated within one to two hours. Compensation for donation varies according to the sperm bank used; it is generally USD $60 to 100 per specimen. Proven fertility is not essential.

If the recipient prefers directed donation with a known donor, the donor must still fulfill the above criteria and undergo the screening procedures required of anonymous donors. In addition, legal issues such as parental rights must be addressed prior to insemination. The cost with a directed donor is typically less than with an anonymous donor.

Screening — Donors should be made aware of their responsibility to give accurate medical information. A complete medical history, physical examination (refer to www.sart.org for male donation physical examination form), and routine blood tests including blood type/Rh testing (and possibly a complete blood count, liver function tests, and a chemistry panel) are performed to identify healthy men without evidence of sexually transmitted diseases or known or suspected heritable disease. A complete list of screening questions is available online at "Uniform Donor Application" at www.sart.org.

A complete sexual history is taken to exclude men who might be at high risk for HIV or other sexually transmitted diseases (table 1). Evidence of urethral discharge, genital warts, and/or genital ulcers precludes sperm donation. The United States Food and Drug Administration (FDA) requires that donors be screened for risk factors and evidence of several communicable diseases, including [20]:

●HIV, types 1 and 2

●Hepatitis B

●Hepatitis C

●Treponema pallidum

●Chlamydia trachomatis

●Neisseria gonorrhea

●Human T-lymphotropic virus (HTLV), types I and II

●Cytomegalovirus (CMV)

Potential donors also undergo a genetic evaluation. In the United States, the ASRM has published minimum genetic testing for sperm donors [5]. The FDA does not mandate an extensive evaluation for heritable diseases. Most sperm banks advertise that a three-generation family history is taken to evaluate for any heritable diseases. The donor and his first-degree relatives should not have any major Mendelian disorders, major congenital malformations, familial disease with a major genetic component, or known karyotype abnormalities. Although some sperm banks perform a chromosomal analysis, this is not required. The low risk of chromosomal abnormality in these men was illustrated by a large retrospective study that determined the karyotype of over 10,000 normal fertile sperm donors over a 25-year period [21]. Thirty-eight karyotype aberrations (0.37 percent) were diagnosed, including 21 balanced chromosomal rearrangements. The frequency of chromosomal aberrations was similar to that in the general population of newborns.

Genetic testing of high-risk groups is performed; however, ASRM recommends testing for cystic fibrosis in all donors [5]. In the United States, guidelines for ethnicity and population-based genetic screening are available from the American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG). If test results reveal a heterozygous state, guidelines do not mandate rejection of the donor, but most donor banks state that they screen donors and exclude donors who have any indication of transmitting a higher risk of a hereditary disease. Genetic testing of sperm donors varies among sperm banks; the specific tests performed should be ascertained when using sperm from one of these banks [22]. Concerns have been raised about the frequency of genetic traits in the pool of young sperm donors, since these genes may be asymptomatic and thus unknowingly transmitted. Therefore it is important that intended parents be made aware of the limitations of current genetic testing of prospective donors [23,24].

Testing for infection

Risk of infection — A California cryobank reported 47 infections among 48,000 recipients of donor insemination between 1986 and 2004 (1 infection per 1000 recipients) [25]. The rate dropped to 1 in 25,000 for the last 10 years of the study, when semen specimens were processed more intensively. It was not possible to ascertain the proportion of these infections attributable to infection in the semen sample versus recipient factors.

Precautions — Donor sperm samples are quarantined for at least 180 days/six months after the date of donation to allow testing and retesting of the donors for communicable diseases. The panel of laboratory tests listed above are performed prior to donation or within seven days after recovery of the specimen, after quarantine, and at six month intervals. These tests must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or CLIA-exempt laboratory. The tests used must be FDA licensed, approved or cleared donor-screening tests.

●If the tests are negative on initial screening, donor samples are prepared for cryopreservation. If the donor tests negative again, after a minimum of 180 days, samples can be released for use.

●If test results are initially positive, the results should be verified and then the individual should be contacted, counseled, and treated according to standard medical practice guidelines.

Although physical separation of specimens that are eligible or quarantined is not required, specimens must be clearly identified and labeled appropriately. Specimens that are ineligible must be physically separated from eligible and quarantined specimens. The FDA requires that donor eligibility records must be maintained for 10 years after the date of distribution, disposition, or expiration, whichever is later. The ASRM recommends that a permanent record of the initial evaluation, test results, and outcomes from each cycle be maintained permanently [5].

Infection-specific protocols — The timing for sperm donation after infection varies based on the type of infection.

●Cytomegalovirus (CMV): Donors whose serological results are positive for CMV undergo testing to determine whether the infection is likely to be recent or old. Sperm samples from recently infected donors are discarded [26]. Some providers will use sperm samples from men with evidence of remote CMV infection if the recipient is also positive for CMV, but practice patterns vary [27]. If the recipient is CMV-negative, she should be counseled that ideally she should receive sperm from a CMV-negative donor. However, it is reasonable to allow a patient to choose a donor who is CMV-positive (remote infection), but who meets all other criteria, as long as she provides informed consent indicating that she understands that it is possible to contract CMV from the washed donor sperm. (See "Epidemiology, clinical manifestations, and treatment of cytomegalovirus infection in immunocompetent adults" and "Overview of diagnostic tests for cytomegalovirus infection".)

●Zika virus: Based on cases of sexual transmission of the Zika virus, the US Food and Drug Administration (FDA) recommends that sperm donors be considered ineligible if they have been diagnosed with Zika virus infection, were in an area with active Zika virus transmission, or had sex with a male with either of those risk factors, within the past six months [28]. (See "Zika virus infection: An overview".)

●West Nile virus: It is recommended that gamete donors with confirmed or suspected West Nile virus infection be deferred until 14 days after resolution of the infection or 28 days from the onset of symptoms, whichever is later [29]. (See "Epidemiology and pathogenesis of West Nile virus infection".)

●Smallpox: Donors who have received smallpox vaccine and individuals who have been infected by a recent recipient of the vaccine are advised to defer donation until the vaccine scab has spontaneously separated or until 14 days after resolution of any vaccine-related complications. (See "Variola virus (smallpox)" and "Vaccinia virus as the smallpox vaccine".)

●Viral syndromes: Donors with recent significant fever, flu-like illnesses, viral meningitis, encephalitis, or meningoencephalitis should be deferred until healthy [30].

●Ebola: Ebola virus has been detected in semen 199 days from the onset of infection in male survivors [31]. It is not known how long the virus can persist in semen and potentially be transmitted. The World Health Organization has released interim guidelines suggesting that all Ebola survivors "be offered semen testing for Ebola virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) three months after disease onset, and every month thereafter until two consecutive semen specimens collected at least one week apart test negative for Ebola virus RNA" [32].

Semen specimen — A single donor produces several semen specimens. Donors produce each specimen in a private room on site. These specimens should meet minimal semen parameters (table 2) (see "Approach to the male with infertility", section on 'Semen analysis'). Studies indicate that donor sperm can result in pregnancy over a wide range of donor sperm concentration, motility, and morphology [33,34].

Proper sperm processing is crucial to successful insemination. Processing for intrauterine insemination separates the sperm from the seminal fluid so that only the most motile, morphologically normal sperm are inseminated. These two characteristics are the most important specimen-related factors affecting outcome [35]. This process is also critical in removing the prostaglandins, inflammatory cells, debris, and proteins from the whole semen specimen, and concentrating the specimen in a small volume. Details of procedure for sperm processing are outside the scope of this topic review.

Unwashed sperm can be used for intracervical insemination or for self-insemination. Pregnancy rates are lower with unwashed sperm, thus washed sperm and intrauterine insemination are typically recommended.

Screening recipients — A routine medical and reproductive history is taken and a general physical examination is performed. Laboratory screening is similar to a standard prenatal panel and includes blood type, Rh factor, antibody screen; testing for immunity to rubella and varicella; testing for active cytomegalovirus infection; and appropriate assessments for the presence of sexually transmitted diseases (HIV, syphilis, gonorrhea, chlamydia, hepatitis B and C) and HTLV type I and II when clinically indicated [5]. ACOG prenatal/preconception guidelines also suggest screening women for cystic fibrosis and other genetic diseases for which they are at risk (see "The preconception office visit"). Theoretically, patients could opt out of this recommendation since the donors are screened for genetic diseases.

Rh-negative women are counseled that they can avoid the risk of hemolytic disease of the fetus and newborn and the need for RhoGAM if they select an Rh-negative donor, but this is generally not a major criterion for donor selection. (See "Postnatal diagnosis and management of hemolytic disease of the fetus and newborn" and "RhD alloimmunization: Prevention in pregnant and postpartum patients".)

Since most pregnancies occur within six cycles, an infertility evaluation should be initiated in woman who have not conceived after six months of inseminations and have not had a previous evaluation. Given the costs of TDI, it makes sense to assess the recipient's fertility even before proceeding with the procedure, especially in women with risk factors for subfertility. As an example, women with risk factors for tubal occlusion should have hysterosalpingography. Screening for ovarian reserve with a day 3 FSH and estradiol testing provides additional potentially prognostic information in women over 40 years of age.

Choosing the donor — Patients can refer to the American Association of Tissue Banks website to find accredited sperm banks. Sperm banks offer varying levels of information about their donors. Some types of information provided include donor profiles (race; height; weight; hair, eye and skin color; educational level; religion; ethnic background), audio tapes, hobbies, baby photos, personality profiles, staff impression reports, essays written by the donor, a report of facial features, and prior history of success in producing a pregnancy [36]. This information may be free; however, some banks will charge for more detailed descriptions or photos. Some banks also offer a consultation service for donor matching.

Documentation — All medical records, including screening evaluations and cycle outcomes, are maintained as permanent records. Informed consent is obtained from the donor to collect sperm and from the recipient for the insemination.

PROCEDURE — The patient lies in a dorsal lithotomy position on a standard gynecologic examination table with her feet in stirrups. A speculum is placed in the vagina and the cervix is visualized. Neither local anesthetic nor antibiotic prophylaxis is needed.

The sperm specimen is aspirated into a 1.0 cc syringe. The needle is removed and the plastic syringe is attached to a flexible 18-cm polyethylene catheter (a standard intrauterine insemination catheter) (picture 1). All air is removed from the syringe and catheter and the catheter is inserted through the endocervical canal and should extend 5.5 cm in a typical uterus. The sperm are then injected. Mild cramping may occur. After the injection, the catheter is slowly removed and the patient instructed to remain lying flat and still for 15 minutes. A single intrauterine insemination appears to be adequate [37,38]; most observational data from studies of IUI with donor sperm suggest that pregnancy rates are not significantly higher if the procedure is repeated the following day [39-41].

The woman should be able to resume her normal activities upon leaving the office. Subsequent sexual intercourse has not been shown to impede fertilization, but most clinicians suggest abstinence for 24 hours after insemination.

Intrauterine inseminations should be performed by certified health professionals including physicians and nurses who are experienced in administering gynecologic care.

FACTORS AFFECTING SUCCESS — Efforts to improve pregnancy rates have focused upon the number of inseminated sperm, timing of insemination(s), and methods for insemination. The major non-modifiable variables which reduce the likelihood of a successful outcome from the procedure include advanced maternal age and use of frozen sperm.

Maternal age — Maternal age plays a major role in determining a woman's fertility, regardless of the means used to achieve pregnancy (except donor egg) [42] (see "Effects of advanced maternal age on pregnancy"). The effect of advanced maternal age on success of TDI was illustrated in a review of cumulative pregnancy rates in women under and over 30 years of age and included data from almost 3000 cycles over a 10-year interval [43]. Women under 30 years old had higher pregnancy rates at 3, 6, and 12 months than women over 30 years old (21, 40, and 62 percent versus 17, 26, and 44 percent respectively) [43]. The maximum maternal age for administering TDI is at the discretion of the health professional or facility providing the recipient with her care.

Fresh versus frozen sperm — Cryopreservation and thaw methods decrease sperm motility and viability, which, in turn, appear to result in lower pregnancy rates. Concerns over a difference in success rates with use of fresh versus frozen donor sperm are mostly academic as current guidelines prohibit insemination of fresh donor sperm.

The lower fecundity with frozen compared with fresh sperm was illustrated in two large, randomized, crossover trials:

●In the first trial, 381 patients received alternating cycles of fresh or cryopreserved semen [44]. Fresh and frozen sperm cycles resulted in fecundity of 18.9 and 5.0 percent, respectively.

●The second trial involved 288 patients with a similar crossover design, but a higher number of motile sperm were inseminated in women in the cryopreserved arm by using a more concentrated cryoprotectant [45]. Despite this intervention, fresh sperm cycles still resulted in greater fecundity than in the group receiving cryopreserved semen (27.4 and 10.4 percent, respectively).

Recent evidence suggests that long-term cryo-storage of sperm does not impact sperm motility, which is viewed as a predictor of sperm function after thawing [46].

Number of inseminated sperm — Data from studies in cattle show that the number of fresh sperm inseminated must be over a critical threshold to achieve maximum pregnancy rates. When declining pregnancy rates in women after insemination of cryopreserved donor sperm were noted, the possibility of a critical threshold in humans was investigated, with variable findings:

●Data from the Central Semen Bank of Denmark (n = 3418 frozen ejaculates) showed that increasing the total motile sperm count from <10x10⁶ to 11 to 19x10⁶ to >19x10⁶ increased the likelihood of achieving pregnancy [47]. However, once the count was above 19x10⁶, no additional benefit was observed.

●Another study found that frozen ejaculates with at least 20x10⁶ sperm yielded pregnancy rates that compared favorably with fresh samples containing more sperm [48].

●By contrast, a third study found no increase in pregnancy rate when inseminating with 1x10⁶ versus >5x10⁶ motile sperm [49].

Although these data are discordant and there is no consensus on the optimal sperm count for insemination with cryopreserved sperm, most centers make an effort to select donors with consistently high sperm concentrations in their ejaculates. A large number of potential donors are rejected due to inadequate sperm counts. Our minimal criteria are shown in the table (table 2).

Timing of insemination — The procedure must be done on the expected day of ovulation. Cryopreserved sperm have a shorter lifespan than fresh sperm, thus accurate timing is thought to be imperative. Insemination can be timed using basal body temperature charting, urinary LH surge, serum LH surge, and/or ultrasound findings (dominant follicle ≥18 mm) for determining ovulation. Double insemination (on two consecutive days) does not appear to increase clinical pregnancy rates [38].

Most centers perform a single insemination one day after the LH surge is detected in urine since the rise in urine LH occurs on the day before ovulation [50]. The rise in serum LH typically occurs approximately 36 hours before the oocyte is released from the follicle into the fallopian tube, and LH appears in the urine 12 hours after it appears in serum. (See "Evaluation of the menstrual cycle and timing of ovulation", section on 'Timing of ovulation' and "Evaluation of the menstrual cycle and timing of ovulation", section on 'Measurement of LH surge and estradiol rise'.)

Women receiving donor insemination without any infertility diagnoses can pursue TDI in natural (fresh) cycles. After 3 to 6 natural (fresh) cycles, ovulation induction with clomiphene citrate or gonadotropins can be considered.

Intrauterine versus intracervical insemination — Traditionally, intracervical inseminations (ICI) were performed with fresh donor semen. A volume of 1.5 to 2.5 mL was injected into the endocervical canal; fresh specimens were not injected into the uterus due to the potential for serious reactions to proteins, prostaglandins, and bacteria. Alternative modes of insemination have been explored because of increasing concerns about transmission of sexually transmitted diseases, the mandate for use of frozen specimens, and the subsequent decrease in pregnancy rates.

Currently, the highest pregnancy rates are achieved with intrauterine insemination (IUI) using washed sperm. This technique bypasses vaginal and cervical factors that might impair fertility and increases 100-fold the number of sperm reaching the uterine cavity. A systematic review of randomized trials comparing IUI with intracervical inseminations showed IUI led to significantly higher pregnancy rates (odds ratio [OR] 3.37, 95% CI 1.90-5.96) and higher live birth rates (OR 1.98, 95% CI 1.02-3.86), without increasing multiple birth rates [51].

OUTCOME — Pregnancy rates and pregnancy outcomes in fertile women undergoing TDI with fresh semen are comparable to those in normal controls matched for age. The success of TDI can be illustrated by the following representative examples:

●A study of couples undergoing TDI with fresh semen reported a fecundity rate (number of pregnancies/number of treatment cycles) of 20 percent and a six-cycle cumulative pregnancy rate of 74 percent, which approached the pregnancy rate in women who discontinued oral contraceptive pills to attempt pregnancy [52].

●A retrospective study compared TDI success rates in single (n = 122) versus lesbian (n = 35) women over 675 cycles [12]. The clinical pregnancy rate was 36 percent in single women and their cumulative pregnancy rate after six cycles was 47 percent. Lesbian women had a pregnancy rate of 57 percent and cumulative pregnancy rate of 70 percent. The difference in success rate could be explained by the older average age of the single women and disappeared when pregnancy rates were adjusted for this confounder.

●The French CECOS Federation has collected the largest amount of data on TDI pregnancies [53]. Outcomes from 21,597 pregnancies from TDI were registered. The mean weight at delivery, sex ratio, premature delivery rate, incidence of intrauterine growth retardation, presence of congenital anomalies and birth defects, ectopic pregnancy rate, and miscarriage rate were similar to those of the general French population. The multiple pregnancy rate was higher in the TDI group, reflecting the effects of ovarian hyperstimulation with ovulation induction medications. The incidence of chromosomal abnormalities was not increased.

In general, studies have shown that families created via donor insemination did not differ from families with naturally conceived children with respect to the quality of parenting or the psychological development or adjustment of the child [54-59]. Exceptions to this general conclusion are some reports of hyperactivity in a proportion of TDI children, a small group of DI fathers who had problems relating to their children, and a study which reported TDI parents were over-anxious about their children [60,61]. Most early studies involved families in which the method of conception was not disclosed. Other studies where disclosure was practiced continue to show good psychological outcomes [2,62-64].

COST — Fees for donor sperm vary by sperm bank and are based upon how sperm were prepared (washed versus unwashed sperm) and donor characteristics (level of education). Typical prices for unwashed sperm are USD $180 to $600, and USD $250 to $800 for washed sperm. These prices do not include storage, shipment, routine evaluation and blood tests, or the physician fees for performing the inseminations.

LEGAL AND ETHICAL CONCERNS — Sperm donors and recipients should be informed about potential legal, medical, and emotional issues associated with donor insemination [14].

Donors should be provided with results of their medical evaluation and laboratory tests and offered referral for further evaluation, care, and counseling, as appropriate. They should understand that they do not have control over the disposition of their sperm after it has been collected.

Programs vary in the information disclosed to donors about the outcome of their donation. Some sperm banks have donors willing to be contacted by future children when they reach age 18 years, but the social or legal ramifications are unknown.

In the United States and abroad, social fathers are legally recognized as the child's father. The donor has no legal rights or duties with respect to children conceived with his sperm. However, donors and recipients have an obligation to authorize the disclosure of non-identifying medical information where appropriate. Several sperm banks offer an identity-release option, which allows banks to contact donors in the future for updated medical information and to provide identifying information to adult offspring who request it.

As gamete donation has become more acceptable, other new areas of debate have arisen. Previously, only the use of third party, anonymous donors was supported; however, in the 2012 ASRM guidelines, the Ethics Committee discusses and supports the use of family members (intragenerational and some intergenerational) as gamete donors [65]. The Committee distinguished appropriate intrafamilial reproductive arrangements from those that involved consanguinity, placed undue influence (emotional or financial) on decisions to participate, and those that raised questions about lineage and parenting relations. Additional issues that should be addressed by a qualified counselor include emotional risks, potential impact on family relationships, the donor-recipient relationship, the future role of the donor in the offspring's life, and what information will be disclosed to the offspring [66]. The ethical and legal issues of related donor insemination have been reviewed in detail elsewhere [66].

Other ethical dilemmas, as yet unresolved, include the concept of whether or not it should be mandated that donors' identity be available to allow later contact (if needed medically or desired), and whether or not parents should be required to disclose to their children their method of conception. In the United States, the ethics committee of the ASRM strongly encourages disclosure to donor-conceived persons, but acknowledges that recipient parents have the right to make this decision [67]. Although selecting an anonymous donor remains an option in the United States, some other countries have mandated that all programs use only open-identity donors. The number of programs offering open-identity donors in the United States is growing, and the ratio of open-identity donors to anonymous donors tends to increase over time in programs that offer this service [68].

The ASRM has advised parents to disclose the method of conception to their offspring. Reasons for disclosure include the child's fundamental right to know his biologic origin and avoidance of the stress that arises when secrets are kept or the information is disclosed by accident. There is no good evidence that disclosure is harmful to the child. The ASRM similarly supports disclosure of a donor's identity; however, forced disclosure is not regulated or required by any governing body in the United States.

Disclosure to donor offspring occurs earlier in lesbian couples and single mothers when compared with heterosexual couples. Even in heterosexual couples who expressed intent to disclose donor information to their offspring, fewer than 5 percent had done so by the time their child was 3 years old [69]. A survey of donor offspring suggests that later disclosure is associated with more negative feelings regarding their donor conception [70].

Most donor offspring want to be told about their means of conception, desire in depth information about their donor's medical and social history, and express interest in meeting their donor and extended biologic family [71]. In one study, for example, more than 80 percent of adolescents conceived with open-identity sperm donors expressed a moderate interest in requesting the identity and pursuing contact with their donor, and almost 90 percent expressed an interest in contacting others with the same sperm donor [63].

The impact of mandated disclosure on donor recruitment remains a point of concern. In Sweden, where legislation was passed mandating that a donor's identity be retained and made available to requesting offspring upon maturity, donor recruitment declined only transiently after the new regulations were implemented [72]. A small survey of donors in London showed that half would still donate if mandated to participate in an open-identity program; however, these were older men with children, characteristics that tend to be associated with more altruistically motivated donations [73].

Demand for donors willing to release their identity is unknown. Data from Canada showed that only 21 percent of 240 patients who purchased donor sperm from April 2003 through March 2005 requested sperm from donors who would agree to release their identity; however, 95 percent of women without male partners made this choice [74]. As with other ethical and legal aspects of TDI, these issues have no easy solution. However, as guidelines addressing them are developed it will be interesting to see their effect on the practice of TDI.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Female infertility".)

SUMMARY AND RECOMMENDATIONS

●Therapeutic donor insemination refers to the introduction of semen into the vagina, uterus, or oviduct by a means other than sexual intercourse. (See 'Introduction' above.)

●Indications for donor insemination include male partner infertility, avoidance of diseases that may be transmitted or inherited from the male partner, and absence of a male partner. (See 'Indications' above.)

●Guidelines for the recruitment and screening of donors for the protection of both the donor and recipient are available. (See 'Guidelines' above.)

●The procedure is performed on the expected day of ovulation using a catheter to place washed donor sperm into the uterus. Older maternal age and use of frozen sperm decrease the success rate. (See 'Procedure' above and 'Factors affecting success' above.)

●Pregnancy rates and pregnancy outcomes in fertile women undergoing TDI with fresh semen are comparable to those in normal controls matched for age. (See 'Outcome' above.)