Donor insemination

INTRODUCTION — Insemination, the introduction of sperm into the vagina, cervix, uterus, or oviduct by means other than sexual intercourse, is one type of assisted reproductive technology (ART). This topic will review use of donor sperm for insemination, also known as therapeutic donor insemination (TDI). Additional content on ART can be found separately:

●(See "In vitro fertilization: Overview of clinical issues and questions".)

●(See "Assisted reproductive technology: Infant and child outcomes".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender-expansive individuals.

DEFINITIONS — Commonly used terminology includes:

●Insemination – Insemination refers to the introduction of sperm into the vagina, cervix, uterus, or oviduct by a means other than sexual intercourse.

●Therapeutic donor insemination (TDI) – 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]. TDI has been in use longer than any other assisted reproductive technique for treatment for male infertility.

●Nonidentified donor – The increased prevalence of nonmedical genetic testing and large genetic data sets may allow previously "anonymous" sperm donors to be identified. Therefore, the term "anonymous" donor is no longer being used and has been replaced by "nonidentified" [4,5].

●Identified donor – Previously referred to as "known donors," these individuals are now called "directed (identified) donors" [5]. This text will use "identified donor" for simplicity.

INDICATIONS AND CONTRAINDICATIONS — 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 (table 1) [4].

●Male partner infertility – When the male partner has azoospermia, severe oligospermia, or other severe sperm abnormalities resulting in infertility, the main treatment options are: (1) adoption, (2) TDI, (3) intracytoplasmic sperm injection (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 some couples to undergo TDI for financial reasons. (See "Intracytoplasmic sperm injection".)

●Absence of a male partner or with transmasculine partner – TDI is commonly used to achieve pregnancy in females without a male partner or whose partner is transmale. Various ethics committees advise providing fertility services to individuals regardless of their marital status, sexual orientation, or gender identity, in accordance with local guidelines [7,8].

In 2019, a US survey-based study using a cohort from the National Survey of Family Growth reported that 46 percent of females who used donor sperm from 1995 to 2017 were unmarried and 43 percent were other than heterosexual [9]. The number of single or lesbian patients who perform self-inseminations is unknown. This could possibly be because self-inseminations do not require a physician and single or coupled patients can do self-inseminations with a known donor's fresh sperm without medical oversight or a physician's order.

●Heritable disease – TDI can benefit couples in whom either one or both partners are affected by a heritable disease or when an affected child has been born to asymptomatic carriers. Depending upon the genetics of the disorder, such couples may opt for TDI from a noncarrier or phenotypically normal donor. Preimplantation genetic testing 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".)

●Unsuccessful assisted reproductive technology (ART) – TDI is an option for patients who have had unsuccessful testicular sperm retrieval procedures (eg, testicular sperm extraction, microsurgical epididymal sperm aspiration) or in vitro fertilization (IVF) or ICSI cycles [10-12]. In a study of 45 couples with severe male factor infertility undergoing TDI after unsuccessful ICSI, 90 TDI cycles were completed and 20 out of the 45 couples (44.4 percent) conceived within four cycles [11]. The pregnancy rate per cycle was 22.2 percent and the live birth rate per cycle was 18.9 percent with an average of 1.5 TDI cycles per couple.

●Incompatible red cell antigens – Partners whose red cell antigens may result in hemolytic disease of the newborn may elect TDI.

•(See "Red blood cell antigens and antibodies".)

•(See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management".)

●Serodiscordance for viral infection – Prior to wide availability of drugs to prevent sexual transmission of viruses such as HIV and hepatitis C, males with infection and a seronegative partner risked infecting the uninfected partner with their semen [13]. TDI from an uninfected donor avoids transmitting the infection. In a 2003 survey of serodiscordant couples, 48 percent of respondents stated they would prefer TDI to timed unprotected intercourse [14].

Alternatives to TDI include for couples who are serodiscordant for viral infection include:

•Prevention of HIV transmission – HIV serodiscordant couples may elect use of pre-exposure prophylaxis (PrEP) and/or antiretroviral medications with resultant undetectable viral load [15]. Maintenance of undetectable HIV viral load for at least six months appears to prevent sexual transmission of HIV, a concept that is referred to as U=U, or undetectable equals untransmissible [16-18].

-(See "HIV pre-exposure prophylaxis".)

-(See "Use of assisted reproduction in HIV- and hepatitis-infected couples".)

•Prevention of hepatitis B transmission – Sexual transmission of hepatitis B infection is prevented by vaccination of the seronegative partner. (See "Use of assisted reproduction in HIV- and hepatitis-infected couples", section on 'Hepatitis B'.)

•Sperm washing – Sperm washing coupled with ART (eg, intrauterine insemination [IUI], IVF, ICSI) can be safely utilized in serodiscordant couples to prevent transmission to the uninfected partner [19,20]. There are no reports of HIV seroconversion with use of ART to date [20]. There have yet to be any studies evaluating the opinion of serodiscordant couples on the use of semen washing of the affected partner versus TDI.

●Lack of access to other assisted reproductive technologies – Patients with male factor infertility who are unable to access IVF or ICSI because of availability, cost, or other reasons may elect trials of TDI.

●Contraindications – Patients with subfertility due to tubal factors, incompletely evaluated uterine malformations, active pelvic infection, uncorrected anovulation, or unexplained/abnormal uterine bleeding are not good candidates for donor insemination (table 1).

SPERM BANK AND DONOR SELECTION AND DONOR LIMITATIONS — Patients seeking nonidentified donor sperm generally work through a sperm bank and are then provided with a range of donor characteristics and medical information to aid donor selection.

●Finding a sperm bank – Patients should work through accredited sperm banks in their region. As one example, the American Association of Tissue Banks (AATB) website provides information on US accredited sperm banks.

●Information about donors – 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 [21]. 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.

●Limits on number of births per donor – 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 [22].

Data from France found nonidentified donor insemination was estimated to be responsible for 0.46 percent of consanguineous births and 0.01 percent of recessive diseases [23]. Consanguineous unions between descendants of nonidentified sperm donors were four times less numerous than those between descendants with false paternities.

DONOR EVALUATION

General requirements — Individuals considering sperm donation should generally be healthy and have no history that suggests a heritable disease [4]. Established fertility is preferred but not required.

While criteria vary by region, the American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology's guidance regarding gamete and embryo donation is representative of the issues to consider [4]. Brief summaries are presented below.

●Age – Donors should be of legal adult age according to their local laws but ideally >21 years old and generally younger than age 40 years. 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 or autism 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 [24], 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 [25]. (See "Effect of advanced paternal age on fertility and pregnancy".)

●Psychological evaluation – A psychological assessment by a qualified mental health professional is advised for all donors, especially donors <21 years old [4]. 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 'Specific legal and ethical concerns' below.)

●Donor obligations to maintain medical documentation – Donors should be informed of their responsibility to update their records with future changes in their health status including relevant changes to family history (eg, newly diagnosed genetic disease) [4].

●Specific to directed donors – If the recipient prefers directed donation with an identified donor, the donor must still fulfill the above criteria and undergo the screening procedures required of nonidentified donors [4]. In addition, legal issues such as parental rights must be addressed prior to insemination. The cost with a identified donor can be more than with a nonidentified donor due to the out-of-pocket cost for sexually transmitted infection (STI) testing, semen analysis, and storage fee.

Initial evaluation — At minimum, donors should provide a medical history, undergo a physical examination, and have a laboratory evaluation including blood type and Rh testing; additional blood tests may include a complete blood count, liver function tests, and a chemistry panel [4]. Testing for genetic carrier status and STIs are discussed below. (See 'Genetic assessment' below.)

Genetic assessment — Potential donors undergo a genetic assessment that includes a detailed family history and ascertainment of carrier status for common genetic diseases. Chromosomal analysis with karyotype is offered to high-risk patients and optional for others. Additional genetic testing can be performed if indicated by history or patient preference. As genetic testing of sperm donors varies among sperm banks, donors and recipients should ask about the specific tests performed when using a bank [26].

●Family history – A three-generation family history is taken to evaluate for potential heritable diseases [4]. The donor and their first-degree relatives should not have any major Mendelian disorders, major congenital malformations, familial disease with a major genetic component, or known karyotype abnormalities. (See "Genetic counseling: Family history interpretation and risk assessment".)

●Routine carrier testing – Most sperm banks perform expanded carrier screening and karyotype on potential sperm donors. Testing typically includes cystic fibrosis, spinal muscular dystrophy, and thalassemia/hemoglobinopathy carrier status [4,27]. Directed donors are offered the same testing, or it is recommended the recipient undergo testing to reduce risk. (See "Prenatal care: Initial assessment", section on 'Carrier screening'.)

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.

•Expanded carrier screening – Expanded carrier screening has become routine within ART. If performed, a panethnic, rather than ethnicity-based, approach is advised [4]. Donors and recipients should be aware that different panels may test for different conditions. A 2021 European study reported that 17.6 percent of donor sperm applicants were rejected based on the results of expanded carrier screening; the most prevalent genetic reasons for exclusion were being carriers for alpha thalassemia, spinal muscular atrophy, and cystic fibrosis [27].

•Chromosomal analysis with karyotype – Donors should not have a known karyotypic abnormality such as balanced translocation. Chromosomal analysis with karyotype is recommended for high-risk individuals and optional for all other donors [4].

●Testing limitations – 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 are made aware of the limitations of current genetic testing of prospective donors. Most sperm cryobanks use expanded carrier screening on all sperm donors. Expanded carrier screening includes the most common transmissible genetic conditions (ie, cystic fibroids, spinal muscular atrophy) and many others. However, expanded carrier screening only evaluates genetic mutations from a specific panel and does not identify every possible genetic mutation in a person's genome; therefore, some mutations may be missed. If a recipient is concerned about carrying a specific mutation or condition that was not tested with an expanded carrier screening panel, they can request additional genetic testing from the donor if he is willing to undergo additional testing.

General risk of infection — The risk of transmitting an infection through TDI is less than 1 in 10,000 with contemporary testing methods. A California cryobank that reported 47 infections among 48,000 recipients of donor insemination between 1986 and 2004 (1 infection per 1000 recipients) noted the rate dropped to 1 in 25,000 during the last 10 years of the study, when semen specimens were processed more intensively [28]. It was not possible to ascertain the proportion of these infections attributable to infection in the semen sample versus recipient factors.

Approach to screening for sexually transmitted infection (STI) — Potential donors are screened for STIs using a combination of sexual history, physical examination, and laboratory testing [4].

●Sexual history – A complete sexual history is taken to exclude those who might be at high risk for HIV or other STIs (table 2). Clinicians should be aware of regional guidelines regarding donor exclusion criteria.

●Physical examination findings – In the US, evidence of anal intercourse, urethral discharge, genital warts, genital ulcers, nonmedical intravenous (IV) or percutaneous drug use, disseminated lymphadenopathy, recent nonsterile tattooing or piercings, unexplained oral thrush, jaundice, hepatomegaly, or icterus, and/or rash concerning for smallpox infection or Kaposi sarcoma precludes sperm donation [29].

●Laboratory tests – Tests for STIs should be licensed, approved or cleared donor-screening tests and performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or CLIA-exempt laboratory, or similar.

The US Food and Drug Administration (FDA) requires that donors be screened for the following infections [4,29]:

•HIV – HIV 1 and 2 nucleic acid amplification tests, HIV 1 and 2 antibody tests, and HIV group 0 antibody

•Hepatitis B (surface antigen and immunoglobulin G [IgG]/ immunoglobulin M [IgM] core antibodies)

•Hepatitis C antibody

•Treponema pallidum (rapid plasma reagin, RPR)

•Chlamydia trachomatis

•Neisseria gonorrhea

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

•Cytomegalovirus (CMV) IgG and IgM antibody tests

•West Nile virus nucleic acid amplification test

The full description of the US donor eligibility testing is available online.

Quarantine and retesting of specimens — While there is no approach that eliminates 100 percent of infectious disease risk, approaches to minimize the risk include testing, quarantining, and then retesting the donor sperm samples [4].

●Initial testing – The panel of laboratory tests listed above are performed prior to donation or within seven days after recovery of the specimen.

•Negative test results – If the tests are negative on initial screening, donor samples are prepared for cryopreservation.

•Positive test results – 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.

●Quarantine and repeat testing – In the US, nonidentified 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 [4]. While identified donor specimens may be exempt from quarantine in some regions, the ASRM advises quarantine of directed donor specimens for 35 days and then repeat testing. The panel of laboratory tests is the same for both donor types. If the donor specimen tests negative again on repeat testing, samples can be released for use.

●Storage of specimens during testing and quarantine process – Although is it not required to physically separate specimens that are eligible for use from those still in quarantine, 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 [4].

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. Detailed discussion of CMV testing is available separately. (See "Overview of diagnostic tests for cytomegalovirus infection".)

•Recent CMV infection – Sperm samples from recently infected donors are discarded [30].

•Remote CMV infection – 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 [4,31].

•Disclosure to CMV-negative recipients – 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 with evidence of 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.

●Zika virus – Based on cases of sexual transmission of the Zika virus, sperm donors are 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 [4,32]. (See "Zika virus infection: An overview".)

●West Nile virus – According to the FDA, it is recommended that gamete donors with confirmed or suspected West Nile virus infection be deferred for 120 days after the onset of symptoms or diagnosis, whichever is later [33-35]. (See "Epidemiology and pathogenesis of West Nile virus infection".)

●Smallpox – Donors who have received smallpox vaccine in the previous eight weeks should be deferred until the vaccination scab spontaneously separates or for 21 days after vaccination, whichever is the later date [4]. Confirmation for scab removal should be performed by physical examination or physical assessment prior to using donor. Intended donors who have experienced complications from the vaccine should wait 14 days after symptom resolution prior to donating. Individuals who have been infected by a recent recipient of the vaccine are advised to defer donation until the vaccine scab has spontaneously separated, three months from the date of vaccination of the vaccine recipient in which the living donor's scab was removed, or until 14 days after resolution of any vaccine-related complications [36]. (See "Variola virus (smallpox)" and "Vaccines to prevent smallpox, mpox (monkeypox), and other orthopoxviruses".)

●Viral syndromes – Donors with recent significant fever, flu-like illnesses, viral meningitis, encephalitis, or meningoencephalitis should be deferred until healthy [37].

●Ebola – Ebola virus has been detected in semen 199 days from the onset of infection in male survivors [38]. It is not known how long the virus can persist in semen and potentially be transmitted. The World Health Organization (WHO) 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" [39].

●Coronavirus – Although guidelines regarding the use of donors who have been infected with COVID-19 are lacking, the risk of coronavirus transmission through cryopreserved donor sperm has been determined to be zero [40]. The use of donor sperm by patients with active COVID-19 infection may vary by clinic. We suggest deferring use of donor sperm from an individual with COVID-19 infection until 14 days after onset of symptoms.

●Mpox – Viral strands of mpox (formerly monkeypox) have been detected in semen up to seven days after infection [41]. However, there have been no confirmed reports of transmission through semen. In the US, additional laboratory diagnostic testing of sperm donors beyond standard screening regulations is not advised [42]. However, clinicians should be aware of their regional guidelines and the eligibility of donors should be determined on a case-by-case basis based on local screening regulations.

Donors are generally considered ineligible if they have had any of the following in the 21 days prior to donation:

•Diagnosed with or suspected of having a mpox infection

•Close contact with a person or animal diagnosed with or suspected of having a mpox infection regardless of vaccination status

•Developed a rash or other symptoms suggestive of mpox infection

Donors who have received the smallpox vaccine to combat mpox should follow smallpox vaccine guidelines, as stated earlier. Donors who have received the nonreplicating mpox vaccine (JYNNEOS) do not need to follow the smallpox vaccine guidelines.

Specimen procurement

●Pre-donation counseling – Donors are advised to abstain from ejaculation for 48 to 72 hours prior to producing a specimen [43,44]. If the donor has not ejaculated for >7 days, then they should be advised to do so because mature sperm in the epididymis begin to degrade after seven days. To optimize sperm quality, many clinics advise potential sperm donors to maintain a healthy lifestyle, avoid smoking, minimize alcohol consumption, avoid illicit drugs/cannabis, avoid hot tubs and tight underwear, and exercise regularly.

●Specimen collection – A single donor produces several semen specimens, over multiple visits, in a private room on site. (See "Procedure for intrauterine insemination (IUI) using processed sperm", section on 'Semen collection'.)

●Initial semen evaluation – Each specimen is evaluated within one to two hours from ejaculation should meet at least minimal semen parameters (table 3). Donor sperm have resulted in pregnancy over a wide range of donor sperm concentration, motility, and morphology [45,46]. Detailed discussion of semen analysis is available in related content. (See "Approach to the male with infertility", section on 'Semen analysis'.)

●Sperm processing – Sperm processing (washing) separates the sperm from the ejaculatory fluid. The process removes prostaglandins, inflammatory cells, debris, and proteins and then concentrates the sperm in a small volume. Processing ultimately results in use of only the most motile, morphologically normal sperm for insemination; motility and morphology are the critical specimen-related factors impacting outcome [47]. Details of procedure for sperm processing are discussed in related content. (See "Procedure for intrauterine insemination (IUI) using processed sperm", section on 'Sperm processing'.)

Fresh, unwashed sperm can be used for intracervical insemination (ICI) or for self-insemination. Pregnancy rates are lower with unwashed sperm, thus washed sperm and intrauterine insemination (IUI) are typically recommended. Information on self-insemination and ICI can be found below. (See 'Self-insemination techniques' below and 'Variable impact' below.)

RECIPIENT EVALUATION — The same preconception screening standards are used as for any person attempting pregnancy. (See "The preconception office visit".)

●Initial evaluation – A routine medical and reproductive history is obtained and a physical examination is performed.

•(See "The preconception office visit", section on 'History'.)

•(See "The preconception office visit", section on 'Physical examination'.)

●Laboratory testing – Laboratory testing is similar to standard preconception or prenatal panels (see "The preconception office visit", section on 'Laboratory assessment') and includes [4]:

•Blood type, Rh factor, antibody screen

•Testing for immunity to rubella and varicella

•Testing for active cytomegalovirus (CMV) infection

•Testing for sexually transmitted infections (STIs), including HIV, syphilis, gonorrhea, chlamydia, hepatitis B surface antigen, and hepatitis C antibody [4]. (See "Screening for sexually transmitted infections".)

•Testing for human T-cell lymphocytic virus (HTLV) types I and II, Chagas disease, and latent tuberculosis, as indicated.

•Genetic carrier screening as desired – Preconception guidelines suggest screening patients for cystic fibrosis and other genetic diseases for which they are at risk. Theoretically, patients could opt out of this recommendation since the donors are screened for genetic diseases.

●Impact of Rh status – Rh-negative patients 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 "RhD alloimmunization in pregnancy: Overview".)

•(See "RhD alloimmunization: Prevention in pregnant and postpartum patients".)

•(See "Alloimmune hemolytic disease of the newborn: Postnatal diagnosis and management".)

●Fertility evaluation – Since most pregnancies occur within six cycles, an infertility evaluation should be initiated in patients who have not conceived after six months of inseminations and have not had a previous evaluation. Given the costs of TDI, patients may benefit from fertility assessment prior to the procedure, particularly those with risk factors for subfertility such as advancing age or prior pelvic inflammatory disease. (See "Female infertility: Evaluation".)

INSEMINATION PROCEDURES — Insemination is typically performed by a trained clinician in a medical facility. However, some patients elect self-insemination techniques.

Medical intrauterine insemination — In general, TDI involves intrauterine placement of donor sperm (ie, intrauterine insemination [IUI]). Compared with intracervical insemination (ICI), intrauterine placement bypasses vaginal and cervical factors that might impair fertility and increases the number of sperm reaching the uterine cavity 100-fold with the goal of increasing pregnancy rates. (See 'Pregnancy and live birth rates' below.)

IUI should be performed by certified health professionals, including physicians and nurses who are experienced in administering gynecologic care. The timing of insemination, equipment, patient preparation, and procedure are described in detail in related content.

●(See "Procedure for intrauterine insemination (IUI) using processed sperm", section on 'Timing the insemination'.)

●(See "Procedure for intrauterine insemination (IUI) using processed sperm", section on 'IUI procedure'.)

Self-insemination techniques — Patients who are free of fertility issues and prefer to avoid undergoing insemination in a clinical setting may choose self-insemination methods to achieve pregnancy. The two main methods of self-insemination include the soft cup method and ICI (ie, turkey baster method). While intracervical techniques typically place sperm at or near the cervix, rather than directly into the cervical canal, the term "intracervical" is often used in reference studies and results.

●Potential patient groups – Patients who may prefer self-insemination include same-sex female couples, transmasculine individuals, planned single parents, and heterosexual couples in whom the female partner has a viral infection that they do not want to pass to the male partner.

●Methods

•Soft cup method – In this technique a menstrual cup or cervical cap is used to hold the sperm near the cervix. Conceptually, this allows for the sperm to be closer to the cervix and helps sperm with lower motility reach the cervix. However, it is unclear if this approach increases the number of sperm in the uterus and fallopian tubes as cervical mucus typically prevents sperm with lower motility and poor morphology from entering the uterus. One study reported cup use did not lessen sperm functional characteristics compared with unexposed sperm, but data are limited [48]. A 1997 study reported 38 patients conceived in 250 cervical cap cycles (15 percent per cycle pregnancy rate) [49].

•Self-cervical insemination (ie, turkey baster method) – This technique is what most marketed self-insemination kits use. It involves using a needleless syringe that is inserted into the vagina to inject sperm near or at the cervix. After injection, patients are instructed to remain lying down for 15 to 30 minutes prior to removing the syringe or sitting up. This method has been shown to be superior to the soft cup method [50]; however, true efficacy is hard to determine due to use outside of the clinical setting.

●Sperm sources – Patients may use fresh sperm from a donor or purchase washed or unwashed frozen donor sperm from a sperm bank. Sperm from a known donor implies that medical and psychological evaluation of the donor is not undertaken. Most sperm banks require a signed order from a medical provider prior to shipping donor sperm.

●Outcomes and comparative data – Per-cycle pregnancy rates of 6 to 8 percent per cycle have been reported for use of a soft cup [50,51]. Data on intracervical self-insemination are lacking as this technique is typically performed by patients at home.

Studies directly comparing the two self-insemination techniques are lacking and existing older studies are limited by use of clinician-performed insemination techniques as the comparator. (See 'Variable impact' below.)

•A study including 198 patients reported similar per-cycle pregnancy rates for cervical cap compared with standard ICI (7.8 versus 9.8 percent per cycle), but it is not known if comparison with patient-performed ICI would have yielded the same results [50].

•A study of 42 women reported higher pregnancy rates with standard IUI compared with cervical cap use (16 versus 6 percent) [51], but subsequent data have reported lower pregnancy rates for ICI compared with IUI so the lower pregnancy rate when compared with cap use is not surprising [51,52].

●Benefits and risks – Benefits of self-insemination include comfort, privacy, flexibility, lower cost, and reduced stress. Risks include infection and vaginal bleeding due to cervical friability or trauma during insertion of device. Patients should be encouraged to talk to their medical provider before purchasing or using these kits to optimize safety and mitigate potential risks of infection.

OUTCOMES

Pregnancy and live birth rates

Summary — In our practice, we typically quote a 10 to 20 percent live birth rate following donor sperm insemination. Age of the female partner (or donor oocyte) remains the major determinant of fecundity; increasing female age results in decreasing live birth rates (see 'Negative impact' below). Recipients who do not become pregnant within three to four TDI cycles are typically offered in vitro fertilization (IVF) to improve the odds of conception and live birth [53,54]. (See "In vitro fertilization: Overview of clinical issues and questions".)

Studies that inform our counseling include:

●A 2021 study including 6192 TDI cycles (3,837 natural cycles and 2,355 ovulation induction cycles [primarily with clomiphene citrate]) from 2343 patients reported the clinical pregnancy rate and ongoing pregnancy rate for natural cycles and ovulation induction cycles to be 18.7 versus 22.4 percent and 14.9 versus 15.4 percent, respectively [55].

●Studies on donor sperm intrauterine insemination (IUI) cycles in other countries reported live birth rates ranging from 12 to 24 percent [56-58].  

Intrauterine insemination (IUI) — The highest pregnancy rates have been achieved IUI using washed sperm. While pregnancy rates decline with increasing age of the female patient, general pregnancy rates of 12 to 24 percent have been reported [56-58].

●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 approaches the pregnancy rate of individuals who discontinue oral contraceptive pills to attempt pregnancy [59]. As fresh sperm are not typically used in contemporary cycles, updated data are not available.

●A retrospective, multicenter study evaluated donor sperm IUI success rates in single women (n = 1402), lesbian couples (n = 585), and heterosexual couples (n = 528) compared with autologous IUI in heterosexual couples (n = 1292) over 7228 cycles [60].

•Similar live birth rate with donor sperm – Similar live birth rates were reported for all women ≤37 years of age who underwent TDI (16.5 percent for single women, 17.6 percent for lesbian couples, and 18.8 percent for heterosexual couples) compared with a lower live birth rate in heterosexual couples using autologous sperm (11 percent). The lower success rate in heterosexual women ≤37 years old using autologous sperm is most likely due to the higher incidence of female factor infertility in this population compared with women using TDI in the other groups.

•Impact of female age – Women aged ≥38 years had similar live birth rates in all groups regardless of TDI versus autologous sperm. For all groups, live birth rate was <7 percent for patients aged ≥40 years.

Comparison of intrauterine versus intracervical insemination (ICI) — Historically, ICIs were performed with fresh donor semen. Fresh specimens were not injected into the uterus because of concerns for potential serious reactions to proteins, prostaglandins, and bacteria. A volume of 1.5 to 2.5 mL was injected into the endocervical canal.

Although live birth data are limited, IUI appears superior to ICI. In a meta-analysis of two trial totaling 69 patients, IUI resulted in higher clinical pregnancy rates in natural cycles (odds ratio [OR] 6.18, 95% CI 1.91-20.03) and stimulated cycles (OR 2.83, 95% CI 1.-5.78) when compared with ICI [61]. As only one live birth occurred during the study period, definitive conclusions could not be made. A subsequent trial in natural cycles reported IUI using cryopreserved sperm resulted in a higher live birth rate compared with ICI with cryopreserved sperm (39 versus 24 percent, risk difference with ICI -15 percent, 95% CI -24 to -6.9 percent, 266 women completed treatment according to protocol) [52].

Obstetric and perinatal outcomes — Compared with using partner sperm, use of donor sperm is associated with a roughly 50 percent increased risk of preeclampsia and hypertensive disorders of pregnancy; the impact on other pregnancy outcomes is less consistent [62,63]. While concerning, definitive conclusions are limited by lack of trial data.

●A meta-analysis including 24 studies (no trials were identified) comparing TDI versus partner sperm found an increased risk for preeclampsia (pooled adjusted odds ratio [aOR] 1.77, 95% CI 1.26-2.48) and hypertensive disorders of pregnancy (pooled aOR 1.55, 95% CI 1.20-2.00) in pregnancies that resulted from TDI [62]. Low birth weight, preterm birth, or sex ratio were similar between groups. While risk of congenital anomalies did not appear to increase with TDI, the included studies were noted to have moderate to severe risk of bias and thus limited definitive conclusions.

●A different meta-analysis of 37 studies comparing TDI versus partner sperm reported that, when compared with partner sperm, use of donor sperm was associated with an increased relative risk (RR) of combined hypertensive disorders of pregnancy (RR 1.44, 95% CI 1.17-1.78), preeclampsia (RR 1.49, 95% CI 1.05-2.09), and small for gestational age (RR 1.42, 95% CI 1.17- 1.79) [63]. The risk of ectopic pregnancy was reduced (RR 0.69, 95% CI 0.48-0.98) [63]. Similar outcomes between the two groups were reported for pregnancy loss (ie, miscarriage), gestational diabetes, pregnancy-induced hypertension, placental abruption, placenta previa, preterm birth, low birth weight, high birth weight, large for gestational age, stillbirth, neonatal death, and congenital anomaly.

Detailed discussions of reproductive and childhood outcomes following use of ART are presented separately.

●(See "Assisted reproductive technology: Pregnancy and maternal outcomes".)

●(See "Assisted reproductive technology: Infant and child outcomes".)

Psychological outcomes — Data have shown that most men elect to become sperm donors for altruistic reasons rather than for financial gain [64-66]. In general, studies have reported 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 [67-70]. Although there are conflicting results regarding the effects of disclosure of origin on the parent-child relationship and psychological well-being [71], we generally advise early disclosure. Overall, the body of evidence does not support differences in psychological well-being of donor offspring in disclosing or nondisclosing families [71], but one study reported that a primary motivator for donor offspring to seek out a donor was to find out medical history information, especially for donor offspring with self-reported anxiety or depression [72].

FACTORS IMPACTING SUCCESS — Efforts to improve pregnancy rates have focused upon the number of inseminated sperm, timing of insemination(s), and methods for insemination.

Negative impact — Advancing maternal age and use of frozen sperm are the major nonmodifiable variables which reduce the likelihood of pregnancy. However, most cycles use frozen sperm because of concerns for infection transmission with fresh sperm.

●Advancing maternal age – Age of the female partner, or donor oocyte, is a major determinant of fertility regardless of the means used to achieve pregnancy [73]. (See "Evaluation and management of infertility in females of advancing age", section on 'Biology of female fertility'.)

In a review of cumulative pregnancy rates in women under and over 30 years of age that included data from almost 3000 cycles over a 10-year interval, the pregnancy rates at 3, 6, and 12 months were consistently higher for women <30 years compared with those ≥30 years (21, 40, and 62 percent versus 17, 26, and 44 percent, respectively) [74]. The maximum maternal age for administering TDI is at the discretion of the health professional or facility providing the recipient with her care.

●Use of frozen sperm – Insemination with frozen sperm results in lower pregnancy rates compared with use of fresh sperm because the cryopreservation and thaw techniques decrease sperm motility and viability [75,76]. However, TDI with fresh sperm is rarely performed because of concerns for infection transmission. Patients performing self-insemination may opt to use fresh, unwashed sperm from known partners.

Two crossover trials including 669 patients receiving alternating cycles of fresh or cryopreserved sperm reported fecundity rates of 19 to 27 percent with fresh sperm compared with 5 to 10 percent for frozen sperm [75,76]. Overall fecundity rates were higher in the trial because a higher number of motile sperm were inseminated in the cryopreserved cycles by using a more concentrated cryoprotectant [76].

Long-term cryo-storage does not appear to further reduce sperm motility, nor does it negatively impact clinical pregnancy rates following TDI [77,78].

Variable impact

●Number of inseminated sperm – Although animal data indicate a critical number of fresh sperm are needed to achieve maximum pregnancy rates, data in humans conflict. As 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. Most cryobanks seek a goal of 10 million motile sperm per vial for TDI [79,80]. Our minimal criteria are shown in the table (table 3).

•Increasing pregnancy rates with increasing sperm numbers – A study from the Central Semen Bank of Denmark (n = 3418 frozen ejaculates) reported that increasing the total motile sperm count from <10x10⁶ to 11 to 19x10⁶ to >19x10⁶ increased the likelihood of achieving pregnancy [81]. However, once the count was above 19x10⁶, no additional benefit was observed.

•Possible minimum sperm threshold – A study of 155 patients reported that frozen ejaculates with at least 20x10⁶ sperm yielded pregnancy rates that compared favorably with fresh samples containing more sperm [82]. A different study including 332 infertile couples undergoing 1115 TDI cycles reported similar pregnancy rates when inseminating with 1x10⁶ versus >5x10⁶ motile sperm [83]. Updated data are not available as fresh donor sperm are not typically used in contemporary TDI cycles because of concerns for potential infection.

●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 luteinizing hormone (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 [84,85].

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 [86]. 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 'Predicting ovulation' and "Evaluation of the menstrual cycle and timing of ovulation", section on 'Measurement of LH surge and estradiol rise'.)

●Use of ovulation induction – Patients 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, letrozole, or gonadotropins can be considered.

No impact — Vaccination for COVID-19 does not appear to impact pregnancy rates following insemination with donor or partner sperm [87].

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 approximately USD $490 to $1125 [88,89] and USD $490 to $1250 for washed sperm [88,90]. These prices do not include storage, shipment, routine evaluation and blood tests, or the physician fees for performing the inseminations. There are cheap online self-insemination kits; however, these are primarily intracervical inseminations (ICIs), which have lower success rates than intrauterine inseminations (IUIs).

ETHICAL AND REGULATORY ISSUES — Although TDI has been an established medical practice since the early 20^th 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 [91]. Since this study, the field of sperm donation has been revolutionized with increased regulation regarding selection criteria and screening for sexually transmitted infections (STIs) and genetic disorders.

Examples of policies and guidelines — As guidelines for TDI differ based on country and region, clinicians should be aware of the laws and regulations in their location of practice. Guideline and policy examples include:

●The European Society of Human Reproduction and Embryology (ESHRE) provides online guidelines, consensus documents, and recommendations, statements by the Task Force Ethics and Law groups, and specific papers on gamete and embryo donation [92,93].

●The American Society of Reproductive Medicine (ASRM) Ethics Committee Opinions address many issues in reproductive health, including the interests, obligations, and rights of the [egg or sperm] donor in gamete donation [94]. A synopsis of these guidelines, and additional information, are described below.

●US federal regulations for gamete and embryo donation are available online and include regulations for donors of human tissues and cells as well as donor testing criteria.

General ethical issues — General ethical issues include [94-96]:

●Donor eligibility – As an example, no individual associated with a facility performing the TDI, including the physician, can serve as a donor in that practice. Donors can be nonidentified or directed, which can include family members in some settings [4].

●Informed consent for process, testing, and use of gametes – Donors must be willing to undergo appropriate testing and screening. They must also be willing to update the cryobank of any changes to their health or family history so that their profile may be updated with the most relevant information for the safety and knowledge of potential recipients.

●Disposition of unused gametes – Donors must be aware of and agreeable to the terms and policies set by cryobanks regarding storage and disposition of gametes.

●Information around disclosure of donor identity and/or medical information – Donors may elect to disclose information for future contact by offspring. However, complete anonymity cannot be guaranteed due to advancements in genetic testing technology and social media. (See 'Psychological outcomes' above.)

●Interests and rights of donors, recipients, and offspring.

●Compensation – Compensation for donation varies according to the sperm bank used; it is generally USD $100 per specimen (approximately $1500 per month) [97].

●Disclosure to offspring about their conception with donor gametes. (See 'Psychological outcomes' above.)

Specific legal and ethical concerns — Sperm donors and recipients should be informed about potential legal, medical, and emotional issues associated with donor insemination [4,94].

●Test results – 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.

●Disclosures to donor and offspring – Programs vary in the information disclosed to donors about the outcome of their donation. In regions where sperm donation can remain undisclosed, donors can elect to be contacted by future children when they reach age 18 years, but the social or legal ramifications are unknown.

●Legal rights and updated medical information – Social fathers are typically 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 nonidentifying 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.

●Ethical use of family members as gamete donors – In the 2017 ASRM guidelines, the Ethics Committee discusses and supports the use of family members as gamete donors except when the arrangements are consanguineous or simulate incestuous relations [95]. 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 [98]. The ethical and legal issues of related donor insemination have been reviewed in detail elsewhere [98].

●Disclosure of donor identity – Local regulations determine whether sperm donors remain anonymous to offspring. Many argue that donors' identity should be available to allow later contact (if medically needed or desired). With the advent of genetic testing, donor-conceived children may find their half-genetic siblings in online groups. Recognition of increasing prevalence of nonmedical genetic testing that may allow previously "anonymous" donors to be identified prompted discontinuation of the term "anonymous" donor and replacement with "nonidentified" [4].

•Mandated disclosure – Some countries and states have mandated that all programs use only open-identity donors [99]. While the ASRM supports disclosure of a donor's identity, forced disclosure is not regulated or required by any governing body in the United States. The number of US programs offering open-identity donors is growing, and the ratio of open-identity donors to anonymous donors tends to increase over time in programs that offer this service [100].

•Impact of mandated disclosure on donor recruitment – 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 [101]. 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 [102].

•Demand for identified donors – 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 [103].

●Disclosure of TDI to offspring – Consensus is lacking as to whether or not parents should be required to disclose to their children their method of conception. While some organizations strongly encourage disclosure to donor-conceived persons, they acknowledge that recipient parents have the right to make this decision [92,96]. Reasons for disclosure include the child's fundamental right to know their biologic origin and avoidance of the stress that arises when secrets are kept or the information is disclosed by accident [104]. There is no good evidence that disclosure is harmful to the child.

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 [105]. A longitudinal survey study of donor offspring found no overall differences in parent-child relationships or adolescent adjustment between disclosed and nondisclosed families; however, donor offspring who are told of their origins by age 7 had a better family relationship and psychological well-being in adolescence [106].

●Offspring preferences regarding disclosure – 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 [107]. 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 [108].

RESOURCES FOR PATIENT AND CLINICIANS — The resources below offer free online information for patients and clinicians.

●American Society for Reproductive Medicine (ASRM) offers free online information for patients and clinicians.

●European Society of Human Reproduction and Biology (ESHRE) offers free online information for patients and clinicians.  

●International Federation of Fertility Societies (IFFS) represents over 65 United Nations country-specific fertility societies.

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

●Definition – 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). Sperm donors may be nonidentified (formerly anonymous) or directed (ie, identified). (See 'Definitions' above.)

●Indications and contraindications – Indications for donor insemination include male partner infertility, avoidance of diseases that may be transmitted or inherited from the male partner, absence of a male partner, and/or transmasculine partner (table 1). Patients with subfertility due to tubal factors, incompletely evaluated uterine malformations, active pelvic infection, or uncorrected anovulation are not good candidates for donor insemination. (See 'Indications and contraindications' above.)

●Sperm donor evaluation – In general, individuals considering sperm donation should be healthy and have no history that suggests a heritable disease. Established fertility is preferred but not required. At minimum, nonidentified donors should provide a medical history, undergo physical examination, and have a laboratory evaluation including blood type and Rh testing, assessment of genetic carrier status, and tests for sexually transmitted infections (STIs). (See 'General requirements' above and 'Donor evaluation' above.)

●Recipient evaluation – The same preconception screening standards are used as for any person attempting pregnancy. This generally includes a medical history, physical examination, and laboratory testing for Rh and blood type, genetic carrier status, and STIs. (See 'Recipient evaluation' above.)

●Procedure – Insemination is typically performed by a trained clinician in a medical facility. However, some patients elect self-insemination techniques.

•Medical intrauterine insemination – For patients with infertility, we suggest intrauterine insemination (IUI) rather than self-insemination (Grade 2C). In general, IUI results in higher pregnancy rates compared with medical intracervical insemination (ICI), which is a proxy for self-insemination. Patients without infertility who place a higher value on avoiding the clinical setting for insemination and are willing to accept a lower success rate may reasonably opt for self-insemination at home. The procedure is performed on the expected day of ovulation using a catheter to place washed donor sperm into the uterus. Use of IUI may be limited by insurance coverage. (See 'Medical intrauterine insemination' above.)

•Self-insemination techniques – Patients without infertility who prefer to avoid undergoing insemination in a clinical setting may choose self-insemination methods to achieve pregnancy. The two main methods of self-insemination include the soft cup method and self-cervical insemination (ie, turkey baster method). (See 'Self-insemination techniques' above.)

●Pregnancy rates and outcomes – In our practice, we typically quote a 10 to 20 percent live birth rate following donor sperm insemination. The clinical and ongoing pregnancy rates are approximately 18 to 22 percent for TDI natural cycles and 15 percent for TDI with ovulation induction. Other countries have reported live birth rates ranging from 12 to 24 percent following donor sperm IUI cycles. Factors that lower the pregnancy rate include advancing maternal (or donor oocyte) age and use of frozen sperm. Factors with variable impact include the number of sperm used for insemination, timing of insemination relative to ovulation, use of ovulation induction, and choice of IUI or ICI techniques. Recipients who do not become pregnant within three cycles are offered in vitro fertilization (IVF). (See 'Outcomes' above.)

●Ethical and regulatory issues – General ethical issues include informed consent, use and disposition of gametes, disclosure of medical information, donor identification, and disclosure to offspring. As guidelines for TDI differ based on country and region, clinicians should be aware of the laws and regulations in their location of practice. (See 'Ethical and regulatory issues' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Serene S Srouji, MD, who contributed to earlier versions of this topic review.