Clinical UM Guideline

This document addresses the use of intracytoplasmic sperm injection (ICSI) during an infertility treatment cycle. This technique can allow some infertile individuals to attain live birth rates similar to those achieved with in vitro fertilization (IVF) using conventional methods of fertilization.

Note: Please see the following related documents for additional information:

• CG-MED-66 Cryopreservation of Oocytes or Ovarian Tissue
• CG-MED-103 Assisted Reproductive Technology
• CG-SURG-34 Diagnostic Hysteroscopy for Infertility
• LAB.00045 Selected Tests for the Evaluation and Management of Infertility

Note: For a high-level overview of this document, please see “Summary for Members and Families” below.

A maximum of three cycles of ICSI per attempted pregnancy is considered medically necessary in covered individuals who meet ANY of the following criteria:

1. Severe infertility due to any of the following semen analysis parameters;
   1. Asthenozoospermia (less than 40% moving sperm) (see definition section); or
   2. Oligozoospermia (less than 15 million/ml); or
   3. Teratozoospermia (normal morphology in 4% or fewer observed sperm); or
2. Previous IVF treatment cycle has resulted in failed or poor fertilization (equal to or greater than 50% of oocytes unfertilized in a prior cycle); or
3. Anti-sperm antibodies have been documented; or
4. Spinal cord injury individuals requiring electroejaculated sperm; or
5. Surgically retrieved sperm (epididymal or testicular); or
6. When using cryopreserved sperm for individuals in remission from cancer; or
7. When required to support an IVF cycle that includes medically necessary preimplantation genetic testing (PGT); or
8. To support IVF when using cryopreserved oocytes.

Note:  Two semen analyses are required prior to categorization of the infertility. A comprehensive semen analysis must be completed prior to infertility treatment cycles.

Not Medically Necessary:

More than three cycles of ICSI per attempted pregnancy is considered not medically necessary.

ICSI is considered not medically necessary when the criteria above are not met including, but not limited to all of the following:

1. Unexplained infertility;
2. Tubal occlusion;
3. Advanced maternal age;
4. Low oocyte yield at retrieval;
5. Routine insemination of oocytes for IVF.

This document describes clinical studies and expert recommendations, and explains when a procedure that injects a sperm directly into an egg is clinically appropriate. This procedure is called intracytoplasmic sperm injection (ICSI). The following summary does not replace the medical necessity criteria or other information in this document. The summary may not contain all of the relevant criteria or information. This summary is not medical advice. Please check with your healthcare provider for any advice about your health.

Key Information

ICSI is a type of fertility treatment used during in vitro fertilization, or IVF. In this process, a doctor injects a single sperm directly into an egg using a very fine needle under a microscope. ICSI can help some people with male factor infertility. Male factor infertility is caused by problems with sperm number, movement, or shape. ICSI may help couples have a baby when standard IVF fertilization has not worked. However, it is not helpful for all causes of infertility. Using ICSI when not needed does not improve pregnancy rates and may expose families to risks that do not provide benefit.

What the Studies Show

ICSI is most often used when there are serious sperm problems. These include a very low sperm count, poor sperm movement, abnormal sperm shape, sperm that must be removed from the testicle or collecting duct (epididymis) by surgery, or sperm obtained after a spinal cord injury. It may also be used when sperm have antibodies attached, when frozen sperm are used after cancer treatment, when frozen eggs are used, or when preimplantation genetic testing (a procedure that involves selection of the sperm based on genetic makeup) is planned. In these cases, ICSI can help the egg become fertilized. After fertilization, the embryo is placed into the uterus, as in standard IVF.

Expert groups such as the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technology (SART) state that ICSI is safe and effective for infertility caused by sperm factors. Studies show that ICSI does not improve pregnancy outcomes for unexplained infertility, low egg number, or older maternal age. When ICSI is used in these situations, it does not increase success rates compared to standard IVF. Unnecessary or unproven tests and treatments can lead to needless risks, worry, or to treatment that does not help. There is also a small risk of birth defects with any pregnancy.

When is ICSI Clinically Appropriate?

ICSI may be appropriate in these situations:

• Severe male factor infertility based on at least two semen analyses showing:
  • Less than 15 million sperm per milliliter;
  • Less than 40 percent moving sperm;
  • Normal shape in 4 percent or fewer sperm;
• A prior IVF cycle with poor or failed fertilization, meaning 50 percent or more eggs did not fertilize;
• Documented anti sperm antibodies;
• Sperm obtained after spinal cord injury using electrical stimulation;
• Sperm surgically retrieved from the epididymis or testicle;
• Use of frozen sperm in a person in remission from cancer;
• IVF cycles that include preimplantation genetic testing;
• IVF using previously frozen eggs.

Up to three ICSI cycles per attempted pregnancy are considered appropriate when one of the above criteria is met.

When is this not Clinically Appropriate?

ICSI is not clinically appropriate in scenarios other than those listed above.

ICSI is not appropriate for:

• More than three cycles per attempted pregnancy;
• Unexplained infertility;
• Blocked fallopian tubes;
• Advanced maternal age alone;
• Low number of eggs retrieved;
• Routine use with IVF when there is no male factor infertility.

Studies from expert groups show that ICSI does not improve pregnancy or live birth rates in these situations. Using ICSI when it is not needed does not increase success and may expose people to added risks without benefit. Better studies are needed to know if ICSI improves health in groups outside the approved indications.

(Return to Description)

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services may be Medically Necessary when criteria are met:

When services are Not Medically Necessary:
For the procedure codes listed above when criteria are not met or for situations designated in the Clinical Indications section as not medically necessary.

Summary

This document outlines the medical necessity criteria for intracytoplasmic sperm injection (ICSI), a technique used during in vitro fertilization (IVF) in which a single sperm is injected directly into an egg to assist fertilization. Up to three ICSI cycles per attempted pregnancy are considered medically necessary when specific criteria are met, including severe male factor infertility (such as oligozoospermia, asthenozoospermia, or teratozoospermia), prior failed or poor IVF fertilization, documented anti-sperm antibodies, use of surgically retrieved or electroejaculated sperm, use of cryopreserved sperm in cancer remission, preimplantation genetic testing (PGT), or fertilization of cryopreserved oocytes. Because semen parameters can vary significantly between samples, specialty societies recommend obtaining two comprehensive semen analyses before diagnosing infertility due to sperm abnormalities. ICSI is not considered medically necessary beyond three cycles or when used for unexplained infertility, tubal occlusion, advanced maternal age, low oocyte yield, or routine IVF insemination without qualifying factors.

The document also reviews clinical background and professional guidelines related to infertility and ICSI. Infertility affects approximately one in six couples, with male factors contributing to 30-40% of cases. Professional organizations including the American Society of Reproductive Medicine (ASRM), Society for Assisted Reproductive Technology (SART), American Urological Association (AUA), and World Health Organization (WHO) provide definitions, diagnostic standards, and semen parameter thresholds for severe infertility. Evidence supports ICSI as safe and effective for infertility due to sperm-related factors, though routine use outside these indications has not demonstrated improved outcomes. While ICSI carries a low risk of birth defects, some genetic risks may be associated with underlying infertility. Clinical data suggest diminishing returns after multiple unsuccessful fertility treatment cycles, supporting limits on repeated ICSI attempts.

Discussion

The ASRM (2023) defines infertility as follows:

“Infertility” is a disease, condition, or status characterized by any of the following:

• The inability to achieve a successful pregnancy based on a patient’s medical, sexual, and reproductive history, age, physical findings, diagnostic testing, or any combination of those factors.
• The need for medical intervention, including, but not limited to, the use of donor gametes or donor embryos in order to achieve a successful pregnancy either as an individual or with a partner.
• In patients having regular, unprotected intercourse and without any known etiology for either partner suggestive of impaired reproductive ability, evaluation should be initiated at 12 months when the female partner is under 35 years of age and at 6 months when the female partner is 35 years of age or older (ASRM, 2023).

Infertility can be caused by the inability to ejaculate or an insufficient number of sperm. Work-up for the diagnosis of infertility should include a comprehensive medical, reproductive, and family history and a physical exam. Laboratory testing and diagnostic evaluation may also be appropriate with emphasis on a systematic, expeditious manner and the least invasive method for diagnosis of infertility.

According to the National Institutes of Health (NIH), approximately one in six couples has difficulty conceiving. It is estimated that infertility related to sperm factors occurs in about 30-40% of these cases. The most common cause for reduced sperm production is an enlarged mass of veins in the spermatic cord within the scrotum. The spermatic cord is made up of veins, arteries, lymphatic vessels, nerves, and the duct that carries sperm from the testes to the seminal vesicles.

The ASRM recommends two semen analyses (SAs) in the evaluation of male factor infertility. Azoospermia is established when no spermatozoa can be detected on high-powered microscopic examination of a pellet after centrifugation of the seminal fluid on at least two separate occasions (2008). A joint AUA/ASRM guideline (2021) also states:

The SA is an important component in the initial clinical evaluation of the male and his reproductive health. Semen parameter values falling above or below the lower limit do not by themselves predict either fertility or infertility. In the interpretation of the SA, the clinician should remember that semen parameters are highly variable biological measures and may vary substantially from ejaculate to ejaculate. Therefore, at least two SAs, ideally obtained at least one month apart, are important to obtain, especially if the first SA has abnormal parameters.

Normal semen parameters established by the WHO laboratory manual for the examination and processing of human semen (2021) are as follows:

• Semen volume: 1.4 ml or more;
• Sperm concentration: 15 million spermatozoa per ml or more;
• Total sperm number: 39 million spermatozoa per ejaculate or more;
• Total motility (percentage of progressive motility and non-progressive motility): 42% or more motile or 30% or more with progressive motility;
• Vitality: 54% or more live spermatozoa;
• Sperm morphology (normal forms): 4% or more.

WHO (2021) considers infertility due to sperm factors to be severe when any of the following semen analysis parameters are present:

• Oligozoospermia (less than 15 million/ml)
• Asthenozoospermia (less than 40% moving sperm)
• Teratozoospermia (normal morphology in 4% or fewer observed sperm)
• Positive anti-sperm antibodies
• Spinal cord injury individuals requiring electroejaculated sperm
• Surgically retrieved sperm (epididymal or testicular)

ICSI is a potential component of an IVF cycle. This technique has expanded treatment options for infertility, allowing previously infertile individuals to conceive. The procedure is completed under a microscope using a microscopic glass needle to inject a single sperm directly into the egg. Once the egg is fertilized, it is transferred to the uterus. ICSI is used for individuals who have very poor semen quality or lack of sperm in the semen caused by an obstruction or testicular failure. In some cases, sperm may be surgically extracted from the testicles or epididymis for this procedure.

According to the SART (2008):

If a woman gets pregnant naturally, there is a 1.5% to 3% chance that the baby will have a major birth defect. The chances of birth defects after ICSI are rare. Certain conditions that have been associated with the use of ICSI (Beckwith-Wiedemann syndrome, Angelman syndrome, hypospadias, or sex chromosome abnormalities) are thought to occur in far less than 1% of children conceived using this technique. Some of the problems that caused your infertility may be genetic. Therefore, boys conceived with the use of ICSI may have infertility issues as adults.

Smith and colleagues (2010) reported results from a prospective fertility cohort study of 408 couples undergoing cycle-based treatment in the United States. The authors concluded that cycle-based fertility treatments offer clinically significant increases in the pregnancy rate; however, this benefit does not persist indefinitely.

Couples not achieving a pregnancy with medications alone after two cycles or intrauterine insemination (IUI) after three cycles may be best counseled to pursue a higher level of infertility treatment. Those failing IVF after two cycles may want to consider other treatment strategies, such as donor sperm, donor egg, or further modifications in the IVF or ICSI protocol because additional cycles seem less likely to increase reproductive success as much as earlier cycles.

A 2020 committee opinion of the ASRM and SART stated that ICSI is a safe and effective treatment for infertility due to sperm factors. The document also stated that ICSI for unexplained fertility, low oocyte yield and advanced maternal age does not improve clinical outcomes. Their opinion included a statement that ICSI may be beneficial for individuals undergoing IVF with PGT, fertilization after in vitro matured oocytes and cryopreserved oocytes. Cryopreservation of oocytes involves the removal of the cumulus cells before freezing which leads to changes in the zona pellucida that could reduce fertilization by conventional methods. For this reason, ICSI is the preferred method of achieving fertilization of cryopreserved oocytes. The authors concluded that the use of ICSI is a safe and effective therapy for the treatment of infertility related to sperm factors; currently there is no data to support the routine use of ICSI for other causes of infertility.

Azoospermia: Lack of live spermatozoa in the semen; classified as obstructive or nonobstructive depending on whether cause is blockage of the tubules or ducts.

Infertility: The Practice Committee of the American Society for Reproductive Medicine (ASRM) published their Definition of Infertility in 2023. That definition is:

“Infertility” is a disease, condition, or status characterized by any of the following:

• The inability to achieve a successful pregnancy based on a patient’s medical, sexual, and reproductive history, age, physical findings, diagnostic testing, or any combination of those factors.
• The need for medical intervention, including, but not limited to, the use of donor gametes or donor embryos in order to achieve a successful pregnancy either as an individual or with a partner.
• In patients having regular, unprotected intercourse and without any known etiology for either partner suggestive of impaired reproductive ability, evaluation should be initiated at 12 months when the female partner is under 35 years of age and at 6 months when the female partner is 35 years of age or older (ASRM, 2023).

Intracytoplasmic sperm injection (ICSI): A fertility treatment that is used to treat sperm related problems by injecting a single sperm into a mature egg. The fertilized egg is then placed in a woman's uterus or fallopian tube.

Oligospermia: Decreased number of spermatozoa in the semen.

Teratozoospermia: The sperm shape is abnormal and incapable of fertilizing the egg, with normal morphology observed in 4% or fewer sperm.

Peer Reviewed Publications:

1. Anderson JE, Farr SL, Jamieson DJ, et al. Infertility services reported by men in the United States: national survey data. Fertility and Sterility. 2009; (6):2466-2470.
2. Boulet SL, Mehta A, Kissin DM, et al. Trends in use of and reproductive outcomes associated with intracytoplasmic sperm injection. JAMA. 2015; 313(3):255-263.
3. Kathiresan AS, Ibrahim E, Aballa TC, et al. Comparison of in vitro fertilization/intracytoplasmic sperm injection outcomes in male factor infertility patients with and without spinal cord injuries. Fertil Steril. 2011; 96(3):562-566.
4. Pandian Z, Bhattacharya S, Ozturk O, et al. Number of embryos for transfer following in-vitro fertilization or intra-cytoplasmic sperm injection. Cochrane Database of Systematic Reviews 2009;(2):CD003416.
5. Smith JF, Eisenberg ML, Millstein SG, et al. Fertility treatments and outcomes among couples seeking fertility care: data from a prospective fertility cohort in the United States. Fertil Steril. 2011; 95:79-84.

Government Agency, Medical Society, and Other Authoritative Publications:

1. The American College of Obstetricians and Gynecologists (ACOG). ACOG Committee on Obstetric Practice Committee on Gynecologic practice. Committee on Genetics. Number 671, September 2016, Reaffirmed 2020. Perinatal risks associated with assisted reproductive technology. Obstet Gynecol. 2016; 128:e61-68.
2. Boitrelle F, Shah R, Saleh R, et al. The sixth edition of the WHO manual for human semen analysis: a critical review and SWOT analysis. 2021. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706130/pdf/life-11-01368.pdf. Accessed on May 5, 2026.
3. Cooper TG, Noonan E, von Eckardstein S, World Health Organization reference values for human semen characteristics. Human Reproduction Update. 2010; 16:(3)231-245.
4. Practice Committee of American Society for Reproductive Medicine. Definition of infertility: a committee opinion (2023). Fertil Steril. 2020; 113(3):533-535..
5. Practice Committee of American Society for Reproductive Medicine and Society for Assisted Reproductive Technology. Intracytoplasmic sperm injection (ICSI) for non-male factor infertility: a committee opinion. Fertil Steril. 2020; 114:239-245.
6. Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Male Reproduction and Urology. Evaluation of the azoospermic male. Fertil Steril. 2008; 90:74-77.
7. Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Male Reproduction and Urology. The management of infertility due to obstructive azoospermia. Fertil Steril. 2008; 90:121-124.
8. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and treatment of infertility in men: AUA/ASRM guideline part I. J Urol. 2021; 205(1):36-43.
9. World Health Organization (WHO) Department of Reproductive Health and Research. WHO laboratory manual for the examination and processing of human semen. Sixth edition. 2021. Available at: https://www.who.int/publications/i/item/9789240030787. Accessed on May 5 , 2026.

1. American Society for Reproductive Medicine. Available at: http://www.asrm.org/. Accessed on May 5, 2026.
2. National Library of Medicine. Medline Plus. Male Infertility. Updated August 7, 2024. Available at: http://www.nlm.nih.gov/medlineplus/maleinfertility.html. Accessed on May 5, 2026.

Intracytoplasmic sperm injection (ICSI)

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