Clinical UM Guideline

This document addresses the use of assisted reproductive technology (ART) during infertility treatment, as well as fertility preservation. This document also addresses the use of ART as part of a medically necessary preimplantation genetic testing (PGT) procedure performed to detect a known or suspected heritable genetic disorder or chromosomal abnormality.

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

• CG-MED-66 Cryopreservation of Oocytes or Ovarian Tissue
• CG-MED-88 Preimplantation Embryo Biopsy
• CG-SURG-34 Diagnostic Hysteroscopy for Infertility
• LAB.00045 Selected Tests for the Evaluation and Management of Infertility
• CG-SURG-35 Intracytoplasmic Sperm Injection (ICSI)

Note: The gender descriptions used in this document, ‘biological female’ and ‘biological male’, are used to clarify the reproductive capacity of the individual, regardless of gender identity or expression:

• The term ‘biological female’ refers to sex assignment at birth.
• The term ‘biological male’ refers to sex assignment at birth.

Note: Federal and State mandates, as well as benefit language supersede the content of this document. Some plans may exclude or limit coverage of infertility treatment and other associated services. Please check benefit plan descriptions for details.   

Note: Some plans may exclude or limit coverage of fees related to the payment of the egg donor; donor identification; legal services; or selection, purchase and transportation of frozen donor eggs, including the purchase of donated frozen eggs or donated frozen embryos. Please check benefit plan descriptions for details.

Medically Necessary:

The following treatments for infertility are considered medically necessary when all of the following General Criteria are met and the following Procedure-Specific Criteria also are met.

I.  General Criteria:

1. The use of ART is indicated for one of the following reasons (1 or 2):
   1. The individual has been diagnosed with infertility defined as any of the following:
      1. Biological female with a biological male partner:
         1. The inability to conceive or produce a conception during a period of one year if the biological female is under the age of 35 years; or
         2. The inability to conceive or produce a conception during a period of six months if the biological female is age 35 or older, following exposure to fresh sperm.
            or
      2. Biological female without a biological male partner:
         1. If under the age of 35 years, the inability to conceive or produce a conception after 12 cycles of documented medically supervised stimulated intrauterine insemination (IUI); or
         2. If 35 years of age or older, the inability to conceive or produce a conception after 6 cycles of documented medically supervised stimulated intrauterine insemination (IUI);
            or
   2. When required to support medically necessary preimplantation genetic testing (PGT);
      and
2. The biological female is of normal reproductive age (see definition); and 
3. Reversible or iatrogenic causes of infertility are not present, including all of the following:
   1. Infertility is NOT the result of sterilization services, except when the sterilization was performed for treatment of an illness, injury or disease or its symptoms, unless a successful surgical reversal has been documented; and
   2. Infertility is NOT the result of medical treatment or use of other fertility-reducing substances, for example, hormonal contraception or gonadotropin-releasing hormone agonists used therapeutically) or when fertility is suppressed due to use of other substances (for example spermatogenesis inhibition due to cannabis use); and
   3. Suppression must be resolved before infertility can be evaluated. Infertility services are considered medically necessary when other criteria are met and the following is documented:
      1. In biological females:
         1. Failure to resume ovulation within 3 months after discontinuing oral contraceptive drugs; or
         2. Failure to resume ovulation 4 months after removal of an intrauterine device; or
         3. Failure to resume ovulation 9 months after the last injection of depot medroxyprogesterone acetate (DMPA); or
      2. In biological males: failure to return to a normal sperm count (≥10 million motile sperm per mL after processing) within 3 months after cessation of exposure to fertility-reducing substance(s).

II.  Procedure-Specific Criteria

In Vitro Fertilization (IVF)/ Zygote Intra-Fallopian Transfer (ZIFT)/ Gamete Intra-Fallopian Transfer (GIFT):

IVF/ZIFT/GIFT is considered to be medically necessary when all of the following criteria (A, B and C) are met:

1. The general criteria above have been met; and
2. No more than the maximum number of embryos recommended by the ASRM are transferred (see Discussion); and
3. Any of the following conditions are present:
   1. Endometriosis Stage III or IV, following either of the following:
      1. Failure to conceive following conservative surgery; or
      2. Contraindications to surgery are present;
         or
   2. Failure to have a live birth after 3 cycles of IUI with oral medications for unexplained infertility; or
   3. For ovulatory disorders, failure to have a live birth after 6 months of conservative treatment, oral agents for 3 cycles, and 3 follicular stimulating hormone (FSH) IUIs; or
   4. Male factor infertility; or
   5. Pelvic adhesive disease; or
   6. Tubal factor infertility unrelated to prior sterilization; or
   7. IVF is being performed to support medically necessary preimplantation genetic testing (PGT).

Note: Before proceeding to a fresh ART cycle, frozen embryo transfer (FET) using previously cryopreserved embryos must be attempted if a reasonable quality of cryopreserved embryo(s) is available. Similarly, previously frozen oocytes must be used (for example, fertilized and transferred) before proceeding to the next fresh ART cycle.

Donor Egg

Donor egg use is considered medically necessary when all of the criteria below (A, B, and C) are met:

1. The egg donor is less than 34 years of age (as recommended by ASRM); and
2. The treated individual has a medical illness that has caused unnatural loss of egg quality or quantity; and
3. Any of the following circumstances are present:
   1. There have been at least two IVF treatment cycles in which 5 or fewer eggs were retrieved with maximum ovarian stimulation; or
   2. Ovaries are absent; or
   3. Premature ovarian insufficiency, defined by FSH > 25 mIU/mL not due to other disorders.

Donor Sperm

Up to 2 vials of donor sperm per IVF/IUI cycle are considered medically necessary when both criteria below (A and B) are met:

1. A diagnosis of infertility has been excluded in the intended gestational parent, or there is a diagnosis of unexplained infertility; and
2. At least 2 processed semen analyses demonstrate < 6 million total motile and viable sperm.

Frozen Embryo Transfer (FET)

Frozen embryo transfer (FET) is considered medically necessary when both of the following criteria (A and B) are met:

1. No more than the maximum number of embryos recommended by the ASRM are transferred (see Discussion); and
2. One or more of the following criteria (1 or 2 or 3) are met:
   1. Embryos were created during a medically necessary IVF cycle; or
   2. Embryos were created previously and individual has met the infertility criteria in this policy, either at time of freezing or prior to transfer; or
   3. The individual meets criteria for use of a donor egg/embryo and will be using donor egg/embryo for FET.

Fertility Preservation

Note: IVF with oocyte/embryo/sperm collection may be covered in accordance with Federal or State law when an individual is facing anticipated infertility resulting from medical or surgical treatment. Please refer to appropriate guidance.

Ovarian transposition is considered medically necessary when all of the criteria (A, B, and C) have been met:

1. The individual is undergoing radiation therapy of the pelvic area; and
2. The ovaries are within the planned radiation field; and
3. There is concern that the radiation treatment would permanently harm the ovaries.

Note: See CG-MED-66 for criteria related to cryopreservation of oocytes or ovarian tissue.

Cryopreservation of Sperm or Testicular Tissue

Cryopreservation of sperm or testicular tissue is considered medically necessary for individuals undergoing active infertility treatment, when the following criteria are met:

1. Sperm storage/banking in individuals who have undergone covered microepididymal sperm aspiration (MESA) or microdissection-testicular excisional sperm extraction (mTESE); or
2. Cryopreservation of testicular tissue/sperm in adult biological males with azoospermia in conjunction with the testicular biopsy to identify sperm in preparation for an intracytoplasmic sperm injection procedure, if sperm are found.

Gestational Carrier (surrogate)

The following procedures are considered medically necessary for a gestational carrier* when both criteria (A and B) below are met:

1. Medical Procedures for a covered member with infertility:
   1. Infertility evaluation; and
   2. Ovarian stimulation; and
   3. Oocyte retrieval; and
   4. Fertilization;
      and
2. Conditions:
   1. There is a confirmed medical contraindication to pregnancy.

*Please refer to the plan benefits for details regarding coverage of infertility services relating to use of a gestational carrier.

Microepididymal Sperm Aspiration (MESA)

Microepididymal sperm aspiration is considered medically necessary when either of the following conditions are present and confirmed by medical exam:

1. Congenital absence of the vas deferens; or
2. Obstruction of the vas deferens.

Microdissection- Testicular Excisional Sperm Extraction (mTESE)

Microdissection-TESE is considered medically necessary when either of the following conditions are present:

1. Non-obstructive azoospermia; or
2. Spinal cord injury resulting in inability to ejaculate.

Conversion from IUI to IVF

Conversion from IUI to IVF-Embryo Transfer (IVF-ET) is considered medically necessary to reduce the risks of high-order multiple gestations when both of the criteria below (A and B) have been met:

1. The intended outcome of gonadotropin IUI is the development of either of the following:
   1. 2 or more mature follicles greater than 16 mm at the time of human chorionic gonadotropin (hCG) administration; or
   2. 3 or more mature follicles greater than 14 mm develop at the time of hCG administration;
      and
2. Either of the following:
   1. There are 4 or more follicles greater than or equal to 15 mm on the day of hCG administration; or
   2. The estradiol (E2) level is 1,000 pg/ml or greater on the day of hCG administration.

Infertility Treatment After Reversal of Sterilization

Infertility treatment following reversal of sterilization** in biological females (for example, microsurgical tubal anastomosis) is considered medically necessary when tubal patency on at least one side has been proven.

Infertility treatment following reversal of sterilization** in biological males is considered medically necessary when restoration of fertility has been demonstrated by meeting both of the following criteria:

1. Submission of 2 post- reversal semen analyses showing ≥ 20 million total motile sperm and ≥ 3% normal forms; and
2. The first analysis must be conducted within 6 months of the reversal procedure and the second 6 months after the first analysis (6 months apart).

**Please refer to the plan benefits for details regarding coverage of reversal of sterilization that was not performed for treatment of an illness, injury or disease or its symptoms.

Not Medically Necessary:

Use of the techniques and procedures mentioned above are considered not medically necessary when the criteria above are not met, including but not limited to the following:

1. Conversion from IUI to IVF-ET is not medically necessary for situations where monofollicular ovulation was the goal and stimulation medication did not follow international protocols.
2. Donor eggs for a decline in egg quantity or quality as a result of normal aging.
3. Donor sperm use without documented biological male factor infertility proven with two abnormal semen analyses.
4. Health services provided to a gestational carrier who is not a member, including, but not limited to embryo transfer, pregnancy costs, or cryopreservation of embryos.
5. Sperm storage/banking for biological males requesting this service for convenience or “backup” for a fresh specimen

Due to the low likelihood of success, IUI is considered not medically necessary after initiation of IVF until an intervening live birth has occurred.

The following procedures and techniques are considered not medically necessary:

1. Assisted embryo hatching
2. Co-culture of embryos
3. Direct intraperitoneal insemination (DIPI)
4. Egg harvesting or other infertility treatment performed during an operation not related to an infertility diagnosis
5. Embryo toxic factor test (ETFL)
6. Genetic engineering
7. Human zona binding assay (hemizona test)
8. In vitro maturation of oocytes
9. IVF or other infertility treatment for gender selection
10. Mock transfer
11. Ovulation kits
12. Percutaneous Epididymal Sperm Aspiration (PESA)
13. Peritoneal ovum and sperm transfer (POST)
14. Post-coital testing
15. Reciprocal IVF
16. Serum anti-sperm antibody testing
17. Sperm acrosome reaction test
18. Testicular sperm aspiration (TESA) (a different procedure than testicular sperm extraction [TESE] and mTESE - see definitions)
19. Treatment to reverse sterilization, except when the sterilization was performed for treatment of an illness, injury or disease or its symptoms
20. Use of donor sperm or eggs with genetic defects

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, or for the following diagnosis.

When services are also Not Medically Necessary:
For the following procedure codes, or when the code describes a procedure designated in the Clinical Indications section as not medically necessary.

Summary

Infertility is defined by the American Society for Reproductive Medicine (ASRM) as the inability to achieve pregnancy due to medical, sexual, and reproductive factors or the need for medical intervention to achieve pregnancy. Evaluation is recommended after 12 months of unprotected intercourse or after 6 months if the biological female is over 35. The use of ART to increase the likelihood of pregnancy and live birth are usually only recommended when there is a good chance of success. Factors such as age, smoking, obesity, alcohol use, and caffeine intake significantly affect fertility and treatment success. For instance, biological females over the age of 43 have less than a 5% IVF success rate, smoking reduces IVF success by nearly 50%, and BMI extremes (underweight or severely overweight) can disrupt ovulation and increase miscarriage risks. Lifestyle modifications, ovulation-inducing agents, and diagnostic tests such as hormone tests, semen analysis, and uterine assessments are essential components of infertility treatment, especially for conditions such as polycystic ovarian syndrome (PCOS) and premature ovarian insufficiency (POI).

ART, such as IVF, cryopreservation, and use of gestational carriers or donor gametes, play a critical role in treatment, particularly for individuals facing infertility near the end of their normal reproductive age, POI, or undergoing gonadotoxic therapies. Guidelines emphasize individualized care based on the clinical presentation of the individuals seeking parenthood. Male infertility is often addressed with techniques such as mTESE for sperm retrieval. Ethical considerations, long-term outcomes of FETs, and fertility preservation options are integrated into care planning.

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.

Infertility services are not medically necessary when the treatment is considered “futile” or has a “very poor prognosis,” as defined by the ASRM (2019). ASRM defines futile treatments as those having less than a 1% chance of achieving a live birth. Treatments with a very poor prognosis are defined as having a 1-5% chance of achieving a live birth. The determination of whether or not a treatment is futile or has a very poor prognosis is specific to each individual based on their medical history, physical exam findings, lab results, prior infertility treatments, and data from population and national Society for Assisted Reproductive Technology (SART) annual statistics.

Lifestyle Factors

Smoking reduces fertility and reduces the success of IVF by nearly 50%, even when the biological male smoked and the biological female did not (ASRM, 2024c). It can lead to preterm delivery, intrauterine growth restriction, placental abruption, placenta previa, premature rupture of membranes, early menopause, and increased perinatal mortality (American College of Obstetricians and Gynecologists [ACOG], 2019). A study showed that the occurrence of conception delay over 1 year was 54% higher in smokers and the impact of passive cigarette smoke exposure alone was only slightly smaller than for active smoking (ASRM, 2024c). Nicotine replacement therapy has different U.S. Food and Drug Administration (FDA) pregnancy risk categories depending on formulation: transdermal patches are category D (known fetal risk but may be used if benefits outweigh the risks), while gum, lozenges, nasal spray, and inhalers are category C (risk cannot be ruled out and potential benefits must justify the risk).

Obesity is associated with an increase in spontaneous abortion after assisted reproductive treatment (Wang, 2002). The spontaneous abortion rate is 18% for normal weight and 31% for biological females with a Body Mass Index (BMI) of 35 or greater. Obesity is also associated with an increased surgical risk in oocyte retrieval. Obesity may be associated with PCOS which may require medical treatment. It has been demonstrated that weight loss can improve the fertility of biological females with obesity through the recovery of spontaneous ovulation for some, and improved response to ovarian stimulation for others. The live birth rate was 9% lower for biological females with a BMI over 30 undergoing IVF. For adults of Asian descent, obesity is defined at a lower body mass index (BMI) threshold than for the general population due to higher body fat percentage and greater metabolic risk at lower BMI levels. A BMI calculator reflecting health risks for adults of Asian descent can be found at https://www.cchrchealth.org/body-mass-index-bmi-for-adults/. Biological females whose BMI is in the obese range should undertake a weight-reduction program that includes nutritional counselling, a structured diet plan, regular exercise, and behavior-modification counselling. A BMI of less than 18.5 (underweight) may cause irregular menstrual cycles and an increased risk of anovulatory infertility (Boutari, 2020).  Biological females who are underweight should be counseled to increase their BMI above the lower limits of normal. For most biological females, this will restore natural fertility and increase the potential for a good pregnancy outcome.

The World Health Organization (WHO) Class I ovulatory disorders (hypogonadotropic hypogonadal anovulation) often respond to lifestyle modification and WHO Class II disorders (normogonadotropic normoestrogenic anovulation) such as PCOS often respond to weight loss (Teede, 2023). For biological females with obesity and PCOS, the loss of just 5 to 10 percent of body weight is often sufficient to restore ovulation in 55% to 100% within six months (ASRM, 2008). Various ovulation-inducing agents (for example, clomiphene citrate, aromatase inhibitors, gonadotropins) and insulin-sensitizing drugs (for example, metformin) have been used to treat those who need intervention. Individuals with PCOS can be very sensitive to gonadotropins. The goal of treatment of ovulatory disorders is to restore normal monofollicular development and to avoid superovulation. A stepwise approach of medications (oral and then injectable) must be used. A step-up protocol has been shown to successfully induce ovulation with a low rate of multiple gestations (Shamonki, 2003)

Alcohol use disorder and alcoholism are associated with disorders of reproductive function in both biological males and biological females. There is a clearly established high risk of serious harm to a child associated with prenatal alcohol abuse (ACOG, 2019). Maternal alcohol use is the leading known cause of intellectual disabilities and is a preventable cause of birth defects. Children exposed to alcohol in utero are at risk for growth deficiencies, facial deformities, central nervous system impairment, behavioral disorders, and impaired intellectual development. Consuming alcohol during pregnancy also increases the risk of miscarriage, low birth weight, and stillbirth. Biological females should avoid alcohol entirely while pregnant or trying to conceive because damage can occur in the earliest weeks of pregnancy, even before an individual knows that they are pregnant. Even 1-2 drinks per day can be associated with decreased fertility.

High intake of caffeine (more than 5 cups of coffee/day) can be associated with decreased fertility, and 2-3 cups/day may increase the risk of miscarriage in biological females (Kukkonen, 2024; Lyngsø, 2017; Qian, 2020). Maternal caffeine consumption during pregnancy increases the risk of pregnancy failure or gestational complications such as fetal growth restriction and low birth weight by unknown mechanisms (Qian, 2020). Results of a systematic review and meta-analysis that evaluated the relationship between coffee or caffeine consumption and fertility support an association between caffeine intake and the risk of spontaneous abortion (Lyngsø, 2017). The European Food Safety Authority (EFSA, 2025) and WHO (2023) recommend that pregnant individuals restrict intake to no more than 2-3 cups of coffee (200-300 mg caffeine) per day.

Fertility after Discontinuation of Contraception

Mansour and colleagues (2011) investigated the effects on subsequent fertility following reversible contraceptive use. A total of 17 prospective studies reporting pregnancy rates following cessation of reversible contraceptive use were evaluated. Typical 1-year pregnancy rates following cessation of oral contraceptives ranged between about 79% and 96% with the median time to pregnancy being 2.5-3 months. Pregnancy rates for copper intrauterine devices (IUDs) were almost as high, ranging between about 71% and 91%, with a median time to pregnancy being 2-3.7 months. For injectable contraceptives such as DMPA, a study of 796 individuals who stopped using this long-acting medication showed that the median delay to conception was approximately 9 months after the last injection, with a 1-year pregnancy rate of about 78% (Pardthaisong, 1980).

Obesity

The ASRM published a committee opinion on obesity and reproduction in 2021 (2021d). In that document they state that obesity has been associated with an increased risk of pregnancy loss in many studies. They propose that BMI can influence pregnancy outcomes through a wide variety of mechanisms including thyroid dysfunction, insulin resistance, leptin resistance, lipotoxicity and inflammation, sleep dysfunction, mental health effects, and others. Additionally, obesity also has been shown to impact male fertility due to factors including endocrine alterations, sexual dysfunction, diabetes mellitus, sleep apnea, or scrotal hyperthermia. They provide the following conclusions:

• On the basis of available evidence, there is no medical or ethical directive for adopting a society-wide BMI threshold for offering infertility treatment; rather, there is considerable evidence arguing against such a policy. Before an IVF cycle, women with obesity should be carefully evaluated with a multidisciplinary team to determine the safety of oocyte retrieval under anesthesia, considering factors such as BMI and comorbidities.
• Obesity should not be the sole criteria for denying a patient or couple access to infertility treatment.
• Additional research is needed to determine best practices, validate safety data, and optimize access to oocyte retrievals in the setting of class 3 and 4 obesity. Women with obesity are at increased risk of infertility and of developing maternal and fetal complications during pregnancy.
• Weight loss intervention trials in women with obesity and infertility have not shown an improvement in the outcome of live birth after treatment. However, weight loss may improve the chance of unassisted conception.

Impact of Aging on Female Fertility

Research has shown a direct relationship between a decline in female fertility and advancing maternal age. In a collaborative Committee Opinion from the ASRM and ACOG, the authors point out that volume of oocytes in the ovaries declines naturally and progressively through the process of atresia. The female fetus at 20 weeks gestation has a maximum complement 6-7 million oocytes. However, the number of oocytes continues to decrease to “approximately 1-2 million oocytes at birth; 300,000-500,000 at puberty; 25,000 at age 37 years; and 1,000 at age 51 years, the average age of menopause in the United States” (ACOG, 2014).

Live-birth delivery rates inversely correlate with maternal age. As the number of oocytes decreases over time, the quality of oocytes and the likelihood of live birth also decreases. Declining fertility with age is also accompanied by significant escalations in the rates of spontaneous abortion, miscarriage, and stillbirths. (ACOG, 2014).

As age increases, there is also an increase in the risk of other disorders that may adversely affect fertility. Biological females with a history of prior radiation therapy, chemotherapy, ovarian surgery, or a strong family history of early menopause may be at an increased risk of having a premature reduction in the size of their follicular pool and decline in fertility (ACOG, 2014). In a study reported by Spandorfer and colleagues (2007), IVF yielded live births for individuals up to 45 years of age, but success was limited to those participants producing more than 5 oocytes in response to ovarian stimulation. Although pregnancy rates for participants 46 and 47 years of age were 17% and 9%, respectively, none of these pregnancies yielded a live birth.

Menopause is the permanent cessation of menstruation resulting from the natural depletion of ovarian follicles. It is a normal physiological process, not a disease, and treatment of infertility resulting from menopause is not considered medically necessary.

Diagnosis of Infertility Unrelated to Natural Aging

The initial evaluation of infertility includes basal (cycle days 2-4) FSH and estradiol levels, tubal patency evaluation if IUIs are to be done, a uterine cavity evaluation completed within the last year, 2 semen analyses following 2-5 days of abstinence, smoking history, BMI calculation, and alcohol use history.

A basic panel of laboratory tests is sufficient for biological females under age 40 who have a low likelihood of diminished ovarian reserve related to natural aging. However, before initiating a fresh IVF cycle for biological females aged 40 to under 45 without documented premature diminished ovarian reserve, a clomiphene citrate challenge test (CCCT) should be performed annually. If six months or more have elapsed since the most recent CCCT, basal FSH and estradiol should be repeated.

The CCCT is used to assess ovarian reserve (the remaining quantity and quality of oocytes) and to help predict how the ovaries will respond to fertility medications during IVF or other assisted reproductive treatments. In this test, clomiphene citrate is administered daily on days 5 - 9 of the menstrual cycle. FSH and estradiol are measured on cycle day 3 (before clomiphene citrate) and on cycle day10 (after clomiphene citrate). Both the day 3 and day 10 FSH values should be 12 mIU/mL or lower. The day 3 estradiol should be < 100 pg/mL. The ASRM (2020) considers that a normal FSH level with an elevated Day 3 estradiol, in the absence of another explanation such as an ovarian cyst or exogenous estrogen, indicates abnormal ovarian function and a poor prognosis for response to ovarian stimulation. A Day 10 estradiol that does not exceed 100 pg/mL suggests that clomiphene citrate was not taken correctly or that diminished ovarian reserve is present.

For individuals with a documented contraindication to clomiphene or an ovulation disorder (for example, polycystic ovary syndrome [PCOS], hypothalamic amenorrhea), the following alternative testing may be considered:

• Exogenous follicle-stimulating hormone ovarian reserve test (EFORT) showing an Inhibin B difference of < 78.6 pg/mL between Day 3 and Day 4; or
• A combination of basal FSH, estradiol, and antral follicle count (AFC) obtained on the same day, along with an anti-Müllerian hormone (AMH) level drawn within one month.

Premature Ovarian Insufficiency

Premature ovarian insufficiency (POI) is a rare cause of infertility characterized by loss of ovarian function leading to irregular menstrual cycles together with biochemical indicators of ovarian insufficiency before the age of 40 years.

The European Society of Human Reproduction and Embryology (ESHRE), ASRM, Centre for Research Excellence in Women’s Health in Reproductive Life (CRE WHiRL) and International Menopause Society (IMS) published an evidence-based guideline on POI in 2024. The guideline states that only one elevated FSH > 25 mIU/mL is required for diagnosis of POI. Measurements of FSH and anti-mullerian hormone (AMH) may help to confirm the diagnosis. The guideline provides the following recommendations (with the strength of the recommendation in parentheses):

• Women with POI should be informed that oocyte donation is an established option to achieve pregnancy after a diagnosis of POI. (STRONG)
• Women with non-iatrogenic POI and considering assisted reproduction using oocytes donated by their sister should be informed that this includes shared genetic risk and carries a higher risk of ovarian stimulation cycle cancellation. (STRONG)
• For iatrogenic causes of POI, fertility preservation can be considered prior to treatment. (CONDITIONAL)
• The guideline group recommends that fertility preservation is discussed with women at risk of POI. In most women with POI, there is no opportunity for fertility preservation as the follicle pool is depleted. (GOOD PRACTICE POINTS)

Gonadotoxic Therapy or Gonadectomy

The ASRM published recommendations for fertility preservation in individuals undergoing gonadotoxic therapy or gonadectomy in 2019. In that document they provided the following statements:

• Embryo, oocyte, and ejaculated or testicular sperm cryopreservation remain the principle established modalities for fertility preservation.
• Testicular tissue cryopreservation in prepubertal males is still considered experimental and should be conducted under research protocols when no other options are feasible.
• Ovarian transposition may be offered to women undergoing pelvic radiation.

Similarly, the American Society of Clinical Oncology (ASCO) published a clinical practice guideline in 2018 regarding fertility preservation before treatment for cancer. The guideline states that cryopreservation of embryos, oocytes and sperm is an effective and established fertility preservation method. Ovarian transposition can be offered when pelvic irradiation is performed as cancer treatment. ASCO also states that testicular tissue cryopreservation and reimplantation or grafting of human testicular tissue should be performed only as part of clinical trials or approved experimental protocols. For prepubertal children, the only fertility preservation options are ovarian and testicular cryopreservation.

Tubal Surgery

In 2021, the ASRM published a committee opinion that reviewed surgical options for reparative tubal surgery and the factors that must be considered when deciding between surgical repair and IVF (2021e). Tubal disease accounts for 25%-35% of female factor infertility. Factors to be considered when counseling individuals with tubal infertility about corrective surgery or IVF include the age of the biological female, ovarian reserve, number and quality of sperm in the ejaculate, number of children desired, site and extent of tubal disease, presence of other infertility factors, risk of ectopic pregnancy and other complications, experience of the surgeon, success rates of the IVF program, cost, and individual preference. There are no adequate trials comparing pregnancy rates after tubal surgery with those following IVF.

Sastre and colleagues (2023) conducted a systematic review and meta-analysis of microsurgical anastomosis of the fallopian tubes after tubal ligation. The overall pregnancy rate after anastomosis was found to be 65.3% (95% CI: 61.0-69.6). The individual’s age was identified as the most significant determining factor for fertility restoration. When comparing the results of tubal reversal with IVF, reversal procedures appeared more favorable for patients over 35 years old, while the results of IVF and tubal reversal were similar for patients under 35 years old, but the authors note that more data is needed to confirm this finding.

Intrauterine Insemination (IUI)

IUI involves placement of prepared sperm directly into the uterine cavity at the time of ovulation to facilitate fertilization. Compared with timed intercourse, IUI increases gamete proximity to the oocyte and bypasses cervical mucus abnormalities. It is the least invasive form of assisted reproduction and serves as an intermediate step before in-vitro fertilization (IVF).

ASRM’s 2020 evidence-based guideline for unexplained infertility and subsequent practice committee opinions establish that IUI is appropriate as first-line or early therapy for individuals with adequate ovarian reserve, patent tubes, and for mild male-factor infertility. IUI is typically combined with ovulation-inducing agents to increase per-cycle fecundity.

ASRM recommends that IUI be performed only after a basic infertility evaluation including confirmation of ovulation, tubal patency, and semen analysis to ensure a treatable factor is not overlooked. IUI is ineffective when the tubes are obstructed or severe male-factor infertility exists, since fertilization cannot occur without contact between the sperm and egg.

Randomized controlled trials and meta-analyses reviewed by ASRM show that IUI with ovulation-stimulating agents results in higher live-birth rates than expectant management or timed intercourse for unexplained infertility, though cumulative benefit plateaus after several cycles. For mildly abnormal semen parameters (total motile sperm count ≥5-10 million after processing), IUI improves the probability of conception compared with intercourse, whereas IVF/ICSI is preferred in more severe male-factor cases. When infertility results from hostile cervical mucus, ejaculatory dysfunction, or vaginismus, IUI bypasses the cervix and permits conception using ejaculated or retrieved sperm (ASRM, 2021g; Brannigan, 2024).

IUI combined with ovarian stimulation may increase risk for high-order multiple gestations. Conversion from IUI to IVF may be necessary to reduce this risk, as discussed in the section on Multiple Gestation Associated with Infertility Therapy below.

In Vitro Fertilization (IVF), Gamete Intrafallopian Transfer (GIFT), and Zygote Intrafallopian Transfer (ZIFT)

IVF involves controlled ovarian stimulation, oocyte retrieval, extracorporeal fertilization, and embryo transfer into the uterus. IVF is the reference ART in modern practice because it avoids pelvic access surgery, permits embryo assessment, supports single-embryo transfer to mitigate multiples, and is compatible with sperm-retrieval and preimplantation testing when indicated (ASRM, 2021b).

Gamete intrafallopian transfer (GIFT) places oocytes and sperm together directly into a patent fallopian tube via laparoscopy; zygote intrafallopian transfer (ZIFT) places a laboratory-fertilized zygote into a fallopian tube. Both require laparoscopy and at least one open tube. IVF offers treatment without laparoscopy, controlled embryo selection and euploid single embryo transfer, compatibility with sperm-retrieval and PGT, and a superior safety profile regarding multiple gestation via single embryo transfer. Comparative evidence and historical reviews show no advantage of GIFT/ZIFT over IVF for live-birth, while exposing individuals to operative risks and requiring tubal patency. Consequently, most guidelines default to IVF when ART is indicated (Fluker, 1993; Niederberger, 2018).

Modern guidance recommends ART, most commonly IVF, for infertility associated with moderate to severe endometriosis, particularly after prior conservative surgery or when surgery is not appropriate, to bypass distorted pelvic anatomy and tubal-ovarian dysfunction. ASRM and ESHRE documents note IVF is often a better therapeutic pathway than repeat surgery for Stage III/IV disease with infertility (ASRM, 2012; ESHRE, 2022).

Fallopian tube adhesions can be caused by endometriosis or other conditions such as pelvic inflammatory disease, prior pelvic surgery, peritonitis, abdominal or pelvic trauma, or radiation treatments. Such adhesions can impair gamete pickup and transport. IVF bypasses the peritoneal and tubal environments and is favored over reconstructive surgery when adhesive burden is considerable or other factors coexist. ASRM’s tubal-surgery opinion emphasizes individualized selection between repair and IVF, with IVF commonly preferred in extensive disease or when multiple factors are present (ASRM, 2021e).

When there is significant tubal pathology such as hydrosalpinx, proximal occlusion not amenable to repair, or failed prior repair, IVF provides higher pregnancy efficiency than additional surgery in many contexts. Salpingectomy or proximal occlusion for hydrosalpinx prior to IVF may improve outcomes (ASRM, 2021e).

ASRM’s 2020 evidence-based guideline for unexplained infertility supports an escalation pathway from oral-agent IUI, to gonadotropin-IUI (with careful multiple-gestation risk control), then IVF when pregnancy has not been achieved after a reasonable trial. IVF has the highest per-cycle live-birth rates and allows single-embryo transfer to minimize multiple gestations (ASRM, 2020a).

For anovulation (for example, WHO class II/PCOS), first-line therapy is ovulation induction with oral agents. IUI may succeed when ovulation induction alone is insufficient. IVF may be appropriate when ovulation induction and IUI fail to produce a pregnancy. Contemporary guidance supports this stepped approach, reserving IVF for failures of less invasive therapy or where additional factors coexist (ASRM, 2021g; Tay, 2024).

After 6 consecutive IVF non-donor cycles without a live birth, data show a 7th cycle will have less than a 5% live birth rate per cycle (Smith, 2015). Attempting IUI after failing IVF is also associated with less than a 5% live birth rate per cycle (Alorf, 2024).

Use of Assisted Reproductive Technology for Preimplantation Genetic Testing (PGT):

Preimplantation genetic testing (PGT) is performed on embryos created through IVF to identify specific genetic or chromosomal abnormalities before transfer to the uterus. IVF is an essential prerequisite for PGT, as embryo biopsy and genetic analysis require fertilization and embryo culture outside the body. The ASRM Ethics Committee affirms that use of PGT to prevent transmission of serious heritable genetic disorders is ethically acceptable and clinically justified, provided it is directed toward avoiding significant disease or disability in offspring (ASRM, 2024a). The ACOG similarly supports offering IVF with PGT to individuals or couples who are known carriers of serious heritable genetic or chromosomal disorders (ACOG, 2019). When ART is required to perform medically necessary PGT, its use is consistent with these professional recommendations and should be considered medically necessary.

Gamete and Embryo Donation

In 2024, the ASRM provided recommendations for the evaluation of potential sperm, oocyte, and embryo donors, as well as their recipients. (ASRM, 2024b) These recommendations incorporate recent information from the U.S. Centers for Disease Control and Prevention (CDC), the FDA, and the American Association of Tissue Banks (AATB).

Donors are individuals who are not sexual partners of the recipients. Donor eligibility determination is required for donor sperm, donor oocytes, donor embryos, and sperm and oocyte sources when planning to use a gestational carrier. Sperm donors should ideally be 21 years or older and should be young enough that the risks to offspring associated with increased paternal age are minimized. Oocyte donors should preferably be between the ages of 21 and 34 years old. When a prospective oocyte donor is older than 34 years, the age of the donor should be revealed to the recipient as part of the informed consent discussion concerning cytogenetic risks and the effect of donor age on pregnancy rates. Donors of all types should be healthy and have no history to suggest hereditary disease. All donors should also undergo an appropriate genetic evaluation, including screening for cystic fibrosis, spinal muscular atrophy, and thalassemia/hemoglobinopathy carrier status.

Cryopreservation for Donor Oocytes

In 2021, the ASRM published a guideline on cryopreservation for donor oocyte IVF and planned oocyte cryopreservation (OC) (2021c). The technology for OC has improved in recent years including rapid cooling (also called vitrification) resulting in widespread use. A summary of their recommendations is below:

• There is insufficient evidence to predict live birth rates after planned OC.
• On the basis of limited data, ongoing and live birth rates appear to be higher for women who undergo planned OC at a younger vs. older ages.
• Ovarian reserve tests can be used to estimate the anticipated oocyte yield.
• There are no significant differences in per transfer pregnancy rates with cryopreserved vs. fresh donor oocytes.
• Neonatal outcomes appear similar with cryopreserved oocytes.
• There is a pressing need for additional data about long term outcomes and cumulative live birth rates with cryopreserved oocytes, after planned OC and use of cryopreserved donor eggs.

In 2024, Tocariu and colleagues conducted a systematic review and meta-analysis of neonatal outcomes following fresh versus FET in IVF. Twenty studies including 171,481 participants were analyzed. A significant increase in preterm birth rates was noted with fresh embryo transfer compared to FET in the overall population (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.18-1.35; p<0.00001), as well as greater odds of having a low-birth-weight infant (OR, 1.37; 95% CI, 1.27-1.48; p<0.00001). The data support cryopreservation and favor FET in reducing risks such as preterm birth and low birth weight.

Coverage for health services provided to a gestational carrier, including fertility evaluation, ART, and pregnancy care may be subject to limits under the applicable benefit plan.

Multiple Gestation Associated with Infertility Therapy

The ASRM (2022) published a committee opinion on multiple gestation associated with infertility therapy. The purpose of the document is to provide information to help prevent or avoid multiple gestations and to improve counseling regarding the risk of multiple gestation associated with treatment. A summary of key recommendations is as follows:

• The goal of infertility treatment is for each patient to have one healthy child at a time. The challenges associated with achieving that goal differ by treatment and clinical context.
• A desire to achieve pregnancy expeditiously with fertility treatment must be balanced against the substantial family, medical, social, and economic consequences of multiple gestations.
• It is recommended that intentional strategies to reduce multiple gestation be employed in all infertility treatments, as multiple gestations are associated with major maternal and fetal risks.
• It is recommended that cycle cancellation should be considered if > 2 follicles ≥ 16 mm develop or > 3 follicles ≥ 14 mm develop in non-ART treatments in women < 40 years of age. It should be noted that OI [ovulation induction] and OS [ovarian stimulation] result in more twin gestation than do ART treatments. Most of the high-order multiple gestations result from OI and OS rather than from ART or natural conception.
• It is recommended that in women with anovulatory infertility who require gonadotropins, the lowest dose possible be used to induce ovulation of a single follicle. Starting doses of 37.5-75 IU are recommended with small incremental increases as needed on the basis of ovarian response.
• It is not recommended to use gonadotropins for ovulatory women utilizing timed intercourse or IUI.
• It is recommended to use SET [single embryo transfer] in all good-prognosis ART cycles. Elective SET is the most effective strategy for reducing the risk of multiple pregnancy with ART.
• SET should be strongly recommended in all GC [gestational carrier] cycles, given the health risks associated with multiple gestation for the GC. At a minimum, it is recommended to follow age-related limits on the number of embryos to transfer in GC cycles, on the basis of age of the oocytes from the intended parent or oocyte donor.
• It is not recommended to use alternate embryo and endometrial testing strategies purely for the purpose of increasing SET, as alternate strategies have not been proven to improve live birth or reduce multiple gestation compared to SET in good-prognosis patients.
• It is recommended to use patient educational strategies regarding the risks of multiple gestation to increase acceptance of SET and safe OS.

Evans and colleagues (2020) estimated the risk of a multiple gestation pregnancy in ovarian stimulation IUI cycles when stratified by age and mature follicle number. A total of 24,649 women who underwent 50,473 IUI cycles were included in the analysis. The per pregnancy twin and higher order multiple gestation risk significantly increased (3.9% to 23.3%, p<0.01 and 0.2% to 10.6%, p<0.01, respectively) when comparing 1 versus 5 mature follicles present at the time of IUI (p<0.01). In women younger than 40 years with more than 3 follicles present, over a quarter of all pregnancies were multiples. The authors concluded that caution should be used in proceeding with IUI following ovarian stimulation when there are more than 2 mature follicles in women under the age of 40 due to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.

Limits to the Number of Embryos to Transfer (Return to Clinical Indications)

The goal of ART is to achieve a healthy singleton gestation. In accordance with ASRM guidance, for biological females undergoing IVF, a single embryo transfer should be attempted for at least the first cycle. A single embryo transfer leads to better infant and maternal health outcomes. The ASRM has published guidelines for the limits on the number of embryos to be transferred during IVF cycles in order to promote singleton gestation and reduce the number of multiple pregnancies while maximizing the cumulative live birth rates (2021b). The following guidelines (summarized in Table 1) are recommended for upper limits of embryo transfers in individuals with a favorable prognosis (see definition):

• Transfer of a euploid embryo should be limited to one, regardless of patient age.
• Patients < 35 years of age should be strongly encouraged to receive a single-embryo transfer, regardless of the embryo stage.
• For patients between 35 and 37 years of age, strong consideration should be made for a single-embryo transfer.
• For patients between 38 and 40 years of age, no more than 3 untested cleavage-stage embryos or 2 blastocysts should be transferred.
• Patients 41-42 years of age should plan to receive no more than 4 untested cleavage-stage embryos or 3 blastocysts.

Individuals in each of the preceding age groups who do not meet the criteria for a favorable prognosis may have an additional embryo transferred but should be counseled regarding the additional risk of twin or higher-order multiple pregnancy. If otherwise favorable individuals fail to conceive after multiple cycles with high-quality embryo(s) transferred, the individuals and their physicians may consider proceeding with an additional embryo to be transferred. Counseling and the justification for transfer of embryos exceeding the recommended limits must be documented in the individual’s permanent medical record.

Table 1. Recommendations for the limit to the number of embryos to transfer

^a Demonstrated euploid embryos, best prognosis
^b Other Favorable = Any ONE of these criteria: Fresh cycle: expectation of 1 or more high-quality embryos available for cryopreservation or previous live birth after a prior transfer with sibling embryo(s); FET cycle: availability of vitrified day-5 or day-6 blastocysts, euploid embryos, 1st FET cycle, or previous live birth after an IVF cycle.

Selective Fetal Reduction

Both ACOG and ASRM recognize that multifetal pregnancy reduction (MFPR), also called selective fetal reduction, may be ethically permissible when undertaken to reduce maternal and perinatal risks associated with high-order multiple gestations. ACOG emphasizes that counseling regarding MFPR must be nondirective and patient-centered, supporting the pregnant individuals’ autonomous decision-making, and that clinicians who object should provide timely referral rather than abandon care (ACOG, 2017). ASRM similarly advises that MFPR may decrease, but does not eliminate, the risks of multiple pregnancy and it should not be viewed as a substitute for prevention through appropriate embryo transfer limits and ovulation-induction management (ASRM, 2021b and 2022). In cases involving gestational carriers, ASRM recommends that agreements explicitly address MFPR and pregnancy-termination decisions prior to treatment initiation (ASRM, 2018a).

Poor Response to Ovarian Stimulation

The ESHRE created a standardized definition of poor ovarian response (POR) to stimulation, known as the Bologna criteria (Ferraretti, 2011). POR usually indicates a reduction in follicular response, resulting in a reduced number of retrieved oocytes. The minimal criteria needed to define POR require that at least two of the following three features must be present:

• Advanced maternal age (≥ 40 years) or any other risk factor for POR;
• A previous POR (≤ 3 oocytes with a conventional stimulation protocol);
• An abnormal ovarian reserve test (for example, AFC [antral follicle count], 5-7 follicles or AMH [anti-Mullerian hormone], 0.5 -1.1 ng/ml).

In 2022, Lebovitz and colleagues evaluated reproductive outcomes after fresh autologous IVF/ICSI cycles in individuals fulfilling the Bologna criteria for POR. They performed a retrospective study of 751 IVF/ICSI cycles using autologous oocytes in infertile individuals with POR aged 18 to 45 who underwent ovarian stimulation that yielded up to three oocytes. Pregnancy and live birth rates per cycle were significantly higher among younger individuals compared to those older than 40 years (9.8% and 6.8% vs 4.5% and 2.1%, p<0.01, respectively). Multivariable regression identified age and the number of retrieved oocytes as independent predicting factors of live birth in individuals with POR according to the Bologna criteria. The data demonstrate that the probabilities of individuals with POR achieving a live birth are best with younger age and higher number of retrieved oocytes. The authors concluded that egg donation is a good alternative for this POR population, with the substantial benefit being the greater chance of live birth.

Male Infertility

The American Urological Association (AUA) and the ASRM published an update to their guideline on male infertility in 2024 (Brannigan, 2024). For about one-half of all infertile couples, infertility is due in whole or in part to factors affecting the biological male. Guideline statements address assessment, diagnosis and evaluation, lifestyle factors, imaging, sperm retrieval, obstructive azoospermia, medical and nutraceutical interventions, and preservation of fertility during gonadotoxic therapies. Key recommendations include the following:

• Clinicians may manage male infertility with assisted reproductive technologies.
• For males with non-obstructive azoospermia undergoing sperm retrieval, clinicians should perform a micro-TESE [microdissection testicular sperm extraction].
• In males with azoospermia due to obstruction undergoing surgical sperm retrieval, clinicians may extract sperm from either the testis or the epididymis.
• Clinicians should encourage males to bank sperm, preferably multiple specimens when possible, prior to commencement of gonadotoxic therapy or other cancer treatment that may affect fertility in males.
• Clinicians should inform males seeking paternity who are persistently azoospermic after gonadotoxic therapies that microdissection testicular sperm extraction is a treatment option.

In 2015, Bernie and colleagues reported the results of a systematic review and meta-analysis comparing micro-TESE, conventional testicular sperm extraction (cTESE), and testicular sperm aspiration (TESA) for nonobstructive azoospermia. Fifteen studies including 1890 participants were analyzed. Micro-TESE was 1.5 times more likely (95% CI, 1.4-1.6) to result in successful sperm retrieval when compared with cTESE, and cTESE was 2.0 times more likely (95% CI, 1.8-2.2) to be successful when compared with TESA. The authors concluded that micro-TESE was superior to cTESE, and cTESE was superior to TESA. Micro-TESE may be the more successful technique because spermatogenesis in men with nonobstructive azoospermia is often only found in small foci within the testes.

Azoospermia

Azoospemia is the absence of spermatozoa in the semen. It is classified as obstructive or nonobstructive depending on whether the cause is blockage of the seminal tubules or ducts.

The ASRM (2018b) published a committee opinion on the management of nonobstructive azoospermia (NOA). They noted that approximately 5-10% of biological males evaluated for infertility are azoospermic, and most of them are found to have NOA. NOA results from severe deficits in spermatogenesis that most commonly result from primary testicular dysfunction.

An IVF procedure called intracytoplasmic sperm injection (ICSI) has enabled affected individuals to become biological parents using surgically retrieved spermatozoa. The process begins with surgical extraction of sperm from the testes (cTESE, mTESE, or TESA) or from the epididymis PESA or MESA. Extracted sperm are examined under a microscope to select the healthiest, most motile, sperm. The biological female partner undergoes ovarian stimulation and egg retrieval. Under a high-powered microscope, an embryologist uses a micromanipulator to hold an egg steady with a holding pipette and inject a single sperm directly into its cytoplasm with a very fine needle. This bypasses the natural barriers to fertilization, such as poor sperm motility or binding to the zona pellucida. Typically, several eggs are fertilized in this way. The fertilized eggs are monitored in culture, and one or more of the resulting embryos is transferred into the uterus. Remaining viable embryos may be frozen for potential future use.

ASRM concludes the following with regard to NOA:

• Optimal care for men with NOA requires a multidisciplinary clinical team that includes a reproductive urologist or other specialist in male reproductive medicine.
• Preimplantation genetic testing may be helpful to minimize the risks to offspring of affected men.
• Men who harbor complete AZFa or AZFb Y-chromosome microdeletions should be counseled to consider donor sperm or adoption in conjunction with psychosocial counseling, given that sperm identification is rare.
• Varicocelectomy should be considered in men with varicocele-associated NOA prior to sperm retrieval.
• Patients with NOA should be counseled about the advantages and disadvantages of available sperm-retrieval techniques.
• Other options, including donor insemination and adoption, should be discussed with the patient.

Same-sex couples, Transgender, and Nonbinary Persons

The ASRM Ethics Committee holds that fertility services should be equally available to all individuals and couples regardless of marital status, sexual orientation, or gender identity. The Committee affirms that interest in having and rearing children is a fundamental human value not dependent on these factors, and that evidence does not support claims that the well-being of children is adversely affected by being raised in nontraditional families. Therefore, fertility programs are ethically obligated to provide assisted reproductive services without discrimination, unless there are well-substantiated concerns about the ability to provide minimally adequate care for offspring (ASRM, 2021f).

The ASRM (2021a) published a committee opinion concerning the ethical considerations surrounding the provision of fertility services to transgender and nonbinary individuals. They noted that many transgender and nonbinary persons have the same interests in having children and accessing fertility services as other persons. The committee concluded that requests for assisted reproduction should be considered without regard to gender identity status, and that denial of access to fertility services for transgender and nonbinary individuals is not justified.

Gestational Carriers

A gestational carrier is a person who carries a pregnancy resulting from the transfer of an embryo created by the genetic parents or gamete donors. A committee opinion from the ASRM (2022) provides the latest recommendations for the screening, evaluation, and psychoeducational and legal counseling of gestational carriers and intended parents. Gestational carriers may be used when a medical condition prevents the intended parent from safely carrying a pregnancy or would pose a significant risk of death or harm to the parent or the fetus. Examples of such medical indications include the following:

• Absence of uterus (congenital or acquired).
• Significant uterine anomaly (for example, irreparable Asherman syndrome; unicornuate uterus associated with recurrent pregnancy loss.
• Absolute psychological or medical contraindication to pregnancy (for example, pulmonary hypertension).
• Serious psychological or medical condition that could be exacerbated by pregnancy or cause significant risk to the mother or fetus.
• Biologic inability to conceive or bear a child, such as single male or homosexual male couple.

Acrosome: A cap-like structure on the front portion of the sperm head that is enclosed by a membrane and contains enzymes that help the sperm break through the zona pellucida surrounding the egg.

Assisted embryo hatching: A micromanipulation technique in which the zona pellucida (the outer layer of the embryo) is artificially thinned or breached to facilitate implantation. The ASRM notes that assisted hatching may improve implantation rates in select patients but is not recommended for routine use.

Assisted reproductive technology (ART): ART encompasses all fertility treatments in which eggs or embryos are manipulated to achieve pregnancy. These procedures typically involve surgically retrieving oocytes from the ovaries, fertilizing them with sperm in the laboratory, and transferring the resulting embryos into the uterus of the patient or a gestational carrier. ART also includes the cryopreservation (freezing) of eggs or embryos, as well as the use of donor eggs or embryos. The most common ART procedure is in IVF, while others, such as gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT), are rarely performed. Importantly, ART does not include treatments where only sperm are manipulated (for example, IUI), nor does it include ovarian stimulation with medications alone when no surgical egg retrieval is planned.

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

Co-culture of embryos: An in vitro technique in which embryos are grown on a layer of somatic cells (such as endometrial or tubal epithelial cells) to mimic the natural environment and potentially improve embryo development. ASRM does not recommend this approach for routine practice due to lack of consistent benefit.

Conception: Conception refers to the biological process by which a new human life is initiated. The precise point of “conception” varies depending on medical, scientific, and policy perspectives:

• Fertilization Perspective - Conception may be defined as the union of a sperm and an ovum, creating a zygote. This emphasizes the very beginning of the reproductive process, often used in embryology and some legal or ethical discussions.
• Implantation Perspective - Many medical authorities, including the American College of Obstetricians and Gynecologists (ACOG), define conception in practice as beginning when a fertilized egg successfully implants into the uterine lining, marking the onset of pregnancy. This distinction is important for clinical and regulatory contexts (for example, infertility definitions, pregnancy detection, and policy on assisted reproductive technologies).
• Policy and Coverage Use - In health policy and insurance, “producing a conception” may encompass achieving fertilization (naturally or through assisted reproductive technologies such as in vitro fertilization), whereas “conceiving” often implies the establishment of pregnancy within the uterus.

Cryopreservation: The process of preserving and storing living systems in a viable condition at low temperatures for future use.

Direct intraperitoneal insemination: A procedure in which washed sperm are introduced directly into the peritoneal cavity, usually via laparoscopy.

Donor egg or sperm: Gametes provided by an individual other than the intended parent for use in assisted reproductive technology. The donor may be known or anonymous. ASRM and ACOG provide ethical and medical guidance for donor screening and use.

Embryo - The initial phase in human development during the period from approximately the second to the eighth week after fertilization (after which the product of conception is usually termed a fetus). An embryo forms when a fertilized egg (zygote) begins to divide into multiple cells.

Endometriosis: A condition resulting from the appearance of endometrial tissue outside the uterus. It can cause significant pelvic pain and infertility. The ASRM defines endometriosis as minimal (stage 1), mild (stage 2), moderate (stage 3), or severe (stage 4) based on factors including the size, depth of penetration into tissue, and anatomic locations of the lesions.

Favorable prognosis for pregnancy: The presence of characteristics that predict a positive expectation of pregnancy such as young age, the availability of one or more high-quality embryos available for cryopreservation or vitrified high-quality blastocysts for transfer, euploid embryos, and previous live birth after an IVF cycle.

Fertility preservation: The use of medical or surgical techniques to safeguard reproductive potential in individuals at risk of infertility due to disease, medical treatments (such as chemotherapy or radiation), or other conditions. Common methods include cryopreservation of sperm, oocytes, embryos, or ovarian/testicular tissue.

Fetus: An unborn offspring in the postembryonic period, which in humans is from the third month after fertilization until birth. See also embryo. 

Frozen Embryo Transfer (FET): A procedure in which a previously cryopreserved embryo is thawed and transferred into the uterus. FET allows for embryo transfer at a later time and is widely used in ART cycles.

Gamete Intra-Fallopian Transfer (GIFT): An ART procedure that involves removing eggs from the woman's ovary and using a laparoscope to place the unfertilized gametes (eggs and sperm) into the woman's fallopian tube through small incisions in her abdomen.

Gestational Carrier (Surrogate): A biological female who gestates, or carries, an embryo that was formed from the egg of another biological female with the expectation of returning the infant to its intended parents.

Gonad: An organ that produces gametes (reproductive cells) and sex hormones. In humans, the female gonads are the ovaries, and the male gonads are the testes.

Gonadotoxic: Treatments, drugs, radiation fields or exposures that damage gonadal tissue.

Human zona binding assay (hemizona test): A laboratory bioassay that measures the ability of human sperm to bind to the zona pellucida of a bisected human oocyte. By comparing sperm binding to paired hemizona halves (one with a fertile control, the other with a test sample), the HZA provides a reproducible assessment of fertilization potential and has demonstrated predictive value for IUI and in IVF outcomes.

Infertility: The ASRM defines infertility as 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.

Intrauterine insemination (IUI): A medical procedure that involves placing sperm into a woman's uterus to facilitate fertilization. IUI is not considered an ART procedure because it does not involve the manipulation of eggs.

Male factor infertility: Any cause of infertility due to low sperm count or problems with sperm function that makes it difficult for a sperm to fertilize an egg under normal conditions.

Menopause: The permanent cessation of menstruation resulting from the loss of ovarian follicular activity. Practically and retroactively defined by ACOG as the absence of menstruation over 12 months without another identified cause.

Microdissection- Testicular Excisional Sperm Extraction: See Testicular Excisional Sperm Extraction below

Microepididymal Sperm Aspiration (MESA): A surgical sperm retrieval method in which an operating microscope is used to aspirate sperm-rich fluid from selected areas of the epididymis. The retrieved sperm are typically used for intracytoplasmic sperm injection (ICSI), and MESA is widely regarded as the gold standard for biological males with obstructive azoospermia due to its high sperm yield, strong fertilization and pregnancy outcomes, and low complication risk.

Mock transfer: A practice trial for an IVF procedure that involves simulating the steps of an embryo transfer without actually transferring any embryos. The purpose is to assess the uterine anatomy and identify any potential obstacles to embryo transfer with the goal of improving the chances of a successful IVF.

Normal reproductive age: See Reproductive Age below

Percutaneous Epididymal Sperm Aspiration (PESA); A surgical procedure in which a needle is passed through the skin into the epididymis to obtain sperm.

Peritoneal ovum and sperm transfer (POST): An assisted reproductive technique in which retrieved oocytes and prepared sperm are deposited together into the peritoneal cavity (the space within the abdomen around the reproductive organs) via a transvaginal, ultrasound-guided approach.

Reciprocal IVF: An ART technique used by couples in which two partners with female reproductive potential participate: one partner provides the oocyte, while the other carries the pregnancy.

Reproductive age: The period during which a person is biologically capable of conceiving and bearing children (for individuals born with female reproductive anatomy) or fathering children (for individuals born with male reproductive anatomy). The CDC specifies that the reproductive age for biological females ranges between the ages of 15 and 45.

Reversal of sterilization: A surgical procedure to restore fertility after a prior sterilization (for example, tubal ligation reversal in biological females or vasectomy reversal in biological males). Success depends on the type of sterilization, time since the procedure, and remaining reproductive function.

Serum anti-sperm antibody testing: A laboratory test used to detect antibodies that impair sperm function and fertilization. Its clinical utility is limited, and ASRM does not recommend it as part of the routine infertility evaluation.

Single embryo transfer (SET): Multiple births result in substantial excess perinatal and maternal morbidity and include maternal hospitalization and neonatal intensive care and potential lifelong need for care of chronic illness, rehabilitation, and special education. To help the member’s desire to take home a healthy baby, for members < 38 years old undergoing their first IVF cycle, donor egg IVF cycle, or donor embryo FET, single embryo transfer (SET) should be done. If there are no top-quality embryos after thawing, then two or more embryos of any quality may be transferred. For biological females undergoing a second treatment cycle who are <35, or 35 up to 38 who had a live birth from their first IVF cycle, or those using donor egg should receive a SET. If the member has one or more embryos frozen, then a single thawed embryo transfer must be done for any age group. If there are no top-quality embryos after thawing, then two or more embryos of any quality may be transferred.

Sperm acrosome reaction test: A laboratory assay used to evaluate the ability of sperm to undergo the acrosome reaction, a process in which the acrosomal membrane of the sperm head breaks down and releases enzymes needed to penetrate the zona pellucida of the oocyte. The test can be performed using chemical inducers (for example, calcium ionophore, progesterone) or zona pellucida-related stimuli, and outcomes are typically assessed by staining or fluorescent labeling of the acrosomal region. It provides information about sperm function beyond basic semen analysis and is sometimes used in the evaluation of male infertility.

Testicular sperm aspiration/extraction (TESA/TESE): A surgical technique in which sperm are collected from the testes through one or more biopsies or needle aspirations, for use in IVF or intracytoplasmic sperm injection (ICSI).

• TESA uses a needle inserted into the testicle under local anesthesia or mild sedation to aspirate fluid and testicular tissue containing sperm. Because sampling is blind, done by needle insertion rather than targeted biopsy, and tissue yield is smaller, the sperm‐retrieval rate may be lower in certain scenarios (especially non‐obstructive azoospermia) compared to TESE.
• TESE involves making a small incision in the testicle to remove small samples of testicular parenchyma including seminiferous tubules for processing in a laboratory to obtain sperm. Compared to TESA, Microscopic TESE (mTESE) has a higher likelihood of retrieving sperm than TESA or conventional TESE.

Zygote: A fertilized egg before it begins to divide.

Zygote Intra-Fallopian Transfer (ZIFT): An assisted reproductive technology (ART) procedure in which eggs are retrieved from a woman’s ovaries, fertilized in the laboratory, and the resulting zygote is placed into the fallopian tube using a laparoscope through a small abdominal incision.

Peer Reviewed Publications:

1. Alorf F, Alani S, Steiner N, Dahan M. How successful is intrauterine insemination after failed IVF? A study of 551 women. Reprod Biomed Online. 2024; 48(3):103684.
2. Bernie AM, Mata DA, Ramasamy R, Schlegel PN. Comparison of microdissection testicular sperm extraction, conventional testicular sperm extraction, and testicular sperm aspiration for nonobstructive azoospermia: a systematic review and meta-analysis. Fertil Steril. 2015; 104(5):1099-1103.
3. Boutari C, Pappas PD, Mintziori G, et al. The effect of underweight on female and male reproduction. Metabolism. 2020; 107:154229.
4. Eijkemans MJ, van Poppel F, Habbema DF, et al. Too old to have children? Lessons from natural fertility populations. Hum Reprod. 2014; 29(6):1304-1312.
5. Evans MB, Stentz NC, Richter KS, et al. Mature follicle count and multiple gestation risk based on patient age in intrauterine insemination cycles with ovarian stimulation. Obstet Gynecol. 2020; 135(5):1005-1014.
6. Fluker MR, Zouves CG, Bebbington MW. A prospective randomized comparison of zygote intrafallopian transfer and in vitro fertilization-embryo transfer for nontubal factor infertility. Fertil Steril. 1993; 60(3):515-519.
7. Kukkonen A, Hantunen S, Voutilainen A, et al. Maternal caffeine intake during pregnancy and the risk of delivering a small for gestational age baby: Kuopio Birth Cohort. Arch Gynecol Obstet. 2024; 310(1):359-368.
8. Lebovitz O, Haas J, Mor N, et al. Predicting IVF outcome in poor ovarian responders. BMC Womens Health. 2022; 22(1):395.
9. Lyngsø J, Ramlau-Hansen CH, Bay B, et al. Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose-response meta-analysis. Clin Epidemiol. 2017; 9:699-719.
10. Mansour D, Gemzell-Danielsson K, Inki P, Jensen JT. Fertility after discontinuation of contraception: a comprehensive review of the literature. Contraception. 2011; 84(5):465-477.
11. Niederberger C, Pellicer A, Cohen J, et al.  Forty years of IVF. Fertil Steril. 2018; 110(2):185-324.e5.
12. Pardthaisong T, Gray RH, McDaniel EB. Return of fertility after discontinuation of depot medroxyprogesterone acetate and intra-uterine devices in Northern Thailand. Lancet. 1980; 315(8167):509-512.
13. Qian J, Chen Q, Ward SM, et al. Impacts of caffeine during pregnancy. Trends Endocrinol Metab. 2020; 31(3):218-227.
14. Sastre J, Mínguez JA, Alcázar JL, Chiva L. Microsurgical anastomosis of the fallopian tubes after tubal ligation: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2023; 291:168-177.
15. Shamonki MI, Spandorfer SD, Roberts JE, et al. Low-dose gonadotropin step-up protocol is highly successful for the PCOS patient. Fertil Steril. 2003; 80(S3):S171.
16. Smith ADAC, Tilling K, Nelson SM, Lawlor DA. Live-birth rate associated with repeat in vitro fertilization treatment cycles. JAMA. 2015; 314(24): 2654-2662.
17. Spandorfer SD, Bendikson K, Dragisic K, et al. Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes. Fertil Steril. 2007; 87(1):74-76.
18. Talwar P, Hayatnagarkar S. Sperm function test. J Hum Reprod Sci. 2015; 8(2):61-69.
19. Tan SL, Pampiglione J, Steer C, et al. Transvaginal peritoneal oocyte and sperm transfer for the treatment of nontubal infertility. Fertil Steril. 1992; 57(4):850-853.
20. Tocariu R, Niculae LE, Niculae AS, et al. Fresh versus frozen embryo transfer in in vitro fertilization/intracytoplasmic sperm injection cycles: a systematic review and meta-analysis of neonatal outcomes. Medicina (Kaunas). 2024; 60(8):1373.
21. Wang JX, Davies MJ, Norman RJ. Obesity increases the risk of spontaneous abortion during infertility treatment. Obes Res. 2002; 10(6):551-554.

Government Agency, Medical Society, and Other Authoritative Publications:

1. American College of Obstetricians and Gynecologists Committee on Ethics. Ethical issues with multifetal pregnancy reduction. Committee Opinion No. 719. Obstet Gynecol. 2017; 130(2):e152-e157.
2. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and the Practice Committee of the American Society for Reproductive Medicine. Female age-related fertility decline. Committee Opinion No. 589. Fertil Steril. 2014; 101(3):633-634.
3. American College of Obstetricians and Gynecologists Committee on Gynecologic Practice and the American Society for Reproductive Medicine. Prepregnancy Counseling. Committee Opinion No. 762. Fertil Steril. 2019; 111(1):32-42.
4. American College of Radiology. Expert Panel on Women’s Imaging. ACR appropriateness criteria female infertility. J Am Coll Radiol. 2020; 17:S113-S124.
5. American Society for Reproductive Medicine. ASRM/ESHRE Consensus on infertility treatment related to PCOS. Hum Reprod. 2008; 23(3):462-477.
6. American Society for Reproductive Medicine; American College of Obstetricians and Gynecologists' Committee on Gynecologic Practice. Prepregnancy counseling: Committee Opinion No. 762. Fertil Steril. 2019; 111(1):32-42.
7. American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012; 98(3):591-598.
8. American Society for Reproductive Medicine. Ethics Committee of the American Society for Reproductive Medicine. Access to fertility services by transgender and nonbinary persons: an Ethics Committee opinion. Fertil Steril. 2021a; 115:874-878.
9. American Society for Reproductive Medicine. Ethics Committee of the American Society for Reproductive Medicine. Access to fertility treatment irrespective of marital status, sexual orientation, or gender identity: an Ethics Committee opinion. Fertil Steril. 2021f; 116:326-330.
10. American Society for Reproductive Medicine. Ethics Committee of the American Society for Reproductive Medicine. Consideration of the gestational carrier: an Ethics Committee opinion. Fertil Steril. 2018a; 110:1017-1021.
11. American Society for Reproductive Medicine. Ethics Committee of the American Society for Reproductive Medicine. Fertility treatment when the prognosis is very poor or futile: an Ethics Committee opinion. Fertil Steril. 2019; 111(4):659-663.
12. American Society for Reproductive Medicine. Ethics Committee of the American Society for Reproductive Medicine. Use of preimplantation genetic testing for monogenic adult-onset conditions: an Ethics Committee opinion. Fertil Steril. 2024; 122(4):607-611.
13. American Society for Reproductive Medicine. The International Glossary on Infertility and Fertility Care. 2017. Available at: https://www.asrm.org/practice-guidance/practice-committee-documents/the-international-glossary-on-infertility-and-fertility-care-2017-2017/. Accessed on October 30, 2025.
14. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. Gamete and embryo donation guidance. Fertil Steril. 2024a; 122:799-813.
15. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. Guidance on the limits to the number of embryos to transfer: a committee opinion. Fertil Steril. 2021b; 116:651-654.
16. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine. Definition of infertility: a committee opinion (2023). Available at: https://www.asrm.org/globalassets/_asrm/practice-guidance/practice-guidelines/pdf/definition-of-infertility.pdf.  Accessed on October 30, 2025.
17. American Society for Reproductive Medicine: Practice Committee of the American Society for Reproductive Medicine. Evidence-based outcomes after oocyte cryopreservation for donor oocyte in vitro fertilization and planned oocyte cryopreservation: a guideline. Fertil Steril. 2021c; 116:36-47.
18. American Society for Reproductive Medicine: Practice Committee of the American Society for Reproductive Medicine. Evidence-based treatments for couples with unexplained infertility: a guideline. Fertil Steril. 2020a; 113:305-322.
19. American Society for Reproductive Medicine: Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women: a committee opinion. Fertil Steril. 2021g; 116:1255-1265.
20. American Society for Reproductive Medicine: Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019; 112(6):1022-1033.
21. American Society for Reproductive Medicine: Practice Committee of the American Society for Reproductive Medicine. Management of nonobstructive azoospermia: a committee opinion. Fertil Steril. 2018b; 110:1239-1245.
22. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine. Obesity and reproduction: a committee opinion. Fertil Steril. 2021d; 116(5):1266-1285.
23. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine. Role of tubal surgery in the era of assisted reproductive technology: a committee opinion. Fertil Steril. 2021e; 115:1143-1150.
24. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine and Practice Committee of the Society for Assisted Reproductive Technology. Recommendations for practices using gestational carriers: a committee opinion. Fertil Steril. 2022; 118:65-74.
25. American Society for Reproductive Medicine: Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve: a committee opinion. Fertil Steril. 2020b; 114:1151-1157.
26. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine. The role of assisted hatching in in vitro fertilization: a guideline. Fertil Steril. 2022; 117(6): 1177-1182.
27. American Society for Reproductive Medicine. Practice Committee of the American Society for Reproductive Medicine. Tobacco or marijuana use and infertility: a committee opinion. Fertil Steril. 2024b; 121(4):589-603.
28. American Society for Reproductive Medicine. Practice Committee of the Society for Reproductive Endocrinology and Infertility, Quality Assurance Committee of the Society for Assisted Reproductive Technology, and the Practice Committee of the American Society for Reproductive Medicine. Multiple gestation associated with infertility therapy: a committee opinion. Fertil Steril. 2022; 117(3):498-511.
29. Brannigan RE, Hermanson L, Kaczmarek J, et al. Updates to male infertility: AUA/ASRM guideline. J Urol. 2024; 212:789-799.
30. Center for Disease Control and Prevention. About assisted reproductive technology (ART). December 10, 2024. Available at: https://www.cdc.gov/art/about/index.html. Accessed on October 30, 2025.
31. Center for Disease Control and Prevention. CDC’s Division of Reproductive Health works to improve mental health among women of reproductive age. 2014. Available at: https://www.cdc.gov/ccindex/pdf/MentalHealthAmongWomenofReproductiveAge_vB.pdf?utm_source=chatgpt.com. Accessed on October 30, 2025.
32. Centers for Disease Control and Prevention (CDC). National Center for Health Statistics. Infertility. Last Reviewed: March 17, 2025. Available at: https://www.cdc.gov/nchs/fastats/infertility.htm. Accessed on October 30, 2025.
33. ESHRE, ASRM, CREWHIRL and IMS Guideline Group on POI; Panay N, Anderson RA, Bennie A, et al. Evidence-based guideline: premature ovarian insufficiency. Fertil Steril. 2025; 123(2):221-236.
34. ESHRE Endometriosis Guideline Core Group; Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022; 2022(2):1-22.
35. European Food Safety Authority (EFSA). Scientific opinion on the safety of caffeine. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). EFSA Journal 2015; 13(5):4102.
36. Ferraretti AP, La Marca A, Fauser BCJM, et al. ESHRE consensus on the definition of ‘poor response’ to ovarian stimulation for in vitro fertilization: the Bologna criteria. Hum Reprod. 2011; 26(7):1616-1624.
37. National Cancer Institute. Testicular sperm extraction. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/testicular-sperm-extraction. Accessed on October 30, 2025.
38. Oktay K, Harvey BE, Partridge AH, et al. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2018; 36:1994-2001.
39. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part I. J Urol. 2021a; 205(1):36-43. 
40. Schlegel PN, Sigman M, Collura B, et al. Diagnosis and Treatment of Infertility in Men: AUA/ASRM Guideline Part II. J Urol. 2021b; 205(1):44-51. 
41. Society for Assisted Reproductive Technology. Preliminary National Summary Reports. Available at: https://www.sart.org/. Accessed on October 30, 2025. 
42. StatPearls: Semen Analysis. Meera Sunder; Stephen W. Leslie. Last Update: October 24, 2022. Available at: https://www.ncbi.nlm.nih.gov/books/NBK564369/. Accessed on October 30, 2025.
43. Tay CT, Mousa A, Vyas A, et al. 2023 international evidence-based polycystic ovary syndrome guideline update: insights from a systematic review and meta-analysis on elevated clinical cardiovascular disease in polycystic ovary syndrome. J Am Heart Assoc. 2024; 13(16):e033572.
44. Teede HJ, Tay CT, Laven J, et al.: on behalf of the International PCOS Network. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Fertil Steril. 2023; 120(4):767-793.
45. University of California, San Francisco. Center for Reproductive Health. Reciprocal IVF. Available at: https://crh.ucsf.edu/fertility-treatment/reciprocal-ivf. Accessed on October 30, 2025. 
46. Weil Cornell Medical Center. Endometrial Coculture. Available at: https://ivf.org/treatments-and-services/advanced-ivf-techniques/endometrial-coculture. Accessed on October 30, 2025
47. World Health Organization. WHO indicator metadata registry list: Women of reproductive age (15-49 years) population. 2025. Available at: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/women-of-reproductive-age-%2815-49-years%29-population-%28thousands%29?utm_source=chatgpt.com. Accessed on October 30, 2025.
48. World Health Organization. Restricting caffeine intake during pregnancy. Last updated August 9, 2023. Available at: https://www.who.int/tools/elena/interventions/caffeine-pregnancy. Accessed on October 30, 2025.

1. American Society for Reproductive Medicine (ASRM). Available at: https://www.asrm.org/. Accessed on October 30, 2025.
2. The American College of Obstetricians and Gynecologists (ACOG). Available at: https://www.acog.org/. Accessed on October 30, 2025.
3. American Urological Association (AUA). Available at: https://www.auanet.org/. Accessed on October 30, 2025.

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Infertility

Federal and State law, as well as contract language, and Medical Policy take precedence over Clinical UM Guidelines. We reserve the right to review and update Clinical UM Guidelines periodically. Clinical guidelines approved by the Medical Policy & Technology Assessment Committee are available for general adoption by plans or lines of business for consistent review of the medical necessity of services related to the clinical guideline when the plan performs utilization review for the subject. Due to variances in utilization patterns, each plan may choose whether to adopt a particular Clinical UM Guideline. To determine if review is required for this Clinical UM Guideline, please contact the customer service number on the member's card.

Alternatively, commercial or FEP plans or lines of business which determine there is not a need to adopt the guideline to review services generally across all providers delivering services to Plan’s or line of business’s members may instead use the clinical guideline for provider education and/or to review the medical necessity of services for any provider who has been notified that his/her/its claims will be reviewed for medical necessity due to billing practices or claims that are not consistent with other providers, in terms of frequency or in some other manner.

No part of this publication may be reproduced, stored in a retrieval system or transmitted, in any form or by any means, electronic, mechanical, photocopying, or otherwise, without permission from the health plan.

© CPT Only - American Medical Association