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Reproductive and hormonal considerations in women at increased risk for hereditary gynecologic cancers: Society of Gynecologic Oncology and American Society for Reproductive Medicine Evidence-Based Review (2019)


  • Women at risk for hereditary gynecologic cancers have unique concerns regarding fertility and hormonal health.
  • There are multiple fertility preservation strategies that can be used to help women achieve their procreative goals.
  • Genetic testing can be used before embryo transfer to identify whether an embryo carries a pathogenic gene variant.
  • For women with who don't have a personal history of breast cancer, hormone therapy can be considered.


Approximately 5–10% of all cancers can be attributed to hereditary cancer syndromes. Recognition of these conditions facilitates the ability to screen and identify individuals at increased risk and intervene for those found to carry pathogenic gene variants. Identification and intervention have consequences beyond the obvious goals of cancer prevention and early detection. There can also be an impact on reproductive choices, decisions about fertility, family building and hormonal status.

Inherited pathogenic variants that are associated with gynecologic cancers are particularly unique because they may require interventions that interrupt normal reproductive function including hormone production and fertility. Some pathogenic variants also increase the risk of other cancers such as breast cancer, for which treatment (particularly chemotherapy or oophorectomy) may also negatively impact reproductive function. Women who are carriers of a hereditary pathogenic gene variant that increases their risk for gynecologic cancer should be counseled on strategies for cancer prevention, their future fertility, risk of transmitting pathogenic gene variants to their offspring, and the potential use of hormone therapy (HT) after risk-reducing oophorectomy. An understanding of cancer risk and the preventive strategies that are used to mitigate this risk can help reproductive specialists counsel affected women on topics such as timing of fertility preservation and the availability of preimplantation genetic testing. Similarly, an understanding of the logistics of assisted reproductive technology (ART) can assist gynecologic oncologists in treatment planning and facilitate early referral to reproductive specialists to ensure that a woman's fertility concerns are met in a timely fashion. The purpose of this document is to highlight the reproductive and hormonal consequences that women who are at high risk of developing a gynecologic cancer face, and to unite efforts of gynecologic oncologists and reproductive medicine specialists in providing and optimizing care of this unique population.


The most common conditions associated with gynecologic cancers include Hereditary Breast and Ovarian Cancer (HBOC) and Lynch (Hereditary Nonpolyposis Colorectal Cancer or HNPCC) syndromes. Both are inherited in an autosomal dominant pattern. HBOC is characterized by pathogenic variants in tumor suppressor genes (1) that increase the risk of breast, ovarian, pancreatic, and prostate cancer. Approximately 5% of breast cancers and 10% to 25% of ovarian cancers are due to HBOC. The risk of developing ovarian cancer by age 70 in BReast CAncer gene 1 (BRCA1) carriers is 39–46% and 10–27% for BReast CAncer gene 2 (BRCA2) carriers (2, 3). The risk of ovarian cancer increases after age 40, with up to 20% of women with pathogenic BRCA1 variants developing ovarian cancer by age 50, compared with 3% of BRCA2 mutation carriers (1). Additionally, women carrying a germline pathogenic variant in BRIP1 have an 8 to 11-fold increased relative risk (RR) for developing ovarian cancer, without a significantly increased risk for breast cancer. Pathogenic variants in RAD51C and RAD51D are also associated with an increased risk for ovarian cancer without a significantly increased risk for breast cancer. In contrast, pathogenic variants in TP53, CDH1, CHEK2, and ATM are associated with an increased risk of breast cancer without a significantly increased risk for ovarian cancer (1). Pathogenic variants in STK11 are associated with sex-cord stromal ovarian tumors, and variants in PTEN are associated with an increased risk of breast and endometrial cancer, but not ovarian cancer.

Lynch Syndrome is associated with pathogenic variants in one of a family of mismatch repair genes (4). Each gene mutation is associated with a different cancer risk profile and distribution of lifetime cancer incidence. Lynch Syndrome is associated with an increased risk of colorectal cancer as well as endometrial, stomach, breast, ovarian, small bowel, pancreatic, prostate, urinary tract, liver, kidney, and bile duct cancers. About 3% to 5% of all cases of colorectal cancer and 2% to 3% of all cases of endometrial cancer are thought to be due to Lynch Syndrome (4, 5). The Lynch genes vary in penetrance, with a lifetime risk of up to 60% for endometrial and up to 24% for ovarian cancer (5), depending on the gene. (See Table 1).

Table 1. Selected cancer risk gene variants and their impact.

Gene Risk of ovarian cancer Risk of breast cancer Risk of endometrial cancer
ATM No increase Increased No increase
BRCA1 Increased Increased No increase
BRCA2 Increased Increased No increase
BRIP1 Increased No increase No increase
CDH1 No increase Increased No increase
CHEK2 No increase Increased No increase
Lynch Syndrome Genes:
PMS2, and EpCAM
Increased Insufficient evidence Increased
PALB2 No increase Increased No increase
PTEN No increase Increased Increased
STK11 Increased Increased No increase
RAD51C Increased No increase No increase
RAD51D Increased No increase No increase
TP53 No increase Increased No increase
Adapted from ACOG Practice Bulletin 182, 2017


To reduce gynecologic cancer risk, women may opt for surgeries such as risk-reducing bilateral salpingo-oophorectomy (RRSO), bilateral salpingectomy or hysterectomy. Because hereditary cancers are associated with a relatively younger age of onset, risk-reducing surgeries are generally recommended between the ages of 35–45, or when childbearing is complete. These risk-reducing procedures may result in premature menopause and infertility, consequences which significantly impact general health
status and quality of life.

3.1.Women at Highest Risk for Hereditary Ovarian Cancer

3.1.1. Surveillance.

To date, there are no effective screening tests for early identification of ovarian cancer, even in high-risk BRCA1 and BRCA2 mutation carrier populations. Screening by CA-125 and transvaginal ultrasound may be an option for high risk women who elect to defer or decline risk-reducing salpingo-oophorectomy (6). Cancer detected through high risk screening programs may be detected at a point of lower clinical disease burden, although the impact of diagnosis at earlier stage on survival remains unclear (7).

3.1.2. Chemoprevention.

Several classes of drugs, including oral contraceptives (OCPs), non-steroidal anti-inflammatory drugs, retinoids, angiopreventive agents, poly(ADP-ribose) polymerase (PARP) inhibitors, and tyrosine kinase inhibitors have been investigated for chemoprevention of ovarian cancer. However, the data are not conclusive except for OCPs. Oral contraceptive pills have been shown to reduce the risk of ovarian cancer by approximately half in women at average risk for ovarian cancer (8) as well as in women who carry pathogenic variants in BRCA1 and BRCA2 (summary relative risk [SRR], 0.50; 95% CI, 0.33–0.75) (9). The protective benefit of OCPS increases with duration of use. However, the safety of OCP use with regard to the development of breast cancer in BRCA mutation carriers is not entirely clear. While OCP use has been shown in some studies to be associated with a small increase in risk of breast cancer in the general population (10, 11), this was not demonstrated in case control studies of women who carry BRCA1 and BRCA2 mutations (9); however, cohort studies showed an increased risk of breast cancer for women with BRCA1 mutations (ES = 1.59; 95% CI = 1.32 to 1.92) and women with BRCA2 mutations (ES = 1.85; 95% CI = 1.30 to 2.64) who had used OCPs (10). OCPs can be used to reduce the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers without a personal history of breast cancer (11), with the understanding that the impact on breast cancer risk is indeterminate. Further studies are needed to determine the optimal timing for administration of OCPS and quantify actual breast cancer risk.

3.1.3. Risk-reducing surgery Risk-reducing Salpingo-oophorectomy

(RRSO). RRSO is the most effective method for reducing the risk of ovarian cancer in high-risk women, with reported reductions in incidence of up to 70–85% (12, 13). In addition to decreased ovarian cancer mortality, RRSO has been associated with reductions in breast cancer mortality and all-cause mortality in this population, and is recommended on completion of childbearing, between the ages of 35–40 for BRCA1 mutation carriers, and between the ages of 40–45 for BRCA2 mutation carriers (14). This reduction in all-cause mortality with RRSO in BRCA1 and BRCA2 mutation carriers contrasts with the findings in the general population, where ovarian conservation is reported to significantly lower the hazard of all-cause mortality (13, 15).

Occult underlying ovarian cancers have been identified in pathology specimens from RRSO procedures (16, 17). Given the risk of occult malignancy, pathologists should section the ovaries and fallopian tubes serially at two-millimeter intervals using the ‘‘Sectioning and Extensively Examining the Fimbriated End’’ (SEE-FIM) protocol (17). As the distal fallopian tube is the dominant site for the origin for early malignancies in women undergoing RRSO, salpingectomy is essential for optimal risk-reduction (18). Up to 10% of women will have neoplasia (pre-cancers and cancers) on pathology at time of RRSO and are at risk of recurrent disease.

Women considering RRSO should be informed about the common sequelae of surgical menopause, including vasomotor symptoms, osteoporosis, decreased libido, symptoms of vaginal atrophy and cardiovascular disease. Hormone therapy (HT) can prevent and alleviate many of the symptoms associated with surgical menopause (19). Nonhormonal treatment strategies are also available for women who have contraindications to HT. Decisions about whether or not to use HT should be individualized, considering symptom severity and cancer history. Risk reducing salpingectomy.

A significant number of women with BRCA1 and BRCA2 pathogenic variants
opt not to pursue RRSO to preserve fertility and/or avoid the development of surgical menopause. It has been proposed that since many high-grade serous cancers originate in the fallopian tube, complete removal of the fallopian tubes and fimbriae may decrease the risk of ovarian cancer. However, there are no data on actual risk reduction and patients should understand that RRSO is the standard of care. Bilateral salpingectomy should be reserved for women who decline RRSO at the recommended age. These women should also be informed that unlike RRSO, bilateral salpingectomy does not decrease breast cancer risk and they should be encouraged to undergo eventual completion bilateral oophorectomy (12). Hysterectomy.

The role of hysterectomy in BRCAmutation carriers is controversial. In one study, the presence of BRCA1 mutations was documented in four out of 20 Jewish women with uterine papillary serous carcinoma (UPSC) (20). Studies to date on the association of BRCA mutations with UPSC have been small and have reported conflicting results. Although the overall risk of endometrial cancer after risk-reducing salpingo-oophorectomy is low, there seems to be a higher risk of serous and serous-like endometrial cancers in BRCA1mutation carrier women, relative to grade 1 endometrioid endometrial cancers (21). Hysterectomy may also be considered to simplify and lower the risk of post-op HT regimens, allowing replacement of estrogen only instead of estrogen and progestin.

3.2. Women at Highest Risk for Hereditary Uterine Cancer

3.2.1. Surveillance.

Multiple strategies for endometrial cancer screening have been proposed, including transvaginal ultrasound, endometrial biopsy, a combination of both, office hysteroscopy with biopsy and endometrial washings. Though there is no clear evidence to support screening in women with Lynch Syndrome, the National Comprehensive Cancer Network (NCCN) guidelines state that office endometrial sampling every 1–2 years is a viable option (14).

3.2.2. Chemoprevention.

Oral contraceptives have been shown to decrease the risk of endometrial cancer by 50% in the general population (22). It has been shown that the endometrium of women with Lynch Syndrome that are exposed to Depo-Medroxyprogesterone or OCPs for three months show decreased epithelial proliferation and inactive/secretory histology, suggesting that these agents may be useful for chemoprevention of uterine and possibly, ovarian cancer. However, whether these effects result in an actual reduction in the risk of endometrial cancer is unknown (23). The levonorgestrol intrauterine system is also associated with lower endometrial cancer risk and has been used in treating early low-grade disease, but there are limited data for chemoprevention in Lynch Syndrome (24, 25).

3.2.3. Risk reducing surgery.

Women with Lynch Syndrome should consider prophylactic total hysterectomy and bilateral salpingo-oophorectomy (THBSO) at the completion of childbearing, especially after the age of 40 years (4). THBSO has been demonstrated to decrease the risk of endometrial and ovarian cancer in this patient population (26). Exact timing should be individualized, based on additional factors including menopause status, comorbidities, and specific gene mutation (5). Prior to THBSO, women should undergo endometrial biopsy to rule out the possibility of an occult cancer. Women should be fully informed of the sequelae of premature menopause.


4.1. Fertility Preservation

Ideally, women should complete their childbearing prior to definitive surgery. The recommended timing for RRSO occurs during women's childbearing years (ages 35–45) and may be even sooner, such as in cases where a family member was diagnosed with cancer at a very young age. In these instances, women may experience a narrower window for fertility. While decreasing cancer risk, RRSO prematurely eliminates the possibility of having a future biological child unless a woman has cryopreserved oocytes or embryos through ART. Additionally, BRCA1 and BRCA2 mutation carriers who have been diagnosed with cancer that requires chemotherapy may be at risk of experiencing treatment-related infertility and premature ovarian insufficiency or menopause. Considering options for fertility preservation (FP) is an important component of care for these women.

Early referral (age late 20s-early 30s) of women with BRCA1 and BRCA2 pathogenic variants to reproductive endocrinologists is strongly encouraged so that they can be informed of the availability of fertility preservation and the potential for preimplantation genetic testing (PGT). This also facilitates establishment of baseline ovarian reserve and allows women who are interested to pursue FP at younger ages when methods are most likely to be successful (27, 28). Transvaginal ultrasound ovarian antral follicle count (AFC), antim€ullerian hormone (AMH) testing or day 3 follicle–stimulating hormone (FSH) paired with estradiol levels can be used to assess ovarian reserve and predict response to controlled ovarian hyperstimulation. The results of ovarian reserve testing may help inform patient's decisions on if/when to pursue fertility preservation. These measurements should not be used to counsel patients about their fertility potential versus pregnancy (29).

There are data that suggest that BRCA1 and BRCA2 mutation carriers have diminished ovarian reserve, however this is controversial. Several cohort studies have shown earlier menopause among women with BRCA1 and BRCA2 mutations relative to controls, with premature menopause four times more likely in BRCA carriers than in controls (30, 31). Others demonstrated diminished ovarian reserve among mutation carriers as measured by response to stimulation, AMH levels and follicle count (32–35). However, other studies have not confirmed these findings (36, 37). Furthermore, studies have not shown that women with BRCA pathogenic variants have fewer pregnancies or more fertility problems (38–41).

Through ART, women have the option to cryopreserve and store oocytes, embryos or both. During an ART cycle, the ovaries are stimulated with exogenous gonadotropins followed by ultrasound-guided transvaginal needle aspiration of the oocytes. Once the oocytes are retrieved, they can be immediately cryopreserved or inseminated with sperm and then the resultant embryos may be cryopreserved. Oocytes and embryos may be stored effectively for many years. Of note, oocyte cryopreservation is no longer considered an experimental treatment (42).

Oocyte and embryo cryopreservation are effective strategies for FP, however, there are many important topics to discuss with patients who are considering these options. Patients should understand that by pursuing FP, live birth is not guaranteed; rather, oocyte and embryo cryopreservation are efforts to retain the opportunity to try to have a child using their own gametes. They should understand that success rates are highly dependent on age and may be influenced by other medical and lifestyle factors. In addition, success rates can vary by clinic. Women should also consider the optimal timing for FP, as well as the number of cycles they are willing to undergo to improve their chance of achieving a successful live birth. The risks of ART should be thoroughly reviewed. The use of fertility drugs is not associated with an increased risk for invasive breast, ovarian or uterine cancer in the general population of infertile women (43). However, many women who are at increased risk for these cancers have concerns about the effect of the high estradiol levels that are generated during ovarian stimulation on cancer risk. Fortunately, the use of fertility medications does not appear to increase the risk of breast cancer in breast cancer patients or BRCA mutation carriers (43). Nevertheless, efforts should be made to minimize the rise in estradiol levels by using an aromastase inhibitor (letrozole) plus gonadotropin stimulation protocol, which results in estradiol levels that are physiologic. In a study comparing a group of 120 breast cancer patients undergoing FP using gonadotropins with letrozole and 217 breast cancer patients who did not pursue FP, survival was not compromised. (44) In spite of limited data regarding safety of ART in women at high risk for gynecologic cancers, the data that do exist suggest that ART does not increase the risk of ovarian cancer in BRCA carriers, at least in the short term (45, 46).

4.2. Additional Options for Parenthood

4.2.1. Options for women after RRSO.

If a woman has cryopreserved oocytes or embryos prior to RRSO, pregnancy can still be achieved by hormonally priming her uterus and performing an embryo transfer. However, if a woman does not have her own oocytes or embryos available to her, she may consider using donor oocytes, donor embryos or pursuing adoption.

4.2.2. Options for women who have had a hysterectomy.

For a woman of reproductive age who has had a hysterectomy for endometrial cancer or for risk-reduction, but has retained her ovaries, having a child using her own gametes is still possible through IVF with a gestational carrier. Medical, legal, and psychological counseling is recommended for both the intended parents and the gestational carrier. The availability, legality and cost of gestational carrier IVF vary throughout the United States.

Uterine transplantation is a novel procedure that has recently resulted in live births, however, its role in preserving fertility in women with an increased risk for hereditary gynecologic cancers has not been determined (47).


Individuals who carry an autosomal dominant pathogenic gene variant have a 50% risk of transmitting their gene mutation to offspring. As a result, some women who carry genes associated with hereditary cancer gene mutations face uncertainty about having children due to fear of having a child who will be at high risk for developing cancer. Unfortunately, many women are not aware of medical technologies such as preimplantation genetic testing (testing an embryo prior to implantation) and prenatal diagnosis (testing a fetus during pregnancy) that can help minimize the risk of having a child who has the pathogenic variant.

5.1. Preimplantation Genetic Testing

Women who carry pathogenic gene variants that place themat high risk for cancer should be educated and counseled about preimplantation genetic testing (PGT) (48). For PGT, embryos are biopsied (typically at the blastocyst stage) and cryopreserved. The biopsies are analyzed in a genetics lab for monogenic/single gene defects (PGT-M), and based on the results, patients can preferentially select embryos for intrauterine transfer. Individuals who choose PGT-M also have the option of testing for aneuploidy (PGT-A). Many patients will elect to use both PGT-A and PGT-Mbecause it allows identification of embryos that are both euploid and unaffected/non-pathogenic carriers. Thorough patient counseling by a reproductive endocrinologist
and/or genetic counselor with detailed knowledge of the advantages and limitations of testing is essential.

For many people, PGT-M offers a desirable alternative to prenatal testing. Unlike prenatal testing, PGT-M allows identification of affected embryos prior to pregnancy, which may circumvent the stress associated with the knowledge of an affected pregnancy and prevent pregnancy termination. However, there are a number of important considerations that should be discussed when individuals contemplate its use. Women should be counseled that the number of embryos reaching the blastocyst stage is determined by multiple factors, such as age and ovarian reserve. Although it would be expected that approximately 50% of embryos would be affected by pathogenic gene variants patients should be aware of the possibility of having fewer embryos than expected (or even none) that are euploid and non-affected. In an observational study on the suitability of preimplantation genetic diagnosis for both BRCA-positive unaffected carriers and breast cancer survivors, 720 embryos were tested, identifying 294 (40.8%) as BRCA–negative (49). It is also important to discuss timing; women who cryopreserve oocytes should be informed that they can pursue PGT-M once they decide to fertilize their oocytes. Women who cryopreserve embryos but who are not yet ready to have a child may wish to defer testing until later, as identification of genes and genetic testing techniques continue to evolve. Finally, cost may influence whether women pursue this option or not. Unfortunately, fertility treatment (including IVF) is often not covered by insurance, and genetic testing may pose an additional cost to an already expensive treatment.

Interestingly, utilization of PGT-M is variable, even when individuals are aware of the technology. In a study of high-risk women, it was found that only 32.5% would theoretically use PGT-M themselves (50). Other studies have shown similar findings (51–53). However, it is imperative that patients are educated and counseled about its availability, as it may influence and promote informed reproductive decision-making.

5.2. Prenatal Diagnosis

Making decisions about PGT-M and prenatal diagnosis can be challenging. Prenatal diagnosis involves testing a fetus for the presence of a genetic mutation. For decades, physicians have used chorionic villus sampling (CVS) and amniocentesis to test for aneuploidy or structural chromosomal aberrations in a developing fetus at 10–14 weeks and 15–20 weeks respectively. Physicians now also use CVS and/or amniocentesis to generate a fetal karyotype as well as to detect the presence of a specific pathogenic variant. More recently, physicians have employed the technique of cell-free fetal DNA at approximately 10 weeks to evaluate for certain chromosomal abnormalities, but as of 2018 this test is still considered a screening test primarily for aneuploidy, and should not be used for prenatal diagnosis of a cancer risk gene (54). Based on the information from CVS or amniocentesis, parents may then decide whether or not to terminate a pregnancy. There may be moral and ethical considerations surrounding the decision to terminate a pregnancy for a pathogenic genetic variant which may or may not cause a future malignancy.


Approximately 60% of women with a BRCA1 or BRCA2 mutation undergo RRSO between the ages of 35–40 and thus enter menopause (55). Many women with Lynch Syndrome also elect THBSO to reduce uterine and ovarian cancer risk. There is a lack of guidelines specific to the follow up of women after RRSO. Proposed guidelines for follow up and health maintenance include yearly pelvic examination, discussion about CA-125 monitoring, encouragement for weight bearing exercise, calcium/vitamin D supplementation, dual-energy X-ray absorptiometry (DEXA) bone scan 1–2 years after RRSO, and consideration of HT in eligible patients (56). Surgical menopause in younger women can result in multiple symptoms that include severe vasomotor symptoms, vaginal dryness, sexual dysfunction, and cognitive changes, all of which may significantly affect quality of life (57). In addition, the risks of coronary heart disease and osteoporosis also increase (58).

The use of HT after oophorectomy in women at increased risk for gynecologic (and breast) cancers is controversial. Although HT is highly effective at reducing symptoms associated with menopause, the relationship between HT use and breast cancer risk even amongwomen in the general population is complicated (59). Few studies have evaluated the safety of hormone therapy in women who have undergone risk-reducing surgery for BRCA mutations and there are no data on safety in women with Lynch Syndrome. A prospective study evaluating a cohort of women with BRCA1 or BRCA2 mutations after RRSO demonstrated that use of HT after oophorectomy in BRCA1 carriers was not associated with an increased risk of breast cancer, although the cumulative incidence of breast cancer who used estrogen and progesterone was higher (22%) than in those who used estrogen alone (12%). Elective oophorectomy at the time of hysterectomy for the general population ofwomen prior to age 50 has been associatedwith a significant risk of cardiovascular disease and an increase in all-cause mortality (60, 61). Given these risks as well as premature loss of estrogen exposure in these patients, the benefits of HT may potentially outweigh the risks without an apparent increased risk of breast cancer (59). Therefore, it is reasonable to consider HT forwomen without a personal history of breast cancer. For women who are not candidates for HT or wish to avoid HT, non-hormonal options exist for treatment of vasomotor symptomsand include selective serotonin reuptake inhibitors (SSRIs), alpha 2 adrenergic agonists, dietary and lifestyle modifications, and alternative medicine approaches. Treatment of menopausal symptoms should be individualized and consider the potential risk versus benefit, medical history and therapeutic goals.


  • Women at risk for hereditary gynecologic cancers have unique concerns regarding cancer prevention, early detection, fertility and hormonal health.
  • Surveillance, chemoprevention, and risk reducing surgical options are used to reduce gynecologic cancer risk but some may result in infertility and surgical premature menopause.
  • There are multiple fertility preservation and family building strategies that can be used to help women achieve their procreative goals including oocyte and/or embryo cryopreservation, donor oocytes, donor embryos, gestational carriers, and adoption.
  • Genetic testing can be used before embryo transfer or during pregnancy to identify whether embryos or fetuses carry a pathogenic gene variant, thereby reducing the risk of transmission.
  • For women with surgical menopause who don't have a personal history of breast cancer, hormone therapy can be considered to avoid the negative consequences of hypoestrogenism.


Women at risk for hereditary gynecologic cancers can pro-actively reduce cancer risk through chemoprevention and risk reducing surgery, but these interventions may affect future fertility and hormonal function. As access to genetic testing improves and the technologies of assisted reproductive technology advance, options available for management of at-risk individuals and couples will likely expand. Hormone therapy can improve symptoms of menopause and improve quality of life for women who experience premature surgical menopause. Collaboration between gynecologic oncologists and reproductive endocrinologists will further advance and improve the quality of care we provide to this unique patient population.


This report was developed under the direction of the Practice Committee of the American Society for Reproductive Medicine (ASRM) in collaboration with the Society of Gynecologic Oncology (SGO) as a service to its members and other practicing clinicians. Although this document reflects appropriate management of a problem encountered in the practice of reproductive medicine, it is not intended to be the only approved standard of practice or to dictate an exclusive course of treatment. Other plans of management
may be appropriate, taking into account the needs of the individual patient, available resources, and institutional or clinical practice limitations. The Practice Committee and the Board of Directors of ASRM and the Publications and Executive Committees of SGO have approved this report.

This document was reviewed by ASRM members and their input was considered in the preparation of the final document. ASRM and SGO acknowledge the special contribution of Erika Johnston-MacAnanny, MD; Terri Lynn Woodard, MD; Lee-may Chen, MD; Stephanie V. Blank, MD; Samantha Pfeifer, MD; Karen Glass, MD; Emily Penick, MD; Elizabeth Burton, MD in the preparation of this document. The following members of the ASRM Practice Committee participated in the development of this document. All Committee members disclosed commercial and financial relationships with manufacturers or distributors of goods or services used to treat patients. Members of the Committee who were found to have conflicts of interest based on the relationships disclosed did not participate in the discussion or development of this document.

Alan Penzias, MD; Kristin Bendikson, MD; Samantha Butts, MD, MSCE; Tommaso Falcone, MD; Susan Gitlin, PhD; Clarisa Gracia, MD, MSCE; Karl Hansen, MD, PhD; Sangita Jindal, PhD; Jennifer Mersereau, MD; Randall Odem, MD; Robert Rebar, MD; Richard Reindollar, MD; Mitchell Rosen, MD; Jay Sandlow, MD; Peter Schlegel, MD; Dale Stovall, MD.

Declaration of Competing Interest:

Dr. Karen Glass reports I am on the executive of the Fertility Preservation Special Interest Group of the CFAS. I am on a team that created the CKN/CFAS National Oncofertility database in Canada. EMD Serono gave a grant to CKN to support the database build and launch. I didn't receive any of the funding and I don't have any other affiliation with CKN. I am the director of the Fertility Preservation Program at CReATe Fertility Centre. Lee-may Chen, Stephanie Blank, Elizabeth Burton, Emily Penick and Terri Woodard have no conflicts to declare.


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  25. Pal N, Broaddus RR, Urbauer DL, Balakrishnan N, Milbourne A, Schmeler KM, et al. Treatment of low-risk endometrial cancer and complex atypical hyperplasia with the Levonorgetrel-releasing intrauterine device. Obstet Gynecol 2018;131:109–16.
  26. Schmeler KM,Lynch HT,ChenLM, et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome.NEngl JMed2006;354:261–9.
  27. Kim J, Skrzynia C, Mersereau JE. A pilot study of BRCA mutation carriers' knowledge about the clinical impact of prophylactic oophorectomy and views on fertility consultation: a single–center pilot study. J Genet Counsel 2015;24:149–57.
  28. Chan JL, Johnson LNC, Sammel MD, DiGiovanni L, Voong C, Domchek SM, et al. Reproductive decision–making in women with BRCA1/2 mutations. J Genet Counsel. (ePub ahead of print).
  29. Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, Baird DD. Association between biomarkers of ovarian reserve an infertility among older women of reproductive age. JAMA 2017;318:1367–76.
  30. Lin WT, Beattie M, Chen LM, Oktay K, Crawford SL, Gold EB, Cedars M, Rosen M. Comparison of age at natural menopause in BRCA1/2 mutation carriers with a non-clinic-based sample of women in northern California. Cancer 2013;119:1652–9.
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  34. Wang ET, Pisarska MD, Bresee C, Chen YD, Lester Y, Afshar Y, et al. BRCA1 germline mutations may be associated with reduced ovarian reserve. Fertil Steril 2014;102:1723–8.
  35. Giordano S, Garrett–Mayer E, Mittal N, Smith K, Passaglia Shulman L, Gradishar W, et al. Association of BRCA1 mutations with impaired ovarian reserve: connection between infertility and breast/ovarian Cancer risk. J Adolesc Young Adult Oncol 2016;5:337–43.
  36. Michaelson-Cohen R, Mor P, Srebnik N, Beller U, Levy-Lahad E, Eldar-Geva T. BRCA mutation carriers do not have compromised ovarian reserve. Int J Gynecol Cancer 2014;24:233–7.
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  38. Moslehi R, Singh R, Lessner L, Friedman JM. Impact of BRCA mutations on female fertility and offspring sex ratio. Am J Hum Biol 2010;22:201–5.
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Practice Documents

ASRM Practice Documents have been developed to assist physicians with clinical decisions regarding the care of their patients.
Practice Committee Documents teaser

Current evaluation of amenorrhea: a committee opinion (2024)

Amenorrhea is the absence or abnormal cessation of the menses.
Practice Committee Documents teaser

Inclusive language and environment to welcome lesbian, gay, bisexual, transgender, queer, questioning, intersex, and asexual+ patients (2024)

Creating an inclusive clinical environment to serve lesbian, gay, bisexual, transgender, queer, questioning, intersex, and asexual+ patients is vital.
Practice Committee Documents teaser

Subclinical hypothyroidism in the infertile female population: a guideline (2024)

This guideline reviews the risks and benefits of treating subclinical hypothyroidism in female patients with a history of infertility and miscarriage.
Practice Committee Documents teaser

Tobacco or marijuana use and infertility: a committee opinion (2023)

In the United States, approximately 21% of adults report some form of tobacco use, although 18% report marijuana use.

More Resources

MAC 2021 teaser
ASRM Academy on the Go

ASRM MAC Tool 2021

The ASRM Müllerian Anomaly Classification 2021 (MAC2021) includes cervical and vaginal anomalies and standardize terminology within an interactive tool format.

View the MAC Tool
EMR Phrases teaser
Practice Guidance

EMR Shared Phrases/Template Library

This resource includes phrases shared by ASRM physician members to provide a template for individuals to create their own EMR phrases.

View the library
Practice Committee Documents teaser

ASRM Practice Documents

These guidelines have been developed by the ASRM Practice Committee to assist physicians with clinical decisions regarding the care of their patients.

View ASRM Practice Documents
Ethics Committee teaser

ASRM Ethics Opinions

Ethics Committee Reports are drafted by the members of the ASRM Ethics Committee on the tough ethical dilemmas of reproductive medicine.

View ASRM Ethics Opinions
Coding Corner general teaser
Practice Guidance

Coding Corner Q & A

The Coding Corner Q & A is a list of previously submitted and answered questions from ASRM members about coding. Answers are available to ASRM Members only.

View the Q & A
Covid-19 teaser
Practice Guidance

COVID-19 Resources

A compendium of ASRM resources concerning the Novel Corona virus (SARS-COV-2) and COVID-19.

View the resources
Couple looking at laptop for online patient education materials

Patient Resources provides a wide range of information related to reproductive health and infertility through patient education fact sheets, infographics, videos, and other resources.

View Website

Topic Resources

View more on the topic of genetic screening/testing
Podcast Icon

Fertility and Sterility On Air - TOC: May 2024

Topics this month include Iatrogenic and demographic determinants of the national plural birth increase, outcomes between ICSI and IVF with PGT-A. Listen to the Episode
Videos Icon

Journal Club Global: Recent clinical trials in Fertility and Sterility from the Asia Pacific region

Join ASPIRE 2024 for a Journal Club Global on PGT-A and IVF. Learn from top experts discussing recent clinical trial data and pregnancy outcomes View the Video
Coding Icon

Coding for an endometrial biopsy/Mock cycle

We had patients request us to bill their insurance for the two monitoring visits and the Endo BX and change the diagnosis code to something that is payable.  View the Answer
Podcast Icon

Fertility and Sterility On Air - Unplugged: March 2024

Topics include: melatonin and implantation (4:38), whole-genome screening of embryos, and bioengineering assisted reproductive technology. Listen to the Episode
Videos Icon

Journal Club Global: Cost effectiveness analyses of PGT-A

Infertility treatments can be financially burdensome, often without insurance coverage, making understanding the cost effectiveness of PGT-A crucial. View the Video
Podcast Icon

Fertility and Sterility On Air - TOC: February 2024

Topics this month include the optimial AMH level in oocyte donors, the role of mean number of DNA breakpoints (MDB) in sperm DNA integrity, and more. Listen to the Episode
Coding Icon

Coding PGT requisitions to the PGT lab

Do you have any recommended codes to use for PGT requisitions to the PGT lab?   View the Answer
Document Icon

Clinical management of mosaic results from preimplantation genetic testing for aneuploidy of blastocysts: a committee opinion (2023)

This document incorporates studies about mosaic embryo transfer and provides evidence-based considerations for embryos with mosaic results on PGT-A. View the Committee Opinion
Videos Icon

Journal Club Global - Revisiting the STAR trial: The Fellows debate PGT-A

We are excited to host a debate covering the pros and cons of PGT-A and how new technologies should be validated before clinical implementation. View the Video
Coding Icon

Sperm DNA Fragmentation

Is there a CPT code for HALO DNA Fragmentation for sperm? View the Answer
Coding Icon

Results Review

What CPT code is most appropriate to submit for Physician Time to review CCS/PGS/PGD results? View the Answer
Coding Icon

ICSI and Embryo Biopsy

How to bill for ICSI or embryo biopsies that occur in different days?  View the Answer
Coding Icon

Genetic Counseling

Does ASRM have any guidance for how to bill for genetic counseling services provided by a genetic counselor?
View the Answer
Coding Icon

Embryo Biopsy

Have any new codes been introduced for the lab portion of PGT? View the Answer
Coding Icon

Embryo Biopsy Embryologist Travel Costs

Can we bill insurance for the biopsy procedure? Can we bill for travel expenses? View the Answer
Coding Icon

Embryo Biopsy PGS Testing

What codes are appropriate for PGS testing? View the Answer
Coding Icon

Assisted Zona Hatching

Can assisted hatching and embryo biopsy for PGT-A; PGT-M or PGT-SR be billed during the same cycle? View the Answer
Document Icon

Indications and management of preimplantation genetic testing for monogenic conditions: a committee opinion (2023)

ASRM has updated its opinion on PGT for monogenic conditions, providing guidance on clinical and technical complexities. View the Committee Opinion
Videos Icon

Journal Club Global - PGT-A - Can non-invasive approaches based on spent medium analysis

PGT-A by trophectoderm biopsy aims to select available euploid embryos for transfer. View the Video
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ASRM müllerian anomalies classification 2021

The Task Force set goals for a new classification and chose to base it on the iconic AFS classification from 1988 because of its simplicity and recognizability. View the Committee Opinion
Videos Icon

Journal Club Global - Accuracy of Preimplantation Genetic Testing for Aneuploidies

One of the highest aspirations in reproductive medicine is to develop a technology allowing for ID of embryos that have true reproductive potential.
View the Video
Document Icon

Disclosure of sex when incidentally revealed as part of preimplantation genetic testing (PGT): an Ethics Committee opinion (2018)

Clinics may develop a policy to disallow selecting which embryos to transfer based on sex and choose to use only embryo quality as selection criteria. View the Committee Opinion
Document Icon

Use of preimplantation genetic testing for monogenic defects (PGT-M) for adult-onset conditions: an Ethics Committee opinion (2018)

Preimplantation genetic testing for monogenic diseases for adult-onset conditions is ethically permissible for a range of conditions including when the condition is serious and no safe, effective interventions are available. View the Committee Document
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Transferring embryos with genetic anomalies detected in preimplantation testing: an Ethics Committee Opinion (2018)

Patient requests for transfer of embryos with genetic anomalies linked to serious health-affecting disorders detected in preimplantation testing are rare but do exist. View the Committee Document
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Best practices of ASRM and ESHRE: a journey through reproductive medicine (2012)

ASRM and ESHRE are the two largest societies in the world whose members comprise the major experts and professionals working in reproductive medicine. View the Committee Joint Guideline
Membership Icon

Preimplantation Genetic Testing Special Interest Group (PGTSIG)

The ASRM PGTSIG coordinates research, education, and training in preimplantation genetic diagnosis (PGT). Learn more about the PGTSIG

Topic Resources

View more on the topic of cancer and fertility
News Icon

What's New from the Fertility and Sterility Family of Journals

Here’s a peek at this month’s issues from our family of journals! As an ASRM Member, you can access all of our journals.
Read More about the newest articles
News Icon

What's New from the Fertility and Sterility Family of Journals

Here’s a peek at this month’s issues from our family of journals! As an ASRM Member, you can access all of our journals.
Read More about the newest articles
Podcast Icon

Fertility and Sterility On Air - TOC: April 2024

Topics this month include the use of ICSI, fertility treatments among reproductive-aged women after cancer, and more. Listen to the Episode
News Icon

What's New from the Fertility and Sterility Family of Journals

Here’s a peek at this month’s issues from our family of journals! As an ASRM Member, you can access all of our journals.
Read More about the newest articles
Coding Icon

Medication Administration

 Is CPT code 96402 applicable to a Depo-Lupron or Zoladex injection by nurse at REI practice, even if there is no diagnosis of cancer?  View the Answer
Coding Icon

Fertility Preservation Consult

What code are we supposed to use for counseling regarding fertility preservation for an individual with cancer... View the Answer
Coding Icon

D&C Under Ultrasound Guidance

What are the CPT codes and ICD-10 codes for coding a surgical case for a patient with history of Stage B adenocarcinoma of the cervix ... View the Answer
Coding Icon

Cycle Monitoring Fertility Preservation

If the patient is undergoing ultrasound tracking visits for fertility preservation, what I ICD-10 code do you use for the monitoring? View the Answer
Document Icon

Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion (2018)

Chemotherapy and radiation therapy often result in reduced fertility. View the Committee Opinion
Document Icon

Best practices of ASRM and ESHRE: a journey through reproductive medicine (2012)

ASRM and ESHRE are the two largest societies in the world whose members comprise the major experts and professionals working in reproductive medicine. View the Committee Joint Guideline