Registration is open for the 2024 ASRM Scientific Congress & Expo

Menu
Close Close Icon

Combined hormonal contraception and the risk of venous thromboembolism: a guideline (2016)


BACKGROUND

Venous thromboembolism (VTE) refers to the formation of a blood clot in a deep vein and is a rare but potentially preventable cause of death in women of reproductive age. Deep venous thromboses, which commonly occur in the legs, may break off and move into the pulmonary vasculature, which can be life-threatening. However, most venous thromboses do not result in death. Common risk factors for VTE include hypercoagulability and vascular injury. Pregnancy and the postpartum period in particular are associated with an increased risk of VTE compared with the non-pregnant state: The incidence of VTE is 5–20/ 10,000 woman-years in pregnancy and 40 65/10,000 woman-years postpartum, compared with 1–5/10,000 woman-years outside of pregnancy (1).

Overall, it appears that combined hormonal contraceptives (CHCs) are associated with an increased risk of VTE compared with non-use (3–15/10,000 woman-years in users vs. 1–5/10,000 risk in non-users), but this risk is still smaller than the risk in pregnancy and appears to decline over time (1). In general, the risk of VTE while on hormonal contraception must be weighed against potential contraceptive benefits and the risks of VTE during pregnancy and postpartum to determine whether a woman should take CHCs.

While there is good evidence that CHCs are associated with an increased risk of VTE, there has been substantial controversy surrounding the actual risk associated with various different formulations of CHCs. A variety of CHC methods are available with different doses of estrogen and types of progestin, which are delivered through various routes of administration.

METHODS

This clinical practice guideline was based on a systematic review of the literature. A systematic literature search of relevant articles was performed in the electronic database MEDLINE through PubMed (February and June 2015), with a filter for human subject research. This electronic search and examination of reference lists from primary and review articles yielded 1,254 studies, of which 86 studies were included.

A combination of the following medical subject headings or text words/keywords were used: birth control; contraception; combined hormonal contraception; combined oral contraceptive; combined oral contraceptives; contraceptives, oral; contraceptives, oral/administration and dosage; contraceptives, oral, combined; contraceptives, oral, combined/administration and dosage; hormonal contraception; oral contraceptive; oral contraceptives; desogestrel; drospirenone; estradiol; estrogen; oestrogen; ethynodiol diacetate; etynodiol diacetate; levonorgestrel; nomegestrol; norethisterone; norethisteron; norethindrone; norethindron; norethynodrel; norgestimat; norgestimate; norgestrel; AND ethinyl estradiol; ethinyl estradiol; ethinylestradiol; mestranol; progesterone; progestin; progestins; progestogen; progestogens; AND cerebral vein thrombosis; clot; deep vein thrombosis; deep venous thrombosis; DVT; embolism; hepatic thrombosis; mesenteric venous thrombosis; pulmonary emboli*; pulmonary embolism; thrombosis; thrombus; thromboembolism; thrombophlebitis; vein embolism; vein thrombosis; venous embolism; venous thromboembolism; venous thrombosis; venous thrombosis; venous thrombotic; first generation, second generation, third generation, fourth generation; AND obese; obesity; body weight; body weight; body mass index; BMI; PCOS; polycystic ovaries; polycystic ovary; polycystic ovary syndrome; polycystic ovarian syndrome; smoking; age; risk, risks, risk factor, risk factors.

An independent panel of experts reviewed the full articles of all citations that possibly matched the predefined selection criteria. Final inclusion or exclusion decisions were made on examination of the articles in full. Disagreements about inclusion among reviewers were discussed and solved by consensus or arbitration after consultation with an independent reviewer/epidemiologist. Studies were eligible if they met one of the following criteria: primary evidence (clinical trials) that assessed the effectiveness of a treatment correlated with an outcome measure (VTE); meta-analyses; and relevant articles from bibliographies of identified articles.

The quality of the evidence for each reference in the bibliography was evaluated using the following grading system:

  • Level I: Evidence obtained from at least one properly designed randomized, controlled trial.
  • Level II-1: Evidence obtained from well-designed controlled trials without randomization.
  • Level II-2: Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one center or research group.
  • Level II-3: Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled trials might also be regarded as this type of evidence.
  • Level III: Opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.

Systematic reviews/meta-analyses were individually considered and included if they followed a strict methodological process and assessed relevant evidence.

The strength of the evidence was evaluated as follows:

  • Grade A: There is good evidence to support the recommendations, either for or against.
  • Grade B: There is fair evidence to support the recommendations, either for or against.
  • Grade C: There is insufficient evidence to support the recommendations, either for or against.


OVERVIEW OF THE LITERATURE

There are no large, prospective randomized studies comparing the risk of VTE among various doses of estrogen, types of progestin, or routes of administration. Only level II-2 studies exist, including large cohort and case-control studies that are limited by a number of methodological issues which may skew results. For example, without randomization, it is difficult to control for different patient populations and prescriber bias (2). It is also important to recognize that VTE risk is greater in new hormonal contraceptive users during the first year (3), in older women, and in obese women. Many studies do not adequately account for imbalances in these risk factors between treatment groups. In addition, the diagnosis of venous thrombosis may not always be accurate in studies since cases are not always confirmed by hospital records or radiologic studies. Finally, given that the incidence of VTE is low, large numbers of observations are required to compare cases among various treatment groups.

CLASSIFICATION OF COMBINED HORMONAL CONTRACEPTIVES

Combined hormonal contraceptives (CHCs) are classified into several categories. Combined oral contraceptives (COCs) with 50 mg of ethinyl estradiol (EE) are considered first generation. Second-generation combined oral contraceptive pills contain lower doses of estradiol (20, 30, or 35 mg) and the progestin norethindrone and its derivatives, including levonorgestrel (4). Third-generation combined oral contraceptive pills containing the progestins desogestrel and gestodene were formulated to be less androgenic than the second-generation progestins (5). Norgestimate is technically a third generation progestin; however, its bioactivity is mediated mainly through levonorgestrel, which distinguishes it from other third-generation progestins (6). Finally, fourthgeneration contraceptive pills include, among others, the progestin drospirenone, which is derived from spironolactone and has anti-androgenic activity (7). In addition, CHCs are available in several routes of administration including pills, transdermal patches, and vaginal ring. For the purpose of this document, only preparations available in the United States will be discussed.

SCIENTIFIC QUESTIONS

Does the Dose of Estrogen Affect VTE Rates?

Modern combined oral contraception may contain 10, 15, 20, 30, or 35 μg of EE administered continuously for 21 or 24 out of 28 days. In addition, semicontinuous oral contraceptive pills are available, which contain 84 days of EE followed by a 7-day progestin-free window. It is difficult to compare the effect of EE dose since preparations often differ with respect to the progestin component. Despite this limitation, there is a good deal of evidence that increased estrogen dose is associated with VTE risk. The best evidence suggests that by lowering the estrogen content of the pill to ≤50 μg of EE, VTE incidence decreases (8–17). A number of large studies found that preparations of COCs with 50 μg EE have a higher risk of thrombosis compared with sub-50 μg EE formulations (12–14), which likely informed conclusions made in subsequent reviews/ meta-analyses that there is an overall increased risk of VTE in COCs containing 50 μg EE and select progestins (15–17). A 2014 Cochrane review concluded that a 50 μg EE pill containing levonorgestrel was associated with relative risks (RR) for VTE of 2.1 (95% CI, 1.4–3.2) and 2.3 (95% CI, 1.3–4.2) compared with a 30 μg and 20 μg pill containing levonorgestrel, respectively (16, 17). However, a number of studies did not find that reductions in dose from 50 μg to <50 μg EE COC decreased the risk of VTE (18–26). There is no evidence that lowering the estrogen content of the COCs below 35 μg further lowers the risk of VTE (Table 1) (12, 14, 15, 18–20, 23, 24, 26, 27, 29, 30).

Table 1. Relative risk compared with absolute risk for venous thromboembolism by characteristic


Variable Relative risk compared with non-pregnant women without the risk factor Absolute risk
Nonpregnant, not
taking hormones
1.0 VTE: 1–5/10,000 woman-years (1)
Pregnancy 4.29 (95% CI, 3.49–5.22; P<.001) compared with non-pregnant women (27)  VTE: 5–20/10,000 woman-years (1)
PE: 1/10,000 woman-years
Postpartum 4.29 (95% CI, 3.49–5.22; P<.001) compared with non-pregnant women (27) VTE: 40–65/10,000 woman-years (1)
PE: 16 per 10,000 woman-years
Progestin type RR of VTE (16, 17):
Non-use vs. 1st generation (norethindrone COC) users: 3.2 (95% CI, 2.0–5.1)
Non-use vs. 2nd generation (levonorgestrel COC) users: 2.8 (95% CI, 2.0–4.1)
Non-use vs. 3rd generation (desogestrel COC users): 3.8 (95% CI, 2.7–5.4)
2nd vs. 1st generation: 0.9 (95% CI, 0.6–1.4)
3rd vs. 1st generation: 1.2 (95% CI, 0.8–1.9)
3rd generation vs. 2nd generation: 1.3 (95% CI, 1.0–1.8)
 
Estrogen dose 20 μg ethinyl estradiol with levonorgestrel vs. non-use: 2.2 (95% CI, 1.3–3.6)
30 μg ethinyl estradiol with levonorgestrel vs. 20 μg ethinyl estradiol with
levonorgestrel: 1.1 (95% CI, 0.7–1.7)
50 μg ethinyl estradiol with levonorgestrel vs. 20 μg ethinyl estradiol with
levonorgestrel: 2.3 (95% CI, 1.3–4.2) (16, 17)
Thrombophilias Factor V Leiden: 2.6 no OC, 64.7 1st/2nd generation, 29.6 3rd generation
Other heritable thrombophilia: 2.6 no OC, 63.3 1st/2nd generation; 52.5
3rd generation (28)
Note: CI = confidence interval; COC = combined oral contraceptives; OC = oral contraceptives; PE = pulmonary embolism; RR = relative risk; VTE = venous thromboembolism.
Summary statement.
There are no randomized trials large enough to compare thrombosis risk in patients on oral contraceptives containing different doses of EE. Only level II 2 studies exist, including large cohort and case-control studies. It is difficult to compare the effect of the EE dose since preparations differ with respect to the progestin component. In addition, observational studies are limited by a number of unmeasured confounders and bias. The following may be concluded from the literature:

  • While no longer available in the United States, high-dose combined oral contraception (>50 μg) is associated with higher risks of VTE than lower-dose formulations. (Grade B)
  • There is fair evidence that combined oral contraception with 50 μg EE has a higher risk of thrombosis compared with sub-50 μg EE formulations. (Grade B). However, data are conflicting and difficult to interpret due to the variable progestin component of the pills studied.
  • There is fair evidence that COCs containing EE doses lower than 35 μg have similar VTE risk to 35 μg formulations. (Grade B)


Does Type of Progestin Contribute to VTE Risk?

A particular area of controversy is whether the type of progestin in COCs affects VTE rates. Specifically, there have been conflicting results from large epidemiologic studies, none of which are randomized, as to whether there is an increased risk of VTE rates in COCs containing the newer progestins desogestrel, gestodene (not available in the United States), norgestimate, and drospirenone compared with the progestins levonorgestrel and norethindrone.

Beginning in the mid-1990s, cohort and case-control studies reported a 2-fold increased risk of VTE with COCs containing the third-generation progestins desogestrel and gestodene compared with second-generation preparations (21, 31, 32). However, further studies questioned the initial findings, attributing the increased risk to confounding factors including new-user and prescriber bias (3, 4, 23–26, 33–40). It is known that new users of oral contraception have a higher rate of VTE that gradually decreases as the length of time taking combined oral contraception increases (3). Therefore, the increased risk seen in early studies of thirdgeneration progestins may have been the result of differences in the populations taking the second- vs. third-generation progestins (2, 4, 40, 41). However, additional studies have shown an increased risk of VTE with third-generation progestins (with the exception of norgestimate, which has been found to have a risk similar to levonorgestrel) even when potential confounders are taken into account (Table 1) (9, 10, 12–14, 28, 42–51).

Cohort and case-control studies have also shown an increased VTE risk with the fourth-generation progestin drospirenone (12, 13, 30, 51–55). A recent large US cohort study of over 100,000 women who were new users of drospirenone compared with over 300,000 women who were new users of second-generation combined oral contraception noted an increased risk of VTE in the drospirenone group (hazard ratio [HR] 1.77; 95% CI, 1.33–2.35) (55). However, other studies, including large cohort and case-control studies controlling for multiple factors including the new-user effect, show no increased risk with drospirenone (56–60). Similarly, the International Active Surveillance Study of Women Taking Oral Contraceptives did not find a difference in VTE rates among different progestins. This large, European, prospective observational study found VTE incidence rates of approximately 7.2–9.8/10,000 woman-years among combined oral contraception users, with similar rates for drospirenone and third-generation progestins compared with levonorgestrel, and an adjusted HR of 0.8 (95% CI, 0.5–1.3) between drospirenone and levonorgestrel (61). Another case-control study, which included 311 combined oral contraception users with first-time VTE, found an increased risk, the adjusted odds ratio (OR) of 2.5 (95% CI, 1.2–5.1) for desogestrel compared with levonorgestrel. However, there were no significantly higher risks with other progestin types, including drosperinone (OR 1.9; 95% CI, 0.9–4.1) (62).

Recent meta-analyses and systematic reviews have consistently shown a small but significant increased risk of VTE among users of third-generation progestins and drospirenone compared with second-generation progestins (15–17, 63–65). One meta-analysis, which included 23 studies, reported that COCs increased the risk of venous thrombosis 4- fold. The relative risk of VTE compared with non-use in norethindrone COC users was 3.2 (95% CI, 2.0–5.1), levonorgestrel COC users 2.8 (2.0–4.1), and desogestrel COC users 3.8 (2.7–5.4) (16). Similarly, a Cochrane review of 26 studies showed a 50%–80% increased relative risk of VTE among third-generation or drosperinone COC users compared with levonorgestrel COC users at the same dose of EE (30–35 μg). The relative risk for third-generation compared with second-generation users was 1.3 (95% CI, 1.0–1.8). Overall, the relative risk of VTE among COC users was 3.5 (95% CI, 2.9–4.3) (Table 1) (17).

Since none of the studies were randomized, they may be limited by confounding VTE risk factors such as new use, older age, obesity, family history of VTE, or prolonged immobilization. They may also be subject to bias including the healthy-user effect, misclassification bias of VTE events, and prescriber bias (39, 41). The EE dose is also not consistent among combined oral contraception preparations, making direct comparisons of the progestin component difficult. Finally, it is important to note that even in the studies that have found an increased risk of VTE with newer progestins, the absolute increase in risk is very small relative to the overall increased risk with combined oral contraception. The absolute risk of thirdgeneration or drospirenone-containing COCs was estimated in one meta-analysis to be 10–15 VTE/10,000 women per year compared with 8 VTE/10,000 women in levonorgestrel COC users and 2 VTE/10,000 women with no use (63). This is still lower than the overall risk in pregnancy (5–20/ 10,000 woman-years).

Summary statement.
There are no randomized trials large enough to compare the risk of VTE in patients on different types of oral contraceptives. Only level II-2 studies exist, including large cohort and case-control studies. It is difficult to compare the effect of the progestin component alone, as some studies include preparations with different doses of EE. In addition, observational studies are limited by a number of confounders and bias (including differences in users and non-users of COCs, duration of combined oral contraception use, and misclassification of VTE due to differences in diagnostic criteria used).

Because of the lack of high-quality level I studies comparing progestins, it is possible that methodological problems in the present studies are responsible for the small increased risk in VTE events, and that there is actually no increased risk with third- or fourth-generation progestins, such as desogestrel or drospirenone. If there is indeed an increased RR, the absolute risk increase is extremely small. Therefore, in the appropriately selected patient, the choice of COC method does not need to be made based on the type of progestin. If a woman has estrogen-related COC risk for VTE, then no route of administration or dose of estrogen has been found to be safer. All estrogen-containing hormonal methods are contraindicated in that setting.
  • There is fair evidence that all available CHC preparations increase the risk of VTE over the non-pregnant state.
  • There is fair evidence that women using preparations of COC with drospirenone or third-generation progestins have a slightly higher risk of VTE compared with those using norethindrone or levonorgestrel. (Grade B). These results may in part be related to characteristics of the populations using these preparations.


Does Route of Administration of CHC Contribute to VTE Risk?

CHC is commonly delivered by an oral route but may also be administered by vaginal ring, which is a transmucosal route, or as a transdermal preparation. Although it has been suggested that transdermal estradiol for hormone therapy in postmenopausal women may confer a lower risk of VTE due to the first-pass effect in the liver, this has not been noted with non-oral hormonal contraceptive preparations. There have been reports that the non-oral route of administration increases the risk of VTE. However, there are no prospective, randomized trials large enough to determine a difference in VTE risk of transdermal or vaginal ring CHC compared with oral administration.

The only currently available contraceptive vaginal ring (NuvaRing®, Merck) contains 11.7 mg etonogestrel (the biologically active metabolite of desogestrel, a third-generation progestin) and 2.7 μg EE, with approximately 120 μg mg of etonogestrel and 15 μg of EE released per day. Users of the ring have the same systemic exposure to the progestin component but approximately half of the systemic exposure to EE when compared with users of an oral preparation of 150 μg desogestrel and 30 μg EE (66).

Observational studies have shown that similar to users of COCs, ring users have an elevated risk of VTE compared with non-users of hormonal contraception (67). A retrospective cohort study from Denmark found a slightly increased risk of VTE among users of the vaginal ring compared with users of COCs containing levonorgestrel (RR 1.9; 95% CI, 1.3 to 2.7) (67). However, a large retrospective cohort study, using data from four US health plans, which separated new from established users, showed no difference in VTE risk among vaginal ring users compared with COC users; the incidence of VTE events among vaginal ring users was 11.3 per 10,000 women per year (55). A large, European prospective observational study similarly found no increased risk of VTE among vaginal ring users compared with COC users (HR 0.8; 95% CI, 0.5–1.5) (68). The evidence, therefore, suggests that the risk of VTE related to the vaginal ring is similar, neither decreased nor increased, from oral CHC.

There has been controversy as well regarding the transdermal CHC patch which contains 6 mg norelgestromin (the active metabolite of norgestimate, a third-generation progestin) and 0.75 mg EE, and delivers approximately 150 μg of norelgestromin and 20 μg of EE per day (69). The amount of estradiol and progestin delivered has been considered equivalent to an oral pill containing 250 μg norgestimate and 35 μg EE; however, pharmacokinetic studies have shown that the systemic exposure is higher but the peak levels are lower with the transdermal patch (70, 71).

Post-marketing studies comparing the risks of VTE among users of the transdermal patch and combined oral contraception have shown conflicting results. Three casecontrol studies (including a follow-up to the first study that added 56 additional cases) showed no difference in VTE risk between users of the transdermal patch compared with users of comparable combined oral contraception containing the progestins norgestimate and levonorgestrel (72–75). However, a third case-control study found a higher risk in transdermal patch users, with an incidence rate of 2.2 (95% CI, 1.3–3.8) (76). More recent studies have also demonstrated inconsistent results. A case-control study of 152 women with thrombotic or cardiovascular events and 606 matched controls found a 2-fold higher increase in transdermal patch users compared with users of COCs containing norgestimate (RR 2.0; 95% CI, 1.2–3.3) (77). However, the same large, US retrospective cohort study discussed above (which found no difference in VTE risk among vaginal ring users) also found no increased risk of VTE among transdermal patch users, with an overall incidence of VTE of 12.3 per 10,000 woman-years for patch users (55).

Summary statement.
All of the studies addressing this question were Level II-III.
  • There is insufficient evidence that the contraceptive patch or contraceptive vaginal ring has a different risk of VTE compared with COCs. (Grade C)


Are Smoking, Obesity, or Inherited Thrombophilias Risk Factors for VTE in CHC Users?

Several Level II and III studies have identified risk factors associated with VTE. However, determining to what degree a specific risk factor increases the risk of VTE is difficult as these studies are heterogeneous, are often affected by biases, and analyze risk factors as confounders rather than as primary predictors of outcomes. But, a number of risk factors have been found in multiple studies examining the risk of VTE in oral contraceptive users, including prolonged immobilization, age over 35 years, increased body mass index (BMI) in patients over 35 years, personal history of VTE, family history of deep vein thrombosis (DVT), inherited thrombophilia (most commonly factor V Leiden or prothrombin G20210A) mutation, antiphospholipid syndrome, active systemic lupus, and current cancer diagnosis. None of these risk factors increases the risk of VTE more than pregnancy (5–20/10,000 woman-years); however, they are additive.

The overall likelihood of VTE is greatest in the postpartum period for 6 weeks (approximately 40–65 per 10,000 woman-years, and is increased until 12 weeks) (1, 78). Women with familial thrombophilia syndromes, including factor V Leiden mutation, prothrombin G20210 A mutation, protein C, protein S, or antithrombin deficiency, have a several-fold increased risk of VTE (depending on the type of thrombophilia), and oral contraceptive use further increases the risk of thrombosis in these patients (9, 15, 28, 43, 62, 65, 79–84). One populationbased case-control study found that among women with thrombophilia, the risk of developing DVT during the first 6 months of oral contraceptive use (compared with prolonged use) was increased 19-fold (95% CI, 1.9–175.7), and in the first year of use, it was increased 11-fold (95% CI, 2.1–57.3) (83). Given the rarity of fatal VTE, one group of investigators concluded that screening more than 1 million CHC candidates for thrombophilia would at best prevent two oral contraceptive-associated deaths (85). Therefore, the Centers for Disease Control and Prevention (CDC) does not recommend screening for thrombophilias with laboratory testing during routine care (Table 1) (86).

Other factors associated with VTE in those women who use CHCs include smoking, age, and obesity, although smoking and obesity alone are weak risk factors for VTE. Women who smoke, particularly more than 15 cigarettes daily, have a greater risk (18, 20, 26, 31, 32, 34, 37, 39, 40, 49, 54, 87, 88). This risk increases substantially if women are over age 35 years and smoke, as age has been found to be an independent risk factor for VTE in several studies (10, 12–14, 18, 20, 23, 31, 39, 43, 44, 51, 80, 87). Given the increasing epidemic of obesity in the United States and even worldwide, the association between obesity and thrombosis is particularly important. Some studies have revealed that oral contraceptive use further increases the effect of obesity on the risk of thrombosis leading up to a 10-fold increased risk of VTE among obese oral contraceptive users compared with non-users (12, 22, 24, 26, 31, 32, 34, 40, 49, 54, 59, 60, 64, 65, 88–91).

Summary statement.
Several level II and III studies have identified risk factors associated with VTE; however, determining to what degree a specific risk factor increases the risk of VTE is difficult as these studies are heterogeneous and are often confounded by biases.
  • There is fair evidence that tobacco use, age (>35 years), obesity, and the presence of hereditary thrombophilias (including factor V Leiden mutation, prothrombin G20210A mutation and protein C, protein S, or antithrombin deficiency) increase the risk of thrombotic events in the setting of CHC use. (Grade B)


CONCLUSIONS

While VTE is a rare event in young women of reproductive age (1–5/10,000 woman-years), COCs increase the risk of VTE. Women taking preparations containing drospirinone and third-generation progestins appear to be at slightly increased risk of VTE compared with those taking first- and second-generation preparations. Nonetheless, the overall risk of VTE even with these preparations is low, approximately 10–15 VTE/10,000 women. The benefits of any currently available COC to prevent pregnancy outweighs the risks for most women. It is important to recognize that the risk of VTE is substantially higher in pregnancy (5–20/ 10,000 woman-years) and postpartum (40–65/10,000 women years) than in women on CHC. Nonetheless, when selecting a particular CHC preparation, any potential increased risk of VTE should be balanced with the potential benefits associated with each preparation.

SUMMARY


  • High-dose combined oral contraception (>50 μg) is associated with higher risks of VTE than lower-dose formulations. (Grade B)
  • Evidence is conflicting whether preparations of COC with 50 μg EE have a higher risk of thrombosis compared with sub-50 μg EE formulations, although several large studies have seen an increased risk of VTE in 50 μg EE COCs. (Grade B)
  • There is no reliable evidence that EE doses lower than 35 μg have less VTE risk than 35 μg formulations. (Grade B)
  • There is fair evidence that preparations of COCs with drospirenone or third-generation progestins have only a slightly higher risk of VTE compared with those containing norethindrone or levonorgestrel. (Grade B)
  • There is insufficient evidence that the contraceptive patch or contraceptive vaginal ring has a different risk of VTE compared with COCs. (Grade C)
  • There is fair evidence that tobacco use, age (>35 years), obesity, hypertension, and the presence of hereditary thrombophilias (including factor V Leiden mutation, prothrombin G20210A mutation and protein C, protein S, or antithrombin deficiency) increase the risk of thrombotic events in the setting of CHC use. (Grade B)


RECOMMENDATION


  • In the patient in whom combined hormonal contraception is appropriate, it is reasonable to use any currently available preparation.

Acknowledgments:
This report was developed under the direction of the Practice Committee of the American Society for Reproductive Medicine 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 the American Society for Reproductive Medicine have approved this report.

This document was reviewed by ASRM members and their input was considered in the preparation of the final document. The Practice Committee acknowledges the special contribution of Steven Sondheimer, MD, Kathleen O'Neill, MD, and Rachel Weinerman, 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.

Samantha Pfeifer, M.D.; Samantha Butts, M.D., M.S.C.E.; Daniel Dumesic, M.D.; Gregory Fossum, M.D.; Clarisa Gracia, M.D., M.S.C.E.; Andrew La Barbera, Ph.D.; Jennifer Mersereau, M.D.; Randall Odem, M.D.; Alan Penzias, M.D.; Margareta Pisarska, M.D.; Robert Rebar, M.D.; Richard Reindollar, M.D.; Mitchell Rosen, M.D.; Jay Sandlow, M.D.; Rebecca Sokol, M.D., M.P.H.; Michael Vernon, Ph.D.; Eric Widra, M.D.

REFERENCES

  1. Committee on Gynecologic Practice. ACOG Committee Opinion Number 540: Risk of venous thromboembolism among users of drospirenonecontaining oral contraceptive pills. Obstet Gynecol 2012;120:1239–42. Level III.
  2. van Lunsen HW. Recent oral contraceptive use patterns in four European countries: evidence for selective prescribing of oral contraceptives containing third-generation progestogens. Euro J Contracept Reprod Health Care 1996;1:39–45. Level II-2.
  3. Suissa S, Blais L, SpitzerWO, Cusson J, Lewis M, Heinemann L. First-time use of newer oral contraceptives and the risk of venous thromboembolism. Contraception 1997;56:141–6. Level II-2.
  4. Lewis MA. The Transnational Study on Oral Contraceptives and the Health of Young Women. Methods, results, new analyses and the healthy user effect. Hum Reprod Update 1999;5:707–20. Level II-2.
  5. Speroff L, DeCherney A. Evaluation of a new generation of oral contraceptives. The Advisory Board for the New Progestins. Obstet Gynecol 1993;81:1034–47. Level III.
  6. Hammond GL, Abrams LS, Creasy GW, Natarajan J, Allen JG, Siiteri PK. Serum distribution of the major metabolites of norgestimate in relation to its pharmacological properties. Contraception 2003;67:93–9. Level II-2.
  7. Muhn P, Krattenmacher R, Beier S, Elger W, Schillinger E. Drospirenone: a novel progestogen with antimineralocorticoid and antiandrogenic activity. Pharmacological characterization in animal models. Contraception 1995;51:99–110.
  8. Gerstman BB, Piper JM, Freiman JP, Tomita DK, Kennedy DL, Ferguson WJ, et al. Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism. Int J Epidemiol 1990;19:931–6. Level II-2.
  9. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Buller HR, Vandenbroucke JP. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 1995;346:1593–6. Level II-2.
  10. Lewis MA, Heinemann LA, MacRae KD, Bruppacher R, Spitzer WO. The increased risk of venous thromboembolism and the use of third generation progestagens: role of bias in observational research. The Transnational Research Group on Oral Contraceptives and the Health of Young Women. Contraception 1996;54:5–13. Level II-2.
  11. Hannaford PC, Kay CR. The risk of serious illness among oral contraceptive users: evidence from the RCGP's oral contraceptive study. Br J Gen Pract 1998;48:1657–62. Level II-2.
  12. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA casecontrol study. BMJ 2009;339:b2921. Level II-2.
  13. Lidegaard O, Lokkegaard E, Svendsen AL, Agger C. Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 2009;339:b2890. Level II-2.
  14. Lidegaard O, Nielsen LH, Skovlund CW, Skjeldestad FE, Lokkegaard E. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001–9. BMJ 2011;343:d6423. Level II-2.
  15. Plu-Bureau G, Maitrot-Mantelet L, Hugon-Rodin J, Canonico M. Hormonal contraceptives and venous thromboembolism: an epidemiological update.Best Pract Res Clin Endocrinol Metab 2013;27:25–34. Level III.
  16. Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network metaanalysis. BMJ 2013;347:f5298. Level III.
  17. de Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Combined oral contraceptives: venous thrombosis. The Cochrane database of systematic reviews 2014;CD010813. Level III.
  18. Beaumont V, Lemort N, Beaumont JL. Evaluation of risk factors associated with vascular thrombosis in women on oral contraceptives. Possible role of anti-sex steroid hormone antibodies. Artery 1983;11:331–44. Level II-2.
  19. Kierkegaard A. Deep vein thrombosis and the oestrogen content in oral contraceptives. An epidemiological analysis. Contraception 1985;31:29–41. Level II-2.
  20. Beaumont V, Lemort N, Beaumont JL. Oral contraceptives, sex steroidinduced antibodies and vascular thrombosis: results from 1318 cases. Eur Heart J 1991;12:1219–24. Level II-2.
  21. Spitzer WO, Lewis MA, Heinemann LA, Thorogood M, MacRae KD. Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women. BMJ 1996;312:83–8. Level II-2.
  22. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception/Poulter. Venous thromboembolic disease and combined oral contraceptives: results of international multicentre case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1995;346:1575–82. Level II-2.
  23. Farmer RD, Lawrenson RA, Thompson CR, Kennedy JG, Hambleton IR. Population-based study of risk of venous thromboembolism associated with various oral contraceptives. Lancet 1997;349:83–8. Level II-2.
  24. Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism. A case-control study. Contraception 1998;57:291–301. Level II-2.
  25. Lidegaard O. Smoking and use of oral contraceptives: impact on thrombotic diseases. Am J Obstet Gynecol 1999;180:S357–63. Level II-2.
  26. Farmer RD, Lawrenson RA, Todd JC, Williams TJ, MacRae KD, Tyrer F, et al. A comparison of the risks of venous thromboembolic disease in association with different combined oral contraceptives. Br J Clin Pharmacol 2000;49:580–90. Level II-2.
  27. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ. 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005;143:697–706. Level II-2.
  28. Andersen BS, Olsen J, Nielsen GL, Steffensen FH, Sorensen HT, Baech J, et al. Third generation oral contraceptives and heritable thrombophilia as risk factors of non-fatal venous thromboembolism. Thromb Haemost 1998;79:28–31. Level II-2.
  29. Royal College of General Practitioners' Oral Contraception Study. Oral contraceptives, venous thrombosis, and varicose veins. Royal College of General Practitioners' Oral Contraception Study. J R Coll Gen Pract 1978;28:393–9. Level II-2.
  30. Bird ST, Delaney JA, Etminan M, Brophy JM, Hartzema AG. Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol? J Thromb Haemost 2013;11:1059–68. Level II-2.
  31. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception/Meirik. Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1995;346:1582–8. Level II-2.
  32. Jick H, Jick SS, Gurewich V, Myers MW, Vasilakis C. Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components. Lancet 1995;346:1589–93. Level II-2.
  33. Farmer RD, Lawrenson RA. Oral contraceptives and venous thromboembolic disease: the findings from database studies in the United Kingdom and Germany. Am J Obstet Gynecol 1998;179:S78–86. Level II-2.
  34. Farmer RD, Lawrenson RA, Todd JC, Williams TJ, MacRae K. Oral contraceptives and venous thromboembolic disease. Analyses of the UK General Practice Research Database and the UK Mediplus database. Hum Reprod Update 1999;5:688–706. Level II-2.
  35. Farmer RD, Williams TJ, Simpson EL, Nightingale AL. Effect of 1995 pill scare on rates of venous thromboembolism among women taking combined oral contraceptives: analysis of general practice research database. BMJ 2000;321:477–9. Level II-3.
  36. Farmer RD, Todd JC, Lewis MA, MacRae KD, Williams TJ. The risks of venous thromboembolic disease among German women using oral contraceptives: a database study. Contraception 1998;57:67–70. Level II-2.
  37. Lidegaard O, Edstrom B, Kreiner S. Oral contraceptives and venous thromboembolism: a five-year national case-control study. Contraception 2002;65:187–96. Level II-2.
  38. Lidegaard O. Thrombotic diseases in young women and the influence of oral contraceptives. Am J Obstet Gynecol 1998;179:S62–7. Level II-2.
  39. Lawrenson R, Farmer R. Venous thromboembolism and combined oral contraceptives: does the type of progestogen make a difference? Contraception 2000;62:21S–8S. discussion 37S–8S. Level II-2.
  40. Lewis MA, MacRae KD, Kuhl-Habichl D, Bruppacher R, Heinemann LA, Spitzer WO. The differential risk of oral contraceptives: the impact of full exposure history. Hum Reprod 1999;14:1493–9. Level II-2.
  41. Heinemann LA, Lewis MA, Assmann A, Thiel C. Case-control studies on venous thromboembolism: bias due to design? A methodological study on venous thromboembolism and steroid hormone use. Contraception 2002;65:207–14. Level II-2.
  42. Black C, Kaye JA, Jick H. Clinical risk factors for venous thromboembolus in users of the combined oral contraceptive pill. Br J Clin Pharmacol 2002;53:637–40. Level II-2.
  43. Bloemenkamp KW, Rosendaal FR, Buller HR, Helmerhorst FM, Colly LP, Vandenbroucke JP. Risk of venous thrombosis with use of current lowdose oral contraceptives is not explained by diagnostic suspicion and referral bias. Arch Intern Med 1999;159:65–70. Level II-2.
  44. Hedenmalm K, Samuelsson E, Spigset O. Pulmonary embolism associated with combined oral contraceptives: reporting incidences and potential risk factors for a fatal outcome. Acta Obstet Gynecol Scand 2004;83:576–85. Level II-2.
  45. Herings RM, Urquhart J, LeufkensHG. Venous thromboembolismamong new users of different oral contraceptives. Lancet 1999;354:127–8. Level II-2.
  46. Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel. Contraception 2006;73:566–70. Level II-2.
  47. Kemmeren JM, Algra A, Grobbee DE. Third generation oral contraceptives and risk of venous thrombosis: meta-analysis. BMJ 2001;323:131–4. Level III.
  48. Parkin L, Skegg DC, WilsonM, Herbison GP, Paul C. Oral contraceptives and fatal pulmonary embolism. Lancet 2000;355:2133–4. Level II-2.
  49. Samuelsson E, Hagg S. Incidence of venous thromboembolism in young Swedish women and possibly preventable cases among combined oral contraceptive users. Acta Obstet Gynecol Scand 2004;83:674–81. Level II-2.
  50. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2015;350:h2135. Level II-2.
  51. Ziller M, Ziller V, Haas G, Rex J, Kostev K. Risk of venous thrombosis in users of hormonal contraceptives in German gynaecological practices: a patient database analysis. Arch Gynecol Obstet 2014;289:413–9. Level II-2.
  52. Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ 2011;342:d2151. Level II-2.
  53. Gronich N, Lavi I, Rennert G. Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study. CMAJ 2011;183:E1319–25. Level II-2.
  54. Parkin L, Sharples K, Hernandez RK, Jick SS. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ 2011;342:d2139. Level II-2.
  55. Sidney S, Cheetham TC, Connell FA, Ouellet-Hellstrom R, Graham DJ, Davis D, et al. Recent combined hormonal contraceptives (CHCs) and the risk of thromboembolism and other cardiovascular events in new users. Contraception 2013;87:93–100. Level II-2.
  56. Burnhill MS. The use of a large-scale surveillance system in Planned Parenthood Federation of America clinics to monitor cardiovascular events in users of combination oral contraceptives. Int J Fertil Womens Med 1999;44:19–30. Level II-2.
  57. Eng PM, Seeger JD, Loughlin J, Clifford CR, Mentor S, Walker AM. Supplementary data collection with case-cohort analysis to address potential confounding in a cohort study of thromboembolism in oral contraceptive initiators matched on claims-based propensity scores. Pharmacoepidemiol Drug Saf 2008;17:297–305. Level II-2.
  58. Seeger JD, Loughlin J, Eng PM, Clifford CR, Cutone J, Walker AM. Risk of thromboembolism in women taking ethinylestradiol/drospirenone and other oral contraceptives. Obstet Gynecol 2007;110:587–93. Level II-2.
  59. Dinger JC, Heinemann LA, Kuhl-Habich D. The safety of a drospirenonecontaining oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives based on 142,475 women-years of observation. Contraception 2007;75:344–54. Level II-2.
  60. Dinger J, Assmann A, Mohner S, Minh TD. Risk of venous thromboembolism and the use of dienogest- and drospirenone-containing oral contraceptives: results from a German case-control study. J Fam Plann Reprod Health Care 2010;36:123–9. Level II-2.
  61. Dinger J, Bardenheuer K, Heinemann K. Cardiovascular and general safety of a 24-day regimen of drospirenone-containing combined oral contraceptives: final results from the International Active Surveillance Study of Women Taking Oral Contraceptives. Contraception 2014;89:253–63. Level II-1.
  62. Bergendal A, Persson I, Odeberg J, Sundstrom A, HolmstromM, Schulman S, et al. Association of venous thromboembolism with hormonal contraception and thrombophilic genotypes. Obstet Gynecol 2014;124:600–9. Level II-2.
  63. Martinez F, Ramirez I, Perez-Campos E, Latorre K, Lete I. Venous and pulmonary thromboembolism and combined hormonal contraceptives. Systematic review and meta-analysis. Eur J Contracept Reprod Health Care 2012;17:7–29. Level III.
  64. Lidegaard O,Milsom I, Geirsson RT, Skjeldestad FE. Hormonal contraception and venous thromboembolism. Acta Obstet Gynecol Scand 2012;91:769–78. Level III.
  65. Maxwell WD, Jacob M, Spiryda LB, Bennett CL. Selection of contraceptive therapy for patients with thrombophilia: a review of the evidence. J Womens Health 2014;23:318–26. Level III.
  66. Timmer CJ, Mulders TM. Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet 2000;39:233–42. Level I.
  67. Lidegaard O, Nielsen LH, Skovlund CW, Lokkegaard E. Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ 2012;344:e2990. Level II-2.
  68. Dinger J, Mohner S, Heinemann K. Cardiovascular risk associated with the use of an etonogestrel-containing vaginal ring. Obstet Gynecol 2013;122:800–8. Level II-1.
  69. Abrams LS, Skee DM, Natarajan J, Wong FA, Lasseter KC. Multiple-dose pharmacokinetics of a contraceptive patch in healthy women participants. Contraception 2001;64:287–94. Level I.
  70. Abrams LS, Skee D, Natarajan J, Wong FA. Pharmacokinetic overview of Ortho Evra/Evra. Fertil Steril 2002;77:S3–12. Level III.
  71. van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC. Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception 2005;72:168–74. Level I.
  72. Jick SS, Kaye JA, Russmann S, Jick H. Risk of nonfatal venous thromboembolism in women using a contraceptive transdermal patch and oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception 2006;73:223–8. Level II-2.
  73. Jick SS, Jick H. Cerebral venous sinus thrombosis in users of four hormonal contraceptives: levonorgestrel-containing oral contraceptives, norgestimate-containing oral contraceptives, desogestrel-containing oral contraceptives and the contraceptive patch. Contraception 2006;74:290–2. Level II-2.
  74. Jick S, Kaye JA, Li L, Jick H. Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol. Contraception 2007;76:4–7. Level II-2.
  75. Jick SS, Hagberg KW, Hernandez RK, Kaye JA. Postmarketing study of ORTHO EVRA and levonorgestrel oral contraceptives containing hormonal contraceptives with 30 mcg of ethinyl estradiol in relation to nonfatal venous thromboembolism. Contraception 2010;81:16–21. Level II-2.
  76. Cole JA, Norman H, Doherty M, Walker AM. Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol 2007;109:339–46. Level II-2.
  77. Dore DD, Norman H, Loughlin J, Seeger JD. Extended case-control study results on thromboembolic outcomes among transdermal contraceptive users. Contraception 2010;81:408–13. Level II-2.
  78. Kamel H, Navi BB, Sriram N, Hovsepian DA, Devereux RB, Elkind MS. Risk of a thrombotic event after the 6-week postpartum period. N Engl J Med 2014;370:1307–15. Level II-2.
  79. Martinelli I, Taioli E, Bucciarelli P, Akhavan S, Mannucci PM. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol 1999;19:700–3. Level II-2.
  80. Girolami A, Spiezia L, Girolami B, Zocca N, Luzzatto G. Effect of age on oral contraceptive-induced venous thrombosis. Clin Appl Thromb Hemost 2004;10:259–63. Level II-2.
  81. Lopez M, Vaya A, Martinez Triguero ML, Contreras MT, Todoli J, Ricart A, et al. Yasmin and venous thromboembolism: new case reports. Clin Hemorheol Microcirc 2009;42:65–9. Level II-3.
  82. Vaillant-Roussel H, Ouchchane L, Dauphin C, Philippe P, Ruivard M. Risk factors for recurrence of venous thromboembolism associated with the use of oral contraceptives. Contraception 2011;84:e23–30. Level II-2.
  83. Bloemenkamp KW, Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Higher risk of venous thrombosis during early use of oral contraceptives in women with inherited clotting defects. Arch Intern Med 2000;160:49–52. Level II-2.
  84. Vessey M, Mant D, Smith A, Yeates D. Oral contraceptives and venous thromboembolism: findings in a large prospective study. Br Med J (Clin Res Ed) 1986;292:526. Level II-2.
  85. Price DT, Ridker PM, Factor V. Leiden mutation and the risks for thromboembolic disease: a clinical perspective. Ann Intern Med 1997;127:895–903. Level III.
  86. Jack BW, Atrash H, Coonrod DV, Moos MK, O'Donnell J, Johnson K. The clinical content of preconception care: an overview and preparation of this supplement. Am J Obstet Gynecol 2008;199:S266–79. Level III.
  87. Farley TM, Meirik O, Chang CL, Poulter NR. Combined oral contraceptives, smoking, and cardiovascular risk. J Epidemiol Community Health 1998;52:775–85. Level II-2.
  88. Vasilakis-Scaramozza C, Jick H. Risk of venous thromboembolism with cyproterone or levonorgestrel contraceptives. Lancet 2001;358:1427–9. Level II-2.
  89. Nightingale AL, Lawrenson RA, Simpson EL, Williams TJ, MacRae KD, Farmer RD. The effects of age, body mass index, smoking and general health on the risk of venous thromboembolism in users of combined oral contraceptives. Eur J Contracept Reprod Health Care 2000;5:265–74. Level III.
  90. Abdollahi M, CushmanM, Rosendaal FR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost 2003;89:493–8. Level II-2.
  91. Huerta C, Johansson S, Wallander MA, Garcia Rodriguez LA. Risk factors and short-term mortality of venous thromboembolism diagnosed in the primary care setting in the United Kingdom. Arch Intern Med 2007;167:935–43. Level II-2.

Practice Documents

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

The use of preimplantation genetic testing for aneuploidy: a committee opinion (2024)

PGT-A use in the U.S. is rising, but its value as a routine IVF screening test is unclear, with mixed results from various studies.
PracticeDocument_Teaser.webp

Evidence-based diagnosis and treatment for uterine septum: a guideline (2024)

To provide evidence-based recommendations regarding the diagnosis and effectiveness of surgical treatment of a uterine septum.
PracticeDocument_Teaser.webp

The use of hormonal contraceptives in fertility treatments: a committee opinion (2024)

Hormonal contraception aids in the timing of ART cycles, reduce ovarian cysts at IVF cycle initiation, and optimize visualization before hysteroscopy.
Practice Committee Documents teaser

Current evaluation of amenorrhea: a committee opinion (2024)

Amenorrhea is the absence or abnormal cessation of the menses.

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

ReproductiveFacts.org 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 contraception
Document Icon

The use of hormonal contraceptives in fertility treatments: a committee opinion (2024)

Hormonal contraception aids in the timing of ART cycles, reduce ovarian cysts at IVF cycle initiation, and optimize visualization before hysteroscopy. View the Committee Opinion
Coding Icon

Contraception and Menopause

A summary of common codes for Contraception and Menopause compiled by the ASRM Coding Committee View the Coding Summary
Coding Icon

3D Ultrasound

How should I bill for 3-D sonography? View the Answer
Document Icon

Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ ASRM-Sponsored 3rd PCOS Consensus Workshop Group (2012)

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females, with a high prevalence. View the Committee Guideline
Membership Icon

Complex Family Planning Special Interest Group (CFPSIG)

The Complex Family Planning Special Interest Group is committed to the promotion and support of basic and applied research in contraception.

Learn more about the CFPSIG