History of Present Illness

A 25-year-old G4P4004 presents to the office for an annual well-woman exam. She reports light menses every 28 days for one day duration. She has no other complaints. She is currently using a levonorgestrel intrauterine device (IUD) for contraception that was placed six weeks postpartum after her last delivery. She has had four uncomplicated pregnancies with normal vaginal deliveries. Her youngest child just completed her first birthday. The patient is sexually active with one partner and reports no problems with sexual intercourse. Cervical cytology screening is current and last reported as negative. She has no other gynecologic complaints.

Her past medical history is negative. She had a hernia repair as a child. Her family history is significant for maternal hypertension. She has no known drug allergies and her social history is negative for alcohol or illicit drug use.

Physical Examination

General appearance

Well-developed, overweight female in no acute distress

Temperature

37.0°C

Pulse

65 beats/min

Blood pressure

132/81 mmHg

Respiratory rate

18 breaths/min

Oxygen saturation

98% on room air

BMI

28.6 kg/m²

Height

67.2 inches

Weight

177 lb

Neck

No masses or lymphadenopathy

Axillae

No masses or lymphadenopathy

Chest

Clear to auscultation

Abdomen

Soft, non-tender, non-distended, normal active bowel sounds, no palpable masses, no hepatosplenomegaly, no fluid wave

External genitalia

Unremarkable, no lesions or lymphadenopathy

Vagina

Normal in appearance, scant discharge

Cervix

No lesions or cervical motion tenderness; no IUD strings visible at the cervical os

Uterus

normal size, mobile, non-tender, no masses

Adnexa

Palpable bilaterally, not enlarged, and non-tender

Pelvic Ultrasound

Uterus 8 × 4.5 × 6 cm with IUD noted at the uterine fundus. Left ovary 3.7 × 2.2 × 2.4 cm with several sub-centimeter follicles. Right ovary not visualized (Figure 22.1)

Figure 22.1 Characteristic acoustic shadowing of IUD within the uterine cavity.

How Would You Evaluate and Manage This Patient?

IUD strings were not visualized at the cervical os during the exam for this patient. The differential diagnosis for this case includes displaced IUD strings into the cervix or uterus, a displaced IUD versus IUD expulsion. The patient’s history of continued light menses is reassuring that the IUD has not been expulsed. On exam, the IUD strings were not visible at the cervical os; a cytobrush was used to sweep the endocervical canal in an attempt to draw the IUD strings through the cervical os into the vagina. The IUD strings were not successfully visualized with the cytobrush technique and a transvaginal ultrasound was subsequently performed to identify intrauterine placement and position. On ultrasound, the IUD was visualized in the uterine cavity and is appropriately oriented at the fundus. The patient was counseled about the findings and was instructed to return with any change in menses. Repeat pelvic ultrasonography was planned for a follow-up exam if the IUD strings are not visualized or with reported change of menses.

Misplaced Intrauterine Device

The levonorgestrel intrauterine system and the copper T380A are the two most commonly used IUDs in the United States. The copper T380A IUD, which is wrapped with copper wire around the stem and arms, is approved for ten years and has a failure rate at one year of 0.8 per 100 women. The copper IUD also has ten-year failure rate comparable to that of female sterilization, which is 1.9 per 100 women over ten years. The proposed mechanisms of action include inhibition of sperm migration and viability, change in transport speed of the ovum, and damage to or destruction of the ovum [1]. The most common side effects are increased menstrual bleeding and dysmenorrhea.

The levonorgestrel intrauterine system (52 mg) is FDA approved for five years, but may be effective for up to seven years and releases 20 µg of levonorgestrel daily. It has a failure rate at one year of 0.2 per 100 women. The mechanism of action is similar to that of the copper IUD, but in addition the levonorgestrel intrauterine system causes endometrial suppression and changes the amount and viscosity of cervical mucus. Women may have hormonal side effects such as breast tenderness, nausea, depression, headaches, and cyst formation. Menses can be lighter and less painful [1].

Additional lower dose levonorgestrel devices (13.5 and 19.5 mg) are now available, but they are used less widely than the aforementioned devices.

On follow-up exam after IUD placement, the provider may not see the IUD string(s) protruding from the cervical os during a speculum exam [2]. Often the string is displaced just inside the cervical os. A cytobrush or similar device may be used to sweep the string from the cervical canal through the cervical os into the vagina. If this technique is unsuccessful in visualizing the strings, the uterus should be imaged with ultrasound to determine if the IUD is in the uterus and appropriately placed. The levonorgestrel IUD has a characteristic appearance, with acoustic shadowing between the echogenic proximal and distal ends, whereas copper IUDs are more completely echogenic. The IUD should be visualized as centrally located within the endometrial cavity, with the crossbar in the fundal portion of the endometrial cavity [3]. The distance from the top of the uterine cavity to the IUD should be 3 mm or less [4]. If the IUD is visible on ultrasound and appropriately placed in the uterus near the fundus, then the provider can reassure the patient that the IUD is in the correct position. A 3D transvaginal ultrasound coronal view of the uterus can also be performed to evaluate for an embedded IUD if available (Figure 22.2) [5]. If the patient desires removal of the IUD or it is incorrectly located in the uterus, an attempt to perform removal of the IUD with or without ultrasound guidance can be considered utilizing an IUD hook or other instrumentation in the office setting. Alternatively, IUD removal via operative hysteroscopy can be performed.

Figure 22.2 IUD visualized utilizing 3D ultrasound.

If the IUD is not visualized within the uterus on the ultrasound, the patient should be offered back-up pregnancy protection. An anteroposterior and lateral radiograph may then be ordered to determine if the IUD is located within the peritoneal cavity. The levonorgestrel and copper TCu-380A frames contain barium sulfate for radiopacity [6]. If there is no extrauterine IUD on x-ray, then IUD expulsion has been confirmed.

The approximate first-year expulsion rates are commonly quoted as 2–10 percent and vary by IUD type [7]. If the IUD is identified on x-ray, then the patient should be informed that she has had a uterine perforation and she should be counseled regarding the expulsion retrieval via laparoscopy or a laparotomy. The potential for bowel perforation and fistula formation has been reported and should be considered when counseling [8].

According to the World Health Organization (1987), the risk of IUD perforation is 1 per 1,000 [9]. Similarly, in the European Active Surveillance Study on Intrauterine Devices, perforation rates were 1.1 per 1,000 in LNG-IUS and 1.1 per 1,000 in copper IUD users [10]. Of the baseline characteristics, the authors of this study concluded that breastfeeding at time of insertion and a time interval less than 36 weeks from delivery were the strongest risk factors for uterine perforation. Heartwell and Schlesselman found that breastfeeding and not “time since last delivery” increased the risk of perforation [2].

When counseling a patient for contraception after the management of a migrated or expulsed IUD, repeat placement of an IUD is not contraindicated. If an IUD is the preferred contraceptive method of the patient and no other contraindications have emerged further limiting an IUD as a safe option, an IUD may be placed. However, uterine size is an important variable; uterine cavities measuring less than 6 cm may have an increased rate of expulsion. Understandably, patients with IUD migration or expulsion may be reluctant to use an IUD again as a preferred contraceptive agent.

Key Teaching Points

• 
  

  If IUD strings are not visualized at the time of IUD surveillance, in many cases, a cytobrush can be utilized to sweep the endocervical canal to draw IUD strings into the vagina.

  
  
• 
  

  Transvaginal ultrasound is the best imaging modality to determine IUD placement and position within the uterus.

  
  
• 
  

  An anteroposterior and lateral radiograph should be used to determine if the IUD is located within the peritoneal cavity or has been expulsed when ultrasound fails to identify intrauterine IUD placement.

History of Present Illness

A 29-year-old gravida 1, para 1, female presents to the office requesting a refill of her oral contraception. Her medical history is significant for human immunodeficiency virus (HIV), diagnosed three years ago. She reports regular follow-up with the infectious disease clinic and daily compliance with her antiretroviral therapy. She is currently taking two nucleoside reverse transcriptase inhibitors, Zidovudine and Stavudine, and one non-nucleoside reverse transcriptase inhibitor, efavirenz, to manage her HIV. She reports regular monthly withdrawal bleeds and is overall very happy with her current method of contraception. She is in a monogamous, heterosexual relationship and uses condoms regularly as her partner is HIV negative.

Past medical history

HIV – diagnosed three years prior. Compliant with medications

Past surgical history

Cesarean section at term for breech presentation, uncomplicated

Medications

Zidovudine, stavudine, efavirenz, and ethinyl estradiol 0.03 mg/desogestrel 0.15 mg

Physical Examination

General appearance

Healthy-appearing woman, in no apparent distress

Temperature

37.1°C

Pulse

72 beats/min

Blood pressure

110/62 mmHg

Respiratory rate

16 breaths/min

Lungs

Clear bilaterally, no rhonchi, rales, or wheezes

Cardiovascular

Regular rate and rhythm, no murmurs

Abdomen

Soft, non-tender, non-distended, no masses

Pelvic

Deferred

CD4 count

1,200 cells/mm³

Viral load

undetectable

How Would You Manage the Patient?

Although hormonal contraception is safe and effective in HIV-infected women on multidrug antiretroviral therapy, studies have shown decreased hormonal contraceptive levels in the setting of efavirenz and certain other HIV medications. Therefore, this patient should be counseled on the theoretical decreased efficacy of her hormonal contraception. She should be encouraged to continue with dual therapy, with consistent use of condoms and oral contraception. Alternatively, she may be offered an intrauterine device for improved contraceptive efficacy.

HIV Medications and Oral Contraceptive Pills

Around the world, an estimated 35.3 million people are living with HIV and women comprise nearly half of those infected [1, 2]. While the spread of HIV has slowed, addressing the health needs of women infected with HIV remains a priority. Women living with HIV are often of reproductive age, and many desire and need effective contraception to prevent pregnancy. This is not only essential to the health of the woman but also to her future children. The majority of children acquire HIV through vertical transmission from mother to fetus, so effective contraception is essential [1].

Oral contraceptives, including combined oral contraceptive pills (COCs) and progestin-only pills (POPs), are highly effective methods of contraception, with failure rates of 1 percent with perfect use and 8 percent with typical use [3]. Contraceptive hormones are metabolized by the hepatic cytochrome (CYP) P450 pathway, which is also responsible for the metabolism of many antiretroviral drugs (ARVs). Orally administered contraceptive hormones are subject to extensive first-pass hepatic metabolism. Systemic hormonal contraceptives work by negative feedback inhibition of the hypothalamic-pituitary-ovarian (HPO) axis, with additive effects on cervical mucus and the endometrium. Both exogenous estrogen and progestin suppress the HPO axis. However, most of the contraceptive effects, including ovulation suppression, endometrial thinning, and cervical mucus thickening, are due to progestin and are dose-dependent [1]. Ethinyl estradiol (EE), the estrogenic component of most currently marketed COCs, induces ovulation suppression and is primarily metabolized through the hepatic CYP pathway. Specifically, hydroxylation of EE is catalyzed by the hepatic enzymes CYP3A4 and CYP2C9 [2, 3].

Management of patients with HIV typically involves a combination of ARVs, commonly referred to as highly active antiretroviral therapy (HAART), as monotherapy frequently leads to the development of viral resistance to drug therapy. Typically, a patient will be started on a HAART regimen that includes two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor (PI), two NRTIs and a non-nucleoside reverse transcriptase inhibitor (NNRTI), or three NRTIs [1]. Ritonavir, a PI, is rarely used for its own antiretroviral activity, but is used for its inhibitory effect on CYP3A4, the liver enzyme that normally metabolizes PIs. Ritonavir is used to enhance other PIs, thereby improving ARV efficacy.

Since ARVs and contraceptive pills are both metabolized by the CYP system, ARVs could theoretically decrease contraceptive efficacy, leading to unintended pregnancy, or increase levels of the contraceptive method, leading to toxicity. Similarly, hormonal contraceptives could theoretically decrease efficacy of ARVs, leading to increased likelihood of treatment failure, or conversely toxicity. Unfortunately, most evidence regarding hormonal contraception and ARV therapy is based on pharmacokinetic studies and secondary analysis, rather than prospective clinical trials assessing pregnancy failure [4]. Given the theoretical concern of drug interactions between hormonal contraception and ARV therapy, as both are metabolized by the CYP pathway, patients must be advised that full efficacy cannot be guaranteed. This is particularly true for estrogen-containing COCs, as estrogen is primarily metabolized through the hepatic CYP pathway.

The Centers for Disease Control (CDC) annually publishes recommendations on the safe use of contraceptive methods for women with various medical conditions [5]. Health-care providers can use the medical eligibility categories (Box 23.1) when assessing the safety of a contraceptive method for a particular patient’s medical condition. On an annual basis, the most recent medical literature is reviewed and updates are made to the guidelines. Table 23.1 summarizes the 2016 medical eligibility criteria for HIV-infected women on ARV therapy. Notably the recommendations can be summarized as follows:

• 
  

  NRTIs do not appear to have significant risk for interactions with oral contraceptive pills.

  
  
• 
  

  Drug interactions exist between POPs/COCs and efavirenz, which may reduce contraceptive hormone levels.

  
  
• 
  

  Drug interactions exist between POPs/COCs and Ritonavir-boosted PIs, as well as certain unboosted PIs, which may reduce contraceptive hormone levels.

  
  
• 
  

  Specific studies of fosamprenavir and COCs demonstrated decreased concentration of fosamprenavir and theoretical decreased efficacy of the ARV, resulting in the only Category 3 rating among all ARVs.

An equally important question for providers and patients is whether hormonal contraception affects transmission and progression of HIV and AIDS. Overall, evidence does not support an association between oral contraceptives and risk for HIV acquisition, nor progression of disease [6, 7].

Based on the available evidence, women using oral contraceptive pills should either use an additional contraceptive method or change methods if they are using efavirenz or a boosted PI. In women seeking hormonal contraception using fosamprenavir, the risk of decreased ARV efficacy outweighs the benefit and an alternative contraceptive method should be recommended by health-care providers. Interactions are not problematic with NRTIs and patients can be reassured of full clinical efficacy with their oral contraceptive method. Additionally, all patients with HIV should be counseled that dual contraception, with the concomitant use of condoms and additional contraception, is the optimal contraceptive strategy to reduce heterosexual transmission of HIV and other sexually transmitted infections, and to minimize the risk of unintended pregnancy [8].

Key Teaching Points

• 
  

  Contraception is important in order to optimize women’s health care and to prevent vertical transmission, the leading cause of HIV acquisition for children.

  
  
• 
  

  Hormonal contraception, including COCs and POPs, generally is considered safe for use by HIV-infected women, including those who use ARV therapy.

  
  
• 
  

  Health-care providers should consider drug-specific interactions between ARV therapy and certain hormonal contraceptives when counseling patients about the best options, particularly when patients are taking efavirenz, ritonavir-boosted PIs, and fosamprenavir.

History of Present Illness

A 42-year-old, gravida 3, para 2–0-1–2, woman presents for her routine well-woman visit and the review of systems is without specific complaints. She has a history of copper T380 intrauterine device (IUD) insertion five years prior to presentation. When discussing her reproductive life planning, she states that she and her husband are finished child-bearing. She is satisfied with her IUD and desires to keep her current contraceptive method for several more years. She has been in a monogamous relationship for 12 years and denies concerns for sexually transmitted infection.

Her pap history includes no history of previously abnormal testing with her last screen five years prior to this visit. Her menstrual history is unremarkable, with moderate menstrual bleeding for four to five days every four weeks. She denies intermenstrual bleeding or dysmenorrhea.

She has no significant medical or surgical history. Her pregnancies were uncomplicated.

Physical Examination

General appearance

Well-appearing, appears stated age and no acute distress

Temp

36.8°C

Pulse

65 beats/min

BP

111/69 mmHg

Weight

134 lb

Height

64 inches

BMI

26 kg/m²

HEENT

Normocephalic, conjunctiva anicteric. Neck without thyromegaly or lymphadenopathy

Cardiovascular

Regular rate and rhythm, no murmurs/rubs/gallops

Pulmonary

Lungs clear bilaterally, normal effort

Abdomen

Soft, non-tender. No masses or surgical scars. Normoactive bowel sounds

Extremities

No edema or clubbing. No calf tenderness

External genitalia

Normal architecture, without lesions

Urethra

Normal meatus, no hypermobility or masses

Bartholin’s, Skene’s ducts

Normal openings without masses

Vagina

Moist with normal rugae. No abnormal discharge or blood. No cystocele or rectocele

Cervix

Parous without lesions. IUD strings not visualized. No cervical motion tenderness. Liquid cytology/HPV testing was performed

Uterus

Six weeks’ size, anteverted, non-tender, and mobile

Adnexa

Non-palpable, non-tender

Liquid-based pap

Negative for intraepithelial lesion or malignancy. Adequate cellularity with endocervical cells seen. Actinomyces seen on cytology (Figure 24.1).

HPV testing

Negative for high-risk HPV types

Transvaginal ultrasound

Small, anteverted uterus with IUD in normal position in the endometrial cavity. Normal bilateral adnexa and no free fluid in the pelvis.

Figure 24.1 Actinomyces: Branching clusters of Gram-positive bacilli on liquid-based cervical cytology from a patient with an IUD.

Courtesy of Lananh N. Nguyen

How Would You Manage This Patient?

The patient has a copper IUD correctly positioned in her uterus, and the device is colonized with Actinomyces. On follow-up visit, the patient denies any pelvic pain. She has no unusual vaginal discharge, fever, dyspareunia, or urinary symptoms. She is relieved to know that her IUD is appropriately located in her uterus and prefers to continue her current contraceptive device if it is a safe option for her.

Because she is asymptomatic and desires to continue her IUD as her preferred contraceptive method, a plan is made for routine annual follow-up and precautions given to call the office should she develop any pelvic pain or fevers.

Actinomyces Colonization in IUD Users

Detection of Actinomyces israelii and other Actinomyces species in the cervical and vaginal smears of women with intrauterine contraceptive devices is a phenomenon that has been recognized for decades. Gram-positive bacteria in the Actinomyces genus are uniquely recognizable on cytology and Gram stain because of their arrangement of bacilli in branching, filamentous “spider” formations (Figure 24.1). Several species of Actinomyces are known to be members of the female genital flora, with Actinomyces israelii being the most usual cause of pelvic pathology. Actinomyces urogenitalis and other species have been identified in urogenital specimens, and other non-Actinomyces organisms can look similar to Actinomyces bacilli on pap cytology [1]. Given this heterogeneity of species known to reside in the urogenital tract, the literature often refers to detection of Actinomyces-like organisms (ALOs) on cervical cytology [2]. One study has compared rates of ALO detection between liquid-based cytology and conventional smear specimens, with markedly higher detection rates noted in liquid-based cytology specimens [3].

Prevalence of Actinomyces colonization increases with duration of IUD use, reaching colonization rates of 25 percent after several years of IUD use in some studies [4, 5]. The finding of Actinomyces in pap smears of non-IUD users is exceedingly rare, with most studies reporting 0 percent incidence. IUD-specific genital colonization may be related to formation of biofilms, as has been demonstrated in vitro on the surface of copper-containing devices [6]. Many studies have sought to answer the question of whether specific devices are more prone than others for colonization with ALOs. These studies have found conflicting results, with some suggesting higher colonization of plastic devices and some finding higher colonization rates with copper IUDs. The most consistent finding among these studies has been a correlation between increased colonization rate and longer time of IUD use.

As in the case described above, Actinomyces is often diagnosed as an incidental finding during routine cervical cancer screening. Actinomyces on cytology in the absence of other symptoms rarely (0.001 percent) leads to pelvic Actinomyces. Treatment with antibiotics and/or removal of the device are/is not recommended [7, 8].

Multiple case reports have described pelvic actinomycosis with tubo-ovarian abscesses and bowel collections mimicking malignant processes [9, 10]. Such cases may be associated with fever and other systemic symptoms and may present with or without acute pelvic inflammatory disease. Cases of pelvic actinomycosis may occur in the presence or absence of an IUD and should be suspected in the setting of complex, disseminated pelvic disease. For patients with symptomatic pelvic actinomycosis, antimicrobial therapy should be initiated. If an IUD is present, it should be removed. Actinomyces species are sensitive to penicillin, with the treatment of choice being oral or parenteral ampicillin or amoxicillin/clavulanate for cases of Gram stain confirmed pelvic actinomycosis.

Key Teaching Points

• 
  

  A finding of Actinomyces on screening cervical cytology is associated with the presence of an intrauterine contraceptive device.

  
  
• 
  

  Actinomyces colonization of the female genital tract is largely asymptomatic and does not require treatment.

  
  
• 
  

  The IUD may remain in situ in the presence of asymptomatic Actinomyces colonization.

History of Present Illness

A 25-year-old nulliparous woman presents to the office for contraceptive counseling. She reports regular menstrual cycles of normal duration and flow with her stated last menstrual period three weeks prior to this visit. Her past medical history is significant for a pulmonary embolus diagnosed at age 23, which occurred two months after initiation of combination oral contraceptives. The pulmonary embolus was not associated with trauma, surgery, or other exacerbating events. She was treated initially with Lovenox and transitioned to warfarin, which was discontinued after three months since she had no known risk factors. Her initial evaluation included screenings for antithrombin III, protein C and protein S deficiency, Lupus anticoagulant, Factor V Leiden mutation, and prothrombin mutation due to a family history of a deep vein thrombosis (DVT) that were reported as normal.

The patient is not currently on anticoagulation therapy and review of symptoms is negative for dizziness, dyspnea, calf tenderness, and chest pain. She has been sexually active, using barrier contraceptives inconsistently. She desires a more reliable contraceptive method.

Her past medical history is otherwise unremarkable and her past surgical history is negative. She had negative cervical cytology performed at the time of initiation of oral contraceptives.

She has no known drug allergies, does not smoke, and only drinks socially. Her medications include a vitamin B supplement, fish oil, and a daily multivitamin.

Physical Examination

General appearance

Well-nourished, well-developed young woman, appearing her stated age, in no acute distress, alert, and oriented

Temperature

36.1°C

Pulse

72 beats/min

Blood pressure

118/56 mmHg

Respiratory rate

16 breaths/min

Oxygen saturation

100% on room air

Weight

150 lb

Height

5 feet 6 inches

BMI

24.2 kg/m²

Heart

Regular rate and rhythm

Lungs

Clear to auscultation

How Would You Manage This Patient?

Given this patient’s past medical history of pulmonary embolus presumably induced with estrogen exposure in combined oral contraceptive, her options for effective and reliable contraception as advised by the US Medical Education Criteria (US MEC) published by the CDC include

• 
  

  Copper intrauterine device (first-line option-US MEC 1)

  
  
• 
  

  Progesterone contraceptives (second-line option-US MEC 2) including

  
  
  
  
  1. 
     

     – Levonorgestrel (LNG) intrauterine device

     
     
  2. 
     

     – Depomedroxyprogesterone acetate (DMPA)

     
     
  3. 
     

     – Etonorgestrel implant (Nexplanon)

     
     
  4. 
     

     – Progesterone-only oral contraceptive pill (POP)

  
  

Additionally, the patient should be counseled on less effective alternatives such as barrier methods, fertility awareness-based methods, and withdrawal. The limited efficacy of these methods should be discussed, focusing on the patient’s increased risk of recurrent thromboembolus in pregnancy should failure occur.

Given her normal menstrual cycle, a nonhormonal agent such as a copper-containing intrauterine device would be the best recommendation for this patient. A copper-containing IUD has a low failure rate and does not have the hormonal agent that could potentiate her risk of a recurrent DVT. If mutually agreed upon, the IUD can be placed without difficulty and the patient educated on the appropriate confirmation of IUD placement. Although a pelvic exam is not mandatory for contraceptive counseling, this patient should be offered STI screening given her history of inconsistent condom use.

If the patient desires same-day placement, STI screening can be performed concomitantly. If there are findings concerning for an active STI at the time of placement, treatment can be initiated and placement delayed for three to four weeks days.

Deep Vein Thrombosis and Combined Hormonal Contraceptives

DVT and pulmonary embolism (PE) affect as many as 900,000 people in the United States [1]. Risk factors for DVT/PE include cigarette smoking, obesity, pregnancy, exposure to estrogen-containing contraceptive and hormone replacement therapy, immobilization, surgery, and trauma. Predisposing genetic factors such as Factor V Leiden mutation have been found in about 5–8 percent of cases. Certain chronic medical illnesses such as congestive heart failure and cancer also predispose to DVT/PE. In women of childbearing age who are not using hormonal contraceptives, the incidence of DVT/PE is about 1 in 10,000. The risk is increased three- to fivefold for women on estrogen-containing hormonal contraceptives and is significantly higher during pregnancy (four- to fivefold), especially in the postpartum period [2, 3].

The link between estrogen-containing oral contraceptives and thromboembolism has been established since the introduction of the oral contraceptive pill (OCP) in 1960 [4]. Epidemiological studies identified both a time- and dose-dependent link between estrogen and the risk of thromboembolism, i.e., the longer the duration of use and the lower the dose of estrogen, the lower the risk of DVT/PE [5]. This evidence spurred the reformulation of the oral contraceptive pill with lower doses of estrogen.

The link between progestogens and DVT/PE has been difficult to demonstrate and an association was not thought to exist until studies comparing third-generation progestogens such as gestodene, drospironone, and desogestrel to second-generation progestogens such as levonorgestrel indicated a slight increased risk of DVT/PE [5, 6].

Estrogen increases DVT/PE risk by increasing the concentration of clotting factors II, VII, X, and XII, factor VIII, and fibrinogen and predisposing the clotting system toward clot formation. Data also indicate that third-generation progestogens increase plasma concentration of factor VII, thus further increasing the risk of DVT/PE. [7].

Based on the CDC’s 2016 US Medical Eligibility Criteria (US MEC) for contraceptive use, a history of PE on estrogen-containing oral contraceptives increases the risk for recurrent thromboembolic event [8]. A copper intrauterine device is considered MEC 1, providing a safe, reliable, long-acting reversible contraceptive that will not increase the risk of a thromboembolic event. Progesterone contraceptives, including levonorgestrel intrauterine devices, subdermal implants, depo-medroxyprogesterone injections, and progestin-only pills, are considered acceptable but second-line agents for this patient due to the potential risk of thromboembolism associated with progesterone [8].

Regarding the risk of DVT/PE, the 2016 US MEC for contraceptive use provides the following guidelines [8]:

1. 
   

   – Women without risk factors for recurrence of thromboembolic events should be counseled similarly as those with risk factors, with the exception that combined hormonal contraceptives (CHC) are considered US MEC 3, meaning CHC are not recommended unless there are no viable alternatives for the patient.

   
   
2. 
   

   – For women with acute DVT/PE, whether on anticoagulant therapy or not, both copper-containing IUDs and progesterone-only contraceptives are considered US MEC 2, secondary to the potential risk of increased bleeding that is associated with both categories of these contraceptives.

   
   
3. 
   

   – Again in these women the risk of recurrence determines whether CHC are considered US MEC 3 or US MEC 4 category.

   
   
4. 
   

   – In women with a family history of a first-degree relative with DVT/PE but no personal history of thromboembolic event, the copper-containing IUD and progesterone-only contraceptives are considered MEC 1, while CHC are MEC 2 and can be offered as an alternative to the patient.

   
   
5. 
   

   – For women undergoing major surgery who are facing prolonged immobilization, CHC are considered US MEC 4 and should not be offered due to the significant risk they pose to the patient. Alternative options include the copper-containing IUD (US MEC 1) or progesterone-only contraceptives (US MEC 2). If a patient is having minor surgery or is not anticipating prolonged immobilization after major surgery, she can be offered any method safely, including CHC (MEC2).

Other nonhormonal forms of contraception, including barrier methods, fertility awareness-based methods, and withdrawal, should also be discussed as alternatives for patients presenting with history of deep venous thrombosis or pulmonary embolus. Though less effective, these methods may be more acceptable to the patient and are a better option than not providing any contraception and putting the patient at risk for pregnancy, which is associated with a higher rate of recurrent DVT/PE and concomitant complications. The high failure rate associated with these methods should be discussed.