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Year : 2018  |  Volume : 8  |  Issue : 3  |  Page : 114-116

Human menopausal gonadotropin-induced bioprosthetic valve thrombosis

Department of Cardiology, Prince Sultan Cardiac Center Qassim, King Fahad Specialist Hospital, Buraydah, Al-Qassim Province, Saudi Arabia

Date of Web Publication11-Jul-2018

Correspondence Address:
Dr. Rami Mahmood Abazid
Department of Cardiology, Prince Sultan Cardiac Center Qassim, Noninvasive Cardiac Imaging, Buryadah, Qassim
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajm.AJM_83_18

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Bioprosthetic valve thrombosis (BPVT) is a rare but potentially life-threatening complication. Human menopausal gonadotropin (hMG) is commonly used for ovulation induction and has been associated with arterial and venous thrombosis. We reported a case of BPVT related to in vitro fertilization in a 39-year-old female, who underwent redo mitral valve replacement. To the best of our knowledge, this is the first case of hMG-induced BPVT in a young female patient.

Keywords: Bioprosthetic valve thrombosis, human menopausal gonadotropin, in vitro fertilization

How to cite this article:
Abazid RM, Shoman M, Smettie OA, Elamin OA. Human menopausal gonadotropin-induced bioprosthetic valve thrombosis. Avicenna J Med 2018;8:114-6

How to cite this URL:
Abazid RM, Shoman M, Smettie OA, Elamin OA. Human menopausal gonadotropin-induced bioprosthetic valve thrombosis. Avicenna J Med [serial online] 2018 [cited 2020 Aug 11];8:114-6. Available from: http://www.avicennajmed.com/text.asp?2018/8/3/114/236395

   Introduction Top

Bioprosthetic valves are the most common artificial valves used in women of childbearing age. It has good hemodynamic properties and obviating the need for long-term anticoagulation.[1] The incidence of bioprosthetic valve thrombosis (BPVT) is low, but it may result in fatal consequences.[1] BPVT has high mortality, and the treatment varies from medical treatment in mild cases to surgical intervention in severely symptomatic patients.[1] Human menopausal gonadotropin (hMG) is commonly used to induce ovulation during in vitro fertilization (IVF). In fact, various adverse effects have been reported including venous and arterial thrombosis.[2]

   Case Report Top

A 39-year-old female had a history of mitral bioprosthetic valve replacement (Medtronic Mosaic®) due to rheumatic heart disease 2 years prior to hospitalization. Regular follow-ups with her cardiologists were maintained, and the patient was asymptomatic with a normal prosthetic function on serial echocardiograms. One month prior, the patient sought treatment with in vitro fertilization and received 14 injections of (450 IU) hMG. Few days later, she started complaining of progressively worsening shortness of breath until she presented to the emergency department with a blood pressure level of 70/40 mmHg, heart rate of 125 beat/min, and oxygen saturation around 84%. She was hemodynamically unstable needing inotropic and ventilatory support. Ultimately, she was transferred to the Intensive Care Unit for further management.

An emergent echocardiogram was performed. This was followed by a transesophageal echocardiography (TEE) that showed ejection fraction of 55%, two oval-shaped masses on the mitral valve leaflets (arrow) with restricted leaflet motion and a mean gradient of 34 mmHg, a peak gradient of 51 mmHg, and velocity time integral (VTI) of 93 cm. The findings with highly suggestive of BPVT are shown in [Figure 1].
Figure 1: (a) Transesophageal echocardiography: two-dimensional showed thickened mitral valve leaflets (arrow) and color Doppler showed diastolic mitral inflow flow aliasing jet due to blood flow acceleration, and (b) Continuous wave Doppler of mitral valve inflow showed a significant increase in velocity

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The initial complete blood count showed white blood cells of 8.1 × 103/μL, hematocrit of 27.9%, and platelet count of 114 × 103/μL. Blood urea nitrogen was 36.7 mmol/l, creatinine of 264 μmol/l, alanine transaminase (ALT) of 64 U/l, and international normalized ratio was 1.9.

Cardiac surgery was immediately consulted, and the patient underwent emergent redo mitral valve replacement surgery with a St. Jude mechanical valve. Intraoperative findings of the thrombosed mitral valve are seen in [Figure 2]. While on cardiopulmonary bypass and after replacing the valve, a freely mobile thrombus was seen in the left atrium [Figure 3]a and [Video 1] impinging on the leaflets of the mechanical valve [Figure 3]b. After exploring the pulmonary veins and removal of any existing thrombi, the final TEE confirms normally functioning metallic mitral valve [Video 2]. Patient had uneventful postoperative course and discharged 16 days after surgery; the follow-up echocardiography showed normal mechanical valve function [Figure 4].
Figure 2: Intraoperative image showed a large thrombus in the bioprosthetic mitral valve (arrows)

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Figure 3: (a) First intraoperative transesophageal echocardiography showed freely mobile large thrombus in the left atrium (arrows) and (b) second intraoperative transesophageal echocardiography revealed immobile mitral valve leaflet (arrowhead)

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Figure 4: Follow-up echocardiography. (a) The mitral mean gradient 8.7 mmHg peak gradient 25 mmHg, pressure half-time of 68 ms, and (b) the VTImv/VTIlvot = 1.8, indicating a normal prosthetic valve function

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   Discussion Top

Although the exact mechanisms of BPVT are not well understood, there are various underlying factors related to valve thrombosis such as hemostatic activation which results in hypercoagulable state, leaflets wall shear stress produced by blood flow perturbations, and patient-related factors such as atrial fibrillation, renal insufficiency, obesity, diabetes mellitus, and low cardiac output states.[3] The incidence of valve thrombosis is around (6%) post bioprosthetic mitral valve implantation;[4],[5] moreover, BPVT represents 11.6% of totally explanted valves due to bioprosthetic valve dysfunction.[6]

The diagnosis and differentiation of BPV dysfunction as a result of pannus versus thrombus formation is challenging. However, thrombosed prosthetic valves have more acute onset of symptoms which our patient had.[1] BPVT can be asymptomatic and detected by a routine echocardiography.[7] On the other hand, BPVT can be life-threatening and may result in severe symptoms, hemodynamic instability, and rapid deterioration.[1] Commonly used echocardiographic features to help diagnose BPVT are an increase in the mean transvalvular gradient >50% above baseline values within 5 years, thickened leaflets, and restriction in leaflets mobility.[1],[8],[9]

The initial treatment of subclinical or mild BPVT in hemodynamically stable individuals is a Vitamin K antagonist if no contraindications to anticoagulation.[1] However, in severely symptomatic and hemodynamically unstable patients, surgical valve replacement might be indicated.[1]

Thromboembolic disease associated with ovarian stimulation syndrome is an uncommon yet potentially fatal complication of IVF. A literature review by Jing and Yanping [2] reported that a total of 112 cases of thromboembolism associated with ovulation induction, 35.7% were arterial in origin, and 64.3% were venous, but no BPVT was reported. Interestingly, Udell et al.[10] conducted a population-based cohort of 1,186,753 women, of whom 6979 gave birth after fertility therapy and reported that women who had received fertility treatment had significantly lower death, hospitalization for a major adverse cardiovascular, thromboembolism, and heart failure after 10 years of follow-up. However, a very recent analysis by Sennström et al.[11] reported that IVF results in twofold increase in the risk of thromboembolic events when compared to non-IVF pregnancies. Moreover, hospitalized IVF patients due to ovarian hyperstimulation syndrome had 100-fold increased risk of thromboembolic events when compared to non-IVF pregnant population.

   Conclusion Top

To the best of our knowledge, this is the first case of BPVT induced by hMG treatment for IVF, successfully treated with surgery.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Fleisher LA, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. J Am Coll Cardiol 2017;70:252-89.  Back to cited text no. 1
Jing Z, Yanping L. Middle cerebral artery thrombosis after IVF and ovarian hyperstimulation: A case report. Fertil Steril 2011;95:2435.e13-5.  Back to cited text no. 2
Egbe AC, Pislaru SV, Pellikka PA, Poterucha JT, Schaff HV, Maleszewski JJ, et al. Bioprosthetic valve thrombosis versus structural failure: Clinical and echocardiographic predictors. J Am Coll Cardiol 2015;66:2285-94.  Back to cited text no. 3
Butnaru A, Shaheen J, Tzivoni D, Tauber R, Bitran D, Silberman S, et al. Diagnosis and treatment of early bioprosthetic malfunction in the mitral valve position due to thrombus formation. Am J Cardiol 2013;112:1439-44.  Back to cited text no. 4
Oliver JM, Gallego P, Gonzalez A, Dominguez FJ, Gamallo C, Mesa JM, et al. Bioprosthetic mitral valve thrombosis: Clinical profile, transesophageal echocardiographic features, and follow-up after anticoagulant therapy. J Am Soc Echocardiogr 1996;9:691-9.  Back to cited text no. 5
Puri R, Auffret V, Rodés-Cabau J. Bioprosthetic valve thrombosis. J Am Coll Cardiol 2017;69:2193-211.  Back to cited text no. 6
Laschinger JC, Wu C, Ibrahim NG, Shuren JE. Reduced leaflet motion in bioprosthetic aortic valves – the FDA perspective. N Engl J Med 2015;373:1996-8.  Back to cited text no. 7
Pislaru SV, Hussain I, Pellikka PA, Maleszewski JJ, Hanna RD, Schaff HV, et al. Misconceptions, diagnostic challenges and treatment opportunities in bioprosthetic valve thrombosis: Lessons from a case series. Eur J Cardiothorac Surg 2015;47:725-32.  Back to cited text no. 8
Butnaru A, Shaheen J, Tzivoni D, Tauber R, Bitran D, Silberman S, et al. Diagnosis and treatment of early bioprosthetic malfunction in the mitral valve position due to thrombus formation. Am J Cardiol 2013;112:1439-44.  Back to cited text no. 9
Udell JA, Lu H, Redelmeier DA. Long-term cardiovascular risk in women prescribed fertility therapy. J Am Coll Cardiol 2013;62:1704-12.  Back to cited text no. 10
Sennström M, Rova K, Hellgren M, Hjertberg R, Nord E, Thurn L, et al. Thromboembolism and in vitro fertilization – A systematic review. Acta Obstet Gynecol Scand 2017;96:1045-52.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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