RETINAL VASCULAR OCCLUSION DURING IN VITRO FERTILIZATION Byung-Ro Lee, MD, PhD,*† Yoo Mi Song, MD,* Igor Kozak, MD, PhD†
Purpose: To describe a case of human retinal vascular occlusion during in vitro fertilization. Methods: A single case report of a 30-year-old woman who developed decreased central vision in her left eye with inferonasal scotoma while on a gonadotropin-releasing hormone agonist treatment protocol. Results: The patient’s laboratory tests and biochemical profile were normal. Fundoscopy revealed moderate tortuosity of both temporal vascular arcades and dilation of the inferior temporal vein with a blotchy hemorrhage. The superotemporal macular area was swollen and pale. Fluorescein angiography demonstrated an incomplete central retinal vein occlusion accompanied by branch retinal arterial occlusion in the left eye. Six months later, her vision improved to 20/32, and the retina recovered normal color. Conclusion: Retinal vascular occlusion can occur during a controlled ovarian hyperstimulation with gonadotropin-releasing hormone agonists. RETINAL CASES & BRIEF REPORTS 4:81– 83, 2010
From the *Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Korea; and †Department of Ophthalmology, University of California San Diego, Shiley Eye Center, La Jolla, California.
She was being injected with subcutaneous 75 IU Gonal-f (follitropin alpha, Merck KGaA, Darmstadt, Germany), 3 ampules daily for 10 days, and 3 mg Cetrotide (cetrorelix acetate, Merck KGaA) daily for 4 days from July 13, 2003, to August 5, 2003. The visual acuity in the right eye was 20/20 and the fundus examination was normal (Figure 1A). The visual acuity in the left eye was 20/60, no pinhole improvement. The intraocular pressure was normal. There was an inferonasal scotoma on the visual field test. The fundus examination in the left eye revealed a moderate tortuosity of both temporal vascular arcades and dilation of the inferior temporal vein with a hemorrhage. The superotemporal macular area was swollen and pale (Figure 1B). On fluorescein angiogram, there was a moderate leakage from the involved vessels in the late phase (Figures 2A–B). Six months later, she recovered her sight to 20/32 without any treatment. The vascular tortuosity, dilation, and a retinal hemorrhage in the left eye disappeared. The white, swollen, and pale retina recovered to normal color (Figure 3).
S
ince the late 1980s, great development has been made in increasing pregnancy rates thanks to the introduction of the gonadotropin-releasing hormone (GnRH) agonists to the in vitro fertilization protocol. Recently, several complications of GnRH agonists were reported.1 Ocular complications from GnRH agonists have not yet been published. We describe a case of incomplete nonischemic central retinal vein occlusion accompanied by branch retinal artery occlusion in association with the GnRH agonist in vitro fertilization protocol.
Discussion
Case Report
Several reports describe retinal vein occlusion caused by high blood estrogen levels induced by the oral contraceptive pill or hormone replacement therapy.2 However, to our knowledge, there has not been any report about retinal vasculopathy caused by the GnRH agonist. The GnRH agonist for ovarian hyperstimulation induces an estrogen surge by binding the GnRH ago-
On August 12, 2003, a 30-year-old woman was seen with sudden decreased visual acuity in the left eye for 2 weeks. She had no family history of any ocular disease, was not diabetic, hypertensive, did not have liver or kidney disease, or blood coagulopathy.
Reprint requests: Igor Kozak, MD, PhD, University of California San Diego, Shiley Eye Center, 0946, 9415 Campus Point Dr, La Jolla, CA 92093; e-mail: [email protected]
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Fig. 1. Color fundus photograph showing the normal right eye (A). The left eye fundus shows moderate tortuosity of both temporal vascular arcades and dilation of the inferior temporal vein with a hemorrhage (arrowhead). The retina encompassing the macula and along the superotemporal artery is pale and swollen (arrow) (B).
nist to the GnRH receptor in the pituitary gland, after which gonadotropin is secreted. A follicle-stimulating hormone then stimulates a secretion of estrogen in the target organ such as the ovary, adrenal gland, and adipose tissue, which then causes a flareup of blood estrogen. Because the GnRH agonist occupies the GnRH receptor, the gonadotropin in a reserve pool is decreased and luteinizing hormone and follicle-stimulating hormone decrease in the blood. In our case, incomplete central retinal vein occlusion accompanied by branch retinal artery occlusion developed suddenly 10 days after the start of the GnRH agonist protocol. During that time, the patient was in the middle of an estrogen flareup in the blood. Therefore, it is highly possible that the vascular event was a consequence of a high blood estrogen level induced by the GnRH agonist. The presence of ovarian hyperstimulation syndrome has also been implicated in increasing thrombembolism as a complication of hormonal ovarian stimulation in the context of artificial reproductive techniques.3 The differential diagnosis includes papillophlebitis or benign retinal vasculitis in young adults.
However, this patient did not present with papilledema and recovered without any intervention. Traditionally suggested treatments for papillophlebitis, such as steroids, platelet inhibitors, or anticoagulation, lack conclusive evidence that any of them alters natural history of the disease. Given the mentioned association of hyperestrogenism and thrombovascular events, we assume a thrombembolic rather than inflammatory mechanism of the ischemic process. It is also possible that this patient had a preexisting condition leading to this vascular event of which we were not aware. Central retinal vein occlusion accompanied by branch retinal artery occlusion has rarely been reported but has been well defined clinically.4,5 In our case, we assume that the vein occlusion was the primary vascular occlusive episode producing subsequent blockage of branch retinal artery inflow by increased intravascular pressure transferred across the capillary bed to the arterial side. This mechanism is proposed for cilioretinal artery occlusion associated with central retinal vein occlusion. Clinicians should be vigilant of occlusive diseases in young
Fig. 2. Fluorescein angiography. A, Arterial filling phase. B, Late phase. There is leakage along the inferotemporal retinal vein and the macula.
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patients on systemic GnRH agonist protocol in the future. Key words: retinal vascular occlusion, in vitro fertilization, gonadotropin-releasing hormone agonists. References 1.
2.
3.
4.
5. Fig. 3. Color fundus photograph showing the left eye 6 months after the vascular event. The retina is well perfused and the vessels look normal.
Chang YS, Kim CH, Kim SH, et al. Use of GnRH agonist in IVF Program. In: Mori T, Tominaga T, Aono T, Hiroi M, eds. Frontiers in Endocrinology: Perspectives on Assisted Reproduction. Vol. 4. Serono Symposia Publications; 1994:285. Kirwan JF, Tsaloumas MD, Vinall H, Prior P, Kritzinger EE, Dodson PM. Sex hormone preparations and retinal vein occlusion. Eye 1997;11:53–56. Baumann P, Diedrich K. Thrombembolic complications associated with reproductive endocrinologic procedures. Hematol Oncol Clin North Am 2000;14:431– 443. Rubio JE Jr, Charles S. Interferon-associated combined branch retinal artery and central retinal vein obstruction. Retina 2003; 23:546 –548. Duker JS, Cohen MS, Brown GC, Sergott RC, McNamara JA. Combined branch retinal artery and central retinal vein obstruction. Retina 1990;10:105–112.
Purpose: To describe a case of human retinal vascular occlusion during in vitro fertilization. Methods: A single case report of a 30-year-old woman who developed decreased central vision in her left eye with inferonasal scotoma while on a gonadotropin-releasing hormone agonist treatment protocol. Results: The patient’s laboratory tests and biochemical profile were normal. Fundoscopy revealed moderate tortuosity of both temporal vascular arcades and dilation of the inferior temporal vein with a blotchy hemorrhage. The superotemporal macular area was swollen and pale. Fluorescein angiography demonstrated an incomplete central retinal vein occlusion accompanied by branch retinal arterial occlusion in the left eye. Six months later, her vision improved to 20/32, and the retina recovered normal color. Conclusion: Retinal vascular occlusion can occur during a controlled ovarian hyperstimulation with gonadotropin-releasing hormone agonists. RETINAL CASES & BRIEF REPORTS 4:81– 83, 2010
From the *Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Korea; and †Department of Ophthalmology, University of California San Diego, Shiley Eye Center, La Jolla, California.
She was being injected with subcutaneous 75 IU Gonal-f (follitropin alpha, Merck KGaA, Darmstadt, Germany), 3 ampules daily for 10 days, and 3 mg Cetrotide (cetrorelix acetate, Merck KGaA) daily for 4 days from July 13, 2003, to August 5, 2003. The visual acuity in the right eye was 20/20 and the fundus examination was normal (Figure 1A). The visual acuity in the left eye was 20/60, no pinhole improvement. The intraocular pressure was normal. There was an inferonasal scotoma on the visual field test. The fundus examination in the left eye revealed a moderate tortuosity of both temporal vascular arcades and dilation of the inferior temporal vein with a hemorrhage. The superotemporal macular area was swollen and pale (Figure 1B). On fluorescein angiogram, there was a moderate leakage from the involved vessels in the late phase (Figures 2A–B). Six months later, she recovered her sight to 20/32 without any treatment. The vascular tortuosity, dilation, and a retinal hemorrhage in the left eye disappeared. The white, swollen, and pale retina recovered to normal color (Figure 3).
S
ince the late 1980s, great development has been made in increasing pregnancy rates thanks to the introduction of the gonadotropin-releasing hormone (GnRH) agonists to the in vitro fertilization protocol. Recently, several complications of GnRH agonists were reported.1 Ocular complications from GnRH agonists have not yet been published. We describe a case of incomplete nonischemic central retinal vein occlusion accompanied by branch retinal artery occlusion in association with the GnRH agonist in vitro fertilization protocol.
Discussion
Case Report
Several reports describe retinal vein occlusion caused by high blood estrogen levels induced by the oral contraceptive pill or hormone replacement therapy.2 However, to our knowledge, there has not been any report about retinal vasculopathy caused by the GnRH agonist. The GnRH agonist for ovarian hyperstimulation induces an estrogen surge by binding the GnRH ago-
On August 12, 2003, a 30-year-old woman was seen with sudden decreased visual acuity in the left eye for 2 weeks. She had no family history of any ocular disease, was not diabetic, hypertensive, did not have liver or kidney disease, or blood coagulopathy.
Reprint requests: Igor Kozak, MD, PhD, University of California San Diego, Shiley Eye Center, 0946, 9415 Campus Point Dr, La Jolla, CA 92093; e-mail: [email protected]
81
82
RETINAL CASES & BRIEF REPORTSℜ
●
2010
●
VOLUME 4
●
NUMBER 1
Fig. 1. Color fundus photograph showing the normal right eye (A). The left eye fundus shows moderate tortuosity of both temporal vascular arcades and dilation of the inferior temporal vein with a hemorrhage (arrowhead). The retina encompassing the macula and along the superotemporal artery is pale and swollen (arrow) (B).
nist to the GnRH receptor in the pituitary gland, after which gonadotropin is secreted. A follicle-stimulating hormone then stimulates a secretion of estrogen in the target organ such as the ovary, adrenal gland, and adipose tissue, which then causes a flareup of blood estrogen. Because the GnRH agonist occupies the GnRH receptor, the gonadotropin in a reserve pool is decreased and luteinizing hormone and follicle-stimulating hormone decrease in the blood. In our case, incomplete central retinal vein occlusion accompanied by branch retinal artery occlusion developed suddenly 10 days after the start of the GnRH agonist protocol. During that time, the patient was in the middle of an estrogen flareup in the blood. Therefore, it is highly possible that the vascular event was a consequence of a high blood estrogen level induced by the GnRH agonist. The presence of ovarian hyperstimulation syndrome has also been implicated in increasing thrombembolism as a complication of hormonal ovarian stimulation in the context of artificial reproductive techniques.3 The differential diagnosis includes papillophlebitis or benign retinal vasculitis in young adults.
However, this patient did not present with papilledema and recovered without any intervention. Traditionally suggested treatments for papillophlebitis, such as steroids, platelet inhibitors, or anticoagulation, lack conclusive evidence that any of them alters natural history of the disease. Given the mentioned association of hyperestrogenism and thrombovascular events, we assume a thrombembolic rather than inflammatory mechanism of the ischemic process. It is also possible that this patient had a preexisting condition leading to this vascular event of which we were not aware. Central retinal vein occlusion accompanied by branch retinal artery occlusion has rarely been reported but has been well defined clinically.4,5 In our case, we assume that the vein occlusion was the primary vascular occlusive episode producing subsequent blockage of branch retinal artery inflow by increased intravascular pressure transferred across the capillary bed to the arterial side. This mechanism is proposed for cilioretinal artery occlusion associated with central retinal vein occlusion. Clinicians should be vigilant of occlusive diseases in young
Fig. 2. Fluorescein angiography. A, Arterial filling phase. B, Late phase. There is leakage along the inferotemporal retinal vein and the macula.
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RETINAL VASCULAR OCCLUSION DURING IN VITRO FERTILIZATION
patients on systemic GnRH agonist protocol in the future. Key words: retinal vascular occlusion, in vitro fertilization, gonadotropin-releasing hormone agonists. References 1.
2.
3.
4.
5. Fig. 3. Color fundus photograph showing the left eye 6 months after the vascular event. The retina is well perfused and the vessels look normal.
Chang YS, Kim CH, Kim SH, et al. Use of GnRH agonist in IVF Program. In: Mori T, Tominaga T, Aono T, Hiroi M, eds. Frontiers in Endocrinology: Perspectives on Assisted Reproduction. Vol. 4. Serono Symposia Publications; 1994:285. Kirwan JF, Tsaloumas MD, Vinall H, Prior P, Kritzinger EE, Dodson PM. Sex hormone preparations and retinal vein occlusion. Eye 1997;11:53–56. Baumann P, Diedrich K. Thrombembolic complications associated with reproductive endocrinologic procedures. Hematol Oncol Clin North Am 2000;14:431– 443. Rubio JE Jr, Charles S. Interferon-associated combined branch retinal artery and central retinal vein obstruction. Retina 2003; 23:546 –548. Duker JS, Cohen MS, Brown GC, Sergott RC, McNamara JA. Combined branch retinal artery and central retinal vein obstruction. Retina 1990;10:105–112.
