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A fatal case of ovarian hyperstimulation syndrome with cerebral infarction
Pathology
ISSN: 0031-3025 (Print) 1465-3931 (Online) Journal homepage: http://www.tandfonline.com/loi/ipat20
A fatal case of ovarian hyperstimulation syndrome with cerebral infarction Alison D. Cluroe & Beth J. Synek To cite this article: Alison D. Cluroe & Beth J. Synek (1995) A fatal case of ovarian hyperstimulation syndrome with cerebral infarction, Pathology, 27:4, 344-346 To link to this article: http://dx.doi.org/10.1080/00313029500169273
Published online: 06 Jul 2009.
Submit your article to this journal
Article views: 15
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Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipat20 Download by: [New York University]
Date: 30 August 2016, At: 06:32
Pathology (1995), 27, pp. 344-346
A FATAL CASE OF OVARIAN HYPERSTIMULATION SYNDROME WITH CEREBRAL INFARCTION A L I S O N D . C L U R O E AND B E T H J . SYNEK
Department o f Pathology, Auckland University School o f Medicine, Auckland, New Zealand
Summary The ovarian hyperstimulation syndrome (OHSS) as a cause of death in infertile patients involved in in vitro fertilization is an extremely rare phenomenon. Reported here are the clinical and pathological features of just such a case together with a discussion of the pathophysiology thought to be involved. Key words: Maternal death, the ovarian hyperstimulation syndrome. Accepted t8 July 1995
INTRODUCTION The o v a r i a n h y p e r s t i m u l a t i o n s y n d r o m e ( O H S S ) is iatrogenically i n d u c e d , arising as a r a r e c o m p l i c a t i o n o f the h o r m o n a l t r e a t m e n t for i n d u c t i o n o f o v u l a t i o n a n d p r e v e n t i o n o f early i n v o l u t i o n o f the c o r p u s l u t e u m in in vitro f e r t i l i z a t i o n p r o g r a m m e s . E a r l y f e a t u r e s o f the s y n d r o m e i n c l u d e n a u s e a , v o m i t i n g , d i a r r h e a , evidence o f ascites a n d / o r h y d r o t h o r a x a n d o v a r i a n e n l a r g e m e n t . W i t h i n c r e a s i n g severity changes in b l o o d v o l u m e d u e to fluid shifts, i n c r e a s e d b l o o d viscosity d u e to h e m o c o n c e n t r a t i o n , reduced renal p e r f u s i o n a n d c o a g u l o p a t h y occur. P r e s e n t e d b e l o w is a case o f r a p i d l y d e v e l o p i n g fatal O H S S in a 40 yr o l d C a u c a s i a n f e m a l e a n d the findings n o t e d at a u t o p s y . CASE HISTORY Following stimulation with Buserelin and human menopausal gonadotrophin, as part of an in vitro fertilization programme, a 40 yr old Caucasian female with a history of tubal infertility had 3 embryos implanted. On days 1 and 4 following implantation, the patient received
/~-human chorionic gonadotrophin as part of the treatment programme. On days 4 and 5 following the implantation, she complained of abdominal pain and it was noticed that there were ascites and a raised hematocrit at 54 (normal range 35-49), 2600 mL of ascites was drained and fluid replaced intravenously with Plasmalyte. The subject was a regular migraine sufferer and on the evening of day 5 developed tingling in the left hand, severe pain in the right eye and some nausea. These were her usual symptoms of migraine. The following morning, day 6, the deceased was found on the floor, incoherent and having vomited, with obvious left sided weakness. Over the next few hours the patient became less drowsy and spoke more coherently. On examination she was not febrile and had no neck stiffness or photophobia. Neurological examination revealed drowsiness with a Glasgow coma score of 15/15, slightly slurred speech, eyes deviated to the right, decreased facial sensation to pin prick over the left side of the face, left sided facial droop, inability to shrug the left shoulder and deviation of the tongue to the left side. There was marked left sided arm weakness and mild left sided leg weakness. An enhanced
CAT scan appeared suggestive of a large right middle cerebral artery territory infarct with mass effect. The appearances looked patchy, raising the possibility of an embolic origin. The patient was polycythemic with a hemoglobin of 180 g/L.
Over the course of the next few days there was a progressive deterioration in neurological signs together with a falling urine output, bilateral pleural effusions, respiratory distress and re-accumulating ascites. During this time a low dose heparin infusion was commenced to try to prevent any further thrombosis, but to avoid possible bleeding into the infarcted brain tissue. Day t 1 following in vitro fertilization, the patient was diagnosed to be brain dead. Further medical support was withdrawn and she died shortly afterwards. POST MORTEM FINDINGS
External examination T h e b o d y was t h a t o f a female C a u c a s i a n with a weight o f 54 kg a n d a height o f 159 cm. T h e a p p e a r a n c e s were c o m p a t i b l e with the s t a t e d age o f 40 yrs. T h e r e were no n o t a b l e e x t e r n a l features, a p a r t f r o m evidence o f the ascitic t a p site to the left a n t e r i o r a b d o m i n a l wall.
Internal examination A p a r t f r o m a small increase in p e r i c a r d i a l fluid v o l u m e a n d d i l a t a t i o n o f t h e right v e n t r i c u l a r c h a m b e r , the c a r d i o v a s c u l a r system was u n r e m a r k a b l e a n d no source o f e m b o l i was l o c a t e d . T h e r e were 60 m L o f straw c o l o u r e d fluid in the left p l e u r a l cavity a n d 200 m L o f straw c o l o u r e d fluid in the right pleural cavity. The lungs were e d e m a t o u s , the left lung weighing 443 g a n d the right lung 499 g. T h e p e r i t o n e a l c a v i t y c o n t a i n e d 1700 m L o f s t r a w c o l o u r e d fluid a n d the liver a p p e a r e d to be c o n g e s t e d . T h e k i d n e y s were n o r m a l a n d the uterus, cervix a n d v a g i n a were u n r e m a r k a b l e . Both ovaries were e n l a r g e d (Fig. 1), each m e a s u r i n g a p p r o x i m a t e l y 8 cm x 10 c m in size. T h e external surface o f each o v a r y was i r r e g u l a r a n d on sectioning n u m e r o u s h e m o r r h a g i c yellow lined cysts c o u l d be identified. The s u r r o u n d i n g s t r o m a was m a r k e d l y e d e m a t o u s . T h e f a l l o p i a n tubes were t i g h t l y stretched over the ovaries b u t otherwise appeared unremarkable. The endocrine and hemopoietic systems r e v e a l e d n o t h i n g o f n o t e . W i t h i n t h e central n e r v o u s system the e x t e r n a l s u r f a c e o f the b r a i n was m a r k e d l y swollen, p a r t i c u l a r l y on the right side. T h e f l o o r o f the t h i r d ventricle was flattened. M a j o r i n t r a c r a n i a l arteries were free o f a t h e r o m a . N o t h r o m b u s was d e t e c t e d in m a j o r arteries a n d especially in the right m i d d l e c e r e b r a l artery. T h e r e was a c a u d a l shift o f the b r a i n s t e m t h r o u g h the t e n t o r i a l notch, producing a zone o f compression o f the right third cranial
OVARIAN HYPERST1MULATION SYNDROME
Fig. 1 Specimen of uterus and ovaries showing enlarged ovaries with numerous hemorrhagic corpus luteum cysts within an edematous stroma.
nerve root. Some congestion was seen in the right medial occipital cortex. No old infarcts were seen. There was fresh patchy hemorrhagic infarction of tissue supplied by the right middle cerebral artery including the deep cerebral white matter, the lenticular nucleus and thalamus and the depths of some sulci in the posterior frontal and parietal lobes. The ventricles were closed and there was a right to left shift of the mid-line structures by about 8 mm. The brain weighed 1319 g.
Significant histology Brain: Microscopic sections showed true infarction of the right caudate tissue and the lateral parietal cortex, including some subcortical white matter on the right side. There was microscopic focal neuronal ischemia in the right media] frontal cortex. Both medial occipital regions showed cortical edema, marked congestion and acute neuronal ischemia, which could have been due to the secondary effects of tentoria] herniation with compression of the posterior cerebral arteries. The right and left thalamus both showed only focal edema, and neuronal ischemia, but very marked small vessel congestion and some perivascular hemorrhages. There were also some microscopic foci of acute neuronal ischemic change in the left lateral parietal cortex. The pontine hemorrhages and thalamic changes appeared secondary to tentoria] herniation. The arteries were free of atheroma. No laminated thrombi were seen microscopically. The pattern of ischemia was in keeping with the changes being arterial rather than of venous type. Given the marked congestion of the vessels and the variation in size of the multiple areas involved by ischemia in both cerebral hemispheres, it was possible that they were due to multiple areas of local thrombosis with hemoconcentration or were thrombo-embolic.
Lungs: Sections showed edema, marked vascular congestion and focal intra-alveolar hemorrhage. Uterus: Sections through the endometrium showed decidualization of the endometrial stroma, some edema of the endometrial stroma and secretory changes within endometrial glands. The myometrium was normal.
345
Fig. 2 Photomicrograph of ovarian histology- showing a portion of one of the many hemorrhagic corpus leutum cysts seen within the ovaries (hematoxylin and eosin, original magnification × 10).
Fallopian tubes: The fallopian tubes appeared histologically normal. Ovary: Sections showed large numbers of corpus luteum cysts composed of a thin outer layer of non-luteinized theca cells. Beneath lay a prominent layer of luteinized granulosa cells covered by a thin fibrinous layer and central hemorrhage. The surrounding ovarian stroma was edematous. Theca lutein cysts were not identified.
DISCUSSION The deceased was involved in an in vitro fertilization programme and had received injections of 3-human chorionic gonadotrophin hormone after the implantation of 3 embryos. Following this she developed a rare complication, OHSS. This syndrome is characterized by enormous cystic ovarian enlargement due, as previously reported, to numerous hemorrhagic corpus luteum cysts, 1'2 massive extra-vascular fluid shifts, with resulting increases in peritoneal and pleura] fluid, and secondary intravascular volume depletion (causing increased blood viscosity). Autopsy revealed many of the features of OHSS. Most significant were the findings within the brain of widespread patchy infarction confined mainly to the grey matter. This was in keeping with the ischemic changes being arterial rather than venous in type. There was also marked congestion and multiple separate areas involved by ischemia, which were of varying size. It was most likely that these multiple areas were related to numerous small vessel thromboses occurring locally. They were unlikely to be related to embolism. The hyperviscosity associated with intravascular volume depletion, related to shifting of fluid from the vascular compartment into the body cavities, was associated with reduced cerebral blood flow and local sludging of red cells within the small cerebra] vessels and in this particular case, manifested as a left hemiparesis. The possible role of vascular spasm (set against a background history of migraine and the high level of ovarian hormones, particularly estrogen and progesterone, that are known to provoke or aggravate migraine) was considered. Obviously arterial spasm cannot be assessed post mortem, however, vascular spasm
346
CLUROEAND SYNEK
may have complicated and exacerbated the pre-existing hyperviscosity. The extensive area of infarction in the right middle cerebral artery territory was possibly because of the combination of hyperviscosity and superimposed vascular spasm. The final cause of death was given as cerebral infarction secondary to the hyperviscosity related to ovarian hyperstimulation syndrome. The OHSS has been classified into mild, moderate and severe forms with 6 grades of severity, 2 in each of the categories. The incidence of OHSS within these categories was reviewed by Schenker and Weinstein in 19783 and despite the passage of time, this incidence does not seem to have altered significantly.4 The sample population was taken from Schenker and Weinstein's review of 9 different studies looking at the incidence of OHSS in combined HMG-HCG treatment. Data were presented in different ways by the 9 separate groups but involved the response to treatment in 2081 patients and additionally 1460 menstrual cycles,a The incidence of mild OHSS was 8 to 23%, moderate 0.005 to 7% and severe 0.008 to 10% (below 2% in most series). 3 It is necessary for ovulation to have occurred for the development of OHSS, the syndrome usually becoming obvious 3 to 6 days after HCG administration. 4 0 H S S appears to occur more commonly in cycles where conception has been achieved,s A good review of the patho-physiology of OHSS is provided by Bergh and Navot. 6 An increase in capillary permeability of mesotheliaI surfaces appears to be the basis for the development of OHSS. 7 OHSS would appear to be an exaggeration of normal ovarian physiology with excessive follicular development, ovulation and corpus luteum formation. Many possible mediators of this syndrome have and are being considered, including prostaglandins, s histamines, 9'1° cytokines6 and in particular, the renin angiotensin system. There appears to be a direct correlation between the severity of OHSS and plasma renin levels. 1~ Various investigators have produced findings that would support the renin angiotensin system as a mediator for increased ovarian and peritoneal permeability. ~z
Pathology (1995), 27, October
ACKNOWLEDGEMENTS The authors would like to thank Dr Judith Baranyai for her comments and Janet Clements for her secretarial assistance.
Address for correspondence: A.D.C., Department of Pathology, Auckland University School of Medicine, Private Bag 92019, Auckland, New Zealand.
References 1. Neuwirth RS, Turksoy RN, Vande Wiele RL. Acute Meig's syndrome secondary to ovarian stimulation with human menopausal gonadotrophins. Am J Obst Gynae 1965; 91: 977-81. 2. Buxton CL, Herrmann W. Induction of ovulation in the human with human gonadotrophins. Am J Obst Gynae 1961; 81: 584-90. 3. Schenker JG, Weinstein D. Ovarian hyperstimulation syndrome: A current survey. Fertil Steril 1978; 30: 225-68. 4. Golan A, Ron-E1 R, Herman A et al. Ovarian hyperstimulation syndrome: An update review. Obstet Gynecol Surv 1989; 6: 430-40. 5. Scommegna A, Lash SR. Ovarian overstimulation, massive ascites and singleton pregnancy after ctomiphene. JAMA 1969; 207: 753-5. 6. Bergh PA, Navot D. Ovarian hyperstimulation syndrome: A review of pathophysiology. J Assist Reprod Gyn 1992; 9: 429-38. 7. Polishuk WZ, Schenker JG. Ovarian hyperstimulation syndrome. Fertil Steril 1969; 20: 443-50. 8. Schenker JG, Polishuk WZ. The role of prostaglandins in ovarian hyperstimulation syndrome. Eur J Obstet Gynecol Reprod Biol 1976; 6: 47-50. 9. Gergely RZ, Paldi E, Erlik Y e t al. Treatment of ovarian hyperstimulation syndrome by antihistamine. Obstet Gynecol 1976; 47: 83-5. 10. Erlik Y, Naot Y, Freidman M et al. Histamine levels in the ovarian hyperstimulation syndrome. Obstet Gynecol 1979; 53: 580-2. 11. Navot D, Margalioth E J, Laufer Net al. Direct correlation between plasma renin activity and severity of the ovarian hyperstimulation syndrome. Fertil Steril 1987; 48: 57-61. 12. Ong ACM, Eisen V, Rennie DP et al. The pathogenesis of the ovarian hyperstimulation syndrome: A possible role for ovarian renin. Clin Endocrinol t991; 34: 43-9.
ISSN: 0031-3025 (Print) 1465-3931 (Online) Journal homepage: http://www.tandfonline.com/loi/ipat20
A fatal case of ovarian hyperstimulation syndrome with cerebral infarction Alison D. Cluroe & Beth J. Synek To cite this article: Alison D. Cluroe & Beth J. Synek (1995) A fatal case of ovarian hyperstimulation syndrome with cerebral infarction, Pathology, 27:4, 344-346 To link to this article: http://dx.doi.org/10.1080/00313029500169273
Published online: 06 Jul 2009.
Submit your article to this journal
Article views: 15
View related articles
Citing articles: 3 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipat20 Download by: [New York University]
Date: 30 August 2016, At: 06:32
Pathology (1995), 27, pp. 344-346
A FATAL CASE OF OVARIAN HYPERSTIMULATION SYNDROME WITH CEREBRAL INFARCTION A L I S O N D . C L U R O E AND B E T H J . SYNEK
Department o f Pathology, Auckland University School o f Medicine, Auckland, New Zealand
Summary The ovarian hyperstimulation syndrome (OHSS) as a cause of death in infertile patients involved in in vitro fertilization is an extremely rare phenomenon. Reported here are the clinical and pathological features of just such a case together with a discussion of the pathophysiology thought to be involved. Key words: Maternal death, the ovarian hyperstimulation syndrome. Accepted t8 July 1995
INTRODUCTION The o v a r i a n h y p e r s t i m u l a t i o n s y n d r o m e ( O H S S ) is iatrogenically i n d u c e d , arising as a r a r e c o m p l i c a t i o n o f the h o r m o n a l t r e a t m e n t for i n d u c t i o n o f o v u l a t i o n a n d p r e v e n t i o n o f early i n v o l u t i o n o f the c o r p u s l u t e u m in in vitro f e r t i l i z a t i o n p r o g r a m m e s . E a r l y f e a t u r e s o f the s y n d r o m e i n c l u d e n a u s e a , v o m i t i n g , d i a r r h e a , evidence o f ascites a n d / o r h y d r o t h o r a x a n d o v a r i a n e n l a r g e m e n t . W i t h i n c r e a s i n g severity changes in b l o o d v o l u m e d u e to fluid shifts, i n c r e a s e d b l o o d viscosity d u e to h e m o c o n c e n t r a t i o n , reduced renal p e r f u s i o n a n d c o a g u l o p a t h y occur. P r e s e n t e d b e l o w is a case o f r a p i d l y d e v e l o p i n g fatal O H S S in a 40 yr o l d C a u c a s i a n f e m a l e a n d the findings n o t e d at a u t o p s y . CASE HISTORY Following stimulation with Buserelin and human menopausal gonadotrophin, as part of an in vitro fertilization programme, a 40 yr old Caucasian female with a history of tubal infertility had 3 embryos implanted. On days 1 and 4 following implantation, the patient received
/~-human chorionic gonadotrophin as part of the treatment programme. On days 4 and 5 following the implantation, she complained of abdominal pain and it was noticed that there were ascites and a raised hematocrit at 54 (normal range 35-49), 2600 mL of ascites was drained and fluid replaced intravenously with Plasmalyte. The subject was a regular migraine sufferer and on the evening of day 5 developed tingling in the left hand, severe pain in the right eye and some nausea. These were her usual symptoms of migraine. The following morning, day 6, the deceased was found on the floor, incoherent and having vomited, with obvious left sided weakness. Over the next few hours the patient became less drowsy and spoke more coherently. On examination she was not febrile and had no neck stiffness or photophobia. Neurological examination revealed drowsiness with a Glasgow coma score of 15/15, slightly slurred speech, eyes deviated to the right, decreased facial sensation to pin prick over the left side of the face, left sided facial droop, inability to shrug the left shoulder and deviation of the tongue to the left side. There was marked left sided arm weakness and mild left sided leg weakness. An enhanced
CAT scan appeared suggestive of a large right middle cerebral artery territory infarct with mass effect. The appearances looked patchy, raising the possibility of an embolic origin. The patient was polycythemic with a hemoglobin of 180 g/L.
Over the course of the next few days there was a progressive deterioration in neurological signs together with a falling urine output, bilateral pleural effusions, respiratory distress and re-accumulating ascites. During this time a low dose heparin infusion was commenced to try to prevent any further thrombosis, but to avoid possible bleeding into the infarcted brain tissue. Day t 1 following in vitro fertilization, the patient was diagnosed to be brain dead. Further medical support was withdrawn and she died shortly afterwards. POST MORTEM FINDINGS
External examination T h e b o d y was t h a t o f a female C a u c a s i a n with a weight o f 54 kg a n d a height o f 159 cm. T h e a p p e a r a n c e s were c o m p a t i b l e with the s t a t e d age o f 40 yrs. T h e r e were no n o t a b l e e x t e r n a l features, a p a r t f r o m evidence o f the ascitic t a p site to the left a n t e r i o r a b d o m i n a l wall.
Internal examination A p a r t f r o m a small increase in p e r i c a r d i a l fluid v o l u m e a n d d i l a t a t i o n o f t h e right v e n t r i c u l a r c h a m b e r , the c a r d i o v a s c u l a r system was u n r e m a r k a b l e a n d no source o f e m b o l i was l o c a t e d . T h e r e were 60 m L o f straw c o l o u r e d fluid in the left p l e u r a l cavity a n d 200 m L o f straw c o l o u r e d fluid in the right pleural cavity. The lungs were e d e m a t o u s , the left lung weighing 443 g a n d the right lung 499 g. T h e p e r i t o n e a l c a v i t y c o n t a i n e d 1700 m L o f s t r a w c o l o u r e d fluid a n d the liver a p p e a r e d to be c o n g e s t e d . T h e k i d n e y s were n o r m a l a n d the uterus, cervix a n d v a g i n a were u n r e m a r k a b l e . Both ovaries were e n l a r g e d (Fig. 1), each m e a s u r i n g a p p r o x i m a t e l y 8 cm x 10 c m in size. T h e external surface o f each o v a r y was i r r e g u l a r a n d on sectioning n u m e r o u s h e m o r r h a g i c yellow lined cysts c o u l d be identified. The s u r r o u n d i n g s t r o m a was m a r k e d l y e d e m a t o u s . T h e f a l l o p i a n tubes were t i g h t l y stretched over the ovaries b u t otherwise appeared unremarkable. The endocrine and hemopoietic systems r e v e a l e d n o t h i n g o f n o t e . W i t h i n t h e central n e r v o u s system the e x t e r n a l s u r f a c e o f the b r a i n was m a r k e d l y swollen, p a r t i c u l a r l y on the right side. T h e f l o o r o f the t h i r d ventricle was flattened. M a j o r i n t r a c r a n i a l arteries were free o f a t h e r o m a . N o t h r o m b u s was d e t e c t e d in m a j o r arteries a n d especially in the right m i d d l e c e r e b r a l artery. T h e r e was a c a u d a l shift o f the b r a i n s t e m t h r o u g h the t e n t o r i a l notch, producing a zone o f compression o f the right third cranial
OVARIAN HYPERST1MULATION SYNDROME
Fig. 1 Specimen of uterus and ovaries showing enlarged ovaries with numerous hemorrhagic corpus luteum cysts within an edematous stroma.
nerve root. Some congestion was seen in the right medial occipital cortex. No old infarcts were seen. There was fresh patchy hemorrhagic infarction of tissue supplied by the right middle cerebral artery including the deep cerebral white matter, the lenticular nucleus and thalamus and the depths of some sulci in the posterior frontal and parietal lobes. The ventricles were closed and there was a right to left shift of the mid-line structures by about 8 mm. The brain weighed 1319 g.
Significant histology Brain: Microscopic sections showed true infarction of the right caudate tissue and the lateral parietal cortex, including some subcortical white matter on the right side. There was microscopic focal neuronal ischemia in the right media] frontal cortex. Both medial occipital regions showed cortical edema, marked congestion and acute neuronal ischemia, which could have been due to the secondary effects of tentoria] herniation with compression of the posterior cerebral arteries. The right and left thalamus both showed only focal edema, and neuronal ischemia, but very marked small vessel congestion and some perivascular hemorrhages. There were also some microscopic foci of acute neuronal ischemic change in the left lateral parietal cortex. The pontine hemorrhages and thalamic changes appeared secondary to tentoria] herniation. The arteries were free of atheroma. No laminated thrombi were seen microscopically. The pattern of ischemia was in keeping with the changes being arterial rather than of venous type. Given the marked congestion of the vessels and the variation in size of the multiple areas involved by ischemia in both cerebral hemispheres, it was possible that they were due to multiple areas of local thrombosis with hemoconcentration or were thrombo-embolic.
Lungs: Sections showed edema, marked vascular congestion and focal intra-alveolar hemorrhage. Uterus: Sections through the endometrium showed decidualization of the endometrial stroma, some edema of the endometrial stroma and secretory changes within endometrial glands. The myometrium was normal.
345
Fig. 2 Photomicrograph of ovarian histology- showing a portion of one of the many hemorrhagic corpus leutum cysts seen within the ovaries (hematoxylin and eosin, original magnification × 10).
Fallopian tubes: The fallopian tubes appeared histologically normal. Ovary: Sections showed large numbers of corpus luteum cysts composed of a thin outer layer of non-luteinized theca cells. Beneath lay a prominent layer of luteinized granulosa cells covered by a thin fibrinous layer and central hemorrhage. The surrounding ovarian stroma was edematous. Theca lutein cysts were not identified.
DISCUSSION The deceased was involved in an in vitro fertilization programme and had received injections of 3-human chorionic gonadotrophin hormone after the implantation of 3 embryos. Following this she developed a rare complication, OHSS. This syndrome is characterized by enormous cystic ovarian enlargement due, as previously reported, to numerous hemorrhagic corpus luteum cysts, 1'2 massive extra-vascular fluid shifts, with resulting increases in peritoneal and pleura] fluid, and secondary intravascular volume depletion (causing increased blood viscosity). Autopsy revealed many of the features of OHSS. Most significant were the findings within the brain of widespread patchy infarction confined mainly to the grey matter. This was in keeping with the ischemic changes being arterial rather than venous in type. There was also marked congestion and multiple separate areas involved by ischemia, which were of varying size. It was most likely that these multiple areas were related to numerous small vessel thromboses occurring locally. They were unlikely to be related to embolism. The hyperviscosity associated with intravascular volume depletion, related to shifting of fluid from the vascular compartment into the body cavities, was associated with reduced cerebral blood flow and local sludging of red cells within the small cerebra] vessels and in this particular case, manifested as a left hemiparesis. The possible role of vascular spasm (set against a background history of migraine and the high level of ovarian hormones, particularly estrogen and progesterone, that are known to provoke or aggravate migraine) was considered. Obviously arterial spasm cannot be assessed post mortem, however, vascular spasm
346
CLUROEAND SYNEK
may have complicated and exacerbated the pre-existing hyperviscosity. The extensive area of infarction in the right middle cerebral artery territory was possibly because of the combination of hyperviscosity and superimposed vascular spasm. The final cause of death was given as cerebral infarction secondary to the hyperviscosity related to ovarian hyperstimulation syndrome. The OHSS has been classified into mild, moderate and severe forms with 6 grades of severity, 2 in each of the categories. The incidence of OHSS within these categories was reviewed by Schenker and Weinstein in 19783 and despite the passage of time, this incidence does not seem to have altered significantly.4 The sample population was taken from Schenker and Weinstein's review of 9 different studies looking at the incidence of OHSS in combined HMG-HCG treatment. Data were presented in different ways by the 9 separate groups but involved the response to treatment in 2081 patients and additionally 1460 menstrual cycles,a The incidence of mild OHSS was 8 to 23%, moderate 0.005 to 7% and severe 0.008 to 10% (below 2% in most series). 3 It is necessary for ovulation to have occurred for the development of OHSS, the syndrome usually becoming obvious 3 to 6 days after HCG administration. 4 0 H S S appears to occur more commonly in cycles where conception has been achieved,s A good review of the patho-physiology of OHSS is provided by Bergh and Navot. 6 An increase in capillary permeability of mesotheliaI surfaces appears to be the basis for the development of OHSS. 7 OHSS would appear to be an exaggeration of normal ovarian physiology with excessive follicular development, ovulation and corpus luteum formation. Many possible mediators of this syndrome have and are being considered, including prostaglandins, s histamines, 9'1° cytokines6 and in particular, the renin angiotensin system. There appears to be a direct correlation between the severity of OHSS and plasma renin levels. 1~ Various investigators have produced findings that would support the renin angiotensin system as a mediator for increased ovarian and peritoneal permeability. ~z
Pathology (1995), 27, October
ACKNOWLEDGEMENTS The authors would like to thank Dr Judith Baranyai for her comments and Janet Clements for her secretarial assistance.
Address for correspondence: A.D.C., Department of Pathology, Auckland University School of Medicine, Private Bag 92019, Auckland, New Zealand.
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