Spontaneous ovarian hyperstimulation syndrome concomitant with spontaneous pregnancy in a woman with polycystic ovary disease Varon ZaIeI, MD, Zvi Katz, MD, Benjamin Caspi, MD, Herzel Ben-Hur, MD, Rami Dgani, MD, and Vaclav InsIer, MD Rehovot, Israel Ovarian hyperstimulation syndrome has been described after treatment with exogenous gonadotropins, clomiphene citrate, and gonadotropin-releasing hormone. Spontaneous ovarian hyperstimulation syndrome has not been described before, except in association with hypothyroidism. We report on a case associated with spontaneous pregnancy, occurring in a woman with polycystic ovary disease. (AM J OBSTET GVNECOL 1992;167:122-4.)
Key words: Spontaneous hyperstimulation, pregnancy, polycystic ovary disease A case of ovarian hyperstimulation syndrome in association with pregnancy and polycystic ovary disease is reported. Case report A 19-year-old woman, gravida I, para 0, was admitted to the hospital because of abdominal pain at lO weeks' gestation. Her medical and gynecologic history was unremarkable. Menarche occurred at the age of 14 years, and menses have subsequently been regular. Her last menstrual period occurred 10 weeks before admission. She was receiving no medication, including oral contraceptives. Physical examination revealed a lean-appearing young woman with normal blood pressure, pulse, and temperature. The abdomen was mildly distended with tenderness and palpable masses in both lower quadrants. Vaginal examination revealed a normal cervix, a uterus enlarged to lO weeks' gestation, and ovaries on both sides enlarged lO cm each and tender. A pelvic sonogram revealed an intrauterine sac with fetal pole and heartbeat. The Crown-rump length was 40 mm, corresponding to a lO weeks' gestation. The ovaries were multilobulated, measured 9 and lO cm in diameter, and contained cystic structures (Fig. 1). A significant amount of free fluid was observed in the pouch of Douglas. Laboratory results included human chorionic gonadotropin levels 52,000 mIU I ml, hemoglobin 11.0 gml dl, hematocrit 38.0%, follicle-stimulating hormone 3.4 mIU Iml, luteinizing hormone 300 mIU Iml, prolactin 32 ng/ml, estradiol 5000 pg/ml, progesterone 48 ng/ml, testosterone 1.8 ng/ml, and cholesterol 194 mg/dl. Liver and kidney function test From the Department of Obstetrics and Gynecology, Kaplan Hospital. Received for publication November 7,1991; revised January 31, 1992; accepted February 18, 1992. Reprint requests: Yaron Zalel, MD, Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel. 611137251
122
results were within normal limits. Elective termination of pregnancy was undertaken the day after admission. Three months later, the patient was reexamined. Results of physical examination were unremarkable. Repeat ultrasonography revealed a uterus of normal size. Both ovaries were of normal size, 3 and 4 cm in diameter, with a typical appearance of polycystic ovary disease (i.e., polymicrofollicular reactions of the ovaries). There was no fluid in the cul-de-sac (Fig. 2). Laboratory results in early follicular phase included human chorionic gonadotropin negative. Follicle-stimulating hormone 3.2 mIU I ml, luteinizing hormone 14.8 mIU/ml, prolactin 6.7 ng/ml, estradiol 90 pg/ml, testosterone 0.3 ng/ml, dehydroepiandrosterone sulfate 2.6 ng/ml, thyroxine 7.9 /-Lg/dl, triiodothyronine resin uptake 28%, thyroid-stimulating hormone 0.9 /-LU/ml (within normal limits). Comment
We report a case of grade 2 ovarian hyperstimulation syndrome (by a combination of multilobulated ovarian cysts, abdominal pain, and free fluid in the cul-de-sac), occurring spontaneously in association with a 10-week gestation. The patient was not treated with any drug, including ovulation induction. Diagnosis was further confirmed by complete resolution of the ovarian hyperstimulation, as demonstrated by clinical, ultrasonographic, and laboratory data. To the best of our knowledge spontaneous ovarian hyperstimulation syndrome has not been described before. Rotmensch and Scommegna' have described a case associated with hypothyroidism and suggested a causal link between both conditions. We ruled out any thyroid disturbances. However, our patient showed both laboratory and ultrasonographic characteristics of polycystic ovary disease. The etiologic and pathophysiologic characteristics of ovarian hyperstimulation syndrome are poorly un-
Spontaneous hyperstimulation
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Fig. 1. Transvaginal longitudinal ultrasonographic section showing both ovaries enlarged with multiple cystic structures.
Fig. 2. Transvaginal longitudinal ultrasonographic section showing lefl ovary with polymicrofollicular reaction.
derstood. Various factors , including estrogen, histamine, prostaglandins, prolactin, aldosterone, and (pro)renin,2 have been suggested to be involved in the development of the condition. Others found that treatment with a preparation with a high follicle-stimulating hormone/luteinizing hormone ratio causes less ovarian hyperstimulation, and thus ovarian hyperstimulation syndrome might be eliminated by reducing the dosage of luteinizing. Ovarian hyperstimulation syndrome is the result of massive luteinization of a large number of follicles and occurs in 1% to 5% of ovulation-induction
treatment cycles. The incidence of hyper stimulation syndrome is higher in women with polycystic ovary disease, probably because of a larger number of follicles ready to respond to stimulation and a higher sensitivity of functional ovarian elements to gonadotropic stimulation. However, clinical experience showed that one of the essential conditions for the development of ovarian hyperstimulation syndrome is the administration of a relatively high dose of human chorionic gonadotropin required for ovulation induction. It has been presumed that the presence of a functioning feedback mechanism
Zalel et al.
should be adequate to prevent a spontaneous luteinizing hormone surge of height or duration sufficient for luteinizing an excessive number of follicles. Thus withholding of the ovulation-inducing human chorionic gonadotropin injection was advocated as one of the best means for preventing ovarian hyperstimulation. The case presented suggests that, at least in patients with polycystic ovary disease, endogenous follicle-stimulating hormone is sufficient to stimulate the development of an abnormally large follicular cohort, which may then be luteinized by a spontaneous luteinizing hormone surge. Endogenous human chorionic gonadotropin, secreted by the trophoblast 7 to 8 days after fertilization, could represent an additional factor in sus-
July 1992 Am J Obstet Gynecol
taining or exacerbating the ovarian hyperstimulation in this case. Although less common now, ovarian hyperstimulation syndrome still has a very serious impact on the patient'S health and may cause severe morbidity. The purpose of our report is to emphasize that, although it is usually a complication of ovulation induction, it can also occur spontaneously. REFERENCES L Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. AM J OBSTET GYNECOL 1989;160:1220-2. 2. Golan A, Ron-EI R, Herman A, Soffer Y. Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989;44:430-40.
Screening for Down syndrome with the femur length/biparietal diameter ratio: A new twist of the data Lawrence D. Platt, MD,. Arnold L. Medearis, MD,. Dru E. Carlson, MD,. Rena E. Falk, MD,b Greggory R. DeVore, MD,. Janet Horenstein, MD,. and Catherine A. Walla, RN, MA, MNa Los Angeles, California OBJECTIVE: The purpose of this study was to determine the value of discordant morphometric measurements as identifiers of Down syndrome by evaluating the relationship of biparietal diameter, femur length, biparietal diameter/femur length ratio, and cephalic index between a group of fetuses with trisomy 21 and a control population. STUDY DESIGN: Biometric measurements from 48 fetuses with trisomy were reviewed and compared with 107 normal fetuses of similar gestational age. Data were analyzed in 2-week gestational age intervals to determine the effect of gestational age on ultrasonographic detection of Down syndrome. Outcome measures were subject to least-squares linear regression and the t test for analysis. RESULTS: A positive relationship between abnormal morphometric measurements and fetuses with Down syndrome was detected but only during specific weeks of pregnancy. CONCLUSION: Although it appears that biometric measurements may be useful for Down syndrome, further study is needed before its widespread introduction into clinical practice. (AM J OaSTET GYNECOL 1992;167:124-8.)
Key words: Fetus, Down syndrome, ultrasonography From the Department of Obstetrics and Gynecology' and Pediatrics/ University of Southern California School of Medicine and Women's Hospital, Los Angeles County-University of Southern California Medical Center. Receivedfor publication july 18,1991; revised December 12,1991; accepted December 30,1991. Reprint requests: Lawrence D. Platt, MD, Cedars-Sinai Medical Center/ UCLA, 8700 Beverly Blvd., Suite 1738, Los Angeles, CA 90048.
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Antenatal identification of congenital abnormalities in the fetus has increased over the past decade. As a new generation of ultrasonographic equipment became available, numerous publications ' -7 demonstrated its increasing ability to identify dysmorphic features of the fetus, leading to the antenatal diagnosis of specific genetic syndromes. Recent studies have also suggested
Key words: Spontaneous hyperstimulation, pregnancy, polycystic ovary disease A case of ovarian hyperstimulation syndrome in association with pregnancy and polycystic ovary disease is reported. Case report A 19-year-old woman, gravida I, para 0, was admitted to the hospital because of abdominal pain at lO weeks' gestation. Her medical and gynecologic history was unremarkable. Menarche occurred at the age of 14 years, and menses have subsequently been regular. Her last menstrual period occurred 10 weeks before admission. She was receiving no medication, including oral contraceptives. Physical examination revealed a lean-appearing young woman with normal blood pressure, pulse, and temperature. The abdomen was mildly distended with tenderness and palpable masses in both lower quadrants. Vaginal examination revealed a normal cervix, a uterus enlarged to lO weeks' gestation, and ovaries on both sides enlarged lO cm each and tender. A pelvic sonogram revealed an intrauterine sac with fetal pole and heartbeat. The Crown-rump length was 40 mm, corresponding to a lO weeks' gestation. The ovaries were multilobulated, measured 9 and lO cm in diameter, and contained cystic structures (Fig. 1). A significant amount of free fluid was observed in the pouch of Douglas. Laboratory results included human chorionic gonadotropin levels 52,000 mIU I ml, hemoglobin 11.0 gml dl, hematocrit 38.0%, follicle-stimulating hormone 3.4 mIU Iml, luteinizing hormone 300 mIU Iml, prolactin 32 ng/ml, estradiol 5000 pg/ml, progesterone 48 ng/ml, testosterone 1.8 ng/ml, and cholesterol 194 mg/dl. Liver and kidney function test From the Department of Obstetrics and Gynecology, Kaplan Hospital. Received for publication November 7,1991; revised January 31, 1992; accepted February 18, 1992. Reprint requests: Yaron Zalel, MD, Department of Obstetrics and Gynecology, Kaplan Hospital, Rehovot, Israel. 611137251
122
results were within normal limits. Elective termination of pregnancy was undertaken the day after admission. Three months later, the patient was reexamined. Results of physical examination were unremarkable. Repeat ultrasonography revealed a uterus of normal size. Both ovaries were of normal size, 3 and 4 cm in diameter, with a typical appearance of polycystic ovary disease (i.e., polymicrofollicular reactions of the ovaries). There was no fluid in the cul-de-sac (Fig. 2). Laboratory results in early follicular phase included human chorionic gonadotropin negative. Follicle-stimulating hormone 3.2 mIU I ml, luteinizing hormone 14.8 mIU/ml, prolactin 6.7 ng/ml, estradiol 90 pg/ml, testosterone 0.3 ng/ml, dehydroepiandrosterone sulfate 2.6 ng/ml, thyroxine 7.9 /-Lg/dl, triiodothyronine resin uptake 28%, thyroid-stimulating hormone 0.9 /-LU/ml (within normal limits). Comment
We report a case of grade 2 ovarian hyperstimulation syndrome (by a combination of multilobulated ovarian cysts, abdominal pain, and free fluid in the cul-de-sac), occurring spontaneously in association with a 10-week gestation. The patient was not treated with any drug, including ovulation induction. Diagnosis was further confirmed by complete resolution of the ovarian hyperstimulation, as demonstrated by clinical, ultrasonographic, and laboratory data. To the best of our knowledge spontaneous ovarian hyperstimulation syndrome has not been described before. Rotmensch and Scommegna' have described a case associated with hypothyroidism and suggested a causal link between both conditions. We ruled out any thyroid disturbances. However, our patient showed both laboratory and ultrasonographic characteristics of polycystic ovary disease. The etiologic and pathophysiologic characteristics of ovarian hyperstimulation syndrome are poorly un-
Spontaneous hyperstimulation
Volume 167 Number I
123
Fig. 1. Transvaginal longitudinal ultrasonographic section showing both ovaries enlarged with multiple cystic structures.
Fig. 2. Transvaginal longitudinal ultrasonographic section showing lefl ovary with polymicrofollicular reaction.
derstood. Various factors , including estrogen, histamine, prostaglandins, prolactin, aldosterone, and (pro)renin,2 have been suggested to be involved in the development of the condition. Others found that treatment with a preparation with a high follicle-stimulating hormone/luteinizing hormone ratio causes less ovarian hyperstimulation, and thus ovarian hyperstimulation syndrome might be eliminated by reducing the dosage of luteinizing. Ovarian hyperstimulation syndrome is the result of massive luteinization of a large number of follicles and occurs in 1% to 5% of ovulation-induction
treatment cycles. The incidence of hyper stimulation syndrome is higher in women with polycystic ovary disease, probably because of a larger number of follicles ready to respond to stimulation and a higher sensitivity of functional ovarian elements to gonadotropic stimulation. However, clinical experience showed that one of the essential conditions for the development of ovarian hyperstimulation syndrome is the administration of a relatively high dose of human chorionic gonadotropin required for ovulation induction. It has been presumed that the presence of a functioning feedback mechanism
Zalel et al.
should be adequate to prevent a spontaneous luteinizing hormone surge of height or duration sufficient for luteinizing an excessive number of follicles. Thus withholding of the ovulation-inducing human chorionic gonadotropin injection was advocated as one of the best means for preventing ovarian hyperstimulation. The case presented suggests that, at least in patients with polycystic ovary disease, endogenous follicle-stimulating hormone is sufficient to stimulate the development of an abnormally large follicular cohort, which may then be luteinized by a spontaneous luteinizing hormone surge. Endogenous human chorionic gonadotropin, secreted by the trophoblast 7 to 8 days after fertilization, could represent an additional factor in sus-
July 1992 Am J Obstet Gynecol
taining or exacerbating the ovarian hyperstimulation in this case. Although less common now, ovarian hyperstimulation syndrome still has a very serious impact on the patient'S health and may cause severe morbidity. The purpose of our report is to emphasize that, although it is usually a complication of ovulation induction, it can also occur spontaneously. REFERENCES L Rotmensch S, Scommegna A. Spontaneous ovarian hyperstimulation syndrome associated with hypothyroidism. AM J OBSTET GYNECOL 1989;160:1220-2. 2. Golan A, Ron-EI R, Herman A, Soffer Y. Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome: an update review. Obstet Gynecol Surv 1989;44:430-40.
Screening for Down syndrome with the femur length/biparietal diameter ratio: A new twist of the data Lawrence D. Platt, MD,. Arnold L. Medearis, MD,. Dru E. Carlson, MD,. Rena E. Falk, MD,b Greggory R. DeVore, MD,. Janet Horenstein, MD,. and Catherine A. Walla, RN, MA, MNa Los Angeles, California OBJECTIVE: The purpose of this study was to determine the value of discordant morphometric measurements as identifiers of Down syndrome by evaluating the relationship of biparietal diameter, femur length, biparietal diameter/femur length ratio, and cephalic index between a group of fetuses with trisomy 21 and a control population. STUDY DESIGN: Biometric measurements from 48 fetuses with trisomy were reviewed and compared with 107 normal fetuses of similar gestational age. Data were analyzed in 2-week gestational age intervals to determine the effect of gestational age on ultrasonographic detection of Down syndrome. Outcome measures were subject to least-squares linear regression and the t test for analysis. RESULTS: A positive relationship between abnormal morphometric measurements and fetuses with Down syndrome was detected but only during specific weeks of pregnancy. CONCLUSION: Although it appears that biometric measurements may be useful for Down syndrome, further study is needed before its widespread introduction into clinical practice. (AM J OaSTET GYNECOL 1992;167:124-8.)
Key words: Fetus, Down syndrome, ultrasonography From the Department of Obstetrics and Gynecology' and Pediatrics/ University of Southern California School of Medicine and Women's Hospital, Los Angeles County-University of Southern California Medical Center. Receivedfor publication july 18,1991; revised December 12,1991; accepted December 30,1991. Reprint requests: Lawrence D. Platt, MD, Cedars-Sinai Medical Center/ UCLA, 8700 Beverly Blvd., Suite 1738, Los Angeles, CA 90048.
6/1/37392
124
Antenatal identification of congenital abnormalities in the fetus has increased over the past decade. As a new generation of ultrasonographic equipment became available, numerous publications ' -7 demonstrated its increasing ability to identify dysmorphic features of the fetus, leading to the antenatal diagnosis of specific genetic syndromes. Recent studies have also suggested
