Case Report Pregnancy by Ovulation Induction and Intrauterine Insemination then Fetus Discovered To Have Isolated Agenesis of the Corpus Callosum: A Case Report Chi-Feng Wei1,* Failure of development of the callosal commissural fibers connecting the cerebral hemispheres results in complete or partial agenesis of the corpus callosum (ACC). The incidence of ACC ranges 3%~5% to 1:4000 live births. This paper reports a 34-year-old woman married for 5 years with primary infertility due to ovulation dysfunction who received ovulation induction (OI) and intrauterine insemination (IUI) 3 times. She became pregnant after the third OI and IUI procedures. Unfortunately, it was found that the occipital portion of the bilateral lateral ventricles of her fetus were dilated with narrowing of the anterior part, creating the so-called “teardropshaped” ventricles (colpocephaly) at 24 gestational weeks on a routine antenatal ultrasound check. After this discovery, isolated ACC with no associated anomalies was the impression. The diagnosis was confirmed at another hospital by MRI, and then the patient decided to terminate the pregnancy. Keywords: agenesis of the corpus callosum, ultrasound, MRI, ovulation induction, intra-uterine insemination INTRODUCTION of callosal fibers as visualized through neuroimaging (ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI)). ACC is typi- The most extreme form of developmental mal- cally accompanied by characteristic dilation of the formation of the corpus callosum (CC) is agenesis. posterior lateral ventricles (colpocephaly)[1,2], and Agenesis of the CC (ACC) including both com- often the presence of atypical fiber bundles (Probst plete and partial callosal absence, is an anatomi- bundles) that run anterior to posterior just lateral cally defined condition that results from disruption to the interhemispheric fissure[3]. Recent neonatal of the early stages of fetal callosal development. and prenatal imaging studies suggested that ACC The diagnosis is based on a finding of the absence occurs in at least 1: 4000 live births[4,5], and other Department of Obstetrics and Gynecology, Si-Jhih Cathay General Hospital, Sijhih District, New Taipei City, Taiwan Submitted March, 23, 2012; final version accepted June, 8, 2012. *Correspondence author: [email protected] 輔仁醫學期刊　第 10 卷　第 2 期　2012 111 Chi-Feng Wei imaging studies demonstrated that 3%~5% of indi- given with 200 mg Utrogestan® BID vaginal sup- viduals assessed for neurodevelopmental disorders port. She became pregnant after the third OI and [6,7] . Involvement of the CC occurs in a IUI. Unfortunately, it was found that her baby had variety of developmental disorders that are current- dilatation of the occipital portion of the bilateral ly exclusively defined by genetics, developmental lateral ventricles with narrowing of the anterior insults, and/or behavior. This followed a review of part, creating the so-called “teardrop-shaped” ven- several genetic disorders that commonly result in tricles (colpocephaly) at 24 gestational weeks on a social impairments and/or psychopathology similar routine antenatal ultrasound check. After this dis- to ACC (neurofibromatosis-1, Turner syndrome, covery, isolated ACC with no associated anomalies 22q11.2 deletion syndrome, Williams syndrome, was the impression. The diagnosis was confirmed and fragile X) and 2 forms of prenatal injury (pre- at another hospital by magnetic resonance imaging mature birth and fetal alcohol syndrome) known to (MRI), after which the patient decided to terminate have ACC [8] impact callosal development . Callosal involve- the pregnancy. After that, she tried OI with IUI ment occurs in several common developmental once again, and fortunately she became pregnant disorders exclusively defined by behavioral pat- and had a health baby by term delivery. terns (developmental language delay, dyslexia, DISCUSSION attention-deficit hyperactive disorder, autism spec[8] trum disorders, and Tourette syndrome) . From an embryological point of view, the CC CASE REPORT represents the major telencephalic commissure. It is composed of 4 parts (from front to back): A 34-year-old woman married for 5 years the rostrum, genu, body, and splenium. At 11~12 with primary infertility due to ovulation dysfunc- weeks’ gestation, the CC begins to develop dorsal- tion had received ovulation induction (OI) and in- ly, and it completes its formation at 18~20 weeks trauterine insemination (IUI) 3 times. The OI pro- of gestation. If the normal developmental process tocol used 100 mg clomiphene citrate daily from is disturbed, the CC may be partially or completely menstrual days 3~7, combined with 150 IU recom- absent[9]. binant follicle-stimulating hormone (FSH) QOD In a comparison of the diagnostic methods of on menstrual days 4, 6, 8, and 10. Follicles were ACC with ultrasound and MRI, demonstration of measured on day 12 by transvaginal sonography. the CC with ultrasound requires some degree of Human chorionic gonadotropin (HCG) at 5000 IU technical skill. As the formation of the CC is not was given when the leading follicle had reached completed until mid-gestation, early diagnosis of 18 mm or 2 follicles had reached 16 mm. IUI was the direct absence of the CC is not possible[10]. As- performed 36 h after HCG administration with sociated signs such as an interhemispheric cyst and swim-up method preparation. Luteal support was colpocephaly (dilatation of the occipital portion of 112 Fu-Jen Journal of Medicine Vol.10 No.2 2012 Fetus with Isolated Agenesis of the Corpus Callosum the lateral ventricles with narrowing of the ante- In my opinion, counseling patients is greatly en- rior part, creating the so-called “teardrop-shaped” hanced with confirmatory MRI findings when the ventricles) (Figs. 1, 2), may be recognizable in the MRI agrees with the US findings earlier in the late first trimester and imaged using transvaginal gestation and in a more-specific diagnosis later in [11] sonography . the gestation to help prepare for delivery. In many instances when an inconclusive US examination is referred for a second opinion, the MR images are normal, providing reassuring information for the patient. MRI confirmation provides the referring physician with a measure of confidence and valuable information for counseling patients. The most common reason for referral is isolated ventriculomegaly. Additional abnormalities commonly associated with ventriculomegaly might not be defined on an US examination. The most common change in diagnosis is from marked ventriculomegaly to a more-precise diagnostic category, such as aqueductal stenosis or hydrocephaly, and from mild ventriculomegaly to more-specific diagnoses, including ACC and migrational abnormalities[14]. A more-exact diagnosis impacts patient counseling and to a lesser degree clinical management[14]. This is the first case report of a pregnancy Figs 1,2 D ilatation of the occipital portion of the lateral ventricles with narrowing of the anterior part, creating the so-called “teardrop-shaped” ventricles (colpocephaly). through OI and IUI with isolated ACC noted in the fetus. Clomiphene citrate has been prescribed for use in OI since the late 1950s, and to the present, Some studies assessed a second-opinion MRI clomiphene citrate is the most often applied drug examination in the setting of a suspected central for infertility therapy worldwide, accounting for nervous system (CNS) abnormality demonstrated around two-thirds of all prescriptions. Use of re- on ultrasound (US) in regards to its ability to con- combinant FSH in OI with a successful pregnancy firm, change the diagnosis, and possibly alter clini- was reported in 1992. In a review of the literature, cal management. MRI is more likely to confirm no correlation of these two OI drugs with ACC an US diagnosis prior to 24 weeks; but beyond 24 was reported, so far. In conclusion, the pregnancy weeks, a change in the diagnosis occurs or addi- obtained through OI and IUI and the fetus with tional information is gleaned more frequently 輔仁醫學期刊　第 10 卷　第 2 期　2012 [12-14] . isolated ACC seemed to have occurred inciden- 113 Chi-Feng Wei 6. Bodensteiner J, Schaefer GB, Breeding L, et tally. In summary, taken together, the neuropsy- al. Hypoplasia of the corpus callosum: a study chological findings of primary ACC highlight a of 445 consecutive MRI scans. J Child Neurol pattern of deficits in problem solving, processing 1994; 9: 47-49. speed, and the social pragmatics of language and 7. Jeret JS, Serur D, Wisniewski K, et al. Fre- communication, which may result in significant quency of agenesis of the corpus callosum in [8] complications in daily life . But the prognosis of the developmentally disabled population as de- a fetal anomaly with isolated ACC remains uncer- termined by computerized tomography. Pediatr tain. And the decision to terminate the pregnancy Neurosci 1985; 12: 101-103. should be made by the mother and professionals 8. Paul LK. Developmental malformation of the when faced with a fetal anomaly with isolated corpus callosum: a review of typical callosal ACC which would lead to substantial physical and/ development and examples of developmental [15] or mental disabilities . disorders with callosal involvement. J Neurodevelop Disord 2011; 3: 3-27. REFERENCES 9. Volpe P, Paladini D, Resta M, et al. Characteristics, associations and outcome of partial 1. Baker LL, Barkovich AJ. The large temporal agenesis of the corpus callosum in the fetus. horn: MR analysis in developmental brain Ultrasound Obstet Gynecol 2006; 27: 509-516. anomalies versus hydrocephalus. Am J Neuro- 10.Nicolaides KH, Salvesen DR, Snijders RJ, et radiol 1992; 13: 115-122. 2. Mori K. Giant interhemispheric cysts associated with agenesis of the corpus callosum. J Neurosurg 1992; 76: 224-230. 3. 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Sec- apparently normal term neonates. Neuroradiol- ond-opinion magnetic resonance imaging for ogy 2004; 46: 368-373. suspected fetal central nervous system abnor- Fu-Jen Journal of Medicine Vol.10 No.2 2012 Fetus with Isolated Agenesis of the Corpus Callosum malities. Am J Obstet Gynecol 2003; 188: 492- prenatal diagnosis in France: how severe are 496. the foetal anomalies? Prenat Diagn 2010; 30: 15.Dommergues M, Mandelbrot L, Mahieu-Capu- 531-539. to D, et al. Termination of pregnancy following 輔仁醫學期刊　第 10 卷　第 2 期　2012 115 Chi-Feng Wei 藉由卵巢排卵刺激及人工受孕懷孕胎兒發生單獨胼胝體缺損：單一病例報告魏琦峰 1,* 胼胝體缺損是連結大腦左右半球胼胝體連接纖維沒有發育或發育不良。活產兒發生胼胝體缺損發生機率為 3%~5% 到 1: 4000。此病例報告為一位 34 歲婦女結婚 5 年因排卵異常而致原發性不孕症並接受 3 次卵巢排卵刺激及人工受孕。在第三次卵巢排卵刺激及人工受孕後懷孕，不幸的是在懷孕 24 週例行產檢超音波發現胎兒大腦兩側側腦室枕角極度擴大及前角狹窄，即所謂淚滴型腦室，除此之外並無其他異常。當時超音波診斷為單獨胼胝體缺損。病人到其他醫院以核磁共振檢查確認診斷後，選擇終止妊娠。關鍵字：胼胝體缺損，超音波，核磁共振，卵巢排卵刺激，人工受孕汐止國泰醫院婦產科投稿日期：2012 年 03 月 23 日接受日期：2012 年 06 月 08 日 * 通訊作者：魏琦峰　電子信箱 : [email protected] 116 Fu-Jen Journal of Medicine Vol.10 No.2 2012