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A Spontaneous and Uneventful Pregnancy in a Turner Mosaic with Previous Recurrent Miscarriages
J Pediatr Adolesc Gynecol (2003) 16:87–88
Original Studies A Spontaneous and Uneventful Pregnancy in a Turner Mosaic with Previous Recurrent Miscarriages Diaa E.E. Rizk, MD1 and Purnima Deb, MD2 1 Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates; 2Department of Obstetrics and Gynecology, Al-Ain Hospital, Al-Ain, United Arab Emirates
Abstract. Background: Conception without ovum donation is very rare in patients with Turner syndrome, occurring mainly in mosaics, and only a third of these natural pregnancies are associated with normal outcome. Case Report: A spontaneous pregnancy is described in a Turner mosaic (45,X/46,XX) with normal puberty and nine previous first-trimester miscarriages who had refused ovum donation. She also declined antenatal genetic diagnosis. Pregnancy remained uneventful with frequent surveillance and psychosocial support. She delivered a live boy weighing 3260 g (50th percentile) and measuring 48 cm (50th percentile) with normal karyotype at term. Conclusion: The diagnosis of mosaic Turner syndrome should be considered in women who have recurrent abortion. Pregnancy may have a good outcome in these patients despite the greater likelihood of recurrent miscarriage.
Key Words. Miscarriage—Mosaic—Pregnancy— Recurrent—Turner syndrome
Introduction Turner syndrome (TS) is a sex chromosomal disorder where all or part of the paternal X chromosome is missing from all or some cell lines that affect approximately 1 in 2500 live births.1,2 Most patients lack functional ovarian tissue, although 5% to 10% achieve puberty or menarche spontaneously.1–4 Conception without ovum donation is, however, extremely uncommon, with 74 such reported cases, occurring mainly in mosaics.2,3 Only 30% of these natural pregnancies have normal outcome, while the rest are additionally complicated by spontaneous abortion, chromosomal
Address reprint requests to: Diaa E.E. Rizk, P.O. Box 17666, AlAin, United Arab Emirates; E-mail: [email protected]
쑖 2003 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Science Inc.
abnormalities such as recurrence of an X-chromosome defect in female offspring and trisomy 21, congenital malformations, and stillbirth.1–6 We report a spontaneous but uncomplicated pregnancy in a Turner mosaic (45,X/46,XX) who had had nine previous miscarriages.
Case Presentation A 38-yr-old Syrian teacher presented for antenatal care at 8 weeks gestation in her tenth natural pregnancy with a history of mosaic TS (45,X/46,XX). This diagnosis was established by karyotyping of lymphocytes and skin fibroblasts during evaluation of recurrent miscarriage where 20% of cultured lymphocytes showed 45,X karyotype. All her previous pregnancies, managed elsewhere, had been spontaneous but resulted in first-trimester abortion, with no cause identified apart from a broad uterine fundus at hysterography. Menarche was at age 16 with normal menstrual history and serum estradiol and FSH levels. Medical and family history was unremarkable, with no consanguineous relation to her husband. The couple had previously expressed religious objections to ovum donation and antenatal genetic diagnosis. The patient had normal secondary sexual characteristics on physical examination. Her weight was 66 kg (50th percentile) and height 158 cm (25th percentile), with no evidence of external or internal Turner phenotype. Routine pregnancy examination and investigations were normal. The couple was counseled about the potential antenatal complications, particularly genetic abnormalities, but decided to proceed with the pregnancy. They were offered continuous and frequent access to their obstetric team, which included two consultants, two chief residents, and a senior obstetric nurse. 1083-3188/03/$22.00 doi:10.1016/S1083-3188(03)00009-3
88
Rizk and Deb: Uneventful Pregnancy in a Turner Mosaic
Ultrasound scan at 18 weeks suggested a structurally normal fetus. Subsequently, the pregnancy was closely monitored using serial ultrasound measurements of cervical length and frequent biophysical assessments of fetal well-being for evidence of complications, but remained uneventful. Spontaneous labor occurred at 38 weeks gestation and progressed normally. She delivered a live baby boy weighing 3260 g (50th percentile) and measuring 48 cm (50th percentile) without external malformations. Apgar score was 8 and 9 at 1 and 5 minutes, respectively. Fetal karyotype was 46,XY. She breastfed her baby and both were discharged in good condition 4 days postpartum. Now, 3 months later, the couple wishes to conceive and remains optimistic about the outcome of future pregnancies.
Discussion Mosaicism (45,X/46,XX; 45,X/46,XY; 45,X/47,XXX) constitutes 16% of the karyotypic abnormalities in TS.1 Diagnosis is established by advanced cytogenetic studies of several cell lines to exclude the Y-chromosome variant with its associated risk of gonadoblastoma, as performed in this case before presenting to our institution. Women with TS have normal intelligence and are phenotypically females with dysgenetic ovaries and somatic stigmata, especially short stature.1–4 These are often absent in mosaics, like our patient, since the short arm of the X chromosome is present in some cell lines.1–3 Spontaneous puberty and menarche are furthermore likely because the ovaries may have residual function. Mosaics are therefore rarely detected during adolescence and can have natural conceptions similar to the index case.1,3,5 Adverse pregnancy outcome is, however, expected, with greater risk of recurrent miscarriage because of genetic fetal defects,1–3 significant alteration in the utero-ovarian vascular anatomy with underperfusion and hypoplasia of the uterus,6 and subclinical uterine abnormalities.5 In retrospect, it is possible that all three factors had contributed to repeated
miscarriage in our patient. This finding, therefore, has an important bearing on the reproductive advice given to mosaics and necessitates screening for mosaic TS, despite its rarity, in women with recurrent abortion. Management of mosaics with recurrent abortions becomes extremely difficult in certain countries, like Arab countries, where having children is a deeply rooted cultural value and ovum donation is either unavailable or socio-religiously unacceptable.1–6 Such patients will always desire pregnancy irrespective of associated risks or number of previous abortions, and this factor increases the management quandary. After genetic counseling, no specific antenatal therapeutic intervention is available for these patients, although frequent surveillance and continuous psychosocial support may be of value, as shown here. We therefore recommend this approach in pregnant mosaics after careful counseling of the couple and believe that, although it is important to spare those patients and their husbands more suffering, frustration, and potential guilt after losing another pregnancy, the final decision should be left to them and should be respected. In conclusion, infertility is not inevitable in mosaic TS (45,X/46,XX) with normal puberty, but pregnancy should be closely monitored because the incidence of miscarriage is increased. References 1. Lippe B: Turner syndrome. Endocrinol Metab Clin North Am 1991; 30:121 2. Abir R, Fisch B, Nahum R, et al: Turner’s syndrome and fertility: current status and possible putative prospects. Hum Reprod Update 2001; 7:603 3. Tarani L, Lampariello G, Raguso F, et al: Pregnancy in patients with Turner’s syndrome: six new cases and review of the literature. Gynecol Endocrinol 1998; 12:83 4. Vockrodt L, Williams JK: A reproductive option for women with Turner’s syndrome. J Pediatr Nurs 1994; 9:321 5. Check JH, Schubert B, Chase JS: Fetal outcome of triplets in a turner mosaic. J Perinat Med 1993; 21:279 6. Foudila T, Soderstrom-Anttila V, Hovatta O: Turner’s syndrome and pregnancy after oocyte donation. Hum Reprod 1999; 14:532
Original Studies A Spontaneous and Uneventful Pregnancy in a Turner Mosaic with Previous Recurrent Miscarriages Diaa E.E. Rizk, MD1 and Purnima Deb, MD2 1 Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates; 2Department of Obstetrics and Gynecology, Al-Ain Hospital, Al-Ain, United Arab Emirates
Abstract. Background: Conception without ovum donation is very rare in patients with Turner syndrome, occurring mainly in mosaics, and only a third of these natural pregnancies are associated with normal outcome. Case Report: A spontaneous pregnancy is described in a Turner mosaic (45,X/46,XX) with normal puberty and nine previous first-trimester miscarriages who had refused ovum donation. She also declined antenatal genetic diagnosis. Pregnancy remained uneventful with frequent surveillance and psychosocial support. She delivered a live boy weighing 3260 g (50th percentile) and measuring 48 cm (50th percentile) with normal karyotype at term. Conclusion: The diagnosis of mosaic Turner syndrome should be considered in women who have recurrent abortion. Pregnancy may have a good outcome in these patients despite the greater likelihood of recurrent miscarriage.
Key Words. Miscarriage—Mosaic—Pregnancy— Recurrent—Turner syndrome
Introduction Turner syndrome (TS) is a sex chromosomal disorder where all or part of the paternal X chromosome is missing from all or some cell lines that affect approximately 1 in 2500 live births.1,2 Most patients lack functional ovarian tissue, although 5% to 10% achieve puberty or menarche spontaneously.1–4 Conception without ovum donation is, however, extremely uncommon, with 74 such reported cases, occurring mainly in mosaics.2,3 Only 30% of these natural pregnancies have normal outcome, while the rest are additionally complicated by spontaneous abortion, chromosomal
Address reprint requests to: Diaa E.E. Rizk, P.O. Box 17666, AlAin, United Arab Emirates; E-mail: [email protected]
쑖 2003 North American Society for Pediatric and Adolescent Gynecology Published by Elsevier Science Inc.
abnormalities such as recurrence of an X-chromosome defect in female offspring and trisomy 21, congenital malformations, and stillbirth.1–6 We report a spontaneous but uncomplicated pregnancy in a Turner mosaic (45,X/46,XX) who had had nine previous miscarriages.
Case Presentation A 38-yr-old Syrian teacher presented for antenatal care at 8 weeks gestation in her tenth natural pregnancy with a history of mosaic TS (45,X/46,XX). This diagnosis was established by karyotyping of lymphocytes and skin fibroblasts during evaluation of recurrent miscarriage where 20% of cultured lymphocytes showed 45,X karyotype. All her previous pregnancies, managed elsewhere, had been spontaneous but resulted in first-trimester abortion, with no cause identified apart from a broad uterine fundus at hysterography. Menarche was at age 16 with normal menstrual history and serum estradiol and FSH levels. Medical and family history was unremarkable, with no consanguineous relation to her husband. The couple had previously expressed religious objections to ovum donation and antenatal genetic diagnosis. The patient had normal secondary sexual characteristics on physical examination. Her weight was 66 kg (50th percentile) and height 158 cm (25th percentile), with no evidence of external or internal Turner phenotype. Routine pregnancy examination and investigations were normal. The couple was counseled about the potential antenatal complications, particularly genetic abnormalities, but decided to proceed with the pregnancy. They were offered continuous and frequent access to their obstetric team, which included two consultants, two chief residents, and a senior obstetric nurse. 1083-3188/03/$22.00 doi:10.1016/S1083-3188(03)00009-3
88
Rizk and Deb: Uneventful Pregnancy in a Turner Mosaic
Ultrasound scan at 18 weeks suggested a structurally normal fetus. Subsequently, the pregnancy was closely monitored using serial ultrasound measurements of cervical length and frequent biophysical assessments of fetal well-being for evidence of complications, but remained uneventful. Spontaneous labor occurred at 38 weeks gestation and progressed normally. She delivered a live baby boy weighing 3260 g (50th percentile) and measuring 48 cm (50th percentile) without external malformations. Apgar score was 8 and 9 at 1 and 5 minutes, respectively. Fetal karyotype was 46,XY. She breastfed her baby and both were discharged in good condition 4 days postpartum. Now, 3 months later, the couple wishes to conceive and remains optimistic about the outcome of future pregnancies.
Discussion Mosaicism (45,X/46,XX; 45,X/46,XY; 45,X/47,XXX) constitutes 16% of the karyotypic abnormalities in TS.1 Diagnosis is established by advanced cytogenetic studies of several cell lines to exclude the Y-chromosome variant with its associated risk of gonadoblastoma, as performed in this case before presenting to our institution. Women with TS have normal intelligence and are phenotypically females with dysgenetic ovaries and somatic stigmata, especially short stature.1–4 These are often absent in mosaics, like our patient, since the short arm of the X chromosome is present in some cell lines.1–3 Spontaneous puberty and menarche are furthermore likely because the ovaries may have residual function. Mosaics are therefore rarely detected during adolescence and can have natural conceptions similar to the index case.1,3,5 Adverse pregnancy outcome is, however, expected, with greater risk of recurrent miscarriage because of genetic fetal defects,1–3 significant alteration in the utero-ovarian vascular anatomy with underperfusion and hypoplasia of the uterus,6 and subclinical uterine abnormalities.5 In retrospect, it is possible that all three factors had contributed to repeated
miscarriage in our patient. This finding, therefore, has an important bearing on the reproductive advice given to mosaics and necessitates screening for mosaic TS, despite its rarity, in women with recurrent abortion. Management of mosaics with recurrent abortions becomes extremely difficult in certain countries, like Arab countries, where having children is a deeply rooted cultural value and ovum donation is either unavailable or socio-religiously unacceptable.1–6 Such patients will always desire pregnancy irrespective of associated risks or number of previous abortions, and this factor increases the management quandary. After genetic counseling, no specific antenatal therapeutic intervention is available for these patients, although frequent surveillance and continuous psychosocial support may be of value, as shown here. We therefore recommend this approach in pregnant mosaics after careful counseling of the couple and believe that, although it is important to spare those patients and their husbands more suffering, frustration, and potential guilt after losing another pregnancy, the final decision should be left to them and should be respected. In conclusion, infertility is not inevitable in mosaic TS (45,X/46,XX) with normal puberty, but pregnancy should be closely monitored because the incidence of miscarriage is increased. References 1. Lippe B: Turner syndrome. Endocrinol Metab Clin North Am 1991; 30:121 2. Abir R, Fisch B, Nahum R, et al: Turner’s syndrome and fertility: current status and possible putative prospects. Hum Reprod Update 2001; 7:603 3. Tarani L, Lampariello G, Raguso F, et al: Pregnancy in patients with Turner’s syndrome: six new cases and review of the literature. Gynecol Endocrinol 1998; 12:83 4. Vockrodt L, Williams JK: A reproductive option for women with Turner’s syndrome. J Pediatr Nurs 1994; 9:321 5. Check JH, Schubert B, Chase JS: Fetal outcome of triplets in a turner mosaic. J Perinat Med 1993; 21:279 6. Foudila T, Soderstrom-Anttila V, Hovatta O: Turner’s syndrome and pregnancy after oocyte donation. Hum Reprod 1999; 14:532