- Email: [email protected]
Pregnancy rate and outcome in Swedish women with Turner syndrome
Pregnancy rate and outcome in Swedish women with Turner syndrome Pregnancies occurred in 57 (12%) of 482 Swedish women with Turner syndrome with a liveborn rate of 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40%, mainly in women with 45,X/46,XX mosaicism, and oocyte donation in 53% where miscarriages were less frequent, odds ratio ¼ 0.43 (95% confidence interval 0.17–1.04). (Fertil Steril 2011;95:2507–10. 2011 by American Society for Reproductive Medicine.) Key Words: Turner syndrome, pregnancy, oocyte donation, liveborn rate, pregnancy outcome, aortic dissection
Turner syndrome (TS) is a chromosomal aberration with a total or partial loss of one of the two sex chromosomes. Turner syndrome occurs in approximately 1 in 2,500 girls (1). The classic features are short stature and ovarian insufficiency due to ovarian dysgenesis. Inger Bryman, M.D., Ph.D.a Lisskulla Sylven, M.D., Ph.D.b Kerstin Berntorp, M.D., Ph.D.c Eva Innala, M.D., Ph.D.d Ingrid Bergstr€om, M.D., Ph.D.e Charles Hanson, Ph.D.a Marianne Oxholm, M.D.f Kerstin Landin-Wilhelmsen, M.D., Ph.D.g a Unit of Clinical Sciences, Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden b Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden c Department of Endocrinology, Sk ane University Hospital, Malm€o, Sweden d Department of Gynecology, Ume a University Hospital, Ume a, Sweden e Division of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Huddinge, Sweden f € Women’s Hospital, Northern Regional Hospital of Alvsborg, Trollh€attan, Sweden g Section for Endocrinology, Department of Medicine, Sahlgrenska University Hospital at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Received September 1, 2010; revised December 17, 2010; accepted December 20, 2010; published online January 22, 2011. I.B. has nothing to disclose. L.S. has nothing to disclose. K.B. has nothing to disclose. E.I. has nothing to disclose. I.B. has nothing to disclose. C.H. has nothing to disclose. M.O. has nothing to disclose. K.L-W. has nothing to disclose. Supported by grants from the Swedish Board of Health and Welfare; Swedish Heart Lung Foundation; the Faculty of Medicine, University €stra of Gothenburg; the Health and Medical Care Committee of the Va € taland Region; the Gothenburg Medical Association; and the Go Swedish Council for Working Life and Social Research. Reprint requests: Inger Bryman, M.D., Ph.D., Reproductive Medicine, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden (E-mail: [email protected]).
0015-0282/$36.00 doi:10.1016/j.fertnstert.2010.12.039
Spontaneous puberty appears in 5% to 10% of girls with TS, and spontaneous pregnancies have been reported in 2% to 5% (2). Oocyte donation has made it possible for many women with TS to become pregnant (3). Recent reports on serious cardiac events, especially aortic dissection, in 2% of women with TS during pregnancy (4, 5) have raised questions whether pregnancy induction in TS is to be recommended at all. The aim was to report pregnancy rate and pregnancy outcome from the Swedish Turner Centers, in relation to karyotype, as well as morbidity in the mothers and children. Turner Centers are established at five university hospitals in Sweden. The patients were recruited via a letter to all chief gynecologists and endocrinologists in Sweden or were already known patients at the hospitals. The women with TS were invited in 1993 to participate in a voluntary screening program with examination by a gynecologist and an endocrinologist, and 482 women with TS have been examined since then. The patients have been followed according to the Swedish national guidelines for care and treatment of TS in line with the established international guidelines (6). The cytogenetic karyotype was analyzed on leukocytes cultured from human peripheral blood. A minimum of 10 metaphases was accepted though most karyotypes consisted of 30 or more metaphases. More than 5% 46,XX cells was defined as mosaicism (7, 8). Institutional Review Board approval was obtained. The national study was approved by the Ethics Committee at the University of Gothenburg, and all participants gave their informed consent. Human rights were respected in accordance with the Helsinki Declaration. Means and medians were calculated with conventional methods. The c2 test was used for comparisons between groups, and odds ratio and 95% confidence limits were shown. A P value < .05 was considered statistically significant. Among women with TS, 57 of 482 (12%) had had 124 pregnancies compared with a 74% birth rate in the general female population of similar age (9). There were 67 deliveries resulting in 68 children born. One set of twins was born after IVF treatment (Table 1). Spontaneous pregnancies had occurred in 23 of 57 women (40%), IVF in 3 (5%), and insemination in 1 (2%); of these, 27 (47%) used the patient’s own oocytes and oocyte donation was
Fertility and Sterility Vol. 95, No. 8, June 30, 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
2507
TABLE 1 Background data and pregnancy outcome in women with TS. Characteristic Background data No. of women Spontaneous pregnancy (n) IVF (n) Insemination (n) Age, y, median (range) Marital status, n (%) Married/cohabitant Socioeconomic status, n (%) Student Employed Unemployed Chromosomal constitution, n (%) 45,X 45,X/46,XX Y Iso, ring, trisomy X Pregnancy outcome No. of pregnancies Delivery, n (%) (liveborn rate) Liveborn children (n) Miscarriage, n (%) Legal abortion, n (%) Extrauterine pregnancy, n (%) a
Own oocytes
Oocyte donation
All TS
27 23 3 1 27 (16–42)
30
57
37 (24–44)
32 (16–44)
27 (100)
30 (100)
57 (100)
5 (18) 22 (82) 0 (0)
9 (30) 20 (67) 1 (3)
14 (24) 42 (74) 1 (2)
1 (4) 25 (92) 1 (4) 0
16 (53) 2 (7) 3 (10) 9 (30)
17 (30) 27 (47) 4 (7) 9 (16)
82 36a (44) 37 37 (45) 8 (10) 1 (1)
42 31 (74) 31 11 (26) 0 0
124 67 (54) 68 48 (39) 8 (7) 1 (1)
One set of twins.
Bryman. Correspondence. Fertil Steril 2011.
used in 30 (53%) of the 57 pregnant women with TS. Most pregnancies with own oocytes occurred in TS with 45,X/46,XX mosaic karyotype.
(37%) were delivered vaginally, and after oocyte donation 3 of 30 (10%) by Ventouse and 3 of 33 (10%) vaginally.
The miscarriage rate was lower among women with TS with oocyte donation, 26%, versus spontaneous pregnancies, IVF, and insemination, that is, with own oocytes, 45% (odds ratio ¼ 0.43, 95% confidence limits 0.17–1.04, P¼.04) (Table 1).
Of all 68 children born, five (7%) had a birth defect or a serious illness. These were cerebral paresis (n ¼ 1), neuropsychological disorder (n ¼ 1), coarctation of the aorta (n ¼ 1), cleft lip and palate (n ¼ 1), and congenital tumor (n ¼ 1). Four of these five children were born after spontaneous pregnancies.
Six of the 57 pregnant women with TS had eight legal abortions. Two were advised legal abortion because of their TS diagnosis, two already had two children each, and two did not know that they had TS at the time of legal abortion.
Among this fairly large cohort of 482 Swedish women with TS 57 (12%) had been pregnant including spontaneous, IVF, insemination, and oocyte donation pregnancies. The liveborn rate was 67 of 124 (54%).
One woman with TS, 38 years old, with a Y-chromosome fragment and with two spontaneous pregnancies, had aortic dissection during the seventh month of the second pregnancy. The child was delivered with an acute cesarean section and the mother was later operated on and survived. She turned out to have coarctation of the aorta as well. Her TS diagnosis was not known before pregnancy (10). Three women (5%) had gestational diabetes, and one of them was given treatment with insulin during pregnancy. Three women (5%) had pregnancy-induced hypertension. The corresponding figures in the population are 1% and 8%, respectively. One woman with TS had kidney transplantation 7 years before the pregnancy, and the procedure was uncomplicated.
Previously, mostly older, studies have reported spontaneous pregnancy rates of approximately 2% of women with TS. There are reports on spontaneous pregnancies in women with TS with a 45,X karyotype (11, 12) and even in a woman with Turner syndrome with an apparently intact Y chromosome (10). However, some studies imply predominance among women with a 45,X/46,XX mosaic karyotype (13, 14).
After pregnancy with own oocytes 17 of 27 (63%) were delivered by cesarean section versus 24 of 30 (80%) after oocyte donation (not significant). The cesarean section rate is 16% in the Swedish population. In pregnancies with own oocytes 10 of 27
2508
Bryman et al.
Correspondence
The present study confirms the finding of more women with TS with mosaicism being pregnant, but the difference between women with TS with mosaicism and monosomy has decreased from earlier reports (4, 14) mainly because of oocyte donation treatment. However, according to previous results (15), women with TS with 45,X karyotype may also have follicles and can get spontaneously pregnant. This might indicate that there are genetic factors, genes, or alleles on the autosomal genes, which can compensate for the deletion of a sex chromosome. Another explanation may be
Vol. 95, No. 8, June 30, 2011
a difference in karyotype in ovaries and peripheral blood. The karyotype was presented in four groups as 45,X, true 45,X/46,XX mosaicism, Y-fragment, and iso, ring, trisomy X in a separate group because of more similarities with the 45,X karyotype (8). A cutoff limit of >5% was used for definition of a low-grade mosaicism (7, 8). In comparison with earlier studies (11, 12), we found a higher frequency of spontaneous pregnancies, which might be explained by a greater percentage of patients with a true mosaicism. The mosaics were often diagnosed during infertility investigations or after recurrent miscarriages. Oocyte donation is an option for women with TS with infertility and has been available in Sweden since 2003. One third of the patients with TS applied for oocyte donation abroad before that time. Of the women with TS who became pregnant with their own oocytes, 45% of the pregnancies ended in a miscarriage, which was in the same range as earlier reported (16, 17). After oocyte donation a higher frequency of miscarriages, up to 50%, has been reported (18), which has been attributed to hypoplastic uterus and/ or possible low uterine blood flow (17). In our study, however, only 26% had miscarriage after oocyte donation. This low frequency supports that an oocyte factor may be an explanation for the high frequency of miscarriage in women with TS with their own oocytes. Birth defect or not healthy child occurred in 5 of 68 (7%) of the children in our study. Both chromosomal aberrations and major and minor birth defects have been reported earlier. Tarani et al. (3) reported birth defects in 20% of children born after spontaneous pregnancies in women with TS. Transmission of the Turner syndrome per se from mother to daughter, as well as Down syndrome, has been found in offspring after spontaneous pregnancies in TS (19). Karyotyping of the children in the present study was not performed regularly. Consequently, we do not know whether any of the reported birth defects were due to chromosomal aberrations. Cesarean section was performed frequently in TS. Besides a general precaution the short stature predisposes for disproportion
of the pelvis, and therefore cesarean section has been taken into consideration (14, 18). Complication rate (diabetes, hypertension) was 10%, but higher complication rates have been reported for oocyte donation in TS (20). Of greatest concern is the high risk for aortic dissection during pregnancy in TS. Recommendations regarding pregnancy in TS have been stated by the American Society for Reproductive Medicine (5). Recently, a case report described a woman with TS with a Y-fragment who passed an oocyte donation but died because of acute aortic dissection in the 38th week of the pregnancy (21). In retrospect, she had a bicuspid aortic valve, which might have predisposed her dissection (21–23). Maternal death in aortic dissection during pregnancy in TS was 86% (23). The only patient with TS who survived in that review from the literature was our case (10). One limitation of the present study was that karyotyping was not performed in the offspring of the women with TS. However, this is an ethical problem and difficult to handle in case of a finding of a chromosomal aberration in the newborn infant. A strength was the fairly large cohort of women with TS. All were well characterized and monitored during at least 15 years at our Turner Centers in Sweden. In conclusion, pregnancies occurred in 57 (12%) in this Swedish survey of 482 women with TS. Liveborn rate was 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40% of the women, mainly in those with 45,X/46,XX mosaics. Miscarriages were less frequent after oocyte donation. A thorough cardiac evaluation is important before pregnancy is planned in TS because of the risk for aortic dissection. Acknowledgments: The excellent help from Christina Larsson, R.N., and Gunilla Borg, R.N. in coordinating the patients and examinations is gratefully acknowledged. Eva Ekerstad, M.D., Elisabeth Almstr€om, Trollh€attan, M.D., M arten Torle, M.D., H akan Widell, Bor as, M.D., Lars Hogstr€om, M.D., and Erik Almqvist, Sk€ovde, M.D., Ph.D., are gratefully acknowledged.
REFERENCES 1. Sylven L, Hagenfeldt K, Brondum-Nielsen K, von Schoultz B. Middle-aged women with Turner’s syndrome. Medical status, hormonal treatment and social life. Acta Endocrinol 1991;125:359–65. 2. Hovatta O. Pregnancies in women with Turner’s syndrome. Ann Med 1999;31:106–10. 3. Tarani L, Lampariello S, Raguso G, Colloridi F, Pucarelli I, Pasquino AM, et al. Pregnancy in patients with Turner’s syndrome: six new cases and review of literature. Gynecol Endocrinol 1998;12:83–7. 4. Karnis MF, Zimon AE, Lalwani SI, Timmreck LS, Klipstein S, Reindollar RH. Risk of death in pregnancy achieved through oocyte donation in patients with Turner syndrome: a national survey. Fertil Steril 2003;88:498–501. 5. The Practice Committee of the American Society for Reproductive Medicine. Increased maternal cardiovascular mortality associated with pregnancy in women with Turner syndrome. Fertil Steril 2008;90:185–6. 6. Bondy CA for the Turner Syndrome Consensus Study Group. Clinical Practice Guideline. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab 2007;92:10–25.
Fertility and Sterility
7. Hanson L, Bryman I, Barren€as M-L, Janson PO, Wahlstr€om J, Albertsson-Wikland K, et al. Genetic analysis of mosaicism in 53 women with Turner syndrome. Hereditas 2001;134: 153–9. 8. El-Mansoury M, Barren€as M-L, Bryman I, Hanson C, Larsson C, Wilhelmsen L, et al. Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome. Clin Endocrinol (Oxf) 2007;66: 744–51. 9. Amundson E, Wide Boman U, Barren€as M-L, Bryman I, Landin-Wilhelmsen K. Impact of growth hormone therapy on quality of life in adults with Turner syndrome. J Clin Endocrinol Metab 2010;95:1355–9. 10. Landin-Wilhelmsen K, Bryman I, Hanson C, Hanson L. Spontaneous pregnancies in a Turner syndrome woman with Y-chromosome mosaicism. J Assist Reprod Genet 2004;21:229–30. 11. Swapp GH, Johnston AW, Watt JL, Couzin DA, Stephen GS. A fertile woman with non-mosaic Turner’s syndrome. Case report and review of the literature. Br J Obstet Gynaecol 1989;96: 876–80.
12. Cools M, Rooman RP, Wauters J, Jacqemyn Y, Du Caju MV. A nonmosaic 45,X karyotype in a mother with Turner’s syndrome and in her daughter. Fertil Steril 2004;82:923–5. 13. Bryman I, Landin-Wilhelmsen K, Innala E, Simberg N, Sylven L, Windh M. Pregnancies in Swedish Turner Women. Proceedings of the Fifth International Turner Symposium, Optimizing Health Care for Patients in the 21st Century; 2000 March 23–25; Naples, Italy:D4. 14. Birkebaek NH, Cr€uger D, Hansen J, Nielsen J, Bruun-Petersen G. Fertility and pregnancy outcome in Danish women with Turner syndrome. Clin Genet 2002;61:35–9. 15. Hreinsson JG, Otala M, Fridstr€om M, Borgstr€om B, Rasmussen C, Lundqvist M, et al. Follicles are found in the ovaries of adolescent girls with Turner’s syndrome. J Clin Endocrinol Metab 2002;87:3618–23. 16. Yaron Y, Ochshorn Y, Amit A, Yovel I, Kogosowski A, Lessing JB. Patients with Turner’s syndrome may have an inherent endometrial abnormality affecting receptivity in oocyte donation. Fertil Steril 1996;65:1249–52.
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17. Khastgir G, Abdalla H, Thomas A, Korea L, Latarche L, Studd J. Oocyte donation in Turner’s syndrome: an analysis of the factors affecting the outcome. Hum Reprod 1997;12:279–85. 18. Foudila T, S€ oderstr€ om-Anttila V, Hovatta O. Turner’s syndrome and pregnancies after oocyte donation. Hum Reprod 1999;14:532–5. 19. Blumenthal AL, Allanson JE. Turner syndrome in a mother and daughter: r(X) and fertility. Clin Genet 1997;52:187–91.
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Correspondence
20. Bodri D, Vernaeve V, Figueras F, Vidal R, Guillen JJ, Coll O. Oocyte donation in patients with Turner’s syndrome: a successful technique but with an accompanying high risk of hypertensive disorders during pregnancy. Hum Reprod 2006;21:829–32. 21. Boissonnas CC, Davy C, Bornes M, Arnaout L, Meune C, Tsatsatris V, et al. Careful cardiovascular screening and follow-up of women
with Turner syndrome before and during pregnancy is necessary to prevent maternal mortality. Fertil Steril 2009;91:5–7. 22. Gravholt CH, Landin-Wilhelmsen K, Stochholm K, Hjerrild BE, Ledet T, Djurhuus CB, et al. Aortic dissection in Turner syndrome. Cardiol Young 2006;16:430–6. 23. Carlsson M, Silberbach M. Dissection of the aorta in Turner syndrome: two cases and review of 85 cases in the literature. J Med Genet 2007;44:745–9.
Vol. 95, No. 8, June 30, 2011
Turner syndrome (TS) is a chromosomal aberration with a total or partial loss of one of the two sex chromosomes. Turner syndrome occurs in approximately 1 in 2,500 girls (1). The classic features are short stature and ovarian insufficiency due to ovarian dysgenesis. Inger Bryman, M.D., Ph.D.a Lisskulla Sylven, M.D., Ph.D.b Kerstin Berntorp, M.D., Ph.D.c Eva Innala, M.D., Ph.D.d Ingrid Bergstr€om, M.D., Ph.D.e Charles Hanson, Ph.D.a Marianne Oxholm, M.D.f Kerstin Landin-Wilhelmsen, M.D., Ph.D.g a Unit of Clinical Sciences, Department of Obstetrics and Gynecology, Sahlgrenska University Hospital, Gothenburg, Sweden b Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm, Sweden c Department of Endocrinology, Sk ane University Hospital, Malm€o, Sweden d Department of Gynecology, Ume a University Hospital, Ume a, Sweden e Division of Endocrinology, Metabolism, and Diabetes, Karolinska University Hospital, Huddinge, Sweden f € Women’s Hospital, Northern Regional Hospital of Alvsborg, Trollh€attan, Sweden g Section for Endocrinology, Department of Medicine, Sahlgrenska University Hospital at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden Received September 1, 2010; revised December 17, 2010; accepted December 20, 2010; published online January 22, 2011. I.B. has nothing to disclose. L.S. has nothing to disclose. K.B. has nothing to disclose. E.I. has nothing to disclose. I.B. has nothing to disclose. C.H. has nothing to disclose. M.O. has nothing to disclose. K.L-W. has nothing to disclose. Supported by grants from the Swedish Board of Health and Welfare; Swedish Heart Lung Foundation; the Faculty of Medicine, University €stra of Gothenburg; the Health and Medical Care Committee of the Va € taland Region; the Gothenburg Medical Association; and the Go Swedish Council for Working Life and Social Research. Reprint requests: Inger Bryman, M.D., Ph.D., Reproductive Medicine, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden (E-mail: [email protected]).
0015-0282/$36.00 doi:10.1016/j.fertnstert.2010.12.039
Spontaneous puberty appears in 5% to 10% of girls with TS, and spontaneous pregnancies have been reported in 2% to 5% (2). Oocyte donation has made it possible for many women with TS to become pregnant (3). Recent reports on serious cardiac events, especially aortic dissection, in 2% of women with TS during pregnancy (4, 5) have raised questions whether pregnancy induction in TS is to be recommended at all. The aim was to report pregnancy rate and pregnancy outcome from the Swedish Turner Centers, in relation to karyotype, as well as morbidity in the mothers and children. Turner Centers are established at five university hospitals in Sweden. The patients were recruited via a letter to all chief gynecologists and endocrinologists in Sweden or were already known patients at the hospitals. The women with TS were invited in 1993 to participate in a voluntary screening program with examination by a gynecologist and an endocrinologist, and 482 women with TS have been examined since then. The patients have been followed according to the Swedish national guidelines for care and treatment of TS in line with the established international guidelines (6). The cytogenetic karyotype was analyzed on leukocytes cultured from human peripheral blood. A minimum of 10 metaphases was accepted though most karyotypes consisted of 30 or more metaphases. More than 5% 46,XX cells was defined as mosaicism (7, 8). Institutional Review Board approval was obtained. The national study was approved by the Ethics Committee at the University of Gothenburg, and all participants gave their informed consent. Human rights were respected in accordance with the Helsinki Declaration. Means and medians were calculated with conventional methods. The c2 test was used for comparisons between groups, and odds ratio and 95% confidence limits were shown. A P value < .05 was considered statistically significant. Among women with TS, 57 of 482 (12%) had had 124 pregnancies compared with a 74% birth rate in the general female population of similar age (9). There were 67 deliveries resulting in 68 children born. One set of twins was born after IVF treatment (Table 1). Spontaneous pregnancies had occurred in 23 of 57 women (40%), IVF in 3 (5%), and insemination in 1 (2%); of these, 27 (47%) used the patient’s own oocytes and oocyte donation was
Fertility and Sterility Vol. 95, No. 8, June 30, 2011 Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.
2507
TABLE 1 Background data and pregnancy outcome in women with TS. Characteristic Background data No. of women Spontaneous pregnancy (n) IVF (n) Insemination (n) Age, y, median (range) Marital status, n (%) Married/cohabitant Socioeconomic status, n (%) Student Employed Unemployed Chromosomal constitution, n (%) 45,X 45,X/46,XX Y Iso, ring, trisomy X Pregnancy outcome No. of pregnancies Delivery, n (%) (liveborn rate) Liveborn children (n) Miscarriage, n (%) Legal abortion, n (%) Extrauterine pregnancy, n (%) a
Own oocytes
Oocyte donation
All TS
27 23 3 1 27 (16–42)
30
57
37 (24–44)
32 (16–44)
27 (100)
30 (100)
57 (100)
5 (18) 22 (82) 0 (0)
9 (30) 20 (67) 1 (3)
14 (24) 42 (74) 1 (2)
1 (4) 25 (92) 1 (4) 0
16 (53) 2 (7) 3 (10) 9 (30)
17 (30) 27 (47) 4 (7) 9 (16)
82 36a (44) 37 37 (45) 8 (10) 1 (1)
42 31 (74) 31 11 (26) 0 0
124 67 (54) 68 48 (39) 8 (7) 1 (1)
One set of twins.
Bryman. Correspondence. Fertil Steril 2011.
used in 30 (53%) of the 57 pregnant women with TS. Most pregnancies with own oocytes occurred in TS with 45,X/46,XX mosaic karyotype.
(37%) were delivered vaginally, and after oocyte donation 3 of 30 (10%) by Ventouse and 3 of 33 (10%) vaginally.
The miscarriage rate was lower among women with TS with oocyte donation, 26%, versus spontaneous pregnancies, IVF, and insemination, that is, with own oocytes, 45% (odds ratio ¼ 0.43, 95% confidence limits 0.17–1.04, P¼.04) (Table 1).
Of all 68 children born, five (7%) had a birth defect or a serious illness. These were cerebral paresis (n ¼ 1), neuropsychological disorder (n ¼ 1), coarctation of the aorta (n ¼ 1), cleft lip and palate (n ¼ 1), and congenital tumor (n ¼ 1). Four of these five children were born after spontaneous pregnancies.
Six of the 57 pregnant women with TS had eight legal abortions. Two were advised legal abortion because of their TS diagnosis, two already had two children each, and two did not know that they had TS at the time of legal abortion.
Among this fairly large cohort of 482 Swedish women with TS 57 (12%) had been pregnant including spontaneous, IVF, insemination, and oocyte donation pregnancies. The liveborn rate was 67 of 124 (54%).
One woman with TS, 38 years old, with a Y-chromosome fragment and with two spontaneous pregnancies, had aortic dissection during the seventh month of the second pregnancy. The child was delivered with an acute cesarean section and the mother was later operated on and survived. She turned out to have coarctation of the aorta as well. Her TS diagnosis was not known before pregnancy (10). Three women (5%) had gestational diabetes, and one of them was given treatment with insulin during pregnancy. Three women (5%) had pregnancy-induced hypertension. The corresponding figures in the population are 1% and 8%, respectively. One woman with TS had kidney transplantation 7 years before the pregnancy, and the procedure was uncomplicated.
Previously, mostly older, studies have reported spontaneous pregnancy rates of approximately 2% of women with TS. There are reports on spontaneous pregnancies in women with TS with a 45,X karyotype (11, 12) and even in a woman with Turner syndrome with an apparently intact Y chromosome (10). However, some studies imply predominance among women with a 45,X/46,XX mosaic karyotype (13, 14).
After pregnancy with own oocytes 17 of 27 (63%) were delivered by cesarean section versus 24 of 30 (80%) after oocyte donation (not significant). The cesarean section rate is 16% in the Swedish population. In pregnancies with own oocytes 10 of 27
2508
Bryman et al.
Correspondence
The present study confirms the finding of more women with TS with mosaicism being pregnant, but the difference between women with TS with mosaicism and monosomy has decreased from earlier reports (4, 14) mainly because of oocyte donation treatment. However, according to previous results (15), women with TS with 45,X karyotype may also have follicles and can get spontaneously pregnant. This might indicate that there are genetic factors, genes, or alleles on the autosomal genes, which can compensate for the deletion of a sex chromosome. Another explanation may be
Vol. 95, No. 8, June 30, 2011
a difference in karyotype in ovaries and peripheral blood. The karyotype was presented in four groups as 45,X, true 45,X/46,XX mosaicism, Y-fragment, and iso, ring, trisomy X in a separate group because of more similarities with the 45,X karyotype (8). A cutoff limit of >5% was used for definition of a low-grade mosaicism (7, 8). In comparison with earlier studies (11, 12), we found a higher frequency of spontaneous pregnancies, which might be explained by a greater percentage of patients with a true mosaicism. The mosaics were often diagnosed during infertility investigations or after recurrent miscarriages. Oocyte donation is an option for women with TS with infertility and has been available in Sweden since 2003. One third of the patients with TS applied for oocyte donation abroad before that time. Of the women with TS who became pregnant with their own oocytes, 45% of the pregnancies ended in a miscarriage, which was in the same range as earlier reported (16, 17). After oocyte donation a higher frequency of miscarriages, up to 50%, has been reported (18), which has been attributed to hypoplastic uterus and/ or possible low uterine blood flow (17). In our study, however, only 26% had miscarriage after oocyte donation. This low frequency supports that an oocyte factor may be an explanation for the high frequency of miscarriage in women with TS with their own oocytes. Birth defect or not healthy child occurred in 5 of 68 (7%) of the children in our study. Both chromosomal aberrations and major and minor birth defects have been reported earlier. Tarani et al. (3) reported birth defects in 20% of children born after spontaneous pregnancies in women with TS. Transmission of the Turner syndrome per se from mother to daughter, as well as Down syndrome, has been found in offspring after spontaneous pregnancies in TS (19). Karyotyping of the children in the present study was not performed regularly. Consequently, we do not know whether any of the reported birth defects were due to chromosomal aberrations. Cesarean section was performed frequently in TS. Besides a general precaution the short stature predisposes for disproportion
of the pelvis, and therefore cesarean section has been taken into consideration (14, 18). Complication rate (diabetes, hypertension) was 10%, but higher complication rates have been reported for oocyte donation in TS (20). Of greatest concern is the high risk for aortic dissection during pregnancy in TS. Recommendations regarding pregnancy in TS have been stated by the American Society for Reproductive Medicine (5). Recently, a case report described a woman with TS with a Y-fragment who passed an oocyte donation but died because of acute aortic dissection in the 38th week of the pregnancy (21). In retrospect, she had a bicuspid aortic valve, which might have predisposed her dissection (21–23). Maternal death in aortic dissection during pregnancy in TS was 86% (23). The only patient with TS who survived in that review from the literature was our case (10). One limitation of the present study was that karyotyping was not performed in the offspring of the women with TS. However, this is an ethical problem and difficult to handle in case of a finding of a chromosomal aberration in the newborn infant. A strength was the fairly large cohort of women with TS. All were well characterized and monitored during at least 15 years at our Turner Centers in Sweden. In conclusion, pregnancies occurred in 57 (12%) in this Swedish survey of 482 women with TS. Liveborn rate was 54% in 124 pregnancies. Spontaneous pregnancies occurred in 40% of the women, mainly in those with 45,X/46,XX mosaics. Miscarriages were less frequent after oocyte donation. A thorough cardiac evaluation is important before pregnancy is planned in TS because of the risk for aortic dissection. Acknowledgments: The excellent help from Christina Larsson, R.N., and Gunilla Borg, R.N. in coordinating the patients and examinations is gratefully acknowledged. Eva Ekerstad, M.D., Elisabeth Almstr€om, Trollh€attan, M.D., M arten Torle, M.D., H akan Widell, Bor as, M.D., Lars Hogstr€om, M.D., and Erik Almqvist, Sk€ovde, M.D., Ph.D., are gratefully acknowledged.
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Vol. 95, No. 8, June 30, 2011