特纳综合征患者生育及妊娠管理的研究进展

doi:10.3969/j.issn.1006-7795.2023.04.010

摘要/Abstract

摘要： 妊娠是特纳综合征（Turner syndrome, TS）患者的关键问题，尽管4%~7%的TS患者有自然妊娠可能，但大多数女性需要借助卵母细胞捐献和生育力保护。由于卵巢功能减退通常发生在TS患者的生命早期，且妊娠可加重TS孕产妇基础心血管疾病进展或恶化的风险，如主动脉夹层或破裂等致死性并发症。因此，TS女性应该在孕前、妊娠期间和产后接受全面的心血管评估和多学科团队管理，以确保TS女性良好的生育结果。卵巢组织冻存技术是一种具有特定益处、适应证的个性化保护策略，有可能成为TS患者保护生育能力的重要工具。本文主要综述TS患者生育及妊娠管理的研究进展。

关键词: 特纳综合征, 生育力保护, 卵巢组织冻存, 妊娠风险, 孕期监测

Abstract: Pregnancy is a key problem for patients with Turner syndrome (TS). Although 4%-7% of TS patients have the possibility of natural pregnancy, most TS patients need oocyte donation and fertility protection (FP). As premature ovarian failure generally occurs early in life of women with TS, and pregnancy can increase the risk of cardiovascular abnormalities, such as aortic dissection or rupture, these patients should be counseled and evaluated as early as possible for discussion of optimal cardiovascular assessment as well as multidisciplinary team management strategies. This supervision mode is also applicable to pre-pregnancy, pregnancy, and post-pregnancy. Ovarian tissue cryopreservation is a viable option for FP in young individuals with TS. This review summarizes the research progresses of fertility and pregnancy management for women with TS.

Key words: Turner syndrome, fertility preservation, ovarian tissue cryopreservation, pregnancy risk, pregnancy monitoring

中图分类号:

R711

赵越, 阮祥燕, 谷牧青, 程姣姣, 王月姣, 金婧. 特纳综合征患者生育及妊娠管理的研究进展[J]. 首都医科大学学报, 2023, 44(4): 561-567.

Zhao Yue, Ruan Xiangyan, Gu Muqing, Cheng Jiaojiao, Wang Yuejiao, Jin Jing. Research progresses in fertility and pregnancy management in patients with Turner syndrome[J]. Journal of Capital Medical University, 2023, 44(4): 561-567.

参考文献

［1］ Gravholt C H, Viuff M H, Brun S, et al. Turner syndrome: mechanisms and management［J］. Nat Rev Endocrinol, 2019, 15(10): 601-614.
［2］ Steiner M, Saenger P. Turner syndrome: an update［J］. Adv Pediatr, 2022, 69(1): 177-202.
［3］ Aly J, Kruszka P. Novel insights in Turner syndrome［J］. Curr Opin Pediatr, 2022, 34(4): 447-460.
［4］ Bryant P H, Jacoby D, Bunch M, et al. Turner syndrome mosaicism: challenges in identification and management in primary care［J］. J Am Assoc Nurse Pract, 2021, 34(2): 400-404.
［5］ Soares J S, Da Silva Lago R M R, Toralles M B P, et al. Searching chromosome mosaicisms in 45,X Turner syndrome: how relevant is it?［J］. Arch Endocrinol Metab, 2021, 65(6): 739-746.
［6］ Więcek M, Gawlik J, Nowak Z, et al. Questions concerning fertility preservation during transition in girls with Turner syndrome: review of the literature［J］. Endocr Connect, 2022, 11(12): e220344.
［7］ Dowlut-McElroy T, Gomez-Lobo V. Gonadectomy in individuals with Turner syndrome and Y chromosome material: fertility considerations［J］. J Pediatr Adolesc Gynecol, 2022, 35(4): 415-416.
［8］ Theroux C I, Elliott V, Davis S, et al. Fertility counseling practices for patients with Turner syndrome in pediatric endocrine clinics: results of a pediatric endocrine society survey［J］. Horm Res Paediatr, 2022, 95(4): 321-330.
［9］朱岷. Turner综合征的卵巢功能评估和激素替代治疗［J］. 中国实用儿科杂志, 2021, 36(8): 613-616.
［10］ Oktay K, Bedoschi G. Fertility preservation in girls with Turner syndrome: limitations, current success and future prospects［J］. Fertil Steril, 2019, 111(6): 1124-1126.
［11］ Whigham C A, Vollenhoven B, Vincent A J. Reproductive health in Turner syndrome: a narrative review［J］. Prenat Diagn, 2023, 43(2): 261-271.
［12］ La Marca A, Mastellari E. Fertility preservation for genetic diseases leading to premature ovarian insufficiency (POI)［J］. J Assist Reprod Genet, 2021, 38(4): 759-777.
［13］ Xie Q G, Xing Y X, Zhou J H, et al. The effect of lysophosphatidic acid-supplemented culture medium on human immature oocytes matured in vitro［J］. Reprod Biol Endocrinol, 2021, 19(1): 83.
［14］ Prakash S K, Lugo-Ruiz S, Rivera-Dávila M, et al. The Turner syndrome research registry: creating equipoise between investigators and participants［J］. Am J Med Genet C Semin Med Genet, 2019, 181(1): 135-140.
［15］ Abir R, Oron G, Shufaro Y. Fertility in patients with Turner syndrome［J］. Fertil Steril, 2020, 114(1): 73-74.
［16］ Bollig K J, Mainigi M, Senapati S, et al. Turner syndrome: fertility counselling in childhood and through the reproductive lifespan［J］. Curr Opin Endocrinol Diabetes Obes, 2023, 30(1): 16-26.
［17］ Viuff M, Gravholt C H. Turner syndrome and fertility［J］. Ann Endocrinol (Paris), 2022, 83(4): 244-249.
［18］ Calanchini M, Aye C Y L, Orchard E, et al. Fertility issues and pregnancy outcomes in Turner syndrome［J］. Fertil Steril, 2020, 114(1): 144-154.
［19］ Ye M D, Yeh J, Kosteria I, et al. Progress in fertility preservation strategies in Turner syndrome［J］. Front Med (Lausanne), 2020, 7: 3.
［20］程姣姣, 阮祥燕, 杜娟, 等. 卵巢组织冻存移植安全性的研究进展［J］. 首都医科大学学报, 2021, 42(4): 505-510.
［21］ Blakemore J K, Wei L S, Quinn G P. Addressing practical concerns surrounding fertility preservation in patients with Turner syndrome［J］. Fertil Steril, 2019, 112(4): 651-652.
［22］ Ito A, Katagiri Y, Tamaki Y, et al. DuoStim: a new option for fertility preservation for a woman with Turner syndrome［J］. Gynecol Endocrinol, 2020, 36(12): 1144-1148.
［23］ Strypstein L, Van Moer E, Nekkebroeck J, et al. First live birth after fertility preservation using vitrification of oocytes in a woman with mosaic Turner syndrome［J］. J Assist Reprod Genet, 2022, 39(2): 543-549.
［24］ Söderström-Anttila V, Pinborg A, Karnis M F, et al. Should women with Turner syndrome be allowed to carry their own pregnancies?［J］. Fertil Steril, 2019, 112(2): 220-225.
［25］ Schleedoorn M, Van Der Velden J, Braat D, et al. Turner fertility trial: PROTOCOL for an observational cohort study to describe the efficacy of ovarian tissue cryopreservation for fertility preservation in females with Turner syndrome［J］. BMJ Open, 2019, 9(12): e030855.
［26］ Mavridi A, Ntali G, Theodora M, et al. A spontaneous pregnancy in a patient with turner syndrome with 45,X/47,XXX mosaicism: a case report and review of the literature［J］. J Pediatr Adolesc Gynecol, 2018, 31(6): 651-654.
［27］ Schleedoorn M J, Fleischer K, Braat D, et al. Why turner patients with 45, X monosomy should not be excluded from fertility preservation services［J］. Reprod Biol Endocrinol, 2022, 20(1): 143.
［28］ Nordenström A, Ahmed S F, Van Den Akker E, et al. Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline［J］. Eur J Endocrinol, 2022, 186(6): G9-G49.
［29］ Ulrich N D, Raja N, Ellman E, et al. Outcomes of fertility preservation consults for women at risk for primary ovarian insufficiency due to history of cancer treatment or mosaic Turner syndrome［J］. J Adolesc Young Adult Oncol, 2022, 11(4): 427-432.
［30］ Nadesapillai S, Van Der Velden J, Braat D, et al. The challenge of defining predictive parameters for fertility preservation counseling in young females with Turner syndrome［J］. Acta Obstet Gynecol Scand, 2021, 100(6): 1155-1156.
［31］ Schleedoorn M J, Van Der Velden A A E M, Braat D D M, et al. To freeze or not to freeze? An update on fertility preservation in females with Turner syndrome［J］. Pediatr Endocrinol Rev, 2019, 16(3): 369-382.
［32］中国人体健康科技促进会生育力保护与保存专业委员会. 特纳综合征中国专家共识(2022年版)［J］. 中国实用妇科与产科杂志, 2022, 38(4): 424-433.
［33］ Cheng J J, Ruan X Y, Du J, et al. Ovarian tissue cryopreservation for a 3-year-old girl with mosaic Turner syndrome in China: first case report and literature review［J］. Front Endocrinol (Lausanne), 2022, 13: 959912.
［34］ Arapaki A, Christopoulos P, Kalampokas E, et al. Ovarian tissue cryopreservation in children and adolescents［J］. Children (Basel), 2022, 9(8): 1256.
［35］ Mamsen L S, Charkiewicz K, Anderson R A, et al. Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation［J］. Fertil Steril, 2019, 111(6): 1217-1225.e3.
［36］ Ladjouze A, Donaldson M. Primary gonadal failure［J］. Best Pract Res Clin Endocrinol Metab, 2019, 33(3): 101295.
［37］ Cadenas J, Nikiforov D, Pors S E, et al. A threshold concentration of FSH is needed during IVM of ex vivo collected human oocytes［J］. J Assist Reprod Genet, 2021, 38(6): 1341-1348.
［38］ Dowlut-McElroy T, Shankar R K. The care of adolescents and young adults with Turner syndrome: a pediatric and adolescent gynecology perspective［J］. J Pediatr Adolesc Gynecol, 2022, 35(4): 429-434.
［39］ Schleedoorn M J, Mulder B H, Braat D D M, et al. International consensus: ovarian tissue cryopreservation in young Turner syndrome patients: outcomes of an ethical Delphi study including 55 experts from 16 different countries［J］. Hum Reprod, 2020, 35(5): 1061-1072.
［40］ Donadille B, Christin-Maitre S. Heart and Turner syndrome［J］. Ann Endocrinol (Paris), 2021, 82(3/4): 135-140.
［41］ Cauldwell M, Steer P J, Adamson D, et al. Pregnancies in women with Turner syndrome: a retrospective multicentre UK study［J］. BJOG, 2022, 129(5): 796-803.
［42］ Dowlut-McElroy T, Davis S, Howell S, et al. Cell-free DNA screening positive for monosomy X: clinical evaluation and management of suspected maternal or fetal Turner syndrome［J］. Am J Obstet Gynecol, 2022, 227(6): 862-870.
［43］ Obata S, Tsuburai T, Shindo R, et al. Current situation and outcomes of pregnancy in women with Turner syndrome in Japan［J］. J Obstet Gynaecol Res, 2020, 46(9): 1728-1734.
［44］ Thunström S, Krantz E, Thunstrm E, et al. Incidence of aortic dissection in Turner syndrome［J］. Circulation, 2019, 139(24): 2802-2804.
［45］ Rodriguez-Wallberg K A, Landin-Wilhelmsen K. The complexity of fertility preservation for women with Turner syndrome and the potential risks of pregnancy and cardiovascular complications［J］. Acta Obstet Gynecol Scand, 2020, 99(12): 1577-1578.
［46］ Lin A, Rajagopalan A, Nguyen H H, et al. Dilatation of the ascending aorta in Turner syndrome: influence of bicuspid aortic valve morphology and body composition［J］. Heart Lung Circ, 2021, 30(1): e29-e36.
［47］ Grewal J, Valente A M, Egbe A C, et al. Cardiovascular outcomes of pregnancy in Turner syndrome［J］. Heart, 2021, 107(1): 61-66.
［48］ Bernard V, Donadille B, Zenaty D, et al. Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome［J］. Hum Reprod, 2016, 31(4): 782-788.
［49］ Van Der Coelen S, Van Der Velden J, Nadesapillai S, et al. The decision-making process regarding ovarian tissue cryopreservation in girls with Turner syndrome by patients, parents, and healthcare providers: a mixed-methods study［J］. Horm Res Paediatr, 2022, 95(4): 374-383.
［50］ Donadille B, Bernard V, Christin-Maitre S. How can we make pregnancy safe for women with Turner syndrome?［J］. Am J Med Genet C Semin Med Genet, 2019, 181(1): 100-107.
［51］ Kostopoulou E, Bosdou J K, Anagnostis P, et al. Cardiovascular complications in patients with Turner's syndrome［J］. Curr Pharm Des, 2020, 26(43): 5650-5659.
［52］ Shin J Y, Kim B H, Kim Y K, et al. Pheochromocytoma as a rare cause of hypertension in a 46 X, i(X)(q10) Turner syndrome: a case report and literature review［J］. BMC Endocr Disord, 2018, 18(1): 27.
［53］ Uçar A, Wong J S C, Darendeliler F, et al. Editorial: hot topics of debate on Turner syndrome: growth, puberty, cardiovascular risks, fertility and psychosocial development［J］. Front Endocrinol (Lausanne), 2019, 10: 644.
［54］ Vergier J, Bottin P, Saias J, et al. Fertility preservation in Turner syndrome: karyotype does not predict ovarian response to stimulation［J］. Clin Endocrinol (Oxf), 2019, 91(5): 646-651.
［55］ Borini A, Coticchio G. Importance of early and precise ascertainment of mosaic Turner syndrome for fertility preservation and assisted reproduction counseling［J］. Fertil Steril, 2020, 114(2): 269-270.
［56］ Bouet P E, Godbout A, El Hachem H, et al. Fertility and pregnancy in Turner syndrome［J］. J Obstet Gynaecol Can, 2016, 38(8): 712-718.
［57］ Burt E, Davies M C, Yasmin E, et al. Reduced uterine volume after induction of puberty in women with hypogonadism［J］. Clin Endocrinol (Oxf), 2019, 91(6): 798-804.
［58］ Morgan T L, Kapa H M, Crerand C E, et al. Fertility counseling and preservation discussions for females with Turner syndrome in pediatric centers: practice patterns and predictors［J］. Fertil Steril, 2019, 112(4): 740-748.
［59］ Nawroth F, Schüring A N, Von Wolff M. The indication for fertility preservation in women with Turner syndrome should not only be based on the ovarian reserve but also on the genotype and expected future health status［J］. Acta Obstet Gynecol Scand, 2020, 99(12): 1579-1583.
［60］ Gravholt C H, Andersen N H, Conway G S, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting［J］. Eur J Endocrinol, 2017, 177(3): G1-G70.
［61］ Fiot E, Alauze B, Donadille B, et al. Turner syndrome: French National Diagnosis and Care Protocol (NDCP; National Diagnosis and Care Protocol)［J］. Orphanet J Rare Dis, 2022, 17(Suppl 1): 261.

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