Navigating Fertility Dilemmas Across the Lifespan in Girls with Turner Syndrome-a Scoping Review

Overview

Journal Hum Reprod Update

Specialty Reproductive Medicine

Date 2024 Mar 7

PMID 38452347

Authors

Sanne van der Coelen

Janielle van der Velden

Sapthami Nadesapillai

Didi Braat

Ronald Peek

Kathrin Fleischer

Affiliations

Soon will be listed here.

Abstract

Background: Girls with Turner syndrome (TS) lack a partial or complete sex chromosome, which causes an accelerated decline of their ovarian reserve. Girls have to deal with several dilemmas related to their fertility, while only a limited number of them are referred to a fertility specialist and counselled about options of family planning on time.

Objective And Rationale: This scoping review provides an update of the literature on fertility in girls with TS throughout their lifespan and aims to propose a clinical practice guideline on fertility in TS.

Search Methods: Databases of PubMed, Embase, and Web of science were searched using the following key terms: Turner syndrome, fertility, puberty, pregnancy, sex-hormones, karyotype, fertility preservation, assisted reproductive techniques, and counselling, alongside relevant subject headings and synonymous terms. English language articles published since 2007 were critically reviewed. Pregnancies after using donated oocytes and data about girls with TS with Y-chromosomal content were excluded.

Outcomes: This search identified 1269 studies of which 120 were extracted for the review. The prevalence of natural conception ranged from 15% to 48% in women with 45,X/46,XX, 1% to 3% in women with 45,X, and 4% to 9% in women with other TS karyotypes. When assessing a girl's fertility potential, it was crucial to determine the karyotype in two cell lines, because hidden mosaicism may exist. In addition to karyotype, assessment of anti-Müllerian hormone (AMH) played a significant role in estimating ovarian function. Girls with AMH above the detection limit were most likely to experience spontaneous thelarche, menarche, and ongoing ovarian function during the reproductive lifespan. Fertility preservation became more routine practice: vitrification of oocytes was reported in 58 girls with TS and a median of five oocytes were preserved per stimulation. Ovarian tissue cryopreservation has demonstrated the presence of follicles in approximately 30% of girls with TS, mostly in girls with mosaic-TS, spontaneous puberty, and AMH above the detection limit. Although girls and their parents appreciated receiving counselling on fertility in TS, only one in ten girls with TS received specialized counselling. Unfamiliarity with fertility preservation techniques or uncertainties regarding the eligibility of a girl for fertility preservation constituted barriers for healthcare professionals when discussing fertility with girls with TS.

Wider Implications: There currently is a high demand for fertility preservation techniques in girls with TS. A reliable prognostic model to determine which girls with TS might benefit from fertility preservation is lacking. Only a minority of these girls received comprehensive fertility counselling on the full spectrum of fertility, including uncertainties of fertility preservation, pregnancy risks, and alternatives, such as adoption. Fertility preservation could be a viable option for girls with TS. However, the question remains whether enough oocytes can be obtained for a realistic prospect of a live birth. It is important that girls and parents are empowered with the necessary information to make a well-informed decision.

Citing Articles

Gene expression analysis of ovarian follicles and stromal cells in girls with Turner syndrome.

Peek R, van der Coelen S, Dolmans M Mol Hum Reprod. 2024; 30(12).

PMID: 39673521 PMC: 11655625. DOI: 10.1093/molehr/gaae043.

[Reflections on the clinical diagnosis and management of Turner syndrome].

Gu W, Zhao X Zhongguo Dang Dai Er Ke Za Zhi. 2024; 26(11):1135-1140.

PMID: 39587740 PMC: 11601105. DOI: 10.7499/j.issn.1008-8830.2407176.

References

Rodriguez-Wallberg K, Sergouniotis F, Nilsson H, Lundberg F . Trends and outcomes of fertility preservation for girls, adolescents and young adults with Turner syndrome: A prospective cohort study. Front Endocrinol (Lausanne). 2023; 14:1135249. PMC: 10022431. DOI: 10.3389/fendo.2023.1135249. View

Lin A, Karnis M, Calderwood L, Crenshaw M, Bhatt A, Souter I . Proposal for a national registry to monitor women with Turner syndrome seeking assisted reproductive technology. Fertil Steril. 2016; 105(6):1446-8. DOI: 10.1016/j.fertnstert.2016.01.042. View

Peek R, Nadesapillai S, Thi Nguyen T, Vassart S, Smeets D, van de Zande G . Assessment of folliculogenesis in ovarian tissue from young patients with Turner syndrome using a murine xenograft model. Fertil Steril. 2023; 120(2):371-381. DOI: 10.1016/j.fertnstert.2023.04.008. View

Aso K, Koto S, Higuchi A, Ariyasu D, Izawa M, Igaki J . Serum FSH level below 10 mIU/mL at twelve years old is an index of spontaneous and cyclical menstruation in Turner syndrome. Endocr J. 2010; 57(10):909-13. DOI: 10.1507/endocrj.k10e-092. View

Magnus M, Wilcox A, Morken N, Weinberg C, Haberg S . Role of maternal age and pregnancy history in risk of miscarriage: prospective register based study. BMJ. 2019; 364:l869. PMC: 6425455. DOI: 10.1136/bmj.l869. View

Johnson E, Rosoklija I, Shurba A, DOro A, Gordon E, Chen D . Future fertility for individuals with differences of sex development: Parent attitudes and perspectives about decision-making. J Pediatr Urol. 2017; 13(4):402-413. DOI: 10.1016/j.jpurol.2017.06.002. View

Mamsen L, Charkiewicz K, Anderson R, Telfer E, Mclaughlin M, Kelsey T . Characterization of follicles in girls and young women with Turner syndrome who underwent ovarian tissue cryopreservation. Fertil Steril. 2019; 111(6):1217-1225.e3. DOI: 10.1016/j.fertnstert.2019.02.003. View

Lambalk C, de Koning C, Flett A, Van Kasteren Y, Gosden R, Homburg R . Assessment of ovarian reserve. Ovarian biopsy is not a valid method for the prediction of ovarian reserve. Hum Reprod. 2004; 19(5):1055-9. DOI: 10.1093/humrep/deh216. View

Nadesapillai S, van der Velden J, Braat D, Peek R, Fleischer K . The challenge of defining predictive parameters for fertility preservation counseling in young females with Turner syndrome. Acta Obstet Gynecol Scand. 2021; 100(6):1155-1156. DOI: 10.1111/aogs.14094. View

10.

Radkowska-Walkowicz M, Maciejewska-Mroczek E . 'Should I Buy Her a Doll'? Motherhood and Turner Syndrome in Poland. Med Anthropol. 2023; 42(2):177-190. DOI: 10.1080/01459740.2023.2170797. View

11.

Borgstrom B, Birgit B, Hreinsson J, Julius H, Rasmussen C, Carsten R . Fertility preservation in girls with turner syndrome: prognostic signs of the presence of ovarian follicles. J Clin Endocrinol Metab. 2008; 94(1):74-80. DOI: 10.1210/jc.2008-0708. View

12.

Soderstrom-Anttila V, Pinborg A, Karnis M, Reindollar R, Paulson R . Should women with Turner syndrome be allowed to carry their own pregnancies?. Fertil Steril. 2019; 112(2):220-225. DOI: 10.1016/j.fertnstert.2019.06.003. View

13.

Martin M, Adeba A, De la Hera J, Martinez J, Cigarran H, Alvarez-Cabo R . Turner syndrome, unicuspid aortopathy, and pregnancy: Difficult decisions for complex scenarios. Arch Cardiol Mex. 2021; 91(2):252-254. PMC: 8295873. DOI: 10.24875/ACM.20000176. View

14.

Strypstein L, Van Moer E, Nekkebroeck J, Segers I, Tournaye H, Demeestere I . First live birth after fertility preservation using vitrification of oocytes in a woman with mosaic Turner syndrome. J Assist Reprod Genet. 2022; 39(2):543-549. PMC: 8956750. DOI: 10.1007/s10815-022-02420-4. View

15.

Andersen N, Gravholt C . Re: Pregnancies in women with Turner syndrome: A retrospective multicentre UK study. BJOG. 2022; 129(8):1413-1414. DOI: 10.1111/1471-0528.17097. View

16.

Rogers P, Murphy C, Leeton J, Hoise M, Beaton L . Turner's syndrome patients lack tight junctions between uterine epithelial cells. Hum Reprod. 1992; 7(6):883-5. DOI: 10.1093/oxfordjournals.humrep.a137754. View

17.

Peek R, Schleedoorn M, Smeets D, van de Zande G, Groenman F, Braat D . Ovarian follicles of young patients with Turner's syndrome contain normal oocytes but monosomic 45,X granulosa cells. Hum Reprod. 2019; 34(9):1686-1696. PMC: 6736193. DOI: 10.1093/humrep/dez135. View

18.

Fitz V, Law J, Peavey M . Karyotype is associated with timing of ovarian failure in women with Turner syndrome. J Pediatr Endocrinol Metab. 2021; 34(3):319-323. DOI: 10.1515/jpem-2020-0304. View

19.

Ruszala A, Wojcik M, Starzyk J . Evaluation of the usefulness of antymüllerian hormone and inhibin B as markers of ovarian activity in patients with Turner syndrome - preliminary results. Pediatr Endocrinol Diabetes Metab. 2020; 26(2):84-88. DOI: 10.5114/pedm.2020.95622. View

20.

Modi D, Sane S, Bhartiya D . Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads. Mol Hum Reprod. 2003; 9(4):219-25. DOI: 10.1093/molehr/gag031. View