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Hot Topics on Fertility Preservation for Women and Girls—Current Research, Knowledge Gaps, and Future Possibilities

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Hot Topics on Fertility Preservation for Women and Girls—Current Research, Knowledge Gaps, and Future Possibilities Journal of Clinical Medicine Review Hot Topics on Fertility Preservation for Women and Girls—Current Research, Knowledge Gaps, and Future Possibilities Kenny A. Rodriguez-Wallberg 1,2,* , Xia Hao 1, Anna Marklund 1, Gry Johansen 1, Birgit Borgström 1 and Frida E. Lundberg 1 1 Department of Oncology and Pathology, Karolinska Institutet, SE-171 64 Stockholm, Sweden; [email protected] (X.H.); [email protected] (A.M.); [email protected] (G.J.); [email protected] (B.B.); [email protected] (F.E.L.) 2 Department of Reproductive Medicine, Division of Gynecology and Reproduction, Karolinska University Hospital, SE-141 86 Stockholm, Sweden * Correspondence: [email protected] Abstract: Fertility preservation is a novel clinical discipline aiming to protect the fertility potential of young adults and children at risk of infertility. The field is evolving quickly, enriched by advances in assisted reproductive technologies and cryopreservation methods, in addition to surgical devel- opments. The best-characterized target group for fertility preservation is the patient population diagnosed with cancer at a young age since the bulk of the data indicates that the gonadotoxicity inherent to most cancer treatments induces iatrogenic infertility. Since improvements in cancer therapy have resulted in increasing numbers of long-term survivors, survivorship issues and the Citation: Rodriguez-Wallberg, K.A.; negative impact of infertility on the quality of life have come to the front line. These facts are reflected Hao, X.; Marklund, A.; Johansen, G.; in an increasing number of scientific publications referring to clinical medicine and research in Borgström, B.; Lundberg, F.E. Hot the field of fertility preservation. Cryopreservation of gametes, embryos, and gonadal tissue has Topics on Fertility Preservation for achieved quality standards for clinical use, with the retrieval of gonadal tissue for cryopreservation Women and Girls—Current Research, being currently the only method feasible in prepubertal children. Additionally, the indications for Knowledge Gaps, and Future fertility preservation beyond cancer are also increasing since a number of benign diseases and chronic Possibilities. J. Clin. Med. 2021, 10, conditions either require gonadotoxic treatments or are associated with premature follicle depletion. 1650. https://doi.org/10.3390/ There are many remaining challenges, and current research encompasses clinical health care and jcm10081650 caring sciences, ethics, societal, epidemiological, experimental studies, etc. Academic Editor: Alberto Revelli Keywords: fertility preservation; cancer; chemotherapy; obstetric outcome; reproductive epidemiol- Received: 7 March 2021 ogy; genetic conditions; infertility; cryopreservation; assisted reproductive technology; premature Accepted: 8 April 2021 gonadal failure Published: 13 April 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 1. Introduction published maps and institutional affil- The preservation of fertility potential is an important issue for young people at risk iations. of becoming infertile due to clinical conditions, diseases, or treatments. For patients with cancer, the current international guidelines recommend timely information on the risk of fertility loss associated with planned treatment, and referral to appropriate reproductive medicine centers to discuss further options for fertility preservation [1–3]. Cancer is a Copyright: © 2021 by the authors. heterogeneous disease; Figure1 illustrates the various approaches for cancer treatment Licensee MDPI, Basel, Switzerland. and the options for fertility preservation that can be considered in the respective cases. This article is an open access article Although several methods of fertility preservation are clinically available, studies have distributed under the terms and shown that young patients at risk of infertility are not always aware of these options. conditions of the Creative Commons Some patients are not offered fertility counseling at all due to the lack of appropriate Attribution (CC BY) license (https:// information and education of the medical teams, while other patients are not able to recall creativecommons.org/licenses/by/ the information that is provided at a time of emotional distress [4–8]. 4.0/). J. Clin. Med. 2021, 10, 1650. https://doi.org/10.3390/jcm10081650 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021, 10, x FOR PEER REVIEW 2 of 16 information and education of the medical teams, while other patients are not able to re- J. Clin. Med. 2021, 10, 1650 call the information that is provided at a time of emotional distress [4–8]. 2 of 15 Figure 1. Fertility preservation strategies depending on the type of oncological treatment in females and Figuremales. 1. Fertility Reprinted preservation with permission strategies from Rodriguez-Wallbergdepending on the type and of Oktay. oncologicalCancer Managementtreatment in and fe- Research males2014, and 6, males. 105–117; Reprinted originally with published permission by and from used Rodriguez with permission-Wallberg from and Dove Oktay. Medical Cancer Press Man- Limited. agement and Research 2014, 6, 105–117; originally published by and used with permission from Dove MedicalFertility Press preservation Limited. is also indicated when treatment of benign conditions may en- compass a risk of infertility, either through medical treatments or surgery [9,10]. Some geneticFertility conditions, preservation such asis thealso Turner indicated syndrome, when aretreatment associated of withbenign a shorter conditions reproductive may encompassspan and a predisposition risk of infertility, to premature either through gonadal medical insufficiency treatments in females,or surgery and [9,10 consequently,]. Some geneticthese condi havetions, also become such as indications the Turner for syndrome, fertility counseling are associated and fertility with a preservation.shorter repro- The ductivelist of span indications and predisposition is growing, rangingto premature from commongonadal gynecologicinsufficiency diseases in females, such and as en- consequentlydometriosis, these to chronic have autoimmunealso become diseasesindications or rare for geneticfertility syndromes, counseling andand the fertility number preservation.of patients The who list undergo of indications procedures is growing, for fertility ranging preservation from common is continuously gynecologic increasing. dis- easesSome such of as the endometriosis most common to diagnoses chronic autoimmune indicative of diseases procedures or rare for fertilitygenetic preservationsyndromes, in andwomen the number and girls of patients and their who current undergo challenges procedures are outlined for fertility below. preservation Research in is thecontin- field is uouslywell increa supplied,sing. highlighting Some of the themost need common to investigate diagnoses clinical indicative outcomes of procedures by follow for up fer- of all individuals undergoing interventions for fertility preservation to determine the safety of tility preservation in women and girls and their current challenges are outlined below. the procedures in the long term and their efficacy. Experimental research is also needed Research in the field is well supplied, highlighting the need to investigate clinical out- since several of the methods are still under development [2–4]. comes by follow up of all individuals undergoing interventions for fertility preservation to 2.determine Fertility the Preservation safety of inthe Children procedures in the long term and their efficacy. Experi- mental research is also needed since several of the methods are still under development Cryopreservation of gonadal tissue aiming at its potential use in future reproductive [2–4]. treatments has been done successfully for many years in adult patients. In the case of pre-pubertal children, this method is their current only option to cryopreserve reproductive 2. Fertility Preservation in Children potential [11,12]. In adolescents, additional methods to cryopreserve mature gametes can beCryopreservation practiced, similarly of gonadal to as in adults,tissue aiming if they at have its potential completed use puberty in future development reproductive [13 ]. treatmentsAs evidenced has been in an done increasing successfully number for of publications,many years in fertility adult preservationpatients. In inthe prepubertal case of prechildren-pubertal is children a specifically, this demandingmethod is areatheir for current research only due option to the to naturally cryopreserve immature repro- status ductiveof the potential gonads. [11,12 The situation]. In adolescents is similar, additional for children methods in early to puberty, cryopreserve at Tanner mature stages gametes2–3 [14 can]. To be retrieve practiced, the ovariansimilarly tissue to as for in cryopreservation, adults, if they have the performancecompleted puberty of a unilateral de- velopmentoophorectomy [13]. As or evidenced retrievalof in small an increasing ovarian biopsiesnumber viaof publications, laparoscopy hasfertility been preser- reported vationby severalin prepubertal centers [children11,15,16 ].is Ita isspecifically important demanding to highlight area that for the research methods due chosen to the for naturallyfertility immature preservation status should of the not gonads. cause anyThe delaysituation in startingis similar planned for children cancer in treatment early and that surgery for gonadal tissue retrieval in children should only
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