Fertility preservation in women with cervical, endometrial or ovarian cancers
Identifieur interne : 000F46 ( Pmc/Corpus ); précédent : 000F45; suivant : 000F47Fertility preservation in women with cervical, endometrial or ovarian cancers
Auteurs : Michael Feichtinger ; Kenny A. Rodriguez-WallbergSource :
- Gynecologic Oncology Research and Practice [ 2053-6844 ] ; 2016.
Abstract
Although cancer in general affects an aged population, a significant number of women develop cancer at childbearing age. Long-term survival rates after gynecological cancer, especially in young patients are increasing and all quality-of-life aspects, including preservation of fertility have become of major relevance.
Surgical techniques aimed at sparing reproductive organs and preserving fertility have been developed for women presenting with gynecological cancer found at early stages. Indications for fertility-sparing surgery are in general restricted to women presenting with a well-differentiated low-grade tumor in its early stages or with low malignant potential. Up to now, use of fertility-sparing techniques in well-selected patients has not been shown to affect overall survival negatively and fertility outcomes reported have been favorable. Still larger amounts of data and longer follow-up periods are needed. Several current fertility-sparing cancer treatments may result in sub-fertility and in those cases assisted reproductive techniques are indicated. Overall quality of life has been satisfactory in cancer patients after fertility-sparing surgery.
Fertility-sparing surgery is a viable tool to enable gynecological cancer patients of young age to fulfill their family building without impairment of oncological outcome. Cancer patients of reproductive age should undergo fertility counseling to analyze this sensitive subject. Further studies are needed to investigate the role of fertility-sparing treatment and combined adjuvant therapy in higher-grade cancers.
Url:
DOI: 10.1186/s40661-016-0029-2
PubMed: 27468354
PubMed Central: 4962474
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PMC:4962474Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Fertility preservation in women with cervical, endometrial or ovarian cancers</title><author><name sortKey="Feichtinger, Michael" sort="Feichtinger, Michael" uniqKey="Feichtinger M" first="Michael" last="Feichtinger">Michael Feichtinger</name><affiliation><nlm:aff id="Aff1">Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Wunschbaby Institut Feichtinger, Vienna, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4">Department of Obstetrics and Gynecology, Section of Reproductive Medicine, Karolinska University Hospital, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rodriguez Wallberg, Kenny A" sort="Rodriguez Wallberg, Kenny A" uniqKey="Rodriguez Wallberg K" first="Kenny A." last="Rodriguez-Wallberg">Kenny A. Rodriguez-Wallberg</name><affiliation><nlm:aff id="Aff3">Department of Oncology – Pathology, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4">Department of Obstetrics and Gynecology, Section of Reproductive Medicine, Karolinska University Hospital, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27468354</idno><idno type="pmc">4962474</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962474</idno><idno type="RBID">PMC:4962474</idno><idno type="doi">10.1186/s40661-016-0029-2</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000F46</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F46</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Fertility preservation in women with cervical, endometrial or ovarian cancers</title><author><name sortKey="Feichtinger, Michael" sort="Feichtinger, Michael" uniqKey="Feichtinger M" first="Michael" last="Feichtinger">Michael Feichtinger</name><affiliation><nlm:aff id="Aff1">Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2">Wunschbaby Institut Feichtinger, Vienna, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4">Department of Obstetrics and Gynecology, Section of Reproductive Medicine, Karolinska University Hospital, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden</nlm:aff></affiliation></author><author><name sortKey="Rodriguez Wallberg, Kenny A" sort="Rodriguez Wallberg, Kenny A" uniqKey="Rodriguez Wallberg K" first="Kenny A." last="Rodriguez-Wallberg">Kenny A. Rodriguez-Wallberg</name><affiliation><nlm:aff id="Aff3">Department of Oncology – Pathology, Karolinska Institutet, Stockholm, Sweden</nlm:aff></affiliation><affiliation><nlm:aff id="Aff4">Department of Obstetrics and Gynecology, Section of Reproductive Medicine, Karolinska University Hospital, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden</nlm:aff></affiliation></author></analytic><series><title level="j">Gynecologic Oncology Research and Practice</title><idno type="eISSN">2053-6844</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Although cancer in general affects an aged population, a significant number of women develop cancer at childbearing age. Long-term survival rates after gynecological cancer, especially in young patients are increasing and all quality-of-life aspects, including preservation of fertility have become of major relevance.</p></sec><sec><title>Outcomes</title><p>Surgical techniques aimed at sparing reproductive organs and preserving fertility have been developed for women presenting with gynecological cancer found at early stages. Indications for fertility-sparing surgery are in general restricted to women presenting with a well-differentiated low-grade tumor in its early stages or with low malignant potential. Up to now, use of fertility-sparing techniques in well-selected patients has not been shown to affect overall survival negatively and fertility outcomes reported have been favorable. Still larger amounts of data and longer follow-up periods are needed. Several current fertility-sparing cancer treatments may result in sub-fertility and in those cases assisted reproductive techniques are indicated. Overall quality of life has been satisfactory in cancer patients after fertility-sparing surgery.</p></sec><sec><title>Conclusions</title><p>Fertility-sparing surgery is a viable tool to enable gynecological cancer patients of young age to fulfill their family building without impairment of oncological outcome. Cancer patients of reproductive age should undergo fertility counseling to analyze this sensitive subject. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Gynecol Oncol Res Pract</journal-id><journal-id journal-id-type="iso-abbrev">Gynecol Oncol Res Pract</journal-id><journal-title-group><journal-title>Gynecologic Oncology Research and Practice</journal-title></journal-title-group><issn pub-type="epub">2053-6844</issn><publisher><publisher-name>BioMed Central</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27468354</article-id><article-id pub-id-type="pmc">4962474</article-id><article-id pub-id-type="publisher-id">29</article-id><article-id pub-id-type="doi">10.1186/s40661-016-0029-2</article-id><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Fertility preservation in women with cervical, endometrial or ovarian cancers</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Feichtinger</surname><given-names>Michael</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Rodriguez-Wallberg</surname><given-names>Kenny A.</given-names></name><address><email>kenny.rodriguez-wallberg@karolinska.se</email></address><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><aff id="Aff1"><label>1</label>Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria</aff><aff id="Aff2"><label>2</label>Wunschbaby Institut Feichtinger, Vienna, Austria</aff><aff id="Aff3"><label>3</label>Department of Oncology – Pathology, Karolinska Institutet, Stockholm, Sweden</aff><aff id="Aff4"><label>4</label>Department of Obstetrics and Gynecology, Section of Reproductive Medicine, Karolinska University Hospital, Novumhuset Plan 4, SE-141 86 Stockholm, Sweden</aff></contrib-group><pub-date pub-type="epub"><day>27</day><month>7</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>27</day><month>7</month><year>2016</year></pub-date><pub-date pub-type="collection"><year>2016</year></pub-date><volume>3</volume><elocation-id>8</elocation-id><history><date date-type="received"><day>12</day><month>5</month><year>2016</year></date><date date-type="accepted"><day>6</day><month>7</month><year>2016</year></date></history><permissions><copyright-statement>© The Author(s). 2016</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold>This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>) applies to the data made available in this article, unless otherwise stated.</license-p></license></permissions><abstract id="Abs1"><sec><title>Background</title><p>Although cancer in general affects an aged population, a significant number of women develop cancer at childbearing age. Long-term survival rates after gynecological cancer, especially in young patients are increasing and all quality-of-life aspects, including preservation of fertility have become of major relevance.</p></sec><sec><title>Outcomes</title><p>Surgical techniques aimed at sparing reproductive organs and preserving fertility have been developed for women presenting with gynecological cancer found at early stages. Indications for fertility-sparing surgery are in general restricted to women presenting with a well-differentiated low-grade tumor in its early stages or with low malignant potential. Up to now, use of fertility-sparing techniques in well-selected patients has not been shown to affect overall survival negatively and fertility outcomes reported have been favorable. Still larger amounts of data and longer follow-up periods are needed. Several current fertility-sparing cancer treatments may result in sub-fertility and in those cases assisted reproductive techniques are indicated. Overall quality of life has been satisfactory in cancer patients after fertility-sparing surgery.</p></sec><sec><title>Conclusions</title><p>Fertility-sparing surgery is a viable tool to enable gynecological cancer patients of young age to fulfill their family building without impairment of oncological outcome. Cancer patients of reproductive age should undergo fertility counseling to analyze this sensitive subject. Further studies are needed to investigate the role of fertility-sparing treatment and combined adjuvant therapy in higher-grade cancers.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Fertility preservation</kwd><kwd>Gynecological cancer</kwd><kwd>QoL</kwd><kwd>IVF</kwd><kwd>Cervical cancer</kwd><kwd>Ovarian cancer</kwd><kwd>Endometrial cancer</kwd><kwd>Pregnancy</kwd></kwd-group><funding-group><award-group><funding-source><institution>The Swedish Society of Medicine</institution></funding-source></award-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100004047</institution-id><institution>Karolinska Institutet</institution></institution-wrap></funding-source></award-group><award-group><funding-source><institution>Stockholm County Council</institution></funding-source><award-id>Clinical Investigator Grant</award-id><principal-award-recipient><name><surname>Rodriguez-Wallberg</surname><given-names>Kenny A.</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2016</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Background</title><p>The overall cancer risk in women below the age of 39 years is estimated to be one in 39 [<xref ref-type="bibr" rid="CR1">1</xref>]. Of all gynecological cancer cases, young women comprise 2 % of cervix cancer cases, 5 % of endometrial cancers and up to approximately 12 % of ovarian cancers [<xref ref-type="bibr" rid="CR1">1</xref>]. Five-year survival rates range from 46 % in ovarian cancer to more than 80 % in endometrial cancer and over 90 % in cases of borderline ovarian tumors [<xref ref-type="bibr" rid="CR2">2</xref>, <xref ref-type="bibr" rid="CR3">3</xref>]. Infertility following cancer treatment has been recognized as a main concern as regards quality of life (QoL) in cancer patients [<xref ref-type="bibr" rid="CR4">4</xref>, <xref ref-type="bibr" rid="CR5">5</xref>]. As a result of improved long-term survival rates in young people, all QoL aspects are of major importance. Additionally, due to current social trends, childbearing nowadays is delayed, hence an increasing number of women that present with cancer at a young age might have not yet fulfilled their family building plans and will be interested in undergoing treatments that would preserve their chances to have children in the future [<xref ref-type="bibr" rid="CR6">6</xref>]. Most oncologic treatments have detrimental effects on female reproductive potential, in particular those including chemotherapy with agents of high gonadotoxicity, or radiation therapy in a field involving the ovaries, the uterus and the vagina, which may be compromised and damaged by direct irradiation [<xref ref-type="bibr" rid="CR7">7</xref>]. The resumption of menstrual cycles indicates that some ovarian function is maintained, but it does not guarantee fertility, and early onset of menopause in women previously treated for cancer is a common finding [<xref ref-type="bibr" rid="CR7">7</xref>–<xref ref-type="bibr" rid="CR9">9</xref>].</p><p>Surgery is currently the most effective treatment for cancer and eventually up to 100 % of patients may be cured when complete removal of a tumor is achieved. Surgery may also be indicated for treatment of premalignant disease of the cervix or the endometrium in female patients, as cancer prophylaxis. Conization, for example, may lead to completely disease-free follow-up, but it may induce sub-fertility by affecting the normal function of the cervix and its glandular secretion. Infertility induced by such forms of intervention may be overcome by treatments involving assisted reproductive technologies, such as intrauterine insemination or in vitro fertilization, IVF.</p><p>In gynecologic oncologic surgery, there has been gradual development of fertility-sparing surgery with the aim of preserving the reproductive organs. Survival should not be compromised and thus indications are restricted to patients of a young age with a desire to preserve fertility and presenting with a well-differentiated cervical, ovarian or endometrial low-grade tumor in its early stages or with low malignant potential.</p><p>In this article we will discuss indications for fertility-sparing methods available to women with gynecological cancer, and up-to-date data on safety and efficacy as regards oncologic outcomes and reproductive outcomes including obstetric outcomes and quality of life.</p><sec id="Sec2"><title>Cervical cancer</title><p>Cervical cancer makes up 1.5 % of all new cancer cases in females. In 2015, 12 900 patients with a median age of 49 years had newly diagnosed cervical cancer in the US. Of these, 38.5 % were under the age of 45 years [<xref ref-type="bibr" rid="CR1">1</xref>, <xref ref-type="bibr" rid="CR2">2</xref>]. The different approaches regarding fertility-sparing surgery in cases of cervical cancer are summarized in Table <xref rid="Tab1" ref-type="table">1</xref>.<table-wrap id="Tab1"><label>Table 1</label><caption><p>Fertility-sparing interventions in women with cervical or endometrial cancer</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Diagnosis</th><th>Type of Surgery</th><th>Description</th><th>Reproductive and Obstetric Outcomes</th><th>Oncologic Outcome</th><th>Quality of Life</th></tr></thead><tbody><tr><td>Cervical Cancer<break></break>FIGO Stage IA1 (microinvasion <3 mm)</td><td>Large loop excision of the transformation zone (LLETZ) or conization if absence of lymph vascular space invasion and negative margins are confirmed</td><td>Complete resection of the transformation zone</td><td>No fertility impairment reported. OR 1.7 for preterm delivery and 2.69 for premature rupture of membranes; associated with resection size. No difference in neonatal outcome [<xref ref-type="bibr" rid="CR130">130</xref>]</td><td>Similar oncologic outcomes reported in comparison with hysterectomy [<xref ref-type="bibr" rid="CR10">10</xref>]</td><td>Conization has not been associated with reduced quality of life or sexual satisfaction [<xref ref-type="bibr" rid="CR49">49</xref>]</td></tr><tr><td>FIGO Stages IA2, IB1 < 2 cm</td><td>Cervical conization and laparoscopic lymphadenectomy</td><td>Conization of the cervix and laparoscopic pelvic lymphadenectomy</td><td>Spontaneous conceptions of about 47 %. Prematurity rates reported with 14.3 % of infants born <32 weeks of gestation [<xref ref-type="bibr" rid="CR21">21</xref>]</td><td>Excellent rates of 5-year disease-free survival (97 %) [<xref ref-type="bibr" rid="CR21">21</xref>]</td><td>Conization with laparoscopic lymphadenectomy has not been associated with reduced quality of life or sexual satisfaction [<xref ref-type="bibr" rid="CR49">49</xref>]</td></tr><tr><td>FIGO Stages IA2, IB1</td><td>Radical trachelectomy. Techniques described for vaginal, abdominal, laparoscopic or robotic trachelectomy</td><td>Resection of the cervix and surrounding parametria with conservation of the uterus and the ovaries, pelvic lymphadenectomy</td><td>Spontaneous pregnancy rates in >60 % of patients<break></break>Preterm deliveries with 28 % of infants born <32 weeks of gestation [<xref ref-type="bibr" rid="CR17">17</xref>, <xref ref-type="bibr" rid="CR132">132</xref>]</td><td>Rates of recurrence and mortality are comparable with those described for similar cases treated with radical hysterectomy; long-term survival 98.4 %. Low relapse rates (4.5 %) [<xref ref-type="bibr" rid="CR16">16</xref>, <xref ref-type="bibr" rid="CR17">17</xref>]</td><td>Lower quality of life than healthy controls but similar to radical hysterectomy<break></break>No significant impairment in sexual satisfaction<break></break>Long-term bladder complications (40 %) and lymphedema (10 %) [<xref ref-type="bibr" rid="CR46">46</xref>–<xref ref-type="bibr" rid="CR48">48</xref>]</td></tr><tr><td>FIGO Stage IB1, >2 cm</td><td>Neoadjuvant chemotherapy followed by radical trachelectomy</td><td>Three cycles of paclitaxel, cisplatin and ifosfamide followed by radical trachelectomy</td><td>After neoadjuvant chemotherapy and trachelectomy up to 86 % live-birth rates with 86 % spontaneous conception rate [<xref ref-type="bibr" rid="CR134">134</xref>]</td><td>Reported relapse rate of 7.6 % with 90 % survival [<xref ref-type="bibr" rid="CR23">23</xref>, <xref ref-type="bibr" rid="CR24">24</xref>]</td><td>Lack of data</td></tr><tr><td>Endometrial Cancer<break></break>FIGO stage IA</td><td>Medical conservative treatment with hormone therapy using progestational agents either orally or by IUD for >6 months<break></break>Myometrial evaluation by MRI should be performed to confirm absence of myometrial infiltration and no extrauterine involvement [<xref ref-type="bibr" rid="CR52">52</xref>].</td><td>Follow-up by hysteroscopic exams with endometrial biopsies every 3 months</td><td>Pregnancy rates of >60 %<break></break>Uneventful pregnancies reported [<xref ref-type="bibr" rid="CR63">63</xref>, <xref ref-type="bibr" rid="CR72">72</xref>]</td><td>Positive response rate to progesterone treatment of 72 %. Either oral or local IUD treatments proposed, as well as a combination of both. Relapse rate of 50 %. A second round of progesterone therapy in cases of relapse has been associated with a response rate of up 89 % [<xref ref-type="bibr" rid="CR55">55</xref>, <xref ref-type="bibr" rid="CR57">57</xref>, <xref ref-type="bibr" rid="CR60">60</xref>, <xref ref-type="bibr" rid="CR62">62</xref>]. A levonorgestrel IUD has shown greater regression on histology, lower relapse rates and lower rates of hysterectomy for treatment of complex endometrial hyperplasia vs. oral progesterone [<xref ref-type="bibr" rid="CR57">57</xref>–<xref ref-type="bibr" rid="CR59">59</xref>].</td><td>Levonorgestrel IUD treatment has been associated with fewer systemic side effects compared with oral progesterone administration [<xref ref-type="bibr" rid="CR79">79</xref>, <xref ref-type="bibr" rid="CR80">80</xref>]</td></tr></tbody></table><table-wrap-foot><p>Modified from: Rodriguez-Wallberg KA, Oktay K. Fertility preservation during cancer treatment: clinical guidelines. Cancer management and research. 2014;6:105-17</p><p>Abbreviations: <italic>FIGO</italic> International Federation of Gynecology and Obstetrics, <italic>LLETZ</italic> large loop excision of the transformation zone; <italic>IUD</italic> intrauterine device, <italic>OR</italic> odds ratio</p></table-wrap-foot></table-wrap></p><p>In cases of micro-invasion (< 3 mm), FIGO stage IA1, cervical carcinoma can be treated with simple large loop excision of the transformation zone (LLETZ), without further affecting fertility potential. Compared with this approach, hysterectomy has not been associated with improved survival rates if no lymph vascular space invasion and negative cancer margins are confirmed [<xref ref-type="bibr" rid="CR10">10</xref>]. This approach can be applied in micro-invasive squamous cell carcinoma as well as adenocarcinoma, with similar outcomes [<xref ref-type="bibr" rid="CR11">11</xref>].</p><p>In patients affected by cervical cancer at FIGO stages IA2–IB1 who wish to preserve fertility, radical trachelectomy with pelvic lymphadenectomy (confirming negative lymph node status) is the treatment of choice [<xref ref-type="bibr" rid="CR12">12</xref>, <xref ref-type="bibr" rid="CR13">13</xref>]. Radical trachelectomy was first described by Dargent in 1994 [<xref ref-type="bibr" rid="CR14">14</xref>] and it represents the most established surgical procedure for fertility preservation in women. The procedure has been reported for the treatment of squamous cell carcinomas and adenocarcinomas, with similar outcomes [<xref ref-type="bibr" rid="CR15">15</xref>]. As operative techniques, vaginal, laparascopic, abdominal and robot-assisted trachelectomy have been described [<xref ref-type="bibr" rid="CR13">13</xref>]. Long-term oncologic outcomes of trachelectomy seem not to differ compared with radical hysterectomy, and a long-term survival rate of 98.4 % and a relapse rate of only 4.5 % have been reported [<xref ref-type="bibr" rid="CR16">16</xref>, <xref ref-type="bibr" rid="CR17">17</xref>]. Perioperative complications have also been similar when compared with radical hysterectomy [<xref ref-type="bibr" rid="CR13">13</xref>]. Further development of non-invasive nuclear methods to identify lymph nodes in patients with early-stage cervical cancer might improve future patient selection for this type of fertility-sparing surgery [<xref ref-type="bibr" rid="CR18">18</xref>].</p><p>After trachelectomy, over 60 % of tissue samples have demonstrated absence of residual tumor [<xref ref-type="bibr" rid="CR19">19</xref>]. Therefore, conization in combination with laparoscopic lymphadenectomy has also been described as an appropriate procedure in selected patients presenting with early-stage cervical cancer (FIGO IA2 and IB1) and tumors < 20 mm. Women thus treated have succeeded in conceiving in 47 % of cases and the 5-year disease free survival reported of 97 % [<xref ref-type="bibr" rid="CR20">20</xref>, <xref ref-type="bibr" rid="CR21">21</xref>]. However, although data are promising, the number of cases published is still small and further research is needed to implement this technique as a clinical routine.</p><p>In cases of more advanced disease with a tumor size >2 cm, initial neoadjuvant chemotherapy followed by radical trachelectomy and lymphadenectomy has been suggested by some authors [<xref ref-type="bibr" rid="CR22">22</xref>, <xref ref-type="bibr" rid="CR23">23</xref>]. This approach has been shown to correlate with high fertility rates and no differences in oncologic outcome compared with immediate trachelectomy without chemotherapy [<xref ref-type="bibr" rid="CR24">24</xref>]. Because of few reported cases and no long-term follow-up outcomes, this procedure should still be regarded as experimental.</p><p>In selected cases where radiotherapy or chemoradiation are necessary, the ovaries can be protected by ovarian transposition to remove them from the radiation field [<xref ref-type="bibr" rid="CR25">25</xref>–<xref ref-type="bibr" rid="CR27">27</xref>]. However, depending on the radiation dose and radiation scatter, the efficacy of this procedure has been reported to be about 50 % [<xref ref-type="bibr" rid="CR28">28</xref>, <xref ref-type="bibr" rid="CR29">29</xref>]. If assisted reproductive treatments involving IVF are needed thereafter, the ovaries are often difficult to access for ovum pickup. Ovarian stimulation in connection with subsequent cryopreservation of oocytes or embryos before cancer treatment is thus indicated in such cases [<xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR30">30</xref>–<xref ref-type="bibr" rid="CR34">34</xref>]. However, even if ovarian function is preserved, or oocytes or embryos have been cryopreserved, irradiation of the uterus may cause irreversible damage. Although cases of good obstetric outcome have been reported after fertility preservation among women with a heavily irradiated uterus [<xref ref-type="bibr" rid="CR35">35</xref>], unsuccessful results should be expected and in many cases surrogacy will be necessary [<xref ref-type="bibr" rid="CR36">36</xref>].</p><p>If oocyte or embryo cryopreservation are not feasible, the emerging technique of cryopreserving ovarian tissue for later retransplantation might serve as a viable tool to preserve fertility in some cancer patients. Heterotopic and orthotopic transplantation sites have been described, with resumption of ovarian function [<xref ref-type="bibr" rid="CR35">35</xref>, <xref ref-type="bibr" rid="CR37">37</xref>–<xref ref-type="bibr" rid="CR39">39</xref>]. Up to now more than 60 children have been born worldwide after ovarian tissue transplantation [<xref ref-type="bibr" rid="CR39">39</xref>, <xref ref-type="bibr" rid="CR40">40</xref>].</p><p>In cases of ovarian tissue cryopreservation, concerns have been raised as regards the risk of reseeding cancer cells at time of retransplantation, if they are present in the tissue preserved. Ovarian metastasis has been reported in 6 % of patients with adenocarcinoma of the cervix and 1 % of patients with squamous cell carcinoma [<xref ref-type="bibr" rid="CR41">41</xref>]. Nevertheless, of five published cases of retransplantation of ovarian tissue in women with previous cervical carcinoma, none have resulted in relapse [<xref ref-type="bibr" rid="CR32">32</xref>, <xref ref-type="bibr" rid="CR37">37</xref>].</p><p>For women undergoing radical surgery with hysterectomy, the chance of childbearing is only possible by means of a womb transplant. Successful results have been obtained by a Swedish team that has led this project over many years [<xref ref-type="bibr" rid="CR42">42</xref>] and these procedures are expected to extend to several US centers in the future [<xref ref-type="bibr" rid="CR43">43</xref>].</p><p>Data on assisted reproductive treatments after cervical cancer are scarce. In one study a prevalence of infertility of 13.5 % among patients with previous vaginal trachelectomy was reported [<xref ref-type="bibr" rid="CR44">44</xref>]. Of these, cervical factor infertility was found in about 40 % of cases, indicating a need for intrauterine insemination as the first-line treatment approach. In other series of cases reported, 80 % of women conceived after subsequent fertility treatments [<xref ref-type="bibr" rid="CR44">44</xref>, <xref ref-type="bibr" rid="CR45">45</xref>].</p><p>Regarding quality of life, compared with women with radical hysterectomy who had at least one ovary, patients who had undergone trachelectomy had similar sexual satisfaction and quality of life after surgery [<xref ref-type="bibr" rid="CR46">46</xref>]. However, another study group reported low sexual satisfaction in the first year after surgery compared with healthy subjects and patients after abdominal hysterectomy. However, this effect decreased over time and after one year these patients had similar sexual satisfaction (but with a persistently reduced QoL) when compared with healthy controls [<xref ref-type="bibr" rid="CR47">47</xref>]. These results are consistent with those of another study reporting bladder-emptying problems in more than 40 % and lymphedema in more than 10 % of cases, reflecting a lower QoL in patients after vaginal or abdominal trachelectomy compared with healthy controls [<xref ref-type="bibr" rid="CR48">48</xref>].</p><p>Cold-knife conization and laparoscopic lymphadenectomy, on the other hand, are not associated with reduced sexual satisfaction and quality of life [<xref ref-type="bibr" rid="CR49">49</xref>].</p></sec><sec id="Sec3"><title>Endometrial cancer</title><p>Endometrial cancer comprises 7.1 % of all new cancer cases in females. In the US, 55,000 new cases of endometrial cancer cases were expected in 2015, with a median patient age of 62 years. Seven percent of endometrial cancer patients are under the age of 45 years [<xref ref-type="bibr" rid="CR1">1</xref>, <xref ref-type="bibr" rid="CR2">2</xref>]. Patients at higher risk of presenting endometrial carcinoma are overweight women and those with polycystic ovarian syndrome (PCOS) [<xref ref-type="bibr" rid="CR50">50</xref>]. The standard treatment of endometrial cancer involves hysterectomy and bilateral salpingo-oophorectomy, due to the hormonal sensitivity of endometrial tumors [<xref ref-type="bibr" rid="CR51">51</xref>]. In endometrial cancer IA without infiltration to the myometrium and no extrauterine involvement, conservative treatment can be offered to women who wish to maintain fertility. To counsel a women wishing fertility-sparing treatment options properly, myometrial evaluation by MRI should be performed [<xref ref-type="bibr" rid="CR52">52</xref>].</p><p>For women with early-stage endometrial cancer, treatments involving use of progesterone either orally (600 mg medroxyprogesterone acetate daily or 160 mg megestrol acetate daily) or delivered by an intrauterine device (levonorgestrel-releasing IUD) have been described. The combination of IUD and oral progesterone treatment has also been proposed [<xref ref-type="bibr" rid="CR53">53</xref>]. In retrospective studies a 72 % positive response rate to treatment has been reported [<xref ref-type="bibr" rid="CR54">54</xref>–<xref ref-type="bibr" rid="CR56">56</xref>]. In prospective studies, the treatment of complex endometrial hyperplasia using a levonorgestrel IUD has been shown to achieve greater regression in histology, and lower relapse rates than treatment with oral progesterone [<xref ref-type="bibr" rid="CR57">57</xref>–<xref ref-type="bibr" rid="CR59">59</xref>]. Lower rates of hysterectomy have also been reported after treatment with levonorgestrel IUDs [<xref ref-type="bibr" rid="CR57">57</xref>–<xref ref-type="bibr" rid="CR59">59</xref>].</p><p>Generally, relapses are frequent and occur in up to 50 % of cases that undergo conservative treatment [<xref ref-type="bibr" rid="CR60">60</xref>]. Standard conservative treatments should be followed-up by hysteroscopic examinations every third month and endometrial sampling [<xref ref-type="bibr" rid="CR61">61</xref>]. In cases of recurrence a second cycle of progesterone treatment has been associated with response rates of up to 89 % [<xref ref-type="bibr" rid="CR62">62</xref>].</p><p>The combination of surgical resection and progesterone treatment has been associated with good oncologic and pregnancy outcomes in a small number of patients (Table <xref rid="Tab1" ref-type="table">1</xref>) [<xref ref-type="bibr" rid="CR63">63</xref>].</p><p>In women free of relapse, pregnancy should be achieved within the shortest period of time, and assisted reproductive treatments may have a place in reducing time to conception, thus reducing the time at risk of recurrence. Ovarian stimulation in cases of endometrial cancer has been an issue because of the supraphysiological estrogen levels attained during hormone treatments required for recovery of oocytes for IVF, and possible tumor stimulation. A few cases of successful live-births after IVF in women with previous endometrial cancer have been reported [<xref ref-type="bibr" rid="CR64">64</xref>–<xref ref-type="bibr" rid="CR71">71</xref>]. In these patients infertility treatment was not associated with an increased cancer recurrence rate [<xref ref-type="bibr" rid="CR72">72</xref>].</p><p>The addition of letrozole to standard gonadotropin protocols has been proposed for ovarian stimulation among women with estrogen-sensitive tumors [<xref ref-type="bibr" rid="CR73">73</xref>, <xref ref-type="bibr" rid="CR74">74</xref>]. The protocols, initially developed for women with breast cancer, could also be used in patients with endometrial cancers [<xref ref-type="bibr" rid="CR75">75</xref>]. The performance of ovarian stimulation with a levonorgestrel IUD in situ has also been found to minimize the effect of estrogenic stimulation on the endometrium [<xref ref-type="bibr" rid="CR76">76</xref>].</p><p>Whenever the desired family size has been reached, patients should undergo hysterectomy and bilateral salpingo-oophorectomy as a result of the persistent relapse risk [<xref ref-type="bibr" rid="CR77">77</xref>].</p><p>A proportion of women treated for cancer might achieve pregnancy by surrogacy agreement, which is the carrying of a pregnancy by a third party (surrogate), a procedure that is allowed in some countries. Surrogacy gives the possibility of having biologically related children if gametes have been previously cryopreserved [<xref ref-type="bibr" rid="CR76">76</xref>, <xref ref-type="bibr" rid="CR78">78</xref>].</p><p>As regards the QoL of women who have undergone fertility-sparing treatments in connection with early-stage endometrial cancer, the results of a meta-analysis indicated improved outcomes after treatment with levonorgestrel IUDs compared with oral progesterone, with reduced weight gain, sleep disorders, headaches, mood and libido disorders [<xref ref-type="bibr" rid="CR79">79</xref>, <xref ref-type="bibr" rid="CR80">80</xref>].</p></sec><sec id="Sec4"><title>Ovarian cancer</title><p>Ovarian cancers make up 2.6 % of all female cancers. In 2015 around 21 300 new cases of ovarian cancer were diagnosed in the US. The median age at diagnosis is 63 years, with 12 % of patients under the age of 44 years [<xref ref-type="bibr" rid="CR1">1</xref>, <xref ref-type="bibr" rid="CR2">2</xref>]. The different approaches in fertility-sparing surgery in cases of ovarian cancer and borderline ovarian tumors are summarized in Table <xref rid="Tab2" ref-type="table">2</xref>.<table-wrap id="Tab2"><label>Table 2</label><caption><p>Fertility-sparing interventions in women with borderline ovarian tumors or ovarian cancer</p></caption><table frame="hsides" rules="groups"><thead><tr><th>Diagnosis</th><th>Type of Surgery</th><th>Description</th><th>Reproductive and Obstetric Outcomes</th><th>Oncologic Outcome</th><th>Quality of Life</th></tr></thead><tbody><tr><td>Borderline Ovarian Tumor FIGO Stage Ia</td><td>Unilateral oophorectomy/bilateral cystectomy</td><td>Removing the affected ovary only, keeping in place the unaffected one and the uterus</td><td>Spontaneous pregnancies have been reported with favorable obstetric outcome [<xref ref-type="bibr" rid="CR99">99</xref>]</td><td>Higher recurrence rates in fertility-sparing surgery compared with radical surgery, with no difference in mortality [<xref ref-type="bibr" rid="CR97">97</xref>, <xref ref-type="bibr" rid="CR98">98</xref>]. Recurrence 0 %–20 % versus 12 %–58 % when only cystectomy was performed [<xref ref-type="bibr" rid="CR6">6</xref>]</td><td>High quality of life and higher sexual satisfaction scores after fertility-sparing surgery [<xref ref-type="bibr" rid="CR103">103</xref>]</td></tr><tr><td>Borderline Ovarian Tumor FIGO Stages Ic–III</td><td>Unilateral oophorectomy/bilateral cystectomy, peritoneal staging, pelvic & para-aortic lymphadenectomy, omentectomy</td><td>Removing the affected ovary only, thorough oncological staging</td><td>Pregnancy rate of 86 %, more than half of the patients required fertility treatment [<xref ref-type="bibr" rid="CR99">99</xref>]</td><td>No difference in recurrence or survival compared with radical surgery removing both ovaries and the uterus [<xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR99">99</xref>].</td><td>Lack of data</td></tr><tr><td>Ovarian Epithelial Cancer FIGO Stage IA, grade 1</td><td>Unilateral oophorectomy, peritoneal staging, pelvic & para-aortic lymphadenectomy and omentectomy</td><td>Removing the affected ovary only, thorough oncological staging</td><td>Pregnancy rates of >60 % Pregnancies have been reported with favorable obstetric outcome [<xref ref-type="bibr" rid="CR145">145</xref>]</td><td>5-year survival 87 %, recurrence 7–12 % [<xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR17">17</xref>]</td><td>No difference in quality of life aspects or sexual satisfaction scores compared with radical surgery [<xref ref-type="bibr" rid="CR46">46</xref>]</td></tr><tr><td>Ovarian Epithelial Cancer – FIGO Stage IA, grade 2–3 or Clear Cell Carcinoma</td><td>Unilateral oophorectomy, peritoneal staging, pelvic & para-aortic lymphadenectomy, omentectomy and adjuvant chemotherapy</td><td>Removing the affected ovary only, thorough oncological staging<break></break>Adjuvant platinum-based chemotherapy</td><td>Pregnancy rate of 80 % with live-birth rate of 65 % in women presenting with cancer grades 1–3. Higher number of women with cancer grades 1–2 attempting pregnancy in comparison with women with grade 3 cancers [<xref ref-type="bibr" rid="CR87">87</xref>]</td><td>No difference in recurrence or survival compared with radical surgery [<xref ref-type="bibr" rid="CR86">86</xref>]</td><td>Lack of data</td></tr><tr><td>Malignant Germ Cell Cancers grade I</td><td>Unilateral oophorectomy, peritoneal staging, omentectomy, pelvic & para-aortic lymphadenectomy and adjuvant chemotherapy</td><td>Removing the affected ovary only, adjuvant BEP chemotherapy has been recommended, or expectant management</td><td>76 % pregnancy rate. Pregnancies have been reported with favorable obstetric outcome [<xref ref-type="bibr" rid="CR147">147</xref>, <xref ref-type="bibr" rid="CR148">148</xref>]</td><td>Fertility-sparing surgery has not been associated with impaired oncological outcome [<xref ref-type="bibr" rid="CR108">108</xref>]</td><td>Good quality of life reported with good psychological health and sexual function [<xref ref-type="bibr" rid="CR129">129</xref>]</td></tr></tbody></table><table-wrap-foot><p>Modified from: Rodriguez-Wallberg KA, Oktay K. Fertility preservation during cancer treatment: clinical guidelines. Cancer management and research. 2014;6:105-17</p><p>Abbreviations: <italic>FIGO</italic> International Federation of Gynecology and Obstetrics, <italic>BEP</italic> bleomycin, etoposide and cisplatin</p></table-wrap-foot></table-wrap></p><sec id="Sec5"><title>Epithelial ovarian cancer</title><p>Most cases of epithelial ovarian cancer are diagnosed at an advanced stage, making it the most lethal tumor of all gynecological malignancies. Standard treatment consists of bilateral salpingo-oophorectomy, hysterectomy, omentectomy as well as pelvic and para-aortic lymphadenectomy [<xref ref-type="bibr" rid="CR81">81</xref>].</p><p>In women presenting with epithelial ovarian cancer diagnosed at an early stage (typically FIGO stage IA) who wish to preserve fertility, unilateral salpingo-oophorectomy together with appropriate staging, omentectomy, pelvic and para-aortic lymphadenectomy can be performed to preserve the uterus and one healthy ovary [<xref ref-type="bibr" rid="CR82">82</xref>]. If the contralateral ovary appears macroscopically normal, most authors discourage sampling of it due to impairment of ovarian reserve and causation of additional adhesions by performing the biopsies [<xref ref-type="bibr" rid="CR82">82</xref>]. In cases of epithelial ovarian cancer with bilateral ovarian involvement a conservative approach should not be applied [<xref ref-type="bibr" rid="CR83">83</xref>].</p><p>Laparoscopic fertility-sparing surgery has been shown to be a feasible approach in cancers of FIGO stage IA and the 3-year survival rate is about 95 % [<xref ref-type="bibr" rid="CR84">84</xref>]. In patients presenting with a higher-risk early-stage ovarian cancer (IAG3 or higher) some authors have described fertility-sparing procedures in connection with non-impaired survival rates. However, the level of evidence regarding fertility-sparing surgery in high-risk ovarian cancer is limited due to the very small number of cases published [<xref ref-type="bibr" rid="CR85">85</xref>]. In one study, if recurrence after fertility-sparing surgery occurred, long-term survival was 87 % as regards ovarian and 48 % as regards extra-ovarian relapse [<xref ref-type="bibr" rid="CR82">82</xref>]. Data are still insufficient as regards other tumor types such as clear-cell carcinoma, but no differences in survival rates after fertility-sparing surgery have been reported in these patients when compared with women who have undergone radical surgery or fertility-sparing surgery in connection with non-clear-cell carcinoma [<xref ref-type="bibr" rid="CR86">86</xref>]. Overall 5-year survival rates have been reported to be as high as 87 %, with approximately 12 % of patients suffering cancer recurrence after fertility-sparing surgery, when combining both low- and high-risk cancers [<xref ref-type="bibr" rid="CR17">17</xref>].</p><p>The use of platinum-based adjuvant chemotherapy has been proposed for patients with high-risk ovarian cancer (IAG2 or higher) as well as clear-cell carcinoma after fertility-sparing surgery [<xref ref-type="bibr" rid="CR85">85</xref>, <xref ref-type="bibr" rid="CR87">87</xref>].</p><p>Some authors have suggested the addition of assisted reproductive techniques using gonadotropic ovarian stimulation for egg retrieval after the performance of fertility-sparing unilateral oophorectomy. These procedures are aimed at safeguarding fertility potential by cryopreservation of embryos or oocytes for the future. The patient, thereafter, may undergo adnexectomy of the remnant ovary in a subsequent operation [<xref ref-type="bibr" rid="CR88">88</xref>]. Reduced ovarian reserve may be a concern in women with previous ovarian operations [<xref ref-type="bibr" rid="CR89">89</xref>]. Up to now, data are lacking on ovarian cancer relapse rates after gonadotropic stimulation. However, data on women at high risk of ovarian cancer as a result of BRCA mutations are reassuring and no association between gonadotropic ovarian stimulation and ovarian cancer has been observed in these patients [<xref ref-type="bibr" rid="CR74">74</xref>, <xref ref-type="bibr" rid="CR90">90</xref>].</p><p>Ovarian tissue cryopreservation in patients with early ovarian cancers or borderline tumors is highly controversial but has been described by some authors [<xref ref-type="bibr" rid="CR32">32</xref>]. As autotransplantation of the retrieved ovarian tissue is not feasible due to the risk of reintroducing malignant cells, alternatives have been discussed, such as culture and maturation of oocytes gained from the tissue in vitro, a procedure still under development which could be used in the future [<xref ref-type="bibr" rid="CR91">91</xref>].</p><p>As regards QoL, available data indicate no major differences in sexual satisfaction or sexual concerns in women who have undergone fertility-sparing surgery compared with women who have undergone radical surgery [<xref ref-type="bibr" rid="CR46">46</xref>].</p></sec><sec id="Sec6"><title>Borderline ovarian tumors</title><p>Borderline ovarian tumors (BOTs) comprise 10–20 % of ovarian epithelial tumors [<xref ref-type="bibr" rid="CR92">92</xref>]. In one study, among patients younger than 40 years, one third of ovarian cancer cases had borderline ovarian tumors [<xref ref-type="bibr" rid="CR92">92</xref>]. Survival rates are about 99 %, with 70-month disease-free survival in cases of stage I tumors, and the survival rate in cases of stage III tumors is about 89 % [<xref ref-type="bibr" rid="CR3">3</xref>].</p><p>Because of relatively young age and good prognosis of the disease, conservative surgery can be performed in most BOT patients. Usually, adnexectomy on the affected side is performed, since cystectomy of the tumor has been associated with higher recurrence rates [<xref ref-type="bibr" rid="CR3">3</xref>]. In case of bilateral BOTs, unilateral adnexectomy and contralateral cystectomy can be performed in women who wish to maintain reproductive potential. Even though fertility outcomes are uncertain, oncological prognoses similar to those of patients treated by means of radical surgery have been described [<xref ref-type="bibr" rid="CR93">93</xref>, <xref ref-type="bibr" rid="CR94">94</xref>]. Surgical staging and histological subtypes (micropapillary and stromal micro-invasion) of BOTs have had no impact on recurrence [<xref ref-type="bibr" rid="CR95">95</xref>]. Although associated with good prognosis overall, a higher level of lethal recurrence has been reported in cases of micopapillary serous BOT [<xref ref-type="bibr" rid="CR96">96</xref>].</p><p>In general, conservative treatment of BOTs is associated with higher recurrence rates compared with radical treatment [<xref ref-type="bibr" rid="CR3">3</xref>, <xref ref-type="bibr" rid="CR97">97</xref>]. However, after a follow-up period of seven years mortality has been reported to be very low and most authors regard conservative surgery as safe [<xref ref-type="bibr" rid="CR98">98</xref>]. In a recent study on 59 patients concerning the role of fertility-sparing surgery in cases of advanced borderline tumors (FIGO stages IC–FIGO III) it was concluded that fertility-sparing surgery was not associated with relapse or mortality [<xref ref-type="bibr" rid="CR99">99</xref>].</p><p>After conservative treatment of BOTs, patients should be counseled about the risk of diminished ovarian reserve following repeated conservative ovarian surgery or adnexectomy, and fertility counseling should be provided. Oocyte cryopreservation for future use can be an option for many of those women who do not have the intention to attempt pregnancy in the short term [<xref ref-type="bibr" rid="CR89">89</xref>]. Due to the limited amount of data available it is not clear whether ovarian stimulation affects relapse time [<xref ref-type="bibr" rid="CR100">100</xref>, <xref ref-type="bibr" rid="CR101">101</xref>]. In in vitro models no detrimental stimulatory effects of FSH or estradiol (E2) were found in BOT cells [<xref ref-type="bibr" rid="CR102">102</xref>].</p><p>After suffering BOTs patients report a good quality of life and good sexual function. Fertility-sparing surgery is not associated with a higher QoL, but patients after such surgery showed higher-level sexual activity than patients treated radically [<xref ref-type="bibr" rid="CR103">103</xref>].</p></sec><sec id="Sec7"><title>Germ cell tumors</title><p>Malignant ovarian germ cell tumors are rare (3–5 % of ovarian tumors), but are the most common ovarian tumors in very young women (< 20 years of age) [<xref ref-type="bibr" rid="CR104">104</xref>, <xref ref-type="bibr" rid="CR105">105</xref>].</p><p>The majority of patients with malignant ovarian germ cell tumors are diagnosed with stage 1 disease as a result of the rapidly growing character of this kind of tumor [<xref ref-type="bibr" rid="CR105">105</xref>]. Overall survival rates in cases of germ cell tumors are encouraging and fertility-sparing surgery is not associated with worsening of outcome [<xref ref-type="bibr" rid="CR106">106</xref>–<xref ref-type="bibr" rid="CR108">108</xref>].</p><p>Ovarian germ cell tumors are relatively heterogeneous, and there is great variation in management. In cases of immature teratoma, 5-year survival rates at stages I and II have been described as being as high as > 93 %, with higher recurrence rates in cases of grade 2–3 tumors and advanced-stage tumors [<xref ref-type="bibr" rid="CR109">109</xref>, <xref ref-type="bibr" rid="CR110">110</xref>]. In yolk-sac tumors after fertility-sparing surgery and standard neoadjuvant chemotherapy 5-year survival has been found to be > 90 % and a fertility-sparing approach has been suggested irrespective of cancer stage [<xref ref-type="bibr" rid="CR111">111</xref>–<xref ref-type="bibr" rid="CR113">113</xref>]. In pure dysgerminoma, 10-year disease-free survival was > 90 %, with overall survival around 100 % [<xref ref-type="bibr" rid="CR114">114</xref>, <xref ref-type="bibr" rid="CR115">115</xref>]. Due to this excellent long-term outcome, several authors suggest fertility-sparing treatment at all stages of ovarian dysgerminoma [<xref ref-type="bibr" rid="CR116">116</xref>]. The usual treatment of ovarian germ cell tumors consists of unilateral adnexectomy, peritoneal staging and omentectomy [<xref ref-type="bibr" rid="CR117">117</xref>]. However, some authors have described less invasive surgical procedures involving unilateral adnexectomy, cytology and peritoneal sampling in cases of dysgerminoma and immature teratoma limited to the ovary [<xref ref-type="bibr" rid="CR110">110</xref>, <xref ref-type="bibr" rid="CR114">114</xref>]. In yolk-sac tumors, however, complete staging has been associated with a favorable outcome as a result of different adjuvant treatment at advanced stages [<xref ref-type="bibr" rid="CR111">111</xref>, <xref ref-type="bibr" rid="CR113">113</xref>].</p><p>Bilateral disease is uncommon in cases of germ cell tumors and if the contralateral ovary appears macroscopically normal no biopsy is advised owing to the risk of extra adhesions and impairment of ovarian reserve [<xref ref-type="bibr" rid="CR118">118</xref>, <xref ref-type="bibr" rid="CR119">119</xref>]. After fertility-sparing surgery, chemotherapy with bleomycin, etoposide and cisplatin (BEP) has been associated with improved disease-free survival [<xref ref-type="bibr" rid="CR120">120</xref>]. However, recently a surveillance approach has been suggested for 50 % of patients with early stage I tumors [<xref ref-type="bibr" rid="CR121">121</xref>]. In cases of early-stage yolk-sac tumors (stage I) surgery patients (with chemotherapy limited only to cases of relapse) showed higher recurrence rates but no difference in overall survival, saving 77 % of patients from chemotherapy [<xref ref-type="bibr" rid="CR122">122</xref>]. However, in cases of higher-stage yolk-sac tumors standard-dose BEP chemotherapy has been associated with favorable overall survival rates and no apparent compromise of fertility rates [<xref ref-type="bibr" rid="CR113">113</xref>, <xref ref-type="bibr" rid="CR123">123</xref>]. In early-stage pure dysgerminoma also, chemotherapy is only recommended in cases of relapse, according to several authors [<xref ref-type="bibr" rid="CR114">114</xref>, <xref ref-type="bibr" rid="CR115">115</xref>]. In patients with immature ovarian teratoma, stage I, grade 2–3, adjuvant chemotherapy has been recommended by some authors, while the results of several studies suggest that an expectant approach with chemotherapy only in relapse situations in these patients may be more appropriate [<xref ref-type="bibr" rid="CR124">124</xref>–<xref ref-type="bibr" rid="CR126">126</xref>]. This is important because germ-cell cancer survivors treated with chemotherapy have shown relatively high chemotherapy-related secondary malignancy rates later in life [<xref ref-type="bibr" rid="CR127">127</xref>]. Reproductive function, on the other hand, has been reported to be relatively good, with more than 80 % of patients retaining reproductive function after chemotherapy and surgery [<xref ref-type="bibr" rid="CR116">116</xref>, <xref ref-type="bibr" rid="CR119">119</xref>]. IVF treatment in patients after germ-cell tumor therapy has been described in only a few cases [<xref ref-type="bibr" rid="CR128">128</xref>].</p><p>Overall quality of life scores in germ-cell tumor survivors are good, with fertility preservation playing an important part [<xref ref-type="bibr" rid="CR129">129</xref>].</p></sec></sec><sec id="Sec8"><title>Reproductive outcomes after fertility-sparing surgery in cases of gynecological cancer</title><p>Gestation in women treated for gynecological cancer may require specialized surveillance, in particular if the treatment has resulted in anatomic disturbance of the cervix or the uterus due to operative procedures or radiation therapy.</p><p>In one study, in cases of early-stage cervical cancer, after LLETZ resection no impairment of fertility was observed. However, depending on the depth of resection, patients showed a higher risk of preterm delivery (OR 1.7) and premature rupture of the membranes (OR 2.69), with no effect on neonatal outcome [<xref ref-type="bibr" rid="CR130">130</xref>]. Many spontaneous conceptions have been reported after radical trachelectomy, with rates of over 80 % when robot-assisted trachelectomy was performed [<xref ref-type="bibr" rid="CR131">131</xref>]. Pregnancy rates of up to 60 % have been reported after abdominal and vaginal trachelectomy [<xref ref-type="bibr" rid="CR132">132</xref>, <xref ref-type="bibr" rid="CR133">133</xref>]. Interestingly, even after neoadjuvant chemotherapy and vaginal trachelectomy in cases of IB1 cancer, a pregnancy rate of 86 % has been reported in women who attempted to conceive [<xref ref-type="bibr" rid="CR134">134</xref>]. Performance of assisted reproductive techniques to achieve pregnancy has been reported to be necessary in up to 50 % of cases [<xref ref-type="bibr" rid="CR135">135</xref>].</p><p>In general, rates of pregnancy loss after trachelectomy are higher than in the general population [<xref ref-type="bibr" rid="CR133">133</xref>]. As a result of amputation of the cervix, high risks of preterm delivery and premature rupture of the membranes have been described [<xref ref-type="bibr" rid="CR136">136</xref>, <xref ref-type="bibr" rid="CR137">137</xref>]. Recent data indicate relatively favorable outcomes, with more than 90 % of patients delivering in the third trimester [<xref ref-type="bibr" rid="CR131">131</xref>]. However, the data are conflicting and whereas one study group reported 65 % of infants prematurely born (< 37 weeks) but only 4 % at less than 32 weeks of gestation [<xref ref-type="bibr" rid="CR44">44</xref>], a recent review reported 28 % of premature children born before the 32nd week of gestation in a large population of > 300 live-births after trachelectomy [<xref ref-type="bibr" rid="CR17">17</xref>]. Routine performance of cerclage is still a matter of controversy, and cerclage-related complications have been described [<xref ref-type="bibr" rid="CR133">133</xref>, <xref ref-type="bibr" rid="CR138">138</xref>]. Several studies describe higher delivery rates achieved at term or during the third trimester after cerclage [<xref ref-type="bibr" rid="CR139">139</xref>, <xref ref-type="bibr" rid="CR140">140</xref>]. In any case, the risk of prematurity should be considered as well as access to a center with specialized neonatal care. Frequent vaginal ultrasonography should be performed to assess the risk of prematurity associated with shortness of the cervix, and fetal lung maturation should be induced when necessary [<xref ref-type="bibr" rid="CR141">141</xref>].</p><p>As a result of postoperative scar tissue after trachelectomy, elective cesarean section after 37 weeks of gestation is recommended [<xref ref-type="bibr" rid="CR136">136</xref>].</p><p>Pregnancies in women with previous endometrial cancer have been reported, with success rates of over 60 % in women who attempted pregnancy [<xref ref-type="bibr" rid="CR63">63</xref>, <xref ref-type="bibr" rid="CR72">72</xref>]. Pregnancy is achieved faster after treatments involving assisted reproductive techniques and miscarriage rates seem to be comparable to those in the general population [<xref ref-type="bibr" rid="CR72">72</xref>, <xref ref-type="bibr" rid="CR142">142</xref>]. Overall, no adverse outcomes related to cancer treatment have been observed in over 75 live-births reported after endometrial cancer [<xref ref-type="bibr" rid="CR17">17</xref>, <xref ref-type="bibr" rid="CR72">72</xref>].</p><p>In women with fertility-sparing surgery for ovarian cancer, use of assisted reproductive treatments involving IVF is indicated in many cases owing to a reduced ovarian reserve after repeated ovarian surgery or unilateral adnexectomy [<xref ref-type="bibr" rid="CR143">143</xref>]. In series of cases reported, over 60 % of women who actively attempted pregnancy conceived, and miscarriage rates were low (< 30 %) [<xref ref-type="bibr" rid="CR144">144</xref>, <xref ref-type="bibr" rid="CR145">145</xref>]. At present more than 220 pregnancies after ovarian cancer have been reported, with an overall miscarriage rate of 17 % [<xref ref-type="bibr" rid="CR17">17</xref>]. Similar data have been reported for women treated for BOTs [<xref ref-type="bibr" rid="CR99">99</xref>]. Interestingly, adjuvant chemotherapy has not been associated with infertility, but young age at the time of chemotherapy has been associated with premature menopause later in life [<xref ref-type="bibr" rid="CR145">145</xref>, <xref ref-type="bibr" rid="CR146">146</xref>]. After fertility-sparing surgery in connection with germ-cell tumors, 76 % of patients who sought pregnancy conceived naturally [<xref ref-type="bibr" rid="CR147">147</xref>], and pregnancies in patients after fertility-sparing surgery and germ-cell tumor treatment did not show any complications [<xref ref-type="bibr" rid="CR148">148</xref>].</p><p>International guidelines for fertility preservation have been published and access to fertility preservation for young female cancer patients encouraged, in particular by use of assisted reproductive methods globally available and regarded as clinical routines, such as cryopreservation of oocytes or embryos after emergency IVF [<xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR30">30</xref>–<xref ref-type="bibr" rid="CR33">33</xref>, <xref ref-type="bibr" rid="CR149">149</xref>]. As regards fertility-sparing surgery for fertility preservation among women with gynecological cancer, global utilization of the methods available is currently unknown. In a recent European study, data was collected from several countries, demonstrating a low incidence of fertility-preserving surgery and it raised concerns as regards the need to centralize such treatments at accredited units, to ensure a sufficient number of patients at each center, with maintenance of good healthcare quality [<xref ref-type="bibr" rid="CR150">150</xref>].</p></sec><sec id="Sec9"><title>Risk-reducing salpingo-oophorectomy in women at high risk of ovarian cancer who wish to preserve fertility</title><p>Women who are carriers of BRCA1 mutations present with a 39–46 % lifetime risk of developing ovarian cancer, and for carriers of BRCA2 mutations the lifetime risk is 12–20 %. The ovarian cancers that predominantly develop in BRCA1 and BRCA2 mutation-carriers are of serous or endometrioid histology and of high grade. In women with known BRCA mutations, periodic screening for ovarian cancer by way of assay of CA125 and transvaginal ultrasonography is recommended after the age of 30–35 years, or 5–10 years before the youngest age at which ovarian cancer was first diagnosed in the family [<xref ref-type="bibr" rid="CR151">151</xref>].</p><p>Risk-reducing salpingo-oophorectomy has been shown to reduce the risk of ovarian cancer by 85–90 % and it should be offered to women with a BRCA mutation by age 40, or after the conclusion of childbearing [<xref ref-type="bibr" rid="CR151">151</xref>].</p><p>Women who are carriers of BRCA mutations may have not yet built their families at the recommended age of risk-reducing salpingo-oophorectomy, and some of them may wish to undergo procedures to preserve fertility. Data on fertility preservation for BRCA mutation-carriers are largely linked to their concomitant risk of breast cancer, and in that respect reports are reassuring, as the ovarian stimulation and IVF procedures required to cryopreserve embryos or oocytes have not been shown to negatively affect the risks of breast cancer or breast cancer relapse in reported patient series [<xref ref-type="bibr" rid="CR74">74</xref>, <xref ref-type="bibr" rid="CR90">90</xref>, <xref ref-type="bibr" rid="CR152">152</xref>]. Although pregnancy appears to be safe for BRCA mutation-carriers after breast cancer, specific studies on women with BRCA mutations are lacking. Such women may elect to utilize preimplantation genetic diagnosis during IVF to avoid transmitting the mutation to their children, but this option may create additional psychological distress, and, therefore, thorough counseling and psychosocial evaluation are essential [<xref ref-type="bibr" rid="CR153">153</xref>]. Additionally, it has been noted that carriers of BRCA mutations may have lower ovarian reserves and can experience earlier menopause than non-mutation carriers, and thus the reproductive span of BRCA carriers may be 2–4 years shorter than that in the general population [<xref ref-type="bibr" rid="CR74">74</xref>, <xref ref-type="bibr" rid="CR154">154</xref>].</p></sec></sec><sec id="Sec10"><title>Conclusions</title><p>Current data on fertility-preservation options for women with early-stage gynecological cancer indicate oncological safety and high efficacy of fertility-sparing surgery. Some women presenting with sub-fertility may need to undergo assisted reproductive treatments to achieve pregnancy, which has not been shown to affect the oncologic outcome negatively. International guidelines for fertility preservation have been published and these underline the importance of timely discussion of the impact of cancer treatment on future fertility, and options for fertility preservation in all patients of reproductive age. The role of fertility-sparing treatment at more advanced stages of gynecological cancer has to be analyzed in further studies as a result of scarce data in this field.</p></sec><sec id="Sec11"><title>Abbreviations</title><p>BEP, bleomycin, etoposide and cisplatin; BOT, borderline ovarian tumor; BRCA, breast cancer 1/2 mutation; E2, estradiol; FSH, follicle-stimulating hormone; IUD, intrauterine device; IVF, in vitro fertilization; LLETZ, large loop excision of the transformation zone; OR, odds ratio; PCOS, polycystic ovary syndrome; QoL, quality of life</p></sec></body><back><ack><title>Acknowledgements</title><p>None.</p><sec id="FPar1"><title>Funding</title><p>This work has been supported by grants from The Swedish Society of Medicine, and Karolinska Institutet (KAR-W). Dr Rodriguez-Wallberg is supported by a Clinical Investigator Grant from Stockholm County Council.</p></sec><sec id="FPar2"><title>Availability of data and materials</title><p>Not applicable.</p></sec><sec id="FPar3"><title>Authors’ contributions</title><p>MF and KAR-W equally contributed to the writing and revision of the manuscript. 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