Simple Summary
Due to the increasing incidence of malignant tumors among adolescents and young adults, as well as the growing demand for improved quality of life, physicians must know how to manage fertility preservation in oncological patients. Indeed, although guidelines have been developed, the management practices remain debatable for some tumors. The present survey highlights the controversies in fertility preservation for gynecological cancers and directs attention to knowledge gaps in these guidelines.
Keywords: fertility preservation, controversies, gynecological cancer, survey
Abstract
Guidelines on fertility preservation (FP) have been developed to help young women preserve their fertility, which may have been impaired due to cancer. Nevertheless, the correct management of oncological patients of childbearing age remains controversial, especially regarding gynecological malignancies. For this reason, we explored the current knowledge, attitudes, and clinical practices of physicians towards the challenges of FP in this population. A specially developed questionnaire on fertility-related issues in patients with gynecological cancer was administered via email to 167 people, representing 167 centers of the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group. A total of 56 physicians, who represented 56 out of these 167 centers, responded to our survey (response rate: 33.5%). Approximately half of these physicians stated that they had adequate knowledge about the use of gonadotropin-releasing analog (GnRHa) injections (n = 30; 53.6%), the cryopreservation of oocytes (n = 25; 44.6%), and the cryopreservation of ovarian tissue (n = 27; 48.2%) in patients with gynecological tumors. Meanwhile, regarding (borderline) ovarian tumors, endometrial or cervical cancer, and genetic mutation carriers, attitudes varied substantially. In conclusion, the results of our survey highlight the different perspectives on controversial topics among physicians directly involved in the treatment of these tumors. These findings also demonstrate the lack of evidence on these issues to adequately counsel this specific patient population.
1. Introduction
The incidence rate of all cancers increased by 29% between 1973 and 2015 in adolescents and young adults of both sexes [1]. In Italy, every day, at least 30 new cancer cases are diagnosed in patients younger than 40 years of age, which equals 3% of new cancer diagnoses [2]. Interest in fertility preservation (FP) has increased in recent decades. Firstly, this is due to the fact that women are more often delay childbearing; in Italy, the percentage of pregnancies registered among women over the age of 35 years was a mere 12% in 1990 and is currently estimated to be 25% [3]. Secondly, anti-cancer therapies have significantly improved the survival of young cancer patients and, therefore, the possibility to resume life following cancer treatment [4].
Gynecological cancer directly affects fertility, as standard treatment consists of surgical removal of the reproductive organ and/or exposure to gonadotoxic treatment modalities. However, patients who present with early-stage gynecological cancer who meet strict criteria might be treated with fertility-sparing surgeries, thereby achieving oncological results equivalent to those undergoing traditional treatments [5]. Furthermore, FP techniques such as the cryopreservation of oocytes, embryos, and ovarian tissue might be offered in some situations [6,7]. Accordingly, the recent guidelines from the European Society of Gynaecological Oncology (ESGO), the European Society of Human Reproduction and Embryology (ESHRE), and the European Society for Gynaecological Endoscopy (ESGE) recommend FP counseling with a reproductive specialist who has an in-depth understanding of the patient and the couple’s history [8].
We decided to explore the current knowledge, attitudes, and clinical practices of physicians involved in the treatment of gynecological cancer towards the current controversies related to FP in young gynecological cancer patients.
2. Material and Methods
A specially developed questionnaire on fertility issues in gynecologic cancer patients was administered by email to 167 representatives of 167 centers of the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group. The MITO group represents the most important Italian scientific society, in which gynecologic oncologists, medical oncologists, radiation oncologists, or reproductive endocrinology and infertility (REI) physicians are involved in 167 centers across the country.
The survey was open for responses from 1 February 2023 to 30 July 2023. The email contained a link through which representatives could access the survey. The email address was not linked to the survey and no personal information was required. The entire process was anonymous.
Characteristics of the Survey
The questionnaire was approved by the MITO internal review board. It consisted of 53 items and was divided into 4 main sections—(1) sociodemographic information; (2) knowledge and availability of FP procedures; (3) attitudes about FP controversies in gynecological cancers; and (4) attitudes about controversies on artificial reproductive technologies and genetic issues.
The data were analyzed using descriptive statistical methods, calculating the absolute and percentage frequencies (N, %) for all qualitative variables. Statistics were calculated using SPSS version 27 (IBM, Armonk, NY, USA).
3. Results
A total of 56 out of 167 MITO centers responded to our survey (response rate: 33.5%). Most respondents were women (64.3%). A total of 87.5% of respondents were Catholic and 53.6% of respondents were from northern Italy. The responding physicians were gynecologists (58.9%), followed by medical oncologists (33.9%), radiation oncologists (3.6%), and fertility specialists (3.6%). More than half of them (60.7%) worked in a Gynecological Oncology unit. Further details are displayed in Table 1.
Table 1.
Demographic information of physicians who responded to the survey.
| Respondents | N = 56 | % |
|---|---|---|
| Age (years) | ||
| <40 | 21 | 37.5 |
| 40–50 | 16 | 28.6 |
| >50 | 19 | 33.9 |
| Gender | ||
| Male | 20 | 35.7 |
| Female | 36 | 64.3 |
| Religion | ||
| Catholic | 49 | 87.5 |
| Protestant | 0 | 0.0 |
| Muslim | 0 | 0.0 |
| Hindu | 1 | 1.8 |
| Jewish | 0 | 0.0 |
| Atheist/none | 4 | 7.1 |
| Prefer not to answer | 2 | 3.6 |
| Region of practice | ||
| Northern Italy | 30 | 53.6 |
| Central Italy | 12 | 21.4 |
| Southern Italy | 10 | 17.9 |
| Italian islands (i.e., Sicily, Sardinia) | 4 | 7.1 |
| Specialty | ||
| Gynecology | 33 | 58.9 |
| Medical oncology | 19 | 33.9 |
| Radiation oncology | 2 | 3.6 |
| Fertility specialist | 2 | 3.6 |
| Practice environment—1 | ||
| Specialized cancer center | 18 | 32.1 |
| Academic general hospital | 20 | 35.7 |
| Non-academic general hospital | 17 | 30.4 |
| Other | 1 | 1.8 |
| Practice environment—2 | ||
| Public | 44 | 78.6 |
| Private | 5 | 8.9 |
| Both | 7 | 12.5 |
| Working in a Gynecologic Oncology Unit | ||
| No | 22 | 39.3 |
| Yes | 34 | 60.7 |
| Years of clinical experience | ||
| <5 years | 12 | 21.4 |
| 5–10 years | 10 | 17.9 |
| 11–19 years | 15 | 26.8 |
| 20–29 years | 13 | 23.2 |
| >30 years | 6 | 10.7 |
The vast majority of respondents (91.1%) reported consulting current national and international guidelines on FP in patients with cancer and/or cancer survivors on a regular basis. Only three respondents (5.4%) declared not to be aware of the availability of guidelines on this topic.
3.1. Knowledge About Fertility Preservation Techniques
Approximately half of the physicians who participated in the survey stated that they had adequate knowledge about the use of gonadotropin-releasing analog (GnRHa) injections (n = 30; 53.6%), the cryopreservation of oocytes (n = 25; 44.6%), and the cryopreservation of ovarian tissue (n = 27; 48.2%). However, a total of 7 (12.5%), 10 (17.9%), and 14 (25.0%) respondents reported that they were aware of GnRHa, the cryopreservation of oocytes, and the cryopreservation of ovarian tissue, respectively, but did not consider themselves well-informed (Figure 1).
Figure 1.
Knowledge of FP procedures as stated by respondents (N = 56).
The availability of the administration of GnRHa, oocyte cryopreservation, and ovarian tissue cryopreservation within the respondents’ work settings was 92.9%, 67.9%, and 44.6%, respectively (Figure 2).
Figure 2.
Availability of FP procedures for patients diagnosed with gynecological cancer at the 56 MITO centers (N = 56) wherein the respondents are employed.
Furthermore, respondents were asked to indicate what suggestions might help to improve FP services in cancer patients. The following items were considered valuable or highly valuable: the increment of patient awareness (n = 49; 87.5%), FP training for professionals involved in the treatment of cancer patients (n = 54; 96.4%), the role of specialized nurses (n = 43; 76.8%), the standard offering of onco-fertility consultations with a gynecologist for all women affected by cancer at reproductive age (n = 49; 87.5%), and agreement between departments on who is responsible for discussing FP in young patients with cancer (n = 51; 91.1%). Further details are displayed in Table 2.
Table 2.
Knowledge and availability of fertility preservation procedures in gynecological cancers.
| Respondents | N = 56 | % |
|---|---|---|
| Have you ever consulted some (inter)national guidelines on fertility preservation in patients with cancer and cancer survivors? | ||
| No, I am not aware of available guidelines on this topic | 3 | 5.4 |
| No, but I know where to find these guidelines, if needed | 2 | 3.6 |
| Yes | 51 | 91.1 |
| How would you describe your knowledge of the use of GnRH analogs in patients with gynecological cancer? | ||
| Not at all knowledgeable | 3 | 5.4 |
| Aware, but not very knowledgeable | 7 | 12.5 |
| Knowledgeable | 30 | 53.6 |
| Very knowledgeable | 16 | 28.6 |
| How would you describe your knowledge of oocyte cryopreservation in patients with gynecological cancer? | ||
| Not at all knowledgeable | 2 | 3.6 |
| Aware, but not very knowledgeable | 10 | 17.9 |
| Knowledgeable | 25 | 44.6 |
| Very knowledgeable | 19 | 33.9 |
| How would you describe your knowledge of ovarian tissue cryopreservation in patients with gynecological cancer? | ||
| Not at all knowledgeable | 0 | 0.0 |
| Aware, but not very knowledgeable | 14 | 25.0 |
| Knowledgeable | 27 | 48.2 |
| Very knowledgeable | 15 | 26.8 |
| Is ovarian suppression with GnRH analogs during chemotherapy available in your setting? | ||
| No | 4 | 7.1 |
| Yes | 52 | 92.9 |
| Is oocyte cryopreservation available in your setting? | ||
| No | 18 | 32.1 |
| Yes | 38 | 67.9 |
| Is ovarian tissue cryopreservation available in your setting? | ||
| No | 31 | 55.4 |
| Yes | 25 | 44.6 |
| To what extent do you think each of the following suggestions that may improve female oncofertility care might be of value in your setting? | ||
| Increment of patient awareness | ||
| Useless | 1 | 1.8 |
| Not valuable | 1 | 1.8 |
| Neutral | 5 | 8.9 |
| Valuable | 25 | 44.6 |
| Highly valuable | 24 | 42.9 |
| Development and provision of patient information materials (e.g., decision aids, leaflets) | ||
| Useless | 2 | 3.6 |
| Not valuable | 7 | 12.5 |
| Neutral | 0 | 0.0 |
| Valuable | 27 | 48.2 |
| Highly valuable | 20 | 35.7 |
| Education of professionals | ||
| Useless | 1 | 1.8 |
| Not valuable | 0 | 0.0 |
| Neutral | 1 | 1.8 |
| Valuable | 15 | 26.8 |
| Highly valuable | 39 | 69.6 |
| Feedback to professionals on their performance | ||
| Useless | 1 | 1.8 |
| Not valuable | 0 | 0.0 |
| Neutral | 5 | 8.9 |
| Valuable | 29 | 51.8 |
| Highly valuable | 21 | 37.5 |
| Role of specialized nurses | ||
| Useless | 1 | 1.8 |
| Not valuable | 2 | 3.6 |
| Neutral | 10 | 17.9 |
| Valuable | 21 | 37.5 |
| Highly valuable | 22 | 39.3 |
| Fertility as a standard item at the multidisciplinary tumor board | ||
| Useless | 1 | 1.8 |
| Not valuable | 0 | 0.0 |
| Neutral | 2 | 3.6 |
| Valuable | 24 | 42.9 |
| Highly valuable | 29 | 51.8 |
| Standard consultations with a gynecologist for all female cancer patients of reproductive age | ||
| Useless | 1 | 1.8 |
| Not valuable | 2 | 3.6 |
| Neutral | 4 | 7.1 |
| Valuable | 15 | 26.8 |
| Highly valuable | 34 | 60.7 |
| Reminders in medical records | ||
| Useless | 1 | 1.8 |
| Not valuable | 0 | 0.0 |
| Neutral | 7 | 12.5 |
| Valuable | 24 | 42.9 |
| Highly valuable | 24 | 42.9 |
| Agreement between healthcare departments on who is responsible for fertility discussions | ||
| Useless | 1 | 1.8 |
| Not valuable | 0 | 0.0 |
| Neutral | 4 | 7.1 |
| Valuable | 20 | 35.7 |
| Highly valuable | 31 | 55.4 |
| Improved referral to fertility centers | ||
| Useless | 1 | 1.8 |
| Not valuable | 1 | 1.8 |
| Neutral | 2 | 3.6 |
| Valuable | 16 | 28.6 |
| Highly valuable | 36 | 64.3 |
3.2. Artificial Reproduction Techniques
Overall, 52 respondents (92.9%) agreed on the statement that the cryopreservation and autotransplantation of ovarian tissue must be performed exclusively in highly specialized referral centers. Furthermore, 31 of the respondents (55.3%) declared that the cryopreservation of ovarian tissue must be performed only in patients who have not yet been exposed to potentially gonadotoxic chemotherapy regimens.
Contrasting opinions were found on the proposition that the cryopreservation of ovarian tissue should be limited to patients under the age of 35 years in order to increase the potential for the restoration of ovarian function at the time of the autotransplantation of frozen and thawed ovarian tissue fragments. Similarly, opinions were divided as to whether ovarian suppression with GnRH analogs should exclusively be offered to patients in whom the cryopreservation of oocytes or ovarian tissue is not considered feasible.
Physicians’ attitudes towards controversies over artificial reproductive technologies are shown in Table 3.
Table 3.
Attitudes towards controversies on fertility preservation in gynecological cancers.
| Respondents | N = 56 | % |
|---|---|---|
| Borderline ovarian tumors and ovarian cancer | ||
| Ovarian stimulation with subsequent oocyte cryopreservation could be considered in patients who underwent surgery because of borderline ovarian tumor | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 8 | 14.3 |
| Neutral | 10 | 17.9 |
| Agree | 27 | 48.2 |
| Strongly agree | 11 | 19.6 |
| Ovarian tissue cryopreservation of the normally appearing contralateral ovary in patients who underwent unilateral surgery because of borderline ovarian tumor should be considered | ||
| Strongly disagree | 2 | 3.6 |
| Disagree | 12 | 21.4 |
| Neutral | 12 | 21.4 |
| Agree | 19 | 33.9 |
| Strongly agree | 11 | 19.6 |
| Oocyte cryopreservation should be proposed to women diagnosed with malignant ovarian germ cell tumors | ||
| Strongly disagree | 2 | 3.6 |
| Disagree | 8 | 14.3 |
| Neutral | 13 | 23.2 |
| Agree | 27 | 48.2 |
| Strongly agree | 6 | 10.7 |
| Patients diagnosed with granulosa cell tumors with concomitant atypical endometrial hyperplasia should be withheld from fertility preservation | ||
| Strongly disagree | 2 | 3.6 |
| Disagree | 21 | 37.5 |
| Neutral | 12 | 21.4 |
| Agree | 19 | 33.9 |
| Strongly agree | 2 | 3.6 |
| Endometrial cancer | ||
| Conservative management can be considered in patients with grade 2 endometrial cancers without myometrial invasion | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 15 | 26.8 |
| Neutral | 10 | 17.9 |
| Agree | 28 | 50.0 |
| Strongly agree | 3 | 5.4 |
| Oral progesterone and progesterone intrauterine devices are equally effective as a form of conservative management in patients with endometrial cancers | ||
| Strongly disagree | 4 | 7.1 |
| Disagree | 18 | 32.1 |
| Neutral | 13 | 23.2 |
| Agree | 19 | 33.9 |
| Strongly agree | 2 | 3.6 |
| Patients with low-risk endometrial cancer who had complete histological response following progesterone therapy and who have not yet become spontaneously | ||
| pregnant six months after progesterone treatment should be offered artificial reproductive technologies (e.g., in vitro fertilization) to increase fecundity | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 2 | 3.6 |
| Neutral | 8 | 14.3 |
| Agree | 34 | 60.7 |
| Strongly agree | 11 | 19.6 |
| Reinstatement of progesterone treatment should be considered in patients with recurrent endometrial cancer who had complete response | ||
| following initial progesterone treatment and who have not yet fulfilled their childbearing wishes | ||
| Strongly disagree | 4 | 7.1 |
| Disagree | 13 | 23.2 |
| Neutral | 12 | 21.4 |
| Agree | 27 | 48.2 |
| Strongly agree | 0 | 0.0 |
| Hysterectomy should always be performed following childbearing in patients with former endometrial cancer diagnosis, irrespective of histological response status | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 9 | 16.1 |
| Neutral | 5 | 8.9 |
| Agree | 32 | 57.1 |
| Strongly agree | 9 | 16.1 |
| Cervical cancer | ||
| Frozen sections of sentinel lymph nodes could be considered as an intra-operative decision tool for fertility preservation in early-stage cervical cancers | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 12 | 21.4 |
| Neutral | 7 | 12.5 |
| Agree | 31 | 55.4 |
| Strongly agree | 5 | 8.9 |
| Neoadjuvant chemotherapy in patients with cervical cancers larger than 2 cm should be exclusively administered to those who participate in clinical trials | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 12 | 21.4 |
| Neutral | 5 | 8.9 |
| Agree | 29 | 51.8 |
| Strongly agree | 10 | 17.9 |
| Ovarian transposition and ovarian tissue autotransplantation should not be considered safe in patients with cervical adenocarcinoma | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 18 | 32.1 |
| Neutral | 12 | 21.4 |
| Agree | 23 | 41.1 |
| Strongly agree | 2 | 3.6 |
| Ovarian transposition and ovarian tissue autotransplantation should be considered safe in patients with early-stage cervical cancer | ||
| showing lymph-vascular space invasion (LVSI) | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 12 | 21.4 |
| Neutral | 15 | 26.8 |
| Agree | 27 | 48.2 |
| Strongly agree | 2 | 3.6 |
| Oocyte cryopreservation and/or ovarian transposition should be considered in cervical cancer patients in whom adjuvant radiotherapy following | ||
| hysterectomy is advised based on final pathology results to preserve the option of genetic motherhood using a surrogate mother | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 6 | 10.7 |
| Neutral | 18 | 32.1 |
| Agree | 26 | 46.4 |
| Strongly agree | 5 | 8.9 |
| Uterine transplantation should be further explored as an option to preserve motherhood in patients who underwent radical hysterectomy | ||
| because of early-stage cervical cancer | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 15 | 26.8 |
| Neutral | 20 | 35.7 |
| Agree | 16 | 28.6 |
| Strongly agree | 4 | 7.1 |
3.3. Fertility Preservation in Borderline Ovarian Tumors or Malignant Ovarian Tumors
Physicians’ attitudes towards controversies on FP in gynecological cancers are shown in Table 4.
Table 4.
Attitudes towards controversies on artificial reproductive technologies and genetics.
| Respondents | N = 56 | % |
|---|---|---|
| Artificial reproductive technologies | ||
| Ovarian tissue cryopreservation and autotransplantation should exclusively be performed in highly specialized referral centers | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 3 | 5.4 |
| Neutral | 0 | 0.0 |
| Agree | 17 | 30.4 |
| Strongly agree | 35 | 62.5 |
| Ovarian tissue cryopreservation should only be performed in patients who have not yet been exposed to potentially gonadotoxic chemotherapeutic regimens | ||
| Strongly disagree | 5 | 8.9 |
| Disagree | 9 | 16.1 |
| Neutral | 11 | 19.6 |
| Agree | 25 | 44.6 |
| Strongly agree | 6 | 10.7 |
| Ovarian tissue cryopreservation should be limited to patients younger than 35 years of age to increase the potential for ovarian function restoration | ||
| upon autotransplantation of freeze–thawed ovarian tissue fragments | ||
| Strongly disagree | 3 | 5.4 |
| Disagree | 12 | 21.4 |
| Neutral | 10 | 17.9 |
| Agree | 27 | 48.2 |
| Strongly agree | 4 | 7.1 |
| Ovarian suppression with GnRH analogs should only be offered to patients in whom the cryopreservation of either oocytes or ovarian tissue is not deemed feasible | ||
| Strongly disagree | 6 | 10.7 |
| Disagree | 14 | 25.0 |
| Neutral | 11 | 19.6 |
| Agree | 20 | 35.7 |
| Strongly agree | 5 | 8.9 |
| Genetic screening and genetic mutation carriers | ||
| Patients younger than 40 years of age at the time of primary diagnosis of endometrial cancer should be referred to a clinical geneticist, | ||
| irrespective of mismatch repair status | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 12 | 21.4 |
| Neutral | 8 | 14.3 |
| Agree | 23 | 41.1 |
| Strongly agree | 12 | 21.4 |
| In patients with endometrial atypical hyperplasia or endometrial cancer who carry gene mutations associated with Lynch syndrome, | ||
| progesterone treatment should not be prescribed | ||
| Strongly disagree | 2 | 3.6 |
| Disagree | 18 | 32.1 |
| Neutral | 21 | 37.5 |
| Agree | 14 | 25.0 |
| Strongly agree | 1 | 1.8 |
| Since BRCA genetic mutation carriers may have a diminished ovarian reserve, fertility preservation should always be offered | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 4 | 7.1 |
| Neutral | 13 | 23.2 |
| Agree | 29 | 51.8 |
| Strongly agree | 10 | 17.9 |
| Preimplantation genetic testing should be discussed with patients who carry pathogenic BRCA mutation variants | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 7 | 12.5 |
| Neutral | 7 | 12.5 |
| Agree | 31 | 55.4 |
| Strongly agree | 11 | 19.6 |
| Preimplantation genetic testing should be discussed with Lynch syndrome carriers in whom endometrial aberrations have not yet occurred | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 9 | 16.1 |
| Neutral | 9 | 16.1 |
| Agree | 33 | 58.9 |
| Strongly agree | 5 | 8.9 |
| Preimplantation genetic testing should be discussed with patients who carry genetic variants in homologous recombination genes | ||
| other than BRCA1 or BRCA2 (e.g., RAD51C, RAD51D, BRIP1, etc.) | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 9 | 16.1 |
| Neutral | 11 | 19.6 |
| Agree | 28 | 50.0 |
| Strongly agree | 8 | 14.3 |
| Preimplantation genetic testing should be discussed with patients who carry BRCA genetic variants of unknown significance (VUSs) | ||
| Strongly disagree | 5 | 8.9 |
| Disagree | 16 | 28.6 |
| Neutral | 13 | 23.2 |
| Agree | 17 | 30.4 |
| Strongly agree | 5 | 8.9 |
| Ovarian tissue transplantation can be considered safe in BRCA genetic mutation carriers, as long as ovarian transplants are placed back | ||
| in the remaining ovary rather than the peritoneum | ||
| Strongly disagree | 6 | 10.7 |
| Disagree | 23 | 41.1 |
| Neutral | 15 | 26.8 |
| Agree | 12 | 21.4 |
| Strongly agree | 0 | 0.0 |
A total of 38 respondents (67.8%) agreed on the option to perform controlled ovarian stimulation with subsequent oocyte cryopreservation in patients undergoing surgery for borderline ovarian tumors (BOTs). In contrast, only 19 (33.9%) of the respondents agreed on the proposition that the ovarian tissue cryopreservation of the normal-appearing contralateral ovary could be performed in patients undergoing unilateral adnexectomy because of BOTs. A total of 24 respondents (42.8%) were neutral or disagreed.
A total of 33 respondents (58.9%) agreed on the statement that oocyte cryopreservation should be offered to women diagnosed with malignant ovarian germ cell tumors.
Finally, 19 respondents (33.9%) would not consider FP in patients diagnosed with granulosa cell tumor with concomitant atypical endometrial hyperplasia.
3.4. Endometrial Cancer
For patients with low-risk endometrial cancer who have had a complete histological response after progesterone therapy and who have not yet spontaneously become pregnant six months after progesterone treatment, 45 respondents (80.3%) believed these patients should be offered artificial reproductive technologies (e.g., in vitro fertilization) to increase fecundity. Furthermore, 27 respondents (48.2%) felt it is opportune to consider reinitiating progesterone treatment in patients with recurrent endometrial cancer who had a complete response after initial progesterone treatment and who had not yet completed their childbearing wishes. Nevertheless, a total of 13 (23.2%) and 12 (21.4%) respondents disagreed or were neutral, respectively, in attempting conservative treatment again.
A substantial proportion of respondents (57.1%) stated that hysterectomy should always be performed after a fulfilled child wish in patients with a previous diagnosis of endometrial cancer, regardless of the histological response status following progesterone treatment.
Furthermore, a total of 28 respondents (50.0%) agreed that conservative management can be considered in patients with grade 2 endometrial cancers without myometrial invasion. Finally, 31 respondents (55.2%) expressed disagreement or neutrality to the statement that oral progesterone or an intrauterine progesterone device is equally effective for conservative management in patients with endometrial tumors.
3.5. Cervical Cancer
The majority of respondents (n = 36; 64.3%) felt that frozen sections on resected sentinel lymph nodes can be used as an intraoperative decision-making tool for FP in early-stage cervical cancers. In addition, 29 respondents (51.8%) agreed on administering neoadjuvant chemotherapy exclusively in patients participating in clinical trials with cervical tumors larger than 2 cm. Ovarian transposition and ovarian tissue autotransplantation were deemed safe in patients with cervical cancer with lymphovascular space invasion (LVSI) according to 27 respondents (48.2%). This was considerably higher as compared to those who remained neutral or expressed disagreement, at 26.8% and 21.4%, respectively.
A total of 49 respondents (87.5%) agreed or were neutral on considering oocyte cryopreservation and/or ovarian transposition in cervical cancer patients in whom adjuvant radiotherapy is recommended after hysterectomy. Moreover, 20 respondents (35.7%) also considered uterine transplantation in patients undergoing radical hysterectomy for early-stage cervical cancer, while 15 respondents (26.8%) disagreed.
3.6. Genetic Issues
Physicians’ attitudes towards controversies on genetic issues are shown in Table 5.
Table 5.
Physicians’ attitudes towards controversies on genetic issues.
| Respondents | N = 56 | % |
|---|---|---|
| Artificial reproductive technologies | ||
| Ovarian tissue cryopreservation and autotransplantation should exclusively be performed in highly specialized referral centers | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 3 | 5.4 |
| Neutral | 0 | 0.0 |
| Agree | 17 | 30.4 |
| Strongly agree | 35 | 62.5 |
| Ovarian tissue cryopreservation should only be performed in patients who have not yet been exposed to potentially gonadotoxic chemotherapeutic regimens | ||
| Strongly disagree | 5 | 8.9 |
| Disagree | 9 | 16.1 |
| Neutral | 11 | 19.6 |
| Agree | 25 | 44.6 |
| Strongly agree | 6 | 10.7 |
| Ovarian tissue cryopreservation should be limited to patients younger than 35 years of age to increase the potential for ovarian function restoration upon autotransplantation of freeze–thawed ovarian tissue fragments | ||
| Strongly disagree | 3 | 5.4 |
| Disagree | 12 | 21.4 |
| Neutral | 10 | 17.9 |
| Agree | 27 | 48.2 |
| Strongly agree | 4 | 7.1 |
| Ovarian suppression with GnRH analogs should only be offered to patients in whom cryopreservation of either oocytes or ovarian tissue is not deemed feasible | ||
| Strongly disagree | 6 | 10.7 |
| Disagree | 14 | 25.0 |
| Neutral | 11 | 19.6 |
| Agree | 20 | 35.7 |
| Strongly agree | 5 | 8.9 |
| Genetic screening and genetic mutation carriers | ||
| Patients younger than 40 years of age at the time of primary diagnosis of endometrial cancer should be referred to a clinical geneticist, irrespective of mismatch repair status | ||
| Strongly disagree | 1 | 1.8 |
| Disagree | 12 | 21.4 |
| Neutral | 8 | 14..3 |
| Agree | 23 | 41.1 |
| Strongly agree | 12 | 21.4 |
| In patients with endometrial atypical hyperplasia or endometrial cancer who carry gene mutations associated with Lynch syndrome, progesterone treatment should not be prescribed | ||
| Strongly disagree | 2 | 3.6 |
| Disagree | 18 | 32.1 |
| Neutral | 21 | 37.5 |
| Agree | 14 | 25.0 |
| Strongly agree | 1 | 1.8 |
| Since BRCA genetic mutation carriers may have a diminished ovarian reserve, fertility preservation should always be offered | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 4 | 7.1 |
| Neutral | 13 | 23.2 |
| Agree | 29 | 51.8 |
| Strongly agree | 10 | 17.9 |
| Preimplantation genetic testing should be discussed with patents who carry pathogenic BRCA mutation variants | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 7 | 12.5 |
| Neutral | 7 | 12.5 |
| Agree | 31 | 55.4 |
| Strongly agree | 11 | 19.6 |
| Preimplantation genetic testing should be discussed with Lynch syndrome carriers in whom endometrial aberrations have not yet occurred | ||
| Strongly disagree | 0 | 0.0 |
| Disagree | 9 | 16.1 |
| Neutral | 9 | 16.1 |
| Agree | 33 | 58.9 |
| Strongly agree | 5 | 8.9 |
| Preimplantation genetic testing should be discussed with patients who carry genetic variants in homologous recombination genes other than BRCA1 or BRCA2 (e.g., RAD51C, RAD51D, BRIP1, etc.) | ||
| Strongly disagree | C | 0.0 |
| Disagree | 9 | 16.1 |
| Neutral | 11 | 19.6 |
| Agree | 23 | 50.0 |
| Strongly agree | 14.3 | |
| Preimplantation genetic testing should be discussed with patients who carry BRCA genetic variants of unknown significance (VUSs) | ||
| Strongly disagree | 5 | 8.9 |
| Disagree | 16 | 28.6 |
| Neutral | 13 | 23.2. |
| Agree | 17 | 30.4 |
| Strongly agree | 5 | 8.9 |
| Ovarian tissue transplantation can be considered safe in BRCA genetic mutation carriers, as long as ovarian transplants are placed back the remaining ovary rather than the peritoneum | ||
| Strongly disagree | 6 | 10.7 |
| Disagree | 23 | 41.1 |
| Neutral | 15 | 26.8 |
| Agree | 12 | 21.4 |
| Strongly agree | 0 | 0.0 |
Approximately 35 respondents (62.5%) believed that patients younger than 40 years of age at the time of primary diagnosis of endometrial cancer should be referred to a clinical geneticist, regardless of mismatch repair status. Prescribing progesterone treatment in patients with atypical endometrial hyperplasia or endometrial cancer carrying genetic mutations associated with Lynch syndrome produced conflicting results. In fact, 20 survey participants (35.6%) did not agree with the use of these drugs, whereas 21 (37.5%) did not provide an answer.
Many respondents (n = 39, 69.7%) agreed to always offer fertility cryopreservation in BRCA gene mutation carriers as these patients may have a reduced ovarian reserve. A substantial proportion of respondents believed that preimplantation genetic testing should be discussed with patients who harbor pathogenic BRCA mutation variants (n = 42, 75%), those who are diagnosed with Lynch syndrome in whom endometrial aberrations have not yet occurred (n = 38, 67.8%), and those who are known to have genetic variants in homologous recombination genes other than BRCA1 or BRCA2 (e.g., RAD51C, RAD51D, BRIP1, etc.) (n = 36, 64.3%).
On the other hand, the respondents’ perspectives on offering pre-implantation genetic testing to patients carrying BRCA genetic variants of unknown significance (VUSs) were less consistent, as follows: 22 (39.8%) agreed, 13 (23.2%) remained neutral, and 21 (37.5%) disagreed. Regarding ovarian tissue autotransplantation, 51.8% (n = 29) did not agree on the proposition that this procedure is safe in carriers of BRCA genetic mutations, even if the ovarian tissue fragments would be re-implanted to the remaining ovary rather than the peritoneum. Conversely, 12 (21.4%) and 15 (26.8%) of the respondents expressed agreement or neutrality, respectively.
4. Discussion
This survey, conducted among MITO centers, highlighted the current landscape of awareness, attitudes, and practices in relation to FP among gynecologic oncology professionals in Italy. To our knowledge, this was the first survey to examine these aspects among physicians working in the gynecologic cancer field. Overall, our survey showed that physicians have divergent perspectives and approaches towards this topic. This is likely due to the relatively limited evidence available in the literature on FP in gynecologic cancer, which makes it difficult to provide unequivocal advice to gynecologic cancer patients who wish to preserve their fertility.
A notable finding was the high proportion of respondents (91.1%) who reported regularly consulting national and international guidelines on FP in cancer patients and survivors. This was consistent with previous studies indicating that standardized guidelines are critical to ensure best practice in oncofertility care [9].
4.1. Fertility Preservation Techniques
A considerable proportion of respondents expressed uncertainty about FP techniques, in accordance with previous studies highlighting gaps in FP education among oncology professionals [10]. Moreover, the availability of FP techniques was not equal between respondents’ workplaces; in particular, limited access to ovarian tissue cryopreservation reflects the need for increased infrastructure and training in this field [11].
Participants identified several key strategies to improve FP services, including increased patient awareness (87.5%) and FP training for professionals (96.4%). These findings were congruent with previous reports suggesting that educational interventions for both patients and providers improve FP decision-making [10]. Furthermore, agreement on defining responsibilities for discussing FP in young cancer patients (91.1%) demonstrated the importance of structured and multidisciplinary approaches in relation to oncofertility care [12,13].
Considering ovarian tissue cryopreservation, respondents had opposing opinions with respect to patient selection criteria [14]. For instance, 55.3% stated that ovarian tissue cryopreservation should be performed only in patients who had never undergone potentially gonadotoxic chemotherapy treatments. However, data are emerging in the literature that show the possibility of performing this treatment even after chemotherapy exposure [15,16,17].
4.2. Borderline Ovarian Tumors
Considering gynecological tumors, BOTs represent a unique challenge due to their uncertain malignant potential. While fertility-sparing surgery is an option for many women with BOTs [18], concerns about future fertility remain as ovarian cyst removal may lead to a reduced ovarian reserve, while the risk of recurrent disease cannot be ruled out. As a consequence, oocyte cryopreservation could be a valuable option for FP in individuals diagnosed with BOTs [19]. In our survey, the attitudes regarding ovarian tissue cryopreservation in BOT patients were conservative (33.9% agreement). This reflects ongoing ethical and clinical concerns about the safety and efficacy of FP interventions in specific tumor types [20].
4.3. Endometrial Cancer
For women with early, low-grade endometrial cancer who wish to preserve fertility, hysteroscopic endometrial resection followed by hormonal treatment is often considered a viable option [21]. In contrast, limited data are available on the impact of oocyte cryopreservation on oncological outcomes in women with endometrial cancer. Although ovarian stimulation did not seem to increase the risk of cancer recurrence or progression per se, more research is needed to determine the safety and efficacy of this approach in women with endometrial cancer [22,23,24]. Regarding secondary conservative treatment for recurrent endometrial cancer in patients who have had a complete response after initial diagnosis, 13 (23.2%) and 12 (21.4%) responding centers disagreed or were neutral, respectively, in relation to offering conservative treatment again. The ESGO/ESHRE/ESGE guidelines for the fertility-conserving treatment of patients with endometrial cancer indicate that a second conservative approach may be considered on a case-by-case basis, but the level of evidence remains low (level of evidence IV, grade B) [8].
4.4. Cervical Cancer
Treatment of cervical cancer may require radical hysterectomy or chemoradiation, compromising a woman’s ability to carry a pregnancy to term [25]. In these cases, surrogacy offers hope and provides the opportunity to have children despite cancer treatment [26]. Our survey shows that most physicians are positive regarding oocyte cryopreservation and/or ovarian transposition in relation to maintaining surrogacy as a viable option in cervical cancer patients who will undergo radical hysterectomy and/or chemoradiation. However, surrogacy in cervical cancer involves complex ethical and legal issues [27]. In patients in urgent need of anti-cancer treatments at risk of gonadotoxicity, ovarian tissue cryopreservation and autotransplantation have been proposed [28,29]. However, tumor cell reimplantation along with ovarian tissue transplantation cannot be excluded, particularly in non-squamous histology and advanced FIGO stages [30]. Furthermore, to date, no pregnancies have been reported following orthotopic transplantation of ovarian tissue fragments following pelvic radiotherapy [31].
4.5. Genetic Issues
About 30% of the respondents were not favorable to providing FP counseling to patients who carry a BRCA mutation. However, patients with BRCA mutations might have a higher risk of developing cancer and impaired fertility. For this reason, tailored oncofertility counseling should be provided to women at the time of BRCA mutation diagnosis [32]. Furthermore, significant uncertainty persists concerning the safety of preimplantation genetic testing and ovarian tissue autotransplantation in this population, underscoring the need for research on fertility interventions in individuals who have a genetic predisposition [33].
4.6. Limitations
The current study has several limitations. First, the response rate among MITO representatives was relatively low. Second, the degree of knowledge was self-reported and we did not test the respondents’ experience. Finally, although we believe that the questionnaire comprehensively addressed the current controversies regarding FP in gynecological cancer, it was not officially validated for this purpose.
In conclusion, our survey results demonstrated a wide variety of physicians’ perspectives, attitudes, and practices in relation to FP in young gynecological cancer patients. These findings emphasize the lack of evidence regarding many of these issues. In order to improve oncofertility counseling and adherence to available guidelines, training courses are urgently needed, as well as conducting research regarding the many gray areas in the field.
Abbreviations
The following abbreviations are used in this manuscript:
| BOT | Borderline Ovarian Tumor |
| BRCA | BReast CAncer gene |
| BRIP1 | BReast CAncer 1 Interacting Protein 1 |
| ESGE | European Society for Gynaecological Endoscopy |
| ESGO | European Society of Gynaecological Oncology |
| ESHRE | European Society of Human Reproduction and Embryology |
| FP | Fertility Preservation |
| GnRHa | Gonadotropin-Releasing Hormone Analog |
| MITO | Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies |
| RAD51C | Radiation-Sensitive Protein 51C |
| RAD51D | Radiation-Sensitive Protein 51D |
| REI | Reproductive Endocrinology and Infertility |
| SPSS | Statistical Package for the Social Sciences |
| VUS | Variant of Unknown Significance |
Author Contributions
Conceptualization: G.C. (Giacomo Corrado) and I.P.; methodology: G.C. (Giacomo Corrado), I.P. and R.C.; software: M.I.; validation: R.V.; formal analysis: G.C. (Giacomo Corrado), I.P. and E.M.; investigation: G.C. (Giacomo Corrado) and G.C. (Gennaro Cormio); resources: S.P. and G.M.; data curation: G.C. (Giacomo Corrado) and G.C. (Gennaro Cormio); writing—original draft preparation: G.C. (Giacomo Corrado); writing—review and editing: I.P., E.S. and S.T.; visualization: S.P.; supervision: S.P. and G.M.; project administration: E.S. and S.P. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board Statement
The survey was authorized by the clinical protocols committee of the MITO group (Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies) on 24 January 2023. It was published on the official MITO website: https://www.mito-group.it/survey/survey-oncofertility/ (accessed on 1 August 2025).
Informed Consent Statement
Since the study population included healthy physicians working in the field of gynecological oncology affiliated with the MITO group, informed consent was not applicable. Participation was voluntary and there were no financial incentives.
Data Availability Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.
Conflicts of Interest
The authors declare no conflicts of interest.
Funding Statement
This research received no external funding.
Footnotes
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References
- 1.Scott A.R., Stoltzfus K.C., Tchelebi L.T., Trifiletti D.M., Lehrer E.J., Rao P., Bleyer A., Zaorsky N.G. Trends in Cancer Incidence in US Adolescents and Young Adults, 1973–2015. JAMA Netw. Open. 2020;3:e2027738. doi: 10.1001/jamanetworkopen.2020.27738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Associazione Italiana di Oncologia Medica . I Numeri del Cancro in Italia 2020. Associazione Italiana di Oncologia Medica; Milan, Italy: 2020. Rapporto AIOM–AIRTUM. [Google Scholar]
- 3.Astolfi P., Zonta L.A. Delayed maternity and risk at delivery. Paediatr. Perinat. Epidemiol. 2002;16:67–72. doi: 10.1046/j.1365-3016.2002.00375.x. [DOI] [PubMed] [Google Scholar]
- 4.Lee S.J., Schover L.R., Partridge A.H., Patrizio P., Wallace W.H., Hagerty K., Beck L.N., Brennan L.V., Oktay K. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2006;24:2917–2931. doi: 10.1200/JCO.2006.06.5888. [DOI] [PubMed] [Google Scholar]
- 5.Bhatia S., Pappo A.S., Acquazzino M., Allen-Rhoades W.A., Barnett M., Borinstein S.C., Casey R., Choo S., Chugh R., Dinner S., et al. Adolescent and Young Adult (AYA) Oncology, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21:851–880. doi: 10.6004/jnccn.2023.0040. [DOI] [PubMed] [Google Scholar]
- 6.Oktay K., Harvey B.E., Partridge A.H., Quinn G.P., Reinecke J., Taylor H.S., Wallace W.H., Wang E.T., Loren A.W. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update. J. Clin. Oncol. 2018;36:1994–2001. doi: 10.1200/JCO.2018.78.1914. [DOI] [PubMed] [Google Scholar]
- 7.Hagege E., Sokteang S., Ayoubi J.M., de Ziegler D. Fertility preservation counseling: Old indications, novel perspectives. Fertil. Steril. 2024;121:553–554. doi: 10.1016/j.fertnstert.2024.01.004. [DOI] [PubMed] [Google Scholar]
- 8.Morice P., Scambia G., Abu-Rustum N.R., Acien M., Arena A., Brucker S., Cheong Y., Collinet P., Fanfani F., Filippi F., et al. Fertility-sparing treatment and follow-up in patients with cervical cancer, ovarian cancer, and borderline ovarian tumours: Guidelines from ESGO, ESHRE, and ESGE. Lancet Oncol. 2024;25:e602–e610. doi: 10.1016/S1470-2045(24)00262-6. [DOI] [PubMed] [Google Scholar]
- 9.Practice Committee of the Oncofertility Consortium Installing oncofertility programs for common cancers in optimum resource settings (Repro-Can-OPEN Study Part II): A committee opinion. J. Assist. Reprod. Genet. 2021;38:163–176. doi: 10.1007/s10815-020-02012-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Rodriguez-Wallberg K.A., Oktay K. Fertility preservation during cancer treatment: Clinical guidelines. Cancer Manag. Res. 2014;6:105–117. doi: 10.2147/cmar.s32380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Lambertini M., Peccatori F.A., Demeestere I., Amant F., Wyns C., Stukenborg J.B., Paluch-Shimon S., Halaska M.J., Uzan C., Meissner J., et al. Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines. Ann. Oncol. 2020;31:1664–1678. doi: 10.1016/j.annonc.2020.09.006. [DOI] [PubMed] [Google Scholar]
- 12.Roberts J.E., Benoit J., Foong S., Saumet J., Korkidakis A., Marr K., McQuillan S., Todd N. Fertility preservation in patients undergoing gonadotoxic treatments: A Canadian Fertility and Andrology Society clinical practice guideline. Reprod. Biomed. Online. 2024;48:103767. doi: 10.1016/j.rbmo.2023.103767. [DOI] [PubMed] [Google Scholar]
- 13.Donnez J., Dolmans M.M. Fertility Preservation in Women. N. Engl. J. Med. 2018;378:400–401. doi: 10.1056/NEJMc1715731. [DOI] [PubMed] [Google Scholar]
- 14.Duffin K., Howie R., Kelsey T.W., Wallace H.B., Anderson R.A. Long-term follow-up to assess criteria for ovarian tissue cryopreservation for fertility preservation in young women and girls with cancer. Hum. Reprod. 2023;38:1076–1085. doi: 10.1093/humrep/dead060. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Poirot C., Fortin A., Lacorte J.M., Akakpo J.P., Genestie C., Vernant J.P., Brice P., Morice P., Leblanc T., Gabarre J., et al. Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation. Hum. Reprod. 2019;34:1083–1094. doi: 10.1093/humrep/dez047. [DOI] [PubMed] [Google Scholar]
- 16.Khattak H., Malhas R., Craciunas L., Afifi Y., Amorim C.A., Fishel S., Silber S., Gook D., Demeestere I., Bystrova O., et al. Correction to: Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: A systematic review and individual patient data meta-analysis. Hum. Reprod. Update. 2022;28:455. doi: 10.1093/humupd/dmac015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Cioffi R., Cervini L., Taccagni G., Papaleo E., Pagliardini L., Bergamini A., Ferrari S., Mangili G., Candiani M. A prospective, observational study of chemotherapy-induced ovarian damage on follicular reserve and maturation. Arch. Gynecol. Obstet. 2022;306:1723–1729. doi: 10.1007/s00404-022-06692-0. [DOI] [PubMed] [Google Scholar]
- 18.Ledermann J.A., Matias-Guiu X., Amant F., Concin N., Davidson B., Fotopoulou C., González-Martin A., Gourley C., Leary A., Lorusso D., et al. ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: Pathology and molecular biology and early, advanced and recurrent disease. Ann. Oncol. 2024;35:248–266. doi: 10.1016/j.annonc.2023.11.015. [DOI] [PubMed] [Google Scholar]
- 19.Zhang M., Feng J., Ma W., Qiu L., Wang D., Yang Z. Current status of fertility preservation procedures in gynecologic oncology: From a Chinese perspective. J. Assist. Reprod. Genet. 2025;42:635–645. doi: 10.1007/s10815-024-03341-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Geoffron S., Lier A., de Kermadec E., Sermondade N., Varinot J., Thomassin-Naggara I., Bendifallah S., Daraï E., Chabbert-Buffet N., Kolanska K. Fertility preservation in women with malignant and borderline ovarian tumors: Experience of the French ESGO-certified center and pregnancy-associated cancer network (CALG) Gynecol. Oncol. 2021;161:817–824. doi: 10.1016/j.ygyno.2021.03.030. [DOI] [PubMed] [Google Scholar]
- 21.Mazzon I., Masciullo V., Scambia G., Ferrandina G., Corrado G. Long-term survival of young endometrial cancer patients desiring fertility preservation treated with hysteroscopic resection followed by hormone therapy (NEMO technique) Int. J. Gynaecol. Obstet. 2020;151:305–307. doi: 10.1002/ijgo.13253. [DOI] [PubMed] [Google Scholar]
- 22.Tsonis O., Kopeika J. Fertility preservation in patients with gynaecologic malignancy: Response to ovarian stimulation and long-term outcomes. Eur. J. Obs. Gynecol. Reprod. Biol. 2023;290:93–100. doi: 10.1016/j.ejogrb.2023.09.020. [DOI] [PubMed] [Google Scholar]
- 23.Gallo A., Di Spiezio Sardo A., Conforti A., Iorio G.G., Zizolfi B., Buonfantino C., De Angelis M.C., Strina I., Marrone V., Bifulco G., et al. Assessing ovarian stimulation with letrozole and levonorgestrel intrauterine system after combined fertility-sparing approach for atypical endometrial lesions: A retrospective case-control study. Reprod. Biomed. Online. 2023;48:103750. doi: 10.1016/j.rbmo.2023.103750. [DOI] [PubMed] [Google Scholar]
- 24.Rodolakis A., Scambia G., Planchamp F., Acien M., Di Spiezio Sardo A., Farrugia M., Grynberg M., Pakiz M., Pavlakis K., Vermeulen N., et al. ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma. Hum. Reprod. Open. 2023;2023:hoac057. doi: 10.1093/hropen/hoac057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Cibula D., Rosaria Raspollini M., Planchamp F., Centeno C., Chargari C., Felix A., Fischerová D., Jahnn-Kuch D., Joly F., Kohler C., et al. ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer—Update 2023. Radiother. Oncol. 2023;184:109682. doi: 10.1016/j.radonc.2023.109682. [DOI] [PubMed] [Google Scholar]
- 26.Söderström-Anttila V., Wennerholm U.B., Loft A., Pinborg A., Aittomäki K., Romundstad L.B., Bergh C. Surrogacy: Outcomes for surrogate mothers, children and the resulting families-a systematic review. Hum. Reprod. Update. 2016;22:260–276. doi: 10.1093/humupd/dmv046. [DOI] [PubMed] [Google Scholar]
- 27.Jadva V., Blake L., Casey P., Golombok S. Surrogacy families 10 years on: Relationship with the surrogate, decisions over disclosure and children’s understanding of their surrogacy origins. Hum. Reprod. 2012;27:3008–3014. doi: 10.1093/humrep/des273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Salman L., Covens A. Fertility Preservation in Cervical Cancer-Treatment Strategies and Indications. Curr. Oncol. 2024;31:296–306. doi: 10.3390/curroncol31010019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Tomao F., Corrado G., Peccatori F.A., Boveri S., Preti E.P., Colombo N., Landoni F. Fertility-Sparing Options in Young Women with Cervical Cancer. Curr. Treat. Options Oncol. 2016;17:5. doi: 10.1007/s11864-015-0386-9. [DOI] [PubMed] [Google Scholar]
- 30.Bizzarri N., Pavone M., Loverro M., Querleu D., Fagotti A., Scambia G. Ovarian preservation in gynecologic oncology: Current indications and techniques. Curr. Opin. Oncol. 2023;35:401–411. doi: 10.1097/CCO.0000000000000969. [DOI] [PubMed] [Google Scholar]
- 31.Chaudhri E.N., Salman A., Awartani K., Khan Z., Hashmi S.K. Ovarian Tissue Cryopreservation versus Other Fertility Techniques for Chemoradiation-Induced Premature Ovarian Insufficiency in Women: A Systematic Review and Future Directions. Life. 2024;14:393. doi: 10.3390/life14030393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Corrado G., Marchetti C., Trozzi R., Scambia G., Fagotti A. Fertility preservation in patients with BRCA mutations or Lynch syndrome. Int. J. Gynecol. Cancer. 2021;31:332–338. doi: 10.1136/ijgc-2020-002071. [DOI] [PubMed] [Google Scholar]
- 33.Shapira M., Raanani H., Feldman B., Srebnik N., Dereck-Haim S., Manela D., Brenghausen M., Geva-Lerner L., Friedman E., Levi-Lahad E., et al. BRCA mutation carriers show normal ovarian response in in vitro fertilization cycles. Fertil. Steril. 2015;104:1162–1167. doi: 10.1016/j.fertnstert.2015.07.1162. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The original contributions presented in this study are included in the article. Further inquiries can be directed to the corresponding author.