Reproductive Outcomes in Young Women with Early-Stage Cervical Cancer Greater than 2 cm Undergoing Fertility-Sparing Treatment: A Systematic Review.

Background and Objectives: Despite advancements in detection and treatment, cervical cancer remains a significant health concern, particularly among young women of reproductive age. Limited data exists in the literature regarding fertility-sparing treatment (FST) of cervical cancers with tumor sizes greater than 2 cm. The objective of this systematic review was to evaluate the reproductive outcomes of women diagnosed with cervical cancer greater than 2 cm who underwent FST. Materials and Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies (retrospective or prospective) that reported reproductive outcomes of patients with cervical cancer >2 cm were considered eligible for inclusion in this systematic review (CRD42024521964). Studies describing only the oncologic outcomes, involving FST for cervical cancers less than 2 cm in size, and case reports were excluded. Results: Seventeen papers that met the abovementioned inclusion criteria were included in the present systematic review. In total, 443 patients with a cervical cancer larger than 2 cm were included in this systematic review. Eighty pregnancies occurred, with 24 miscarriages and 54 live births. Conclusions: FST appears to be a viable option for women of childbearing age diagnosed with cervical cancer larger than 2 cm. However, careful consideration is advised in interpreting these encouraging results, as they are subject to limitations, such as variability in study designs and potential biases. In addition, reproductive outcomes should be further cross-referenced with oncologic outcomes to clarify the potential risk-benefit ratio. It is critical to conduct further research using standardized approaches and larger participant groups to strengthen the validity of the conclusions drawn.

Outcomes and cost-effectiveness comparisons of progestin-primed ovarian stimulation, GnRH antagonist protocol, and luteal phase stimulation for fertility preservation.

OBJECTIVE: To compare the clinical outcomes and cost-effectiveness of progestin-primed ovarian stimulation (PPOS) and the gonadotropin-releasing hormone-antagonist (GnRH-A) protocol in fertility preservation (FP) in cancer patients. The stimulation option when patients were in the luteal phase was also explored. METHODS: This retrospective study analyzed clinical data from 163 patients who underwent FP. The number of retrieved oocytes and vitrified oocytes/embryos, total dose of gonadotropin, duration of stimulation, number of injections, and cost were compared among the PPOS, GnRH-A, and luteal phase stimulation (LPS) groups. RESULTS: No significant differences were noted in the numbers of retrieved oocytes and vitrified oocytes/embryos among the three groups. In the multiple regression model, age (P = 0.02) and antral follicle count (AFC) (P < 0.001), but not the controlled ovarian stimulation (COS) protocols (P = 0.586), were associated with the number of retrieved oocytes. The number of injections and the cost were all significantly lower in the PPOS and LPS groups than in the GnRH-A group(P < 0.001). CONCLUSION: PPOS had similar clinical results but was superior medically and economically to GnRH-A. For patients in the luteal phase, LPS was an optional protocol with similar outcomes and costs to PPOS.

Development, Usability Testing, and Implementation Assessment of Cancer Related Infertility Score Predictor, an Online Cancer Related Infertility Risk Counseling Tool.

Purpose: Oncofertility counseling of female cancer patients lacks efficient access to tailored and valid infertility risk estimates to support shared decision-making on fertility preservation treatments. The objective was to develop, conduct user-centered design, and plan clinic-based implementation of the Cancer Related Infertility Score Predictor (CRISP), a web-based tool to support infertility risk counseling. Methods: Using a mixed methods design, literature review was undertaken to abstract data on infertility, primary ovarian insufficiency, and amenorrhea risks of common cancer treatments. The CRISP website was programmed to take user input about patient ages and cancer treatments and generate a risk summary. Using user experience methodology and semistructured interviews, usability testing and implementation assessment were conducted with 12 providers recruited from 5 medical centers in Southern California. Results: The web-based CRISP tool encompasses infertility risk data for 60 treatment regimens among 10 cancer types. Usability testing demonstrated that the tool is intuitive and informed minor modifications, including adding crowd-sourced submission of additional cancer treatments. Participants rated the tool as credible, advantageous over current provider methods to ascertain infertility risks, and useful for tailoring treatment planning and counseling patients. A key barrier was lack of information on some cancer treatments. Fit within clinical workflow was feasible, particularly with electronic health record integration. Conclusions: The novel, web-based CRISP tool is a feasible, acceptable, and appropriate tool to address provider knowledge gap about cancer related infertility risks and use for patient counseling. CRISP has significant potential to support tailored oncofertility counseling in the heterogeneous young cancer patient population.

Cost-effectiveness analysis of ovarian function preservation with GnRH agonist during chemotherapy in premenopausal women with early breast cancer.

STUDY QUESTION: Is it economically worthwhile to use GnRH agonist (GnRHa) to prevent menopausal symptoms (MS) and protect fertility in premenopausal women with breast cancer (BC) during chemotherapy from the US perspective? SUMMARY ANSWER: It is cost-effective to administer GnRHa during chemotherapy in order to forefend MS in premenopausal patients with BC when the willingness-to-pay (WTP) threshold is $50 000.00 per quality-adjusted life-year (QALY), and to preserve fertility in young patients with BC who undergo oocyte cryopreservation (OC), or no OC, when the WTP thresholds per live birth are $71 333.33 and $61 920.00, respectively. WHAT IS KNOWN ALREADY: Chemotherapy often results in premature ovarian insufficiency (POI) in premenopausal survivors of BC, causing MS and infertility. Administering GnRHa during chemotherapy has been recommended for ovarian function preservation by international guidelines. STUDY DESIGN, SIZE, DURATION: Two decision-analytic models were developed, respectively, for preventing MS and protecting fertility over a 5-year period, which compared the cost-effectiveness of two strategies: adding GnRHa during chemotherapy (GnRHa plus Chemo) or chemotherapy alone (Chemo). PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were early premenopausal women with BC aged 18-49 years who were undergoing chemotherapy. Two decision tree models were constructed: one for MS prevention and one for fertility protection from the US perspective. All data were obtained from published literature and official websites. The models' primary outcomes included QALYs and incremental cost-effectiveness ratios (ICERs). The robustness of the models was tested by sensitivity analyses. MAIN RESULTS AND THE ROLE OF CHANCE: In the MS model, GnRHa plus Chemo resulted in an ICER of $17 900.85 per QALY compared with Chemo, which was greater than the WTP threshold of $50 000.00 per QALY; therefore, GnRHa plus Chemo was a cost-effective strategy for premenopausal women with BC in the USA. Probabilistic sensitivity analysis (PSA) results showed an 81.76% probability of cost-effectiveness in the strategy. In the fertility model, adding GnRHa for patients undergoing OC and those who were unable to undergo OC resulted in ICERs of $67 933.50 and $60 209.00 per live birth in the USA, respectively. PSA indicated that GnRHa plus Chemo was more likely to be cost-effective over Chemo when the WTP for an additional live birth exceed $71 333.33 in Context I (adding GnRHa to preserve fertility in young patients with BC after OC) and $61 920.00 in Context II (adding GnRHa to preserve fertility in young patients with BC who cannot accept OC). LIMITATIONS, REASONS FOR CAUTION: The indirect costs, such as disease-related mental impairment and non-medical costs (e.g. transportation cost) were not included. All data were derived from previously published literature and databases, which might yield some differences from the real world. In addition, the POI-induced MS with a lower prevalence and the specific strategy of chemotherapy were not considered in the MS model, and the 5-year time horizon for having a child might not be suitable for all patients in the fertility model. WIDER IMPLICATIONS OF THE FINDINGS: When considering the economic burden of cancer survivors, the results of this study provide an evidence-based reference for clinical decision-making, showing that it is worthwhile to employ GnRHa during chemotherapy to prevent MS and preserve fertility. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Natural Science Foundation of Fujian Province [2021J02038]; and the Startup Fund for Scientific Research, Fujian Medical University [2021QH1059]. All authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Exploring fertility knowledge amongst healthcare professional and lay population groups in the UK: a mixed methods study.

As the average age of first-time parents continues to rise, there has been a concerted effort by educators, policy makers and several reproductive health groups to improve fertility awareness. This study explored fertility knowledge of lay men and women and healthcare professionals (HCPs) using the same test instrument, providing a new and unique perspective compared with previous studies. Results were obtained from 1082 survey respondents: 347 HCPs, 319 men and 413 women, 105 of whom were trying to conceive (TTC). A total of 35 interviewees were purposively sampled to include 9 HCPs, 13 men and 13 women from the reproductive age range and of varying ethnic and educational backgrounds. Interview data were transcribed and analysed using the framework method. The proportion of HCPs correctly answering the survey knowledge questions was 47.1 (95% CI = 41.7%, 52.5%) compared to 44.4% for women (95% CI = 38.9%, 50.1%); 49.9% (95% CI = 39.0, 59.9%) for women TTC; and 32.5% (95% CI = 27.1%, 37.9%) for men. HCPs were ranked as the most trusted source for seeking fertility information. Overall HCPs did not demonstrate better fertility knowledge than lay participants, with inconsistencies regarding where responsibility lies for providing the right information to patients. HCPs need to improve their knowledge about fertility to help improve patient's fertility awareness.

How Accurate Is Oncologist Knowledge of Fertility Preservation Options, Cost, and Time in Female Adolescents and Young Adults?

Purpose: Often cited barriers to fertility preservation (FP) among female adolescent and young adult (AYA) cancer patients include cost and time. We hypothesized that oncologists overestimate the time and costs required for female FP. Methods: We distributed an electronic survey to physicians in oncology-related departments. The survey assessed the knowledge and utilization of gonadotoxic therapies, FP options and requirements, and FP referral patterns. Student's t, Fisher's exact, ANOVA, and Wilcoxon signed-rank tests were used for continuous variables as appropriate; the chi-squared test was used for categorical variables. Results: Among respondents who reported prescribing gonadotoxic agents to AYAs (n = 38), 79% reported often/always discussing FP options, while only half referred to a reproductive specialist often/always. A smaller proportion of pediatric oncologists discussed FP often/always (p = 0.04) and most referred <25% of patients to a reproductive specialist; however, the majority of other specialists referred ≥75% of patients to a reproductive specialist (p = 0.001). While most respondents accurately estimated the time required to complete FP, the majority overestimated the cost of an FP procedure. Knowledge of FP options was inconsistent, with 63.2% reporting that suppression of the hypothalamic-pituitary-ovarian-axis is an option for FP, with 82.6% of these classifying it as standard of care. Conclusions: With variation across specialties, most oncology specialists prescribing gonadotoxic therapies for AYA females discuss FP, while a smaller proportion refer patients for FP. Despite relative accuracy in estimating the time required for FP, they overestimate costs of FP. Educational curricula related to FP are necessary across oncology specialties, especially pediatric oncology.

Fertility preservation in male cancer patients: A mixed methods assessment of experiences and needs.

INTRODUCTION: As fertility may be impaired due to gonadotoxic cancer treatment, fertility preservation should be offered to young cancer patients. Despite affirmative guidelines, sperm cryopreservation rates are still unsatisfying. OBJECTIVE: To examine how male cancer patients experience the current practice of counseling regarding fertility preservation and the needs they have for additional online support tools. METHODS: A cross-sectional mixed methods study of men above 18 years old with a cancer diagnosis within the last 10 years. The quantitative part was a retrospective questionnaire-based online survey; the qualitative part used focus-group methodology. The mean age of participants (n=72) was 32.94 years (SD 8.38) and the predominant cancer types were testicular cancer (55.6%), lymphomas (16.7%), and leukemias (13.9%). RESULTS: Participants rated the significance of the counseling as high (M=4.2, SD=1.05) and experienced professionals as supportive (M=4.37, SD=0.66). A majority of participants (70.8%) stated that they would use an additional support tool designed for male cancer patients. The tool should contain not only information about fertility preservation, but also about sexuality, virility, consequences for partners, and experience reports from other patients. CONCLUSIONS: Cancer patients undergoing gonadotoxic therapies should be counseled about fertility preservation. Professional, individualized information and a well-organized fertility preservation process improve the subjective experience of cancer patients. An online support tool that provides information about fertility preservation and general reproductive health was considered as a helpful, low-threshold offer that would be appreciated.

Update Knowledge Assessment and Influencing Predictor of Female Fertility Preservation in Oncologists.

OBJECTIVE: This study aims to offer an update assessment of the knowledge of Chinese oncologists on female fertility preservation, and identify the determinants that influence the implementation of fertility preservation. METHODS: A total of 713 Chinese oncologists with different specialties completed the online self-report questionnaire to assess their understanding of fertility risks in cancer treatment, knowledge on female fertility preservation, and perceptions on the barriers in referring patients for fertility preservation. RESULTS: Although most oncologists were familiar with fertility risk in cancer treatment, half of them lacked the knowledge for reproduction and preservation methods. In the multivariable model, oncologists in a hospital with a specialized reproductive institution, positive precaution for fertility risk, and fertility preservation discussion with patients were significantly correlated with the possibility of fertility preservation referral. CONCLUSIONS: The intervention targets based on the update evaluation and identified influencing determinants will be helpful for all the oncofertility researchers, oncologists and institutions in future efforts for well-established female fertility preservation services.

Assessment of female fertility preservation in Auvergne 3 years after implementation of the PREFERA platform (PREservation FERtilité Auvergne).

INTRODUCTION: Fertility preservation (FP) in patients with cancer or pathology at risk of gonadotoxicity is now according to legislation, an integral part of the treatment protocol. for this reason, clinical-biological platforms have emerged with the aim of developing and improving this practice, such as the PREFERA platform (PREservation FERtilité Auvergne) MATERIAL ET METHOD: This is an observational cohort study to evaluate female fertility preservation activity in Auvergne at the AMP-CECOS center of the Clermont-Ferrand University Hospital from March 2013 to March 2019. This period covering 3 years before and after the creation of PREFERA in 2015. RESULTS: 205 patients were referred for fertility preservation consultations, including 77 before the platform was set up and 128 after, corresponding to an increase of 66%. 190 patients (92.7%) referred were eligible for FP, of whom 169 (88.9%) received treatment. Thirty-nine patients underwent oocyte vitrification before the platform was set up and 74 after (+89.7%), twenty patients underwent ovarian cortex freezing before the platform was set up and 27 after (+35%). Only 54 patients (26.2%) were seen for follow-up with an increased number of consultations following the implementation of PREFERA. (8% vs 33%, p<0.001). CONCLUSION: Creation of the PREFERA platform facilitated patient access and management of fertility preservation procedures. However, at the regional level, it is necessary to continue to raise awareness of fertility issues, particularly in the context of post-cancer follow-up, both among patients and health professionals.

Cost-effectiveness analysis of ovarian tissue cryopreservation and transplantation for preservation of fertility in post-pubertal oncological women submitted to high-risk gonadotoxic chemotherapy.

OBJECTIVE: To study the economic impact of ovarian tissue cryopreservation and transplantation (OTC) in post-pubertal patients who underwent high-risk gonadotoxic chemotherapy. METHODS: A decision tree model was used to determine the live birth rate and cost-effectiveness of OTC versus non-OTC. The incremental cost-effectiveness ratio (ICER) was calculated. A sensitivity analysis was performed under the assumption that the costs of ovarian cortex retrieval, cryopreservation, and storage for patients with cancer might be covered by the national health system or health insurance. RESULTS: Patients had the greatest probability of achieving live birth after high-risk chemotherapy when they underwent OTC versus non-OTC. Although cryopreservation of ovarian tissue results in higher live birth rates, it is always more expensive. Cost-effectiveness increases when the majority of patients completes the path of tissue cryopreservation plus transplantation after 5 years. CONCLUSION: Although OCT has been demonstrated as a procedure for effective fertility preservation in fertility-age women with cancer, no cost-effectiveness analysis has been performed until now. This model could help healthcare systems to allocate coverage for OCT.

Assessment of the architecture and integrity of frozen-thawed testicular tissue from (pre)pubertal boys with cancer.

BACKGROUND: Testicular tissue freezing is proposed for fertility preservation to (pre)pubertal boys with cancer before highly gonadotoxic treatment. Studies accurately comparing human (pre)pubertal testicular tissue quality before freezing and after thawing are exceptional. No study has reported this approach in a systematic manner and routine care. OBJECTIVES: To assess the impact of a control slow freezing protocol on testicular tissue architecture and integrity of (pre)pubertal boys after thawing. MATERIALS AND METHODS: (Pre)pubertal boys (n = 87) with cancer from 8 Reproductive Biology Laboratories of the French CECOS network benefited from testicular tissue freezing before hematopoietic stem cell transplantation. Seminiferous tubule cryodamage was determined histologically by scoring morphological alterations and by quantifying intratubular spermatogonia and the expression of DNA replication and repair marker in frozen-thawed testicular fragments. RESULTS: A significant increase in nuclear and epithelial score alterations was observed after thawing (p < 0.0001). The global lesional score remained lower than 1.5 and comparable to fresh testicular tissue. The number of intratubular spermatogonia and the expression of DNA replication and repair marker in spermatogonia and Sertoli cells did not vary significantly after thawing. These data showed the good preservation of the seminiferous tubule integrity and architecture after thawing, as previously reported in our studies performed in prepubertal mice and rats. DISCUSSION: The current study reports, for the first time, the development of a semi-quantitative analysis of cryodamage in human (pre)pubertal testicular tissue, using a rapid and useful tool that can be proposed in routine care to develop an internal and external quality control for testicular tissue freezing. This tool can also be used when changing one or several parameters of the freezing-thawing procedure. CONCLUSION: Control slow freezing protocol without seeding maintains the seminiferous tubule architecture and integrity, the concentration of spermatogonia and the expression of DNA replication and repair marker in spermatogonia and Sertoli cells after thawing.

How can fertility counseling be implemented for every newly diagnosed pediatric patient facing gonadotoxic treatment?-A single-center experience.

Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.

Cervical conization and lymph node assessment for early stage low-risk cervical cancer.

OBJECTIVE: There has been a contemporary shift in clinical practice towards tailoring treatment in patients with early cervical cancer and low-risk features to non-radical surgery. The objective of this study was to evaluate the oncologic, fertility, and obstetric outcomes after cervical conization and sentinel lymph node (SLN) biopsy in patients with early stage low-risk cervical cancer. METHODS: We conducted a retrospective review in patients with early cervical cancer treated with cervical conization and lymph node assessment between November 2008 and February 2020. Eligibility criteria included patients with a histologic diagnosis of invasive squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage IA1 with positive lymphovascular space invasion (LVSI), stage IA2, or stage IB1 (≤2 cm) with less than two-thirds (<10 mm) cervical stromal invasion. RESULTS: A total of 44 patients were included in the analysis. The median age was 31 years (range 19-61) and 20 patients (45%) were nulliparous. One patient had a 25 mm tumor while the remaining patients had tumors smaller than 20 mm. Eighteen (41%) patients had LVSI. Median follow-up was 44 months (range 6-137). A total of 17 (39%) patients had negative margins on the diagnostic excisional procedure, and none had residual disease on the repeat cone biopsy. Three (6.8%) patients had micrometastases detected in the SLNs and underwent ipsilateral lymphadenectomy; all remaining non-SLN lymph nodes were negative. Six (13.6%) patients required more definitive surgical or adjuvant treatment due to high-risk pathologic features. There were no recurrences documented. Three patients developed cervical stenosis. The live birth rate was 85% and 16 (94%) of 17 patients had live births at term. CONCLUSION: Cervical conization with SLN biopsy appears to be a safe treatment option in selected patients with early cervical cancer. Future results of prospective trials may shed definitive light on fertility-sparing options in this group of patients.

Prospective assessment of urinary and bowel symptoms, and sexual function between laparoscopic assisted vaginal radical trachelectomy and radical hysterectomy.

OBJECTIVE: Radical trachelectomy is a valid alternative to radical hysterectomy in women with a desire to retain their fertility. Data regarding the oncological outcomes of radical trachelectomy are comparable with those of radical hysterectomy but information regarding urinary and sexual function is limited. The aim of this study was to prospectively evaluate and compare quality of life, urinary and bowel symptoms, and sexual dysfunction between patients who underwent laparoscopic assisted vaginal radical trachelectomy versus radical hysterectomy for early-stage cervical cancer. METHODS: Patients who underwent laparoscopic assisted vaginal radical trachelectomy or radical hysterectomy along with sentinel or systemic pelvic lymphadenectomy were included between May 2015 and January 2017. Patients were asked to complete a validated questionnaire (German pelvic symptom questionnaire) on bladder, bowel, prolapse, and sexual function, and total pelvic score, at least 48 hours before surgery and 6 months after surgery. RESULTS: A total of 51 patients were included. Of these, 26 patients (50.9%) underwent laparoscopic assisted vaginal radical trachelectomy and 25 (49.1%) underwent radical hysterectomy. No patient was converted to laparotomy. The majority of patients (76%) were diagnosed with International Federation of Gynecology and Obstetrics (FIGO 2018) stage 1B1 disease, with squamous cell carcinoma (54%) and grade II tumors (52%). Four patients (7.8 %) experienced perioperative complications (two grade II and two grade III complications according to the Clavien-Dindo classification). In the preoperative evaluation, the median scores for the four items of the questionnaire (bladder, bowel, prolapse, and sexual items) and total pelvic score were comparable between the two groups. The mean scores for radical hysterectomy and radical trachelectomy at the beginning of the study for bladder, bowel, prolapse, and sexual function were 0.93 versus 0.71, 0.71 versus 1.01, 0.12 versus 0.1, and 1.06 versus 1.0, respectively. On preoperative testing, the median scores for all four items of the questionnaire (pbladder=0.821, pbowel=0.126, pprolapse=0.449, psexual=0.965) and the total pelvic score (p=0.756) were comparable between the two groups. The radical hysterectomy group had worse total pelvic scores at the 6 month postoperative survey compared with baseline (p=0.03). There was no difference in bladder (p=0.07) or bowel symptoms (p=0.07) in the radical hysterectomy group comparing baseline with the 6 month assessment. Women undergoing radical hysterectomy experienced more urinary morbidity than women undergoing vaginal trachelectomy at 6 weeks (p=0.025). However, the mean bladder and pelvic scores in the 6 month control were comparable between patients who had and those who had not experienced urinary morbidity (pbladder=0.127, ptotal pelvic score=0.480). CONCLUSION: Patients undergoing laparoscopic assisted vaginal radical trachelectomy had similar pelvic scores in both the preoperative and postoperative periods. However, patients undergoing radical hysterectomy showed worse total pelvic scores on the postoperative assessment compared with the baseline evaluation. Urinary dysfunction in the early postoperative phase was more common in the radical hysterectomy group than in trachelectomy group.

The validity of the subsequent pregnancy index score for fertility-sparing trachelectomy in early-stage cervical cancer.

OBJECTIVE: To evaluate timing and a prediction model for pregnancy in early-stage cervical cancer patients who underwent fertility-sparing trachelectomy. DESIGN: Retrospective cohort. SETTING: Academic multicenter. PATIENT(S): Women ages <45 years with clinical stage I-II cervical cancer were enrolled between 2009 and 2013 (n = 393). INTERVENTION(S): Planned fertility-sparing trachelectomy. MAIN OUTCOME MEASURE(S): Cumulative incidences and clinicopathological characteristics of those who developed subsequent pregnancy were examined. RESULT(S): There were 77 (21.6%) women who had subsequent pregnancies after fertility-sparing trachelectomy with 1-, 2-, and 5-year cumulative pregnancy rates of 2.8%, 6.2%, and 17.4%, respectively. The median time to develop subsequent pregnancy was 3.2 years. In a competing risk analysis, women had a higher risk of recurrent cancer than conception during the first 11 months postsurgery. On multivariable analysis, younger age, being married, and postoperative reproductive treatment were independently associated with an increased chance of developing a subsequent pregnancy. The subsequent pregnancy index (SPI) score to predict the likelihood of having pregnancy was proposed, and it was calculated based on age, marital status, and reproductive treatment (2, 2, and 4 points, respectively). Women with a higher SPI score had significantly higher subsequent pregnancy rates (5-year pregnancy rate; the score was 3 in 4.7% of cases; 4 to 5 in 11.3%; 6 to 7 in 27.4%; and 8 in 50.8%), but they had similar recurrence rates (5.0%). CONCLUSION(S): The SPI score proposed in our study is useful in predicting subsequent pregnancy in women with early-stage cervical cancer undergoing fertility-sparing trachelectomy.

Planned oocyte cryopreservation (Planned OC): systematic review and meta-analysis of cost-efficiency and patients' perspective.

BACKGROUND: Advances in vitrification techniques have enabled planned oocyte cryopreservation ('Planned OC'). OBJECTIVES: To explore the cost-efficiency and utilisation of planned OC, as well as patients' perspectives on the process. SEARCH STRATEGY: A systematic search in PubMed/MEDLINE, Embase, Cochrane Database and PsychINFO, for all relevant studies published between January 2007 and December 2019. SELECTION CRITERIA: The protocol followed PRISMA guidelines in PECO format, and was registered with PROSPERO. DATA COLLECTION AND ANALYSIS: Two independent reviewers evaluated all manuscripts for inclusion eligibility. Authors were contacted for missing data. Included studies were assessed for risk of bias and for heterogeneity. Weighted effects were measured and plotted. MAIN RESULTS: The search yielded 12 545 records, of which 43 were included. Planned OC is cost-efficient at 35, assuming 60% utilisation; and at 37 assuming utilising donor sperm when necessary. At 38 it is cost-efficient to defer planned OC in favour of undergoing 2 IVF cycles. Currently, utilisation of banked-oocytes within 22-58 months, is up to 15%. Nine percent of warmed banked oocytes result in life births. Online resources and treating physicians are equally important sources of information regarding planned OC. Most patients think planned OC is ideal before age 35 and are not fully aware of what the process entails and tend to overestimate the success rates. The main barrier to wider endorsement of planned OC is being wary of potential health implications or of limited success. CONCLUSION: Planned OC is an adequate method for preserving fertility. However, knowledge gaps result in under-utilisation leading to reduced cost-efficiency. TWEETABLE ABSTRACT: Identifying facilitators and barriers for wider adoption of banking oocytes can enhance the cost-efficiency of this modality.

Male infertility treatment for cancer survivors: does anticancer treatment affect infertility treatment?

We investigated the impact of prior anticancer treatments such as chemotherapy and radiotherapy on subsequent infertility treatment in cancer survivors who consulted our male infertility division. Of 1,525 male infertility patients who consulted our division between 2008 and 2018, 56 (3.7%) were cancer survivors. Of these, 32 received anticancer treatment (group A) and 24 were treated with surgery alone or were seen before anticancer treatment (group B). Semen analysis revealed that azoospermia in 26 subjects (81.3%) and 14 (58.3%) in groups A and B respectively. Ejaculatory dysfunction was observed 1 in group A and in 2 group B subjects. Sperm cryopreservation before anticancer treatment was performed 4 subjects. Sperm retrieval surgery for intracytoplasmic sperm injection (ICSI) was performed in 13 cases in group A and 10 in group B. Motile sperm were recovered in 7 subjects and in 8 subjects in group A and B respectively. Overall pregnancies and deliveries with ICSI were achieved for 7 subjects (21.9%) in group A, and 9 (37.5%) in group B. Successful sperm retrieval may not be affected by prior anticancer treatment as shown in this study. However, some patients abandoned infertility treatment due to the cost of testing and sperm retrieval surgery. Support for the cost of infertility treatment in cancer survivors is necessary.

The indication for fertility preservation in women with Turner syndrome should not only be based on the ovarian reserve but also on the genotype and expected future health status.

Fertility preservation in women with Turner syndrome is highly controversial. Some strongly recommend freezing of ovarian tissue at a young age, others do not. The controversy is partly due to different perspectives and professions. Biologists prefer to freeze young ovaries with high follicle density, reproductive physicians want to avoid risky operations and iatrogenic infertility by removing one ovary, and cardiologists and obstetricians warn against the risks of later pregnancies. Accordingly, fertility preservation in young women with Turner syndrome is more than just the freezing of ovarian tissue or oocytes. Fertility preservation requires a balanced decision considering the conservation of fertility, the protection of reproductive health, and future health consequences. Therefore, fertility preservation strategies should be based not only on the individual ovarian reserve but also on the genotype and the expected cardiac health status to decide what is the best option: to freeze tissue or alternatively to wait and see.

Trends in guideline-adherent fertility-sparing surgery for early-stage cervical cancer before and after the Affordable Care Act.

OBJECTIVE: To assess trends in guideline-adherent fertility-sparing surgery (GA-FSS) for early-stage cervical cancer relative to Patient Protection and Affordable Care Act (ACA) implementation. METHODS: National Cancer Database patients treated for Stage IA1-IB1 cervical cancer from 2004 to 2016 were included. Multivariable logistic regression was used to determined trends in GA-FSS relative to the ACA and identify patient factors independently associated with GA-FSS. RESULTS: Odds of GA-FSS increased in the post- compared to pre-ACA cohort (aOR = 1.65; 95%CI: 1.34-2.03). Decreasing age, Asian/Pacific Islander race, higher education and income levels, more recent treatment year, and lower clinical stage were independently associated with increased odds of receiving GA-FSS. In the pre- and post-ACA samples, decreasing age (per 1 year age increase; pre-ACA aOR = 0.87, 95%CI:0.85-0.90; post-ACA aOR = 0.85, 95%CI:0.83-0.87), higher education level (top vs. lowest education quartile; pre-ACA aOR = 2.08, 95%CI:1.19-3.65; post-ACA aOR = 2.00, 95%CI:1.43-2.80), and lower clinical stage (stages IA2 [pre-ACA aOR = 0.19, 95%CI:0.09-0.41; post-ACA aOR = 0.29, 95%CI:0.19-0.45] and IB1 [pre-ACA aOR = 0.06, 95%CI:0.06-0.16; post-ACA aOR = 0.16, 95%CI: 0.12-0.20] relative to stage IA1) were independently associated with increased odds of GA-FSS receipt. After the ACA, Asian/Pacific Islander race (aOR = 2.81, 95%CI: 1.81-4.36) and more recent treatment year (Spearman's ρ = 0.0348, p-value = 0.008) were also independently associated with increased odds of GA-FSS receipt. When adjusted for the pre- vs. post-ACA treatment periods, Medicaid patients were less likely to undergo GA-FSS than privately-insured patients (aOR = 1.65; 95%CI:1.34-2.03). CONCLUSIONS: Patients were more likely to receive GA-FSS post-ACA. Though the proportion of publicly-insured women increased after ACA implementation, women on Medicaid remained less likely to receive GA-FSS than women with private insurance.

Installing oncofertility programs for common cancers in limited resource settings (Repro-Can-OPEN Study): An extrapolation during the global crisis of Coronavirus (COVID-19) pandemic.

PURPOSE: The state of limited resource settings that Coronavirus (COVID-19) pandemic has created globally should be taken seriously into account especially in healthcare sector. In oncofertility, patients should receive their fertility preservation treatments urgently even in limited resource settings before initiation of anticancer therapy. Therefore, it is very crucial to learn more about oncofertility practice in limited resource settings such as in developing countries that suffer often from shortage of healthcare services provided to young patients with cancer. METHODS: As an extrapolation during the global crisis of COVID-19 pandemic, we surveyed oncofertility centers from 14 developing countries (Egypt, Tunisia, Brazil, Peru, Panama, Mexico, Colombia, Guatemala, Argentina, Chile, Nigeria, South Africa, Saudi Arabia, and India). Survey questionnaire included questions on the availability and degree of utilization of fertility preservation options in case of childhood cancer, breast cancer, and blood cancer. RESULTS: All surveyed centers responded to all questions. Responses and their calculated oncofertility scores showed different domestic standards for oncofertility practice in case of childhood cancer, breast cancer, and blood cancer in the developing countries under limited resource settings. CONCLUSIONS: Medical practice in limited resource settings has become a critical topic especially after the global crisis of COVID-19 pandemic. Understanding the resources necessary to provide oncofertility treatments is important until the current COVID-19 pandemic resolves. Lessons learned will be valuable to future potential worldwide disruptions due to infectious diseases or other global crises.