Indications For Fertility Preservation Research Articles

Clinical and ethical perspectives of ovarian stimulation and oocyte cryopreservation in adolescents: 6 years experience from a tertiary Centre

Abstract STUDY QUESTION What are the clinical and ethical challenges of performing ovarian stimulation and oocyte cryopreservation in adolescents and the barriers to providing treatment? SUMMARY ANSWER Our study shows that, in one of the largest case series to date in this population, post-pubertal adolescents as young as age 13 years can undergo ovarian stimulation and oocyte cryopreservation with a response comparable to adults. WHAT IS KNOWN ALREADY Fertility preservation in adolescents has not been well studied, with little data available in the existing literature. Referrals for fertility preservation in adolescents are increasing due to developments in childhood cancer treatments, which have led to a growing population of children at risk of developing premature ovarian insufficiency. Those with certain benign conditions or gender incongruence also face this challenge. All established fertility preservation guidelines state that where there is a risk to fertility, oocyte cryopreservation should be offered to post-pubertal females. However, counselling and consenting young people about fertility decisions is an ethically complex area and assessing capacity to consent in this age group is not straightforward. STUDY DESIGN, SIZE, DURATION This was a retrospective observational cohort study of 182 referrals for fertility preservation counselling to a specialist unit and we present outcomes for the 33 adolescents who underwent 36 cycles of ovarian stimulation and oocyte cryopreservation between January 2018 and January 2024. PARTICIPANTS/MATERIALS, SETTING, METHODS We included patients aged 13 to 18 years who underwent ovarian stimulation and oocyte cryopreservation for fertility preservation due to high or intermediate risk of gonadotoxicity from medical or surgical treatment at a public-funded specialist unit. The primary outcome was oocyte yield; secondary outcomes included oocyte maturity rate, complications and dropout rate. Data were retrieved from a prospectively managed database. MAIN RESULTS AND THE ROLE OF CHANCE There was a total of 182 referrals received and of these 33 patients underwent 36 cycles of ovarian stimulation and oocyte cryopreservation. Indications for fertility preservation included malignancy n = 19/36 (54%), ovarian cyst surgery n = 7/36 (19%), immunological disorders n = 4/36 (11%), benign haematological disease n = 2/36 (6%), gender reassignment treatment 3/36 (8%) and genetic conditions n = 1/36 (3%). The youngest child who underwent ovarian stimulation was aged 13 years and 10 months at the time of egg collection, minimum time from menarche to ovarian stimulation was 4 months, median AMH (anti-Müllerian hormone) was 16.7 pmol/L (range 2.8–36.9 pmol/L) and antral follicle count (AFC) 11 (3-36). The median number of cryopreserved oocytes was 14 (range 4-39) and oocyte maturity rate 85% (35-100%). Ultrasound monitoring was performed transabdominally in 5/33 (15%) and transvaginally in 28/33 (85%). Egg collection was performed transvaginally in all cases in this cohort. All cycles proceeded to completion. All adolescents were counselled in association with a family member to obtain informed consent and all were assessed as able to comprehend discussions. LIMITATIONS, REASONS FOR CAUTION In view of concerns regarding increased aneuploidy rates in this age group compared to women in their 20 s, there is a need for long-term outcome studies expanding on our findings with data on livebirths, to support clinicians needing to counsel patients and perform oocyte cryopreservation in adolescents. WIDER IMPLICATIONS OF THE FINDINGS Clinician experience, correct setting and availability of funding will enable a permissive environment for oocyte cryopreservation in adolescents. In our experience transvaginal egg collection is an accepted procedure when counselled appropriately. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this work. No competing interests are declared. TRIAL REGISTRATION NUMBER Not applicable

O-234 Indication for fertility preservation in patients with endometriosis

Abstract Endometriosis is a complex gynecological condition that not only causes debilitating symptoms but also significantly impacts fertility. As the disease affects approximately 10% of women of reproductive age, addressing fertility preservation strategies becomes paramount. The conventional treatments for endometriosis, such as medical therapy and surgery, often fail to fully address its adverse effects on ovarian reserve and reproductive potential. Consequently, there is a growing interest in exploring fertility preservation options, particularly oocyte cryopreservation (OOC), for endometriosis patients. Despite the prevalence and impact of endometriosis on fertility, comprehensive data and guidelines specifically tailored to fertility preservation in this population remain scarce. The available evidence suggests that endometriosis, particularly when it involves ovarian endometriomas, is associated with a significant reduction in ovarian reserve, as indicated by lower levels of anti-Müllerian hormone (AMH). Surgical interventions, often necessary for managing endometriosis-related complications, can further compromise ovarian function and diminish fertility prospects. However, recent studies have shed light on the potential benefits of OOC in preserving fertility for endometriosis patients. OOC offers a minimally invasive approach with no impact on ovarian reserve compared to other fertility preservation techniques. Despite the lack of randomized controlled trials, our retrospective data have demonstrated promising outcomes, with a notable number needed to treat (NNT) of 16 for one successful pregnancy. This underscores the significance of discussing and considering OOC as part of the treatment plan for endometriosis patients, especially those at risk of ovarian compromise due to the disease or its management. The decision to pursue fertility preservation through OOC should be made on a case-by-case basis, taking into account various factors such as disease severity, patient age, ovarian reserve, and treatment history. French guidelines recommend considering OOC for endometriosis patients with bilateral ovarian endometriomas larger than 3 cm or those with endometriomas on a single ovary. Initiating fertility preservation discussions early, preferably before surgical intervention, allows patients to make informed decisions regarding their reproductive future. It is crucial to acknowledge the challenges and uncertainties associated with fertility preservation in endometriosis patients. Socio-economic factors, patient preferences, and the lack of clear criteria for selecting candidates for OOC pose significant hurdles. Furthermore, the effectiveness and cost-effectiveness of OOC in this population warrant further investigation. In addition to OOC, alternative fertility preservation options, such as ovarian tissue preservation, could be considered, particularly in cases where ovarian stimulation is not feasible or declined by the patient. However, data on the efficacy and safety of ovarian tissue preservation specifically in endometriosis patients are limited, highlighting the need for further research in this area. In conclusion, fertility preservation, particularly through OOC, holds promise for mitigating the adverse effects of endometriosis on ovarian function and fertility. While uncertainties persist, integrating fertility preservation discussions into the comprehensive management of endometriosis is essential. This ensures that patients are empowered to make informed decisions about their reproductive health and maximizes their chances of achieving desired fertility outcomes despite the challenges posed by endometriosis.

A 12-year overview of fertility preservation practice in Nordic pediatric oncology centers.

Fertility preservation is the only option to safeguard fertility following gonadotoxic treatments. This study aimed to provide an updated status on fertility preservation for pediatric cancer patients in the Nordic countries. A questionnaire consisting of 14 questions was sent to directors of 18 main pediatric oncology centers in the Nordic countries in 2010 and 2022. We received information regarding indications, guidelines, counseling, and available fertility preservation options. The response rates were 89% in 2010 and 72% in 2022. The results reveal an increase in clinical practice guidelines on fertility preservation for cancer patients, from 25% in 2010 to 70% in 2022. Counseling on fertility preservation options in 2022 was more specific and offered to most patients who fulfilled indications for fertility preservation (from 19 to 77%). Sperm cryopreservation continues to be the predominant fertility preservation method for pubertal boys in the Nordic countries. However, there has been a notable increase in the availability of testicular tissue preservation for prepubertal boys (0 to 62%). A similar increase in the offer of ovarian tissue preservation for prepubertal girls (0 to 92%) was observed among pediatric cancer patients. The past decade has shown commendable advancements in fertility preservation for pediatric cancer patients in the Nordic countries. As fertility care evolves globally, continuous assessment of regional practices and challenges is imperative to enhance the quality of care and life for pediatric cancer survivors in the Nordic regions.

Gonadotropin-Releasing Hormone (GnRH) Agonists Do Not Protect Ovarian Function in Patients Undergoing Stem Cell Transplants.

Introduction Medical indications for fertility preservation include any malignancy, chronic illness, or disease that would require gonadotoxic chemotherapy or radiation (conditioning regimens), which would impede a woman's ability to conceive in the future. Thus, any patient who plans to undergo a gonadotoxic regimen is advised to cryopreserve oocytes or embryos, which can be used in the future at the patient's convenience. Attempts have been made to suppress ovarian function with gonadotropin-releasing hormone agonists (GnRH-a) to induce ovarian quiescence and, thereby, theoretically limit the gonadotoxicimpact onthe follicular pool. We explored the use of leuprolide (a type of GnRH-a) inpreventing primary ovarian insufficiency (POI) in a cohort study of patients who underwent hematopoietic stem cell transplants (HSCT) at the National Institutes of Health(NIH); since the conditioning regimens for HSCT include cyclophosphamide and other gonadotoxic therapies, we hypothesized that GnRH-a would be ineffective in preventing POI. Methods We assessedpatients who underwent fertility preservation prior to their stem cell transplant, as their follicular-stimulating hormone(FSH) levels were evaluated prior to and post-chemotherapy. Twenty-nine patients who underwent hormonal evaluation prior to and post-chemotherapy were included. The control group did not receive GnRH-a prior to chemotherapy, while the treatment group did receive GnRH-a pre-chemotherapy. Results Our data revealed that 80% of the control group had menopausal levels post-chemotherapy, while 91% of the treatment group still had menopausal levels post-chemotherapy (p=0.33). Conclusions Thus, our hypothesis that GnRH-a is ineffective in reducing the risk of POI in a cohort of patients who receive conditioning regimens for HSCT was confirmed.

Fertility preservation in women affectedbyagynecologic carcinoma

Gynecological cancers quite often affect young women who wish to preserve their fertility. In addition, with the advancement in age of first pregnancies, this problem has currently taken on a significant scale. Most often, fertility preservation is possible provided that the cancerous tumor is discovered at an early stage and of a non-aggressive histological nature. For uterine cancers (cervix and endometrium), surgery preserving uterine function (associated with hormone therapy for endometrial cancers) is often possible for early tumor stages. For ovarian cancers, indications for fertility preservation are rare and reserved for certain histological types, mainly borderline tumors.

Comparison of the diagnostic value of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer: a prospective study.

To compare the diagnostic value of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer patients. Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT within 2weeks, and surgical treatment was performed within 10days after PET. Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [18F]FDG and [68Ga]Ga-FAPI-04 lymph node high metabolism were staged as FIGO IIIC1r, and concurrent chemoradiation therapy (CCRT) was performed. [18F]FDG and [68Ga]Ga-FAPI-04 had equivalent detection ability on primary tumors, with a positive detection rate of 96.0%. The accuracy of T staging using [18F]FDG and [68Ga]Ga-FAPI-04 was relatively 50% and 55.0%. Elevated and underrated staging was due to misdiagnosis of either vaginal infiltration or tumor size. In terms of lymph node metastasis detection, the specificity of [68Ga]Ga-FAPI-04 was 100% (95% CI, 84.6% ~ 100.0%), which was significantly higher than [18F]FDG (59.1% (95% CI, 36.4% ~ 79.3%)) (p = 0.004). [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT demonstrated an equivalent detection ability on cervical cancer primary tumors. However, [68Ga]Ga-FAPI-04 PET/MR's diagnostic value in lymph node metastasis was significantly higher than [18F]FDG PET/CT. [68Ga]Ga-FAPI-04 PET/MR has the potential for more accurate treatment planning, thus clarifying fertility preservation indications for early-stage young patients.

Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

BackgroundThe indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation.MethodsWe conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome.ResultsForty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births.ConclusionsOocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

P-399 Oocyte vitrification does not impair clinical outcomes in women of advanced maternal age. An analysis of 1268 cycles using fresh and vitrified oocytes

Abstract Study question Does oocyte vitrification impair clinical outcomes in women of advanced maternal age (AMA, &amp;gt;35 years old)? Summary answer Up to the age of 39 years, clinical outcomes were comparable amongst cycles using fresh and vitrified oocytes. What is known already Primarily recommended for young women, oocyte vitrification is the most efficient method for elective fertility preservation. Nevertheless, various social and economic circumstances often compel women to undergo fertility preservation when already at an AMA. Recent studies in mouse suggest that AMA increases the vulnerability of oocytes to molecular and subcellular damage during vitrification, ultimately compromising embryo viability and implantation potential. However, the effects of oocyte vitrification on human preimplantation development and clinical outcomes in women of AMA currently remain unknown. Study design, size, duration This is a retrospective cohort single-center study. We compared outcomes of 1268 patients undergoing their first fresh ICSI cycle using autologous fresh (n = 1087) or vitrified oocytes (n = 181), performed between January 2019 and October 2022. All vitrified oocytes were obtained following elective fertility preservation for age-related fertility decline. Outcomes were stratified according to maternal age at oocyte pick-up: control group (≤35) and AMA groups (36-37, 38-39 and ≥40 years). Participants/materials, setting, methods We compared outcomes between fresh and vitrified oocytes across matching maternal age groups. These included fertilization rates, proportion of viable embryos on day 3, clinical pregnancy and live birth rates. Univariate and multivariate analyses (2-contrast linear and logistic regression) were used to establish correlations. Analyses were adjusting for sperm origin (partner or donor), day of transfer (3 or 5), number of embryos transferred and endometrial age. All p values &amp;lt;0.05 were considered significant. Main results and the role of chance Sperm donation and homologous cycles were equally distributed among the study groups (45% sperm donor and 55% male partner across the entire cohort). In our cohort, blastocyst transfer was performed less frequently in older women, 23.8% for women ≥40 years compared to 45.6% for women ≤35 years (p &amp;lt; 0.0001). When comparing oocyte status across matching maternal age groups, fertilization rates were ∼10% lower when vitrified oocytes were used (p &amp;lt; 0.05). Our adjusted analysis confirmed this negative impact of oocyte vitrification on fertilization rates. Oocyte vitrification also affected ongoing cleavage, as the proportion of viable embryos on day 3 was significantly lower across all groups when vitrified oocytes were used (p &amp;lt; 0.05). Nevertheless, this effect did not translate to clinical pregnancy rates, which were comparable across all maternal age groups regardless of oocyte status. As expected, live birth rate decreased steadily with advancing maternal age (from 38.5% in women ≤35 to 15.0% in women ≥40). While our adjusted analysis showed a negative effect of oocyte vitrification on live birth rates for patients ≥40 (OR: 0.60, 95%CI: 0.18-2.06), we observed no such effect in AMA patients ≤39 years. Limitations, reasons for caution The main limitation of this study is its retrospective design. The low number of women ≥40 undergoing fertility presentation (n = 39) warrants careful interpretation. Our results cannot be generalized to all patient populations and indications for fertility preservation. Wider implications of the findings Clinical outcomes were comparable between fresh and vitrified oocytes up to the age of 39 years. While oocyte vitrification before 35 years old remains the most established and effective method for preventing age-related fertility decline, our findings offer a valuable clinical resource for counselling AMA patients considering elective fertility preservation. Trial registration number Not applicable

O-278 Medical and ethical perspectives of performing ovarian stimulation and oocyte cryopreservation for fertility preservation (FP) in adolescents: 5 years’ experience from a tertiary centre

Abstract Study question What are the medical and ethical challenges of performing ovarian stimulation and oocyte cryopreservation in adolescents and what are the barriers to provision? Summary answer Oocyte cryopreservation for benign and malignant indications in adolescents is associated with unique medical and ethical challenges. What is known already An improvement in childhood cancer survival, increased transgender care and benign conditions such as haemoglobinopathies requiring stem cell transplant have led to higher representation of adolescent birth-registered females in FP clinics. FP in adolescents has increased complexities, both physical (pubertal stage, diagnosis) and psychological (accepting diagnosis, processing information, decision-making). Concerns relate to reliability of AMH in adolescents, anticipated response to ovarian stimulation and oocyte quality. Counselling and consenting young people and their families about fertility decisions, often alongside receiving a life-changing diagnosis, is an ethically complex area. Assessing capacity to consent is not straightforward. We report our clinical experience. Study design, size, duration This was a retrospective, observational cohort study of 26 adolescent birth-registered females aged 13 to 18 years who underwent ovarian stimulation and oocyte cryopreservation in a specialist unit for fertility preservation between 2018 and 2022. The primary outcome was oocyte yield, secondary outcomes included complications and drop-out rate. Participants/materials, setting, methods We included post-pubertal adolescent birth-registered females aged 13 to 18 years who were referred for fertility preservation for high risk of gonadotoxicity from treatment and who commenced ovarian stimulation for oocyte cryopreservation. Data was retrieved from a prospectively managed database. We noted demographic data, ovarian reserve, method of monitoring, response to ovarian stimulation and oocyte cryopreservation and route of egg collection. Documentation on counselling conversations and psychological maturity was retrieved from clinical records. Main results and the role of chance There were a total of 29 ovarian stimulation cycles performed in 26 adolescent birth-registered females aged between 13 and 18 years. Indications for fertility preservation included malignancy 62% (16/26), immunological disorders 19% (5/26), gender reassignment treatment 8% (2/26), recurrent ovarian cyst surgery 8% (2/26) and benign haematological disease 4% (1/26). The youngest was aged 13 years and 10 months at the time of egg collection. Minimum time from menarche to ovarian stimulation was 11 months. 23% (6/26) adolescents had previously received chemotherapy. AMH was 2.8-37 pmol/L and AFC 2-36. AFC correlated well with AMH in the majority. Random-start was performed in 54% (14/26) and dual stimulation in 12% (3/26). Number of cryopreserved oocytes was 3-45 and number of MII oocytes cryopreserved 3-35. Ultrasound monitoring was performed transabdominally in 88% (23/26) and transvaginally in 12% (3/26). Egg collection was performed transvaginally in all cases in this cohort, comprising adolescents from varying ethnicities. All cycles proceeded to completion. There were no complications in any cycle, including the 42% (11/26) performed for haematological malignancy. All adolescents were counselled in association with a family member to obtain informed consent. All were assessed as able to comprehend discussions. Limitations, reasons for caution There is limited data on performing oocyte cryopreservation in adolescents. Further studies expanding on our findings are needed to support clinicians to perform oocyte cryopreservation in this population. Concerns remain regarding increased aneuploidy rates in this age group compared to women in their 20s. Livebirth outcome data is needed. Wider implications of the findings This is the largest case series to date. Post-pubertal adolescents as young as age 13 can undergo ovarian stimulation and oocyte cryopreservation. Transvaginal egg collection is an accepted procedure when counselled appropriately. Clinician experience, correct setting and funding enable a permissive environment for oocyte cryopreservation in this population. Trial registration number N/A

Relapse Rates and Disease-Specific Mortality Following Procedures for Fertility Preservation at Time of Breast Cancer Diagnosis

Breast cancer (BC) is the most common indication for fertility preservation (FP) in women of reproductive age. Procedures for FP often include hormonal stimulation, but current data are scarce regarding whether using hormonal stimulation for FP is associated with any deterioration in BC prognosis. To investigate the risk of disease-specific mortality and relapse in women who underwent FP with or without hormonal stimulation compared with women who did not at time of BC diagnosis. This Swedish nationwide prospective cohort study was conducted to assess the safety of hormonal and nonhormonal FP procedures indicated by BC in Sweden from January 1, 1994, through June 30, 2017. Women were identified from any of the regional FP programs located at Swedish university hospitals. A total of 425 women were found to have undergone FP, and 850 population comparators who had not undergone FP were sampled from regional BC registers and matched on age, calendar period of diagnosis, and region. Relapse-free survival was assessed in a subcohort of 241 women who underwent FP and 482 women who had not, with complete data. Nationwide demographic and health care registers provided data on outcome, disease- and treatment-related variables, and socioeconomic characteristics. Data analyses were performed between November 2021 and March 2022 and completed in June 2022. Relapse and disease-specific mortality after a diagnosis of BC. The final study population included 1275 women (mean [SD] age, 32.9 [3.8] years) at the time of BC diagnosis. After stratification by the matching variables age, calendar period, and region, and adjustment for country of birth, education, parity at diagnosis, tumor size, number of lymph node metastases, and estrogen receptor status, disease-specific mortality was similar in women who underwent hormonal FP (adjusted hazard ratio [aHR], 0.59; 95% CI, 0.32-1.09), women who underwent nonhormonal FP (aHR, 0.51; 95% CI, 0.20-1.29), and women who were not exposed to FP (reference). In a subcohort with detailed data on relapse, adjusted rate of disease-specific mortality and relapse were also similar among the groups who underwent hormonal FP (aHR, 0.81; 95% CI, 0.49-1.37), underwent nonhormonal FP (aHR, 0.75; 95% CI, 0.35-1.62), and were not exposed to FP (reference). In this cohort study, FP with or without hormonal stimulation was not associated with any increased risk of relapse or disease-specific mortality in women with BC. Results of this study provide much needed additional evidence on the safety of FP procedures in women with BC and may influence current health care practice to the benefit of young women with BC who wish to preserve their fertility.

Fertility preservation in women: where we are now and the path we need to take

Background: In its short history, reproductive medicine has achieved many fertility-related milestones, including: the arrival of in vitro fertilization in the late 1970s, the development of intracytoplasmic sperm injection in the early 1990s, the first ovarian transplant a decade ago, and the first livebirth after uterine transplantation in 2014. This paper provides a brief overview of the indications and methods, as well as future perspectives, available for fertility preservation.Current Concepts: More women are undergoing fertility preservation for medical or social reasons. Fertility preservation aids cancer patients in retaining the ability to procreate. Despite the high survival rate of malignancies in young patients, chemotherapy and whole abdominal irradiation have cytotoxic effects on reproductive organs. Cancer treatments can significantly reduce a patient’s reproductive capacity and thus result in irreversible infertility. Early ovarian failure is also a common by-product of additional cancer treatment, bone marrow transplantation, or autologous transplantation. The current options for fertility preservation in cancer patients include cryopreservation (of embryos, oocytes, and ovarian tissue) and gonadotropic-releasing hormone agonist treatment (before and during chemotherapy). Fertility preservation is a means for female cancer patients to preserve their fertility and delay childbearing. Fertility preservation can also aid women who wish to delay childbearing for personal reasons. Since the indications for fertility preservation are different for each patient, individualized treatment strategies should be employed depending on the patient’s situation.Discussion and Conclusion: Health professionals must inform women who are undergoing cancer treatments or purposefully delaying childbearing about the risks of decreased fertility. Appropriate fertility preservation options must be provided for these female patients.

Chinese expert consensus on clinical practice of female fertility preservation

Abstract Many female fertility preservation-related technologies have recently been developed in response to increasing demand for such treatments. To establish standard practices of female fertility preservation in China, the Chinese Maternal and Child Health Association Affiliated Fertility Preservation Professional Committee assembled specialists to construct a consensus, referring to the current clinical guidelines of some countries combined with clinical practice and expert opinions. The consensus includes two parts: (1) indications for female fertility preservation and related techniques, in which we sought to be inclusive regarding the indications for fertility preservation; and (2) practical guidance for the clinical application of the female fertility preservation technologies.

Effect of Previous Alkylating Agent Exposure on Follicle Numbers in Cryopreserved Prepubertal and Young Adult Ovarian Tissue after Long-Term Xenografting.

Simple SummaryCryopreservation of ovarian tissue is a promising technique for fertility preservation in cancer patients at increased risk for subfertility. The International Guideline Harmonization Group recommends ovarian tissue cryopreservation for children and young adults before therapy with cumulative doses of alkylating agent at or above 6000–8000 mg/m2. A therapy that poses a high risk of subfertility is rarely the first-line therapy and many of the patients have already undergone several regimens of chemotherapy. The aim of our study was to assess the effects of chemotherapy exposures on the quality of cryopreserved ovarian tissue. We confirmed the harmful effects of alkylating agents on xenografted ovarian tissue and suggest that cumulative doses which are not regarded as an indication for fertility preservation in children and young adult may decrease the quality of cryopreserved follicles.Purpose and methods: To elucidate whether previous cancer treatment affects graft recovery and follicle numbers, morphology, and development in grafts, cryopreserved ovarian biopsies obtained from 18 cancer patients aged 1–24 years with and without exposure to chemotherapy were xenografted as 1 mm3 fragments to immunodeficient mice for 22 weeks with exogenous stimulation. Results: Graft recovery showed no association with chemotherapy exposure, pubertal stage, or leukemia contamination. Total follicle number per recovered graft varied between 0 and 1031 in the chemotherapy-exposed and between 0 and 502 in the non-chemotherapy-exposed group. Atretic follicles formed the largest proportion of the follicle pool in chemotherapy-exposed grafts. Increased atresia correlated with exposure to alkylating agents (mean ± SD 8866.2 ± 9316.3 mg/m2) but not with anthracyclines, pubertal stage, or leukemia contamination. Conclusion: The observation confirms the harmful effects of alkylating agents on ovarian tissue. Therapy at the median cumulative dose of 8866 mg/m2 leads to the decreased quality of cryopreserved ovarian follicles in children and young adults.

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

Fertility preservation is a novel clinical discipline aiming to protect the fertility potential of young adults and children at risk of infertility. The field is evolving quickly, enriched by advances in assisted reproductive technologies and cryopreservation methods, in addition to surgical developments. The best-characterized target group for fertility preservation is the patient population diagnosed with cancer at a young age since the bulk of the data indicates that the gonadotoxicity inherent to most cancer treatments induces iatrogenic infertility. Since improvements in cancer therapy have resulted in increasing numbers of long-term survivors, survivorship issues and the negative impact of infertility on the quality of life have come to the front line. These facts are reflected in an increasing number of scientific publications referring to clinical medicine and research in the field of fertility preservation. Cryopreservation of gametes, embryos, and gonadal tissue has achieved quality standards for clinical use, with the retrieval of gonadal tissue for cryopreservation being currently the only method feasible in prepubertal children. Additionally, the indications for fertility preservation beyond cancer are also increasing since a number of benign diseases and chronic conditions either require gonadotoxic treatments or are associated with premature follicle depletion. There are many remaining challenges, and current research encompasses clinical health care and caring sciences, ethics, societal, epidemiological, experimental studies, etc.

Evaluation of physicians’ practice patterns in France concerning fertility preservation in women with endometriosis

ObjectiveWe aim to evaluate the knowledge and physicians’ practices concerning fertility preservation in women with endometriosis. DesignDescriptive, observational, national study using an online self-questionnaire, sent by email to French gynaecologists in October 2019 within 2 months. ResultsWe obtained 110 analyzable responses from mainly surgeons (54 %) and reproductive clinicians (19 %) with a good experience (average 15 years of practice). Amongst these practitioners, 91 % seemed aware of latest French recommendations on endometriosis issued in December 2017. The most commonly used surgical techniques for management of endometriomas were intra-peritoneal cystectomy (51 %), vaporization by plasma energy (29 %) and destruction by bipolar coagulation (8.5 %). Preoperative AMH was systematically or often prescribed by 78 % of the practitioners against 37.3 % who did it postoperatively. Furthermore, 74 % also considered and performed fertility preservation strategy to manage endometriosis. It was offered in situations of bilateral or recurrent endometrioma, but only 33 % offered it in unilateral endometrioma cases. In the cases recorded, vitrification of mature oocytes appears to be the most common fertility preservation technique (used by 87 % of the practitioners). ConclusionWe observed in our population of sensitized practitioners a good and adequate knowledge concerning endometriosis physiopathology and recommendations for its management, with good information delivery to women. Operating techniques are adapted although information and education concerning fertility preservation indications seem necessary. The place of multidisciplinary concertation meeting in endometriosis appears essential both for discussion of surgical indications and for fertility preservation possibilities. Creation of dedicated structures should be encouraged.

Impact of disease activity and treatments on ovarian reserve in patients with rheumatoid arthritis in the ESPOIR cohort.

Patients with RA have a higher prevalence of infertility than the general population. This study sought to examine the impact of RA disease activity and treatments on ovarian reserve measured by serum anti-Müllerian hormone (AMH) levels in the ESPOIR cohort. We sought to better define the indications for fertility preservation. Patients and serum analysis data were derived from the French national cohort ESPOIR. Enrolled patients (n = 102; 18-37-year-olds) fulfilled ACR/EULAR 2010 criteria for RA. Serum AMH levels were measured at T0, T6, T12, T24 and T36 months post-diagnosis. The impacts of RA activity (DAS28 and CRP level) and treatments (MTX only or with other medications) were evaluated at each study visit. A gradual decrease in patients' serum AMH levels was observed over time, in line with the descending curve described for healthy women. Serum AMH levels of RA patients in comparison with the values considered normal for age did not reveal any significant differences (P > 0.05). We did not observe any impact of RA treatments. We demonstrated an inverse correlation between AMH variation and disease activity (DAS28: r = -0.27, P = 0.003; CRP: r = -0.16, P = 0.06). This is the first study to determine serum AMH levels of a large cohort of RA patients over 36 months. Rapid disease activity control appears to be required to limit changes in the ovarian reserve. Fertility preservation is not likely to be necessary if inflammation is promptly controlled. NCT03666091.

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.

Fertility preservation in women for medical and social reasons: Oocytes vs ovarian tissue.

Approximately 10% of cancers occur in women under 45 years of age. Chemotherapy, radiotherapy, and bone marrow transplantation cure more than 90% of cancer in women, but can result in premature ovarian insufficiency depending on follicular reserve, age, and drugs used. Some benign diseases are also indications for fertility preservation, particularly those requiring chemotherapy (like thalassemia and lupus), recurrent endometriosis, and family history of premature menopause. Social reasons also account for a large proportion of women who wish to postpone pregnancy. This article discusses the two main strategies for fertility preservation, namely oocyte vitrification and ovarian tissue cryopreservation, examining the indications and results of these options. Oocyte cryopreservation is an effective approach, but further studies are needed in cancer patients to ensure the excellent outcomes obtained in women without cancer or in egg donation programs. For prepubertal girls or cases where immediate therapy is required, cryopreservation of ovarian tissue is the only available option.

Understanding Patients' Knowledge and Feelings Regarding Their Cryopreserved Ovarian Tissue: A Qualitative Interviewing Study.

Purpose: For prepubertal girls, or when gonadotoxic treatment is urgent, ovarian tissue cryopreservation (OTC) represents the only option for fertility preservation. We sought to determine patients' knowledge and feelings about their cryopreserved ovarian tissue. Methods: We conducted qualitative interviews with women aged 18 years or older who underwent OTC at our academic fertility center between 2006 and 2017. Subjects were recruited by phone and participated in a single telephone interview using a standardized guide. Interviews were performed until data saturation was reached. Atlas.ti software was used for content analysis. Results: We interviewed eight women with a mean age of 25.8 ± 6.1 years (range, 19-37 years). The mean age at OTC was 20.4 ± 7.5 years (range, 13-35 years). Indications for fertility preservation included hematologic cancer/disease (4/8) or gynecological cancer/BRCA2 positive (4/8). Most patients (7/8) desired future fertility. Although half of the interviewees understood the OTC procedure, only two knew that the tissue can be used for future fertility and only one was aware of the benefits for vasomotor symptoms. Five subjects expressed positive emotions regarding OTC; one felt angry that the decision was made by her parents and two were concerned that OTC might not have been a good choice. However, most subjects (5/8) expressed a desire to better understand OTC and most (5/8) wished for more education about it. Conclusion: This study identifies a significant knowledge gap among patients with cryopreserved ovarian tissue about its uses and benefits as well as a strong desire among these women for improved education about this fertility preservation modality.

The Role of Fertility Preservation in Women with Endometriosis: A Systematic Review

To summarize the available evidence concerning fertility preservation techniques in the context of women with endometriosis. We searched for studies published between 1984 and 2019 on endometriosis and Assisted Reproductive Technology outcomes. We searched MEDLINE and PubMed and performed a manual search of reference lists within identified studies. A total of 426 articles were identified, and 7 studies were eligible to be included for the systematic review. We included all published studies, excluding reviews, case reports, and animal studies. Despite a significant increase in the number of studies addressing fertility preservation over the study period, we found a relative lack of evidence addressing the use of fertility preservation techniques in women with endometriosis. The studies identified included 2 case reports, 1 histological science study, and 4 retrospective cohort studies. Women with endometriosis may benefit from fertility preservation techniques. However, there currently is a paucity of data in this population, especially when compared with other indications for fertility preservation. Although much knowledge can be translated from the oncofertility discipline, we have identified and discussed endometriosis-related changes to ovarian reserve and oocyte health that justify further well-designed research to confirm that fertility preservation outcomes are similar for women with endometriosis.