scholarly journals Combining fertility preservation procedures to spread the eggs across different baskets: a feasibility study

2020 ◽  
Vol 35 (11) ◽  
pp. 2524-2536 ◽  
Author(s):  
S Delattre ◽  
I Segers ◽  
E Van Moer ◽  
P Drakopoulos ◽  
I Mateizel ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Ovarian Function ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Reproductive Outcomes ◽  
Female Patients ◽  
Clinical Scenarios

Abstract STUDY QUESTION What is the reproductive potential following combinations of ovarian stimulation, IVM and ovarian tissue cryopreservation (OTC) in female patients seeking fertility preservation (FP)? SUMMARY ANSWER In selected patients, combining different FP procedures is a feasible approach and reproductive outcomes after FP in patients who return to attempt pregnancy are promising. WHAT IS KNOWN ALREADY FP is increasingly performed in fertility clinics but an algorithm to select the most suitable FP procedure according to patient characteristics and available timeframe is currently lacking. Vitrification of mature oocytes (OV) and OTC are most commonly performed, although in some clinical scenarios a combination of procedures including IVM, to spread the sources of gametes, may be considered in order to enhance reproductive options for the future. STUDY DESIGN, SIZE, DURATION Retrospective, observational study in a university-based, tertiary fertility centre involving all female patients who underwent urgent medical FP between January 2012 and December 2018. Descriptive analysis of various FP procedures, either stand-alone or combined, was performed, and reproductive outcomes of patients who attempted pregnancy in the follow-up period were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 207 patients underwent medical FP. Patient-tailored strategies and procedures were selected after multidisciplinary discussion. When deemed feasible, FP procedures were combined to cryopreserve different types of reproductive tissue for future use. The main primary outcome measure was the number of mature oocytes. Live birth rates were evaluated in patients who returned for reproductive treatment. MAIN RESULTS AND THE ROLE OF CHANCE Among patients seeking FP, 95/207 (46%) had breast cancer, 43/207 (21%) had haematological malignancies and 31/207 (15%) had a gynaecological tumour. Mean ± SD age was 27.0 ± 8.3 years. Eighty-five (41.1%) patients underwent controlled ovarian stimulation (COS), resulting in 10.8 ± 7.1 metaphase II (MII) oocytes for vitrification. Eleven (5.3%) patients had multiple COS cycles. Transvaginal oocyte retrieval for IVM was performed in 17 (8.2%) patients, yielding 9.2 ± 10.1 MII oocytes. Thirty-four (16.4%) patients underwent OTC combined with IVM of oocytes retrieved from ovarian tissue ‘ex vivo’ (OTO-IVM), yielding 4.0 ± 4.3 MII oocytes in addition to ovarian fragments. Seventeen (8.2%) patients had OTC combined with OTO-IVM and transvaginal retrieval of oocytes for IVM from the contralateral ovary, resulting in 13.5 ± 9.7 MII oocytes. In 13 (6.3%) patients, OTC with OTO-IVM was followed by controlled stimulation of the contralateral ovary, yielding 11.3 ± 6.6 MII oocytes in total. During the timeframe of the study, 31/207 (15%) patients have returned to the fertility clinic with a desire for pregnancy. Of those, 12 (38.7%) patients had preserved ovarian function and underwent ART treatment with fresh oocytes, resulting in nine (75%) livebirth. The remaining 19 (61.3%) patients requested warming of their cryopreserved material because of ovarian insufficiency. Of those, eight (42.1%) patients had a livebirth, of whom three after OTO-IVM. To date, 5/207 patients (2.4%) achieved an ongoing pregnancy or livebirth after spontaneous conception. LIMITATIONS, REASONS FOR CAUTION Our FP programme is based on a patient-tailored approach rather than based on an efficiency-driven algorithm. The data presented are descriptive, which precludes firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS Combining different FP procedures is likely to enhance the reproductive fitness of patients undergoing gonadotoxic treatment but further follow-up studies are needed to confirm this. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used for this study and the authors have no competing interests. TRIAL REGISTRATION NUMBER N/A.

P–462 First live birth after fertility preservation using vitrified oocytes in a woman with mosaic Turner syndrome

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
L Strypstein ◽  
E Va. Moer ◽  
J Nekkebroeck ◽  
I Segers ◽  
H Tournaye ◽  
...  
Keyword(s):  
Turner Syndrome ◽  
Fertility Preservation ◽  
Live Birth ◽  
Ovarian Stimulation ◽  
Pregnancy Loss ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
University Hospital ◽  
Ovarian Tissue Cryopreservation ◽  
Oocyte Vitrification

Abstract Study question Is oocyte vitrification an option for preserving the fertility of women diagnosed with Turner syndrome (TS)? Summary answer We report the first live birth achieved using cryopreserved oocytes in a woman diagnosed with mosaic Turner syndrome. What is known already Women with TS are at extremely high risk for premature ovarian insufficiency (POI) and infertility. Although the desire of becoming parents may be fulfilled through egg donation or adoption, fertility preservation using ovarian tissue cryopreservation or oocyte vitrification has been offered to adolescents with TS before complete exhaustion of their follicular stockpile. However, women with TS exhibit higher rates of pregnancy loss and obstetric complications, and the feasibility of fertility preservation in TS is hampered by the reduced follicular pool and by concerns about the X chromosomal content of oocytes and follicular cells. Study design, size, duration Case report in a university hospital. Participants/materials, setting, methods A 25-year-old woman with Turner syndrome mosaicism (45,X0[14]/46,XX[86]) was referred for fertility preservation (FP) counseling. Serum antimüllerian hormone (AMH) level was normal (6.4 µg/L). In view of parenthood postponement and because of the unpredictable rate of follicle loss, the woman underwent two cycles of ovarian stimulation using recombinant follicle stimulating hormone (rFSH), 200–250 IU/day for 8 resp. 12 days, in a GnRH antagonist protocol. Main results and the role of chance In total, 29 metaphase II oocytes (MII) were vitrified. Five years later, the patient returned to the clinic with a desire for pregnancy. Because of evidence of considerable AMH decline (–56% in an interval of four years), the patient was advised to utilize her cryopreserved oocytes for in-vitro fertilization with preimplantation genetic testing for aneuploidy screening (PGT-A). All 29 MII oocytes were thawed; 26 oocytes survived (89.7%) and were inseminated using intracytoplasmic sperm injection (ICSI). Thirteen oocytes were fertilized normally. Three good quality blastocysts ensued and were vitrified after trophectoderm biopsy for PGT-A using array-CGH. Two blastocysts were found euploid. One was thawed and transferred into the uterus using a HRT priming protocol. An uneventful pregnancy occurred. The patient delivered a healthy baby girl weighing 3490 g at 40 weeks of gestation. Limitations, reasons for caution Cryopreservation of oocytes and/or ovarian tissue in selected postmenarchal girls or young women with Turner syndrome is an investigational FP approach that may result in genetic parenthood. The feasibility of FP in TS individuals is limited to those with evidence of ovarian function, before POI occurs. Wider implications of the findings: Cryopreservation of mature oocytes after ovarian stimulation is a realistic option for FP in selected postmenarchal individuals with mosaic TS. Whether PGT-A may reduce the risk of pregnancy loss in TS has to be confirmed by further studies. Trial registration number Not applicable

Prospective observational study on fertility preservation in young early breast cancer patients: The PREFER (Pregnancy and Fertility) trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17548-e17548
Author(s):  
Matteo Lambertini ◽  
Paola Anserini ◽  
Valeria Fontana ◽  
Annalisa Abate ◽  
Fausta Sozzi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Young Patients ◽  
Ovarian Tissue Cryopreservation ◽  
Breast Cancers ◽  
Breast Cancer Patients

e17548 Background: Approximately 4.5% of breast cancers are diagnosed in women younger than 40 years. Chemotherapy (CT)-induced loss of fertility is a major concern for young patients. Different strategies are available to attempt to preserve ovarian function. We evaluated feasibility and patient preferences of 3 different strategies: oocyte cryopreservation (OC), ovarian tissue cryopreservation (OTC) and temporary ovarian suppression with the administration of LHRH analogue (LHRHa) during CT. Methods: From March 2010 to January 2013 49 breast cancer patients younger than 45 years (median age: 38 [range 25-45]), referred to our institution. They were offered the possibility to reduce the gonadotoxic effects of anticancer treatments: the oncologist proposed both the administration of LHRHa during CT, and a reproductive counselling performed by the gynecologist, where OC and OTC were discussed. The first analysis was planned after 2 years; preliminary data are presented. Results: The majority of patients (42 [85.7%]) accepted the treatment with LHRHa, started at least 1 week before CT. Thirty-eight patients (77.6%) refused the reproductive counselling; the main reason for refusal was previous pregnancies (19 patients [38.8%]). Out of 11 patients (22.4%) who accepted the reproductive counselling, only 3 (6.1%) accepted to undergo OC and 1 (2.0%) OTC. The reasons for refusal were: not eligible for comorbidities 3 patients [6.1%]), fear of delaying cancer treatment (2 patients [4.1%]), fear of the ovarian stimulation required (1 patients [2.0%]) and low successful rate of the technique (1 patients [2.0%]). The 3 patients undergoing OC received a controlled ovarian stimulation with the use of daily injections of recombinant FSH: median length of stimulation was 9 days (range, 8 to 9 days); peak estradiol levels ranged from 280 to 521 pg/ml. An average of 13.3 ± 5.7 oocytes was retrieved, and 8.3 ± 3.1 oocytes cryopreserved per patient. Conclusions: This preliminary analysis suggests that the majority of patients (85.7%) accept the administration of LHRHa during CT and approximately 8.2% of patients undergoes surgical fertility preservation techniques.

P–449 Evaluation of ovarian reserve in female children and adolescents with non-iatrogenic primary ovarian insufficiency to establish criteria for ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Volodarsky-Perel ◽  
M Zajicek ◽  
D Shai ◽  
H Raanani ◽  
N Gruber ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Predictive Value ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Antral Follicle ◽  
Ovarian Tissue Cryopreservation ◽  
Positive Parameter ◽  
Primordial Follicles

Abstract Study question What is the predictive value of ovarian reserve evaluation in patients with non-iatrogenic primary ovarian insufficiency (NIPOI) for follicle detection in ovarian tissue harvested for cryopreservation? Summary answer Ovarian tissue cryopreservation (OTCP) should be considered if patients present at least one of the following parameters: detectable AMH, FSH≤20mIU/ml, detection of ≥ 1 antral follicle. What is known already In pre-pubertal girls suffering from NIPOI, which majorly has a genetic etiology, fertility preservation using OTCP is commonly practiced. When OTCP was performed in an unselected group of children and adolescents with NIPOI, only 26% of them had follicles in ovarian tissue while 74% did not benefit from the surgery. The role of preoperative evaluation of anti-müllerian hormone (AMH) serum level, follicular stimulating hormone (FSH) serum level, and trans-abdominal ultrasound for the antral follicle count to predict the detection of primordial follicles in the harvested ovarian tissue is unclear. Study design, size, duration We conducted a retrospective analysis of all patients ≤ 18 years old who were referred for fertility preservation counseling due to NIPOI at a single tertiary hospital between 2010 and 2020. If initial evaluation suggested a diminished ovarian reserve and at least one positive parameter indicating a follicular activity (AMH > 0.16ng/ml, FSH ≤ 20mIU/ml, detection of ≥ 1 antral follicle by transabdominal sonography), OTCP was offered. Patients with 46XY gonadal dysgenesis were excluded. Participants/materials, setting, methods OTCP was performed laparoscopically in all cases. A fresh sample of cortical tissue was fixed in buffered formaldehyde for histological analysis. The rest of the ovarian tissue was cut into small cuboidal slices 1–2 mm in thickness and cryopreserved. After the serial sections, the histological slides were evaluated for the presence of follicles by a certified pathologist. Follicles were counted and categorized as primordial, primary, and secondary. Main results and the role of chance During the study period, 39 patients with suspected NIPOI were referred to the fertility preservation center. Thirty-seven patients included in the study were diagnosed with Turner’s syndrome (n = 28), Galactosemia (n = 3), Blepharophimosis-Ptosis-Epicanthus Inversus syndrome (n = 1), and idiopathic NIPOI (n = 6). Of 28 patients with Turner’s syndrome, 6 had 45X monosomy, 15 had mosaicism and 7 had structural anomalies in X-chromosome. One patient with gonadal dysgenesis and one with the presence of Y-chromosome in 20% of somatic cells were excluded from the study. OTCP was conducted in 14 patients with at least one positive parameter suggesting ovarian function. No complications of the surgical procedure or the anesthesia were observed. Primordial follicles were found in all patients with two or three positive parameters (100%) and in three of six cases with one positive parameter (50%). In total, of the 14 patients who underwent OTCP with at least one positive parameter, 11 (79%) had primordial follicles at biopsy (mean 23.9, range 2–47). This study demonstrates a positive predictive value of 79% for the detection of primordial follicles in patients who had at least one positive parameter of ovarian reserve evaluation. If two or three parameters were positive, the positive predictive value increased to 100%. Limitations, reasons for caution This study did not examine the negative predictive value of our protocol as OTCP was not recommended in the absence of positive parameters. The future fertility potential of cryopreserved tissue in the population with NIPOI is unclear and should be discovered in further studies. Wider implications of the findings: We suggest the evaluation of ovarian reserve by antral follicles count, AMH, and FSH serum levels prior to OTCP in patients with NIPOI. By recommendation of OTCP only if ≥ 1 parameter suggesting the ovarian function is positive, unnecessary procedures can be avoided. Trial registration number Not applicable

scholarly journals FERTILITY PRESERVATION: Freezing of ovarian tissue and clinical opportunities

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. F27-F34 ◽  
Author(s):  
C Yding Andersen ◽  
L S Mamsen ◽  
S G Kristensen
Keyword(s):  
Fertility Preservation ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Genetic Diseases ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Insufficiency ◽  
Technical Aspects ◽  
Increased Risk ◽  
Tissue Cryopreservation

Ovarian tissue cryopreservation (OTC) is mainly used for fertility preservation in girls and women facing a gonadotoxic treatment. If the woman subsequently becomes menopausal, the ovarian tissue may be transplanted to regain ovarian function, including fertility. The method was developed more than two decades ago and today thousands of women worldwide have undergone OTC. Fewer than 500 patients have had tissue transplanted and close to 100% of those regain ovarian function. Several technical aspects of OTC are now becoming more established, including high quantitative follicle survival, defining the size of the tissue resulting in optimal tissue revascularisation and follicle loss resulting from transport of ovarian tissue prior to freezing. We have used OTC to safeguard fertility in patients with genetic diseases, which for some diagnoses is purely experimental, as no transplantations is yet been performed. Usage of OTC beyond fertility is now also being considered; here, the endocrine function of follicles is the focus. It has been suggested that ovarian tissue stored in the reproductive years may be used to avoid premature ovarian insufficiency (POI) when there is a familial disposition or to postpone menopause in patients with an increased risk of osteoporosis or cardiovascular diseases. The benefit of OTC beyond fertility requires, however, actual clinical studies. The current review includes several recent technical aspects with contributions from Denmark building on some of the early work by Roger Gosden.

scholarly journals Hormonal Characteristics of Women Receiving Ovarian Tissue Transplantation with or without Endogenous Ovarian Activity

2021 ◽  
Vol 10 (22) ◽  
pp. 5217
Author(s):  
Vinnie Hornshøj Greve ◽  
Margit Dueholm ◽  
Linn Salto Mamsen ◽  
Stine Gry Kristensen ◽  
Erik Ernst ◽  
...  
Keyword(s):  
Detection Limit ◽  
Fertility Preservation ◽  
Ovarian Reserve ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Ovarian Activity ◽  
Concomitant Increase ◽  
Ovarian Tissue Transplantation ◽  
Tissue Cryopreservation

Ovarian tissue cryopreservation (OTC) and transplantation of frozen/thawed ovarian tissue (OTT) are used for fertility preservation in girls and women. Here, we evaluated the hormonal characteristics of women with or without postmenopausal levels of FSH at the time of OTT to study differences and conditions that best support the initiation of ovarian function. A total of 74 women undergoing OTT (n = 51 with menopausal levels of FSH; n = 23 with premenopausal levels) were followed by measurements of FSH, LH, AMH, and oestradiol. Concentrations of FSH and LH returned to premenopausal levels after 20 weeks on average, with a concomitant increase in oestradiol. Despite resumption of ovarian activity, AMH concentrations were in most instances below the detection limit in the menopausal group, suggesting a low ovarian reserve. Despite a higher age in the premenopausal group, they more often experienced an AMH increase than the menopausal group, suggesting that conditions in the premenopausal ovary better sustain follicle survival, perhaps due to the higher concentrations of oestradiol. Collectively, this study highlights the need for improving follicle survival after OTT. Age and the amount of tissue transplanted are important factors that influence the ability to regain ovarian activity and levels of FSH may need to be downregulated and oestradiol increased prior to OTT.

scholarly journals Chemotherapy-based gonadotoxicity risk evaluation as a predictor of reproductive outcomes in post-pubertal patients following ovarian tissue cryopreservation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gilad Karavani ◽  
Amihai Rottenstreich ◽  
Natali Schachter-Safrai ◽  
Adiel Cohen ◽  
Michael Weintraub ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Fertility Preservation ◽  
Chemotherapy Regimen ◽  
Ovarian Tissue ◽  
Low Risk ◽  
Ovarian Tissue Cryopreservation ◽  
Reproductive Outcomes

Abstract Background The sterilizing effect of cancer treatment depends mostly on the chemotherapy regimen and extent of radiotherapy. Prediction of long-term reproductive outcomes among cancer survivors according to chemo-radiotherapy regimen may improve pre-treatment fertility preservation counseling and future reproductive outcomes. Methods The aim of this study was to evaluate long term reproductive outcomes in cancer survivors according to gonadotoxicity risk estimation of the chemo-radiotherapy regimens utilized. This retrospective cohort study was comprised of post-pubertal female patients referred for fertility preservation during 1997 and 2017 was performed. Eligible adult patients were addressed and asked to complete a clinical survey regarding their ovarian function, menstruation, reproductive experience and ovarian tissue auto-transplantation procedures. Results were stratified according to the gonadotoxic potential of chemotherapy and radiotherapy they received—low, moderate and high-risk, defined by the regimen used, the cumulative dose of chemotherapy administered and radiation therapy extent. Results A total of 120 patients were eligible for the survey. Of those, 92 patients agreed to answer the questionnaire. Data regarding chemotherapy regimen were available for 77 of the 92 patients who answered the questionnaire. Menopause symptoms were much more prevalent in patients undergoing high vs moderate and low-risk chemotherapy protocol. (51.4% vs. 27.3% and 16.7%, respectively; p < 0.05). Spontaneous pregnancy rates were also significantly lower in the high-risk compared with the low-risk gonadotoxicity regimen group (32.0% vs. 58.3% and 87.5%, respectively; p < 0.05). Conclusion Patients scheduled for aggressive cancer treatment have significantly higher rates of menopause symptoms and more than double the risk of struggling to conceive spontaneously. Improving prediction of future reproductive outcomes according to treatment protocol and counseling in early stages of cancer diagnosis and treatment may contribute to a tailored fertility related consultation among cancer survivors.

scholarly journals Fertility Preservation: A Case Series

2011 ◽  
Vol 2 (3) ◽  
pp. 114-117 ◽  
Author(s):  
Korula George ◽  
Vaibhav Londhe ◽  
K Muthukumar
Keyword(s):  
Fertility Preservation ◽  
Ovarian Tissue ◽  
Survival Rates ◽  
Case Series ◽  
Female Fertility ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Clinical Scenarios ◽  
Female Fertility Preservation ◽  
Improvement In Survival

ABSTRACT Improvement in survival rates of cancer patients has lead to a shift in focus toward fertility issues, especially in young survivors. Male fertility preservation is well established. Embryo cryopreservation remains most successful female fertility preservation option. Other female fertility preservation procedures like oocyte/ovarian tissue cryopreservation either have limited efficacy or in experimental stages. We have highlighted not uncommon clinical scenarios where the fertility preservation option was exercised. There is an urgent need to spread awareness among clinicians and patients regarding the various available fertility preservation measures. Timely referral will help in improving the quality of life of cancer survivors.

scholarly journals A challenge of fertility preservation in the setting of cervical cancer - a clinical case

2021 ◽  
pp. 28-32
Author(s):  
I. E. Dmitrieva ◽  
Y. O. Martirosyan ◽  
L. G. Dzhanashvili ◽  
V. O. Dementyeva ◽  
L. V. Adamyan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Clinical Case ◽  
Ovarian Tissue ◽  
Oocyte Retrieval ◽  
Ovarian Tissue Cryopreservation ◽  
Embryo Cryopreservation ◽  
Ovarian Transposition

The issue of fertility preservation in patients with cervical cancer is getting more and more common considering the improved effectiveness of early diagnosis and treatment of cancer. There is a number of evidence-based tactics available to the patients with diagnosed cervical cancer. These tactics have been proved effective and include methods such as ovarian transposition; oocyte, embryo and ovarian tissue cryopreservation. Nonetheless, there are no existing medical algorithms to define the priority of actions that should be taken in such cases of restricted time. The objective of this clinical case report is to highlight an existing concern towards the decision-making process regarding fertility preservation in patients with cervical cancer.In this paper we report a clinical case of fertility preservation tactics in a patient undergone ovarian transposition. We pay attention to particular features of the controlled ovarian stimulation (COS) and oocyte retrieval process typical for such patients. The article discusses the subject of COS and oocyte retrieval effectiveness compared to patients who did not undergo ovarian transposition. The 35-year old patient presented 9 month after ovarian transposition to perform oocyte cryopreservation. As a result of COS 3 oocytes were aspirated, compared to 20 oocytes in another patient of comparable age and medical history, but with no ovarian transposition performed.Regarding particular conditions constraining ovarian stimulation and oocyte retrieval after ovarian transposition, we recommend to consider the possibility of performing oocyte/embryo cryopreservation before ovarian transposition in patients with cervical cancer. Prioritizing oocyte and embryo cryopreservation in case of having sufficient time before treatment could significantly improve possibilities of achieving genetically related offspring in a long-term perspective.

O-062 In vitro maturation of oocytes in connection with ovarian tissue cryopreservation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M De Vos
Keyword(s):  
Cancer Patients ◽  
In Vitro Maturation ◽  
Ex Vivo ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Tissue Processing ◽  
Novel Approach ◽  
Tissue Cryopreservation

Abstract Abstract text Discussing fertility preservation (FP) in young cancer patients has become a key component of routine oncological health care. Although ovarian stimulation followed by oocyte cryopreservation has been recommended in cases where two to three weeks are available before the start of chemotherapy, ovarian tissue cryopreservation (OTC) is the preferred option when this timeframe is not available and when the potential gonadotoxic impact of cancer therapy is deemed moderate or severe, or in prepubertal girls. During ovarian tissue processing in the laboratory, cumulus-oocyte complexes can be identified. In vitro maturation and further vitrification of oocytes retrieved in ex vivo from the extracted ovarian tissue (ovarian tissue oocytes in vitro maturation; OTO-IVM) can be attempted to enhance the future reproductive options of the patient. Although the number of reported live births after OTO-IVM are limited, this experimental FP procedure has potential to become a standard appended procedure in conjunction with OTC. In cancer patients with haematological tumours and ovarian invasion, or patients with primary tumours of the ovary, ovarian tissue grafting may be contraindicated because of the risk of reintroducing malignant cells. Utilisation of vitrified oocytes after OTO-IVM may be the only hope for genetic offspring for these patients. Moreover, exogenous hormonal pretreatment is not required and COC can be recovered during ovarian tissue processing in the majority of patients who undergo partial or total unilateral oophorectomy. Nevertheless, maturation rates after OTO-IVM vary and are generally lower compared to IVM of transvaginally harvested IVM oocytes; currently available IVM systems registered for clinical use will have to be adapted to accommodate the in vitro requirements of oocytes derived from extracorporeal ovarian tissue, and follow-up data are needed to assess the success rate and safety of this novel approach.

O-002 Expanding the ovary’s reproductive lifespan: Preservation and Rejuvenation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Pellicer
Keyword(s):  
Ovarian Function ◽  
Ovarian Tissue ◽  
Reproductive Function ◽  
Primordial Follicle ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Poor Responders ◽  
Hippo Signaling

Abstract Study question The ovary has short lifespan. Genetic and pathologic alterations make it shorter. Moreover, many women delay fertility requiring expanded ovarian function. Can be realistically achieved? Summary answer The reproductive lifespan of the ovary can be expanded to a certain extent in physiologic and pathologic (premature ovarian insufficiency (POI)) conditions. What is known already In ovaries functioning in physiologic conditions, oocyte cryopreservation (OC) is an established method to expand the reproductive lifespan allowing women to postpone fertility without compromising oocyte’s performance. In oncology, ovarian tissue cryopreservation/ ovarian tissue transplantation (OTC/OTT) and OC are widely employed. In POI patients, there are resting follicles in 1/3 of patients. Different techniques have been developed to “awake” these follicles. Some surgical procedures disrupt Hippo signaling to induce primordial follicle growth; , others intend to employ the growth factors contained in blood; some others use bone marrow-derived stem cells to reach similar goals. Study design, size, duration A literature search was done to identify the most recent and informative studies on the different techniques applied to increase the reproductive lifespan of the ovaries, including those clinically available, such as OC, and others still considered experimental, such as OCT/OTT, injection of platelets-enriched plasma (PRP), culture-free in vitro activation(CF-IVA), and autologous stem cell ovarian transplantation (ASCOT). Participants/materials, setting, methods Outcome of 641 healthy women performing OC and ART cycles. In oncology, OC in 80 women and OTC/OTT in 285 patients willing to conceive was analyzed. Both techniques were compared in the same setting in oncology : 1024 undergoing OC and 800 performing OCT. In POI, we analyzed the outcome of 304 women after PRP; 11 undergoing CF-IVA; and 28 ASCOT patients. The most relevant experimental techniques were also analyzed to understand future directions. Main results and the role of chance When it comes to expanding the reproductive function in physiologic conditions, mostly due to delay in childbearing, the follow-up of 641 women out of 1073 who underwent OC and subsequent embryo transfer (ET) has shown 68.8% cumulative live birth rates (C-LBR). Age matters because C-LBR decreased &gt;50% after age 35 yrs. If only the endocrine function of the ovary is considered, OCT/OTT has consistently shown almost 86% efficacy. In Oncology, OC provided 42.1% C-LBR in 80 individuals after cure, while the follow-up of 285 women from 5 different centers after OCT/OTT yield 26% LBR. Both OC and OTT were compared in the same setting and OC proved to be slightly better, with 32.6% LBR as compared to 22.8% in OCT/OTT. Regarding POI, the use of intraovarian PRP injection in 304 women displayed 8% LBR; CF-IVA 36.3% LBR in 11 women; and ASCOT 10% LBR in 10 POI patients and 27.8% in 18 poor responders (PR). Experimental data suggest that a combination of ASCOT and PRP must be the best alternative to activate dormant follicles in POI women. Limitations, reasons for caution: None of the studies was a RCT, and many had not controls, most are descriptive. Regarding oncology patients OC is save and reassuring. The experience shows that OCT/OTT is also safe, although some Scientific Societies label OCT/OTT still as experimental. All the techniques employed in POI are ­experimental yet. Wider implications of the findings Expanding the reproductive lifespan of the ovary in health and disease (oncology and others) employing OC is a routine; OCT/OTT can be also applied to expand the endocrine function of the ovaries. The best and less invasive method to activate follicles in POI and PR still needs to be defined. Trial registration number NCT02240342; NCT03535480; NCT04475744; NCT02354963

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