Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review.
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ABSTRACT: Objective
Review the safety of fertility preservation through ovarian stimulation with oocyte or embryo cryopreservation, including cycle and medication options.Evidence review
A systematic review of peer-reviewed sources revealed 2 applicable randomized control trials and 60 cohort studies as well as 20 additional expert opinions or reviews.Results
The capacity for future family building is important for the majority of reproductive age people, despite life-altering medical or oncologic diagnosis. Modern fertility preservation generates a high rate of oocyte yield while utilizing protocols that can be started at multiple points in the menstrual cycle and suppressing supra-physiologic levels of estrogen. Finally, more than one quarter of fertility preservation patients will return to later utilize fertility services.Conclusion
For most patients, fertility preservation can safely be pursued and completed within 2 weeks without affecting disease severity or long-term survival.
SUBMITTER: Ozcan MC
PROVIDER: S-EPMC8829712 | biostudies-literature | 2022 Jan-Dec
REPOSITORIES: biostudies-literature
Publications
Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review.
Ozcan Meghan Ch MC Snegovskikh Victoria V Adamson G David GD
Women's health (London, England) 20220101
<h4>Objective</h4>Review the safety of fertility preservation through ovarian stimulation with oocyte or embryo cryopreservation, including cycle and medication options.<h4>Evidence review</h4>A systematic review of peer-reviewed sources revealed 2 applicable randomized control trials and 60 cohort studies as well as 20 additional expert opinions or reviews.<h4>Results</h4>The capacity for future family building is important for the majority of reproductive age people, despite life-altering medi ...[more]
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Project description:BackgroundFertility preservation is an important healthcare focus in the paediatric and adolescent population when gonadotoxic treatments are required. Ovarian stimulation (OS) resulting in oocyte cryopreservation is a well-established fertility preservation option in the adult population. It's utility, however, is little known in young patients. The purpose of this review was to synthesise the available literature on OS in patients ≤18 years old, to identify gaps in current research and provide suggestions for future research directions.MethodsUsing PRISMA guidelines, a systematic review of the literature was performed for all relevant full-text articles published in English in Medline, Embase, the Cochrane Library and Google Scholar databases. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Two reviewers independently screened studies for eligibility, extracted data and assessed the risk of bias. Characteristics of the studies, objectives and key findings were extracted and summarised in a narrative synthesis.ResultsDatabase search and manual review identified 922 studies, 899 were eliminated based on defined exclusion criteria. Twenty-three studies were included and comprised 468 participants aged ≤18 years who underwent OS (median 15.2, range 7-18 years old). Only three patients were premenarchal, and four patients were on treatment to suppress puberty. Patients had OS for a broad range of indications including oncology treatment, transgender care and Turner syndrome. A total of 488 cycles of OS were completed, with all but 18 of these cycles (96.3%) successfully resulting in cryopreserved mature oocytes (median 10 oocytes, range 0-35). Fifty-three cycles (9.8%) were cancelled. Complications were rare (<1%). One pregnancy was reported from a female who had OS aged 17 years old.ConclusionThis systematic review demonstrates that OS and oocyte cryopreservation is achievable in young females however there are only a few cases in the literature describing OS in premenarcheal children or those who have suppressed puberty. There is little proof that OS can lead to pregnancy in adolescents, and no proof that this can be achieved in premenarchal girls. Therefore it should be regarded as an innovative procedure for adolescents and experimental for premenarcheal girls.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=265705, identifier CRD42021265705.
| S-EPMC10315913 | biostudies-literature
Project description:Study questionWhat is the live-birth rate (LBR) and cost-effectiveness of fertility preservation with oocyte cryopreservation (FP-OC) compared to expectant management in cancer patients age 25-40 based on estimated gonadotoxicity of treatments 5 years after cancer diagnosis?Summary answerOocyte cryopreservation prior to cancer treatment is more costly, yet more effective (producing more live births), than not undergoing oocyte cryopreservation but it is most beneficial for patients undergoing high-risk chemotherapy (HRC).What is known alreadyThe decision to undergo FP prior to treatment is multifactorial and can be costly and delay treatment. Not all treatments carry the same gonadotoxicity and patients may choose to undergo FP-OC based on the probability of premature ovarian insufficiency, predicted outcomes and cost. A comprehensive model that incorporates age at diagnosis and toxicity of treatment to help guide patients in the decision to undergo FP-OC does not yet exist.Study design, size durationThis study used a Decision Analysis Model to estimate effectiveness and cost of FP for cancer patients.Participants/materials, setting, methodsAge-based estimates of LBR and cost per live birth were calculated for ages 25-40 years based on gonadotoxicity of treatment. A decision analysis model was constructed using Treeage Pro 2015 with case base probabilities derived from national registries, practice guidelines and medical records from a national network of infertility practices (IntegraMed).Main results and the role of chanceCompared to no FP-OC, FP-OC improved LBRs for women of all ages undergoing either low-risk chemotherapy (LRC) or HRC; however, it was most cost effective for women undergoing LRC at older ages or HRC at younger ages. Although FP-OC results in higher LBRs, it was always more costly. Using donor oocyte IVF can be a successful alternative to autologous FP-OC.Limitations reasons for cautionDecision tree results reflect probabilities of certain events and are compiled from multiple reputable sources but are not directly derived from a recruited cohort of patients. Outcomes are based on United States estimates and should be interpreted in the broader context of individual patient diagnoses, treatment care plans and country of origin.Wider implications of the findingsThe development of this analytic model will help guide practitioners in their counseling of women from age 25 to 40 years, who are considering FP-OC at the time of cancer diagnosis. It provides a realistic pathway from diagnosis to LB and accounts for the majority of costs and outcome possibilities.Study funding/competing interest(s)This study was partially funded by a grant from National Institute of Health (NIH)/National Institute of Child Health and Human Development (NICHD) (R01 HD67683) to A.Z.S. There are no conflicts of interest to declare.Trial registration numberN/A.
| S-EPMC5850300 | biostudies-literature
Project description:PurposeVitrification permits long-term banking of oocytes and embryos. It is a technically challenging procedure requiring direct handling and movement of cells between potentially cytotoxic cryoprotectant solutions. Variation in adherence to timing, and ability to trace cells during the procedure, affects survival post-warming. We hypothesized that minimizing direct handling will simplify the procedure and improve traceability. To address this, we present a novel photopolymerized device that houses the sample during vitrification.MethodsThe fabricated device consisted of two components: the Pod and Garage. Single mouse oocytes or embryos were housed in a Pod, with multiple Pods docked into a Garage. The suitability of the device for cryogenic application was assessed by repeated vitrification and warming cycles. Oocytes or early blastocyst-stage embryos were vitrified either using standard practice or within Pods and a Garage and compared to non-vitrified control groups. Post-warming, we assessed survival rate, oocyte developmental potential (fertilization and subsequent development) and metabolism (autofluorescence).ResultsVitrification within the device occurred within ~ 3 nL of cryoprotectant: this volume being ~ 1000-fold lower than standard vitrification. Compared to standard practice, vitrification and warming within our device showed no differences in viability, developmental competency, or metabolism for oocytes and embryos. The device housed the sample during processing, which improved traceability and minimized handling. Interestingly, vitrification-warming itself, altered oocyte and embryo metabolism.ConclusionThe Pod and Garage system minimized the volume of cryoprotectant at vitrification-by ~ 1000-fold-improved traceability and reduced direct handling of the sample. This is a major step in simplifying the procedure.
| S-EPMC9474789 | biostudies-literature
Project description:Cryopreservation of mature oocytes is a critical means for female fertility preservation. Despite clinical advances using vitrification preservation method, the high concentrations of toxic penetrating cryoprotectant agents (CPA, up to 4.3 M) and low throughput (only one every experiment) put forward a challenge. Here, we report a synergetic ice inhibition platform via PVA/Fe3O4/GO nanoparticles (PFG NPs), that achieves sharp ice morphology, ice recrystallization, and devitrification inhibition, thus reducing cryodamage both in cooling and warming stages. Oocyte cryopreservation experiment demonstrates the survival rate can attain 98.6% using 2.5 M penetrating CPA while ensuring the scalability (ten oocytes each cryopreservation procedure). In contrast, recovered oocytes via PFG platform show 85 gene variation compared with fresh oocytes, whereas tradition CPA (TCPA) formulation induces 1396 gene changes. Meanwhile, the PFG-cryopreservation oocytes maintain normal ability of fertilization, development, and birth of offspring.
2025-04-30 | GSE244977 | GEO
Project description:Study questionDoes cancer itself, before any gonadotoxic treatment, affect ovarian function in reproductive-aged patients?Summary answerOur study revealed that women with cancer may have decreased ovarian reserve markers even before cancer therapy.What is known alreadyWith the field 'oncofertility' improving rapidly, cancer therapy-mediated ovarian damage is well characterized. However, there is a controversy about whether cancer itself affects ovarian function before gonadotoxic treatment.Study design size durationWe conducted a systematic meta-analysis investigating the association between cancer and ovarian function prior to gonadotoxic treatment. Titles or abstracts related to ovarian reserve (e.g. anti-Müllerian hormone (AMH), antral follicle count (AFC), or basal follicle-stimulating hormone (FSH)) combined with titles or abstracts related to the exposure (e.g. cancer*, oncolog*, or malignan*) were searched in PubMed, Embase, and Web of Science databases from inception to 1 February 2022.Participants/materials setting methodsWe included cohort, case-control, and cross-sectional studies in English that examined ovarian reserve in reproductive-aged patients (18-45 years) with cancer compared to age-matched controls before cancer treatment. The quality of the included studies was assessed by ROBINS-I. Fixed or random effects were conducted to estimate standard or weighted mean difference (SMD or WMD, respectively) and CI. Heterogeneity was assessed by the Q test and I2 statistics, and publication bias was evaluated by Egger's and Begg's tests.Main results and the role of chanceThe review identified 17 eligible studies for inclusion. The results showed that cancer patients had lower serum AMH levels compared to healthy controls (SMD = -0.19, 95% CI = -0.34 to -0.03, P = 0.001), especially women with hematological malignancies (SMD = -0.62, 95% CI = -0.99 to -0.24, P = 0.001). The AFC was also decreased in patients with cancer (WMD = -0.93, 95% CI = -1.79 to -0.07, P = 0.033) compared to controls, while inhibin B and basal FSH levels showed no statistically significant differences.Limitations reasons for cautionSerum AMH and basal FSH levels in this meta-analysis showed high heterogeneity, and the small number of studies contributing to most subgroup analyses limited the heterogeneity analysis. Moreover, the studies for specific cancer subtypes may be too small to draw conclusions; more studies are needed to investigate the possible impact of cancer type and stage on ovarian function.Wider implications of the findingsOur study confirmed the findings that cancer per se, especially hematological malignancies, negatively affects serum AMH level, and AFC values of reproductive-aged women. However, the lower AMH levels and AFC values may also be due to the changes in ovarian physiology under oncological conditions, rather than actual lower ovarian reserves. Based on the meta-analysis, clinicians should raise awareness about the possible need for personalized approaches for young women with cancer who are interested in pursuing fertility preservation strategies before anticancer treatments.Study funding/competing interestsThis work was financially supported by the National Natural Science Foundation of China (nos 81873824, 82001514, and 81902669) and the Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology (2019020701011436). The authors declare that they have no conflicts of interest.Registration numberPROSPERO (CRD42021235954).
| S-EPMC10266964 | biostudies-literature
Project description:PurposeThe target population for fertility preservation recently has been expanded from adolescents with cancer undergoing gonadotoxic chemotherapy to include transgender youth before initiating gender-affirming hormone therapy. Patients and providers may have knowledge deficits regarding options for fertility preservation, accessibility, and feasibility of its techniques, and impact of treatment on future fertility. This study describes outcomes of sperm cryopreservation in transgender male-to-female (affirmed female) youth and compares semen parameters with adolescents diagnosed with cancer.MethodsMedical records of transgender-affirmed female adolescents and adolescent males diagnosed with cancer who underwent sperm cryopreservation at the Fertility and Advanced Reproductive Medicine clinic of the University of Texas (UT) Southwestern Medical Center between March 2015 and March 2020 were reviewed. Demographic data were recorded and values for sperm parameters (volume, count, total count, motility (%), total motile) were collected. When available, hormone levels (luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol) and Tanner stages were also assessed. The two populations were compared using chi-square analysis and two-sample student's t-test. Data are presented as mean±standard deviation.ResultsWhile semen quality parameters trended lower in transgender youth compared with adolescents with cancer, there was no statistically significant difference between groups. While four out of 18 patients in the transgender group had azoospermia, mean semen quality parameters fell within normal adult reference ranges for both groups.ConclusionSperm cryopreservation for transgender youth and adolescents with cancer is feasible, inexpensive, and does not result in significant treatment delays. This information can improve counseling and access to these procedures, particularly in the transgender population.
| S-EPMC9829158 | biostudies-literature
Project description: Not available
| S-EPMC6276651 | biostudies-literature
Project description:ImportancePoor ovarian response (POR) to stimulation may impact patients' desire or need to utilize cryopreserved oocytes for family building in the future. These findings, captured by Society for Assisted Reproductive Technology (SART) national data, underscore the need for tailored counseling and further research into the decision-making processes influencing oocyte utilization.ObjectiveTo examine the association of ovarian response to stimulation and the number of vitrified oocytes with the likelihood and timing of patients returning for oocyte utilization following planned oocyte cryopreservation (OC).Design, setting, and participantsThis cohort study used data in the SART Clinical Outcome Reporting System for patients in US fertility clinics and data was used for eligible patients who underwent planned OC from January 2014 through December 2020. Data were analyzed from November 2022 to June 2023.Main outcomes and measuresThe association between number of oocytes cryopreserved on return rate to utilize cryopreserved oocytes and the time from vitrification to warming.ResultsA total of 67 893 autologous oocyte freezing cycles were performed in the US between 2014 and 2020, among 47 363 patients (mean [SD] age, 34.5 [4.7] years). Of these, 6421 (13.5%) were classified as patients with POR, with fewer than 5 oocytes vitrified across all ovarian stimulation cycles. A total of 1203 patients (2.5%) returned for oocyte warming and utilization. The rate of return was significantly higher in the POR group, with 260 (4.0%) returning compared with 943 (2.3%) in the normal responder group (P < .001). This trend was most notable in the age 30 to 34 years (warm cycle, 46 of 275 [16.7%] vs no warm cycle, 982 of 11 743 [8.4%]; P < .001) and age 35 to 39 years groups (warm cycle, 124 of 587 [21.1%] vs no warm cycle, 3433 of 23 012 [14.9%]; P < .001). The time elapsed from vitrification to warming was comparable between patients with POR (mean [SD], 716.1 [156.1] days) and normal responders (803.8 [160.7] days). A multivariate analysis adjusted for age, clinic region in the US, body mass index, and history of endometriosis was conducted to identify factors associated with the utilization of oocytes. The analysis revealed that having fewer than 5 oocytes vitrified was associated with higher odds of utilizing oocytes (OR, 1.52; 95% CI, 1.32-1.76).Conclusions and relevanceThis cohort study reveals a distinct pattern in the utilization of cryopreserved oocytes among patients undergoing planned OC in the US. Despite the increase in number of patients pursuing OC, there is a notably low rate of return to utilize previously vitrified oocytes; notably, patients with POR are more likely to return, although the time to return is similar to those with normal ovarian response.
| S-EPMC10762568 | biostudies-literature
Project description:ObjectivesOur review aimed to consolidate the latest update on the application of in vitro maturation among immature oocyte harvest in combination with ovarian tissue cryopreservation known as ovarian tissue oocyte-in vitro maturation.MethodsA thorough search for relevant studies was conducted via PubMed, Google Scholar, EMBASE, and clinical.gov databases up to December 2020. The primary outcome was the oocyte maturation rate, which measured the number of immature oocytes (geminal vesicle stage) that progressed to mature oocytes (meiosis II stage) following in vitro maturation. The secondary outcomes were the fertilization rate following intracytoplasmic sperm injection/in vitro fertilization of these oocytes for the embryo cryopreservation cohort. Our review included pre-pubertal girls and women with cancer who underwent ovarian tissue oocyte-in vitro maturation as fertility preservation.ResultsThe primary search identified 207 studies. Twelve manuscripts were selected for inclusion in our review following duplication assessment, title and abstract screening, and full-text evaluation tailored to our inclusion criteria. All the population belonged to a cancer group and underwent concurrent ovarian tissue oocyte-in vitro maturation. A total of 5724 immature oocytes were obtained following ovarian tissue cryopreservation. Approximately 33.84% of the immature oocytes successfully matured via in vitro maturation, which were cryopreserved as oocytes or fertilized as embryos and subsequently stored for future use.ConclusionOur review proposed the potential application of ovarian tissue oocyte-in vitro maturation in increasing the number of mature oocytes. The acceptable improvement in oocyte maturation rate following in vitro maturation indicates that improving oocyte outcomes is an excellent cost-effective strategy for fertility preservation among women with cancer.
| S-EPMC9393350 | biostudies-literature