Fertility Preservation Research Articles

Effect of Elamipretide on the Vitrification of Mouse Ovarian Tissue by Freezing.

The importance of ovarian cortical cryopreservation in fertility preservation is receiving increasing attention from reproductive specialists, and mitochondrial dysfunction is an important cause of reduced ovarian tissue cryopreservation. Elamipretide (SS-31) is a novel mitochondria-targeted antioxidant. However, whether it has a protective effect on mouse ovarian tissue cryopreservation remains to be studied. In this study, we examined follicular morphology and viability, mitochondrial function and oxidative stress levels, apoptosis, and culture in vitro after vitrification cryoresuscitation operation by treating ovarian tissues with SS-31 in cryoprotectant resuscitation solution. At the end of the experiment, the addition of 100 μmol/L SS-31 significantly improved follicle quality and oocyte maturation rate in vitro (p < 0.05) and significantly reduced apoptosis (p < 0.05) and oxidative stress levels (superoxide dismutase, catalase, malondialdehyde, p < 0.05). Meanwhile, mitochondrial respiratory chain complex enzyme activity, mtDNA copy number (p < 0.05), and adenosine triphosphate (p < 0.05) content were significantly increased in the 100 μmol/L SS-31-treated group. In addition, the mRNA expression levels of mitochondrial energy metabolism- and biosynthesis-related genes (STRT1, PGC-1a, PPAR-a, TFAM, p < 0.05) were markedly upregulated (p < 0.05) in the 100 μmol/L SS-31 group. In conclusion, SS-31 improved the cryopreservation of ovarian tissues, and 100 μmol/L SS-31 was found to be the most effective.

The impact of internal iliac artery ligation on hormonal and functional ovarian reserve parameters: A case-control study in patients with postpartum hemorrhage in sub-Saharan Africa.

The study aims to evaluate the long-term impact of internal iliac artery ligation (IIAL) on ovarian hormonal and functional changes in women. The procedure is often used for postpartum hemorrhage and is considered uterus-sparing. However, its effects on ovarian reserve and fertility preservation remain controversial. This is a retrospective, case-control study involving consecutive female patients aged 17-47 years. These patients underwent successful bilateral IIAL due to severe postpartum hemorrhage between January 2022 and December 2022. The control group included women of matching age, parity, and body mass index (BMI) who did not undergo IIAL. Both groups were followed for 6 months to measure follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, antral follicle counts, and ovarian volume. The study comprised 62 patients in the IIAL group and 86 in the control group. No significant differences were found in FSH and LH levels between the two groups (P > 0.05). However, the numbers of antral follicles in both the right and left ovaries were significantly lower in the IIAL group than in the control group (P < 0.05). Ovarian volume did not show a significant difference between the groups (P > 0.05). The findings suggest that IIAL leads to a significant decrease in the number of ovarian follicles at 6 months post-operation. However, it does not significantly impact FSH and LH levels or ovarian volume.

Changing the Perspective on Fertility Preservation for Women with Metastatic or Advanced Stage Cancer.

In this Perspective we share the personal story of a 33-year-old patient diagnosed with metastatic breast cancer and her journey through fertility preservation, surrogacy, and eventually motherhood, highlighting misconceptions about fertility preservation in this population. There are nearly 1 million women under the age of 50 diagnosed and living with cancer in the USA. These patients are met with life-altering decisions, including those that may limit their reproductive ability. While there have been tremendous advances and advocacy in the field of oncofertility, there has been limited focus on patients with advanced stage or metastatic cancer. We describe five key misconceptions surrounding fertility preservation in patients with advanced stage cancer, offering a review of the literature and our approach to challenging topics like desiring fertility preservation in the face of Stage 4 disease, the safety and timing of ovarian stimulation during cancer treatment, and passing away following fertility preservation. We review the importance of assessing perceptions of fertility preservation in patients with metastatic cancer and highlight the lack of research in this area as a call to action.

Fertility Preservation in the Era of Immuno-Oncology: Lights and Shadows.

In recent years, immuno-oncology has revolutionized the cancer treatment field by harnessing the immune system's power to counteract cancer cells. While this innovative approach holds great promise for improving cancer outcomes, it also raises important considerations related to fertility and reproductive toxicity. In fact, most young females receiving gonadotoxic anti-cancer treatments undergo iatrogenic ovarian exhaustion, resulting in a permanent illness that precludes the vocation of motherhood as a natural female sexual identity. Although commonly used, oocyte cryopreservation for future in vitro fertilization and even ovarian cortex transplantation are considered unsafe procedures in cancer patients due to their oncogenic risks; whereas, ovarian stem cells might support neo-oogenesis, providing a novel stemness model of regenerative medicine for future fertility preservation programs in oncology. Recent scientific evidence has postulated that immune checkpoint inhibitors (ICIs) might in some way reduce fertility by inducing either primary or secondary hypogonadism, whose incidence and mechanisms are not yet known. Therefore, considering the lack of data, it is currently not possible to define the most suitable FP procedure for young patients who are candidates for ICIs. In this report, we will investigate the few available data concerning the molecular regulation of ICI therapy and their resulting gonadal toxicity, to hypothesize the most suitable fertility preservation strategy for patients receiving these drugs.

Prevalence, incidence, and treatment trends of adenomyosis in South Korean women for 15 years: A national population-based study.

Adenomyosis is associated with female infertility worldwide. With improvements in imaging methods, such as pelvic magnetic resonance imaging, the diagnosis and treatment of adenomyosis have changed. This study aimed to evaluate the overall prevalence, incidence, and treatment trends of adenomyosis in South Korea using data from the Korean National Health Insurance Service Database (NHIS). Data were collected from the Korean NHIS, a population-based complete enumeration database. A total of 678 641 women aged 11-55 years diagnosed with adenomyosis (N80.0 ICD-10 code) from the database from 2002 to 2016 were enrolled. After applying a one-year look-back method, 629 592 patients were analyzed to estimate the prevalence, incidence, and treatment trends of adenomyosis. The overall prevalence during the study period was 3.86 per 1000 people. The prevalence of adenomyosis has increased from 1.42 per 1000 individuals in 2002 to 7.50 per 1000 individuals in 2016. The crude annual incidence rate of adenomyosis was 1.62 per 1000 people in 2003, which increased to 4.12 per 1000 people in 2016. In addition, the proportion of uterus-preserving surgeries in adenomyosis treatments has increased from 7.51% to 21.29% over 15 years. The prevalence and incidence of adenomyosis in South Korea increased between 2002 and 2016. Furthermore, the proportion of uterus-preserving surgeries and progestin prescriptions for adenomyosis treatment has increased. We expect that our findings will raise awareness of the necessity for fertility preservation through earlier diagnosis and proper management of patients with adenomyosis.

French national survey on breast cancer care: caregiver and patient views.

To improve the quality of care for patients with breast cancer, an analysis of the health-care pathway, considering feedback from both health-care practitioners (HCPs) and patients, is needed. Between 2020 and 2022, we conducted a survey at French breast cancer centers and analyzed information from questionnaires completed by HCPs and patients. We collected information on center organization, diagnostic processes, treatment decisions and modalities, supportive care, patient advocacy groups, and work issues. Twenty-three breast cancer centers were included and questionnaires completed by 247 HCPs and 249 patients were analyzed. The centers closely followed the legal French framework for cancer treatments, which includes formal diagnostic announcements, multidisciplinary tumor boards, personalized treatment summaries, and supportive care access. HCPs and patients were satisfied with the time to diagnosis (≤ 2weeks as evaluated by 75% of patients), time to surgery (mean 61days), time between surgery and chemotherapy (mean 47days), and time between surgery and radiotherapy (mean 81days). Fertility preservation counseling for women under 40years of age was systematically offered by 67% of the HCPs. The majority (67%) of the patients indicated that they had received a personalized treatment summary; the topics discussed included treatments (92%), tumor characteristics (84%), care pathways (79%), supportive care (52%), and breast reconstruction (33%). Among HCPs, 44% stated that reconstructive surgery was offered to all eligible patients and 57% and 45% indicated coordination between centers and primary care physicians for adverse effects management and access to supportive care should be improved, for chemotherapy and radiotherapy, respectively. Regarding patient advocacy groups, 34% of HCPs did not know whether patients had contact and only 23% of patients declared that they had such contact. For one-third of working patients, work issues were not discussed. Twenty-eight percent of patients claimed that they had faced difficulties for supportive care access. Among HCPs, 13% stated that a formal personalized survivorship treatment program was administered to almost all patients and 37% almost never introduced the program to their patients. Compliance to oral treatments was considered very good for 75-100% of patients by 62% of HCPs. This study provides an updated analysis of breast cancer care pathways in France. Overall, the initial processes of diagnosis, announcement, and treatment were swift and were in agreement with the best care standards. No barriers to accessing care were identified. Based on the study findings, we proposed several strategies to improve the quality of care for patients in supportive care, coordination with primary care physicians, reconstructive surgery, and fertility preservation access.

The impact of using ovarian-adnexal reporting data system magnetic resonance imaging (O-RADS MRI) score on risk stratification of sonographically indeterminate adnexal masses

BackgroundAdnexal masses (AMs) are prevalent, leading to a substantial clinical effort including imaging for diagnosis, surgery, and pathology.Aim of the studyThe goal of this research was to evaluate the reliability of the Ovarian-Adnexal Reporting Data System Magnetic Resonance Imaging (O-RADS MRI) scale for diagnosing the sonographically indeterminate adnexal masses and to discriminate between malignant and benign ones using the O-RADS MRI scoring system.MethodsThis study included 72 cases with indeterminate adnexal masses in any age group. We excluded patients with previous history of operated adnexal lesion and patients who had contraindications for MRI as pacemakers or iron clips.ResultsBased on O-RADS MRI score, 44.4% of masses were diagnosed as O-RADS II indicating that they were almost certainly benign, 11.1% as O-RADS III indicating low risk malignancy, 8.3% as O-RADS IV indicating intermediate risk malignancy and 36.1% were diagnosed as O-RADS V indicating high risk malignancy. O-RADS MRI score for malignancy gave sensitivity of 92.31% (95%CI 63.97–99.81), specificity of 82.61% (95%CI 61.22–95.05), PPV of 75% (95%CI 54.84–88.11) and NPV of 95% (95%CI 74.12–99.21) with an overall accuracy of 86.11% (95%CI 70.50–95.33).ConclusionsThe O-RADS MRI score has excellent accuracy and validity in determining whether an AM is malignant or benign. Using this score in clinical practice may enable a tailored, patient-centered approach for masses that are sonographically indeterminate, avoiding unnecessary surgery, and in certain cases allows less extensive surgery, or even fertility preservation when appropriate.

Microwave-assisted dehydration, long-term storage at non-freezing temperatures, and rehydration of cat germinal vesicles.

Germinal vesicles (GVs) are alternative targets for female fertility preservation due to their availability and high resilience against non-physiological conditions. Preserved GVs can then be transferred to fresh cytoplasts to reconstitute viable oocytes. Here, we describe a GV preservation method that employs non-ionizing microwave radiations imparting energy to water molecules, which results in rapid and homogeneous drying of the sample. Trehalose is added as a xero-protectant before the radiations, enabling isothermal vitrification of the disaccharide sugar during drying. While the technique is still considered experimental, studies have shown that DNA and structural integrity can be effectively maintained in dried/rehydrated GVs. Importantly, the dry-preservation approach allows supra-zero temperature storage of the samples, offering a cost-effective and energy-saving alternative to traditional methods relying on ultra-low freezing temperatures. The protocol outlines a comprehensive procedure involving GV oocyte collection, trehalose loading, microwave drying, storage, and rehydration. The simplicity of the protocol facilitates ease of manipulation, making it an accessible method for researchers. While initially developed for domestic cats, the protocol can be adapted for other species with necessary modifications, considering potential species-specific responses to dehydration stress.

Bibliometric analysis and global trends in uterus transplantation

Aim: The purpose of this study was to characterize publication patterns, academic influence, research trends, and the recent developments in uterus transplantation (UTx) across the globe. Methods: The Web of Science Core Collection database was searched for documents published from the time the database began to include relevant articles to December 15, 2023. With the use of VOSviewer, Citespace, BICOMB, and Incites, a cross-sectional bibliometric analysis was conducted to extract or calculate the evaluative indexes. Publications were categorized by country, institution, author, journal, highly cited papers, and keywords. The variables were compared in terms of publication and academic influence, which further included citation count, citation impact, Hirsh index, journal impact factor, total link strength, collaboration metrics, and impact relative to the world. Results: A total of 581 papers concerning UTx were initially identified after retrieval, and 425 documents were included. Of the 41 countries participating in relevant studies, the USA and Sweden were in leading positions in terms of publications, citations, and academic influence. The most versatile institution was the University of Gothenburg, which is followed by Baylor University. The most productive scholars and journals were Brännström M. and Fertility and Sterility, respectively. Five groups of cutting-edge keywords were identified: venous drainage, donors and donation, women, fertility preservation, and fertility. Topics about surgery, first live birth, risk, and in vitro fertilization remain hot in this field. Conclusions: UTx is anticipated to enter a golden era in the coming years. This study provides some guidance concerning the authors involved in promoting UTx research, the current development of UTx, and journals to submit their innovative research. This also helps to reach a comprehensive insight and prospect in the near future. In order to establish recognized standards and benefit more patients who are disturbed by uterine infertility, large-scale and well-designed clinical trials are required.

Utilizing artificial intelligence in academic writing: an in-depth evaluation of a scientific review on fertility preservation written by ChatGPT-4.

To evaluate the ability of ChatGPT-4 to generate a biomedical review article on fertility preservation. ChatGPT-4 was prompted to create an outline for a review on fertility preservation in men and prepubertal boys. The outline provided by ChatGPT-4 was subsequently used to prompt ChatGPT-4 to write the different parts of the review and providefive references for each section. The different parts of the article and the references provided were combined to create a single scientific review that was evaluated by the authors, who are experts in fertility preservation. The experts assessed the article and the references for accuracy and checked for plagiarism using online tools. In addition, both experts independently scored the relevance, depth, and currentness of the ChatGPT-4's article using a scoring matrix ranging from 0 to 5 where higher scores indicate higher quality. ChatGPT-4 successfully generated a relevant scientific article with references. Among 27 statements needing citations, four were inaccurate. Of 25 references, 36% were accurate, 48% had correct titles but other errors, and 16% were completely fabricated. Plagiarism was minimal (mean = 3%). Experts rated the article's relevance highly (5/5) but gave lower scores for depth (2-3/5) and currentness (3/5). ChatGPT-4 can produce a scientific review on fertility preservation with minimal plagiarism. While precise in content, it showed factual and contextual inaccuracies and inconsistent reference reliability. These issues limit ChatGPT-4 as a sole tool for scientific writing but suggest its potential as an aid in the writing process.

Current Fertility Preservation Steps in Young Women Suffering from Cancer and Future Perspectives.

Childhood cancer incidence, especially in high-income countries, has led to a focus on preserving fertility in this vulnerable population. The common treatments, such as radiation and certain chemotherapeutic agents, though effective, pose a risk to fertility. For adult women, established techniques like embryo and egg freezing are standard, requiring ovarian stimulation. However, for prepubescent girls, ovarian tissue freezing has become the primary option, eliminating the need for hormonal preparation. This review describes the beginning, evolution, and current situation of the fertility preservation options for this young population. A total of 75 studies were included, covering the steps in the current fertility preservation protocols: (i) ovarian tissue extraction, (ii) the freezing method, and (iii) thawing and transplantation. Cryopreservation and the subsequent transplantation of ovarian tissue have resulted in successful fertility restoration, with over 200 recorded live births, including cases involving ovarian tissue cryopreserved from prepubescent girls. Despite promising results, challenges persist, such as follicular loss during transplantation, which is attributed to ischemic and oxidative damage. Optimizing ovarian tissue-freezing processes and exploring alternatives to transplantation, like in vitro systems for follicles to establish maturation, are essential to mitigating associated risks. Further research is required in fertility preservation techniques to enhance clinical outcomes in the future. Ovarian tissue cryopreservation appears to be a method with specific benefits, indications, and risks, which can be an important tool in terms of preserving fertility in younger women.

Mechanisms underlying human sperm cryodamage: the role of reactive oxygen species (ROS) and antioxidants

Sperm cryopreservation is an efficient procedure for male fertility preservation, although the freeze-thaw procedure causes irreversible structural and functional changes in human spermatozoa. Indeed, the procedure is responsible for harmful changes that may affect sperm biology. In mammalian cells, cryopreservation induces a shift of redox homeostasis towards increasing generation of reactive oxygen species (ROS). The characteristics of ROS and the cellular outcomes depend on the cell type. Supra-physiological ROS levels during cryopreservation severely impact sperm survival, reproductive potential and DNA integrity, the latter a fundamental factor for fertilisation and transmission of paternal genetic information to offspring. The aim of this review is to summarise current knowledge of the main molecular mechanisms underlying ROS generation during sperm cryopreservation and its subsequent effects. In addition, we report current experimental approaches based on the supplementation of cryopreservation media with enzymatic and non-enzymatic antioxidants with the aim of minimising the harmful effects of ROS, and thus improving post-thaw sperm quality. Current data indicate that the potential use of antioxidants as constituents of the sperm freezing solution in clinical settings would require considerable attention. KEY WORDS: Spermatozoa, cryopreservation, ROS, oxidative stress, antioxidants.

Future Fertility Among Pediatric Cancer Patients: Experiences and Perspectives of Health Workers in a Low-Resource Setting.

Purpose:Although fertility preservation for patients with childhood and adolescent cancer is considered standard of care in the high-resource settings, it is rarely offered in low-resource settings. This study explores the experiences and perspectives of oncology health care professionals in Uganda to identify contextual barriers and facilitators to addressing oncofertility in low-resource settings. Methods: Using ground theory, we conducted in-depth face-to-face interviews of health care professionals managing pediatric patients at the Uganda Cancer Institute (UCI). Using a systematic, semi-structured interview guide, participants were asked open-ended questions about their understanding of fertility preservation and their perspectives on implementing this care at their institution. Although all the eligible health care providers were interviewed, interview transcripts were uploaded into NVivo version 12 and openly coded as per theoretical requirements. Codes were refined into categories and later into structured themes. Results: Twelve health care professionals were interviewed. Most participants identified as female (n = 9). Their role in the medical team varied from nurses (n = 6), medical officers (n = 3), pediatric oncologists (n = 2), and pediatric oncology fellow (n = 1). Six themes were noted as follows: (1) importance of information, (2) importance of future fertility, (3) inadequate consideration to future fertility, (4) communication barriers, (5) inadequate knowledge, and (6) resource barriers. Conclusion: Although health care providers at the UCI face contextual barriers to addressing future fertility among patients with pediatric cancer, they value preserving fertility in this population. Future initiatives that aim to introduce oncofertility care in low-resource settings should prioritize educating providers and building capacity to meet the oncofertility needs in this setting.

Optimal human ovarian follicle isolation: A review focused on enzymatic digestion.

The damage or depletion of ovarian reserves due to aging or cancer treatment can increase the need for fertility preservation techniques. One of the most common ways of supporting fertility in prepubertal girls and women who require immediate cancer treatment is through ovarian tissue cryopreservation and re-transplantation following cancer treatment. However, a more appropriate method should be employed in diseases such as leukemia, where malignant cells may be present in cryopreserved tissue, instead of ovarian tissue transplantation. Human ovarian follicle isolation for in vitro culture or the use of artificial ovaries for their growth can decrease the risk of reintroducing cancer cells into these individuals. Here we review the methods for the isolation of human ovarian follicles.

Chemoprotection of the ovary: a leading role or a complementary strategy in fertility preservation?

Chemoprotection of the ovary: a leading role or a complementary strategy in fertility preservation?

Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists

Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists

Borderline tumours of ovary and fertility preservation–Outcomes from a tertiary care center in India

ObjectiveBorderline ovarian tumors (BOT) are characterized by atypical epithelial proliferation without stromal invasion and majority are diagnosed in women of reproductive age group desirous of fertility preservation. MethodsA retrospective review of medical records of patients diagnosed with BOT and on regular follow up at the All India Institute of Medical Sciences New Delhi, during a nine-year study period from March 2014 to March 2023 was performed. Surgical treatment was classified as radical or fertility sparing surgery (FSS). Surgical staging was defined as complete, partial or un-staged. ResultsMedian age of 91 women was 34 years. Follow up period ranged from 4 to 222 months (median 77 months). Among 68 premenopausal women, 31 (46 %) underwent radical surgery and FSS in 37 (54 %) cases. Median time to conception in 29 women with future fertility wishes was 13 months (range, 4 to38 m). Seven of 29 cases (29 %) required ovulation induction. The pregnancy rate was 82.7 % and live birth rate was 80 %. Eight cases (8.7 %) had a recurrence (7- un-staged, 1- partially staged) and median time to recur was 36 months. There was no significant difference in recurrence between cystectomy/oophorectomy. Ovary was the site of recurrence in all surgically salvaged cases except peritoneal cavity in 1 case with mortality. Relapse free survival at 5 and 10 years in FSS and radical surgery group were similar. ConclusionFSS is a safe procedure and should be considered in young patients desirous of future fertility along with a comprehensive peritoneal staging. Reproductive outcomes are excellent.

Assessing Attitudes and Understanding After Ovarian Tissue Cryopreservation: A Follow-Up Telephone Interview Survey.

Purpose: Assessing patient and guardian experiences regarding their history of ovarian tissue cryopreservation (OTC) years after initial procedure. Methods: Cross-sectional follow-up telephone survey. A questionnaire developed by The Pediatric Initiative Network of the Oncofertility Consortium, modified to assess intent and attitudes regarding OTC, tissue access knowledge, financial burden of tissue storage, and intent to use tissue, was utilized. Interviews were conducted for those who underwent OTC at a metropolitan children's hospital between 2013 and 2022. Results: Of 60 eligible patients, 39 interviews were completed. Contacted patients were 3-28 years old, with minors accompanied by guardians. Average age at OTC was 8.5 years old, and 5.1% (2/39) were deceased at the time of contact. All interviewees underwent OTC for fertility preservation before gonadotoxic treatment. Seventy percent of patients (7/10) and 48.1% (13/27) of guardians stated they would use frozen tissue for pregnancy, with 50% (5/10) of patients and 59.3% (16/27) of guardians not understanding tissue access. Regret occurred in 10% (1/10) of patients and 3.4% (1/29) of guardians. It was associated with 10.8% (4/37) of tissue discard due to failed storage payments. Financial concerns occurred in 29.7% (11/37) of interviewees. Overall, 92.3% (36/39) would recommend OTC, and 94.9% (37/39) would repeat their choice to undergo OTC. Conclusion: Follow-up after OTC is essential to patient understanding of tissue status, access, and payments. Most do not regret OTC, except in cases of financial burden leading to tissue discard. Follow-up should be sequentially scheduled and include counseling on financial assistance programs.

Adoption as an Alternative Family-Building Strategy: Perceptions of Female, Young Adult Cancer Survivors Receiving Gonadotoxic Treatments.

Female survivors of young adult (YA) cancers are at risk of fertility impacts following cancer treatment. For these women, fertility-related distress is both prevalent and persistent. Yet there is little research regarding survivors' perspectives on alternative family-building options, particularly adoption. This exploratory secondary data analysis analyzed semistructured interviews and explored survivors' views of adoption. Overall, female YA survivors reported openness to adoption as a possible substitute for biological conception and an alternative to fertility preservation. It is imperative that this population receives support in decision-making around and consideration of the unique barriers to adoption for cancer survivors.

Multi‐Scale Ice Inhibition Platform Enables Full‐Cycle Cryogenic Protection for Mouse Oocyte

AbstractCryopreservation of metaphase II (MII) oocytes is crucial to preserve female fertility. However, the existing vitrification technology just provides partial cryogenic protection for oocytes and must use high concentrations of toxic penetrating cryoprotective agents (CPAs, up to 4.8 M). Here, a multi‐scale ice inhibition platform is proposed, which effectively suppresses ice crystal morphology, ice recrystallization (IR), temperature gradient, and devitrification. This platform achieves mouse oocyte survival rate of 98.6% using the low concentration of CPA (3.1 M) while also possessing batch oocyte cryopreservation ability. In contrast, recovered oocytes show a much more modest variation of genes compared with the conventional method (85 vs. 1396 genes), retaining normal fertilization, embryonic development, and birth to healthy offspring. Diverging from the conventional vitrification method with partial cryogenic protection capability, this platform introduces full‐cycle ice inhibition, offering promising prospects for achieving high‐quality and scalable fertility preservation.