Fertility Preservation In Cancer Patients Research Articles

Oocyte vitrification for oncological and social reasons.

The aim of this review is to present information related to oocyte cryopreservation, and particularly oocyte vitrification, performed to preserve fertility in oncologic and social indications. The success rates of oocyte cryopreservation have increased with the widespread use of the vitrification technique and are currently similar to those of in vitro fertilization performed with fresh oocytes. Vitrification is the most successful technique for oocyte cryopreservation. The most important factors that influence the success rate are the patient's age at the time of vitrification and the number of mature oocytes frozen. Thus, live birth rates differ for each age depending on the number of oocytes thawed and the freezing method. The American Society of Reproductive Medicine and the American Society of Clinical Oncology recommend presenting the option of oocyte cryopreservation for fertility preservation in cancer patients. Besides cancer patients, use of oocyte vitrification is increasing in women who wish to postpone pregnancy age and to have reproductive freedom with the development of the cryopreservation technique and the achievement of pregnancy rates similar to the use of fresh oocytes. Patients are provided consultancy service in terms of indication, the success rates by age, and the total number of oocytes frozen. It should be emphasized that this procedure is not a type of insurance policy for fertility, especially in elective oocyte cryopreservation.

Oncofertility awareness among primary care physicians in India.

Primary carephysicians not only coordinate referrals tooncologyservicesbut can play a crucial role in successful fertility preservation referrals in cancer-diagnosed patients. Hence, it is important to assess their knowledge and attitudes towards fertility preservation. An eighteen-itemoncofertilitysurvey was administered toprimary carephysicians between May 2019 to September 2020. Results: A total of forty-six responses were received and analysed.About 60% of primary carephysicians did not have adequate knowledge about available fertility preservation options and only 26-32% were aware ofinternational guidelines recommending fertility preservation in cancer patients. Conclusions: Impartingawareness and knowledge of fertility preservation and its optionsto primary care physicians could enable an integrated cancer care model while also facilitating successfuloncofertilityreferralsin countries like India.

The Knowledge, Attitude, and Practice about Fertility Preservation among Oncologist-A Cross-Sectional Study

Background Fertility Preservation is the process of saving or protecting a person’s ability to have children in the future. It is often considered for individuals who are about to undergo medical treatments that may impact their fertility, such as chemotherapy. Hence, the current study is aimed to assess clinical practitioners’ knowledge, practice, and attitude toward fertility preservation among oncologists. Methods A cross-sectional survey was carried out to identify the current knowledge, attitudes, and practices regarding fertility preservation among oncologists—a total of seventy-nine oncologists in Karachi working in different public and private sectors. The study was conducted between January to August 2022. The data was gathered using a self-designed questionnaire that was distributed via email. Result One hundred and eighty oncologists were provided with the survey form via email. The response rate was 47.22% (n=85). Out of which, six questionnaires were excluded due to incomplete information. The total questionnaire analyzed was n=79, which included 58 (73.41%) males and 21 (16.59%) females. Conclusion The results revealed that oncologists had a compromised knowledge regarding fertility preservation for cancer patients. Despite weak knowledge, most oncologists believe that more elaborative measures should be taken to overcome this issue. Keywords Attitude, Fertility Preservation, Knowledge, Oncologist

The Knowledge, Attitude, and Practice about Fertility Preservation among Oncologist-A Cross-Sectional Study

Background Fertility Preservation is the process of saving or protecting a person’s ability to have children in the future. It is often considered for individuals who are about to undergo medical treatments that may impact their fertility, such as chemotherapy. Hence, the current study is aimed to assess clinical practitioners’ knowledge, practice, and attitude toward fertility preservation among oncologists. Methods A cross-sectional survey was carried out to identify the current knowledge, attitudes, and practices regarding fertility preservation among oncologists—a total of seventy-nine oncologists in Karachi working in different public and private sectors. The study was conducted between January to August 2022. The data was gathered using a self-designed questionnaire that was distributed via email. Result One hundred and eighty oncologists were provided with the survey form via email. The response rate was 47.22% (n=85). Out of which, six questionnaires were excluded due to incomplete information. The total questionnaire analyzed was n=79, which included 58 (73.41%) males and 21 (16.59%) females. Conclusion The results revealed that oncologists had a compromised knowledge regarding fertility preservation for cancer patients. Despite weak knowledge, most oncologists believe that more elaborative measures should be taken to overcome this issue. Keywords Attitude, Fertility Preservation, Knowledge, Oncologist

Routine double-ovarian-stimulation (DuoStim) in poor responders lacks rationale, evidence, and follow-up.

Double ovarian stimulation (DuoStim), initially only suggested for fertility preservation in cancer patients, is now increasingly also used in routine clinical IVF, especially in poor responders. The claimed rational for this is the alleged existence of multiple follicular waves in a single intermenstrual interval, allowing for retrieval of more oocytes in a single IVF cycle. This commentary argues that this expansion of purpose lacks rationale, evidence, and follow-up. Consequently, we suggest that, unless valid clinical indications have been established, DuoStim be only subject of controlled clinical trials with appropriate experimental consents.

Outcomes of Fertility Preservation for Female Cancer Patients in a Single Tertiary Center.

To report our experience of fertility preservation (FP) in female cancer patients. We retrospectively analyzed the medical records of female who underwent elective oocyte or embryo cryopreservation before cancer treatment between January 2015 and December 2020 at Asan Medical Center. We analyzed the type of cancer, the rate of reuse of cryopreserved oocytes or embryos, and fertility outcomes such as the resumption of menstruation or pregnancy. A total of 174 patients underwent 182 oocyte retrieval cycles after controlled ovarian stimulation for oocyte or embryo cryopreservation. The median age of patients was 33.0 (range 19-46) years, and the patients were most unmarried female (65.52%). The majority of patients were diagnosed with breast cancer (78.16%), and the remaining were diagnosed with gastrointestinal (6.33%) and hematologic malignancies (5.75%). The maturation rate of oocyte cryopreservation was 83.33%, and the fertilization rate of embryo cryopreservation was 72.07%. Of the 57 patients currently not undergoing cancer treatment, 34 resumed menstruating and 19 (33.33%, 19/57) returned to attempt a pregnancy. Among them, five patients succeeded in natural pregnancy. Eleven patients received frozen-thawed embryo transfer, and four patients succeeded in becoming pregnant (36.36%, 4/11). Only 6.3% of patients returned to use their gametes, and 93.7% of gametes are still in storage. FP in cancer patients should be considered before cancer treatment. Through continuous research on oncofertility, it is necessary to consider how to increase the return rate and provide appropriate information to cancer patients of reproductive age.

IVF characteristics and the molecular luteal features of random start IVF cycles are not different from conventional cycles in cancer patients.

Are the IVF parameters and the steroidogenic luteal characteristics of random-start IVF cycles different from conventional cycles in cancer patients? No; controlled ovarian stimulation cycles randomly started at late follicular phase (LFP) and luteal phase (LP) are totally comparable to those conventional IVF cycles started at early follicular phase (EFP) in terms of the expression of the enzymes involved in cholesterol utilization and steroid hormone biosynthesis pathways, gonadotropin receptor expression and, estradiol (E2) and progesterone (P4) production in addition to the similarities in ovarian response to gonadotropin stimulation, oocyte yield, fertilization rate and embryo development competency in cancer patients. Random start ovarian stimulation protocols are commonly employed for oocyte and embryo freezing for fertility preservation in cancer patients with time constraints who do not have sufficient time to undergo ovarian stimulation initiated conventionally at EFP of the next cycle. No data is available regarding the molecular steroidogenic features of these cycles analyzed together with the clinical IVF characteristics in cancer patients. We aimed to address this question in this study to help understand how similar the random start cycles are to the conventional start ones. A clinical translational research study conducted in 62 cancer patients undergoing IVF for fertility preservation between the years 2017 and 2022. Sixty-two patients who were diagnosed with different types of cancer and underwent ovarian stimulation for oocyte (n = 41) and embryo (n = 21) cryopreservation using GnRH antagonist protocol and human menopausal gonadotropins before receiving cancer treatment/surgery were enrolled in the study. For patients with breast cancer and endometrial cancer the aromatase inhibitor letrozole was used with gonadotropin stimulation. Ovarian stimulation was initiated conventionally at EFP in 22 patients and served as control while it was started at LFP in 20, and mid-LP in the other 20 patients. The luteinized granulosa cells (GCs) were recovered from follicular aspirates during oocyte retrieval procedure and used for the experiments separately for each individual patient. The expression of the enzymes involved in sex steroid biosynthesis (StAR, 3β-HSD, Aromatase) and cholesterol synthesis (3-hydroxy 3-methylglutaryl Co-A reductase (HMG-Co-A reductase)), utilization (hormone sensitive lipase (HSL)), and storage (Acetyl-Coenzyme A acetyltransferase 1 (ACAT-1)), and gonadotropin receptor expression status were analyzed using immunoblotting and RT-PCR methods. Laser confocal immunofluorescence imaging was applied to analyze and compare the expression patterns of the steroidogenic enzymes and their relation with mitochondria. In vitro E2 and P4 production by the cells were compared among the groups. Baseline demographic and IVF characteristics of the patients undergoing the conventional start and random start IVF cycles were similar. Duration of gonadotropin stimulation was significantly longer in LFP and LP start cycles in comparison to the conventional ones. Ovarian response to gonadotropin stimulation, mature and total oocyte yield, fertilization and Day 5 blastulation rates of the embryos were comparable between the conventional versus random start cycles. When the luteal GCs of these random start cycles were analyzed we could not find any gross differences between these cycles in terms of the viability index and gross light microscopic morphologic features. More detailed analysis of the molecular luteal characteristics of the cells using RT-PCR, immunoblotting methods revealed that the expression profiles of the gonadotropin receptors, and the enzymes involved in sex steroid biosynthesis and cholesterol synthesis/utilization, and the steroidogenic activity of the luteal GCs of the random start cycles are almost identical to those of the conventional start cycles. Confocal image analysis demonstrated similar patterns in the signal expression profiles of the steroidogenic enzymes and their co-localization within mitochondria. N/A. Caution should be exercised when interpreting our data and counseling cancer patients seeking fertility preservation because it is still unclear if previous exposure to cancer drugs, different ovarian pathologies or infertility etiologies, previous ovarian surgery and/or any other underlying diseases that are concomitantly present with cancer may cause a difference between conventional and random start stimulation protocols in terms of IVF parameters, luteal function and reproductive outcome. Relatively low number of patients in each stimulation protocol and pooling of luteal GCs for each patient rather than individual analysis of each follicle and oocyte are additional limitations of our study. Our findings provide reassurance that random start protocol offers cancer patients an equally good prospect of fertility preservation as conventional IVF. Funded by the School of Medicine, the Graduate School of Health Sciences of Koc University and Koç University Research Center for Translational Medicine (KUTTAM), equally funded by the Republic of Turkey Ministry of Development Research Infrastructure Support Program. All authors declare no conflict of interest. N/A.

Female fertility preservation in cancer patients.

Fertility preservation in cancer patients or oncofertility is a relatively new trend in modern medicine. In patients with unfulfilled reproductive plans, the possibility of starting a family is one of the key parameters of quality of life after overcoming a cancer. Guidelines have existed since 2013 and in 2020 the European Society of Human Reproduction and Embryology has also published a guideline, but the main problem of their application in clinical practice is the lack of information for both patients and, unfortunately, professionals, as well as the high cost of treatment. From 2022, health insurance companies in the Czech Republic partially cover the expenses for fertility preservation treatment for cancer patients. The possibilities of oncofertility are based, on the one hand, on improving the results of oncological treatment, on the other hand, on the development of reproductive technologies. Thanks to progress in treatment, up to 80% of pediatric oncology patients survive into adulthood, but chemotherapy, especially highly effective alkylating agents, is associated with a high risk of impaired fertility. This article overviewed9 modern global trends of fertility preservation in women undergoing cancer treatment based on an analysis of the English-language literature over the past 5 years.

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles.

Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation? The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS. Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF. This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample. Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 μg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy). FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)). The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age. The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase. This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests. The study was registered at Clinical Trials Gov (NCT03555942).

Application of Ex-Vivo In Vitro Maturation (IVM) to Fertility Preservation in Cancer Patients

Background: Oocyte in vitro maturation (IVM) is a reproductive technology that generates mature oocytes from patients who have received minimal or no ovarian stimulation (OS). The minimal-stimulation feature of IVM makes it a valuable option for cancer patients requiring fertility preservation (FP), before chemo- or radiotherapy. When ovarian tissue is collected for cryopreservation (OTC), only the ovarian cortex is preserved whereas the ovarian medulla containing growing follicles is discarded. To maximise the future fertility prospects for cancer patients, OTC should be coupled with a modified form of IVM, termed ex-vivo IVM, in which immature cumulus-oocyte complexes (COCs) are collected from antral follicles. Aim: To examine the utility of emergency ex-vivo IVM for FP. Method: A 31-year-old woman diagnosed with locally invasive appendiceal cancer required urgent FP as there was no time for conventional OS egg freeze before surgery, and OTC was contra-indicated due to the possibility of later regrafting of cancer cells. She underwent peritonectomy with bilateral oophorectomy with no prior ovarian stimulation or cycle management. Visible antral follicles were aspirated ex-vivo, the ovaries were then manually dissected, antral follicles punctured and intact COCs collected. COCs were washed and matured for 30-46h in G-2 PLUS medium supplemented with 0.1IU/mL rec-FSH, 0.5IU/mL rec-hCG, and 10% (v/v) autologous heat-inactivated patient serum. Results: 40 COCs were collected and 18 (45%) reached metaphase II, 1 was cryopreserved and 17 were inseminated by ICSI. 13/17 oocytes fertilised (2PN; 76%) and 7/13 (54%) blastocysts were generated (D5: 1× HB-1-1, 3× B-1-1, 1× B-2-1. D6: 1× HB-1-2, 1× B-2-2). Seven blastocysts and one oocyte were vitrified for future use by the patient. Conclusion: Ex-vivo IVM is a viable FP option for patients diagnosed with cancer. It can readily be coupled with OTC and/or a regular IVM oocyte pickup to maximise a cancer patient’s future fertility prospects.

Fertility Preservation in Oncological Patients

Background: Lately, attention is given to fertility preservation in reproductive-age patients undergoing oncological treatment. This should become a routine part of today’s assisted reproductive technologies. Methods: Available oncofertility preservation methods, next to their clinical, ethical and legal implications are discussed, within the context of the right to health and its broader aspects as delineated in the 1946 Constitution of the World Health Organization. Results: Possible egg and sperm freezing. as well as ovarian tissue cryopreservation, should always be explained and suggested to fertility-age patients before starting oncological treatment. Sperm, oocyte, and embryo cryopreservation should become standard practice. Conclusions: All ethical, cultural, and moral aspects of fertility preservation in cancer patients are multifaceted and need to rely on principles that are based on widely-accepted guidelines and evidence-based practices. Adequate policy, legislation, and regulations should be agreed upon and implemented.

Oncofertility and Fertility Preservation in Cancer Patients Across the Twitterverse.

PurposeInfertility is a major problem affecting children, adolescents, and young adults (AYAs) with cancer, either due to the disease itself or because of oncologic treatment. Oncofertility (OF) focuses on counseling cancer patients about fertility risks and preservation options. However, OF and fertility preservation (FP) conversations on Twitter and their impact are unknown. We aim to characterize the users and type of content of these conversations.Materials and MethodsThis observational study analyzed tweets with the hashtags “#Oncofertility” and “#FertilityPreservation” over eight months. We classified Twitter accounts by user type and country. Tweets were categorized by content type, and retweets and likes were quantified. Descriptive statistics were used for analysis.ResultsA total of 399 tweets from 223 different accounts were evaluated. Twitter accounts comprised 22 countries and stemmed from high, upper-middle, and lower-middle-income countries in 86.5%, 5.4%, and 6.3%, respectively; no accounts from low-income countries were found. Accounts were mostly from physicians (37%) and healthcare centers (20%); we did not find any patient accounts. The most common content category was informative tweets directed to patients (30.8%), followed by discussion/sharing of medical papers (25.6%). Only 14.5% of tweets contained information about children and adolescents. Still, only 4.5% were aimed at children. Retweets were absent in 16.5% of the tweets, and 80.7% did not have comments.ConclusionOF and FP discussions on Twitter were limited to interactions among medical professionals. Also, advocacy groups showed limited activity on social media. Even though a significant proportion of tweets directed to patients were found, no active involvement of patients was observed. Finally, limited number of tweets (4.5%) were directed to children and adolescents. There is a need to raise awareness about the effects of cancer on fertility in this group. Currently, Twitter is not a resource of information for children and AYAs with cancer who need OF counseling and fertility preservation. Our results open a debate on how to promote the use of social media in the future to improve the quality of OF information available, awareness, and care since there is an unmet need for fertility preservation access in young cancer patients.

P-716 The impact of the SARS-CoV-2 pandemic on ART activity in Italy during 2020

Study questionEvaluate the impact of restrictive measures, implemented to contain the spread SARS-CoV-2, on ART activity in Italy during 2020.Summary answerDue to periods of suspension of certain medical procedures in 2020, ART activity has undergone a substantial reduction.What is known alreadySince the end of February 2020, the spread of SARS-CoV-2 has taken a dramatic toll, especially in Northern Italy. In order to ensure that the majority of National Health System resources were employed to control the epidemic, non-urgent medical procedures such as ART treatments, were suspended or postponed by a Government Decree issued on March 9, 2020. Only fertility preservation in cancer patients continued as these procedures could not be deferred. The first suspension of activity lasted about two months. Then, throughout 2020 many ART centers were forced to suspend their activity again because of flairs in SARS-CoV-2 infection rates.Study design, size, durationThe Italian Assisted Reproductive Technology Register (IARTR) retrospectively analyzed ART cycles applied in Italy in 2020 (67,928 ART cycles performed on 57,423 patients). The 2020 ART cycles were compared to those applied in 2019 (82,476 ART cycles performed on 67,633 patients). Data collection was organized yearly in two different time frames: the first regards the activity conducted during the year until pregnancy and the second regards pregnancy outcomes.Participants/materials, setting, methodsA total of 205 ART clinics have sent data to the IARTR in 2019 and/or 2020. Among those clinics 54.1% were private, 37.1% were public and 8.9% were private covered by NHS. Records were securely kept in the IARTR archive. The analysis has been performed utilizing SPSS 27.0Main results and the role of chanceIn 2020, the number of total ART cycles reported was 67,928 including 38,728 homologous fresh cycles (Fresh), 1,099 frozen/thawed oocytes (FO), 19,314 frozen embryo (FER) and 8,787 ART donation cycles. In 2019, 82,476 cycles were reported, including 50,324 Fresh, 1,361 FO, 21,796 FER and 8,995 gametes donation. In 2020, there have been 14,548 less ART cycles than in 2019, equivalent to a 17.6% of reduction in overall activity. However, the reduction was not homogeneous for all ART techniques, in particular there was a reduction of -23% in fresh cycles, of -11.4% in FER, of -19.3% in FO and of -2.3% for gametes donation. This overall reduction led to 3,325 fewer pregnancies. The reduction of treatment cycles observed in 2020 brings to 2,119 fewer deliveries (-18.0%) and to 2,539 fewer live born babies (-19.8%) compared to 2019. The percentage reduction of births is not homogeneous for the different ART techniques, ranging from -0.3% in donation cycles to -36.9% in fresh cycles. Lastly, during 2020 a reduction in multiple births (-2.1%) has been observed.Limitations, reasons for cautionSince the national ART Register collect only summary data more deep analysis could not be performed. For some ART techniques the reduction may have been greater (i.e. donation cycles) if considering the growing trends of previous years.Wider implications of the findingsCovid-19 pandemic has had a strong impact on Italian Health System. ART procedures suffered a reduction of availability. Since Italy has the lowest birth rate in Europe and ART plays an important role answering to the need of infertile couples, Government should support access to these treatments with dedicated actions.Trial registration numbernot applicable

P-442 A new option to thaw slow-frozen human ovarian tissue in cancer patients: efficacy and safety of the combination of different cryopreservation kits

Abstract Study question Is follicular viability of slow-frozen human ovarian tissue preserved if rapid thawing is performed using a solution containing extracellular cryoprotectant only? Summary answer Follicular viability is preserved even using thawing solutions containing extracellular cryoprotectant only, combining kits with different composition. What is known already Ovarian tissue cryopreservation is an alternative option to oocytes or embryos for fertility preservation in cancer patients facing gonadotoxic treatments. To date, each brand producing kits approved for the slow-freezing of human ovarian tissue recommends the use of its own thawing kit. However, a potential single protocol based on the use of any extracellular cryoprotectant has already been proposed for human oocytes and embryos. The current study aims at finding alternative options to thaw cryopreserved human ovarian tissue when the original kit was withdrawn from the market and only one CE-marked kit was available, even with different composition in cryoprotectants. Study design, size, duration Ovarian tissue cryopreservation of ten cancer patients (18.3 ± 7.6 years) undergoing fertility preservation between 2001 and 2012 was performed following a slow-freezing protocol with 1.5M 1,2 PROH and 0.5M Sucrose. Once deceased, for each patient, cortical fragments were prospectively thawed and equally allocated into two groups: i) fragments thawed using 0.5-1M 1,2 PROH and 0.3M Sucrose (PROH+S Group, n = 73); ii) fragments thawed following an adjusted protocol with 0.5M Sucrose only (S Group, n = 73). Participants/materials, setting, methods Post thawing follicular density/mm2, integrity (%) and the presence of interstitial oedema were assessed by histological and ultrastructural analysis performed after formalin fixation and haematoxylin/eosin staining. Follicular viability was evaluated by the expression of markers of proliferation (Ki67) and of vascularization (CD31) by immunohistochemistry after a 24h culture in Iscove’s modified Dulbecco’s medium at 37 °C and 6% CO2. A paired comparison was performed referring to the fresh tissue of the same patient as control. Main results and the role of chance The histological evaluation performed after thawing revealed that follicles were predominantly primordial (91%), with no follicles larger than the proliferating primary stage. A significant reduction of follicular density per mm2 was observed in both study groups (14.2 ± 12.0 vs. 15.1 ± 14.0 for PROH+S and S Group, respectively; p = 0.4) compared to the fresh tissue (27.2 ± 31.6; p = 0.04) as well as a remarkable decreased of the proportion of intact follicles (39.3 ± 17.1 vs. 25.5 ± 9.8; p = 0.2) compared to the fresh tissue (98.1 ± 1.4; p = 0.002). Thawed samples equally showed interstitial oedema and increased stromal cell vacuolization and chromatin clumping. Ki67 positive staining of active proliferating cells revealed a comparable proportion of viable follicles between thawed samples (46.3 ± 20.8 vs. 28.3 ± 27.9 for PROH+S and S Group, respectively; p = 0.2). Finally, the expression of the endothelial marker CD31 in the thawed samples suggested an equivalent number of blood vessels per mm2 (43.8 ± 34.3 vs. 41.7 ± 44.8; p = 0.6). Limitations, reasons for caution Single centre study with a limited sample size. Only 24h of in vitro culture was assessed. The use of the freezing medium corresponding to the Sucrose only solution was not tested. Clinical outcomes after ovarian tissue transplantation should be evaluated before drawing final conclusion. Wider implications of the findings First evidence of the feasible application of a “Universal Warming” protocol, irrespective of brand and cryoprotectants, for the rapid thawing of slow-frozen human ovarian tissue. IVF centres would be provided with alternative options to thaw ovarian tissue for restoring reproductive potential in cancer patient undergoing ovarian transplantation. Trial registration number Not applicable

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.

A bibliometric analysis of primary ovarian insufficiency from 2010 to 2020

Objective This study aimed to carry out a bibliometric analysis of primary ovarian insufficiency (POI) from 2010 to 2020 and to reveal the research status and hotspots in the future. Method A total of 3087 articles and reviews related to POI published from 2010 to 2020 retrieved from the Web of Science Core Collection were used for bibliometric analysis. CiteSpace and VOSviewer were adopted to analyze countries and regions, organizations, authors, journals, keywords and co-cited references. Results The number of publications about POI increased year by year. The USA produced the largest number of publications and the most influence in this field. The main research directions of POI can be roughly divided into four aspects according to the analysis of keywords and co-cited references: genetic research of POI; stem cell therapy for patients with POI; prediction of ovarian function; and fertility preservation of cancer patients. Genetic research and stem cell therapy may become research hotspots in the future. Conclusion This study might be the first bibliometric study to analyze publications of POI from multiple indicators, in order to provide new opinions for the research trends and possible hotspots of POI.

Practices, Attitudes, and Knowledge Among Healthcare Providers and Oncologists in China Regarding Male Fertility Preservation.

ObjectiveThe purpose of this study was to help to promote a better understanding of the male fertility preservation status in China.MethodsIn this cross-sectional survey, 1,912 healthcare providers and oncologists were surveyed anonymously using 16 questions carried out at community oncology practices in China from September 2018 to April 2021. 16 questions were designed to evaluate their knowledge on male fertility preservation in cancer patients, assess the factors they considered when deciding whether to discuss male fertility preservation with their patients.ResultsAmong the 1,912 healthcare providers (42.2% male), 1,713 (89.6%) considered that patients with cancer should be recommended for fertility preservation. 1,264 (66.1%) respondents were aware of male fertility preservation, but only 248 (13.0%) respondents knew the correct institutions. Whether a healthcare provide recommended fertility preservation to their patients depended on the provider's educational background, professional qualifications, hospital grade, area, department, and age. Among the healthcare providers, the three main factors for not recommending fertility preservation for patients with cancer were lack of suitability of the patient for fertility (28.2%), lack of knowledge of fertility preservation (28.6%), and lack of knowledge concerning the institutes that provide fertility preservation (25.4%).ConclusionDespite this, healthcare providers and oncologists in China showed a positive attitude toward fertility preservation in patients with cancer. Hence, the education of physicians should include fertility preservation, with the aim of increasing their knowledge and awareness. There should be more collaboration between oncologists and reproductive medicine specialists.

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.

The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan.

PurposeIn 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016–2019) and compared the results with our previous survey (2011–2015). The authors also surveyed reproductive specialists’ awareness of the guidelines and implementation problems.MethodsThe authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology.ResultsThe authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011–2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists’ interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources.ConclusionsThe practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.

Evaluation of Knowledge, Attitude, and Practice of Health Practitioners towards Fertility Preservation in Cancer Patients in an Environmental Region of Saudi Arabia.

Background Cancer patients face multiple challenges, such as infertility caused by exposure to gonadotoxic agents and gonadal irradiation during cancer treatment. Little is known about the health practitioners' knowledge and practice regarding fertility preservation and its available options in Saudi Arabia. Thus, this study is designed to evaluate the level of knowledge, attitude, and practice (KAP) towards fertility preservation in cancer patients among health practitioners in an environmental region in Saudi Arabia. Methods The cross-sectional study was carried out between September 2020 and January 2021. A self-administered questionnaire was distributed among health practitioners from a variety of specialties who work closely with cancer patients. Results Out of 100 participants, 90% need more knowledge about fertility preservation. The lack of fertility preservation clinics in the patient's area and its unaffordable expenses significantly influenced the health practitioners' attitude towards fertility preservation discussion with cancer patients. The results revealed that 92% of the participants agreed that the Saudi Ministry of Health should establish practice guidelines and provide fertility preservation services for cancer patients. Conclusions The present study showed that clinical practitioners' knowledge remains insufficient. Education of health practitioners and the establishment of practice guidelines and fertility preservation clinics for cancer patients are required.