Fertility Preservation In Cancer Patients Research Articles

Fertility Preservation Strategies in Cancer Patients: A Comprehensive Review

Introduction and purpose. Preserving fertility is crucial for cancer patients, aligning with advancements in oncology. As survival rates improve, addressing treatment-related late effects gains importance. Many young patients, aware of therapy toxicity, consider future conception chances, impacting treatment decisions. With a trend toward delayed childbirth and a growing population facing unplanned family planning disruptions, the demand for fertility preservation is expected to rise. This paper provides a brief review of available methods for preserving fertility in cancer patients.   State of knowledge. Freezing semen in liquid nitrogen vapor is a standard method for preserving reproductive potential in male cancer patients. Shielding during total-body radiation limits testicular volume reduction, indicating less damage to the germinal epithelium. Hormone suppression treatments are not protective in male cancer patients. Oocyte and embryo cryopreservation are considered secure methods before anticancer treatments, with oocyte cryopreservation being preferred for post-pubertal women. Ovarian tissue cryopreservation remains an alternative method without preliminary treatment, suitable when time is insufficient for ovarian stimulation. Ovarian transposition beyond the intended radiation area, performed laparoscopically, can retain ovarian function. GnRH agonist administration before and during chemotherapy aims to minimize the likelihood of premature ovarian insufficiency.   Summary. Advancements in fertility preservation for cancer patients, ranging from traditional cryopreservation to innovative methods like ovarian tissue preservation, highlight a commitment to empowering individuals facing cancer diagnoses. Ongoing research expands possibilities, ensuring a diverse range of strategies that offer tangible and hopeful prospects at the intersection of cancer and reproductive health.

The Usage of Cryopreserved Reproductive Material in Cancer Patients Undergoing Fertility Preservation Procedures.

Many cancer treatment methods can affect fertility by damaging the reproductive organs and glands that control fertility. Changes can be temporary or permanent. In order to preserve the fertility of cancer patients and protect the genital organs against gonadotoxicity, methods of fertility preservation are increasingly used. Considering that some patients ultimately decide not to use cryopreserved reproductive material, this review analysed the percentage of post-cancer patients using cryopreserved reproductive material, collected before treatment as part of fertility preservation. A systematic search of studies was carried out in accordance with the Cochrane Collaboration guidelines, based on a previously prepared research protocol. The search was conducted in Medline (via PubMed), Embase (via OVID), and the Cochrane Library. In addition, a manual search was performed for recommendations/clinical practice guidelines regarding fertility preservation in cancer patients. Twenty-six studies met the inclusion criteria. The studies included in the review discussed the results of cryopreservation of oocytes, embryos, ovarian tissue, and semen. In 10 studies, the usage rate of cryopreserved semen ranged from 2.6% to 21.5%. In the case of cryopreserved female reproductive material, the return/usage rate ranged from 3.1% to 8.7% for oocytes, approx. 9% to 22.4% for embryos, and 6.9% to 30.3% for ovarian tissue. In studies analysing patients' decisions about unused reproductive material, continuation of material storage was most often indicated. Recovering fertility or death of the patient were the main reasons for rejecting cryopreserved semen in the case of men. Fertility preservation before gonadotoxic treatment is widely recommended and increasingly used in cancer patients. The usage rate is an important indicator for monitoring the efficacy of these methods. In all of the methods described in the literature, this indicator did not exceed 31%. It is necessary to create legal and organizational solutions regulating material collection and storage and to create clear paths for its usage in the future, including by other recipients.

Oncofertility awareness among primary care physicians in India

Background: Primary care physicians not only coordinate referrals to oncology services but 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. Methods: An eighteen-item oncofertility survey was administered to primary care physicians between May 2019 to September 2020.  Results: A total of forty-six responses were received and analysed. About 60% of primary care physicians did not have adequate knowledge about available fertility preservation options and only 26-32% were aware of international guidelines recommending fertility preservation in cancer patients.  Conclusions: Imparting awareness and knowledge of fertility preservation and its options to primary care physicians could enable an integrated cancer care model while also facilitating successful oncofertility referrals in countries like India.

Impact of low- or moderate-risk gonadotoxic chemotherapy prior to testicular tissue freezing on spermatogonia quantity in human (pre)pubertal testicular tissue.

What is the impact of low- or moderate-risk gonadotoxic chemotherapy received prior to testicular tissue freezing (TTF), and of the cancer itself, on spermatogonia quantity in testicular tissue from (pre)pubertal boys? Vincristine, when associated with alkylating agents, has an additional adverse effect on spermatogonia quantity, while carboplatin has no individual contribution to spermatogonia quantity, in testicular tissue of (pre)pubertal boys, when compared to patients who have received non-alkylating chemotherapy. The improved survival rates after cancer treatment necessitate the inclusion of fertility preservation procedures as part of the comprehensive care for patients, taking into consideration their age. Sperm cryopreservation is an established procedure in post-pubertal males while the TTF proposed for (pre)pubertal boys remains experimental. Several studies exploring testicular tissue of (pre)pubertal boys after TTF have examined the tubular fertility index (TFI, percentage of seminiferous tubule cross-sections containing spermatogonia) and the number of spermatogonia per seminiferous tubule cross-section (S/T). All studies have demonstrated that TFI and S/T always decrease after the introduction of chemotherapeutic agents, especially those which carry high gonadotoxic risks such as alkylating agents. Testicular tissue samples from 79 (pre)pubertal boys diagnosed with cancer (from 6 months to 16 years of age) were cryopreserved between May 2009 and June 2014. Their medical diagnoses and previous chemotherapy exposures were recorded. We examined histological sections of (pre)pubertal testicular tissue to elucidate whether the chemotherapy or the primary diagnosis affects mainly TFI and S/T. (Pre)pubertal boys with cancer diagnosis who had been offered TTF prior to conditioning treatment for hematopoietic stem cell transplantation were included in the study. All the patients had previously received chemotherapy with low- or moderate-risk for future fertility. We have selected patients for whom the information on the chemotherapy received was complete. The quantity of spermatogonia and quality of testicular tissue were assessed by both morphological and immunohistochemical analyses. A significant reduction in the number of spermatogonia was observed in boys treated with alkylating agents. The mean S/T values in boys exposed to alkylating agents were significantly lower compared to boys exposed to non-alkylating agents (P = 0.018). In contrast, no difference was observed for patients treated with carboplatin as the sole administered alkylating agent compared to the group of patients exposed to non-alkylating agents. We observed an increase of S/T with age in the group of patients who did not receive any alkylating agent and a decrease of S/T with age when patients received alkylating agents included in the cyclophosphamide equivalent dose (CED) formula (r = 0.6166, P = 0.0434; r = -0.3759, P = 0.0036, respectively). The TFI and S/T decreased further in the group of patients who received vincristine in combination with alkylating agents (decrease of 22.4%, P = 0.0049 and P < 0.0001, respectively), but in this group the CED was also increased significantly (P < 0.0001). Multivariate analysis, after CED adjustment, showed the persistence of a decrease in TFI correlated with vincristine administration (P = 0.02). This is a descriptive study of testicular tissues obtained from (pre)pubertal boys who were at risk of infertility. The study population is quite heterogeneous, with a small number of patients in each sub-group. Our results are based on comparisons between patients receiving alkylating agents compared to patients receiving non-alkylating agents rather than chemotherapy-naive patients. The French national guidelines for fertility preservation in cancer patients recommend TTF before highly gonadotoxic treatment. Therefore, all the patients had received low- or moderate-risk gonadotoxic chemotherapy before TTF. Access to testicular tissue samples from chemotherapy-naive patients with comparable histological types of cancer was not possible. The functionality of spermatogonia and somatic cells could not be tested by transplantation or in vitro maturation due to limited sample sizes. This study summarizes the spermatogonial quantity of (pre)pubertal boys prior to TTF. We confirmed a negative correlation between the cumulative exposure to alkylating agents and spermatogonial quantity. In addition, the synergistic use of vincristine in combination with alkylating agents showed a cumulative deleterious effect on the TFI. For patients for whom fertility preservation is indicated, TTF should be proposed for chemotherapy with a predicted CED above 4000 mg/m2. However, the data obtained from vincristine and carboplatin use should be confirmed in a subsequent study including more patients. This study had financial support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. The sponsors played no role in the study. The authors declare no conflicts of interest. N/A.

Are There Any Developments in the Attitudes and Practices of Oncologists Regarding Fertility Preservation in Saudi Arabia After 12 Years?

The current practice of offering fertility preservation (FP) counseling and treatment has become one of the focal points in patient care throughout cancer treatment. The turning point was the approval of the Council of Senior Religious Scholars four years ago to freeze tissues from the ovarian membrane, the entire ovary, and the eggs for later use in reproduction to preserve the offspring. Thus, we aimed to assess any development in oncologists' knowledge, attitude, and referral practices regarding FP in Saudi Arabia. This is a cross-sectional survey using a self-administered questionnaire. We assessed oncologists' opinions on the importance of FP, their perception of the patient's preferences, and factors to consider when discussing the subject. Then, we assessed the knowledge and referral practices, including the timing of referral before starting cancer treatment. Most oncologists showed good knowledge and positive attitudes toward FP; however, their referral practices could be better. Most were familiar with FP options. The most significant factors influencing the oncologist-patient FP discussion were the number of existing children, marital status, cost, and type of cancer (96.6%, 76.7%, 65.7%, and 58.9%, respectively). There is a significant improvement in the knowledge and attitude of oncologists toward FP. However, patients' counseling and referral to fertility services still need to be improved. There is a shortfall in the clinical practice guidelines for FP in cancer patients in Saudi Arabia. The implementation of clinical practice guidelines would enhance FP. However, patients' counseling and referral to fertility services still need to be improved. The lack of proper guidelines on FP is affecting oncologists' practice.

Fertility-sparing surgery: a hopeful strategy for young women with cancer.

Fertility preservation in cancer patients is currently based on either assisted reproductive technology or fertility-sparing surgery. Loss of fertility may be caused by excisional surgery associated with an adnexal or uterine pathology or secondary to gonadal insufficiency caused by chemotherapy or radiation. The counseling of these patients is very important, being carried out jointly by the oncologist, gynecologist, and reproductive medicine specialist. Reproductive surgery usually requires avoiding laparotomy to significantly reduce the formation of adhesions and trauma or tissue damage. This is done using standard laparoscopic surgery or robotic surgery (computer-assisted laparoscopy), a method increasingly used and accessible to all specialists who want to maintain the fertility of their patients with various oncological diseases.

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

[This retracts the article DOI: 10.1155/2022/6404837.].

P-405 Nuclear transfer overcomes poor embryo development of in vitro grown mouse oocytes

Abstract Study question Is the nuclear transfer technology able to overcome the compromised embryonic development of in vitro cultured secondary follicles from young B6D2 mice? Summary answer Nuclear transfer technology was able to restore embryonic development to levels similar of in vivo grown oocytes. What is known already In vitro follicle culture has been proposed as a strategy for fertility preservation in cancer patients. Studies in human follicle culture remain scarce, due to the low availability of human tissue. Mouse models have been extensively studied to improve follicle maturation and investigate the potential of in vitro grown (IVG) gametes. Despite significant improvements reported over the years, including increased maturation rates, advanced embryonic development and generation of fertile offspring, the quality of IVG oocytes remains inferior compared to their in vivo grown counterparts. Study design, size, duration The experimental study was conducted between October 2020 and January 2023, after approval by the Animal Ethics Committee of Ghent University Hospital (ECD no 19/60). In total, 108x 16-days-old B6D2 females were used for secondary follicle isolation and in vitro culture, 81x 8-12-week-old females for collection of in vivo grown oocytes, 4x 9-14-week-old B6D2 males for sperm freezing, 5x 10-24-week-old CD1 vasectomised males and 10x 8-12-weeks-old CD1 females as surrogate mothers for embryo transfer. Participants/materials, setting, methods Follicles isolated from 16-days-old B6D2 mice were cultured for 9 days, followed by maturation for 16-18hrs. Mature oocytes were assessed on diameter, spindle morphology, calcium releasing ability, mitochondrial membrane and embryonic developmental potential. In vivo grown oocytes from stimulated mice were used as controls and cytoplasmic donors for nuclear transfer. Spindle (ST) and Pronuclear transfer (PNT) were applied to overcome poor development of IVG embryos, by transferring the spindle/pronuclei of IVG oocytes/zygotes to enucleated controls. Main results and the role of chance In total, 1509 secondary follicles were cultured and 73.6% survived to Day 9. From the 719 cumulus oocyte complexes, 364 (50.6%) oocytes matured. Oocyte diameters were significantly smaller between IVG (67.4μm) and controls (73.1μm) (p &amp;lt; 0.001). Spindle staining revealed a similar number of normal spindles between the two groups (71.4% and 82.6% respectively, p = 0.138). Calcium release was significantly lower in IVG oocytes (1.6) vs controls (5.7) (p &amp;lt; 0.001), as well as mitochondrial membrane potential ((0.9) vs (2.2), p &amp;lt; 0.001). These data implicate a cytoplasmic inferiority in IVG oocytes. Following parthenogenetic activation, 2-cell (59.4%) and blastocyst rate (36.3%) in IVG group was significantly lower than control (89.4% and 88.2% respectively, p &amp;lt; 0.001). For this reason, we performed ST, using controls as cytoplasmic recipients for IVG spindles. The 2-cell rate significantly increased to 100% (p &amp;lt; 0.001) in ST oocytes, reaching 100% blastocyst formation. Next, to create bi-paternal embryos, we performed IVF. From the IVG group, 2-cell (40%) and blastocyst (0%) rates were significantly lower than control (94.4% and 83.3%, p &amp;lt; 0.001). Embryo development was restored following PNT (98% 2-cell and 86% blastocyst rate, p &amp;lt; 0.001). Genetic analysis of PNT embryos revealed that 5/6 were chromosomally normal, similar to controls (8/10). Embryo transfer of PNT and control embryos is ongoing. Limitations, reasons for caution Both ST and PNT are promising technologies to overcome poor embryonic development of IVG oocytes, but the benefit for human IVG oocytes remains to be investigated, along with the safety of the technique. Wider implications of the findings Our results demonstrate that ST and PNT have the potential to restore embryonic developmental competence of IVG oocytes, without increasing chromosomal abnormalities. This technology could be investigated in the future, as a mean to overcome poor quality of IVG oocytes in human. Trial registration number Not applicable

P-392 Controlled ovarian hyperstimulation applied before unilateral oophorectomy improves fertility preservation in cancer patients

Abstract Study question Can ovarian tissue cryopreservation (OTC) be performed after controlled ovarian hyperstimulation (COH)? Summary answer Unilateral oophorectomy after transvaginal oocyte retrieval is feasible on stimulated ovaries during one surgical step. What is known already In the fertility preservation (FP) field, the timeframe between patient referral and start of curative treatment is limited. Combining oocyte pick-up with ovarian tissue (OT) extraction has been reported to improve FP but COH applied before OT extraction is not currently recommended. Study design, size, duration This retrospective cohort-controlled study involved 58 patients who underwent oocyte cryopreservation immediately followed by OTC between September 2009 and November 2021. The exclusion criteria were a delay between oocyte retrieval and OTC of greater than 24 hours (n = 5) and in vitro maturation (IVM) of oocytes obtained ex-vivo in the ovarian cortex (n = 2). This FP strategy was performed either after COH (stimulated group, n = 18) or after IVM (unstimulated group, n = 33). Participants/materials, setting, methods Oocyte retrieval followed by OT extraction on the same day was performed either without previous stimulation or after COH. Adverse effects of surgery and ovarian stimulation, mature oocyte yield and pathology findings of fresh OT were retrospectively analysed. Thawed OTs were analysed prospectively, for vascularisation and apoptosis using immunohistochemistry, when patient consent was obtained. Main results and the role of chance No surgical complication occurred after OTC surgery in either group. In particular, no severe bleeding was associated with COH. The number of mature oocytes obtained increased after COH (8.5 [5.3–12.0] MII oocytes) compared to the unstimulated group (2.0 [1.0–5.3] MII oocytes, p &amp;lt; 0.001). Neither ovarian follicle density nor cell integrity was affected by COH. Fresh OT analysis showed congestion in half of the stimulated OT which was higher than in the unstimulated OT (3.1%, p &amp;lt; 0.001). COH also increased haemorrhagic suffusion (COH+OTC: 66.7%; IVM+OTC: 18.8%, p=0.002) and oedema (COH+OTC: 55.6%; IVM+OTC: 9.4%, p &amp;lt; 0.001). After thawing, the pathological findings were similar between both groups. No statistical difference in the number of blood vessels was observed between the groups. The oocyte apoptotic rate in thawed OT was not statistically different between the groups (ratio of positive cleaved caspase-3 staining oocytes/total number of oocytes equal to median 0.50 [0.33-0.85] and 0.45 [0.23-0.58] in unstimulated and stimulated groups respectively, p = 0.720). Limitations, reasons for caution The study reports FP from a small number of women following OTC. Follicle density and other pathology findings are an estimate only. Wider implications of the findings This approach could be proposed to post pubertal patients when the number of mature oocytes expected is low or when the risk of residual pathology is high. The reduction of surgical steps for cancer patients also has positive implications for introducing this approach into clinical practice. Trial registration number not applicable

Primordial follicles remaining in young cancer survivors who received chemotherapy.

Ovarian tissue cryopreservation (OTC) is performed for fertility preservation in cancer patients undergoing chemotherapy. Although anti-Müllerian hormone is used as a marker for ovarian reserve, serum levels do not always correlate with the number of follicles. Additionally, the follicle development stage most affected by chemotherapy is unclear. We examined the association between serum anti-Müllerian hormone levels and the number of remaining primordial follicles after chemotherapy, as well as which follicle stage is most affected by chemotherapy before ovarian cryopreservation. Thirty-three patients who underwent OTC were divided into the chemotherapy (n = 22) and non-chemotherapy (n = 11) groups; their ovarian tissues underwent histological examination. Pathological ovarian damage induced by chemotherapy was assessed. Ovarian volumes were estimated from weights. We compared the number of follicles at each developmental stage as a percentage of primordial follicles between the groups. The relationship between serum anti-Müllerian hormone level and primordial follicle density was analyzed. The chemotherapy group had a significantly lower serum anti-Müllerian hormone level, ovarian volume, and density of developing follicles than the non-chemotherapy group. Serum anti-Müllerian hormone levels correlated with primordial follicle density only in the non-chemotherapy group. The chemotherapy group had significantly lower numbers of primary and secondary follicles. Chemotherapy induces ovarian damage and follicle loss. However, serum anti-Müllerian hormone level does not always reflect the number of primordial follicles after chemotherapy, and chemotherapy more significantly affects primary and secondary follicles than primordial follicles. Many primordial follicles remain in the ovary after chemotherapy, supporting OTC for fertility preservation.

Differences in oncofertility beliefs, knowledge, and practice between medical oncologists and advanced practice providers: Identifying quality improvement targets.

e18747 Background: Despite the deleterious effects of systemic cancer treatment on fertility, many young adult cancer patients do not receive fertility preservation. Historically, oncofertility was discussed by the medical oncologist (MO), but an increasing advanced practice provider (APP) oncology workforce provides opportunities for quality improvement (QI) in oncofertility care. To identify levers for QI interventions, we explored how fertility beliefs, knowledge, and practice of MOs differ from APPs. Methods: MOs and APPs working in inpatient, outpatient, academic and community clinical settings were identified from providers at The Jonsson Comprehensive Cancer Center (JCCC). Participants completed an online survey prior to a fertility preservation seminar. Survey questions queried beliefs about fertility preservation, knowledge about guideline recommendations, and individual fertility practices in the 3 months prior to survey completion. Responses were collected anonymously through a HIPAA-compliant web platform. Pearson chi-squared and two-sample T tests were used for statistical comparisons between MOs and APPs using STATA v15.1. This study received exempt status from the University of California Los Angeles (UCLA) Institutional Review Board. Results: 32 (52.5%) APPs and 29 (47.5%) MOs completed the survey. APPs were younger than MOs (28% vs. 14% were 30-39 years, p = 0.072) and more frequently female (91% vs. 38%, p &lt; 0.001). Practice specialties varied equally between both groups and they had similar distribution of post-training oncology experience. Participants saw an average of 6.0 (APP) and 5.7 (MO) new cancer patients of reproductive age per month. While APPs and MOs reported concern about the effects of cancer treatment on fertility, APPs were more likely to agree with the statement “Offering fertility preservation to patients before cancer therapy compromises their oncological treatment” than MOs (44% vs. 31%, p = 0.047). APPs reported less familiarity with fertility preservation guidelines (scale 0-10, mean 4.3 vs. 5.8, p = 0.013) and MOs were more comfortable discussing specific fertility preservation techniques. There were no significant differences in referral practices. In the 3 months prior to survey, MOs reported having fertility discussions more frequently than APPs (52% vs 28%, p = 0.047) and more regularly had discussions before treatment initiation (97% vs. 78%, p = 0.033). Conclusions: Improving oncofertility care for young cancer patients is an important quality metric. This exploratory study demonstrated significant differences in beliefs, knowledge, and practice between MOs and APPs regarding fertility preservation for cancer patients. These results will shape our future QI initiatives, which will target system, practice, and education with a specific focus on non-MO providers.

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).