Fertility Preservation In Women Research Articles

The role of Letrozole in IVF treatment: new remedy or old mirage?

Aromatase inhibitors, particularly letrozole, are now established as first-line ovulation induction agents, offering an effective ovarian stimulation strategy to enhance outcomes of intrauterine insemination. In recent years, they have also emerged as potentially valuable adjuvants to gonadotropin ovarian stimulation for IVF, particularly in fertility preservation in women with estrogen-responsive cancers. Their primary mechanism of action is to reduce circulating estrogen levels by inhibiting androgen aromatization. Recent studies have provided evidence that this property may confer therapeutic advantages in other patients undergoing IVF. In this article, evidence supporting the role of adjuvant letrozole in poor responders, as a moderator of OHSS symptoms, and an agent for improving the luteal phase after ovarian stimulation is reviewed. The use of letrozole for endometrial preparation in the frozen-thawed embryo transfer cycle is also considered.

In vitro maturation of oocytes: what is already known?

Assisted reproductive technologies (ARTs) involve the laboratory manipulation of gametes and embryos to help couples with fertility problems become pregnant. One of these procedures controlled ovarian stimulation uses pharmacological agents to induce ovarian and follicular maturation in vivo. Despite the effectiveness in achieving pregnancy and live births, some patients may have complications due to over-response to gonadotropins and develop ovarian hyperstimulation syndrome (OHSS). In vitro maturation of oocytes (IVM) has emerged as a technique to reduce the risk of OHSS, particularly in women with polycystic ovary syndrome (PCOS), and for fertility preservation in women undergoing oncological treatment. Although there are some limitations, primarily due to oocyte quality, recent advances have improved pregnancy success rates and neonatal and infant outcomes. Different terms have been coined to describe variations of IVM, and the technique has evolved with the introduction of hormones to optimize results. This review we provide a comprehensive overview of IVM and its reproductive outcomes during ARTs.

Planned Immediate Chemotherapy and Cryopreservation of Oocytes or Embryos for Fertility Preservation in Women with Malignancies.

Purpose: Oocyte and embryo cryopreservation before gonadotoxic treatment are established methods to increase the likelihood of live births. Although several sociodemographic factors were found to be associated with undergoing fertility preservation (FP) treatment, clinical characteristics such as planned immediate chemotherapy were not fully investigated. We aimed to investigate whether the planned immediate chemotherapy is related to the decision to undergo oocyte/embryo cryopreservation for FP with adjustment for other clinical characteristics. Methods: This institutional cohort study included 491 premenopausal women aged 19 years or older who visited the FP clinic at a tertiary medical center between 2006 and 2019. The primary outcome was whether the participants underwent oocyte/embryo cryopreservation. We evaluated the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of undergoing oocyte/embryo cryopreservation according to whether immediate chemotherapy was planned using univariable and multivariable logistic regression. Results: Women scheduled for immediate chemotherapy were much less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.46, 95% CI 0.27-0.76) in univariable logistic regression analysis. After adjustment for covariates such as marital status, type of malignancies, and calendar year period, women scheduled for immediate chemotherapy were still less likely to undergo oocyte/embryo cryopreservation than women not scheduled for immediate chemotherapy (OR = 0.31, 95% CI: 0.17-0.56). The association was not different according to the type of malignancies (p for interaction = 0.13). Regarding breast cancer, the OR for undergoing oocyte/embryo cryopreservation in women scheduled for immediate chemotherapy was robust compared with those not planned for immediate chemotherapy (OR = 0.25, 95% CI: 0.12-0.53). Conclusion: The present study demonstrated that planned immediate chemotherapy was negatively associated with undergoing oocyte/embryo cryopreservation. This information can be helpful for FP counseling.

Transrectal oocyte retrieval for fertility preservation in virginal women

Research QuestionFertility preservation faces barriers due to sociocultural and religious factors in some countries for nulliparous women who are virgins. Transrectal oocyte retrieval is an alternative technique which can address this by circumventing sensitivities around pelvic procedures in such women who require to have oocyte cryopreservation for medical or social reasons. The study aims to evaluate safety and efficacy of Transrectal oocyte retrieval (TROR) procedure for fertility preservation in these women. DesignA retrospective single centre study of 105 nulliparous women from five satellites of Fakih IVF in the United Arab Emirates, who underwent TROR for oocyte cryopreservation. Extensive bowel preparation and rectal cleansing was performed prior to oocyte retrieval. Outcome and safety data were collected on patient characteristics, stimulation protocols, oocyte yield in relation to age, AMH, number of follicles, and BMI. ResultsThis study evaluated 105 patients who underwent 152 cycles of ovarian stimulation and TROR. The most common indication was social fertility preservation. Correlation with patient characteristics included age, and AMH were performed. AMH showed a statically significant positive correlation with number of oocytes (p≤0.003). No intraoperative or postoperative complications were observed. ConclusionOur study demonstrated that TROR is Our study demonstrated that TROR is an alternative and clinically-effective oocyte harvesting procedure in ART, producing good results in terms of oocyte yield, with no complications and good safety profile. Although Transvaginal oocyte retrieval remains the gold standard treatment, for virginal women where transvaginal oocyte retrieval is not an option, TROR is safe and effective.

Oncofertility and Fertility Preservation for Women with Gynecological Malignancies: Where Do We Stand Today?

Oncofertility is a growing medical and research field that includes two main areas: oncology and reproductive medicine. Nowadays, the percentage of patients surviving cancer has exponentially increased, leading to the need for intervention for fertility preservation in both men and women. Specifically, gynecological malignancies in women pose an additional layer of complexity due to the reproductive organs being affected. In the present review, we report fertility preservation options with a cancer- and stage-specific focus. We explore the drawbacks and the necessity for planning fertility preservation applications during emergency statuses (i.e., the COVID-19 pandemic) and comment on the importance of repro-counseling for multifaceted patients during their oncological and reproductive journey.

P-358 Fertility preservation outcome in patients with onco-hematological malignancies versus solid tumor neoplasms

Abstract Study question Do women diagnosed with onco-hematological malignancies exhibit poorer response to ovarian stimulation in comparison to those with localized neoplasms? Summary answer There are no significant differences between women undergoing fertility preservation for onco-hematological malignancies compared to those with solid tumor malignancies. What is known already Oocyte cryopreservation is now considered the first choice for fertility preservation in post-pubertal women scheduled for gonadotoxic anticancer treatments. Patients with onco-hematological diseases, such as leukemia or lymphoma, encounter unique challenges due to their aggressiveness and multi-organ nature, potentially impacting ovarian function. Conversely, patients with solid malignancies may experience more favorable outcomes, as the impact on their reproductive function is likely less severe. However, comparative data on oocyte cryopreservation outcomes in both groups remain limited, hence further research is essential to guide personalized fertility preservation counselling. Study design, size, duration This is a single center case-control retrospective study that included data collected from 142 patients who underwent oocyte cryopreservation in our center between 2013 to 2023. Laboratory exams, ovarian stimulation and oocyte retrieval were all performed in our center. Participants/materials, setting, methods The main group of patients (or group 1) comprised 71 women with onco-hematological malignancies such as leukemia and lymphoma. Patients from group 1 were matched for age and study period in a 1:1 ratio with solid malignancies (group 2), such as breast cancer. Gynecological tumors were excluded. Significance was considered with a p < 0.05. Data are reported as median [interquartile range - IQR] or number (percentage). Main results and the role of chance In both groups, the mean age at oocyte cryopreservation was 30 years [25-34]. Only a minority of patients were undergoing estroprogestin therapy (10% in group 1 vs. 19% in group 2) (p=ns). Menstrual cycles were found to be regular in 88% and 90% of patients respectively (p=ns). Stimulation protocols were also comparable: 48% and 55% underwent GnRH antagonist, and the remaining underwent progestin-primed ovarian stimulation (p=ns). Duration of stimulation and total dose of gonadotropins did not differ between the two groups. Ovarian stimulation was interrupted due to inadequate response in two patients in the onco-hematological group and one in the control group (p=ns). At oocyte retrieval, the number of oocytes retrieved was 12 [7 - 18] and 15 [7-20] respectively (p=ns), and the number of cryopreserved oocytes was 10 [6-15] and 13 [7-15], respectively (p=ns). This result aligns with the antral follicle counts (AFC) detected before ovarian stimulation: 18 [12 - 24] vs. 20 [12 - 26], respectively (p=ns). However, a notable difference was found in anti-Mullerian hormone (AMH) levels, being 1.96 ng/mL [1.14 - 3.10] in onco-hematological patients and 3.11 ng/ml [1.52 - 4.52] in control patients (p = 0.01). Limitations, reasons for caution This is a retrospective, monocentric study with patients selected from a 10-year period. Wider implications of the findings When planning fertility preservation in women with systemic diseases like cancer, relying solely on AMH levels to estimate ovarian response to stimulation may be limited. In this scenario, AFC proves more reliable. Further evidence is needed to understand the clinical meaning of the lower AMH in onco-hematological cancer patients. Trial registration number NA

Preservation of ovarian function using human pluripotent stem cell-derived mesenchymal progenitor cells.

Ovarian reserve diminishes with age, and older women experience a corresponding shift in sex hormone levels. These changes contribute to an age-dependent decrease in fertility and a decline in overall health. Furthermore, while survival rates following cancer treatment have improved for young female patients, a reduction in ovarian function due to the side effects of such treatments can be difficult to avoid. To date, no effective therapy has been recommended to preserve ovarian health in these patients. Mesenchymal progenitor cells (MPCs) are considered a promising option for cell therapy aimed at maintaining fertility and fecundity. Although MPCs derived from human adult tissues are recognized for their various protective effects against ovarian senescence, they are limited in quantity. Consequently, human pluripotent stem cell-derived MPCs (hPSC-MPCs), which exhibit high proliferative capacity and retain genetic stability during growth, have been utilized to delay reproductive aging. This review highlights the impact of hPSC-MPCs on preserving the functionality of damaged ovaries in female mouse models subjected to chemotherapy and natural aging. It also proposes their potential as a valuable cell source for fertility preservation in women with a variety of diseases.

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.

First pregnancy and live birth from ex vivo-retrieved metaphase II oocytes from a woman with bilateral ovarian carcinoma: a case report

ObjectiveTo report pregnancy and live birth resulting from intracytoplasmic sperm injection of ex vivo retrieved mature oocytes from a woman with bilateral ovarian carcinoma. DesignCase report. Subject(s)A 34-year-old nulliparous woman with bilateral ovarian tumor, with a risk of malignancy at 96.1% according to IOTA-ADNEX, who desired fertility preservation before definitive surgical treatment. Intervention(s)Cryopreservation of ex vivo retrieved mature (MII) oocytes followed by fertilization with donor sperm, and embryo transfer to a gestational carrier. Main outcome measure(s)Fertility preservation. ResultsAfter controlled ovarian stimulation, 12 MII oocytes were retrieved from oophorectomized specimens, and vitrified. ICSI with donor sperm was performed in remission, resulting in 9 cleavage-stage embryos, two of which were transferred to a gestational carrier, resulting in a normal healthy singleton pregnancy, and the live birth of a healthy baby. Conclusion(s): Ex vivo oocyte retrieval after oophorectomy may be a safe alternative to standard oocyte retrieval for fertility preservation in women with ovarian malignancies.

Фототераностика тяжелых дисплазий и преинвазивного рака шейки матки

Due to the high prevalence of pre-cancerous cervical diseases and cervical cancer, the search, pathogenetic reasoning and evaluation of the efficacy of new approaches to the diagnosis and treatment of these pathologies, including those aimed at fertility preservation, are extremely relevant. Objective. To study the clinical efficacy and safety of phototheranostics as a method of diagnosis and treatment of severe dysplasia and pre-invasive cervical cancer. Patients and methods. An open-label, retrospective-prospective, randomized, comparative, clinical trial involving 94 reproductive-aged patients with morphologically confirmed severe cervical intraepithelial neoplasia (CIN) and pre-invasive cervical cancer was conducted. All patients were divided into two groups: group 1 (comparison) included 49 patients who underwent cervical conization with curettage of the remaining cervical canal; group 2 (study) included 45 patients who underwent phototheranostics: photodynamic therapy (PDT) with simultaneous laser-induced fluorescence excitation. Results. After the first course of phototheranostics, most women in the study group had normal cytological results, which were observed 6, 9, and 12 months after treatment. In these periods, all patients who underwent phototheranostics had a normal colposcopic picture, while in the comparison group, some patients showed signs of cervical lesions. Morphological confirmation of the complete therapeutic effect was considered to be elimination of human papillomavirus (HPV) and normalization of the proliferative activity of the epithelial layer (assessed by the levels of Ki-67 and phosphohistone markers) during phototheranostics. Conclusion. The study demonstrated the high clinical efficacy of phototheranostics in the treatment of CIN and pre-invasive cervical cancer: 85–88% of women achieved the desired therapeutic effect after the first session of phototheranostics, and after the second session, all patients in the study group had complete regression of cervical mucosal lesions. In the study group, higher pregnancy rates and favourable outcomes in patients planning pregnancy confirmed that the use of PDT contributes to fertility preservation in women treated for CIN and pre-invasive cervical cancer, which is associated with the preservation of anatomo-functional characteristics of the cervix when using phototheranostics. Key words: PDT, HPV, photodynamic therapy, fluorescence diagnosis, cervical dysplasia, photosensitizers, pre-invasive cervical cancer, phototheranostics, pregnancy after PDT

Pharmacological methods for ovarian function and fertility preservation in women with cancer: A literature review.

Oncofertility is an extremely significant topic that is increasingly being discussed owing to increased evidence indicating that fertility preservation does not affect the treatment outcomes of patients with cancer but significantly contributes to preserving life quality. The effect of chemotherapy can range from minimal effects to complete ovarian atrophy. Limited data are available on the effects of monoclonal antibodies and targeted therapies on the ovaries and fertility. Temporary ovarian suppression by administering a gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy decreases the gonadotoxic effect of chemotherapy, thereby diminishing the chance of developing premature ovarian insufficiency (POI). At present, the concomitant administration of GnRH analogs during chemotherapy is the only accepted pharmacological method for preserving ovarian function. Notably, most randomized studies on the effectiveness of luteinizing hormone-releasing hormone agonists during chemotherapy in preventing POI have been conducted in women with breast cancer, with a considerably small number of studies on patients with hematological malignancies. Furthermore, most randomized controlled trials on breast cancer have revealed a decrease in treatment-induced POI risk, regardless of the hormone receptor status. In addition, studies on hematological malignancies have yielded negative results; nevertheless, the findings must be interpreted with caution owing to numerous limitations. Current guidelines from the American Society of Clinical Oncology and ESMO Clinical Practice Guidelines recommend sperm, oocyte, and embryo cryopreservation as a standard practice and only offering GnRHa to patients when proven fertility preservation methods are not feasible. In this manuscript, we present a comprehensive literature overview on the application of ovarian suppression with GnRHa during chemotherapy in patients with cancer by addressing preclinical and clinical data, as well as future perspectives in this field that upcoming research should focus on.

Reproductive health in Turner's syndrome: from puberty to pregnancy.

Turner syndrome (TS) is a genetic pathology that affects about 1/2500 newborn females. Turner's syndrome is characterized by highly variable genetic anomalies that consist in a partial or complete deletion of the X sexual chromosome; it can be present as a monosomy or as a mosaicism with two o three different cellular lines. 50% of the patients with Turner's syndrome has a 45 XO karyotype while the remaining cases have karyotypes with mosaicism or X isochromosome or with partial or whole Y chromosome. This pathology is characterized by multiple anomalies that involve physical and cognitive development and in particular endocrine, cardiovascular, reproductive, auditive and visual systems. Integrity of the X chromosome in essential for fertility. In TS is accelerated germ cells apoptosis. About 30% of TS girls have some pubertal development, 10-20% undergo menarche and 2-8% go through spontaneous pregnancy. Women with TS should be informed about the risk of premature menopause and should be referred, if possible, to a specialist evaluation with a doctor expert in assisted reproductive techniques. In adolescents and in adults, Premature Ovarian Insufficiency (POI) can be evaluated clinically and biochemically with the classic combination of amenorrhea and elevated FSH concentrations (hypergonadotropic hypogonadism). However, in postpubertal adolescents and adult women, reproductive hormones may remain within the normal range before POI is clinically evident, despite significant depletion of the ovarian reserve. Today, reproductive medicine offers the opportunity of fertility preservation in women with premature ovarian insufficiency (POI). Two techniques have been suggested such as ovarian cortex cryopreservation and oocytes cryopreservation.

Breast Cancer and Fertility Preservation in Young Female Patients: A Systematic Review of the Literature.

Breast cancer affects almost 1.5 million women worldwide below the age of 45 years each year. Many of these women will be advised to undergo adjuvant chemotherapy to minimize the risk of death or recurrence of the tumor. For these patients, chemotherapy is a known cause of infertility, as it can damage primordial follicles, which can lead to early menopause or premature ovarian insufficiency. This systematic review aims to synthesize the current evidence of the most suitable treatments for fertility preservation. This review was performed following the PRISMA guidelines. The authors conducted an extensive search from the last 15 years. Relevant studies were pursued in PubMed, Embase, and the Cochrane Library up until 31 July 2023. A total of seven eligible studies were identified. From the reviewed literature, ovarian suppression with gonadotropin-releasing hormone agonists showed promising results in preserving fertility for breast cancer patients undergoing chemotherapy. Additionally, oocyte and embryo cryopreservation demonstrated successful outcomes, with embryo cryopreservation being the most effective option. Notably, the slow-freezing and vitrification methods were both effective in preserving embryos, with vitrification showing superior results in clinical-assisted reproductive technologies. Ovarian tissue cryopreservation emerged as a viable option for prepubertal girls and those unable to undergo conventional ovarian stimulation. The potential of in vitro maturation (IVM) as an alternative method presents a promising avenue for future fertility preservation research. The most suitable treatments for fertility preservation in young patients is the temporary suppression with luteinizing hormone-releasing analogs, while the patient undergoes chemotherapy and cryopreservation. For cryopreservation, the physicians might deem it necessary to either cryopreserve ovarian tissue taken from the patient before any treatment or cryopreserve embryos/oocytes. Cryopreservation of oocytes and/or embryos is the most effective solution for fertility preservation in women of reproductive age, who have a sufficient ovarian reserve and are diagnosed with breast cancer, regardless of the histological type of the tumor. Because approximately 50% of young breast cancer patients are interested in becoming pregnant right after completion of therapy, the evolution and development of fertility preservation techniques promise to be very exciting.

Redox reactions in vitrified-warmed ovary

Ovary vitrification is a way for the preservation of fertility in women undergoing chemotherapy and for protecting the valuable or the endangered species. However, cryopreservation of complex tissues, which are composed of different cells and materials, encountered various challenges including oxidative stress damage. This study aimed to evaluate some oxidative stress indices in the vitrified bovine ovaries. The pieces of the bovine ovarian cortex (1 × 1 × 1 mm3) were vitrified with final concentrations of ethylene glycol (25%) and glycerol (25%) and 0.5 M sucrose and then, after 48 h, were warmed with descending concentrations (0.5, 0.25, and 0.125 M) of sucrose. The ovaries were processed and some biochemical indicators of oxidative stresses were assayed. Total antioxidant capacity had a 45% decrease after vitrification (P<.0001). This reduction was associated with a 4 times increase in malondialdehyde (P=.0002) and a 53% decrease in superoxide dismutase (P=.0081). The levels of protein carbonyl in vitrified-warmed ovaries were less than in fresh ovaries (P=.0325). Regression analysis showed that the components of oxidative stress indices in vitrified tissues are different from those of fresh tissues. An extensive alteration was seen in oxidant/antioxidant balance during vitrification.

What are the most common controversial clinical issues in fertility preservation? A content analysis of a collaborative professional online consultation group

Research questionClinicians involved in fertility preservation (FP) are often required to make prompt and consequential decisions despite the absence of evidence-based data. We established a collaborative professional online consultation group for fertility preservation issues. We sought to determine the main controversial clinical issues in FP as raised by participants of this group.DesignContent analysis of a dedicated community of practice interacting via a messaging application (WhatsApp) and a survey of group participants.ResultsBetween January 2019 and July 2022, group members posed 39 clinical questions which were discussed and debated by the group. Common themes included management of oncofertility cases (33%), potential gonadotoxicity of various therapies (23%), fertility preservation in women and girls with premature ovarian insufficiency (POI) (18%), and technical aspects of ovarian tissue cryopreservation (10%). All but one query received prompt response (mean time for first response for 95% of queries 7.1 ± 9.0 min) from a mean of 5.4 ± 3.2 members.An anonymous online survey of group members was conducted during August 2022 (n = 31, response rate 94%). The majority of respondents stated they gained knowledge and assistance in clinical decision making from participation in the discussion group (90% and 58% of respondents, respectively).ConclusionsManagement of clinical oncofertility cases, potential gonadotoxic effect of therapeutics and fertility preservation in women and girls with POI were the most common controversial issues in our fertility preservation community of practice. Intra-professional collaborative communication via a messaging application can aid in clinical management of fertility preservation and augment clinician’s knowledge.

Fertility Preservation as an Option for Women with Genetic Disorders: Insights from a SWOT Analysis on Elective Oocyte Freezing and Preimplantation Genetic Testing.

This paper uses a SWOT (strengths, weaknesses, opportunities, and threats) analysis to overview the option of fertility preservation in women with genetic diseases, who would later use preimplantation genetic testing for monogenic disorders, in order to not transmit their condition. Strengths associated with elective oocyte freezing are ethical considerations, overall maternal and fetal safety, and effectiveness, if performed at <35 years of age. Weaknesses are related to costs and rare but present (<1-3%) risks of maternal complications. Counselling on fertility management aimed at preventing infertility offers a valuable opportunity, the same as it has been in oncological patients' care. The potentially high percentage of women with genetic conditions who would return to use their frozen oocytes also represents an opportunity together with the minimization of the need for egg donation, which has higher obstetrical risks compared to the use of autologous oocytes. Finally, a threat is represented by the potential psychological distress to young women who could never attempt to become pregnant through preimplantation genetic testing, or do it before any decline in their fertility. Potential unknown future long-term health risks for children conceived after egg vitrification/thawing are also a threat, but current knowledge is reassuring. Altogether, early counselling on the option of fertility preservation should thus be incorporated into standard care of all patients with any genetic condition.

Fertility Preservation in Women with Endometriosis.

Several mechanisms have been implicated in the pathogenesis of endometriosis-related infertility. For patients considering surgery, the risk of iatrogenic injury is among the most important factors in the context of fertility preservation, along with age and individual reproductive goals. In the case of endometrioma excision, evidence overwhelmingly demonstrates the negative impact of surgery on ovarian reserve, with significant reductions in antimullerian hormone (up to 30% in unilateral versus up to 44% in bilateral endometriomas). The surgical endometriosis patient should be thoroughly counseled regarding fertility preservation and discussion should include tissue, embryo, and oocyte cryopreservation options. For the latter, data support cryopreservation of 10-15 oocytes in women ≤35 years and over 20 for those >35 years for a realistic chance to achieve one or more live births. When performing surgical interventions for endometriosis, reproductive surgeons should employ fertility-conserving surgical methods to reduce the likelihood of postoperative iatrogenic diminished ovarian reserve.

P-421 Return rates and outcome of fertility preservation in women with cervical cancer.

Abstract Study question What are the return rates and reproductive outcome after fertility preservation (FP) in women with cervical cancer (CC)? Summary answer Return rates after FP in women with CC seem to be comparable with those after FP for other indications. What is known already Cervical cancer is the fourth most common cancer among women. Approximately 42% of the affected women are under the age of 45, and many of them wish to preserve fertility at the time of diagnosis. Fertility sparing treatment modalities and FP with cryopreservation of oocytes, embryos or/and ovarian tissue can be offered for this purpose to carefully selected patients. These treatments are offered at Swedish academic centers within the health insurance coverage available to all citizens. To date, data on return rates, reproductive outcome and survival in women with cervical cancer undergoing FP are scarce. Study design, size, duration Prospective, single center study aiming to report long-term outcomes in women with CC who have versus have not undergone FP at Karolinska University Hospital between January 1st 1999 and September 30th 2018. Participants/materials, setting, methods During the study period, 74 women with CC received FP counseling at Karolinska University Hospital, and 52 of them women proceeded to FP. Data on return rates, reproductive outcomes and overall survival were extracted using the clinical registries. Main results and the role of chance By January 15th, 2023, 22 of 52 women with FP returned for a new fertility counselling or treatment, mean time between FP and return was 4 years (1-7 years). Among women with cryopreserved ovarian tissue (n = 40), 17 have been in contact with the clinic with fertility wish, 3 of them had re-transplantation of the tissue, but none of them achieved oocyte retrieval yet. Additionally, one woman is planned for re-transplantation in February 2023, and one woman is awaiting the decision. In two cases the decision not to re-transplant ovarian tissue was based on absence of endometrial growth following attempts of hormonal substitutive therapy. Among women with cryopreserved oocytes (n = 5), 1 returned for thawing but no pregnancy has been achieved. Among women with cryopreserved embryos (n = 5), 3 returned during follow-up, 2 proceeded to thawing and transfer, 1 got pregnant and gave birth to a child. Of two women with combination of oocytes and ovarian tissue cryopreserved, one returned for fertility treatment, but no pregnancy has been achieved after thawing and re-transplantation. Eight women died during follow-up because of recurrence of their cancer, 4 of 22 in the group without FP and 4 of 52 in the group with FP. Limitations, reasons for caution This study provides much needed data on real-world outcome in women with FP indicated by diagnosis of CC, but it has the limitations related to its descriptive character. The use of gestational carriers is not permitted in Sweden and FP program may differ from those in other countries. Wider implications of the findings The study results provide much needed data on real-world reproductive and oncologic outcome following FP in women with CC. Trial registration number NTC04602962

P-419 Oocytes quality in random start protocols for fertility preservation: insights from follicular steroidogenesis.

Abstract Study question Is follicular steroidogenesis impaired in women undergoing random start protocols for fertility preservation? Summary answer The phase of menstrual cycle at initiation of ovarian stimulation does not influence the endocrine microenvironment surrounding oocytes. What is known already Cryopreservation of oocytes is the gold standard for fertility preservation in women with cancer. Random start protocols have been introduced for oocytes cryopreservation in these patients to shorten the duration of ovarian stimulation. However, albeit generally reassuring, available evidence is still insufficient to rule out a sub-optimal cycle outcome of random start protocols. Study design, size, duration The present study was conducted to provide evidence on the validity of random start protocols by exploring the quality of ovarian steroidogenesis. The primary outcome was comparing levels of steroids in the follicular fluid between women initiating the random start protocol in the luteal phase and those initiating in the follicular phase (considered as controls since equivalent to the conventional protocols). We excluded those requiring concomitant letrozole assumption. Participants/materials, setting, methods Seventy-one women with cancer were prospectively recruited during a 24-month period. Thirty-three initiated in luteal phase while 38 in follicular phase. All women were stimulated with recombinant FSH and GnRH antagonists. At the time of oocytes retrieval, follicular fluids were pooled, and a sample was frozen at -80 °C. All samples were assayed concomitantly after thawing, by liquid chromatography tandem mass spectrometry. The concentration of 15 different steroid hormones was determined. Main results and the role of chance Baseline characteristics of the two groups were similar. No differences emerged in anamnestic data and ovarian reserve variables. Cycle outcome did not also differ, the two study groups being similar in terms of total dose of gonadotropins, duration of stimulation, number of developed follicles and number of oocytes retrieved. The median [interquartile range] number of frozen mature oocytes was 9 [5-14] and 10 [5-21] in women who initiated in the luteal and the follicular phase, respectively (p = 0.42). None of the 15 tested steroid hormones differed. Two subgroup secondary analyses were performed to rule out confounders. First, we excluded women who were on estroprogestins at the time of recruitment (leaving 31 women initiating in the follicular phase and 32 in the luteal phase). Levels of steroids in the follicular fluids were still mainly similar. We observed a significant difference only for androstenedione, levels being higher for women initiating stimulation in the follicular phase. Second, we compared women in the early (up to day 5) and late follicular phase (26 and 12 cases, respectively). Levels of steroids in the follicular fluids did not differ except for cortisone, the concentration being higher in the early follicular phase. Limitations, reasons for caution Our study is not randomized, inevitably exposing our results to confounders. Assessment of intraovarian steroidogenesis is an indirect evidence of oocyte quality. Multiple comparisons were done, exposing our findings to type I errors (such as, in our opinion, the differences that emerged in the secondary analyses). Wider implications of the findings Random start protocols have become the standard of care for fertility preservation in women with cancer in the absence of robust evidence. Our data supports the validity of random start protocols in terms of quality of ovarian response since none of the tested hormones differed. Trial registration number Not applicable

Fertility and fertility preservation in women

Advances in the treatment of cancer and in reproductive medicine make it possible for many patients to start their family planning even after cytotoxic therapy. Depending on the age of the patient, the planned oncological therapy and its urgency, various methods can be used to preserve the fertility of affected women. Presentation of facts about fertility, as well as information about fertility-preserving methods for women, so that they can be discussed with and offered to patients. Presentation and discussion of basic research, clinical data, and expert recommendations on fertility and fertility preservation. Well-established fertility-protective techniques now exist for women that offer arealistic chance of subsequent pregnancy. These include transposition of the gonads prior to radiotherapy, gonadal protection with gonadotropin-releasing hormone (GnRH) analogues and cryopreservation of fertilized and unfertilized oocytes, as well as cryopreservation of ovarian tissue. Fertility-protective techniques are an integral part of oncological treatments for prepubertal girls and patients of reproductive age. The various measures must be discussed individually with the patient as part of amultimodal concept. Prompt and timely collaboration with aspecialized center is essential.