Oocyte Cryopreservation Cycles Research Articles

Follicular challenge test to predict suboptimal response to gonadotropin releasing hormone agonist trigger in elective oocyte cryopreservation cycles

This prospective study aimed to test the ability of follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger, assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program. The study included 91 women that underwent non-medical fertility preservation. On day two to menstrual cycle, blood tests were drawn (basal Estradiol, basal FSH, basal LH, Progesterone) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist (FACT) and arrive for repeated blood workup 10–12 h later in the next morning, followed by a flexible antagonist protocol. LH levels on the morning after ovulation trigger were compared to FACT LH levels. The results demonstrated that LH levels following agonist ovulation trigger below 15IU/L occurred in 1.09% of cycles and were predicted by FACT, r = 0.57, p < 0.001. ROC analysis demonstrated that FACT LH > 42.70 IU/L would predict LH post trigger of more than 30 IU/L with 75% sensitivity and 70% specificity, AUC = 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p < 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the number of frozen oocytes was progesterone levels post agonist trigger (r = 0.746, p < 0.001). We concluded that suboptimal response to agonist trigger, as assessed by post trigger LH levels was a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate LH levels elevation after agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders.

Progestins for pituitary suppression during ovarian stimulation in artificial reproductive technology

Background: Progestins can suppress endogenous luteinizing hormone secretion from the pituitary gland. Progestins can be used orally and are less expensive than gonadotrophin-releasing hormone (GnRH) analogs. However, early endometrial exposure to progestin precludes fresh embryo transfer (ET), but the emergence of vitrification for oocyte cryopreservation cycles allows more opportunities for using progestins for pituitary suppression.&#x0D; Objective: To assess the mechanism of pituitary suppression by progestins, the effectiveness of progestins compared with GnRH analogs, the effect of progestins on oocyte and embryo developmental potential and euploidy status, and the cost-effectiveness of progestin-primed stimulation. &#x0D; Methods: A literature search using the keywords “multiple waves of antral ovarian follicular development, In Vitro Fertilization, Ovarian stimulation ” was performed in the PubMed database.&#x0D; Results: The duration of stimulation, gonadotrophin consumption, and oocyte yield were similar in progestins and GnRH analogs. However, progestins were associated with significantly lower gonadotrophin consumption than their analogs. Overall, live birth and clinical pregnancy rates per ET were similar to those of progestins and GnRH analogs. Studies comparing medroxyprogesterone acetate, dydrogesterone, and micronized progesterone suggest similar ovarian responses and pregnancy outcomes. The euploidy status of embryos and obstetric and neonatal outcomes from progestin-primed cycles are similar to those of embryos from conventional stimulation cycles. Despite the lower cost of progestins than GnRH analogs, the mandatory cryopreservation of all embryos followed by a deferred transfer may increase the cost per live birth with progestins compared with an artificial reproductive technology cycle culminating in a fresh ET.&#x0D; Conclusion: Progestins present an effective option for women who do not contemplate a fresh ET, e.g., fertility preservation, anticipated hyper responders, preimplantation genetic testing, oocyte donors, and double stimulation cycles.

P-396 Modified Flare/GnRH antagonist protocol versus GnRH antagonist protocol in oocyte cryopreservation cycles

Abstract Study question Is there an advantage for modified flare/ GnRH antagonist protocol in comparison to antagonist protocol in oocyte cryopreservation cycles? Summary answer Modified flare/ GnRH antagonist protocol is at least as good as antagonist protocol in oocyte cryopreservation cycles, potentially improving maturity rate in subgroup of patients. What is known already Ultrashort flare GnRH agonist (GnRHa)/GnRH -antagonist protocol offer benefits of stimulatory effect of repeated microdose flare on endogenous FSH and the advantages of GnRH antagonist suppression, including the option to use GnRHa ovulation trigger to avoid ovarian hyperstimulation syndrome. GnRHa ovulation trigger has been associated with suboptimal response that refers to lesser than expected oocyte yield. Our research group previously demonstrated the value of GnRHa follicular challenge test (FACT) in prediction of suboptimal response assessed by post ovulation trigger LH levels and as a dynamic ovarian reserve test (not published yet). Study design, size, duration A retrospective, age- matched, cohort study that included all non-medical oocyte cryopreservation cycles from October 2020 to December 2021. The study group included 110 women that received modified flare/ GnRH antagonist protocol and were matched with 110 women that received antagonist protocol. Participants/materials, setting, methods Women in the modified flare/ GnRH antagonist protocol were administered GnRHa (Decapeptyl 0.2 mg) on day 2 to menstrual cycle followed by flexible antagonist protocol. They were compared to age matched women that received flexible antagonist protocol. In both study groups GnRHa final ovulation trigger was administered. Main results and the role of chance Among 110 women that underwent non-medical fertility preservation with modified Flare/GnRH antagonist protocol, in comparison to 110 women that received antagonist protocol, a reduced dosage of gonadotropins was consumed with more oocytes retrieved (14.63 vs. 13.86) and more mature oocytes cryopreserved (11.32 vs. 10.14), but differences were not significantly different. In a subgroup with more than 6 oocytes retrieved significantly more mature oocytes were cryopreserved in women that received modified flare/antagonist protocol (14.03± 0.90 vs. 11.63± 0.71, p = 0.03) in comparison to women that received antagonist protocol. Limitations, reasons for caution Limitations of our study are its retrospective nature and lack of information on the oocyte’s fertilization competence and pregnancy outcomes. Wider implications of the findings Future studies will further explore the advantages of this protocol in terms of higher oocytes maturity rate, intra cycle prediction of ovarian response and suboptimal response to GnRHa triggering. Trial registration number not applicable

P-268 Artificial intelligence (AI) image analysis outperforms patient age as a surrogate marker for oocyte quality, demonstrating an increased accuracy in predicting blastocyst development

Abstract Study question Can an AI image analysis tool (VIOLET) provide better predictions of oocyte potential than the current standard, patient age, as it relates to blastocyst development? Summary answer While increasing patient age slightly correlates with decreases in blastocyst development, VIOLET provides personalized assessments of individual oocytes correlated to blastocyst development with improved accuracy. What is known already Increasing patient age correlates to decreases in oocyte competency, leading to greater challenges in successful fertility treatment. Clinically, patient age is used to estimate probabilities of success based on national databases. Such as the case in oocyte cryopreservation cycles, considering only age and number of mature oocytes vitrified. However, oocyte quality may vary widely between patients of the same age, and even within each cohort of oocytes. VIOLET is an AI tool that assesses images of mature denuded oocytes to provide an analysis shown to significantly correlate with subsequent blastocyst development and quality, consistently outperforming embryologists in this task. Study design, size, duration This large-scale retrospective study assessed 9,120 mature denuded oocytes retrieved during 2014-2022, representing 1,384 patients between ages 19-49, attending 7 fertility clinics across 5 countries. The VIOLET prediction model is based on image analysis of mature denuded oocytes, without incorporating clinical variables, such as age. Patient age was used to build a separate predictive model of blastocyst development (10,947 training and 3,750 validation samples) to assess the predictive value of age in comparison to VIOLET. Participants/materials, setting, methods Blastocyst development was determined by embryos achieving a Gardner grade by Day5/6 post-ICSI. Blastocyst rates per oocyte cohort were calculated by number of blastocysts divided by total number of mature oocytes retrieved. Various machine learning techniques were trialed to build the predictive model strictly using age; with Random Forest model providing the best-balanced performance. VIOLET and the age model assessed the images and age of 9,120 mature denuded oocytes, respectively, providing predictions of blastocyst development. Main results and the role of chance Blastocyst development was significantly different between patients &amp;lt;35 years old compared to those ≥35 years old [47% vs 42%; p &amp;lt; 0.05 by Two Proportion Z-test]; however, not when the older age group was stratified further. On a patient level, the cohort of oocytes was evaluated by the blastocyst development ratio. Among four age groups (&amp;lt;35, 35-37, 37-40, &amp;gt;40), the blastocyst development ratios per cohort were very similar, with overlapping distributions of 84-94% using Kernel Density estimates. Thus, patient age group does not provide enough information to explain blastocyst development success for an individual oocyte or within an oocyte cohort. In comparison, VIOLET probability is significantly correlated to blastocyst development (p &amp;lt; 0.05; Welch’s Two sample t-test). And blastocyst development rates display a stepwise positive correlation that is significantly different between VIOLET probability quartiles [24% vs 39% vs 47% vs 53%; p &amp;lt; 0.05 by Two Proportion Z-test], providing meaningful information on individual oocytes. Additionally, the predictive model built with age as the only feature had poor ability to predict blastocyst success of an individual oocyte with a limited area-under-the-curve (AUC) of 0.5—unable to separate positive and negative classes. This was outperformed by VIOLET, which displayed an AUC of 0.62 on the same unseen dataset. Limitations, reasons for caution Increasing maternal age causes increased chromosomal abnormalities in oocytes, which translates to lower efficacy with treatment outcomes; therefore, further research to assess VIOLET correlation with PGT-A and implantation outcomes is needed and underway. Wider implications of the findings Patient age correlates with blastocyst development on a general level; however, it does not provide meaningful insights to distinguish rates of blastocyst success on an individual oocyte or oocyte cohort level. VIOLET augments oocyte understanding over the current standard of care, which can be utilized to support personalized clinical decision-making. Trial registration number Not applicable.

P-592 Follicular GnRH agonist challenge test (FACT) to predict suboptimal response to GnRH agonist trigger in oocyte cryopreservation cycles

Abstract Study question Can follicular GnRH agonist administration predict suboptimal response to GnRH agonist trigger assessed by LH levels post ovulation trigger in non-medical oocyte cryopreservation program? Summary answer Follicular agonist challenge test (FACT) can serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist trigger. What is known already Suboptimal response to GnRH agonist ovulation trigger refers to failure to retrieve the expected number of oocytes. It was demonstrated in up to 5.5% of cycles based on relatively low number of studies with heterogenous suboptimal response definitions and prevalence, no clear cut-offs and mainly post - stimulation tools to predict unsuccessful cycle. The most studied variable associated with suboptimal response was LH levels 10-12 hours after ovulation trigger below 12-15IU. Study design, size, duration We prospectively recruited all women that underwent non-medical fertility preservation in our tertiary university affiliated medical center between October 2020 and February 2022 and agreed to participate in the study. The study included 91 women. Participants/materials, setting, methods On day 2 to menstrual cycle, blood tests were drawn (basal Estradiol/E2, basal FSH/FSH2, basal LH/LH2, Progesterone/P2) and ultrasound (US) was performed. On that evening, the women were instructed to inject 0.2 mg GnRH agonist and arrive for repeated blood workup 10-12 hours later at the next morning, followed by a flexible antagonist protocol. On the morning after ovulation trigger blood tests were again taken and LH levels were compared to FACT LH levels. Main results and the role of chance LH levels following agonist ovulation trigger below 15IU occurred in 1.09 % of cycles and were predicted by FACT, r = 0.57, p &amp;lt; 0.001. ROC analysis demonstrated that FACT LH &amp;gt; 42.70 IU would predict LH post trigger of more than 30 IU with 75% sensitivity and 70% specificity, AUC= 0.81. LH levels post trigger also displayed significant positive correlation to basal FSH (r = 0.35, p = 0.002) and basal LH (r = 0.54, p &amp;lt; 0.001). LH levels post ovulation trigger were not associated with total oocytes number or maturity rate. The strongest correlation to the total number of retrieved oocytes and mature oocytes was progesterone level post ovulation trigger (r = 0.74, p &amp;lt; 0.001). Limitations, reasons for caution Limitation of our study include the relatively small sample size designed to detect 5% suboptimal proportion and might have been insufficient to allow identification of very rare suboptimal responses Wider implications of the findings Suboptimal response to agonist trigger, as assessed with post trigger LH levels is a rare event. FACT could serve as an adjunct pre-trigger, intracycle tool to predict adequate response to agonist ovulation trigger. Future studies should focus on optimization of agonist trigger efficacy assessment and prediction, especially in high responders. Trial registration number 0304-20-ASF

P-403 Oocyte usage and disposition outcomes following oocyte cryopreservation

Abstract Study question What is the fate of cryopreserved oocytes? Summary answer Very few people return to use their cryopreserved oocytes in assisted reproduction and while some surplus oocytes are donated for reproduction, the majority are discarded. What is known already The number of oocyte cryopreservation cycles performed around the world dramatically outpaces the number of people who return to use their oocytes in assisted reproduction. This imbalance is leading to the rapid accumulation of oocytes in cryostorage. Previous studies have reported that many people intend to donate their surplus cryopreserved oocytes, and some commentators suggest that this may help relieve donor shortages. However, there have been no reports to date about what actually happens to surplus oocytes following oocyte cryopreservation. Study design, size, duration A retrospective cohort study was performed, analysing the outcomes for cryopreserved oocytes from 2012 - 2022. Participants/materials, setting, methods Data were collected from seven IVF clinics, located in Victoria, Australia. De-identified data were aggregated on the outcomes following oocyte cryopreservation, including duration of cryostorage, assisted reproduction involving thawed oocytes, and disposition outcomes of surplus oocytes. Main results and the role of chance Across the study period, the number of patients with oocytes in storage grew rapidly from 144 in 2012 to 2015 in 2022. Regarding the current status of oocytes in storage, in 2022, 73% of patients had had their oocytes in storage for &amp;lt;5 years; 25% for 5 - 10 years, and 2% for ≥10 years. The majority of oocyte thaw cycles (600/645) involved oocytes frozen for &amp;lt;5 years; of which 47% were frozen for &amp;lt;6 months. Overall, the live birth rate from the total number of oocyte thaw cycles initiated was 12% (78/645), however, this varied depending on the reason oocytes were frozen. In comparison to the number of patients still with oocytes in storage, very few patients relinquished surplus oocytes across the study period (2015 vs 151, respectively). Of the 128 patients whose surplus oocytes were discarded, 32% had had their oocytes stored for &amp;lt;5 years; 32% for 5-10 years, and 36% for &amp;gt;10 years. Among patients who elected to donate their surplus oocytes (n = 23), all but four patients made this decision having had their oocytes in storage for &amp;lt;5 years. Although a legal option in Australia, no oocytes were donated to research over the period analysed. Limitations, reasons for caution Data were collected from one fertility group based in one state of Australia, thus it may not be representative of wider trends seen across other clinics or states/territories. Further, specific state laws govern the management, storage, and use of surplus oocytes, which may influence the reported disposition outcomes. Wider implications of the findings Our findings suggest that cryopreserved oocytes are rarely used or donated, rather they are left in storage, often for long durations. To relieve some of the pressure this may create on cryostorage facilities, more attention is needed to better understand the experience of oocyte disposition and the barriers to donation. Trial registration number not applicable

OVARIAN RESPONSE AND ANTI-MULLERIAN HORMONE IN FERTILITY PRESERVATION VERSUS ELECTIVE OOCYTE CRYOPRESERVATION CYCLES: A SOCIETY FOR ASSISTED REPRODUCTIVE TECHNOLOGY REGISTRY STUDY OF 10,040 CYCLES

The relationship between anti-Mullerian hormone (AMH) and response to controlled ovarian hyperstimulation (COH) is well established, however, it is unknown whether this relationship is preserved in cancer patients. Thus, we investigated the association between ovarian response and AMH for medically indicated fertility preservation (FP) and elective oocyte cryopreservation (OC) cycles.

DOES RACIAL DISPARITY EXIST IN PLANNED OOCYTE CRYOPRESERVATION CYCLES? A SART DATABASE ANALYSIS OF 15,806 CYCLES

To determine if FSH treatment dosage, number of mature oocytes, and treatment duration differ by race/ethnicity in planned oocyte cryopreservation (OC) cycles.

HOW MANY EGGS WILL I GET AND HOW MUCH MEDICATION DO I NEED? A SART DATABASE PREDICTOR MODEL FOR EGG FREEZING

To develop a model for predicting individualized gonadotropin starting dose and estimating number of retrieved mature oocytes in planned oocyte cryopreservation (OC) cycles.

DOES TYPE OF TRIGGER INFLUENCE OOCYTE MATURITY IN PATIENTS UNDERGOING OOCYTE CRYOPRESERVATION, EMBRYO BANKING AND IN VITRO FERTILIZATION CYCLES USING LETROZOLE?

Letrozole is an aromatase inhibitor that is used during oocyte cryopreservation cycles to lower estradiol levels in patients with conditions such as breast cancer, lymphoma, seizures, BRCA mutation carriers and history of venous thromboembolic events (VTE). Many studies have determined that using letrozole has no effect on the number of oocytes retrieved or maturity. The purpose of this study is to determine if the type of trigger affected the percent of mature oocytes retrieved in patients undergoing controlled ovarian stimulation with letrozole.

IMPACT OF THE COVID-19 PANDEMIC ON SOCIAL OOCYTE CRYOPRESERVATION TRENDS

We aimed (1) to quantify the impact of COVID-19 on the number of oocyte cryopreservation cycles performed, and (2) to characterize the demographics of fertility preservation patients both before and during the pandemic.

Reproductive outcomes from ten years of elective oocyte cryopreservation

Research questionTo assess the relationship between the number of oocytes retrieved during elective oocyte cryopreservation (EOC) cycles with various clinical, biochemical, and radiological markers, including age, body mass index (BMI), baseline anti-Müllerian hormone (AMH), antral follicle count (AFC), Oestradiol level (E2) and total number of follicles ≥ 12 mm on the day of trigger. To also report the reproductive outcomes from women who underwent EOC.MethodsA retrospective cohort of 373 women embarking on EOC and autologous oocyte thaw cycles between 2008 and 2018 from a single London clinic in the United Kingdom.Results483 stimulation cycles were undertaken amongst 373 women. The median (range) age at cryopreservation was 38 (26–47) years old. The median numbers of oocytes retrieved per cycle was 8 (0–37) and the median total oocytes cryopreserved per woman was 8 (0–45). BMI, E2 level and number of follicles ≥ 12 mm at trigger were all significant predictors of oocyte yield. Multivariate analysis confirmed there was no significant relationship between AFC or AMH, whilst on univariate analysis statistical significance was proven. Thirty six women returned to use their cryopreserved oocytes, of which there were 41 autologous oocyte thaw cycles undertaken. There were 12 successful livebirths achieved by 11 women. The overall livebirth rate was 26.8% per cycle. No livebirths were achieved in women who underwent EOC ≥ 40 years old, and 82% of all livebirths were achieved in women who had done so between 36 and 39 years old.ConclusionClinical, biochemical and radiological markers can predict oocyte yield in EOC cycles. Reproductive outcomes are more favourable when cryopreservation is performed before the age of 36, with lower success rates of livebirth observed in women aged 40 years and above.

P-657 Administration of an extra Gonadotropin dose on trigger day in patients undergoing elective egg freezing

Abstract Study question Does an extra Gonadotropin (GT) dose on trigger day during a gonadotropin-releasing hormone (GnRH) antagonist cycle for oocyte cryopreservation result in improved cycle outcomes? Summary answer An extra GT dose on trigger day in patients undergoing elective egg freezing is not associated with increased oocyte yield. What is known already The most common controlled ovarian hyperstimulation (COHS) protocol used in elective oocyte cryopreservation cycles is a GnRH antagonist protocol with a GnRH agonist trigger. There is no consensus about the timing of the final gonadotropin dose administration. Some physicians add an extra GT dose during the ovulation trigger day and others advise to receive the last GT dose the day before. The yield of this extra GT dose was not previously evaluated. Study design, size, duration A retrospective cohort study, consisting of cycles of elective oocyte cryopreservation at Hadassah Medical Center from 1.2017 through 5.2021. Patients were divided into 2 groups- women who received their last GT dose a day before the GnRH agonist trigger, and women who received the last GT on the trigger day. Background and gynecologic characteristics, as well as COHS cycle parameters, were compared. The primary outcome was the average number of mature oocytes in each group. Participants/materials, setting, methods Women 30-41 years who were admitted for elective oocyte cryopreservation. Women who were referred due to medical reasons or cycles with a protocol other than GnRH antagonist were excluded. Ovarian stimulation with GT began on the 3rd day of the cycle, and five days later, a GnRH antagonist was added. When more than two mature follicles were demonstrated, a GnRH agonist trigger was administrated and approximately 36 hours later, the oocyte aspiration procedure was performed Main results and the role of chance During the study period, 448 elective egg freezing cycles were performed, 151 cycles with an extra dose on the trigger day and 297 cycles without an extra GT dose. The groups did not differ in their background characteristics, age, BMI, GT used, and the number of induction days. However, the extra GT group had significantly higher day 3 follicular stimulating hormone (FSH), lower anti-Mullerian hormone (AMH), and lower maximal Estradiol (E2) levels. The extra GT dose group had a significantly lower mean number of mature oocytes (11.1±7.1 vs. 6.4±4.5, p &amp;lt; 0.001). To adjust for the maximal E2 parameter, that differed between the groups, an additional analysis was performed, dividing the two groups into subgroups of cycles with maximal E2 above and below 10,000 pmol\l. Interestingly, even in cycles with maximal E2 above 10,000 pmol\l, the extra dose group had poorer results (10.3±4.3 vs. 12.7±7.2, p &amp;lt; 0.001). This difference was also noted in cycles with E2 below 10,000 pmol\l (5.4±4.0 vs 8.7±6.1 mature oocytes, p = 0.011). Additionally, a multiple regression model for the prediction of several oocytes retrieved showed that the extra GT dose parameter was not associated with increased oocytes number. Limitations, reasons for caution The retrospective design of this study and the differences in cycle characteristics between patients that did or did not receive an extra GT dose on trigger day make it prone to selection bias. Wider implications of the findings Our study shows that administration of an extra GT dose on trigger day in oocyte cryopreservation cycles does not yields more mature oocytes. However, wider prospective studies are needed to thoroughly investigate the implications of this treatment’s effect on cycle outcomes. Trial registration number Not applicable

P-464 Long-acting GnRH agonist ovulation trigger to avoid ovarian hyperstimulation and to combine oocyte cryopreservation with ovarian suppression during chemotherapy

Abstract Study question Is long-acting GnRH agonist (GnRHa) trigger an efficacious and safe option in oocyte cryopreservation cycles before chemotherapy, when ovarian suppression is planned? Summary answer The flare-up effect of long-acting GnRHa is able to induce the final oocytes’ maturation and subsequently suppress ovarian function for chemotherapy What is known already When both oocyte cryopreservation and gonadal suppression during chemotherapy with long-acting GnRHa are accepted by the patient for fertility preservation (FP), the first injection of GnRHa is administered few days after oocyte retrieval in order to start oncological therapies as soon as possible. Some cases of ovarian hyperstimulation (OHSS) have been described in this setting, as a consequence of the initial flare-up effect on recently stimulated ovaries. The subsequent risks (including a possible delay in the start of chemotherapy) may discourage physicians from proposing gonadal suppression in combination with oocyte cryopreservation, denying women a FP opportunity with proven efficacy. Study design, size, duration Prospectively collected data from 75 oncological patients who underwent ovarian stimulation for oocyte cryopreservation from 2016 to 2021 were evaluated. From 2020 all patients for whom ovarian suppression after cryopreservation was planned were offered long-acting GnRHa trigger. All other patients were enrolled as controls, stratified for triggering method used (highly purified Chorionic Gonadotrophin 10000 UI or short acting GnRHa 0.2 mg). Participants/materials, setting, methods All the ovarian stimulation cycles for oocyte cryopreservation in oncological patients before chemotherapy were performed in a single tertiary level public fertility centre. Cycle outcomes were evaluated accordingly to the trigger method. Maturation rate was defined as number of cryopreserved mature oocytes/total number of oocytes retrieved. Results were compared by Mann-Whitney U test or Chi-Square test, as appropriate. When the long-acting GnRHa was used for triggering, luteal phase hormones were assessed. Main results and the role of chance After controlled ovarian stimulation (COS) with standard or random start antagonist protocol, 13 women received the long-acting GnRHa trigger (Triptorelin 3.75 mg. Group A) 36 hours before oocyte retrieval, 37 women received highly purified Chorionic Gonadotrophin 10000 UI (Group B) and 25 women the short-acting GnRHa (Triptorelin 0.2 mg. Group C). The groups were comparable in terms of demographic and clinical parameters. Median number of mature cryopreserved oocytes in group A was 11 (range 7-18) with a maturation rate of 80% (68-100), 9 (0-24) with a maturation rate of 78% (43-100) in group B, and 12 (0-34), 79% (50-100) in group C (no statistically significative difference). There was no case of OHSS in Group A. One patient in group B and one in group C developed OHSS after administration of long-acting GnRH in the luteal phase after COS (five days after oocytes retrieval). Five days after oocyte retrieval (7 days after trigger), serum FSH median level in group A was 1.29 mUI/ml (0.48-2.50) and LH median level was 1.04 mUI/ml (0.26-2.46). Limitations, reasons for caution We are aware that our data should be confirmed by more robust randomized studies and higher numbers. Wider implications of the findings We report for the first time the efficacy of long-acting GnRHa in obtaining mature oocytes and in guaranteeing complete suppression by chemotherapy initiation. The feasibility of this strategy is an important step in reducing the risk of OHSS, giving the opportunity to combine oocyte cryopreservation and ovarian suppression during chemotherapy. Trial registration number not applicable

P-661 dydrogesterone as an alternative to supress LH surge in single stimulus protocols with follitropin delta

Abstract Study question Is oral dydrogesterone (DYG) 30 mg daily efficient on prevention of premature luteinizing hormone (LH) surge in ART cycles? Summary answer Oral dydrogesterone demonstrated to be as safe and effective as GnRH-ant in IVF/ICSI cycles intended to freeze-all / PGT-A, oocyte preservation and embryo banking programs What is known already The use of progesterone (PG) to inhibit pituitary LH surge during ovarian stimulation have been described over the last decades. Due to its harmful effect on the endometrium, PG suppression is mainly reserved for freeze-all cycles. Dydrogesterone (DYG), a known and safe synthetic progesterone, has been tested for this purpose based on the concept of its more selective PG receptors activity, which could reduce the inconveniences of side effects with less relevant androgenic, estrogenic, glyco or mineralocorticoid activity. Accordind to some recent work, DYG would be an effective tool both in cycles intended to freeze-all or in oocyte preservation strategies. Study design, size, duration Observational, comparative single center study, comparing the effect of DYG and gonadotropin releasing hormone (GnRH) antagonists on prevention of premature luteinizing hormone (LH) surge as well as to evaluate the number of metaphase II oocytes. From January 2019 to January 2020, 143 no age restrictions patients underwent both IVF/ICSI or oocyte preservation, all of them receiving the same single stimulus protocol with follitropin delta (Rekovelle). Participants/materials, setting, methods 92 IVF/ICSI plus 51 oocyte cryopreservation cycles underwent deltafollitropin (Rekovelle®, Ferring Pharmaceuticals) in a fixed daily and individualized SC-dose. Clinical decision led to a GnRH-antagonist (CTA-Cetrorelix acetate, Cetrotide®, Merck) 0,25 mg/d initiated in a flexible schedule in presence of one follicle ≥14 mm and continued throughout the stimulation period (48 cycles) or dydrogesterone (DYG), 10mg 8/8 hours (Duphaston®, Abbott) combined to gonadotrophin from the beginning of stimulation until the day after the trigger (95 cycles). Main results and the role of chance DYG-group had a mean age significantly higher (37.8 x 35.8-p 0.002) but there were no differences in mean parameters of BMI (24.08 x 24.81), days of stimulation (9.95 x 10.08), AMH (2.30 x 2.52), AFC (14.6 x 16.2). In the same way, no differences were observed between follicles 15 mm to 18 mm (3.06 x 3.68) and ≥ 18 mm (4.56 x 3.9), with a tendency for a greater number of larger follicles in the DYG-group. Metaphase II oocytes (7.48 x 7.33) was similar in both groups. One patient from each group experienced a premature LH surge (3.54 x 3.06) and one case in the DYG-group had no oocyte in a single 20mm aspirated follicle. There happened no cancelling. No patients experienced moderate to severe ovarian hyper stimulation syndrome, even when AMH&amp;gt;3 ng/mL. Cancelling criteria: no follicles with a diameter 17 mm by day 15. Oocyte retrieval took place 36 hours after trigging. Primary outcome was the incidence of premature LH surge. Secondary outcomes included follicles ≥ 15 mm and &amp;lt; 18 mm and ≥ 18 mm on hCG day, metaphase II oocytes, number of cancelled cycles and OHSS symptoms. Statistics were performed by Mann-Whitney test. Limitations, reasons for caution The main limitation point is the small number of patients. Despite having relative experience with the use of DYG, in this work we limited the sample to consider only one type of stimulus protocol, making the groups more homogeneous for the analysis. Wider implications of the findings Dydrogesterone is as effective as GnRH-ant in reducing premature LH surge. It can be considered for IVF/ICSI cycles intended to freeze-all / PGT-A, oocyte preservation and for embryo banking strategies, representing lower costs in these cases. Trial registration number not applicable

P-476 Why are they not coming back? A single-center follow-up study on oncological women oocyte's storing for fertility preservation

Abstract Study question Which is the return rate and which factors are responsible for the non-return in cancer patients who underwent oocyte cryopreservation for fertility preservation? Summary answer Return rate was 11.7%. Young age at freezing, lack of a partner and type of cancer were the main factors responsible for the non-return. What is known already Improvements in oncological early diagnoses and therapies have significantly increased the survival rates of patients, allowing clinicians to focus on long-term quality-of-life issues, such as access to motherhood. An extensive literature on the importance of fertility preservation (FP) has been produced thanks to the growing number of patients undergoing FP cycles over the years. Nevertheless, the rates of patients returning to use their cryopreserved material have shown to be considerably low, ranging from 5 to 8%. Significant data regarding the reasons that might explain such low return rates are still scarce. Study design, size, duration This is a single-center follow-up retrospective study that includes all women who underwent oocyte cryopreservation cycles for oncological purposes at referral University affiliated center, from January 2001 to December 2017. Participants/materials, setting, methods The database consists of 171 patients, among those 110 (64%) were diagnosed with breast cancer, 45 (26%) hematological cancer, 5 (3%) gynecologic cancer and 11 (7%) other cancers. Data about returned patients were retrieved from internal registries. Non-returned patients were assessed by standardized phone survey on health and marital status, family projects, spontaneous conceptions, and reasons why they had not returned to use their gametes. A univariate analysis between returned and non-returned patients was performed. Main results and the role of chance Among the 171 women who underwent oocyte cryopreservation, 9 (5%) died and 17 (10%) were lost at follow up. In the remaining 145-patient group, the mean age at freezing was 32.2±6.1 and at follow-up 38.2±6.7 years. A total of 20 patients (11.7%) returned to use their frozen material and 125 did not. In the non-returned group, 37 (29.6%) did not have a partner, 10 (8%) had a previous spontaneous conception and 15 (12%) had recurrent malignancy at the time of follow-up. In the univariate analysis, younger age at freezing (31.8±6.2 vs 35.2±4.7; p 0.018), lack of a partner (p 0.002), type of cancer (other than breast cancer; p 0.024) were the significant factors in the non-returned group. As for the personal reason for not coming back, patients mainly answered as follows: lack of a partner (29, 23.2%), desire of spontaneous motherhood (24, 19.2%), previous spontaneous pregnancies after FP procedures (16, 12.8%), and still ongoing hormonal therapy for breast cancer (13, 10.4%). Nonetheless all of them confirmed their will to keep the storage of their oocytes. Limitations, reasons for caution The study population consists of a limited number of patients from a single Italian Fertility Center. Since the Italian law limits ART access to heterosexual couples, this setting may limit any possible adaptation of the study to other countries, with different legislations. Wider implications of the findings The impact of a cancer diagnosis on a woman’s maternal desire, sentimental status and life priorities should be studied more thoroughly. Moreover, it is important to encourage studies investigating so long hormonal therapy suppression in breast cancer patients seeking pregnancy in order to reduce their time to pregnancy. Trial registration number na

Pfizer SARS-CoV-2 BNT162b2 mRNA vaccination (BNT162b2) has no adverse effect on elective oocyte cryopreservation outcomes

Research questionDo elective oocyte cryopreservation outcomes in women 1–13 months after SARS-CoV-2 vaccination alter compared with unvaccinated women and do different time intervals between vaccination and ovarian stimulation impact these outcomes? DesignThis retrospective cohort study, conducted in a university-affiliated IVF centre, included 232 elective oocyte cryopreservation cycles of vaccinated and unvaccinated patients, without previous infection with the SARS-CoV-2 virus, between December 2020 and January 2022. Two control groups – pre-pandemic (January 2019 to February 2020) and intra-pandemic (December 2020 to January 2022) unvaccinated groups – were compared with the vaccinated group, further divided into four subgroups (under 3, 3–6, 6–9 and 9–13 months). The primary outcome was the elective oocyte cryopreservation cycle outcomes – number of retrieved and number of mature oocytes. ResultsThe vaccinated group demonstrated comparable outcomes with regards to number of retrieved and mature oocytes compared with the pre-pandemic and intra-pandemic unvaccinated groups (12.6 ± 8.0 versus 13.0 ± 8.2 and 12.5 ± 7.4 retrieved and 10.1 ± 6.9 versus 9.5 ± 6.4 and 10.1 ± 6.3 mature oocytes, respectively; not significant for both). Similar results were noted in a comparison between the intra-pandemic unvaccinated group and the four vaccinated subgroups. No correlation was found between the parameter of days from vaccination and cycle outcomes. Similarly, analysis of covariance showed no association between vaccination status and timing and number of mature oocytes. ConclusionsThe SARS-CoV-2 vaccination does not alter the outcomes of elective oocyte cryopreservation procedures. This is true even in a relatively long time interval of 9 to 13 months from vaccination.

Employer-based insurance coverage increases utilization of planned oocyte cryopreservation.

To determine the utilization of planned oocyte cryopreservation (OC) in the year immediately prior to, and the year of, insurance coverage commencement for employees at our institution. Patient demographics and cycle outcomes were retrospectively compared between the first OC cycles occurring in 2017 vs. 2018 according to insurance coverage and type, age, and the number of oocytes retrieved and cryopreserved. Continuous demographic variables including age, BMI, day 3 FSH and E2, AMH, gravidity, and parity were compared using student T-tests. Cycle outcomes, including the number of oocytes retrieved and cryopreserved were compared using linear regression models, adjusting for potential confounders including age, BMI, and ovarian reserve parameters. Between January 2017 and December 2018, 123 patients underwent planned OC at our institution. Patient age ranged from 23 to 44years and did not significantly differ from 2017 to 2018 (mean 34.9 vs. 35.2). There was a 12% increase in planned OC utilization from 2017 (N = 58) to 2018 (N = 65). Significantly, more patients had any insurance coverage in 2018 vs. 2017 (71.9% vs. 40.4%, p = 0.001), a 78% increase. From 2017 to 2018, the number of patients with hospital-based insurance coverage undergoing planned OC increased by a factor of 8 (5 to 41.5%, p < 0.001), while the number of self-pay patients significantly decreased (p = 0.001). No differences were found regarding cycle outcomes. A greater proportion of women at our institution had insurance coverage for planned OC in 2018 vs. 2017. Employer-based insurance coverage for planned OC was associated with a significant increase in utilization by hospital employees.

The use of oocyte cryopreservation for fertility preservation in patients with sex chromosome disorders: a case series describing outcomes.

Characterize outcomes among adolescents and young adults (AYAs) with sex chromosome disorders (SCDs) after oocyte cryopreservation (OC) consultation. Retrospective case series of all AYA (< 25years) patients with SCDs seen for OC consultation from 2011 to 2019 at a large, urban, academic fertility center. All AYA patients with an SCD seen for OC consult in the study time period were reviewed and included. Data collected included patient age, SCD type, number of patients who attempted OC, number of cycles attempted, and cycle outcomes. Twenty-two patients were included: 9 with Turner syndrome, 12 with mosaic Turner syndrome, and 1 with 47,XXX. Mean age at consult was 14.7 ± 3.5years. Fourteen patients elected for OC: 5 with Turner syndrome, 8 with mosaic Turner syndrome, and 1 47,XXX who pursued 31 OC cycles total. Of those 14 patients, 10 underwent retrieval, 9 froze oocytes, and 8 froze mature (MII) oocytes. Seven patients underwent > 1 cycle and 7 had ≥ 1 cancelation. 3/3 patients who pursued cycles after 1st cancelation never got to retrieval. Age, SCD type, and baseline FSH did not predict ability to freeze MIIs. One patient returned after OC and attempted 4 ovulation induction cycles and 2 IVF cycles; all were canceled for low response. AYA patients with SCDs have a high risk of poor response and cycle cancelation but the majority froze MIIs. Thus, setting expectations is important. A larger sample size is needed to evaluate possible clinical predictors of success.

WHO IS FREEZING EGGS, Y’ALL? DESCRIPTIVE CHARACTERISTICS OF WOMEN UNDERGOING OOCYTE CRYOPRESERVATION AT TWO URBAN FERTILITY CLINICS IN THE SOUTH, WITH A FOCUS ON RACE/ETHNICITY

To describe trends and characteristics of oocyte cryopreservation (OC) cycles at two fertility clinics in an urban, diverse city in the South, and to compare the racial/ethnic backgrounds of women pursuing OC compared to the racial demographic of this city. Retrospective chart review of all OC cycles from 2014-2019 from two Atlanta fertility clinics (one academic and one private). Patient demographics and cycle characteristics were compared between the two clinics using chi-squared analyses for categorical variables and student’s t-tests for continuous variables. A total of 592 patients undergoing OC were included (668 total OC cycles). The majority of patients underwent 1 cycle (n=529, 89.4%), whereas 51 patients did 2 cycles (8.6%), 11 patients did 3 cycles (1.8%), and 1 patient did 5 cycles (0.2%); there was no statistical difference in the number of cycles performed per patient based on the clinic type. The total number of OC cycles increased annually at both clinics; the largest increase in OC use was seen between 2016 to 2018. Mean ovarian reserve testing parameters (AMH, antral follicle count) was similar between clinics. The average age at cryopreservation was 34.8 (private) and 34.0 (academic), with a majority of cycles occurring in women under age 35 (46.8%). The average BMI was similar between clinics (academic 26.5 kg/m2, private 25.2 kg/m2). There was an overall low utilization of frozen oocytes at both clinics; a total of 34 embryo transfer attempts using thawed autologous oocytes were performed. Atlanta is unique in its racial and ethnic diversity and has been used as a model for investigating issues surrounding access to care. Atlanta’s resident census data from 2019 is as follows: 48% black, 39% white, 5% Asian, 5% Hispanic. When compared against the background demographic of Atlanta, OC cycles at both clinics were disproportionately seen in white patients (60.3%), whereas 20.8% of OC cycles were in black patients. OC use among other ethnic groups made up a small percentage of overall cycles, including those in Asian patients (8.3%) and Hispanic patients (3.0%), however this proportion paralleled the racial demographic of Atlanta for these minority residents. When the demographics of Atlanta OC cycles were compared to nationally reported OC trends, the proportion of minorities undergoing OC in Atlanta was greater than the proportion in the national cohort. OC patient demographics were similar at each the private and academic clinics with respect to age, number of OC cycles, race/ethnicity, ovarian reserve testing and BMI. National SART data for race/ethnicity is not available for 47% of OC cycles as previously reported (1), which makes the accuracy of our data unique. Despite the increasing number of OC cycles at both clinics from 2014-2019, there was a disproportionate use of OC among Atlanta’s minority ethnic groups when compared to white patients.