Antagonist Cycles Research Articles

Recombinant LH supplementation improves cumulative live birth rates in the GnRH antagonist protocol: a multicenter retrospective study using a propensity score-matching analysis

BackgroundLuteinizing hormone (LH) is critical in follicle growth and oocyte maturation. However, the value of recombinant LH (r-LH) supplementation to recombinant follicle stimulating hormone (r-FSH) during controlled ovarian stimulation in the gonadotrophin releasing hormone (GnRH) antagonist regimen is controversial.MethodsThis multicenter retrospective cohort study recruited 899 GnRH antagonist cycles stimulated with r-LH and r-FSH in 3 reproductive centers and matched them to 2652 r-FSH stimulating cycles using propensity score matching (PSM) for potential confounders in a 1:3 ratio. The primary outcome was the cumulative live birth rate (CLBR) per complete cycle.ResultsThe baseline characteristics were comparable in the r-FSH/r-LH and r-FSH groups after PSM. The r-FSH/r-LH group achieved a higher CLBR than the r-FSH group (66.95% vs. 61.16%, p = 0.006). R-LH supplementation also resulted in a higher 2-pronuclear embryo rate, usable embryo rate, and live birth rate in both fresh embryo transfer cycles and frozen-thawed embryo transfer (FET) cycles. No significant differences were found in the rate of moderate and severe ovarian hyperstimulation syndrome (OHSS), or cycle cancellation rate in the prevention of OHSS.ConclusionsR-LH supplementation to r-FSH in the GnRH antagonist protocol was significantly associated with a higher CLBR and live birth rate in fresh and FET cycles, and improved embryo quality without increasing the OHSS rate and cycle cancellation rate.

The Association of Serum Progesterone Levels on Day of Oocyte Retrieval with Pregnancy Outcome

Aims and Objectives: To establish the level of serum progesterone (P4) on the day of oocyte retrieval beyond which it can affect the outcome of in vitro fertilisation (IVF), and to further establish the incidence of serum P4 rise in an agonist and antagonist cycle. Methods: This prospective observational cohort study was conducted from November 2020 to November 2021 at the Sarvodaya Fertility and IVF Centre, Delhi, India. For this study, the author recruited 352 couples with infertility who were treated with IVF/intracytoplasmic sperm injection-embryo transfer, of which 279 patients completed an IVF/intracytoplasmic sperm injection-embryo transfer cycle during the study period and were included in the final analysis. The standard gonadotropin-releasing hormone antagonist (fixed or variable) and long gonadotropin-releasing hormone agonist controlled ovarian stimulation protocols were used in all patients. Participants were recruited if they were undergoing controlled ovarian stimulation with all gonadotropins, recombinant follicle-stimulating hormone/urinary human menopausal gonadotropin, or recombinant luteinising hormone. The study population was sub-grouped into two groups according to their P4 level on day of oocyte retrieval (calculated according to receiver operating characteristics curve): Group A (p≤11.6 ng/dL; n=247 out of 27; 88.5%) and Group B (p>11.6 ng/dL; n=32 out of 279; 11.5%). Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS) 17.0 version (IBM, New York City, New York, USA). Results: The percentage of patients with a rise in P4 on the day of oocyte retrieval were found significantly more in the antagonist protocol (13.3% [24 out of 181]) than in the agonist protocol (8.2% [8 out of 98]; p=0.04). Pregnancy rate was significantly higher in Group A (39.3% [97 out of 247]) compared with Group B (12.5% [4 out of 32]). The clinical pregnancy rate was also significantly higher in Group A (34.4% [85 out of 247]) compared with Group B (6.3% [2 out of 32]). Conclusion: Patients with higher levels of P4 (>11.6 ng/mL) were associated with lower pregnancy and clinical pregnancy rates.

Zygote Diameter and Total Cytoplasmic Volume as Useful Predictive Tools of Blastocyst Quality.

Introduction According to the Embryo Protection Act, the selection of embryos with the greatest potential for successful implantation in Germany must be performed in the pronucleus stage. The main aim of this study was to identify morphokinetic parameters that could serve as noninvasive biomarkers of blastocyst quality in countries with restrictive reproductive medicine laws. Materials and Methods The sample comprised 191 embryos from 40 patients undergoing antagonist cycles for intracytoplasmic sperm injection. Blastocysts were cultured in an EmbryoScope chamber and video records were validated to determine the post-injection timing of various developmental stages, cleavage stages, and blastocyst formation. The Gardner and Schoolcraft scoring system was used to characterize blastocyst quality. Results Morphokinetic data showed that the zygote diameter and total cytoplasmic volume were significantly different between good and poor blastocysts quality groups, where zygotes, which formed better blastocyst quality, had smaller diameter and smaller total cytoplasmic volume. Zygotes with more rapid pronuclear disappearance developed in better-quality blastocysts. Differences between good- and poor-quality blastocysts were also observed for late-stage parameters and for the spatial arrangement of blastomere where tetrahedral embryos more frequently forming good-quality blastocyst compare to the non-tetrahedral. Conclusions The study findings could be used to enhance embryo selection, especially in countries with strict Embryo Law Regulations. Further studies, including those in which the implantation potential and pregnancy rate are considered, are warranted to confirm these preliminary results.

Effects of letrozole co-treatment on outcomes of gonadotropin-releasing hormone antagonist cycles in POSEIDON groups 3 and 4 expected poor responders.

To evaluate the effects of adjuvant letrozole administration on outcomes of gonadotropin-releasing hormone (GnRH) antagonist cycles with intra-cytoplasmic sperm injection in POSEIDON groups 3 and 4 expected poor responder women. This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON groups 3 and 4) that underwent GnRH antagonist cycles with intra-cytoplasmic sperm injection between 2010 and 2020. A total of 488 patients with letrozole co-administration and 2564 patients without any adjuvant treatment that underwent GnRH antagonist cycles within the selected period of time were included in the study. Implantation rates, clinical pregnancy rates and live birth delivery rates were significantly higher in letrozole administered patients in comparison to controls among POSEIDON group 3 women (0.39 ± 0.46 vs 0.27 ± 0.40, p = 0.01; 46.1% vs 33%, p = 0.014; 42.7% vs 31.5%, p = 0.034, respectively). Mean total doses of gonadotropins required per cycle were significantly lower in letrozole administered patients among both POSEIDON groups 3 and 4 women (2864.65 ± 878.47IU vs 3757.27 ± 1088.89IU, p < 0.001; 3286.06 ± 770.16IU vs 3666.48 ± 959.66IU, p < 0.001, respectively). Adjuvant letrozole co-administration in intra-cytoplasmic sperm injection cycles following GnRH antagonist protocol appears to improve implantation, clinical pregnancy and live birth delivery rates in women with POSEIDON group 3 expected poor ovarian response.

Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin improves live birth rates in POSEIDON group 3 and 4 expected poor responders

Objective Aim of this study was to evaluate the effects of dual triggering with gonadotropin releasing hormone agonist and human chorionic gonadotropin (hCG) on outcomes of fresh embryo transfers following gonadotropin antagonist cycles in POSEIDON group 3 and group 4 low prognosis women and to compare the outcomes with hCG-only triggering. Methods This study was conducted by retrospective analysis of patients with expected poor ovarian response (POSEIDON group 3 and 4) that underwent fresh embryo transfers following in-vitro fertilization/intracytoplasmic sperm injection cycles with either dual triggering or hCG-only triggering between January 2010 and April 2020. A total of 1068 women that underwent dual triggering and 1931 that underwent hCG-only triggering were included in the study. Results Number of retrieved oocytes, M2 oocytes, oocyte maturation rate, fertilization rate, obtained 2PN embryos, implantation rate, clinical pregnancy rate and live birth delivery rates were found significantly higher in dual-triggering group in comparison to hCG-only group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.02, p < 0.001 respectively). Conclusion Dual trigger with concomitant injections of GnRH agonist and hCG in GnRH antagonist cycles appears to improve IVF outcomes, increase quality of embryos, reduce miscarriage rates and consequently increase live birth delivery rates in POSEIDON groups 3/4 poor responders.

P-673 GnRH Agonist Early Follicular Challenge Test as a Predictor of Ovarian Response in Short Antagonist Cycles for Fertility Preservation

Abstract Study question Does the response to GnRH agonist can be used to predict ovarian function in short GnRH antagonist cycles in women undergoing oocyte cryopreservation IVF cycles? Summary answer Response to a single GnRH agonist dose at the beginning of stimulation during short antagonist cycle can predict the outcome of the fertility preservation cycle What is known already There is a need for a reliable test for ovarian reserve. Gonadotrophin agonist stimulation test (GAST) is considered a valid marker for ovarian reserve but the test was never validated for short antagonist protocol. The reported dose for this test was 0.1 mg, however, from the vast experience with GnRH agonist triggering, it is now agreed that the optimal dose for GnRH agonist flare effect is 0.2 mg. Study design, size, duration A prospective observational study of fertility preservation cycles patient in an academic hospital setting. Seventy-four Short GnRH antagonist cycles that underwent an oocyte retrieval between 1 December 2020 and 1 January 2022. Participants/materials, setting, methods On day 2, blood was sampled for basal FSH, LH, and E2 measurements, followed by a subcutaneous injection of 0.2mg GnRH agonist as part of the initial ovarian stimulation. Twelve hours later blood sampling was repeated. E2 response was used as test parameter. The major outcome was the number of cryopreserved oocytes. Main results and the role of chance Participants were divided to groups according to Day 3 E2 to Day 2 E2 response (E3/E2 ratio) to lower and upper third percentiles (&amp;lt;3.32, n = 24 and &amp;gt;5.41, n = 25). Age (32.68 vs. 32.79, p = 0.965), total gonadotropin dose injected 3216.67 vs. 2773.42 IU p = 0.16) and day 3 FSH levels (7.39 vs. 7.16, p = 0.768) were not significantly different between groups. Ovarian response as measured by E2 levels on ovulation trigger (7879.72 vs. 17572.54 pmol/ml, p = 0.001) and number of M2 oocytes retrieved were significantly different (17.92 vs. 6.24, p &amp;lt; 0.001). Linear correlation between E3/E2 ratio and number of M2 oocytes was calculated (R = 0.48, p &amp;lt; 0.001). ROC curve analysis of E3/E2 ratio for more than fifteen M2 oocytes indicate AUC value of 0.82 (cutoff value of 4.22, p &amp;lt; 0.001, 84.6% sensitivity, 70.8% specificity) and for less than five M2 oocytes AUC value of 0.84 (cutoff value of 3.34, p &amp;lt; 0.001, 76.3% sensitivity, 73.3% specificity). The results suggest that the testing response to 0.2mg GnRH agonist positively correlates with treatment outcome of the current cycle. Limitations, reasons for caution Although all patients were tested for FSH levels for ovarian reserve, they were not tested for AMH levels. Wider implications of the findings The response to single GnRH agonist dose during short antagonist cycle can be used as another biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict accurately the outcome of the specific cycle, and potentially used to adjust the treatment dose. Trial registration number NCT04973969

P-668 The LH endocrine profile in Gonadotropin-Releasing Hormone analogue cycles

Abstract Study question What does the evolution of luteinizing hormone (LH) throughout the follicular phase look like in different treatment protocols for ovarian stimulation in IVF/ICSI? Summary answer Evolution of LH during the follicular phase of ovarian stimulation differs between Gonadotropin-Releasing Hormone (GnRH) analogues, with a significant decrease of LH in antagonist cycles. What is known already Physicians aim to tailor ovarian stimulation protocols to the patient, with protocols varying in type of GnRH analogue and gonadotropin. However, there is no clear consensus on the best treatment protocol and especially the role of LH is still not completely understood as earlier studies focused mainly on suppressing LH levels. Literature has since indicated that excessively suppressed LH levels could be detrimental for clinical outcomes. Research on LH is hampered by multiple measurements during the cycle, different treatment schedules and patients switching schedules over time. Study design, size, duration This was a non-interventional, retrospective, observational cohort study. 2200 ovarian stimulation cycles for assisted reproduction were analyzed, in 1303 individual patients. Patients were treated during the period of January 1st 2015 until September 30th 2020. Cycles were included if the patient was between 18 and 43 years of age, stimulated with human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rec-FSH, follitropin α or β) and using GnRH analogues. Participants/materials, setting, methods Data were extracted from two databases used at a tertiary infertility clinic. Cycles were divided into six treatment protocols: GnRH antagonist/hMG (13.8%), antagonist/rec-FSH (19.7%), long agonist/hMG (35.7%), long agonist/rec-FSH (4.8%), short agonist/hMG (22.5%) and short agonist/rec-FSH (3.5%). 59.5% of cycles were pretreated with an oral contraceptive pill (OCP). LH evolution was visualized by plotting LH levels against the days of the follicular phase and repeated daily LH measures were fitted with a linear mixed model. Main results and the role of chance Basal LH was significantly lower in antagonist/hMG cycles pretreated with OCP compared to no pretreatment (estimated difference -1.23 IU/L, p &amp;lt; 0.001). Mean LH value throughout the follicular phase was significantly lower with OCP pretreatment in antagonist/hMG (estimated difference -1.05 IU/L, p &amp;lt; 0.001) and antagonist/rec-FSH cycles (estimated difference -0.52 IU/L, p &amp;lt; 0.001). When LH evolution throughout the follicular phase was analyzed, no significantly different evolution between cycles with and without OCP was detected (all p &amp;gt; 0.1). Hence further analysis of the LH profiles was performed in the six protocol groups making no distinction between OCP use or not. LH evolution was significantly different between all six protocol groups (p &amp;lt; 0.001). In antagonist/hMG cycles, LH values showed a significant decrease of 0.17 IU/L per day (p &amp;lt; 0.001). In antagonist/rec-FSH cycles, the decrease per day was 0.26 IU/L (p &amp;lt; 0.001).The decrease in LH was significantly larger in rec-FSH cycles than hMG (estimated difference 0.09 IU/L per day, p &amp;lt; 0.001). Short agonist/hMG cycles showed a significant increase in LH of 0.04 IU/L per day (p = 0.002), while the increase of 0.01 IU/L per day in rec-FSH cycles was not significant (p = 1.00). In long agonist cycles, no significant in- or decrease in LH values during the follicular phase was found (p = 1.00). Limitations, reasons for caution Stimulation protocols were chosen by the treating physician which is a limitation of the retrospective design. The authors were able to partly respond to this limitation by adjusting for age and using different cycles per patient in all mixed models. Wider implications of the findings Using profiles to show LH evolution allowed the visualization of the decrease in the evolution of LH in antagonist cycles, even more pronounced in cycles stimulated with rec-FSH compared to hMG. This decrease in LH and the potential impact on estradiol levels and follicle growth needs further examination. Trial registration number not applicable

P-359 Effect of estradiol pretreatment on antagonist ICSI cycles outcome

Abstract Study question Does estrogen pretreatment in antagonist ICSI cycles improves the outcome? Summary answer Pretreatment with estrogen in antagonist cycles reduced the days of stimulation, the number of hMG ampoules and enhanced the implantation rate. What is known already It has been previously reported that, programming of antagonist cycles with E2 only, started in the luteal phase and continued beyond the menses till the first day of stimulation, yielded similar results as the long agonist protocol. E2 pre-treatment in the luteal phase has an inhibiting role on follicular growth through its negative feedback on the FSH increase during the luteal follicular transition phase. This effect stops as soon as E2 administration is terminated. Study design, size, duration This was a prospective randomized controlled trial performed in a private IVF centers from June 2020 to February 2021. One hundred and fourteen infertile couples undergoing intracytoplasmic sperm injection embryo transfer cycles (ICSI-ET) were included. Participants/materials, setting, methods Group A includes 57 patients were pretreated with a dose of 4 mg estradiol valerate (progynova 2 mg; Bayer) once daily starting 10days before expected menses. Ovarian stimulation was started one day after the last estradiol dose, in a dose ranging from 225 to 375 IU of hMG. While in group B , 57 patients received stimulation in a dose of 225 to 375 IU of hMG starting on cycle day 2 without estradiol pretreatment. Main results and the role of chance The daily dose of hMG was significantly lower in The study group (P = 0.048), the stimulation days were significantly higher in the control group (P = 0.049), the total number of hMG ampoules was significantly higher in the control group (P = 0.041), and the implantation rate was higher in the study group (P = 0.045) , also the pregnancy rate (positive pregnancy test) was higher in the study group (p = 0.044) but there was no significant statistical difference detected as regards the clinical pregnancy rate between both groups (P = 0.180) , the serum estradiol on day of hCG ( p = 0.055), serum progesterone level on hCG day (P = 0.71) and the endometrial thickness (p = 0.780) . Also there is no significant statistical difference between the two groups as regarding number of follicles on day of hCG. (P = 0.803), the number of mature oocytes (P = 0.703) and no significant difference in the number of good quality embryos (p = 0.532) and the ratio of mature oocytes to number of follicles on day of hCG (P = 0.835), with no significant statistical difference between both groups. Limitations, reasons for caution The limitation of this study is the small number of patients as we included only 114 patients. Wider implications of the findings Luteal estradiol in antagonist cycles improved the outcomes of ICSI procedure by reducing the number of gonadotropin ampoules used for COH and reduced duration of stimulation, also the implantation rate is improved by luteal estradiol administration. Trial registration number NCT05197374

O-292 Comparison of effect of two different trigger regimens; single (hCG) versus dual (hCG + Leuprolide) on outcome of fresh IVF cycles: A randomized controlled trial

Study questionDoes adding gonadotropin-releasing hormone agonist (GnRHa) to hCG trigger increases the number of high-grade embryos in GnRH antagonist protocol in fresh non-donor IVF?Summary answerFinal oocyte maturation triggered by dual trigger increases the number of MII oocytes thus transferring good-quality embryos and cryopreserving surplus embryos compared to hCG trigger.What is known alreadyhCG has been conventionally used as a ‘faux’ LH surge to bring about final oocyte maturation due to structural similarity between the two. GnRH agonist, on the other hand, induces a more physiological gonadotropin surge for follicular maturation, but is associated with luteal phase deficiency. Recent studies have shown that combining GnRHa with hCG trigger improves oocyte maturation and embryo quality with the added benefit of a luteal phase support, thereby improving IVF outcomes in terms of both embryological and reproductive outcomes.Study design, size, durationA single-center, open labelled, randomized controlled trial including 100 normal responder patients between 21-38 years undergoing IVF using GnRH antagonist protocol between January 2020 to August 2021. The study excluded patients with the presence of other variables of adverse outcomes like diminished ovarian reserve (AFC < 5 or AMH < 1.2 ng/ml), endocrine disorders, thin endometrium (<6mm), previous history of uterine surgeries, and high responders.Participants/materials, setting, methods100 patients undergoing fresh IVF cycle using GnRH antagonist protocol were randomized after informed consent to receive either dual trigger (Leuprolide acetate 1 mg + rhCG 250 mcg, n = 50) or single hCG trigger (rhCG 250 mcg, n = 50). Oocyte retrieval was done 35-37 hours after trigger followed by IVF/ICSI, as indicated. Oocyte and embryo grading was done using Istanbul consensus. Analysis was done by ITT. Outcomes were analyzed using Independent t-test and Chi-square test.Main results and the role of chanceThe baseline characteristics were comparable in both arms. the number of MII oocytes retrieved (7.82 versus 5.92, p = 0.003) and the number of day-3 grade-1 embryos (4.24 versus 1.8, p < 0.001) were higher in the dual trigger group, whereas fertilization rates between the two groups (91.82% versus 88.51%, p=NS) were comparable. Consequently, the number of embryos cryopreserved (2.68 versus 0.94, p < 0.001) were significantly higher in the dual trigger group. However, the implantation rate between the two groups (21% versus 19.6%, p = 0.770) was comparable. The serum LH levels 12 hours post trigger were measured in both the arms and as expected, high serum LH values were documented in the dual trigger group (46.23 mIU/ml vs 0.93 mIU/ml, p < 0.0001).Limitations, reasons for cautionDue to the impact of the Covid-19 pandemic causing an intermittent pause in IVF services at our center, a smaller sample size of 100 patients could be enrolled in the study, and reproductive outcomes in terms of live births and cumulative live births could not be assessedWider implications of the findingsThis study, though small, has contributed to some evidence of redesigning the dual trigger in all antagonist cycles, with the exception of high responders and PCOS patients. The addition of GnRHa to hCG trigger has led to the possibility of cryopreserving surplus embryos thereby increasing the cumulative live births.Trial registration numberCTRI/2020/08/027030

P-691 Assessment of ovarian vascularity by three-dimensional vaginal power Doppler on day seven of menstrual cycle to predict the number of eggs collected in antagonist cycle

Abstract Study question Could ovarian vascularity indices on day 2 and 7 of stimulation, measured by 3-dimensional (3D) vaginal power Doppler, predict after controlled ovarian stimulation? Summary answer Ovarian vascularity index (VI) on day 7 may be an indicator of poor (&amp;lt;three mature eggs collected) ovarian responses to gonadotropins. What is known already Poor and/or hyper ovarian responses to gonadotropins may be related to cycle cancellation during controlled ovarian stimulation (COS). In this context, gonadotropin dose is often individualized using patient features that predict ovarian response (such as age, antral follicular count (AFC) and anti-Müllerian hormone (AMH)). In parallel, ovarian vascularity color doppler is a valuable evaluation method to predict the ovarian hyperstimulation syndrome and the growth/maturity of Graafian follicles. The aim of the present study is to estimate the utility of 3-dimensional vaginal power Doppler and ovarian vascular flow indices in the prediction of the number of mature occytes collected after COS. Study design, size, duration A prospective study was conducted on 296 couples undergoing intracytoplasmic sperm injection cycle at Al Hadi Laboratory and Medical center, Beirut, Lebanon. It was performed between January 2020 and dec 2021. Couples were categorized into poor responders group (3 or less metaphase II (MII) eggs collected) (36.1%), high responders group (16 or more MII eggs collected) group ( 6.7%), and normal responders group (more than 3 and less than 16 MII eggs collected) (57,2%). Participants/materials, setting, methods On the second and seventh day of the menstrual cycle, ovarian volume and vascularity parameters (vascularity index (VI), flow index (FI), and vascularity flow index (VFI)) were measured using the 3D power Doppler and the Virtual Organ Computer-Aided Analysis. On day 2 , the antral follicle count was evaluated and a blood sample for AMH testing was collected. Women included in the study have undergone COS using GnRH antagonist protocol. Main results and the role of chance Mean age was 35,88+/- 6 year , day2 VI and day2 VFI correlates with the number of egg collected (p = 0.014 and 0.045 respectively). 9 parameters were used to predict poor and high ovarian responses (Age, AMH, AFC, day2 VI, day2 FI , day2 VFI , day7 VI, day7 FI and day7 VFI) in a Receiver operator characteristics (ROC) curve model . Ovarian day7 FI significantly predicted poor ovarian response to gonadotropins (p = 0.038) with an area under the curve of 0.679. AFC predicted also poor ovarian response to gonadotropins (p = 0.006) . In parallel, AFC significantly predicted high ovarian response to gonadotropins (p = 0.002) and AUC (0.778) while all other 3D doppler parameters couldn’t predict high responders. Limitations, reasons for caution It will be necessary to perform a prospective analysis on a broad sample size to validate these findings. In addition, it will be interesting to assess the impact of ovarian vascularity on pregnancy outcomes. Wider implications of the findings Assessing ovarian vascularity during ovarian stimulation can help reduce the rate of cycle cancellation. In addition, more studies are welcomed in the field to unravel the mechanisms behind altered ovarian vascularity and to test the possibility of restoring normal ovarian physiology. Trial registration number Not Applicable

O-014 An expected benefit analysis of using an interpretable machine learning model for gonadotropin starting dose selection during ovarian stimulation

Abstract Study question What is the expected benefit of using a machine learning model for predicting the optimal starting dose of gonadotropin during ovarian stimulation? Summary answer Patients who had an optimal starting gonadotropin dose had improved outcomes and used significantly less total FSH compared to propensity matched patients who did not. What is known already The relationship between the starting dose of follicle-stimulating hormones (FSH) and ovarian response is complex. In general, too little starting FSH may lead to inadequate follicle recruitment, while too much may lead to excessive response. In completed cycles, there exists conflicting evidence of whether higher doses are beneficial or detrimental to the number of oocytes retrieved. The field of assisted reproduction has begun to apply machine learning techniques to clinical decision support for ovarian stimulation, but no studies have specifically investigated optimizing starting FSH dose selection. Study design, size, duration We performed a retrospective analysis of patients undergoing autologous, non-cancelled IVF cycles from 2014 - 2020 (n = 18,591) at three different IVF clinics in the United States. The primary outcomes were the average number of MIIs, 2PNs, and usable blastocysts in relation to starting and total doses of FSH. Participants/materials, setting, methods A K-nearest neighbor similarity model was trained on all cycles and used to identify the 100 most similar patients to a patient-of-interest using age, BMI, baseline anti-mullerian hormone (AMH), and baseline antral follicle count (AFC). For each patient, a patient-specific dose response curve was created by fitting a constrained second order polynomial to the number of MII oocytes relative to the starting dose of FSH across all of the neighbors. Main results and the role of chance For each patient, their individual dose response curve was used to determine if there was an optimal dose that maximizes the prediction of MIIs (called dose-responsive patients), or if the dose response curve shows no optimal dose (called non-responsive patients). 30% of cycles were identified as dose-responsive, 64% were identified as non-responsive, and 6% were inconclusive and excluded from analysis. Dose-responsive patients who received an optimal starting dose had, on average, 1.5 more MIIs, 1.0 more 2PNs, and 0.5 more usable blastocysts using 10 IU’s less of starting FSH and 195 IU’s less of total FSH compared to propensity-matched patients with non-optimal doses. Non-responsive patients who received a low starting dose had, on average, 0.3 more MIIs, 0.4 more 2PNs, and 0.3 more usable blastocysts using 150 IU’s less of FSH and 1375 IU’s less of total FSH compared to propensity-matched patients with a high starting dose. Limitations, reasons for caution The primary limitation is the retrospective nature of this study. Further, our calculations of starting FSH combined the contribution of pure FSH plus the FSH component of FSH/LH medication, rather than evaluating each separately. We also did not differentiate between types of protocols, as the majority were antagonist cycles. Wider implications of the findings Our results suggest that a patient similarity model for selecting starting FSH can help increase MII outcomes while reducing the amount of FSH given to a patient. Future work will include continuing to increase the diversity of our dataset and performing validation studies to show improved outcomes with model use. Trial registration number Not applicable

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-320 The Effects of Endometriosis on Oocyte Morphology and Embryo Development

Abstract Study question What is the effect of the endometriosis on oocytes morphological abnormalities in intracytoplasmic sperm injection cycles.? Summary answer An increase in the detection rate of refractile body and polar body fragmentation was observed in the morphology of oocytes obtained from endometriosis patient. What is known already The quality of the oocyte is suspected for the lower clinical success in endometriosis patients compared to other patient groups. The oocyte quality is determined by its morphological, cellular, and molecular evaluations. However, there are limited studies on the association between endometriosis and oocyte morphology. Study design, size, duration This was a retrospective cohort study, conducted between January 2020 and August 2021, at a tertiary care hospital. The women aged 24-35 years and BMI 19-30 kg/m2 ranges who underwent fresh GnRH antagonist cycles and stimulated with 150-300 IU dose of recombinant FSH (rFSH) and then trigerred with 250 micrograms/0.5 ml of rhCG were included. Participants/materials, setting, methods The patients who were cycled with the etiology of endometriosis (n = 46 cycles, Group 1) and those who were cycled with the etiology of male infertility (n = 64 cycles, Group 2) were included in this study. In addition to the comparison of intracytoplasmic and extracytoplasmic (polar body, perivitelline space, zona pellisuda) anomalies observed in oocyte morphology between groups, morphology anomalies that affect fertilization and blastocyst development within the group were evaluated. Main results and the role of chance The patient age, BMI, antral follicle counts, duration of infertility, and basal endocrine parameters among patients who were cycled with the etiology of endometriosis (n = 46 cycles, Group 1) and those who were cycled with the etiology of male infertility (n = 64 cycles, Group 2) were not different (p&amp;gt;0.05). As a result of the comparison of intracytoplasmic anomalies of 800 oocytes in total (n = 263 Group 1; n = 537 Group 2) between the groups; the refractile body determination (OR:1.23; 95% CI 1.08 -1.4, p &amp;lt;0.00) was higher in the endometriosis group compared to the other group. As a result of the comparison of extracytoplasmic anomalies between the groups; the polar body fragmentation (OR:1.3; 95% CI 1.01 - 1.85, p&amp;gt; =0.03) determination was higher in the endometriosis group compared to the other group. When the effect of oocyte morphology anomalies on fertilization and blastocyst development within the groups was evaluated by logistic regression analysis, it was found that granulation of the perivitelline space had a negative effect on blastocyst development only in the endometriosis group (β = -0.69; p&amp;gt; =0.31). Limitations, reasons for caution The main limitation of our study was its retrospective design, which precludes us from reaching a more definitive conclusion on the relation between oocyte morphology of endometriosis an fertility outcomes. Wider implications of the findings The previous studies indicate that PVS and PBI abnormalities may be ascribed to over-mature oocytes and also be negatively correlated with fertilization rate and embryo quality. Our study suggest that endometriosis seems to negatively affect oocyte quality and maturation process. Trial registration number not applicable

O-068 The BISTIM study: first RCT comparing dual ovarian stimulation on the same cycle (duostim) vs 2 conventional ovarian stimulations in poor ovarian responders undergoing IVF

Abstract Study question Is the number of cumulated oocytes with dual ovarian stimulation on the same cycle (duostim) higher compared to 2 consecutive antagonist cycles in poor responders? Summary answer Considering the number of total and mature oocytes collected in poor ovarian responders, there is no benefit of duostim vs two consecutive antagonist cycles. What is known already Several waves of follicular development exist on the same cycle. Recent studies have shown the ability to obtain oocytes with equivalent quality in the luteal phase, even after a previous ovarian stimulation in the follicular phase. During stimulation, smaller follicles are recruited and sensitized, which may increase the selection of follicles available on the second stimulation. In poor ovarian responders (POR) this potentialization may have a great interest, as 2 stimulations on the same cycle could give a higher number of oocytes compared to two conventional stimulations. However, these preliminary data need to be confirmed with a randomized controlled trial. Study design, size, duration This is a multicenter, open-labeled randomized control trial (2018, september – 2021, march). The primary objective was to demonstrate that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) lead to the retrevial of 1.5 more oocytes than the cumulative number of oocytes from two consecutive conventional stimulation, in POR women. According to this hypothesis, 44 patients were needed in each group. Participants/materials, setting, methods 88 POR women, defined with Bologna criteria (AFC≤5 and/or AMH≤1.2ng/ml and ≤3 oocytes if previous IVF) were randomized, 44 in duostim group (D) and 44 in conventional group (C). FertistartKit® 300IU/day with antagonist protocol was used except in luteal phase stimulation of group D. In group D, oocytes were pooled and inseminated after the second retrieval, with freeze all embryos. Fresh transfer was performed in group C. The analysis is presented in intention to treat. Main results and the role of chance There was no difference between the groups regarding demographics, ovarian reserve markers (AFC, AMH) and stimulation parameters. The mean number of cumulated oocytes retrieved with 2 ovarian stimulation was not statistically different in group D and C, respectively 5.0+/-3.4 and 4.6+/-3.4 (p = 0.56). The mean number of cumulated mature oocytes was not statistically different, 3.7+/-3.3 in group D vs 3.1+/-3.0 in group C (p = 0.38). The mean number of embryos was significantly lower in the group D, 0.8+/-1.3 vs group C 1.6+/-1.3 (p &amp;lt; 0.01). There was no statistical difference of the mean number of oocytes retrieved per cycle in cycle 1 vs cycle 2 in both group D and C. The delay, between the first and the second day 1 of stimulation was statistically different in group D 14.4 days (10-19) vs group C 90.6 (28-232). The ongoing pregnancy rate in group D 17.9% (7/39) was not statistically different with group C 29.3% (12/41), (p = 0.23). And the mean time to ongoing pregnancy tends to be longer in group D (144 days) vs group C (115 days) but was not statistically different (p = 0.21). Limitations, reasons for caution The RCT was impacted by Covid pandemia and stop of IVF activities for 10 weeks. Delays were recalculated to exclude this period, however one women in group D cannot have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte pick-up in group C. Wider implications of the findings In routine practice, the benefit of duostim in patients with POR is not confirmed. Firstly, because there is no potentialization on the number of oocyte retrieved in luteal phase after follicular phase stimulation. Secondly, because the freeze all strategy avoids a pregnancy with fresh embryo transfer after the first cycle. Trial registration number 2017-A00498-45

P-664 The effect of LH levels on the day of trigger on the oocyte retrieval and maturation rates in GnRH-antagonist cycles with an agonist trigger

Abstract Study question Are LH levels on day of trigger correlated with the number of oocytes retrieved and oocyte maturation rate in GnRH-antagonist cycles with an agonist trigger? Summary answer Low LH levels on the day of trigger were associated with a lower oocyte retrieval rate yet no correlation with oocyte maturation rates was found. What is known already The concept that a bolus of gonadotrophin-releasing hormone agonist (GnRHa) can replace human chorionic gonadotrophin (HCG) as a trigger of final oocyte maturation was introduced several years ago. GnRHa trigger offers important advantages including the prevention of ovarian hyperstimulation syndrome (OHSS) with the elicitation of an endogenous LH and FSH surge. Therefore, we sought to evaluate whether LH levels on the day of the trigger are associated with the efficacy of the trigger in eliciting endogenous LH surge and thereby influencing oocyte retrieval and oocyte maturation rates. Study design, size, duration This retrospective single center study included all GnRH antagonist cycles triggered with GnRHa trigger (Decapeptyl 0.2mg) performed at our IVF unit between July 2013 and December 2020. We studied the association between LH levels on the day of trigger and the number of oocytes retrieved. Additionally, we studied the effect of LH levels on oocyte maturation rates. Participants/materials, setting, methods All GnRH antagonist cycles triggered with GnRHa trigger were included. Data was acquired through individual review of medical records. Linear regression was used to study the correlation between LH levels and oocyte retrieval and maturation rates. Moreover, LH levels on day of trigger were divided ≤1 IU/L and &amp;gt; 1 IU/L to further investigate this correlation. The ratio between Basal LH and LH on day of trigger was investigated as well. Main results and the role of chance There were 211 GnRH antagonist cycles triggered with GnRH agonist trigger during the study period. The mean age of patients in the study group was 30.1±4.8 y/o, mean basal LH levels were - 6.8±3.4 IU/L, mean Basal FSH levels were - 6.7±1.9IU/L and the mean total dose of gonadotropin administered was 1633.4±680.6 Units. The mean E2 levels were 11,444±7018.5 pmol/L and the mean number of oocytes retrieved was 19.8±10.2. A correlation was found between lower LH levels on the day of trigger and the number of oocytes retrieved (p &amp;lt; 0.001). No correlation was found between LH levels on the day of trigger and oocyte maturation rates (p = 0.82). The ratio between Basal LH and LH on day of trigger was not found to be a significant factor influencing either the number of oocytes retrieved or oocyte maturation rate. When dividing the group by LH on day of trigger to below and above 1, a borderline difference was found relating to oocyte retrieval rate between the two groups (p = 0.06). Limitations, reasons for caution The retrospective nature of the study is the main limitation. Patients receiving GnRHa trigger are mainly a selective population of either high responders or patients for fertility preservation stimulated to retrieve many oocytes, therefore findings may not be applicable to normal or poor responders. Wider implications of the findings Low LH levels on day of trigger were found associated with lower oocyte retrieval rates. GnRHa has become an alternative to standard hCG triggering in certain situations. These are preliminary findings of an ongoing study designed to investigate the efficacy of GnRHa trigger according to cycle parameters including LH levels. Trial registration number not applicable

P-703 Developing individualized treatment strategies using detailed subgroup analysis to optimise pregnancy outcomes for women 40 and above

Abstract Study question What are the prognostic factors and treatment strategies for women 40 and above within different ovarian reserve subgroups? Summary answer Women in each ovarian reserve subgroup have different prognostic factors of pregnancy success and specific treatment strategies are needed for each subgroup. What is known already The number of women 40 and above seeking subfertility treatment is increasing and many are willing to undergo treatment despite extremely poor prognosis. POSEIDON criteria suggested the usage of ovarian reserve and female age as a basis for the study of the management of women in different prognostic categories. However, this classification may not be detailed enough to lead to specific recommendations for individualised management in women 40 and above, as there is rapid decline of oocyte quality and quantity. Large observational studies may lack finer detail due to challenges in recruiting women within different ovarian reserve subgroups. Study design, size, duration We carried out a detailed retrospective analysis of 382 IVF/ICSI cycles for 253 women from January 2019 to December 2021 in a special clinical and academic program for reproductive ageing and fertility. Inclusion criteria were all women who had IVF/ICSI cycles aged 40 and over. Analysis was done for all fresh cycles including cancelled cycles, failed fertilization, no eggs collected and embryo arrest. Cycles resulting in freezing of all embryos were excluded in analysis. Participants/materials, setting, methods The participants were divided into three main subroups: Group A, “normal ovarian reserve” (AMH 2.5-29.9pmol/l, n = 271 cycles); Group B, “extremely poor ovarian reserve” (AMH &amp;lt;2.5pmol/l, n = 85 cycles); and Group C “extremely high ovarian reserve” (PCOS or AMH ≥30.0pmol/l, n = 26 cycles). Chi-square and Mann-Whitney U tests were used to compare pregnant and non-pregnant groups for nominal and continuous data respectively. Multi-variate logistic regression was performed when indicated. All descriptive statistics are stated in median and percentages. Main results and the role of chance In Group A, univariate analysis showed that pregnancies were associated with lower female (41 vs 42) and male age (40 vs 43.5), administering long agonist versus antagonist protocol (73% vs 27%), the absence of androgen pretreatment (12% vs 88%), higher oestradiol level (7681pmol/l vs 6114pmol/l), higher number of oocytes retrieved (8 vs 4) and normally fertilized (4 vs 3), and embryo transfer on day 3 compared to 2 or 5 (all p &amp;lt; 0.05). The use of combined FSH/LH vs FSH only for ovarian stimulation given for 12 days at 300IU daily, higher endometrial thickness (11.3mm vs 10.6mm), IVF versus ICSI (65% vs 35%), and addition of subcutaneous progesterone for luteal support versus vaginal progesterone only (51% vs 43%) were trending towards but were not significant (p &amp;gt; 0.05). Multivariate logistic regression analysis revealed lower female and male age, less number of IVF cycles, and higher number of embryos transferred as independent factors contributing to pregnancy. In Group B, significant predictors of pregnancy included younger female age, higher gravidity, previous successful IVF and higher number of eggs fertilized (p &amp;lt; 0.05). In Group C, factors that contributed to positive pregnancy outcome included antagonist cycles versus agonist and usage of FSH and LH versus FSH alone (p &amp;gt; 0.05). Limitations, reasons for caution The retrospective nature of the study design limits control of potential confounding variables. Although there were clear trends, in a few sub-categories there were insufficient numbers to reach statistical significance. Continuing data collection is necessary to achieve adequate power for smaller groups especially Group B and C. Wider implications of the findings This detailed analysis will allow us to better understand the prognostic factors in women 40 and above, especially for women with extremes of ovarian reserve, who may benefit substantially from individualised care. We recommend standardisation of data collection and development of artificial intelligence algorithms to streamline management in the future. Trial registration number N/A

P-799 To evaluate the effect of Intra-ovarian platelet rich plasma instillation on the clinical outcome of women with diminished ovarian reserve: A prospective interventional study

Abstract Study question Does intra-ovarian instillation of platelet rich plasma (PRP) improves the clinical outcome of IVF cycles in women with Diminished Ovarian reserve (DOR)? Summary answer PRP instillation leads to consistent improvement in Antral follicle count (AFC), thus achieving clinical pregnancy rate of 33.3% per cycle in women with DOR. What is known already There is rising incidence of females with diminished ovarian reserve (DOR) especially among Asian ethnicity. With the emergence of regenerative medicine, multiple studies have evaluated the role of intra-ovarian PRP, demonstrating a beneficial role in improving ovarian reserve parameters (serum Follicular stimulating hormone (FSH), serum anti-Mullerian hormone (AMH), AFC). Despite its’ favorable effects on biochemical markers and AFC, data regarding improvement in clinical outcome remains elusive and led to inception of this study. Study design, size, duration A prospective interventional study was conducted at Division of Reproductive Medicine of a tertiary care institute. 41 infertile females aged 20-39 years with DOR (AMH &amp;lt;1.2 ng /ml; AFC&amp;lt;5) were enrolled in the study during a 6-month period beginning from August 2021. Participants/materials, setting, methods After informed consent, patients received fresh autologous PRP, prepared from 30 ml venous blood. 1.5ml of PRP instilled in each ovarian stroma between day 7-10 of menstrual cycle under sedation. Patients were followed up for three-consecutive months to assess ovarian reserve parameters including serum FSH, AMH and AFC. Patients showing significant improvement in parameters were recruited for fresh IVF cycles using Antagonist protocol with 1% transdermal testosterone. Outcomes were analysed using linear mix effect model. Main results and the role of chance The average platelet concentration in PRP was ∼10,00,000 platelets/µL. The mean age of enrolled patients was 31.22±4.16 years. Linear improvement in AFC (3.63 vs 6.98 vs 7.97 vs 6.90, p&amp;lt;0.001) was observed from baseline to three consecutive follow-up months with maximal response witnessed in second month in 57.1% of those undergoing IVF cycle. However, there was no significant difference in Serum FSH (p=0.11) and AMH (p=0.16) from the baseline post intervention. Of the 41 patients, 35 (85.3%) responded to the treatment and underwent IVF antagonist cycle. 5 out of 35 IVF cycles were cancelled mid-cycle due to poor ovarian response. The mean dose of gonadotropin requirement was 2667.5±281.1 IU (Follicular stimulating hormone) and 1400±337.3 IU (Human menopausal gonadotropin). The average number of oocytes retrieved was 5.7±2.2 whereas mean number of MII oocytes was 4.63±1.85. The fertilization rate and the cleavage rate were 92.4% and 74.1% respectively. Of the thirty patients, eight patients underwent day 2 transfer due to poor grade of embryos. Mean number of grade 1- day 3 embryos was 1.25±0.55 with surplus embryos available for cryopreservation in 14 patients. The overall clinical pregnancy rate per transfer was 33.33%. No adverse events were reported. Limitations, reasons for caution This was a prospective single arm study. A randomized controlled trial comprising a “no-treatment” arm would establish a Level-I evidence. However, “no-treatment” arm in a developing country like ours, imposes financial burden on the couple with no guaranteed clinical success and thus raising ethical concern and need for ovarian rejuvenation. Wider implications of the findings With the impetus to provide a biological child to these DOR women, intra-ovarian PRP instillation as a method of ovarian rejuvenation holds promising results. Evidently, PRP is not only effective in improving ovarian reserve but this translates into an improved reproductive outcome in a population, previously limited to oocyte donation. Trial registration number REF/2022/01/051033

P-569 Reduction of gonadotropin-dosage towards the end of ovarian stimulation for IVF/ICSI improves ART-outcome in a subgroup of patients

Abstract Study question To identify in an unselected patient population those patients, who would benefit from a gonadotropin stepdown towards the end of ovarian stimulation in IVF/ICSI-treatment Summary answer Reduction of gonadotropin-dosage during ovarian stimulation for IVF/ICSI is beneficial in FSH-stimulated patients, aged 26-30 years, and in HMG-stimulated patients, aged 36-40 years of age What is known already Ovarian stimulation with gonadotropins for multi-follicular growth is a crucial part of IVF/ICSI-treatment. Intensive administration of gonadotropins might lead to progesterone elevation (PE) in the late follicular phase, impacting negatively the endometrial receptivity and possibly the embryo quality. During follicular growth, the number of FSH- and LH-receptors shift from predominantly FSH-receptors in the early to predominantly LH-receptors in the late follicular phase, reducing susceptibility of the follicle towards systemic FSH-levels. In a good prognosis population, it was shown that lower systemic FSH-levels on the trigger-day lead to significantly lower progesterone levels without reducing the number of retrieved/mature oocytes. Study design, size, duration Retrospective analysis of 1276 ovarian stimulation cycles, performed as GnRH (Gonadotropin-Releasing-Hormone)-antagonist protocol in an unselected patient population, between January 2018 and December 2020 at ART Fertility Clinic, Abu Dhabi, UAE. Ovarian stimulation cycles were split according to the stimulation medication used (either only recombinant FSH (rFSH) or only human menopausal gonadotropin (HP-HMG)) and whether stimulation-dosage was reduced (reduction group, RG) during the stimulation course or not (non-RG). Furthermore, patients were stratified into age-groups. Participants/materials, setting, methods Couples with primary / secondary infertility and an indication for ovarian stimulation for IVF/ICSI were included, independent of their age or ovarian reserve parameters. Only GnRH antagonist cycles, with either rFSH or HP-HMG as sole medication for ovarian stimulation and available data on Antral Follicle Count (AFC), gonadotropin-dosage at stimulation-start and -end, oocyte yield (number of retrieved / mature) and hormonal parameters of estradiol, progesterone and FSH were included. Main results and the role of chance A total of 1276 ovarian stimulation cycles were included, 495 (38.79%) with rFSH and 781 (61.21%) with HP-HMG as stimulation medication. In the FSH-group, 295 patients reduced (reduction-group=RG) and 200 did not reduce (=non-RG) FSH-dosage during stimulation. In all age-categories (&amp;lt;25; 26-≤30; 31-≤35; 36-≤40; 41-45years), FSH-end-dosage was significantly lower in the RGs compared to the non-RGs (p &amp;lt; 0.001, respectively). Despite not significantly different patient characteristics (AFC, BMI (Body Mass Index), mean age, FSH-starting dosage), in patients aged 26-≤30years, a significantly higher number of oocytes (retrieved/mature) were obtained in the RG (16.0±7.1 vs 20.4±8.3;p&amp;lt;0.001 / 12.6±6.5 vs 15.8±7.0;p=0.004, respectively) without an increase in progesterone-levels (1.0±1.3 vs 0.9±0.6ng/ml;p=0.95). The HP-HMG group was composed of 437 patients in the RG and 344 patients in the non-RG-group. In all age-categories (&amp;lt;25; 26-≤30; 31-≤35; 36-≤40; 41-52years), HP-HMG-end-dosage was significantly lower in the RGs (p &amp;lt; 0.001, respectively). The age-group 36-≤40 showed no significant differences in AFC, BMI, age and HP-HMG-starting-dosage, and still, a significantly higher number of oocytes (retrieved/mature) were obtained in the RG-group (7.2±5.61 vs 9.8±6.13;p&amp;lt;0.001 / 5.7±4.7 vs 7.8±5.0;p&amp;lt;0.001, respectively). The progesterone-levels on trigger day in the nRG-group was 0.5±0.3ng/ml and 0.6±0.4ng/ml in the RG group, which is significantly different (p &amp;lt; 0.001), however, clinically insignificant. Limitations, reasons for caution The retrospective design is a limitation to this study as well as the exclusion of ovarian stimulation cycles, which were cancelled and no oocyte pick-up procedure was performed. Furthermore, in some age-categories, patients in RG and non-RG were different regarding their basic characteristics. Wider implications of the findings This analysis demonstrates, that in specific patient populations, gonadotropin-dosage can be reduced without impacting the oocyte yield and preventing progesterone-elevation despite higher oocyte yield. Furthermore, reduction of gonadotropins towards the end of the follicular phase results in a more physiologic course of the gonadotropin-levels during ovarian stimulation. Trial registration number not applicable

O-128 Letrozole co-treatment during ovarian stimulation in antagonist cycles augments follicle growth and exerts pronounced effects on endocrinology: a randomized controlled trial

Abstract Study question What are the endocrine and paracrine effects of letrozole (LZ) co-treatment during ovarian stimulation (OS) and is follicle growth and recruitment affected? Summary answer Letrozole induces marked changes in the follicular and luteal phase endocrinology causing potentiation of follicle growth and corpus luteum function without affecting follicle recruitment. What is known already Letrozole is a 3rd generation aromatase inhibitor that is well-established as an effective ovulatory agent, while its possible benefits in standard in vitro fertilization (IVF) protocols are less thoroughly investigated. Study design, size, duration Double-blinded, placebo-controlled, randomized study with LZ or placebo intervention during OS for IVF treatment, a preceding baseline natural cycle, and a succeeding follow-up visit, in total three consecutive cycles. Participants were enrolled between August 2016 and November 2018. Participants/materials, setting, methods Thirty-one healthy, normo-responding women underwent a natural baseline cycle and an antagonist stimulation cycle with either LZ 5 mg/day (n = 16) or placebo (n = 15) during the follicular phase. Every third day, monitoring of follicle count and -growth and blood analyses of 12 endocrine and paracrine parameters were performed. Follicle recruitment was correlated to endocrine parameters, and differences in follicle recruitment, follicle growth and hormone parameters between groups were assessed. Main results and the role of chance In the LZ group, the number of follicles &amp;gt; 16 mm at oocyte pick up was increased (+2.0, 95% CI [0.1;3.8], p = 0.036), while the total number of follicles were the same (+0.2, 95% CI [-5.8;6.1], p = 0.958). The FSH concentration was increased in the LZ group at stimulation day 5 (p &amp;lt; 0.05), though the total FSH consumption during OS was similar (difference: -20 IU, 95% CI [-175;136], p= 0.794). Letrozole co-treatment suppressed oestradiol (E2) concentrations in the follicular phase (area under the curve (AUC) -62%, p &amp;lt; 0.001) and luteal phase (AUC -31%, p = 0.046). We found increased follicular phase LH (AUC +20.5%, p = 0.033), androstenedione (AUC +22%, p = 0.016), testosterone (AUC +33%, p = 0.013), and 17-OH-progesterone (+132%, p = 0.027). Interestingly, the corpus luteum (CL) output in the LZ group was increased with elevated luteal phase progesterone (AUC +35%, p = 0.043), Inhibin A (AUC +67%, p = 0.011), androstenedione (AUC +22%, p = 0.006), and testosterone (AUC +22%, p = 0.012). Hormone parameters were similar between groups at the follow-up visit. There was no effect of LZ co-treatment on recruitment of the next follicle cohort (p = 0.821). Limitations, reasons for caution This study included a relatively small, selected group of healthy women with an expected normal ovarian function and reserve, and the effects of LZ may therefore be different in other patient groups. Wider implications of the findings We confirm previous findings concerning increased follicle growth, increased endogenous FSH and androgen production, and support the rationale for use of LZ co-treatment as a form of endogenous androgen priming sensitizing the follicle to FSH. Letrozole appears to improve the luteal phase with better stimulation of CL and P4 secretion. Trial registration number NCT02939898

P-671 Progestin primed ovarian stimulation using dydrogesterone in oocyte donation cycles: a longitudinal study

Abstract Study question Does progestin primed ovarian stimulation (PPOS) with dydrogesterone starting from stimulation day 6 yield similar outcomes compared with a GnRH antagonist protocol in oocyte donors? Summary answer The number of retrieved oocytes and metaphase II oocytes was similar in both stimulation protocols. What is known already The use of progestins in the follicular phase to suppress a premature LH surge as an alternative to the GnRH analogue is an emerging regimen for ovarian stimulation. There is robust evidence of the safety and efficacy of PPOS compared to conventional ovarian stimulation regimens in oocyte donation cycles. Progestins and gonadotropins are typically administered simultaneously from day 2 or day 3 of the cycle onwards. Reports on initiation of progestins at a later stage, from day 6 of stimulation, are scarce. Study design, size, duration This is a retrospective longitudinal cohort study comparing two strategies of ovarian stimulation in the same oocyte donors. Oocyte donors who had a PPOS protocol between January 2021 and December 2021 and who had another ovarian stimulation cycle using a GnRH antagonist protocol within the same year were included in the analysis. Dydrogesterone 10 mg twice daily was started on day 6 of stimulation onwards. In total, 68 cycles from 34 oocyte donors were Included. Participants/materials, setting, methods All oocyte donors had the same type of gonadotropin and daily dose in both stimulation cycles. The primary outcome was the number of retrieved cumulus oocyte complexes (COC) and the number of metaphase II oocytes. Secondary outcomes were the duration of stimulation, the total dose of gonadotropins, the occurrence of premature ovulation and the difference in total cost between the two stimulation protocols. Main results and the role of chance The average female age was 28.3 years (SD 4.3), BMI 24.0 kg/m2 (SD 2.9) and AMH 2.9 µg/l (SD 1.5). When comparing the PPOS cycle with the GnRH antagonist cycle, the mean number of retrieved COCs was 20.0 ± 9.9 and 20.2 ± 9.3, respectively (p = 0.33) and the number of metaphase II oocytes was also similar (15.6 ± 7.9 and 16.9 ± 8.0, respectively; p = 0.35). The duration of stimulation (10.6 ± 1.7 days versus 10.9 ± 1.7 days; p = 0.26) and cumulative dose of gonadotropins (2284.6 ± 494.9 IU versus 2338.2 ± 462.1 IU; p = 0.25) were comparable in the PPOS and the GnRH antagonist group. No events of premature ovulation were observed in both groups. There was a significant difference in total medication cost per cycle between both protocols, 903.3 ± 195.7 € for PPOS versus 1205.3 ± 243.9 € (p &amp;lt; 0.001) for the GnRH antagonist protocol. This means a cost reduction of 25% for the PPOS group compared to the GnRH antagonist group. GEE multivariate regression analysis allowing adjustment for relevant confounders (age, BMI, AMH) showed that the type of protocol was not significantly associated with the number of MII oocytes retrieved (coefficient 1.23, p = 0.33). Limitations, reasons for caution The small sample and the retrospective design are limitations of this study. Wider implications of the findings PPOS is a patient friendly and well-tolerated protocol. A simplified protocol of ovarian stimulation with the advantage of cost reduction. The protocol can easily be applied in oocyte donation and cycles with elective freeze all. Adequately powered RCTs should be performed to confirm our results. Trial registration number not applicable