Controlled Ovarian Stimulation Cycles Research Articles

Assessment of Repetitive Controlled Ovarian Stimulation (COS) Cycles on Oocyte Donors: Impact on Oocyte Quality and Viable Embryo Yield.

The utilization of donor eggs has broadened the options for Assisted Reproductive Technology (ART) among women facing challenges with egg quantity or quality. Given that donors are typically selected from young and fertile individuals, In Vitro Fertilization with egg donation (IVF-ED) tends to exhibit higher rates of implantation, pregnancy, and live births compared to IVF with the woman's own eggs, especially for females over 35years old. This has led to a projected increase in the demand for IVF-ED, surpassing the number of available donors. Consequently, many centers opt to use oocyte donors for multiple cycles. However, the correlation between repeated Controlled Ovarian Stimulation (COS) cycles and the performance of donors in terms of viable blastocyst stage embryo (VEC) or blastocyst embryo rate is not definitively established and remains of interest. This study aims to explore the preimplantation characteristics of embryo development and oocyte maturation status based on the number of donor COS cycles, employing a Generalized Linear Mixed Model (GLMM) framework. The study encompasses 1965 embryo transfer (ET) cycles involving 399 donors who underwent a minimum of two and a maximum of nine controlled ovarian hyperstimulation (COS) cycles. The findings indicate that, with the patient undergoing six or more cycles of ovarian stimulation, despite a 3.9% increase in both maturation and fertilization rates, there is a corresponding decrease of 4.5% in VEC rate and 4.7% in blastulation rates. In essence, an escalating number of donor COS cycles appears to be associated with a disadvantageous reduction in embryo quality.

Fertilization, pregnancy, and neonatal outcomes after IVF, rescue ICSI, and ICSI in unexplained infertility: A retrospective study

AbstractConventional intracytoplasmic sperm injection (ICSI) is not recommended for nonmale infertile patients to avoid fertilization failure (FF) in view of controversies regarding safety issues. Among the strategies that may help to promote the use of in vitro fertilization (IVF) for women with a high risk of FF, rescue ICSI (R‐ICSI) has attracted attention. This study aimed to evaluate the efficacy of short‐term insemination combined with early R‐ICSI in the treatment of unexplained infertility. A total of 952 controlled ovarian stimulation (COS) cycles for unexplained infertility were divided into short‐term IVF (short‐term insemination without R‐ICSI, n = 500), R‐ICSI (short‐term insemination with R‐ICSI, n = 141), and ICSI (conventional ICSI, n = 311) groups. Patients underwent consecutive transfer cycles until live birth, or until all embryos from the first COS cycle were used. Laboratory data and clinical outcomes from short‐term IVF, R‐ICSI, and ICSI groups were compared. Short‐term IVF and ICSI groups were superior to R‐ICSI group in polyspermy rate, available embryo rate, and top‐quality embryos rate. Short‐term IVF, R‐ICSI, and ICSI groups underwent 705 (500 fresh and 205 frozen‐thawed cycles), 190 (141 fresh and 49 frozen‐thawed cycles), and 445 (311 fresh and 134 frozen‐thawed cycles) transfer cycles, resulting in 294, 76, and 190 live birth cycles, respectively. Comparison of pregnancy outcomes among these three groups demonstrated similar clinical pregnancy rates and live birth rates in fresh and frozen‐thawed embryo transfer cycles. There was no significant difference in the cumulative live birth rate among these three groups. R‐ICSI group showed similar neonatal outcomes compared with short‐term IVF and ICSI groups, including the rates of low birth weight, fetal macrosomia, small for gestational age and large for gestational age. Short‐term insemination combined with early R‐ICSI achieved satisfactory pregnancy and neonatal outcomes, albeit with a high polyspermy rate, which was an effective alternative to avoid excessive use of ICSI in unexplained infertility.

Adding L-carnitine to antagonist ovarian stimulation doesn’t improve the outcomes of IVF/ ICSI cycle in patients with polycystic ovarian syndrome: a double-blind randomized clinical trial

ObjectiveTo investigate the effect of L-carnitine supplementation during the controlled ovarian stimulation (COS) cycle with antagonist protocol in patients with polycystic ovary syndrome (PCOS) diagnosis undergoing IVF/ICSI treatment.Methods and materialsThis was a double-blind clinical trial study including 110 patients with PCOS attended to Royan Institute between March 2020 and February 2023. At the beginning of the COS cycle, the eligible patients were allocated into two groups randomly according to the coding list of the drugs prepared by the statistical consultant. In the experimental group, patients received 3 tablets daily (L-carnitine 1000 mg) from the second day of menstruation of the previous cycle until the puncture day in the cases of freeze-all embryos (6 weeks) or until the day of the pregnancy test (8 weeks) in fresh embryo transfer cycle. In the control group, patients received 3 placebo tablets for the same period of time. Weight assessment and fasting blood sugar and insulin tests, as well as serum lipid profile were also measured at the baseline and ovum pick-up day. The results of the COS cycle as well as the implantation and pregnancy rates were compared between groups.ResultsFinally, 45 cases in L-carnitine group versus 47 cases in the placebo group were completed study per protocol. Data analysis showed that the two groups were homogeneous in terms of demographic characteristics and baseline laboratory tests and severity of PCOS. There is no statistically significant difference in terms of the oocyte recovery ratio and oocyte maturity rate, and the number and quality of embryos, as well as the rates of the fertilization, chemical and clinical pregnancy between groups. However, the means of weight (P < 0.001) and serum levels of fasting blood sugar (P = 0.021), fasting insulin (P = 0.004), triglyceride (P < 0.001) and cholesterol (P < 0.001), LDL (P < 0.001) have significantly decreased in women after consuming L-carnitine supplementation.ConclusionThe oral intake of L-carnitine during COS in PCOS women for 6 weeks had no effect on COS and pregnancy outcomes. However, taking this supplement for 6 weeks has been associated with weight loss and improved lipid profile and serum glucose.Trial registrationThe study was registered in the Clinicaltrials.gov site on December 17, 2020 (NCT04672720).

Segmented in vitro fertilization and frozen embryo transfer in levonorgestrel-releasing intrauterine device treated patients with endometrial cancer

PurposeTo evaluate the efficacy of levonorgestrel-releasing intrauterine device (LNG-IUD) during controlled ovarian stimulation (COS) in patients with early-stage endometrioid endometrial cancer (EEC).MethodsA retrospective study was conducted on patients with stage IA1 EEC who achieved complete response after fertility-sparing treatment from December 2018 to December 2021, with all the women who underwent COS having LNG-IUDs inserted in their uterine cavity.Results16 patients were enrolled who underwent 26 COS cycles and average age was 33.19 ± 4.04 years. 12 patients had 19 subsequent frozen-thawed embryo transfer (FET) cycles. Among the other four patients, no embryos were obtained in 1 patient, 1 patient got pregnancy spontaneously with term delivery after COS, 1 patient relapsed before FET, and 1 patient did not receive embryo transfer for personal reason. Among 19 FET cycles, the clinical pregnancy and live birth rates in each ET cycle were 36.84% (7/19) and 26.32% (5/19), respectively. 7 clinical pregnancies resulted in 2 miscarriages (28.6%), and 5 live births (71.4%). Totally 6 patients achieved 7 live births, and the cumulative live birth rate was 37.5% (6/16). Three (18.75%) out of 16 patients relapsed after COS during the follow-up period (31.31 ± 15.89 months) and two of them were initially diagnosed with moderately differentiated EEC. Time interval from COS to relapse was 6.63,11.67 and 16.23 months, respectively.ConclusionThe combination of LNG-IUD treatment and segmented IVF may be a viable treatment strategy to improve oncological and reproductive outcomes for patients with early-stage EEC.

P-583 Is donor age a major factor in egg donation for clinical outcome?

Abstract Study question How significant is the age factor for clinical success of the controlled ovarian stimulation cycles (COS) in various age subgroups of the egg donors? Summary answer There is no significant negative impact of the donor age for clinical outcome in egg donation cycle. What is known already It was shown that the donor age was an independent factor for ovarian stimulation cycles outcomes, which could predict over 80% of IVF success. It also reported that there were no associations between donor oocyte harvest and probability of live birth, adjusting for donor age. Different studies showed that the donor age less than 25 years old doesn’t predict better embryo development or clinical pregnancy outcome for egg donation cycles in the same age group of recipients. Study design, size, duration Three IVF centers having been involved in this study, data used from donors (n = 6319) examined between 2019-2022, they were divided into 3 age groups (A: 19-22, B: 23-29, C: ≥30 years). COS protocols were analyzed including different parameters: number of oocytes retrieved, antral follicle count (AFC), maturation rate (MR), utilization rate (UR) and follicle-to-oocyte index (FOI). The association between COS cycle parameters and the age characteristics was assessed by T-Student (parametric) or U-Mann-Whitney (non-parametric). Participants/materials, setting, methods In group A mean age 19-22 years , group B 23-29 years and group C - over 30 years donors 717, 1000, 1000 respectively COS protocols were analysed including different parameters such as: number of oocytes retrieved, maturation rate (MR), utilization rate (UR) and follicle-to-oocyte index (FOI). Main results and the role of chance Mean age in groups: A (n = 717) - 21,0±1,1; B (n = 1000) - 26,3±1,9 and in group C (n = 1000) - 31,6±1,5. The mean number (SD) of oocytes harvested: 26,94 (12,40), 25,98 (12,03) and 23,22 (11,49) oocytes in groups A, B and C respectively. The same tendency with no statistical difference was observed for values of AFC: 33,24 (14,55), 32,41 (13,86) and 29,77 (12,98). Values of FOI in A and B groups were higher than in C: 81,85 (17,37), 81,06 (18,54) and 78,24 (17,97) in groups A, B and C, respectively with statistically proven difference (p = &amp;lt;0.05) for both. MR was higher in C group (83±15%) vs A (80±16%) and B (81±16%) with proven statistical significance (p = &amp;lt;0.05). Recipients of group A (average age 33,05) - received 94,55% FR, 66,15% used BR and % 57,84 CPR. Group B recipients (age average 35,08) - 92,88% FR, 61,69 used BR and 54,77% CPR. Recipients of Group C ( average age 33,07) - 94,55% FR, 60,01% used BR and 59,05% CPR. Limitations, reasons for caution This study is limited by its retrospective nature and more studies are necessary to investigate not only COS outcomes but also the impact of the age related factors on pregnancy rates. Wider implications of the findings Our findings may bring a controversial spotlight on the doubtful issue of the relationship between donor age and clinical and embryo outcomes of the COS programs. Trial registration number not applicable

P-606 Does trigger timing make a difference in oocyte donation?

Abstract Study question Is there optimal trigger timing in controlled ovarian stimulation (COS) for egg donors for better clinical outcome? Summary answer Different trigger timings may not affect oocyte maturity rate. 35 hour’s trigger may create optional timing for embryology to complete fertilization into a natural concept. What is known already Trigger exposure time is still a debatable clinical issue. Ovulation is triggered by administration of hCG or GnRH agonist, with retrieval taking place between 35th and 38th hour post triggering. There was a tendency to decrease post maturity risk for MII oocytes also early triggering will create optional timing for embryology laboratory for denudation, oocyte vitrification and fertilization process under oocyte cytoplasmic maturity (38 hours post trigger) and natural concept fertilization (till 40 hours post trigger) for better clinical outcome. Study design, size, duration This single center retrospective study included oocyte donors (n = 1289) with different timing of eggs retrieving. They were divided into two groups: group A, with exposure of the medicine trigger for 35 h and group B with timing which was 36 h before egg retrieval. We evaluated the concordance between the follicle-to-oocyte index (FOI), antral follicle count (AFC), number of MII oocytes, maturation rate (MR), utilization rate (UR) and the timing of triggering. Participants/materials, setting, methods The number of donors was 784 and 505 in A and B groups respectively. The mean age of the patients in this study was (SD) 26,2 (3,2) and 26,7 (3,3) years. Cycle characteristics were compared. Data was assessed using the Shapiro-Wilk test for the normality of the distribution of the variables. The association between COS cycle parameters and the differences in COS output was assessed by T-Student (parametric) or U-Mann-Whitney (non-parametric). Main results and the role of chance Donors in groups A and B had a similar mean number of oocytes retrieved (33,50±14,12 vs 30,44±13,00), in groups A and B respectively. The same tendency with no statistical difference was mentioned for values number of MII oocytes (SD): 25,16 (11,73) and 20,50 (10,19), for MR - 81% vs 80% and for AFC: 33,50 (14,18) and 30,44 (13,00) in groups A and B, respectively. Unexpectedly, values for UR and FOI (SD) were statistically significant different (p = &amp;lt;0.05): 94,1% (17,2) vs 89,1% (20,2) and 92,51 (11,43) vs 83,43 (15,63), accordingly, in group A and B respectively. Group A donor oocytes vitrified on 38 hours post trigger and fertilized on 40 hours from sibling oocytes. Group B donor oocytes vitrified on 39 hours and fertilized on 42 hours from sibling oocytes. Values for oocyte survival rate post warming were statistically non-significant different (p &amp;gt; 0.05): 96,64% (10,95) vs 95,08% (10,03). Cleavage arrest rate were statistically significant different; 8,01% vs 28,06% and used blastocysts rate were statistically significant different; 54,67% (5,02) vs 42,36% (4,08). Values for fertilization were statistically non-significant different; (p &amp;gt; 0.05): 98,64% (12,24) vs 97,08% (11.96) and used blastocysts rate were statistically significant different; 67,22% (6,18) vs 51,88%. (5,07) Limitations, reasons for caution This study is limited by its retrospective nature and the established strict time parameters of the study can be considered a limitation. Wider implications of the findings As we can see, the issue of the optimal period for oocyte retrieval after the administration of human chorionic gonadotropin should be considered very individually and in further studies it is possible to take into account wider time intervals in the design of trials. Trial registration number not applicable

POvaStim: An online tool for directing individualized FSH doses in ovarian stimulation

POvaStim: An online tool for directing individualized FSH doses in ovarian stimulation

Comparison of dual-trigger and human chorionic gonadotropin-only trigger among polycystic ovary syndrome couples who underwent controlled ovarian stimulation and intrauterine insemination: A retrospective cohort study.

The dual-trigger regime, consisting of gonadotrophin releasing hormone agonist and human chorionic gonadotropin (HCG), has been shown to offer advantage over the HCG-only trigger regime. However, little is known about the influence of dual-trigger or HCG-only trigger regime on the reproductive outcome of polycystic ovary syndrome (PCOS) couples undergoing controlled ovarian stimulation (COS) and intrauterine insemination (IUI). A total of 404 cycles of COS and IUI treatments from couples with PCOS were enrolled, and divided, according to the regime of trigger, into dual-trigger group (n = 109, 0.1-0.2 mg gonadotrophin releasing hormone agonist plus 6000 IU HCG) and HCG-only group (n = 295, 10,000 IU HCG or 250 μg recombinant HCG). Baseline characteristics of the 2 groups were comparable (all P > .05). In dual-trigger group, live birth rate, clinical pregnancy rate and β -HCG positive rate were all higher as compared to the HCG-only group (20.18% vs 18.98%, 25.69% vs 23.39% and 28.44% vs 25.08% respectively), despite the differences failed to achieve statistical significances (all P > .05). Moreover, early miscarriage rate and multiple pregnancy rate of the dual-trigger group were lower than those of the HCG-only group (17.86% vs 18.84% and 3.57% vs 7.25% respectively), although no statistical significances were found (all P > .05). Additionally, logistic regression analysis revealed that age contributed significantly to the live birth of couples with PCOS ( P = .043, OR = 0.900). Dual-trigger regime for oocyte maturation seems to associate with beneficial improvements in reproductive outcomes of PCOS couples undergoing COS and IUI. Instead of HCG-only trigger, dual-trigger regime might be an alternative option in COS and IUI cycles for couples with PCOS.

Repeated controlled ovarian stimulation-induced ovarian and uterine damage in mice through the PI3K/AKT signaling pathway.

The effects of repeated controlled ovarian stimulation (COS) on the female reproductive system are still controversial. This study investigated the effects of repeated COS on the ovaries and uterus of mice and its possible mechanism. Female ICR (Institute of Cancer Research) mice were subjected to the COS using pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) for 1, 3, 5, and 7 cycles. Serum hormone levels, reactive oxidative stress (ROS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD) in the mouse ovary and uterus were analyzed by ELISA. The morphology of the ovary and endometrium, ovarian apoptosis, and expressions of the vascular endothelial growth factor (VEGF), leukemia inhibitory factor (LIF), PI3K, AKT, Bax, and Bcl-2 in the ovarian and uterine tissues were tested by hematoxylin-eosin (HE) staining, immunohistochemistry, and western blot. The results showed that repeated COS significantly decreased the hormone level (estradiol, progesterone and anti-Müllerian hormone), high-quality of the MII oocyte ratio, oocyte and embryo number, antioxidant capacity (T-AOC, SOD activity), and the protein level of Bcl-2, LIF, and VEGF, but increased the oxidative damage (ROS, 8-OHdG content), embryo fragment ratio, and expression of pro-apoptotic protein Bax. In addition, the expressions of p-PI3K and p-AKT also decreased with the increase of COS cycle. In conclusion, repeated COS causes ovarian and uterus damage possibly through the PI3K/AKT signaling pathway, and this finding may provide some experimental basis for guiding clinical treatment.

Outcomes after assisted reproductive technology in women with cancer: a systematic review and meta-analysis.

What are the associations between a history of cancer and outcomes after ART? Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART. Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes. We conducted a systematic review with meta-analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021. Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-and-fill method to assess funnel plot asymmetry. Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage. Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes. Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis. This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests. N/A.

P-618 Artificial intelligence (AI) to optimize ovarian stimulation for IVF: from stimulation protocols to total and mature oocyte yield

Abstract Study question Can AI, based on demographic and clinical data, enhance IVF success by choosing the optimal controlled ovarian stimulation (COS) to maximize total and mature oocyte yield? Summary answer Using patient demographics, routine preliminary blood tests and antral follicle count, this AI tool enables personalized COS protocol to optimize total/mature oocyte yield (±3.5 oocytes). What is known already Number of retrieved oocytes and mature oocyte yield are major factors in IVF success. When planning an IVF cycle, doctors decide the stimulation protocol based on certain demographics and basic clinical data. Yet, the treatment recommendations based on these parameters vary globally. AI, an umbrella term for multiple data-driven disciplines, has recently been employed to assist in various stages of the IVF process, particularly in embryo selection for transfer, for COS drug dosing, and for tracking follicular growth to better predict the trigger date. Can AI optimize treatment regimen choice and predict oocyte quantity and quality? Study design, size, duration Training of the AI aimed to build a model capable of predicting mature oocyte yield for a given COS protocol. An initial retrospective, anonymized dataset of 1463 autologous cycles from 757 patients collected between 2017-2021 was reduced to 769 cycles with complete data from 461 patients and used as input for the AI model. A multilayer perceptron deep learning network was implemented 100 times to validate statistical predictions of total/mature oocyte yield. Participants/materials, setting, methods Patients underwent IVF treatment at a private ART center using antagonist (77%), micro-dose Lupron flare (20%) or minimal-stimulation (3%) COS protocols. Demographic data including age, diagnoses, ethnicity, body mass index (BMI), anti-Müllerian hormone (AMH), Day-3 AFC, estradiol, and progesterone levels were used as input along with protocol type. An 80%, 10%, 10% split of the data was used for AI training, validation, and testing, respectively. Mean patient age was 36.8±4.3 years. Main results and the role of chance The AI model predictions were generated from baseline data, representing the clinical scenario prior to the start of a COS cycle. The mean absolute error (MAE) for the number of mature oocytes retrieved per cycle was 3.5. To assess the role of chance, performance was compared to a random model that assigned each true mature oocyte yield to a random patient from the dataset, resulting in an MAE of 6.1. (p &amp;lt; 0.001; Mann-Whitney U test). When predicting total oocyte count, MAE was 4.6 and 7.3 for the AI and random models, respectively (p &amp;lt; 0.001). The Spearman correlation coefficient revealed a strong positive correlation between the actual numbers of mature oocyte retrieved and mean predicted oocyte yield (0.748; p &amp;lt; 0.0001). Using this model, a preliminary AI tool was developed which can predict total and mature oocyte yield based on different planned COS protocols. Limitations, reasons for caution The results were generated from a model trained using retrospective, single-center data. To further validate the model, additional testing is needed using data from different ART centers, with additional COS protocols, and analyses comparing the results of the first COS cycle to the subsequent cycles of the same patient. Wider implications of the findings This oocyte yield prediction model, once validated, can be used by infertility specialists worldwide as a data-driven approach to individualized COS, with the potential to assist cycle programing and optimize lab preparations. Further training with data concerning COS drug dosages and complications, including ovarian hyperstimulation syndrome, will increase clinical application. Trial registration number N/A

P-674 Optimal aspiration pressure level of suction pump for oocyte retrieval in IVF-ET

Abstract Study question What is the appropriate suction pump pressure for oocyte retrieval in terms of oocytes and embryos quality? Summary answer The pressure of 150mmHg had a significantly higher number of oocytes retrieved compared with 120mmHg, but the oocyte quality and embryo quality were comparable. What is known already There is no conclusion on the optimal aspiration pressure level for oocyte retrieval in controlled ovarian stimulation (COS), and a variety of pressures between 100 and 200 mmHg are used, often based on manufacturer’s instructions. Study design, size, duration A retrospective analysis was performed on a total of 211 COS cycles of infertilie patients from September 2019 to December 2021 in a single tertiary center. 110 cycles were included in the 120 mmHg pressure group and 101 cycles were included in the 150 mmHg pressure group. Participants/materials, setting, methods Age, AMH, antral follicle count (AFC), the proportion of ICSI, the number of retrieved oocytes, the number of MII oocytes, MII rate, degeneration rate on day 1 of culture, and the number of embryos on day 3 of culture was compared and analyzed between the two groups. Variables such as Age, AMH, and AFC that may affect the results were corrected using analysis of covariance. Main results and the role of chance The number of retrieved oocytes was significantly higher in the 150 mmHg group compared to the 120 mmHg group (10.3 vs. 8.4, p = 0.016). Neither the number of MII oocytes nor the MII rate was significantly different between the two groups (6.1 vs. 5.5, p = 0.509 and 67.2% vs. 73.4%, p = 0.437 respectively). The degeneration rate on day 1 of culture and the number of embryos on day 3 of culture were also not significantly different between the two groups (6.2% vs. 4.4%, p = 0.282 and 5.7% vs. 4.7%, p = 0.109 respectively). Limitations, reasons for caution Since this study analyzed the appropriate pump pressure for oocyte retrieval in infertile patients, caution is needed in extending the study results to patients undergoing oocyte retrieval for the purpose of fertility preservation. Wider implications of the findings The results of this study revealed that oocyte collection could be efficiently performed without damaging the oocytes even with a higher aspiration pressure of 150 mmHg. Trial registration number not applicalbe

P-685 Optimal aspiration pressure level of suction pump for oocyte retrieval in IVF-ET

Abstract Study question What is the appropriate suction pump pressure for oocyte retrieval in terms of oocytes and embryos quality? Summary answer The aspiration pressure of 150mmHg had a significantly higher number of oocytes retrieved compared with 120mmHg, but the oocyte quality and embryo quality were comparable. What is known already There is no conclusion on the optimal aspiration pressure level for oocyte retrieval in controlled ovarian stimulation (COS), and a variety of pressures between 100 and 200 mmHg are used, often based on manufacturer’s instructions. Study design, size, duration A retrospective analysis was performed on a total of 211 COS cycles from September 2019 to December 2021 in a single tertiary center. The analysis was performed on patients who underwent COS for the purpose of infertility treatment. Participants/materials, setting, methods 110 cycles were included in the 120 mmHg pressure group and 101 cycles were included in the 150 mmHg pressure group. Age, AMH, antral follicle count (AFC), the proportion of ICSI, the number of retrieved oocytes, the number of MII oocytes, MII rate, degeneration rate on day 1, and the number of embryos on day 3 were compared between the two groups. Variables such as Age, AMH, and AFC were corrected using analysis of variance. Main results and the role of chance The number of retrieved oocytes was significantly higher in the 150 mmHg group compared to the 120 mmHg group (10.3 vs. 8.4, p = 0.016). Neither the number of MII oocytes nor the MII rate was significantly different between the two groups (6.1 vs. 5.5, p = 0.509 and 67.2% vs. 73.4%, p = 0.437 respectively). The degeneration rate on day 1 and the number of embryos on day 3 were also not significantly different between the two groups (6.2% vs. 4.4%, p = 0.282 and 5.7% vs. 4.7%, p = 0.109 respectively). Limitations, reasons for caution Since this study analyzed the appropriate pump pressure for oocyte retrieval in infertile patients, caution is needed in extending the study results to patients undergoing oocyte retrieval for the purpose of fertility preservation. Wider implications of the findings The results of this study revealed that oocyte collection could be efficiently performed without damaging the oocytes even with a higher aspiration pressure of 150 mmHg. Trial registration number Not applicable

An Online Tool Using Basal or Activated Ovarian Reserve Markers to Predict the Number of Oocytes Retrieved Following Controlled Ovarian Stimulation: A Prospective Observational Cohort Study.

BackgroundPredicting the number of oocytes retrieved (NOR) following controlled ovarian stimulation (COS) is the only way to ensure effective and safe treatment in assisted reproductive technology (ART). To date, there have been limited studies about predicting specific NOR, which hinders the development of individualized treatment in ART.ObjectiveTo establish an online tool for predicting NOR.Materials and MethodsIn total, 621 prospective routine gonadotropin releasing hormone (GnRH) antagonist COS cycles were studied. Independent variables included age, body mass index, antral follicle counts, basal FSH, basal and increment of anti-mullerian hormone, Luteinizing hormon, estradiol, testosterone, androstenedione, and inhibin B. The outcome variable was NOR. The independent variables underwent appropriate transformation to achieve a better fit for a linear relationship with NOR. Pruned forward selection with holdback validation was then used to establish predictive models. Corrected Akaike’s information criterion, Schwarz–Bayesian information criterion, scaled –log[likelihood], and the generalized coefficient of determination (R 2) were used for model evaluation.ResultsA multiple negative binomial regression model was used for predicting NOR because it fitted a negative binomial distribution. We established Model 1, using basal ovarian reserve markers, and Model 2, using both basal and early dynamic markers for predicting NOR following COS. The generalized R 2 values were 0.54 and 0.51 for Model 1 and 0.64 and 0.62 for Model 2 in the training and validation sets, respectively.ConclusionModels 1 and 2 could be applied to different scenarios. For directing the starting dose of recombinant follicle stimulation hormone (rFSH), Model 1 using basic predictors could be used prior to COS. Model 2 could be used for directing the adjustment of rFSH dosages during COS. An online tool (http://121.43.113.123:8002/) based on these two models is also developed. We anticipate that the clinical application of this tool could help the ART clinics to reduce iatrogenic ovarian under- or over-responses, and could reduce costs during COS for ART.

Clinical efficacy of dual trigger with human chorionic gonadotropin and a gonadotropin-releasing hormone agonist for women undergoing fertility preservation.

PurposeTo determine the optimal maturation method to increase the yield of mature oocytes, especially for cancer patients with fewer chances of fertility preservation (FP) before gonadotoxic therapy.MethodsA total of 373 cycles in 293 patients undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin‐releasing hormone (GnRH) antagonist protocol were enrolled. The control group (n = 225) received 250 µg of recombinant human chorionic gonadotropin (rhCG) while the study group (n = 148) received 250 µg of rhCG and 0.2 mg of triptorelin for triggering. Subgroup analyses were performed for stimulation cycles with diminished ovarian reserve (DOR; anti‐Müllerian hormone (AMH) levels <1.1 ng/ml, n = 86), with endometrioma (n = 104), or with breast cancer and endometrial cancer using 5 mg of letrozole during the COS cycles (n = 84).ResultsThere was no significant difference in the baseline characteristics or the number of total and mature oocytes between the two groups. Subgroup analyses for women with endometrioma or DOR showed similar results. However, the dual trigger group had a significantly higher number of mature oocytes than the rhCG trigger group in breast and endometrial cancer patients using letrozole during the COS cycles (6.9 ± 6.0 vs. 4.6 ± 3.6, p = 0.034). The maturation rate was higher in the dual trigger group, although the difference was not statistically significant (59.3 ± 26.7 vs. 50.0 ± 28.0, p = 0.124).ConclusionsDual triggering can be an efficient maturation method to maximize the yield of mature oocytes in breast or endometrial cancer patients using letrozole‐combined GnRH antagonist protocol for FP.

The novel oral gonadotropin‐releasing hormone receptor antagonist relugolix is a new option for controlled ovarian stimulation cycles

PurposeRelugolix is an oral gonadotropin‐releasing hormone antagonist (GnRHant), which was first introduced in 2019. This study investigated the effects of the conventional injectable GnRHant formulation and this new oral GnRHant formulation on controlled ovarian stimulation (COS) cycles.MethodsRelugolix was administered in 126 cycles and conventional GnRHant injection was administered in 658 cycles (controls). The follicle stimulation was performed by an antagonist method, and for final oocyte maturation, recombinant human chorionic gonadotropin (rHCG), or gonadotropin‐releasing hormone agonist (GnRHa), or both (dual trigger) were selected. The number of retrieved oocytes was counted and then they were evaluated for subsequent development up to cleavage stage.ResultsThe number of retrieved oocytes which was the primary outcome of this research was affected by the combination of GnRHant type and the final oocyte maturation agent. The combination of relugolix and a GnRHa trigger showed a significantly lower number of retrieved oocytes (p < 0.001) than the other combinations.ConclusionsRelugolix is a new option for COS cycles, but should be carefully combined with the final maturation agent.Clinical trial approvalThis study was conducted after approval by the Medical Corporation Sankeikai Institutional Ethics Committee (approval number: 2019‐34).

The Significance of Planned Fertility Preservation for Women With Endometrioma Before an Expected Ovarian Cystectomy

Endometrioma is known to reduce the ovarian reserve and the extent of the decrease is more severe when ovarian surgery is performed. Therefore, to prevent this decline in fertility, patients with endometrioma are considered candidates for preoperative fertility preservation (FP). In this study, we evaluate the efficacy of FP in women with endometrioma before planned ovarian surgery. A total of 95 cycles in 62 patients with endometrioma, undergoing controlled ovarian stimulation (COS) for FP using a gonadotropin-releasing hormone (GnRH) antagonist protocol before an expected ovarian surgery, were enrolled retrospectively. COS outcomes were compared according to endometrioma laterality. Additionally, first COS cycle outcomes in patients with endometrioma were compared with those in infertile patients, or in patients with a benign ovarian cyst using propensity score matching. When multiple COS cycles were performed, the results of cumulative cycles were analyzed. Embryo quality was worse in the bilateral endometrioma group. Compared with the infertile patient group, the patients with endometrioma had significantly lower Anti-Müllerian Hormone (AMH) and fewer numbers of oocytes retrieved (median, 3.3 vs. 1.2, p<0.001; 7.0 vs. 4.0, p=0.009, respectively). Compared with mature oocytes in infertile patients or patients with a benign cyst, mature oocytes were fewer in patients with endometrioma, but this was not statistically significant (median, 4.0 vs. 3.0, p=0.085; 5.5 vs. 3.0, p=0.052, respectively). The median value of the cumulative number of cryopreserved oocytes or embryos was 14.5 up to the fourth cycle compared to 3 up to the first cycle, with cumulative effect. Women with endometrioma should be counseled for FP before planned ovarian cystectomy. The number of cryopreserved oocytes or embryos can be increased by repeated cycles.

What is the threshold of mature oocytes to obtain at least one healthy transferable cleavage-stage embryo after preimplantation genetic testing for fragile X syndrome?

What are the chances of obtaining a healthy transferable cleavage-stage embryo according to the number of mature oocytes in fragile X mental retardation 1 (FMR1)-mutated or premutated females undergoing preimplantation genetic testing (PGT)? In our population, a cycle with seven or more mature oocytes has an 83% chance of obtaining one or more healthy embryos. PGT may be an option to achieve a pregnancy with a healthy baby for FMR1 mutation carriers. In addition, FMR1 premutation is associated with a higher risk of diminished ovarian reserve and premature ovarian failure. The number of metaphase II (MII) oocytes needed to allow the transfer of a healthy embryo following PGT has never been investigated. The study is a monocentric retrospective observational study carried out from January 2006 to January 2020 that is associated with a case-control study and that analyzes 38 FMR1 mutation female carriers who are candidates for PGT; 16 carried the FMR1 premutation and 22 had the full FMR1 mutation. A total of 95 controlled ovarian stimulation (COS) cycles for PGT for fragile X syndrome were analyzed, 49 in premutated patients and 46 in fully mutated women. Only patients aged ≤38 years with anti-Müllerian hormone (AMH) >1 ng/ml and antral follicle count (AFC) >10 follicles were eligible for the PGT procedure. Each COS cycle of the FMR1-PGT group was matched with the COS cycles of partners of males carrying any type of translocation (ratio 1:3). Conditional logistic regression was performed to compare the COS outcomes. We then estimated the number of mature oocytes needed to obtain at least one healthy embryo after PGT using receiver operating characteristic curve analysis. Overall, in the FMR1-PGT group, the median number of retrieved and mature oocytes per cycle was 11 (interquartile range 7-15) and 9 (6-12), respectively. The COS outcomes of FMR1 premutation or full mutation female carriers were not altered compared with the matched COS cycles in partners of males carrying a balanced translocation in their karyotype. Among the 6 (4-10) Day 3 embryos obtained in the FMR1-PGT group, a median number of 3 (1-6) embryos were morphologically eligible for biopsy, leading to 1 (1-3) healthy embryo. A cutoff value of seven MII oocytes yielded a sensitivity of 82% and a specificity of 61% of having at least one healthy embryo, whereas a cutoff value of 10 MII oocytes led to a specificity of 85% and improved positive predictive value. This study is retrospective, analyzing a limited number of cycles. Moreover, the patients who were included in a fresh PGT cycle were selected on ovarian reserve parameters and show high values in ovarian reserve tests. This information could influence our conclusion. The results relate only to the target population of this study, with a correct ovarian reserve of AMH >1 and AFC >10. However, the information provided herein extends knowledge about the current state of COS for FMR1 mutation carriers in order to provide patients with proper counseling regarding the optimal number of oocytes needed to have a chance of transferring an unaffected embryo following PGT. None. N/A.

O-113 Effectiveness and treatment cost of assisted reproduction technology for women stimulated by gonadotropin in France: A cohort study using the National Health Database

Abstract Study question How effective is Assisted Reproduction Technology (ART) in terms of cumulative live birth rate (CLBR) in France, depending on the gonadotropin used? Summary answer Among 214,539 stimulations, originator follitropin-alfa was associated with significantly higher CLBR when compared to Highly Purified-Human Menopausal Gonadotropin (HP-HMG) and biosimilars. What is known already Deciding which type of gonadotropin to prescribe for a woman undergoing controlled ovarian stimulation (COS) remains difficult. The effectiveness of different gonadotropins is one factor to consider. However, studies comparing r-hFSH-alfa, its biosimilars and HP-HMG are scarce and are mostly based on a single ART treatment cycle and fresh embryo transfers. Some clinical trials have shown similar pregnancy, pregnancy loss, and live birth rates after fresh embryo transfer (ET) between HP-HMG and r-hFSH. However, because more oocytes are retrieved with r-hFSH when compared to HP-HMG, it is logical to hypothesize that the CLBR is higher with r-hFSH. Study design, size, duration A non-interventional study based on the French National Health System (SNDS) database was designed to assess the CLBR and treatment costs from the national payer perspective of four gonadotropin groups (originator follitropin-alfa (r-hFSH-alfa), its biosimilars, HP-HMG and r-hFSH-beta) used for COS cycles leading to oocyte pick-up (OPU) between 01/01/2013 and 31/12/2017 with a follow-up period up to 31/12/2018. The study compared CLBR, with originator r-hFSH-alfa as the reference. Participants/materials, setting, methods Women with COS cycles resulting in OPU with one of the specified gonadotropins were included. Data were extracted from billing and reimbursement records of outpatient healthcare consumption and national hospital discharge databases using a unique, anonymized patient number. CLBR was estimated using an Andersen–Gill model, adjusted for clinical baseline, stimulation and ET variables. Costs were reported as secondary outcomes. Main results and the role of chance 135,752 women (mean age 34.1), underwent 214,539 stimulations leading to OPU and contributed one (61.5%), two (24.8%), three (9.4%) or four (3.2%) COS cycles. COS cycles were stimulated with either Originator r-hFSH-alfa (46%), HP-HMG (29%), r-hFSH-beta (21%) or r-hFSH-alfa biosimilars (4%). Over the study period, CLBR reached 20.5%; 21.9% with originator r-hFSH-alfa, 17.9% with HP-HMG, 21.3% with r-hFSH-beta and 18.4% with r-hFSH-alfa biosimilars. After adjusting for age, pre-treatment, GnRH analog, ovulation triggering, luteal phase support, previous COS, fresh or frozen ET and type of center, as possible cofounding variables, the adjusted hazard ratio (HR) for CLBR (delivery [originator r-hFSH-alfa as reference]) was 0.88 (95% CI 0.86 to 0.95, p &amp;lt; 0.0001) with HP-HMG; 0.98 (95% CI 0.95 to 1.00, p = 0.1020) with r-hFSH-beta, and 0.84 (95% CI 0.79 to 0.90, p &amp;lt; 0.0001) with r-hFSH-alfa biosimilars. Although the mean acquisition cost of r-hFSH-alfa during the study was 33% higher than HP-HMG and 20% higher than r-hFSH-alfa biosimilars, the global ART management costs were only 4% higher than HP-HMG, 3% higher than r-hFSH-beta, and similar to r-hFSH-alfa biosimilars. Limitations, reasons for caution Patients were included only from oocyte pick-up, due to missing data in the SNDS database, meaning that it was not possible to estimate the proportion of cancelled cycles. Furthermore, as r-hFSH-alfa biosimilars were only available since 2015, results for biosimilars should be interpreted with caution. Wider implications of the findings This population-wide French study confirms other Real-World and meta-analysis evidence that CLBR is higher with originator r-hFSH-alfa than with HP-HMG or r-hFSH-alfa biosimilars, respectively, and are relevant for healthcare professionals to support gonadotropin treatment decision making. To further support this, the cost analysis should be completed by a cost-effectiveness analysis. Trial registration number Not applicable

O-153 Is paternal age associated with timing, stage, morphology, and implantation of the competent blastocyst: a multicenter cohort study

Abstract Study question Is age of men undergoing assisted reproductive technology associated with timing, stage, morphology, and implantation of the competent blastocyst? Summary answer Advanced paternal age was associated with reduced development speed and level of hCG in the competent blastocysts in COS treatments. What is known already We have shown that for every one-year increase in women’s age there is a 5% reduced probability that the competent blastocyst is in an advanced development stage. Likewise, we have shown that the initial hCG rise is associated with women’s age with the youngest women having the lowest hCG level. It is unknown whether the age of men undergoing ART treatment is associated with the timing (day 5 or 6), the development stage, morphology, and the early implantation of the competent blastocyst. Study design, size, duration This is a multicenter historical cohort study based on data from 16 private and university-based public fertility clinics where 7246 men and women, between 2014 and 2018, underwent controlled ovarian stimulation (COS) or Frozen-thawed Embryo Transfer (FET) with a single blastocyst transfer resulting in a singleton pregnancy. These data were linked to the Danish Medical Birth Registry, resulting in inclusion of 4842 men with a partner giving birth. Participants/materials, setting, methods Exposure (age) and outcome data (blastocyst timing (day 5 or 6), development stage (3-6), inner cell mass (ICM)(A,B,C), trophectoderm (TE)(A,B,C) and hCG were collected from the database, Danish Medical Data Center. All COS cycles (IVF and ICSI) and FET cycles (natural and substituted), were included. Exclusion criteria were cycles with pre-implantation genetic testing, donated oocytes and semen. The analyses were adjusted for female age, female smoking, female BMI, diagnosis and clinic. Main results and the role of chance The adjusted association between paternal age and transfer day in COS treatments showed that for every increase of one year, men had a 6% increased probability that the competent blastocyst was transferred on day 6 compared to day 5 (OR 1.06, 95% CI (1.00;1.13). The mean difference in hCG values when comparing paternal age group 30-34, 35-39 and 40-45 with the age group 25-29 in those receiving COS treatment, all showed significantly lower adjusted values for older men. In FET treatments, none of the investigated associations reached statistical significance. Limitations, reasons for caution The blastocyst morphology was subjectively assessed, and information bias may have influenced the results. However, adjusting for clinic takes the potential influence of variation in embryo scoring between clinics into consideration. Wider implications of the findings We hypothesize that the later transfer (day 6) in female partners of older men is likely to be due to longer time spent by the oocyte to repair fragmented DNA of the sperm cells, which should be a focus of future research in men. Trial registration number “not applicable”