Management Strategies for POSEIDON Groups 3 and 4

Background Assisted reproductive technologies have facilitated numerous families in conceiving healthy offspring over the past decades. In vitro fertilization and embryos transfer (IVF-ET) have gained significant popularity, leading to enhanced pregnancy rates through technological advancements. Many women of advanced age seek to conceive through IVF, yet studies have indicated that female age stands as a prominent limiting factor for fertility and reproductive outcomes. Aim and Objectives This research endeavors to ascertain the clinical pregnancy rate disparities among patients classified under Poseidon group 3 and Poseidon group 4. Subjects and Methods This was a prospective observational study conducted at Ain Shams University Maternity Hospital (IVF. unit) on 340 patients until all needed patients had been recruited (about 12 months from February 2022). Result The clinical pregnancy rate was higher in patients classified under Poseidon group 3 compared to those in Poseidon group 4. Pearson’s correlation coefficients (r) between the Total dose of HMG and Clinical pregnancy within Poseidon 3 group was 0.263, indicating a robust positive correlation between the two variables. Similarly, Pearson’s correlation coefficients (r) between the Total dose of HMG and Clinical pregnancy within Poseidon 4 group was 0.130, suggesting a weaker positive relationship between these variables. Conclusion In summary, our investigation indicates that utilizing a standardized and graded classification system such as POSEIDON proves beneficial in predicting cycles and outcomes for patients with Poor Ovarian Response (POR). By employing the POSEIDON criteria, healthcare providers can initially identify and categorize individuals with a diminished prognosis in Assisted Reproductive Technology (ART). Subsequently, they can tailor a personalized treatment regimen to optimize the likelihood of attaining the POSEIDON benchmark of success within each respective subgroup.

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.

A number of live birth predictive model during assisted reproductive technology treatment have been available in recent years, but few targeted evaluating the chances of live birth in poor ovarian response(POR) patients. The aim of this study was to develop a nomogram based on POSEIDON criteria to predict live birth in patients with expected POR. This retrospective cohort study using clinical data from 657 patients in POSEIDON Groups 3 and 4 (antral follicle count [AFC] ≤5 and AMH <1.2 ng/ml) in the CenterforReproductiveMedicine, First Affiliated Hospital of Xinjiang Medical University, and Construction a nomogram model t. Among 657 expected POR patients, 111 (16.89%) had live births, and 546 (83.11%) did not have live births. These were divided into a training set(n=438) and a validation set (n=219). Multivariate logistic regression analysis showed that the age (OR = 0.91, 95% CI: 0.86-0.97), BMI (OR = 1.98, 95% CI: 1.09-3.67), AMH (OR = 3.48, 95% CI: 1.45-8.51), normal fertilized oocytes (OR = 1.40, 95% CI: 1.21-1.63), and the basal FSH (OR = 0.89, 95% CI: 0.80-0.98) of the female were independent factors predicting live birth in patients with expected POR. Then, an individualized nomogram prediction model was built from these five factors. The area under the ROC curve of the live birth prediction model was 0.820 in the training set and 0.879 in the validation set. We have developed a nomogram combining clinical and laboratory factors to predict the probability of live birth in patients with an expected POR during IVF/ICSI, which can helpful for clinician in decision-making. However, the data comes from the same center, needs a prospective multicenter study for further in-depth evaluation and validation of this prediction model.

Additional age-related issues should be considered when managing breast cancer in young women.1 Among them, the potential consequences of anticancer treatments on ovarian function and fertility potential are of particular concern and need to be addressed as early as possible after diagnosis.2,3 Therefore, current guidelines strongly voice the need to provide proper oncofertility counseling with all patients of reproductive age with newly diagnosed cancer irrespective of its stage.2,3 This is a crucial step to discuss with all young women their disease and prognosis, the required treatments including their potential gonadotoxicity, the need for contraception during and after active systemic therapies, their future desire of conception, likelihood of pregnancy, its safety and outcomes as well as the available strategies to avoid the negative impact of the proposed treatment on ovarian function and fertility.

Infertility has been defined as a couple's failure to conceive after regular and unprotected coitus for 1 year or six months, depending on the age of the female counterpart. Although infertility can result from both the male and/or the female, often the female partner faces pressure since it is believed in some African cultures that a woman without children is like a tree without leaves. The aim of this study was to determine the prevalence of successful pregnancy outcomes among infertile women undergoing assisted reproductive technology (ART) treatment at the Cape Windhoek Fertility Clinic. This was a prospective and descriptive cross-sectional case reference study encompassing 178 infertile women visiting the Cape Windhoek Fertility Clinic for ART treatment. The vast majority of the participants (81.5%) were married women. From the 178 infertile women, 96 (53.9%) suffered from primary and 82 (46.1%) from secondary infertility. The predominant cause of complications for infertility among the women studied was defective ovulation (28.7%) and the most common ART treatment administered was IVF/ICSI (52.2%). Only a third (33.1%) of the women who received ART treatment eventually fell pregnant. The outcome of this study may not give a clear indication of the prevalence of infertility among women in the entire Namibian nation due to the costs involved with ART treatment offered mainly at privately owned hospitals and/or clinics, thereby resulting in those who cannot afford treatment to be left out despite being infertile.

Study question Does increasing the dosage of triptorelin acetate from 0.2 mg to 0.3 mg result in higher clinical pregnancy rates in POSEIDON Groups 3 and 4? Summary answer Increasing the dosage of triptorelin acetate from 0.2 mg to 0.3 mg does not significantly enhance oocyte maturation or retrieval outcomes What is known already Emerging research suggests that different doses of GnRH agonists yield varying outcomes, particularly in subgroups with distinct reproductive profiles. However, most randomized controlled trials (RCTs) evaluating GnRH agonist doses have been conducted in predicted good ovarian responders or women with adequate ovarian reserve. There is a paucity of data on the optimal dose of GnRH agonists, particularly triptorelin acetate, in low prognosis patients classified under POSEIDON Groups 3 and 4 . This gap in the literature is significant, as these patients represent a unique challenge in ART due to their reduced ovarian reserve and advanced reproductive aging. Study design, size, duration This multicenter, randomized, open-label, controlled trial included 654 patients classified as POSEIDON Groups 3 and 4 (AMH &amp;lt; 1.2 ng/dL, AFC ≤5) who were randomly assigned to receive either 0.2 mg (Group A) or 0.3 mg (Group B) of triptorelin acetate for triggering final oocyte maturation. Participants/materials, setting, methods An interim analysis was performed when around 50% of the sample was included in the study. Key outcomes included the number of oocytes retrieved, the percentage of mature oocytes (M2), the duration of ovarian stimulation, and clinical pregnancy rates. Main results and the role of chance Of the 295 patients included in the interim analysis (155 in Group A and 140 in Group B), the mean age was 33.89 years, with no significant differences in baseline characteristics. The mean number of oocytes retrieved was similar between groups (4.73 in Group A vs. 4.62 in Group B). Although the percentage of mature oocytes was higher in Group B (65.87%) compared to Group A (61.30%), this difference was not statistically significant (p = 0.293). Notably, clinical pregnancy rates were significantly higher in Group A (61.74%) compared to Group B (45.07%) (p = 0.049). The lower dosage (0.2 mg) was associated with better clinical pregnancy rates, underscoring the importance of personalized treatment strategies in ART for low-prognosis patients Limitations, reasons for caution The population concentrates on low-prognosis patients in POSEIDON groups, which may impair the findings' generalizability to the larger population undergoing ART. Due to its retrospective nature, the capacity to demonstrate causality between triptorelin dosage and outcomes may be limited, and confounding variables may influence the results. Wider implications of the findings The significantly higher clinical pregnancy rates observed in the 0.2 mg group suggests that 0.2 mg triptorelin acetate may be more effective than 0.3 mg in achieving higher clinical pregnancy rates in low prognosis patients classified under POSEIDON Groups 3 and 4. Trial registration number Yes

A panel of experts known as the POSEIDON group has recently redefined the spectrum of poor responder patients and introduced the concept of suboptimal response. Since an ideal management for these patients is still missing, they highlighted the importance of tailoring the ovarian stimulation based on the chance of each woman to obtain an euploid blastocyst. Interestingly, a novel pattern of follicle recruitment has been defined: multiple waves may arise during a single ovarian cycle. This evidence opened important clinical implications for the treatment of poor responders. For instance, double stimulation in the follicular (FPS) and luteal phase (LPS) of the same ovarian cycle (DuoStim) is an intriguing option to perform two oocyte retrievals in the shortest possible time. Here, we reported our 2-year experience of DuoStim application in four private IVF centers. To date, 310 poor prognosis patients completed a DuoStim protocol and underwent IVF with blastocyst-stage preimplantation-genetic-testing. LPS resulted into a higher mean number of oocytes collected than FPS; however, their competence (i.e., fertilization, blastocyst, euploidy rates, and clinical outcomes after euploid single-embryo-transfer) was comparable. Importantly, the rate of patients obtaining at least one euploid blastocyst increased from 42.3% (n = 131/310) after FPS to 65.5% (n = 203/310) with the contribution of LPS. A summary of the putative advantages and disadvantages of DuoStim was reported here through a Strengths–Weaknesses–Opportunities–Threats analysis. The strengths of this approach make it very promising. However, more studies are needed in the future to limit its weaknesses, shed light on its putative threats, and realize its opportunities.

To evaluate the psychosocial support perceived by couples during assisted reproductive technology (ART) treatments. Prospective follow-up of patients undergoing ART. Department of Obstetrics and Gynecology, S. Maria Nuova Hospital, Reggio Emilia, Italy. Eighty-three women and 83 men admitted for ART. Patients completed a sociodemographic questionnaire and the Multidimensional Scale of Perceived Social Support at the beginning of ovarian stimulation, upon oocyte pick-up, and 1 month after ET. Perception of psychosocial support. Men, compared with women, consistently reported poorer perception of psychosocial support, especially from friends and significant others; family support showed no difference. Women showed a decrease in perceived support, especially from friends, in cases of failure. Both reported less support from significant others if they had previously already undergone ART treatments. Men might feel excluded from the treatment because of the greater attention to women, leading to feelings of isolation from friends and partners. Women suffer particularly in cases of failure that reconfirms the trauma of infertility. These psychological risk factors underline the usefulness of psychological support for these couples, especially in cases of prolonged infertility.

BackgroundThere is limited research about the pregnancy outcomes of POSEIDON group 2 patients. This study aims to evaluate the factors related to the clinical outcomes of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) in POSEIDON group 2 patients, so as to provide clinical guidance to improve clinical outcomes.MethodsA total of 1,249 IVF/ICSI cycles of POSEIDON group 2 patients were retrospectively analyzed from July 2019 to September 2024. The patients were divided into different groups according to live birth, maternal age, and endometrial thickness (EMT). The clinical outcomes were compared between groups.ResultsCompared with the non-live birth group, maternal age, gonadotropin (Gn) dosage, and Gn total dosage were significantly lower, while EMT was significantly higher in the live birth group (p < 0.05). The type of infertility showed statistically significant differences (p = 0.013). Multivariate logistic regression analysis indicated that maternal age (OR = 1.195, 95% CI: 1.077–1.327; p = 0.001) and EMT on transfer day (OR = 0.887, 95% CI: 0.820–0.959; p = 0.003) were independent influencing factors for live birth in POSEIDON group 2 patients. According to the receiver operating characteristic (ROC) curve predictive cutoff value, the patients were divided into group A (age < 38 years, n = 249) and group B (age ≥ 38 years, n = 155). Group A had a higher human chorionic gonadotropin (hCG)-positive rate (55.8% vs. 34.2%, p < 0.001), embryo implantation rate (35.2% vs. 19.2%, p < 0.001), clinical pregnancy rate (47.8% vs. 29.7%, p < 0.001), and live birth rate (37.3% vs. 20.0%, p < 0.001) and a lower early miscarriage rate (12.6% vs. 28.3%, p = 0.016) than group B. According to the ROC predictive cutoff value of EMT, group A patients were further divided into group A1 (EMT < 11.65 mm, n = 136) and group A2 (EMT ≥ 11.65 mm, n = 113). Group B patients were divided into group B1 (EMT < 11.65 mm, n = 93) and group B2 (EMT ≥ 11.65 mm, n = 62). Compared with group A1 and group A2, group B1 had a lower hCG-positive rate (28.0% vs. 49.3%, p = 0.001; 28.0% vs. 63.7%, p < 0.001), embryo implantation rate (14.7% vs. 32.2%, p < 0.001; 14.7% vs. 40.2%, p < 0.001), clinical pregnancy rate (23.7% vs. 41.2%, p = 0.006; 23.7% vs. 55.8%, p < 0.001), and live birth rate (16.1% vs. 33.8%, p = 0.003; 16.1% vs. 41.6%, p < 0.001).ConclusionsMaternal age and EMT on transfer day are independent factors affecting IVF/ICSI clinical outcomes in POSEIDON group 2 patients. Among these, maternal age <38 years or EMT ≥ 11.65 mm indicated better clinical outcomes. Further stratification by age and EMT on transfer day may optimize clinical outcomes in POSEIDON group 2 patients.

Objectives: The aim of the study was to assess the prevalence of “low prognosis” patients using POSEIDON criteria undergoing in vitro fertilization (IVF) cycle in Indian population. Study Design: This is a retrospective cohort study. Period of Study: It included data from the recruitment period from January 1, 2018 to December 31, 2021. Study Settings: The study was conducted at the Center for IVF and Human Reproduction, Sir Gangaram Hospital, New Delhi. Methodology: Out of the 3032 IVF stimulation cycles with oocyte aspirations, 596 cycles were excluded based on the exclusion criteria. The study focused on 2436 IVF/ICSI (Intracytoplasmic sperm injection) stimulation cycles that met inclusion criteria. Each cycle was categorized into one of the four groups defined by the POSEIDON criteria along with a fifth non-POSEIDON group. Prevalence was observed for each POSEIDON group and the non-POSEIDON group. Results: Out of the analyzed cycles, 1210 were classified under POSEIDON groups, representing a prevalence of 49.67%. The distribution of cycles in POSEIDON groups 1, 2, 3, and 4 was 31.4, 23.2, 19.17, and 26.19%, respectively. Conclusion: Low prognosis patients based on POSEIDON criteria, represented about half of the population.

Lack of association between receiving ART treatment and parental psychological distress during pregnancy: Preliminary findings of the Japan Environment and Children’s Study

ObjectiveTo establish a predictive model for pregnancy outcomes in patients undergoing assisted reproductive technology (ART) treatment using human chorionic gonadotropin (HCG) day endometrial thickness (EMT), follicle output rate (FORT), serum anti-Müllerian hormone (AMH), and clinical characteristics.MethodsA retrospective study was conducted on 200 patients who underwent ART treatment at our hospital from August 2019 to August 2024. All patient data were obtained from the electronic medical record system, and patients were divided into a clinical pregnancy group and a non-pregnancy group based on whether they achieved pregnancy. Clinical-related data were collected and compared. Two machine learning methods, Lasso regression and Extreme Gradient Boosting (XGBoost), were used for “overlap coverage” screening of risk factors. The XGBoost model was implemented using the “xgboost” package in R, with the following hyperparameters: max_depth = 6, learning_rate = 0.3, n_estimators = 100, objective = “binary:logistic.” These parameters were selected based on common practices for binary classification tasks and were not extensively tuned due to the sample size limitations. Multivariate logistic analysis was performed to identify risk factors for pregnancy outcomes in ART patients. A regression model was established using R software for prediction and validation.ResultsA total of 200 ART patients were included in this study. According to medical record system records, 109 patients did not achieve pregnancy, accounting for 54.50%, and were included in the non-pregnancy group. 91 patients achieved clinical pregnancy, accounting for 45.50%, and were included in the clinical pregnancy group. There were significant statistical differences between the non-pregnant group and the clinically pregnant group in terms of age, body mass index, number of oocytes retrieved, HCG day EMT, AMH, and FORT (p < 0.05); Using LASSO regression and XGBoost machine learning, different risk factors were identified. Through the “overlap coverage” method, six common risk factors for pregnancy outcomes in ART patients were identified and included in the logistic regression model. The results indicated that age and body mass index were both risk factors influencing pregnancy outcomes in ART patients (OR = 1.196, 1.777, p < 0.05); the number of retrieved oocytes, HCG day EMT, AMH, and FORT were protective factors influencing pregnancy outcomes in ART patients (OR = 0.366, 0.382, 0.182, 0.862, p < 0.05); Based on the results of the logistic regression analysis, a risk prediction model for pregnancy outcomes in ART patients was constructed using a nomogram. The ROC curve showed an AUC value of 0.911, with a 95% confidence interval (CI) of 0.871 to 0.951. The model was validated using the Bootstrap method with 1,000 repeated samples, yielding a Cox-Snell R2 of 0.629, Nagelkerke R2 was 0.471, Brier Score was 0.117, model fit p-value was 0.240, and the statistic was 10.369. This indicates that the model’s predictive results align well with the actual occurrence of pregnancy outcomes in patients, with the clinical decision curve generally exceeding the two extreme curves. This suggests that the factors included in the nomogram provide a high net benefit for predicting pregnancy outcomes in ART-treated patients.ConclusionThere are numerous factors influencing pregnancy outcomes in ART patients, primarily including age, body mass index, number of oocytes retrieved, HCG day EMT, AMH, and FORT. The risk prediction nomogram model constructed based on these factors has certain predictive value for pregnancy outcomes in ART patients. Clinicians should identify high-risk populations early and optimize treatment plans accordingly.

How do hematological characteristics affect ovarian reserve, ovarian response to ovarian stimulation, and fertility outcomes? Although lymphoma characteristics impact serum AMH levels, they do not affect, per se, the response to ovarian stimulation and the number of mature oocytes recovered at the time of fertility preservation; in addition, fertility in survivors of hematologic malignancies is relatively conserved. Hematologic cancers can affect young women of reproductive age. While survival rates have improved over the years due to advances in treatment protocols, the treatments used can impact fertility. Fertility preservation methods, such as oocyte or ovarian tissue cryopreservation, are increasingly offered, but concerns remain about reduced ovarian reserve and response to ovarian stimulation in women with these cancers, which may influence the effectiveness of fertility preservation strategies. Moreover, fertility potential after hematologic cancers has been poorly studied. This is a retrospective, observational bi-centric cohort study. All patients with hematologic cancer (lymphoma, leukemia, myeloma, and myelodysplastic syndrome) who underwent fertility preservation before gonadotoxic treatment (n = 286) from January 2013 to March 2023 were included. For fertility after cancer, and use of frozen oocytes/embryos, the endpoint date was 7 July 2023. Only patients with lymphoma were included for analysis of ovarian reserve (n = 238) and ovarian response to ovarian stimulation (n = 230). Low ovarian reserve and impaired ovarian response to ovarian stimulation were defined as AMH <1.2 ng/ml and ≤9 mature oocytes retrieved after ovarian stimulation, respectively, according to POSEIDON criteria. A Cox regression model was used to determine predictive factors of impaired response to ovarian stimulation, low ovarian reserve, and pregnancy after cancer. Cumulative incidence of pregnancy and cumulative use of frozen oocytes/embryos was calculated in all patients suffering from hematological malignancies. There was an impact of lymphoma characteristics on AMH levels independent of age. After adjustment based on POSEIDON Groups 3 and 4, no specific impact of lymphoma characteristics (e.g. stage, clinical, or biologic B signs) on ovarian response to ovarian stimulation was observed. Regarding post-cancer fertility in the whole population, among the women who tried to conceive, 62% achieved at least one pregnancy, and 85% of these occurred naturally. After adjustment, positive predictive factors for pregnancy were age <35 years, being in a relationship at the first oncofertility consultation, and absence of hematopoietic stem cell transplantation. Limitations include potential biases due to the heterogeneity of hematological conditions and the retrospective design, which may lead to missing data. Additionally, the duration of follow-up may not be sufficient to evaluate long-term fertility outcomes. Lymphoma characteristics did not affect the response to ovarian stimulation in terms of mature oocyte retrieval, although AMH levels were impaired. Reassuring post-cancer fertility data support informed decision-making regarding fertility preservation techniques. Larger prospective studies are needed to tailor oncofertility counseling, ensuring optimized care and reproductive outcomes. Medical editorial support was provided by Peter Todd of Tajut Ltd (Kaiapoi, New Zealand) and was funded by AFPR (Advances in Fertility Preservation and Reproduction). The authors declare no conflicts of interest. N/A.

STUDY QUESTIONAre the mean numbers of blastocysts obtained from sibling cohorts of oocytes recruited after follicular phase and luteal phase stimulations (FPS and LPS) in the same ovarian cycle similar?SUMMARY ANSWERThe cohorts of oocytes obtained after LPS are larger than their paired-FPS-derived cohorts and show a comparable competence, thus resulting in a larger mean number of blastocysts.WHAT IS KNOWN ALREADYThree theories of follicle recruitment have been postulated to date: (i) the ‘continuous recruitment’ theory, (ii) the ‘single recruitment episode’ theory and (iii) the ‘wave’ theory. Yet, a clear characterization of this crucial biological process for human reproduction is missing. Recent advances implemented in in vitro fertilization (IVF), such as blastocyst culture, aneuploidy testing and vitrification, have encouraged clinicians to maximize the exploitation of the ovarian reserve through tailored stimulation protocols, which is crucial especially for poor prognosis patients aiming to conceive after IVF. LPS has been already successfully adopted to treat poor prognosis or oncological patients through Duostim, LPS-only or random-start ovarian stimulation approaches. Nevertheless, little, and mainly retrospective, evidence has been produced to support the safety of LPS in general. Feasibility of the LPS approach would severely question the classic ‘single recruitment episode’ theory of follicular development.STUDY DESIGN, SIZE, DURATIONThis case-control study was conducted with paired follicular phase- and luteal phase-derived cohorts of oocytes collected after stimulations in the same ovarian cycle (DuoStim) at two private IVF clinics between October 2015 and December 2017.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study included 188 poor prognosis patients undergoing DuoStim with preimplantation genetic testing for aneuploidies (PGT-A). FPS and LPS were performed with the same daily dose of recombinant-gonadotrophins in an antagonist protocol. Blastocyst culture, trophectoderm biopsy, vitrification and frozen-warmed euploid single blastocyst transfers were performed. The primary outcome was the mean number of blastocysts obtained per oocyte retrieval from paired-FPS- and LPS-derived cohorts (required sample size = 165 patients; power = 90%). Mean blastulation and euploidy rates were monitored, along with the number of oocytes, euploid blastocysts and clinical outcomes.MAIN RESULTS AND THE ROLE OF CHANCESignificantly fewer blastocysts were obtained after FPS than LPS (1.2 ± 1.1 vs. 1.6 ± 1.6, P < 0.01), due to fewer oocytes collected (3.6 ± 2.1 vs. 4.3 ± 2.8, P < 0.01) and a similar mean blastocyst rates per retrieval (33.1% ± 30.3% vs. 37.4% ± 30.8%, P = NS). The number of oocytes collected were correlated (R = 0.5, P < 0.01), while the blastocyst rates were uncorrelated among paired-FPS- and LPS-derived cohorts. Overall, a significantly lower chance of producing blastocyst(s) was reported after FPS than after LPS: 67.6% (n = 127/188, 95%CI: 60.3–74.1) vs. 77.1% (n = 145/188, 95%CI: 70.3–82.8; P = 0.05). The mean euploidy rates per retrieval were similar between FPS- and LPS-derived cohorts of oocytes (13.6% ± 22.8% vs. 16.3% ± 23.4%, P = NS). Therefore, on average fewer euploid blastocysts (0.5 ± 0.8 vs. 0.7 ± 1.0, P = 0.02) resulted from FPS. Similar ongoing-pregnancy/delivery rates were reported, to date, after FPS- and LPS-derived euploid single blastocyst transfers: 42.4% (n = 28/66, 95%CI: 30.5–55.2) vs. 53.8% (n = 35/65, 95%CI: 41.1–66.1; P = NS).LIMITATIONS, REASONS FOR CAUTIONMore studies need to be conducted in the future to confirm the safety of LPS, especially in terms of ovarian and follicular environment, as well as the clinical, peri-natal and post-natal outcomes. Here, we showed preliminary data suggesting a similar ongoing implantation/delivery rate (>22 weeks) between FPS- and LPS-derived euploid blastocysts, that need to be extended in the future, to populations other than poor prognosis patients and using approaches other than DuoStim together with a constant monitoring of the related peri-natal and post-natal outcomes.WIDER IMPLICATIONS OF THE FINDINGSThese data, from a paired study design, highlight that LPS-derived oocytes are as competent as FPS-derived oocytes, thereby adding some evidence to support the use of LPS for poor prognosis and oncological patients and to question the ‘single recruitment episode’ theory of follicle recruitment. These findings also encourage additional studies of the basics of folliculogenesis, with direct clinical implications for the management of ovarian stimulation in IVF.TRIAL REGISTRATIONNone.STUDY FUNDING/COMPETING INTEREST(S)No external funds were used for this study and there are no conflicts of interest.

BackgroundAround 20% of patients undergoing assisted reproductive technology are at risk of hypo-response to ovarian stimulation. The aim of this study was to describe the real-world use of follitropin delta for ovarian stimulation in these patients, as defined by POSEIDON groups 3 and 4 [an anti-Müllerian hormone (AMH) level of <1.2 ng/ml].Materials and methodsThis study was a post-hoc analysis of participants from DELTA, a multi-centre, prospective, observational study conducted in normal care settings in fertility clinics at 14 active sites in France. A subset of 35 patients at risk of hypo-response to ovarian stimulation (mean AMH 0.7 ± 0.29 ng/ml) and treated with follitropin delta were included. Patients were followed for 10–11 weeks after the first fresh or frozen embryo transfer in case of subsequent pregnancy, and data on real-world follitropin delta use collected.ResultsMost patients (92.9%) had undergone their first IVF or ICSI. The prescribed daily dose was usually based on the approved algorithm (N = 26; 74.3%) with a mean daily dose of 14.2 ± 4.1 mcg, resulting in a mean total dose of 187.7 ± 135.6 mcg. The mean duration of ovarian stimulation was 11.6 ± 6.7 days with no premature discontinuations, while the mean number of oocytes retrieved among patients that started stimulation was 6.3 ± 4.3. A fresh transfer was performed for 21 patients (84.0%), with a mean of 1.04 ± 0.98 embryos transferred per patient. Seven patients (20.0%) achieved an ongoing pregnancy (28% per transfer). No adverse drug reactions were reported.ConclusionsThe results describe the real-world use of follitropin delta and demonstrate its suitability for POSEIDON group 3 and 4 patients. These data complement clinical trial outcomes, supporting clinician decision-making and improving IVF/ICSI outcomes.