Search Results (10)

Background/Objectives: Poor responder patients represent the greatest challenge in ART. An inadequate response to COS strongly correlates with a reduced chance of conception. A novel classification of poor responders overcame a deficiency in the Bologna criteria and distinguished an expected and unexpected low ovarian response, allowing for an individual treatment approach to be created. In this study, we compared the clinical outcomes in poor responders, according to two different ovarian stimulation protocols, GnRH agonists and antagonists, classified according to the Poseidon criteria, to determine the most effective protocol for each group. Methods: This retrospective study involved 1323 low-prognosis women ranked according to the Poseidon classification and a control group of normal responders. Results: The GnRH-antagonist protocol showed some advantage in the Poseidon 1b group whereas the GnRH-agonist protocol was more effective in the Poseidon 4 group. There were no differences in live births or miscarriage rates in poor responders among these two protocols. Conclusions: Using both the agonist/antagonist approaches, live birth rates are two or even three times less in Poseidon patients in comparison to normal responders. The number of obtained oocytes, their maturity and quality, and women’s ages were found to be the most influential determinants for a successful outcome. Further investigations into ovarian stimulation strategies are required to enhance oocyte number and live birth occurrence. Full article

Background and Objectives: POSEIDON 4 (P4) patients face the most adverse outcomes among poor responders. Oocyte donation has overcome unsatisfactory live birth rates (LBRs) in P4 patients and has become an indispensable approach. However, many patients refuse oocyte donation despite poor live birth likelihood using autologous oocytes. This study aimed to determine clinical outcomes and live birth chances in P4 patients using autologous and donated oocytes. We also identified influencing factors of fertility outcome in P4 patients who underwent donor cycles. Materials and Methods: Retrospective data of 345 P4 patients who explored the first ovarian stimulation cycle (control group) were compared to 105 patients who failed to conceive and underwent repeated autologous ovarian stimulations with an increased starting gonadotropin dose and 100 unpregnant patients who received donated oocytes. Univariate analysis was used to identify prognostic factors of oocyte donation outcomes in P4 patients. Results: LBRs were significantly higher in the donor oocyte group. A higher number of retrieved and good-quality oocytes without differences in the blastocyst number and LBRs were found in the autologous patient group with adjusted gonadotropin dose compared to the control group. Univariate analysis showed that oocyte and embryo quality as well as blastocyst development had a positive impact on live birth in the donor patient group. Conclusions: Autologous in vitro fertilization (IVF) retreating and oocyte donation should be strongly advised for poor-prognosis P4 patients. Still, efforts in tailoring ovarian stimulation to obtain higher oocyte and embryo numbers in autologous cycles should be continued. Full article

Research Question: To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Design: Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E₂ was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. Results: The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). Conclusion(s): The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients. Full article

Background: Does the presence of single-nucleotide polymorphisms (SNPs) in the leukemia inhibitory factor (LIF) gene affect ovarian response in infertile young women? Methods: This was a case–control study recruiting 1744 infertile women between January 2014 to December 2015. The 1084 eligible patients were stratified into four groups using the POSEIDON criteria. The gonadotropin-releasing hormone receptor (GnRHR), follicle-stimulating hormone receptor (FSHR), anti-Müllerian hormone (AMH), and LIF SNP genotypes were compared among the groups. The distributions of LIF and FSHR among younger and older patients were compared. Clinical outcomes were also compared. Results: The four groups of poor responders had different distributions of SNP in LIF. The prevalence of LIF genotypes among young poor ovarian responders differed from those of normal responders. Genetic model analyses in infertile young women revealed that the TG or GG genotype in the LIF resulted in fewer oocytes retrieved and fewer mature oocytes relative to the TT genotypes. In older women, the FSHR SNP genotype contributed to fewer numbers of mature oocytes. Conclusions: LIF and FSHR SNP genotypes were associated with a statistically significant reduction in ovarian response to controlled ovarian hyperstimulation in younger and older women with an adequate ovarian reserve, respectively. Full article

There is great controversy as to whether women with Diminished Ovarian Reserve (DOR) exhibit only a quantitative decrease in ovarian reserve or also impaired oocyte and embryo quality. In this retrospective study, we aimed to evaluate the impact of DOR on embryo morphokinetic parameters with a time-lapse system. 1314 embryos were obtained from 256 couples undergoing IVF or ICSI cycles, with 242 embryos in the DOR group as classified by the Bologna and POSEIDON criteria and 1072 embryos derived from the Normal Ovarian Reserve (NOR) group. For each morphokinetic parameter (t2, t3, t4, t5, t8, tB, ECC2, cc2a, ECC3, s2, s3), a generalized linear mixed model was created to control for female age, BMI, smoking status, method of insemination and correlation between oocytes from a same cohort. No significant association was found between DOR and any of the morphokinetic parameters studied. In a secondary analysis, we evaluated the influence of maternal aging, comparing morphokinetic characteristics between two age groups (<37 and ≥37 years). In the univariate analysis, we found that embryos from older women displayed a slower embryo development (in particular for t3, t4, t5, tB, and ECC2), although without statistical significance in the multivariate analysis. In conclusion, our study did not reveal any substantial impact of ovarian aging on early morphokinetic parameters and suggested potential biases that may be a source of controversy in the literature. Full article

We retrospectively studied a real-life population of 1470 women undergoing IVF, with poor/suboptimal/normal ovarian responsiveness to controlled ovarian stimulation (COS), comparing the cumulative live birth rate (cLBR) when COS was performed using rFSH alone or rFSH + rLH in a 2:1 ratio. Overall, we observed significantly higher cLBR in the rFSH alone group than in the rFSH + rLH group (29.3% vs. 22.2%, p < 0.01). However, considering only suboptimal/poor responders (n = 309), we observed comparable cLBR (15.6% vs. 15.2%, p = 0.95) despite the fact that patients receiving rFSH + rLH had significantly higher ages and worse ovarian reserve markers. The equivalent effectiveness of rFSH + rLH and rFSH alone was further confirmed after stratification according to the number of oocytes retrieved: despite basal characteristics were still in favor of rFSH alone group, the cLBR always resulted comparable. Even subdividing patients according to the POSEIDON classification, irrespective of differences in the baseline clinical characteristics in favor of FSH alone group, the cLBR resulted comparable in all subgroups. Despite the retrospective, real-life analysis, our data suggest that rLH supplementation in COS may represent a reasonable option for patients with predictable or unexpected poor/suboptimal ovarian responsiveness to FSH, those matching the Bologna criteria for poor responsiveness, and those included in the POSEIDON classification. Full article

The choice of ovarian stimulation protocols in assisted reproduction technology (ART) cycles for low ovarian reserve patients is challenging. Our previous report indicated that the gonadotrophin-releasing (GnRH) agonist (GnRHa) protocol is better than the GnRH antagonist (GnRHant) protocol for young age poor responders. Here, we recruited 269 patients with anti-Müllerian hormone (AMH) < 1.2 ng/mL undergoing their first ART cycles for this nested case-control study. We investigated the genetic variants of the relevant genes, including follicular stimulating hormone receptor (FSHR; rs6166), AMH (rs10407022), GnRH (rs6185), and GnRH receptor (GnRHR; rs3756159) in patients <35 years (n = 86) and patients ≥35 years of age (n = 183). Only the genotype of GnRHR (rs3756159) is distributed differently in young (CC 39.5%, CT/TT 60.5%) versus advanced (CC 24.0%, CT/TT 76.0%) age groups (recessive model, p = 0.0091). Furthermore, the baseline luteinizing hormone (LH) levels (3.60 (2.45 to 5.40) vs. 4.40 (2.91 to 6.48)) are different between CC and CT/TT genotype of GnRHR (rs3756159). In conclusion, the genetic variants of GnRHR (rs3756159) could modulate the release of LH in the pituitary gland and might then affect the outcome of ovarian stimulation by GnRHant or GnRHa protocols for patients with low AMH levels. Full article

Despite recent striking advances in assisted reproductive technology (ART), poor ovarian response (POR) diagnosis and treatment is still considered challenging. Poor responders constitute a heterogeneous cohort with the common denominator of under-responding to controlled ovarian stimulation. Inevitably, respective success rates are significantly compromised. As POR pathophysiology entails the elusive factor of compromised ovarian function, both diagnosis and management fuel an ongoing heated debate depicted in the literature. From the criteria employed for diagnosis to the plethora of strategies and adjuvant therapies proposed, the conundrum of POR still puzzles the practitioner. What is more, novel treatment approaches from stem cell therapy and platelet-rich plasma intra-ovarian infusion to mitochondrial replacement therapy have emerged, albeit not claiming clinical routine status yet. The complex and time sensitive nature of this subgroup of infertile patients indicates the demand for a consensus on a horizontally accepted definition, diagnosis and subsequent effective treating strategy. This critical review analyzes the standing criteria employed in order to diagnose and aptly categorize POR patients, while it proceeds to critically evaluate current and novel strategies regarding their management. Discrepancies in diagnosis and respective implications are discussed, while the existing diversity in management options highlights the need for individualized management. Full article

Poor ovarian response (POR) to controlled ovarian stimulation (OS) presents a major challenge in assisted reproduction. The Bologna criteria represented the first serious attempt to set clear criteria for the definition of POR. However, the Bologna criteria were questioned because of the persistent heterogeneity among POR patients and the inability to provide management strategies. Based on these facts, a more recent classification, the POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) classification, was developed to provide a homogeneous and refined definition of POR that significantly reduces the heterogeneity of the Bologna criteria definition of POR and helps in the clinical handling and counseling of patients. In this review, we discuss the impact of the POSEIDON classification on the clinical management of patients with POR. Full article

Owing to its temporal resolution of 10-day and its polar orbit allowing several crossings over large lakes, the US National Aeronautics and Space Administration (NASA) and the French Centre National d’Etudes Spatiales (CNES) missions including Topex/Poseidon, Jason-1/2/3 demonstrated strong capabilities for the continuous and long-term monitoring (starting in 1992) of large and medium-sized water bodies. However, the presence of heterogeneous targets in the altimeter footprint, such as ice cover in boreal areas, remains a major issue to obtain estimates of water level over subarctic lakes of similar accuracy as over other inland water bodies using satellite altimetry (i.e., R ≥ 0.9 and RMSE ≤ 10 to 20 cm when compared to in-situ water stages). In this study, we aim to automatically identify the Jason-2 altimetry measurements corresponding to open water, ice and transition (water-ice) to improve the estimations of water level during freeze and thaw periods using only the point measurements of open water. Four Canadian lakes were selected to analyze active (waveform parameters) and passive (brightness temperature) microwave data acquired by the Jason-2 radar altimetry mission: Great Slave Lake, Lake Athabasca, Lake Winnipeg, and Lake of the Woods. To determine lake surface states, backscattering coefficient and peakiness at Ku-band derived from the radar altimeter waveform and brightness temperature at 18.7 and 37 GHz measured by the microwave radiometer contained in the geophysical data records (GDR) of Jason-2 were used in two different unsupervised classification techniques to define the thresholds of discrimination between open water and ice measurements. K-means technique provided better results than hierarchical clustering based upon silhouette criteria and the Calinski-Harabz index. Thresholds of discrimination between ice and water were validated with the Normalized Difference Snow Index (NDSI) snow cover products of the MODIS satellite. The use of open water threshold resulted in improved water level estimation compared to in situ water stages, especially in the presence of ice. For the four lakes, the Pearson coefficient (r) increased on average from about 0.8 without the use of the thresholds to more than 0.90. The unbiased RMSE were generally lower than 20 cm when the threshold of open water was used and more than 22 cm over smaller lakes, without using the thresholds. Full article