Background: In medicated frozen embryo transfer (FET) cycles, exogenous progesterone is essential during the luteal phase to support implantation and early pregnancy due to the absence of the corpus luteum. Among the variable forms of exogenous progesterone, intramuscular (IM) progesterone in oil (P-in-oil) is generally considered the most effective. However, some patients experience hypersensitivity reactions, raising concerns about their potential impact on implantation success and early pregnancy development. Progesterone plays a central role in the dynamic immune balance necessary to establish and maintain a successful pregnancy. Progesterone hypersensitivity reaction could disrupt this delicate balance, potentially leading to adverse reproductive outcomes and affecting future fertility care. Although hypersensitivity reactions to P-in-oil are rare, they warrant attention due to their potential implications for clinical management and patient outcomes. Notably, data on reproductive outcomes in patients experiencing hypersensitivity to exogenous progesterone, particularly P-in-oil, remains limited. Objectives: This study aims to evaluate the prevalence of progesterone hypersensitivity in women undergoing medicated FET cycles utilizing P-in-oil and to investigate the clinical implications of such reactions on reproductive outcomes. Methods: A retrospective cohort study was conducted including 814 medicated FET cycles at a private assisted reproductive technology program between April 2022 to August 2023. All patients received exogenous IM P-in-oil for luteal phase support. We excluded cycles involving donor oocytes or embryos, as well as those using gestational carriers, to ensure a homogeneous study population. Cycles that involved alternative or combined progesterone regimens were also excluded to isolate the effects of IM P-in-oil. Statistical analysis included Chi-squared tests for categorical variables and T-tests for continuous variables. Relative risks (RR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression to adjust for potential confounders. A p-value of < 0.05 was considered statistically significant throughout the analysis. This study was approved by the Institutional Review Board of Indiana University. Results: A total of 673 patients who underwent medicated FET cycles were analyzed within the cohort. Approximately 10.3% (n=69) of patients using P-in-oil supplementation reported experiencing a reaction during one of their treatment cycles, resulting in an overall reaction rate per cycle of 8.5%. Symptoms of progesterone hypersensitivity (PH) varied widely and included dermatitis, urticaria, edema, fever, nausea, and dyspnea. Dermatologic manifestations were the most frequently reported symptoms, occurring in 95.5% of patients who experienced adverse reactions. In contrast, systemic adverse reactions were uncommon, reported in less than 5% of cases. The live birth rate was significantly higher in patients who experienced a reaction (68.1%, n=47) compared to those without a reaction (47.7%, n=355) (p = 0.001; RR 2.19, CI 1.35-3.56). No significant difference was found in the miscarriage rate between patients with and without reported reactions (8.7%, n=6 vs. 8.7%, n=65, respectively) (p = 0.99; RR 1.00, CI 0.45 – 2.22). Conclusions: Hypersensitivity to P-in-oil presents a unique and underrecognized challenge in management of patients undergoing medicated FET cycles. This is the largest cohort analyzing progesterone hypersensitivity in patients using P-in-oil. Our data suggests that this rare occurrence has a minimal negative impact on reproductive outcomes. Notably, patients who experienced hypersensitivity reactions during P-in-oil use were more than twice as likely to achieve a live birth compared to those without reactions. Patients who experience hypersensitivity reactions while using P-in-oil can be reassured that their medication regimen is unlikely to negatively impact their success rates. However, given the complex immune-hormonal interactions involved in early pregnancy, larger prospective studies are warranted to validate these findings and better understand their clinical implications.
PurposeInfertility affects 1 in 6 couples, yet male fertility assessments often rely on semen analysis alone, which has limited predictive value for treatment success. This study evaluates an epigenetic tool for assessing sperm quality, aiming to provide a more comprehensive view of male fertility and improve personalized treatment strategies.MethodsDe-identified pregnancy outcomes from 537 couples treated at 10 US fertility clinics were analyzed. Partner ages, total motile sperm count, treatment type, and sperm epigenetic quality were considered to assess associations with fertility treatment outcomes.ResultsMen with abnormal sperm epigenetic profiles had significantly lower pregnancy success rates with intrauterine insemination (IUI) compared to those with normal profiles, despite similar sperm motility and concentration. In contrast, pregnancy rates did not differ between abnormal and normal profiles among couples undergoing in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI), suggesting that ICSI may overcome sperm epigenetic quality issues.ConclusionThis real-world analysis was limited by the availability of detailed clinical and phenotypic data, which may introduce potential confounders. Nevertheless, the findings highlight the clinical value of epigenetic sperm assessment as part of male fertility evaluation and support its potential to guide more effective, personalized fertility treatment pathways.
We present HSTLI, a dataset of Human Semen Time-Lapse Images acquired using two microscopy systems. These were (i) a commercial Computer-Assisted Semen Analysis (CASA) system and, (ii) an optical microscope. The dataset contains samples from 51 healthy male participants and includes 3,266 video clips (approximately 27 hours of imagery). A subset of the clips from both systems was manually annotated with bounding boxes around each visible sperm head, thereby establishing ground truth for detection, tracking, and motility analysis. Specifically, 14 CASA clips and 20 optical-microscope clips (each consisting of 900 frames) were labeled, yielding 29,950 annotated frames and roughly 1.4 million sperm annotations. The dataset also includes thousands of unlabeled clips captured under varying preparation conditions (washed vs. unwashed), dilution levels, magnifications, and regions of interest. When available, motility parameter reports are provided from either clinical technicians or CASA outputs. We demonstrate the use of this dataset in two example applications, (i) automated sperm detection and tracking using YOLOv5 and SORT, and (ii) visualizations of motility parameters. HSTLI offers a comprehensive benchmark for developing and evaluating algorithms for sperm detection, tracking, classification, and motility assessment.
