Reproductive Medicine Research Articles

PRESERVAÇÃO DA FERTILIDADE EM MULHERES COM CÂNCER NO SISTEMA REPRODUTOR FEMININO

The desire to start a family is an innate desire of almost all women, and becomes a relevant reason for discussion when, for some reason, there may be interference due to oncological issues. Recent advances in reproductive medicine are important to benefit women diagnosed with cancer who wish to start a family in the future. The objective of this work is to investigate methods of preserving female fertility, including oophoropexy, cryopreservation of embryos, eggs and ovarian tissue, in addition to in vitro maturation. Indications, advantages, disadvantages, possible complications, symptons and guidelines will be analyzed so that women can choose the best available approach based on their individual circunstances.

Diminished ovarian reserve may have no effect on embryo euploidy: A retrospective cohort study.

Does an association exist between diminished ovarian reserve (DOR) and embryonic aneuploidy risk in young women of reproductive age? This retrospective cohort study included 854 participants treated in the Department of Reproductive Medicine, Women's Hospital of Nanjing Medicine University, Nanjing Maternity and Child Health Care Hospital, from May 2016 to September 2023 for a total of 894 cycles. The relationship between ovarian reserve and embryonic euploidy was evaluated using statistical methods such as generalized estimating equation (GEE) and propensity score matching (PSM). Despite the higher number of biopsied blastocysts in women with normal ovarian reserve, no significant difference in embryonic aneuploidy rates was observed between DOR women and the control group. In addition, there were no significant disparities observed in the rates of metaphase II (MII) oocytes, normal fertilization, transferable embryos, blastocyst formation, and high-scoring blastocysts between the DOR and control groups after PSM. This study showed that DOR had no significant effect on the incidence of aneuploidy in embryos. Young women informed about DOR should be relatively confident about the quality of their eggs and the euploidy status of their embryos before conventional assisted reproduction, thereby mitigating concern regarding adverse maternal outcomes due to aneuploidy.

Evaluating the performance and clinical decision-making impact of ChatGPT-4 in reproductive medicine.

ChatGPT, a sophisticated language model developed by OpenAI, has the potential to offer professional and patient-friendly support. We aimed to assess the accuracy and reproducibility of ChatGPT-4 in answering questions related to knowledge, management, and support within the field of reproductive medicine. ChatGPT-4 was used to respond to queries sourced from a domestic attending physician examination database, as well as to address both local and international treatment guidelines within the field of reproductive medicine. Each response generated by ChatGPT-4 was independently evaluated by a trio of experts specializing in reproductive medicine. The experts used four qualitative measures-relevance, accuracy, completeness, and understandability-to assess each response. We found that ChatGPT-4 demonstrated extensive knowledge in reproductive medicine, with median scores for relevance, accuracy, completeness, and comprehensibility of objective questions being 4, 3.5, 3, and 3, respectively. However, the composite accuracy rate for multiple-choice questions was 63.38%. Significant discrepancies were observed among the three experts' scores across all four measures. Expert 1 generally provided higher and more consistent scores, while Expert 3 awarded lower scores for accuracy. ChatGPT-4's responses to both domestic and international guidelines showed varying levels of understanding, with a lack of knowledge on regional guideline variations. However, it offered practical and multifaceted advice regarding next steps and adjusting to new guidelines. We analyzed the strengths and limitations of ChatGPT-4's responses on the management of reproductive medicine and relevant support. ChatGPT-4 might serve as a supplementary informational tool for patients and physicians to improve outcomes in the field of reproductive medicine.

Long-Term Outcomes of Assisted Reproductive Technologies (ART): A Comparative Study of Pregnancy Complications and Neonatal Outcomes

Assisted Reproductive Technologies (ART) have revolutionized reproductive medicine. However, concerns regarding pregnancy complications and long- term neonatal outcomes are growing. This study examines the increased risk of conditions like preeclampsia, gestational diabetes, thyroid-related disorders, anemia, placental abnormalities, and the increased likelihood of cesarean delivery. Additionally, it evaluates the neonatal risks, including preterm birth, congenital anomalies, cardiometabolic risks, and potential cancer rates in ART-conceived offspring. These findings underscore the importance of continuous research and comprehensive care in ART pregnancies.

A novel step-by-step teaching method improves training outcomes in transvaginal ultrasound for postgraduate reproductive medicine students: an exploratory randomized controlled study

BackgroundTraditional methods of training in ultrasound technology make it difficult for postgraduate reproductive medicine students to rapidly develop into doctors who can perform clinical examinations independently. It is necessary to explore an efficient method for ultrasound training. The purpose of this study was to investigate whether the step-by-step (SBS) teaching improves the ultrasound diagnosis and clinical work level of reproductive medicine graduate students.MethodsA total of fifty postgraduate reproductive medicine students who participated in ultrasound room training were selected at random and divided into two groups: a traditional teaching control group and a stepwise teaching experimental group. A comparison was subsequently conducted between the two groups in terms of theoretical level, skill operation, comprehensive ability and teaching evaluation.ResultsIn terms of theory, skills, and comprehensive assessment, the experimental group exhibited superior performance compared to the control group (P < 0.05). The experimental group rated the instructors’ teaching ability and methods significantly better than did the control group (P < 0.05). The experimental group’s overall satisfaction with the training was better than that of the control group, but the difference was not statistically significant (P > 0.05).ConclusionsThe stepped teaching model has the potential to facilitate the acquisition of clinical ultrasound detection and diagnostic techniques by postgraduate reproductive medicine students, thereby enhancing their overall competence and satisfaction with the teaching process.

The Application of TCM Sentiment Treatment and Narrative Medicine in Infertility

Abstract: This study delves into the integration of Traditional Chinese Medicine (TCM) emotional therapy with modern medical interventions in treating infertility, aiming to enhance the therapeutic outcomes for patients. It posits that infertility encompasses not only physical factors but also significant psychological and emotional dimensions. The synthesis of TCM emotional therapy and contemporary reproductive medicine signifies a paradigm shift in comprehending the interactions among health, emotions, psychology, and physiology. By analyzing the diagnostic and treatment methods of TCM, this study elucidates how emotional therapy can enhance modern treatments, thereby promoting a more holistic, patient-centered approach to infertility care. Furthermore, it underscores the necessity of fostering a comprehensive understanding of health and disease within medical education.

CCDC28A deficiency causes head-tail coupling defects and immotility in murine spermatozoa

Male infertility presents a substantial challenge in reproductive medicine, often attributed to impaired sperm motility. The present study investigates the role of CCDC28A, a protein expressed specifically in male germ cells, whose paralog CCDC28B has been implicated in ciliogenesis. We identify unique expression patterns for CCDC28A and CCDC28B within the mouse testes, where CCDC28A is expressed in germ cells, whereas CCDC28B is expressed in supporting somatic cells. Through knockout mouse models and histological analyses, we reveal that CCDC28A deficiency results in diminished sperm motility and structural aberrations in sperm tails, notably affecting the head-tail coupling apparatus (HTCA), thereby causing male infertility. Fine structural analyses by transmission electron microscopy reveal disruptions at the capitulum-basal plate junction of the HTCA in the CCDC28A mutants. This results in the bending of the head within the neck region, often accompanied by thickening of the tail midpiece. Our discovery demonstrates that CCDC28A plays an essential role in male fertility and sperm tail morphogenesis through the formation of HTCA.

Therapeutic drug monitoring of tenofovir disoproxil and emtricitabine in oral HIV pre-exposure prophylaxis (PrEP) users who have undergone gastrointestinal surgery.

Oral HIV pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV, but its efficacy depends on adequate absorption of drug, which may decrease following gastrointestinal surgery. Clinicians across eight Genito-urinary Medicine clinics in the United Kingdom submitted data on PrEP users with history of gastrointestinal surgery who were referred to a national complex PrEP multi-disciplinary team between June 2021 and April 2023. Anonymised data were submitted on demographics, surgical history, PrEP regimen, and results of therapeutic drug monitoring (TDM) and HIV screening tests. Descriptive analyses were performed in SPSS version 29. Nine cases described cis-gender men-who-have-sex-with-men (MSM) with median age of 47.4 years (IQR = 43 - 56.5) taking tenofovir disoproxil (TDF)/emtricitabine (FTC) daily (n = 8) or event-based (n = 1) as PrEP. Median time between PrEP initiation and TDM was 53 days (IQR = 8.5-1705). The mean (±SD) trough concentration of tenofovir (TFV) and FTC were 90.2 ± 27.7ng/mL and 76.0 ± 45.9ng/mL, respectively. All patients had a negative HIV test at follow-up. Plasma trough concentrations of TFV observed in our cohort taking TDF/FTC were above the expected concentrations associated with PrEP efficacy as previously described in the literature, suggesting that PrEP can be safely given in this population, with TDM used for reassurance.

In vitro gametogenesis: Towards competent oocytes: Limitations and future improvements for generating oocytes from pluripotent stem cells in culture.

Production of oocytes from pluripotent cell cultures in a dish represents a new paradigm in stem cell and developmental biology and has implications for how we think about life. The spark of life for the next generation occurs at fertilization when sperm and oocyte fuse. In animals, gametes are the only cells that transmit their genomes to the next generation. Oocytes contain in addition a large cytoplasm with factors that direct embryonic development. Reconstitution of mouse oocyte and embryonic development in culture provides experimental opportunities and facilitates an unprecedented understanding of molecular mechanisms. However, the application of in vitro gametogenesis to reproductive medicine or infertility treatment remains challenging. One significant concern is the quality of in vitro-derived oocytes. Here, we review the current understanding and identify limitations in generating oocytes in vitro. From this basis, we explore opportunities for future improvements of the in vitro approach to generating high-quality oocytes.

Hypoprolactinemia, a neglected endocrine disorder.

This special issue of Reviews in Endocrine and Metabolic Disorders is dedicated to hypoprolactinemia. Prolactin is known for its actions on the mammary gland including development, preparation for postpartum lactation, as well as synthesis and maintenance of milk secretion. However, prolactin has many other physiological effects on reproduction, embryonic and fetal development, homeostasis, neuroprotection, behavior, and immunoregulation. In clinical practice, physiopathology and clinical consequences of increased prolactin secretion are generally well understood, and medical treatment to decrease prolactin levels is available and effective in most cases. Unlike prolactin excess, hypoprolactinemia has been a neglected endocrine disorder and nospecific replacement therapy is commercially available. Prolactin is the only anterior pituitary hormone not addressed by clinical hypopituitarism guidelines. In recent years, human studies have revealed that hypoprolactinemia is associated with metabolic, sexual and neuropsychologic alterations. Therefore, this special issue of Reviews in Endocrine and Metabolic Disorders is aimed to enhance our incomplete understanding of hypoprolactinemia. A total of 17 articles were authored by respected scientists and clinicians from a variety of disciplines including adult and pediatric endocrinology, pathology, gynecology, reproductive medicine, oncology, and neurosurgery.

Innovations in reproductive medicine, Gartner hype cycle and Dunning–Kruger effect

Research questionIn the dynamic field of reproductive medicine, the introduction of new technologies and interventions often follows the modified Gartner hype cycle, characterised by initial enthusiasm, unmet inflated expectations, and eventual disillusionment. This paper explores how the Dunning-Kruger effect, where individuals overestimate their knowledge and competence, contributes to the hype cycle in reproductive medicine. DesignBy examining the history of the endometrial scratch, the study illustrates the negative impact of prematurely adopted innovations. We stress the urgent need for a more rigorous approach to designating interventions as 'innovative' and call for robust data collection and analysis to evaluate their safety and effectiveness. ResultsThis proposed framework aims to balance the need for innovation with the imperative to protect patients from harm and ensure the cost-effectiveness of reproductive technologies. It reiterates the importance of evidence-based practice, emphasising that interventions should be thoroughly vetted through scientific research before being widely adopted. The paper underscores the role of regulatory bodies in overseeing the introduction of new technologies to prevent the premature implementation of unproven methods. ConclusionsWe propose the creation of comprehensive national and international databases accessible to researchers and clinicians. This would facilitate the rapid and reliable assessment of new treatments, allowing for continuous monitoring of their safety and efficacy. By integrating data from various sources, the framework aims to provide a more holistic understanding of the impacts of new interventions on patient outcomes. This paper advocates for a cautious and measured approach to innovation, ensuring that advancements are scientifically validated and clinically beneficial.

Perrault syndrome: a forgotten presentation for infertile women.

Perrault syndrome (PRLTS) is an uncommon hereditary condition distinguished by ovarian failure in females and sensorineural hearing loss. Infertility can be the presenting problem for a serious disease. History and physical examination is very essential among infertile couples. Perrault syndrome (PRLTS) is an uncommon hereditary condition distinguished by ovarian failure in females and sensorineural hearing loss. This case presentation describes a 22-year-old female from Saudi Arabia with PRLTS. The patient presented with progressive bilateral hearing loss since childhood, impacting her academic achievement. Additionally, she experienced amenorrhea since the age of 18 years, with previous investigations showing no hormonal imbalances. Other laboratory tests, including bone mineral density, kidney and liver function, electrolytes, and lipid profile, showed mostly normal results, except for a slightly abnormal lipid profile with low high-density lipoprotein and high low-density lipoprotein levels. This case highlights the challenges faced by individuals with PRLTS, specifically progressive hearing loss and gonadal dysfunction, leading to infertility. Further evaluation and management are warranted to address the patient's hearing impairment and fertility concerns, with a multidisciplinary approach involving audiology, endocrinology, and reproductive medicine.

Decellularized extracellular matrix from bovine ovarian tissue maintains the protein composition of the native matrisome

Recent approaches of regenerative reproductive medicine investigate the decellularized extracellular matrix to develop a transplantable engineered ovary (TEO). However, a full proteomic analysis is not usually performed after the decellularization process to evaluate the preservation of the extracellular matrix (ECM). In this study, the ECM of the bovine ovarian cortex was analyzed before and after decellularization using mass spectrometry and bioinformatics. A total of 155 matrisome proteins were identified in the native ECM of the bovine ovarian cortex, with 145 matrisome proteins detected in the decellularized ECM. After decellularization, only 10 matrisome proteins were lost, and notably, none belonged to the category of reproductive biological processes. Histology and histochemistry analyses were employed to assess the general morphology of both native and decellularized ECM, allowing for the identification of the most abundant ECM proteins. Moreover, our study highlighted collagen type VI alpha 3 and heparan sulfate proteoglycan 2 as the most abundant components in the bovine ovarian ECM, mirroring the composition observed in the human ovary. These findings enhance our understanding of the composition of both native and decellularized ECM, with the potential implications for the development of a TEO. SignificanceThe significance of the present study lies on the possibility of advancing towards developing a bioengineered ovary, which is the ultimate strategy to regain fertility in women. The results demonstrate that the decellularized extracellular matrix of the bovine ovary maintains the protein composition of the native matrisome, using a recently described decellularization protocol. The decellularized matrix may serve as scaffolding for seeding ovarian stromal cells and follicles to create a bioengineered ovary, and as closer its composition is to the native matrix the better. Also, comparing the bovine ovarian matrisome, which was described for the first time here, with the human ovarian matrisome, we could see a great similarity, suggesting that the bovine ovary decellularized matrix may serve as a model for developing a human bioengineered ovary.

Enhancing IVF Outcomes with Artificial Intelligence: Current Advances and Future Possibilities

The integration of Artificial Intelligence (AI) into In Vitro Fertilization (IVF) practices has marked a revolutionary shift in reproductive medicine, offering enhanced precision, efficiency, and personalized treatment plans. The rapid advancement of Artificial Intelligence (AI) has led to significant innovations in the field of reproductive medicine, particularly in In Vitro Fertilization (IVF). Traditional IVF procedures, while effective, often face challenges such as variable success rates, high costs, and the emotional burden on patients due to multiple treatment cycles. AI offers a promising solution to these issues by enhancing accuracy, personalization, and efficiency throughout the IVF process. AI algorithms have shown remarkable capabilities in diagnosing infertility by analyzing complex datasets from hormone profiles, genetic testing, and medical imaging, enabling early identification of conditions like polycystic ovary syndrome (PCOS) and endometriosis. Moreover, one of the most promising applications of AI in IVF is embryo grading. However, AI systems have been developed to objectively evaluate embryos based on time-lapse imaging, morphology, and other parameters, improving the selection process. Additionally, AI has been instrumental in optimizing ovarian stimulation protocols by analyzing patient data to determine the appropriate medication dosage, minimizing the risk of ovarian hyperstimulation syndrome (OHSS). This review discusses the current state of AI integration in fertility treatments, successful case studies, and ongoing research to develop more sophisticated AI models. Overall, AI holds immense promise in making IVF more accessible, affordable, and successful for patients worldwide, ushering in a new era of precision medicine in reproductive health.

Diagnosis of arcuate uterus using three-dimensional transvaginal ultrasound and investigation of its association withperinatal complications.

Arcuate uterus does not impact the success of infertility treatments, but there is no consensus on whether it influences perinatal outcomes. The objective of the present study was to investigate whether minor congenital uterine anomalies such as an arcuate uterus contribute to perinatal complications. This was a retrospective cohort study at a single institution. The study included 1097 deliveries after 22 weeks of gestation. Transvaginal ultrasound, with three-dimensional functionality, assessed uterine morphology based on American Society for Reproductive Medicine criteria. We compared maternal backgrounds and perinatal complications between arcuate uterus and normal uterus groups. Statistical analyses, including multivariate analysis, aimed to identify independent risk factors. A total of 69 patients (7.5%) with diagnosed arcuate uterus were included. Maternal background factors showed no significant differences between groups. In perinatal complications, an arcuate uterus was associated with a significantly higher incidence of preterm delivery (13% versus 4.7%, P = 0.01), preterm premature rupture of membranes (7.2% versus 1.6%, P = 0.01), fetal growth restriction (FGR; 16% versus 6.7%, P = 0.01), and abnormal placental cord insertion (33% versus 7.6%, P < 0.01). After multivariate analysis, arcuate uterus emerged as an independent risk factor for preterm delivery (adjusted odds ratio [aOR], 4.0 [95% confidence interval (CI), 1.6-9.9], P < 0.01), FGR (aOR, 2.6 [95% CI, 1.2-5.6], P = 0.02), and abnormal placental cord insertion (aOR, 6.0 [95% CI, 3.4-10.6], P < 0.01). Arcuate uterus stands as an independent risk factor for preterm delivery, FGR, and abnormal placental cord insertion. The findings emphasize the importance of recognizing even minor uterine morphological abnormalities in assessing and managing perinatal complications.

Deciphering the link: A cutting-edge exploration of the intriguing connection between recurrent pregnancy loss and rare earth elements-Lutetium, praseodymium, samarium, dysprosium, and cerium.

To evaluate the levels of serum rare earth elements (REEs): lutetium [Lu], praseodymium [Pr], samarium [Sm], dysprosium [Dy], and cerium [Ce] in pregnant women with recurrent pregnancy loss (RPL) and evaluate their relationship with total antioxidant capacity (TAC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA damage. A case-controlled study was conducted on a cohort of 60 female participants, with first-trimester healthy pregnant women as the control group and pregnant women with a history of consecutive abortions as the recurrent pregnancy loss (RPL) group. Following blood collection, serum concentrations of Lu, Pr, Sm, Dy, and Ce were measured using an inductively coupled plasma mass spectrophotometer (ICP-MS). Oxidative stress and DNA damage were evaluated through TAC and DNA damage marker (8-OHdG). Serum levels of Lu, Pr, Sm, Dy, and Ce were higher in women with RPL compared with control (P < 0.001). Intriguingly, a strong significant negative correlation was observed between TAC and REEs (P < 0.05). Lu, Dy, and Ce demonstrated a significant positive correlation with increased DNA damage in the RPL group (P < 0.05). Contrary, there was no evidence of a correlation between 8-OHdG and Pr and Sm. The study highlights a potential association between Lu, Sm, Dy, and Ce and an increased risk of RPL, highlighting REE-induced toxicity as a major risk factor for RPL. The outcome of the study is to advance our understanding of the interplay between rare earth elements and RPL, with potential implications for reproductive medicine, environmental health, and the development of preventive strategies for individuals at risk of RPL.

The effects of fresh embryo transfer and frozen-thawed embryo transfer on the perinatal outcomes of single fetuses from mothers with PCOS.

To investigate the effects of fresh embryo transfer and frozen-thawed embryo transfer on perinatal outcomes among patients with PCOS. Patients who underwent in vitro fertilization and embryo transfer at the reproductive medicine center of the Affiliated Hospital of Guangdong Medical University from February 2013 to March 2021 were retrospectively analyzed. Patients were divided into the fresh embryo transfer group and frozen-thawed embryo transfer group according to whether fresh embryo transfer was performed. According to their conditions, patients were further classified into the ET-PCOS group (group A, n = 104), ET-non-PCOS group (group B, n = 212), FET-PCOS group (group C, n = 102), or FET-non-PCOS group (group D, n = 148); the general data, laboratory indicators and pregnancy outcomes of the patients were statistically analyzed, and the perinatal outcomes and related factors between the groups were compared and analyzed. The level of E2 on the HCG test day in the ET group was lower than that in the FET group. The natural birth rate of group D was lower than that of group A and group B, and the cesarean section rate was higher than that of group A and group B; the clinical pregnancy rate of group A was higher than that of group B and group D, and the difference was statistically significant (P < 0.05). There was no significant difference in the total abortion rate, early abortion rate or late abortion rate between the groups (P > 0.05). There was no significant difference in gestational age, neonatal sex or neonatal weight between the groups (P > 0.05). The incidence of placenta previa in Group B was significantly lower than that in Group D, and the difference was significant (P < 0.05). The incidence of fetal distress in Group B was significantly lower than that in Groups C and D, and the incidence of neonatal jaundice in Group D was significantly higher than that in Groups A and B (P < 0.05). In the multivariate analysis, the number of high-quality embryos was independent factors affecting clinical pregnancy, and the embryo transfer method was an independent factor affecting fetal distress and neonatal jaundice. Young PCOS patients without risk of OHSS have a high clinical pregnancy rate with fresh transplant cycles. PCOS disease itself has no significant effect on the perinatal outcomes of the mother or singleton infant. Frozen-thawed embryo transfer may increase the incidence of low placenta, fetal distress and neonatal jaundice.

Seroepidemiological study of Epstein-Barr virus infection in reproductive age women in Bulgaria

Abstract Background At the present stage, studies on the involvement of Epstein-Barr virus (EBV) in neonatal pathology are rare. Establishing seroprevalence among women of reproductive age has important epidemiological significance in order to determine the risk of infection during pregnancy and intrauterine infection of the fetus. The aim of the study is to determine the seroepidemiological status of EBV in reproductive age women. Methods We conducted a prospective seroepidemiological study in which 96 healthy women of reproductive age (18 to 49 years) were tested during the period December 2023 - January 2024 in Medical Center “Clinical Institute for Reproductive Medicine”- Pleven, Bulgaria. Participants were surveyed on a voluntary basis. The exclusion criteria were: presence of autoimmune disorder, immunosuppressive states, malignancy and populations at risk such as persons under 18 years of age and pregnant women. The presence of specific antibodies were detected using a standardized Anti-EBV VCA IgM, Anti-EBV VCA IgG and Anti-EBV EBNA-1 IgG ELISA kits. The demographic and anamnestic data were collected for each participant in Case Report Form. Results The average age of the women was 34.41±5.44 years. Dominating were women with higher education (76.04%) living in urban areas (91.67%). The results of the seroepidemiological study of markers for EBV show that 98.96% of women of reproductive age are seropositive. There was no significant correlation between the presence of antibodies and socio-demographic indicators (living area, education and number of family members). Conclusions The results of this study imply that only 1.04% of the reproductive age women in Pleven region are susceptible to infection with EBV. Although interpretation of the serological status indicates a low risk of primary infection, active monitoring of high-risk groups pregnant women is necessary because of the possibility of EBV reactivation. Key messages • On-going monitoring of the seroepidemiological EBV status in reproductive age women is necessary to determining the possibility of EBV reactivation and to reduce the teratogenic risk of the infection. • Seroepidemiological surveillance of markers for EBV infection in reproductive age women is part of effective preventive measures at the public health level.

Identify high-risk DOR women ≤ 35 years old following assisted reproduction technology through cutoffs of anti-mullerian hormone and antral follicle counts

BackgroundFemales with diminished ovarian reserve (DOR) have significantly lower cumulative live birth rates (CLBRs) than females with normal ovarian reserve. A subset of young infertile patients, whose ovarian reserve is declining but has not yet met the POSEIDON criteria for DOR, has not received the attention it merited. These individuals have not been identified in a timely manner prior to the initiation of assisted reproductive technology (ART), leading to suboptimal clinical pregnancy outcomes. We categorized this overlooked cohort as the “high-risk DOR” group.ObjectiveThe primary aim of this study was to identify high-risk DOR patients through anti-Mullerian hormone (AMH) and antral follicle counts (AFCs).MethodsA total of 10037 young women (≤ 35 years old) who underwent their first initial oocyte aspiration cycle at a single reproductive medicine center were included and further classified into three groups, based on the thresholds for AMH and AFC established through receiver operating characteristic (ROC) analysis and in alignment with the POSEIDON criteria. Two ROC analyses were performed to identify the cutoff values of AMH and AFC to obtain one viable embryo (one top-quality embryo or one viable blastocyst). The cutoffs of ROC were measured by sensitivity and specificity. The primary outcome was the cumulative live birth rate (CLBR) per oocyte aspiration cycle. The secondary outcomes included the number of oocytes retrieved and the number of viable embryos formed. Pearson’s chi-square tests were conducted to compare the clinical outcomes among the three groups. Furthermore, univariate logistic regression analyses were performed to investigate the associations between ovarian reserve and clinical outcomes. All of the above comparisons between the high-risk DOR and NOR were further confirmed by propensity score matching (PSM) (1:1 nearest-neighbor matching, with a caliper width of 0.02).ResultsAccording to the ROC analyses and POSEIDON criteria, the present study identified a population of high-risk DOR patients (1.20 ng/mL < AMH values < 2.50 ng/mL, with 6 ≤ AFC ≤ 10; n = 682), and their outcomes were further compared to those of DOR patients (positive control, AMH values ≤ 1.2 ng/mL, and/or AFC ≤ 5; n = 1153) and of NOR patients (negative control, 2.5 ng/mL ≤ AMH values ≤ 5.5 ng/mL, and 11 ≤ AFC ≤ 20; n = 2649). Patients in the high-risk DOR group had significantly lower CLBRs than those in the NOR group (p < 0.001) but higher CLBRs than those in the DOR group (p < 0.001). Logistic regression further demonstrated that high-risk DOR was associated with a lower likelihood of cumulative live birth chance (OR 0.401, 95% CI: 0.332–0.486, p < 0.001) than NOR was, with a greater likelihood of cumulative live birth chance (OR 1.911, 95% CI:1.558–2.344, p < 0.001) than DOR was. To investigate the effects of embryo development stage, the outcomes of D3 embryos and blastocysts were analyzed separately. Significant differences in pregnancy outcomes were detected only in D3 embryo ET cycles among the three groups (high-risk DOR vs. NOR, all p < 0.05; DOR vs. NOR, all p < 0.05). DOR/high-risk DOR did not influence the pregnancy loss rates or pregnancy outcomes (clinical pregnancy rates and ongoing pregnancy rates) per positive HCG cycle (all p > 0.05). After PSM, the differences in ovarian response and pregnancy outcomes between the high-risk DOR and NOR groups were consistent with the results before PSM.Conclusion(s)Our study revealed that the CLBR of the high-risk DOR patients was significantly lower than that of females with normal ovarian reserve and greater than that of females with DOR. The values of AMH ranging from 1.2 to 2.5 and AFC ranging from 6 to 10 appeared to constitute meaningful thresholds in females with mildly reduced ovarian reserve.

Non-invasive prediction of human embryonic ploidy using artificial intelligence: a systematic review and meta-analysis

Embryonic ploidy is critical for the success of embryo transfer. Currently, preimplantation genetic testing for aneuploidy (PGT-A) is the gold standard for detecting ploidy abnormalities. However, PGT-A has several inherent limitations, including invasive biopsy, high economic burden, and ethical constraints. This paper provides the first comprehensive systematic review and meta-analysis of the performance of artificial intelligence (AI) algorithms using embryonic images for non-invasive prediction of embryonic ploidy. Comprehensive searches of studies that developed or utilized AI algorithms to predict embryonic ploidy from embryonic imaging, published up until August 10, 2024, across PubMed, MEDLINE, Embase, IEEE, SCOPUS, Web of Science, and the Cochrane Central Register of Controlled Trials were performed. Studies with prospective or retrospective designs were included without language restrictions. The summary receiver operating characteristic curve, along with pooled sensitivity and specificity, was estimated using a bivariate random-effects model. The risk of bias and study quality were evaluated using the QUADAS-AI tool. Heterogeneity was quantified using the inconsistency index (I 2 ), derived from Cochran's Q test. Predefined subgroup analyses and bivariate meta-regression were conducted to explore potential sources of heterogeneity. This study was registered with PROSPERO (CRD42024500409). Twenty eligible studies were identified, with twelve studies included in the meta-analysis. The pooled sensitivity, specificity, and area under the curve of AI for predicting embryonic euploidy were 0.71 (95% CI: 0.59-0.81), 0.75 (95% CI: 0.69-0.80), and 0.80 (95% CI: 0.76-0.83), respectively, based on a total of 6879 embryos (3110 euploid and 3769 aneuploid). Meta-regression and subgroup analyses identified the type of AI-driven decision support system, external validation, risk of bias, and year of publication as the primary contributors to the observed heterogeneity. There was no evidence of publication bias. Our findings indicate that AI algorithms exhibit promising performance in predicting embryonic euploidy based on embryonic imaging. Although the current AI models developed cannot entirely replace invasive methods for determining embryo ploidy, AI demonstrates promise as an auxiliary decision-making tool for embryo selection, particularly for individuals who are unable to undergo PGT-A. To enhance the quality of future research, it is essential to overcome the specific challenges and limitations associated with AI studies in reproductive medicine. This work was supported by the National Key R&D Program of China (2022YFC2702905), the Shengjing Freelance Researcher Plan of Shengjing Hospital and the 345 talent project of Shengjing Hospital.