The study was unveiled at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), one of the foremost global platforms for cutting-edge reproductive science. This extensive population-based research was orchestrated by the EU FEMaLe consortium (Finding Endometriosis through Machine Learning), led by Dr. Lucky Saraswat of the University of Aberdeen, in collaboration with specialists at the University of Edinburgh. By mining an unprecedented dataset that integrates primary care, secondary care, and maternity records over a 30-year span—from 1991 to 2020—the team conducted the largest and most comprehensive analysis addressing the intersection of infertility and endometriosis to date.

Endometriosis is a chronic gynecological disorder characterized by the aberrant growth of endometrial-like tissue outside the uterine cavity, frequently precipitating debilitating pelvic pain and compromised fertility. Worldwide, it affects approximately 190 million women and is a leading cause of female infertility. Despite its high prevalence, endometriosis remains notoriously underdiagnosed, in part due to nonspecific symptoms and diagnostic delays. This study’s scope and duration have enabled a rare examination of the natural history and reproductive trajectories of affected women with an unparalleled level of granularity and clinical relevance.

The cohort encompassed 4,041,770 women aged between 13 and 50 years who sought medical attention in England for infertility or symptoms potentially attributable to endometriosis. Of these, 245,994 presented explicitly with infertility issues, while 111,197 had surgically confirmed endometriosis diagnoses, established via definitive procedures such as laparoscopy or laparotomy. The overall prevalence of female infertility stood at 48.9 per 1,000 women across the study period, peaking among those between 30 to 39 years old—an age range critical to reproductive potential and clinical decision-making.

Intriguingly, among the women identified with infertility, 6.1% (14,904) had a surgical diagnosis of endometriosis. Notably, 57.4% of this subgroup experienced infertility prior to receiving their endometriosis diagnosis, underscoring the persistent challenge of delayed recognition even in symptomatic individuals. This temporal disconnect highlights the urgent need for improved diagnostic tools and clinical vigilance to expedite identification and management of endometriosis in patients presenting with fertility disruptions.

Statistical analysis reaffirmed a robust association between endometriosis and infertility: women grappling with infertility were found to be more than twice as likely to have endometriosis diagnosed compared to those without fertility concerns. This correlation aligns with longstanding clinical observations, reinforcing the role of endometriosis in disrupting normal reproductive physiology through mechanisms such as impaired ovulation, pelvic adhesion formation, and altered immune and inflammatory environments.

Yet, when dissecting pregnancy outcomes among women with infertility, a counterintuitive yet compelling revelation emerged. Those whose infertility was linked to endometriosis demonstrated a fourfold greater likelihood of achieving conception relative to women whose infertility stemmed from other causes—be it ovulatory dysfunction, tubal pathology, or unexplained origins. Overall, 40.5% of women with an endometriosis diagnosis achieved at least one pregnancy during the longitudinal follow-up, a figure that challenges generalized perceptions of inevitable infertility associated with the disease.

Dr. Saraswat elaborated on these surprising findings by suggesting variability in disease phenotype and severity as a critical factor influencing reproductive potential. Women with milder manifestations of endometriosis may retain robust fertility, especially if the condition is identified and managed proactively. Surgical intervention, particularly laparoscopic excision or ablation, has demonstrated moderate-quality evidence of enhancing pregnancy rates, possibly through restoration of pelvic anatomy and reduction of localized inflammation.

Furthermore, heightened awareness among women diagnosed with endometriosis about the reproductive implications of their condition may prompt earlier and more assertive fertility consultations and treatments, thereby improving conception likelihood. This underscores the importance of timely diagnosis and patient education in optimizing fertility outcomes, as well as the multifactorial nature of reproductive success that encompasses age, disease burden, and treatment modalities.

The study’s robust dataset and longitudinal design enable a nuanced understanding of infertility trajectories in the context of endometriosis, delivering invaluable evidence to inform clinical counseling. Women newly diagnosed with endometriosis can now receive more precise prognostic information relating to the probability of infertility, the potential for successful conception, and how these outcomes compare with other infertility etiologies. Such evidence-based guidance is essential to empower patients in reproductive decision-making and to tailor therapeutic strategies to individual risk profiles and aspirations.

Beyond immediate clinical implications, these insights pave the way for future research endeavors to elucidate the interplay between disease stage, anatomical site of lesions, surgical management, and assisted reproductive technologies in shaping fertility outcomes. Understanding the heterogeneity of endometriosis and its impact on reproductive biology at a molecular and systemic level remains a critical frontier in reproductive medicine.

Professor Dr. Anis Feki, Chair-Elect of ESHRE, emphasized the study’s significance, highlighting how it offers reassurance to patients burdened by endometriosis-related infertility and reinforces the imperatives of early diagnosis and personalized treatment strategies. This research contributes to dismantling the stigma and fatalism often associated with endometriosis, fostering a more hopeful and scientifically grounded narrative for affected women.

The findings have been submitted for publication in Human Reproduction, a premier journal in reproductive biology and medicine, ensuring dissemination to global scientific and clinical communities. This study exemplifies the transformative potential of big data and machine learning methodologies in unraveling complex bio-clinical phenomena, heralding a new era of precision reproductive healthcare.

In sum, this landmark investigation not only validates the link between endometriosis and infertility but crucially delineates the nuanced reproductive prospects for these women. It calls for enhanced diagnostic acumen, individualized clinical pathways, and sustained research investment to unravel the intricacies of endometriosis and optimize fertility outcomes, transforming the reproductive landscape for millions worldwide.

Subject of Research: Reproductive outcomes and fertility potential in women with endometriosis-associated infertility based on a 30-year national population study.

Article Title: Not specified in the source content.

News Publication Date: 2 July 2025

Web References:
https://www.who.int/news-room/fact-sheets/detail/endometriosis#:~:text=Overview,period%20and%20last%20until%20menopause

References:
[1] Saraswat, L., et al. (2025). Infertility and endometriosis: a 30-year long national population-based study of prevalence, association and pregnancy outcomes. Human Reproduction.
[2] Rogers, P. A.W., et al. (2009). Priorities for endometriosis research: recommendations from an international consensus workshop. Reproductive sciences (Thousand Oaks, Calif.), 16(4), 335–346.
[3] World Health Organization. (2023). Endometriosis.

Image Credits: Not provided.

Keywords: Endometriosis, Infertility, Reproductive biology, Gynecological disorders, Fertility outcomes, Population-based study, Epidemiology, Surgical diagnosis, Laparoscopy, Assisted reproduction, Women’s health.

The data reveals that in 2022, a total of 960,347 ART cycles were performed across 39 European countries, representing a 15.6% decrease when compared to the 1,137,177 cycles reported in 2021. This decline prompts critical reflection on potential underlying factors, including shifting healthcare policies, access constraints, economic fluctuations, and patient choices. However, within this overall reduction, the persistence of clinical pregnancy rates emphasizes that the quality and effectiveness of these treatments remain uncompromised, reflecting sustained clinical proficiency and possibly improved patient selection criteria.

Delving deeper into the treatment modalities, the report categorizes the ART cycles into several key types: in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), frozen embryo transfers (FET), preimplantation genetic testing (PGT), and oocyte donation (OD). In 2022 alone, IVF accounted for 137,148 cycles, while ICSI constituted a larger segment with 317,415 cycles. Frozen embryo transfers were notably the most prevalent, with 365,905 cycles undertaken. The rise of FET is indicative of the increasingly common “freeze-all” approach, an evolving clinical practice aimed at improving endometrial receptivity and optimizing pregnancy outcomes.

The incorporation of preimplantation genetic testing into standard practice also remains significant, with 92,677 cycles documented. PGT technology facilitates the selection of embryos free from specific genetic abnormalities, thereby increasing the likelihood of successful implantation and miscarriage reduction. The availability of oocyte donation cycles, tallying 41,138 in the reported period, reflects ongoing reliance on donor gametes to address a variety of infertility issues including diminished ovarian reserve and advanced maternal age, underscoring the critical role of third-party reproduction.

Parallel to ART, intrauterine insemination (IUI) continues to be an essential fertility intervention, with 126,185 cycles utilizing partner semen and an additional 42,532 cycles employing donor semen. IUI’s less invasive approach retains its relevance, particularly for couples with unexplained infertility or mild male factor issues. Additionally, the emerging sphere of fertility preservation interventions, encompassing oocyte, ovarian tissue, semen, and testicular tissue banking, registered 30,758 cases across 14 countries. This facet of reproductive medicine addresses the growing needs of oncology patients and individuals opting to preserve fertility ahead of potentially gonadotoxic treatments or personal life choices.

Crucially, despite the quantitative fluctuations in cycle numbers, clinical pregnancy rates have exhibited remarkable stability between 2021 and 2022. IVF pregnancy rates per aspiration and per transfer experienced only marginal decreases, from 26.3% to 25.8% and 33.5% to 32.7% respectively. Similarly, ICSI maintained rates around 24% per aspiration and 32-33% per transfer. Frozen embryo transfers, often regarded as more patient-friendly and physiologically congruent, showed a slight dip from 37.0% to 36.6%. These data points collectively highlight that patient outcomes in assisted reproduction have not been compromised despite fewer cycles being performed.

A striking trend illuminated by the data is the continued rise in the use of single embryo transfer (SET), increasing from 60.5% in 2021 to 62.6% in 2022. The migration towards SET is largely driven by the imperative to reduce multiple gestations, which pose heightened risks for both maternal and neonatal complications. Correspondingly, singleton delivery rates improved to 91.5%, while twin deliveries declined to 8.4%, and triplet deliveries maintained a low prevalence at 0.1%. This shift reflects a growing consensus within the reproductive medicine community that prioritizes safety and long-term health in ART pregnancies.

Professor Dr. Diane De Neubourg, Chair of the EIM Consortium, emphasized the implications of these findings, highlighting that “the report confirms the continued high utilisation of ART and IUI across Europe.” Despite the modest decrease in cycle numbers, stable pregnancy rates and rising singleton birth prevalence collectively demonstrate advances in clinical protocols and patient management. Notably, the magnitude of this dataset — with nearly one million treatment cycles annually — provides an unparalleled resource for transparency, quality assurance, and vigilance in reproductive healthcare.

Echoing these sentiments, Professor Dr. Karen Sermon, Chair of ESHRE, underscored the importance of rigorous and harmonized data collection across diverse European healthcare systems. She noted that “strengthening standardised reporting drives improvements in care quality and outcome for patients undergoing medically assisted reproduction.” This highlights the ongoing need to refine registries and reporting methodologies in order to capture nuanced details that inform clinical best practices and policymaking in an evolving reproductive landscape.

The ESHRE EIM Consortium report, representing the largest aggregation of assisted reproduction data in Europe since 1997, is a cornerstone for examining longitudinal trends and informing future clinical and regulatory strategies. With nearly 14 million ART treatments recorded to date and approximately 2.8 million children born through these technologies, the consortium’s efforts provide an indispensable lens into how reproductive medicine is developing on a continental scale.

Nonetheless, the authors advise caution in interpreting the findings, acknowledging considerable heterogeneity among European countries in terms of data completeness and collection methodologies. Variability in reporting standards, clinical practices, and health system infrastructures present challenges for direct cross-national comparisons but do not diminish the report’s critical role in identifying broad patterns and informing harmonization efforts.

This evolving portrait of ART in Europe captures a mature yet dynamic field combining cutting-edge biomedical science with tailored clinical strategies. The increased reliance on single embryo transfer, coupled with stable clinical pregnancy rates despite lower overall cycle numbers, epitomizes a shift towards safer, patient-centered fertility treatment. Furthermore, the expansion into fertility preservation signals an awareness of reproductive health beyond traditional infertility paradigms, integrating oncology, gender diversity, and elective preservation into the reproductive medicine fold.

As reproductive technologies become ever more sophisticated, this comprehensive European data offers invaluable benchmarks to propel medical innovation and optimize patient care. The findings presented at the ESHRE 41st Annual Meeting not only reinforce the efficacy of current treatments but also catalyze dialogue on how healthcare systems can adapt to patient needs while ensuring rigorous quality and ethical standards. The depth and breadth of the report showcase the power of collaborative registries and scientific exchange in shaping the future of human reproduction.

Subject of Research: Assisted Reproductive Technology (ART) and Intrauterine Insemination (IUI) trends and outcomes in Europe during 2022.

Article Title: — [Not explicitly provided]

News Publication Date: 1 July 2025

Web References: — [Not provided in the content]

References:

1. Presentation “Assisted Reproductive Technology (ART) in Europe 2022 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium.” Presented at the ESHRE 41st Annual Meeting, 1 July 2025.
2. ESHRE European IVF Monitoring (EIM) Consortium reports since 1997, published in Human Reproduction.
3. Smeenk, J., et al. (2024). Assisted reproductive technology (ART) in Europe 2021 and development of a strategy of vigilance: Preliminary results generated from European registers by the ESHRE EIM Consortium. Human Reproduction, 39(Suppl_1).
4. Clinical pregnancy definition per ultrasound confirmation of gestational sac or clinical signs.

Image Credits: — [Not provided]

Keywords: Human reproduction; Human fertilization; In vitro fertilization; Pregnancy; Birth control; Human biology; Human health

Preeclampsia, characterized by dangerously high blood pressure and organ damage during pregnancy, remains a leading cause of maternal and neonatal morbidity and mortality worldwide. Traditional screening methods in the first trimester primarily rely on maternal risk factors and placental biomarkers, which unfortunately fail to identify over 50% of at-risk pregnancies before the disease’s clinical manifestation. Recognizing this diagnostic gap, the collaborative research initiative spearheaded by the Carlos Simón Foundation and iPremom set out to harness advanced genomics and machine learning for more sensitive, timely detection.

The study enrolled an unprecedented cohort of 9,586 pregnant women across 14 major Spanish hospitals between September 2021 and June 2024. Out of these, a nested case-control subset of 216 participants was meticulously selected for intensive molecular profiling. Researchers collected multiple plasma samples at critical gestational windows—specifically between 9 and 14 weeks, 18 to 28 weeks, and beyond 28 weeks or at diagnosis—to assay circulating cfRNA molecules which serve as dynamic indicators of gene expression changes in maternal and placental tissues.

Employing cutting-edge next-generation sequencing on 548 plasma samples using Illumina technology, the team decoded complex cfRNA profiles. These molecular signatures were then analyzed through sophisticated machine learning algorithms to develop predictive models capable of discerning pregnancies at risk for both early-onset (EOPE) and late-onset preeclampsia (LOPE), well in advance of symptomatic detection.

Remarkably, the first-trimester cfRNA model flagged EOPE with 83% sensitivity and 90% specificity, boasting an average area under the curve (AUC) of 0.88. This implies that on average, the test predicted EOPE approximately 18 weeks—nearly five months—prior to clinical diagnosis. Such temporal advantage presents a compelling opportunity to commence preventative therapies and heightened surveillance protocols, potentially averting severe complications for both mother and child.

Molecular investigation into the predictive transcripts revealed close links to genes involved in maternal endometrial function, particularly those associated with decidualisation resistance. Decidualisation refers to the vital transformation of the uterine lining facilitating embryo implantation and placental development, and its impairment is increasingly implicated in EOPE pathogenesis. Nearly half of the identified cfRNA transcripts corresponded to these uterine remodeling pathways, underscoring a key mechanistic role of uterine dysfunction.

In contrast, cfRNA signatures predictive of LOPE emerged as distinct, with minimal overlap in decidualisation-related transcripts. Instead, late-onset preeclampsia exhibited systemic biological signatures involving immune response and hepatic pathways, emphasizing a more localized and temporally delayed pathophysiology. On average, LOPE was predicted roughly 14.9 weeks before symptom onset, allowing a critical window for early detection despite its complex biological roots.

Dr. Nerea Castillo Marco, the study’s lead author, emphasized the novelty of this approach in prenatal medicine: “Our findings demonstrate for the first time that a routine maternal blood draw during early pregnancy can deliver highly accurate forecasts of preeclampsia, creating an invaluable window for intervention before clinical manifestations.” The precision and non-invasiveness of cfRNA liquid biopsy herald a paradigm shift in maternal-fetal medicine, particularly for a condition historically challenging to diagnose preemptively.

Beyond the predictive capabilities, the transcriptomic landscape mapped in this study provides unprecedented molecular insights into the diverse organ systems impacted during EOPE, including liver, kidney, brain, lungs, and placenta. This multisystem involvement confirms that EOPE encompasses widespread systemic dysregulation rather than isolated placental pathology. Conversely, LOPE’s molecular footprint concentrated on immune and liver-related processes further delineates the two forms as distinct clinical and biological entities.

Project leader Dr. Tamara Garrido highlighted the immediate translational potential: “With ongoing prospective clinical validation underway, we anticipate that cfRNA-based screening will soon integrate seamlessly into routine prenatal care, providing obstetricians worldwide with a robust tool to identify high-risk pregnancies proactively.” Regulatory reviews and clinical deployment efforts are progressing rapidly, with potential availability of this revolutionary screening method expected within the next year.

The implications of this study extend far beyond diagnostics. By elucidating molecular pathways implicated in preeclampsia development, it paves the way for targeted therapeutic research and personalized medicine approaches, aiming to improve maternal and neonatal outcomes on a global scale. This aligns closely with broader public health goals to reduce preventable pregnancy complications and enhance reproductive healthcare equity.

Commenting on these seminal findings, Prof. Dr. Karen Sermon, Chair of ESHRE, stated, “This research not only marks a formidable advance in prenatal disease prevention but also deepens our molecular understanding of preeclampsia—a complex and often enigmatic pregnancy disorder—thus fostering future innovation both in science and clinical practice.”

The study abstract is set to be published imminently in Human Reproduction, one of the world’s foremost journals dedicated to reproductive biology and medicine. This milestone discovery underscores the power of integrating omics technologies with clinical obstetrics, heralding an era where early molecular diagnostics will become central to safeguarding maternal and fetal health worldwide.

Subject of Research: Early detection of preeclampsia using cell-free RNA liquid biopsy in maternal plasma during the first trimester.

Article Title: (Not provided)

News Publication Date: Monday, 30 June 2025

References:
[1] Castillo Marco, N., et al. (2025) Maternal plasma cell-free RNA as a liquid biopsy for first-trimester screening of early and late-onset preeclampsia. Nature Communications (Under review) [preprint] & Human Reproduction (abstract forthcoming)
[2] World Health Organization. (2025). Pre-eclampsia – Fact Sheet.
[3] Muñoz-Blat, R., Pérez-Moraga, R., Castillo Marco, N., et al. (2025). Multi-omics-based mapping of decidualisation resistance in patients with a history of severe preeclampsia. Nature Medicine.

Keywords: Human reproduction, Pregnancy, Preeclampsia, Cell-free RNA, Liquid biopsy, First-trimester screening, Prenatal diagnostics, Maternal plasma, Decidualisation resistance, Obstetrics, Molecular biomarkers, Machine learning