Research
De Geyter C et al., 2025·Human Reproduction
**STUDY ** What are the data and trends of ART and IUI cycle numbers and their outcomes, and of fertility preservation (FP) interventions, reported in 2020 as compared to previous years? **SUMMARY ** This 24th ESHRE report highlights the number of ART treatment cycles and children born over the years, showing a decline in the total number of treatment cycles, when comparing 2020 with 2019, alongside a decline in twin deliveries owing to a decrease in transfers of multiple embryos; however, fresh IVF or ICSI cycles and frozen embryo transfers (FET) showed similar pregnancy rates, and the reported IUI cycle numbers decreased while maintaining stable outcomes. **WHAT ** ART aggregated data generated by national registries, clinics, or professional societies have been gathered and analyzed by the European IVF Monitoring (EIM) consortium since 1997 and reported in a total of 23 manuscripts published in *Human Reproduction* and *Human Reproduction Open*. **STUDY DESIGN, SIZE, ** Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE each year. The data on treatment cycles performed between January 1 and December 31, 2020, were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons in the 44 countries that are members of the EIM Consortium. **PARTICIPANTS/MATERIALS, SETTING, ** Overall, 1440 clinics offering ART services in 41 countries reported 923 318 treatment cycles (−14%; in 2019: 1 077 813), including 135 231 with IVF, 356 408 with ICSI, 305 373 with FET, 57 051 with preimplantation genetic testing (PGT), 64 007 with oocyte donation, and 4895 cycles using frozen oocytes. A total of 1288 institutions reported data on IUI cycles using either husband/partner's semen (IUI-H; n = 112 663) or donor semen (IUI-D; n = 38 839) in 30 and 21 countries, respectively. Sixteen countries reported 29 566 interventions in pre-and post-pubertal patients for FP, including oocyte, ovarian tissue, semen, and testicular tissue banking. **MAIN ** In 24 countries (21 in 2019) in which all ART clinics reported to the registry, 356 427 treatment cycles were registered for a total population of approximately 268 million inhabitants in these countries, allowing the best estimate of a mean of 1330 cycles performed per million inhabitants (range: 142–3230). Among the reporting countries, for IVF, the clinical pregnancy rates (PR) per aspiration were similar to that in 2019 (22.1% versus 21.8% in 2019). For ICSI, the corresponding PRs showed similar trends (20.0% in 2020 versus 20.2% in 2019). When freeze-all cycles were excluded from the calculations, the clinical PRs per aspiration were 26.4% (28.5% in 2019) and 25.6% (26.2% in 2019) for IVF and ICSI, respectively. After oocyte donation, the PR per embryo transfer was 51.3% (50.5% in 2019) with freshly donated oocytes and 45.7% (44.8% in 2019) with thawed oocytes. After FET, the PR per thawing was 34.9% (versus 35.1% in 2019). In fresh cycles of both IVF and ICSI, the trend towards the transfer of fewer embryos continued with the transfer of 1, 2, 3, and ≥4 embryos in 57.2%, 37.8%, 4.8%, and 0.2%, of all treatments, respectively (corresponding to 55.4%, 39.9%, 2.6%, and 0.2% in 2019). This resulted in a reduced proportion of twin delivery rates (DRs) of 10.9% (11.9% in 2019) and a similar triplet DR of 0.2%. In FET cycles in 2020, the twin and triplet DRs were 7.9% and 0.1%, respectively (versus 8.9% and 0.1% in 2019). While the number of IUI cycles in 2020 decreased from 2019, the DRs remained stable at 8.8% after IUI-H (8.7% in 2019) and at 12.5% after IUI-D (12.1% in 2019). Twin and triplet DRs after IUI-H were 7.9% and 0.4% (in 2019: 8.7% and 0.4%) and 5.7% and 0.1% after IUI-D (in 2019: 6.2% and 0.2%), respectively. Data on FP were provided by 16 countries (18 in 2019), reporting a total of 29 566 interventions (24 139 in 2019). Cryopreservation of ejaculated sperm (n = 21 864 versus n = 11 592 in 2019) and cryopreservation of oocytes (n = 6077 versus n = 10 784 in 2019) were the most frequently reported forms of FP. **LIMITATIONS, ** Caution with the interpretation of results should remain as data collection systems and completeness of reporting vary among European countries.
Research
Jing M et al., 2025·Human Reproduction
Study What gut microbiota and metabolic alterations are associated with Polycystic ovary syndrome (PCOS) and linked to adverse pregnancy outcomes (APOs)? In PCOS, P. merdae decreases, BCAAs increase, raising the risk of APOs. Meanwhile, endometrial senescence and decidualization impairment are found, worsening with higher Ile concentration. PCOS, a prevalent and complex endocrine disorder, stands as the primary cause of anovulatory infertility. The rising prevalence of PCOS in China over the past decade has led to a substantial increase in disease burden. Our previous ten-year retrospective analysis revealed that PCOS patients undergoing their first fresh embryo transfer faced a heightened risk of APOs, such as miscarriage. However, the factors influencing disease progression and future obstetric outcomes in PCOS remain elusive. Study design, size, This prospective cohort study encompassed a diverse cohort of 220 women (110 with PCOS and 110 controls) from 44 cities across China, with a median follow-up duration of 16.6 months. Participants/materials, setting, Women aged < 35 years with PCOS (Rotterdam criteria) and age-/BMI-matched controls were recruited. Fecal microbiomes were analyzed using 16S rRNA sequencing and metagenomics, while serum metabolites were assessed through both untargeted and targeted metabolomics. Endometrial stromal cell senescence was evaluated based on a constellation of markers, including cell proliferation, senescence-associated secretory phenotype factors, cell cycle, ROS levels, and SA-β-Gal activity. Endometrial decidualization was gauged by measuring prolactin and IGFBP-1 levels using ELISA. Main Our study revealed significant gut microbiota alterations, including reduced α-diversity and a notable decline in Parabacteroides merdae (P. merdae), a key species differentiating PCOS from controls. Serum metabolomics identified 45 differential metabolites, with branched-chain amino acids (BCAAs), especially isoleucine (Ile), exhibiting strong diagnostic potential. Targeted metabolomics further validated BCAAs’ (Valine, Leucine, and Ile) upregulation and short-chain fatty acids’ downregulation in PCOS.
During follow - up, PCOS patients had a higher cumulative incidence of APOs despite similar pregnancy rates. And the adjustment for potential confounders did not substantially change the estimates. Intriguingly, individuals who experienced APOs showed a reduction in gut P. merdae levels and an elevation in serum BCAAs, suggesting their potential association with APOs occurrence.
Further analysis revealed increased Ile levels in the endometrial tissue of PCOS (P < 0.05) and higher proportions of cells positive for senescence markers (P21, P16, IL6, and IL1β), indicating aggravated cellular senescence, particularly in endometrial stromal cells (ESCs). ESCs from PCOS patients displayed classical senescence features, including proliferation loss, increased SA-β-Gal activity, cell cycle arrest, and elevated ROS levels. The accumulation of senescent ESCs in PCOS endometrium ultimately resulted in a disrupted decidualization process, which was exacerbated by increasing concentrations of Ile supplementation. Limitations, However, we must acknowledge certain limitations of this study. While our study makes a significant contribution to existing scientific knowledge, it is crucial to validate these findings in diverse populations. In addition, clinical translatability of biomarkers needs further exploration. This study highlights gut microbiota-metabolite crosstalk as a novel axis influencing reproductive health in PCOS. Moreover, the identification of P. merdae and BCAAs as potential biomarkers for PCOS patients and the associated APOs risk opens up new avenues for risk stratification and personalized interventions. No
Research
Somigliana E et al., 2025·Human Reproduction
The use of hormonal treatments for endometriosis has increased in recent years. Their effectiveness lies in creating a stable hormonal environment, reducing peripheral estrogen levels, and suppressing ovulation and menstruation. Although these agents do not cure endometriosis and symptoms often return after discontinuation, they effectively relieve pain in most cases and help prevent disease progression or recurrence. Women are therefore typically managed with long-term hormonal treatments, with or without surgery. However, this approach is unsuitable for those seeking natural pregnancy or undergoing IVF, as all hormonal treatments hinder conception. For women pursuing natural pregnancy, these treatments should be discontinued for about 1 year, the time needed to diagnose infertility. However, this suspension exposes women to the risk of recurrence or progression and is therefore clinically acceptable only if the woman has a reasonable likelihood of achieving pregnancy naturally. In women with endometriosis who are infertile and therefore require IVF, ovarian stimulation significantly raises estrogen levels-up to 10 times those of a natural cycle-potentially boosting the risk of endometriosis relapse. Evidence is reassuring on this issue even if some limited data suggest that ovarian stimulation may promote deep invasive endometriosis progression. Overall, physicians and patients must balance the chances of natural or ART-assisted pregnancy against the risk of disease recurrence or progression during treatment discontinuation or IVF. This choice is also complicated by the increased risk of severe pregnancy complications in women with endometriosis, possibly depending on the conception method. This review discusses the available evidence that can be helpful in guiding the decision-making process.
Research
C Edenius et al., 2025·Human Reproduction
Prostaglandin E2 (PGE2) is a key driver of endometriosis pathogenesis. Vipoglanstat selectively inhibits mPGES-1 enzyme activity. A Phase I trial involved 72 healthy volunteers receiving single or repeated doses, while Phase II included 69 subjects with chronic inflammatory disease receiving daily treatment. Results demonstrated the compound was safe and well tolerated at therapeutic doses and achieved complete mPGES-1 inhibition while preserving protective prostacyclin production. A Phase II endometriosis trial is scheduled to begin in 2025, focusing on pain reduction and lesion assessment via imaging.