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Reproductive Biomedicine Online[JOURNAL]

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Risk of placenta accreta spectrum in fresh versus natural, stimulated and programmed cycle frozen-thawed embryo transfer.

Fujita T, Yoshizato T, Murotani K … +2 more , Obara H, Tsuda N

Reprod Biomed Online · 2026 May · PMID 41832102 · Publisher ↗

RESEARCH QUESTION: How does the risk of placenta accreta spectrum (PAS) in pregnancies from natural cycle (NC-FET), stimulated cycle (SC-FET) and programmed cycle (PC-FET) frozen-thawed embryo transfers compare with that... RESEARCH QUESTION: How does the risk of placenta accreta spectrum (PAS) in pregnancies from natural cycle (NC-FET), stimulated cycle (SC-FET) and programmed cycle (PC-FET) frozen-thawed embryo transfers compare with that in fresh embryo transfer? DESIGN: A total of 174,591 embryo transfer cycles resulting in singleton live births were obtained from the Japanese assisted reproductive technology (ART) registry from 2017 to 2020. A multivariate logistic regression model compared the risk of PAS across different embryo transfer methods. Adjusted factors were maternal age at embryo transfer, indication for ART, number and stage of embryos transferred, use of assisted hatching, presence of placenta praevia and mode of delivery. RESULTS: The incidence of PAS was 0.16% (39/23,827), 0.17% (66/37,787), 0.14% (11/8,143) and 1.48% (1,549/104,834) for fresh embryo transfer, NC-FET, SC-FET and PC-FET, respectively. PC-FET carried a higher risk of PAS versus fresh embryo transfer (adjusted odds ratio [aOR] 9.12, 95% confidence interval [CI] 6.54-12.73), whereas there was no significantly increased risk with NC-FET and SC-FET. Subgroup analyses revealed that, for single cleavage-stage embryo transfer, PC-FET was associated with a higher risk of PAS versus fresh embryo transfer (aOR 11.19, 95% CI 6.55-19.11). NC-FET and SC-FET showed no significantly increased risk. For single-blastocyst transfer, PC-FET carried a higher risk of PAS versus fresh embryo transfer (aOR 5.44, 95% CI 3.26-9.09), whereas NC-FET and SC-FET had a similar risk to fresh embryo transfer. CONCLUSIONS: PC-FET carried a higher risk of PAS than fresh embryo transfer, while NC-FET and SC-FET did not. When planning embryo transfer reproductive physicians should recognize that PC-FET is a potential risk factor for PAS.

Evaluating the concordance between AI-based and conventional embryo selection: implications for clinical decision-making.

Wygocki P, Gilewicz T, Pawlik P … +12 more , Siennicki M, Brzozowski M, Kuśmierczyk-Kubiak J, Sankowska U, Milewski R, Chmielowska A, Kordalewska M, Różańska M, Kuczyński W, Wojtasik B, Sankowski P, Liebermann J

Reprod Biomed Online · 2026 Apr · PMID 41826106 · Full text

RESEARCH QUESTION: Can artificial intelligence (AI) standardize embryo scoring, and help embryologists to identify embryos with the highest likelihood of pregnancy and live birth? DESIGN: Multicentre, retrospective, head... RESEARCH QUESTION: Can artificial intelligence (AI) standardize embryo scoring, and help embryologists to identify embryos with the highest likelihood of pregnancy and live birth? DESIGN: Multicentre, retrospective, head-to-head analysis across six centres in five countries. An embryo selection algorithm (ESA) and 20 embryologists of varying seniority independently selected the implanting (i.e. 'best') embryo from 1681 pairs (1237 pairs with biochemical pregnancy; 444 pairs with live births), with each pair comprising one embryo with a positive outcome and one embryo with a negative outcome. Accuracy was computed for the ESA and for the embryologists; differences were assessed using McNemar's test. RESULTS: The accuracy of the ESA was 70.1%. The accuracy of individual embryologists ranged from 64.2% to 68.9% (mean value for embryologists 67.7%), and the accuracy of the expert committee (i.e. majority vote across the 20 embryologists) was 69.5%. McNemar's test indicated a significant advantage for the ESA compared with 14 of 20 embryologists, and the mean value for embryologists (P < 0.05), but no significant difference between the ESA and the remaining six embryologists or the expert committee. CONCLUSIONS: The ESA achieved higher accuracy than most individual embryologists and the mean value for embryologists, supporting its potential as a standardized adjunct to expert judgement. Confirmation of effectiveness and generalizability requires adequately powered, prospective multicentre trials.

AI-driven paradigm shift in follicle ultrasound monitoring: from automated segmentation to clinical decision support.

Kuang C, Liu Z, Huang Y … +3 more , Xiao Y, Du M, Chen Z

Reprod Biomed Online · 2026 May · PMID 41826105 · Publisher ↗

This commentary delineates the developmental pathway of artificial intelligence (AI) in ultrasound follicular monitoring, highlighting a paradigm shift from automated segmentation to clinical decision support. The deep l... This commentary delineates the developmental pathway of artificial intelligence (AI) in ultrasound follicular monitoring, highlighting a paradigm shift from automated segmentation to clinical decision support. The deep learning-based CR-Unet and C-Rend models have enabled accurate follicle segmentation and measurement from two-dimensional to three-dimensional imaging, substantially improving boundary segmentation accuracy and measurement consistency. Building on this foundation, the study further establishes two-dimensional follicle area and three-dimensional follicle volume as novel biomarkers, providing quantitative criteria for predicting oocyte maturity and optimizing the timing of human chorionic gonadotrophin triggering. Through seamless integration of algorithms into the Acclarix LXK9 ultrasonography equipment, an intelligent monitoring platform with real-time analytical capabilities has been developed, demonstrating significantly superior measurement accuracy and consistency compared with manual operations. These advancements represent a transformative leap from image segmentation to AI-driven clinical decision making, offering robust technical support for standardized and precise management in assisted reproduction.

Response to: Is the eternal dilemma dependent on embryo number?

Bartolacci A, de Girolamo S, Fraire-Zamora JJ … +2 more , Pagliardini L, Papaleo E

Reprod Biomed Online · 2026 Apr · PMID 41820124 · Publisher ↗

Abstract loading — click title to view on PubMed.

Biochemical or clinical pregnancy loss after first embryo transfer does not affect subsequent transfer outcome.

Barrett F, Kalafat E, Vessa B … +5 more , Margolis C, Whitehead C, Werner M, Ata B, Seli E

Reprod Biomed Online · 2026 Apr · PMID 41819682 · Publisher ↗

RESEARCH QUESTION: Does biochemical or clinical pregnancy loss after frozen embryo transfer (FET) increase the odds of pregnancy loss in a subsequent transfer? DESIGN: Retrospective cohort study evaluating patients who u... RESEARCH QUESTION: Does biochemical or clinical pregnancy loss after frozen embryo transfer (FET) increase the odds of pregnancy loss in a subsequent transfer? DESIGN: Retrospective cohort study evaluating patients who underwent two consecutive single FETs using either euploid or untested embryos at a university-affiliated fertility centre between January 2017 and December 2021. Patients who had experienced a biochemical or clinical pregnancy loss after the first FET were compared with those who had experienced implantation failure in the subsequent FET. RESULTS: Among 2103 patients who underwent two consecutive euploid FETs, those who had experienced a biochemical loss after their first euploid FET had a subsequent biochemical loss rate of 9.9% and a clinical loss rate of 10.5% in their second euploid FET. These rates did not significantly differ from those who had experienced previous implantation failure (9.6%, P = 0.890; 10.9%, P = 0.556, respectively). Similarly, among patients who had experienced a clinical loss in their first euploid FET, rates of biochemical and clinical loss in the second euploid transfer were comparable to those who had experienced previous implantation failure (11.5% versus 9.6%, P = 0.272; and 12.5% versus 10.9%, P = 0.456, respectively). These findings remained consistent when analysing untested (n = 282) FETs, with no significant differences in subsequent pregnancy loss rates between patients who had experienced previous pregnancy loss and those who had experienced implantation failure. CONCLUSIONS: Biochemical or clinical pregnancy loss after a euploid or untested FET is not associated with an increased risk of pregnancy loss in the subsequent transfer.

No difference in live birth rates observed between alternative endometrial preparation regimens in thin endometrium.

Selntigia A, Coticchio G, Cozzolino M

Reprod Biomed Online · 2026 Apr · PMID 41812401 · Publisher ↗

RESEARCH QUESTION: Does the type of endometrial preparation protocol influence reproductive outcomes in women with thin endometrium (<7 mm) undergoing single blastocyst embryo transfer (SET). DESIGN: Retrospective cohort... RESEARCH QUESTION: Does the type of endometrial preparation protocol influence reproductive outcomes in women with thin endometrium (<7 mm) undergoing single blastocyst embryo transfer (SET). DESIGN: Retrospective cohort study including infertile women aged 25-48 years with thin trilaminar endometrium (<7 mm) who underwent blastocyst SET between January 2021 and December 2024. Patients were allocated to the modified natural cycle (mNC) or artificial cycle groups according to endometrial preparation protocol. Only patients undergoing SET with euploid blastocysts from autologous PGT-A or donor oocyte cycles were included. Primary outcome was live birth rate (LBR); secondary outcomes included positive beta-HCG test, clinical pregnancy and miscarriage rates. RESULTS: A total of 762 SETs were carried out in 619 patients (mNC [n = 106], artificial cycle [n = 656). Patients who underwent artificial cycles were significantly older (P < 0.001); endometrial thickness and preparation time were comparable. The artificial cycle group showed more day-5 blastocyst transfers (P = 0.03). Reproductive outcomes, including LBR, did not differ between mNC and artificial cycles in the overall cohort and in subgroups (autologous and oocyte donation). Multivariate analysis confirmed no effect of endometrial preparation; day-6 transfers and low blastocyst grade were independently associated with decreased outcomes. CONCLUSIONS: Reproductive outcomes in women with thin endometrium (<7 mm) were comparable and sustainable after mNC and artificial cycle preparation, suggesting that this condition is not an absolute contraindication to embryo transfer. The practice of cancelling embryo transfers in cases of thin endometrium and shifting to an alternative preparation protocol is not supported.

Post-warming culture and single vitrified-warmed blastocyst transfer with hyaluronic acid and prolactin: a randomized controlled trial.

Ezoe K, Miki T, Fujiwara N … +11 more , Ueno S, Narisawa M, Shimazaki K, Akino R, Nishii S, Onogi S, Tsuchiyama S, Wada K, Kuroda T, Gardner DK, Kato K

Reprod Biomed Online · 2026 Apr · PMID 41806715 · Publisher ↗

RESEARCH QUESTION: Does combined treatment with hyaluronic acid and prolactin (PRL) for post-warming culture and embryo transfer increase the live birth rate after single vitrified-warmed blastocyst transfer (SVBT)? DESI... RESEARCH QUESTION: Does combined treatment with hyaluronic acid and prolactin (PRL) for post-warming culture and embryo transfer increase the live birth rate after single vitrified-warmed blastocyst transfer (SVBT)? DESIGN: A three-arm, double-blind, randomized controlled trial (RCT) was conducted between October 2020 and May 2021. Overall, 1236 couples undergoing SVBT were randomized using a 1:1:1 ratio into three groups: after removing the zona pellucida, warmed blastocysts were incubated in a medium without hyaluronic acid or PRL (control group), a hyaluronic-acid-enriched transfer medium (EmbryoGlue group), or EmbryoGlue supplemented with PRL (EGP group) for 2-4 h prior to transfer in the same medium. The primary outcome was the live birth rate. RESULTS: The live birth rate was higher in the EGP group compared with the control (OR 1.40; P = 0.0219) and EmbryoGlue (OR 1.38; P = 0.0266) groups. Although positive pregnancy and clinical pregnancy rates were comparable among the three groups, the ongoing pregnancy rate was higher in the EGP group compared with the control (P = 0.0142) and EmbryoGlue (P = 0.0249) groups. Furthermore, the rate of early pregnancy loss was lower in the EGP group compared with the control (P = 0.0073) and EmbryoGlue (P = 0.0053) groups. Subgroup analysis demonstrated significant interactions for embryo culture time (P = 0.0494) and serum progesterone (P = 0.0045): EGP treatment was effective for day 4-5 blastocysts and patients with insufficient serum progesterone. CONCLUSIONS: This RCT suggests that combined treatment with hyaluronic acid and PRL is effective for improving the live birth rate in good-prognosis patients by reducing early pregnancy loss.

Fertility preservation in patients with Turner syndrome: a SWOT analysis.

Ferro R, Vento FD, Streuli I

Reprod Biomed Online · 2026 Apr · PMID 41806714 · Publisher ↗

Turner syndrome, a chromosomal disorder characterized by premature ovarian insufficiency and infertility, presents significant reproductive challenges. Fertility preservation is critical for enabling individuals with Tur... Turner syndrome, a chromosomal disorder characterized by premature ovarian insufficiency and infertility, presents significant reproductive challenges. Fertility preservation is critical for enabling individuals with Turner syndrome to pursue biological parenthood. However, implementation is hindered by limited provider awareness, ethical concerns, and restricted access to specialized care. This review underscores the importance of fertility preservation in Turner syndrome, evaluates current methods, and addresses barriers and ethical complexities. Methods such as ovarian tissue cryopreservation, in-vitro maturation, and vitrification offer promise, while novel strategies such as in-vitro activation and gene expression profiling may improve outcomes. Nevertheless, success rates remain variable, and accessibility is limited. Major barriers include delayed diagnosis of Turner syndrome, inadequate fertility counselling, and insufficient provider training. Ethical challenges involve assessing the autonomy and psychological readiness of paediatric patients. Socio-economic disparities and inconsistent insurance coverage further impede access. Effective fertility preservation in patients with Turner syndrome requires early diagnosis, timely counselling, and a coordinated multidisciplinary approach. While advancements in fertility preservation are promising, broader implementation demands improved provider education, ethical guidance, and public policy reform. Ensuring equitable access to fertility preservation can significantly enhance reproductive autonomy and quality of life for individuals with Turner syndrome.

Disclosing donor conception: a mixed methods study exploring the experience and attitudes of French sperm donor-conceived adults born within heterosexual couples.

Martin A, Gallissian S, Daoud-Deveze C … +4 more , Gnisci A, Faust C, Martial A, Metzler-Guillemain C

Reprod Biomed Online · 2026 Apr · PMID 41806713 · Publisher ↗

RESEARCH QUESTION: How can the experiences and attitudes of donor-conceived people regarding the disclosure of their conception be understood, given the emphasis on openness and the ongoing challenges faced by donor-conc... RESEARCH QUESTION: How can the experiences and attitudes of donor-conceived people regarding the disclosure of their conception be understood, given the emphasis on openness and the ongoing challenges faced by donor-conceived families? DESIGN: A mixed-method exploratory study (March 2019 to September 2020) involving an online survey and in-depth interviews with French sperm donor-conceived adults born to heterosexual couples. The survey included 107 respondents aged 20-54 years, mostly women (86.9%) with high academic standards, informed of their conception at an average age of 18.6 (± 11.9). The interview involved 20 participants aged 21-53 years, most of whom were women (85%) and employed as managers (35%), informed between the ages of 5 and 49 years (average: 19.7 years). RESULTS: Age was not the primary factor for understanding how donor-conceived participants experienced and perceived disclosure. The circumstances of disclosure emerged as an independent factor, with four paths identified: disclosure as a mutually agreed parental strategy; disclosure perceived as necessary owing to events in the donor offspring's life; disclosure as a breach in a prior agreement between partners after a family event; and disclosure initiated by donor-conceived people themselves. Additionally, three factors explained the gendered gap that positioned mothers as the main actors in disclosure experiences: the organization of MAR protocols, the social perception of male infertility and the gendered division of labour within families. CONCLUSIONS: A contextualised approach to information-sharing practices is needed. Disclosure should be understood within its temporal and relational context to grasp how donor-conceived people experience learning the facts of their conception.

Is the eternal dilemma dependent on embryo number?

Dirican EK

Reprod Biomed Online · 2026 Apr · PMID 41802387 · Publisher ↗

Abstract loading — click title to view on PubMed.

Meeting the sperm donor for the first time: what can shape the experiences of donor-conceived people?

van Rooij FB, Mochtar MH, van Brouwershaven AC … +5 more , Schrijvers AM, Bolt SH, Visser M, Maas AJBM, Bos HMW

Reprod Biomed Online · 2026 Apr · PMID 41795335 · Publisher ↗

RESEARCH QUESTION: How do donor-conceived people experience being linked with and meeting the sperm donor for the first time, and how are these experiences shaped by individual contexts and professional support? DESIGN:... RESEARCH QUESTION: How do donor-conceived people experience being linked with and meeting the sperm donor for the first time, and how are these experiences shaped by individual contexts and professional support? DESIGN: A qualitative semi-structured interview study was conducted with 17 donor-conceived people [mean ± SD age 31.94 ± 7.25 years; 15 females, two males; 14 with (previously) anonymous donors, three with identifiable donors]. Participants were recruited through a previous study with donor-conceived people, and announcements on the website and social media of two relevant organizations. Interviews, based on previous literature and consultation with an advisory board, lasted for approximately 1 h, and were audio-taped and transcribed verbatim. The transcripts were analysed in MAXQDA2020 using a constant comparative method. RESULTS: Overall, participants reported positive experiences around the first meeting with the donor in terms of feelings (e.g. relief, happiness), flow of the meeting, and sense of recognition and connection. Some participants also reported negative experiences (e.g. negative or ambiguous feelings, negative flow of the meeting, lack of recognition or connection). Experiences seemed to be influenced by motivations, strength of desire to meet the donor, search process, expectations regarding the donor, interactions with the donor, and support from a counsellor around the meeting. CONCLUSION: The findings indicate that donor-conceived people value meeting the sperm donor, with various aspects shaping their experiences. Counselling was recognized as helpful in managing expectations, but should be tailored to address individual needs regarding intensity and content before, during and after the meeting.

Can machine learning models predict oocyte yield during assisted conception?: a systematic review.

Wilkinson J, Gogna K, Gallagher M … +7 more , Richardson A, Devall A, Sephton V, Campbell A, Dhillon-Smith R, Bamford T, Coomarasamy A

Reprod Biomed Online · 2026 Apr · PMID 41780078 · Publisher ↗

Accurately predicting oocyte yield is key to individualizing gonadotrophin dosing in assisted reproduction, where excessive responses carry significant risks and inadequate responses may compromise treatment success. Mac... Accurately predicting oocyte yield is key to individualizing gonadotrophin dosing in assisted reproduction, where excessive responses carry significant risks and inadequate responses may compromise treatment success. Machine learning models are being developed to support this. This review evaluates the accuracy and clinical readiness of such models for predicting oocyte yield at transvaginal oocyte retrieval. A literature search of OVID MEDLINE, OVID EMBASE and the Cochrane Database identified nine relevant studies, eight retrospective and one prospective cohort, and encompassing 62,354 cycles. Study quality was assessed using the TRIPOD checklist and risk of bias was assessed with PROBAST. Accuracy was variably reported; the most frequent measure was mean absolute error, ranging from 0.62 to 4.13. A meta-analysis was not possible due to heterogeneity. Neural network models generally performed best. None of the studies were externally validated, limiting the generalizability. Most lacked transparency around data pre-processing, including handling missing data and variable transformation, reducing reproducibility. Although several models demonstrated promising internal performance, they remain at high risk of bias. Clinicians should be cautious in applying these models to practice until independently validated. Overall, machine learning-based prediction of oocyte yield remains in the early phase, and future development should prioritize external validation and transparent reporting.

Oocyte quality in the era of AI: integration of morphology, metabolic activity and time-lapse imaging.

Gardner DK, O'Neill HC, Balaban B … +3 more , Meseguer M, Freour T, Rienzi L

Reprod Biomed Online · 2026 Apr · PMID 41775050 · Publisher ↗

Significant advances have been made with regards to quantifying the viability of the preimplantation-stage human embryo, through the analysis of morphokinetics, quantification of biomarkers and trophectoderm biopsy to fa... Significant advances have been made with regards to quantifying the viability of the preimplantation-stage human embryo, through the analysis of morphokinetics, quantification of biomarkers and trophectoderm biopsy to facilitate preimplantation genetic testing for aneuploidies (PGT). However, there is still limited capacity to determine the inherent potential of gametes. In particular, assessing the viability of an oocyte has been elusive, and the standard means of determining oocyte quality remains assessing its morphology. Unfortunately, except for grossly abnormal features, such as giant eggs, oocyte morphology is not strongly associated with clinical outcomes. With the rise of oocyte donation and social oocyte freezing, there is an immediate need to improve the ability to determine gamete health and developmental potential to better counsel patients about their reproductive future. Furthermore, the outcomes of successive stimulation cycles can vary within an individual, heightening the need to ensure that the quality of a given oocyte cohort can be quantified and stimulation regimens optimized per patient. Developments in artificial intelligence and in media analysis and microscopies to assess metabolic state could provide valuable insights into oocyte health, thereby increasing the ability to not only improve oocyte health and selection, but also provide a much-needed tool to assist in optimizing ovarian stimulation.

First births using a closed, simplified IVF culture system in a mobile IVF laboratory: a proof-of-concept study.

Boshoff GM, Huyser C, Ombelet W

Reprod Biomed Online · 2026 Apr · PMID 41775049 · Publisher ↗

RESEARCH QUESTION: Can pregnancy be achieved using a simplified embryo culture system within a mobile IVF laboratory? DESIGN: Case series design, describing the results of a pilot study investigating the use of a simplif... RESEARCH QUESTION: Can pregnancy be achieved using a simplified embryo culture system within a mobile IVF laboratory? DESIGN: Case series design, describing the results of a pilot study investigating the use of a simplified, closed, low-cost embryo culture system in a prototype mobile IVF laboratory. A mild ovarian stimulation protocol was used in all cycles. Follicular aspiration was performed in a clinical setting, while oocyte fertilization, embryo culture and embryo transfers were carried out in a mobile unit using the Walking Egg simplified embryo culture system. RESULTS: From 12 cycles initiated, no oocytes were obtained in one cycle, fertilization failed in another cycle due to a low number of oocytes which were predominantly immature, and 10 cycles continued to embryo culture. Of these 10 cycles, a single embryo transfer was performed in five cycles, and two embryos were transferred in the remaining five cycles. Five of the 10 women became pregnant; of these, one miscarried and four had a live birth. CONCLUSION: Proof of concept, even with a limited sample size, for the use of mild stimulation and low-cost embryo culture in a mobile laboratory is presented. These promising results support the use of a mobile IVF laboratory in areas where access to ART is costly and limited due to few IVF centres which are mainly located in cosmopolitan centres.

Chronic air pollution exposure is associated with lower chance of live birth after frozen embryo transfer.

Crouzat A, Cremoni M, Boukaïdi S … +2 more , Seitz-Polski B, Gauci PA

Reprod Biomed Online · 2026 Apr · PMID 41771213 · Publisher ↗

RESEARCH QUESTION: To evaluate the effect of 1 year's exposure to ambient air pollution on live birth and ovarian response in women undergoing frozen embryo transfer (FET), using the European air quality limit values in... RESEARCH QUESTION: To evaluate the effect of 1 year's exposure to ambient air pollution on live birth and ovarian response in women undergoing frozen embryo transfer (FET), using the European air quality limit values in 2030 (LV2030). DESIGN: Retrospective monocentric study of 255 patients who underwent FET in 2023. Data were leveraged from a prospectively collected clinical cohort, combined with prospective air pollution measurements. Primary outcome was live birth; secondary outcome was the number of oocytes retrieved. Individual exposures to fine particulate matter smaller than 2.5 μm (PM, smaller than 10μm (PM, nitrogen dioxide (NO, ozone (O and two multi-pollutant indices (CSA, ICAIR) were estimated via high-resolution spatial modelling. Multivariable logistics and linear regression models were used, adjusting for key confounders. RESULTS: Exposure to air pollution during the year preceding embryo transfer was associated with a lower odds of live birth success up to 77% and 66% for pollutant levels exceeded LV2030 respectively for PM (OR  0.23, 95% CI 0.06 to 0.79, P = 0.020) and NO (OR 0.34, 95% CI 0.12 to 0.98, P = 0.046) and for continuous concentrations for PM (OR 0.86, 95% CI 0.74 to 0.99, P = 0.044), NO (OR 0.95, 95% CI 0.90 to 0.99, P = 0.028) and CSA (OR  0.78, 95% CI 0.62 to 0.99, P = 0.049). Exposure during the pre-retrieval period showed no significant association with live birth. PM exposure in that period was consistently linked to fewer oocytes retrieved (β = -2.61, P = 0.010 for LV2030; β = -0.44, P = 0.007 for continuous exposure). CONCLUSION: Chronic exposure to air pollutants in the year preceding FET was independently associated with lower odds of live birth success. These results highlight that compliance with European limit values may contribute to improved reproductive outcomes.

Can large language models provide accurate and empathetic answers to the most frequently asked questions by infertile patients? A pilot study.

Gély L, Chaillot M, Fréour T

Reprod Biomed Online · 2026 Apr · PMID 41771212 · Publisher ↗

RESEARCH QUESTION: Is the quality, relevance and empathy of the answers provided by large language models (LLMs) in response to the most frequently asked patient questions in reproductive medicine comparable to those pro... RESEARCH QUESTION: Is the quality, relevance and empathy of the answers provided by large language models (LLMs) in response to the most frequently asked patient questions in reproductive medicine comparable to those provided by human specialists? DESIGN: This monocentric, double blind, prospective study involved two clinicians and two embryologists who answered 13 frequently asked questions in their respective field. The same questions were asked to a free online LLM, with the same constraint of text length as practitioners. All answers were blindly evaluated by four assessors (two gynaecologists and two embryologists depending on the topic) for quality and accuracy. A psychologist also evaluated empathy. RESULTS: The mean number of words per answer was significantly higher (P < 0.001) for LLM than for humans. The average quality of answers was not statistically different between LLM and professionals. No answer provided by LLM was evaluated as completely aberrant, and only a minority contained false or inappropriate information or was scored as being very poor by assessors. Answers provided by embryologists, but not clinicians, ranked significantly higher (P = 0.02) than LLM. The psychologist chose LLM answers as most empathetic, clear, or both, in 14 out of 26 questions. CONCLUSIONS: LLMs could be used as an educational tool within assisted reproductive technology centres to answer frequently asked patient questions. Although the potential applications of LLMs' capabilities in answering medical questions are numerous, this should be carefully evaluated and regulated to prevent the dissemination of inaccurate information to patients.

TUBB8 variants in infertile Japanese women, including a novel homozygous nonsense variant causing zygote multinucleation.

Sako Y, Inagaki H, Yanagihara A … +15 more , Asada Y, Fukunaga N, Fukuda A, Kobayashi R, Shimizu M, Yamada Y, Kinoshita K, Nakayama K, Inoue T, Nagatakidani Y, Morimoto Y, Ochi M, Matsunaga R, Nishizawa H, Kurahashi H

Reprod Biomed Online · 2026 Apr · PMID 41762928 · Publisher ↗

RESEARCH QUESTION: What is the prevalence of tubulin beta 8 class VIII (TUBB8) variants in Japanese women with oocyte/zygote/embryo maturation arrest (OZEMA), and what are the phenotype-genotype correlations in this popu... RESEARCH QUESTION: What is the prevalence of tubulin beta 8 class VIII (TUBB8) variants in Japanese women with oocyte/zygote/embryo maturation arrest (OZEMA), and what are the phenotype-genotype correlations in this population? DESIGN: This multicentre retrospective study analysed 39 Japanese women with primary infertility characterized by OZEMA. Whole-exome sequencing was performed to identify TUBB8 variants, followed by Sanger sequencing, in-silico analysis, and structural modelling. Clinical data were collected across multiple treatment cycles, including oocyte maturation, fertilization, and embryonic development. Time-lapse imaging observed abnormal fertilization processes. RESULTS: Six TUBB8 variants were identified in 15.4% (6/39) of participants, including one novel homozygous nonsense variant (p.Thr136*) and two novel heterozygous missense variants (p.Phe294Leu and p.Trp344Arg). All six patients exhibited degrees of oocyte maturation arrest, predominantly at metaphase I. The novel homozygous nonsense variant was uniquely associated with multipronuclear (MPN) zygote formation. Both novel heterozygous missense variants, one confirmed de novo, caused complete metaphase I arrest. Time-lapse imaging in the patient with the homozygous nonsense variant demonstrated impaired polar body extrusion characterized by unusually broad cytoplasmic protrusions. These protrusions were reabsorbed into the oocyte, resulting in MPN zygotes. CONCLUSIONS: In this first study of TUBB8 in Japanese patients with OZEMA, three novel variants with unique phenotype-genotype correlations were identified. The phenotypes observed with the homozygous p.Thr136* variant suggest that complete TUBB8 loss disrupts not only meiotic progression but also post-fertilization events, including second polar body extrusion and pronuclear formation. These findings expand the spectrum of TUBB8-related reproductive phenotypes, and suggest that genetic testing can help avoid repeated unsuccessful treatments for primary infertility.

Iron dysmetabolism in ovarian follicles: implications for oocyte quality and embryo development in endometriosis.

Xiang Y, Zhang Y, Wang X … +9 more , Xu T, Xu C, Zhang L, Zhou S, Zhu Q, Cai J, Weng L, Liang N, Ge H

Reprod Biomed Online · 2026 Apr · PMID 41740452 · Publisher ↗

RESEARCH QUESTION: Do iron metabolism and ferroptosis influence oocyte and embryo quality in patients with endometriosis undergoing IVF/intracytoplasmic sperm injection (ICSI), or in a mouse model? DESIGN: Fifty-seven pa... RESEARCH QUESTION: Do iron metabolism and ferroptosis influence oocyte and embryo quality in patients with endometriosis undergoing IVF/intracytoplasmic sperm injection (ICSI), or in a mouse model? DESIGN: Fifty-seven patients with laparoscopically confirmed endometriosis and 153 age-matched controls (1:3 ratio) were included in this study. Embryological outcomes were assessed, and follicular fluid was analysed for iron and oxidative stress markers. Ferroptosis-related protein expression in granulosa cells was evaluated by Western blot. Mechanistic insights were explored using human KGN granulosa cells and mouse oocyte/embryo models under iron overload [100 μM ferroptosis activator (FAC)] with or without ferrostatin-1 (Fer-1; 2 μM). RESULTS: Patients with endometriosis showed impaired oocyte maturation and poorer embryo quality compared with controls. Follicular fluid of patients with endometriosis exhibited elevated Fe (P = 0.0017), malondialdehyde (P < 0.001) and total superoxide dismutase (P < 0.001), indicating iron overload and oxidative stress. Granulosa cells displayed enhanced ferroptosis. In KGN cells, iron overload (100 μM FAC) reduced glutathione peroxidase 4 (P < 0.001), and increased peroxiredoxin 3 (P = 0.044) and reactive oxygen species; these effects were reversed by Fer-1. In mice, iron overload decreased oocyte maturation (P = 0.0429), increased abnormal spindle formation (P = 0.0034) and chromatin misalignment (P = 0.002), and reduced mitochondrial membrane potential (P < 0.001). Fer-1 treatment restored oocyte maturation (P = 0.0109), and improved spindle morphology (P = 0.0322), chromatin alignment (P = 0.0271) and mitochondrial function (P  <  0.001) significantly. CONCLUSIONS: This study reveals that follicles from patients with endometriosis display iron overload and lipid peroxidation, potentially contributing to diminished oocyte quality and embryonic developmental potential. These findings advance understanding of the pathophysiology of endometriosis-related infertility, and suggest that interventions targeting iron metabolism and ferroptosis may improve fertility outcomes in patients with endometriosis undergoing IVF/ICSI.

Association between the adherence to different dietary patterns and sperm chromatin integrity in healthy men.

Llavanera M, Fernández de la Puente M, Davila-Cordova E … +7 more , Eigbefoh-Addeh A, Agarwal R, Valle-Hita C, Babio N, Salas-Salvadó J, Yeste M, Salas-Huetos A

Reprod Biomed Online · 2026 Apr · PMID 41734444 · Publisher ↗

RESEARCH QUESTION: Are healthy and unhealthy diets associated with sperm DNA fragmentation and chromatin deprotamination in healthy men of reproductive age? DESIGN: A cross-sectional analysis conducted using healthy male... RESEARCH QUESTION: Are healthy and unhealthy diets associated with sperm DNA fragmentation and chromatin deprotamination in healthy men of reproductive age? DESIGN: A cross-sectional analysis conducted using healthy male volunteers (n = 200), aged 18-40 years, participating in the Led-Fertyl study. Adherence to five dietary patterns were estimated using a-priori indices: Mediterranean diet (Mediterranean Diet Adherence Screener; [MEDAS]); healthy and unhealthy plant-based diets; EAT-Lancet diet and Western diet. Dietary intake was assessed using a validated 143-item Food Frequency Questionnaire. Double-strand DNA fragmentation in spermatozoa evaluated by the Neutral Comet assay and chromatin deprotamination evaluated through chromomycin A3 (CMA3) staining by flow cytometry, were considered the main outcomes. RESULTS: No association between adherence to MEDAS, healthy and unhealthy plant-based, EAT-Lancet or Western dietary patterns with sperm DNA fragmentation was observed. Furthermore, adherence to MEDAS, healthy plant-based, EAT-Lancet or Western dietary patterns did not differ in sperm chromatin deprotamination. Yet, adherence to the unhealthy plant-based diet was non-linearly associated with increased chromatin deprotamination in all statistical models. Compared with the lowest tertile, participants in the highest unhealthy plant-based tertile had greater sperm chromatin deprotamination (β = 12.4, 95% CI 2.7 to 22.1, P = 0.026), suggesting a higher occurrence of abnormalities in sperm chromatin condensation. CONCLUSION: To the best of our knowledge, this study is the first to epidemiologically investigate the relationship between dietary patterns and sperm chromatin integrity, highlighting that adherence to unhealthy plant-based diets may lead to sperm chromatin abnormalities. These findings underscore the potential effect of specific dietary patterns on molecular sperm quality parameters and support further research into dietary strategies for optimizing sperm integrity and improving male fertility.

Is surgery for endometriomas ever indicated?

Urman B, Muzii L, Ertas S … +4 more , Aksakal E, Usta I, Seyhan A, Ata B

Reprod Biomed Online · 2026 Apr · PMID 41722480 · Publisher ↗

Endometriomas can be managed through various approaches, including careful observation, medical suppressive therapy, or surgical intervention. Malignancy is rarely a concern in women of reproductive age, making pain reli... Endometriomas can be managed through various approaches, including careful observation, medical suppressive therapy, or surgical intervention. Malignancy is rarely a concern in women of reproductive age, making pain relief and the management of infertility the primary foci of treatment. Pain is seldom due to endometriomas per se, and is most often associated with deep endometriotic lesions, usually involving the parametria and the bowel. Patients with infertility are better served with assisted reproductive technology (ART), as endometriomas do not appear to affect oocyte developmental potential or implantation rate. In addition, endometriomas do not increase the complications associated with ART. On the other hand, surgery is associated with decreased ovarian reserve, a considerable risk of recurrence, and tubal obstruction that may inflict irreversible harm. Moreover, surgical complications may delay further fertility-promoting treatment. It is argued that, unless it is performed for acute indications such as cyst rupture or infection, there are remnant indications for surgery, mainly the presence of hydrosalpinx and the size and location of endometriomas, that may impede oocyte retrieval. Surgery for endometriomas does not adhere to the three fundamental principles of surgical indications: preserving life, alleviating suffering, and correcting deformities or dysfunction.
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