Pub Date : 2026-01-16DOI: 10.1016/j.rbmo.2026.105465
Alberto Vaiarelli, Carlo Alviggi, Juan Antonio Garcia Velasco, Marcos Horton, Peter Humaidan, Antonio La Marca, Marilena Taggi, Danilo Cimadomo, Laura Rienzi, Filippo M Ubaldi
Recent advances in IVF have shifted the focus towards maximizing treatment efficacy and efficiency. Traditionally, IVF success has been evaluated on a cycle-by-cycle basis. Advancements such as individualized ovarian stimulation protocols, gonadotrophin-releasing hormone agonist triggers, cryopreservation techniques and embryo selection strategies, including preimplantation genetic testing for aneuploidies, have improved precision medicine in IVF, optimizing clinical outcomes. Despite these developments, certain patient groups - especially those with low ovarian response and/or advanced age - still face lower success rates per IVF cycle initiated. Considering the reproductive system's physiology, which often requires multiple attempts for success, and drawing from the experience of intrauterine insemination, a shift from a single-cycle focus to a multicycle strategy is now needed. A multicycle approach, adopting approaches such as oocyte/embryo accumulation from several stimulations or two consecutive stimulations (e.g. DuoStim), enables the advance planning of multiple attempts. It helps shorten time to pregnancy, reduces treatment discontinuation and offers support for patients facing setbacks. To be effective, this strategy must include personalized psychological counselling to manage emotional stress and prepare patients for possible failures, which are major causes of discontinuation. Evidence shows that well-informed, supported patients are more likely to persist in treatment, leading to higher cumulative success rates.
{"title":"Changing the narrative for poor-prognosis patients in IVF: unlocking success through a multicycle approach.","authors":"Alberto Vaiarelli, Carlo Alviggi, Juan Antonio Garcia Velasco, Marcos Horton, Peter Humaidan, Antonio La Marca, Marilena Taggi, Danilo Cimadomo, Laura Rienzi, Filippo M Ubaldi","doi":"10.1016/j.rbmo.2026.105465","DOIUrl":"https://doi.org/10.1016/j.rbmo.2026.105465","url":null,"abstract":"<p><p>Recent advances in IVF have shifted the focus towards maximizing treatment efficacy and efficiency. Traditionally, IVF success has been evaluated on a cycle-by-cycle basis. Advancements such as individualized ovarian stimulation protocols, gonadotrophin-releasing hormone agonist triggers, cryopreservation techniques and embryo selection strategies, including preimplantation genetic testing for aneuploidies, have improved precision medicine in IVF, optimizing clinical outcomes. Despite these developments, certain patient groups - especially those with low ovarian response and/or advanced age - still face lower success rates per IVF cycle initiated. Considering the reproductive system's physiology, which often requires multiple attempts for success, and drawing from the experience of intrauterine insemination, a shift from a single-cycle focus to a multicycle strategy is now needed. A multicycle approach, adopting approaches such as oocyte/embryo accumulation from several stimulations or two consecutive stimulations (e.g. DuoStim), enables the advance planning of multiple attempts. It helps shorten time to pregnancy, reduces treatment discontinuation and offers support for patients facing setbacks. To be effective, this strategy must include personalized psychological counselling to manage emotional stress and prepare patients for possible failures, which are major causes of discontinuation. Evidence shows that well-informed, supported patients are more likely to persist in treatment, leading to higher cumulative success rates.</p>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 5","pages":"105465"},"PeriodicalIF":3.5,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-07-18DOI: 10.1016/j.rbmo.2025.105166
Noemie Ranisavljevic , Anaïs Rolland , Marie-Christine Picot , Manuela Lotierzo , Fanchon Herman , Martha Duraes , Sophie Brouillet , Tal Anahory
Research question
Does use of male condoms during sexual intercourse affect serum progesterone levels in women taking hormonal replacement therapy (HRT) with vaginal progesterone, compared with unprotected sexual intercourse and sexual abstinence as the reference for progesterone absorption?
Design
A prospective, randomized, crossover pilot study was conducted (n = 40 couples). Eligible participants were infertile heterosexual couples. Women (aged 18–40 years; BMI <32 kg/m2) received oestradiol and vaginal micronized progesterone suppositories. Couples were excluded if men reported erectile or ejaculatory disorders. Upon initiation of progesterone, sexual abstinence was mandated, except for two planned intercourses as part of the study, one with and one without a condom. Progesterone serum levels were assessed three times: on day 2 of progesterone (during abstinence), on day 3 (10 h after the first planned sexual intercourse) and day 7 of progesterone (10 h after the second planned sexual intercourse).
Results
Among the 40 couples included, 30 couples were suitable for per protocol analysis. On average, serum progesterone levels were 0.21 ng/ml (± 5.26) lower after an unprotected intercourse compared with sexual abstinence; serum progesterone levels were 1.52 ng/ml (± 5.09) higher after an intercourse with a condom compared with sexual abstinence. The linear mixed model showed no significant effect for condom use to affect the variation in progesterone levels (P = 0.08).
Conclusion
Sexual intercourse did not significantly affect serum progesterone levels during an HRT cycle using vaginal progesterone suppositories. Vaginal absorption of progesterone was similar regardless of whether a male condom was used.
{"title":"Sexual intercourse and vaginal absorption of progesterone (SexVAP): a cross-over randomized prospective pilot study","authors":"Noemie Ranisavljevic , Anaïs Rolland , Marie-Christine Picot , Manuela Lotierzo , Fanchon Herman , Martha Duraes , Sophie Brouillet , Tal Anahory","doi":"10.1016/j.rbmo.2025.105166","DOIUrl":"10.1016/j.rbmo.2025.105166","url":null,"abstract":"<div><h3>Research question</h3><div>Does use of male condoms during sexual intercourse affect serum progesterone levels in women taking hormonal replacement therapy (HRT) with vaginal progesterone, compared with unprotected sexual intercourse and sexual abstinence as the reference for progesterone absorption?</div></div><div><h3>Design</h3><div>A prospective, randomized, crossover pilot study was conducted (<em>n</em> = 40 couples). Eligible participants were infertile heterosexual couples. Women (aged 18–40 years; BMI <32 kg/m<sup>2</sup>) received oestradiol and vaginal micronized progesterone suppositories. Couples were excluded if men reported erectile or ejaculatory disorders. Upon initiation of progesterone, sexual abstinence was mandated, except for two planned intercourses as part of the study, one with and one without a condom. Progesterone serum levels were assessed three times: on day 2 of progesterone (during abstinence), on day 3 (10 h after the first planned sexual intercourse) and day 7 of progesterone (10 h after the second planned sexual intercourse).</div></div><div><h3>Results</h3><div>Among the 40 couples included, 30 couples were suitable for per protocol analysis. On average, serum progesterone levels were 0.21 ng/ml (± 5.26) lower after an unprotected intercourse compared with sexual abstinence; serum progesterone levels were 1.52 ng/ml (± 5.09) higher after an intercourse with a condom compared with sexual abstinence. The linear mixed model showed no significant effect for condom use to affect the variation in progesterone levels (<em>P</em> = 0.08).</div></div><div><h3>Conclusion</h3><div>Sexual intercourse did not significantly affect serum progesterone levels during an HRT cycle using vaginal progesterone suppositories. Vaginal absorption of progesterone was similar regardless of whether a male condom was used.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105166"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
What is the association of peri-conceptional maternal vulnerability, assessed through a weighted multi-domain risk score with embryonic growth?
Design
638 pregnancies were included from the Rotterdam Periconception Cohort. Data on nine vulnerability factors (encompassing lifestyle, mental health and environmental factors) were obtained through self-administered questionnaires. The Periconceptional Vulnerability Risk Score (PVRS) was calculated using weighted estimates of associations between vulnerability factors and ‘Big 3’ pregnancy outcomes (congenital anomalies, preterm birth and small for gestational age). Embryonic growth was assessed by repeated first-trimester 3D transvaginal ultrasound measurements of crown-rump length and embyronic volume, analyzed with VR-software.
Results
For the total study population, the PVRS ranged from –0.071 to 0.320 (median 0.131). Higher PVRS values were significantly associated with reduced embryonic growth trajectories (CRL: β = –0.58 mm, 95% CI –0.94 to –0.23, P = 0.001; embryonic volume: β = –0.31 cm³, 95% CI –0.49 to –0.13, P = 0.001). Subgroup analyses revealed significant negative associations in naturally conceived pregnancies (CRL: β = –0.82 mm, 95% CI –1.48 to –0.16, P = 0.015; embryonic volume: β = –0.39 cm³, 95% CI –0.71 to –0.08, P = 0.015) and in overweight women (CRL: β = –0.91 mm, 95% CI –1.55 to –0.27, P = 0.006; embryonic volume: β = –0.51 cm³, 95% CI –0.82 to –0.21, P = 0.001).
Conclusions
The PVRS provides a weighted measure of maternal vulnerability, significantly associated with reduced embryonic growth, particularly in naturally conceived pregnancies and overweight women. Although no causality can be inferred from this study, the observed associations suggest that a broad peri-conceptional vulnerability assessment could help to identify potentially modifiable risk factors.
{"title":"Peri-conceptional maternal vulnerability risk score and embryonic growth: the Rotterdam Periconception Cohort","authors":"Teuntje Wieles , Hilmar Bijma , Sharissa Smith , Lotte Voskamp , Sten Willemsen , Régine Steegers-Theunissen","doi":"10.1016/j.rbmo.2025.105085","DOIUrl":"10.1016/j.rbmo.2025.105085","url":null,"abstract":"<div><h3>Research question</h3><div>What is the association of peri-conceptional maternal vulnerability, assessed through a weighted multi-domain risk score with embryonic growth?</div></div><div><h3>Design</h3><div>638 pregnancies were included from the Rotterdam Periconception Cohort. Data on nine vulnerability factors (encompassing lifestyle, mental health and environmental factors) were obtained through self-administered questionnaires. The Periconceptional Vulnerability Risk Score (PVRS) was calculated using weighted estimates of associations between vulnerability factors and ‘Big 3’ pregnancy outcomes (congenital anomalies, preterm birth and small for gestational age). Embryonic growth was assessed by repeated first-trimester 3D transvaginal ultrasound measurements of crown-rump length and embyronic volume, analyzed with VR-software.</div></div><div><h3>Results</h3><div>For the total study population, the PVRS ranged from –0.071 to 0.320 (median 0.131). Higher PVRS values were significantly associated with reduced embryonic growth trajectories (CRL: β = –0.58 mm, 95% CI –0.94 to –0.23, <em>P</em> = 0.001; embryonic volume: β = –0.31 cm³, 95% CI –0.49 to –0.13, <em>P</em> = 0.001). Subgroup analyses revealed significant negative associations in naturally conceived pregnancies (CRL: β = –0.82 mm, 95% CI –1.48 to –0.16, <em>P</em> = 0.015; embryonic volume: β = –0.39 cm³, 95% CI –0.71 to –0.08, <em>P</em> = 0.015) and in overweight women (CRL: β = –0.91 mm, 95% CI –1.55 to –0.27, <em>P</em> = 0.006; embryonic volume: β = –0.51 cm³, 95% CI –0.82 to –0.21, <em>P</em> = 0.001).</div></div><div><h3>Conclusions</h3><div>The PVRS provides a weighted measure of maternal vulnerability, significantly associated with reduced embryonic growth, particularly in naturally conceived pregnancies and overweight women. Although no causality can be inferred from this study, the observed associations suggest that a broad peri-conceptional vulnerability assessment could help to identify potentially modifiable risk factors.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105085"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145605544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-08-18DOI: 10.1016/j.rbmo.2025.105219
Mitchel C Schiewe
With the publication of several recent papers on new vitrification and post-warming protocols, Reproductive BioMedicine Online has brought well-deserved attention to the evolving landscape of cryopreservation practices for human oocytes and embryos. These new protocols aim to improve efficiency, reliability, cost-effectiveness and, potentially, safety and the developmental trajectory. Vitrification protocols have changed from long to short (as in ‘fast and furious’) and post-warming dilutions have changed from a multistep process to a fast single-step process. However, we may yet see warming protocols that forgo elution in non-permeable solutes in favour of an even faster method – rehydration directly in culture medium.
{"title":"Fast to fastest: single-step sucrose dilution to direct hydration of vitrified-warmed human blastocysts","authors":"Mitchel C Schiewe","doi":"10.1016/j.rbmo.2025.105219","DOIUrl":"10.1016/j.rbmo.2025.105219","url":null,"abstract":"<div><div>With the publication of several recent papers on new vitrification and post-warming protocols, <em>Reproductive BioMedicine Online</em> has brought well-deserved attention to the evolving landscape of cryopreservation practices for human oocytes and embryos. These new protocols aim to improve efficiency, reliability, cost-effectiveness and, potentially, safety and the developmental trajectory. Vitrification protocols have changed from long to short (as in ‘fast and furious’) and post-warming dilutions have changed from a multistep process to a fast single-step process. However, we may yet see warming protocols that forgo elution in non-permeable solutes in favour of an even faster method – rehydration directly in culture medium.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105219"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-07-24DOI: 10.1016/j.rbmo.2025.105175
Marie Claire Aquilina , Julien Camard , Wisdom Igiogbe , Taylor Sanderson , Lucy Abbott , Darren K. Griffin , Adrian Podoleanu , Peter Ellis , Giuseppe Silvestri , Manuel J. Marques
Research question
Does exposure to near-infra-red optical coherence tomography (OCT) laser radiation induce phototoxic effects in porcine and human spermatozoa?
Design
Computer-assisted sperm analysis (CASA) was used to determine whether OCT laser illumination at or above levels typically used for imaging alters sperm motility. Flow cytometry was used to determine the impact of irradiation on sperm acrosome reaction status, DNA fragmentation, and membrane integrity. Additionally, in-vitro time-lapse OCT imaging of a porcine cumulus–oocyte complex with irradiated spermatozoa was performed to determine whether irradiated spermatozoa interact with and penetrate the cumulus oophorus. Finally, human spermatozoa were irradiated and analysed using CASA and flow cytometric techniques.
Results
All irradiated samples showed no significant difference in sperm DNA damage or CASA sperm motility parameters, including average path velocity, straight line velocity or curvilinear velocity, compared with their matched manipulation control, suggesting that sample irradiation did not compromise sperm viability, even when using an optical power of more than one order of magnitude greater than that typically required to image embryos. Proof-of-concept OCT imaging suggested that motility of irradiated spermatozoa during cumulus interaction was not affected by radiation.
Conclusions
No significant effect on the kinetics of boar and human spermatozoa was observed following near-infra-red OCT laser radiation. Future work will investigate the fertilization process and embryo development following near-infra-red OCT laser radiation.
{"title":"Investigating phototoxicity of optical coherence tomography imaging in porcine and human spermatozoa","authors":"Marie Claire Aquilina , Julien Camard , Wisdom Igiogbe , Taylor Sanderson , Lucy Abbott , Darren K. Griffin , Adrian Podoleanu , Peter Ellis , Giuseppe Silvestri , Manuel J. Marques","doi":"10.1016/j.rbmo.2025.105175","DOIUrl":"10.1016/j.rbmo.2025.105175","url":null,"abstract":"<div><h3>Research question</h3><div>Does exposure to near-infra-red optical coherence tomography (OCT) laser radiation induce phototoxic effects in porcine and human spermatozoa?</div></div><div><h3>Design</h3><div>Computer-assisted sperm analysis (CASA) was used to determine whether OCT laser illumination at or above levels typically used for imaging alters sperm motility. Flow cytometry was used to determine the impact of irradiation on sperm acrosome reaction status, DNA fragmentation, and membrane integrity. Additionally, in-vitro time-lapse OCT imaging of a porcine cumulus–oocyte complex with irradiated spermatozoa was performed to determine whether irradiated spermatozoa interact with and penetrate the cumulus oophorus. Finally, human spermatozoa were irradiated and analysed using CASA and flow cytometric techniques.</div></div><div><h3>Results</h3><div>All irradiated samples showed no significant difference in sperm DNA damage or CASA sperm motility parameters, including average path velocity, straight line velocity or curvilinear velocity, compared with their matched manipulation control, suggesting that sample irradiation did not compromise sperm viability, even when using an optical power of more than one order of magnitude greater than that typically required to image embryos. Proof-of-concept OCT imaging suggested that motility of irradiated spermatozoa during cumulus interaction was not affected by radiation.</div></div><div><h3>Conclusions</h3><div>No significant effect on the kinetics of boar and human spermatozoa was observed following near-infra-red OCT laser radiation. Future work will investigate the fertilization process and embryo development following near-infra-red OCT laser radiation.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105175"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-08-07DOI: 10.1016/j.rbmo.2025.105207
Peter Slatinšek , Milan Reljič , Borut Kovačič
Research question
Does a gradient of oxygen concentration, decreasing from 8% to 2% during prolonged embryo culture, yield a higher percentage of morphologically optimal blastocysts compared with a static 5% oxygen atmosphere?
Design
This prospective sibling-split study included 658 cumulus-oocyte complexes from 44 intracytoplasmic sperm injection (ICSI) cycles (January 2022 to January 2023), alternately assigned to a control group (static 5% oxygen) or an intervention group (stepwise oxygen reduction: 8% on days 0-3, 5% on day 3, and 2% until days 5 or 6).
Results
Early embryo morphology was similar between groups. By day 5, following exposure to 2% oxygen from day 3, the control group produced a significantly higher proportion of clinically used blastocysts (47.3%, 122/258 vs. 36.9%, 97/263; P = 0.0161). Rates of morphologically optimal day-5 blastocysts were comparable (14.7%, 38/258 vs. 10.3%, 27/263; P = 0.2373). Time-lapse analysis showed delayed initiation of blastulation (P = 0.0024), blastocyst formation (P < 0.001), and expansion (P < 0.001) in the intervention group. Because of this delay, embryologists were more likely to select blastocysts for fresh transfer from the control group in a blinded procedure (P = 0.0088). Morphometric analysis showed significantly larger blastocyst cross-sectional area in the control group (28,198 ± 4139 vs. 25,994 ± 4657 µm2; P = 0.0014), consistent with more advanced expansion under constant 5% oxygen.
Conclusions
Gradually lowering oxygen from 8% to 2% during the second half of embryo culture resulted in delayed blastulation and fewer clinically used blastocysts when compared with culture under static 5% oxygen.
研究问题:在长时间的胚胎培养过程中,氧气浓度从8%下降到2%的梯度,与静态的5%氧气环境相比,是否能产生更高比例的形态最佳囊胚?设计:这项前瞻性的兄弟姐妹分离研究包括来自44个胞浆内单精子注射(ICSI)周期(2022年1月至2023年1月)的658个卵母细胞堆积复合物,交替分配到对照组(静态5%氧气)或干预组(逐步氧气减少:0-3天8%,第3天5%,第5或6天2%)。结果:两组间早期胚胎形态相似。第5天,从第3天开始暴露于2%的氧气中,对照组产生的临床使用囊胚比例显著高于对照组(47.3%,122/258 vs. 36.9%, 97/263; P = 0.0161)。形态学最佳的第5天囊胚率具有可比性(14.7%,38/258 vs. 10.3%, 27/263; P = 0.2373)。延时分析显示,干预组囊胚起始延迟(P = 0.0024),囊胚形成延迟(P < 0.001),囊胚扩张延迟(P < 0.001)。由于这种延迟,胚胎学家更有可能在盲法程序中从对照组中选择囊胚进行新鲜移植(P = 0.0088)。形态计量学分析显示,对照组囊胚截面积显著增大(28,198±4139 vs. 25,994±4657µm2; P = 0.0014),与5%恒定氧气条件下更晚期的扩张相一致。结论:在胚胎培养的后半段,将氧气浓度从8%逐渐降低到2%,与5%的静态氧气培养相比,会导致囊胚发育延迟,临床使用囊胚数量减少。
{"title":"Effect of constant (5%) versus gradient (8%–2%) oxygen concentration on sibling human blastocyst development","authors":"Peter Slatinšek , Milan Reljič , Borut Kovačič","doi":"10.1016/j.rbmo.2025.105207","DOIUrl":"10.1016/j.rbmo.2025.105207","url":null,"abstract":"<div><h3>Research question</h3><div>Does a gradient of oxygen concentration, decreasing from 8% to 2% during prolonged embryo culture, yield a higher percentage of morphologically optimal blastocysts compared with a static 5% oxygen atmosphere?</div></div><div><h3>Design</h3><div>This prospective sibling-split study included 658 cumulus-oocyte complexes from 44 intracytoplasmic sperm injection (ICSI) cycles (January 2022 to January 2023), alternately assigned to a control group (static 5% oxygen) or an intervention group (stepwise oxygen reduction: 8% on days 0-3, 5% on day 3, and 2% until days 5 or 6).</div></div><div><h3>Results</h3><div>Early embryo morphology was similar between groups. By day 5, following exposure to 2% oxygen from day 3, the control group produced a significantly higher proportion of clinically used blastocysts (47.3%, 122/258 vs. 36.9%, 97/263; <em>P</em> = 0.0161). Rates of morphologically optimal day-5 blastocysts were comparable (14.7%, 38/258 vs. 10.3%, 27/263; P = 0.2373). Time-lapse analysis showed delayed initiation of blastulation (P = 0.0024), blastocyst formation (<em>P</em> < 0.001), and expansion (<em>P</em> < 0.001) in the intervention group. Because of this delay, embryologists were more likely to select blastocysts for fresh transfer from the control group in a blinded procedure (<em>P</em> = 0.0088). Morphometric analysis showed significantly larger blastocyst cross-sectional area in the control group (28,198 ± 4139 vs. 25,994 ± 4657 µm<sup>2</sup>; <em>P</em> = 0.0014), consistent with more advanced expansion under constant 5% oxygen.</div></div><div><h3>Conclusions</h3><div>Gradually lowering oxygen from 8% to 2% during the second half of embryo culture resulted in delayed blastulation and fewer clinically used blastocysts when compared with culture under static 5% oxygen.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105207"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145669600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-08-05DOI: 10.1016/j.rbmo.2025.105184
Andrew Drakeley , Rebecca L. Lunt , Emily Newton , Rachel C. Gregoire , Linda Watkins , Katerina Bambang , Ann-Maria Ellard , Craig J. Ledgerwood , Lewis Rae , Alastair Sloan , Martin Lawlor , Lynsey Poots , Luca Moore , Elizabeth Bailie , Sara H. McDowell , Jordi Ribas-Maynou , Tara Moore
Research question
Do men attending a recurrent miscarriage clinic have high double-stranded sperm DNA damage compared with a sperm donor population?
Design
This prospective cohort study included 100 men attending a recurrent miscarriage clinic, and 81 sperm donors from a European sperm bank who had proven fertility. All semen samples were evaluated using the Examen Lab alkaline (Exact) comet assay, which identifies the global (single and double strand) DNA damage, and the neutral (Extend) comet assay, measuring only double-stranded sperm DNA fragmentation (dsSDF).
Results
Semen analysis showed that 66 male partners of women with a history of recurrent miscarriage were classified as being within normal parameters. Of these, however, 66 men (61%) had raised global SDF, and 52% had raised dsSDF. When evaluating each test separately, the Exact comet (global SDF) assay presented an area under the curve (AUC) of 0.690 (95% CI 0.623–0.756), with the neutral Extend comet (dsSDF only) assay having an AUC of 0.876 (95% CI 0.834–0.914), and the incidence of damage showed an improved AUC of 0.909 (95% CI 0.874–0.940).
Conclusions
This study of male factor SDF in a large cohort of men attending a recurrent miscarriage clinic, where they are rarely the focus of clinical investigation, shows a strong association with dsSDF and male factor-driven miscarriage contribution, highlighting the importance of male investigation in couples experiencing recurrent pregnancy loss.
研究问题:与精子捐赠者相比,参加复发性流产诊所的男性是否有较高的双链精子DNA损伤?设计:这项前瞻性队列研究包括100名在复发性流产诊所就诊的男性,以及81名来自欧洲精子库的证明有生育能力的捐精者。所有精液样本均使用Examen Lab碱性(Exact)彗星测定法进行评估,该方法可识别整体(单链和双链)DNA损伤,而中性(Extend)彗星测定法仅测量双链精子DNA片段(dsSDF)。结果:精液分析显示66例有反复流产史的女性的男性伴侣在正常范围内。然而,其中66名男性(61%)提高了全球SDF, 52%提高了dsSDF。当单独评估每个测试时,精确彗星(全球SDF)检测的曲线下面积(AUC)为0.690 (95% CI 0.623-0.756),中性延伸彗星(仅dsSDF)检测的AUC为0.876 (95% CI 0.834-0.914),损伤发生率的AUC为0.909 (95% CI 0.874-0.940)。结论:本研究对在复发性流产诊所就诊的大量男性进行了男性因子SDF的研究,该研究显示,dsSDF与男性因素驱动的流产贡献有很强的关联,突出了男性调查在复发性流产夫妇中的重要性。
{"title":"Double-stranded sperm DNA fragmentation assessed using comet assay is associated with recurrent pregnancy loss","authors":"Andrew Drakeley , Rebecca L. Lunt , Emily Newton , Rachel C. Gregoire , Linda Watkins , Katerina Bambang , Ann-Maria Ellard , Craig J. Ledgerwood , Lewis Rae , Alastair Sloan , Martin Lawlor , Lynsey Poots , Luca Moore , Elizabeth Bailie , Sara H. McDowell , Jordi Ribas-Maynou , Tara Moore","doi":"10.1016/j.rbmo.2025.105184","DOIUrl":"10.1016/j.rbmo.2025.105184","url":null,"abstract":"<div><h3>Research question</h3><div>Do men attending a recurrent miscarriage clinic have high double-stranded sperm DNA damage compared with a sperm donor population?</div></div><div><h3>Design</h3><div>This prospective cohort study included 100 men attending a recurrent miscarriage clinic, and 81 sperm donors from a European sperm bank who had proven fertility. All semen samples were evaluated using the Examen Lab alkaline (Exact) comet assay, which identifies the global (single and double strand) DNA damage, and the neutral (Extend) comet assay, measuring only double-stranded sperm DNA fragmentation (dsSDF).</div></div><div><h3>Results</h3><div>Semen analysis showed that 66 male partners of women with a history of recurrent miscarriage were classified as being within normal parameters. Of these, however, 66 men (61%) had raised global SDF, and 52% had raised dsSDF. When evaluating each test separately, the Exact comet (global SDF) assay presented an area under the curve (AUC) of 0.690 (95% CI 0.623–0.756), with the neutral Extend comet (dsSDF only) assay having an AUC of 0.876 (95% CI 0.834–0.914), and the incidence of damage showed an improved AUC of 0.909 (95% CI 0.874–0.940).</div></div><div><h3>Conclusions</h3><div>This study of male factor SDF in a large cohort of men attending a recurrent miscarriage clinic, where they are rarely the focus of clinical investigation, shows a strong association with dsSDF and male factor-driven miscarriage contribution, highlighting the importance of male investigation in couples experiencing recurrent pregnancy loss.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105184"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145725627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-08-31DOI: 10.1016/j.rbmo.2025.105238
Juergen Liebermann, Rebecca Brohammer, Yuri Wagner, Allison Parus, Cynthia Macias, Nivek Suda, Alexis Vanderpool, Gabija Petrus, Olivia Sarris, Kelly Even, Ru Smith, Shelby Sutherland, Sue Jasulaitis, Jennifer Hirshfeld-Cytron, Christopher Sipe, Meike Uhler
Research question
Does one-step rehydration in the warming protocol for human blastocysts result in healthy live births?
Design
A total of 2411 frozen embryo transfers using a short one-step rehydration protocol and 2606 frozen embryo transfers using the multi-step protocol were available for analysis. One-step warming was performed at 37°C in 1M sucrose for 1 min. This study examined the gestational age at delivery and birth weight of male and female infants for both protocols.
Results
In the one-step warming protocol, 1266 infants were born. The overall live birth rate was 51.3%, average gestational age was 37.6 weeks, and average birth weight was 3267 g. The sex distribution was 49% male versus 51% female. Male infants were, on average, 70 g heavier than female infants (3305 g versus 3235 g, respectively). In the multi-step warming protocol, 1323 infants were born. The average gestational age was 37.6 weeks, and average birth weight was 3252 g. The sex distribution was 52% male versus 48% female. Male infants were, on average, 139 g heavier than female infants (3318 g vs 3179 g, respectively). There were no significant differences between the two warming groups in terms of live birth and miscarriage rates, gestational age and birth weight.
Conclusions
Short one-step rehydration during warming of human blastocysts for 1 min in 1M sucrose led to healthy infants born at term with corresponding birth weight. This one-step rehydration protocol has been shown to be safe and effective, and it has now been validated with 1266 live births.
{"title":"Fast and furious: live birth outcomes in 1266 infants born after one-step warming of vitrified human blastocysts","authors":"Juergen Liebermann, Rebecca Brohammer, Yuri Wagner, Allison Parus, Cynthia Macias, Nivek Suda, Alexis Vanderpool, Gabija Petrus, Olivia Sarris, Kelly Even, Ru Smith, Shelby Sutherland, Sue Jasulaitis, Jennifer Hirshfeld-Cytron, Christopher Sipe, Meike Uhler","doi":"10.1016/j.rbmo.2025.105238","DOIUrl":"10.1016/j.rbmo.2025.105238","url":null,"abstract":"<div><h3>Research question</h3><div>Does one-step rehydration in the warming protocol for human blastocysts result in healthy live births?</div></div><div><h3>Design</h3><div>A total of 2411 frozen embryo transfers using a short one-step rehydration protocol and 2606 frozen embryo transfers using the multi-step protocol were available for analysis. One-step warming was performed at 37°C in 1M sucrose for 1 min. This study examined the gestational age at delivery and birth weight of male and female infants for both protocols.</div></div><div><h3>Results</h3><div>In the one-step warming protocol, 1266 infants were born. The overall live birth rate was 51.3%, average gestational age was 37.6 weeks, and average birth weight was 3267 g. The sex distribution was 49% male versus 51% female. Male infants were, on average, 70 g heavier than female infants (3305 g versus 3235 g, respectively). In the multi-step warming protocol, 1323 infants were born. The average gestational age was 37.6 weeks, and average birth weight was 3252 g. The sex distribution was 52% male versus 48% female. Male infants were, on average, 139 g heavier than female infants (3318 g vs 3179 g, respectively). There were no significant differences between the two warming groups in terms of live birth and miscarriage rates, gestational age and birth weight.</div></div><div><h3>Conclusions</h3><div>Short one-step rehydration during warming of human blastocysts for 1 min in 1M sucrose led to healthy infants born at term with corresponding birth weight. This one-step rehydration protocol has been shown to be safe and effective, and it has now been validated with 1266 live births.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105238"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-06-14DOI: 10.1016/j.rbmo.2025.105104
María Cerrillo , Javier Martínez-Salazar , Cristina Fernández , Pedro Royo , Alberto Vázquez , Elkin Muñoz , Víctor H. Gómez , José Puente , Antonio Requena , Juan A. García-Velasco
Research question
Transvaginal radiofrequency ablation (TRFA) may offer a safe and effective alternative to surgery for infertile women with type 2 or 3 fibroids under 4 cm diameter that compromise the uterine cavity.
Methods
In this study, 36 patients underwent ultrasound-guided TRFA between 2020 and 2023. Main outcomes were fibroid volume reduction at 1, 3, and 6 months, and post-procedure reproductive results.
Results
Mean baseline fibroid volume was 19.29 cm3, decreasing to 9.6 cm3 at 1 month, 4.39 cm3 at 3 months, and 4.07 cm3 at 6 months, reflecting >75% reduction. Mild pain and minimal bleeding occurred in 22% of patients; hysteroscopic removal of protruding fibroids was required in 22%. Among the 25 women undergoing subsequent ART, pregnancy and miscarriage rates per treated patient were 68% and 16%, respectively; live births occurred in 52%, with most deliveries at full-term. Caesarean delivery rate was 69.2%.
Conclusions
TRFA appears to be a safe and effective alternative to surgery for infertile women with type 2 or 3 fibroids under 4 cm in diameter that compromise the uterine cavity. The procedure does not seem to affect reproductive outcomes, and this study is the first to assess the effect of TRFA on ART.
{"title":"Real-life experience with transvaginal radiofrequency ablation in infertile patients with types 2 and 3 fibroids","authors":"María Cerrillo , Javier Martínez-Salazar , Cristina Fernández , Pedro Royo , Alberto Vázquez , Elkin Muñoz , Víctor H. Gómez , José Puente , Antonio Requena , Juan A. García-Velasco","doi":"10.1016/j.rbmo.2025.105104","DOIUrl":"10.1016/j.rbmo.2025.105104","url":null,"abstract":"<div><h3>Research question</h3><div>Transvaginal radiofrequency ablation (TRFA) may offer a safe and effective alternative to surgery for infertile women with type 2 or 3 fibroids under 4 cm diameter that compromise the uterine cavity.</div></div><div><h3>Methods</h3><div>In this study, 36 patients underwent ultrasound-guided TRFA between 2020 and 2023. Main outcomes were fibroid volume reduction at 1, 3, and 6 months, and post-procedure reproductive results.</div></div><div><h3>Results</h3><div>Mean baseline fibroid volume was 19.29 cm<sup>3</sup>, decreasing to 9.6 cm<sup>3</sup> at 1 month, 4.39 cm<sup>3</sup> at 3 months, and 4.07 cm<sup>3</sup> at 6 months, reflecting >75% reduction. Mild pain and minimal bleeding occurred in 22% of patients; hysteroscopic removal of protruding fibroids was required in 22%. Among the 25 women undergoing subsequent ART, pregnancy and miscarriage rates per treated patient were 68% and 16%, respectively; live births occurred in 52%, with most deliveries at full-term. Caesarean delivery rate was 69.2%.</div></div><div><h3>Conclusions</h3><div>TRFA appears to be a safe and effective alternative to surgery for infertile women with type 2 or 3 fibroids under 4 cm in diameter that compromise the uterine cavity. The procedure does not seem to affect reproductive outcomes, and this study is the first to assess the effect of TRFA on ART.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105104"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01Epub Date: 2025-08-16DOI: 10.1016/j.rbmo.2025.105216
Fernando Zegers-Hochschild , Javier A Crosby , Carolina Musri , Fanny Petermann-Rocha , Gustavo Martinez , Hitomi Nakagawa , Carlos Morente , Armando Roque , Ana Palma-Govea , Latin American Network of Assisted Reproduction
Research question
What are the trends and effects of assisted reproductive technology (ART) interventions on the effectiveness and safety of ART carried out in Latin America during 2022.
Design
Retrospective collection of cycle-based multinational data obtained from ART procedures carried out by 204 accredited institutions in 16 countries.
Results
In total 123,265 initiated cycles resulted in 19,663 deliveries and 22,203 births. Use of ART varied greatly, from 643.3 cycles/million inhabitants in Uruguay to 28.8 in Guatemala. In autologous cycles, the proportion of women aged ≥40 years represents 35.1% of cycles, whereas women <34 years represents only 18.8%. The proportion of single embryo transfers (SET) increased from 42.4% in 2021 to 47.3% in 2022. Out of 22,203 babies born, 77.4% were singletons, 21.7% twins and 0.9% triplets or more. Intracytoplasmic sperm injection represented 85.4% of fertilization techniques, and blastocyst transfer increased from 79.3% in 2021 to 85.3% in 2022. Delivery rate after fresh blastocyst elective single embryo transfer (32.6%) was significantly higher than after the transfer of one frozen embryo transfer (FET) from freeze-all cycle (25.2%) (P = 0.0001). The number of aspirations leading to preimplantation genetic testing increased 2.6 times in 6 years, and significantly increased delivery rates/transfer (P ≤ 0.008) and reduced miscarriage at all ages (P ≤ 0.004) in autologous cycles, but not in oocyte donation cycles. Delivery rates after fresh transfer of embryos from vitrified–warmed donated oocytes, generated similar outcome to FET from fresh oocyte donation cycles (P = 0.5621). Perinatal mortality increased from 7.5‰ in singletons to 22.8‰ in twins.
Conclusion
Systematic collection of cycle-based multinational data contributes to cooperative sustained development and helps implement evidence-based reproductive decisions.
{"title":"Assisted reproductive technology in Latin America: the Latin American Registry, 2022","authors":"Fernando Zegers-Hochschild , Javier A Crosby , Carolina Musri , Fanny Petermann-Rocha , Gustavo Martinez , Hitomi Nakagawa , Carlos Morente , Armando Roque , Ana Palma-Govea , Latin American Network of Assisted Reproduction","doi":"10.1016/j.rbmo.2025.105216","DOIUrl":"10.1016/j.rbmo.2025.105216","url":null,"abstract":"<div><h3>Research question</h3><div>What are the trends and effects of assisted reproductive technology (ART) interventions on the effectiveness and safety of ART carried out in Latin America during 2022.</div></div><div><h3>Design</h3><div>Retrospective collection of cycle-based multinational data obtained from ART procedures carried out by 204 accredited institutions in 16 countries.</div></div><div><h3>Results</h3><div>In total 123,265 initiated cycles resulted in 19,663 deliveries and 22,203 births. Use of ART varied greatly, from 643.3 cycles/million inhabitants in Uruguay to 28.8 in Guatemala. In autologous cycles, the proportion of women aged ≥40 years represents 35.1% of cycles, whereas women <34 years represents only 18.8%. The proportion of single embryo transfers (SET) increased from 42.4% in 2021 to 47.3% in 2022. Out of 22,203 babies born, 77.4% were singletons, 21.7% twins and 0.9% triplets or more. Intracytoplasmic sperm injection represented 85.4% of fertilization techniques, and blastocyst transfer increased from 79.3% in 2021 to 85.3% in 2022. Delivery rate after fresh blastocyst elective single embryo transfer (32.6%) was significantly higher than after the transfer of one frozen embryo transfer (FET) from freeze-all cycle (25.2%) (<em>P</em> = 0.0001). The number of aspirations leading to preimplantation genetic testing increased 2.6 times in 6 years, and significantly increased delivery rates/transfer (<em>P</em> ≤ 0.008) and reduced miscarriage at all ages (<em>P</em> ≤ 0.004) in autologous cycles, but not in oocyte donation cycles. Delivery rates after fresh transfer of embryos from vitrified–warmed donated oocytes, generated similar outcome to FET from fresh oocyte donation cycles (<em>P</em> = 0.5621). Perinatal mortality increased from 7.5‰ in singletons to 22.8‰ in twins.</div></div><div><h3>Conclusion</h3><div>Systematic collection of cycle-based multinational data contributes to cooperative sustained development and helps implement evidence-based reproductive decisions.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"52 1","pages":"Article 105216"},"PeriodicalIF":3.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}