Reproductive Biomedicine Online[JOURNAL]
Sun
200 papers
Size matters: breaking the decades-old dogma of universal follicle size for timing egg retrieval.
Gleicher N, Gayete-Lafuente S, Guijarro-Baude L … +4 more , Patrizio P, Nicholas C, Albertini DF, Barad DH
Reprod Biomed Online · 2026 Feb · PMID 42119547 · Publisher ↗
RESEARCH QUESTION: Is the routine practice of triggering ovulation at a fixed follicle size (18-22 mm) in IVF optimal across all age groups? DESIGN: An analysis of 109 autologous IVF cycles with fresh embryo transfer per...
RESEARCH QUESTION: Is the routine practice of triggering ovulation at a fixed follicle size (18-22 mm) in IVF optimal across all age groups? DESIGN: An analysis of 109 autologous IVF cycles with fresh embryo transfer performed in 2025 was undertaken at the authors' New York fertility centre, following the approach of trigger-timing optimization from a 10-year experience with the Highly Individualized Egg Retrieval (HIER) protocol. HIER is based on the longitudinal understanding of age-related changes in follicular dynamics and oocyte maturity, involving lowering follicle size thresholds for triggering with advancing ovarian age - often to less than 12-14 mm in patients over 43 years of age - combined with routine rescue in-vitro maturation (rIVM) of all immature oocytes. The main outcome was clinical pregnancy rate, both global (median age 42.8 years, range 26.6-51.9 years) and over age 43 (median age 46.9 years, range 44.0-51.9 years), a decade after implementation of HIER with rIVM. RESULTS: In 2025, a 12% overall clinical pregnancy rate per transfer was achieved in women with a median age of 42.8 years, and 8% in the subset of patients aged 44 years or older. CONCLUSIONS: The universal application of a fixed follicle size (18-22 mm) for ovulation triggering may be outdated. Age-adjusted protocols such as HIER optimize IVF success, especially in older or poor-prognosis patients in whom there tends to be a rapid acceleration of premature luteinization. This warrants further validation for broader clinical adoption.
Can oral dydrogesterone mitigate adverse outcomes with low progesterone on transfer day in natural-cycle frozen embryo transfer?
Roelens C, Van Overberghe C, Aktoz F … +5 more , Van Landuyt L, Mackens S, De Vos M, Tournaye H, Blockeel C
Reprod Biomed Online · 2026 Feb · PMID 42119546 · Publisher ↗
RESEARCH QUESTION: Is oral dydrogesterone administration associated with comparable pregnancy rates when suboptimal serum progesterone concentrations are identified on the day of transfer in true and modified natural-cyc...
RESEARCH QUESTION: Is oral dydrogesterone administration associated with comparable pregnancy rates when suboptimal serum progesterone concentrations are identified on the day of transfer in true and modified natural-cycle frozen embryo transfer (NC-FET)? DESIGN: This retrospective study, conducted at a tertiary university-based referral centre, included 886 patients undergoing NC-FET without luteal phase support before FET who had serum progesterone measured on the day of transfer. Patients with serum progesterone <10 µg/l (group A) received oral dydrogesterone from the day of embryo transfer onward, whereas most patients with progesterone ≥10 µg/l (group B) received no luteal phase support. RESULTS: In total, 160/886 (18%) patients had serum progesterone <10 µg/l on the day of transfer. Demographic characteristics were largely comparable between groups, except for body mass index, which was significantly higher in group A (P < 0.01). Reproductive outcomes did not differ significantly: ongoing pregnancy rates were 47.5% and 50.4% for groups A and B (P = 0.51); early pregnancy loss occurred in 18.1% and 19.6%, respectively (P = 0.74); and live birth rates were 46.5% and 48.8% in groups A and B (P = 0.60). CONCLUSIONS: These findings suggest that the potentially deleterious impact of low serum progesterone on the day of blastocyst transfer in NC-FET cycles may be avoided when oral dydrogesterone is administered. This supports a personalized approach to luteal phase support in true and modified natural cycles.
An advanced SWOT analysis of elective vitrification: today's standard IVF procedure.
Blockeel C, Antunes RA, Ata B … +14 more , Barrenetxea G, Fatemi H, Franasiak J, Velasco JG, Griesinger G, Pirtea P, Polyzos NP, Popovic M, Rienzi L, Stoop D, Tremellen K, Venetis C, Santos-Ribeiro S, Global Freeze-all Expert Forum
Reprod Biomed Online · 2026 Jan · PMID 42119545 · Publisher ↗
In clinical practice, treatment cycles are routinely started without the intention of undertaking fresh embryo transfer, as the freeze-all strategy is suitable for a multitude of alternative stimulation protocols as well...
In clinical practice, treatment cycles are routinely started without the intention of undertaking fresh embryo transfer, as the freeze-all strategy is suitable for a multitude of alternative stimulation protocols as well as preimplantation genetic testing of embryos. Based on strengths, weaknesses, opportunities and threats (SWOT) analysis, it was evaluated whether a freeze-all strategy may be advised for all patients regardless of their (predicted) ovarian response. Therefore, the latest literature including the outcome of all randomized controlled trials (RCT) and their combined analysis were reviewed. Only two large trials, both from China, were considered conclusive and showed (following first embryo transfer) a higher chance of live birth following elective vitrification in comparison with fresh embryo transfer in women with polycystic ovary syndrome and in ovulatory women with a good prognosis. The other six trials showed either no difference in clinical outcome or were inconclusive by design. It is concluded that elective vitrification is likely favourable for high responders as it results in an improved chance of live birth following single embryo transfer, and is likely equally successful for normal responders. One trial in low responders indicated that the live birth rate may be compromised, which needs further confirmation in the future. This SWOT analysis of embryo transfer deferral also concluded that this approach allows the number of oocytes per stimulation cycle to be maximized safely in order to improve the chance of pregnancy. To minimize the risk for obstetric and perinatal complications in frozen-thawed embryo transfer cycles, (modified) natural cycles should be considered as the preferred approach for regular cycling women.
Oocyte vitrification reduces blastocyst yield but preserves reproductive competence in advanced maternal age patients undergoing oocyte accumulation with PGT-A.
Canosa S, Cimadomo D, Maggiulli R … +7 more , Revelli A, Gennarelli G, Ottolini CS, Capalbo A, Bongioanni F, Rienzi L, Coticchio G
Reprod Biomed Online · 2026 Jan · PMID 42119544 · Publisher ↗
RESEARCH QUESTION: Does oocyte vitrification affect embryological and reproductive outcomes in women of advanced maternal age undergoing oocyte accumulation for PGT-A? DESIGN: Retrospective observational study (n = 122,...
RESEARCH QUESTION: Does oocyte vitrification affect embryological and reproductive outcomes in women of advanced maternal age undergoing oocyte accumulation for PGT-A? DESIGN: Retrospective observational study (n = 122, mean age: 39.7 ± 2.7 years) undergoing IVF with oocyte accumulation for PGT-A. Each patient contributed vitrified‒warmed cohort (VW) and sibling fresh cohort (F) MII oocytes. The first oocyte cohort was vitrified after the first oocyte retrieval and warmed for insemination alongside fresh oocytes from the second oocyte retrieval. Trophectoderm biopsy and next-generation sequencing-based PGT-A were conducted at the blastocyst stage. Primary outcome was blastocyst formation rate per MII; secondary outcomes were euploidy rate, pregnancy and neonatal outcomes, from the proceeding frozen embryo transfer. RESULTS: Vitrification significantly reduced blastulation rate per MII-allocated oocyte (24.6 ± 34.1% VW versus 44.2 ± 33.9% F; P < 0.0001). Despite lower blastocyst yield, euploidy rates per biopsied blastocyst were comparable (38.8% VW versus 38.0% F; P = 0.91) as were the aneuploidy types. Clinical pregnancy (40.9% VW versus 61.2% F, P = 0.11), miscarriage (11.1% VW versus 10.0% F, P = 0.92) and live birth rates (36.4% VW versus 55.1% F, P = 0.14) per single euploid embryo transfer did not differ. No differences were found in neonatal outcomes, including gestational age, birth weight and sex distribution. CONCLUSIONS: Oocyte vitrification does not affect euploidy rates or chance of live birth per euploid embryo transfer. The reduction in blastocyst yield observed in older patients indicates that this population should be appropriately counselled about the potential effect on embryo availability and cumulative outcomes.
Using corpus luteum formation with dominant follicle collapse to improve the criteria for identifying ovulation.
Bouchard TP, Pierson R, Ecochard R … +6 more , Lane M, Alger GE, Diment CJ, Bedaiwy M, Yong PJ, Doyle-Baker PK
Reprod Biomed Online · 2026 Mar · PMID 42105719 · Publisher ↗
RESEARCH QUESTION: Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the da...
RESEARCH QUESTION: Does formation of the corpus luteum help to identify the day of ovulation on ultrasound when follicular collapse is missed, and how reliable are sonographers versus a review panel in identifying the day of ovulation on ultrasound? DESIGN: Sonographers in a clinic in Canada performed serial endovaginal ultrasound scans (six to eight per cycle) to identify the day of ovulation in regularly cycling women (n = 40) who were followed for one to five cycles (n = 85). The day of ovulation was identified by: (i) identification of the dominant follicle; (ii) disappearance of the dominant follicle; and (iii) identification and dating of the corpus luteum. The main outcome measures were inter-rater reliability between two sonographers, and Bland-Altman agreement between the supervising sonographer and a panel that reviewed each scan to identify the day of ovulation. RESULTS: Of the 85 menstrual cycles reviewed, two cycles did not have sufficient data to date ovulation, one cycle showed an incidental dermoid cyst, and 11 cycles showed anovulatory patterns. This left a total of 71 cycles (84%) for which intra-rater reliability between two sonographers for identifying the day of ovulation was high (intraclass correlation coefficient = 0.99, P < 0.0001), and Bland-Altman agreement showed no significant difference in the estimated day of ovulation between the supervising sonographer and the panel (t = -0.28, P = 0.78). Corpus luteum criteria were necessary to help identify the day of ovulation in 14 of 71 cycles (20%). CONCLUSIONS: The estimated day of ovulation can be determined reliably on ultrasound by trained sonographers using collapse of the dominant follicle and formation of the corpus luteum based on six to eight scans per cycle.
Ex-vivo preservation of ovine ovarian tissue using PEGylated fibrin hydrogel: a practical biomaterial-based strategy.
Sobhani K, Farzinpour A, Amidi F … +4 more , Moghassemi S, Dadashzadeh A, Storder S, Amorim CA
Reprod Biomed Online · 2025 Dec · PMID 42102666 · Publisher ↗
RESEARCH QUESTION: Can PEGylated fibrin hydrogel serve as a supportive three-dimensional scaffold to improve short-term survival of ovarian cortical tissue, which has implications for fertility preservation? DESIGN: Ovin...
RESEARCH QUESTION: Can PEGylated fibrin hydrogel serve as a supportive three-dimensional scaffold to improve short-term survival of ovarian cortical tissue, which has implications for fertility preservation? DESIGN: Ovine ovarian cortical fragments were encapsulated in PEGylated fibrin hydrogel, synthesized by conjugating four-arm PEG-succinimidyl glutarate with fibrinogen (10:1 ratio) and cross-linked with thrombin and CaCl₂. Encapsulated and non-encapsulated tissues were cultured for 96 h. Morphological and functional assessments included histology, Masson's trichrome staining, immunohistochemistry for caspase-3 and vascular endothelial growth factor (VEGF), immunofluorescence for CD31, and lactate dehydrogenase cytotoxicity assays. RESULTS: Encapsulation significantly preserved primordial follicle density at 48 h (P = 0.01), and reduced degeneration of growing follicles at 72 h (P = 0.006). Stromal cell density was maintained in the encapsulated group at 48 h (P = 0.01), 72 h (P = 0.02) and 96 h (P = 0.001). The proportions of caspase-3-positive stromal cells and follicles were lower in encapsulated tissues at 72 h (P = 0.009 and P = 0.007, respectively), indicating that apoptosis may be reduced. Moreover, in the encapsulated group, the CD31-positive percentage area was elevated at 24 h (P = 0.05), 48 h (P < 0.0001) and 72 h (P = 0.001), whereas the proportion of VEGF-positive cells was higher at 48 h (P = 0.01) and 72 h (P = 0.05), suggesting enhanced angiogenic signalling. CONCLUSIONS: PEGylated fibrin hydrogel provides short-term cryoprotection by supporting stromal and follicular viability, and stimulating angiogenesis during ex-vivo ovarian tissue culture. These findings highlight its potential as a biomimetic scaffold in ovarian tissue engineering, although further optimization is required for extended culture periods and clinical translation.
Effect of prolonged oocyte cryopreservation for >10 years on reproductive outcomes - a systematic review and meta-analysis.
Kauffman A, Karol D, Jones CA … +3 more , Li Q, Huszti E, Michaeli J
Reprod Biomed Online · 2025 Nov · PMID 42092266 · Publisher ↗
Oocyte cryopreservation is essential for fertility preservation, yet the impact of prolonged cryostorage on cryosurvival, embryological and reproductive outcomes remains unclear. A systematic review and meta-analysis of...
Oocyte cryopreservation is essential for fertility preservation, yet the impact of prolonged cryostorage on cryosurvival, embryological and reproductive outcomes remains unclear. A systematic review and meta-analysis of 20 studies (2008-2023) from MEDLINE, Embase and Cochrane databases included 9901 patients. Nine large studies (mean cryostorage 3.76 years) were compared with 11 case studies (mean storage 10.2 years) to assess the impact of a longer period of cryostorage, as none of the large studies had ≥10 years of cryostorage. In large studies, cryosurvival was 81%, fertilization was 72%, and blastulation was 47%. Per embryo transferred (n = 9530), implantation, clinical pregnancy and live birth rates were 35%, 40% and 28%, respectively. Case studies showed comparable cryosurvival (76%), fertilization (76%) and blastulation (36%), with all reproductive outcomes exceeding 49%. A subanalysis of the case studies stratified by length of cryostorage comparing outcomes for ≥10 years (n = 6, mean 12.86 years) with <10 years (n = 5, mean 4.27 years) showed similar cryosurvival (74% versus 81%), lower fertilization (69% versus 91%; P = 0.028), comparable blastulation (37% versus 33%), and higher, although non-significant, clinical pregnancy and live birth rates (61% versus 33%). Available evidence, predominantly from case studies, suggests that prolonged cryostorage of oocytes does not compromise reproductive outcomes, although large prospective studies are needed.
Mastering the move: kinematic signatures of expertise in embryo transfer simulation.
Sall NR, Duros S, Huaulmé A … +3 more , Le Lous M, Jannin P, Nyangoh Timoh K
Reprod Biomed Online · 2026 Jan · PMID 42085956 · Publisher ↗
RESEARCH QUESTION: How does embryo transfer technique, assessed through a simulator validated by the American Society for Reproductive Medicine, vary according to procedural difficulty and practitioner expertise? DESIGN:...
RESEARCH QUESTION: How does embryo transfer technique, assessed through a simulator validated by the American Society for Reproductive Medicine, vary according to procedural difficulty and practitioner expertise? DESIGN: This observational prospective study was conducted from February to May 2024 in assisted reproductive technology centres in western France. Twenty-seven fertility specialists from six centres performed nine embryo transfer simulations at the University of Rennes, using a one-step approach across three pelvic models of increasing difficulty (A1, E1, C). Kinematic data from the simulator were analysed according to scenario difficulty and provider experience. Parameters included the catheter's linear velocity during introduction and, during ejection, the distance from the fundus, ejection speed, mean jerk and total duration. RESULTS: The mean linear velocity of the catheter guide decreased with model difficulty (A1: 2.8 ± 1.4; E1: 2.1 ± 0.95; C: 2.1 ± 0.87 cm/s; P < 0.001). The mean fundus distance increased from 13 ± 5 mm (A1) to 18 ± 6 mm (E1) and 16 ± 7 mm (C) (P < 0.001). Average jerk values were 7046 ± 7822, 3641 ± 3028 and 3452 ± 3402 cm/s⁻³, respectively (P = 0.001). The ejection speed did not differ significantly (P = 0.844). The total duration increased with the difficulty (18 ± 8 s, 36 ± 25 s and 40 ± 51 s, respectively; P < 0.001). Practitioners with higher pregnancy rates showed slower catheter introduction and lower ejection speeds (P = 0.006 and P = 0.0002, respectively). CONCLUSIONS: The embryo transfer kinematics varied with both procedural complexity and operator expertise. Slower, more controlled movements correlated with higher standardized pregnancy rates. Simulation appears valuable for identifying performance-linked metrics and refining training toward safer, more effective embryo transfer practices.
Exploring the association between lifestyle factors and anti-Müllerian hormone concentration and rate of decline.
Werner L, Verschuren WM, Picavet HSJ … +3 more , Broekmans F, van der Schouw YT, de Kat AC
Reprod Biomed Online · 2025 Dec · PMID 42070497 · Publisher ↗
RESEARCH QUESTION: How do lifestyle factors relate to level and decline rate of anti-Müllerian hormone (AMH)? DESIGN: Longitudinal follow-up study including 2761 women of the population-based Doetinchem Cohort Study with...
RESEARCH QUESTION: How do lifestyle factors relate to level and decline rate of anti-Müllerian hormone (AMH)? DESIGN: Longitudinal follow-up study including 2761 women of the population-based Doetinchem Cohort Study with five measurements over a 20-year period. The following lifestyle factors were assessed at follow-up visits: smoking; oral contraceptive use; coffee and tea intake; alcohol intake; physical exercise; body mass index (BMI); and waist-hip ratio (WHR). The associations between lifestyle factors and the outcome measures AMH level (ng/ml) and AMH decline rate (ng/ml/year) were studied in a multivariable linear mixed model. RESULTS: After confounder adjustment, current oral contraceptive use was associated with 41.5% (95% CI ‒49.9 to ‒31.4%) lower AMH levels and a 0.11 ng/ml/year (95% CI 0.08 to 0.13) slower decline than never use. Current and former smokers had 20.3% (95% CI ‒29.2 to ‒10.3%) and 12.7% (‒21.2 to ‒3.2%) lower AMH levels, respectively, but the AMH decline rate did not differ from non-smokers. Women who stopped smoking, however, had temporary stagnation of their AMH decline. Women with high coffee and tea intake had 10.2% (CI 0.2 to 21.2%) higher AMH levels compared with women with low intake. No associations were found between BMI, WHR, physical exercise and alcohol consumption and AMH or AMH decline rate in the multivariable analysis. CONCLUSIONS: These findings can be used for the interpretation of AMH levels in the context of reproductive health counselling.
Sperm DNA fragmentation and embryo aneuploidy: a comprehensive systematic review and meta-analysis.
Zou M, Raffi NA, Noor MM
Reprod Biomed Online · 2026 Feb · PMID 42070496 · Publisher ↗
RESEARCH QUESTION: What is the association between an elevated sperm DNA fragmentation index (DFI) and the risk of embryonic aneuploidy in couples undergoing assisted reproductive technology (ART) treatment? DESIGN: This...
RESEARCH QUESTION: What is the association between an elevated sperm DNA fragmentation index (DFI) and the risk of embryonic aneuploidy in couples undergoing assisted reproductive technology (ART) treatment? DESIGN: This PROSPERO-registered systematic review and meta-analysis (CRD420251067930) searched PubMed, Embase, Cochrane Library and Web of Science from inception to 10 July 2025 for observational studies. Studies were included if they reported on couples undergoing ART treatment with sperm DFI testing and preimplantation genetic testing. Heterogeneity was explored via pre-specified subgroup analyses. Robustness was evaluated through sensitivity analyses (leave-one-out method) and assessment of publication bias using funnel plots and Egger's test. RESULTS: From 601 records, 11 studies were systematically reviewed. Meta-analysis of seven studies (3563 embryos) revealed a significant, albeit modest, positive association (pooled RR = 1.16, 95% CI 1.03 to 1.31), with considerable heterogeneity (I² = 55%). The significance of this association varied across subgroups. No significant publication bias was detected, and sensitivity analyses confirmed the robustness of the primary finding. CONCLUSIONS: Current evidence, derived solely from retrospective studies, establishes a modest link but is insufficient to recommend sperm DFI testing as an independent guide for clinical decisions, highlighting the need for prospective validation.
UK Guidelines for the Medical and Laboratory Procurement and Use of Sperm, Egg and Embryo Donors (2025): Association of Reproductive and Clinical Scientists, British Fertility Society, British Association for Sexual Health and HIV, British HIV Association.
Martins da Silva S, Clarke H, Jansa Perez M … +3 more , Mackie NE, Barber TJ, Kirkman-Brown JC
Reprod Biomed Online · 2026 Jun · PMID 42069474 · Publisher ↗
These guidelines replace the previous (2019) UK guidelines for the medical and laboratory screening of sperm, egg and embryo donors and were achieved by a joint working group composed of representatives from the Associat...
These guidelines replace the previous (2019) UK guidelines for the medical and laboratory screening of sperm, egg and embryo donors and were achieved by a joint working group composed of representatives from the Association of Reproductive and Clinical Scientists (ARCS), the British Fertility Society (BFS), the British Association for Sexual Health and HIV (BASHH) and the British HIV Association (BHIVA), with review and comments from their respective memberships. It was written to guide best practice in clinics but is not intended as a tool to judge the practice of centres within the UK or beyond. Guidance on core information that should be supplied to all parties involved in donation is provided. Screening tests and standards required are summarized, as are specific considerations for known donation and embryo donation. The assessment of genetic risk and heritable disorders has been fundamentally reviewed in light of technological advances. Extended carrier screening is also discussed, although we do not suggest that this is routinely performed.
Live birth rate after ART with donor semen in single women, lesbian couples and heterosexual couples: a systematic review and meta-analysis.
Pont JC, Begon E, Bouée S … +5 more , Domin-Bernhard M, Jaffré F, Languille S, Simon V, Fréour T
Reprod Biomed Online · 2026 Feb · PMID 42068970 · Publisher ↗
This systematic review and meta-analysis compared the live birth rate (LBR) after assisted reproductive technology (ART) with donor semen among single women, lesbian couples and heterosexual couples. Searches of PubMed,...
This systematic review and meta-analysis compared the live birth rate (LBR) after assisted reproductive technology (ART) with donor semen among single women, lesbian couples and heterosexual couples. Searches of PubMed, EMBASE and the Cochrane Library up to September 2025 identified seven eligible studies including 19,457 women. Separate analyses were performed for intrauterine insemination (IUI) and IVF. For IUI, single women had a significantly lower LBR than heterosexual couples [risk ratio (RR) = 0.70, 95% CI 0.66-0.74] and lesbian couples (RR = 0.67, 95% CI 0.63-0.72), whereas no significant difference was observed between heterosexual couples and lesbian couples. The clinical pregnancy rate was lower in single women compared with lesbian couples, but the pregnancy loss rate was similar across both groups. Sensitivity analyses confirmed these findings. Importantly, meta-regressions indicated that differences in LBR were no longer significant after adjusting for female age. Results from IVF studies were consistent with those from IUI analyses. Overall, single women using donor semen for ART showed lower success rates, largely explained by older maternal age. These findings highlight the importance of age adjustment, and provide evidence-based data for counselling individuals and couples considering ART with donor semen.
Managing suspected endometrial polyps during IVF/ICSI stimulation: retrospective cohort study of fresh versus freeze-all strategies.
Schutyser V, Agius MP, Drakopoulos P … +5 more , van Landuyt L, De Vos M, Tournaye H, Blockeel C, Soares M
Reprod Biomed Online · 2025 Oct · PMID 42061057 · Publisher ↗
RESEARCH QUESTION: In patients in whom endometrial polyps are diagnosed during ovarian stimulation for IVF, are there differences in reproductive outcomes in women continuing to undergo fresh embryo transfer, and those i...
RESEARCH QUESTION: In patients in whom endometrial polyps are diagnosed during ovarian stimulation for IVF, are there differences in reproductive outcomes in women continuing to undergo fresh embryo transfer, and those in whom embryos are cryopreserved and hysteroscopic polypectomy carried out after subsequent frozen embryo transfer? DESIGN: This single centre retrospective cohort analysis in a tertiary fertility centre included patients aged between 18 and 42 years with a newly diagnosed endometrial polyp during ovarian stimulation for IVF/ICSI between May 2008 and July 2021. A total of 372 patients were divided into two groups based on strategy: fresh embryo transfer (n = 256) and cryopreservation of embryos followed by hysteroscopy and subsequent frozen embryo transfer, referred to as the 'freeze-all' group (n = 116). RESULTS: A minimal difference in polyp size (maximum diameter measured on ultrasound) was observed in the fresh embryo transfer (10.1 ± 4.3 mm) versus freeze-all group (11.2 ± 4.4 mm) (P < 0.001), with no significant difference in the various polyp locations. The freeze-all group had a higher oocyte yield (8.1 ± 5.0 versus 12.5 ± 8.3, P < 0.001) with a significantly higher proportion of blastocysts transferred in this group (35.2% versus 68.1%, P < 0.001). No significant difference was observed in clinical pregnancy (94/256 versus 47/116) or live birth rates (68/256 versus 33/116), only for early pregnancy rate (18/256 versus 16/116, P = 0.036). After adjustment for relevant confounding factors, body mass index, age, number of oocytes retrieved, day of embryo transfer and polyp size, no association was observed between the freeze-all or fresh embryo transfer strategy and live birth rate. CONCLUSION: No difference was found in reproductive outcome between a fresh embryo transfer compared with a freeze all strategy and hysteroscopy before frozen embryo transfer.
Diagnostic delay in endometriosis: is there any progress?
de Kok L, Boersen Z, Coppus S … +12 more , van Haaps A, van Hanegem N, Klinkert E, Maas J, Mijatovic V, Smeets M, Steensma A, Teklenburg G, van Vliet H, Braat D, Schers H, Nap A
Reprod Biomed Online · 2025 Nov · PMID 42054959 · Publisher ↗
RESEARCH QUESTION: What is the current time to diagnosis among patients with endometriosis in the Netherlands, and what factors influence this time? DESIGN: A retrospective questionnaire study was conducted in 11 hospita...
RESEARCH QUESTION: What is the current time to diagnosis among patients with endometriosis in the Netherlands, and what factors influence this time? DESIGN: A retrospective questionnaire study was conducted in 11 hospitals in the Netherlands between 2021 and 2023. A total of 9551 medical charts were screened, and 2289 patients with a confirmed diagnosis (ultrasound, magnetic resonance imaging or surgery) of endometriosis between 2018 and 2020 were included. Information about demographics, type of endometriosis, time to diagnosis, leading symptoms and referral was collected, and supplemented with information from the electronic health record. RESULTS: A total of 837 participants returned the questionnaire (response rate 36.6%). The total median diagnostic delay was 7 years (IQR 2-15 years). The median patient delay was 1 year (IQR 0-2 years), the median general practitioner delay was 1 year (IQR 0-9 years), and the median gynaecologist delay was <1 year (IQR 0-1 year). The longest diagnostic delays were found in patients who presented with dysmenorrhoea or bleeding problems. Diagnostic delay was significantly shorter in patients presenting with pelvic pain, infertility or an abdominal wall mass (P < 0.001). In patients with abdominal wall endometriosis, the diagnostic delay was significantly shorter compared with patients with combined peritoneal and deep endometriosis (P < 0.001). CONCLUSIONS: The total diagnostic delay from symptom onset until confirmed diagnosis of endometriosis among patients in large general and university hospitals in the Netherlands is 7 years.
Declining global fertility and our future dependence on ART.
Aitken RJ
Reprod Biomed Online · 2026 Mar · PMID 42048936 · Publisher ↗
Since the early 1960s the world has witnessed a dramatic reduction in total fertility rates. This decline in fertility has been particularly evident in socioeconomically advanced countries including Europe, North America...
Since the early 1960s the world has witnessed a dramatic reduction in total fertility rates. This decline in fertility has been particularly evident in socioeconomically advanced countries including Europe, North America and the Tiger economies of East and South-East Asia. However, even in Sub-Saharan Africa, which has some of the highest fertility rates in the world, the trend has been robustly downwards over the past 25 years. Many modern economies including the USA, the UK, the European Union and Australia have used immigration as a powerful instrument to ensure consistent population growth despite sub-replacement levels of fertility. In the geographical East, immigration has not played such a key role in the management of population dynamics, with the result that countries such as Japan, China, South Korea, and Taiwan are now exhibiting negative growth. Assisted reproduction will play an important part in managing our reproductive future, although there are risks associated with becoming too dependent on this technology. If we are to manage the population's future, rather than become its hapless victims, we must develop an acute awareness of the demographic challenges facing our species and achieve a deeper understanding of the underlying mechanisms.
The DIVINE dose-selection model in daily ART practice: effects on live birth rate and safety.
Schouten NE, van Tilborg TC, Cianci D … +3 more , Eijkemans MJC, Lambers MJ, Broekmans FJM
Reprod Biomed Online · 2026 Jun · PMID 42033979 · Publisher ↗
RESEARCH QUESTION: Does implementation of the DIVINE dose calculator in routine care reduce treatment risk due to ovarian hyperstimulation whilst maintaining treatment efficacy? DESIGN: A retrospective cohort study compa...
RESEARCH QUESTION: Does implementation of the DIVINE dose calculator in routine care reduce treatment risk due to ovarian hyperstimulation whilst maintaining treatment efficacy? DESIGN: A retrospective cohort study comparing assisted reproductive technology outcomes from women treated before and after implementation of the DIVINE dose calculator. Data were collected from two Dutch fertility centres. The dose calculator included female age, anti-Müllerian hormone concentration, and gonadotrophin-releasing hormone-(ant)agonist protocol to select the most appropriate starting dose of FSH between 100 and 225 IU. Baseline characteristics of subfertile women aged <39 years starting their first IVF/intracytoplasmic sperm injection (ICSI) treatment cycle, and fresh cycle treatment outcomes were collected. Inverse propensity weighting was applied to balance potential confounders. Weighted regression was performed using general linear models or ordered logistic regression models, according to the outcome variable. The primary outcome variables were live birth rate and safety risk. RESULTS: Data were obtained for 601 women: 472 in the pre-dose calculator group and 129 in the post-dose calculator group. There was no difference in the live birth rate per fresh cycle before and after implementation of the dose calculator: 25.8% versus 24.0% respectively (OR 0.96, 95% CI 0.62-1.51). The treatment risk due to ovarian hyperstimulation decreased after implementation of the dose calculator from 10.8% in the pre-dose calculator period to 3.1% in the post-dose calculator period (OR 0.28, 95% CI 0.10-0.78), and the incidence of ovarian hyperstimulation syndrome decreased from 6.4% to 0% after implementation of the dose calculator. CONCLUSION: Implementation of the DIVINE dose calculator significantly reduces treatment risks caused by ovarian hyperstimulation, without affecting treatment efficacy in terms of the live birth rate in first fresh IVF/ICSI cycles.
Re-evaluating endometrial injury for IVF: was a promising approach abandoned prematurely? A critical review.
Shoham Z, Broekmans FJM, Casper RF … +10 more , Dekel N, Fauser BCJM, Fischer R, García-Velasco JA, Gleicher N, Leong M, Orvieto R, Pellicer A, Weissman A, Mol BW
Reprod Biomed Online · 2026 Jun · PMID 42030757 · Publisher ↗
Since the early 2000s, endometrial injury has been proposed to enhance receptivity and improve pregnancy outcomes, particularly in individuals with recurrent implantation failure (RIF). However, randomized controlled tri...
Since the early 2000s, endometrial injury has been proposed to enhance receptivity and improve pregnancy outcomes, particularly in individuals with recurrent implantation failure (RIF). However, randomized controlled trials have yielded conflicting results, creating ongoing debate about their clinical utility. This review synthesizes over 20 years of research through to 31 January 2025, examining whether methodological variations explain conflicting outcomes and assessing the clinical significance of reported benefits. The most comprehensive individual participant data meta-analysis to date, including 4112 patients from 13 randomized controlled trials, demonstrated a modest but statistically significant improvement in live birth rate following endometrial injury (OR 1.29, 95% CI 1.02-1.64), with a number needed to treat of 26. Analysis revealed significant heterogeneity: studies using multiple biopsies, particularly in RIF patients, showed more pronounced benefits than single-biopsy protocols in unselected populations. The biological heterogeneity of implantation failure probably explains inconsistent outcomes, as different aetiologies require distinct therapeutic approaches. Current evidence suggests that endometrial injury may provide modest improvements using multiple-biopsy protocols in carefully selected patients, particularly those with RIF, while highlighting the need for appropriate counselling regarding the modest benefits. Future research should transition from empirical application to biomarker-guided patient selection to identify which molecular subtypes benefit from specific interventions.
Adenomyosis and chronic endometritis: cause, consequence or coincidence? A systematic review and meta-analysis.
Steinmann M, Kalaitzopoulos DR, Schwartz ASK … +3 more , Karrer T, von Wolff M, Vidal A
Reprod Biomed Online · 2026 Jun · PMID 42030756 · Publisher ↗
Chronic endometritis is persistent inflammation of the endometrium, often underdiagnosed due to its oligosymptomatic presentation. Both chronic endometritis and adenomyosis share inflammatory and structural alterations o...
Chronic endometritis is persistent inflammation of the endometrium, often underdiagnosed due to its oligosymptomatic presentation. Both chronic endometritis and adenomyosis share inflammatory and structural alterations of the endometrial-myometrial interface that may impair reproductive outcomes. This systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines, and registered in PROSPERO. MEDLINE, Embase, CENTRAL, Cochrane Database of Systematic Reviews, Scopus and trial registries were searched from 2000 to May 2025 to determine the prevalence of chronic endometritis in women with adenomyosis, and assess the strength of their association. Of 713 identified records, 10 studies (n = 2877 women) met the inclusion criteria. The pooled prevalence of chronic endometritis in women with adenomyosis was 32% (95% CI 16-53; I² = 94%). In subgroup analyses, prevalence varied by the diagnostic method used for adenomyosis: hysterectomy (21%), magnetic resonance imaging (64%), and hysteroscopy (8%). Meta-analysis demonstrated a significantly higher prevalence of chronic endometritis in women with adenomyosis compared with controls (OR = 3.81, 95% CI 2.23-6.50; I² = 11%). This systematic review and meta-analysis suggest that adenomyosis and chronic endometritis frequently coexist, with women with adenomyosis showing a significantly higher risk of chronic endometritis. Standardized diagnostic criteria, adenomyosis subtype classification, and high-quality randomized controlled trials are needed to clarify the underlying mechanisms, and are necessary to demonstrate an association between adenomyosis and chronic endometritis.
Pregnancy outcome in patients with idiopathic premature ovarian insufficiency: a systematic review of the literature.
Deneer JJ, Louwers YV, Lashley EE
Reprod Biomed Online · 2026 Jun · PMID 42025142 · Publisher ↗
Premature ovarian insufficiency (POI) is defined as the loss of ovarian function before the age of 40 years, characterized by elevated gonadotrophin and low oestradiol concentrations. Although the probability of pregnanc...
Premature ovarian insufficiency (POI) is defined as the loss of ovarian function before the age of 40 years, characterized by elevated gonadotrophin and low oestradiol concentrations. Although the probability of pregnancy is markedly reduced in women with POI, natural conception remains possible, with reported rates of approximately 5-10%. Premature ovarian insufficiency has been associated with increased risks of cardiovascular disease, autoimmune disorders and accumulation of unrepaired DNA damage. On the basis of these associations, a higher risk for developing early pregnancy complications, late pregnancy complications, or both, was hypothesized. Obstetric and neonatal risks in this population, however, have received limited attention to date. The aim of this systematic review was to summarize and evaluate studies primarily investigating pregnancy outcomes in women with idiopathic POI compared with women without POI, following both natural and assisted conceptions. Despite screening 3640 articles, none met predefined inclusion criteria. Nevertheless, comparison of available data on POI pregnancies with outcomes in the general population suggests an increased risk of early pregnancy loss, after (non-) donor ART. Given that POI is a complex condition with profound effects on physical and mental health, it is essential to further explore its potential effect on pregnancy. The need for well-designed future studies in this field, is therefore, emphasized.
Haematopoietic loss of the X chromosome is associated with a lower likelihood of natural conception.
Kikuchi T, Yoshida N, Yoneyama S … +9 more , Maki Y, Kitada K, Hamuro A, Misugi T, Kubo T, Nakamura Y, Haruki A, Tachibana D, Sano S
Reprod Biomed Online · 2026 Jun · PMID 42025141 · Publisher ↗
RESEARCH QUESTION: Is haematopoietic loss of the X chromosome (LOX), which increases with age in women, but whose reproductive relevance is unclear, associated with the likelihood of natural conception? DESIGN: Multicent...
RESEARCH QUESTION: Is haematopoietic loss of the X chromosome (LOX), which increases with age in women, but whose reproductive relevance is unclear, associated with the likelihood of natural conception? DESIGN: Multicentre case-control study at three hospitals in Osaka, Japan. Cases were women who did not achieve natural conception after exclusion of male-factor infertility (n = 381). Controls were women who conceived naturally (n = 123). The LOX burden in peripheral blood (%LOX) was quantified by multiplex single-cell droplet digital polymerase chain reaction. Serum anti-Müllerian hormone (AMH) was measured by standardized chemiluminescent enzyme assays. The primary outcome was the difference in %LOX between cases and controls. Secondary analyses assessed assisted reproductive technology (ART) outcomes (pregnancy within three embryo-transfer cycles) among a prospectively followed subset. Exploratory analyses examined correlations of %LOX with age and AMH. RESULTS: %LOX increased with age (P < 0.001) and was higher in cases than controls (P < 0.001). This difference remained significant after adjusting for age, body mass index (BMI) and prior pregnancy (β = 0.82, 95% CI 0.70 to 0.96, P = 0.013). Receiver operating characteristic curve analysis identified an optimal %LOX threshold of 0.87% (area under the curve 0.60, 95% CI 0.54 to 0.66). Women with %LOX 0.87% or above had over twofold higher odds of not achieving natural conception (OR 2.16, 95% CI 1.40 to 3.32, P < 0.001; age-stratified, BMI-adjusted). In contrast, %LOX was not associated with pregnancy within three ART cycles (adjusted P = 0.23) and did not correlate with AMH (ρ = ‒0.06; P = 0.25) or FSH (ρ = ‒0.01; P = 0.84) levels. CONCLUSIONS: Haematopoietic LOX was associated with a lower likelihood of natural conception, whereas no clear association was found with ART outcomes was observed.
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