Reproductive Biomedicine Online[JOURNAL]
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200 papers
Time to reconsider who the freeze-all approach benefits: a matched cohort analysis of over 9000 embryo transfers.
Garratt J, Macklon N, Ellis PJ … +6 more , Goswami M, Kovats T, Al-Hashimi B, Shah T, Linara-Demakakou E, Ahuja KK
Reprod Biomed Online · 2026 May · PMID 42400998 · Publisher ↗
RESEARCH QUESTION: Is a fresh embryo transfer superior to a frozen embryo transfer after a freeze-all approach in achieving a live birth in IVF cycles? DESIGN: A retrospective matched analysis of 9923 autologous oocyte r...
RESEARCH QUESTION: Is a fresh embryo transfer superior to a frozen embryo transfer after a freeze-all approach in achieving a live birth in IVF cycles? DESIGN: A retrospective matched analysis of 9923 autologous oocyte retrievals and 9716 embryo transfers performed between 2016 and 2023 at a single UK centre was undertaken. Patients underwent a fresh transfer or the decision was made to freeze all embryos. First embryo transfer outcomes from each cycle were assessed, and a separate analysis was undertaken to assess the hazard ratio of live birth across multiple embryo transfers arising from a single oocyte retrieval, with 1664 cumulative live births after 4202 fresh transfer cycles and 1354 cumulative live births after 2312 freeze-all embryo cycles. RESULTS: No difference in the odds of live birth was seen when stratifying by age. Among low responders (fewer than six oocytes), fresh and first frozen embryo transfers demonstrated comparable live birth rates [adjusted OR (aOR) 1, 95% CI 0.7-1.5; 26% versus 27%; P = 1]. In high responders (≥16 oocytes) and high-embryo-yield cycles (five embryos or more), higher outcomes were observed in fresh transfers, but the difference was non-significant. Low-embryo-yield cycles (fewer than three embryos) were associated with significantly improved outcomes after a freeze-all approach controlled for embryo quality (aOR 1.6, 95% CI 1.2-2.1; 38% versus 29%; P = 0.02), with potential greater benefit for patients aged ≥38 years. In transfers of suboptimal-grade embryos, the freeze-all approach was associated with a 2-fold increase in the odds of live birth in patients aged <38 years, but this lost significance after correction. Cumulatively, while a higher live birth rate was observed for fresh cycles compared with freeze-all cycles in patients aged <38 years, overall there was no significant difference in the live birth rate per cycle. CONCLUSIONS: A freeze-all approach may improve outcomes in low-embryo-yield cycles and in younger patients with suboptimal-grade embryos, but confirmatory analyses are required.
Structured counselling and its association with IVF cycle cancellations and patient adherence.
Selim S, Lawrenz B, Samir S … +4 more , Edades J, Didar H, Fatemi H, Gallego RD
Reprod Biomed Online · 2026 Jun · PMID 42400997 · Publisher ↗
RESEARCH QUESTION: Is structured pre-stimulation counselling associated with reduced cycle cancellation and improved patient adherence during ovarian stimulation and endometrial preparation for frozen embryo transfer (FE...
RESEARCH QUESTION: Is structured pre-stimulation counselling associated with reduced cycle cancellation and improved patient adherence during ovarian stimulation and endometrial preparation for frozen embryo transfer (FET)? DESIGN: This retrospective cohort study included 8084 women initiating IVF treatment at a tertiary centre in the United Arab Emirates. First ovarian stimulation cycles performed between June 2015 and August 2025 and first endometrial preparation cycles for FET between January 2017 and July 2025 were analysed. Exposure was defined as completion of a structured pre-stimulation counselling session before treatment initiation. Outcomes were compared between counselled (n = 6813) and non-counselled (n = 1271) women. Modified Poisson regression models were used to estimate adjusted relative risks (aRR). RESULTS: During ovarian stimulation, cancellation rates were lower among counselled women compared with non-counselled women (6.4% versus 23.0%), corresponding to an aRR of 0.31 (95% CI 0.27-0.36). Preventable cancellations (patient decision and medication errors) were also reduced (2.9% versus 13.3%; aRR 0.23, 95% CI 0.19-0.29). Non-adherence behaviours during ovarian stimulation were less frequent among counselled women (3.6% versus 14.8%; P = 0.001). In contrast, cancellation rates during endometrial preparation for FET did not differ between counselled and non-counselled women (27.8% versus 30.2%; aRR 0.96, 95% CI 0.79-1.16 for hormone replacement therapy cycles; 37.8% versus 43.5%; aRR 0.86, 95% CI 0.72-1.01 for natural cycles). CONCLUSIONS: Structured counselling was associated with reduced preventable cancellations and improved adherence during ovarian stimulation. However, patients who declined counselling may differ systematically from those who accepted counselling.
hsa-miR-375-3p in embryo culture medium exosomes as a preimplantation non-invasive biomarker for predicting live birth after IVF.
Zhang L, Mahemuti M, Yakupu Z … +7 more , Li C, Maimaiti Y, Pang M, Gan X, Zhao Q, Huang W, Jiapaer Z
Reprod Biomed Online · 2026 Jan · PMID 42400996 · Publisher ↗
RESEARCH QUESTION: Can non-coding RNAs in exosomes from IVF embryo culture media serve as non-invasive markers for evaluating embryo quality? DESIGN: Spent culture medium (SCM) was prospectively collected from grade 1 ei...
RESEARCH QUESTION: Can non-coding RNAs in exosomes from IVF embryo culture media serve as non-invasive markers for evaluating embryo quality? DESIGN: Spent culture medium (SCM) was prospectively collected from grade 1 eight-cell-stage embryos that resulted in pregnancy success (defined as live birth, n = 34) or failure (n = 33) among patients who underwent IVF and single embryo transfer at a single centre over 5 months. Exosomes were isolated by precipitation, followed by high-throughput small RNA sequencing to profile exosomal non-coding RNAs, including miRNAs, tRFs and piRNAs. The diagnostic potential of validated differentially expressed miRNAs was then evaluated by receiver operating characteristic (ROC) analysis. Specific inhibitors targeting differentially expressed miRNAs were designed and microinjected into mouse embryos to assess their effects on embryonic development. RESULTS: Single-particle immunofluorescence analysis confirmed the presence of exosome-specific markers (CD63, CD9 and CD81) in isolated exosomes. Small RNA sequencing of exosomes identified 51 miRNAs, 547 piRNAs, and 39 tRFs, among which five, 11 and eight were differentially expressed, respectively. Validated by qRT-PCR, expression of hsa-miR-375-3p and hsa-miR-215-5p in SCM-derived exosomes was higher in the successful pregnancy group than in the pregnancy failure group. The ROC curve analysis indicated that hsa-miR-375-3p (AUC = 0.763, sensitivity 85%, specificity 70%) is a potential marker of embryo quality, laying the foundation for a miRNA-based predictive model to improve IVF outcomes. Inhibition of miR-375-3p significantly reduced the eight-cell mouse embryo formation rate (P = 0.0358). CONCLUSIONS: hsa-miR-375-3p in exosomes from SCM of embryos is a non-invasive predictive biomarker of live birth after IVF. miR-375-3p is critical for embryonic development during the four- to eight-cell stage transition.
Promoting family-building strategies among key stakeholders: the International Federation of Fertility Societies More Joy™ campaign.
Horton M, Mocanu E, Fauser BC
Reprod Biomed Online · 2026 May · PMID 42398492 · Publisher ↗
A total fertility rate (the average number of children born per woman during their reproductive lifespan) of 2.1, termed the 'replacement level', is needed to keep a population size stable. This index is already below 2...
A total fertility rate (the average number of children born per woman during their reproductive lifespan) of 2.1, termed the 'replacement level', is needed to keep a population size stable. This index is already below 2 in the great majority of developed and middle-income countries, and current estimates show that by the year 2100, many countries will experience a population decline of more than 50%. This poses an extraordinary challenge to our societies, as a shrinking workforce will produce fewer products and services and therefore less income from taxes to sustain children and elderly individuals. Economic factors such as household income and the cost of housing and childcare have been shown to be strong drivers of the willingness to establish a family; however, current trends in attitudes to childbearing reveal a high percentage of voluntary childlessness, i.e. individuals not willing to have children. The International Federation of Fertility Societies (IFFS) MoreJoy™ campaign seeks to explore the reasons for these cultural changes, is raising awareness of the fertility decline and is committed to promoting education on fertility and infertility prevention, and access to infertility care to all, irrespective of gender or marital status.
Ovarian reserve markers in World Health Organization type 1 anovulatory disorders: a systematic review and meta-analysis.
de Jong SMH, de Kat AC, Schoonmade LJ … +3 more , Hillebrand JJ, van Wely M, van Loendersloot LL
Reprod Biomed Online · 2026 May · PMID 42378732 · Publisher ↗
Ovarian reserve markers such as anti-Müllerian hormone (AMH) and antral follicle count (AFC) are widely used in fertility assessment. However, to the authors' knowledge, no systematic reviews to date have evaluated these...
Ovarian reserve markers such as anti-Müllerian hormone (AMH) and antral follicle count (AFC) are widely used in fertility assessment. However, to the authors' knowledge, no systematic reviews to date have evaluated these markers specifically for World Health Organization (WHO) type 1 (hypogonadotropic hypogonadism) anovulation. This review examines the relationship between ovarian reserve markers and WHO type 1 anovulation. A systematic search was conducted in PubMed, Embase, Web of Science, Scopus and the Cochrane Library up to 9 July 2025 using the term 'anti-Müllerian hormone' combined with synonyms of 'hypothalamic amenorrhoea'. Out of 769 identified studies, 29 met the inclusion criteria, and 14 (n = 920 participants) were included in the meta-analysis. Risk of bias was assessed using Joanna Briggs Institute critical appraisal checklists. The remaining 15 studies were synthesized narratively and presented in a summary table. AMH concentration and AFC varied widely in women with WHO type 1 anovulation compared with normo-ovulatory controls. The pooled standardized mean difference for AMH was 0.23 (95% CI -0.06 to 0.51). Notably, ovarian reserve markers tended to decrease with longer anovulatory periods. In this population, low AMH concentration and/or AFC may not provide an accurate reflection of true ovarian reserve. Prolonged hypothalamic suppression likely contributes to underestimation of these markers, emphasizing the need for cautious clinical interpretation.
Effect of embryo culture medium pH on live birth rate after IVF/ICSI: a double-blind, multicentre, randomized trial.
Gatimel N, Chansel-Debordeaux L, Zokpe J … +11 more , Bettiol C, Bacus J, Chauvel J, Besnier P, Cens S, Huet S, Bouko-Levy E, Depuydt C, Lepage B, Moreau J, Léandri R
Reprod Biomed Online · 2026 May · PMID 42365831 · Publisher ↗
RESEARCH QUESTION: Does live birth rate differ according to the pH of the embryo culture medium after IVF with intracytoplasmic sperm injection (ICSI)? DESIGN: Multicentre, randomized, controlled, double-blind trial cond...
RESEARCH QUESTION: Does live birth rate differ according to the pH of the embryo culture medium after IVF with intracytoplasmic sperm injection (ICSI)? DESIGN: Multicentre, randomized, controlled, double-blind trial conducted in three IVF centres. From ICSI to fresh day-3 embryo transfer, embryos were cultured at a target medium pH either 7.22 ± 0.02 or 7.38 ± 0.02. Overall, 424 women aged 40 years or younger undergoing a first or second fresh ICSI cycle with autologous oocytes were included between October 2020 and November 2023. Recruitment stopped before the planned sample size was reached because of feasibility constraints. Randomization (1:1) occurred on the day of oocyte retrieval. The pH was measured daily using a validated method under routine IVF culture conditions. The primary outcome was live birth rate per oocyte retrieval. RESULTS: Embryos from 211 couples were cultured at pH 7.22 ± 0.02 and from 212 couples at pH 7.38 ± 0.02. Baseline characteristics, stimulation parameters and sperm characteristics were comparable between groups. Live birth rate per oocyte retrieval did not differ significantly between culture conditions (29.3% versus 27.0%, OR 1.13, 95% CI 0.72 to 1.75, P = 0.60). No significant differences were observed in fertilization rate, implantation rate, ongoing clinical pregnancy rate, miscarriage rate or embryo morphology. CONCLUSIONS: Maintaining a strict pH of 7.22 ± 0.02 from day 0 to day 3 after ICSI does not significantly affect live birth rate compared with a pH of 7.38 ± 0.02. Early human embryos effectively adapt to pH variations within this range without affecting live birth rate.
Response to: Clarifying Molecular Specificity and Outcome Definitions in Progestogen Route Meta-Analysis.
Griesinger G, Wang Q, Labarta E … +4 more , Li R, Manipalviratn S, Murdia K, Pabuccu E
Reprod Biomed Online · 2026 Jun · PMID 42364289 · Publisher ↗
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Polyendocrine metabolic ovarian syndrome and cardiometabolic profile in offspring: a propensity score matched cohort study.
Tang M, Deng X, Liu S … +4 more , Wang H, Yang Y, Xing L, Zhu Y
Reprod Biomed Online · 2026 May · PMID 42364288 · Publisher ↗
RESEARCH QUESTION: Do the offspring of women with polyendocrine metabolic ovarian syndrome (PMOS) exhibit altered cardiometabolic profiles in early childhood? DESIGN: Of 2688 singletons born to women with or without PMOS...
RESEARCH QUESTION: Do the offspring of women with polyendocrine metabolic ovarian syndrome (PMOS) exhibit altered cardiometabolic profiles in early childhood? DESIGN: Of 2688 singletons born to women with or without PMOS who were conceived through assisted reproductive technology (ART), 2549 were eligible for study analysis. Propensity score matching was employed to mitigate confounding variables. Cardiometabolic profiles at 3-6 years of age were assessed. RESULTS: Compared with control participants, the offspring of PMOS mothers showed marginally higher total cholesterol concentrations (4.40 versus 4.23 mmol/l, P = 0.013, Q = 0.046), and a lower proportion had total cholesterol concentrations in the ideal range (49.3%, 107/217 versus 59.6%, 469/787; P = 0.007, Q = 0.046). Although these differences survived Benjamini-Hochberg FDR correction, they were small and the central tendency of all lipid measures remained within the normal paediatric range. In sex-stratified analyses, small but significant differences in lipids (PMOS versus controls: total cholesterol, 4.45 versus 4.27 mmol/l, P = 0.024, Q = 0.042; LDL-C, 2.53 versus 2.36 mmol/l, P = 0.007, Q = 0.042) were observed exclusively in female offspring. CONCLUSION: Although total cholesterol was higher in ART-conceived PMOS offspring during early childhood, the minimal lipid differences were within normal paediatric ranges. Longitudinal follow-up is warranted to determine whether these subtle deviations have long-term clinical significance.
Antinuclear antibodies in women with recurrent early pregnancy loss: prevalence and impact on subsequent pregnancy outcome.
Uvin V, Lerner L, Melsens K … +7 more , Demeester S, Buyl R, Evers-Lebrun C, De Brucker M, Tournaye H, Unuane D, Mackens S
Reprod Biomed Online · 2025 Nov · PMID 42364287 · Publisher ↗
RESEARCH QUESTION: What is the prevalence of antinuclear antibodies (ANA) in women with recurrent early pregnancy loss (REPL), and do they affect subsequent pregnancy outcome? DESIGN: This single-centre, retrospective co...
RESEARCH QUESTION: What is the prevalence of antinuclear antibodies (ANA) in women with recurrent early pregnancy loss (REPL), and do they affect subsequent pregnancy outcome? DESIGN: This single-centre, retrospective cohort study included 960 women consulting for REPL between January 2014 and December 2019. REPL was defined as ≥2 pregnancy losses before 10 weeks' gestation, including natural and autologous IVF/intracytoplasmic sperm injection pregnancies. ANA testing via indirect immunofluorescence on HEp-20-10 cells was part of routine evaluation. Confirmed systemic autoimmune diseases, uterine anomalies, parental chromosomal abnormalities, uncontrolled endocrine disorders and age ≥40 years were exclusion criteria. ANA prevalence and its association with subsequent pregnancy outcomes were assessed. The primary outcome was early pregnancy loss (EPL); secondary outcomes were biochemical pregnancy loss, clinical miscarriage and live birth rates. RESULTS: ANA screening of ≥1:80 was observed in 125/960 women (13.0%), comparable to the general population. No significant differences were seen in maternal age, body mass index, ethnicity or conception method between ANA-positive and ANA-negative women. The mean number of prior EPL was similar (2.7 versus 2.8, P = 0.06), but the percentage of women with thyroid antibodies was higher among ANA-positive women (21.6% versus 10.2%, P < 0.001). The subsequent EPL rate was similar (34.9% versus 40.5%, P = 0.33). Logistic regression showed no independent effect of ANA positivity for additional EPL (odds ratio 0.73, 95% CI 0.45-1.20, P = 0.22). Live birth rates were also similar (P = 0.50). CONCLUSIONS: ANA prevalence in women experiencing REPL was 13.0%, comparable to general population rates. ANA positivity did not negatively impact subsequent pregnancy outcomes. These findings do not support routine ANA testing in REPL or use of immunological add-ons based solely on ANA positivity.
Effect of adenomyosis on the cumulative live birth rate in oocyte donation cycles: a retrospective analysis.
Cozzolino M, Exacoustos C, Cosentino M … +4 more , Pellegrini L, Seltingia A, Galliano D, Pellicer A
Reprod Biomed Online · 2026 Jan · PMID 42364276 · Publisher ↗
RESEARCH QUESTION: What is the effect of adenomyosis on cumulative live birth rate (CLBR) in women undergoing single embryo transfer in donor-oocyte cycles, with specific attention to type, location and severity of disea...
RESEARCH QUESTION: What is the effect of adenomyosis on cumulative live birth rate (CLBR) in women undergoing single embryo transfer in donor-oocyte cycles, with specific attention to type, location and severity of disease. DESIGN: Retrospective observational study of 228 infertile women treated at IVI Roma between 2019 and 2024. Adenomyosis was diagnosed via ultrasound using the MUSA criteria and classified by type, location and severity. Endometrial preparation involved hormone replacement therapy or modified natural cycles. Primary outcome was CLBR per woman; secondary outcome was serum progesterone concentrations on embryo transfer day in the adenomyosis and control groups. RESULTS: The CLBR did not differ significantly between the adenomyosis group and controls (both 74.29%, P = 0.81). Women with adenomyosis in the outer myometrium and junctional zone had a lower CLBR (62.5%) compared with those with adenomyosis limited to the junctional zone (83.33%) or outer myometrium (78.57%). The estimated number of transfers for 50% CLBR was also higher in the outer myometrium and junctional zone group (median 3) versus junctional zone or outer myometrium alone (median 2) (P = 0.04). Multivariate analysis confirmed outer myometrium and junctional zone adenomyosis as a negative predictor of live birth (hazard ratio 0.44, P = 0.03). No significant differences were found in CLBR by type or severity of adenomyosis or in serum progesterone concentrations. CONCLUSIONS: Ultrasound mapping to identify adenomyosis location is crucial in fertility counselling. Adenomyosis involving outer myometrium and junctional zone presented a lower CLBR. No differences were found in serum progesterone concentrations.
Intermediate FMR1 cytosine‒guanine‒guanine repeats do not impair assisted reproductive technology outcomes in a large real-world cohort.
Dayan-Schwartz A, Sela ND, Izhaki I … +3 more , Khayat M, Baram S, Beck-Fruchter R
Reprod Biomed Online · 2026 May · PMID 42330760 · Publisher ↗
RESEARCH QUESTION: Does the presence of moderately elevated FMR1 cytosine‒guanine‒guanine (CGG) repeat numbers (40-70 repeats), identified through routine pre-pregnancy screening, adversely affect assisted reproductive t...
RESEARCH QUESTION: Does the presence of moderately elevated FMR1 cytosine‒guanine‒guanine (CGG) repeat numbers (40-70 repeats), identified through routine pre-pregnancy screening, adversely affect assisted reproductive technology (ART) outcomes in a real-world population? DESIGN: Retrospective cohort study including 760 first ART cycles conducted between 2010 and 2021 at a university-affiliated centre. FMR1 CGG repeat testing was conducted independently of infertility evaluation. Patients were categorized by repeat status in both alleles using two thresholds: 40 or more repeats (primary analysis) and 34 or more repeats (secondary analysis). Ovarian reserve markers, stimulation characteristics, oocyte yield, embryologic outcomes, positive beta-HCG and live birth rates were compared across groups. RESULTS: Among 760 patients, 669 (88%) had no allele of 40 or more repeats, 85 (11%) had one allele of 40 or more repeats and six (0.8%) had two alleles of 40 or more repats. The maximum observed repeat length was 71. Baseline demographics and ovarian reserve markers were similar between groups. No differences were observed in ovarian response, oocyte yield, fertilization or embryo development by FMR1 repeat category. Pregnancy and live birth rates were comparable between controls and patients with one expanded allele. Although elevated pregnancy and live birth rates were observed in patients with two expanded alleles, this subgroup was small, limiting interpretation. Analyses using the 34 or more repeat threshold yielded similar findings. CONCLUSIONS: Moderately elevated FMR1 CGG repeat numbers are not associated with impaired ART outcomes. Standard ART protocols remain appropriate, and FMR1 repeat length alone should not guide treatment modification in the absence of clinical ovarian insufficiency.
Integrating PGT-A into PGT-M protocols in young ART-naïve patients undergoing single embryo transfer.
Vanden Meerschaut F, Deweirdt E, Kint M … +8 more , Baetens M, Symoens S, Tilleman K, Menten B, De Croo I, Dhaenens L, Janssens S, Stoop D
Reprod Biomed Online · 2026 May · PMID 42330759 · Publisher ↗
RESEARCH QUESTION: What are the effects of integrating preimplantation genetic testing for aneuploidy into preimplantation genetic testing for monogenic/single gene disorders (PGT-M), termed 'comprehensive PGT' (coPGT-M)...
RESEARCH QUESTION: What are the effects of integrating preimplantation genetic testing for aneuploidy into preimplantation genetic testing for monogenic/single gene disorders (PGT-M), termed 'comprehensive PGT' (coPGT-M)? DESIGN: A retrospective cohort of frozen embryo transfer cycles, derived from intracytoplasmic sperm injection, with single embryo transfers (SET) performed between 2019 and 2022 in patients undergoing their first round of assisted reproductive technology. CoPGT-M was implemented from July 2021. Only cycles with at least one biopsied blastocyst were included. Outcomes were compared between 701 embryos from 126 PGT-M cycles and 801 embryos from 131 coPGT-M cycles. RESULTS: The median female age at oocyte retrieval was similar between the PGT-M and coPGT-M cohorts [29.5 (IQR 27.0-33.0) versus 29.5 (IQR 28.0-33.0) years], as were male age, body mass index, and anti-Müllerian hormone concentration. The PGT-M cohort had a significantly lower median number of cumulus-oocyte complexes [15.0 (IQR 10.0-20.0) versus 15.5 (IQR 11.0-26.0); P = 0.039], while the number of zygotes, blastocysts biopsied, and blastocysts eligible for transfer after genetic analysis were comparable. The percentage of cycles resulting in at least one live birth (PGT-M 42.1% versus coPGT-M 51.9%) and the median number of embryo transfers required to reach the first live birth among patients who achieved a live birth [PGT-M 1 (IQR 1-2) versus coPGT-M 1 (1-2)] were comparable. Generalized estimating equation analysis, adjusted for embryo quality, showed higher odds of live birth per SET [adjusted OR (aOR) 1.86, 95% CI 1.21-2.87; P = 0.005] and lower odds of pregnancy loss (aOR 0.50, 95% CI 0.27-0.93; P = 0.028) in the coPGT-M cohort. CONCLUSIONS: While cumulative outcomes per cycle were similar, coPGT-M was associated with significantly higher odds of live birth per embryo transfer and lower risk of pregnancy loss, indicating clinical benefit, even in younger patients.
Evolutionary and epigenetic drivers of the global trajectory of sperm count decline: an integrative framework for male reproductive health.
Dirican EK
Reprod Biomed Online · 2026 May · PMID 42330758 · Publisher ↗
Global meta-analyses have documented a decline in sperm concentration of approximately 50% since the 1970s, with rates accelerating from 1.16% to 2.64% annually. A parallel decline in serum testosterone (approximately 1....
Global meta-analyses have documented a decline in sperm concentration of approximately 50% since the 1970s, with rates accelerating from 1.16% to 2.64% annually. A parallel decline in serum testosterone (approximately 1.2%/year) has been documented. Integrating evolutionary, epigenetic and epidemiological perspectives may clarify the vulnerability of human spermatogenesis to contemporary environmental conditions. This narrative review synthesizes epidemiological evidence with evolutionary biology (sperm competition, life-history trade-offs) and molecular epigenetics (DNA methylation, histone-protamine remodelling, sperm-borne small RNA), and trajectory modelling employed four-parameter logistic decline models. The evolutionary history of humans - moderate sperm competition and relaxed modern selection - creates baseline fertility vulnerability. Extensive epigenetic reprogramming during spermatogenesis opens pathways for environmental exposures to impair sperm production. Trajectory modelling suggests that, under baseline assumptions, the mean sperm concentration could approach the World Health Organization's reference limit within the coming decades, and testosterone may reach the hypogonadism-relevant threshold earlier, although projections carry substantial uncertainty and are conditional on continued current trends. Evolutionary vulnerability and epigenetic susceptibility may contribute to the decline in male reproductive health. Priorities include coordinated semen surveillance, preconception risk reduction, strengthened chemical regulation, and longitudinal exposure-outcome studies.
Effect of a pro-fertility diet combined with omega-3 supplementation on embryo quality in infertile women undergoing IVF: a randomized controlled trial.
Ghadimi Yari M, Ghasemi-Tehrani H, Feizi A … +3 more , Ziaei R, Derakhshan M, Rouhani MH
Reprod Biomed Online · 2026 Feb · PMID 42330757 · Publisher ↗
RESEARCH QUESTION: Does adherence to a pro-fertility diet (PFD) combined with omega-3 supplementation improve the fertilization rate and embryo quality in infertile women undergoing IVF? DESIGN: A randomized, single-blin...
RESEARCH QUESTION: Does adherence to a pro-fertility diet (PFD) combined with omega-3 supplementation improve the fertilization rate and embryo quality in infertile women undergoing IVF? DESIGN: A randomized, single-blind, parallel clinical trial was conducted from June 2024 to June 2025 among 180 infertile women aged 18-42 years undergoing IVF at Hazrat Maryam Fertility Center, Isfahan, Iran. Participants were randomized (1:1) to receive either a structured PFD with daily omega-3 (1000 mg), vitamin D (1000 IU), folate (1 mg) and vitamin B12 (500 µg) supplementation for 60 days, or general dietary advice based on the Healthy Eating Plate model plus 500 µg/day folic acid. Fertilization rate, embryo formation rate and embryo quality (grades A-D) were evaluated. RESULTS: Compared with controls, the intervention group had significantly higher fertilization rates (0.81 ± 0.16 versus 0.66 ± 0.24; P < 0.001) and embryo formation rates (0.79 ± 0.26 versus 0.62 ± 0.30; P < 0.001), and an increased number of embryos formed (3.78 ± 2.34 versus 2.22 ± 1.46; P < 0.001). Additionally, the proportion of grade A embryos was markedly higher in the intervention group (45.2% versus 21.7%; P = 0.003). CONCLUSION: Adherence to a PFD combined with omega-3 supplementation significantly improved the fertilization rate and embryo quality in women undergoing IVF. This combined nutritional intervention represents a safe, feasible and cost-effective adjunctive approach to optimize embryological outcomes in assisted reproductive technology.
Advancing maternal age worsens pregnancy outcomes following single frozen embryo transfer with preimplantation genetic testing.
Luo C, Zhang X, Li J … +5 more , Du YB, Lv H, Li X, Zhao RS, Yan L
Reprod Biomed Online · 2026 May · PMID 42330756 · Publisher ↗
RESEARCH QUESTION: What is the critical age for the onset of deterioration in pregnancy outcomes associated with advancing maternal age in frozen embryo transfer (FET) cycles following preimplantation genetic testing (PG...
RESEARCH QUESTION: What is the critical age for the onset of deterioration in pregnancy outcomes associated with advancing maternal age in frozen embryo transfer (FET) cycles following preimplantation genetic testing (PGT)? DESIGN: This retrospective analysis included 6354 women (aged 20-45 years) who underwent PGT with single blastocyst transfer within 1 year of oocyte retrieval at a single centre, utilizing data collected from February 2017 to December 2024. Only the first FET cycle after oocyte retrieval was included, and fertilization was performed via intracytoplasmic sperm injection. Maternal characteristics were examined by transfer age; outcomes included clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate, implantation failure rate (IFR) and abortion rate. Locally estimated scatterplot smoothing (LOESS) curves were used to visualize continuous trends. Restricted cubic spline (RCS) curves were used to assess age-related associations and non-linear effects. Threshold effect analysis identified the pivotal age at which endometrial aging has an adverse effect on outcomes. RESULTS: Advancing maternal age at embryo transfer was associated with declining CPR and LBR, and increasing IFR and abortion rate. Non-linear associations between maternal age at embryo transfer and clinical pregnancy (P non-linear = 0.009), live birth (P non-linear = 0.026), and implantation failure (P non-linear=0.009) were identified based on RCS analysis. Each year beyond 33 years of age was associated with a relative 5.8% decrease in the likelihood of clinical pregnancy [adjusted hazard ratio (aHR) = 0.942, 95% CI 0.908-0.977; P = 0.001], a relative 7.2% decrease in the probability of live birth (aHR = 0.928, 95% CI 0.895-0.963; P = 0.006), and a relative 6.1% increase in the risk of implantation failure (aHR = 1.061, 95% CI 1.023-1.101; P = 0.001). CONCLUSIONS: Endometrial aging may be associated with significantly worsened pregnancy outcomes in women aged >33 years.
Endometrial metabolomic profiling reveals disruption of fatty-acid metabolism in unexplained recurrent pregnancy loss.
Boguenet M, Michel M, Bocca C … +4 more , Chao de la Barca JM, Reynier P, May-Panloup P, Bouet PE
Reprod Biomed Online · 2026 May · PMID 42330755 · Publisher ↗
RESEARCH QUESTION: Are specific plasma or endometrial metabolomic profiles associated with recurrent implantation failure (RIF), unexplained recurrent pregnancy loss (U-RPL), or both? DESIGN: Prospective observational st...
RESEARCH QUESTION: Are specific plasma or endometrial metabolomic profiles associated with recurrent implantation failure (RIF), unexplained recurrent pregnancy loss (U-RPL), or both? DESIGN: Prospective observational study of the plasma and endometrium from 80 women undergoing assisted reproductive technology. The women were classified into three groups: U-RPL (n = 19), RIF (n = 41) and controls (fertile women with male factor infertility, n = 20). A blood sample and an endometrial biopsy were collected during the window of implantation, 5-9 days after ovulation. Targeted and quantitative metabolomics analyses were conducted using high-performance liquid chromatography coupled with tandem mass spectrometry, using the Biocrates® MxP Quant 500 kit. A total of 630 metabolites were assessed using machine learning (ML) to identify specific metabolic profiles, and multivariate and univariate statistical approaches applied. RESULTS: Of the 630 metabolites analysed, 494 were accurately quantified in plasma and 228 in endometrial samples. A distinct metabolomic signature was identified in the endometrium of patients who had experienced U-RPL, characterized by 16 highly relevant metabolites. This signature includes an overall decrease in medium chain acylcarnitines, along with a significant increase in diglycerides and triglycerides, as well as in certain phospholipids (glycerophosphates) and several ceramides. CONCLUSION: A disruption of fatty acid metabolism was observed in the endometrium during the implantation window in U-RPL, paving the way for the identification of novel biomarkers of endometrial receptivity.
Helping patients achieve their expected live birth rate: an ART paradigm shift.
Gianaroli L, Mocanu E, Fatemi H … +3 more , Sgargi S, Ata B, Fauser BC
Reprod Biomed Online · 2026 May · PMID 42320429 · Publisher ↗
Since its early days, assisted reproductive technology (ART) has undergone tremendous developments and is now largely used to treat a wide range of causes of infertility and to prevent the transmission of genetic disorde...
Since its early days, assisted reproductive technology (ART) has undergone tremendous developments and is now largely used to treat a wide range of causes of infertility and to prevent the transmission of genetic disorders. Nevertheless, success rates per cycle remain relatively low (especially in poor-prognosis patients), while the high costs associated with treatment frequently limit the completion of an adequate number of cycles, thus increasing drop-out rates. In this context, the availability of reliable data and provision of comprehensive information by reproductive medicine specialists are essential. However, current metrics and indicators are not up to date with recent innovations in clinical and laboratory practice. This paper supports an approach based on identifying, before starting a treatment, the realistic number of embryo transfers required by a specific couple to achieve the expected chance of a live birth, defined as expected live birth rate, based on a thorough diagnostic assessment. Furthermore, once a treatment strategy is agreed upon by clinicians and patients, postponing embryo transfer until the necessary number of embryos has been cryopreserved may reduce the risk of treatment discontinuation before all the embryos are used. This approach may also improve clinical outcomes and enhance the cost-effectiveness of ART treatments.
Pregnancy outcomes after warm, biopsy and refreeze cycles of previously untested vitrified blastocysts.
Chen V, Lee SW, Walker DL … +4 more , Zhao Y, Babayev SN, Shenoy CC, Neblett MF
Reprod Biomed Online · 2026 Apr · PMID 42320066 · Publisher ↗
RESEARCH QUESTION: Do pregnancy outcomes differ between euploid embryos after warm, biopsy and refreeze (WBR) of previously vitrified blastocysts and euploid blastocysts biopsied before initial vitrification? DESIGN: All...
RESEARCH QUESTION: Do pregnancy outcomes differ between euploid embryos after warm, biopsy and refreeze (WBR) of previously vitrified blastocysts and euploid blastocysts biopsied before initial vitrification? DESIGN: All WBR cycles and euploid frozen blastocyst transfers carried out at a single academic institution between 1 January 2014 and 31 December 2021 were included. Pregnancy outcomes were restricted to each patient's first planned euploid frozen embryo transfer (FET). Blastocyst survival was calculated for warming cycles. Pregnancy outcomes were compared between euploid embryos undergoing WBR before transfer and traditional single-warmed euploid embryos. RESULTS: In total, 295 blastocysts from 50 patients underwent WBR with planned FET. In the control group, 1348 blastocysts from 221 patients underwent trophectoderm biopsy before vitrification. Mean patient age was higher in the controls compared with the WBR group (35.9 versus 32.2 years, P < 0.001). Cumulative blastocyst survival after WBR was 92.5%, reflecting survival across two warming events, compared with 97.4% in the control group, which underwent a single warming before transfer. The odds of biochemical pregnancy (OR 0.85, 95% CI 0.43 to 1.65), clinical pregnancy (OR 1.04, 95% CI 0.54 to 2.00) and live birth (OR 0.86, 95% CI 0.44 to 1.65) did not significantly differ between the groups after adjustment for BMI and endometrial stripe thickness at transfer and age at egg retrieval. Implantation rates per embryo transferred were similar between the WBR and control groups (50.9% versus 48.2%). CONCLUSIONS: Frozen euploid transfers after WBR of previously vitrified blastocysts were not associated with differences in pregnancy outcomes compared with traditional single-warmed euploid transfers. Findings, however, are limited by sample size, retrospective design, potential selection bias in the decision to pursue WBR and lack of long-term obstetric outcomes.
A plan for universal access to fertility care.
Sable D
Reprod Biomed Online · 2026 May · PMID 42314454 · Publisher ↗
In the 66 years since the introduction of clomiphene citrate, the 64 years since the first pregnancy using menotrophin stimulation and the 48 years since the birth of the first baby conceived through IVF, the procedures...
In the 66 years since the introduction of clomiphene citrate, the 64 years since the first pregnancy using menotrophin stimulation and the 48 years since the birth of the first baby conceived through IVF, the procedures that have been developed to help millions of families to overcome infertility have become increasingly safe and effective. Our ability to provide access to the much larger population of underserved and unserved has, however, lagged far behind. As declining fertility rates bring renewed attention to access to fertility care, the challenge for reproductive medicine is to leverage the progress made in developing safe and effective treatment and make it universally available to those patients in need. This requires a strategy to address both cost of care and treatment capacity constraints, challenges made less daunting due to recent innovation and technology.
Incidence of abnormal cleavage patterns in conventional IVF versus ICSI: a retrospective analysis of 125,570 normally fertilised embryos.
Liu W, Shuai J, Guo X … +3 more , Zhang Q, Han W, Huang G
Reprod Biomed Online · 2026 May · PMID 42308646 · Publisher ↗
RESEARCH QUESTION: Do the different fertilisation methods of conventional in vitro fertilisation (cIVF) or intracytoplasmic sperm injection (ICSI) affect abnormal cleavage (ABNCL) of early embryos? DESIGN: A retrospectiv...
RESEARCH QUESTION: Do the different fertilisation methods of conventional in vitro fertilisation (cIVF) or intracytoplasmic sperm injection (ICSI) affect abnormal cleavage (ABNCL) of early embryos? DESIGN: A retrospective cohort study on 125,570 normally fertilised embryos from a large reproductive medicine centre. Normal cleavage (NC) and ABNCL embryos in the entire cohort were identified. Multivariable logistic regression with generalised estimating equations (GEE), stratified analysis and inverse probability weighting (IPW) were used to assess the incidence of ABNCL events in cIVF- and ICSI-derived embryos. RESULTS: GEE analysis adjusted for multiple variables showed that the incidence of ABNCL was significantly higher in ICSI than cIVF (52.14 % vs 40.82 %, adjusted odds ratio [aOR] = 1.674, 95% confidence interval [CI]: 1.590-1.762, P < 0.001). Among the different female ages and ovarian stimulation regimens, higher incidences of ABNCL embryos were observed in ICSI compared with cIVF, and stratified analysis of sperm parameters showed that the incidence of ABNCL was significantly higher in ICSI than cIVF for the normozoospermia, mildly abnormal semen, and multiple abnormal semen groups (all P < 0.05). CONCLUSIONS: Embryos derived from ICSI were more prone to ABNCL than those derived from cIVF, and this association persists across female ages, different stimulation regimens and sperm parameter subgroups. Although semen parameters may modulate this risk, the consistent trend suggests that the ICSI procedure may be associated with an increased incidence of ABNCL.
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