- FSP1+ stromal cell-associated macrophage efferocytosis contributes to impaired decidualization in adenomyosis. [Journal Article]Hum Reprod. 2026 Oct 10. [Online ahead of print]HR
- CONCLUSIONS: Expanded Fibroblast-Specific Protein 1 (FSP1)+ stromal cell populations in adenomyosis may promote GAS6-associated macrophage efferocytosis, which correlates with increased macrophage TNF-α secretion and senescence of adjacent stromal cells.The integration of in-house samples with public data and the relatively small discovery cohort may have introduced bias. The control samples in GSE183837 were obtained from women undergoing IVF for male-factor infertility and may not fully represent unassisted physiological mid-secretory endometrium. Tamnorzatinib is a dual AXL/MERTK inhibitor, so the efferocytosis effects cannot be attributed solely to MERTK signaling. Further studies in larger clinical cohorts, knockout mouse models, and human endometrial assembloids are needed to substantiate the proposed mechanism.FSP1+ stromal cells play a crucial role in macrophage efferocytosis and decidualization defects. Targeting the GAS6-MERTK-TNF-α pathway may provide a potential therapeutic strategy for treating decidualization impairment in adenomyosis.
- Publisher Full Text (DOI)
- Conception methods and perinatal outcomes among women with kidney disorders: an Australian population-based cohort study. [Journal Article]Hum Reprod. 2026 Oct 10. [Online ahead of print]HR
- CONCLUSIONS: In this cohort, 3.3% of births among women with kidney disorders were conceived using ART, 1.9% were conceived following IUI and ovulation induction (OI), and 94.8% were conceived spontaneously; however, women with kidney disorders consistently experienced higher risks of adverse pregnancy outcomes than those without, regardless of conception method.As our study included only women who achieved a birth, it did not include those who underwent MAR but did not conceive or those who experienced miscarriage; therefore, MAR success rates could not be assessed. The association between kidney disorders and adverse pregnancy outcomes should not be interpreted as causal.Although most births among women with kidney disorders were spontaneously conceived, MAR was utilized by a substantial proportion of women with and without kidney disorders, particularly among older women. Women with kidney disorders experienced higher risks of adverse pregnancy outcomes regardless of conception method, emphasizing the importance of early identification and specialized multidisciplinary care throughout the reproductive journey.
- Publisher Full Text (DOI)
- Ovarian reserve after chemotherapy in premenopausal women with breast cancer undergoing fertility preservation counselling with and without unilateral ovarian tissue cryopreservation. [Journal Article]Hum Reprod. 2026 Oct 09. [Online ahead of print]HR
- CONCLUSIONS: Chemotherapy reduces ovarian reserve in women with breast cancer, with the greatest reductions observed among women who underwent ovarian tissue cryopreservation (OTC) and those of advanced reproductive age (≥35 years).Not all women completed assessments at all three follow-up visits, likely reflecting emotional exhaustion, hospital fatigue, reluctance to attend additional appointments, or changes in reproductive intentions. Furthermore, the observed reduction in ovarian reserve may, to some extent, also reflect the natural age-related decline in ovarian reserve.These findings may support counselling women with breast cancer about chemotherapy-related ovarian damage and thus the need for FP.
- Publisher Full Text (DOI)
- Planned egg freezing over 15 years: return to treatment and success rates in Australia and New Zealand. [Journal Article]Hum Reprod. 2026 Oct 06. [Online ahead of print]HR
- CONCLUSIONS: There has been an average year-on-year increase in the uptake of PEF of 35%, with most women undergoing a single PEF procedure in their mid-thirties and given 10 years follow-up, a little over one in four women return to thaw their eggs, with nearly half of those using donor sperm and one-third achieving a live birth.In the timeframe 2009-2019, we did not have information on whether egg freezing occurred because of a cancer diagnosis, a cohort we wished to exclude from the study. As a result, for this timeframe, we weighted observations by the probability that egg freezing occurred due to cancer, with the prediction model developed on the years 2020-2023. Changes in laboratory and clinical practice over time, along with shifting indications for PEF may limit the generalizability of the study egg thaw outcomes, which are biased towards 'early adopters' of PEF.This study provides recent and comprehensive data on PEF to guide prospective patients and clinicians and inform policy. The exponential growth in PEF in Australia and New Zealand mirrors trends in other high-income countries, suggesting a doubling time of 2-3 years. Study findings highlight the need for setting realistic expectations about the likelihood of returning to use frozen eggs and live birth rates.
- Publisher Full Text (DOI)
- Advanced paternal age affects miscarriages and live birth outcomes in oocyte donation cycles. [Journal Article]Hum Reprod. 2026 Oct 06. [Online ahead of print]HR
- CONCLUSIONS: Paternal age has a gradual but cumulative effect that becomes apparent above 45 years of age, where it evidently increases miscarriage rates and decreases live birth rates following the first transfer in oocyte donation cycles.This study is limited by its retrospective nature. No data on the chromosomal status of the blastocysts transferred was available. Caution is warranted when generalizing results to different embryo transfer strategies or other patient populations.Our results indicate that paternal age can affect clinical outcomes in oocyte donation cycles. If confirmed in a larger cohort of patients, these results would suggest considering patient counseling in relation to advanced paternal age when delaying childbearing.
- Publisher Full Text (DOI)
- Publisher's Note: Addendum to Volume 41, Supplement 1, July 2026, Abstracts 42nd Annual Meeting of the European Society of Human Reproduction and Embryology Conference. [Journal Article]Hum Reprod. 2026 Oct 06. [Online ahead of print]HR
- Publisher Full Text (DOI)
- Infertility and inequality: a plea for action. [Journal Article]Hum Reprod. 2026 Oct 06. [Online ahead of print]HR
- The recent global guidelines from the World Health Organization on diagnosis, prevention, and treatment of infertility invites us to consider infertility beyond the traditional framing as a clinical condition, recognizing it as a profound issue of equity. The guideline explicitly states that fertility care should be founded on equity, evidence-based information, and respect for human rights while…
- Publisher Full Text (DOI)
- Granular assessment of paediatric and adolescent ovaries following low levels of alkylating treatment reveals significant morphologic differences in early stage follicles. [Journal Article]Hum Reprod. 2026 Sep 30. [Online ahead of print]HR
- CONCLUSIONS: Low-dose alkylating agents impact the ovaries of pre- and post-pubertal participants with significant alterations to the follicle and oocyte area, number of granulosa cells (GCs) per follicle, and number of immature vessels, when compared to ovaries from untreated participants.This study analyzed 3-4 mm ovarian biopsies, which may not be representative of the whole ovary, and provide a snapshot in time and not a functional assessment. Additionally, no participants in the study have yet opted for ovarian tissue transplantation, so the ability of this tissue to restore fertility and hormones after transplant cannot be correlated with these histological assessments. Due to tissue size and sections available for research, immunohistological assessments were limited.This is one of the few studies to assess the short-term consequences of alkylating agents on paediatric and adolescent human ovarian tissue. We did not find any significant differences in the follicle density between exposed and untreated cohorts. However, upon a more detailed analysis, significant differences in follicle area, oocyte area, and number of GCs per follicle were found between exposed and untreated cohorts and the observations differed based on pubertal status. Additionally, these findings improve our understanding of the short-term effects of non-alkylating and low levels of alkylating agents on human paediatric and adolescent ovarian tissue. Future research defining the functional impact of these differences is required to determine if they can inform clinicians how and when to counsel potential OTC patients. This work describes the importance of analyzing more granular parameters in addition to follicle counts and provides an example of how such analyses can uncover otherwise hidden differences.
- Publisher Full Text (DOI)
- Virulent bacterial pathogens disassemble the epididymal amyloid matrix to evade host defense. [Journal Article]Hum Reprod. 2026 Sep 29. [Online ahead of print]HR
- CONCLUSIONS: While the monomeric and preformed amyloids of cystatin-related epididymal spermatogenic (CRES), a component of the epididymal amyloid matrix, exhibited antimicrobial activity against S. aureus and N. gonorrhoeae in vitro, the epididymal amyloid matrix did not.The assays were carried out in vitro using biochemically enriched populations of epididymal amyloid matrix. We cannot rule out that altered structure or disruption of the native composition and physiochemical environment of the epididymal amyloid matrix hindered its host defense functions against S. aureus and N. gonorrhoeae. We also have not established the presence of a functional amyloid matrix in the human epididymis.Our studies provide insight of the interactions between mammalian and bacterial host defense mechanisms including how virulent strains can disable a first line of defense in the epididymis. Our results have direct relevance for human and suggest a possible mechanism why S. aureus and N. gonorrhoeae can cause profound inflammation, scarring, tubule blockage, and permanent infertility in cases of epididymitis. Because these strains alter a host defense structure in the epididymal lumen allowing their growth/survival, more robust immune responses from the host may be necessary to counter the loss of amyloid matrix function resulting in inflammatory responses and possible tubule scarring. Our studies also highlight the potential significance of developing functional amyloids as new antibiotics.
- Publisher Full Text (DOI)
- Endometrial scratching in patients with unexplained infertility who have a good prognosis for natural conception: a randomized controlled trial (SCRaTCH-OFO). [Journal Article]Hum Reprod. 2026 Sep 29. [Online ahead of print]HR
- CONCLUSIONS: The cumulative live birth rate per intention-to-treat (ITT) was 64% and 57% in the endometrial scratch and control group, respectively (not statistically significant).The scheduled sample size target (792 subjects) was not reached because of suboptimal enrolment due to a lower-than-expected participation rate and competition with a concurrent national study in the same study population.The final analysis of the SCRaTCH-OFO study did not demonstrate a statistically significant effect of endometrial scratching on live birth rates in patients with unexplained infertility and a good prognosis for natural conception. Well-designed meta-analyses and/or trials in different patient phenotypes and under different intervention timings should provide more statistical power to assess a potential clinical benefit of endometrial scratching.
- Publisher Full Text (DOI)
- The two-shot protocol. A randomized controlled trial of a novel two-injection ovarian stimulation strategy. [Journal Article]Hum Reprod. 2026 Sep 25. [Online ahead of print]HR
- CONCLUSIONS: Although the mean number of MII oocytes did not differ significantly between the two-shot protocol and the control group, non-inferiority was not statistically met.The current study focused only in elective fertility preservation women, preventing conclusions on embryological differences between the protocols. Furthermore, since the sample size was powered to detect differences in the number of MII oocytes, findings for secondary outcomes, such as the hormonal profile, should be interpreted with caution.The two-shot protocol yielded a comparable number of MII oocytes to conventional stimulation; however, the pre-specified non-inferiority margin was not met, as the CI could not exclude a true reduction exceeding 1.5 MII oocytes. The point estimate of approximately one fewer MII oocyte is unlikely to be clinically meaningful, but larger studies are required before the protocol can be formally established as non-inferior.
- Publisher Full Text (DOI)
- Birthweight trends for babies born using Assisted Reproductive Treatments between 1991 and 2018: a national cohort study. [Journal Article]Hum Reprod. 2026 Sep 25. [Online ahead of print]HR
- CONCLUSIONS: The average gestation-adjusted BW for ART singletons increased steadily between 1991 and 2012 before becoming almost static until 2018; these changes were not observed in the general UK population.We could only explore factors available in the dataset, possibly missing some unobserved/unrecorded covariates such as socio-economic and lifestyle factors. The ART dataset used required patient consent, leading to the exclusion of ∼40% of all cycles conducted during the study period.ART singletons getting bigger over time is reassuring, as fewer ART babies now have adverse birth outcomes such as LBW. This is desirable within the developmental origins of health and disease (DOHaD) framework, which links adverse child outcomes to later-life disease predisposition. These changes in ART singletons (not observed in the general population) might be the result of changes or improvements in ART technologies, clinic practices, and ART patient population characteristics. Therefore, there is a need to continue monitoring BW-related outcomes such as large for gestational age and macrosomia, which are more prevalent in frozen ET ART babies and, though directly associated with the observed increase in average ART BW, can be detrimental to child health.
- Publisher Full Text (DOI)
- Interindividual variability of sperm DNA methylation is associated with reduced fecundability in couples attempting natural conception. [Journal Article]Hum Reprod. 2026 Sep 25. [Online ahead of print]HR
- CONCLUSIONS: Higher sperm EVOS is linked to reduced fecundability in couples attempting to conceive naturally.Identification of normospermic men was performed irrespective of sperm motility, which was measured after overnight transport on ice.Sperm EVOS captures inter-individual epigenetic variability characterized by the accumulation of deviations from normal site-specific DNA methylation patterns throughout the sperm methylome, which may reflect DNA damage and alterations in epigenetic maintenance. Our findings indicate that the accumulation of DNA methylation outliers in sperm is associated with lower pregnancy probabilities in the general population. Such findings suggest that sperm EVOS may represent a novel epigenetic biomarker of fecundability in couples attempting natural conception, including couples in which men are classified as having normal semen parameters.
- Publisher Full Text (DOI)
- Semen, stigma, and spectacle: reclaiming the narrative around male reproductive health. [Journal Article]Hum Reprod. 2026 Sep 24. [Online ahead of print]HR
- Male infertility contributes to nearly half of all cases of infertility worldwide, yet male reproductive health remains under-recognized in research, clinical practice, and public health. Paradoxically, male fertility has recently gained cultural visibility-not through medical initiatives but through spectacle. In 2025, staged 'sperm races' in Los Angeles presented motile spermatozoa as competito…
- Publisher Full Text (DOI)
- Reproductive outcomes among Canadian-born and immigrant women with infertility in Ontario: a population-based cohort study. [Journal Article]Hum Reprod. 2026 Sep 24. [Online ahead of print]HR
- CONCLUSIONS: Immigrant women with infertility, particularly refugees, had lower probabilities of live birth within 2 years of diagnosis compared with Canadian-born counterparts.Administrative data capture physician-diagnosed infertility, which may under-represent immigrants who are less likely to receive a diagnosis, leading to potential selection bias and underestimation of disparities. Residual confounding and incomplete ascertainment of conception type or social determinants remain possible.Despite universal health coverage and a publicly funded IVF program, inequities in fertility outcomes persist for immigrants, especially refugees. These findings underscore the need for equity-focused fertility policy that addresses cultural acceptability, diagnostic access, and integration of mental-health supports in reproductive care.
- Publisher Full Text (DOI)