Journal of Assisted Reproduction and Genetics最新文献

Purpose: The use of in vitro fertilization (IVF) has increased substantially, raising interest in the long-term health outcomes of women undergoing these treatments.

Objective: To assess the association between conception through autologous IVF and the long-term incidence of chronic diseases, compared with two reference groups: women who conceived through medically unassisted conception (UC) and age-matched nulliparous women.

Methods: This retrospective cohort study used electronic health records from a large health maintenance organization and included women who delivered before age 45 between 2000 and 2018. Three pairwise comparisons were performed: IVF mothers versus UC mothers, IVF mothers versus nulliparous women, and UC mothers versus nulliparous women. For the IVF versus UC comparison, each IVF mother was matched to a UC mother by age and parity at delivery. For comparisons with nulliparous women, controls were matched by age according to the mother's age at first delivery. The delivery date served as the index date for follow-up. Primary outcomes were chronic diseases diagnosed after the index pregnancy and persisting for at least three years.

Results: The study included 17,425 IVF mothers matched to 17,425 UC mothers, 10,358 IVF mothers matched to 10,358 nulliparous women, and 38,810 UC mothers matched to 38,810 nulliparous women. Compared with UC, IVF was associated with a higher risk of thyroid disease (HR 1.11, p < 0.05). Compared with nulliparous women, IVF mothers had higher risks of thyroid disease (HR 2.07), rheumatologic disease (HR 1.87), neurologic disease (HR 2.51), and psychiatric conditions (HR 1.34) (all p < 0.05). UC mothers also had higher risks of thyroid disease (HR 1.67), rheumatologic disease (HR 1.79), cardiology disease (HR 1.47), and psychiatric conditions (HR 1.47) compared with nulliparous women (all p < 0.05).

Conclusions: Long-term health outcomes after autologous IVF were largely comparable to those after UC, except for a modestly increased risk of thyroid disease. Compared with nulliparous women, both IVF and UC mothers had higher risks of several chronic conditions, suggesting that pregnancy itself may contribute to long-term maternal health trajectories. Thyroid function monitoring may be considered for women who conceive through autologous IVF.

Background: The rising incidence of endometrial cancer (EC) in young women presents a significant challenge in balancing oncologic safety with fertility preservation. While fertility-sparing treatment is an option for carefully selected patients with early-stage, well-differentiated EC, management of recurrence and optimization of fertility outcomes remain complex.

Case presentation: A 33-year-old nulliparous woman was diagnosed with Grade 1 endometrioid adenocarcinoma confined to the endometrium (ER/PR positive). After multidisciplinary team (MDT) evaluation confirmed eligibility, she received first-line high-dose progestin therapy. Complete remission (CR) was achieved and confirmed by hysteroscopy at 3 months, followed by 3 months of consolidation therapy. During preparation for embryo transfer after successful oocyte retrieval via a progestin-primed ovarian stimulation (PPOS) protocol, recurrence was detected hysteroscopically. Retreatment with the same progestin regimen led to a second CR after 6 months. Subsequently, a thawed embryo transfer resulted in a successful pregnancy, culminating in the delivery of a healthy infant at term.

Conclusion: This case suggests that successful fertility preservation and live birth may be achievable in young patients with early-stage EC when a structured approach is applied-including strict MDT selection, standardized progestin therapy with diligent surveillance, proactive management of recurrence, and well-timed assisted reproductive technology (ART). Notably, repeat conservative treatment for localized recurrence was successfully employed in this patient. Integrating weight management and comprehensive molecular profiling into future treatment paradigms could further optimize outcomes, but these observations require validation in larger cohorts.

Purpose: Immunological response to paternal antigens in semen and sperm has been implicated in the aetiology of preeclampsia. Although donor sperm conception has been associated with increased preeclampsia risk, evidence specifically regarding IVF with donor sperm remains limited. We aimed to assess whether pregnancies achieved via IVF with donor sperm are associated with a higher risk of preeclampsia or perinatal complications compared to IVF pregnancies using partner sperm.

Methods: This prospective registry-linkage study included women undergoing IVF using donor versus partner sperm between 2009 and 2017 at the Reproductive Clinic of Karolinska University Hospital, Stockholm, Sweden. Data on demographics and IVF treatments were collected from the clinic's database, while obstetric data were obtained from the Swedish Medical Birth Register by linking individual records across the two databases.

Results: Compared with partner sperm, donor sperm was not associated with increased risk of preeclampsia. However, donor sperm was associated with an increased risk of 5-min Apgar score < 7 (OR 2.13, 1.21-3.78), but lower risks of preterm birth (OR 0.55, 0.35-0.86), preterm premature rupture of membranes (OR 0.35, 0.18-0.67), and low birth weight (OR 0.54, 0.33-0.88). Body mass index > 25 kg/m² was associated with a higher rate of preeclampsia (aOR 2.20, 1.32-3.68).

Conclusions: Our study does not support the hypothesis that sperm donation in IVF increases preeclampsia risk. However, donor sperm was associated with differences in obstetric and neonatal outcomes, suggesting that sperm source or related treatment characteristics may influence pregnancy outcomes beyond preeclampsia.

Assisted reproductive technologies (ART) have significantly improved infertility treatment outcomes, with success traditionally defined by pregnancy and live birth rates. However, this endpoint-driven definition provides a limited perspective on reproductive success and does not fully capture the biological complexity underlying maternal and offspring health. Emerging evidence indicates that ART procedures may induce subtle molecular, cellular, and epigenetic alterations during early developmental stages, which may influence both short-term clinical outcomes and long-term health trajectories. In addition to embryonic factors, maternal physiology, including hormonal stimulation, metabolic status, and endometrial receptivity, plays a critical role in shaping pregnancy outcomes and fetal development. Furthermore, paternal and broader parental contributions, such as sperm DNA integrity and epigenetic factors, add another layer of complexity to ART outcomes. These interconnected determinants highlight the need for a more comprehensive approach to evaluating ART success. This review proposes the Embryo-Maternal-Offspring Continuum Framework, a conceptual model that redefines ART outcomes as a dynamic and integrated process spanning early embryonic events, maternal adaptation, and long-term offspring health. By linking subclinical biological changes with clinical endpoints, this framework emphasizes the importance of multidimensional outcome assessment and longitudinal evaluation. Adopting this continuum-based perspective may improve both clinical decision-making and research strategies by promoting individualized treatment approaches, identifying early biomarkers of developmental competence, and addressing long-term health implications. Ultimately, redefining ART success beyond live birth is essential to ensure optimal and sustainable reproductive outcomes for both mothers and their children.

Purpose: Anti-Müllerian hormone (AMH) is widely used as a clinical biomarker of ovarian reserve and is traditionallyinterpreted as a surrogate measure of remaining oocyte quantity. However, accumulating biological and clinicalevidence challenges this quantitative paradigm. AMH is exclusively produced by granulosa cells of growing folliclesrather than by primordial follicles themselves, suggesting that circulating AMH primarily refl ects somatic follicularactivity instead of dormant oocyte pool size. Here, we propose a conceptual framework redefi ning ovarian aging as aprocess that may be strongly infl uenced by progressive somatic ovarian dysfunction.

Methods: In this model, granulosa cells, stromal integrity, vascular support, immune regulation, and metabolicenvironment collectively form a somatic support network that determines follicular survival and developmentalcompetence. Disruption of this somatic ecosystem, through aging, surgery, chemotherapy, autoimmunity,environmental toxicants, smoking, or metabolic stress, results in reduced granulosa cell functionality, declining AMHsecretion, impaired follicle maturation, and secondary oocyte loss. Evidence from granulosa cell biology, controlledovarian stimulation, ovarian surgery, autoimmune ovarian disease, chemotherapy exposure, and fertility outcomestudies consistently demonstrates that AMH responds dynamically to changes in somatic ovarian health and doesnot reliably predict natural fecundability or absolute follicle number.

Results: Primordial follicle depletion progresses continuously throughout life, yet circulating AMH levels often showabrupt declines in response to somatic ovarian injury such as surgery, chemotherapy, or metabolic stress.Continuous primordial follicle attrition therefore does not translate into continuous AMH decline, supporting the viewthat AMH represents the functional cohort of biologically supported follicles rather than the total ovarian reserve. It isimportant to recognize, however, that ovarian reserve markers including AMH have limited predictive value fornatural fecundability with area under the curve values ranging from 0.60 to 0.65.

Conclusion: We introduce the concept of somatic ovarian function as an integrated framework for AMHinterpretation, proposing AMH as a biomarker of ovarian functional capacity. Reframing AMH from a purelyquantitative reserve marker to a functional systems biomarker that refl ects granulosa cell integrity, metabolichealth, and environmental infl uences may help reconcile longstanding clinical paradoxes and open new translationalavenues for fertility preservation, ovarian aging research, and therapeutic intervention.

Purpose: To evaluate whether the outcomes and characteristics of a first IVF/ICSI cycle are associated with embryological and clinical outcomes in a subsequent cycle performed within 2 years.

Methods: This retrospective single-center observational study included 1190 couples undergoing two stimulated ICSI cycles with planned blastocyst culture between 2015 and 2020. Associations between first- and second-cycle outcomes were analyzed, including oocyte yield, blastocyst development, and live birth. The effect of the inter-cycle interval was assessed using multivariate models.

Results: The mean maternal age was 38.7 years, and the mean AMH level was 1.7 ng/ml. Second cycles showed improved embryological outcomes, including higher numbers of retrieved cumulus-oocyte complexes (COCs), increased blastocyst yield, and higher blastocyst rate per COC. Overall, 50% of patients retrieved more COCs in the second cycle, and 87% of those with no COCs in the first cycle obtained ≥ 1 in the second. A longer inter-cycle interval was negatively associated with outcomes, reducing the likelihood of retrieving more COCs (OR 0.96 per month, 95% CI 0.93-0.98), obtaining more blastocysts (OR 0.95, 95% CI 0.93-0.98), and improving blastocyst rate (OR 0.96, 95% CI 0.94-0.99). First-cycle outcomes were not associated with live birth probability in the second cycle, which was instead associated with maternal age and the number of COCs previously retrieved.

Conclusions: First-cycle outcomes should not discourage further attempts, as subsequent cycles may yield improved embryological results. A shorter interval between cycles represents a modifiable factor associated with better outcomes. These findings support early re-treatment and a multicycle counseling approach to optimize cumulative live birth rates, especially as maternal age and ovarian reserve remain the most important predictors of success even in second attempts.

Background: Whereas luteinizing hormone (LH) contributes to steroidogenesis and oocyte maturation, its influence on embryo developmental kinetics has not been previously investigated using time-lapse technology. The aim of this retrospective analysis was to assess embryo morphokinetics following rLH supplementation in expected normal responders undergoing ovarian stimulation and evaluate associated embryological and reproductive outcomes.

Methods: A total of 120 patients were stimulated with either rFSH + rLH (n = 60) or rFSH alone (n = 60). Overall, 927 embryos were cultured in the Geri plus® time-lapse system and annotated for key morphokinetic parameters, including pronuclear dynamics, cleavage stages, morula formation, and blastocyst development. Clinical outcomes following fresh and frozen embryo transfer were also compared between groups.

Results: No differences were observed in baseline characteristics or ovarian stimulation outcomes, including oocyte yield, fertilization rate, cleavage rate, or usable blastocyst rate. Clinical pregnancy, miscarriage, live birth, and cumulative live birth rates were comparable between the two treatment groups. Embryo morphological quality was similar in both groups. Time-lapse analysis revealed that embryos derived from rFSH + rLH cycles exhibited accelerated early developmental kinetics, characterized by earlier pronuclear appearance, pronuclear fading, and first cleavage. In contrast, subsequent cleavage timings and later-stage morphokinetic parameters were comparable between groups. No differences in morphological or morphokinetic features were observed among implanted blastocysts.

Conclusion: rLH supplementation during ovarian stimulation modulates specific early zygotic events without affecting later embryo development, implantation, or live birth, indicating that routine rLH addition does not alter embryo competence in expected normal responders.

Purpose: Amino acids are vital biomolecules that can provide important insights into sperm functional competence. However, the level of amino acids (AAs) in seminal plasma and their implications on sperm characteristics remain less understood.

Methods: For the first time, high-performance liquid chromatography (HPLC) in combination with a laser-stimulated fluorescence (LSF) system was used to profile AAs from the seminal plasma of 30 normozoospermic and 51 nonnormozoospermic ejaculates. Sperm characteristics, along with DNA integrity, were assessed and correlated with individual AAs.

Results: The HPLC-LSF system was able to detect a total of 18 AAs in the seminal plasma. A significant variation was observed between the two groups for all AAs (p < 0.05), except for aspartate. Notably, the relative intensities of AAs were significantly lower in the non-normozoospermic group. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) further highlighted distinct clusters based on the AA profiles of the two groups. The pathway analysis indicated differences in the metabolic pathways between the normozoospermic and nonnormozoospermic groups.

Conclusion: The HPLC-LSF platform could serve as a potential tool in identifying seminal plasma AA levels. The low relative abundance of AA in the non-normozoospermic men could be attributed to aberrant metabolic pathways, underscoring their significance in male infertility.

Purpose: Female physicians spend a substantial proportion of their fertile years in academic and clinical training. The present study assessed fertility-related knowledge, concerns, and barriers to family planning among female physicians in Germany and their potential impact on career development.

Material and methods: In this cross-sectional study, cisgender female physicians from all disciplines and career stages practicing in Germany were recruited via online platforms, printed flyers, and women physicians' associations. An anonymous online survey was conducted between August 2024 and September 2025. It collected data on demographics, clinical, and academic career trajectories, fertility knowledge (using a modified FIT-KS and classified according to Bloom's cut-off values), as well as motherhood and career intentions. Associations were examined using Pearson and Spearman correlation coefficients and chi-square tests. p-values were interpreted descriptively, with a significant threshold set at p < 0.05.

Results: Of the 250 participating physicians, 214 completed the survey. The median age was 36.5 years (IQR 32-44). Respondents included residents (43.8%), specialists (22.3%), and senior physicians (19.5%). Overall fertility knowledge was moderate with a mean correct response rate of 70.2%. A total of 9.2% participants aspired to the highest academic rank, while 10.7% aimed for the highest clinical leadership position. Most respondents (90.2%) considered leadership positions compatible with part-time work. More than half reported postponing family planning, primarily due to limited career opportunities, long and inflexible working hours, and inadequate childcare support. Overall, 59% were mothers, with a mean of 1.99 children, and the mean age at first childbirth was 31.8 years. A higher age at first childbirth was significantly associated with retrospective regret about delaying parenthood. Physicians with children were more likely to work part-time. Among childless respondents, the main reasons were lack of suitable time due to studies or work (60.2%) and prioritization of career (45.5%).

Conclusions: Fertility knowledge was moderate, suggesting that additional education may be needed to support informed family planning decisions. Greater acceptance and implementation of flexible working models, together with improved childcare infrastructure, may contribute to reducing barriers to balancing family and career.