Abstracts

Study question: Can a rapid point-of-care FSHR N680S genotyping be applied in in vitro fertilization (IVF) clinics?

Summary answer: Rapid on-site FSHR N680S genotyping may easily be incorporated in IVF settings.

What is known already: Ovarian stimulation prior to IVF is often performed using recombinant FSH (rFSH) or human menopausal gonadotropin (hMG). The response to stimulation varies among patients and is partly explained by the FSH receptor N680S polymorphism. Previous work suggests that S-carriers benefit from hMG, whereas NN-carriers respond better to rFSH, affecting live birth rates and oocyte yield. However, current genotyping methods are costly, time-consuming and rely on blood samples. Therefore, a rapid, user-friendly genotyping approach is needed.

Study design, duration: A colorimetric loop-mediated isothermal amplification (LAMP) assay was developed. Analytical performance was evaluated in 400 blood-derived DNA samples from n=400 women attending the reproductive medicine centre, Malmö, Sweden, during 2016-2021, and validated in 100 buccal swabs collected from n=50 patients attending during 2024-2025.

Sample Size Calculation: Based on the expected 95% accuracy, the required sample size was 73 buccal swabs (80% power, 95% confidence interval, ± 5% margin of errors). Subsequently, 100 buccal samples were collected.

Participants/materials, setting, methods: Venous blood (n=400) and buccal swabs (n=100) were assessed. The LAMP assay was optimized for colorimetric detection using a pH-indicator and validated by fluorescence amplification. Buccal swabs were lysed in sodium hydroxide at 65°C for 15 minutes prior to reaction at 65°C for 30 minutes. Results were validated using Sanger sequencing.

Results: The LAMP-based assay delivered FSHR N680S results within 60 minutes from sample collection. Colorimetric readout showed strong agreement with fluorescence-based detection. In blood-derived samples, genotyping accuracy was 95%. When applied to buccal swabs, the assay correctly identified all NN-carriers and most S-carriers, with a clinical sensitivity of 86.8% and specificity of 100%. Based on its validated performance and previous clinical indication, this assay has the potential to support genotype-guided gonadotropin selection in IVF.

Limitations, reasons for caution: The assay was evaluated in a limited number of buccal samples (n=100) and at a single centre. Most misclassifications occurred in heterozygous genotypes. Larger, multicentre prospective randomized studies are needed to confirm the clinical impact on IVF outcomes.

Wider implications of the findings: This LAMP-based assay enables rapid, non-invasive, point-of-care genotyping of the FSHR N680S and offers a tool for stratifying gonadotropins used in ovarian stimulation prior to IVF.

Trial registration number: Not applicable.

Background

Bacterial vaginosis (BV) affects nearly 1 of 3 women of reproductive age worldwide and is characterized by high recurrence rates despite treatment. Although BV is associated with a shift from Lactobacillus-dominated vaginal communities to polymicrobial dysbiosis, the combined microbial and metabolic processes underlying BV remain insufficiently understood.

Methods

In this cross-sectional study, 111 women of reproductive-age were recruited from outpatient gynecology clinics in Stockholm, including 29 women presenting with BV and 82 controls. Vaginal samples were analyzed using whole-metagenome sequencing to characterize microbial composition and functional potential, to profile vaginal metabolites. Microbiome and metabolite data were analysed together using complementary statistical approaches, both guided by BV diagnosis and independent of predefined groups, to ensure robustness of the findings.

Results

BV status explained 23.5% of overall microbial community variation. BV was marked by a pronounced depletion of Lactobacillus species, particularly Lactobacillus crispatus, alongside enrichment of anaerobic bacteria commonly associated with BV, including Gardnerella vaginalis and Fannyhessea vaginae.

There were an enrichment of polyamines metabolites, including cadaverine and putrescine, consistent with increased bacterial amino acid decarboxylation, alongside reduced nucleoside levels reflecting reduced activity associated with normal vaginal epithelial metabolism.

Detailed genomic analysis of Gardnerella species showed no specific strain-level gene patterns uniquely associated with BV. However, variation in Gardnerella gene content was significantly associated with metabolomic differences, independent of BV diagnosis or healthy status, suggesting that Gardnerella species has a distributed metabolic contribution rather than being single virulence determinants.

Conclusions

Metabolite profiles outperformed individual taxa in distinguishing BV from healthy controls. Our study indicates that BV represents a distinct, multidimensional dysbiotic state defined by coordinated changes in both the vaginal microbiome and metabolome. The findings indicate that BV pathogenesis is driven primarily by community-level metabolic interactions rather than strain-specific microbial factors. These results support a shift toward diagnostic strategies targeting metabolic pathways by means the vaginal microbial function rather than eradication of individual taxa.

Keywords

bacterial vaginosis, vaginal microbiome, vaginal metabolome, multi-omics, Gardnerella

This retrospective time lapse study evaluated 3103 transferred blastocysts to determine how early division patterns, morula compaction behavior and blastocyst quality influence clinical outcomes. Embryos were categorised as normal or abnormal cleavage, full or partial morula compaction, and top, good or low blastocyst quality, based on the Gardner Schoolcraft criteria. Most transferred blastocysts, 92.5%, originated from normally dividing embryos, of which 63.8% developed into fully compacted morulas. In unadjusted analyses, fully compacted morulas resulted in higher pregnancy, clinical pregnancy and live birth rates than partially compacted morulas across all morphology categories. Embryos with abnormal cleavage represented a small proportion of the cohort, 7.5%, but developed almost exclusively into partial morulas and showed reduced reproductive potential, with lower pregnancy and clinical pregnancy rates compared with normally dividing embryos, and lower live birth rates when compared with partial morulas originating from normally dividing embryos. The highest live birth rate (38.9%) was observed for top quality blastocysts originating from normally cleaving, fully compacted morulas. In multivariable models adjusting for maternal age and blastocyst developmental day, blastocyst morphology and blastocyst age were the strongest independent predictors of clinical outcome, while maternal age showed a consistent negative association. Abnormal cleavage remained associated with reduced pregnancy and clinical pregnancy rates, although this effect did not persist for live birth, and compaction pattern did not retain significance after adjustment. Overall, early developmental behavior, particularly cleavage pattern and morula compaction, aligns with downstream morphology to shape embryo competence, while blastocyst morphology and blastocyst developmental day remain the primary determinants of live birth after single blastocyst transfer.

Aim: To evaluate the association between premenstrual syndrome (PMS) and systemic inflammatory markers in reproductive-aged women, and to assess whether these markers relate to PMS symptom severity.

Methods:In this case–control study, 98 women with PMS and 105 healthy controls aged 18–49 years were included. Participants completed a sociodemographic questionnaire and the Premenstrual Syndrome Scale (PMSS), which was administered face-to-face by the same researcher to ensure consistency. Blood samples were obtained during the luteal phase of the menstrual cycle. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were calculated from complete blood count parameters, and C-reactive protein (CRP) levels were recorded. Anthropometric measurements and blood pressure values were also assessed. Statistical analyses were performed using SPSS 26.0; p<0.05 was considered significant.

Results: The median age was 32 years in the PMS group and 31 years in the control group. No significant differences were observed between groups regarding sociodemographic characteristics, smoking status, exercise habits, BMI, obstetric history, or dysmenorrhea. Age at menarche was significantly lower in the PMS group (p=0.012). Both systolic and diastolic blood pressure values were significantly higher in women with PMS compared to controls (both p<0.001). Among laboratory parameters, SII was significantly higher in the PMS group (p=0.032), while NLR, PLR, CRP, MPV, and hemoglobin levels showed no significant differences. PMSS total score was not significantly correlated with inflammatory parameters; however, SII showed a weak positive, non-significant correlation with PMSS score (r=0.12, p=0.08). In ROC analysis, SII showed limited discrimination for PMS (AUC=0.587, p=0.032). A cut-off value of 468.2 yielded 60% sensitivity and 57% specificity. NLR (AUC=0.446, p=0.040) and PLR (AUC=0.455, p=0.041) also reached statistical significance, but overall discriminatory performance was poor.

Conclusion:PMS was associated with higher SII values, supporting a possible low-grade inflammatory component. However, the weak discriminatory performance of inflammatory indices and the lack of association with symptom severity indicate that inflammation alone is unlikely to explain PMS severity. Earlier menarche and higher blood pressure in the PMS group may represent clinically relevant accompanying features. Given the burden of PMS during the reproductive years, these findings support a broader clinical assessment framework and warrant larger, multicenter prospective studies to clarify the role of SII in PMS.

Keywords: Premenstrual Syndrome, Inflammation, Inflammatory Biomarkers, Systemic Immune-Inflammation Index, Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio

Cryopreservation technology used in ART treatment has significantly improved the live birth rate (LBR), allowing multiple embryo transfers with frozen embryos from a single ovarian stimulation cycle. Additionally, the elective freeze of all embryos is becoming more frequent as pregnancy rates after frozen embryo transfers (FETs) equal those of fresh transfer cycles. Furthermore, the freeze-all strategy offers the advantage of allowing the application of gonadotropin-releasing hormone agonist to finalize oocyte maturation and thus minimize the risk of ovarian hyperstimulation syndrome.

This nationwide cohort study includes all frozen embryo transfers (FET) from 2012 to 2019. Biochemical pregnancy, clinical pregnancy, and live births were analysed based on blastocyst storage time, stratified into five groups: ≤3, 4-6, 7-12, 13-24 and ≥25 months. With the shortest group (≤3) as the reference. We also examined the risk of preterm birth, small- and large for gestational age (SGA and LGA), and congenital malformations among live-born children.

Multivariable analysis was used to estimate the odd ratios of the reproductive outcomes, accounting for potential confounders.

We identified 7042 women with 12,599 FETs. The cohort comprised 1047 blastocysts transferred after 13–24 months of storage, and 1097 with ≥25 months of storage before transfer. The mean storage time in the ≥25 months group was 3 years and 3 months. The mean maternal age at embryo transfer was 32.3 ± 4.9 years. Characteristics of women at embryo transfer did not vary significantly by storage time, except for PCOS, which increased from 2.6 % in the reference group to 6.7% in the ≥ 25-month group.

The Biochemical pregnancy rates were 45.3%, with no significant decrease on adjusted odd ratios: aOR 0.94, 95% CI: 0.80-1.11 and aOR 0.96, 95% CI: 0.82-1.12 for 13–24-month and ≥25-month groups, respectively.

The clinical pregnancy rates were 35.7% and did not decrease with storage time (aOR 0.96, 95% CI: 0.82-1.13) for ≥25 months.

The LBR was 28.6%, with no significant decrease during storage (aOR 0.89, 95% CI: 0.75-1.06) for ≥25 months. However, the risk of LGA was slightly, but not significantly, increased from 6.0% to 11.7% (aOR: 1.42, 95% CI: 0.84-2.42).

Our data indicates that storing blastocyst for over 25 months does not significantly affect pregnancy chances following assisted reproductive technology treatment.

We expect the number of blastocysts with long storage times to increase, providing more power to future estimates. However, current results are reassuring

Background

Two randomized controlled trials (RCTs) on artificial cycle FET show similar or better outcomes in immediate versus postponed FET. Whether mNC-FET can be performed in the cycle immediately following a failed stimulated IVF cycle or a freeze-all cycle remains debated.

Some clinics postpone mNC-FET to avoid potential negative effects of ovarian stimulation on endometrial receptivity or difficulties identifying the dominant follicle from multiple corpora lutea.

Delaying FET prolongs time to pregnancy and may increase the emotional burden for couples wishing to conceive. The aim of this study was to assess the optimal timing of mNC-FET following an unsuccessful fresh or freeze all IVF cycle.

Methods

This multicenter RCT included 494 participants from seven Danish fertility clinics between 2021 and 2025. Participants were randomized 1:1 to undergo mNC-FET either in the cycle immediately following IVF or in a subsequent cycle. A non-inferiority design with a 10% margin was predefined.

Participants were 18-40 years with regular menstrual cycles scheduled for mNC-FET. Ovulation was triggered when the leading follicle reached ≥17 mm followed by blastocyst transfer six/seven days later. The primary outcome was live birth rate (LBR) in intention-to-treat (ITT) and per-protocol (PP) analyses to determine whether immediate FET is non-inferior to postponed FET. Secondary outcomes included LBR per-transfer, pregnancy rate, cancellation rate, miscarriage rate, and obstetric and perinatal outcomes.

Results

Baseline and the preceding IVF cycle characteristics were similar in the immediate and postponed group.

In the ITT analysis (N=494) LBR was 32.4% in immediate FET compared to 36.0% in postponed FET, corresponding to a non-significant risk difference (RD) of -3.6% in favor of postponed mNC-FET (p=0.393) and a 90% CI of (-10.7, 3.4) crossing the predefined non-inferiority margin of -10.0%.

LBR in the PP analysis (n=472) was 32.7% in immediate FET compared to 39.2% in postponed FET, yielding a RD of – 6.6% in favor of postponed mNC-FET (p=0.138), and a 90% CI of (-13.8, 0.71) also crossing the non-inferiority margin.

Pregnancy rates were significantly higher in postponed compared to immediate mNC-FET in the PP and per-transfer analyses. In the PP analysis, pregnancy rates were 44.9% in immediate FET and 57.3% in postponed FET (RD -12.4%, 95%CI -21.3, -3.4; p= 0.007). In the per-transfer analysis pregnancy rates were 50.7% in immediate versus 60.8% in postponed FET (RD -11.0%, 95%CI -20.3, -1.7; p=0.021).

Conclusion

Inferiority of immediate compared to postponed mNC-FET in terms of LBR cannot be excluded.

This prospective multicenter study investigated whether a biphasic oxygen culture strategy, designed to mimic the physiological decline in oxygen tension from the fallopian tubes to the uterine cavity, could improve embryo quality, morphokinetic development, and blastocyst usability in IVF. Standard embryo culture is performed at 5% oxygen, whereas in vivo uterine oxygen levels are closer to 2%. Previous non clinical studies using biphasic oxygen conditions have suggested potential improvements in blastocyst formation and cumulative live birth rates, although these findings were primarily based on surplus embryos. Importantly, no adverse effects of biphasic culture have been reported.

A total of 209 patients were included, each contributing at least eight retrieved oocytes to allow sibling embryo comparison. Altogether, 2983 oocytes were randomized to either monophasic culture (5% oxygen throughout) or biphasic culture (5% oxygen until day 3, then 2%). Embryos were cultured individually in EmbryoScopes, and blastocysts were assessed morphologically and morphokinetically according to the Gardner grading system and ESHRE/ALPHA consensus criteria.

Statistical analyses were adjusted for maternal age at oocyte retrieval, with additional subgroup analyses stratified into three age categories (≤30, 31–35, >35 years). Potential confounders were accounted for throughout.

1554 oocytes were allocated to the control group and 1429 to the biphasic group. Blastocyst formation rates did not differ significantly between groups (35.3% vs. 35.4%; p=0.927), nor did the number of good quality blastocysts (406 vs. 355; p=0.395). Morphokinetic evaluation of good quality blastocysts showed comparable developmental timing, including time to full blastocysts (tB: 103.2h ±6.3h vs. 103.3h ±10.5h; p=0.784) and the interval from t5 to tB (52.7h ±6.2h vs. 52.5h ±10.6h; p=0.881).

We found no significant differences in early clinical outcomes; positive hCG rates were 56% in the control group and 51% in the biphasic group (p=0.552), while fetal heartbeat rates were 40% and 39%, respectively (p=0.918). No age related differences were observed in subgroup analyses. Live birth rates showed no significant group differences; ongoing adjusted analyses will determine the robustness of these preliminary results.

Spent medium samples were collected for antioxidant activity assessment. Due to limited volumes, samples were pooled by age group, not allowing for statistical analysis. However, distinct differences in antioxidant profiles were observed between culture conditions, suggesting that oxygen tension may influence the oxidative environment. These findings require further validation.

Overall, this study demonstrates that biphasic oxygen culture does not improve blastocyst development, morphokinetics, or early clinical outcomes compared with standard monophasic 5% oxygen culture.

Background

Cystic fibrosis (CF) is a progressive autosomal recessive disorder caused by mutations in the CFTR gene. With the introduction of CFTR modulator therapy, life expectancy has increased substantially, bringing fertility and parenthood into greater focus. Although spermatogenesis is typically preserved, most men with CF have congenital bilateral absence of the vas deferens (CBAVD), leading to obstructive infertility and the need for assisted reproductive techniques such as IVF with ICSI. Previous research indicates inconsistent fertility counseling in CF care.

Aim

To explore men’s knowledge of fertility and assisted reproduction, identify perceived gaps in reproductive health information and examine attitudes toward parenthood and preferences regarding fertility counseling.

Methods

This qualitative study included nine men (≥18 years) with CF who had applied for IVF within the past ten years. Participants were recruited from a CF clinic in Sweden. Semi-structured interviews were conducted, transcribed verbatim and analyzed using thematic analysis (Braun & Clarke).

Results

The Knowledge

Most participants became aware of their infertility during adolescence, although timing and delivery of information varied widely. Fertility information was often described as fragmented, unsystematic and rarely revisited. No participant reported receiving structured or written materials about CF-related infertility or treatment options. Many expressed a wish for earlier sperm testing and clearer information about procedural pathways.

The Support

Fertility discussions were often reactivated in adulthood when family planning became relevant. Psychological support during IVF was highly valued. However, overall support was perceived as inconsistent and dependent on individual clinicians’ initiative. Family members rarely addressed fertility proactively. Standardized, updated educational resources were lacking.

The Decision

Participants described dilemmas regarding when to disclose infertility to partners but generally preferred early openness. Several reported that improved health following CFTR modulator therapy increased their interest in parenthood. IVF referrals were accessible but the treatment process was experienced as lengthy and sometimes unclear. Genetic counseling was appreciated, though it also raised ethical considerations.

The Unknown

IVF represented both opportunity and emotional burden. Participants described uncertainty regarding treatment outcomes and genetic risks. The analysis reveals a desire for more explicit treatment information. Emotional strain sometimes affected well-being and relationships.

Conclusion

Men with CF express a need for structured, developmentally appropriate fertility counseling beginning in adolescence and continuing into adulthood. There is a desire for early fertility assessment, standardized information materials and integrated psychosocial support to improve reproductive counseling and support informed decision‑making prior to and throughout IVF treatment for men with CF.

Background:

Children conceived through ART have higher risks of adverse perinatal outcomes, including preterm birth and low birth weight, even among singletons. Studies of compulsory school performance generally show similar outcomes after adjustment, but evidence on upper secondary education and further remains limited.

Methods:

Using Swedish nationwide register data (1987–2002), we included 17,463 ART-conceived and more than 1.6 million naturally conceived (NC) individuals followed from birth to December 2022 (age 21), enabling evaluation of upper secondary school performance and university eligibility. Individuals who emigrated or died before age 21 were excluded. Linkage with national registers provided information on perinatal health, socioeconomic status, and education using unique personal identity numbers. Live births were identified through the Medical Birth Register, with ART-conceived children identified via a separate file.

The main outcome was completion of upper secondary school with university eligibility. Associations between mode of conception (ART vs NC) and educational outcomes were analysed using multivariable logistic regression to estimate adjusted odds ratios (aOR) with 95% confidence intervals (CI), adjusting for sex, birth year, and parental education.

Results:

The study included 1,647,216 liveborn children. After excluding individuals who died or emigrated before age 21 and individuals with no information on any grades, 17,463 ART-conceived individuals (38.5% multiples, 51.4% male) and 1,490,153 NC individuals (2.2% multiples, 51.3% male) were included in the analysis. Mean (SD) maternal and paternal age at childbirth was 33.6 (3.8) and 36.1 (5.3) years in the ART group compared with 29.2 (5.0) and 32.0 (6.0) years in the NC group, respectively. High maternal and paternal education at offspring age 16 years was observed in 42.7% and 34.6% in the ART group, compared with 34.6% and 21.7% in the NC group, respectively.

Eligibility for upper secondary school was observed in 93.9% (n=16,393) ART-conceived individuals and in 90.5% (n=1,348,650) individuals conceived after NC (OR 1.61; 95% CI 1.51 to 1.71, p<0.001 and aOR 1.42; 95% CI 1.33 to 1.52, p<0.001).

Furthermore, of those eligible for upper secondary school, 76.4% of ART individuals (n=12,527/16,393) and 71.7% of NC individuals (n=967,493/1,348,650) completed upper secondary school with university eligibility (OR 1.17; 95% CI 1.11 to 1.23, p<0.001 and aOR 1.36; 95% CI 1.28 to 1.43, p<0.001). Residual confounding should be considered in register-based studies.

Additional analyses of secondary outcomes, sibling comparisons, and subgroups are ongoing.

Our findings provide reassurance regarding long-term educational outcomes among children conceived through ART.

Human reproduction is inefficient, and only one in three fertilized oocytes results in a live birth. One contributing factor is the error‑prone first mitosis that gives rise to the two‑cell embryo. In the two‑cell stage, nuclei form directly after the first mitosis and persist until the second mitotic division. Time‑lapse imaging has revealed distinct nuclear error phenotypes, including micronucleation, multinucleation, split or fragmented nuclei, and mixed error patterns.

In a previous study, we categorized these nuclear error phenotypes and examined the blastocyst formation rate per phenotype. The presence of nuclear errors reduced the likelihood that a two‑cell embryo would develop into a clinically useful blastocyst (≥3BB).

The aim of the present study was to investigate the impact of nuclear errors and phenotypes on clinical outcomes after single embryo transfer. This retrospective observational study included 3,856 transferred embryos with known clinical outcomes.

Nuclear errors were observed in 20.8% (n = 230) of transferred cleavage‑stage embryos. These embryos had significantly reduced clinical outcomes compared with cleavage embryos without nuclear errors (PR 32.2% vs 46.2%, CPR 26.9% vs 40.4%, LBR 22.5% vs 34.4%, all p < .001). Embryos with two affected blastomeres had significantly poorer outcomes than those with only one affected cell (p < .01). The worst outcomes were associated with split nuclei and micronucleation.

In blastocysts transferred on day 5, nuclear errors were noted at the two‑cell stage in 23.9% (n= 556), and in 28.8% ( n=122) of day 6 blastocysts. In contrast to cleavage‑stage transfers, there was no difference in clinical outcomes after blastocyst transfer between embryos with or without nuclear errors.

Across the whole cohort, neither maternal nor paternal age showed a meaningful association with the occurrence of nuclear errors. However, fertilization method had a clear effect: ICSI‑derived embryos had significantly higher odds of exhibiting any nuclear error compared with IVF (OR 1.75, 95% CI 1.50–2.04, p < .001).

We conclude that nuclear error phenotypes observed in the two‑cell embryo are predictive of clinical outcomes after cleavage‑stage transfer, but they do not affect blastocyst competence.

Background

Prolonged time to pregnancy (TTP) is an early marker of reduced fertility. Although several female characteristics have been suggested to influence conception rates, evidence remains sparse. Variation in TTP provides insight into factors that may accelerate or delay conception and is essential for early counselling and reproductive planning.

Methods

We conducted a cross-sectional study among Danish women who reported either being pregnant or trying to conceive in the nationwide Safe Choice questionnaire, and measured TTP as time spent trying to conceive or time to achieving pregnancy. TTP was analyzed using interval-censored regression models adjusted age, body mass index, smoking status, and alcohol consumption (omitting the variable of interest). Associations were estimated as relative rates (RR) of TTP with 95% confidence intervals. RR below 1 indicated that a risk factor increased TTP compared to the reference group.

Results

We included 23,319 women, of whom 12,575 were pregnant (median age: 31 years) and 10,744 were trying to conceive (median age: 32 years). Overweight (RR: 0.82, 95% CI: 0.78-0.86) and obesity (RR: 0.51, 95% CI: 0.48-0.54) were associated with lower RR of TTP, compared to normal weight. Compared with moderate physical activity, sedentary (RR: 0.85, 95% CI: 0.79-0.90) and vigorous activity levels (RR: 0.95, 95% CI: 0.91-0.99) were associated with lower RR. Poorer self-rated health showed a dose-response association with longer TTP, and current smoking was strongly associated with longer TTP (RR: 0.15, 95% CI: 0.13-0.18). Having one or more tubal and adhesion-related factor (RR: 0.70, 95% CI: 0.68-0.73), ovulatory and endocrine factor (RR: 0.63, 95% CI: 0.60-0.67), and uterine and endometrial factor (RR: 0.61, 95% CI: 0.58-0.64) was all associated with lower RR compared with women without the respective factors.

Conclusion

Among lifestyle and behavioral factors, being obese, current smoking and low self-rated health was associated with the lowest RR of TTP, where previous ovarian surgery and PCOS showed the lowest RR of TTP among the reproductive factors examined. These findings highlight the importance of modifiable lifestyle factors and underlying reproductive conditions for TTP.

OBJECTIVE: To evaluate how assisted reproductive technology (ART) impacts next-generation fertility.

SETTING: Using linked nationwide registry data from Denmark (1994–2023), Norway (1988–2022) and Sweden (1988–2022) we included 20,085 ART-conceived women, 21,621 ART-conceived men, 1,419,032 naturally conceived (NC) women and 1,500,734 NC men who were childless at age 18 years. They were followed until first biological parenthood (overall and using ART) or women’s first dispensation of clomiphene, letrozole or gonadotropin, with censoring at emigration, death, or end of follow-up (age 20–35 years if no event).

METHODS: At the population level, we estimated adjusted hazard ratios (aHRs) comparing ART with NC for each event, and within same-sex full sibships for first parenthood. We controlled for characteristics of parents (immigration, age at first parenthood and education) and participants’ own birth (country, birthyear, plurality, and maternal age and parity). We report birthyear-matched event proportions among NC using indirect standardization with inverse probability weights for birthyear and country.

RESULTS: Median age at study end was 23.8 years among ART-conceived (interquartile range 21.7–26.5 years) . Fewer ART-conceived women became parents during follow-up compared to NC women (10.2% vs 13.3%), but their reproduction was higher after adjustments at the population level (aHR, 1.20, 95% CI, 1.15–1.26) and similar within sisterhoods (aHR, 0.91, 95% CI, 0.60–1.38). Moreover, 0.28% of all ART-conceived women became parents using ART, compared to 0.27% of NC women, corresponding to 2.8%, and 2.1%, of all first parenthoods, respectively . In addition, more ART-conceived women dispensed fertility drugs compared to NC women (1.24% vs 1.18%), also after adjustments (aHR, 1.35, 95% CI, 1.18–1.54).

Fewer ART-conceived men became parents during follow-up compared to NC men (6.2% vs 8.0%), but their reproduction was higher after adjustments at the population level (aHR 1.13, 95% CI, 1.07–1.20) and similar within brotherhoods (aHR, 1.22, 95% CI, 0.71–2.11). Moreover, 0.14% of all ART-conceived men became parents using ART, which was similar as NC men, corresponding to 2.3%, and 1.9%, of all first parenthoods, respectively . Furthermore, ART-conceived men more often had a female partner who dispensed fertility drugs compared to NC men (0.68% vs 0.63%), also after adjustments (aHR, 1.32, 95% CI, 1.11–1.57).

CONCLUSION: In this still relatively young cohort of ART-conceived individuals, reproduction was lower than in the NC background population, but similar to NC same-sex full siblings, and higher when controlling for confounding at the population level. Moreover, dispensing fertility drugs was more common among ART-conceived than NC individuals.

Background

Chemotherapy is gonadotoxic and may cause infertility, premature ovarian insufficiency (POI), and related health consequences. Breast cancer is the most common cancer in women of reproductive age, with increasing incidence. Over recent decades, fertility preservation (FP), including ovarian tissue, embryo, and oocyte cryopreservation, has gained increasing emphasis. Few large prospective studies have evaluated the impact of chemotherapy on ovarian reserve in women diagnosed with breast cancer using both AMH and AFC, and no large studies have assessed the impact according to FP choice.

Objective

To evaluate the impact of chemotherapy on ovarian reserve in premenopausal women diagnosed with breast cancer, stratified by FP strategy and age at diagnosis.

Methods

In this combined retro- and prospective cohort study we included 152 women aged 18-42 years diagnosed with breast cancer, who received FP counselling at Rigshospitalet, Copenhagen University Hospital, between 1 January 2018 and 31 August 2023. Exclusion criteria were previous chemotherapy, oophorectomy, and death or emigration within two years of inclusion. Medical and gynecological history and oncological treatment plans were recorded. Ovarian reserve was assessed by anti-Müllerian hormone (AMH) and antral-follicle-count (AFC) at baseline and 6, 12, and 24 months post-chemotherapy. Changes over time were analyzed using linear-mixed-models, adjusting for age and use of hormonal contraception.

Results

Of 152 women, 57 underwent OTC, while 95 underwent oocyte or embryo cryopreservation or no FP. Baseline median AMH was 13.9 [95% CI: 10.7, 18.1] pmol/L among women who did not undergo OTC and 13.3 [95% CI: 10.9, 16.3] pmol/L among those who did. A marked reduction in both AMH and AFC was observed after chemotherapy, with partial recovery within two years after treatment. The reduction was more pronounced, and recovery more limited, in women with OTC and in those of advanced reproductive age (≥35 years). Compared to baseline, median AMH was reduced by 90% [95% CI: 93%, 85%] at 6 months and 75% [95% CI: 83%, 63%] at 24 months in women without OTC and by 92% [95% CI: 95%, 86%] and 85% [95% CI: 90%, 78%] in women with OTC. Similar patterns, however, not as profound was seen for AFC.

Conclusion

These findings will support counselling women with breast cancer about chemotherapy related ovarian damage and the need for FP. It will help weighing risks and benefits of FP options, to avoid possible unnecessary, costly treatments that may further compromise ovarian reserve and potentially increase POI risk and related health consequences.

Introduction

Endometriosis is an inflammatory, estrogen dependent and chronic condition leading to pain and subfertility. The prevalence of endometrioma and/or deep endometriosis in women referred for assisted reproductive technology (ART) treatment in Sweden is estimated to be 21.8%. It is still not known whether surgery of advanced endometriosis prior to ART is beneficial. There is little knowledge about how these women think about surgery as a potential treatment or participating in endometriosis research.

The overall aim of this qualitative study was to explore the thoughts, concerns, fears and hopes in infertile women affected by advanced endometriosis. This will be of great value when designing future research project on endometriosis, especially involving surgery.

Materials and methods

14 women identified at the Department of Gynecology and Reproductive Medicine at Sahlgrenska University hospital participated in an individual one hour long semi-structural interview. The interview had three parts: endometriosis surgery, endometriosis fertility and endometriosis research. Inclusion criteria were age over 18, Swedish speaking, affected by deep infiltrating endometriosis or endometriomas and at the same time infertility. The conversations were recorded and printed. Data were analyzed by thematic content analysis.

Results

The initial 33 codes were merged to 18 final codes. These were organized into three main themes: ”Participation as motivator”, ”Hope as motivator” and ”Guard my boundaries”, each of them with several underlying themes. Most of the participants expressed the importance of more endometriosis research. Many women mentioned the need for a wider perspective than the number of babies born, e.g. Quality of Life. The women also expressed a will to contribute to the endometriosis research, sometimes almost as a duty. However, they were not very keen to participate in studies involving surgery, mostly because of hesitation to let chance decide if they would be selected for surgery or not. Most commonly they wished to avoid surgery, partly due to fear of decreased ovary reserve after ovarian surgery. This group of infertile women with advanced endometriosis has an extremely strong wish for parenthood, often stronger than the wish to become pain-free.

Conclusion

The results of this study directly affect the ongoing RCT Endo-SOFT assessing whether endometriosis surgery prior to ART is beneficial regarding ART outcome, other patient outcome and health economics. In addition, the results generate new insights that are of great importance to improve health care of women with endometriosis and infertility.

Introduction.

Unexplained infertility (UI) accounts for up to one-third of infertility cases. Oxidative stress (OS) has been proposed as a contributing mechanism, potentially impairing oocyte quality, embryo development, and implantation. Endometriosis is also closely associated with OS, as oxidative imbalance may contribute both to its development and progression while further increasing oxidative stress and potentially impairing fertility. However, studies evaluating OS levels following antioxidant supplementation in women with UI, particularly in those with endometriosis, remain limited. This study aimed to evaluate serum concentrations of malondialdehyde (MDA), a commonly used biomarker of OS, in women with UI and to assess the impact of antioxidant supplementation on changes in this biomarker, with particular attention to women with endometriosis.

Methods.

The study included 30 women diagnosed with UI. 15 participants (50%) reported at least one comorbidity, while 20% had conditions with a possible autoimmune or immune-mediated etiology. 13 (43,3 %) of women were diagnosed with endometriosis (stage I-II). Serum MDA concentrations were determined from peripheral blood using the ELISA method. Participants received antioxidant supplementation recommendations: vitamin E 50 mg/day, zinc 15 mg/day, coenzyme Q10 15 mg/day, selenium 70 µg/day). MDA levels were reassessed after 3 (± 1) months of supplementation. Statistical analysis was performed using R (v4.3.3) with the Rcmdr package (v2.9-2) and Python (v3.11.4).

Results.

Mean age of women was 33 (± 7) years. Serum MDA concentrations significantly decreased after antioxidant supplementation in the overall study population, with median levels declining from 228.2 to 173.94 ng/mL (p < 0.001, Wilcoxon signed-rank test). Serum MDA levels of participants were further stratified according to the presence of endometriosis. Median baseline MDA was higher in women with endometriosis (283.8 ng/mL, IQR 226.5–478.8) compared with women without endometriosis (210.4 ng/mL, IQR 162.8–304.9). Antioxidant supplementation significantly reduced MDA levels in both subgroups (p = 0.005 and p = 0.0002, respectively), although post-treatment levels remained higher in women with endometriosis (p = 0.02), suggesting persistently elevated oxidative stress in this subgroup.

Conclusions.

Antioxidant supplementation significantly reduced serum MDA levels in women with unexplained infertility. Women with endometriosis showed higher baseline and post-supplementation MDA levels, highlighting the pronounced oxidative stress–driven nature of the disease. Importantly, the observed MDA reduction in this subgroup suggests that antioxidant therapy may offer clinical benefit for infertile patients with endometriosis. Larger studies are warranted to clarify the role of disease-specific mechanisms and comorbidities in oxidative stress modulation and treatment response.

Study question:

Does ICSI versus c-IVF affect the cumulative number of deliveries, including subsequent live births, from one treatment cycle in patients without severe male factor infertility?

Summary answer:

Extended follow-up of the RCT shows no advantage of ICSI over c-IVF in cumulative number of deliveries.

Background:

ICSI is widely used in ART, including in couples without severe male factor infertility, despite RCTs showing no improvement in live birth with ICSI compared with c-IVF. Whether fertilization method influences the cumulative number of deliveries, including subsequent births from vitrified embryos derived from the first oocyte retrieval, remains uncertain.

Methods:

This was an extended follow-up of an RCT. Women in their first ART cycle were randomized 1:1 to ICSI or c-IVF. Follow-up was extended to capture all deliveries from the initial oocyte retrieval, with a minimum follow-up time of three years.

In total, 824 women undergoing their first treatment were included and randomized to ICSI (n = 414) or c-IVF (n = 410). Elective single embryo transfer was performed at the blastocyst stage. The main outcome was the updated cumulative live birth rate (≥1 delivery) in each group. The secondary outcome was the proportion of women achieving two or more live births. Analyses were ac-cording to the intention-to-treat (ITT) and per-protocol (PP) principle.

Results:

Baseline characteristics were similar between groups.

The ITT analysis showed no significant difference in the cumulative live birth rate between the ICSI and c-IVF groups (179 (43.2%) vs. 197 (48.3%) RR 0.90, 95%CI (0.77-1.04), p=0.15. The proportion of women with two or more live births (siblings) from the same ART cycle (fresh and FET cycles) was 31 (7.5%) after ICSI and 46 (11.3%) after c-IVF (RR 0.66, 95% CI (0.43-1.02)), p=0.07.

The PP analysis (n=766) excluded patients with no oocytes retrieved, sperm count below 2 million progressively motile on day of oocyte retrieval and patients not treated as allocated and showed that 167 (43.0%) women treated with ICSI vs. 190 (50.3%) treated with c-IVF had minimum one de-livery, RR 0.86, 95%CI (0.73-1.00), p=0.046. The proportion of women with two or more deliveries (siblings) from the same ART cycle (fresh and FET cycles) was 27 (7.0%) after ICSI and 44 (11.6%) after c-IVF (RR 0.60, 95%CI 0.37-0.94), p=0.03.

Conclusion:

ICSI offers no advantage over c-IVF in couples without severe male factor infertility, including for total number of children born from a single ART treatment cycle (fresh and FET cycles).

Introduction: Unexplained infertility (UI) affects a substantial proportion of women of reproductive age. Oxidative stress (OS) is implicated in the pathophysiology of infertility by promoting cellular damage that may compromise oocyte quality and embryo implantation. Total antioxidant capacity (T-AOC) reflects systemic antioxidant defense and may respond to targeted antioxidant supplementation.

Materials and Methods: This prospective observational study included 30 women diagnosed with UI. 15 participants (50%) reported at least one comorbidity, and 20% had conditions with a possible autoimmune or immune-mediated etiology, including autoimmune thyroiditis, rheumatoid arthritis, ulcerative colitis, celiac disease, rosacea, type II diabetes, and allergic diseases. Serum T-AOC was measured by ELISA at baseline and after 3 (± 1) months of antioxidant supplementation (vitamin E 50 mg/day, zinc 15 mg/day, coenzyme Q10 15 mg/day, selenium 70 µg/day). Statistical analyses were performed using R (v4.3.3) and Python (v3.11.4). A p-value < 0.05 was considered significant.

Results: Median age of women was 33 (± 7) years. At baseline, women with autoimmune conditions had slightly higher median T-AOC (24.0 U/mL, IQR: 23.0–25.1) compared with women without autoimmune conditions (22.8 U/mL, IQR: 16.7–29.0), (p = 0.67; r = 0.12). Following antioxidant supplementation, T-AOC levels increased modestly in both subgroups. However, the median increase was approximately five-fold higher in women with autoimmune conditions (2.8 U/mL, IQR: 0.1–6.1) compared with women without autoimmune conditions (0.5 U/mL, IQR: –10.8–6.8), (p = 0.53; r = –0.18).

Subgroup analyses by specific comorbidities showed changes in T-AOC levels after supplementation in women with allergic rhinitis (22.82 → 9.72 U/mL), allergic conjunctivitis (31.56 → 9.72 U/mL), bronchial asthma (31.56 → 23.44 U/mL), hyperprolactinemia (20.13 → 9.06 U/mL), and hypothyroidism (24.32 → 14.66 U/mL). However, these differences were not statistically significant (p > 0.05), likely due to the small subgroup sizes and limited statistical power. Overall, antioxidant therapy produced modest improvements in systemic T-AOC regardless of autoimmune status or comorbidity profile.

Conclusions: Antioxidant supplementation appears to slightly enhance total antioxidant capacity in women with unexplained infertility, including those with autoimmune diseases or other chronic comorbidities. However, the observed effect remains modest and relatively consistent across subgroups, underscoring that antioxidant supplementation alone may be insufficient to counteract the complex oxidative mechanisms present in conditions associated with pronounced oxidative stress. Future studies with larger sample sizes would be necessary to increase statistical power and better clarify these associations.

Thyroid autoimmunity is more prevalent among women with infertility than in the general fertile population and has been associated with adverse reproductive outcomes, even in women with otherwise normal thyroid function. Thyroid peroxidase antibodies (TPOAb) are the most commonly measured marker of thyroid autoimmunity in clinical practice.

A recently proposed hypothesis suggests that thyroid antibodies may bind to the surface of the oocyte and interfere with fertilization. Based on this concept, it has been suggested that intracytoplasmic sperm injection (ICSI) could improve outcomes compared with conventional in vitro fertilization (IVF) in TPOAb-positive women by bypassing potential antibody-mediated interference with fertilization.

However, this hypothesis has not been evaluated using randomized data comparing IVF and ICSI in women without severe male factor infertility.

We therefore conducted a secondary analysis of the INVICSI randomized controlled trial to investigate whether TPOAb status modifies the effect of fertilization method on reproductive outcomes.

The INVICSI trial randomized 824 women undergoing their first assisted reproductive technology cycle without severe male factor infertility to either ICSI or conventional IVF. The present analysis will be performed in the per protocol population, including 388 women in the ICSI group and 378 in the IVF group. Thyroid function parameters, including thyroid-stimulating hormone (TSH) and TPOAb, were measured prior to treatment initiation.

The primary outcome is cumulative live birth rate per initiated treatment cycle. Secondary outcomes include fertilization rate and number of usable blastocysts. Interaction between TPOAb status and fertilization method (ICSI versus IVF) will be evaluated using regression models adjusting for relevant clinical covariates.

All data extraction and cohort definition have been completed, and statistical analyses are currently being finalized. The results of the interaction analysis will be presented at the meeting.

Recent evidence does not support routine progesterone luteal-phase support (LPS) in modified natural cycle frozen embryo transfer (mNC-FET), where human chorionic gonadotropin (hCG) trigger induces ovulation and corpus luteum formation, securing endogenous progesterone synthesis. However, identifying subgroups that may benefit from progesterone LPS could help optimise treatment outcomes and support personalised care. As women of advanced reproductive age or with low anti-Müllerian hormone (AMH) generally have poorer treatment outcomes, we investigated whether progesterone LPS improves reproductive outcomes in these groups.

Data from 601 women, collected between 2019 and 2024, were analysed in the as-treated population of a completed Danish multicentre randomised controlled trial investigating the effect of progesterone LPS on live birth rate (LBR) in mNC-FET.

Women aged 18-41 years undergoing mNC-FET with a single, autologous good-quality blastocyst were included from eight public fertility clinics in Denmark. Risk Differences (RD) with 95% Confidence Intervals (CI) were calculated for reproductive outcomes according to progesterone LPS, stratified by age (<37 years vs. ≥37 years) and AMH (≥6.29 pmol/L vs. <6.29 pmol/L). Effect modification by age and AMH as continuous variables was examined using logistic regression with interaction terms.

LBR did not differ with progesterone LPS use in either age group. Among women aged <37 years (n=456), live birth occurred in 35.7% with LPS compared to 36.3% without LPS (RD –0.6%, 95% CI: –13.0 to 11.7; p=0.922). Among women aged ≥37 years (n=145), live birth occurred in 29.2% with LPS compared to 21.9% without LPS (RD 7.2%, 95% CI: –12.7 to 26.5; p=0.346). Pregnancy loss rates (PLR) did not differ with LPS in either age group (<37 years: RD –0.7%, 95% CI: –10.1 to 8.7; p=0.897; ≥37 years: RD –3.8%, 95% CI: –22.2 to 15.0; p=0.686). Among women with AMH ≥6.29 pmol/L (n=504), live birth occurred in 34.7% with LPS and 31.6% without LPS (RD 3.1%, 95% CI: –8.5 to 14.5; p=0.508), with similar PLR (RD –2.3%, 95% CI: –11.6 to 7.2; p=0.560). In women with AMH <6.29 pmol/L (n=47), LBR was numerically lower with LPS than without LPS (20.7% vs. 44.4%; RD –23.8%, 95% CI: –56.4 to 13.8; p=0.108), and PLR higher (RD 9.6%, 95% CI: –23.0 to 35.3; p=0.692). The effect of LPS on live birth did not differ by age (p=0.497) or AMH (p=0.133).

Progesterone LPS did not increase live birth or reduce pregnancy loss across age or AMH groups and should not be used routinely.

Abstract

OBJECTIVE: To examine infant mortality after ART and IUI conception in singletons and multiples in the Nordic countries 1995–2023.

BACKGROUND: Medically assisted reproduction (MAR) includes assisted reproductive technologies (ART), intrauterine insemination (IUI) and ovulation induction (OI). Children conceived through ART have a higher risk of adverse perinatal outcomes, mainly due to a higher rate of multifetal pregnancies. Nevertheless, ART singletons have a higher risk of poor perinatal outcomes than naturally conceived (NC) singletons. Less is known about risks following IUI and OI.

METHODS: This register-based cohort study included all liveborn infants in Denmark (2006–2023), Finland (2004–2023), Norway (2003–2022) and Sweden (1995–2022). Individual-level data on birth year, mother’s age, residence, vital status and MAR treatments were linked. Conceptions were categorized as ART (including IVF and ICSI) and IUI+OI (including IUI, OI and IUI+OI) or NC, resulting in n=228,013 ART-conceived, n=84,563 IUI+OI-conceived and n=5,928,931 NC infants. Birth cohorts were categorized as 1995–2004, 2005–2014 and 2015–2023. Children were followed until death, migration, age one year, or end of follow-up 2022/2023. Mortality rates and hazard ratios adjusted for year, country and mother’s age (aHR) with 95% confidence intervals (CI) are reported.

RESULTS: ART-conceived infants constituted 85.8% singletons, 13.8% twins, and 0.3% higher-order multiples; corresponding rates were 86.7%, 12.7%, and 0.5% for IUI+OI, and 97.5%, 2.4%, and 0.0% for NC. The ART multiple rates declined from 31.5% (1995–2004) to 6.8% (2015–2023) but remained stable at ~12% after IUI+OI. Overall, infant mortality was 4.9/1000 after ART, 4.5/1000 after IUI+OI and 2.6/1000 after NC. Comparing ART to NC, the aHR was 2.55 (95% CI 2.23–2.93) in the first period and 1.51 (95% CI 1.36–1.67) in the last. For IUI+OI, the corresponding estimates were aHR 1.86 (95% CI 1.44–2.41) and 1.63 (95% CI 1.38–1.93). Among singletons, infant mortality was 3.3/1000 after ART, 2.4/1000 after IUI+OI and 2.3/1000 after NC. The risk was increased after ART (aHR 1.46, 95% CI 1.35–1.59) but not after IUI+OI (aHR 0.99, 95% CI 0.85–1.15). Among twins, infant mortality was 13.7/1000 after ART, 16.9/1000 after IUI+OI and 13.0/1000 after NC. The risk was not increased after ART (aHR 1.06, 95% CI 0.95–1.18) but slightly increased after IUI+OI (aHR 1.20, 95% CI 1.02–1.40).

CONCLUSION: Infant mortality was higher after ART and IUI+OI compared with NC children. Multifetal gestations remain a major determinant of infant mortality.

Background: Delayed family formation increases risk of infertility and involuntary childlessness. Fertility Assessment and Counselling (FAC) may assist informed reproductive decision-making. We compared live births among women attending a FAC Clinic and non-attending women in the general population.

Methods: Women attending the FAC Clinic 2011–2022 were linked to Danish population registers and age-matched 1:60 with non-attending women. From 2019 onward, eligibility was restricted to women <41 years, with no age limit before this date. Age-specific cross-sectional analyses estimated the proportion ever having a live birth and mean number of live births at ages 25–45 years, with equivalent analyses for MAR treatment use. Cumulative incidence functions and Cox Regression Models estimated the association between attendance and subsequent live birth, following women from entry until first live birth, migration, death, age 46 years, or December 31, 2023. Cumulative incidence functions were stratified by age (<25, 25–29, 30–34, 35–39, and 40–45 years), and Cox Regression Models was stratified by age <35 and ≥35 years.

Findings: We included 2726 attendees and 158,300 non-attendees (mean age 32.1 sd: 4.6). At entry, attendees were characterized by postponed family formation (nulliparous: 94.6% attendees vs. 48.9% non-attendees). Attendees seeking counseling younger than 35 years mirrored parenthood rates of non-attendees. After age 35 years the gap in live birth rates widened progressively, as did the use of MAR treatment, with 40.2% of attendees having received at least one MAR treatment by age 40 years and 51.4% by age 45 years, compared with 14.4% and 13.9% among non-attending women in comparable age groups. The three-year cumulative incidence of live birth ranged from 28.6% (40-45 years) to 56.3% (25-29 years) among attendees, versus 3.6% and 33.1% among non-attendees in comparable age groups, demonstrating expedited live birth among attendees after FAC. Differences were most pronounced among women aged 35 years and older, reflecting, on the one hand, postponed family formation among attendees and, on the other, already initiated or completed family formation among non-attendees of comparable age. Hazard Ratios (HR) supported increased differences in likelihood of live birth according to attendance with advanced age (adjusted HR <35 years: 1.6 (95%CI: 1.5, 1.7), ≥35 years: 2.7 (95%CI: 2.4, 2.9).

Interpretation: FAC may impact reproductive timing among women prone to delay childbearing. Intervention before age 35 years allows time for more complete family formation and may reduce reliance on MAR treatment, underscoring the public health potential of timely FAC.

Microdissection testicular sperm extraction (MD-TESE) is the most successful method of retrieving spermatozoa in severe cases of male infertility i.e. non-obstructive azoospermia (NOA). NFS recently organized a meeting for colleagues performing this procedure to ensure high quality treatment for this challenging condition in the Nordic countries (NC). A questionnaire of 40 questions has been formulated and circulated among the participating centers so that all professionals working in the field of reproductive medicine can be better informed about real-life availability and results of this treatment.

The first case of MD-TESE was done by professor Sønksen and Ohl in Denmark in 2006. Since then MD-TESE procedure has been started 2008 in Finland, 2013 in Sweden and 2016 in Norway. Most centers in NC, however, have started more recently. There is variation in techniques, equipment and co-ordination with the required ICSI fertilization, which is needed to reach pregnancy with the retrieved spermatozoa.

The initially included centers have performed a respectable number of MD-TESE: 438 in Turku, 365 in Livio, Gothenburg, over 200 in Copenhagen, 236 in Hausken klinik, and over 200 in Odense. The annual number of procedures varies between 20 and 35 in these centers. Overall sperm recovery rate (SRR) is 40-50 % in all included centers, which is reassuring in comparison to large international centers.

Men with Klinefelter syndrome are perhaps the best defined NOA patients and good candidates for MD-TESE to find spermatozoa. The SRR in this group was 55%, 42%, 35% and 40% in the Finnish, Danish, Norwegian and Swedish centers, respectively.

It is previously known that spermatozoa retrieved by MD-TESE produce good quality embryos and pregnancies in comparison to those achieved with spermatozoa from e.g. vasectomized men. The only exception appears to be the men with Y chromosome microdeletion AZFc, in which group more oocytes are required for good quality embryos and pregnancies.

In this abstract, we include initial results from the largest centers. We have distributed the questionnaire to all of the centers that perform MD-TESE in NC and all the responses will be included in detail in the presentation at the NFS 2026. According to this evaluation, the Nordic centers offer high quality treatment for men with NOA. It is important for all professionals that deal with fertility and reproduction to be aware of this effective and safe treatment of severe male infertility.

Introduction Asthenozoospermia is one of the manifestations of impaired male fertility and has been associated with low levels of the omega-3 fatty acid docosahexaenoic acid (DHA) in the sperm membrane. In humans, the DHA synthesis is ineffective and dietary intake of DHA is therefore necessary. A study was carried out where asthenozoospermic men received a high dosage of DHA for 20 weeks. The main aim of the project was to investigate the effects of long-term daily intake of 6 omega-3 EPAX 2050TG capsules (0.810 g eicosapentaenoic acid (EPA), 2.1g DHA and 22.8 mg vitamin E; Biocare Pronova a.s.) on the proportion of DHA in sperm membrane and total sperm motility.

Material and methods Ten asthenozoospermic men that sought help due to reduced fertility at the Department of Infertility, Landspítali-University Hospital completed a 30-week study. The participants provided blood and semen samples to provide a baseline before starting the daily omega-3 capsule intake, after 10 and 20 weeks of intake, and finally after a 10-week washout period. Participants had not used omega-3 fatty acid supplement two years prior to the study. DHA proportions in blood plasma, seminal plasma and sperm membrane were examined, and a semen analysis was performed.

Results At the beginning of the study the proportions of EPA and DHA in blood plasma indicated that the participants did not lack those omega-3 fatty acids from the diet. The omega-3 capsule intake had an effect only in two participants. Compared to the average of the 10 participants at baseline the DHA proportions in their seminal plasma (3.0% and 3.7 % vs. 4.6 ± 0.4 %), and sperm membranes (9.5% and 13.7 % vs. 23.5 ± 2.4 %). were well below the average. After 10 and 20 weeks of omega-3 intake the DHA proportions in their sperm membranes were higher than the average and remained higher after 10-week wash-out period (29.5% and 32.0 % vs. 25.0 ± 1.7 %). Their sperm motility also increased and after 10-week wash-out period their total sperm motility remained above average (40% and 50% vs.18.0 + 5.9%).

Conclusion The results indicate that a long-term daily omega-3 intake may improve a low DHA proportion in sperm membrane of asthenozoospermic men and total sperm motility. The results of this project may have implications for the treatment of a subgroup of men with impaired fertility.