Objective: The objective ofthis study was to assess the association between thyroid hormone (TH) levels in follicular fluid (FF) and serum and to determine whether THs impact assisted reproductive technology (ART) outcomes.Methods: This study enrolled 299 women undergoing ART. Blood samples were drawn on the day of human chorionic gonadotrophin (HCG) administrationand analysed for thyroid-stimulating hormone (TSH), thyroxine(T4), triiodothyronine(T3),free T4 (fT4),free T3(fT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) levels. FF was obtained on the oocyte pick up (OPU) day and analysed forTSH, T4, T3, fT4, fT3, TPOAb, TgAb and estradiol levels.Results: (1) There were significant positive correlations between serum and FF TH and thyroid autoantibody levels. Statistically significant differences were discovered in serum and FF levels of TSH (p ≤ 0.001), T4 (p ≤ 0.001), T3 (p ≤ 0.001), TPOAbs (p ≤ 0.001) and TGAbs (p = 0.021).(2) Serum T4 levels [121.9(104.8,140.8) vs 114.1(98.6,130.6) nmol/l,p = 0.026], serum fT4 levels[(19.0(17.7,21.8) vs 18.6(17.0,20.1) pmol/l,p = 0.026], serum T4/T3 ratios [62.5 (55.7, 66.2) vs 59.4 (53.4, 64.9),p = 0.029], FF fT4 levels [19.0(17.5,21.3) vs 18.1(16.8,19.9) pmol/l,p = 0.009] and FF T4/T3 ratios [52.6 (46.4, 57.3) vs 50.0 (43.7, 53.1),p = 0.004] were significantly higher in the successful pregnancy group than the implantation failure group.(3) Spearman’s rank correlation analysis revealed positive associations of both the FF T4/T3 ratio and serum TSH levels with the numbers of retrieved oocytes (total or MII) and embryos (fertilized, cleavage, and good quality).Conclusions: TH levels in FF are strongly correlated with those in serum on the HCG day, and THs on the HCG day may affect ART outcomes.

Despite numerous studies indicating an imperative role of vitamin D for reproduction, the importance of vitamin D supplementation on in vitro fertilization (IVF) outcomes remains controversial. We therefore performed this meta-analysis to investigate the IVF outcomes of vitamin D supplementation in infertile women with vitamin D deficiency. We systematically searched PubMed, Embase and the Cochrane library for identifying all relevant studies published before August 2021. Pregnancy rate was defined as the primary outcome while good quality embryo, fertilization rate, ongoing pregnancy, and miscarriage were secondary outcomes. We used Review Manager 5.3 (RevMan) to conduct meta-analysis and examined the robustness of the primary outcome by trial sequential analysis. Five studies were included in the final analysis and it suggested that vitamin D supplementation was associated with improved chemical pregnancy rate (risk ratio [RR] = 1.53, 95% confidence interval [CI] = 1.06 to 2.20, p = 0.02) but not benefited in improving clinical pregnancy rate (RR = 1.34, 95% CI = 0.81 to 2.24, p = 0.25) and all secondary outcomes. Trial sequential analysis suggested further studies are needed to confirm this conclusion. We concluded that vitamin D supplementation should be prescribed to improve chemical pregnancy in infertile women with vitamin D deficiency and more studies are required to further confirm this finding.

Preimplantation genetic testing (PGT) is widely used in assisted reproduction to assess the genetic status of embryos. However, increasing evidence suggests that the trophectoderm (TE) may not fully reflect the genetic status of the inner cell mass (ICM), raising controversy about the accuracy of TE biopsy. Research in recent years has focused on cell-free DNA (cfDNA) found in blastocoel fluid (BF) and spent culture medium (SCM), as these may contain genetic information from both the TE and ICM. Therefore, further research and validation are essential to determine the reliability and clinical applicability of these diagnostic methods in PGT. Relevant studies published between January 2000 and August 2024 were identified through PubMed and Web of Science (WOS). Risk assessment and publication bias were evaluated using QUADAS-2 and Deek’s test. Diagnostic meta-analysis was performed using a bivariate model to combine sensitivity and specificity, with results visualized through forest plots and summary receiver operating characteristic (SROC) curves. Out of 6,407 initially screened records, 36 studies involving 4,230 embryos were included. TE biopsy was identified as the best method for diagnosing the genetic status of embryos (sensitivity: 0.839; specificity: 0.791, AUC: 0.878), while SCM had slightly lower accuracy (sensitivity: 0.874; specificity: 0.719, AUC: 0.869). The effectiveness of BF (AUC: 0.656) was significantly lower than that of TE biopsy and SCM. Despite this, TE biopsy has not yet achieved ideal diagnostic performance. However, TE biopsies demonstrate a high level of accuracy in diagnosing PGT-SR (AUC: 0.957). Additionally, multiple TE biopsies (AUC: 0.966) or TE biopsies combined with SCM (AUC: 0.927) can enhance the diagnostic efficiency of PGT. The findings of this study suggest that TE biopsy has yet to achieve optimal diagnostic accuracy, which may result in a significant number of missed embryo diagnoses and misdiagnoses. Our results confirm that SCM has the potential to serve as a supplementary test. Employing multiple biopsies or combining TE with SCM may enhance diagnostic efficiency and yield optimal results.

Background: To explore whether endometrial receptivity is determined by osteopontin (OPN) and integrin αvβ3 expression in women with elevated serum progesterone (P) and/or oestradiol (E₂) who are undergoing in vitro fertilisation (IVF). Methods: According to serum hormone levels on the day of HCG administration, 33 infertile women were divided into 3 groups: the high E₂, high P, and high E₂ and P groups. The control group included 11 fertile, healthy women. Endometrial biopsy was performed on ovulation day + 7 to + 8 for all study participants, and the mRNA and protein expression levels of OPN and integrin αvβ3 were analyzed. Result: No statistically significant differences regarding OPN and integrin αvβ3 expression were found between infertile patients in the high P, high E₂, high E₂ and P and control groups. There was no significant correlation between OPN and integrin αvβ3 staining intensity during the implantation window biopsy in any of the groups studied. Conclusion: Endometrial OPN and integrant αvβ3 expression/co-expression is not impaired during the window of implantation in patients with high P, high E₂, or high E₂ and P levels. The clinical value of assessing endometrial receptivity with OPN and integrin αvβ3 seems to be uncertain. Hintergrund: Ziel der Studie war es zu untersuchen, ob die Rezeptivität des Endometriums von der Osteopontin- (OPN-) und Integrin αvβ3-Expression bestimmt wird bei Frauen mit erhöhten Progesteron-(P-) und/oder Östradiol-(E₂-)Konzentrationen, die sich einer In-vitro-Fertilisation (IVF) unterziehen. Methoden: Basierend auf der Messung des Hormonspiegels am Tage der hCG-Gabe wurden 33 unfruchtbare Frauen in 3 Gruppen wie folgt eingeteilt: hoher E₂-, hoher P- und hoher E₂- und P-Spiegel. Die Kontrollgruppe bestand aus 11 gesunden fruchtbaren Frauen. Eine Biopsie des Endometriums wurde am 7. oder 8. Tag nach der Ovulation bei allen Studienteilnehmende durchgeführt, und die mRNA und Protein-Expressionsspiegeln von OPN und Integrin αvβ3 wurden ausgewertet. Ergebnisse: Bezüglich der Exprimierung von OPN und Integrin αvβ3 fanden sich keine statistisch signifikanten Unterschiede zwischen den unfruchtbaren Patientinnen in den Gruppen mit hohen P- oder E₂-Spiegeln, der Gruppe mit hohen E₂- und P-Spiegeln und der Kontrollgruppe. In den entnommenen Biopsaten konnte bei keiner der untersuchten Gruppen eine signifikante Korrelation zwischen der Färbungsintensität für OPN und Integrin αvβ3 und dem Implantationsfenster festgestellt werden. Schlussfolgerungen: Die Expression und Koexpression von OPN und Integrin αvβ3 im Endometrium sind während des Implantationsfensters nicht beeinträchtigt bei Patientinnen mit hohen P- oder E₂-Spiegeln bzw. hohen E₂- und P-Spiegeln. Der klinische Nutzen einer auf die Messung der Expression von OPN- und Integrin αvβ3 basierenden Bewertung der Rezeptivität des Endometriums scheint fraglich zu sein. ^* Co-author: Zhenlin He and Yanping Ma are joint first authors of this article.

Objective: To assess the impact of serum luteinizing hormone (LH) levels on the day of initiation of controlled ovarian stimulation (COS) after pituitary suppression on early pregnancy loss and assisted reproductive technology (ART) outcomes.Design: Retrospective cohort study.Setting: University-affiliated hospital.Patients: A total of 9540 normogonadotrophic patients were treated with a GnRH agonist for in vitro fertilization (IVF). Based on the serum concentration of LH on the COS initiation day, patients were divided into low (<1 mIU/mL, n=2838), medium (1–1.49 mIU/mL, n=3357), or high (≥1.5 mIU/mL, n=3345) LH groups and received either fresh embryo transfer (ET) or frozen ET (women with high ovarian response, insufficient endometrial thickness, or requesting frozen ET). A total of 6279 cycles were fresh ET (1960, 2222, and 2097 in the low, medium, and high LH groups, respectively).Intervention(s): During IVF/ICSI, a GnRH agonist was used to suppress pituitary function in the midluteal phase or follicular phase, and then gonadotropin was used to induce COS.Main Outcome Measure(s): The early pregnancy loss rate (ePLR) and live-birth rate (LBR) for fresh ET, as well as the cumulative ePLR and LBR for the entire ovarian stimulation cycle, were compared.Results: In the fresh ET cycles, the high, medium and low LH groups had an ePLR of 8.6%, 11.9% and 12.5%, respectively, and LBR of 42.1%, 37.9% and 37.5%, respectively. There were no significant differences in terms of clinical pregnancy rate (CPR), late pregnancy loss rate (lPLR), and ectopic pregnancy rate (EPR) among the three LH groups. For the entire ovarian stimulation cycle, the high LH group had a greater number of retrieved oocytes compared with the low and medium LH groups. Among the groups of high, medium and low LH, the cumulative CPR were 72.8%, 69.8% and 68.8%, respectively, and the cumulative LBR were 63.4%, 60.4% and 58.5%, respectively. There were no significant differences in the cumulative ePLR, lPLR, or EPR. After multivariable logistic regression, compared with the high LH group, the adjusted odds ratio of early pregnancy loss in the low and medium LH group were 1.429 (1.065-1.919, P = 0.018) and 1.389 (1.041-1.853, P = 0.026).Conclusions: After pituitary suppression by a GnRH-agonist during IVF, a low LH level (<1.5 mIU/mL) on the COS initiation day was associated with adverse ART outcomes—including fewer oocytes, higher ePLR and lower LBR in fresh ET—and lower cumulative CPR and LBR in the entire ovarian-stimulation cycle. And LH on the COS initiation day was an independent factor affecting ePLR after multivariate regression.

Background: To assess the impact of the luteinizing hormone level on ovulation trigger day (LHOTD) on in vitro fertilization (IVF) outcomes in gonadotropin-releasing hormone (GnRH) agonist and antagonist regimens during fresh embryo transfer cycles. Methods: A stepwise, progressive multivariate regression model was introduced to assess the effect of the LHOTD on clinical pregnancy and live birth rates. Mantel‒Haenszel stratification analysis was used to examine the association between the LHOTD and clinical outcomes with the antagonist regimen. Results: The LHOTD had different distributions in the agonist and antagonist regimens. The cycles were assigned into three LHOTD tertile groups. In the agonist regimen, compared with the 1^st tertile (T1), in the 2^nd (T2) and 3^rd (T3) tertiles, the adjusted odds ratios (ORs) (95% confidence intervals [CIs], P value) were 1.187 (1.047–1.345, 0.007) and 1.420 (1.252–1.610, < 0.001) for clinical pregnancy, respectively, and 1.149 (1.009–1.309, 0.036) and 1.476 (1.296–1.681, < 0.001) for live birth. In the antagonist regimen, there was no significant difference in clinical pregnancy and live birth rates among the tertiles. However, in the stratified group of patients aged less than 35 years, the ORs (95% CIs, P value) of T2 and T3 were 1.316 (1.051–1.648, 0.017) and 1.354 (1.077–1.703, 0.009) for clinical pregnancy, respectively, and 1.275 (1.008–1.611, 0.043) and1.269 (0.999–1.611, 0.051) for live birth. Moreover, there was a discrepancy in the results among the subdivided LHOTD T1 groups adopting the antagonist regimen. Compared with that of the < 1.06 mIU/mL subgroup, the ORs (95% CIs, P value) of the > 1.5 mIU/mL subgroup were 1.693 (1.194–2.400, 0.003) for clinical pregnancy and 1.532 (1.057–2.220, 0.024) for live birth after eliminating potential confounders. Conclusions: The LHOTD was profoundly suppressed in the agonist regimen, and its level was positively correlated with clinical pregnancy and live birth rates. In contrast, in the flexible antagonist regimen, the LHOTD was significantly higher than that in the agonist regimen and did not correlate with the outcome, except for women in the nonadvanced age group and those with an excessively suppressed LHOTD. Further investigation is required to determine the rationale for these findings.