Paternal age does not jeopardize the live birth rate and perinatal outcomes after in vitro fertilization: an analysis based on 56,113 frozen embryo transfer cycles.

BACKGROUND: The global trend of delaying childbearing has led to an increasing number of couples seeking in vitro fertilization. The adverse effects of advanced maternal age on pregnancy and perinatal outcomes are well documented, regardless of the conception method. In addition, advanced paternal age may contribute to poor reproductive potential because of high levels of sperm DNA fragmentation. However, it remains challenging to guide older men regarding the effect of paternal age on pregnancy and birth outcomes in the field of assisted reproduction. OBJECTIVE: This study aimed to investigate the association of paternal age with live birth and perinatal outcomes following in vitro fertilization-frozen embryo transfer. STUDY DESIGN: A retrospective study was performed at a university-affiliated fertility center, involving women who were younger than 36 years and had undergone frozen embryo transfer from January 2011 to June 2021. Subjects were categorized into 6 groups based on paternal age: <25, 25 to 29, 30 to 34, 35 to 39, 40 to 44, and ≥45 years. A generalized estimating equation logistic regression model was used to account for the clustered nature of data and to adjust for confounders. Paternal age between 25 and 29 years served as the reference group in the logistic regression models. RESULTS: A total of 56,113 cycles who met the inclusion criteria were included in the final analysis. On unadjusted analyses, the reproductive outcome parameters showed a considerable decline with increasing male age. The live birth rate decreased from 47.9% for men aged 25 to 29 years to 40.3% among men aged ≥40 years. Similarly, the clinical pregnancy rate decreased from 54.4% in the reference group to 47.8% in the ≥40 years age group. Conversely, the miscarriage rate increased as male age increased, from 10.2% among men aged 25 to 29 years to 13.5% among men aged ≥45 years. However, the differences in the reproductive outcomes mentioned above were no longer significant in the multivariable models. Compared with the younger controls, advanced paternal age was not associated with a lower chance of live birth (males aged 40-44 years: adjusted odds ratio, 0.94; 95% confidence interval, 0.85-1.04; males aged ≥45 years: adjusted odds ratio, 0.93; 95% confidence interval, 0.79-1.10). In addition, the rates of clinical pregnancy (males aged 40-44 years: adjusted odds ratio, 0.95; 95% confidence interval, 0.85-1.05; males aged ≥45 years: adjusted odds ratio, 0.94; 95% confidence interval, 0.79-1.12) and miscarriage (males aged 40-44 years: adjusted odds ratio, 1.05; 95% confidence interval, 0.85-1.31; males aged ≥45 years: adjusted odds ratio, 1.07; 95% confidence interval, 0.77-1.50) were comparable between the reference and advanced paternal age groups. Furthermore, men in the youngest age group (<25 years) did not have worse pregnancy outcomes than those in the reference group. Regarding perinatal outcomes, there was no difference among the study cohorts in terms of preterm birth, low birthweight, macrosomia, small for gestational age, and large for gestational age, both in the unadjusted and confounder-adjusted models. CONCLUSION: This study did not demonstrate a significant association between paternal age and live birth and perinatal outcomes after in vitro fertilization-frozen embryo transfer when the female partners were younger than 36 years. With the global trend toward delaying childbirth, our findings provide useful information for counseling patients that increasing paternal age may not adversely affect pregnancy and perinatal outcomes in assisted reproduction.

GM-CSF improves endometrial receptivity in a thin endometrium rat model by upregulating HOXA10.

Endometrial receptivity is a prerequisite for the success of assisted reproduction. Patients with a consistently thin endometrium frequently fail to conceive, owing to low endometrial receptivity, and there are currently very few therapeutic options available. Our previous study demonstrated that intrauterine granulocyte-macrophage colony-stimulating factor (GM-CSF) administration resulted in a significant improvement in clinical pregnancy and implantation rates and was an effective means of increasing endometrial thickness on the day of embryo transfer in patients with thin endometrium. In order to explore the underlying process, an animal model with a thin endometrium was constructed, the homeobox A10 gene (HOXA10) was downregulated, and an inhibitor of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway (MAPK/ERK) was employed. Our findings strongly suggest a marked decrease in GM-CSF levels in the thin endometrial rat model, and the suppression of HOXA10 impeded the therapeutic efficacy of GM-CSF in this model. Moreover, we showed that GM-CSF significantly increases endometrial receptivity in the rat model and upregulates HOXA10 via the MAPK/ERK pathway. Our data provide new molecular insights into the mechanisms underlying formation of a thin endometrium and highlight a novel, potential clinical treatment strategy as well as directions for further research.

Comparable Pregnancy Loss and Neonatal Birthweights in Frozen Embryo Transfer Cycles Using Vitrified Embryos from Progestin-Primed Ovarian Stimulation and GnRH Analogue Protocols: A Retrospective Cohort Study.

Background: The potential correlation between progestin-primed ovarian stimulation (PPOS) and the risk of compromised embryo competence still lacks sound evidence. Methods: A large retrospective cohort study was used to compare the incidence of pregnancy loss and neonatal birthweights in frozen embryo transfer (FET) cycles using embryos from PPOS and GnRH analogue protocols. Propensity matched scores were used to balance the baseline confounders. Results: A total of 5744 matched cycles with positive hCG test were included to compare the pregnancy outcomes. The incidence of pregnancy loss was similar between PPOS and GnRH analogue groups (19.2% vs. 18.4%, RR 1.02 (0.97, 1.06), p > 0.05). The neonatal birthweights were comparable between two groups, respectively, for singleton births (3337.0 ± 494.4 g vs. 3346.0 ± 515.5 g) and in twin births (2496.8 ± 429.2 g vs. 2533.2 ± 424.2 g) (p > 0.05). Conclusions: The similar incidence of pregnancy loss and neonatal birthweights in FET cycles using embryos from PPOS provided us with a more complete picture about the safety of PPOS.