The likelihood of a healthy live birth after frozen embryo transfer with endometrium prepared by natural ovulation regimen vs programmed regimen: a propensity-score matching study.

BACKGROUND: The number of frozen embryo transfer cycles is increasing, but the optimal method of endometrial preparation for frozen embryo transfer remains controversial. Few studies have investigated the healthy live birth outcome after the natural ovulation regimen vs the programmed regimen. OBJECTIVE: This study aimed to explore whether the likelihood of a healthy live birth after frozen embryo transfer differs between the natural ovulation regimen and the programmed regimen. STUDY DESIGN: We conducted a retrospective cohort study including 7824 ovulatory women who underwent the first frozen embryo transfer cycle of single-blastocyst transfer with endometrial preparation by natural ovulation regimen vs programmed regimen, between June 2017 and June 2021. Propensity score matching was used to control for confounding variables in a 1:1 ratio. The primary outcome was healthy live birth, defined as birth of a live, singleton infant born at term, with an appropriate birthweight for gestational age. RESULTS: The natural ovulation regimen resulted in a higher probability of achieving healthy live birth compared with the programmed regimen (35.8% vs 30.6%; P<.0001). In addition, a higher rate of singleton live birth was observed after the natural ovulation regimen relative to the programmed regimen (49.6% vs 45.7%; P=.003). Women with the natural ovulation regimen were also less likely to experience clinical pregnancy loss (16.0% vs 19.7%; P=.005) and hypertensive disorders of pregnancy (3.9% vs 6.0%; P=.004) compared with women with the programmed regimen. Singletons born after the programmed regimen had greater mean birthweight (3441.50±539.97 vs 3394.96±503.87; P=.020) and higher risk of being large for gestational age (23.3% vs 18.7%; P=.003) than those conceived after the natural ovulation regimen. CONCLUSION: The natural ovulation regimen may be superior to the programmed regimen with regard to higher likelihood of healthy live birth and lower risk of pregnancy loss and maternal hypertensive disorders of pregnancy.

Is artificial endometrial preparation more associated with early-onset or late-onset preeclampsia after frozen embryo transfer?

PURPOSE: To explore whether the risks of early- or late-onset preeclampsia vary among frozen embryo transfer (FET) with different regimens for endometrial preparation and fresh embryo transfer (FreET). METHODS: We retrospectively included a total of 24129 women who achieved singleton delivery during their first cycles of in vitro fertilization (IVF) between January 2012 and March 2020. The risks of early- and late-onset preeclampsia after FET with endometrial preparation by natural ovulation cycles (FET-NC) or by artificial cycles (FET-AC) were compared to that after FreET. RESULTS: After adjustment via multivariable logistic regression, the total risk of preeclampsia was higher in the FET-AC group compared to the FreET group [2.2% vs. 0.9%; adjusted odds ratio (aOR): 2.00; 95% confidence interval (CI): 1.45-2.76] and FET-NC group (2.2% vs. 0.9%; aOR: 2.17; 95% CI: 1.59-2.96).When stratified by the gestational age at delivery based on < 34 weeks or ≥ 34 weeks, the risk of late-onset preeclampsia remained higher in the FET-AC group than that in the and FreET group (1.8% vs. 0.6%; aOR: 2.56; 95% CI: 1.83-3.58) and the FET-NC group (1.8% vs. 0.6%; aOR: 2.63; 95% CI: 1.86-3.73). We did not find a statistically significant difference in the risk of early-onset preeclampsia among the three groups. CONCLUSIONS: An artificial regimen for endometrial preparation was more associated with an increased risk of late-onset preeclampsia after FET. Given that FET-AC is widely used in clinical practice, the potential maternal risk factors for late-onset preeclampsia when using the FET-AC regimen should be further explored, considering the maternal origin of late-onset preeclampsia.

ANGPTL4 inhibits granulosa cell proliferation in polycystic ovary syndrome by EGFR/JAK1/STAT3-mediated induction of p21.

Polycystic ovary syndrome (PCOS) is one of the most common, heterogenous endocrine disorders and is the leading cause of ovulatory obstacle associated with abnormal folliculogenesis. Dysfunction of ovarian granulosa cells (GCs) is recognized as a major factor that underlies abnormal follicle maturation. Angiopoietin-like 4 (ANGPTL4) expression in GCs differs between patients with and without PCOS. However, the role and mechanism of ANGPTL4 in impaired follicular development are still poorly understood. Here, the case-control study was designed to investigate the predictive value of ANGPTL4 in PCOS while cell experiments in vitro were set for mechanism research. Results found that ANGPTL4 levels in serum and in follicular fluid, and its expression in GCs, were upregulated in patients with PCOS. In KGN and SVOG cells, upregulation of ANGPTL4 inhibited the proliferation of GCs by blocking G1/S cell cycle progression, as well as the molecular activation of the EGFR/JAK1/STAT3 cascade. Moreover, the STAT3-dependent CDKN1A(p21) promoter increased CDKN1A transcription, resulting in remarkable suppression effect on GCs. Together, our results demonstrated that overexpression of ANGPTL4 inhibited the proliferation of GCs through EGFR/JAK1/STAT3-mediated induction of p21, thus providing a novel epigenetic mechanism for the pathogenesis of PCOS.