Advanced age - a critical risk factor for recurrent miscarriage.

Recurrent spontaneous abortion (RSA) is a multifactorial disease that seriously affects womens physical and mental health. With the advent of efficient contraception, the trend for women towards later maternity until their thirties or even forties. Nevertheless, the risk of miscarriage is strongly related to maternal age. We performed a retrospective analysis to evaluate the etiology of RSA through age groups. The results demonstrated that intrauterine adhesions and ovarian dysfunction were responsible for increased miscarriages in older RSA patients. In conclusion, older women will bear a higher risk of miscarriage, mainly due to uterine adhesions or decreased ovarian function.

Single-Dose Versus Multiple-Dose GnRH Agonist for Luteal-Phase Support in Women Undergoing IVF/ICSI Cycles: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Although gonadotropin-releasing hormone (GnRH) agonist has been introduced as a beneficial luteal phase support (LPS), the optimal strategy of GnRH agonist remains unclear. This network meta-analysis was therefore performed to determine the comparative efficacy and safety of multiple-dose versus single-dose GnRH agonist protocol for LPS in patients undergoing IVF/ICSI cycles. Methods: We searched relevant studies in PubMed, Embase and the Cochrane Registry of Controlled Trials (CENTRAL) from their inception util to September 2021. Live birth, clinical pregnancy rate, multiple pregnancy rate, and clinical abortion rate was evaluated. Pairwise and network meta-analysis were conducted using RevMan and ADDIS based on random-effects model, respectively. Moreover, the prioritization of protocols based on ranking probabilities for different outcomes were performed. Results: Sixteen RCTs met our eligibility criteria. Pairwise meta-analysis showed that multiple-dose protocol of GnRH agonist was effective for increasing live birth rate (OR 1.80, 95% CI 1.15 to 2.83, p=0.01) and clinical pregnancy rate (OR 1.89, 95% CI 1.01 to 3.56, p=0.05) as well as decreasing clinical abortion rate (OR 0.55, 95% CI 0.34 to 0.90, p=0.02). Meanwhile, single-dose protocol of GnRH agonist was effective for increasing clinical pregnancy rate (OR 1.45, 95% CI 1.11 to 1.89, p=0.007) and multiple pregnancy rate (OR 2.55, 95% CI 1.12 to 5.78, p=0.03). However, network meta-analysis only confirmed that multiple-dose protocol of GnRH agonist was the best efficacious strategy for live birth rate (OR 2.04, 95% CrI 1.19 to 3.93) and clinical pregnancy rate (OR 2.10, 95% CrI 1.26 to 3.54). Conclusion: Based on the results of NMA, multiple-dose protocol may be the optimal strategy for patients undergoing IVF/ICSI cycles owing to its advantage in increasing live birth and clinical pregnancy rate. Moreover, single-dose protocol may be the optimal strategy for improving multiple pregnancy rate. However, with the limitations, more RCTs are required to confirm our findings.

Factors affecting mode of delivery in women of advanced maternal age.

With the implementation of the two-child policy in China, an increased number of women of advanced maternal age (AMA) have been giving birth. Formulating evidence-based guidance for the clinical management of this population is crucial. This retrospective study aimed to explore factors influencing the mode of delivery in women of AMA. Data on 350 women of AMA who delivered at Shanghai Putuo Maternity & Infant Health Hospital from January to June of 2016 were collected. Results indicated that most (114/134, 85%) of the multiparae chose delivery via cesarean section (CS) because of uterine scarring. There were significant differences in the body mass index (BMI) before pregnancy, BMI at delivery, gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and placenta previa between the CS and vaginal delivery groups (P < 0.05 for all). The current results suggest that vaginal delivery is recommended for the first delivery whenever reasonable. Moreover, management of metabolic disorders during pregnancy is essential to effectively reduce the rate of CS among women of AMA.

Detection of chromosome abnormalities using current noninvasive prenatal testing: A multi-center comparative study.

Noninvasive prenatal testing (NIPT) is increasingly recognized and utilized in the antenatal care field. In the current study, we aimed to evaluate the clinical application and compare test outcomes of two generations of currently used NIPT techniques for detecting fetal chromosome abnormalities in a high-risk prenatal population. A total of 7,252 pregnant women were included from twenty-one hospitals from January 2015 to September 2017. A maternal blood sample of each participant was collected for fetal DNA sequencing. Group I received a first generation NIPT sequencing technique to detect chromosome aneuploidies, and Group II received a second generation NIPT sequencing technique to detect subchromosome abnormalities. An abnormal NIPT result was reported in 0.90% (44/4,868) of the women in Group I and 2.68% (64/2,384) in Group II. In Group I, seventeen (17/37, 45.95%) women with suspected fetal aneuploidy received amniocentesis, which confirmed 100% (10/10) of positive trisomy 21 samples, 100% (1/1) of trisomy 18, 100% (1/1) of sex chromosome abnormality, 0% (0/2) of trisomy 16, 0% (0/2) of trisomy 13, and 0% (0/1) of trisomy 20 and 13. In Group II, aneuploidy accounted for 46.88% (30/64) of the abnormal results. Five underwent amniocentesis and three had an abnormal result, including two cases of trisomy 21 and one case of chromosome 5p deletion syndrome. Whereas one case of 46,XN,del(16q11.2-q22.3) and another case of 46,XN,dup(Xp22.31) were considered as normal. NIPT is a quick and reliable screening method for detecting fetal chromosome aneuploidies and subchromosome deletions/duplications. Challenges remain for the comprehensive clinical application of NIPT.

The pregnancy outcomes of intrauterine insemination with husband's sperm in natural cycles versus ovulation stimulated cycles: A retrospective study.

To compare the clinical outcomes of intrauterine insemination (IUI) with or without ovulation induction (OI), IUI cycles from January 2008 to December 2017 in Zhoushan Maternity and Child Healthcare Hospital were included, consisting of 455 natural cycles and 536 OI cycles. The overall clinical pregnancy rate did not differ between the two groups (P > 0.05). Stratified by OI medications such as clomiphene (CC), human menopausal gonadotropin (HMG) and follicle stimulating hormone (FSH), the pregnancy rates in HMG, CC, CC+HMG, and FSH/FSH+HMG groups were 11.70%, 13.58%, 15.95%, and 13.46%, respectively, but the difference was not significant compared with natural cycles (P > 0.05). Stratified by infertility etiology, the pregnancy rate was significantly higher in stimulated cycles than natural cycles with ovulation disorders (P < 0.01) and unexplained factors (P < 0.01) while it was significantly lower regarding cervical factors (P < 0.01), endometriosis (P < 0.05), male factor (P < 0.01) and other female factors. There was no strong difference of pregnancy rate for biparental causes (P > 0.05). Stratified by age category, women over 35 had higher pregnancy rate in stimulated cycles compared with natural cycles (18.75 vs. 12.24%; P < 0.05), while women under 35 had no significant difference of pregnancy rate between the two groups (13.65 vs 13.05%; P > 0.05). However, there was no significant difference between each ovarian stimulation group and natural cycle group regardless of the infertility causes or age categories. To conclude, IUI-OI could achieve a higher overall pregnancy rate for women over 35 and infertile patients with ovulation disorders and unexplained factors.

Low-density lipoprotein receptor deficiency impaired mice osteoblastogenesis in vitro.

Postmenopausal osteoporosis affected most elderly women with co-existence of lipid and bone metabolism disorders. However, the cellular and molecular mechanisms underlying the parallel progression and cross-talk of these systems remained unclear. In the present study, low-density lipoprotein receptor knockout (LDLR-/-) mice were chosen to elucidate the effect of LDLR in regulating the differentiation of osteoblasts, which were responsible for bone formation and modulation of osteoclastogenesis. Primary osteoblasts were isolated from the calvarium of newborn LDLR-/- or wild-type mice followed by osteoblastic differentiation culture in vitro. Alkaline phosphatase activity was significantly decreased in LDLR-/- osteoblasts compared to wild-type controls, combined with calcium deposit formation delay, implying impaired osteoblastogenesis in vitro. Consistent with these findings, the expression of runt-related transcription factor 2 (Runx2) was decreased 3 days after differentiation in LDLR-/- osteoblasts compared to wild-type controls. Moreover, the expression of Osterix was decreased 7 days after differentiation in LDLR-/- osteoblasts compared to wild-type controls, later than Runx2.However, the osteoclastogenesis modulation role of osteoblasts was unaffected by the LDLR deficiency, evidenced by the same level of osteoprotegerin (OPG)/receptor activator of nuclear factor-κ B ligand (RANKL) axis between LDLR-/- and wild-type control osteoblasts. Our results provide a novel insight into the role of LDLR during osteoblastic differentiation and improve understanding of cross-talk between bone and lipid metabolisms.