Single versus double blastocyst transfer in first and second frozen-thawed embryo transfer cycle in advance-aged women: a two-center retrospective cohort study.

BACKGROUND: The present evidence is deficient for the trade-offs between the pros and cons of single blastocyst transfer (SBT) versus double blastocyst transfer (DBT) in frozen-thawed embryo transfer cycles for women in advanced reproductive age, especially in the second cycle. The current study aimed to investigate the impact of transferred blastocyst numbers on pregnancy outcomes in the first and second embryo transfer for women ≥ 35 years. METHODS: This was a retrospective cohort study including 1284 frozen-thawed blastocyst transfer (FBT) cycles from two reproductive centers. We analyzed the pregnancy outcomes after SBT and DBT in the first and second FBT cycles. Moreover, stratified analysis was conducted by maternal age. RESULTS: In the first FBT cycle, the LBR was higher in the DBT group than that in the SBT group [52.3% vs. 33.9%; adjusted odds ratio (aOR), 1.65; 95% confidence interval (CI), 1.26-2.15, P < 0.001]. However, the LBR of the DBT group showed no remarkable difference compared with that of the SBT group in the second cycle of FBT (44.3% vs. 33.3%; aOR, 1.30; 95% CI, 0.81-2.08; P = 0.271). Furthermore, stratified analysis by age showed a higher LBR for the DBT group than the SBT group in patients aged 38-42 years (43.1% vs. 33.9%; aOR, 2.27; 95% CI, 1.05-4.90; P = 0.036). CONCLUSIONS: The present study demonstrated that the SBT regimen is a better choice for both, the first and second frozen-thawed embryo transfer cycles, for women aged 35-37 years. Additionally, the DBT regimen is still recommended to achieve a high LBR in women aged 38-42 years in the second FBT cycle. These findings may be beneficial for deciding the embryo transfer regimens in women of advanced reproductive age.

Trophectoderm biopsy is associated with adverse obstetric outcomes rather than neonatal outcomes.

BACKGROUND: With the wide application of preimplantation genetic testing (PGT) with trophectoderm (TE) biopsy, the safety of PGT has always been a concern. Since TE subsequently forms the placenta, it is speculated that the removal of these cells was associated with adverse obstetrical or neonatal outcomes after single frozen-thawed blastocyst transfer (FBT). Previous studies report contradictory findings with respect to TE biopsy and obstetric and neonatal outcomes. METHODS: We conducted a retrospective cohort study including 720 patients with singleton pregnancies from single FBT cycles who delivered at the same university-affiliated hospital between January 2019 and March 2022. The cohorts were divided into two groups: the PGT group (blastocysts with TE biopsy, n = 223) and the control group (blastocysts without biopsy, n = 497). The PGT group was matched with the control group by propensity score matching (PSM) analysis at a ratio of 1:2. The enrolled sample sizes in the two groups were 215 and 385, respectively. RESULTS: Patient demographic characteristics were comparable between the groups after PSM except for the proportion of recurrent pregnancy loss, which was significantly higher in the PGT cohort (31.2 vs. 4.2%, P < 0.001). Patients in the PGT group had significantly higher rates of gestational hypertension (6.0 vs. 2.6%, adjusted odds ratio (aOR) 2.91, 95% confidence interval (CI) 1.18-7.18, P = 0.020) and abnormal umbilical cord (13.0 vs. 7.8%, aOR 1.94, 95% CI 1.08-3.48, P = 0.026). However, the occurrence of premature rupture of membranes (PROM) (12.1 vs. 19.7%, aOR 0.59, 95% CI 0.35-0.99, P = 0.047) was significantly lower in biopsied blastocysts than in unbiopsied embryos. There were no significant differences in regard to other obstetric and neonatal outcomes between the two groups. CONCLUSIONS: Trophectoderm biopsy is a safe approach, as the neonatal outcomes from biopsied and unbiopsied embryos were comparable. Furthermore, PGT is associated with higher risks of gestational hypertension and abnormal umbilical cord but may have a protective effect on PROM.

Effect of unplanned spontaneous follicular growth and ovulation on pregnancy outcomes in planned artificial frozen embryo transfer cycles: a propensity score matching study.

STUDY QUESTION: Does unplanned spontaneous follicular growth and ovulation affect clinical outcomes after planned artificial frozen-thawed embryo transfer (AC-FET) cycles? SUMMARY ANSWER: AC-FET and spontaneous follicular growth and ovulation events resulted in notably better pregnancy outcomes with a significantly higher implantation rate (IR), clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR) and live birth rate (LBR) and a significantly lower miscarriage rate. WHAT IS KNOWN ALREADY: The AC-FET protocol without GnRH agonist administration is associated with a low incidence of follicular growth and ovulation. In the literature, authors often refer to these types of cycles with concern due to possibly impaired FET outcomes. However, the real impact of such cycles has yet to be elucidated due to the lack of existing data. STUDY DESIGN, SIZE, DURATION: This was a retrospective clinical study involving 2256 AC-FET cycles conducted between January 2017 and August 2019. Propensity score (PS) matching was used to control for confounding variables. PARTICIPANTS/MATERIALS, SETTING, METHODS: Subjects were divided into two groups: a study group: cycles with spontaneous follicular growth and ovulation (the maximum diameter of follicles in any ovary was ≥14 mm and ovulation was confirmed by consecutive ultrasound examinations) and a control group featuring cycles without growing follicles (the maximum diameter of follicles in both ovaries were <10 mm). The study group was matched by PS with the control group at a ratio of 1:2. The study group consisted of 195 patients before PS matching and 176 patients after matching. The numbers of participants in the control group before and after PS matching were 2061 and 329, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: This analysis showed that patient age (adjusted odds ratio [aOR] 1.05; 95% CI 1.01-1.09; P=0.010) and basal FSH level (aOR 1.06; 95% CI 1.01-1.11; P=0.012) were significantly and positively related with the spontaneous follicular growth and ovulation event. In addition, this event was negatively correlated with BMI (aOR 0.92; 95% CI 0.87-0.97; P=0.002), AMH level (aOR 0.66; 95% CI 0.59-0.74; P<0.001) and a high starting oestrogen dose (aOR 0.53; 95% CI 0.38-0.76 for 6 mg vs. 4 mg; P<0.001). Baseline characteristics were similar between groups after PS matching. Patients in the study group had a significantly higher IR (28.8% vs. 21.8%, P=0.016), CPR (44.9% vs. 33.4%, P=0.011), OPR (39.2% vs. 26.1%, P=0.002) and LBR (39.2% vs. 24.9%, P=0.001) and a lower miscarriage rate (12.7% vs. 25.5%, P=0.030), compared with those in the control group. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study carried out in a single centre and was therefore susceptible to bias. In addition, we only analysed patients with normal ovulation patterns and excluded those with follicular growth but without ovulation. Further studies remain necessary to confirm our results. WIDER IMPLICATIONS OF THE FINDINGS: It is not necessary to cancel cycles that experience spontaneous follicular growth and ovulation. Our data support promising clinical outcomes after this event. Our findings are important as they can better inform clinicians and patients. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by National Natural Science Foundation of China (grant no. 81701507, 81801404, 81871210, 82071648), Natural Science Foundation of Jiangsu Province (grant no. BK20171126, BK20201123) and Jiangsu Province '333' project. The authors declare that they have no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The Effect of Sildenafil Citrate on Poor Endometrium in Patients Undergoing Frozen-Thawed Embryo Transfer following Resection of Intrauterine Adhesions: A Retrospective Study.

BACKGROUND: The recent studies have shown that sildenafil citrate can enhance estrogen-induced proliferation of the endometrium in infertile women. OBJECTIVE: This study was aimed to investigate whether sildenafil citrate could affect pregnancy outcomes in infertile women receiving frozen-thawed embryo transfer (FET) after resection of intrauterine adhesions (IUAs). MATERIALS AND METHODS: A total of 310 subjects who met the inclusion criteria were recruited and divided into the control group (group A) and the sildenafil citrate group (or the SC group, group B). The 2 groups were, respectively, divided into 2 subgroups based on the severity of reformed adhesions: (1) group A1 (with mild IUAs) and group A2 (with moderate to severe IUAs) and (2) group B1 (with mild IUAs) and group B2 (with moderate to severe IUAs). Therapeutic effects of sildenafil citrate on the cases were evaluated after resection of IUAs during FET cycles. Endometrial thickness, endometrial pattern, and pregnancy outcomes were evaluated and compared between the 2 groups. RESULTS: There was no significant difference in the number of embryos transferred between the 2 groups. The endometrial thickness in group B (0.80 [0.68-0.90] cm) was significantly higher than that in group A (0.73 [0.35-0.80] cm). Besides, the biochemical pregnancy rate, clinical pregnancy rate, and live birth rate (LBR) were 71.60, 50.83, and 39.17% in group B, which were significantly higher than those in group A, namely, 57.36, 34.73, and 23.68%, respectively (p < 0.05). The univariate analysis and multivariate logistic regression showed that the LBR in either subgroups of group B after vaginal sildenafil treatment was significantly higher than that in the corresponding control group (p < 0.05). CONCLUSIONS: It was observed that the administration of sildenafil citrate during FET could effectively improve the poor endometrial conditions after FET following the resection of IUAs.

Comparative analysis of macaque and human sperm proteomes: Insights into sperm competition.

Male macaques produce faster sperm than male humans due to a higher pressure of sperm competition in macaques. To explore the molecular basis of this biological difference, we firstly constructed macaque and human sperm proteomes using LC-MS/MS. We then detected the positively selected genes specifically on the branch of macaque based on branch-site likelihood method. We identified 197 positively selected genes specifically on the branch of macaque that are unselected in corresponding human orthologs. These genes are highly associated with mitochondria and axoneme that directly drive sperm motility. We further compared the ultrastructural differences of the midpiece between macaque and human sperms to provide evidence for our findings using transmission electron microscopy. In conclusion, our results provide potential molecular targets for explaining the different phenotypes under sperm competition between macaques and humans, and also provide resources for the analysis of male fertility.

Community-based interventions in hypertensive patients: a comparison of three health education strategies.

BACKGROUND: Community-based health education programs may be helpful in improving health outcomes in patients with chronic illnesses. This study aimed to evaluate community-based health education strategies in the management of hypertensive patients with low socioeconomic status in Dongguan City, China. METHODS: This was a randomized, non-blinded trial involving 360 hypertensive patients enrolled in the community health service centre of Liaobu Town, Dongguan City, China. Participants were randomized to receive one of the three community-based health education programs over 2 years: self-learning reading (Group 1), monthly regular didactic lecture (Group 2), monthly interactive education workshop (Group 3). Outcomes included the changes in the proportion of subjects with normalized blood pressure (BP), hypertension-related knowledge score, adherence to antihypertensive treatment, lifestyle, body mass index and serum lipids. RESULTS: After the 2-y intervention, the proportion of subjects with normalized BP increased significantly in Group 2 (from 41.2% to 63.2%, p<0.001), and increased more substantially in Group 3 (from 40.2% to 86.3%, p<0.001), but did not change significantly in Group 1. Improvements in hypertension-related knowledge score, adherence to regular use of medications, appropriate salt intake and regular physical activity were progressively greater from group 1 to group 2 to group 3. Group 3 had the largest reductions in body mass index and serum LDL cholesterol levels. CONCLUSION: Interactive education workshops may be the most effective strategy in community-based health promotion education programs for hypertensive patients in improving patients' knowledge on hypertension and alleviating clinical risk factors for preventing hypertension-related complications.

Hydroxychloroquine improves pregnancy outcomes in patients undergoing frozen embryo transfer with positive serum autoantibodies.

PROBLEM: Does hydroxychloroquine (HCQ) improve pregnancy outcomes after frozen embryo transfer (FET) cycles in patients who are positive for autoantibodies？ METHOD OF STUDY: This was a retrospective clinical study involving 128 patients who were positive for autoantibodies undergoing FET cycles between October 2017 and December 2022. Subjects were divided into two groups: a study group of 65 cycles with HCQ (HCQ was administered orally over 2 months before transplantation and continued during the first trimester) and a control group consisting of 63 cycles without HCQ (no HCQ was used throughout the FET cycle). Each patient was enrolled in the cohort only once. Then, we analyzed the clinical pregnancy outcomes between the two groups. RESULTS: Analysis showed that HCQ was a factor that independently associated with clinical pregnancy rate (CPR) OR (Odds Ratio): 3.106; 95% confidence interval (CI): 1.458-6.616; p = .003. Furthermore, the implantation rate (IR), CPR and ongoing pregnancy rate (OPR) of the treatment group were significantly higher than those in the control group. The biochemical pregnancy rate (BPR) and early miscarriage rate (EMR) were significantly lower than that in the control group (p = .029, p < .001). CONCLUSION: We found that HCQ improved clinical pregnancy outcomes and reduced the rate of first-trimester abortion in patients who were positive for autoantibodies during FET cycles.

Functional Ovarian Cysts in Artificial Frozen-Thawed Embryo Transfer Cycles With Depot Gonadotropin-Releasing Hormone Agonist.

Objectives: To investigate the incidence of functional ovarian cysts, its influence on clinical rates, and proper management after depot gonadotropin-releasing hormone (GnRH) agonist pretreatment in artificial frozen-thawed embryo transfer cycles (AC-FET). Methods: This retrospective cohort study involved 3375 AC-FET cycles with follicular-phase depot GnRH agonist administration between January 2017 and December 2020. Subjects were divided into a study group (cycles with cyst formation) and a control group (cycles without cyst formation). The study group was matched by propensity scoring matching with the control group at a ratio of 1:2. For patients with ovarian cyst formation, two major managements were used: a conservative approach (i.e., expectant treatment) and a drug approach (i.e., continued agonist administration). The primary outcome was live birth rate (LBR). Results: The incidence of functional ovarian cysts following pituitary downregulation is 10.1% (341/3375). The study group exhibited a LBR similar to the control group (54.5% vs. 50.1%, adjusted odds ratio [aOR] 1.17, 95% confidence interval [CI] 0.88-1.56, P = 0.274). Patients with a lower body mass index and anti-Müllerian hormone, and a higher basal estradiol level were more susceptible to developing functional ovarian cysts. The LBR decreased after the drug approach compared with the conservative approach, but not significantly (aOR 0.63, 95% CI 0.35-1.14, P = 0.125). Following the conservative approach, cycles arrived at live births had a significantly shorter duration from the detection of functional cysts to the start of endometrium preparation (15.7 ± 5.1 days vs. 17.4 ± 5.3 days, P = 0.009) and a significantly higher proportion of ovarian cysts on the initial day of exogenous hormone supplementation (51.4% vs. 30.3%, P = 0.001). After controlling for all confounders, the differences remained statistically significant. Conclusions: It is unnecessary to cancel cycles that experience functional ovarian cyst formation. Conservative management and further agonist suppression protocol had similar pregnancy rates. However, a conservative approach was recommended due to its lower cost and fewer side effects. Our findings support a shorter waiting period when choosing the conservative protocol.

Effect of sildenafil citrate on treatment of infertility in women with a thin endometrium: a systematic review and meta-analysis.

OBJECTIVE: Endometrial thickness is a prognostic factor for successful pregnancy. This meta-analysis aimed to examine the role of sildenafil citrate on infertile women with a thin endometrium. METHODS: Two investigators independently searched the literature on sildenafil citrate and infertile women with a thin endometrium from PubMed, EMBASE, and the Cochrane Controlled Trials Register Database from inception to January 2019. RESULTS: Nine studies involving 1452 patients were included for analysis in our study. We found that endometrial thickness in patients who received sildenafil citrate was significantly higher than that in the control group (placebo or no treatment) (weighted mean difference: 1.22; 95% confidence interval [CI]: 1.07-1.38). The radial artery resistance index was significantly lower (weighted mean difference: -0.12; 95% CI: -0.17 to -0.06), and the clinical pregnancy rate (risk ratio: 1.31; 95% CI: 1.11-1.53) and biochemical pregnancy rate (risk ratio: 1.45; 95% CI: 1.11-1.89) were significantly higher in the sildenafil citrate group compared with the control group. CONCLUSION: Sildenafil citrate is effective in improving endometrial thickness, the clinical pregnancy rate, and the biochemical pregnancy rate in women who have a thin endometrium. This treatment is a potential therapeutic intervention for a thin endometrium.

Autophagy and apoptosis act as partners to induce germ cell death after heat stress in mice.

Testicular heating suppresses spermatogenesis which is marked by germ cell loss via apoptotic pathways. Recently, it is reported that autophagy also can be induced by heat treatment in somatic cells. In this study, the status of autophagy in germ cells after heat treatment, as well as the partnership between autophagy and apoptosis in these cells was investigated. The results demonstrated that besides initiating apoptotic pathways, heat also induced autophagic pathways in germ cells. Exposure of germ cells to hyperthermia resulted in several specific features of the autophagic process, including autophagosome formation and the conversion of LC3-I to LC3-II. Furthermore, the ubiquitin-like protein conjugation system was implicated as being likely responsible for heat-induced autophagy in germ cells since all genes involving this system were found to be expressed in the testes. In addition, the upstream protein in this system, Atg7 (Autophagy-related gene 7), was found to be expressed in all types of spermatogenic cells, and its expression level was positively correlated with the level of autophagy in germ cells. As a result, Atg7 was selected as the investigative target to further analyze the role of autophagy in heat-induced germ cell death. It was shown that down expression of Atg7 protein resulted in the notable decrease in the level of autophagy in heat-treated germ cells, and this down-regulation of autophagy caused by Atg7 knockdown further reduced the apoptotic rate of germ cells. These results suggest that autophagy plays a positive role in the process of germ cell apoptosis after heat treatment. In conclusion, this study demonstrates that heat triggers autophagy and apoptosis in germ cells. These two mechanisms might act as partners, not antagonist, to induce cell death and lead to eventual destruction of spermatogenesis.