Prolonging the time of progesterone supplementation to improve the pregnancy outcomes of single day 6 blastocyst transfer in frozen-thawed cycles: study protocol for a randomized controlled trial.

BACKGROUND: Infertility is one of the most important and underappreciated reproductive health problems in developing countries. Currently, in vitro fertilization and embryo transfer is the most effective treatment strategy for infertility. In a frozen-thawed cycle, single-blastocyst transfer can not only ensure relatively higher pregnancy and live birth rates but also effectively reduce the risk of maternal and neonatal complications. In frozen-thawed cycles, progesterone is initiated to promote the final phase of endometrial preparation prior to embryo transfer. However, the optimal duration of exposure to progesterone has remained inconclusive. Therefore, we designed a randomized controlled trial (RCT) to compare the effects of different prolonged progesterone transformation times (P+6 and P+7) on the pregnancy outcomes of D6 single blastocyst transfer in a frozen-thawed cycle. METHODS: This is a single-center, prospective, randomized controlled clinical trial involving 900 patients with single blastocyst transfer in the frozen-thawed cycle, aged from 20 to 38 years, with less than three transfers, and with HRT-cycle single D6 blastocyst transfer in the current cycle. Participants will be randomly assigned (1:1) into two parallel groups: the transfer of day 6 blastocysts on the 7th day of progesterone supplementation and the transfer of day 6 blastocysts on the 6th day of progesterone supplementation. The primary outcome measure is the clinical pregnancy rate. Secondary outcome measures include the miscarriage rate and live birth rate. DISCUSSION: This is the first randomized controlled trial to compare the transfer of day 6 blastocysts on the 6th and 7th day of progesterone supplementation. The results of this study will provide evidence for whether to prolong the duration of exposure to progesterone prior to embryo transfer. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT04938011. Registered on 19 June 2021.

Effect of recombinant LH supplementation timing on clinical pregnancy outcome in long-acting GnRHa downregulated cycles.

BACKGROUND: Timely and moderate luteinizing hormone (LH) supplementation plays positive roles in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) cycles with long-acting gonadotropin-releasing hormone agonist (GnRHa) pituitary downregulation. However, the appropriate timing of LH supplementation remains unclear. METHODS: We carried out a retrospective cohort study of 2226 cycles at our reproductive medicine centre from 2018 to 2020. We mainly conducted smooth curve fitting to analyse the relationship between the dominant follicle diameter when recombinant LH (rLH) was added and the clinical pregnancy outcomes (clinical pregnancy rate or early miscarriage rate). In addition, total cycles were divided into groups according to different LH levels after GnRHa and dominant follicle diameters for further analysis. RESULTS: Smooth curve fitting showed that with the increase in the dominant follicle diameter when rLH was added, the clinical pregnancy rate gradually increased, and the early miscarriage rate gradually decreased. CONCLUSIONS: In long-acting GnRHa downregulated IVF/ICSI-ET cycles, the appropriate timing of rLH supplementation has a beneficial impact on the clinical pregnancy outcome. Delaying rLH addition is conducive to the clinical pregnancy rate and reduces the risk of early miscarriage.

A high level of KLF12 causes folic acid-resistant neural tube defects by activating the Shh signaling pathway in mice†.

Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of pregnancies affected by neural tube defects (NTDs), the mechanisms underlying FA-resistant NTDs are poorly understood, and thus NTDs still remain a global public health concern. A high level of Krüppel-like factor 12 (KLF12) exerts deleterious effects on heath in most cases, but evidence for its roles in development has not been published. We observed KLF12-overexpressing mice showed disturbed neural tube development. KLF12-overexpressing fetuses died in utero at approximately 10.5 days post-coitus, with 100% presenting cranial NTDs. Neither FA nor formate promoted normal neural tube closure in mutant fetuses. The RNA-seq results showed that a high level of KLF12 caused NTDs in mice via overactivating the sonic hedgehog (Shh) signaling pathway, leading to the upregulation of patched 1, GLI-Krüppel family member GLI1, hedgehog-interacting protein, etc., whereas FA metabolism-related enzymes did not express differently. PF-5274857, an antagonist of the Shh signaling pathway, significantly promoted dorsolateral hinge point formation and partially rescued the NTDs. The regulatory hierarchy between a high level of KLF12 and FA-resistant NTDs might provide new insights into the diagnosis and treatment of unexplained NTDs in the future.

Electroacupuncture decreases the progression of ovarian hyperstimulation syndrome in a rat model.

This study aimed to elucidate the effect of electroacupuncture treatment on preventing early ovarian hyperstimulation syndrome (OHSS) and the potential mechanisms involved using an induced rat model. The ovarian response was examined by measuring ovary weight, vascular permeability, levels of inflammation (interleukin-6), tumour necrosis factor alpha, chemokine ligand 2 (also known as monocyte chemoactic protein 1), vascular endothelial growth factor and hormone concentrations (oestradiol, progesterone, testosterone and prolactin). Sprague-Dawley female rats underwent ovarian stimulation to induce OHSS. Hyperstimulated rats received consecutive electroacupuncture treatment from 3 days before the beginning of pregnant mare serum gonadotrophin treatment or the time point of pregnant mare serum gonadotrophin treatment respectively, and last until 3 days after HCG administration. Electroacupuncture treatment reduced ovary weight and vascular permeability in hyperstimulated rats. Electroacupuncture treatment also reduced the levels of serum steroid hormones (progesterone and testosterone), inflammatory cytokines (interleukin-6, tumour necrosis factor alpha and monocyte chemotactic protein 1 and vascular endothelial growth factor in hyperstimulated rats. The results indicate that electroacupuncture can modulate endocrine hormone secretion and affect the secretion of inflammatory cytokines and vascular endothelial growth factor, and thus prevent the progress of OHSS. Electroacupuncture may provide a simple and effective method for the prevention and treatment of OHSS.

[Application of acupuncture compound anesthesia in transvaginal ultrasound-guided oocyte retrieval].

OBJECTIVE: To observe analgesic effect and safety of acupuncture compound anesthesia in transvaginal ultrasound-guided oocyte retrieval. METHODS: Three hundred and sixteen cases undergoing in vitro fertilization and embryo transfer (IVF-ET) were randomly allocated to an acupuncture compound anesthesia group (n = 146) and a simple Pethidine group (n = 170). They received respectively electroacupuncture combined with intramuscular injection of Pethidine and simple intramuscular injection of Pethidine 30 min before oocyte retrieval. RESULTS: The acupuncture compound anesthesia group was significantly better than the simple Pethidine group in the pain rating and pain score (P < 0.01); the incidence rate of abdominal pain at 1 h and 2-5 h after oocyte retrieval in the acupuncture compound anesthesia group was lower than that in the simple Pethidine group (P < 0.01). CONCLUSION: In transvaginal ultrasound-guided oocyte retrieval, acupuncture compound anesthesia has the advances of safety, high effectiveness, rapid recovery after oocyte retrieval, and few side effects.

[Sperm DNA damage and assisted reproductive technology].

With the introduction of assisted reproductive technology (ART), sperm assessment has developed progressively, from conventional semen routine tests to novel cellular and molecular measures. Sperm DNA damage is a new marker of male fertility, whose genetic mechanism involves abnormal package and segregation of chromatin, oxidative stress, abnormal cell apoptosis, etc. Sperm chromatin structure assay (SCSA) is one of the common techniques to measure sperm DNA damage. Sperm DNA damage might be associated with the pregnancy outcome of ART, recurrent spontaneous abortion and potential genetic risk of ICSI offspring. Some treatment strategies might reduce the percentage of sperm DNA damage and increase the success rate of ART, including oral administration of antioxygen drugs, ICSI with testis sperm, sperm freezing and preservation, removing of etiological factors, traditional Chinese medicine, and so on. This review focuses on the mechanism and detection of sperm DNA damage, its association with reproductive outcomes, and relevant treatment strategies in assisted reproductive technology.

High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections.

The high mortality rate of immunocompromised patients with fungal infections and the limited availability of highly efficacious and safe agents demand the development of new antifungal therapeutics. To rapidly discover such agents, we developed a high-throughput synergy screening (HTSS) strategy for novel microbial natural products. Specifically, a microbial natural product library was screened for hits that synergize the effect of a low dosage of ketoconazole (KTC) that alone shows little detectable fungicidal activity. Through screening of approximately 20,000 microbial extracts, 12 hits were identified with broad-spectrum antifungal activity. Seven of them showed little cytotoxicity against human hepatoma cells. Fractionation of the active extracts revealed beauvericin (BEA) as the most potent component, because it dramatically synergized KTC activity against diverse fungal pathogens by a checkerboard assay. Significantly, in our immunocompromised mouse model, combinations of BEA (0.5 mg/kg) and KTC (0.5 mg/kg) prolonged survival of the host infected with Candida parapsilosis and reduced fungal colony counts in animal organs including kidneys, lungs, and brains. Such an effect was not achieved even with the high dose of 50 mg/kg KTC. These data support synergism between BEA and KTC and thereby a prospective strategy for antifungal therapy.