IntroductionThe choice of trigger drug for the controlled ovarian hyperstimulation (COH) protocol correlates with the outcome of in vitro fertilization/intracytoplasmic sperm injection embryo transfer (IVF/ICSI-ET). The co-administration of gonadotropin releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG), i.e., dual trigger, for final oocyte maturation, has received much attention in recent years. This trial was designed to determine whether a dual trigger approach by lengthening the time between trigger and ovum pick-up (OPU) improves the quantity and quality of mature oocytes/top-quality embryos and pregnancy outcomes in expected normal responders with a high immature oocyte rate.Methods and AnalysisWe propose a study at the Affiliated Hospital of Shandong University of Chinese Medicine. A total of 90 individuals undergoing COH use a fixed GnRH antagonist protocol. They will be assigned randomly into two groups according to the trigger method and timing: recombinant hCG (6500 IU) will be injected only 36 hours before OPU for final oocyte maturation (hCG-only trigger); co-administration of GnRH-a and hCG for final oocyte maturation, 40 and 34 hours prior to OPU, respectively (Dual trigger). The primary outcome is metaphase-II (MII) oocytes rate. Secondary outcomes are number of oocytes retrieved, fertilization rate, top-quality embryos rate, blastula formation rate, embryo implantation rate, clinical pregnancy rate, miscarriage rate, live birth rate, cumulative pregnancy/live birth rates, and ovarian hyperstimulation syndrome (OHSS) rate.Ethics and DisseminationThe reproductive ethics committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine certified this study (Identifier: SDUTCM/2021.7.26) as ethical. All individuals will sign written informed consent. All data and biological samples will be protected according to law. The results of this study will be disseminated in a peer-reviewed scientific journal.Clinical Trial Registration[chictr.gov.cn], identifier [ChiCTR2100049292].

Background Exposure of the female reproductive tract to either seminal plasma or fluid component of the ejaculate is beneficial to achieving successful embryo implantation and normal embryo development. But whether the “physical” component of sexual intercourse during the peri-transfer period have any influence on frozen-thawed embryo transfer (FET) pregnancy outcomes is not clear. Methods We conducted a randomized trial that included 223 patients undergoing in vitro fertilization (IVF) treatment at a university-affiliated reproductive center from 19 July 2018 to 24 February 2019. Enrolled patients undergoing IVF treatment were randomized either to engage sexual intercourse using the barrier contraception (Group A, n = 116) or to abstain (Group B, n = 107) one night before FET. The primary outcome was clinical pregnancy rate. Results Patients having intercourse had higher clinical pregnancy rate (51.72% vs. 37.07%, P = 0.045) and implantation rate (38.31% vs. 24.77%, P = 0.005) compared to those did not engage intercourse. However, there was no significant difference of the spontaneous abortion rate between two groups (11.67% 33 vs. 14.63%, P = 0.662). Conclusions Sexual intercourse before embryo transfer may improve the clinical pregnancy and implantation rates during FET cycles. However, it should be noted that patients choose only one time for sexual intercourse, that is, the night before embryo transfer. Trial registration The present study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR1800017209).

Background: Exposure of the female reproductive tract to either seminal plasma or fluid component of the ejaculate is beneficial to achieving successful embryo implantation and normal embryo development. But whether the "physical" component of sexual intercourse during the peri-transfer period have any influence on frozen-thawed embryo transfer (FET) pregnancy outcomes is not clear. Methods: We conducted a randomized trial that included 223 patients undergoing in vitro fertilization (IVF) treatment at a university-affiliated reproductive center from 19 July 2018 to 24 February 2019. Enrolled patients undergoing IVF treatment were randomized either to engage sexual intercourse using the barrier contraception (Group A, n=116) or to abstain (Group B, n=107) one night before FET. The primary outcome was clinical pregnancy rate. Results: Patients having intercourse had higher clinical pregnancy rate (51.72% vs. 37.07%, P=0.045) and implantation rate (38.31% vs. 24.77%, P=0.005) compared to those did not engage intercourse. However, there was no significant difference of the spontaneous abortion rate between two groups (11.67% 33 vs. 14.63%, P=0.662). Conclusions: Sexual intercourse before embryo transfer may improve the clinical pregnancy and implantation rates during FET cycles. However, it should be noted that patients choose only one time for sexual intercourse, that is, the night before embryo transfer. Trial registration: The present study was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/, ChiCTR1800017209).

Introduction: The psychological well-being of pregnant women following assisted reproductive has increasingly gained attention in recent years. Anxiety and depression may be associated to pregnancy outcomes. This study aims to determine whether peer support and the WeChat group platform will reduce anxiety and depression among in vitro fertilization and embryo transfer (IVF-ET) women. Methods and Analysis: In the present randomized controlled study, 296 patients with confirmed clinical pregnancy following IVF-ET will be randomly assigned to receive standard intervention support or WeChat peer support on a 1:1 basis. The levels of anxiety and depression are the primary endpoints. Assessments will be performed at baseline measurements, first trimester, second trimester, and third trimester, and data will be collected. Ethics and Dissemination: This study has been approved as ethical by the affiliated hospital of Shandong University of Traditional Chinese Medicine’s Reproductive Ethics Committee. Each patient will sign a written statement of informed permission. All information and biological samples will be legally protected. A peer-reviewed academic journal will publish the findings of this investigation. Discussion: Given the inconvenience of visits due to the current pandemic of COVID-19, this study addresses the patient’s visit needs by combining WeChat, the most widely used social software in China, with peer support, while helping improve maternal anxiety, depression, and pregnancy outcomes following IVF-ET.

No studies have been conducted on the impact of different types of ovulatory dysfunction on the outcomes of frozen-thawed embryo transfers (FETs) in a letrozole-stimulated cycle in women with polycystic ovarian syndrome (PCOS). This study aimed to compare whether pregnancy outcomes of the letrozole-induced protocol in FET cycles differed between oligo-ovulatory and anovulatory women with PCOS. In a retrospective cohort study, women with PCOS who had undergone letrozole-induced FET at a university-affiliated fertility clinic from February 2014 to October 2020 were identified. The primary end point was live birth rate (LBR) per embryo transfer. Propensity score matching and multivariate logistic regression analyses were performed to control for the relevant confounders. A total of 652 women with PCOS undergoing letrozole-induced FET were included in the final analysis. Three hundred sixty-three of these women had oligo-ovulatory periods, while 289 had anovulatory periods. Propensity score matching analysis showed that LBR did not differ between groups (36.8% in oligo-ovulatory group vs 32.8% in anovulatory group, P = .431). Nevertheless, after controlling for potential confounding factors, LBR was significantly lower in anovulatory than oligo-ovulatory women (adjusted odds ratio 1.57, 95% confidence interval 1.08-2.29, P = .018). Furthermore, the pregnancy loss rate among the oligo-ovulatory group remained lower than those among the anovulatory group (adjusted odds ratio 0.23, 95% confidence interval 0.12-0.44, P < .001). Despite adjustment for confounding factors, those with oligo-ovulatory PCOS had a higher LBR and lower pregnancy loss rate compared with those with anovulatory PCOS. This may indicate that when oligoovulation is detected, PCOS patients should be intervened in time to conceive as soon as possible. Prospective studies must be conducted in the future to verify our findings.Abbreviations: AFC = antral follicle count, BMI = body mass index, CI = confidence interval, E 2 = estradiol, eFET = elective frozen-thawed embryo transfer, ET = embryo transfer, FET = frozen-thawed embryo transfer, FSH = follicle stimulating hormone, GCs = granulosa cells, Gn = gonadotropin stimulation, HA = hyperandrogenism, hCG = human chorionic gonadotropin, LBR = live birth rate, LH = luteinizing hormone, MC = menstrual cycle, OHSS = ovarian hyperstimulation syndrome, OR = odds ratio, PCOS = polycystic ovarian syndrome, PLR = pregnancy loss rate, PS = propensity score, PSM = propensity score matching.

Objective The aim of this study was to compare whether pregnancy outcomes of the letrozole-induced endometrial preparation protocol in frozen-thawed embryo transfer (FET) cycles differed between oligo-ovulatory and anovulatory women with polycystic ovarian syndrome (PCOS).Materials and Methods In a retrospective study, women with PCOS who had undergone letrozole-induced FET at a university-affiliated fertility clinic from February 2014 to October 2020 were identified. The primary end point was live birth rate (LBR) per embryo transfer. Propensity score matching (PSM) and multivariate logistic regression analyses were performed to control for the relevant confounders.Results A total of 652 women with PCOS undergoing letrozole-induced FET were included in the final analysis. 363 of these women had oligo-ovulatory periods, while 289 had anovulatory periods. PSM analysis showed that LBR did not differ between groups (36.8% in oligo-ovulatory group vs. 32.8% in anovulatory group, P=0.431). Meanwhile, after PSM, the anovulatory group used extra gonadotrophin (Gn) for a longer duration (6.5±2.3 vs. 5.4±1.9, p=0.004, after PSM) and experienced a higher cycle cancellation rate (9.2% vs. 3.4%, p=0.028, after PSM) than the oligo-ovulatory group. Additionally, there were significantly lower crude odds of total pregnancy loss per positive pregnancy among oligo-ovulatory women than among anovulatory women (15.4% vs. 38.3%, p=0.001). Nevertheless, after controlling for potential confounding factors, LBR was significantly higher in anovulatory than oligo-ovulatory women [adjusted odds ratio (aOR) 1.57, 95% confidence interval (CI) 1.08 to 2.29, p=0.018]. Furthermore, the pregnancy loss rate (PLR) among the oligo-ovulatory group remained lower than those among the anovulatory group [aOR 0.23, 95%CI 0.12 to 0.44, p < 0.001].Conclusions PCOS women may experience different effects on pregnancy outcomes depending on their ovulation dysfunction patterns. Despite adjustment for confounding factors, those with oligo-ovulatory PCOS who underwent letrozole-induced FET had a higher LBR and lower PLR compared with those with anovulatory PCOS. This may indicate that when oligo-ovulation is detected, PCOS patients should be intervened in time to conceive as soon as possible. Prospective studies must be conducted in the future to verify our findings.

Background Exposure of the female reproductive tract to either seminal plasma or fluid component of the ejaculate is beneficial to achieving successful embryo implantation and normal embryo development. But whether the "physical" component of of sexual intercourse during the peri-transfer period have any influence on FET pregnancy outcome is not clear. Methods We conducted a randomized trial that included 223 patients undergoing IVF treatment at a University-affiliated reproductive center from 19 July 2018 to 24 February 2019. Enrolled patients undergoing IVF treatment were randomized either to engage sexual intercourse using the barrier contraception (Group A, n = 116) or to abstain (Group B, n = 107) one night before FET. The follow-up parameters included biochemical losses rate, clinical pregnancy, early abortion and implantation rate. Results Patients having intercourse had higher clinical pregnancy rate (51.72% vs. 37.07%, P = 0.045) and implantation rate (38.31% vs. 24.77%, P = 0.005) compared to those did not engage intercourse. However, there was no significant difference of the spontaneous abortion rate between two groups (11.67% 33 vs. 14.63%, P = 0.662). Conclusions Sexual intercourse before the day of embryo transfer may improve the clinical pregnancy and implantation rates during the frozen- thawed embryo transfer (FET) cycle. However, it should be noted that patients choose only one time for sexual intercourse, that is, the night before embryo transfer. TRIAL REGISTRATION NUMBER: This study was registered at the China Clinical Trial Registration Center, with the registration number ChiCTR1800017209.

Objective To explore the mechanism of Cangfu Daotan Decoction (CDD) about improving the in vitro fertilization (IVF) outcomes of patients with polycystic ovary syndrome (PCOS) based on pseudo-targeted metabolomics. Methods We included 95 subjects of infertility patients participating in in vitro fertilization (IVF) protocols, including 65 patients in PCOS intervened with or without CDD (PCOS+CDD Group, n = 33; PCOS Group, n = 32) and 30 healthy women (Control Group, n = 30). We compared the clinical outcomes among the three groups, Pseudo-targeted metabolomics method was used to analyze follicular fluid samples on the day of oocytes retrieval and to further explore related metabolites and metabolic pathways. Based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)，Pseudo-targeted metabolomics was implemented to explore the related metabolites and metabolic pathways among three groups through professional MetaboAnalyst analysis software. The clinical outcomes were collected among the three groups. Follicular fluid samples on the day of oocytes retrieval were analyzed via pseudo-targeted metabolomics to further explore related metabolites and metabolic pathways. Results There were statistically significant differences among three groups’ outcome indexes, including the number of total retrieved oocytes, metaphase II oocytes, 2PN cleavage, transferable embryo, high-quality embryo fertilization rate and cleavage rate (P<0.05). Moreover, these differences before and after Chinese medicine intervention were statistically significant in cleavage rate (76.1% VS 88.3%) and blastogenesis rate (46.2% VS 80.6%) (P < 0.001). Compared with ones in PCOS group, seven metabolites in PCOS+CDD Group, namely Leucine, N-acetyltryptophan, 3-sulfopyruvic acid, uric acid, Acrylamide, creatine, lactate, were up-regulated. And there were others down-regulated substances: progesterone, phytosphingosine, decanoylcarnitine, dihomolinoleic acid, choline, phosphorylcholine, betaine, parahydroxybenzoate. The pathways containing steroid hormone biosynthesis, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, purine metabolism as well as pyruvate metabolism were regulated by CDD treatment. Conclusion CDD could improve the IVF outcomes of patients with polycystic ovary syndrome (PCOS) by increasing total retrieved oocytes, transferable embryos and high-quality embryos and enhancing retrieved oocytes rate, fertilization rate and clinical pregnancy rate. Follicular fluid (FF) metabolites of PCOS patients with spleen deficiency and phlegm-dampness syndrome involving lipids (aminools), organic acids (lactic acid) could be regulated by CDD. These differential metabolites may provide potential biomarkers for PCOS patients with spleen deficiency and phlegm-dampness syndrome. CDD can improve pyruvate metabolism and correct lipid metabolism disorders, which may be the possible mechanism of action for improving ART outcomes in PCOS patients.