Background
Hormone replacement therapy (HRT) regimen was suggested to be associated with a decreased rate of livebirth and a higher risk of hypertensive disorders of pregnancy (HDP) after frozen ...cleavage stage embryo transfer in women with polycystic ovary syndrome (PCOS). With the dramatically increased use of elective single embryo transfer, there is great need to explore the impacts of different endometrial preparation regimens on frozen single-blastocyst transfer in women with PCOS.
Methods
In this study, a total of 3941 women who diagnosed with PCOS and underwent single-blastocyst transfer during their first cycles of frozen embryo transfer (FET) between March 2012 and December 2020 were included. We retrospectively compared the pregnancy and neonatal outcomes after frozen single-blastocyst transfer with endometrial preparation by HRT regimen (n = 3540), ovulation induction by human menopausal gonadotropin (hMG) regimen (n = 226), and ovulation induction by letrozole regimen (n = 175).
Results
After adjustment for confounders with multivariable logistic regression, the hMG regimen group (58.4% vs. 49.6%; adjusted odds ratio (aOR): 1.43; 95% confidence interval (CI): 1.09-1.89) and letrozole regimen group (58.9% vs. 49.6%; aOR: 1.42; 95% CI: 1.04-1.93) were associated with a higher rate of livebirth (primary outcome), compared with the group with HRT regimen. As to the secondary outcomes, the rate of pregnancy loss in the hMG regimen group (22.8% vs. 30.3%; aOR: 0.69; 95% CI: 0.48-1.00) and letrozole regimen group (16.9% vs. 30.3%; aOR: 0.48; 95% CI: 0.30-0.78) was also lower than that in the HRT regimen group. The pregnancy outcomes between the hMG regimen group and the letrozole regimen group were similar. We did not observe significant difference in the incidences of maternal and neonatal complications among these three groups.
Conclusion
Ovulation induction regimen with letrozole or hMG for endometrial preparation was associated with a higher livebirth rate and a lower pregnancy loss rate in frozen single-blastocyst transfer cycles among women with PCOS.
Abstract
Background
Preeclampsia (PE) is a leading cause of maternal and perinatal mortality and morbidity worldwide, but effective early prediction remains a challenge due to the lack of reliable ...biomarkers.
Methods
Based on the extensive human biobank of our large-scale assisted reproductive cohort platform, the first-trimester serum levels of 48 cytokines, total immunoglobulins (Igs), anti-phosphatidylserine (aPS) antibodies, and several previously reported PE biomarkers including placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and activin A were measured in 34 women diagnosed with PE and 34 matched normotensive controls.
Results
The PE group has significantly higher first-trimester serum levels of interleukin (IL)-2Rα, IL-9, tumor necrosis factor-β (TNF-β), RANTES, hepatocyte growth factor (HGF), total IgM, and total IgG, and aPS IgG optical density (OD) value, as well as lower first-trimester serum levels of PlGF and total IgA and aPS-IgG immune complexes (IC) OD value than the control group. Combining top five first-trimester serum biomarkers (total IgM, total IgG, PlGF, aPS IgG, and total IgA) achieved superior predictive value area under the curve (AUC) and 95% confidence interval (CI) 0.983 (0.952–1.000), with a sensitivity of 100% and a specificity of 94.1% for PE development compared to PlGF and PlGF/sFlt-1 independently AUC and 95% CI 0.825 (0.726–0.924) and 0.670 (0.539–0.800), respectively.
Conclusion
We identified novel first-trimester serum biomarkers and developed an effective first-trimester prediction model using immune-related factors and PlGF for PE, which could facilitate the development of early diagnostic strategies and provide immunological insight into the further mechanistic exploration of PE.
Abstract
Background
Recurrent implantation failure (RIF) brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a ...promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF. But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome.
Methods/design
This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial (1:1 ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) or pre-implantation genetic testing for aneuploidy (PGT-A) will be enrolled and randomly assigned to two parallel groups. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant. The primary outcome is live birth rate.
Discussion
The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF.
Trial registration
Chinese Clinical Trial Registry,
ChiCTR1800018783
. Registered on 9 October 2018.
Abstract
Context
Women with polycystic ovary syndrome (PCOS) commonly have intrinsic insulin resistance and are recommended to undergo an oral glucose tolerance test (OGTT) for diabetes screening. ...However, the effect of preconception impaired glucose tolerance (IGT) on pregnancy is still unclear.
Objective
To prospectively assess the effect of preconception IGT on pregnancy outcomes.
Design, Setting, Patients, Interventions, and Main Outcome Measures
This was a secondary analysis of a multicenter randomized trial in 1508 women with PCOS comparing live birth and obstetric complications between fresh and frozen embryo transfer. At baseline, fasting and 2-hour glucose and insulin levels after 75-g OGTT were measured.
Results
Women with preconception IGT had higher risks of gestational diabetes in both singleton pregnancy 9.5% vs 3.2%; odds ratio (OR) 3.13; 95% confidence interval (CI) 1.23to 7.69 and twin pregnancy (20.0% vs 3.2%; OR 7.69; 95% CI 2.78 to 20.00) than women with normoglycemia. Preconception IGT was associated with a higher risk of large for gestational age in singleton newborns compared with normoglycemia (34.7% vs 19.8%; OR 2.13; 95% CI 1.19 to 3.85) or isolated impaired fasting glucose (i-IFG) (34.7% vs 15.4%; OR 2.94; 95% CI 1.33 to 6.25). Women with preconception IGT had a higher singleton pregnancy loss rate than women with i-IFG (31.4% vs 17.5%; OR 2.17; 95% CI 1.11 to 4.17). After adjusting for age, body mass index, duration of infertility, total testosterone level, and treatment groups (frozen vs fresh embryo transfer), these associations remained.
Conclusions
Preconception IGT, independent from BMI, was associated with adverse pregnancy outcome compared with i-IFG and normoglycemia.
Preconception IGT independent from obesity was associated with increased risks of singleton pregnancy loss, gestational diabetes, and large for gestational age in women with PCOS.
Objectives:
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder with heterogeneous manifestations and complex etiology. We used quantitative proteomics analysis based on ...mass spectrometry to identify the differences in proteomics profiles for follicular fluid obtained from patients with or without PCOS and explore possible mechanisms underlying PCOS.
Methods:
Follicular fluid samples were collected from infertile patients with (n = 9) or without (n = 9) PCOS. Total protein was extracted, quantitatively labeled with a tandem mass tag (TMT), and analyzed using liquid chromatography-mass spectrometry (LC‐MS). TMT-based proteomics and bioinformatics analysis were used to determine the differentially expressed proteins (DEPs) and understand the protein networks. The analysis included protein annotation, unsupervised hierarchical clustering, functional classification, functional enrichment and clustering, and protein-protein interaction analysis. Selected DEPs were confirmed by ELISA, and correlation analysis was performed between these DEPs and the clinical characteristics.
Results:
In this study, we have identified 1,216 proteins, including 70 DEPs (32 upregulated proteins, 38 downregulated proteins). Bioinformatics analysis revealed that the inflammatory response, complement and coagulation cascades, activation of the immune response, lipid transport, and regulation of protein metabolic processes were co-enriched in patients with PCOS. Based on ELISA results, insulin-like growth factor binding protein 1 (IGFBP1) and apolipoprotein C2 (APOC2) were differentially expressed between patients with and without PCOS. Follicular IGFBP1 showed a positive correlation with the serum levels of high-density lipoprotein cholesterol (HDL-C) (r = 0.3046,
p
= 0.0419), but negatively correlated with the serum levels of anti-Müllerian hormone (AMH) (r = –0.2924,
p
= 0.0354) and triglycerides (r = –0.3177,
p
= 0.0246). Follicular APOC2 was negatively correlated with the serum apolipoprotein A1 (APOA1) levels (r = 0.4509,
p
= 0.0002).
Conclusion:
Our study identified DEPs in the follicular fluid of patients with PCOS. Inflammatory response, complement and coagulation cascades, activation of the immune response, lipid transport, and regulation of protein metabolic process were deregulated in PCOS, which may play essential roles in the pathogenesis of PCOS.
Women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with poor ovarian respond (POR) always have very low clinical pregnancy rates. In previous data, ...dehydroepiandrosterone (DHEA) was suggested as a promising treatment and maybe has a good pregnancy outcome. But there is no sufficient evidence from randomized clinical trials evaluating the effect of DHEA preconceptional treatment on live birth in POR.
This trial is a multicenter active-placebo double-blind clinical trial (1:1 treatment ratio of active versus placebo). The infertile POR patients undergoing IVF or ICSI will be enrolled and randomly assigned to two parallel groups. Participants in these two groups will be given 4-12 weeks' treatment of DHEA or placebo, respectively. The primary outcome is live birth rate.
The results of this study will provide evidence for the effect of preconceptional DHEA treatment on IVF outcome in POR.
Chinese Clinical Trial Registry, ChiCTR-IPR-15006909 . Registered on November 9, 2015.
Multiple pregnancies are one of the major safety concerns of in vitro fertilization (IVF) due to the increased risk of maternal and neonatal complications. Single embryo transfer is the most ...effective way to reduce the risk of multiple pregnancies. Selection of the embryo and optimization of the implantation environment are crucial to retain the success rate when the number of transferred embryos is diminished. Fresh embryo transfer with supra-physiological levels of hormones has been suggested to have an adverse effect on implantation. Elective frozen embryo transfer has been suggested to result in a higher rate of live birth than fresh embryo transfer. However, there is still a lack of evidence from randomized clinical trials comparing the efficacy and safety between frozen and fresh single blastocyst transfers.
We are conducting a randomized controlled trial in women aged 20-35 undergoing their first cycle of IVF with or without intracytoplasmic sperm injection. After ovarian stimulation with a gonadotropin-releasing hormone antagonist protocol, women who obtain four or more embryos on day 3 of the embryo culture are randomized into two parallel groups: a single fresh blastocyst transfer group and a single frozen blastocyst transfer group (all blastocysts vitrified and a deferred frozen blastocyst transfer). The primary outcome is singleton live birth.
The results of this study will provide evidence for the efficacy and safety of the strategy of elective frozen single blastocyst transfer in women with a good prognosis.
Chinese Clinical Trial Registry, ChiCTR-IOR-14005405 . Registered on 30 Oct 2014.
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