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1.
Environ Pollut ; 257: 113480, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31744678

RESUMO

Etoxazole is an organofluorine insecticide widely used in agriculture. Exposure to insecticides is a serious environmental problem owing to their cytotoxic effects in humans and animals. Reproductive toxicity of various organofluorine insecticides have been shown in previous studies. However, few studies have evaluated the toxicity of etoxazole in mammals. We aimed to examine the toxic effects of etoxazole in porcine trophectoderm (pTr) and uterine luminal epithelial (pLE) cells. To estimate the effects of etoxazole, we conducted assays after treatment with multiple concentration of etoxazole (0, 2, 4, 6 and 9 µM) to pTr and pLE cells for 0-72 h. Etoxazole decreased the cell proliferation, viability, and migration of pTr and pLE cells. Further, etoxazole induced apoptosis via cell cycle arrest and disruption of mitochondrial membrane potential. We also found that pro-apoptotic proteins and endoplasmic reticulum (ER) stress-response proteins were activated in response to etoxazole. Finally, we observed that etoxazole altered the PI3K/AKT and MAPK signaling pathways and the mRNA expression of genes associated with implantation. Collectively, these results suggest that etoxazole disrupts normal cellular physiology and might cause early implantation failure.


Assuntos
Acaricidas/toxicidade , Oxazóis/toxicidade , Animais , Apoptose/efeitos dos fármacos , Morte Celular , Proliferação de Células/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Estresse do Retículo Endoplasmático , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Suínos , Útero/metabolismo
2.
Ecotoxicol Environ Saf ; 190: 110069, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841894

RESUMO

Carbon disulfide (CS2) is regarded as a common occupational poison that is widely used in the textile industry in China. Our previous research suggests that CS2 can induce significant implantation disorders in pregnant mice; however, the specific mechanism remains unclear. Uterine conception in mice must undergo decidualization, which is the prerequisite for propitious blastocyst implantation into the endometrium. Therefore, in this study, we established models of pregnant mice to explore the toxic effects of CS2 on decidualization to elucidate the basic mechanism of implantation disorder after CS2 exposure. The uterine tissues were immediately collected according to the predetermined endpoints to measure the expression levels of IGFBP1 and PRL (markers of decidualization differentiation), IL-11 (representing the secretory function of decidual cells), AKT and pAKT by western blotting, RT-PCR, immunohistochemical staining, H&E staining and ELISA. N-carbamoyl glutamic acid (NCG) acted as an agonist of AKT to verify the upstream regulatory mechanism of decidualization disorder by CS2. The results showed that the normal reaction of decidual transformation was obviously disrupted by CS2 upon 3.5 dpc and 4.5 dpc exposure. The blastocyst did not adhere to the epithelium after 3.5 dpc-exposure and did not invade the endometrium after 4.5 dpc-exposure, resulting in its suspension in the uterine cavity, stagnation and eventual loss. The proteins expression levels were decreased by 95.2% for IGFBP1 and 76.2% for PRL at the 4.5 dpc endpoint after 3.5 dpc CS2 exposure compared with the control. Simultaneously, the mRNA and protein expression levels of IL-11 in uterine tissues were significantly reduced by CS2, and consistent decreasing trends over time were observed for IGFBP1 and PRL, compared with the control. Additionally, the ratio of pAKT/AKT protein expression was decreased by 72.2% and 94.8% at 12 h and 18 h after 3.5 dpc exposure and by 53.3% and 74.3% at 6 h and 12 h after 4.5 dpc exposure, respectively, compared with the corresponding controls. Furthermore, NCG could recover the IGFBP1 and PRL protein expression, which was increased by 27.5% and 52.3% at 4.5 dpc and 6.5 dpc, respectively, after 3.5 dpc exposure for IGFBP1 and by 30.3% at 6.5 dpc after 4.5 dpc exposure for PRL, compared with CS2 exposure alone. Collectively, this study suggested that the decidualization disorder caused by CS2 at the window of implantation in pregnant mice, which is triggered by pAKT, contributed to the implantation disorder and eventually led to embryo loss. It is worth noting that our study may provide a new perspective and reference for exploring the toxic mechanism of implantation disorder and even infertility in harmful circumstances.


Assuntos
Dissulfeto de Carbono/toxicidade , Implantação do Embrião/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Diferenciação Celular , Endométrio/fisiologia , Feminino , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Interleucina-11/genética , Interleucina-11/metabolismo , Camundongos , Gravidez , Prolactina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Útero/metabolismo
3.
Ecotoxicol Environ Saf ; 187: 109816, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31648075

RESUMO

Bisphenol A (BPA) is a substance ubiquitously present in the environment, and its toxicity on reproductive function has been well characterised in animal models. However, it is still controversy about the effects of BPA exposure on human female reproduction. Therefore, in the present study, the associations of urinary BPA concentration with the outcomes of in vitro fertilisation (IVF) and embryo transfer from fresh and frozen cycles were analysed in the same cohort. 351 women who underwent IVF treatment from September 2013 to October 2016, at the Centre of Reproductive Medicine in the Women's Hospital School of Medicine at Zhejiang University were recruited. Single-spot urine samples were collected on the day of oocyte retrieval to detect BPA using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. A multivariable generalised linear mixed model was used to evaluate the association between the urinary BPA concentration and IVF outcomes. After adjustment for age, body mass index, baseline follicle-stimulating hormone level, baseline oestradiol level, and antral follicle count, a significant decrease in the number of retrieved oocytes and in the rates of clinical pregnancy and implantation was observed in the patients with a high urinary BPA concentration. We concluded that BPA exposure exert negative effects on oocyte retrieval and embryo implantation in women undergoing IVF.


Assuntos
Compostos Benzidrílicos/urina , Implantação do Embrião/efeitos dos fármacos , Exposição Ambiental/análise , Poluentes Ambientais/urina , Fertilização In Vitro , Infertilidade Feminina/urina , Recuperação de Oócitos , Fenóis/urina , Adulto , Compostos Benzidrílicos/toxicidade , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Feminino , Humanos , Fenóis/toxicidade , Gravidez
4.
Theriogenology ; 142: 169-176, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31600637

RESUMO

Blood vessel formation is a critical process for successful pregnancy establishment and placenta formation. Angiogenic factors such as vascular endothelial growth factor (VEGF), angiopoietins (ANGPTs) or fibroblast growth factor 2 (FGF2) are known to be involved in angiogenesis. However, the mechanism regulating their expression in the porcine endometrium and trophoblast has not been described during early pregnancy establishment. Recently, we reported an important role for prostaglandin F2α (PGF2α) in supporting processes accompanying the peri-implantation period in the pig. The aim of the present study was to determine the effect of PGF2α on angiogenic factor gene and protein expression at the embryo-maternal interface and on capillary-like structure formation by endometrial endothelial cells. In the present study, we used various in vitro models involving endometrial tissue explants, primary porcine trophoblast and endometrial endothelial cells, as well as a swine umbilical vein endothelial cell line (G1410). ANGPT1, ANGPT2 and FGF2 gene expression was analyzed in porcine endometrial explants and in primary trophoblast cells incubated with PGF2α (100 nM, 1 µM). VEGFA gene expression and protein secretion by porcine primary trophoblast cells were studied in vitro using primary trophoblast cells. A network formation assay using the G1410 cell line and primary endothelial cells of endometrial origin was performed to assess the effect of PGF2α on capillary-like structure formation. We found that PGF2α stimulated VEGFA gene expression (1 µM) and secretion of this protein (100 nM) by porcine trophoblast cells (P < 0.05). In endometrial explants, PGF2α increased the expression of the ANGPT1, ANGPT2 and FGF2 genes (P < 0.05). PGF2α stimulated the formation of capillary-like structures acting on porcine endometrial endothelial cells on days 15 and 20 of pregnancy and in the G1410 cell line (P < 0.05). PGF2α-stimulated endothelial cell network formation was diminished by using a MEK kinase inhibitor in G1410 cells. Our results indicate an important role for PGF2α in the regulation of angiogenesis at the embryo-maternal interface. PGF2α promotes angiogenesis in the porcine endometrium by activating the MAPK signaling pathway. The stimulating effect of PGF2α on the formation of capillary-like structures by endothelial cells, together with our previous findings, supports the hypothesis that PGF2α is an important factor promoting the development of the placenta during early pregnancy in the pig.


Assuntos
Dinoprosta/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Prenhez , Suínos , Trofoblastos/efeitos dos fármacos , Animais , Células Cultivadas , Implantação do Embrião/efeitos dos fármacos , Embrião de Mamíferos , Feminino , Idade Gestacional , Relações Materno-Fetais/efeitos dos fármacos , Placenta/citologia , Placenta/efeitos dos fármacos , Placentação/efeitos dos fármacos , Gravidez , Suínos/embriologia , Trofoblastos/fisiologia , Regulação para Cima/efeitos dos fármacos
5.
Reprod Biol Endocrinol ; 17(1): 103, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783862

RESUMO

BACKGROUND: The addition of a GnRH analogue to the luteal phase in in vitro fertilization programs has been seldom proposed due to the presence of GnRH receptors in the endometrium. The aim of the study was to evaluate the effect of triptorelin addition in short antagonist cycles, compared to cycles where the only supplementation was progesterone. METHODS: The primary objective of this study was the study of the effect of Triptorelin addiction during the luteal phase on the live birth rate. Secondary objectives of efficacy were pregnancy rates and implantation rates, as well as safety in terms of OHSS risks. The study was a prospective, randomized, open study, performed in two independent Centers from July 2013 to October 2015. Patients were divided into three groups: a) Regular antagonist protocol, with only luteal progesterone; b) Antagonist protocol with luteal triptorelin as multiple injections, c) Antagonist protocol with luteal triptorelin as single bolus. Descriptive statistics were obtained for all the parameters. Mean and standard deviation were used for all quantitative parameters. Differences between percentages were studied using Chi-square test generalized to the comparison of several proportions. RESULTS: A total number of 1344 patients completed the study, 786 under the age of 35 years, and 558 over 35 years. It was observed an increase of positive HCG results, Clinical pregnancy rates and Delivery rates when triptorelin was added in the luteal phase, irrespective whether as a single bolus or five injections. This increase was statistically significant both for pregnancy rates and delivery rates. The statistic difference between pregnancies and deliveries obtained with or without luteal triptorelin reached p < 0,01. No increase of OHSS risk was observed. CONCLUSIONS: From this large study it appears that the concept of luteal phase supplementation should be revisited. From our study it appears that triptorelin addition to the luteal phase of antagonist cycles, either as a single bolus or using multiple injections, is a good tool to optimize ART results. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Provincia di Bergamo (n 1203/2013).


Assuntos
Implantação do Embrião/efeitos dos fármacos , Fertilização In Vitro/métodos , Hormônio Liberador de Gonadotropina/agonistas , Fase Luteal/efeitos dos fármacos , Pamoato de Triptorrelina/farmacologia , Adulto , Implantação do Embrião/fisiologia , Feminino , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Nascimento Vivo , Fase Luteal/fisiologia , Síndrome de Hiperestimulação Ovariana/diagnóstico , Gravidez , Taxa de Gravidez , Progesterona/farmacologia , Progestinas/farmacologia , Estudos Prospectivos , Fatores de Risco , Pamoato de Triptorrelina/administração & dosagem
6.
Curr Med Sci ; 39(6): 997-1002, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31845233

RESUMO

Embryo implantation is a complicated physiological process tightly regulated by multiple biological molecules including growth factors. Transforming growth factor-betas (TGF-ßs) and their most specific signal transduction factors, Smads, are expressed in the endometrium during the window of implantation. Recent researches indicated that Smad dependent TGF-ß signaling may play an important role in the process of embryo implantation. In this study, we measured the expression of TGF-ß1, TGF-ß receptor type I (TßRI), Smad3 and p-Smad3 in the endometrium of mice and observed their elevation on day 4, 5 and 6 of pseudopregnancy. Then we administrated a specific Smad3 inhibitor (Sis3) into the uterine cavity of mice on day 3 of pregnancy. The results showed a reduction in insulin-like growth factor-1 (IGFBP-1) expression and the decreased number of implanted embryo after the administration. In addition, Sis3 was found to reduce the IGFBP-1 secretion in decidualized endometrial stromal cells. Taken all together, our findings demonstrated that TGF-ß/Smad3 signaling is involved in the process of embryo implantation.


Assuntos
Implantação do Embrião , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética , Animais , Implantação do Embrião/efeitos dos fármacos , Feminino , Isoquinolinas/administração & dosagem , Isoquinolinas/farmacologia , Camundongos , Fosforilação , Gravidez , Piridinas/administração & dosagem , Piridinas/farmacologia , Pirróis/administração & dosagem , Pirróis/farmacologia , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Transdução de Sinais , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Útero/metabolismo
7.
Fertil Steril ; 112(6): 987-993, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31843098

RESUMO

The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Fármacos para a Fertilidade/uso terapêutico , Fertilidade/efeitos dos fármacos , Fertilização In Vitro , Infertilidade/terapia , Endométrio/fisiopatologia , Medicina Baseada em Evidências , Feminino , Fármacos para a Fertilidade/efeitos adversos , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Masculino , Gravidez , Taxa de Gravidez , Resultado do Tratamento
8.
Reprod Biol Endocrinol ; 17(1): 99, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767010

RESUMO

BACKGROUND: The aim of this study was to explore the impact of endometrial thickness change after progesterone administration on pregnancy outcome in patients transferred with single frozen-thawed blastocyst. METHODS: This observational cohort study included a total of 3091 patients undergoing their first frozen-thawed embryo transfer (FET) cycles between April 2015 to March 2019. Endometrial thickness was measured by trans-vaginal ultrasound twice for each patient: on day of progesterone administration, and on day of embryo transfer. The change of endometrial thickness was recorded. RESULTS: Regardless of endometrial preparation protocol (estrogen-progesterone/natural cycle), female age, body mass index (BMI), and infertility diagnosis were comparable between patients with an increasing endometrium on day of embryo transfer and those without. However, clinical pregnancy rate increases with increasing ratio of endometrial thickness. Compared with patients with Non-increase endometrium, those with an increasing endometrium on day of embryo transfer resulted in significantly higher clinical pregnancy rate (56.21% vs 47.13%, P = 0.00 in estrogen-progesterone cycle; 55.15% vs 49.55%, P = 0.00 in natural cycle). CONCLUSIONS: In most patients, endometrial thickness on day of embryo transfer (after progesterone administration) increased or kept being stable compared with that on day of progesterone administration. An increased endometrium after progesterone administration was associated with better pregnancy outcome.


Assuntos
Blastocisto/fisiologia , Implantação do Embrião/fisiologia , Transferência Embrionária/métodos , Endométrio/anatomia & histologia , Progesterona/administração & dosagem , Adulto , Blastocisto/citologia , Implantação do Embrião/efeitos dos fármacos , Feminino , Humanos , Infertilidade Feminina/terapia , Gravidez , Resultado da Gravidez , Progestinas/administração & dosagem , Estudos Prospectivos , Adulto Jovem
9.
PLoS One ; 14(9): e0222081, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31487323

RESUMO

Lipopolysaccharide (LPS) expressed on the surface of Gram-negative bacteria activates pro-inflammatory pathways, dys-regulates the function of endometrial cells and is a key player in the mechanisms involved in endometritis. This study aimed to investigate the effects of LPS on bovine endometrial epithelial cells (bEEC) from whole transcriptome with a special focus on genes involved in embryo-maternal interactions. Following in vitro culture, bEEC from three cows were exposed to 0, 2, and 8 µg/mL LPS for 24h. RNA samples extracted at 0 and 24 hours were analyzed by RNA sequencing (RNA-seq). At 24h, 2035 differentially expressed genes (DEGs) were identified between controls and samples treated with 2 µg/mL LPS. Gene ontology analysis showed that over-expressed DEGs were associated to immune response, response to stress and external stimuli, catalytic activity, and cell cycle. Genes associated with cell membrane and cell adhesion pathways were under-expressed. LPS induced changes in expression of specific genes related to embryo-maternal interactions including under-expression of eight members of the cadherin superfamily, over-expression of six members of the mucin family, and differential expression of a large set of genes binding the above molecules and of more than 20 transcripts coding for cytokines and their receptors. Type I interferon-τ dependent genes were also over-expressed. From a sub-set of 19 genes, (biological replicates of bEEC from cows taken at time 6 (n = 3), 24 (n = 6) and 48 hours (n = 3), and 2 technical replicates per sample) differential gene expression was confirmed by RT2-qPCR (r2 between fold changes at 24 hours by RT2-qPCR and RNA-seq = 0.97). These results indicate that LPS affects the function of bEEC in many ways by differential transcription, glycolytic metabolism and oxidative stress. Many transcriptomic signatures related to implantation and embryo maternal interactions were strongly affected by LPS. These results pave the way for further studies to investigate the duration of these changes and their possible impact on endometrial function and fertility.


Assuntos
Biomarcadores/análise , Implantação do Embrião/genética , Embrião de Mamíferos/metabolismo , Endométrio/metabolismo , Células Epiteliais/metabolismo , Lipopolissacarídeos/farmacologia , Transcriptoma , Animais , Bovinos , Implantação do Embrião/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica
10.
Endocr Regul ; 53(3): 139-145, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31517635

RESUMO

OBJECTIVE: This study was designed to investigate the effect of sublethal doses (10, 60, and 120 mg/kg of pirimiphos-methyl on implantation and pregnancy in female Sprague-Dawley rats. Pirimiphos-methyl is a pesticide widely used worldwide, especially in Africa to protect food against pests and has gained widespread acceptance. METHODS: Pregnant Sprague-Dawley rats used for this study had access to food and water ad libitum and were divided into a control group and three experimental groups based on dose of chemical given. The pregnant rats were given pirimiphos-methyl orally on days 1-5, 1-7, 7-18th day of gestation and from day 1 to term. Implantation studies were carried out on days 6 and 8 of pregnancy, while the fetal parameters were ascertained on day 19 of pregnancy and at term. Serum levels of progesterone and estradiol were measured on days 6, 8 and 19 of pregnancy. RESULTS: Sublethal administration of pirimiphos-methyl showed decreased number of implantation sites on days 6 and 8, fetal weight, crown-to-rump length, length of umbilical cord and placenta weight (day 19), birth weight, litter size and total number (at term) in rats administered with pirimiphos-methyl when compared with control. CONCLUSION: Administration of pirimiphos-methyl resulted in a reduced implantation rate due to decreased uterine receptivity caused by an imbalance in the level of estradiol and progesterone and impaired reproductive outcome during pregnancy.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Exposição Materna , Compostos Organotiofosforados/toxicidade , Resultado da Gravidez , Animais , Implantação do Embrião/fisiologia , Feminino , Feto/efeitos dos fármacos , Feto/patologia , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Exposição Materna/efeitos adversos , Praguicidas/toxicidade , Placenta/efeitos dos fármacos , Placentação/efeitos dos fármacos , Gravidez , Resultado da Gravidez/veterinária , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade
11.
Taiwan J Obstet Gynecol ; 58(5): 673-679, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542091

RESUMO

OBJECTIVE: General anesthesia is used in most in vitro fertilization (IVF) clinics for oocyte pick-up (OPU), however, there is no consensus on type of anesthetic agent use among clinicians performing OPU. Therefore, we aimed to evaluate the effects of propofol, ketamine, or combination of propofol and ketamine (P + K) for OPU on IVF outcome. MATERIAL AND METHODS: Three hundred and thirty three women (n = 333) undergoing IVF treatment were retrospectively included and were evaluated in three groups depending on whether they received propofol (n = 217), or ketamine (n = 60), or P + K (n = 56) for anesthesia during OPU. RESULTS: Baseline characteristics and duration of anesthesia of each group were comparable except lower motile sperm percentage in the ketamine group compared to the propofol group (p = 0.002). Fertilization rate (FR) was decreased with ketamine compared to propofol (p = 0.013) and P + K (p = 0.008). After adjustment for sperm motility, this negative effect of ketamine on FR persisted. Implantation, clinical pregnancy, take-home baby rates, and oocyte retrieval parameters (number of total retrieved oocyte, metaphase II oocytes, embryo and methaphase II rate, and embryo quality) did not differ between the groups. Extended anesthesia duration (>30 min) was associated with low implantation (p = 0.04) and clinical pregnancy rates (p = 0.02). CONCLUSION: Ketamine use during OPU can affect FR compared to propofol and P + K. Long durations of anesthesia also seem to decrease implantation and clinical pregnancy rates.


Assuntos
Anestésicos Intravenosos/administração & dosagem , Fertilização In Vitro/métodos , Ketamina/administração & dosagem , Recuperação de Oócitos/métodos , Propofol/administração & dosagem , Adulto , Quimioterapia Combinada , Implantação do Embrião/efeitos dos fármacos , Feminino , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento
12.
Medicina (Kaunas) ; 55(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450870

RESUMO

Background and Objectives: Assisted reproductive techniques today have helped many infertile couples achieve their desired pregnancy. However, unsuccessful implantation is usually the key failure in in vitro fertilization cycles. Many factors are now being studied to improve the implantation rate, one being endometrial artificial injury (endometrial scratching). The purpose of this study was to assess whether local endometrial artificial injury improved pregnancy rate, in long agonist and antagonist protocols. Materials and Methods: A retrospective analysis was carried out at the JSC Baltic American Clinic from January 1, 2016 to December 31, 2018. Women who were undergoing in vitro fertilization treatment were enrolled in the study. Medical data including demographic factors, menstrual history, and anamnesis of infertility were collected from medical records. Subjects were divided into intervention and control groups. The outcome of this study was clinical pregnancy rate (CPR). Results: A total of 137 women presenting with primary or secondary infertility were enrolled in the study. Clinical pregnancy was observed in 44/71 (61.9%) patients in the intervention group and 33/66 (50%) in the group without endometrial scratching (p value = 0.16). CPR in the intervention group was significantly higher in the patient group that had undergone ovarian stimulation with a long agonist protocol rather than the antagonist protocol (73.8% vs. 41.4%; p value = 0.006). In the multivariable logistic regression model, previously failed in vitro fertilization (IVF) (odds ratio (OR) = 0.07, 95% confidence interval (CI) 0.01-0.47), stimulation with the long agonist protocol (OR = 19.89, 95% CI 3.57-18.63), antagonist protocol (OR = 0.05, 95% CI 0.01-0.34), number of embryos (OR = 1.37, 95% CI 1.05-1.38), and number of blastocysts (OR = 2.96, 95% CI 1.43-8.36) remained important independent prognostic factors for clinical pregnancy. Conclusions: Our study findings indicate that randomized controlled studies are required to define patients for this procedure and to prove the effect and safety of local endometrial injury, before it is introduced to routine clinical practice.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Endométrio/lesões , Fertilização In Vitro/métodos , Infertilidade Feminina/tratamento farmacológico , Adulto , Implantação do Embrião/fisiologia , Endométrio/fisiopatologia , Feminino , Fertilização In Vitro/estatística & dados numéricos , Humanos , Infertilidade Feminina/fisiopatologia , Lituânia , Modelos Logísticos , Razão de Chances , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
13.
Reprod Toxicol ; 89: 130-135, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31306769

RESUMO

To assess the associations between air pollution and the pregnancy rate of IVF, we performed a retrospective cohort study on 1455 women who underwent the first fresh IVF cycle at a fertility center from January 2014 to April 2018 and lived in Shenyang during treatment. Binary logistic regression models were used to evaluate the effect of an interquartile range increase in each pollutant on the intrauterine pregnancy rate. Both average chronic and daily acute exposure to air pollution were considered. Increased O3 (adjusted OR = 0.87, 95% CI: 0.81, 0.98) during the period from gonadotropins starting to oocyte retrieval was associated with decreased probability of intrauterine pregnancy, especially the day before oocyte retrieval (adjusted OR = 0.86, 95% CI: 0.78, 0.95). Our results suggest that exposure to O3 before oocyte retrieval has an adverse effect on intrauterine pregnancy. Future studies should be performed in order to confirm our findings.


Assuntos
Poluentes Atmosféricos/análise , Implantação do Embrião/efeitos dos fármacos , Exposição Ambiental/análise , Fertilização In Vitro , Ozônio/análise , Taxa de Gravidez/tendências , Adulto , China , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Gravidez , Estudos Retrospectivos
14.
Fertil Steril ; 112(1): 89-97.e1, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31277770

RESUMO

OBJECTIVE: To evaluate whether intrauterine injection of hCG before embryo transfer can improve IVF-ET outcomes. DESIGN: Meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile women who underwent IVF-ET and received an intrauterine injection of hCG before ET. INTERVENTION(S): Infertile women treated with or without intrauterine hCG injection before ET. MAIN OUTCOME MEASURE(S): The primary outcomes were live birth rate (LBR), ongoing pregnancy rate (OPR), and clinical pregnancy rate (CPR), and the secondary outcomes were implantation rate (IR) and miscarriage rate (MR). Odds ratios with 95% confidence intervals (CIs) and successful ET rates were pooled to determine the effects of hCG on IVF-ET outcomes. RESULT(S): Fifteen randomized controlled trials (RCTs) with a total of 2,763 participants were included. Infertile women in the experimental group (treated with intrauterine hCG injection before ET) exhibited significantly higher LBR (44.89% vs. 29.76%), OPR (48.09% vs. 33.42%), CPR (47.80% vs. 32.78%), and IR (31.64% vs. 22.52%) than those in the control group (intrauterine injection of placebo or no injection). Furthermore, MR was significantly lower (12.45% vs. 18.56%) in the experimental group than in the control group. CONCLUSION(S): The findings of this meta-analysis indicate that intrauterine injection of hCG can improve LBR, OPR, CPR, and IR after IVF-ET cycles. In addition, different timing and dosages of hCG administration may exert different effects on IVT-ET outcomes. Notably, infertile women treated with 500 IU hCG within 15 minutes before ET can achieve optimal IVF-ET outcomes.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária , Fármacos para a Fertilidade Feminina/administração & dosagem , Fertilização In Vitro , Infertilidade Feminina/terapia , Gonadotropina Coriônica/efeitos adversos , Implantação do Embrião/efeitos dos fármacos , Transferência Embrionária/efeitos adversos , Feminino , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Feminina/efeitos adversos , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Injeções , Nascimento Vivo , Gravidez , Complicações na Gravidez/etiologia , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
15.
PLoS One ; 14(5): e0217095, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150416

RESUMO

BACKGROUND/AIM: Patients with polycystic ovary syndrome (PCOS), characterized by anovulation, hyperandrogenemia and polycystic ovaries, are still vulnerable to undergo recurrent pregnancy loss and premature labor even though the ovulatory process is pharmacologically recovered. However, its potential mechanism remains unknown. Thus, our aim was to investigate the effect and mechanism of hyperandrogenemia and flutamide (a non-steroidal anti-androgen) on the embryo implantation and pregnancy during mid-pregnancy. METHODS: We used a mouse model in which PCOS-like hyperandrogenemia was induced by subcutaneous injection of testosterone propionate. In this model, we observed the effect of hyperandrogenemia and flutamide on the decidualization, angiogenesis and uNK cells by methods of immunohistochemistry, quantitative PCR, western blotting and Dolichos biflorus agglutinin (DBA) lectin staining. RESULTS: Testosterone and flutamide treatment did not significantly influence the numbers of implanted embryo compared with the control group. However, different doses of testosterone significantly increased the ratio of resorbed /implanted embryo, decreased the level of prl8a2 mRNA and cyclin D3 protein, inhibited the uterine angiogenesis and reduced the numbers of uNK cells, but combined treatment with flutamide markedly decreased the resorbed embryos, increased expressions of prl8a2 mRNA and cyclin D3 protein and angiogenesis and numbers of uNK cells. CONCLUSION: Flutamide treatment can efficiently ameliorate the hyperandrogenemia-induced the disorders in aspects of decidualization, angiogenesis and uNK cells, which further improve the poor endometrial receptivity in PCOS patients.


Assuntos
Decídua/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Flutamida/farmacologia , Hiperandrogenismo/fisiopatologia , Neovascularização Patológica/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Útero/efeitos dos fármacos , Antagonistas de Androgênios/farmacologia , Animais , Decídua/citologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/metabolismo , Gravidez , Testosterona/administração & dosagem , Útero/citologia
16.
Eur J Obstet Gynecol Reprod Biol ; 240: 45-51, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31228675

RESUMO

OBJECTIVE: Does the administration of intravenous intralipid in women with previous implantation failure at the time of embryo transfer improve pregnancy outcomes in terms of biochemical pregnancy rate, clinical pregnancy rate, ongoing pregnancy rate, and ongoing pregnancy rate? STUDY DESIGN: This was a single blinded randomised controlled trial of 105 subjects with previous failed IVF undergoing self donor oocyte IVF/ICSI from January 2017 to May 2018. Randomisation was by computer generated sequence after oocyte pickup. Results were analysed for 102 women, excluding three women due to poor embryo quality. Women in the study arm(n = 52) received 2 doses of 20% intravenous intralipid (Fresenius Kabi), 4 ml diluted in 250 ml normal saline by slow infusion. The first dose was given immediately after oocyte recovery, and the second dose was given on the day of embryo transfer, 1 h prior to the transfer. The control group (n = 50) received normal saline. Flexible ovarian stimulation protocols were used. All the women received routine luteal phase support with micronised vaginal progesterone. RESULTS: 102 women underwent analysis, 52 in the study group and 50 in control group. There was no significant difference in the baseline characteristics. There was a significant difference in the biochemical pregnancy rate in the intralipid group (40.38%) versus control (16%) [(p = 0.006), RR = 2.5 (1.23-5.16 CI)], clinical pregnancy rate [(34.62% vs 14%), p = 0.006, RR = 2.5(1.13-5.40 CI)], implantation rate [(16.6% vs 6.6%), p = 0.012, RR = 2.5(1.18 to 5.41 CI)], and take home baby rate [28.8% vs 10%, p = 0.024, RR = 2.8(1.1-7.3)]. The adjusted odds ratio for clinical pregnancy in women who received intralipid vs placebo was 3.1 (1.02-9.70 95% CI), p = 0.046. No adverse effects of intralipid were observed. CONCLUSION: This study shows a statistically significant increase in implantation rate and live birth rate in women who receive intravenous intralipid with prior implantation failure after IVF/ICSI. These findings concur with other studies; however, literature is limited. The effect of intralipid on the immunological abnormalities in women who experience recurrent implantation failure needs to be investigated further.


Assuntos
Implantação do Embrião/efeitos dos fármacos , Fertilização In Vitro/métodos , Fosfolipídeos/uso terapêutico , Óleo de Soja/uso terapêutico , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Coeficiente de Natalidade , Transferência Embrionária , Emulsões/administração & dosagem , Emulsões/uso terapêutico , Feminino , Humanos , Infusões Intravenosas , Nascimento Vivo , Indução da Ovulação , Fosfolipídeos/administração & dosagem , Gravidez , Resultado da Gravidez , Taxa de Gravidez , Método Simples-Cego , Óleo de Soja/administração & dosagem , Resultado do Tratamento
18.
Fertil Steril ; 112(1): 98-104, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31133384

RESUMO

OBJECTIVE: To compare the influence of dual suppression with the use of GnRH agonist plus aromatase inhibitor compared with suppression with the use of GnRH agonist alone or no suppression at all in patients with idiopathic recurrent implantation failure (RIF). DESIGN: Retrospective cohort study. SETTING: University-affiliated reproductive center. PATIENT(S): A total of 523 infertile women who failed two blastocyst transfers underwent a third frozen blastocyst transfer. Women with known endometriosis were excluded. INTERVENTION(S): A total of 204 subjects were not pretreated, 143 received 2 months of GnRH agonist (3.75 mg intramuscular leuprolide acetate monthly) only, and 176 received GnRH agonist and aromatase inhibitor (5 mg oral letrozole daily for 60 days). Demographic and stimulation information was collected and cycle outcomes reported. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Age, antral follicle count, basal FSH levels, duration of infertility, previous pregnancies, and full-term deliveries were similar (P>.05). Clinical pregnancy rates were higher among women who received GnRH agonist plus letrozole compared with women who received GnRH agonist only or women without pretreatment (63%, 42%, and 40%, respectively; P<.0001). Live birth rates were higher among women who received GnRH agonist plus letrozole compared with the other groups (56%, 36%, and 34%; P<.0001). No differences in pregnancy outcomes were noted between patients who did not receive pretreatment and those in the GnRH agonist only group. CONCLUSION(S): In patients with RIF, treatment with a GnRH agonist plus letrozole may improve live birth rates in subsequent cycles. We hypothesize that this improvement is due to alterations in the endometrium receptivity or treatment of undiagnosed endometriosis.


Assuntos
Inibidores da Aromatase/uso terapêutico , Implantação do Embrião/efeitos dos fármacos , Transferência Embrionária , Fármacos para a Fertilidade Feminina/uso terapêutico , Fertilização In Vitro , Hormônio Liberador de Gonadotropina/agonistas , Infertilidade Feminina/terapia , Letrozol/uso terapêutico , Leuprolida/uso terapêutico , Adulto , Inibidores da Aromatase/efeitos adversos , Quimioterapia Combinada , Transferência Embrionária/efeitos adversos , Feminino , Fertilidade/efeitos dos fármacos , Fármacos para a Fertilidade Feminina/efeitos adversos , Fertilização In Vitro/efeitos adversos , Humanos , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Letrozol/efeitos adversos , Leuprolida/efeitos adversos , Nascimento Vivo , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Risco , Falha de Tratamento
19.
J Assist Reprod Genet ; 36(7): 1481-1487, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104292

RESUMO

PURPOSE: To compare outcomes between daily intramuscular progesterone (IMP) and daily vaginal progesterone (VP) gel plus weekly intramuscular hydroxyprogesterone caproate (IMHPC) for luteal phase support (LPS) in single, autologous euploid frozen-thawed blastocyst transfers (FBTs) following artificial endometrial preparation (EP). METHODS: The retrospective cohort study included 767 single, autologous FBTs from 731 patients between January 2015 and March 2018. LPS was performed either with IMP (100 mg/day) or with VP gel (90 mg, twice daily) plus IMHPC (250 mg/week). Oral estrogen was prescribed in combination of both regimes. Oral estrogen was discontinued following the visualization of fetal cardiac activity on ultrasound and progesterone at 10 weeks of gestation. The primary outcome was live birth rate. The secondary outcomes included implantation, clinical pregnancy, and multiple pregnancy rates. RESULTS: Patient characteristics did not differ in LPS regimes. Of 767 FBTs, 608 had IMP (100 mg/day) for LPS and 159 had VP gel (90 mg, twice daily) plus IMHPC (250 mg/week) for LPS. The live birth rate was 51.8% and 50.3%, respectively (p = 0.737, OR 0.94, 95%CI 0.66-1.33). The implantation rate was 62.7% and 64.2%, respectively (p = 0.730, OR 1.06, 95%CI 0.74-1.53). The clinical pregnancy rates were also similar in both groups (59.5% vs. 61.6%, respectively, p = 0.631, OR 1.09, 95%CI 0.76-1.56). CONCLUSIONS: We did not observe significant differences in the rates of live birth, implantation, and clinical pregnancy between daily IMP and daily VP gel plus weekly IMHPC for LPS in single, autologous euploid FBTs after artificial EP.


Assuntos
Fertilização In Vitro , Infertilidade/tratamento farmacológico , Progesterona/administração & dosagem , Transferência de Embrião Único , Administração Intravaginal , Adulto , Blastocisto/efeitos dos fármacos , Criopreservação , Implantação do Embrião/efeitos dos fármacos , Feminino , Géis/administração & dosagem , Humanos , Infertilidade/patologia , Injeções Intramusculares , Fase Luteal/efeitos dos fármacos , Fase Luteal/genética , Gravidez , Taxa de Gravidez , Progesterona/análogos & derivados
20.
Fertil Steril ; 111(6): 1177-1185.e3, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31029432

RESUMO

OBJECTIVE: To investigate whether the duration of estrogen administration before euploid embryo transfer affects clinical outcome. DESIGN: Retrospective cohort study. SETTING: Private, academic fertility center. PATIENT(S): Patients (n = 1,439) undergoing autologous freeze-only in vitro fertilization with preimplantation genetic testing (PGT) followed by endometrial preparation with estrogen and progesterone in a frozen, euploid blastocyst transfer cycle. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Primary outcome was live birth, and secondary outcomes included implantation, clinical pregnancy, early pregnancy loss, live birth, infant birthweight, low birth weight, infant gestational age at delivery, and preterm birth. RESULT(S): The duration of estrogen administration (mean: 17.5 ± 2.9 days; range: 10-36 days) before frozen embryo transfer did not impact implantation (odds ratio [OR] 0.99; 95% confidence interval [CI], 0.95-1.03), clinical pregnancy (OR 0.98; 95% CI, 0.94-1.01), early pregnancy loss (OR 1.03; 95% CI, 0.95-1.12), or live birth (OR 0.99; 95% CI, 0.95-1.03). The duration of estrogen exposure did not affect infant birthweight (in grams) (ß= -10.65 ± 8.91) or the odds of low birth weight (OR 0.87; 95% CI, 0.68-1.13). For every additional day of estrogen administration, we observed a reduction in gestational age at delivery (in weeks) (ß= -0.07 ± 0.03), but the odds of preterm delivery were not affected (OR 1.05; 95% CI, 0.95-1.17). CONCLUSION(S): Variation in the duration of estradiol supplementation before progesterone initiation does not impact frozen, euploid blastocyst transfer outcome. The duration of estrogen administration was inversely correlated with gestational age at delivery, but this did not translate into an increase in preterm delivery. Further studies are required on the downstream effects of endometrial preparation on the placental-endometrium interface.


Assuntos
Blastocisto , Criopreservação , Implantação do Embrião/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Estradiol/administração & dosagem , Fármacos para a Fertilidade Feminina/administração & dosagem , Fertilização In Vitro , Infertilidade/terapia , Transferência de Embrião Único , Adulto , Esquema de Medicação , Endométrio/fisiopatologia , Estradiol/efeitos adversos , Feminino , Fármacos para a Fertilidade Feminina/efeitos adversos , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Nascimento Vivo , Gravidez , Complicações na Gravidez/etiologia , Taxa de Gravidez , Estudos Retrospectivos , Fatores de Risco , Transferência de Embrião Único/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Vitrificação
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