RESUMEN

OBJECTIVE: Many pieces of literature have reported that inherited and acquired thrombophilia might be a risk factor for recurrent implantation failure (RIF), however, most studies have only focused on RIF patients and not their male partners. We studied the possible association of paternal thrombophilia with RIF risk. METHODS: Forty-two male partners aged 20-45 suffered from RIF compared with 42 males from couples with at least one successful pregnancy. All participants were investigated for thrombophilia markers. RESULTS: The prevalence of coagulation Factor V activity was significantly higher in the case group (42.9%) than in the control group (16.7%) (p=0.008) (OR=3.75; 95% CI, 1.38, 10.12). The prevalence of protein C and protein S deficiencies in RIF patients were 4.8% and 2.4%, respectively, and 0% in the controls. The prevalence of antithrombin III (ATIII) deficiency was significantly higher in the case group (19%) than in the control group (2.4%) (p=0.01). None of MTHFR C677T and MTHFR A1298C were statistically significant between the two groups. Combined thrombophilia was 45.2% in the men of the RIF group when compared with the control, 14.2% (p=0.001) (OR = 4.95; 95% CI, 1.75-13.86). CONCLUSIONS: Paternal thrombophilia may be related to recurrent implantation failure, so evaluation of this factor in RIF patients could be used to identify relevant risk groups and may help in the proper management of these cases to enhance the chance of implantation.

Asunto(s)

Trombofilia , Humanos , Masculino , Trombofilia/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Persona de Mediana Edad , Implantación del Embrión , Adulto Joven , Embarazo , Factores de Riesgo

RESUMEN

OBJECTIVE: The embryo implantation includes a complex sequence of signaling events, comprising numerous molecular mediators, such as ovarian hormones, cytokines, adhesion molecules and, growth factors. One of the critical factors in angiogenesis is the vascular endothelial growth factor (VEGF). The VEGF plays a pivotal role in embryonic development, decidua vascularization and placental angiogenesis. Furthermore, the P53 gene and its negative regulator, murine double minute 2 (MDM2), are major players in reproductive processes. This study aimed to assess the association of polymorphisms of the VEGF and the MDM2 genes with idiopathic recurrent implantation failure. METHODS: We genotyped 60 women with previous idiopathic recurrent implantation failures and 60 fertile women as controls. Restriction Fragment Length Polymorphism (RFLP) and Sanger sequencing were used for genotyping the rs2010963 and the rs1570360 polymorphisms in VEGF; and the rs2279744 in MDM2 genes. RESULTS: Results indicated a higher frequency of the VEGF rs1570360 AA genotype and A allele in patients with a history of idiopathic implantation failure [OR=6.4 (1.22 - 33.64), p-value=0.02)]. However, the frequency of VEGF +405 G/C and MDM2 SNP309 T/G [(OR=3 (0.5 - 16) p-value=0.2, OR=1.18 (0.3 - 3.7) p-value=0.7, respectively)] genotypes were not significantly different between cases and controls. CONCLUSIONS: The VEGF polymorphism may influence embryo implantation and the VEGF rs1570360 AA genotype may predispose to the risk of recurrent implantation failure after IVF.

Asunto(s)

Placenta , Factor A de Crecimiento Endotelial Vascular , Animales , Femenino , Humanos , Ratones , Embarazo , Estudios de Casos y Controles , Irán , Polimorfismo Genético , Proteínas Proto-Oncogénicas c-mdm2/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factores de Crecimiento Endotelial Vascular/genética

RESUMEN

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.

Asunto(s)

Aborto Habitual , Ácidos Grasos Omega-3 , Humanos , Femenino , Embarazo , Fosfolípidos , Aborto Habitual/terapia , Aborto Habitual/etiología , Ácidos Grasos Omega-3/uso terapéutico , Emulsiones Grasas Intravenosas , Cromatografía Liquida

RESUMEN

Recurrent implantation failure (RIF) has been used to describe embryos' failure to implant following IVF, arising concerns about the importance of its treatment. Growth hormone (GH) has been studied as one of the possible co-interventions. Our updated review evaluated GH intervention vs. no intervention from randomized controlled trials (RCTs) in RIF patients. Electronic searches on The Menstrual Disorders and Subfertility Group (MDSG), The Cochrane Central Register for Clinical Trials, PubMed MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, and Google Scholar up to August 2021 identified 2 RCTs and compiled with the above inclusion criteria. The risk of bias (ROB) and the quality of evidence were assessed according to the Cochrane Collaboration tool and GRADE group guidelines. Meta-analysis found higher rates of clinical pregnancy (OR: 4.97 CI 95% 2.05 to 12.05), live birth (OR: 5.13 CI 95% 2.03 to 12.91), and implantation (OR: 3.88 CI 95% 1.91 to 7.88) when compared GH to no intervention; as well as an increased endometrial thickness (mean difference: 1.14 CI 95% -0.0 to 2.28). However, this review cannot provide a strong recommendation due to the quality of evidence rated as "very low quality of evidence" in all the outcomes for reasons such as methodology issues, heterogeneity, intervention regimen, and limited sample sizes with large confidence intervals and a low number of events. We emphasize the importance of upcoming high-quality research and the need for consensus concepts in RIF patients, which may be a minority; it is still one of the highest impacts on life quality.

Asunto(s)

Implantación del Embrión , Embarazo Múltiple , Embarazo , Femenino , Humanos , Nacimiento Vivo , Hormona del Crecimiento , Índice de Embarazo

RESUMEN

OBJECTIVE: Repeated implantation failure (RIF) is a major challenge in reproductive medicine. On the other hand, there has not yet been established a confirmed outcome regarding the usage of platelet-rich plasma (PRP) in women undergoing intracytoplasmic injection (ICSI) or in-vitro fertilization (IVF); hence, the objective of this study was to evaluate the effect of the intrauterine infusion of PRP on pregnancy outcomes in women undergoing ICSI. METHODS: In this prospective double-blind clinical trial, 100 women with at least two previous unexplained RIF, who were candidates for frozen-thawed embryo transfer, were allocated into two groups. One subgroup of patients was treated by intrauterine infusion of PRP (0.5CC, contained platelet 4-5 times more than a peripheral blood sample, which was performed 48 hours before blastocyst transfer) and the other subgroup was treated by intrauterine catheterization only. We compared the implantation rates between the two groups. RESULTS: The pregnancy rate was 20% in the intervention subgroup, while in the control subgroup it was 13.33%; therefore, there was a significant statistical difference between the two groups. CONCLUSIONS: According to this paper, PRP could be successful in improving the pregnancy outcome in RIF patients, and we highly recommend other studies with larger samples to confirm the PRP therapy efficacy in RIF patients.

Asunto(s)

Implantación del Embrión , Plasma Rico en Plaquetas , Transferencia de Embrión , Femenino , Fertilización In Vitro , Humanos , Embarazo , Índice de Embarazo , Estudios Prospectivos

RESUMEN

Proper communication between natural killer cells and the human leukocyte antigens of the embryonic trophoblast at the maternal-fetal interface during pregnancy is essential for successful reproduction. However, specific combinations of embryonic human leukocyte antigen-C with killer immunoglobulin-like receptors on decidual natural killer cells (the immunological code of pregnancy) can be associated with obstetric morbidity and pregnancy loss. This article presents an updated review of the mechanisms underlying the interaction between embryonic human leukocyte antigen-C and maternal killer immunoglobulin-like receptors and their relevance to the physiology and pathophysiology of human reproduction.

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Una adecuada comunicación entre las células asesinas naturales en la interfase materno-fetal con las moléculas de los antígenos de histocompatibilidad del trofoblasto embrionario es clave en el éxito de la reproducción. Sin embargo, combinaciones de determinados antígenos leucocitarios humanos tipo C embrionarios con los receptores tipo inmunoglobulina presentes en las células asesinas naturales deciduales (el código inmunológico del embarazo), pueden asociarse con morbilidad obstétrica y pérdidas gestacionales. En este artículo se presenta una revisión actualizada de los mecanismos subyacentes a la interacción entre el antígeno de histocompatibilidad tipo C embrionario y los receptores tipo inmunoglobulina maternos, y su relevancia tanto en la fisiología como en la fisiopatología de la reproducción humana.

Asunto(s)

Aborto Habitual/inmunología , Antígenos HLA-C/inmunología , Células Asesinas Naturales/inmunología , Placentación/fisiología , Receptores KIR/inmunología , Medicina Reproductiva , Útero/inmunología , Aborto Espontáneo/inmunología , Implantación del Embrión/inmunología , Femenino , Antígenos HLA , Antígenos HLA-C/fisiología , Humanos , Células Asesinas Naturales/fisiología , Embarazo , Receptores KIR/fisiología

RESUMEN

OBJECTIVE: The recent improvement in sequential media has refocused its attention on the role of human blastocysts in ART, not only because of its advantages but also because of the possible cancellation of embryo transfer when relying on blastocyst transfer only. Hence, the idea of sequential transfer on day 3 and day 5 was proposed. Objective: To compare the pregnancy outcomes of sequential embryo transfer on day 3 and day 5, versus cleavage transfer on day 3 and blastocyst transfer on day 5 in cases of recurrent implantation failure. METHODS: This was a prospective and randomized trial, in which 210 qualified patients with recurrent implantation failures undergoing IVF/ICSI were randomized into three groups, each group included 70 patients. Embryo transfer was performed in day 3 in the first group, day 5 (blastocyst transfer) in the second group and sequential embryo transfer in days 3 and 5 in the third group. We assessed pregnancy outcomes from all the three groups. Results: Clinical pregnancy and live birth rates were significantly higher in the sequential group than either group day-3 or day-5 of embryo transfer in cases with recurrent implantation failures. CONCLUSIONS: Sequential embryo transfer in cases with recurrent implantation failures and adequate number of retrieved oocytes is associated with higher implantation and clinical pregnancy rates, and it is advocated for patients having an adequate number of good quality embryos.

Asunto(s)

Fase de Segmentación del Huevo , Transferencia de Embrión , Blastocisto , Femenino , Fertilización In Vitro , Humanos , Embarazo , Índice de Embarazo , Estudios Prospectivos

RESUMEN

PROBLEM: Lymphocyte immunotherapy (LIT) emerged in the early 1980s as a new therapeutic proposal for couples with a history of recurrent miscarriages (RM). However, in the early 2000s, the effectiveness of LIT was questioned. Recently, meta-analyses have observed the effectiveness and safety of LIT in treating couples with RM. Some studies evaluated the use of LIT in recurrent implantation failure (RIF) in in vitro fertilization cycles. METHODS: This systematic and narrative review evaluated the data available in the literature regarding the efficacy and safety of the use of LIT. Searches in PubMed/Medline, Embase, and Cochrane Library databases were conducted, using the following keywords: "recurrent miscarriage," "lymphocyte immunotherapy," and "recurrent implantation failure". RESULTS: This review describes the historical aspects of LIT and discusses its protocols, mechanisms of action, side effects, complications, and current evidence of the effectiveness in cases of reproductive failure. It also discusses the use of LIT during the COVID-19 pandemic and new immunological therapies. CONCLUSION: In the vast majority of studies, the use of LIT for RM couples has shown an improvement in pregnancy outcomes. The most of the current studies that support the evidence are quasi-experimental, with few randomized, double-blind studies (Level of evidence III). However, the current evidence are not convincing for the use of LIT in RIF patients.

Asunto(s)

Aborto Habitual/terapia , COVID-19 , Inmunoterapia , Transfusión de Linfocitos , Linfocitos , Pandemias , SARS-CoV-2 , Femenino , Humanos , Embarazo

RESUMEN

Studies have investigated the gestational outcomes of new immunological therapies in the treatment of patients with recurrent implantation failure (RIF) in assisted reproductive technology (ART). The objective of this article is to assess the current state of evidence available in the literature on intrauterine perfusion immunotherapies in women undergoing ART treatments. By considering the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), the authors performed systematic review by searching the databases of PubMed/MEDLINE and Scopus using the following key words: "recurrent implantation failure," "intrauterine infusion," "Platelet-Rich Plasma (PRP)," "Peripheral Blood Mononuclear Cells (PBMC)," "Granulocyte Colony-Stimulating Factor (G-CSF)," and "Human Chorionic Gonadotropin (hCG)." The authors analyzed the indications and the impact of new immunological therapies with intrauterine infusions on the pregnancy outcomes of patients undergoing ART. PRP, PBMC, G-CSF, and hCG were the four most used immunological therapies with intrauterine infusion. These new therapies appear to improve the results of ART treatments in cases of RIF. However, the small number of studies does not allow definitive conclusions about the effectiveness of these therapies.

Asunto(s)

Transfusión de Sangre Intrauterina/métodos , Inmunoterapia/métodos , Leucocitos Mononucleares/inmunología , Complicaciones del Embarazo/terapia , Embarazo , Gonadotropina Coriónica/metabolismo , Implantación del Embrión , Femenino , Factor Estimulante de Colonias de Granulocitos/metabolismo , Humanos , Leucocitos Mononucleares/trasplante , Plasma Rico en Plaquetas , Complicaciones del Embarazo/inmunología , Resultado del Embarazo

RESUMEN

OBJECTIVE: To evaluate whether or not one should use a new Protocol for Endometrial Receptivity Improvement (PRIMER) based on platelet-rich plasma (PRP) and granulocyte colony-stimulation factor (G-CSF) to enhance ongoing pregnancy rates in patients with recurrent implantation failure (RIF). METHODS: Women undergoing IVF/ICSI were prospectively divided into two groups: - PRIMER/RIF group (n:33): patients with RIF (defined as ≥2embryo transfers (ETs) and at least 5 morphologically good embryos transferred) in which intrauterine PRP injection and subcutaneous G-CSF-injection were performed. - Control group (n:33): patients in their first IVF/ICSI attempt/cycle (without PRP or G-CSF injection). The PRP was prepared using autologous fresh-whole blood processed to increase platelet-concentration in 2 to 4 fold. All patients undergoing the PRP-treatment received 0.7ml of it through intrauterine-injection 48 hours before the ET. G-CSF (300mg/0.5ml) started simultaneously to PRP and was administered subcutaneously every week. RESULTS: Regarding implantation, clinical pregnancy and miscarriage rates, we found no statistically significant difference (18.2% versus 17.6%, p=0.90; 36.4% versus 30.3%, p=0.61 and 25.0% versus 9.0%, p=0.43, respectively). The use of PRIMER enabled RIF patients (previous ET µ: 4.0±1.5) to reach similar ongoing pregnancy and live birth rates like those patients who had their first IVF/ICSI cycle attempt (27.3% versus 27.3%, p=0.99). CONCLUSIONS: Our results showed, for the first time, evidence that this therapeutic protocol (PRIMER) could be used as a feasible treatment based on biological rationale for patients with RIF, considering its promising outcomes, it is a simple procedure and not associated with patient complications.

Asunto(s)

Aborto Habitual/terapia , Transfusión de Componentes Sanguíneos/métodos , Implantación del Embrión , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Plasma Rico en Plaquetas/fisiología , Terapias en Investigación/métodos , Aborto Habitual/patología , Adulto , Implantación del Embrión/efectos de los fármacos , Implantación del Embrión/fisiología , Transferencia de Embrión/métodos , Endometrio/efectos de los fármacos , Endometrio/patología , Femenino , Fertilización In Vitro/métodos , Humanos , Recién Nacido , Nacimiento Vivo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Embarazo , Índice de Embarazo , Insuficiencia del Tratamiento

RESUMEN

Abstract Sirtuin 1 has an important role in cellular processes, including apoptosis and cellular stress. The purpose of this study was to assess serum sirtuin 1 levels in women with recurrent implantation failure (RIF). In this cross-sectional study, we included 28 women with RIF, 29 healthy women who had conceived by in vitro fertilization (IVF), and 30 women with a 1-cycle failure of IVF as controls. Human serum nicotinamide adenine dinucleotide (NAD)-dependent deacetylase sirtuin-1 (SIRT1/SIRT2L1) levels were detected using a commercial colorimetric kit. Recurrent implantation failure patients have higher sirtuin 1 levels than non-pregnant women and healthy pregnant women, but this difference did not reach statistical significance due to the low number of patients in our study. These higher sirtuin 1 levels may result from the inflammation imbalance of RIF patients. The only statistically significant correlation found was between age and sirtuin (r = 0.277, p = 0.009).

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Resumo A sirtuína 1 tem importante função nos processos celulares, incluindo a apoptose e o estresse celular. O objetivo deste estudo é o de avaliar níveis de sirtuína 1 em mulheres com falhas recorrentes de implantação (FRI). Neste estudo cruzado, incluímos 28 mulheres com FRI, 29 mulheres saudáveis que deram à luz por fertilização in vitro (FIV) bem-sucedida, e 30 mulheres com 1 ciclo de FIV malsucedido como controle. Os níveis de sirtuína 1 em soro humano de desacetilase dependente de dinucleotídeo de nicotinamida adenina (DNA) (SIRT1/SIRT2L1) foram detectados usando um kit colorimétrico comercial. Pacientes com FRI tiveram níveis de sirtuína 1 superiores às pacientes grávidas e aos controles, mas esta diferença não atingiu significância estatística devido ao baixo número de pacientes envolvidos. Estes níveis mais altos de sirtuína 1 podem ser resultado da inflamação desigual em pacientes com FRI. A única correlação estatisticamente significante encontrada foi entre idade e sirtuína (r = 0,277, p = 0,009).

Asunto(s)

Humanos , Femenino , Adulto , Implantación del Embrión , Sirtuina 1/sangre , Recurrencia , Fertilización In Vitro , Estudios Transversales , Insuficiencia del Tratamiento

RESUMEN

OBJECTIVE: To determine the role of polyvalent endometrial treatment in patients undergoing IVF-ET who had recurrent implantation failure (RIF) in a program of oocyte donation (OD). The results were expressed in terms of live birth rate (LBR). Secondly analyze changes of endometrial leukocyte population evaluated by flow cytometer (FC) and histopathology. METHODS: Prospective study of a model-based control with analog abductive methodology. Over initial population of 75 patients with RIF in ovodonation, thirty cycles / patient of IVF/ET were selected in this study. A control group of 12 patients was established to variables FC. All patients were transferred to day 5-6 with a maximum of 2 expanded blastocysts with at least one of optimum quality. A versatile treatment was applied in all cases with both assessments in pre and postreatment. RESULTS: Chronic endometritis was diagnosed in 14/30 (46.7%) with endometrial identifying germs in 12/30 (40%) and 6/30 (20%) was associated with endometrial thinning. A significant increase in endometrial thickness associated with a decrease in abnormal histopathology and Li/PC was observed at postreatment in relation with a pretreatment (P=0.047 and P=0.002) respectively. An increase of uterine killer cells (Nku) was observed in postreatment in absence of pregnancy. CD4/CD3 was established with prognostic value when their values are close to those of the control group. CONCLUSION: Our findings demonstrate the reversibility of endometrial histological changes, both sonographics as immunological in RIF group under a polyvalent therapeutic; which is capable of modifying the immunology and endometrial histopathology and to obtain live birth.