Efficacy of luteal supplementation of vaginal sildenafil and oral estrogen on pregnancy rate following IVF-ET in women with a history of thin endometria: A pilot study

Kim, Kwang Rae; Lee, Hee Sun; Ryu, Hyoung Eun; Park, Chun Young; Min, Se Hee; Park, Chan; Jee, Byung Chul

doi:10.5468/jwm.2010.3.4.155

Cited by 11 publications

(11 citation statements)

References 12 publications

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“…However, the inflammatory process caused by TNF-α is crucial for trophoblast invasion, and the development of spiral arteries over the first stages of pregnancy. Thus, the effect of SC on TNF-α concentration in vitro found in the present study might be positive in vivo during pregnancy by supporting trophoblast implantation and angiogenesis in cases of patients with an exhausted immune response [ 62 , 63 , 64 , 65 ].…”

Section: Discussionmentioning

confidence: 75%

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

Kniotek

Zych

Roszczyk

et al. 2021

JCM

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Sildenafil citrate (SC), a PDE5 inhibitor, a drug for erectile dysfunction (ED) and pulmonary hypertension (PAH), was found to exert a positive effect on pregnancy outcomes when administered intravaginally before conception. In our previous studies, sildenafil increased endometrial thickness and significantly decreased peripheral blood NK cell activity after the intravaginal administration in women with recurrent pregnancy loss (RPL). No data are available to confirm the effect of sildenafil on maternal T cell populations involved in shaping fetal-maternal tolerance and NK cell activity. Thus, the present study aimed to establish if SC influences NKT cells or the axis of Th17/Treg cells and Th1/Th2 cytokine production. Materials and methods: Twenty-one healthy fertile women and twenty-two nonpregnant women with idiopathic RPL were studied. The ELISA method was used to evaluate the production of cytokines, including IL-2, IL-12p40, IL-4, IL-10, IL-6, IL-17, IL-21, TGF-β, TNF-α, and IFN-γ in PBMC culture supernatants before and after supplementation with the physiological concentration of SC. The percentages of NKT (CD56+CD3+CD44+CD161+), Treg (CD4+CD25+FOXP3+) and Th17 (CD4+CD25+IL-17A+) cells were determined with flow cytometry method. Results: Unexpectedly, we found that the PBMCs of patients with RPL produced a significantly lower level of inflammatory cytokines (TNF-α and IL-6) and a higher level of anti-inflammatory cytokines (TGF-β and IL-10). SC significantly decreased IL-6, IL-12 and increased TGF-β cytokine concentration in fertile women. In the case of RPL patients’ PBMCs, SC improved the production of TNF-α and IL-10. Conclusions: Lower concentration of proinflammatory cytokines in idiopathic RPL women compared to fertile women might suggest the exhaustion of the immune system. The emphasized production of IL-10 by SC partially explains the previously observed downregulation of NK cell activity in RPL patients. The immunomodulatory effect of the drug might be utilized in anti-inflammatory therapies and help achieve positive pregnancy outcomes in women with reproductive failure due to a Th1/Th2 imbalance.

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Section: Discussionmentioning

confidence: 75%

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

Kniotek

Zych

Roszczyk

et al. 2021

JCM

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“…Of these, 528 records were excluded after title/abstract screening (not relevant to the review). We examined the full text of 28 manuscripts, and, of these, we excluded 16 papers—two trials investigated Tadalafil as the 5-phosphodiesterase inhibitor [ 23 , 24 ], two trials reporting not analyzable data (only abstracts available) [ 25 , 26 ], four papers because the design was retrospective [ 27 , 28 , 29 , 30 ], six because of the observational design [ 31 , 32 , 33 , 34 ], one paper because it was a review [ 35 ]. Another paper was excluded because the results of Sildenafil efficacy in women with unexplained infertility were provided based on a subgroup analysis (duration of infertility) only, and the size of the subgroups was not described [ 36 ].…”

Section: Resultsmentioning

confidence: 99%

Sildenafil Supplementation for Women Undergoing Infertility Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Marin

Andrisani

Bordin

et al. 2021

JCM

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The aim of this systematic review and meta-analysis is to summarize data on the effectiveness of Sildenafil supplementation for women undergoing assisted reproduction techniques. This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of Sildenafil administration during infertility treatments compared with a control group in infertile women. Outcomes evaluated were endometrial thickness (ETh) and the clinical pregnancy rate (CPR). The chemical pregnancy rate (ChPR) was also evaluated. Pooled results were expressed as the risk ratio (RR) or mean differences (MD) with a 95% confidence interval (95% CI). Women undergoing ovulation induction who received Sildenafil showed higher ETh and a higher CPR in comparison to controls. In this group, both the ETh and ChPR resulted in significantly higher values only with delayed start administration. Women undergoing fresh or frozen embryo transfer who received Sildenafil showed no significant advantages regarding ETh and CPR in comparison to controls. In this group, we found a significantly higher ChPR in women receiving Sildenafil. A subgroup analysis revealed significant advantages regarding ETh with oral administration for women undergoing fresh or frozen embryo transfer. Sildenafil therapy appears to improve endometrial thickness and pregnancy rate in women undergoing timed intercourses but it resulted not effective in IUI and IVF treatments. Further RCTs with rigorous methodology are still mandatory.

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“…12 Likewise, Kim et al reported that the use of vaginal sildenafil plus oral oestrogen pills in the luteal phase of patients treated with an IVF-ET cycle increased the pregnancy rate by two-fold, but this increase was not statistically significant. 13…”

Section: Discussionmentioning

confidence: 99%

Outcome of vaginal sildinafil in assisted reproductive technology cycles

Kapoor¹,

Sharma²,

Bakshi³

2021

Int J Reprod Contracept Obstet Gynecol

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Background: The present study assessed the role of sildenafil in endometrial blood flow and successful pregnancy in IVF done in surrogate mothers.Methods: In the present study surrogate mothers were included. Thirty patients were randomized to receive sildenafil 25 mg thrice a day vaginally in addition to standard drugs and technique and another 30 were not given sildenafil.Results: Mean age, anthropometry, duration of infertility and pre-treatment endometrial thickness was similar in the two study groups. After treatment completion, it was observed that the endometrial pattern in ultrasound was similar in the two study groups (p value=0.58). Heterogenic endometrial pattern was observed in 6.7% of the Sildenafil patients and 3.3% in the control patients, while echogenic pattern was seen in 10% of the sildenafil patients and 6.7% of the control patients. Similarly, endometrial thickness was 10.2±1.7 and 9.7±1.8 mm in sildenafil and control group respectively, p value=0.62. Using doppler ultrasound, uterine artery PI was significantly lower in Sildenafil group patients as compared to control group patients. Similarly, we found uterine artery RI was also significantly lower in the Sildenafil group patients as compared to control group patients. We followed the patients and found that clinical pregnancy rate was significantly higher among Sildenafil group (60%) as compared to control group (26.6%), p value<0.05.Conclusions: Vaginal sildenafil resulted in significantly higher pregnancy rates in our study population. The uterine artery PI and RI were significantly lower in patients taking sildenafil.

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Efficacy of luteal supplementation of vaginal sildenafil and oral estrogen on pregnancy rate following IVF-ET in women with a history of thin endometria: A pilot study

Cited by 11 publications

References 12 publications

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

Sildenafil Supplementation for Women Undergoing Infertility Treatments: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Outcome of vaginal sildinafil in assisted reproductive technology cycles

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