Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 1956 word(s) 1956 2021-09-27 04:55:32 |
2 format correct Meta information modification 1956 2021-10-15 03:38:55 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Marin, L. Sildenafil and Infertility Treatments. Encyclopedia. Available online: (accessed on 14 June 2024).
Marin L. Sildenafil and Infertility Treatments. Encyclopedia. Available at: Accessed June 14, 2024.
Marin, Loris. "Sildenafil and Infertility Treatments" Encyclopedia, (accessed June 14, 2024).
Marin, L. (2021, October 14). Sildenafil and Infertility Treatments. In Encyclopedia.
Marin, Loris. "Sildenafil and Infertility Treatments." Encyclopedia. Web. 14 October, 2021.
Sildenafil and Infertility Treatments

One of the adjuvants that showed potential beneficial effects on endometrial thickening in women undergoing infertility treatments is sildenafil citrate, a 5-phosphodiesterase inhibitor widely used for male erectile dysfunction. The Sildenafil pharmacological effect of Sildenafil is based on the prevention of cGMP breakdown thereby increasing smooth muscle relaxation and vasodilation. At the endometrium level, Sildenafil may increase uterine artery flow and exert a positive effect on endometrial growth in response to estrogenic stimulation. Moreover, it may improve endometrial tolerance to the embryo through decreasing local natural killer cell activity and favoring the accomplishment of proper embryo implantation.

Sildenafil endometrial thickness timed intercourse intrauterine insemination in vitro fertilization

1. Introduction

Despite advances in assisted reproductive technologies (ARTs), the cumulative success rate of the procedures remains suboptimal, with an estimated overall pregnancy rate of around 30% [1]. According to several studies, one of the major limiting factors for the success of ART might be represented by impaired endometrial receptivity (ER) [2].
Despite all efforts to validate specific and effective markers to find an optimal window of implantation for embryo transfer [3], endometrial thickness (ETh) is still considered the best surrogate measurement and a crucial factor for implantation. Accordingly, several studies reported a direct correlation between low ETh (<7 mm) and low success rates of ARTs—and medically assisted reproduction—(MAR) procedures, including intrauterine insemination (IUI) and in vitro fertilization (IVF) with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET) [4][5][6].
During the last decades, several strategies (including hormonal and non-hormonal adjuvants) have been tested with the purpose of increasing ETh in women undergoing infertility treatments, with conflicting results [7][8][9][10][11][12][13][14][15][16][17].
One of the adjuvants that showed potential beneficial effects on endometrial thickening in women undergoing infertility treatments is sildenafil citrate, a 5-phosphodiesterase inhibitor widely used for male erectile dysfunction [18]. The Sildenafil pharmacological effect of Sildenafil is based on the prevention of cGMP breakdown thereby increasing smooth muscle relaxation and vasodilation [18]. At the endometrium level, Sildenafil may increase uterine artery flow and exert a positive effect on endometrial growth in response to estrogenic stimulation [19]. Moreover, it may improve endometrial tolerance to the embryo through decreasing local natural killer cell activity and favoring the accomplishment of proper embryo implantation [20]. Mechanisms of action of Sildenafil on the endometrium are not fully understood. Due to its supposed action of favoring implantation both through the increase in endometrial thickness [19] and through the immune action [20], this type of add-therapy has been studied on different types of infertile women, both those with a thin endometrium and those without an apparent endometrial problem. In fact, implantation does not occur in about 1/3 of transfers of euploid blastocyst in women without an apparent endometrial abnormality [21].
Based on these principles, randomized controlled trials investigated the efficacy of oral or vaginal Sildenafil administration in women undergoing infertility treatments. Thus, the aim of this present systematic review and meta-analysis was to summarize the current evidence on the effectiveness of Sildenafil administration for improving ETh and the success of ARTs and MAR procedures.

2. Sildenafil Supplementation for Women Undergoing Infertility Treatments

2.1. General Considerations

Despite the improvement in ARTs, the live birth rate is still low even if top-quality embryos are obtained [22]. A great issue is the obtaining of a receptive endometrium [23][24]. Despite new technologies that allow the detection of the implantation window through an endometrial biopsy performed during the previous menstrual cycle [25][26], the widely used method in the clinical practice to establish if an endometrium is suitable for implantation is the transvaginal ultrasound evaluation of ETh [27][28][29].
The underlying cause of the thin endometrium must be sought and resolved before attempting another cycle for achieving pregnancy. Hysteroscopy is usually the gold standard as a second-line diagnostic investigation [30][31][32], and Asherman’s syndrome is the first pathological condition that must be excluded [33]. Another underlying underdiagnosed condition that has recently been re-examined might be chronic endometritis that can be suspected with diagnostic hysteroscopy and confirmed with endometrial biopsy [34][35][36][37].
Despite these second-line investigations, many times the underlying cause cannot be identified. Although sometimes the endometrium might be receptive even if a thinner value is used as a cut-off [24], an association has been demonstrated between low endometrial thickness, ART failure and adverse pregnancy outcomes related to an abnormal placentation such as hypertension, preeclampsia, intrauterine growth defects [38][39][40].
For these reasons, many efforts have been made in order to obtain a thicker endometrium with different strategies involving hormonal approaches (estradiol administration adjustment, hCG administration during the follicular phase, GnRH agonist administration during the luteal phase), the intrauterine infusion of growth factors such as the granulocyte colony-stimulating factor and platelet-rich plasma and the usage of factors that act on endometrium vascularity [41]. For this latter approach, low dose aspirin has been used and also phosphodiesterase inhibitors [41]. Among phosphodiesterase inhibitors, there are non-specific inhibitors such as pentoxifylline and selective ones such as phosphodiesterase type 5 inhibitor (Tadalafil and Sildenafil) [42][43]. However, despite different approaches that might be available, a lack of solid evidence in the published literature limits their clinical applicability.
In particular, the usage of selective phosphodiesterase type 5 inhibitors seems a promising strategy supported by a valid biological rationale. Indeed, Sildenafil causes vasodilatation preventing cGMP breakdown and increasing relaxation of the smooth muscle [12][44]. This effect is widely used in males for erectile dysfunction [45]. With a similar mechanism, Sildenafil might increase uterine artery flow with subsequent enhanced endometrial vascularization and improved endometrial growth under estrogenic influence [19][44].

2.2. Main Findings

In this meta-analysis, we tested the effect of Sildenafil as an add-therapy during the TI or IUI cycle and during IVF and fresh-ET or frozen-ET on ETh and the pregnancy rate. We found that Sildenafil supplementation significantly improves ETh when administered during a timed intercourse or IUI cycles; on the contrary, it does not seem to take a significant advantage when administered during fresh-ET or frozen-ET. In both groups, there was a bad consistency (I2 86% and 97%, respectively). Similarly, analyzing TI or IUI cycles, we found that the intervention was associated with a higher CPR and ChPR (low inconsistency, I2 = 0%). In fresh-ET or frozen-ET groups, there was a higher rate of ChPR in Sildenafil co-treatment women.
A subgroup analysis for the evaluation of the way of Sildenafil administration was possible only for the IVF Fresh-ET/Frozen-ET groups. Even if only one study evaluated the oral administration of Sildenafil in these groups [46], vaginal administration seems to be more effective, but further studies are needed to confirm these results.
A subgroup analysis revealed that also timing of administration had a significant effect. In fact, only the delayed starting of Sildenafil administration during the TI and IUI cycles led to a thicker endometrium and to a higher biochemical pregnancy rate.

2.3. Interpretation

Based on our results, it would seem that ETh, CPR and ChPR are higher with the use of Sildenafil in women undergoing TI and IUI. In particular, a subgroup analysis evidenced that the delayed start of Sildenafil administration might significantly increase the chances of obtaining a thicker endometrium and pregnancy. Further studies are needed to reveal whether the way of Sildenafil administration has a significant effect on endometrial thickness and the pregnancy rate.
Considering women undergoing TI/IUI [19][47][48][49][50], in all except one trial [51], Sildenafil was orally administered. In this group, a significant improvement was highlighted for Eth, CPR and ChPR. Vaginal administration did not show significant advantages. This way of administration was evaluated in a single trial [51], but this trial compared Sildenafil to estrogen, while the other subgroup studies compared Sildenafil to no intervention.
Regarding the improvement of Eth in women undergoing MAR treated with Sildenafil, it is known that this molecule improves artery blood flow through the prevention of cGMP breakdown [18]. This leads to an increase in smooth muscle relaxation and vasodilation. The possible explanation of the impact of the Sildenafil on the endometrium is that this molecule exerts a positive effect on endometrial growth increasing endometrial vascularization through the described method. This mechanism acts in synergy with estrogens that secrete angiogenic factors to enhance revascularization [52][53]. This improvement in endometrial growth through an increased vascularization led to an improvement in the CPR and ChPR.
Better outcomes in terms of the CPR and ChPR were reported when Sildenafil supplementation was started 7–8 days from ovarian stimulation.
Physiologically, endometrial vascularization increases during the endometrial proliferative phase that generally last from the 7th day of the menstrual cycle under the influence of estrogens through the action of different angiogenic factors [52][53][54]. As natural killer cells release cytokines that are involved in embryo implantation failure through nitric oxide action, it may be beneficial to limit Sildenafil administration only when spiral arteries have already formed to avoid a high concentration of nitric oxide [55]. In fact, if the assumption of Sildenafil administration is to increase the endometrial vascularity, the delayed administration of this molecule adapts better to the physiology of the endometrial cycle, acting in concert with the increase in estrogen.
Considering women undergoing fresh or frozen-ET [12][46][56][57][44][58], vaginal Sildenafil represented the most common way of administration, and only one trial administered oral Sildenafil [46]. In this group, a significant improvement in ETh was not highlighted in patients treated with Sildenafil. Nevertheless, in treated women, a higher pregnancy rate was present. The only trail that considered oral administration in women undergoing the described ART techniques [46] showed a significant improvement in ETh but not in the pregnancy rate. However, considering women undergoing fresh- or frozen-ET, only the ChPR improvement was reported and not the CPR.
Regarding the non-improvement of Eth in women undergoing ART treated with Sildenafil, different explanations can be provided for patients undergoing fresh-ET and for patients undergoing frozen-ET. Women undergoing controlled ovarian stimulation achieve an increase in peak serum estradiol levels up to 10–12 times higher [59]. Since estradiol acts on the growth of the endometrium, the maximum effect on endometrial thickness can be obtained with only the high concentration of estrogen due to ovarian stimulation.
Instead, all women evaluated in the frozen-ET groups underwent an endometrial preparation with an artificial cycle. The dynamics of action of the estrogens administered in the artificial cycles of endometrial preparation on the endometrium are not fully known. It is possible that in this type of treatment, the synergy is present in MAR treatments in which Sildenafil acts in concert with estrogen to increase endometrial vascularization and therefore increase its thickness is lost.
Improvement in the ChPR was reported when the fresh-ET and frozen-ET groups were analyzed together. However, there was no significant improvement when the two groups were analyzed separately. The lack of improvement in the analysis of the frozen-ET group alone may be due to the number of limited studies available. In frozen-ET, the supplementation of Sildenafil might be useful to reach the maximum effect on endometrial vascularization, while maybe this is not possible in women undergoing fresh-ET who have higher levels of estrogens. Further studies are necessary to prove this hypothesis.
In summary, a biological explanation of the apparently different efficacies of Sildenafil among women undergoing TI and IUI compared to women undergoing IVF and fresh or frozen-ET might lie on the different levels of estrogen that are achieved during the different types of treatments [60][61]. In fact, as previously reported, estrogen treatment is an option for achieving a thicker endometrium, and high levels of endogenous estradiol might act as a cotreatment. This aspect may explain the non-significant results in endometrium thickness obtained in women undergoing transfer after treatments that required higher estradiol levels. Moreover, in our meta-analysis, the pregnancy rate resulted higher in Sildenafil treated women (p = 0.05), probably due to higher vascularization and, therefore, higher receptivity.
Regarding the route of administration, further studies are needed to evaluate the efficacy of the vaginal route of administration of sildenafil in women undergoing ART. This route of administration could ensure a higher endometrial concentration of sildenafil. In fact, vaginal absorption occurs through the vaginal mucosa which is highly vascularized, and it does not depend on food intake and avoids hepatic metabolism.


  1. The European IVF-Monitoring Consortium (EIM) for the European Society of Human Reproduction and Embryology (ESHRE); Embryology; Wyns, C.; De Geyter, C.; Calhaz-Jorge, C.; Kupka, M.S.; Motrenko, T.; Smeenk, J.; Bergh, C.; Tandler-Schneider, A.; et al. ART in Europe, 2017: Results generated from European registries by ESHRE†. Hum. Reprod. Open 2021, 2021, hoab026.
  2. Zhang, T.; Li, Z.; Ren, X.; Huang, B.; Zhu, G.; Yang, W.; Jin, L. Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles: A retrospective cohort study of 1512 IVF cycles with morphologically good-quality blastocyst. Med. Baltim. 2018, 97, e9689.
  3. Blesa, D.; Ruiz-Alonso, M.; Simon, C. Clinical management of endometrial receptivity. Semin. Reprod. Med. 2014, 32, 410–413.
  4. Liu, Y.; Ye, X.Y.; Chan, C. The association between endometrial thickness and pregnancy outcome in gonadotropin-stimulated intrauterine insemination cycles. Reprod. Biol. Endocrinol. 2019, 17, 14.
  5. Liu, X.; Qu, P.; Bai, H.; Shi, W.; Shi, J. Endometrial thickness as a predictor of ectopic pregnancy in 1125 in vitro fertilization-embryo transfer cycles: A matched case-control study. Arch. Gynecol. Obstet. 2019, 300, 1797–1803.
  6. Groenewoud, E.R.; Cohlen, B.J.; Al-Oraiby, A.; Brinkhuis, E.A.; Broekmans, F.J.M.; de Bruin, J.P.; van Dool, G.; Fleisher, K.; Friederich, J.; Goddijn, M.; et al. Influence of endometrial thickness on pregnancy rates in modified natural cycle frozen-thawed embryo transfer. Acta Obstet. Gynecol. Scand. 2018, 97, 808–815.
  7. Zolghadri, J.; Haghbin, H.; Dadras, N.; Behdin, S. Vagifem is superior to vaginal Premarin in induction of endometrial thickness in the frozen-thawed cycle patients with refractory endometria: A randomized clinical trial. Iran. J. Reprod. Med. 2014, 12, 415–420.
  8. Noventa, M.; Vitagliano, A.; Andrisani, A.; Blaganje, M.; Viganò, P.; Papaelo, E.; Scioscia, M.; Cavallin, F.; Ambrosini, G.; Cozzolino, M. Testosterone therapy for women with poor ovarian response undergoing IVF: A meta-analysis of randomized controlled trials. J. Assist. Reprod. Genet. 2019, 36, 673–683.
  9. Davar, R.; Miraj, S.; Farid Mojtahedi, M. Effect of adding human chorionic gonadotropin to frozen thawed embryo transfer cycles with history of thin endometrium. Int. J. Reprod. Biomed. 2016, 14, 53–56.
  10. Qublan, H.; Amarin, Z.; Al-Qudah, M.; Diab, F.; Nawasreh, M.; Malkawi, S.; Balawneh, M. Luteal phase support with GnRH-a improves implantation and pregnancy rates in IVF cycles with endometrium of < or =7 mm on day of egg retrieval. Hum. Fertil. (Camb. Engl.) 2008, 11, 43–47.
  11. Weckstein, L.N.; Jacobson, A.; Galen, D.; Hampton, K.; Hammel, J. Low-dose aspirin for oocyte donation recipients with a thin endometrium: Prospective, randomized study. Fertil. Steril. 1997, 68, 927–930.
  12. Firouzabadi, R.D.; Davar, R.; Hojjat, F.; Mahdavi, M. Effect of sildenafil citrate on endometrial preparation and outcome of frozen-thawed embryo transfer cycles: A randomized clinical trial. Iran. J. Reprod. Med. 2013, 11, 151–158.
  13. Acharya, S.; Yasmin, E.; Balen, A.H. The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies—A report of 20 cases. Hum. Fertil. (Camb. Engl.) 2009, 12, 198–203.
  14. Bodombossou-Djobo, M.M.; Zheng, C.; Chen, S.; Yang, D. Neuromuscular electrical stimulation and biofeedback therapy may improve endometrial growth for patients with thin endometrium during frozen-thawed embryo transfer: A preliminary report. Reprod. Biol. Endocrinol. 2011, 9, 122.
  15. Sarvi, F.; Arabahmadi, M.; Alleyassin, A.; Aghahosseini, M.; Ghasemi, M. Effect of increased endometrial thickness and implantation rate by granulocyte colony-stimulating factor on unresponsive thin endometrium in fresh in vitro fertilization cycles: A randomized clinical trial. Obstet. Gynecol. Int. 2017, 2017, 3596079.
  16. Kunicki, M.; Lukaszuk, K.; Liss, J.; Skowronska, P.; Szczyptanska, J. Granulocyte colony stimulating factor treatment of resistant thin endometrium in women with frozen-thawed blastocyst transfer. Syst. Biol. Reprod. Med. 2017, 63, 49–57.
  17. Wang, X.; Liu, L.; Mou, S.; Zhao, H.; Fang, J.; Xiang, Y.; Zhao, T.; Sha, T.; Ding, J.; Hao, C. Investigation of platelet-rich plasma in increasing proliferation and migration of endometrial mesenchymal stem cells and improving pregnancy outcome of patients with thin endometrium. J. Cell. Biochem. 2019, 120, 7403–7411.
  18. Scaglione, F.; Donde, S.; Hassan, T.A.; Jannini, E.A. Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction: Pharmacology and clinical impact of the sildenafil citrate orodispersible tablet formulation. Clin. Ther. 2017, 39, 370–377.
  19. Kortam, M.F.; Mohammad, H.F.; Mobarak, M.H.; Bazazo, A.I. The effect of estradiol valerate with and without oral sildenafil on endometrial thickness and pregnancy rates in infertile women: A R.C.T. Evid. Based Womens Health J. 2018, 8, 5.
  20. Jerzak, M.; Kniotek, M.; Mrozek, J.; Gorski, A.; Baranowski, W. Sildenafil citrate decreased natural killer cell activity and enhanced chance of successful pregnancy in women with a history of recurrent miscarriage. Fertil. Steril. 2008, 90, 1848–1853.
  21. Forman, E.J.; Hong, K.H.; Ferry, K.M.; Tao, X.; Taylor, D.; Levy, B.; Treff, N.R.; Scott, R.T., Jr. In vitro fertilization with single euploid blastocyst transfer: A randomized controlled trial. Fertil. Steril. 2013, 100, 100–107.e101.
  22. Alteri, A.; Corti, L.; Cermisoni, G.C.; Papaleo, E.; Viganò, P.; Noventa, M. Busting the myth of extended blastocyst culture until Day 7: Protocol for systematic review and meta-analysis. Medicine (Baltim.) 2020, 99, e18909.
  23. Hromadová, L.; Tokareva, I.; Veselá, K.; Trávník, P.; Veselý, J. Endometrial Receptivity Analysis—A tool to increase an implantation rate in assisted reproduction. Ceska Gynekol. 2019, 84, 177–183.
  24. Mahajan, N.; Sharma, S. The endometrium in assisted reproductive technology: How thin is thin? J. Hum. Reprod. Sci. 2016, 9, 3–8.
  25. Katzorke, N.; Vilella, F.; Ruiz, M.; Krüssel, J.S.; Simón, C. Diagnosis of endometrial-factor infertility: Current approaches and new avenues for research. Geburtshilfe Frauenheilkd. 2016, 76, 699–703.
  26. Mahajan, N. Endometrial receptivity array: Clinical application. J. Hum. Reprod. Sci. 2015, 8, 121–129.
  27. Craciunas, L.; Gallos, I.; Chu, J.; Bourne, T.; Quenby, S.; Brosens, J.J.; Coomarasamy, A. Conventional and modern markers of endometrial receptivity: A systematic review and meta-analysis. Hum. Reprod. Update 2019, 25, 202–223.
  28. Tomic, V.; Kasum, M.; Vucic, K. Impact of embryo quality and endometrial thickness on implantation in natural cycle IVF. Arch. Gynecol. Obstet. 2020, 301, 1325–1330.
  29. Cozzolino, M.; Vitagliano, A.; Di Giovanni, M.V.; Laganà, A.S.; Vitale, S.G.; Blaganje, M.; Drusany Starič, K.; Borut, K.; Patrelli, T.S.; Noventa, M. Ultrasound-guided embryo transfer: Summary of the evidence and new perspectives. A systematic review and meta-analysis. Reprod. Biomed. Online 2018, 36, 524–542.
  30. Balmaceda, J.P.; Ciuffardi, I. Hysteroscopy and assisted reproductive technology. Obstet. Gynecol. Clin. N. Am. 1995, 22, 507–518.
  31. De Sá Rosa e de Silva, A.C.; Rosa e Silva, J.C.; Cândido dos Reis, F.J.; Nogueira, A.A.; Ferriani, R.A. Routine office hysteroscopy in the investigation of infertile couples before assisted reproduction. J. Reprod. Med. 2005, 50, 501–506.
  32. Cao, H.; You, D.; Yuan, M.; Xi, M. Hysteroscopy after repeated implantation failure of assisted reproductive technology: A meta-analysis. J. Obstet. Gynaecol. Res. 2018, 44, 365–373.
  33. Dreisler, E.; Kjer, J.J. Asherman’s syndrome: Current perspectives on diagnosis and management. Int. J. Womens Health 2019, 11, 191–198.
  34. Cicinelli, E.; Matteo, M.; Trojano, G.; Mitola, P.C.; Tinelli, R.; Vitagliano, A.; Crupano, F.M.; Lepera, A.; Miragliotta, G.; Resta, L. Chronic endometritis in patients with unexplained infertility: Prevalence and effects of antibiotic treatment on spontaneous conception. Am. J. Reprod. Immunol. 2018, 79, e12782.
  35. Cicinelli, E.; Vitagliano, A.; Kumar, A.; Lasmar, R.B.; Bettocchi, S.; Haimovich, S. Unified diagnostic criteria for chronic endometritis at fluid hysteroscopy: Proposal and reliability evaluation through an international randomized-controlled observer study. Fertil. Steril. 2019, 112, 162–173.e162.
  36. Vitagliano, A.; Saccardi, C.; Litta, P.S.; Noventa, M. Chronic endometritis: Really so relevant in repeated IVF failure? Am. J. Reprod. Immunol. 2017, 78, 28921706.
  37. Vitagliano, A.; Saccardi, C.; Noventa, M.; Di Spiezio Sardo, A.; Saccone, G.; Cicinelli, E.; Pizzi, S.; Andrisani, A.; Litta, P.S. Effects of chronic endometritis therapy on in vitro fertilization outcome in women with repeated implantation failure: A systematic review and meta-analysis. Fertil. Steril. 2018, 110, 103–112.e101.
  38. Griesinger, G.; Trevisan, S.; Cometti, B. Endometrial thickness on the day of embryo transfer is a poor predictor of IVF treatment outcome. Hum. Reprod. Open 2018, 2018, hox031.
  39. Kasius, A.; Smit, J.G.; Torrance, H.L.; Eijkemans, M.J.; Mol, B.W.; Opmeer, B.C.; Broekmans, F.J. Endometrial thickness and pregnancy rates after IVF: A systematic review and meta-analysis. Hum. Reprod. Update 2014, 20, 530–541.
  40. Oron, G.; Hiersch, L.; Rona, S.; Prag-Rosenberg, R.; Sapir, O.; Tuttnauer-Hamburger, M.; Shufaro, Y.; Fisch, B.; Ben-Haroush, A. Endometrial thickness of less than 7.5 mm is associated with obstetric complications in fresh IVF cycles: A retrospective cohort study. Reprod. Biomed. Online 2018, 37, 341–348.
  41. Lebovitz, O.; Orvieto, R. Treating patients with “thin” endometrium—An ongoing challenge. Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol. 2014, 30, 409–414.
  42. Mendez Lozano, D.H.; Lenero, M.V.; Gonzalez, R.L.; Scheffer, J.B.; Gonzalez, M.T.; Barron, Y.; Frydman, R. Tadalafil for Endometrial Growth in Clomiphene Citrate stimulated cycles in an IUI programma: A pilot study. Facts Views Vis. ObGyn 2015, 7, 231–237.
  43. Benni, J.M.; Patil, P.A. An overview on sildenafil and female infertility. Indian J. Health Sci. 2016, 9, 6.
  44. Moini, A.; Zafarani, F.; Jahangiri, N.; Jahanian Sadatmahalleh, S.H.; Sadeghi, M.; Chehrazi, M.; Ahmadi, F. The effect of vaginal sildenafil on the outcome of assisted reproductive technology cycles in patients with repeated implantation failures: A randomized placebo-controlled trial. Int. J. Fertil. Steril. 2020, 13, 289–295.
  45. Madeira, C.R.; Tonin, F.S.; Fachi, M.M.; Borba, H.H.; Ferreira, V.L.; Leonart, L.P.; Bonetti, A.F.; Moritz, R.P.; Trindade, A.; Gonçalves, A.G.; et al. Efficacy and safety of oral phosphodiesterase 5 inhibitors for erectile dysfunction: A network meta-analysis and multicriteria decision analysis. World J. Urol. 2020, 39, 953–962.
  46. Ataalla, W.M.; abd Elhamid, T.; Elhalwagy, A.E.E. Adjuvant sildenafil therapy in poor responders undergoing in vitro fertilization: A prospective, randomized, double-blind, placebo-controlled trial. Middle East Fertil. Soc. J. 2016, 21, 5.
  47. Fahmy, A.A.; El Sokkary, M.; Sayed, S. The value of oral sildenafil in the treatment of female infertility: A randomized clinical trial. Life Sci. J. 2015, 12, 5.
  48. Mohamed, T.Y. Oral sildenafil for treatment of female infertility among pco patients: Randomized comparative study. Austin J. Obstet. Gynecol. 2019, 6, 3.
  49. Reddy, L.P.; Madhavi, Y.; Khan, M.I. Role of Sildenafil in ovulation induction—A comparative study of outcomes with Sildenafil in ovulation induction cycles with Clomiphene Citrate. IAIM 2016, 3, 7.
  50. Vardhan, S.; Yadav, P.; Agarwal, R.; Garg, R.; Verma, U.; Pengoria, M. Effect of sildenafil citrate and estradiol valerate on endometrial characteristics in ovulation-induced cycle in women with dysovulatory infertility. J. South Asian Fed. Obstet. Gynaecol. 2019, 11, 3.
  51. Mangal, S.; Mehirishi, S. To study and compare the effect of vaginal sildenafil and estradiol valerate on endometrial thickness, blood flow and pregnancy rates in infertile women undergoing intrauterine insemination. Int. J. Reprod. Contracept. Obstet. Gynecol. 2016, 5, 4.
  52. Gambino, L.S.; Wreford, N.G.; Bertram, J.F.; Dockery, P.; Lederman, F.; Rogers, P.A. Angiogenesis occurs by vessel elongation in proliferative phase human endometrium. Hum. Reprod. (Oxf. Engl.) 2002, 17, 1199–1206.
  53. Girling, J.E.; Rogers, P.A. Recent advances in endometrial angiogenesis research. Angiogenesis 2005, 8, 89–99.
  54. Okada, H.; Tsuzuki, T.; Shindoh, H.; Nishigaki, A.; Yasuda, K.; Kanzaki, H. Regulation of decidualization and angiogenesis in the human endometrium: Mini review. J. Obstet. Gynaecol. Res. 2014, 40, 1180–1187.
  55. Barroso, R.P.; Osuamkpe, C.; Nagamani, M.; Yallampalli, C. Nitric oxide inhibits development of embryos and implantation in mice. Mol. Hum. Reprod. 1998, 4, 503–507.
  56. Check, J.H.; Graziano, V.; Lee, G.; Nazari, A.; Choe, J.K.; Dietterich, C. Neither sildenafil nor vaginal estradiol improves endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages. Clin. Exp. Obstet. Gynecol. 2004, 31, 99–102.
  57. Kansouh, A.M.; El-Naggar, M.A. Value of vaginal sildenafil citrate for endometrial preparation and outcome in frozen thawed embryo transfer cycles. Med. J. Cairo Univ. 2017, 85, 7.
  58. Tehraninejad, E.S.; Khazei, N.; Ayati, E.; Movafegh, A.; Azimaraghi, O. Effect of vaginal sildenafil on in vitro fertilization success rates in women with previous failed in vitro fertilization attempts. Asian J. Pharm. Clin. Res. 2018, 11, 486–488.
  59. Vaughan, D.A.; Harrity, C.; Sills, E.S.; Mocanu, E.V. Serum estradiol:oocyte ratio as a predictor of reproductive outcome: An analysis of data from >9000 IVF cycles in the Republic of Ireland. J. Assist. Reprod. Genet. 2016, 33, 481–488.
  60. Dickey, R.P.; Taylor, S.N.; Lu, P.Y.; Sartor, B.M.; Rye, P.H.; Pyrzak, R. Relationship of follicle numbers and estradiol levels to multiple implantation in 3608 intrauterine insemination cycles. Fertil. Steril. 2001, 75, 69–78.
  61. Hughes, E.G.; Robertson, D.M.; Handelsman, D.J.; Hayward, S.; Healy, D.L.; de Kretser, D.M. Inhibin and estradiol responses to ovarian hyperstimulation: Effects of age and predictive value for in vitro fertilization outcome. J. Clin. Endocrinol. Metab. 1990, 70, 358–364.
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 424
Revisions: 2 times (View History)
Update Date: 15 Oct 2021
Video Production Service