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      Adjuvant Vaginal Use of Sildenafil Citrate in a Hormone Replacement Cycle Improved Live Birth Rates Among 10,069 Women During First Frozen Embryo Transfers

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          To investigate the effects of sildenafil citrate (SC) on live birth rates (LBR) during women undergoing their first frozen embryo transfers (FET) with hormone replacement therapy (HRT).

          Patients and Methods

          This retrospective cohort study included a total of 10,069 infertile women with adequate endometrial thickness (≥7 mm when progesterone was initiated) in their first FET cycle with hormone replacement therapy. Women received either vaginal SC or no adjuvant during their first transfer cycle depending on patient or physician preference. In the sildenafil group, 1098 women underwent HRT FET with adjuvant vaginal use of SC, and 8971 women were included as controls. The primary outcome measure was LBR, defined as the likelihood of live birth per transfer cycle. Endometrial thickness (EMT), implantation, chemical pregnancy, clinical pregnancy, miscarriage, ongoing pregnancy, birth weight and preterm delivery (PTB) were also recorded.


          Baseline characteristics were comparable between the two groups. In the crude analysis, the unadjusted LBR was significantly higher in the vaginal SC group (scHRT-FET) than in the control group (HRT-FET) (40.3% vs 36.1%). After adjustment for 12 pregnancy-related confounding factors, logistic regression analysis showed that LBR remained significantly higher in the scHRT-FET group than in the HRT-FET group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.14–1.49). Furthermore, after adjustment, the ongoing pregnancy rate was significantly higher (aOR 1.29, 95% CI 1.13–1.47), and the miscarriage rate was significantly lower (aOR 0.58, 95% CI 0.43–0.77), in the scHRT-FET group compared to the HRT-FET group. Adjuvant vaginal use of SC did not increase the endometrial thickness and had no significant effect on birth weight or PTB.


          Adjuvant vaginal use of SC in HRT FET was associated with higher LBR and improved pregnancy outcomes in an infertile population with adequate endometrial thickness. The beneficial effect of SC may be due not to an increase in EMT but instead to improve endometrial blood flow and receptivity, which might merit clinicians’ attention for improving general IVF practices.

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          Most cited references 45

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          Medroxyprogesterone acetate is an effective oral alternative for preventing premature luteinizing hormone surges in women undergoing controlled ovarian hyperstimulation for in vitro fertilization.

          To investigate the use of medroxyprogesterone acetate (MPA) to prevent LH surge during controlled ovarian hyperstimulation (COH) and to compare cycle characteristics and pregnancy outcomes in subsequently frozen-thawed ET (FET) cycles.
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            Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer.

            To determine the relationship between blastocyst score and pregnancy outcome. Retrospective review of blastocyst transfer in an IVF clinic. Private assisted reproductive technology unit. 107 patients undergoing blastocyst culture and transfer of two embryos. Culture of all pronucleate embryos in sequential media to the blastocyst stage (day 5), followed by transfer of two blastocysts. Implantation rates, pregnancy rates, and twinning were analyzed. When a patient received two top-scoring blastocysts (64% of patients), implantation and pregnancy rates were 70% and 87%, respectively. The twinning rate in this group was 61%. When only one top-quality blastocyst was available for transfer (21% of patients), the implantation and pregnancy rates were 50% and 70%. The twinning rate for this group was 50%. In contrast, when only low-scoring blastocysts were available for transfer (15% of patients), implantation and pregnancy rates were 28% and 44%, and the twinning rate was 29%. No monozygotic twins were observed in this group of patients. The ability to transfer one high-scoring blastocyst should lead to pregnancy rates greater than 60%, without the complication of twins.
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              Effect of vaginal sildenafil on the outcome of in vitro fertilization (IVF) after multiple IVF failures attributed to poor endometrial development.

              To evaluate the effects of vaginally administered sildenafil on endometrial thickness and IVF outcome in a large cohort of infertile women with poor endometrial development. Retrospective cohort analysis. Private practice setting. A cohort of 105 infertile women aged /=9 mm, whereas 32 (30%; Group B) did not. Implantation and ongoing pregnancy rates were significantly higher for Group A (29% and 45%) than for Group B (2% and 0). Of 11 women in Group B who had embryos transferred in that cycle, only one conception occurred, which resulted in a miscarriage. In Group B, 59% of women had a history of endometritis, compared with 44% in Group A. Vaginal administration of sildenafil enhanced endometrial development in 70% of patients studied. High implantation and ongoing pregnancy rates were achieved in a cohort with a poor prognosis for success. Previous endometritis may decrease the response to sildenafil.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                01 December 2020
                : 14
                : 5289-5297
                [1 ]Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to JiaoTong University School of Medicine , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Ningling Wang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital Affiliated to JiaoTong University School of Medicine , Shanghai, People’s Republic of China, Email 563545972@qq.com
                © 2020 Tao and Wang.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 0, Tables: 12, References: 45, Pages: 9
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Grants supporting this study were provided by the National Natural Science Foundation of China (NSFC) (81501334 to Y.T., 81801527 to N.L.W.).
                Original Research


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