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      Pregnancy And Neonatal Outcomes Of hMG Stimulation With Or Without Letrozole In Endometrial Preparation For Frozen–Thawed Embryo Transfer In Ovulatory Women: A Large Retrospective Cohort Study

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          Frozen–thawed embryo transfer enables surplus embryos derived from IVF or IVF-ICSI treatment to be stored and transferred in subsequent cycles into a more “physiologic environment”. This study aimed to investigate the clinical effect of letrozole use or hMG stimulation on pregnancy and neonatal outcomes in ovulatory patients undergoing FET.


          This study includes a total of 5901 FET cycles with letrozole use (n = 1569), HMG (n =1827) or letrozole + HMG (n = 2505). In the letrozole group, 2.5 mg of letrozole was administered on menstrual cycle day 3 to 5 for 3 days for patients, and then follicle growth was monitored beginning on day 10. If the follicular diameter was ≥14 mm on the 10th day, no other ovarian stimulation drugs were needed. If the follicular diameter was <14 mm on the 10th day, 150 IU human menopausal gonadotropin (hMG) was added to stimulate follicle growth every two days (hMG + letrozole group). In hMG stimulation group, a total of 150 IU of hMG was injected every two days to stimulate development of follicles from cycle day 10 to 12.


          Compared with the patients undergoing hMG stimulation, the group receiving letrozole or letrozole+HMG stimulation exhibits significantly higher clinical pregnancy rates per transfer (hMG: 47.02% vs letrozole: 52.07% vs letrozole+HMG: 52.26%) and implantation rates (hMG: 31.76% vs letrozole: 34.36% vs letrozole+HMG: 34.24%). In addition, the letrozole group was associated with a statistically significantly lower incidence of miscarriage (hMG: 14.78% vs letrozole: 10.53% vs letrozole+HMG: 14.13%) and ectopic pregnancies (hMG: 1.83% vs letrozole: 0.97% vs letrozole+HMG: 1.58%) than the letrozole + HMG and HMG groups. Neonatal outcomes are similar among the three groups.


          Our data demonstrate that the letrozole use may improve clinical pregnancy outcomes and decrease the risk of ectopic pregnancies and miscarriage in ovulatory patients who receive FET cycles.

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          Most cited references 26

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          A formula for scoring human embryo growth rates in in vitro fertilization: Its value in predicting pregnancy and in comparison with visual estimates of embryo quality

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            Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

            The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates.
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              Fecundability in relation to body mass and menstrual cycle patterns.

              Few studies have investigated the association between body mass index and fecundability, that is, the ability to conceive in a menstrual cycle, among fertile women with normal menstrual cycle pattern. We examined the independent and combined effects of duration and regularity of the menstrual cycle, body mass index, and fecundability from records on pregnant women attending antenatal care at Odense University Hospital, Denmark, between 1972 and 1987. We included only the first birth of each woman who had planned pregnancies and no pre-pregnancy disease (N = 10,903). We estimated the fecundability odds ratio (FR) as the odds of conception in a menstrual cycle. After adjusting for confounders, the fecundability for women with a body mass index >25 kg/m2 was lower than for women with a body mass index of 20-25 kg/m2 [FR = 0.77; 95% confidence interval (CI) = 0.70-0.84]. FR was lower for women with long (>35 days) (FR = 0.74; 95% CI = 0.63-0.87) or irregular cycles (FR = 0.78; 95% CI = 0.70-0.87), even when their body mass index was within the normal range (20-25 kg/m2) and/or their cycles were regular.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                14 November 2019
                : 13
                : 3867-3877
                [1 ]Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Yanping Kuang; Yun Wang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine , 639 Zhizaoju Road, Shanghai200011, People’s Republic of China Email kuangyp1506@sh9hospital.com; Helen_982@126.com

                These authors contributed equally to this work

                © 2019 Lin et al.

                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: 1, Tables: 5, References: 33, Pages: 11
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81801526
                Award ID: 81801527and 31770989
                Funded by: Shanghai ninth hospital
                Award ID: JYLJ030
                This research was supported by grants from National Natural Science Foundation of China (81801526, 81801527 and 31770989), Shanghai ninth hospital (JYLJ030).
                Original Research


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