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      Neonatal outcomes and congenital malformations in children born after dydrogesterone application in progestin-primed ovarian stimulation protocol for IVF: a retrospective cohort study


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          Dydrogesterone (DYG) has been demonstrated to be an alternative progestin in the progestin-primed ovarian stimulation (PPOS) protocol with comparable oocyte retrieval and pregnancy outcomes. However, its safety regarding neonatal outcomes and congenital malformations is still unclear.

          Patients and methods

          This retrospective cohort study included 3556 live-born infants after in vitro fertilization and vitrified embryo transfer cycles using the DYG + human menopausal gonadotropin (hMG) protocol (n=1429) or gonadotropin-releasing hormone (GnRH)-agonist short protocol (n=2127) from January 2014 to December 2017. Newborn information was gathered from standardized follow-up questionnaires and/or access to medical records within 7 days after birth. Associations between ovarian stimulation protocols and outcome measures were analyzed by binary logistic regression after adjusting for confounding factors.


          In both singletons and twins, birth characteristics regarding mode of delivery, newborn gender, gestational age, birthweight, length at birth and Z-scores were comparable between the two protocols. For adverse neonatal outcomes, the two protocols showed no significant differences on the rates of low birthweight, very low birthweight, preterm birth, very preterm birth, small-for-gestational age, large-for-gestational age and early neonatal death after adjustment. Furthermore, the incidence of major congenital malformations in the DYG + hMG protocol (1.12%) was similar to that in the GnRH-agonist short protocol (1.08%), with the adjusted odds ratio of 0.98 (95% confidence interval [CI]: 0.40–2.39) and 0.90 (95% CI: 0.33–2.41) in singletons and twins, respectively.


          Our data suggested that compared with the conventional GnRH-agonist short protocol, application of DYG in the PPOS protocol was a safe option for the newborn population without compromising neonatal outcomes or increasing congenital malformation risks.

          Most cited references39

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          Why do singletons conceived after assisted reproduction technology have adverse perinatal outcome? Systematic review and meta-analysis.

          Assisted reproduction technology (ART) is used worldwide, at increasing rates, and data show that some adverse outcomes occur more frequently than following spontaneous conception (SC). Possible explanatory factors for the well-known adverse perinatal outcome in ART singletons were evaluated. PubMed and Cochrane databases from 1982 to 2012 were searched. Studies using donor or frozen oocytes were excluded, as well as those with no control group or including 1 year versus SC singletons in couples with TTP ≤ 1 year [adjusted odds ratio (AOR) 1.35, 95% confidence interval (CI) 1.22, 1.50]; IVF/ICSI versus SC singletons from subfertile couples (TTP > 1 year; AOR 1.55, 95% CI 1.30, 1.85); conception after ovulation induction and/or intrauterine insemination versus SC singletons where TTP ≤ 1 year (AOR 1.45, 95% CI 1.21, 1.74); IVF/ICSI singletons versus their non-ART singleton siblings (AOR 1.27, 95% CI 1.08, 1.49). The risk of PTB in singletons with a 'vanishing co-twin' versus from a single gestation was AOR of 1.73 (95% CI 1.54, 1.94) in the narrative data. ICSI versus IVF (AOR 0.80, 95% CI 0.69-0.93), and frozen embryo transfer versus fresh embryo transfer (AOR 0.85, 95% CI 0.76, 0.94) were associated with a lower risk of PTB. Subfertility is a major risk factor for adverse perinatal outcome in ART singletons, however, even in the same mother an ART singleton has a poorer outcome than the non-ART sibling; hence, factors related to the hormone stimulation and/or IVF methods per se also may play a part. Further research is required into mechanisms of epigenetic modification in human embryos and the effects of cryopreservation on this, whether milder ovarian stimulation regimens can improve embryo quality and endometrial conditions, and whether longer culture times for embryos has a negative influence on the perinatal outcome.
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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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              Birth Weight Reference Percentiles for Chinese

              Objective To develop a reference of population-based gestational age-specific birth weight percentiles for contemporary Chinese. Methods Birth weight data was collected by the China National Population-based Birth Defects Surveillance System. A total of 1,105,214 live singleton births aged ≥28 weeks of gestation without birth defects during 2006–2010 were included. The lambda-mu-sigma method was utilized to generate percentiles and curves. Results Gestational age-specific birth weight percentiles for male and female infants were constructed separately. Significant differences were observed between the current reference and other references developed for Chinese or non-Chinese infants. Conclusion There have been moderate increases in birth weight percentiles for Chinese infants of both sexes and most gestational ages since 1980s, suggesting the importance of utilizing an updated national reference for both clinical and research purposes.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                26 July 2019
                : 13
                : 2553-2563
                [1 ]Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai 200011, People’s Republic of China
                Author notes
                Correspondence: Renfei Cai; Yanping KuangDepartment of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine , 639 Zhizaoju Road, Shanghai200011, People’s Republic of ChinaTel +862 123 271 699 5539Fax +86 216 313 6856Email CaiRF1550@ 123456sh9hospital.org ; kuangyanp@ 123456126.com

                These authors contributed equally to this work

                © 2019 Huang 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).

                : 27 March 2019
                : 11 July 2019
                Page count
                Figures: 2, Tables: 3, References: 45, Pages: 11
                Original Research

                Pharmacology & Pharmaceutical medicine
                neonatal outcomes,congenital malformations,dydrogesterone,progestin-primed ovarian stimulation,in vitro fertilization


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