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      Progestin-Primed Ovarian Stimulation with Dydrogesterone versus Medroxyprogesterone Acetate in Women with Polycystic Ovarian Syndrome for in vitro Fertilization: A Retrospective Cohort Study

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          Dydrogesterone (DYG) is an alternative progestin in progestin-primed ovarian stimulation (PPOS) protocol with weaker pituitary suppression than medroxyprogesterone acetate (MPA) in normal ovulatory women. However, the endocrinological characteristics, oocyte retrieval and pregnancy outcomes of DYG application in polycystic ovarian syndrome (PCOS) patients undergoing in vitro fertilization (IVF) remain unclear.

          Patients and methods

          This retrospective cohort study included 420 PCOS patients who underwent controlled ovarian stimulation with human menopausal gonadotropin (hMG) and DYG (n=105) or MPA (n=315) from January 2014 to December 2017. Baseline characteristics of the two groups were balanced with propensity score matching using the nearest-neighbor random matching algorithm in a ratio of 1:3. The primary outcome measure was the number of oocytes retrieved. Other main outcome measures included the number of viable embryos, incidence of premature luteinizing hormone (LH) surge and live birth rate per frozen-thawed embryo transfer (FET) cycle.


          A similar number of oocytes was retrieved in the two protocols (16.1±6.5 vs 15.1±10.0, P=0.342). Patients in both groups achieved consistent LH suppression with no premature LH surge detected. In the DYG + hMG group, the mean LH levels were significantly higher than the MPA + hMG group on cycle day 9–11 and trigger day (all P<0.001), and the dose of hMG was significantly lower (1710.7±431.6 vs 1891.3±402.2 IU, P<0.001). No significant between-group differences were found in the number of viable embryos (5.3±3.1 vs 5.0±4.1, P=0.139) and live birth rate per FET cycle (43.5% vs 47.7%, P=0.383). None of the participants experienced moderate-to-severe ovarian hyperstimulation syndrome in either group.


          Our results showed that the application of DYG in PPOS protocol could achieve comparable oocyte retrieval and pregnancy outcomes to MPA, but significantly reduce the consumption of gonadotropins in PCOS women for IVF treatment.

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          Most cited references 30

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          A review of the application of propensity score methods yielded increasing use, advantages in specific settings, but not substantially different estimates compared with conventional multivariable methods.

          Propensity score (PS) analyses attempt to control for confounding in nonexperimental studies by adjusting for the likelihood that a given patient is exposed. Such analyses have been proposed to address confounding by indication, but there is little empirical evidence that they achieve better control than conventional multivariate outcome modeling. Using PubMed and Science Citation Index, we assessed the use of propensity scores over time and critically evaluated studies published through 2003. Use of propensity scores increased from a total of 8 reports before 1998 to 71 in 2003. Most of the 177 published studies abstracted assessed medications (N=60) or surgical interventions (N=51), mainly in cardiology and cardiac surgery (N=90). Whether PS methods or conventional outcome models were used to control for confounding had little effect on results in those studies in which such comparison was possible. Only 9 of 69 studies (13%) had an effect estimate that differed by more than 20% from that obtained with a conventional outcome model in all PS analyses presented. Publication of results based on propensity score methods has increased dramatically, but there is little evidence that these methods yield substantially different estimates compared with conventional multivariable methods.
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            The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance.

            Here we describe the consensus guideline methodology, summarise the evidence-based recommendations we provided to the World Health Organisation (WHO) for their consideration in the development of global guidance and present a narrative review on the management of anovulatory infertility in women with polycystic ovary syndrome (PCOS).
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              Consensus on infertility treatment related to polycystic ovary syndrome.

              The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. This paper describes, on the basis of the currently available evidence, the consensus reached by a group of experts regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotrophins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotrophins is associated with increased chances for multiple pregnancy and, therefore, intense monitoring of ovarian response is required. LOS alone is usually effective in <50% of women and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC, gonadotrophin paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%. Recommended third-line treatment is in vitro fertilization. More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-, second- or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                31 December 2019
                : 13
                : 4461-4470
                [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 Kuang Department of Assisted Reproduction, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine , 639 Zhizaoju Road, Shanghai200011, People’s Republic of ChinaTel +86-21-2327 1699 Ext 5539Fax +86-21-6313 6856 Email cairenfei070@sina.com; kuangyp9hospital@126.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).

                Page count
                Figures: 2, Tables: 3, References: 37, Pages: 10
                Original Research


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