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Lotus II, a randomized, open-label, multicenter, international study compared the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) gel for luteal support in IVF. A prespecified subgroup analysis was performed on 239 Chinese mainland subjects from the overall study population (n = 1034), who were randomized to oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily from the day of oocyte retrieval until 12 weeks of gestation. The aim was to demonstrate non-inferiority of oral dydrogesterone to MVP gel, assessed by the presence of a fetal heartbeat at 12 weeks of gestation. In the Chinese mainland subpopulation, there was a numerical difference of 9.4% in favor of oral dydrogesterone, with ongoing pregnancy rates at 12 weeks of gestation of 61.4% and 51.9% in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 9.4%; 95% CI: −3.4 to 22.1); in the overall population, these were 38.7% and 35%, respectively (adjusted difference, 3.7%; 95% CI: −2.3 to 9.7). In both the Chinese mainland subpopulation and the overall population, dydrogesterone had similar efficacy and safety to MVP gel. With convenient oral administration, dydrogesterone has potential to transform luteal support treatment. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is currently considered to have a peri-adolescence onset and continuously influence the reproductive and metabolic health of the patients, while the diagnostic criteria among adolescent population haven't been universally unified till now. This survey seeks to preliminarily evaluate the prevalence of PCOS in the tenth grade schoolgirls in Guangzhou area under NIH criteria and analyze the clinical features of adolescents with PCOS. Methods: The cross-sectional epidemiological survey was carried out among the tenth grade schoolgirls in Guangzhou area by the method of cluster sampling. The contents of this survey included the questionnaire, physical exams and serum measurements. Until now, totally 1294 girls underwent this survey and 1095 serum samples were restored. 235 non-hirsute (mFG < 6), postmenarcheally 2-year girls were randomly selected as the control group, among which the cut-off value of biochemical hyperandrogenemia was set accordingly. The prevalence of PCOS among this population was preliminarily evaluated according to the NIH criteria. Results: Along with the increase of gynecological age, the menstruations of girls was becoming more regular and the incidence of oligomenorrhea or amenorrhea was declining. Even among those who were less than 2 years after menarche, those whose menstrual cycle were longer than 90 days accounted for lower than 5%. The 95th percentile of mFG score was 6 among the girls who were < 2 years after menarche, and 5 among the girls who were > 2 years after menarche. Among the 235 healthy girls, the 95th percentile values of Testosterone (T), Free androgen index (FAI) and Androstenedione (A2) were 2.28 nmol/mL, 4.37, and 5.20 nmol/mL respectively. Based on the NIH criteria, the prevalence of PCOS in this survey was 3.86%. The prevalence of adolescent PCOS tend to slightly increase with age and gynecological age, but the difference was not statistically significant. The prevalence of PCOS among obese girls was markedly higher than that in lean girls. Conclusion: Based on the NIH criteria, the prevalence of PCOS among the tenth grade schoolgirls in Guangzhou area was 3.86%. The diagnosis of hyperandrogenism among adolescents should also be based on both clinical and biochemical parameters. [ABSTRACT FROM AUTHOR]

Study Question: Is oral dydrogesterone 30 mg daily non-inferior to 8% micronized vaginal progesterone (MVP) gel 90 mg daily for luteal phase support in IVF?Summary Answer: Oral dydrogesterone demonstrated non-inferiority to MVP gel for the presence of fetal heartbeats at 12 weeks of gestation (non-inferiority margin 10%).What Is Known Already: The standard of care for luteal phase support in IVF is the use of MVP; however, it is associated with vaginal irritation, discharge and poor patient compliance. Oral dydrogesterone may replace MVP as the standard of care if it is found to be efficacious with an acceptable safety profile.Study Design, Size, Duration: Lotus II was a randomized, open-label, multicenter, Phase III, non-inferiority study conducted at 37 IVF centers in 10 countries worldwide, from August 2015 until May 2017. In total, 1034 premenopausal women (>18 to <42 years of age) undergoing IVF were randomized 1:1 (stratified by country and age group), using an Interactive Web Response System, to receive oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily.Participants/materials, Setting, Methods: Subjects received either oral dydrogesterone (n = 520) or MVP gel (n = 514) on the day of oocyte retrieval, and luteal phase support continued until 12 weeks of gestation. The primary outcome measure was the presence of fetal heartbeats at 12 weeks of gestation, as determined by transvaginal ultrasound.Main Results and the Role Of Chance: Non-inferiority of oral dydrogesterone was demonstrated, with pregnancy rates in the full analysis sample (FAS) at 12 weeks of gestation of 38.7% (191/494) and 35.0% (171/489) in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 3.7%; 95% CI: -2.3 to 9.7). Live birth rates in the FAS of 34.4% (170/494) and 32.5% (159/489) were obtained for the oral dydrogesterone and MVP gel groups, respectively (adjusted difference 1.9%; 95% CI: -4.0 to 7.8). Oral dydrogesterone was well tolerated and had a similar safety profile to MVP gel.Limitations, Reasons For Caution: The analysis of the results was powered to consider the ongoing pregnancy rate, but a primary objective of greater clinical interest may have been the live birth rate. This study was open-label as it was not technically feasible to make a placebo applicator for MVP gel, which may have increased the risk of bias for the subjective endpoints reported in this study. While the use of oral dydrogesterone in fresh-cycle IVF was investigated in this study, further research is needed to investigate its efficacy in programmed frozen-thawed cycles where corpora lutea do not exist.Wider Implications Of the Findings: This study demonstrates that oral dydrogesterone is a viable alternative to MVP gel, due to its comparable efficacy and tolerability profiles. Owing to its patient-friendly oral administration route, dydrogesterone may replace MVP as the standard of care for luteal phase support in fresh-cycle IVF.Study Funding/competing Interests(s): This study was sponsored and supported by Abbott. G.G. has received investigator fees from Abbott during the conduct of the study. Outside of this submitted work, G.G. has received non-financial support from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope and Gedeon Richter, as well as personal fees from MSD, Ferring, Merck-Serono, IBSA, Finox, TEVA, Glycotope, VitroLife, NMC Healthcare, ReprodWissen, Biosilu, Gedeon Richter and ZIVA. C.B. is the President of the Belgian Society of Reproductive Medicine (unpaid) and Section Editor of Reproductive BioMedicine Online. C.B. has received grants from Ferring Pharmaceuticals, participated in an MSD sponsored trial, and has received payment from Ferring, MSD, Biomérieux, Abbott and Merck for lectures. G.S. has no conflicts of interest to be declared. A.P. is the General Secretary of the Indian Society of Assisted Reproduction (2017-2018). B.D. is President of Pune Obstetric and Gynecological Society (2017-2018). D.-Z.Y. has no conflicts of interest to be declared. Z.-J.C. has no conflicts of interest to be declared. E.K. is an employee of Abbott Laboratories GmbH, Hannover, Germany and owns shares in Abbott. C.P.-F. is an employee of Abbott GmbH & Co. KG, Wiesbaden, Germany and owns shares in Abbott. H.T.'s institution has received grants from Merck, MSD, Goodlife, Cook, Roche, Origio, Besins, Ferring and Mithra (now Allergan); and H.T. has received consultancy fees from Finox-Gedeon Richter, Merck, Ferring, Abbott and ObsEva.Trial Registration Number: NCT02491437 (clinicaltrials.gov).Trial Registration Date: 08 July 2015.Date Of First Patient’s Enrollment: 17 August 2015. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS), characterized with menstrual irregularities, hyperandrogenism and ovulatory abnormalities, is usually companied with insulin resistance (IR) and accounts for one of the most prevalent reproductive dysfunction of premenopausal women. Despite accumulating investigations, diagnostic standards of this pathological condition remain obscure. The aim of present study is to characterize the plasma metabolic characteristics of PCOS patients with and without IR, and subsequently identify the potential biomarkers for the diagnosis of PCOS and its IR complication. A total of 59 plasma samples from eligible healthy controls (CON, n = 19), PCOS patients without IR (non-IR PCOS, n = 19) and PCOS patients with IR (IR PCOS, n = 21) were profiled by an ultra high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOFMS) followed by multivariate statistical analysis. Compared to the healthy controls, significant decrease in the levels of phosphocholines (PCs) and lyso PC (18:2), and increase in trilauric glyceride level were observed in the plasma of IR PCOS. Meanwhile, the significant increase in the levels of saturated fatty acids (palmitic acid and stearic acid) and decanoylcarnitine, and decrease in PC (36:2) and PS (36:0) were found in non-IR PCOS patients. Trilauric glyceride and decanoylcarnitine were identified as the potential biomarkers with the highest sensitivity and specificity for the diagnosis of PCOS patients with and without IR, respectively. Furthermore, based on these alterations of metabolites, MetPA network pathway analysis suggested a profound involvement of the abnormalities of glycerophospholipid, glycerolipid and fatty acid metabolisms in the pathogenesis of PCOS and IR complications. Collectively, LC–MS-based metabolomics provides a promising strategy for complementary diagnosis of PCOS and its IR complication and offers a new insight to understand their pathogenesis mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this retrospective study was to determine whether patients undergoing in vitro fertilization (IVF) benefit from reducing the gamete co-incubation time. Methods: Patients ( n = 570) were enrolled, including 281 patients in the reduced incubation time group (2-h incubation) and 289 patients in the standard IVF group (18-h incubation). Results: The observed outcomes, including the clinical pregnancy rate (CPR), implantation rate (IR), live birth rate (LBR), and miscarriage rate (MR), were similar between the two groups. When the data were divided into two subgroups based on the maternal age (≤30 and >30 years), the rates of top-quality embryos (30.83 vs. 25.89 %; p = 0.028), CPR (66.67 vs. 42.11 %; p = 0.013), and IR (41.90 vs. 31.25 %, p = 0.019) of the 2-h incubation group were significantly higher in the younger subgroup. However, for older patients, only a lower MR (7.59 vs. 20.83 %; p = 0.019) was achieved. Reducing the time of incubation still improved the CPR (OR = 1.993, 95 % CI 1.141-3.480) and MR (OR = 3.173, 95 % CI 1.013-9.936) in the younger and older subgroups, respectively, after it was adjusted for potential confounders. Conclusions: Reducing incubation time improves the clinical results of IVF, although the LBR is not statistically different between the 2- and 18-h incubation time groups. And the specific clinical outcomes of reducing incubation time varied between the >30-year-old and the ≤30-year-old. [ABSTRACT FROM AUTHOR]

Purpose: To explore the optimal timing for hCG triggering by investigating the impact of different proportion of dominant follicles on the oocyte developmental competence. Methods: One hundred ninety-eight infertile women were divided into three groups according to the proportion of dominant follicles on hCG day: (1) low: <15 % ( n = 66); (2) middle: 15-27 % ( n = 66); (3) high: >27 % ( n = 66). The grouping criteria were the bottom and top tertiles of the proportion of dominant follicles. Results: The gonadotropin dosage, duration and maximum follicle diameter in the low proportion group were lower than those in the middle and high proportion groups. Oocyte maturation and the abnormal fertilization rate in the low proportion group were lower than those in the middle and high proportion groups. The normal fertilization rate did not differ among the three groups. The cleavage rate and number of transferable embryos in the low proportion group were significantly higher than those in the high proportion group. The high-quality embryo rate, implantation rate, and pregnancy rate in the low proportion group were significantly higher than those in the middle and high proportion groups. Conclusions: A high proportion of dominant follicles are closely associated with impaired oocyte developmental competence and low pregnancy rate. These findings suggest that follicular overgrowth induced by delayed hCG triggering may undermine oocyte developmental competence and the proportion of dominant follicles may be a potential parameters for hCG triggering. [ABSTRACT FROM AUTHOR]

Highlights: [•] Plasma phospholipid fatty acid profile for PCOS patients with and without IR has been characterized. [•] An GC–MS followed by multivariate statistical analysis was employed. [•] C24:1 n-9 and C20:3 n-6 were identified as the potential FA biomarkers of PCOS and its IR, respectively. [•] GC–MS-based FA profile might provide a complementary approach for diagnosis of PCOS and its IR. [ABSTRACT FROM AUTHOR]

Objective: To investigate the physical and mental development of children of assisted reproductive techniques(ART) at 1-3 years, in the limited samples and the limited age range. Methods: A total of 266 ART children, including 106 twins, at 1-3 years were follow-up visited from February 2008 to February 2011. The control group comprised 129 children, including 84 twins, who were naturally bred. The neonatal outcomes, physical and mental development were evaluated. Results: Parent age in the ART children group was elder than that in control group. There were no significant differences in BMI, MDI and PDI between two groups of ART children and control, and between two twins' groups. A multivariate regression analysis indicated that the conception mode did not affect MDI and PDI. Conclusions: There are no significantly differences in the physical and psychomotor development between ART children and normal conception children in this study. [ABSTRACT FROM AUTHOR]

Abstract: The long terminal repeats (LTRs) are the control centers for retrovirus gene expression, which possess all of the requisite signals. It has been proved that the LTRs of Moloney murine leukemia virus (MoMLV) could constitutively activate genes in diverse cell types. Recently, a retrovirus-like element, OSP-1 (ovarian-specific promoter 1), was extracted from rat ovary according to the LTRs of MoMLV, whose name was derived from the fact of ovarian-specific transcription. It was reasonable to speculate that the tissue-specificity was acquired through mutations and that there should be abound other mutants, active or inactive. In the present study, we isolated several homologous sequences to OSP-1 and detected their function. Consequently, one of them could also drive target gene expression specifically to ovarian cell lines and was named OSP-2 which shared 98% similarity to OSP-1. On the other hand, we picked up other two closest sequences and proved them inactive, which was 97% and 95% similar to OSP-1, respectively. Sequence analysis revealed the different mutations around/within the binding sites of transcriptional factors that might play important roles in tissue-specificity. In summary, we extracted a novel ovarian-specific promoter as well as other nonfunctional mutants, which in part shed light on the study of ovarian-specific transcription. In addition, it also provided a new tool in cancer gene therapy and to create transgenic animals. [Copyright &y& Elsevier]

Abstract: Abnormal fluid accumulation in tissues, including the life-threatening cerebral and pulmonary edema, is a severe consequence of bacteria infection. Chlamydia (C.) trachomatis is an obligate intracellular gram-negative human pathogen responsible for a spectrum of diseases, causing tissue fluid accumulation and edema in various organs. However, the underlying mechanism for tissue fluid secretion induced by C. trachomatis and most of other infectious pathogens is not known. Here, we report that in mice C. trachomatis infection models, the expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP activated chloride channel, is up regulated together with increased cytokine release and tissue fluid accumulation that can be reversed by treatment with antibiotic specific for C. trachomatis and CFTR channel blocker. However, C. trachomatis infection cannot induce tissue edema in CFTR tm1Unc mutant mice. Administration of exogenous IL-1β to mice mimics the C. trachomatis infection-induced CFTR upregulation, enhanced CFTR channel activity and fluid accumulation, further confirming the involvement of CFTR in infection-induced tissue fluid secretion. [Copyright &y& Elsevier]

Twelve patients with unilateral polycystic ovarian morphology demonstrated milder degrees of ovarian and other endocrine dysfunction than polycystic ovary syndrome patients and had fewer incidences of hyperprolactinemia and hyperandrogenism. [Copyright &y& Elsevier]