Controlled ovarian stimulation and intrauterine insemination or in vitro-fertilisation for the first line treatment of unexplained infertility

2013 ◽  
Author(s):  
Anupa Nandi
Keyword(s):  
Ovarian Stimulation ◽  
Intrauterine Insemination ◽  
Unexplained Infertility ◽  
Controlled Ovarian Stimulation ◽  
In Vitro Fertilisation ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

scholarly journals 577Inequalities in access to in vitro fertilisation treatment in France

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Khaoula Ben Messaoud ◽  
◽  
Keyword(s):  
Social Status ◽  
Infertility Treatment ◽  
In Vitro Fertilisation ◽  
Line Treatment ◽  
First Line ◽  
Driving Time ◽  
Barriers To Access ◽  
Infertility Treatments ◽  
First Line Treatment

Abstract Background In vitro fertilisation (IVF) treatment is one of the most expensive infertility treatments. Cost has been described as a substantial barrier to access. In France all infertility treatments, including IVF, are fully reimbursed, but are there other barriers to access? Methods Based on the French national health insurance database that exhaustively records reimbursed healthcare, this cohort study included all women aged 18–49 years unsuccessfully treated with ovarian induction (first-line infertility treatment) between January–August 2016. Outcome was IVF access within 24 months of starting first-line treatment. Univariate and multivariate regressions explored age, disadvantaged social status, driving time to nearest IVF centre, and deprivation index of area of residence. Results Over 20,000 women unsuccessfully received first-line treatment. Almost 80% did not access IVF within 24 months. After age 34, probability of access decreased. Disadvantaged social status and living in a disadvantaged area were associated with lower probability of accessing IVF. Driving time to the nearest IVF centre was not significantly associated with access. Conclusions Socio-economic barriers to access IVF exist despite full treatment reimbursement in France. To reduce health inequalities, we need to better understand the nature and patterns of these barriers among less socially advantaged people. Key messages After failure of first-line infertility treatment, only 20% of women access IVF although it is fully reimbursed in France. Age, but most importantly socio-economic status, is a key determinant of access to IVF treatment. Distance from nearest IVF centre does not appear significant in explaining access to treatment in France.

scholarly journals Discovery and Preclinical Development of Orally Active Small Molecules that Exhibit Highly Selective Follicle Stimulating Hormone Receptor Agonism

2021 ◽  
Vol 11 ◽  
Author(s):  
Selva Nataraja ◽  
Henry Yu ◽  
Joie Guner ◽  
Stephen Palmer
Keyword(s):  
Ovarian Stimulation ◽  
Hormone Receptor ◽  
Ovulation Induction ◽  
Low Dose ◽  
Intrauterine Insemination ◽  
Follicle Stimulating Hormone ◽  
Controlled Ovarian Stimulation ◽  
Orally Active ◽  
Stimulating Hormone

An orally active follicle stimulating hormone receptor allosteric agonist would provide a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods (ovulation induction-intrauterine insemination) or in high complexity methods (controlled ovarian stimulation-in vitro fertilization). We present two oral follicle stimulating hormone receptor allosteric agonist compounds that have the desired pharmacology, drug metabolism, pharmacokinetics, and safety profile for clinical use. These molecules provide a single agent suitable for ovulation induction-intrauterine insemination or controlled ovarian stimulation-in vitro fertilization that is more convenient for patients and achieves similar preclinical efficacy as rec-hFSH. TOP5668, TOP5300 were evaluated in vitro in Chinese hamster ovary cells transfected with individual glycoprotein receptors measuring cAMP (FSHR, LH/CGR, thyroid stimulating hormone receptor). TOP5668 was found to have solely follicle stimulating hormone receptor allosteric agonist activity while TOP5300 was found to have mixed follicle stimulating hormone receptor allosteric agonist and LHR-AA activity. Both compounds stimulated concentration-dependent increases in estradiol production from cultured rat granulosa cells in the presence or absence of low dose rec-hFSH, while only TOP5300 stimulated testosterone production from rat primary Leydig cells. In pooled human granulosa cells obtained from patients undergoing controlled ovarian stimulation-in vitro fertilization, TOP5300 stimulated 7-fold greater maximal estradiol response than rec-hFSH and TOP5668 was 10-fold more potent than TOP5300. Both TOP5300 and TOP5668 stimulated follicular development in immature rat to the same efficacy as recombinant follicle stimulating hormone. In mice treated with TOP5300, in the presence of low dose of follicle stimulating hormone, there were no differences in oocyte number, fertilization rate, and hatched blastocyst rate in mice with TOP5300 and low dose follicle stimulating hormone vs. reference proteins pregnant mare serum gonadotropin or high dose rec-hFSH. ADME/PK and safety profiles were favorable. In addition, there was no appreciable activity on thyroid hormones by TOP5300 in 14-days toxicological study in rat or dog. The selected lead compound, TOP5300 stimulated a more robust increase in estradiol production from granulosa-lutein cells from women with polycystic ovarian syndrome patient compared to rec-hFSH. Conclusions: Two novel oral FSHR allosteric agonist, TOP5668 and TOP5300, were found to mimic the biological activity of rec hFSH in preclinical studies. Both compounds led to folliculogenesis and superovulation in rat and mice. Specifically, TOP5300 led to a similar number of ovulated oocytes that fertilized and developed into hatched blastocysts in mice when compared to rec-hFSH. The safety profile demonstrated lack of toxicity.

scholarly journals In VitroAntimicrobial Susceptibility Patterns of Blastocystis

2015 ◽  
Vol 59 (8) ◽  
pp. 4417-4423 ◽  
Author(s):  
Tamalee Roberts ◽  
Stephen Bush ◽  
John Ellis ◽  
John Harkness ◽  
Damien Stark
Keyword(s):  
Current Treatment ◽  
Line Treatment ◽  
First Line ◽  
Content Type ◽  
Treatment Regimens ◽  
Drug Treatments ◽  
Resistant Strains ◽  
Susceptibility Patterns ◽  
First Line Treatment

ABSTRACTBlastocystisis the most common human enteric protist with controversial clinical significance. Metronidazole is considered a first-line treatment forBlastocystisinfection; however, there has been increasing evidence for the lack of efficacy of this treatment. Treatment failure has been reported in several clinical cases, and recentin vitrostudies have suggested the occurrence of metronidazole-resistant strains. In this study, we tested 12Blastocystisisolates from 4 commonBlastocystissubtypes (ST1, ST3, ST4, and ST8) against 12 commonly used antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole, fluconazole, nystatin, and itraconazole) at 10 different concentrationsin vitro. It was found that each subtype showed little sensitivity to the commonly used metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and secnidazole). This study highlights the efficacy of other potential drug treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests that current treatment regimens be revised.

scholarly journals 679. In vitro Activity of Cefiderocol (CFDC), a Novel Siderophore Cephalosporin, Against Difficult-to-Treat-Resistant (DTR) Gram-Negative Bacterial Pathogens From the Multi-National Sentinel Surveillance Study, SIDERO-WT (2014–2017)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S309-S310 ◽  
Author(s):  
Christopher Longshaw ◽  
Masakatsu Tsuji ◽  
Meredith M Hackel ◽  
Daniel F Sahm ◽  
Yoshinori Yamano
Keyword(s):  
Treatment Options ◽  
Vitro Activity ◽  
Surveillance Study ◽  
Line Treatment ◽  
In Vitro Activity ◽  
First Line ◽  
Gram Negative ◽  
Acinetobacter Spp ◽  
First Line Treatment

Abstract Background DTR organisms are defined as nonsusceptible to all high-efficacy, low-toxicity antibiotics (penicillins, cephalosporins, carbapenems, and quinolones), leaving physicians with limited first-line treatment options. Analyses of electronic health records have shown that patients with DTR Gram-negative bacterial infections are more likely to receive inappropriate antibiotic therapy, have longer hospital stay and increased risk of mortality. CFDC is a novel parenteral siderophore cephalosporin with potent activity against aerobic Gram-negative pathogens, including carbapenem-resistant strains. We evaluated the in vitro activity of CFDC and comparators against DTR pathogens collected by the SIDERO-WT surveillance study. Methods A total of 30,459 clinical isolates of Gram-negative bacilli were systematically collected from United States, Canada, and 11 EU countries during 2014–2017. MICs were determined by broth microdilution for a panel of 7 antibiotics, including CFDC, ceftazidime–avibactam (CZA), ceftolozane–tazobactam (C/T), colistin (CST), cefepime (FEP), meropenem (MEM), and ciprofloxacin (CIP) according to CLSI guidelines. All antibiotics were tested in cation-adjusted Mueller–Hinton broth (CAMHB) except CFDC, for which iron-depleted CAMHB was used. Susceptibility was determined according to CLSI interpretive breakpoints except CST, where EUCAST breakpoints were used. DTR pathogens were defined as being nonsusceptible to FEP, MEM, and CIP according to CLSI breakpoints. Results Among 30,459 Gram-negative isolates collected between 2014 and 2017, 9.3% were nonsusceptible to FEP, MEM, and CIP and could be defined as DTR. DTR was most frequently observed in Acinetobacter spp. (55.5%), followed by Burkholderia spp. (19%), Pseudomonas aeruginosa (9.5%), and Enterobacterales (2.7%). Of the 1,173 Stenotrophomonas maltophilia tested, 97% had MEM MIC of ≥8 mg/L; however, only 2.9% could be defined as DTR. Cefiderocol was the most active antibiotic tested against DTR isolates with 94.5% DTR-Acinetobacter spp., 98.3% DTR-P. aeruginosa, and 99.8% DTR-Enterobacterales susceptible (Table 1). Conclusion CFDC demonstrated potent activity against DTR Gram-negative pathogens with limited first-line treatment options. Disclosures All authors: No reported disclosures.

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