scholarly journals A meta-analysis of the efficacy of progestin-primed ovarian stimulation with medroxyprogesterone acetate in ovulation induction in poor ovarian responders

Author(s):  
Ruihong Cai ◽  
Beihong Zheng ◽  
Qiupin Lin ◽  
Jie Deng ◽  
Xiaoping Zeng ◽  
...  
BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e039122
Author(s):  
Huisheng Yang ◽  
Chensi Zheng ◽  
Qiyan Zheng ◽  
Huanfang Xu ◽  
Xiaotong Li ◽  
...  

IntroductionControlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response is a challenge encountered by many clinicians during COH and poor ovarian responders (PORs) usually have higher follicle stimulating hormone levels, lower levels of anti-Mullerian hormone and few oocytes retrieved, which have been attributed mainly to advanced maternal age and poor follicle reserve or other reasons that could impair ovarian response during ovarian stimulation. Over the last few decades, researchers have proposed a series of strategies and ovarian stimulation protocols to improve pregnancy outcomes in patients with POR during their IVF/ICSI treatment. However, clinical decisions regarding COH protocols in PORs during IVF/ICSI treatment remain controversial. Traditional pairwise meta-analysis only allows the direct comparison of two protocols in COH for patients with POR. However, many of these COH protocols have not been compared directly in randomised controlled trials (RCTs). Thus, we aim to use network meta-analysis (NMA) to assess the clinical effectiveness and safety of COH protocols and to generate treatment rankings of these COH protocols for the most clinically important and commonly reported outcomes events.Methods and analysisThe PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang database and Chongqing VIP information databases will be searched for all RCTs of COH for POR women during IVF/ICSI from inception to 31 March 2020. Primary outcomes will include live birth rate and number of oocytes retrieved. Secondary outcomes will include ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, ovarian hyperstimulation syndrome rate, multiple pregnancy rate and cycle cancellation rate. Pairwise meta-analysis and Bayesian NMA will be conducted for each outcome. Subgroup analysis, meta-regression, and sensitivity analysis will be performed to assess the robustness of the findings. The generation of NMA plots and subsequent results will be performed by using R V.4.0.1. The assessment of confidence in network estimates will use the Confidence in Network Meta-Analysis)web application (see https://cinema.ispm.unibe.ch/).Ethics and disseminationThis review does not require ethics approval and the results of the NMA will be submitted to a peer-review journal.


GYNECOLOGY ◽  
2019 ◽  
Vol 21 (4) ◽  
pp. 6-8
Author(s):  
Andrey Y Romanov ◽  
Anastasiya G Syrkasheva ◽  
Nataliya V Dolgushina ◽  
Elena A Kalinina

The paper analyzes the literature data on the use of the growth hormone (GH) in ovarian stimulation in assisted reproductive technologies (ART). Routine use of GH in ovarian stimulation in patients with a normal GH level does not increase pregnancy and childbirth rates in ART. Also, no benefits of using GH have been identified for patients with polycystic ovary syndrome, despite the increase in insulin and IGF-1 blood levels. The main research focus is to study the use of GH in patients with poor ovarian response. According to the meta-analysis conducted by X.-L. Li et al. (2017), GH in ovarian stimulation of poor ovarian responders increases the number of received oocytes, mature oocytes number, reduces the embryo transfer cancellation rate and does not affect the fertilization rate. The pregnancy and live birth rates are significantly higher in the group of GH use - by 1.65 (95% CI 1.23-2.22) and 1.73 (95% CI 1.25-2.40) times, respectively. Thus, it is advisable to use GH in ovarian stimulation in poor ovarian responders, since it allows to increases live birth rate in ART. However, further studies should determine the optimal GH dose and assesse it`s safety in ART programs.


2017 ◽  
Vol 72 (8) ◽  
pp. 484-485
Author(s):  
N. S. Weiss ◽  
M. N. van Vliet ◽  
J. Limpens ◽  
P. G. A. Hompes ◽  
C. B. Lambalk ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Selva Nataraja ◽  
Henry Yu ◽  
Joie Guner ◽  
Stephen Palmer

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.


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