scholarly journals Melatonin Supplementation and Outcomes After Assisted Reproductive Technology: A Systematic Review and Meta-analyses

2020 ◽  
Author(s):  
Jing Zhao ◽  
Jie Hao ◽  
Bin Xu ◽  
Yonggang Wang ◽  
Yanping Li

Abstract Melatonin (MT) regulates a variety of important actions related to reproduction. Many studies have investigated the effect of MT application on the outcome after assisted reproductive technology (ART), with controversial results. The aim of this systematic review was to synthesize evidence from clinical studies that examine the effect of MT on the main outcomes of ART. PubMed, Embase, Web of Science, and Google scholar were searched. Clinical trials, which studied the effect of MT supplementation on outcome after ART and published in English from inception to April 2020, were included. One author assessed the risk of bias in the studies using the Cochrane Collaboration checklist. Dichotomous outcomes were analyzed as risk ratios (RR) using the Mantel-Haenszel statistical method and a random/fixed effect model. Continuous outcomes were analyzed as Mean Difference (MD) using the Inverse Variance statistical method. Eleven studies performed between 2008 and 2019 were included in this meta-analysis. Clinical pregnancy rate (CPR), live birth rate (LBR), Miscarriage rate (MR), fertilization rate (FR), Number of oocyte retrieved, MII oocyte, top-quality embryo were reported in 10, 3, 6, 7, 9, 8, and 6 studies, respectively. MT supplementation significantly increased the CPR (RR, 1.24; 95% confidence interval [CI], 1.04, 1.47), the No. of MII oocyte (MD, 1.39; 95% CI, 0.74, 2.04), the No. of top-quality embryo (MD, 0.56; 95% CI, 0.24, 0.88), and the FR (4 studies with RR, 1.10; 95% CI, 1.03, 1.17; 3 studies with MD, 0.13; 95% CI, 0.01, 0.24). However, there was no significant difference in LBR (RR, 1.23; 95% CI, 0.85, 1.80), No. of oocyte retrieved (MD, 0.58; 95% CI, -0.12, 1.27), and the MR (RR, 0.96; 95% CI, 0.50, 1.82). When studies were sub-grouped by the interventions, no matter the control group is MI+FA or placebo/none, MT supplementation increased No. of MII oocyte (MT+MI+FA vs. MI+FA MD, 0.91; 95% CI, 0.40, 1.41; MT vs. Placebo/none MD, 2.06; 95% CI, 0.73, 3.39) and No. of top embryo (MT+MI+FA vs. MI+FA MD, 0.70; 95% CI, 0.24, 1.16; MT vs. Placebo/none MD, 0.33; 95% CI, 0.11, 0.54), whereas showed similar CPR (MT+MI+FA vs. MI+FA RR, 1.22; 95% CI, 0.96, 1.54; MT vs. Placebo/None RR, 1.26; 95% CI, 0.97, 1.62). When studies were sub-grouped according to women’s characteristic, MT supplementation showed no significant beneficial effect on CPR in women with PCOS (RR, 1.18; 95% CI, 0.92, 1.52), with normal ovary function (RR, 1.15; 95% CI, 0.87, 1.53), and women with previous low fertilization or poor-quality embryo (RR, 1.71; 95% CI, 0.95, 3.07). However, MT supplementation increased the No of MII in women with PCOS (MD, 0.97; 95% CI, 0.22, 1.73), but did not show such benefit in women with normal ovary function (MD, 1.49; 95% CI, -0.33, 3.31). In conclusion, MT supplementation may not improve the clinical pregnancy and live birth of ART. But MT seems to be beneficial to the quality of oocyte and embryo, especially for women with PCOS and DOR, at least to some extent. Further well-designed studies are needed before recommendation of its use in clinical practice.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Klaus F. Bühler ◽  
Robert Fischer ◽  
Patrice Verpillat ◽  
Arthur Allignol ◽  
Sandra Guedes ◽  
...  

Abstract Background This study compared the effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa; GONAL-f®) with urinary highly purified human menopausal gonadotropin (hMG HP; Menogon HP®), during assisted reproductive technology (ART) treatments in Germany. Methods Data were collected from 71 German fertility centres between 01 January 2007 and 31 December 2012, for women undergoing a first stimulation cycle of ART treatment with r-hFSH-alfa or hMG HP. Primary outcomes were live birth, ongoing pregnancy and clinical pregnancy, based on cumulative data (fresh and frozen-thawed embryo transfers), analysed per patient (pP), per complete cycle (pCC) and per first complete cycle (pFC). Secondary outcomes were pregnancy loss (analysed per clinical pregnancy), cancelled cycles (analysed pCC), total drug usage per oocyte retrieved and time-to-live birth (TTLB; per calendar week and per cycle). Results Twenty-eight thousand six hundred forty-one women initiated a first treatment cycle (r-hFSH-alfa: 17,725 [61.9%]; hMG HP: 10,916 [38.1%]). After adjustment for confounding variables, treatment with r-hFSH-alfa versus hMG HP was associated with a significantly higher probability of live birth (hazard ratio [HR]-pP [95% confidence interval (CI)]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; relative risk [RR]-pFC [95% CI]: 1.09 [1.05, 1.15], ongoing pregnancy (HR-pP [95% CI]: 1.10 [1.04, 1.16]; HR-pCC [95% CI]: 1.13 [1.08, 1.19]; RR-pFC [95% CI]: 1.10 [1.05, 1.15]) and clinical pregnancy (HR-pP [95% CI]: 1.10 [1.05, 1.14]; HR-pCC [95% CI]: 1.14 [1.10, 1.19]; RR-pFC [95% CI]: 1.10 [1.06, 1.14]). Women treated with r-hFSH-alfa versus hMG HP had no statistically significant difference in pregnancy loss (HR [95% CI]: 1.07 [0.98, 1.17], were less likely to have a cycle cancellation (HR [95% CI]: 0.91 [0.84, 0.99]) and had no statistically significant difference in TTLB when measured in weeks (HR [95% CI]: 1.02 [0.97, 1.07]; p = 0.548); however, r-hFSH-alfa was associated with a significantly shorter TTLB when measured in cycles versus hMG HP (HR [95% CI]: 1.07 [1.02, 1.13]; p = 0.003). There was an average of 47% less drug used per oocyte retrieved with r-hFSH-alfa versus hMG HP. Conclusions This large (> 28,000 women), real-world study demonstrated significantly higher rates of cumulative live birth, cumulative ongoing pregnancy and cumulative clinical pregnancy with r-hFSH-alfa versus hMG HP.


2021 ◽  
Author(s):  
Jing Zhao ◽  
Jie Hao ◽  
Bin Xu ◽  
Yonggang Wang ◽  
Yanping Li

Abstract To assess the effect of melatonin (MT) supplementation on the outcomes of ART. A meta-analysis and systematic review was conducted. Eleven studies were included in this meta-analysis. Clinical pregnancy rate (CPR), live birth rate (LBR), Miscarriage rate (MR), fertilization rate (FR), Number of oocyte, MII oocyte, top-quality embryo were reported in 10, 3, 6, 7, 9, 8, and 6 studies, respectively. MT supplementation significantly increased the CPR, the No. of MII oocyte, the No. of top-quality embryo, and the FR. However, there was no significant difference in LBR, No. of oocyte, and the MR. When studies were sub-grouped by the interventions, no matter the control group is MI+FA or placebo/none, MT supplementation increased No. of MII oocyte and No. of top embryo, whereas showed similar CPR. When studies were sub-grouped according to women’s characteristic, MT supplementation showed no significant benefit on CPR in women with PCOS, with normal ovary function, and with previous low fertilization or poor-quality embryo. However, MT supplementation increased the No of MII in women with PCOS, but did not show benefit in women with normal ovary function. MT supplementation may not improve the CPR and LBR of ART. But MT seems be beneficial to the quality of oocyte and embryo, especially for women with PCOS and DOR. Further well-designed studies are needed before the recommendation of its clinical use.


2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Zhangshun Liu ◽  
Xiaohong Shi ◽  
Lihong Wang ◽  
Yan Yang ◽  
Qiang Fu ◽  
...  

The present study was designed to investigate the relationships between indicators of male body mass index (BMI), age, reproductive hormone levels, semen parameters, and the outcomes of assisted reproductive technology (ART). The clinical data were collected from 636 couples who underwent ART between January, 2013 and December, 2015 at the reproductive center involved in our study. Pearson’s correlation or Spearman rank correlation was applied to establish the relevant correlation coefficients. The correlation between influence factors’ and pregnancy outcomes was analyzed using the Logistic regression model. Analyses were conducted using SPSS software. Male BMI was found to be negatively correlated with testosterone (T) (P<0.05), while follicle-stimulating hormone (FSH) was negatively correlated with semen parameters (P<0.05). Luteinizing hormone (LH) was found to be negatively correlated with total sperm count, normal sperm morphology, and abortion (all P<0.05). Clinical pregnancy was related to sperm concentration and female age (P<0.05), and live birth was found to be associated only with female age (P<0.05). Male BMI was associated with the secretion of reproductive hormones, but had no effect on sperm parameters or ART outcome. A higher male age was also negatively connected with the outcome of clinical pregnancy. Reproductive hormones were not associated with ART outcome. Sperm concentration and female age were important factors influencing ART clinical pregnancy, while the only significant factor influencing live birth was female age. Levels of obesity-related inflammatory indicators (i.e. free fatty acid (FFA), glutathione peroxidase (GSH-Px), human inhibin-B (IHNB), interleukin-1 (IL-1), insulin-like growth factor-1 (IGF-1), and reactive oxygen species (ROS)) also varied with degrees of BMI. The present study provides information on the associations between male reproductive characteristics and the outcome of ART, which may contribute to improved strategies to help couples achieve better pregnancy outcomes.


2020 ◽  
Author(s):  
Shahintaj Aramesh ◽  
Maryam Azizi Kutenaee ◽  
Fataneh Najafi ◽  
Parvin Ghaffari ◽  
Seyed Abdolvahab Taghavi

Abstract Background: to evaluate the effect of granulocyte colony stimulating factor (GCSF) on fertility outcomes in women with unexplained infertility after intra uterine insemination (IUI).Methods: The patients with unexplained infertility were divided into two groups: one group was received GCSF in their IUI cycle and the other group had the routine IUI. Both groups were stimulated by letrozole, metformin and monotropin during the cycle. When at least one follicle was greater than 18mm, 5000 IU hCG intramuscularly was administered for ovulation induction and IUI was performed 34-36 hours later. In intervention group, 300 ug GCSF subcutaneously administrated in two days after IUI. The main outcome measures were biochemical pregnancy, clinical pregnancy, abortion rate and live birth rate.Results: There was no significant difference in demographic and clinical characteristics between the control group and the G-CSF group. Also, no statistically significant difference was identified in the biochemical pregnancy rates (16.3% vs 12.2%), clinical pregnancy rates(16.3% vs 8.2%), abortion rates (0 vs 2.04%) and live birth rates (8.2% vs 14.2%) between the control group and the G-CSF group (P=0.56, P=0.21, p=0.55 and p=0.32 respectively). Conclusion: Systemic administration of a single dose of 300 μg GCSF subcutaneously two days after IUI may slightly improve clinical pregnancy rate and live birth rate in patients with unexplained infertility. Nevertheless, our findings do not support routine use of G-CSF in unexplained infertility women with normal endometrial thickness. IRCT registration number: IRCT20160524028038N4.


2019 ◽  
Vol 34 (10) ◽  
pp. 1948-1964 ◽  
Author(s):  
Mathilde Bourdon ◽  
Khaled Pocate-Cheriet ◽  
Astri Finet de Bantel ◽  
Veronika Grzegorczyk-Martin ◽  
Aureli Amar Hoffet ◽  
...  

Abstract STUDY QUESTION Is there a difference in clinical pregnancy and live birth rates (LBRs) between blastocysts developing on Day 5 (D5) and blastocysts developing on Day 6 (D6) following fresh and frozen transfers? SUMMARY ANSWER D5 blastocyst transfers (BTs) present higher clinical pregnancy and LBRs than D6 in both fresh and frozen transfers. WHAT IS KNOWN ALREADY BT is increasingly popular in assisted reproductive technology (ART) centers today. To our knowledge, no meta-analysis has focused on clinical outcomes in both fresh and frozen BT. Concerning frozen blastocysts, one meta-analysis in 2010 found no significant difference in pregnancy outcomes between D5 and D6 BT. Since then, ART practices have evolved particularly with the wide use of vitrification, and more articles comparing D5 and D6 BT cycles have been published and described conflicting results. STUDY DESIGN, SIZE, DURATION Systematic review and meta-analysis of published controlled studies. Searches were conducted from 2005 to February 2018 on MEDLINE and Cochrane Library and from 2005 to May 2017 on EMBASE, Eudract and clinicaltrials.gov, using the following search terms: blastocyst, Day 5, Day 6, pregnancy, implantation, live birth and embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 47 full-text articles were preselected from 808 references, based on title and abstract and assessed utilizing the Newcastle–Ottowa Quality Assessment Scales. Study selection and data extraction were carried out by two independent reviewers according to Cochrane methods. Random-effect meta-analysis was performed on all data (overall analysis) followed by subgroup analysis (fresh, vitrified/warmed, slow frozen/thawed). MAIN RESULTS AND THE ROLE OF CHANCE Data from 29 relevant articles were extracted and integrated in the meta-analysis. Meta-analysis of the 23 studies that reported clinical pregnancy rate (CPR) as an outcome, including overall fresh and/or frozen ET cycles, showed a significantly higher CPR following D5 ET compared with D6 ET (risk ratio (RR) = 1.27, 95% CI: 1.15–1.39, P < 0.001). For CPR, calculated subgroup RRs were 2.38 (95% CI: 1.74–3.24, P < 0.001) for fresh BT; 1.27 (95% CI: 1.16–1.39, P < 0.001) for vitrified/warmed BT; and 1.15 (95% CI: 0.93–1.41, P = 0.20) for slow frozen/thawed BT. LBR was also significantly higher after D5 BT (overall RR = 1.50 (95% CI: 1.32–1.69), P < 0.001). The LBR calculated RRs for subgroups were 1.74 (95% CI: 1.37–2.20, P < 0.001) for fresh BT; 1.38 (95% CI: 1.23–1.56, P < 0.001) for vitrified/warmed BT; and 1.44 (95% CI: 0.70–2.96, P = 0.32) for slow frozen/thawed BT. Sensitivity analysis led to similar results and conclusions: CPR and LBR were significantly higher following D5 compared to D6 BT. LIMITATIONS, REASONS FOR CAUTION The validity of meta-analysis results depends mainly on the quality and the number of the published studies available. Indeed, this meta-analysis included no randomized controlled trial (RCT). Slow frozen/thawed subgroups showed substantial heterogeneity. WIDER IMPLICATIONS OF THE FINDINGS In regards to the results of this original meta-analysis, ART practitioners should preferably transfer D5 rather than D6 blastocysts in both fresh and frozen cycles. Further RCTs are needed to address the question of whether D6 embryos should be transferred in a fresh or a frozen cycle. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER CRD42018080151.


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