scholarly journals Comparative effectiveness of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) versus highly purified urinary human menopausal gonadotropin (hMG HP) in assisted reproductive technology (ART) treatments: a non-interventional study in Germany

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.

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 ◽  
Author(s):  
Meilan Mo ◽  
Qizhen Zheng ◽  
Hongzhan Zhang ◽  
Shiru Xu ◽  
Fen Xu ◽  
...  

Abstract Objective: This retrospective study aimed to explore the optimal endometrial preparation method in women with intrauterine adhesions (IUAs).Method: A total of 882 frozen-thawed embryo transfer (FET) cycles were categorized into three groups based on endometrial preparation methods: hormone replacing therapy cycle (HRT, n=636), natural cycle (NC n=174), and HRT with GnRH-a pretreatment (HRT+GnRH-a, n=72. Logistic regression was performed to investigate the association between cycle regimens and pregnancy outcomes. Subgroup analysis of IUAs combined with thin endometrium (≤7mm) was also performed.Results: HRT with GnRH-a pretreatment was associated with higher incidences of clinical pregnancy, ongoing pregnancy, and live birth, but lower early miscarriage compared with either HRT or NC. Logistic regression indicated that after controlling for potential confounders, the incidences of live birth (HRT+GnRH-a as reference; NC: aOR=0.577, 95%CI 0.304-1.093; HRT: aOR=0.434, 95%CI 0.247-0.765) and ongoing pregnancy (NC: aOR=0.614, 95%CI 0.324-1.165; HRT: aOR=0.470, 95%CI 0.267-0.829) remained significantly higher in HRT+GnRH-a compared to those in HRT, but comparable to those in NC. While there was no significant difference with respect to the clinical pregnancy rate (NC: aOR=0.695, 95%CI 0.374-1.291; HRT: aOR=0.650, 95%CI 0.374-1.127) and early miscarriage rate (NC: aOR=1.734, 95%CI 0.417-7.175; HRT: aOR=2.594, 95%CI 0.718-9.378) between groups. Subgroup analysis suggested there was no priority of endometrial preparation method in IUAs combined with thin endometrium.Conclusion: HRT with GnRH-a pretreatment improves pregnancy outcomes in women with history of IUAs. GnRH-a may restore the endometrial receptivity in the FET cycles in IUAs.


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