Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders—an observational pilot study

Mitri, Frederic; Behan, Lucy Ann; Murphy, C.; Klement, Anat Hershko; Casper, Robert F.; Bentov, Yaakov

doi:10.1016/j.fertnstert.2015.09.038

Cited by 12 publications

(6 citation statements)

References 30 publications

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“…Reports have also assessed the efficacy of administering the bioactive androgen, testosterone, in POR patients to improve ovarian response and IVF outcomes (Table 3). Although four RCTs (two with placebo controls) assessing the impact of transdermal testosterone administration for 5-20 days in POR patients showed no significant effect of testosterone pre-treatment (Massin et al 2006, Fabregues et al 2009, Sipe et al 2010, Bosdou et al 2016, since then numerous studies, including a placebo-controlled RCT, have reported on a range of beneficial effects of pre-IVF testosterone pre-treatment (Balasch et al 2006, Kim et al 2011, Mitri et al 2016, Doan et al 2017, Saharkhiz et al 2018. These beneficial effects include improved antral follicle numbers, oocyte retrieval numbers, fertilization rates, embryo implantation rates, embryo quality, clinical pregnancy rates and live birth rates in some women (observations from studies summarized in Table 3).…”

Section: Testosteronementioning

confidence: 99%

Androgens and ovarian function: translation from basic discovery research to clinical impact

Walters

Paris

Aflatounian

et al. 2019

Journal of Endocrinology

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In the last decade, it has been revealed that androgens play a direct and important role in regulating female reproductive function. Androgens mediate their actions via the androgen receptor (AR), and global and cell-specific Ar-knockout mouse models have confirmed that AR-mediated androgen actions play a role in regulating female fertility and follicle health, development and ovulation. This knowledge, along with the clinical data reporting a beneficial effect of androgens or androgen-modulating agents in augmenting in vitro fertilization (IVF) stimulation in women termed poor responders, has supported the adoption of this concept in many IVF clinics worldwide. On the other hand, substantial evidence from human and animal studies now supports the hypothesis that androgens in excess, acting via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). The identification of the target sites of these AR actions and the molecular mechanisms involved in underpinning the development of PCOS is essential to provide the knowledge required for the future development of novel, mechanism-based therapies for the treatment of PCOS. This review will summarize the basic scientific discoveries that have enhanced our knowledge of the roles of androgens in female reproductive function, discuss the impact these findings have had in the clinic and how a greater understanding of the role androgens play in female physiology may shape the future development of effective strategies to improve IVF outcomes in poor responders and the amelioration of symptoms in patients with PCOS.

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Section: Testosteronementioning

confidence: 99%

Androgens and ovarian function: translation from basic discovery research to clinical impact

Walters

Paris

Aflatounian

et al. 2019

Journal of Endocrinology

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“…Of these, 936 records were excluded after title/ abstract screening (not relevant to the review). We examined the full text of 18 remaining manuscripts, and, of these, we excluded 10 papers-one paper due to the lack of data concerning CPR and/or LBR [27], one trial reported data not analyzable [28], three papers because the design was observational [29][30][31], and six papers because they were review/metaanalysis [11-13, 21, 32, 33]. Finally, 7 manuscripts were included in the meta-analysis [10,[22][23][24][34][35][36].…”

Section: Study Selectionmentioning

confidence: 99%

Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials

Noventa

Vitagliano

Andrisani

et al. 2019

J Assist Reprod Genet

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The aim of the present systematic review and meta-analysis was to summarize evidence on the effectiveness of testosterone supplementation for poor ovarian responders (POR) on IVF outcomes. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. Methods This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of testosterone administration before/ during COS compared with a control group in patients defined as POR. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. Pooled results were expressed as risk ratio (RR) or mean differences (MD) with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroup analysis. All analyses were performed by using the randomeffects model. Results Women receiving testosterone showed higher LBR (RR 2.29, 95% CI 1.31-4.01, p = 0.004), CPR (RR 2.32, 95% CI 1.47-3.64, p = 0.0003), total oocytes (MD = 1.28 [95% CI 0.83, 1.73], p < 0.00001), MII oocytes (MD = 0.96 [95% CI 0.28, 1.65], p = 0.006), and total embryos (MD = 1.17 [95% CI 0.67, 1.67], p < 0.00001) in comparison to controls, with no difference in MR (p = ns). Sensitivity and subgroup analysis did not provide statistical changes to the pooled results. Conclusions Testosterone therapy seems promising to improve the success at IVF in POR patients. Further RCTs with rigorous methodology and inclusion criteria are still mandatory.

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“…A poor response to ovarian stimulation is not common, and presents a significant therapeutic challenge. Many approaches have been proposed to improve clinical outcomes of PORs, including a modified ovarian stimulation protocol (7,8), androgen treatment (9,10), and a stem cell ovarian transplant (11).…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Supplementation May Not Improve Live Birth Rate in Poor Responders

et al. 2020

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Backgrounds: Growth hormone (GH) was used for many years to increase ovarian response in poor ovarian responders (PORs). Although meta-analysis suggested that GH therapy improve early clinical outcomes, the benefit of GH usage on chance of live birth was still widely debated. This study was to determine whether or not GH supplementation influences the live birth rate (LBR). Methods: A total of 3,080 expected PORs receiving and not receiving (control) GH adjuvant therapy at Peking University Third Hospital from January 2017 to March 2018 were retrospectively analyzed. The basal characteristics of patients were compared using analysis of variance (continuous variables) and categorical variables were evaluated with a chi-square test. Logistic regression analyses were used to evaluate potential associations of LBR with GH treatment while adjusting other confounding factors. Results: No statistically significant differences existed in miscarriage rate (5.3 vs. 12.5%; p = 0.076) and LBR (37.7 vs. 34.5%; p = 0.426) in young expected PORs (< 35 years of age). Moreover, no significant differences existed in the miscarriage rate (25.6 vs. 23.3%; p = 0.681), and LBR (17.8 vs. 17.9%; p = 0.977) in the old expected PORs (≥35 years of age). Logistic regression suggested that GH adjuvant therapy did not improve the LBR in young (OR, 1.27; 95% CI, 0.88-1.85; p = 0.203) and elderly expected PORs (OR, 1.20; 95% CI, 0.82-1.76; p = 0.342), while GH was not associated with risk of miscarriage in young (OR, 0.37; 95% CI, 0.11-1.24; p = 0.108) and elderly expected PORs (OR, 0.91; 95% CI, 0.43-1.93; p = 0.813). In subgroup analysis, GH treatment significantly increased the day 3 embryos available rate in the subgroup of young PORs with the long down-regulation (63.11 vs. 49.35%; p = 0.004), while significantly reduced the risk of miscarriage in the subgroup of young PORs with GnRH antagonist protocol (0.00 vs. 12. %; p = 0.023). There was no significant difference for LBR in PORs with GnRH antagonist (<35 years [35.19 vs. 28.45%; p = 0.183]; ≥35 years [12.96 vs. 14.03%; p = 0.707]), GnRH-a long (<35 years [33.33 vs. 36.99%; p = 0.597]; ≥35 years [17.44 vs. 20.28%; p = 0.574]) and long down-regulation (<35 years [58.82 vs. 41.90%; p = 0.193]; ≥35 years [43.33 vs. 25.30%; p = 0.065]). Conclusions: Growth hormone treatment may not improve live birth rate in expected poor responders.

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Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders—an observational pilot study

Abstract: The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled.

Cited by 12 publications

References 30 publications

Androgens and ovarian function: translation from basic discovery research to clinical impact

Androgens and ovarian function: translation from basic discovery research to clinical impact

Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials

Growth Hormone Supplementation May Not Improve Live Birth Rate in Poor Responders

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