ORCID Profile
0000-0001-8321-1302
Current Organisation
University of Nottingham
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Publisher: Oxford University Press (OUP)
Date: 23-10-2019
Abstract: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. In idual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment–covariate interaction analyses and therefore offers an opportunity for personalised medicine. We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics. We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs. IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17–1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23–1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38–2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01–1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00–1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00–1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87–1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01–1.06). In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS.
Publisher: Elsevier BV
Date: 09-2012
DOI: 10.1016/J.RBMO.2012.05.010
Abstract: Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on reproductive outcomes after ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. This systematic review and meta-analysis assessed the strength of the association between obesity and ovulation or pregnancy rates after OAT. MEDLINE and several other databases were searched from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the relative risk of reproductive outcomes (ovulation and pregnancy) in lean (body mass index <25 kg/m(2)) compared with overweight or obese women. The study obtained 15 data sets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22-1.66) compared with obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39-2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. It is concluded that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively. Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. We therefore undertook a systematic review and meta-analysis to assess the strength of the association between obesity and ovulation or pregnancy rates after OAT. We searched MEDLINE and several other databases from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the risk ratio of reproductive outcomes (ovulation and pregnancy) in lean (BMI <25 kg/m(2)) as opposed to overweight or obese women. We obtained 15 datasets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22-1.66) as compared to obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39-2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. We conclude that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Saad Amer.