Low cost ovarian stimulation protocol is associated with lower pregnancy rate in normal responders in comparison to long protocol

Elnashar, I.; Farghaly, Tarek; Abdalbadie, A.S.; Badran, Esraa; Abdelaleem, Ahmed A.; Ismail, Alaa M.; Elsenosy, Elwany

doi:10.1016/j.fertnstert.2016.07.565

Cited by 3 publications

(9 citation statements)

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“…All included papers were written in English except one ( Martinez et al , 2003 ), which was written in Spanish and the translation was by Google Translator . Two were conference abstracts with sufficient data for meta-analysis ( Huang et al , 2015 ; Elnashar et al , 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…Consistently, CC was used at 100 mg daily dose for 5 days, commencing on cycle Day 2–4, except the RCT by Ragini et al where 150 mg daily dose was used. The dose for Letrozole was 5 mg daily, starting from Day 2–5, except in two trials: one used 2.5 mg daily ( Goswami et al , 2004 ) and the other 10 mg daily dose ( Elnashar et al , 2016 ). In all trials, the starting dose of gonadotrophin for MD-IVF was 150 IU daily, except in two RCTs on poor responder where a 75 IU dose was used ( Goswami et al , 2004 ; Yu et al , 2018 ); in one trial for the normal ( Tan et al , 2005 ) and one for the high responders ( Oudshoorn et al , 2017 )- 100 IU daily dose was used in both studies.…”

Section: Resultsmentioning

confidence: 99%

“…The definition of cumulative LBR differed among the studies: the RCT by Casano et al (2012) and Liu et al (2020) aggregated the outcome of fresh and all subsequent frozen-thawed transfer; while other three trials included all fresh and frozen cycles within a specified time-period of 12 months ( Heijnen et al , 2007 ) or 18 months ( Oudshoorn et al , 2017 ; van Tilborg et al , 2017 ). Three studies reported pregnancy rates as positive beta-hCG ( Dhont et al , 1995 ; Hohmann et al , 2003 ; Blockeel et al , 2011 ) and two trials did not specify whether it was clinical pregnancy ( Tummon et al , 1992 ; Elnashar et al , 2016 ) and therefore excluded from the meta-analysis on CPR. The criterion for cycle cancellation was not uniform ( Table I ).…”

Section: Resultsmentioning

confidence: 99%

“…All RCTs were found to be ‘low-risk’ for random sequence generation, except five trials where the risk was unclear ( Dhont et al , 1995 ; Ashrafi et al , 2005 ; Mukherjee et al , 2012 ; Elnashar et al , 2016 ; Pilehvari et al , 2016 ). Allocation concealment was deemed to have low risk in all but seven RCTs where the risk was unclear ( Tummon et al , 1992 ; Dhont et al , 1995 ; Martinez et al , 2003 ; Lou and Huang, 2010 ; Pilehvari et al , 2016 ; Yu et al , 2018 ; Liu et al , 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Performance and detection bias: All RCTs were of ‘low-risk’ for performance bias, as the blinding of both patients and assessors was neither possible nor required for these objective outcome measures. Attrition bias: The outcome data were not complete in one trial (high risk) ( Huang et al , 2015 ), and not clear in the three other studies ( Ashrafi et al , 2005 ; Mohsen and El Din, 2013 ; Elnashar et al , 2016 ), the rest were of ‘low risk’. Reporting bias: All RCTs had ‘low risk’ for reporting bias.…”

Section: Resultsmentioning

confidence: 99%

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Mild versus conventional ovarian stimulation for IVF in poor, normal and hyper-responders: a systematic review and meta-analysis

Datta¹,

Maheshwari

Felix³

et al. 2020

Human Reproduction Update

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BACKGROUND Mild ovarian stimulation has emerged as an alternative to conventional IVF with the advantages of being more patient-friendly and less expensive. Inadequate data on pregnancy outcomes and concerns about the cycle cancellation rate (CCR) have prevented mild, or low-dose, IVF from gaining wide acceptance. OBJECTIVE AND RATIONALE To evaluate parallel-group randomised controlled trials (RCTs) on IVF where comparisons were made between a mild (≤150 IU daily dose) and conventional stimulation in terms of clinical outcomes and cost-effectiveness in patients described as poor, normal and non-polycystic ovary syndrome (PCOS) hyper-responders to IVF. SEARCH METHODS Searches with no language restrictions were performed using Medline, Embase, Cochrane central, Pre-Medicine from January 1990 until April 2020, using pre-specified search terms. References of included studies were hand-searched as well as advance access articles to key journals. Only parallel-group RCTs that used ≤150 IU daily dose of gonadotrophin as mild-dose IVF (MD-IVF) and compared with a higher conventional dose (CD-IVF) were included. Studies were grouped under poor, normal or hyper-responders as described by the authors in their inclusion criteria. Women with PCOS were excluded in the hyper-responder group. The risk of bias was assessed as per Cochrane Handbook for the included studies. The quality of evidence (QoE) was assessed according to the GRADE system. PRISMA guidance was followed for review methodology. OUTCOMES A total of 31 RCTs were included in the analysis: 15 in the poor, 14 in the normal and 2 in the hyper-responder group. Live birth rates (LBRs) per randomisation were similar following use of MD-IVF in poor (relative risk (RR) 0.91 (CI 0.68, 1.22)), normal (RR 0.88 (CI 0.69, 1.12)) and hyper-responders (RR 0.98 (CI 0.79, 1.22)) when compared to CD-IVF. QoE was moderate. Cumulative LBRs (5 RCTs, n = 2037) also were similar in all three patient types (RR 0.96 (CI 0.86 1.07) (moderate QoE). Risk of ovarian hyperstimulation syndrome was significantly less with MD-IVF than CD-IVF in both normal (RR 0.22 (CI 0.10, 0.50)) and hyper-responders (RR 0.47 (CI 0.31, 0.72)), with moderate QoE. The CCRs were comparable in poor (RR 1.33 (CI 0.96, 1.85)) and hyper-responders (RR 1.31 (CI 0.98, 1.77)) but increased with MD-IVF among normal responders (RR 2.08 (CI 1.38, 3.14)); all low to very low QoE. Although fewer oocytes were retrieved and fewer embryos created with MD-IVF, the proportion of high-grade embryos was similar in all three population types (low QoE). Compared to CD-IVF, MD-IVF was associated with less gonadotrophin use and lower cost. WIDER IMPLICATIONS This updated review provides reassurance on using MD-IVF not only for the LBR per cycle but also for the cumulative LBR, with moderate QoE. With risks identified with ‘freeze-all’ strategies, it may be time to recommend mild-dose ovarian stimulation for IVF for all categories of women i.e. hyper, poor and normal responders to IVF.

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Section: Resultsmentioning

confidence: 99%