Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation
Kushnir, V. A., Darmon, S. K., Barad, D. H., & Gleicher, N. (2018). Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation. BMJ Open. https://doi.org/10.1136/bmjopen-2018-023124
Kushnir VA, Darmon SK, Barad DH, Gleicher N. Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation. BMJ Open. 2018. doi:10.1136/bmjopen-2018-023124
Kushnir, V. A., et al. "Observational retrospective study of US national utilisation patterns and live birth rates for various ovarian stimulation protocols for in vitro fertilisation." BMJ Open, 2018.
Conventional IVF stimulation had the highest live birth rates
Conventional ovarian stimulation produced the highest live birth rates in every age group in a retrospective cohort of US national IVF cycles from 2014 and 2015. Minimal stimulation, natural cycle IVF and in vitro maturation (IVM) had lower rates. The lead of conventional stimulation widened as women got older.
Key Findings
Across five age groups (under 35, 35-37, 38-40, 41-42, over 42), conventional stimulation gave live birth rates of 42.4%, 33.1%, 22.1%, 11.7% and 3.9%.
Under age 35, live birth rates were 26.1% (22.9 to 29.5) with minimal stimulation, 15.7% (12.7 to 19.4) with natural cycle IVF and 10.8% (6.4 to 17.7) with IVM.
Conventional stimulation had live birth rates 1.6-fold to 3.9-fold higher than the other protocols under age 35, and 4.4-fold to 6.6-fold higher above age 42.
Among women with diminished ovarian reserve, the difference between conventional stimulation and the other protocols widened from 2.8-fold under age 35 to 5.2-fold above age 42.
Cycles numbered 205 705 conventional, 4397 minimal stimulation, 2785 natural and 514 IVM. Two centers accounted for 57.9% of the minimal stimulation and natural IVF cycles.
Interpretation
The study is a retrospective cohort. Researchers looked back at completed cycles in aggregate national data from the Society for Assisted Reproductive Technology. Repeat cycles by one woman could not be identified. Age and diminished ovarian reserve were the only patient factors available. Each clinic chose the protocol label for its cycles, and minimal stimulation has no standard definition. The authors say hidden selection bias cannot be ruled out, but they consider it unlikely that adjusting for it would change the main findings. Limiting the analysis to diminished ovarian reserve did not substantially alter the findings. Other diagnoses were not analyzed.
RRM Context
The study compares IVF protocols with one another. IVF bypasses the reproductive system without establishing why conception fails. Restorative reproductive medicine asks what causes infertility in each partner and treats that cause. Diminished ovarian reserve, the diagnosis analyzed here, calls for a restorative look at why the reserve is low.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
Alternative ovarian stimulation protocols for in vitro fertilisation (IVF) have grown in popularity. Yet, patient populations best suited for these protocols have not been defined. Our objective was, therefore, to determine national IVF utilisation patterns and live birth rates of various ovarian stimulation protocols.
Design
Retrospective cohort study.
Setting
Academic-affiliated private fertility centre.
Participants
Aggregate data published by Society for Assisted Reproductive Technology for autologous IVF cycles performed in the USA during 2014 and 2015 were analysed. IVF cycles were stratified based on ovarian stimulation protocol: 205 705 conventional stimulations, 4397 minimal stimulations, 2785 natural cycles and 514 in vitro maturation (IVM) cycles. Repeat cycles could not be determined in this analysis.
Outcome Measures
Utilisation patterns and age-specific live birth rates for various ovarian stimulation protocols.
Results
With advancing female age, utilisation of conventional stimulation protocols decreased, while minimal stimulation and natural cycle IVF increased. Diminished ovarian reserve diagnoses were in all age groups less prevalent in patients undergoing conventional stimulation than with all other protocols. Live birth rates were highest with conventional stimulation at 42.4%, 33.1%, 22.1%, 11.7% and 3.9% for <35, 35-37, 38-40, 41-42 and >42 female age groups, respectively. The difference in live birth rates between conventional stimulation and other protocols widened with advancing age from 1.6-fold to 3.9-fold among women <35 years of age, reaching 4.4-fold to 6.6-fold among women >42 years of age.
Conclusions
In comparison to conventional stimulation IVF-minimal stimulation, natural cycle IVF and IVM protocols offer lower but still acceptable live birth rates among young women. These alternative protocols are frequently used in older women and those with diminished ovarian reserve, despite their lower live birth rates. The reasons for this apparent incongruity warrant further careful exploration.
