Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysis Article Swipe
N Schouten
,
Rui Wang
,
Helen L. Torrance
,
Theodora Van Tilborg
,
Ercan Baştu
,
Christina Bergh
,
Thomas D’Hooghe
,
Jesper Friis Petersen
,
Kannamannadiar Jayaprakasan
,
Yacoub Khalaf
,
Ellen R Klinkert
,
Antonio La Marca
,
Lan N. Vuong
,
Louise Lapensée
,
Sarah Lensen
,
Åsa Magnusson
,
Adolfo Allegra
,
A. Nyboe Andersen
,
Simone C Oudshoorn
,
Biljana Popovic-Todorovic
,
Ben W. Mol
,
Marinus J.C. Eijkemans
,
Frank J. Broekmans
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/humupd/dmae032
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1093/humupd/dmae032
BACKGROUND The ovarian response to gonadotropin stimulation varies widely among women, and could impact the probability of live birth as well as treatment risks. Many studies have evaluated the impact of different gonadotropin starting doses, mainly based on predictive variables like ovarian reserve tests (ORT) including anti-Müllerian hormone (AMH), antral follicle count (AFC), and basal follicle-stimulating hormone (bFSH). A Cochrane systematic review revealed that individualizing the gonadotropin starting dose does not affect efficacy in terms of ongoing pregnancy/live birth rates, but may reduce treatment risks such as the development of ovarian hyperstimulation syndrome (OHSS). An individual patient data meta-analysis (IPD-MA) offers a unique opportunity to develop and validate a universal prediction model to help choose the optimal gonadotropin starting dose to minimize treatment risks without affecting efficacy. OBJECTIVE AND RATIONALE The objective of this IPD-MA is to develop and validate a gonadotropin dose-selection model to guide the choice of a gonadotropin starting dose in IVF/ICSI, with the purpose of minimizing treatment risks without compromising live birth rates. SEARCH METHODS Electronic databases including MEDLINE, EMBASE, and CRSO were searched to identify eligible studies. The last search was performed on 13 July 2022. Randomized controlled trials (RCTs) were included if they compared different doses of gonadotropins in women undergoing IVF/ICSI, presented at least one type of ORT, and reported on live birth or ongoing pregnancy. Authors of eligible studies were contacted to share their individual participant data (IPD). IPD and information within publications were used to determine the risk of bias. Generalized linear mixed multilevel models were applied for predictor selection and model development. OUTCOMES A total of 14 RCTs with data of 3455 participants were included. After extensive modeling, women aged 39 years and over were excluded, which resulted in the definitive inclusion of 2907 women. The optimal prediction model for live birth included six predictors: age, gonadotropin starting dose, body mass index, AFC, IVF/ICSI, and AMH. This model had an area under the curve (AUC) of 0.557 (95% confidence interval (CI) from 0.536 to 0.577). The clinically feasible live birth model included age, starting dose, and AMH and had an AUC of 0.554 (95% CI from 0.530 to 0.578). Two models were selected as the optimal model for combined treatment risk, as their performance was equal. One included age, starting dose, AMH, and bFSH; the other also included gonadotropin-releasing hormone (GnRH) analog. The AUCs for both models were 0.769 (95% CI from 0.729 to 0.809). The clinically feasible model for combined treatment risk included age, starting dose, AMH, and GnRH analog, and had an AUC of 0.748 (95% CI from 0.709 to 0.787). WIDER IMPLICATIONS The aim of this study was to create a model including patient characteristics whereby gonadotropin starting dose was predictive of both live birth and treatment risks. The model performed poorly on predicting live birth by modifying the FSH starting dose. On the contrary, predicting treatment risks in terms of OHSS occurrence and management by modifying the gonadotropin starting dose was adequate. This dose-selection model, consisting of easily obtainable patient characteristics, aids in the choice of the optimal gonadotropin starting dose for each individual patient to lower treatment risks and potentially reduce treatment costs.
Related Topics
Concepts
Ovarian hyperstimulation syndrome
Live birth
Antral follicle
Medicine
Gonadotropin
Ovarian reserve
Pregnancy
Randomized controlled trial
Pregnancy rate
Meta-analysis
Gynecology
In vitro fertilisation
Obstetrics
Infertility
Internal medicine
Ovary
Hormone
Biology
Genetics
Metadata
- Type
- review
- Language
- en
- Landing Page
- https://doi.org/10.1093/humupd/dmae032
- https://academic.oup.com/humupd/advance-article-pdf/doi/10.1093/humupd/dmae032/61250443/dmae032.pdf
- OA Status
- hybrid
- Cited By
- 2
- References
- 69
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4405628128
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4405628128Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/humupd/dmae032Digital Object Identifier
- Title
-
Development and validation of a gonadotropin dose selection model for optimized ovarian stimulation in IVF/ICSI: an individual participant data meta-analysisWork title
- Type
-
reviewOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-12-20Full publication date if available
- Authors
-
N Schouten, Rui Wang, Helen L. Torrance, Theodora Van Tilborg, Ercan Baştu, Christina Bergh, Thomas D’Hooghe, Jesper Friis Petersen, Kannamannadiar Jayaprakasan, Yacoub Khalaf, Ellen R Klinkert, Antonio La Marca, Lan N. Vuong, Louise Lapensée, Sarah Lensen, Åsa Magnusson, Adolfo Allegra, A. Nyboe Andersen, Simone C Oudshoorn, Biljana Popovic-Todorovic, Ben W. Mol, Marinus J.C. Eijkemans, Frank J. BroekmansList of authors in order
- Landing page
-
https://doi.org/10.1093/humupd/dmae032Publisher landing page
- PDF URL
-
https://academic.oup.com/humupd/advance-article-pdf/doi/10.1093/humupd/dmae032/61250443/dmae032.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
-
https://academic.oup.com/humupd/advance-article-pdf/doi/10.1093/humupd/dmae032/61250443/dmae032.pdfDirect OA link when available
- Concepts
-
Ovarian hyperstimulation syndrome, Live birth, Antral follicle, Medicine, Gonadotropin, Ovarian reserve, Pregnancy, Randomized controlled trial, Pregnancy rate, Meta-analysis, Gynecology, In vitro fertilisation, Obstetrics, Infertility, Internal medicine, Ovary, Hormone, Biology, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
2Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 2Per-year citation counts (last 5 years)
- References (count)
-
69Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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