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Can Ratios Between Prognostic Factors Predict the Clinical Pregnancy Rate in an IVF/ICSI Program with a GnRH Agonist-FSH/hMG Protocol? An Assessment of 2421 Embryo Transfers, and a Review of the Literature

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Abstract

None of the models developed in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is sufficiently good predictors of pregnancy. The aim of this study was to determine whether ratios between prognostic factors could predict the clinical pregnancy rate in IVF/ICSI. We analyzed IVF/ICSI cycles (based on long GnRH agonist—FSH protocols) at two ART centers (the second to validate externally the data). The ratios studied were (i) the total FSH dose divided by the serum estradiol level on the hCG trigger day, (ii) the total FSH dose divided by the number of mature oocytes, (iii) the serum estradiol level on the trigger day divided by the number of mature oocytes, (iv) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day, (v) the serum estradiol level on the trigger day divided by the number of mature oocytes and then by the number of grade 1 or 2 embryos obtained, and (vi) the serum estradiol level on the trigger day divided by the endometrial thickness on the trigger day and then by the number of grade 1 or 2 embryos obtained. The analysis covered 2421 IVF/ICSI cycles with an embryo transfer, leading to 753 clinical pregnancies (31.1% per transfer). Four ratios were significantly predictive in both centers; their discriminant power remained moderate (area under the receiver operating characteristic curve between 0.574 and 0.610). In contrast, the models’ calibration was excellent (coefficients: 0.943–0.978; p < 0.001). Our ratios were no better than existing models in IVF/ICSI programs. In fact, a strongly discriminant predictive model will be probably never be obtained, given the many factors that influence the occurrence of a pregnancy.

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Data Availability

The material contained in this manuscript has not been published, has not been submitted, or is not being submitted elsewhere. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ART:

assisted reproductive technology

IVF:

in vitro fertilization

ICSI:

intracytoplasmic sperm injection

GnRH:

gonadotropin releasing hormone

FSH:

follicle stimulating hormone

CP:

clinical pregnancy

OP:

ongoing pregnancy

AMH:

anti-Müllerian hormone

AFC:

antral follicle count

E2:

estradiol

LH:

luteinizing hormone

hCG:

human chorionic gonadotropin

Ooc:

oocyte

Endo:

endometrial thickness

E:

grade I and II embryo

FSH/E2:

the total FSH dose (in IU) divided by the serum E2 level (in pg/ml) on the trigger day

FSH/Ooc:

the total FSH dose (in IU) divided by the number of mature oocytes (Ooc) retrieved

E2/Ooc:

the serum E2 level on the trigger day (in pg/ml) divided by the number of mature oocytes retrieved

E2/Endo:

the serum E2 level on the trigger day (in pg/ml) divided by the endometrial thickness (Endo) on the trigger day (in mm)

(E2/Ooc)/E:

the serum E2 level on the trigger day (in pg/ml) divided by the number of mature oocytes retrieved, and then by the number of grade I and II embryos obtained (E)

(E2/Endo)/E:

the serum E2 level (in pg/ml) divided by the endometrial thickness (Endo) on the trigger day (mm), and then by the number of grade I and II embryos obtained

ROC:

receiver operating curve

AUC:

area under the curve

OR:

odd-ratio

95%CI:

confidence interval at 95%

OSI:

ovarian sensitivity index

FORT:

follicular output rate

FSI:

follicular sensitivity index

BMI:

body mass index

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Acknowledgments

The authors thank David Fraser for their comments, suggestions, and critical reading of the manuscript.

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Authors and Affiliations

  1. ART Center, Brest University Hospital, 2 avenue Foch, 29200, Brest, France

    Philippe Merviel, Michel Menard, Marie-Thérèse Le Martelot, Sylvie Roche, Jean-Jacques Chabaud, Hortense Drapier & Damien Beauvillard

  2. Department of Gynecology, Obstetrics and Reproductive Medicine, Brest University Hospital, 2 avenue Foch, F-29200, Brest, France

    Philippe Merviel

  3. ART Center, Amiens University Hospital, 1 rond-point du professeur Christian Cabrol, 80054, Amiens, France

    Rosalie Cabry, Florence Scheffler, Emmanuelle Lourdel, Henri Copin & Moncef Benkhalifa

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  1. Philippe Merviel
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Contributions

Philippe Merviel: substantial contributions to the conception, design of the work, the acquisition, analysis, and interpretation of data; have drafted the work or substantively revised it. Michel Ménard: substantial contributions to the conception, design of the work; the acquisition, analysis, and interpretation of data; have drafted the work or substantively revised it. Rosalie Cabry: the acquisition of data. Florence Scheffler: the acquisition of data. Emmanuelle Lourdel: the acquisition of data. Marie-Thérèse Le Martelot: substantial contributions to the conception, design of the work; the acquisition, analysis, and interpretation of data. Sylvie Roche: the acquisition of data. Jean-Jacques Chabaud: the acquisition of data. Henri Copin: substantial contributions to the conception (head of the Amiens ART center). Hortense Drapier: the acquisition of data. Moncef Benkhalifa: substantial contributions to the conception, design of the work; the acquisition, analysis, and interpretation of data; have drafted the work or substantively revised it. Damien Beauvillard: the acquisition of data (Head of the Brest ART center). Each author has approved the submitted version and has agreed both to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

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Correspondence to Philippe Merviel.

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The authors declare that they have no conflict of interest.

Ethical Approval and Consent to Participate

All the couples have signed consent to the infertility treatment. Given that the couples had already consented (non-opposition) to exploitation of their personal medical data for research purposes and in line with the French legislation on studies of routine medical care (Loi no. 78-17 du 6 janvier 1978 modifiée en 2004 relative à l’informatique, aux fichiers et aux libertés: for all research involving human participants, informed consent to participate in the study should be obtained from participants (or their parent or legal guardian in the case of children under 16)), approval by an independent ethics committee was not required (Ethic committee report of Brest university hospital, 2019). The consents of each couple are available in their medical record and with the corresponding author.

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Merviel, P., Menard, M., Cabry, R. et al. Can Ratios Between Prognostic Factors Predict the Clinical Pregnancy Rate in an IVF/ICSI Program with a GnRH Agonist-FSH/hMG Protocol? An Assessment of 2421 Embryo Transfers, and a Review of the Literature. Reprod. Sci. 28, 495–509 (2021). https://doi.org/10.1007/s43032-020-00307-2

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