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Are extremely high progesterone levels still an issue in IVF?

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Abstract

Background

Premature luteinization of one or more developing follicles complicates 1–2 % of controlled ovarian stimulation cycles for assisted reproduction. The management of this complication is controversial, with cycle cancellation likely representing the most commonly used strategy. The aim of this study was to evaluate the efficacy of the “freeze-all” policy—where the entire cohort of blastocysts is cryopreserved for subsequent frozen-thawed embryo transfer—in treating cases of premature luteinization.

Methods

Patients experiencing premature luteinization during controlled ovarian stimulation—identified by extremely high progesterone levels at induction (P levels ≥3.0 ng/ml and/or P/estradiol ratio ≥1, n = 42)—were included in a “freeze-all” program and compared to controls undergoing a “freeze-all” program with normal progesterone levels at induction (P < 1.5 ng/ml, n = 67).

Results

Blastulation rate was comparable between patients with premature luteinization and controls (48.1 ± 20.5 % in Cases vs. 52.3 ± 24.9 % in Controls, p = 0.36). Ongoing pregnancy rates after the first frozen-thawed embryo transfer (38.1 % in Cases and 41.0 % in Controls, p = 0.83) and cumulative ongoing pregnancy rates after three frozen-thawed embryo transfer cycles (40.5 % in Cases vs. 47.8 % in Controls, p = 0.55) were also similar.

Conclusions

These results show that extremely marked progesterone elevation throughout controlled ovarian stimulation does not impair blastocyst development and implantation potential in the context of a “freeze-all” strategy. Based on this, adoption of the “freeze-all” strategy represents a valuable tool in treating premature luteinization. In contrast, cycle cancellation—likely the most frequently used method for management of this complication—currently represents a misconduct.

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Abbreviations

AMH:

Anti-mullerian hormone

BMI:

Body mass index

CI:

Confidence interval

COS:

Controlled ovarian stimulation

E 2 :

17β estradiol

FET:

Frozen-thawed embryo transfer

FSH:

Follicle-stimulating hormone

GnRH:

Gonadotropin-releasing hormone

HAS:

Human serum albumin

hCG:

Human chorionic gonadotropin

HP-hMG:

Highly purified human menopausal gonadotropin

ICSI:

Intracytoplasmic sperm injection

IVF:

In vitro fertilization

MII:

Metaphase II

OHSS:

Ovarian hyperstimulation syndrome

OR:

Odds ratio

P:

Progesterone

rFSH:

Recombinant FSH

rLH:

Recombinant luteinizing hormone

SD:

Standard deviation

SSS:

Serum substitute supplement

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Author’s contribution

VSV, VP, PL, QL, CM and PE participated in designing, analysis of results and preparation of manuscript. GP, MM and MM participated in the collection of data. All authors have read and approved the final manuscript.

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Authors and Affiliations

  1. IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20136, Milan, Italy

    V. S. Vanni, L. Quaranta, P. Giardina, M. Molgora, M. Munaretto & E. Papaleo

  2. Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20136, Milan, Italy

    P. Viganò & L. Pagliardini

  3. Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20136, Milan, Italy

    M. Candiani

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  1. V. S. Vanni
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  2. P. Viganò
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  3. L. Quaranta
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  4. L. Pagliardini
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  5. P. Giardina
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  6. M. Molgora
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  7. M. Munaretto
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  9. E. Papaleo
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Correspondence to E. Papaleo.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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All women provided informed consent for their clinical data and anonymized records to be used for research purposes.

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Vanni, V.S., Viganò, P., Quaranta, L. et al. Are extremely high progesterone levels still an issue in IVF?. J Endocrinol Invest 40, 69–75 (2017). https://doi.org/10.1007/s40618-016-0531-8

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  • DOI: https://doi.org/10.1007/s40618-016-0531-8

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