Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy  and Live Birth Rates in ART: Systematic Review and Meta-Analyses

Noemie Ranisavljevic; Stephanie Huberlant; Marie Montagut; Pierre-Marie Alonzo; Bernadette Darné; Solène Languille; Tal Anahory; Isabelle Cédrin-Durnerin

doi:10.3389/fendo.2022.892753

Reproductive Endocrinology Luteal Phase

Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses

Ranisavljevic N, Huberlant S, Montagut M, Alonzo PM, Darné B, Languille S, Anahory T, Cédrin-Durnerin I

Published June 28, 2022 Frontiers in Endocrinology, 13, 892753

DOI 10.3389/fendo.2022.892753 PMID 35757393 PMC PMC9229589

RRM Academy Synopsis

Low Progesterone Is Linked to Fewer ART Births Without a Corpus Luteum

A 2022 review of 32 studies in ART found that low luteal progesterone went with fewer live births when no corpus luteum was present. Low progesterone also went with more miscarriage when no corpus luteum was present. Cycles with several corpora lutea gave mixed results.

Study at a glance, systematic review of 32 studies: Low luteal progesterone went with fewer live births, no corpus luteum. Source: Ranisavljevic N et al., 2022, PMID 35757393.

Key Findings

With no corpus luteum, low luteal progesterone went with less ongoing pregnancy: risk ratio 0.72 (0.62–0.84), from 3,501 cycles in nine studies.
With no corpus luteum, low progesterone went with less live birth: risk ratio 0.73 (0.59–0.90), 4,841 cycles, eight studies. Miscarriage was more likely with no corpus luteum: 1.48 (1.17–1.86), 13 studies.
With one or few corpora lutea, the live birth risk ratio was 0.60 (0.45–0.78), from 632 cycles in three studies.
With several corpora lutea, risk ratios showed no significant association: 0.59 (0.32–1.07) for ongoing pregnancy and 0.87 (0.53–1.43) for live birth.
The 32 studies included 17 retrospective and 15 prospective designs, and none were randomized.

Interpretation

The review pools 32 studies, none randomized, so it shows association and cannot show cause. The authors judge the estimates probably biased. Studies set low progesterone at different cut-offs, and the authors report high heterogeneity. The authors rate certainty low for cycles with no corpus luteum and very low for several corpora lutea. Participants were women in ART cycles. The review did not test whether changing progesterone support changes birth rates.

RRM Context

After ovulation, the corpus luteum makes the body's own progesterone. The review says artificial cycles have no corpus luteum, so all progesterone comes from outside. It calls the luteal phase of a stimulated cycle with several corpora lutea deficient. The authors cite reports linking a missing corpus luteum to obstetric complications. Restorative reproductive medicine centers on ovulation and luteal function as the source of progesterone.

Our editorial summary of this paper, not the article's abstract.

Abstract

Progesterone plays a key role in implantation. Several studies reported that lower luteal progesterone levels might be related to decreased chances of pregnancy. This systematic review was conducted using appropriate key words, on MEDLINE, EMBASE, and the Cochrane Library, from 1990 up to March 2021 to assess if luteal serum progesterone levels are associated with ongoing pregnancy (OP) and live birth (LB) rates (primary outcomes) and miscarriage rate (secondary outcome), according to the number of corpora lutea (CLs). Overall 2,632 non-duplicate records were identified, of which 32 relevant studies were available for quantitative analysis. In artificial cycles with no CL, OP and LB rates were significantly decreased when the luteal progesterone level falls below a certain threshold (risk ratio [RR] 0.72; 95% confidence interval [CI] 0.62-0.84 and 0.73; 95% CI 0.59-0.90, respectively), while the miscarriage rate was increased (RR 1.48; 95% CI 1.17-1.86). In stimulated cycles with several CLs, the mean luteal progesterone level in the no OP and no LB groups was significantly lower than in the OP and LB groups [difference in means 68.8 (95% CI 45.6-92.0) and 272.4 (95% CI 10.8-533.9), ng/ml, respectively]. Monitoring luteal serum progesterone levels could help in individualizing progesterone administration to enhance OP and LB rates, especially in cycles without corpus luteum.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=139019, identifier 139019.

Topics

Reproductive Endocrinology › Luteal Phase › Luteal Phase Deficiency · Pregnancy › Early Pregnancy › Progesterone Support · Diagnostics › Hormone Testing › Serum Panels

Noemie Ranisavljevic, Stephanie Huberlant, Marie Montagut, Pierre-Marie Alonzo, Bernadette Darné, Solène Languille, Tal Anahory, Isabelle Cédrin-Durnerin

N Ranisavljevic, S Huberlant, M Montagut, P Alonzo, B Darné, S Languille, T Anahory, I Cédrin-Durnerin

PMID 35757393 35757393 DOI 10.3389/fendo.2022.892753 10.3389/fendo.2022.892753 Ranisavljevic et al. 2022, Ranisavljevic 2022

Keywords

Progesterone

Low Luteal Serum Progesterone Levels Are Associated With Lower Ongoing Pregnancy and Live Birth Rates in ART: Systematic Review and Meta-Analyses

Low Progesterone Is Linked to Fewer ART Births Without a Corpus Luteum

Key Findings

Interpretation

RRM Context

Abstract

Topics

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Keywords