Dataset Information

Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression.

ABSTRACT:

Study question

What doses of secretory phase progesterone (P) in women are associated with altered endometrial structure and/or function?

Summary answer

Consistently delayed histological maturation was seen at the lowest tested daily P dose (2.5 mg), whereas consistently altered functional response, as reflected by microarray analysis of gene expression was seen at both the 5 and 2.5 mg doses.

What is known already

Progesterone is absolutely required for normal embryo implantation and pregnancy survival. Progesterone supplementation is beneficial in ART cycles.

Study design, size, duration

In this case-control experimental trial, 46 healthy young female volunteers (age 19-34) underwent a single modeled endometrial cycle after GnRH down-regulation or monitored in natural cycles.

Participants/materials, setting, methods

In a university hospital, modeled cycles were obtained by GnRH agonist down-regulation, transdermal estradiol (E2) (0.2 mg/d), and daily injections of P in oil for 10 days: 2.5 mg (n = 6), 5 mg (n = 6), 10 mg (n = 12) or 40 mg (n = 12), after the 10th day of E2. Ten healthy, ovulatory women were used as controls. Endometrial biopsies were obtained on the 10th day of P exposure, or urinary LH surge (in controls). Analysis included histological dating, serum progesterone levels, microarray analysis of the whole genome, RT-PCR, western blot and comparison with the GEO database.

Main results and the role of chance

In endometrial biopsies, a morphological delay appears in the 2.5 mg/day of P group. Higher sub-physiological levels of P (?5 mg/day) resulted in normal histology, but aberrant gene expression. P levels required for consistent histological delay were lower than those in all ovulatory women. Gene expression abnormalities occurred at higher sub-physiological P concentrations, without a change in histology, a functional-morphological disassociation. The expression of some endometrial receptivity-associated genes appeared multiphasic, with peak or nadir of mean or median expression levels between the lowest and highest doses, suggesting sustained supraphysiological doses seen in ART treatment cycles may not be optimal.

Large scale data

GEO DataSets ID: 200056980; GSE 56980.

Limitations, reasons for caution

These results were obtained in fertile women, who may respond differently from infertile subjects.

Wider implications of the findings

The dose of P required for normal endometrial structure (5 mg/day) corresponds to a P concentration well below that seen in ovulatory women, suggesting that persistently delayed mid-secretory histology cannot be solely due to inadequate P concentrations in an ovulatory cycle. Endometrial gene expression is differentially regulated by different doses of progesterone. The apparent multiphasic response of some genes to P dose suggests the possibility that P concentration kinetics may play a role in normal endometrial preparation for receptivity. These findings strongly confirm that histologic development is not a reliable measure of endometrial P action.

Study funding/competing interest(s)

Supported by The Eunice Kennedy Shriver National Institute for Child Health and Disease, National Institute of Health, USA (NICHD/NIH) (R01HD067721 and U54HD30476; SLY and BAL) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 240239/2012-1 (RFS). All authors have no competing interests.

SUBMITTER: Young SL

PROVIDER: S-EPMC5850604 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression.

Young Steven L SL Savaris Ricardo F RF Lessey Bruce A BA Sharkey Andrew M AM Balthazar Ursula U Zaino Richard J RJ Sherwin Robert A RA Fritz Marc A MA

Human reproduction (Oxford, England) 20170901 9

<h4>Study question</h4>What doses of secretory phase progesterone (P) in women are associated with altered endometrial structure and/or function?<h4>Summary answer</h4>Consistently delayed histological maturation was seen at the lowest tested daily P dose (2.5 mg), whereas consistently altered functional response, as reflected by microarray analysis of gene expression was seen at both the 5 and 2.5 mg doses.<h4>What is known already</h4>Progesterone is absolutely required for normal embryo impla ...[more]

PMID: 28854727

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Dataset Information

Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression.

Study question

Summary answer

What is known already

Study design, size, duration

Participants/materials, setting, methods

Main results and the role of chance

Large scale data

Limitations, reasons for caution

Wider implications of the findings

Study funding/competing interest(s)

Publications

Effect of randomized serum progesterone concentration on secretory endometrial histologic development and gene expression.

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