Progesterone Action on Endometrium of PCOS

NCT05062135 | Completed DMC

• 1 other identifier: 21253613.6.0000.0068
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

Objective: To study the influence of metabolic factors on the action of progesterone on the endometrium of women with PCOS. Design: A prospective open-label clinical trial. Setting: Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care center from 2014 to 2019. Subjects: To assess the sole effect of progesterone (P4) on the endometrium we studied amenorrheic (cycles\> 90 days) women with PCOS (n=23), comparing them to healthy eumenorrheic control women ( n=13). Intervention(s): All subjects underwent an endometrial biopsy (EB) in the follicular phase of the first study cycle. They were then treated with micronized P4 (400 mg/day x 10 days intravaginally) from days 14-28 of the cycle, and a second EB was performed between days 20-24 of the cycle (second phase). Main Outcome Measure(s): EB samples were analyzed under light microscopy for histomorphometric analysis.

Conditions

Polycystic Ovary; Progesterone Resistance

Keywords

PCOS; Progesterone; endometrium

Outcome Measures

Primary Outcomes (1)

• Endometrial biopsy

  Number of patients with adequate changes of endometrium similar to luteal phase.

  3 months

Study Arms (1)

Morphological analysis of endometrium

EXPERIMENTAL

PCOS: Seventeen PCOS subjects underwent two endometrial biopsies after the first P4-treated cycle, the first between days 5-9 of the cycle and the other between days 20-22 (i.e., under P4 treatment) of the cycle. Controls: Thirteen ovulatory control women under two endometrial biopsies, performed after the first month of luteal P4 treatment, the first between days 5-9 and the second between days 20-22 of the cycle To quantify the parameters of interest, images were captured using a high-resolution camera (AxioCam-MCR, Carl Zeiss) adapted to a light microscope (Axiolab, Carl Zeiss) and adjusted with 40× objective lenses. The images were transmitted to a computer with AxioVision Rel 4.2 software (Carl Zeiss). For assessment of glandular and surface epithelial thickness, cell count, and counting newly formed blood vessels, ten images of each endometrial sample were made for each patient. For VEGF-C determination, the numerical density of blood vessels per mm2 was established

Drug: Progesterone 400 Mg Vaginal Suppository on PCOS

Interventions

Progesterone 400 Mg Vaginal Suppository on PCOS DRUG

The same drug will be used in control group

Also known as: Progesterone 400 Mg Vaginal Suppository on control group

Morphological analysis of endometrium

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of Polycystic ovarian syndrome (defined by the Rotterdam criteria, which includes two of the following three features: a) oligo-amenorrhea; b) clinical or biochemical signs of hyperandrogenism; and c) polycystic ovaries) ages 18 to 35 years; must be able to swallow tables
• Controls - the family planning outpatient office and healthy women ages 18 to 35 years with regular menstrual cycles, no evidence of hirsutism; must be able to swallow tables

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead

Related Publications (28)

• Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Hum Reprod. 2018 Sep 1;33(9):1602-1618. doi: 10.1093/humrep/dey256.

  PMID: 30052961 BACKGROUND

• Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006 Nov;91(11):4237-45. doi: 10.1210/jc.2006-0178. Epub 2006 Aug 29.

  PMID: 16940456 BACKGROUND

• Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril. 2009 Feb;91(2):456-88. doi: 10.1016/j.fertnstert.2008.06.035. Epub 2008 Oct 23.

  PMID: 18950759 BACKGROUND

• Trivax B, Azziz R. Diagnosis of polycystic ovary syndrome. Clin Obstet Gynecol. 2007 Mar;50(1):168-77. doi: 10.1097/GRF.0b013e31802f351b.

  PMID: 17304034 BACKGROUND

• Giudice LC. Endometrium in PCOS: Implantation and predisposition to endocrine CA. Best Pract Res Clin Endocrinol Metab. 2006 Jun;20(2):235-44. doi: 10.1016/j.beem.2006.03.005.

  PMID: 16772154 BACKGROUND

• Slayden OD, Nayak NR, Burton KA, Chwalisz K, Cameron ST, Critchley HO, Baird DT, Brenner RM. Progesterone antagonists increase androgen receptor expression in the rhesus macaque and human endometrium. J Clin Endocrinol Metab. 2001 Jun;86(6):2668-79. doi: 10.1210/jcem.86.6.7606.

  PMID: 11397870 BACKGROUND

• Ochoa-Bernal MA, Fazleabas AT. Physiologic Events of Embryo Implantation and Decidualization in Human and Non-Human Primates. Int J Mol Sci. 2020 Mar 13;21(6):1973. doi: 10.3390/ijms21061973.

  PMID: 32183093 BACKGROUND

• Sharpe A, Morley LC, Tang T, Norman RJ, Balen AH. Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2019 Dec 17;12(12):CD013505. doi: 10.1002/14651858.CD013505.

  PMID: 31845767 BACKGROUND

• Walls ML, Hunter T, Ryan JP, Keelan JA, Nathan E, Hart RJ. In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes. Hum Reprod. 2015 Jan;30(1):88-96. doi: 10.1093/humrep/deu248. Epub 2014 Oct 29.

  PMID: 25355587 BACKGROUND

• Simoes RS, Soares JM Jr, Simoes MJ, Nader HB, Baracat MCP, Maciel GAR, Serafini PC, Azziz R, Baracat EC. Small leucine-rich proteoglycans (SLRPs) in the endometrium of polycystic ovary syndrome women: a pilot study. J Ovarian Res. 2017 Aug 8;10(1):54. doi: 10.1186/s13048-017-0349-9.

  PMID: 28789706 BACKGROUND

• Munro MG, Critchley HOD, Fraser IS; FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 2018 Dec;143(3):393-408. doi: 10.1002/ijgo.12666. Epub 2018 Oct 10.

  PMID: 30198563 BACKGROUND

• Lai TH, Zhao Y, Shih IeM, Ho CL, Bankowski B, Vlahos N. Expression of L-selectin ligands in human endometrium during the implantation window after controlled ovarian stimulation for oocyte donation. Fertil Steril. 2006 Mar;85(3):761-3. doi: 10.1016/j.fertnstert.2005.08.023.

  PMID: 16500358 BACKGROUND

• Quezada S, Avellaira C, Johnson MC, Gabler F, Fuentes A, Vega M. Evaluation of steroid receptors, coregulators, and molecules associated with uterine receptivity in secretory endometria from untreated women with polycystic ovary syndrome. Fertil Steril. 2006 Apr;85(4):1017-26. doi: 10.1016/j.fertnstert.2005.09.053. Epub 2006 Mar 9.

  PMID: 16580389 BACKGROUND

• Qiao J, Wang L, Li R, Zhang X. Microarray evaluation of endometrial receptivity in Chinese women with polycystic ovary syndrome. Reprod Biomed Online. 2008 Sep;17(3):425-35. doi: 10.1016/s1472-6483(10)60228-3.

  PMID: 18765015 BACKGROUND

• Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Consensus on women's health aspects of polycystic ovary syndrome (PCOS). Hum Reprod. 2012 Jan;27(1):14-24. doi: 10.1093/humrep/der396. Epub 2011 Dec 5.

  PMID: 22147920 BACKGROUND

• Griukova A, Deryabin P, Shatrova A, Burova E, Severino V, Farina A, Nikolsky N, Borodkina A. Molecular basis of senescence transmitting in the population of human endometrial stromal cells. Aging (Albany NY). 2019 Nov 5;11(21):9912-9931. doi: 10.18632/aging.102441. Epub 2019 Nov 5.

  PMID: 31689238 BACKGROUND

• Apparao KB, Lovely LP, Gui Y, Lininger RA, Lessey BA. Elevated endometrial androgen receptor expression in women with polycystic ovarian syndrome. Biol Reprod. 2002 Feb;66(2):297-304. doi: 10.1095/biolreprod66.2.297.

  PMID: 11804942 BACKGROUND

• Cheung AP. Ultrasound and menstrual history in predicting endometrial hyperplasia in polycystic ovary syndrome. Obstet Gynecol. 2001 Aug;98(2):325-31. doi: 10.1016/s0029-7844(01)01432-6.

  PMID: 11506853 BACKGROUND

• Maliqueo M, Clementi M, Gabler F, Johnson MC, Palomino A, Sir-Petermann T, Vega M. Expression of steroid receptors and proteins related to apoptosis in endometria of women with polycystic ovary syndrome. Fertil Steril. 2003 Sep;80 Suppl 2:812-9. doi: 10.1016/s0015-0282(03)00987-7.

  PMID: 14505758 BACKGROUND

• Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006 Jan-Feb;12(1):13-21. doi: 10.1093/humupd/dmi036. Epub 2005 Aug 25.

  PMID: 16123051 BACKGROUND

• Lopes IM, Baracat MC, Simoes Mde J, Simoes RS, Baracat EC, Soares JM Jr. Endometrium in women with polycystic ovary syndrome during the window of implantation. Rev Assoc Med Bras (1992). 2011 Nov-Dec;57(6):702-9. doi: 10.1590/s0104-42302011000600020. English, Portuguese.

  PMID: 22249553 RESULT

• de Medeiros SF, Yamamoto MMW, Souto de Medeiros MA, Barbosa BB, Soares JM, Baracat EC. Changes in clinical and biochemical characteristics of polycystic ovary syndrome with advancing age. Endocr Connect. 2020 Feb;9(2):74-89. doi: 10.1530/EC-19-0496.

  PMID: 31905164 RESULT

• Baracat MC, Serafini PC, Simoes Rdos S, Maciel GA, Soares JM Jr, Baracat EC. Systematic review of cell adhesion molecules and estrogen receptor expression in the endometrium of patients with polycystic ovary syndrome. Int J Gynaecol Obstet. 2015 Apr;129(1):1-4. doi: 10.1016/j.ijgo.2014.10.022. Epub 2014 Dec 18.

  PMID: 25554522 RESULT

• Lopes IM, Maganhin CC, Oliveira-Filho RM, Simoes RS, Simoes MJ, Iwata MC, Baracat EC, Soares JM Jr. Histomorphometric Analysis and Markers of Endometrial Receptivity Embryonic Implantation in Women With Polycystic Ovary Syndrome During the Treatment With Progesterone. Reprod Sci. 2014 Jul;21(7):930-938. doi: 10.1177/1933719113519169. Epub 2014 Jan 23.

  PMID: 24458485 RESULT

• Ejzenberg D, Simoes Mde J, Pinheiro W, Soares JM Junior, Serafini PC, Baracat EC. Blind aspiration biopsy versus a guided hysteroscopic technique for investigation of the endometrium in infertile women. Histol Histopathol. 2016 Sep;31(9):981-6. doi: 10.14670/HH-11-725. Epub 2016 Jan 25.

  PMID: 26806353 RESULT

• Ejzenberg D, Gomes TJO, Monteleone PAA, Serafini PC, Soares-Jr JM, Baracat EC. Prognostic factors for pregnancy after intrauterine insemination. Int J Gynaecol Obstet. 2019 Oct;147(1):65-72. doi: 10.1002/ijgo.12898. Epub 2019 Jul 23.

  PMID: 31242330 RESULT

• Savaris RF, Groll JM, Young SL, DeMayo FJ, Jeong JW, Hamilton AE, Giudice LC, Lessey BA. Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles. J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.

  PMID: 21411543 RESULT

• Giordano MV, Giordano LA, Gomes RC, Simoes RS, Nader HB, Giordano MG, Baracat EC, Soares Junior JM. The evaluation of endometrial sulfate glycosaminoglycans in women with polycystic ovary syndrome. Gynecol Endocrinol. 2015 Apr;31(4):278-81. doi: 10.3109/09513590.2014.989980. Epub 2014 Dec 1.

  PMID: 25434369 RESULT

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Progesterone Resistance

Interventions

Progesterone

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor and head of Discipline

Model Details: A prospective open-label clinical trial

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 30, 2021
• Study Start: February 10, 2014
• Primary Completion: September 10, 2014
• Study Completion: April 21, 2019
• Last Updated: January 20, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share