Heritability of Polycystic Ovary Syndrome: Role of Antimullerian Hormone, Steroids and Leptin

NCT03483792 | Completed DMC

• 2 other identifiers: 2017_112017-A02628-45
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Polycystic ovary syndrome (PCOS) is the most common cause of ovulation disorders and affects 10 to 15% of women. Despite its frequency, its physiopathology remains unknown. In women, Anti-Müllerian hormone (AMH) is secreted by granulosa cells located in the ovaries within the follicles. Compared to control women, serum AMH level is higher in PCOS women and could play a role in its pathophysiology. The severity of the PCOS phenotype is correlated with the production of AMH. It is currently described in the literature that daughters of women with PCOS have a 50% risk of developing PCOS, but no genetic cause of transmission is known. In mice (article in press), pregnant females injected with AMH give birth to offspring with PCOS symptoms. The AMH could thus also play a role in the heritability of PCOS in women. Our team demonstrated that AMH, in its active cleaved form, had a direct central action on the hypothalamus by increasing the pulsatility of GnRH, inducing LH hypersecretion. The hypothesis is that AMH remains higher in pregnant women with PCOS and may affect the fetus by altering fetal and maternal hypothalamic secretions or by modifying placental steroid production. Leptin has a role in reproduction, through its receptors located at the central (hypothalamus) and peripheral (granulosa cells) levels. In excessively high serum concentration, as observed in obesity, it would lead to a dysregulation of GnRH secretion, an alteration of ovarian steroidogenesis and a dysregulation of folliculogenesis. Will be compare leptin levels in first trimester patients with and without PCOS to look for possible correlations between AMH and leptin and eliminate possible bias.

Conditions

Polycystic Ovary Syndrome

Keywords

PCOS; AMH; Pregnancy; Heritability; LH

Outcome Measures

Primary Outcomes (1)

• Rate of plasma AMH in the 3rd trimester of pregnancy

  between 29 and 44 amenorrhea weeks

Secondary Outcomes (5)

• The variation of maternal plasma AMH

  At baseline, between 5 and 15 amenorrhea weeks, between 15+1 day and 28+ 6 days amenorrhea weeks, between 29 and 44 amenorrhea weeks

• The percentage change in the different forms of AMH (pro-AMH and cleaved forms)

  At baseline, between 5 and 15 amenorrhea weeks, between 15+1 day and 28+ 6 days amenorrhea weeks, between 29 and 44 amenorrhea weeks

• The variation in oestradiol, testosterone and LH levels

  At baseline, between 5 and 15 amenorrhea weeks, between 15+1 day and 28+ 6 days amenorrhea weeks, between 29 and 44 amenorrhea weeks

• The rate of leptin (only dosage in fasting patients)

  between 5 and 15 amenorrhea weeks

• The level of expression of aromatase, AMH and AMH Receptor II in the placenta

  at delivery

Study Arms (2)

PCOS group

Biological: Plasma dosage; Genetic: placental biopsy

Control group

Biological: Plasma dosage; Genetic: placental biopsy

Interventions

Plasma dosage BIOLOGICAL

4 x 7 ml of blood punction at each control visit of the three trimesters of pregnancy

Control group; PCOS group

placental biopsy GENETIC

Immediately following delivery (\<12h postpartum), placental biopsies (Collection of 4 placental fragments)

Control group; PCOS group

Eligibility Criteria

• Age: 18 Years - 43 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients having a pre-conceptionnal infertility assessment in the gynecology-Endocrinology department of the CHRU of Lille, in the first trimester of monofetal pregnancy (between 5 and 10 weeks of gestation), obtained spontaneously, after induction of ovulation or Assisted Reproductive Techniques (ART)

You may qualify if:

• Having a pre-conceptional infertility assessment in the gynecology-Endocrinology department of University Hospital of Lille
• in the first trimester of mono fetal pregnancy (between 5 and 10 weeks of gestation), obtained spontaneously, after induction of ovulation or Assisted Reproductive Techniques (ART)
• Pregnancy followed at University Hospital of Lille
• PCOS group: defined according to modified Rotterdam criteria (2003 and 2011)
• At least 2 of the following 3 criterion:
• Cycle disorder
• Clinical and / or biological hyperandrogenism
• Ovarian volume \> 10cm³ and/or more than 19 follicles from 2 to 9 mm per ovary
• Control group: patient with severe male and / or tubal infertility, no cycling disorder, normal ovarian reserve (FSH\<10 IU / L, E2\<50 pg / ml, AMH\>7 and \<35 pmol / L and Follicles count between \>5 and \<20 per ovary at day 3 of the cycle).
• In the group of female controls, the fertility problem is not related to a female pathology of the hypothalamic-pituitary-ovarian axis (tubal or male infertility). They are women without ovarian personal pathology. The problem of fertility being of other origin.

You may not qualify if:

• Multiple pregnancy
• Pregnancy after egg donation
• Long-term drug therapy (excluding routine pregnancy supplementation)
• Previous Diabetes
• Bariatric surgery
• Patients with ovulatory infertility of central or idiopathic origin
• Patients already included in another protocol

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Hôpital Jeanne de Flandres, CHU

Lille, France

Location

Related Publications (1)

• Peigne M, Simon V, Pigny P, Mimouni NEH, Martin C, Dewailly D, Catteau-Jonard S, Giacobini P. Changes in circulating forms of anti-Muullerian hormone and androgens in women with and without PCOS: a systematic longitudinal study throughout pregnancy. Hum Reprod. 2023 May 2;38(5):938-950. doi: 10.1093/humrep/dead050.

  PMID: 36921289 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

plasma placenta fragment

MeSH Terms

Conditions

Polycystic Ovary Syndrome

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

Study Officials

• Sophie Catteau-Jonard, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2018
• First Posted: March 30, 2018
• Study Start: April 20, 2018
• Primary Completion: June 2, 2022
• Study Completion: June 2, 2022
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

FR (1)