Heritability of Polycystic Ovary Syndrome: Role of Antimullerian Hormone, Steroids and Leptin
- Conditions
- Polycystic Ovary Syndrome
- Interventions
- Biological: Plasma dosageGenetic: placental biopsy
- Registration Number
- NCT03483792
- Lead Sponsor
- University Hospital, Lille
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- Female
- Target Recruitment
- 58
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Having a pre-conceptional infertility assessment in the gynecology-Endocrinology department of University Hospital of Lille
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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)
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Pregnancy followed at University Hospital of Lille
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PCOS group: defined according to modified Rotterdam criteria (2003 and 2011)
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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
-
After exclusion of other causes of cycle disorder or hyperandrogenism
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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.
- 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
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description PCOS group placental biopsy - Control group Plasma dosage - Control group placental biopsy - PCOS group Plasma dosage -
- Primary Outcome Measures
Name Time Method Rate of plasma AMH in the 3rd trimester of pregnancy between 29 and 44 amenorrhea weeks
- Secondary Outcome Measures
Name Time Method 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 rate of leptin (only dosage in fasting patients) between 5 and 15 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 level of expression of aromatase, AMH and AMH Receptor II in the placenta at delivery
Trial Locations
- Locations (1)
Hôpital Jeanne de Flandres, CHU
🇫🇷Lille, France