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ID
Source
Brief title
Health condition
BRCA1/2, ovarian reserve (AFC, AMH, ovarian response), ongoing pregnancy BRCA1/2, ovariele reserve (AFC, AMH, ovariele response), doorgaande zwangerschap
Sponsors and support
Intervention
Outcome measures
Primary outcome
Serum AMH level
Secondary outcome
- AFC
- Amount of poor response (less than 4 oocytes at retrieval or cancellation due to insufficient follicle growths, i.e. < 4 dominant follicles sized ¡Ý14 mm growing)
- Number of retrieved oocytes (total amount and MII) after first cycle COH
- Ongoing and clinical pregnancy rate
Background summary
Rationale:
The study proposal aims to confirm the observation of a reduced quantity of the follicle pool in BRCA (Breast Cancer) mutation-positive women. If confirmed, advanced ovarian ageing in BRCA mutated women will have a major impact on their general health and fertility prospects. Furthermore, identification of genes that contribute to the endowment and wastage of follicles in the ovaries and thus timing of menopause will add to the understanding of the physiological mechanism of the ovarian ageing process.
In the current study we will be able to study the effect of BRCA mutations on the ovarian ageing process, by comparing serum anti-Müllerian hormone (AMH) levels between cohorts of BRCA mutation-positive women and normal controls, applying for in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD).
The main hypothesis is that normo-ovulatory women with a deleterious BRCA mutation have lower levels of AMH compared to normal controls, with at least a difference of 0.90 ng/ml, suggesting an effect size of approximately five years in menopausal age.
Objective:
To demonstrate the presence of a reduced age specific ovarian reserve status in BRCA mutation carriers by:
1.using serum AMH as ovarian reserve test
2.using the antral follicle count (AFC) as ovarian reserve test
3.using ovarian response to ovarian hyperstimulation for IVF as proxy variable of ovarian reserve status
Study design: The study is designed as an observational prospective cohort study in exposed and non-exposed women during their first IVF with ICSI and PGD treatment cycle
Study population: Couples, with normo-ovulatory women between 18 and 41 years old, applying for their first IVF with ICSI and PGD treatment cycle in view of their status as carrier of a female BRCA mutation will be asked to participate. Normo-ovulatory women between 18 and 41 years old, who visit the department of Reproductive Medicine for their first IVF, with ICSI and PGD treatment cycle unsuspected for reduced ovarian reserve, are asked to participate as control group.
Main study endpoints: The main study endpoint will be advanced ovarian ageing measured by serum AMH levels.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The nature and extent of the burden and risks associated with participation can be stated as negligible. Participating is not associated with (medical) benefits.
Study objective
The main hypothesis is that normo-ovulatory women with a deleterious BRCA mutation have lower levels of AMH compared to normal controls, with at least a difference of 0.90 ng/ml, suggesting an effect size of approximately five years in menopausal age.
Study design
The aim is to investigate a total of 34 BRCA mutation positive women and 91 controls in a period of approximately 4 years. Data analysis and publishing results will take ½ year, resulting in a total study duration of approximately 5 years.
Intervention
blood sample
F.J. Broekmans
UMC Utrecht
Utrecht 3584 CX
The Netherlands
+31 (0)88 7551041
f.broekmans@umcutrecht.nl
F.J. Broekmans
UMC Utrecht
Utrecht 3584 CX
The Netherlands
+31 (0)88 7551041
f.broekmans@umcutrecht.nl
Inclusion criteria
Case group (BRCA mutation carriers)
- Female age > 18 years and < 40 years
- Regular menstrual cycles (i.e. mean cycle length of 21-35 days)
- First IVF with ICSI and PGD treatment cycle due to a female pathogenic BRCA mutation
- Written informed consent
Controle group (non suspected for BRCA mutation):
- Female age > 18 years and < 40 years
- Regular menstrual cycles (i.e. mean cycle length of 21-35 days)
- First IVF with ICSI and PGD treatment cycle due to an indication unsuspected for reduced ovarian reserve status
- Written informed consent
Exclusion criteria
Case group (BRCA mutation carriers)
- Ovarian surgery
- Chemo therapy
- Radiation therapy to the pelvis, lower abdomen or total body radiation
- Known female endocrine or autoimmune abnormalities (i.e. Cushing syndrome, type I Diabetes Mellitus, hypothyroidism, hyperprolactinemia, adrenal insufficiency, hypoparathyriodism, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)
- Body Mass Index > 35 kg/m2
- Polycystic Ovarian Syndrome (Rotterdam criteria)
- Early follicular FSH > 15 IU/L
- Known Human immunodeficiency virus (HIV) infection
- Known female genetic abnormalities suspected for subfertility (structural or numerical abnormalities of the X-chromosome (i.e. Turner¡¯s syndrome, fragile X syndrome), or abnormalities of human autosomal functionally relevant genes, other than a BRCA mutation, suspected for subfertility
Controle group (non suspected for BRCA mutation):
- Ovarian surgery
- Chemo therapy
- Radiation therapy to the pelvis, lower abdomen or total body radiation
- Known female endocrine or autoimmune abnormalities (i.e. Cushing syndrome, type I Diabetes Mellitus, hypothyroidism, hyperprolactinemia, adrenal insufficiency, hypoparathyriodism, myasthenia gravis, rheumatoid arthritis, systemic lupus erythematosus)
- Body Mass Index > 35 kg/m2
- Polycystic Ovarian Syndrome (Rotterdam criteria)
- Early follicular FSH > 15 IU/L
- Known HIV infection
- Known genetic abnormalities, suspected for subfertility (structural or numerical abnormalities of the X-chromosome (i.e. Turner¡¯s syndrome, fragile X syndrome), or abnormalities of human autosomal functionally relevant genes suspected for subfertility
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| NTR-new | NL4347 |
| NTR-old | NTR4703 |
| Other | UMC Utrecht : 14-175 |