The goal of this project is to identify autocrine, paracrine and endocrine factors which are associated with intercycle variation in cyclical follicle recruitment. Patients will be monitored in a natural cycle, a stimulated cycle and a follow up. In the stimulated cycle patients will be randomized to co-treatment with aromatase inhibitor or placebo during ovarian stimulation.
The primary aim of this project is to explore the putative cyclic recruitment 'gatekeeping' functions of gonadotropins, sex steroids, anti-muellarian hormone and pregnancy associated plasma protein A in normal ovulatory cycles, and the impact of ovarian stimulation on cyclic follicle recruitment in the following cycle. It is further proposed that supra-physiological levels of estradiol and progesterone which arise from ovarian stimulation may modulate the size of the secondarily recruited follicle cohort in the next cycle. In order to explore the relative contribution of sex steroids as determinants of the size of the next cycle 'wave' of recruitment further, a second aim of this study will be investigate whether limiting the rise in sex steroid levels during ovarian stimulation, by co-treatment with aromatase inhibitor impacts on cyclic recruitment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
33
Unit of Reproductive Medicine, Herlev Hospital
Herlev, Capital Region, Denmark
Size of follicle cohort in relation to serum endocrine and paracrine markers
Markers for analysis include: anti-muellerian hormone, estradiol, follicle stimulating hormone, luteinizing hormone, testosterone, androstenedione, progesterone,17-hydroxyprogesterone, pregnancy associated plasma protein A and A2, Inhibin A and B, Bone morphogenic protein
Time frame: The change in size of follicle cohort in relation to change in endocrine and paracrine markers assessed throughout the study completion, up to 3 years.
Size of the cyclically recruited follicle cohort after ovarian stimulation with and without co-treatment with Aromatase Inhibitor.
Time frame: The change in size of follicle cohort throughout the study completion, up to 3 years.
Expression of cytokine and growth factors in endometrial secretions following co-treatment with Aromatase Inhibitor compared with placebo control.
Time frame: Assessed in stimulated cycle at time of embryo transfer (throughout study completion, up to 3 years).
Serum E2, P, Tst and Androstenedione levels
Time frame: The change in levels throughout the study completion, up to 3 years.
Area under the curve for P and 17-hydroxyprogesterone.
Time frame: The change in levels throughout the study completion, up to 3 years.
Total International Units of Follicle Stimulating Hormone used per treatment cycle.
Time frame: Assessed throughout study completion, up to 3 years.
Number of follicles > 12 mm
Time frame: Assessed throughout the study completion, up to 3 years.
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Number of oocytes obtained
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Proportion of oocytes resulting in top quality day 2, day 3 embryos or day 5/6 embryos according to validated morphological criteria.
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Oocyte fertilization rate
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Number and quality of embryos obtained.
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Endometrial thickness
Time frame: Assessed throughout the study completion, up to 3 years.
Uterine contraction rate (contractions/minute)
Time frame: Assessed throughout the study completion, up to 3 years.
Implantation rate
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Reported side effects
Time frame: From start of stimulation and administration of study medication to pregnancy scan week gestational age 7-8. Assessed throughout the study completion, up to 3 years.
Morphokinetic parameters of embryo quality as measured using a Time Lapse analysis.
Time frame: Assessed from time of oocyte pick-up to embryo transfer following stimulation (throughout study completion, up to 3 years)
Clinical pregnancy rate
Time frame: Pregnancy scan at gestational age week 7-8 (3-4 weeks after the positive hCG in serum) Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Follicular fluid endocrine and paracrine markers following co-treatment with Aromatase Inhibitor compared with placebo control.
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Biochemical pregnancy rate
Time frame: Assessed during stimulation treatment (throughout the study completion, up to 3 years).
Area under the curve for E2, P and LH
Time frame: The change in levels throughout the study completion, up to 3 years.