Effect of Different Ovarian Stimulation Protocols on Endometrial Receptivity
Infertility, Female, Endometrial Diseases
About this trial
This is an interventional diagnostic trial for Infertility, Female focused on measuring Endometrial receptivity, Ovarian stimulation
Eligibility Criteria
Inclusion Criteria:
- Informed consent form (ICF) dated and signed.
- Age: ≥18 and <40 years old.
- AFC ≥5 and <20.
- AMH ≥1.1 ng/mL and <2.5 ng/mL, performed in the 12 months prior to inclusion.
- Body Mass Index (BMI): ≥18.5 Kg/m2 and <30 Kg/m2.
- Weight: ≥50 kg and <80 kg.
- First or second ART cycle or fertility preservation cycle.
- Regular menstrual cycles (between 22 and 35 days).
- Two ovaries present.
- Pregnancy-wish.
- Planned for single blastocyst transfer.
Exclusion Criteria:
- Simultaneous participation in another clinical study.
- Previous history of poor ovarian response (<4 oocytes retrieved) with a maximal dose of OS (≥300 IU/day) or OHSS, regardless of gonadotropin dose.
- Known reasons for impaired implantation (i.e. hydrosalpinx, fibroid distorting the endometrial cavity, Asherman's syndrome, thrombophilia or endometrial tuberculosis).
- Repeated miscarriages (>2 previous biochemical pregnancies or >2 spontaneous miscarriages).
- Recurrent implantation failure (>3 failed cycles with good quality embryos).
- Polycystic ovary syndrome (PCOS).
- Tumours of the ovary, breast, uterus, pituitary or hypothalamus.
- Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
- Ovarian cysts or enlarged ovaries.
- Fibroid tumours of the uterus incompatible with pregnancy.
- Malformations of the reproductive organs incompatible with pregnancy.
- Primary gonadal failure.
- Renal impairment defined as estimated glomerular filtration rate of 90 ml/min/1.73 m2 determined by the Modified Diet and Renal Disease (MDRD) equation at screening.
- Previous antibiotic hypersensitivity reactions (streptomycin and/or neomycin).
- Risk factors for thromboembolic events, such as a personal or family history, severe obesity or thrombophilia.
- Moderate or severe hepatic impairment.
- Untreated and uncontrolled thyroid dysfunction.
- Current use of oral contraceptive, anti-depressants, anti-psychotics, steroids, anti-epileptics or chemotherapy.
- Administration of exogenous Estradiol (E2), Progesterone (P4) or gonadotropins in the preceding menstrual cycle.
- Active female smoking.
- Acceptors of donated oocytes/embryos.
- Ongoing pregnancy.
- Women who have previously enrolled in the trial.
- Those unable to comprehend the investigational nature of the proposed study.
Sites / Locations
- Instituto Valenciano de Infertilidade
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Active Comparator
CFA plus step-down rFSH (1A)
CFA plus fixed daily dose rFSH (1B)
Fixed daily dose rFSH only
A single dose of 150 IU of CFA followed by daily rFSH will be administered. The initial rFSH administration will be dosed between 100 IU and 200 IU according to the following criteria: 200 or 300 IU: <3 follicles above 13 mm visible on transvaginal ultrasound; 150 IU, >2 follicles above 13 mm and circulating day-8 follicle-stimulating hormone (FSH) levels ≤20 IU/mL. 100 IU, >2 follicles above 13 mm and circulating day-8 FSH levels >20 IU/mL; Subjects will perform a step-down daily rFSH dose (fixed decreases in the dosing of 25 IU/day) until the triggering criteria are met or a minimum of 50 IU/day is reached. Subjects with <3 follicles above 13 mm visible will maintain 200 IU/day of rFSH until this criterion is met, initiating a fixed 25 IU/day stepdown protocol only from then onwards.
A single dose of 150 IU of CFA followed by a fixed daily rFSH dosing protocol of 200 or 300 IU will be administered as ovarian stimulation
A fixed daily rFSH dosing protocol of 200 or 300 IU will be administered as ovarian stimulation