Supplementation With Human Chorionic Gonadotropin (hCG) During Controlled Ovarian Stimulation With Recombinant Follicle-stimulating Hormone (FSH) for In Vitro Fertilisation

Study Overview
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Brief Summary
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The purpose of this trial is to study whether addition of different doses of human chorionic gonadotropins during controlled ovarian stimulation for patients undergoing IVF will improve the number of top-quality embryos.

Official Title
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Supplementation With hCG During Controlled Ovarian Stimulation With Recombinant FSH for in Vitro Fertilisation. A Randomized Controlled Clinical Study. Clinical, Embryological, Endocrine and Genetic Aspects.

Conditions
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Infertility

Intervention / Treatment
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* Drug: rFSH
* Drug: human chorionic gonadotropin
* Drug: human chorionic gonadotropin
* Drug: human chorionic gonadotropin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females with indication for COS and IVF; Age between 25-37 years; BMI >18 and < 30 kg/m2; A regular menstrual cycle between 24 and 35 days and presumed to be ovulatory; Two ovaries; Tubal or unexplained infertility, including endometriosis stage I/II; A uterus consistent with expected normal function (e.g. no clinically interfering uterine fibroids) documented by transvaginal ultrasound at the screening; Male partner with sperm quality compatible with fertilization via IVF procedure or previous clinical pregnancy; Early follicular phase serum FSH levels of 1-12 IU/l; Early follicular phase total antral follicle (2-10mm) count ≥ 6; Confirmation of down-regulation before randomisation by transvaginal ultrasound; Willing and able to sign informed consent. Exclusion Criteria: History of or current PCOS, endometriosis stage III/IV or severe male factor requiring ICSI; History of severe ovarian hyperstimulation syndrome (OHSS); Presence of unilateral or bilateral hydrosalpinx at ultrasound; More than three previously COS cycles; Previous poor response on an IVF-cycle, defined as >20 days of gonadotrophin stimulation, cancellation due to limited follicular response or less than four follicles of ³15 mm diameter; Previous IVF cycle with unsuccessful fertilization, defined as fertilisation of £20% of the retrieved oocytes; History of recurrent miscarriage; FSH>12IU/L or LH>12UI/L (early follicular phase); Contraindications for the use of gonadotropins or GnRH analogues; Recent history of current epilepsy, HIV infection, diabetes or cardiovascular gastrointestinal, hepatic, renal or pulmonary disease; Pregnancy, lactation or contraindication to pregnancy; Current past (last 12 months) abuse of alcohol or drugs; History of chemotherapy (except for gestational conditions) of radiotherapy; Undiagnosed vaginal bleeding; Tumours of the ovary, breast, adrenal gland, pituitary or hypothalamus and malformation of sexual organs incompatible with pregnancy; Abnormal karyotyping of the patient (if karyotyping is performed); Hypersensitivity to any trial product.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control arm<br>150 iu/day of rFSH alone | Drug: rFSH<br>* 150 iu/day of rFSH<br>|
| Experimental: hCG low dose<br>150 iu/day of rFSH + 50 iu/day of hCG from stimulation day 1 | Drug: rFSH<br>* 150 iu/day of rFSH<br>Drug: human chorionic gonadotropin<br>* 50 iu/day of hCG from stimulation day 1<br>|
| Experimental: hCG medium dose<br>150 iu/day of rFSH + 100 iu/day of hCG from stimulation day 1 | Drug: rFSH<br>* 150 iu/day of rFSH<br>Drug: human chorionic gonadotropin<br>* 100 iu/day of hCG from stimulation day 1<br>|
| Experimental: hCG high dose<br>150 iu/day of rFSH + 150 iu/day of hCG from stimulation day 1 | Drug: rFSH<br>* 150 iu/day of rFSH<br>Drug: human chorionic gonadotropin<br>* 150 iu/day of hCG from stimulation day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total number of top-quality embryos at day 3 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate; Dose of rFSH needed; Serum levels of endocrine parameters; Ongoing pregnancy; Follicular fluid levels of endocrine parameters and cytokines; Expressions of gene families in granulosa cells and the cumulus complex. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hCG, human chorionic gonadotropin