Clinical trial NCT00844311: Supplementation With Human Chorionic Gonadotropin (hCG) During Controlled Ovarian Stimulation With Recombinant Follicle-stimulating Hormone (FSH) for In Vitro Fertilisation
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Keywords: hCG
human chorionic gonadotropin
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2009-02-16
Enrollment: 60
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Females with indication for COS and IVF;
2. Age between 25-37 years;
3. BMI \>18 and \< 30 kg/m2;
4. A regular menstrual cycle between 24 and 35 days and presumed to be ovulatory;
5. Two ovaries;
6. Tubal or unexplained infertility, including endometriosis stage I/II;
7. A uterus consistent with expected normal function (e.g. no clinically interfering uterine fibroids) documented by transvaginal ultrasound at the screening;
8. Male partner with sperm quality compatible with fertilization via IVF procedure or previous clinical pregnancy;
9. Early follicular phase serum FSH levels of 1-12 IU/l;
10. Early follicular phase total antral follicle (2-10mm) count ≥ 6;
11. Confirmation of down-regulation before randomisation by transvaginal ultrasound;
12. Willing and able to sign informed consent.

Exclusion Criteria:

1. History of or current PCOS, endometriosis stage III/IV or severe male factor requiring ICSI;
2. History of severe ovarian hyperstimulation syndrome (OHSS);
3. Presence of unilateral or bilateral hydrosalpinx at ultrasound;
4. More than three previously COS cycles;
5. 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;
6. Previous IVF cycle with unsuccessful fertilization, defined as fertilisation of £20% of the retrieved oocytes;
7. History of recurrent miscarriage;
8. FSH\>12IU/L or LH\>12UI/L (early follicular phase);
9. Contraindications for the use of gonadotropins or GnRH analogues;
10. Recent history of current epilepsy, HIV infection, diabetes or cardiovascular gastrointestinal, hepatic, renal or pulmonary disease;
11. Pregnancy, lactation or contraindication to pregnancy;
12. Current past (last 12 months) abuse of alcohol or drugs;
13. History of chemotherapy (except for gestational conditions) of radiotherapy;
14. Undiagnosed vaginal bleeding;
15. Tumours of the ovary, breast, adrenal gland, pituitary or hypothalamus and malformation of sexual organs incompatible with pregnancy;
16. Abnormal karyotyping of the patient (if karyotyping is performed);
17. Hypersensitivity to any trial product.

Primary outcomes:
measure: Total number of top-quality embryos at day 3
Secondary outcomes:
measure: 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.
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: The Fertility Clinic, Rigshospitalet
Study officials:
References:
citation: Thuesen LL, Andersen AN, Loft A, Smitz J. Intrafollicular endocrine milieu after addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization. J Clin Endocrinol Metab. 2014 Feb;99(2):517-26. doi: 10.1210/jc.2013-1528. Epub 2013 Dec 2.
citation: Thuesen LL, Loft A, Egeberg AN, Smitz J, Petersen JH, Andersen AN. A randomized controlled dose-response pilot study of addition of hCG to recombinant FSH during controlled ovarian stimulation for in vitro fertilization. Hum Reprod. 2012 Oct;27(10):3074-84. doi: 10.1093/humrep/des256. Epub 2012 Jul 12.