Recombinant Follicle Stimulating Hormone (FSH) (Gonal-f®): Use in Ovulation Induction

• Status: Completed
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: Female

Summary

This is an open-label, prospective, randomized, controlled, multicentric, multinational, phase IV study to evaluate the use of Gonal-f in inducing ovulation in female subjects with chronic anovulation. It has been observed that conventional high dose set up regimen of gonadotropin and human chorionic gonadotropin (hCG) is effective in anovulatory subjects in terms of overall pregnancy rates. However, development of multiple follicles leading to multiple pregnancy and/or ovarian hyperstimulation syndrome (OHSS) is the major complications associated with this high dose set up. Chronic low-dose (CLD) protocols of follicle stimulating hormone (FSH), aimed at finding the threshold amount of FSH necessary to promote monofolliculogenesis, have been found to be successful in reducing the rate of OHSS almost to nil and the rate of multiple pregnancies to a minimum. This post-marketing study will investigate tailoring of recombinant follicle stimulating hormone (r-FSH) in a large population (N=310) of subjects from a region (North Africa/Middle East) that has not been included in previous studies of ovulation induction in subjects with chronic anovulation. The study aims to increase current knowledge of the efficacy and safety of Gonal-f, and provide fertility physicians with experience in Gonal-f treatment in anovulatory infertility, thereby contributing to the development of FSH dosing guidelines for ovulation induction by defining the optimal CLD and Low dose (LD) regimens.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck KGaA; Merck KGaA, Darmstadt, Germany
• Collaborator: Merck Serono Middle East FZ-LLC, United Arab Emirates, an affiliate of Merck KGaA, Darmstadt, Germany
• Treatments: Follicle Stimulating Hormone

Criteria

Inclusion Criteria:

• Premenopausal female subjects, aged between 18 and 37 years inclusive

• Subjects willing to conceive

• Subjects who are infertile due to chronic anovulation demonstrated by a cycle duration of > 35 days, or regular cycles with progesterone (P4) levels < 1 nanomole/milliliter (nmol/mL) during luteal phase (Day 25)

• Subjects who have experienced spontaneous menses, menses induced by clomiphene citrate therapy, or a positive progestin-induced withdrawal within the previous year

• Subjects with FSH and PRL serum values within the normal range in the early follicular phase

• Subjects with total antral follicle count (AFC) > 10 (of follicle size ≥ 2 mm and < 11 mm) in both ovaries

• Subjects with at least 1 patent tube, as documented by recent (within 2 years before treatment assignment) hysterosalpingography (HSG)

• Subjects with normal uterine cavity, as documented by recent (within 2 years before treatment assignment) hysteroscopy, HSG or ultrasound scan

• Subjects with body mass index (BMI) >20 and ≤32 kilogram square per meter (kg/m^2)

• Subjects with negative cervical Papanicolaou (PAP) test within the 6 months prior to screening

• Male partners of female subjects with sperm compatible with non assisted fertilization

• Subjects who are willing and able to participate in the study and have provided written, informed consent

Exclusion Criteria:

• Subjects with history of hypersensitivity to the active substance follitropin alpha, FSH, or to any of the excipients of Gonal-f

• Subjects with ovarian enlargement or ovarian cyst unrelated to PCOS, and of unknown origin on ultrasound

• Subjects with evidence of diminished ovarian reserve (cycle length < 26 days; FSH above the upper limit of local serum FSH values, total AFC in both ovaries < 10)

• Subjects with myomatous uterus, which in the opinion of the investigator could impair pregnancy evolution

• Subjects who have undergone 3 or more previous miscarriages

• Subjects with any previous extrauterine pregnancy

• Pregnant or lactating female subjects

• Subjects with abnormal gynecological bleeding of unknown etiology

• Subjects with previous history of severe OHSS

• Subjects who have undergone operative pelvic surgery which could induce mechanical infertility (e.g tubes blockage) or pelvic inflammatory disease (PID) before treatment assignment excluding curettage and hysteroscopy

• Subjects with tumors of the hypothalamus and pituitary gland

• Subjects with ovarian, uterine or mammary carcinoma

• Subjects treated with clomiphene citrate or gonadotropins within 1 month of the screening evaluation

• Subjects with any medical condition which, in the opinion of the investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy

• Subjects with any medical condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the drug

• Subjects with any clinically significant systemic disease (e.g. insulin-dependent diabetes) or any contraindication to being pregnant and/or carrying a pregnancy to term; also including subjects with non insulin dependent diabetes mellitus (NIDDM)

• An active substance abuser

• Subjects with known infection with Human Immunodeficiency Virus (HIV), Hepatitis B or C virus in the trial subject or her male partner

• Subjects who have simultaneously participated in another clinical trial