Clinical trial: Efficacy of Corifollitropin Alfa Versus Follitropin Beta in Aged IVF (In-vitro Fertilization) Patients (NCT02466204)

Eligibility criteria:
Inclusion Criteria:

          -  Each subject must be willing and able to provide written informed consent for the
             study.

          -  Each subject must be female with years of age ≥35 to ≤42 at the time of recruitment..

          -  Each subject must have an indication for controlled ovarian stimulation and IVF

          -  Each subject must have a body weight ≥ 50.0 kg, with a body mass index (BMI) ≥18.0 to
             ≤32.0 kg/m2.

          -  Each subject must have a regular spontaneous menstrual cycle with an intra-individual
             variation not outside the 24 to 35 days range.

          -  For each subject, ejaculatory sperm must be available (use of donated and/or
             cryopreserved sperm is allowed; sperm obtained via surgical sperm retrieval is not
             allowed).

          -  Each subject must have results of clinical laboratory test (complete blood count,
             blood chemistries, and urinalysis) within normal limits or clinically acceptable to
             the investigator, as measured by the local laboratory at screening. A normal cervical
             smear result, obtained within 12 months, otherwise it must be obtained during
             screening.

          -  Each subject must have results of a physical examination, including blood pressure,
             within normal limits or clinically acceptable limits to the investigator.

          -  Each subject must have normal ovarian reserve, based on anti-Mullerian hormon (AMH) of
             1.38 - 3.25ng/ml or an antral follicle count (AFC) of 7-20, taken within 2 months
             prior to corifollitropin alfa start.

          -  Each subject must be able to adhere to dose and visit schedules and willing to
             disclose any medical events to the investigator.

        Exclusion Criteria:

          -  The subject has a recent (ie, within 3 years) history of/ or any current endocrine
             abnormality (irrespective whether the patient is stabilized on treatment).

          -  The subject has a history of ovarian hyper-response (ie, previous IVF cycle with more
             than 30 follicles ≥11 mm on ultrasound) or ovarian hyperstimulation syndrome (OHSS).

          -  The subject has a history of/or current polycystic ovary syndrome (PCOS)

          -  The subject has more 20 basal antral follicles <11 mm (both ovaries combined) as
             measured on ultrasound in the early follicle phase (menstrual cycle day 2-5).

          -  The subject has less than 2 ovaries in any other ovarian abnormality (including
             endometrioma > 10 mm; visible on ultrasound).

          -  The subject has unilateral or bilateral hydrosalpinx (visible on ultrasound, less
             clipped).

          -  The subject has any intra-uterine fibroids >5 cm or any clinically relevant pathology,
             which could impair embryo implantation or pregnancy continuation.

          -  The subject has more than three unsuccessful treatment cycles for IVF/ICSI.

          -  The subject has a history of non- or low avarian response to FSH / Human Menopausal
             Gonadotropin (hMG) treatment (ie, previous COS cycle cancelled due to insufficient
             ovarian response or ≤3 oocytes obtained).

          -  The subject has a history of current miscarriage (3 or more, even when explained).

          -  The subject has FSH > 15.0 IU/L or LH > 12 .0 IU/L as measured by the local laboratory
             (sample taken during the early follicle phase: menstrual cycle day 2 to 5).

          -  The subject has tested positive for human immunodeficiency virus (HIV) or Hepatitis B
             (results obtained within one year) .

          -  The subject has contra-indications for the use of gonadotropins (eg, tumors,
             pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, or ovarian cysts)
             or GnRH antagonist (eg, hypersensitivity, pregnancy/lactation).

          -  The subject has a concomitant use of either LH or hMG/urinary FSH preparations in
             study cycle.

          -  The subject has a recent history of/or current epilepsy, thrombophilia, diabetes,
             cardiovascular, gastro-intestinal, hepatic, renal or pulmonary or auto-immune disease
             requiring regular treatment.

          -  The subject or the sperm donor has known gene defects, genetic abnormalities, or
             abnormal karyotyping, relevant for the current indications or for the health of the
             offspring.

          -  The subject smokes or has recently stopped smoking (ie, within the last 3 months prior
             to signing ICF).

          -  The subject has a history or presence of alcohol or drug abuse within 12 months prior
             to signing informed consent.

          -  The subject has an allergy/ sensitivity to investigational drugs or their excipients.

          -  The subject has used any experimental drugs within 3 months prior to signing informed
             consent.

          -  The subject is participating in any other clinical study (excluding surveys).
Female
No healthy subjects accepted to join the trial.
Subject must be at least 35 Years old.
Subject must be at most 42 Years

Patient description (medical language): A 32-year-old woman comes to the hospital with vaginal spotting.  Her last menstrual period was 10 weeks ago. She has regular menses lasting for 6 days and repeating every 29 days. Medical history is significant for appendectomy and several complicated UTIs. She has multiple male partners, and she is inconsistent with using barrier contraceptives. Vital signs are normal.  Serum β-hCG level is 1800 mIU/mL, and a repeat level after 2 days shows an abnormal rise to 2100 mIU/mL.  Pelvic ultrasound reveals a thin endometrium with no gestational sac in the uterus.

Patient description (patient's own words): I just turned 32 and last morning I woke up with strange blood stains on my underwear. My last periods were more than 2 months ago, which is unusual for me because I used to have regular periods lasting for 6 days every 29 days, more or less. I had several UTIs in the past. I also had appendicitis. I'm currently seeing several men and, to be honest, some of them do struggle to wear a condom. I went to the hospital to check myself up and they told me that my vitals were normal. I also had a blood test on Monday, and my β-hCG level was 1800 mIU/mL, and then on Wednesday, it went up to 2100 mIU/mL. The gynecologist also did an ultrasound and she told me that, hopefully, there was no ovule.

Does the patient match the trial criteria? Contradiction