Levonorgestrel Contraceptive Intrauterine Systems (LCS) Pearl Index Study

• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 1 [ Time Frame: Day 1 to Day 90 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 2 [ Time Frame: Day 91 to Day 180 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 3 [ Time Frame: Day 181 to Day 270 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 4 [ Time Frame: Day 271 to Day 360 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 90-day Reference Periods - Reference Period 12 [ Time Frame: Day 991 to Day 1080 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 1 [ Time Frame: Day 1 to Day 30 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 2 [ Time Frame: Day 31 to Day 60 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 3 [ Time Frame: Day 61 to Day 90 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 4 [ Time Frame: Day 91 to Day 120 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Bleeding Patterns in Days by 30-day Reference Periods - Reference Period 12 [ Time Frame: Day 331 to Day 360 ] [ Designated as safety issue: No ]
  The occurrence of genital bleeding was to be recorded by study subjects every day in a diary. Bleeding was to be recorded as light, normal or heavy, no bleeding, or spotting only. Spotting was defined as slight genital bleeding relative to the participant's experience.
• Number of Participants With/Without Ovulation - Year 1 [ Time Frame: For six weeks in the second half of Year 1 ] [ Designated as safety issue: No ]
  Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
• Number of Participants With/Without Ovulation - Year 2 [ Time Frame: For six weeks in the second half of Year 2 ] [ Designated as safety issue: No ]
  Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
• Number of Participants With/Without Ovulation - Year 3 [ Time Frame: For six weeks in the second half of Year 3 ] [ Designated as safety issue: No ]
  Serum concentrations of progesterone were analyzed. All subjects with progesterone values equal to or greater than 2.5 ng/ml were assessed as having an ovulation.
• Average Total Cervical Score - Year 1 [ Time Frame: For six weeks in the second half of Year 1 ] [ Designated as safety issue: No ]
  Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
• Average Total Cervical Score - Year 2 [ Time Frame: For six weeks in the second half of Year 2 ] [ Designated as safety issue: No ]

  Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus.

  Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)

• Average Total Cervical Score - Year 3 [ Time Frame: For six weeks in the second half of Year 3 ] [ Designated as safety issue: No ]
  Cervical mucus samples were analyzed to determine any effects of progesterone on the cervical mucus. Range of score: 0 (high contraceptive efficacy) to 12 (low contraceptive efficacy)
• Classification of Endometrium - Year 1 [ Time Frame: At Year 1 ] [ Designated as safety issue: No ]
  The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
• Classification of Endometrium - Year 2 [ Time Frame: At Year 2 ] [ Designated as safety issue: No ]
  The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
• Classification of Endometrium - Year 3 / End of Study [ Time Frame: At Year 3 / End of study ] [ Designated as safety issue: No ]
  The histological evaluation of the endometrium examined the effects of progesterone on the endometrium
• Degree of User Overall Satisfaction With Study Treatment [ Time Frame: At the end of study/Year 3 ] [ Designated as safety issue: No ]
  Overall user satisfaction was assessed by a questionnaire given to participants at the end of the study. The questionnaire was only given to participants whose end-of-study visit occurred after implementation of Protocol Amendment 3.
• Number of Participants With Partial or Total Expulsion [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  If LCS was displaced, but still in the cervical canal, it was assessed as being partially displaced. If LCS was expelled from the uterus, it was assessed as a total expulsion.

This is a study on a new low dose levonorgestrel contraceptive intrauterine systems (LCS). The purpose of the study is to investigate which of the 2 administered doses is the lowest effective intrauterine dose of Levonorgestrel (LNG) administered via the LCS for contraception during 3 years. The study was amended: the LCS16 arm will be extended up to 5 years

Drop out-rate will be covered in Participant flow section.

• Drug: LCS12
  Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 12 microg/24 h
• Drug: LCS16
  Intrauterine system (IUS) with Levonorgestrel, in vitro releasing rate 16 microg/24 h

• Experimental: LCS12
  Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 12 microg/24 h in vitro
  Intervention: Drug: LCS12
• Experimental: LCS16
  Intrauterine levonorgestrel contraceptive system (LCS), releasing levonorgestrel (LNG) 16 microg/24 h in vitro
  Intervention: Drug: LCS16

Inclusion Criteria:

• Age between 18 and 35 years (inclusive), in good general health and requesting contraception.
• Has regular menstrual cycles (length of cycle 21-35 days) (i.e., endogenous cyclicity without hormonal contraceptive use).

Exclusion Criteria:

• Known or suspected pregnancy or is lactating.
• History of ectopic pregnancies.
• Any genital infection (until successfully treated).
• Abnormal uterine bleeding of unknown origin.