Comparison of MENOPUR Liquid and Powder in Women Undergoing Assisted Reproductive Technology (ART)

Ferring Pharmaceuticals405 enrolled

Overview

Development of multiple follicles and pregnancy in ovulatory women undergoing controlled ovarian stimulation as part of an assisted reproductive technology (ART) cycle.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

405

Conditions

Infertility

Interventions

MENOPUR solution for injection in pre-filled pen, 1200 IU/1.92 mLDRUG

Solution for injection in pre-filled pen, subcutaneous administration

MENOPUR powder and solvent for solution for injection, 75 IUDRUG

Solution for injection in vials (powder and diluent), subcutaneous administration

Placebo (for MENOPUR solution for injection in pre-filled pen)OTHER

Solution for injection in pre-filled pen, subcutaneous administration

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 42 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consents, prior to any trial-related procedure. * Females between the ages of 18 and 42 years. The participants must be at least 18 years (including the 18th birthday) when they sign the informed consent and no more than 42 years (up to the day before the 43rd birthday) at the time of randomization who desire pregnancy. * Body mass index (BMI) between 17.5 and 38.0 kg/m\^2 (both inclusive) at screening. * Regular menstrual cycles of 24 to 35 days, presumed to be ovulatory. * Documented history of infertility for at least 12 months before randomization for women ≤35 years or for at least 6 months for women ≥36 years. Women with documented bilateral tubal occlusion or male factor infertility requiring the use of donor sperm established as a cause of infertility are eligible at diagnosis. * Early follicular phase (cycle day 2-4) serum FSH level between 1 and 12 IU/L (results obtained within 3 months prior to randomization). * Male partner with semen analysis that is at least adequate for intracytoplasmic sperm injection (ICSI) at screening or within 6 months prior to the screening date. Partners with severe male factors requiring invasive or surgical sperm retrieval may not be used. Use of donor sperm is allowed. * At least 1 cycle with no fertility medication immediately prior to screening. * Hysterosalpingography, hysteroscopy, or saline hysterosonogram documenting uterine anatomy appropriate for ART at screening or within 12 months prior to screening. * Transvaginal ultrasound documenting presence and adequate visualization of both ovaries, without evidence of clinically significant abnormality (e.g., endometrioma ≥3 cm, no dermoid cysts) and normal adnexa (e.g., no hydrosalpinx) at screening. Both ovaries must be accessible for oocyte retrieval. Exclusion Criteria: * More than two previous controlled ovarian stimulation cycles for in vitro fertilization (IVF)/ICSI * Known stage III-IV endometriosis (American Society for Reproductive Medicine, 2012). * Oocyte donor or embryo recipient; gestational or surrogate carrier. * Known history of recurrent miscarriage (defined as three consecutive losses after ultrasound confirmation of pregnancy \[excluding ectopic pregnancy\] and before week 24 of pregnancy). * Participant's male partner, with obvious leukospermia (\>2 million white blood cells/mL) or signs of infection in semen sample within 6 months of the participant's screening. If either of these conditions exists, the male should be treated with antibiotics and retested prior to the participant's randomization. * Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events. * Any known endocrine (total testosterone, prolactin and TSH) or metabolic abnormalities (pituitary, adrenal, pancreas, liver or kidney) with the exception of controlled thyroid function disease. * Known tumors of the ovary, breast, uterus, adrenal gland, pituitary or hypothalamus which would contraindicate the use of gonadotrophins. * Any abnormal finding of clinical chemistry, hematology and vital signs at screening, which is judged clinically significant by the investigator. * Pregnancy (negative urine pregnancy test must be documented at screening and prior to the first investigational medicinal product \[IMP\] administration), or contraindication to pregnancy. * Hypersensitivity to any active ingredient or excipients in the medicinal products used in this trial.

Locations (20)

Fertility Treatment Center

Tempe, Arizona, United States

Outcomes

Primary Outcomes

Number of Fertilized (2 Pronuclei [2PN]) Oocytes

Fertilized oocytes with 2PN were regarded as correctly fertilized.

Time frame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)

Secondary Outcomes

Positive Beta Human Chorionic Gonadotropin (βhCG) Rate

A blood serum βhCG test was obtained 10-14 days after blastocyst transfer. If the test was positive according to the local laboratory's reference ranges, this confirmed a positive βhCG.

Time frame: 10-14 days after blastocyst transfer (up to approximately 6 weeks after start of stimulation)

Clinical Pregnancy Rate

Clinical pregnancy was based on detection of at least 1 intrauterine gestational sac with fetal heart beat on transvaginal ultrasound.

Time frame: 5-6 weeks after blastocyst transfer (up to approximately 10 weeks after start of stimulation)

Ongoing Pregnancy Rate

Ongoing pregnancy was based on detection of at least 1 intrauterine viable fetus by transvaginal or abdominal ultrasound

Time frame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)

Early Pregnancy Loss

Number of participants with early pregnancy loss defined as a positive βhCG tests but no ongoing pregnancy.

Time frame: 8-9 weeks after blastocyst transfer (up to approximately 13 weeks after start of stimulation)

Follicular Development on Stimulation Day 6

The total number of follicles and the number of follicles per size category were reported.

Time frame: At stimulation Day 6

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Solution for injection in vials (powder and diluent); subcutaneous administration

Fertility Specialists Medical Group - San Diego Center for Reproductive Surgery

San Diego, California, United States

Center for Advanced Reproductive Services PC

Farmington, Connecticut, United States

Yale Fertility Center

New Haven, Connecticut, United States

Fertility and IVF Center of Miami

Miami, Florida, United States

Center for Reproductive Medicine

Winter Park, Florida, United States

Idaho Center for Reproductive Medicine

Boise, Idaho, United States

Fertility Centers of Illinois

Chicago, Illinois, United States

InVia Fertility Specialists, SC

Hoffman Estates, Illinois, United States

Fertility Answers, LLC

Baton Rouge, Louisiana, United States

...and 10 more locations

Follicular Development on Last Day of Stimulation

The total number of follicles and the number of follicles per size category were reported.

Time frame: At last day of stimulation (up to 20 stimulation days)

Serum Follicle-stimulating Hormone (FSH) Concentration

The concentration of serum FSH was measured. The median and IQR of FSH levels on stimulation day 6, End of stimulation and Oocyte Retrieval visit are presented.

Time frame: At Day 6, last day of stimulation (up to 20 stimulation days) and at oocyte retrieval (up to 22 days after start of stimulation)

Serum Anti-Müllerian Hormone (AMH) Concentration

The concentration of serum AMH was measured. The median and IQR of AMH levels on End of stimulation and End of Trial are presented.

Time frame: At the last day of stimulation (up to 20 stimulation days) and at end-of-trial (up to approximately 6 months from the start of screening)

Human Chorionic Gonadotropin (hCG) Concentration

The concentration of hCG was measured. The median and IQR of hCG levels on stimulation day 6 and End of stimulation are presented.

Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)

Luteinizing Hormone (LH) Concentration

The concentration of LH was measured. The median and IQR of LH levels on stimulation day 6 and End of stimulation are presented.

Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)

Progesterone (P4) Concentration

The concentration of P4 was measured. The median and IQR of P4 levels on stimulation day 6 and End of stimulation are presented.

Time frame: At Day 6 and last day of stimulation (up to 20 stimulation days)

Estradiol (E2) Concentration

The concentration of E2 was measured. The median and IQR of E2 levels on stimulation day 6 and End of stimulation are presented.

Time frame: At stimulation Day 6 and last day of stimulation (up to 20 stimulation days)

Number of Oocytes Retrieved

The number of oocytes retrieved was recorded at the oocyte retrieval visit.

Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

Number of Metaphase II (MII) Oocytes

Maturity stage was assessed prior to undergoing ICSI. Maturity stage was categorized as germinal vesicle, metaphase I, metaphase II, degenerated or other.

Time frame: On day of oocyte retrieval (up to 22 days after start of stimulation)

Fertilization Rate

Fertilization rate(%) is the number of 2PN oocytes divided by the number of oocytes retrieved.

Time frame: On Day 1 after oocyte retrieval (up to 23 days after start of stimulation)

Number of Blastocysts and Number of Good-Quality Blastocysts 5 Days After Oocyte Retrieval

The number of blastocysts (total and good-quality) was reported. Blastocyst quality was assessed by blastocyst expansion and hatching status, blastocyst inner cell mass grading, and trophectoderm grading. The scoring was based on the classification system by Gardner and Schoolcraft, with additional categories for inner cell mass (degenerative or no inner cell mass) and trophectoderm (degenerative or very large cells)

Time frame: On Day 5 after oocyte retrieval (up to 27 days after start of stimulation)

Total Gonadotropin Dose

The gonadotropin starting dose was 225 IU for the first 5 days, followed by individual adjustments according to the participant's follicular response. Dose adjustment should be 75 IU per adjustment. Gonadotropin was to be initiated within 3 days of confirmed downregulation.

Time frame: Up to 20 stimulation days

Number of Stimulation Days

Calculated by start dates and end dates.

Time frame: Up to 20 stimulation days

Proportion of Participants With Ovarian Hyperstimulation Syndrome (OHSS)

OHSS was defined as the total of early OHSS with onset ≤9 days after triggering of final follicular maturation, and late OHSS with onset \>9 days after triggering of final follicular maturation.

Time frame: ≤9 days after triggering of final follicular maturation (early OHSS), >9 days after triggering of final follicular maturation until 21-28 days after last IMP dose or up to ongoing pregnancy 8-9 weeks after transfer in pregnant participants (late OHSS)

Frequency of Adverse Events (AEs)

Any AE occurring after start of IMP and before the end-of-trial visit, or a pre-treatment AE or pre-existing medical condition that worsens in intensity after start of IMP and before the end-of-trial visit was considered treatment-emergent, and is presented for this endpoint.

Time frame: From the time of signed informed consent for participation in the trial until the end-of-trial visit (up to approximately 6 months)

Intensity of AEs

The intensity of an AE was classified using the following 3-point scale: Mild = Awareness of signs or symptoms, but no disruption of usual activity. Moderate = Event sufficient to affect usual activity (disturbing). Severe = Inability to work or perform usual activities (unacceptable).