Progesterone Serum Levels in Subfertile Female Patients Undergoing in Vitro Fertilisation (IVF)

Phase 4

Completed

Conditions: Infertility

Interventions: Drug: Menotrophin
Drug: Follitrophin alpha
Drug: Cetrorelix
Drug: Choriongonadotropin
Drug: Progesterone

Registration Number: NCT01225835

Lead Sponsor: Ferring Pharmaceuticals

Brief Summary: This study is aimed to demonstrate that highly purified Menotrophin produces significant lower progesterone serum levels during the follicular phase in comparison to Follitropin alpha in the treatment of subfertile females undergoing an in vitro fertilisation (IVF) and to investigate if the progesterone serum levels might be a useful predictor for the success rate of the ongoing pregnancy rates

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 124

Inclusion Criteria

Signed informed consent
Subfertile premenopausal female patients eligible for in vitro fertilisation (IVF) treatment
Aged ≥34 and ≤42 years
Body mass index of >18 and <28 kg/m^2
Normal pelvic ultrasound at Screening
No more than two previous gonadotrophin stimulated cycles of IVF or intracytoplasmic sperm injection (ICSI) in the history of infertility treatment (gonadotrophin stimulated cycles not used for IVF or ICSI do not count; Clomifen cycles are no exclusion criterion)
At least 3 consecutive ovulatory menstrual cycles of 24-35 days
No fertility stimulating drugs at all
Sperm of partner classified as normal according to World Health Organisation (WHO) 2010 criteria
Clinically normal baseline haematology, clinical chemistry, and urinalysis values
Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within the last 6 months prior to Screening
Endocrine test results within the clinically normal limits at Screening

Exclusion Criteria

Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus)
A history of or current endocrine disease (excluding treated hypothyreosis), including polycystic ovary syndrome (PCOS) and hyperprolactinaemia
A history of coagulation disorders
Persistent ovarian cysts (>3 months)
A history of hypersensitivity to any of the constituents of the study medication or related compounds
Diagnosed poor (<3 oocytes) responders to prior gonadotrophin stimulated ART-cycle
History of severe ovarian hyperstimulation syndrome in former gonadotrophin stimulated assisted reproductive technology (ART)-cycle

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Menotrophin	Choriongonadotropin	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin Alpha	Choriongonadotropin	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Menotrophin	Menotrophin	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Menotrophin	Cetrorelix	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Menotrophin	Progesterone	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin Alpha	Follitrophin alpha	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin Alpha	Cetrorelix	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.
Follitrophin Alpha	Progesterone	Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms.

Primary Outcome Measures

Name	Time	Method
Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration	approximately day 10	Ovulation induction was performed by administration of hCG once three follicles \>=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (\<39 years and \>=39 years).

Secondary Outcome Measures

Name	Time	Method
Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration	Day 7, approximately Day 10 (hCG Administration)	The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect.
Number of Follicles at hCG Administration	approximately day 10	Number of follicles \>=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.
Percentage of Participants With Ongoing Pregnancy	approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)	Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.
Average Follicle Diameter at hCG Administration	approximately day 10
Number of Cumulus-oocyte Complexes Retrieved	approximately day 12 after study start	Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.
Number of Pronuclear Oocytes	approximately day 13 after study start	Pronuclear oocytes are fertilized oocytes.
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade	approximately day 13	The count of participants with different quality grades of pronuclear stage oocytes is offered. Pronuclear stage oocytes are categorized into seven grades (0A, 0B, 1-5) representing different patterns of pronuclear morphology, according to the German Pronuclear Morphology Study Group. 0A is the highest quality oocyte and grade 5 is the lowest quality. Participants can have pronuclear stage oocytes of different grades and therefore are counted more than once.
Number of Embryos Transferred	approximately day 14	Mean number of embryos transferred 2-3 days following oocyte retrieval.
Best Quality of an Embryo Transferred	approximately day 14	Embryo quality was measured by the following grades: * Grade 1: Evenly sized cells, regular cleavage, no fragmentation * Grade 2: Regular or slightly irregular cleavage, \<=20% fragmentation * Grade 2.5: Regular or slightly irregular cleavage, \>20%and \<=50% fragmentation * Grade 3: Irregular cleavage, \>50% fragmentation, \>1 intact cell * Grade 4: Extensive fragmentation, only 1 cell intact * Grade 5: Totally fragmented, no viable cells. Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable.
Number of Frozen Oocytes at Pronuclear Stage	approximately day 14	No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.
Endometrial Thickness on Day of hCG Administration	approximately day 10	Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.
Estradiol (E2) Levels on Day of hCG Administration	approximately day 10
Percentage of Participants With Successful Embryo Transfer	approximately day 18
Number of Days Stimulated With Gonadotrophins	Day 1 up to Day 12	Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study.
Number of Ampoules of Gonadotrophins Used	Day 1 up to Day 12	Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.
Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test	approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test	A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy.
Summary of Pregnancy Outcome	up to 10 months	Pregnancy outcomes were reported at the optional long-term follow up visit.

Trial Locations

Locations (8): IVF Zentrum
🇩🇪
Saar, Germany
Endokrinologikum Ulm
🇩🇪
Ulm, Germany
Fertility Center Berlin
🇩🇪
Berlin, Germany
Praxisklinik Sydow am Gendarmenmarkt
🇩🇪
Berlin, Germany
Kinderwunschzentrum Dortmund
🇩🇪
Dortmund, Germany
Praxis für Kinderwunschbehandlung
🇩🇪
Erlangen, Germany
NOVUM Zentrum
🇩🇪
Essen, Germany
Universitätsklinikum Duesseldorf, Frauenklinik
🇩🇪
Dusseldorf, Germany