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

Ferring Pharmaceuticals124 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

124

Conditions

Infertility

Interventions

MenotrophinDRUG

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.

Follitrophin alphaDRUG

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.

CetrorelixDRUG

Participants self-inject subcutaneously Cetrorelix in the morning at a daily dose of 0.25 mg/day from Day 5 of gonadotrophin administration on and continue throughout the period of gonadotrophin treatment up to day 12 as a maximum. The last dose of Cetrorelix is given on the day of ovulation induction.

Eligibility

Sex: FEMALEMin age: 34 YearsMax age: 42 Years

Medical Language ↔ Plain English

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

Locations (8)

Fertility Center Berlin

Berlin, Germany

Praxisklinik Sydow am Gendarmenmarkt

Berlin, Germany

Kinderwunschzentrum Dortmund

Dortmund, Germany

Universitätsklinikum Duesseldorf, Frauenklinik

Düsseldorf, Germany

Outcomes

Primary Outcomes

Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration

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).

Time frame: approximately day 10

Secondary Outcomes

Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of 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.

Time frame: Day 7, approximately Day 10 (hCG Administration)

Percentage of Participants With Ongoing Pregnancy

Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.

Time frame: approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)

Number of Follicles at hCG Administration

Number of follicles \>=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.

Time frame: approximately day 10

Average Follicle Diameter at hCG Administration

Time frame: approximately day 10

Number of Cumulus-oocyte Complexes Retrieved

Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.

Data from ClinicalTrials.gov

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ChoriongonadotropinDRUG

10,000 IU administered by the Investigator or designated personnel in the evening of the day on which the hCG criterion is met (no later than Day 13). The criterion for hCG administration is three follicles \>+17 mm diameter as shown by pelvic ultrasound examination.

ProgesteroneDRUG

Vaginal gel progesterone is used once daily at a dose of 90 mg for a period of 30 days starting on the day of oocyte retrieval (approximately Day 14).

Praxis für Kinderwunschbehandlung

Erlangen, Germany

NOVUM Zentrum

Essen, Germany

IVF Zentrum

Saar, Germany

Endokrinologikum Ulm

Ulm, Germany

Time frame: approximately day 12 after study start

Number of Pronuclear Oocytes

Pronuclear oocytes are fertilized oocytes.

Time frame: approximately day 13 after study start

Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade

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.

Time frame: approximately day 13

Number of Embryos Transferred

Mean number of embryos transferred 2-3 days following oocyte retrieval.

Time frame: approximately day 14

Best Quality of an Embryo Transferred

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.

Time frame: approximately day 14

Number of Frozen Oocytes at Pronuclear Stage

No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.

Time frame: approximately day 14

Endometrial Thickness on Day of hCG Administration

Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.

Time frame: approximately day 10

Estradiol (E2) Levels on Day of hCG Administration

Time frame: approximately day 10

Percentage of Participants With Successful Embryo Transfer

Time frame: approximately day 18

Number of Days Stimulated With Gonadotrophins

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.

Time frame: Day 1 up to Day 12

Number of Ampoules of Gonadotrophins Used

Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.

Time frame: Day 1 up to Day 12

Percentage of Participants With Clinical Pregnancy 6 Weeks After the 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.

Time frame: approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test

Summary of Pregnancy Outcome

Pregnancy outcomes were reported at the optional long-term follow up visit.

Time frame: up to 10 months